TREA

Antifungal carbinols

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  • Patent Grant
  • 4980367
  • Patent Number
    4,980,367
  • Date Filed
    Wednesday, October 18, 1989
    35 years ago
  • Date Issued
    Tuesday, December 25, 1990
    34 years ago
Information
Abstract
Antifungal carbionols, particularly .alpha.-styryl carbinols, and the corresponding epoxy carbinols are provided. These carbinol compounds have the formula: ##STR1## or a pharmaceutically or agriculturally suitable salt thereof wherein E is a bond or an oxygen atom with the proviso that when E is oxygen; R, R.sup.1 are not halogen; andL, A, B, Q, R.sup.2, R.sup.3, R.sup.4 and n are as defined inthe specification.
Description

FIELD OF THE INVENTION
This invention relates to antifungal carbinols, particularly .alpha.-styryl carbinols, and the corresponding epoxy carbinols, pharmaceutical and agricultural compositions containing them, processes for preparing them and methods of using them as antifungal agents in mammals and plants.
BACKGROUND INCLUDING PRIOR ART
Systemic fungal infections are of increasing importance because of continued and expanded use of immunosuppressive therapies, antimicrobial therapies and indwelling catheters. Currently there are limited therapies available to treat such fungal infections. Amphotericin B remains the drug of choice because it has the widest spectrum of antifungal activity of any systemic antifungal drug, however its utility is limited by its toxicity. Because of the potential seriousness of its toxic effects, intravenous use of amphotericin B is primarily for patients with progressive, potentially fatal infections in which the patient is hospitalized during the course of therapy. Thus, there is a continuing need to develop safer and more effective drugs which are useful for the treatment of fungal infections.
Plant pathogenic fungi and other disease incitants also cause extensive losses in crops annually. While there are commercially available materials used to control many plant diseases, further improvement in this art is needed if full food and fiber production is to be realized.
There are a large number of patent and literature references in the area of azole antifungal drugs and plant disease control agents. Most pertinent to the .alpha.-styryl carbinol compounds of this invention are the following references:
B. Sugavanam in U.S. Pat. No. 4,507,140 issued Mar. 26, 1985 discloses fungicidal or plant growth regulating .beta.-styryl triazoles or imidazoles, amongst others of the formula: ##STR2## where R.sup.1 is CH.dbd.CH--X; --C.tbd.C--X or --CH.sub.2 --CH.sub.2 --X;
X is substituted aryl, aralkyl, or heterocycle;
R.sup.2 is alkyl, cycloalkyl, or optionally substituted aryl;
Z is OR.sup.3 ;
R.sup.3 is H, acetyl;
Y is --N-- or --CH--.
German Patent No. 3,018,865, published May 16, 1980 discloses antimycotic agents of the formula: ##STR3## where amongst others R is alkyl, optionally substituted cycloalkyl or optionally substituted phenyl radical;
X is N, or a CH group;
Y is --OCH.sub.2 --, --CH.sub.2 CH.sub.2 -- or CH.dbd.CH;
Z is halogen, alkyl, cycloalkyl, alkoxy, alkythio, etc.
German Patent No. 3,314,548-A, published Apr. 21, 1983 discloses substituted 1-hydroxy-ethyl-thiazole derivatives of the formula: ##STR4## where amongst others R is alkyl, cycloalkyl or phenyl optionally substituted;
X is --OCH.sub.2 --, --SCH.sub.2 --, --(CH.sub.2).sub.p or --CH.dbd.CH--;
Z is halogen, alkyl, alkoxy, alkylthio, haloalkyl, haloalkoxy, or haloalkylthio;
m and p are 0, 1 and 2.
The compounds are antimycotics for treating dermatophytomycoses and systemic mycoses caused, e.g., by Candida sp., Aspergillus sp., Trichophyton sp.
The above three references, which pertain to .beta.-styryl azoles, are believed to be the most relevant. The .beta.-styryl azole analog of one of the preferred compounds of the instant invention was prepared and found to be significantly less active.
European Patent Application No. 114,487 which published Aug. 1, 1984 discloses azolylethanol derivatives of the formula: ##STR5##
Where amongst others R.sup.1 and R.sup.2 which may be the same or different are hydrogen, alkyl, cycloalkyl, alkenyl, heterocyclyl aryl, or aralkyl optionally substituted; W is N or CH; and X is C.dbd.O. The compounds have fungicidal activity and plant growth regulating activity.
European Patent No. 117,578-A, published Feb. 23, 1984 discloses heterocyclic-hydroxy-alkyl alkyl ketone(s) and analogues of the formula: ##STR6## where A is CO amongst others;
Q is imidazoyl or 1H- or 4H-1,2,4-triazol-1-yl;
R.sup.1 is H, 1-5C alkyl, or 1-8C acyl;
R.sup.2 and R.sup.3 are 1-5C alkyl, 3-6C cycloalkyl, 2-6C alkenyl, benzyl (optionally substituted by 1-3 halogen), pyridyl, furyl, thienyl, or phenyl optionally substitutes by 1-3 halogen, 1-3 alkyl, or 1-3C alkoxy.
Belgian Patent No. 900,594-A published Sept. 22, 1983 discloses 1-phenyl-1-azolyl-hydroxyethyl cycloalkane derivatives of the formula: ##STR7## where R.sub.1 and R.sub.2 =H, halo, NO.sub.2, lower alkyl, alkenyl, alkynyl, alkoxy or alkylthio (all optionally substituted by 1 or more halo), or optionally substituted phenyl or phenoxy;
R.sub.3 =H or lower alkyl;
R.sub.4 and R.sub.5 =H or halo;
Y=CH or N;
A=2-7C alkylene;
n=0 or 1.
The compounds are useful as agricultural fungicides and antimycotics.
None of the cited references nor any known references suggest the novel antifungal compounds of this invention.
SUMMARY OF THE INVENTION
According to the present invention compounds are provided having the formula: ##STR8## or a pharmaceutically or agriculturally suitable salt thereof wherein E is a bond or an oxygen atom with the proviso that when E is oxygen; R, R.sup.1 are not halogen;
A is perfluoroalkyl of 1-8 carbon atoms, N(CH.sub.3).sub.2, OH, naphthyl optionally substituted with a total of 1-3 substituents each of which is independently selected from halogen and CF.sub.3, ##STR9## optionally substituted with 1 or 2 methyl groups, phenyl optionally substituted with a total of 1-3 substituents each of which is independently selected from:
halogen, alkyl of 1-4 carbon atoms, haloalkyl of 1-4 carbon atoms, alkoxy of 1-4 carbon atoms, and with no more than one group selected from:
haloalkoxy of 1-4 carbon atoms, CN, CO.sub.2 R.sub.14, CH.dbd.NOR.sub.14, S(O).sub.m R.sup.5, R.sub.6, 2-,3-, or 4-pyridyl or an N-oxide thereof, imidazol-1-yl, 1,2,4-triazol-1-yl, and ##STR10## optionally substituted with 1 and 2 methyl groups, or a heterocycle selected from imidazol-1-yl, 1,2,4-triazol-1-yl, 2- or 3-thienyl, and 2-,3-, or 4-pyridyl or an N-oxide thereof, optionally substituted with one or two substituents each of which is independently selected from:
halogen, alkyl of 1-4 carbon atoms, CF.sub.3, alkoxy of 1--4 carbon atoms, haloalkoxy of 1-4 carbon atoms, and S(O).sub.m R.sup.5 ;
B is alkyl of 1-8 carbon atoms, naphthyl, biphenyl, ##STR11## perfluoroalkyl of 1-8 carbon atoms, phenyl optionally substituted with 1-3 substituents each of which is independently selected from: halogen, alkyl of 1-4 carbon atoms, haloalkyl of 1-4 carbon atoms, alkoxy of 1-4 carbon atoms, and with no more than one group selected from haloalkoxy of 1-4 carbon atoms, CN, CO.sub.2 R.sub.14, CH.dbd.NOR.sub.14, S(O).sub.m R.sup.5, 2-,3-,4-pyridyl or an N oxide thereof,
benzyl optionally substituted on the phenyl ring with halogen or alkyl of 1-4 carbon atoms, or optionally .alpha.-substituted with 1 or 2 methyl groups, or
a heterocycle selected from 2- or 3-thienyl, and 2-,3-, or 4-pyridyl, said heterocycles being optionally substituted with one or two substituents each of which is independently selected from:
halogen, alkyl of 1-4 carbon atoms, haloalkyloxy of 1-4 carbon atoms, CF.sub.3, or S(O).sub.m R.sup.5 ;
Q is H, halogen, S(O).sub.m R.sup.11, ##STR12## CO.sub.2 R.sup.13, SCN, SSR.sup.12, or SH or its corresponding disulfide, provided however that when Q is other than H, then n is O, R, R.sup.1, and R.sup.4 are independently H or CH.sub.3, R.sup.3 is H, and A and B are each phenyl optionally substituted with from 1-3 substituents each of which is independently halogen, CH.sub.3, CF.sub.3, OCH.sub.3, or S(O).sub.m R.sup.5 ;
L is CH or N with the proviso that when L=CH then Q=H;
n is 0-4 with the proviso that when A is ##STR13## N(CH.sub.3).sub.2, or OH, then n is other than O; m each occurrence is 0, 1 or 2;
X is C, NR.sup.10, or 0;
R and R.sup.1 independently are H, alkyl of 1-4 carbon atoms, halogen, or phenyl, or taken together form cycloalkyl of 3-7 carbon atoms;
R.sup.2 is H, allyl, propargyl, alkyl of 1-4 carbon atoms, ##STR14## or haloalkyl of 1-4 carbon atoms; R.sup.3 and R.sup.4 independently are H, F, or allyl of 1-4 carbon atoms;
R.sup.5 is alkyl of 1-4 carbon atoms;
R.sup.6 is phenyl optionally substituted with a total of 1-3 substituents each of which is independently selected from halogen and CF.sub.3 ;
R.sup.7 is alkyl of 1-4 carbon atoms, phenyl, or benzyl;
R.sup.8 and R.sup.9 independently are H, alkyl of 1-4 carbon atoms, phenyl or benzyl;
R.sup.10 is H, alkyl of 1-4 carbon atoms, or acetyl;
R.sup.11 is alkyl of 1-4 carbon atoms, haloalkyl of 1-2 carbon atoms, CH.sub.2 CN, CH.sub.2 SCN, CH(CH.sub.3)CN, CH.sub.2 CO.sub.2 CH.sub.3, or CH.sub.2 CO.sub.2 CH.sub.2 CH.sub.3 ;
R.sup.12 is alkyl of 1-4 carbon atoms, allyl, phenyl optionally substituted with 1-2 substituents each of which is independently halogen, CH.sub.3, or OCH.sub.3, or benzyl optionally substituted with 1-2 substituents each of which is independently halogen, CH.sub.3, or OCH.sub.3 ;
R.sup.13 is H, or alkyl of 1-4 carbon atoms; and
R.sup.14 is alkyl of 1-4 carbon atoms.
Also provided are pharmaceutical compositions comprising a suitable pharmaceutical carrier and a therapeutically effective amount of a compound of Formula (I) or its pharmaceutically suitable salt and methods of using the compounds of Formula (I) as antifungal agents.
This invention further provides agricultural compositions comprising a compound of Formula (I) or its agriculturally suitable salt together with an agriculturally acceptable diluent or carrier and a method of controlling fungal diseases in plants.
Certain compounds of this invention are useful as herbicides and plant growth regulants. This invention, therefore, also relates to the herbicidal composition of these compounds and their method of use as herbicides.
The herbicidal compounds are those of Formula (I) wherein:
E is a bond;
L is N;
A is perfluoroalkyl of 1-4 carbon atoms, naphthyl optionally substituted with a total of 1-2 substituents each of which is independently selected from halogen and CF.sub.3, ##STR15## optionally substituted with 1 or 2 methyl groups, phenyl optionally substituted with a total of 1-3 substituents each of which is independently selected from:
halogen, alkyl of 1-3 carbon atoms, haloalkyl of 1-3 carbon atoms, alkoxy of 1-3 carbon atoms, and with no more than one group selected from:
haloalkoxy of 1-3 carbon atoms, CN, CO.sub.2 R.sup.14, CH.dbd.NOR.sup.14, R.sub.6, 2-,3-, or 4-pyridyl, or an N-oxide thereof, imidazol-1-yl, 1,2,4-triazol-1-yl, and ##STR16## optionally substituted with 1 or 2 methyl groups, or a heterocycle selected from imidazol-1-yl, 1,2,4-triazol-1-yl, 2- or 3-thienyl, and 2-,3-, or 4-pyridyl, said heterocycles being optionally substituted with one or two substituents each of which is independently selected from:
halogen, alkyl of 1-2 carbon atoms, and CF.sub.3 ;
B is alkyl of 1-4 carbon atoms, naphthyl, perfluoroalkyl of 1-4 carbon atoms, phenyl optionally substituted with 1-2 substituents each of which is independently selected from: halogen, alkyl of 1-3 carbon atoms, haloalkyl of 1-3 carbon atoms, alkoxy of 1-3 carbon atoms, and with no more than one group selected from haloalkoxy of 1-3 carbon atoms, and CN,
benzyl optionally substituted on the phenyl ring with halogen or alkyl of 1-3 carbon atoms, or optionally .alpha.-substituted with 1 or 2 methyl groups, or
a heterocycle selected from 2- or 3-thienyl, and 2-,3-, or 4-pyridyl, said heterocycles being optionally substituted with one or two substituents each of which is independently selected from:
halogen, alkyl of 1-3 carbon atoms, of CF.sub.3 ;
Q is H, halogen, S(O).sub.m R.sup.11, ##STR17## CO.sub.2 R.sup.13, SCN, SSR.sup.12, or SH or its corresponding disulfide, provided however that when Q is other than H, then n is O, R, R.sup.1, and R.sup.4 are independently H or CH.sub.3, R.sup.3 is H, and A and B are each phenyl optionally substituted with from 1-3 substituents each of which is independently halogen, CH.sub.3, CH.sub.3, or OCH.sub.3 ;
n is 0-2 with the proviso that when A is ##STR18## then n is other than O; m each occurrence is 0, 1 or 2;
X is C, NR.sup.10, or O;
R and R.sup.1 independently are H, alkyl of 1-2 carbon atoms, halogen, or phenyl, or taken together form cycloalkyl of 3-6 carbon atoms;
R.sup.2 is H, allyl, propargyl, alkyl of 1-2 carbon atoms, ##STR19## or haloalkyl of 1-4 carbon atoms; R.sup.3 and R.sup.4 independently are H, F, or alkyl of 1-2 carbon atoms;
R.sup.6 is phenyl optionally substituted with a total of 1-3 substituents each of which is independently selected from halogen and CF.sub.3 ;
R.sup.7 is alkyl of 1-2 carbon atoms, phenyl, or benzyl;
R.sup.8 and R.sup.9 independently are H, alkyl of 1-2 carbon atoms, phenyl or benzyl;
R.sup.10 is H, alkyl of 1-2 carbon atoms, or acetyl;
R.sup.11 is alkyl of 1-2 carbon atoms, haloalkyl of 1-2 carbon atoms, CH.sub.2 CN, CH.sub.2 SCN, CH(CH.sub.3)CN, CH.sub.2 CO.sub.2 CH.sub.3, or CH.sub.2 CO.sub.2 CH.sub.2 CH.sub.3 ;
R.sup.12 is alkyl or 1-2 carbon atoms, allyl, phenyl optionally substituted with 1-2 substituents each of which is independently halogen, CH.sub.3, or OCH.sub.3, or benzyl optionally substituted with 1-2 substituents each of which is independently halogen, CH.sub.3, or OCH.sub.3 ; and
R.sup.13 is H, or alkyl of 1-2 carbon atoms.
Further provided are processes for the preparation of the aforesaid compounds, which processes are described hereinafter.
Additionally provided are novel intermediates having the formulas (II) and (IIa) shown below: ##STR20## wherein A, B, R, R.sup.1, R.sup.3, R.sup.4 and n are as defined above, except that R.sup.3, R.sup.4 are not F and not both alkyl.
PREFERRED EMBODIMENTS
Preferred compounds are the .alpha.-styryl compounds of formula (I) (E is a bond) where:
(1) n=0, or 1; and/or
(2) R.sup.3 and R.sup.4 independently are H, CH.sub.3, or F.
More preferred compounds are preferred compounds where:
(1) A, and B independently are phenyl optionally substituted with from 1-3 substituents each of which is halogen, alkyl of 1-4 carbon atoms, haloalkyl of 1-4 carbon atoms, alkoxy of 1-4 carbon atoms, or S(O).sub.m R.sup.5 ; and/or
(2) n=0; and/or
(3) R and R.sup.1 independently are H, CH.sub.3 or halogen; and/or
(4) R.sup.2 =H, alkyl of 1-4 carbon atoms, allyl, or propargyl; and/or
(5) Q is H, I, SH.
Most preferred compounds are more preferred compounds where:
(1) A and B independently are phenyl optionally substituted with from 1-3 halogen atoms, CH.sub.3, OCH.sub.3, CF.sub.3, or SCH.sub.3 ; and/or;
(2) R, R.sup.1, R.sup.2, R.sup.3, R.sup.4 and Q are all H.
Specifically preferred because of their biological activity are the following compounds or salts thereof;
(a) 2-(4-Fluorophenyl)-3-phenyl-1-(1H-1,2,4-triazol-1-yl)-3-buten-2-ol; and the (S) enantiomer thereof.
(b) 2,3-Bis(4-fluorophenyl)-1-(1H-1,2,4-triazol-1-yl)-3-buten-2-ol; and the (S) enantiomer thereof.
(c) 2-(2,4-Dichlorophenyl)-3-(4-chlorophenyl)-1-(1H-1,2,4-triazol-1-yl) -3-buten-2-ol; and the (S) enantiomer thereof.
(d) 2-(4-Chlorophenyl)-3-(2-chlorophenyl)-1-(1H-1,2,4-triazol-1-yl) -3-buten-2-ol; and the (S) enantiomer thereof.
(e) 2-(2,4-Dichlorophenyl)-3-(3-fluorophenyl)-1-(1H-1,2,4-triazol-1-yl) -3-buten-2-ol; and the (S) enantiomer thereof.
(f) 2-(2-Chlorophenyl)-3-(2-chlorophenyl)-1-(1H-1,2,4-triazol-1-yl) -3-buten-2-ol; and the (S) enantiomer thereof.
(g) 2-(2,4-Dichlorophenyl)-3-(3-chlorophenyl)-1-(1H-1,2,4-triazol-1-yl) -3-buten-2-ol; and the (S) enantiomer thereof.
(h) 2-(4-Fluorophenyl)-3-(4-trifluoromethylphenyl)-1-(1H-1,2,4-triazol-1-yl) -3-buten-2-ol; and the (S) enantiomer thereof.
(i) 2-(2,4-Dichlorophenyl)-3-phenyl-1-(1H-1,2,4-triazol-1-yl) -3-buten-2-ol; and the (S) enantiomer thereof.
(j) 2-(3,4-Dichlorophenyl)-3-(4-fluorophenyl)-1-(1H-1,2-4-triazol-1-yl) -3-buten-2-ol; and the (S) enantiomer thereof.
(k) 2-(4-Chlorophenyl)-3-(3-chlorophenyl)-1-(1H-1,2,4-triazol-1-yl) -3-buten-2-ol; and the (S) enantiomer thereof.
(l) 2-(4-Fluorophenyl)-3-(2,4-difluorophenyl)-1-(1H-1,2,4-triazol-1-yl) -3-buten-2-ol; and the (S) enantiomer thereof.
(m) 2-(2,4-Difluorophenyl)-3-(2-chlorophenyl)-(1H-1,2,4-triazol-1-yl)-3-buten-2-ol; and the (S) enantiomer thereof.
(n) 2-(2,4-Dichlorophenyl)-3-(2-chlorophenyl)-1-(1H-1,2,4-triazol-1-yl) -3-buten-2-ol; and the (S) enantiomer thereof.
(o) 2-(2,4-Difluorophenyl)-3-phenyl)-1-(1H-imidazol-1-yl)-3-buten-2-ol; and the (S) enantiomer thereof.
(p) 2-(2,4-Difluorophenyl)-3-(4-fluorophenyl)-1-(1H-imidazol-1-yl)-3-buten-2-ol; and the (S) enantiomer thereof.
(q) 2-(2,4-Difluorophenyl)-3-(2-chlorophenyl)-1-(1H-imidazol-1-yl)-3-buten-2-ol; and the (S) enantiomer thereof.
(r) 2-(2,4-Difluorophenyl)-3-phenyl-1-(1H-1,2,4-triazol-1-yl)-3-buten-2-ol; and the (S) enantiomer thereof.
(s) 2-(2,4-Difluorophenyl)-3-(4-fluorophenyl)-1-(1H-1,2,4-triazol-1-yl) -3-buten-2-ol; and the (S) enantiomer thereof.
(t) 2-(2-Fluorophenyl)-3-(4-fluorophenyl)-1-(1H-1,2,4-triazol-1-yl) -3-buten-2-ol; and the (S) enantiomer thereof.
(u) 2-(2-Fluorophenyl)-3-(4-chlorophenyl)-1-(1H-1,2,4-triazol-1-yl) -3-buten-2-ol; and the (S) enantiomer thereof.
(v) 2-(2-(2,4-Difluorophenyl)-3-(4-chlorophenyl)-1-(1H-1,2,4-triazol-1yl) -3-buten-2-ol; and the (S) enantiomer thereof.
(w) 2-(2-Chlorophenyl)-3-(4-fluorophenyl)-1-(1H-1,2,4-triazol-1-yl) -3-buten-2-ol; and the (S) enantiomer thereof.
(x) 2-(4-Chlorophenyl)-3-phenyl-1-(1H-1,2,4-triazol-1-yl)-3-buten-2-ol; and the (S) enantiomer thereof.
All of the compounds within the scope of this invention are active in either pharmaceutical or agricultural fungicidal assays. Thus, it should be recognized that there are compounds which are not always active in both assays as is shown with some compounds in the Examples. Of the above listed specifically preferred compounds, compounds (a)-(r) or their salts are preferred for pharmaceutical uses and compounds (r)-(x) or their salts are preferred for agricultural uses.
DETAILED DESCRIPTION OF THE INVENTION
Synthesis
The novel compounds of Formula (I) can be prepared using the reactions and techniques described in this section. The reactions are usually performed in a solvent appropriate to the reagents and materials employed, and suitable for the transformation being effected. In some cases functional groups on the starting materials may need to be protected by standard protecting groups reported in the chemical literature which are well known to one skilled in the art.
In some cases, substituents on the starting materials may be incompatible with some of the reaction conditions required in some of the methods described. Such restrictions to the substituents which are compatible with the reaction conditions will be readily apparent to one skilled in the art and alternative methods described must then be used.
The compounds of the present invention can contain at least one chiral center and as such can exist as two individual isomers or as a racemic mixture of both. This invention relates to the (S) isomer, as well as to racemic mixtures containing both isomers.
For the purposes of this invention, the (S)-isomer of compounds of Formula (I) is intended to mean compounds of the configuration depicted: ##STR21##
When a single chiral center is present the resolution can be performed by reacting the compound with a chiral strong acid (e.g. substituted camphorsulfonic acids) in a suitable solvent (e.g. acetonitrile) or mixture of solvents (e.g. 3/1 etheracetone). This reaction is carried out at a temperature between 25.degree. C. to 100.degree. C., preferably at the reflux temperature of the solvent(s) employed. The reaction produces two diastereomeric adducts that can be separated by fractional crystallization. The adduct can then be cleaved in basic medium (e.g. sat. NaHCO.sub.3, sat. Na.sub.2 CO.sub.3) to give the resolved product.
The compounds of Formula I, where E is a bond, R.sup.2 and Q are H and R.sup.3, R.sup.4 are not F and not both alkyl, can be prepared by contacting an oxirane of Formula (II) or a halohydrin of Formula (IIa), or a mixture of (II) or (IIa) with imidazole or triazole or a corresponding alkali metal salt (preferably the Na.sup.+ or K.sup.+ salt) in a suitable solvent (Scheme I). ##STR22##
When imidazole or triazole is used, an acid acceptor, such as potassium carbonate, sodium methoxide or sodium hydride, is added to the reaction mixture. Suitable inert solvents include polar, aprotic solvents such as dimethylformamide (DMF), dimethylsulfoxide (DMSO) and ethereal solvents such as tetrahydrofuran (THF). Non-polar solvents, such as toluene, may be used if a phase transfer catalyst, such as tetrabutylammonium bromide, is added. The reaction is carried out at a temperature in the range of 10.degree. to 150.degree. C., preferably from 50.degree. to 120.degree. C., for a period of 0.25 to 24 hours. It is recognized that varying amounts of the 4H-1,2,4-triazol-4-yl isomers of Formula (I) may be formed when triazole is used in the above reaction. The isomers can be separated, if desired, using standard separation techniques, e.g., chromatography.
The 4H-1,2,4-triazol-4-yl isomers of Formula (I) can be converted to the compounds of Formula (I) by isomerization with base as described in EP No. 143384A2, or by heating with 2-100 mol % of oxiranes of Formula (II), halohydrins of Formula (IIa), reactive alkyl or benzyl bromides or iodides, such as benzyl bromide or methyl iodide, or commercial oxiranes such as styrene oxide, at temperatures of 100.degree.-200.degree. C.; preferably in a polar aprotic solvent such as DMF, or a non-polar solvent such as one of the xylenes.
The oxiranes of Formula (II) can be prepared using one or both of the following methods; (Scheme 2). In the first, vinyl organometallic reagents, e.g., vinyl Grignard reagents, of Formula (III) are allowed to react with haloketones of Formula (IV) in the presence of ethereal solvents, such as THF or diethyl ether, at a temperature ranging from -90.degree. to 60.degree. C., preferably -10.degree. to 50.degree. C., for 0.5 to 24 hours. Depending on the reaction conditions and the value of X in the haloketone starting material (IV), the product may be an oxirane (II), a halohydrin (IIa) or a mixture of (II) and (IIa). If desired, the halohydrins (IIa) may be converted to oxiranes (II) by treatment with base, e.g., potassium hydride (KH), in a solvent such as THF. ##STR23##
In the second method, keto-oxiranes of formula (V) are olefinated with, for example, Wittig reagents, which provide epoxy-olefins of Formula (II).
Unsaturated ketones of Formula (VII) can be converted to expoxy-olefins (II) by treatment with dimethylsulfonium methylide. The enones (VII) can be prepared by treatment of ketones of Formula (VI) with carbonyl compounds and appropriate catalysts (Scheme 3). ##STR24##
Unsaturated ketones of Formula (VIII) can be converted to epoxyketones (V) using basic hydrogen peroxide. Olefination of (V), as described above, provides epoxyolefins (II) (Scheme 4). ##STR25##
The vinyl organometallics of Formula (III) are prepared using standard procedures from the corresponding chlorides, bromides or iodides. The haloolefins, the haloketones of Formula (IV), the ketooxiranes of Formula (V) and the ketones of Formula (VI) are known, or can be prepared using methods known to one skilled in the art.
Compounds of Formula (I) can also be prepared by olefinations of ketones (IX) with, for example, Wittig reagents (Scheme 5). Ketones of Formula (IX) where R.sup.2, R.sup.3 and R.sup.4 =H are known (EP No. 117578A). ##STR26##
Compounds of general Formula (I) where R.sup.3 and/or R.sup.4 .noteq.H can be made as shown in Scheme 6 by reacting ketones of general Formula (X) with the appropriate organometallic reagent (e.g. Grignard reagent, organolithium reagent). The ketones (X) are prepared by conventional methods from the corresponding .alpha.-haloketones (IV) (see e.g. EP No. 0044605, UK No. 2099818A, UK No. 146224, EP No. 1337718, and EP No. 0153803). ##STR27##
Compounds of Formula (I) where A=(heterocycle)-phenyl can be prepared from appropriately substituted precursors using the methods described above, or by using substitution reactions on (I) wherein A is halophenyl. For example, compounds of Formula (I) where A is (pyridyl)phenyl can be prepared by treatment of (I), wherein A is bromophenyl or iodophenyl, with the appropriate pyridylstannanes in the presence of palladium catalysts (see Tetrahedron Letters, 27, 4407, 1986). Copper assisted displacement of halogen (Tetrahedron, 40, 1433, 1984) with heterocyclic nucleophiles provides compounds of Formula (I) where A is for example 1-imidazolylphenyl.
In some cases, it may be desirable to begin with compounds of Formula I, wherein A is aminophenyl, and construct the heterocyclic ring using X(CH.sub.2 CH.sub.2 Cl).sub.2 (see ES No. 8603-473-A).
The compounds of Formula (I) where Q.noteq.H and L=N can be prepared as shown in Scheme 7. Metalation of (I), Q=H with strong base provides the 5-metalated triazoles (Ia) (See Heterocycles, 23, 1645-49, 1985). When R.sup.2 is H, 2 equivalents of base are required. Typical conditions involve treatment of a solution of (I) in THF at -70.degree. with n-butyllithium for 15-30 minutes. Where the metalated triazole (Ia) is less soluble than (I), the addition of co-solvents, such as dimethylpropyleneurea (DMPU) may be beneficial. ##STR28##
The treatment of (Ia) with electrophiles gives a wide variety of (I) where Q.noteq.H. Electrophiles of relevance to the present invention include halogenating agents, sulfur, disulfides, carbon dioxide, dimethylamides and sulfur dioxide followed by alkyl halides. Subsequent functionalization, using methods known to one skilled in the art, provide other compounds of Formula (I) wherein Q.noteq.H. For example, the treatment of (I), where Q is SH with isocyanates or phthalimidosulfides provides thiocarbamates (I; ##STR29## or disulfides (I; Q=SSR.sup.12), respectively.
The compounds of general Formula (I) where E is oxygen can be prepared by oxidation of compounds of general Formula (I) where E is a bond provided that R, R.sup.1 .noteq.halogen using methods described in the literature (Scheme 8): ##STR30##
Suitable reagents which can effect his oxidation, depending on the nature of the substituents, include peracids such as m-chloroperbenzoic acid; hydroperoxides such as tert-butyl hydroperoxide in the presence of an appropriate catalyst such as vanadium acetonylacetonate; or hydrogen peroxide. Alternatively, the transformation can be effected by first forming the halohydrin with a hypohalous acid such as hypobromous acid and then reacting the intermediate halohydrin with a proton acceptor such as potassium tert-butoxide.
It will be noted by those skilled in the art that, depending on the nature of the compound to be oxidized, a mixture of diastereomers can be obtained. This can be controlled through selection of appropriate oxidation methods or, alternatively, the resulting mixture of diastereomers can be separated in a conventional manner (e.g. chromatography, fractional crystallization).
Compounds of Formula (I) where R.sup.2 is H can be alkylated, acylated and carbamoylated, using standard procedures, to prepare functional derivatives of the alcohol moiety.





The compounds of this invention and their preparation can be understood further by the following examples, but should not constitute a limitation thereof. In these examples, unless otherwise indicated, all temperatures are in degrees centigrade and parts and percentages are by weight.
Nuclear magnetic resonance (nmr) spectra were obtained in CDCl.sub.3 solution, unless otherwise noted. Abbreviations for nmr spectra are s=singlet, d=doublet, t=triplet, q=quartet, m=multiplet; peak positions are reported as parts per million downfield from tetramethylsilane.
EXAMPLE 1
PART A
2-(4-Fluorophenyl)-2-[1-(4-fluorophenyl)ethenyl] oxirane
PROCESS 1: Grignard Addition to an .alpha.-Haloketone
To a 25.degree. solution of Grignard reagent prepared from 6.0 g (0.030 mol) of 1-bromo-4'-fluorostyrene and 0.85 g (0.035 mol) of magnesium turnings in 60 mL of THF was added a solution of 5.2 g (0.030 mol) of 2-chloro-4'-fluoroacetophenone in 10 mL of THF. The solution was stirred for 2 hours at 25.degree.. Saturated aqueous NH.sub.4 Cl (10 mL) was added, the aqueous layer was extracted with 1:1 Et.sub.2 O/hexane and the combined organic layers were washed with brine, dried over MgSO.sub.4 and evaporated to give 10.2 g of an amber oil. Analysis by NMR (CDCl.sub.3) indicated that the desired oxirane was the major product: .delta.3.1, 3.3 (two d, epoxide protons; 5.5, 5.8 (two s, vinyl protons). The material was of sufficient purity to be used in the next step.
PROCESS 2: Olefination of 2-(4-Fluorophenyl)-2-(4-fluorobenzoyl)oxirane
To a suspension of 4.3 g (0.012 mol) of methyltriphenylphosphonium bromide in 15 mL of THF cooled to -70.degree. was added 8.4 mL (0.013 mol) of 1.55 M n-butyllithium over 3 min., keeping the temperature at less than -55.degree.. The resulting yellow suspension was allowed to warm to 0.degree. over 10 min, and was then treated with 2.6 g (0.010 mol) of 2-(4-fluorophenyl)-2-(4-fluorobenzyl)oxirane in 5 mL of THF. The light-brown suspension was stirred for 6 hours at 25.degree.. Standard workup gave 3.4 g of crude product which was flash chromatographed (Et.sub.2 O) to give 1.7 g of the desired product, which was of sufficient purity to be used in the next step. NMR (CDCl.sub.3).delta.3.1 (d): 3.3 (d); 5.5 (s); 5.8 (s).
PART B
2,3-Bis (4-Fluorophenyl)-1-(1H-1,2,4-triazol-1-yl)-3-buten-2-ol
A mixture of 10.2 g (0.040 ) of crude 2-(4-fluorophenyl)-2-[1-(4-fluorophenyl)ethenyl]oxirane and 7.0 g (0.065 mol) of potassium triazole in 60 mL of DMF was heated at 60.degree. overnight, then cooled and poured into 100 mL of 1:1 Et.sub.2 O/hexanes. After washing the organic layer three times with H.sub.2 O and once with brine, a precipitate formed in the organic layer. Filtering gave 4.8 g of a brown solid which was recrystallized from 500 mL of cyclohexane to yield 2.5 g of a light-tan powder, mp 136.degree.-137.degree. C.: NMR (CDCl.sub.3).delta.1.7 (br s, OH); 4.7 (q, 2H); 5.3 (s, 1H); 5.5 (s, 1H); 6.8-7.1 (m, 6H); 7.4 (m, 2H); 7.8 (s, 1H); 7.9 (s, 1H); IR (nujol) 3120 (br), 1900, 1600, 1505, 1220, 1139, 835 cm.sup.-1.
The compounds shown in Table 1 were prepared or can be prepared by the method described hereinabove.
In the tables, Ph means phenyl and substituted aryl groups are abbreviated, e.g., 4-F-Ph is 4-fluorophenyl, 2,4-Cl.sub.2 -Ph is 2,4-dichlorophenyl and 2-thienyl is thiophen-2-yl.
TABLE 1 ##STR31## Ex. No. A B n R R.sup.1 R.sup.2 R.sup.3 R.sup.4 M.P. .degree.C. 1 4-FPh 4-FPh 0 H H H H H 136-137 (HCl salt 182-184) 2 4-FPh 2,4-Cl.sub.2Ph 0 H H H H H 139-143 3 4-FPh 4-ClPh 0 H H H H H (oil).sup.a 4 4-FPh 2,4-F.sub.2Ph 0 H H H H H 102-103.5 5 4-FPh 4-CF.sub. 3Ph 0 H H H H H 6 4-FPh -n-C.sub.4 H.sub.9 0 H H H H H 72-73 7 4-FPh -n-C.sub.4 F.sub.9 0 H H H H H 8 2-FPh Ph 0 H H H H H 9 2-FPh 2-FPh 0 H H H H H 89-93 10 2-FPh 4-FPh 0 H H H H H (oil).sup.b 11 2-FPh 2,4-F.sub.2P h 0 H H H H H 121-122 12 2-FPh 2-ClPh 0 H H H H H 13 2-FPh 4-ClPh 0 H H H H H 116-117 14 2-FPh 2,4-Cl.sub.2Ph 0 H H H H H 115-116 15 3-FPh 4-FPh 0 H H H H H 106-109 16 3-FPh 2,4-Cl.sub.2Ph 0 H H H H H 145-147 17 3-FPh 4-ClPh 0 H H H H H 101-102 18 3-FPh 2,4-F.sub.2Ph 0 H H H H H 92-93 19 3-FPh 4-CF.sub.3Ph 0 H H H H H 20 3-FPh -n-C.sub.4 H.sub.9 0 H H H H H 21 3-FPh - n-C.sub.4 F.sub.9 0 H H H H H 22 3-FPh Ph 0 H H H H H 23 3-FPh 2-FPh 0 H H H H H 122-124 24 3-FPh 2-ClPh 0 H H H H H 25 4-ClPh P 4-Fh 0 H H H H H 110-115 26 4-ClPh 2,4-Cl.sub.2Ph 0 H H H H H 89-91 (HCl salt 184-190) 27 4-ClPh 4-ClPh 0 H H H H H 132-135 28 4-ClPh 2,4-F.sub.2Ph 0 H H H H H 124-125.5 29 4-ClPh 4-CF.sub.3Ph 0 H H H H H 30 4-ClPh -n-C.sub.4 H.sub.9 0 H H H H H 31 4-ClPh -n-C.sub.4 F.sub.9 0 H H H H H 32 2-ClPh 4-FPh 0 H H H H H (oil).sup.c 33 2-ClPh 2,4-Cl.sub.2Ph 0 H H H H H 150-152 (HCl salt 124-127) 34 2-Cl Ph 4-ClPh 0 H H H H H 153-154 HNO.sub.3 salt 138-141 (HCl salt H.sub.2 SO.sub.4 salt 180-182 175-180) H.sub.3 PO.sub.4 salt 158-160 35 2-ClPh 2,4-F.sub.2Ph 0 H H H H H 128-129 H.sub.2 SO.sub.4 salt 184-187 (HCl salt HNO.sub.3 salt 158-159 156-161) H.sub.3 PO.sub.4 salt 141-143 36 2-ClPh 4-CF.sub.3Ph 0 H H H H H 37 2-ClPh -n-C.sub.4 H.sub.9 0 H H H H H 38 2-ClPh -n-C.sub.4 F.sub.9 0 H H H H H 39 3-ClPh 4-FPh 0 H H H H H 95-96.5 40 3-ClPh 2,4-Cl.sub.2Ph 0 H H H H H 144-146 41 3-ClPh 4-ClPh 0 H H H H H 112-115 42 3-ClPh 2,4-F.sub.2Ph 0 H H H H H 115-116 43 3-ClPh 4-CF.sub.3Ph 0 H H H H H 44 3-ClPh -n-C.sub.4 H.sub.9 0 H H H H H 45 3-ClPh -n-C.sub.4 F.sub.9 46 3-ClPh Ph 0 H H H H H 47 3-ClPh 2-FPh 0 H H H H H 91-93 48 3-ClPh 2-ClPh 0 H H H H H 49 Ph 4-FPh 0 H H H H H 125-126 50 Ph 2,4-Cl.sub.2Ph 0 H H H H H 117-120 51 Ph 4-ClPh 0 H H H H H 111 52 Ph 2,4-F.sub.2Ph 0 H H H H H 119.5-122 (HCl salt 152-154) 53 Ph 4-CF.sub.3Ph 0 H H H H H 54 Ph -n-C.sub.4 H.sub.9 0 H H H H H 55 Ph -n-C.sub.4 F.sub.9 0 H H H H H 56 2-CF.sub.3Ph Ph 0 H H H H H (oil).sup.r 57 2-CF.sub.3Ph 2-FPh 0 H H H H H 127.5-130 58 2-CF.sub.3Ph 2-ClPh 0 H H H H H 152-156 59 3-CF.sub.3Ph Ph 0 H H H H H 101-103 60 3-CF.sub.3Ph 2-FPh 0 H H H H H (oil).sup.s 61 3-CF.sub.3Ph 2-ClPh 0 H H H H H 101-104 62 4-CF.sub.3Ph Ph 0 H H H H H 63 4-CF.sub.3Ph 2-FPh 0 H H H H H 64 4-CF.sub.3Ph 2-ClPh 0 H H H H H 65 4-CF.sub.3Ph 4-FPh 0 H H H H H 152-154 66 4-CF.sub.3Ph 2,4-Cl.sub.2Ph 0 H H H H H (oil).sup.t 67 4-CF.sub.3Ph 4-ClPh 0 H H H H H 144-145 68 4-CF.sub.3Ph 2,4-F.sub.2Ph 0 H H H H H 69 4-CF.sub.3Ph 4-CF.sub.3Ph 0 H H H H H 70 4-CF.sub.3Ph -n-C.sub.4 H.sub.9 0 H H H H H 71 4-CF.sub.3Ph -n-C.sub.4 F.sub.9 0 H H H H H 72 2-BrPh Ph 0 H H H H H 73 2-BrPh 2-FPh 0 H H H H H 74 2-BrPh 2-FPh 0 H H H H H 75 2-BrPh 2,4-F.sub.2Ph 0 H H H H H 76 2-BrPh 2-ClPh 0 H H H H H 77 2-BrPh 4-ClPh 0 H H H H H 78 2-BrPh 2,4-Cl.sub.2Ph 0 H H H H H 79 3-BrPh Ph 0 H H H H H 80 3-BrPh 2-FPh 0 H H H H H 81 3-BrPh 2-ClPh 0 H H H H H 82 4-BrPh Ph 0 H H H H H 83 4-BrPh 2-FPh 0 H H H H H 84 4-BrPh 2-ClPh 0 H H H H H 123-126 85 4-BrPh 4-FPh 0 H H H H H (oil).sup.d 86 4-BrPh 2,4-Cl.sub.2Ph 0 H H H H H 87 4-BrPh P 4-Clh 0 H H H H H 145-148 88 4-BrPh 2,4-F.sub.2Ph 0 H H H H H 123-125 89 4-BrPh 4-CF.sub.3Ph 0 H H H H H 90 4-BrPh -n-C.sub.4 H.sub.9 0 H H H H H 91 4-BrPh -n-C.sub.4 F.sub.9 0 H H H H H 92 2,4-F.sub.2Ph Ph 0 H H H H H 93 2,4-F.sub.2Ph 2-FPh 0 H H H H H 106-108 94 2,4-F.sub.2Ph 4-FPh 0 H H H H H 100-103 95 2,4-F.sub.2Ph 2,4-F.sub.2Ph 0 H H H H H 116-120 96 2,4-F.sub.2Ph 2-ClPh 0 H H H H H 97 2,4-F.sub.2Ph 4-ClPh 0 H H H H H 98 2,4-F.sub.2Ph 2,4-Cl.sub.2Ph 0 H H H H H 99 2,4-Cl.sub.2Ph 4-FPh 0 H H H H H (oil).sup.e 100 2,4-Cl.sub.2Ph 2,4-Cl.sub.2Ph 0 H H H H H 75-78 101 2,4-Cl.sub.2Ph 4-ClPh 0 H H H H H 60-62 102 2,4-Cl.sub.2Ph 2,4-F.sub.2Ph 0 H H H H H 106-109 103 2,4-Cl.sub.2Ph 4-CF.sub.3Ph 0 H H H H H 104 2,4-Cl.sub.2Ph -n-C.sub.4 H.sub.9 0 H H H H H 105 2,4-Cl.sub.2Ph -n-C.sub.4 F.sub.9 0 H H H H H 106 2,4-Cl.sub.2Ph Ph 0 H H H H H 45-54 107 2,4-Cl.sub.2Ph 2-FPh 0 H H H H H 68-73 108 2,4-Cl.sub.2Ph 2-ClPh 0 H H H H H (oil).sup.u 109 3,4-Cl.sub.2Ph Ph 0 H H H H H 110 3,4-Cl.sub.2Ph 2-FPh 0 H H H H H 111 3,4-Cl.sub.2Ph 2-ClPh 0 H H H H H 112 4-.sub.-t-BuP h Ph 0 H H H H H 113 4-.sub.-t-BuPh 2-FPh 0 H H H H H 114 4-.sub.-t-BuPh 4-FPh 0 H H H H H 110-113 115 4-.sub.-t-BuPh 2,4-F.sub.2Ph 0 H H H H H 116 4-.sub.-t-BuPh 2-ClPh 0 H H H H H 117 4-.sub.-t-BuPh 4-ClPh 0 H H H H H (oil).sup.f 118 4-.sub.-t-BuPh 2,4-Cl.sub.2Ph 0 H H H H H 119 2-CH.sub.3 SPh Ph 0 H H H H H 120 2-CH.sub.3 SPh 2-FPh 0 H H H H H 121 2-CH.sub.3 SPh 4-FPh 0 H H H H H 122 2-CH.sub.3 SPh 2,4-F.sub.2Ph 0 H H H H H 123 2-CH.sub.3 SPh 2-ClPh 0 H H H H H 124 2-CH.sub.3 SPh 4-ClPh 0 H H H H H 125 2-CH.sub.3 SPh 2,4-Cl.sub.2Ph 0 H H H H H 126 2-CH.sub.3 S(O)Ph Ph 0 H H H H H 127 2-CH.sub.3 S(O)Ph 2-FPh 0 H H H H H 128 2-CH.sub.3 S(O)Ph 4-FPh 0 H H H H H 129 2-CH.sub.3 S(O)Ph 2,4-F.sub.2Ph 0 H H H H H 130 2-CH.sub.3 S(O)Ph 2-ClPh 0 H H H H H 131 2-CH.sub.3 S(O)Ph 4-ClPh 0 H H H H H 132 2-CH.sub.3 S(O)Ph 2,4-Cl.sub.2Ph 0 H H H H H 133 2-CH.sub.3 S(O).sub.2Ph Ph 0 H H H H H 134 2-CH.sub.3 S(O).sub.2Ph 2-FPh 0 H H H H H 135 2-CH.sub.3 S(O).sub.2Ph 4-FPh 0 H H H H H 136 2-CH.sub.3 S(O).sub.2Ph 2,4-F.sub.2Ph 0 H H H H H 137 2-CH.sub.3 S(O).sub.2Ph 2-ClPh 0 H H H H H 138 2-CH.sub.3 S(O).sub.2Ph 4-ClPh 0 H H H H H 139 2-CH.sub.3 S(O).sub.2Ph 2,4-Cl.sub.2Ph 0 H H H H H 140 3-CH.sub.3 SPh Ph 0 H H H H H 141 3-CH.sub.3 SPh 2-FPh 0 H H H H H 142 3-CH.sub.3 SPh 4-FPh 0 H H H H H 143 3-CH.sub.3 SPh 2,4-F.sub.2Ph 0 H H H H H 144 3-CH.sub.3 SPh 2-ClPh 0 H H H H H 145 3-CH.sub.3 SPh 4-ClPh 0 H H H H H 146 3-CH.sub.3 SPh 2,4-Cl.sub.2Ph 0 H H H H H 147 3-CH.sub.3 S(O)Ph Ph 0 H H H H H 148 3-CH.sub.3 S(O)Ph 2-FPh 0 H H H H H 149 3-CH.sub.3 S(O)Ph 4-FPh 0 H H H H H 150 3-CH.sub.3 S(O)Ph 2,4-F.sub.2Ph 0 H H H H H 151 3-CH.sub.3 S(O)Ph 2-ClPh 0 H H H H H 152 3-CH.sub.3 S(O)Ph 4-ClPh 0 H H H H H 153 3-CH.sub.3 S(O)Ph 2,4-Cl.sub.2Ph 0 H H H H H 154 3-CH.sub.3 S(O).sub.2Ph Ph 0 H H H H H 155 3-CH.sub.3 S(O).sub.2Ph 2-FPh 0 H H H H H 156 3-CH.sub.3 S(O).sub.2Ph 4-FPh 0 H H H H H 157 3-CH.sub.3 S(O).sub.2Ph 2,4-F.sub.2Ph 0 H H H H H 158 3-CH.sub.3 S(O).sub.2Ph 2-ClPh 0 H H H H H 159 3-CH.sub.3 S(O).sub.2Ph 4-Cl Ph 0 H H H H H 160 3-CH.sub.3 S(O).sub.2Ph 2,4-Cl.sub.2Ph 0 H H H H H 161 4-CH.sub.3 SPh Ph 0 H H H H H 162 4-CH.sub.3 SPh 2-FPh 0 H H H H H 163 4-CH.sub.3 SPh 4-FPh 0 H H H H H 140-142 164 4-CH.sub.3 SPh 2,4-F.sub.2Ph 0 H H H H H 81-83 165 4-CH.sub.3 SPh 2-ClPh 0 H H H H H 166 4-CH.sub.3 SPh 4-ClPh 0 H H H H H 167 4-CH.sub.3 SPh 2,4-Cl.sub.2Ph 0 H H H H H 168 4-CH.sub.3 S(O)Ph Ph 0 H H H H H 169 4-CH.sub.3 S(O)Ph 2-FPh 0 H H H H H 170 4-CH.sub.3 S(O)Ph 4-FPh 0 H H H H H 81-84 171 4-CH.sub.3 S(O)Ph 2,4-F.sub.2Ph 0 H H H H H 131-134 172 4-CH.sub.3 S(O)Ph 2-ClPh 0 H H H H H 173 4-CH.sub.3 S(O)Ph 4-ClPh 0 H H H H H 174 4-CH.sub.3 S(O)Ph 2,4-Cl.sub.2Ph 0 H H H H H 175 4-CH.sub.3 S(O).sub.2Ph Ph 0 H H H H H 176 4-CH.sub.3 S(O).sub.2Ph 2-FPh 0 H H H H H 177 4-CH.sub.3 S(O).sub.2Ph 4-FPh 0 H H H H H 135 178 4-CH.sub.3 S(O).sub.2Ph 2,4-F.sub.2Ph 0 H H H H H 179 4-CH.sub.3 S(O).sub.2Ph 2-ClPh 0 H H H H H 180 4-CH.sub.3 S(O).sub.2Ph 4-ClPh 0 H H H H H 181 4-CH.sub.3 S(O).sub.2Ph 2,4-Cl.sub.2Ph 0 H H H H H 182 3--n-BuS(O)Ph 4-FPh 0 H H H H H 183 3--n-BuS(O)Ph 2,4-F.sub.2Ph 0 H H H H H 184 3--n-BuS(O)Ph 4-ClPh 0 H H H H H 185 3--n-BuS(O)Ph 2-4-Cl.sub.2Ph 0 H H H H H 186 2-CF.sub.3 OPh Ph 0 H H H H H 187 2-CF.sub.3 OPh 2-FPh 0 H H H H H 188 2-CF.sub.3 OPh 4-FPh 0 H H H H H 189 2-CF.sub.3 OPh 2,4-F.sub.2Ph 0 H H H H H 190 2-CF.sub.3 OPh 2-ClPh 0 H H H H H 191 2-CF.sub.3 OPh 4-ClPh 0 H H H H H 192 2-CF.sub.3 OPh 2,4-Cl.sub.2Ph 0 H H H H H 193 3-CF.sub.3 OPh Ph 0 H H H H H 194 3-CF.sub.3 OPh 2-FPh 0 H H H H H 195 3-CF.sub.3 OPh 4-FPh 0 H H H H H 196 3-CF.sub.3 P OPh 2,4-F.sub.2h 0 H H H H H 197 3-CF.sub.3 OPh 2-ClPh 0 H H H H H 198 3-CF.sub.3 OPh 4-ClPh 0 H H H H H 199 3-CF.sub.3 OPh 2,4-Cl.sub.2Ph 0 H H H H H 200 4-CF.sub.3 OPh Ph 0 H H H H H 201 4-CF.sub.3 OPh 2-FPh 0 H H H H H 202 4-CF.sub.3 OPh 4-FPh 0 H H H H H 203 4-CF.sub. 3 OPh 2,4-F.sub.2Ph 0 H H H H H 204 4-CF.sub.3 OPh 2-ClPh 0 H H H H H 205 4-CF.sub.3 OPh 4-ClPh 0 H H H H H 206 4-CF.sub.3 OPh 2,4-Cl.sub.2Ph 0 H H H H H 207 4-F-1-naphthyl 2-FPh 0 H H H H H 208 1-naphthyl 4-FPh 0 H H H H H 104-106 209 1-naphthyl 2,4-F.sub.2Ph 0 H H H H H 210 1-naphthyl 2-ClPh 0 H H H H H 211 2-Cl-1-naphthyl 4-ClPh 0 H H H H H 212 1-naphthyl 2,4-Cl.sub.2Ph 0 H H H H H 213 2-naphthyl 2-FPh 0 H H H H H 214 2-naphthy l 4-FPh 0 H H H H H 215 2-naphthyl 2,4-F.sub.2Ph 0 H H H H H 216 2-naphthyl 2-Cl 0 H H H H H 217 1-Cl-2-naphthyl 4-ClPh 0 H H H H H 218 2-naphthyl 2,4-Cl.sub.2Ph 0 H H H H H 219 2-thienyl Ph 0 H H H H H 220 2-thienyl 2-FPh 0 H H H H H 221 2-thienyl 4-FPh 0 H H H H H 222 2-thienyl 2,4-F.sub.2Ph 0 H H H H H 223 2-thienyl 2-ClPh 0 H H H H H 224 2-thienyl 4-ClPh 0 H H H H H 225 2-thienyl 2,4-Cl.sub.2Ph 0 H H H H H 226 3-thienyl Ph 0 H H H H H 227 3-thienyl 2-FPh 0 H H H H H 228 3-thienyl 4-FPh 0 H H H H H 229 3-thienyl 2,4-F.sub.2Ph 0 H H H H H 230 3-thienyl 2-ClPh 0 H H H H H 231 3-thienyl 4-ClPh 0 H H H H H 232 3-thienyl 2,4-Cl.sub.2Ph 0 H H H H H 233 2-Cl-3-thienyl Ph 0 H H H H H 234 2-Cl-3-thienyl 2-FPh 0 H H H H H 235 2-Cl-3-thienyl 2-ClPh 0 H H H H H 236 5-Cl-2-thienyl Ph 0 H H H H H 237 5-Cl-2-thienyl 2-FPh 0 H H H H H 238 5-Cl-2-thienyl 2-ClPh 0 H H H H H 239 2,5-Cl.sub.2 -3-thienyl Ph 0 H H H H H 240 2,5-Cl.sub.2 -3-thienyl 2-FPh 0 H H H H H 241 2,5-Cl.sub.2 -3-thienyl 4-FPh 0 H H H H H 242 2,5-Cl.sub.2 -3-thienyl 2,4-F.sub.2Ph 0 H H H H H 243 2,5-Cl.sub.2 -3-thienyl 2-ClPh 0 H H H H H 244 2,5-Cl.sub.2 -3-thienyl 4-ClPh 0 H H H H H 245 2,5-Cl.sub.2 -3-thienyl 2,4-Cl.sub.2Ph 0 H H H H H 246 5-bromo-2-thienyl Ph 0 H H H H H 247 5-bromo-2-thienyl 2-FPh 0 H H H H H 248 5-bromo-2-thienyl 4-FPh 0 H H H H H 249 5-bromo-2-thienyl 2,4-F.sub.2P h 0 H H H H H 250 5-bromo-2-thienyl 2-ClPh 0 H H H H H 251 5-bromo-2-thie nyl 4-ClPh 0 H H H H H 252 5-bromo-2-thienyl 2,4-Cl.sub.2Ph 0 H H H H H 253 2-pyridyl Ph 0 H H H H H 254 2-pyridyl 2-FPh 0 H H H H H 255 2-pyridyl 2-ClPh 0 H H H H H 256 3-pyridyl Ph 0 H H H H H 257 3-pyridyl 2-FPh 0 H H H H H 258 3-pyridyl 2-ClPh 0 H H H H H 259 4-pyridyl Ph 0 H H H H H 260 4-pryidyl 2-FPh 0 H H H H H 261 4-pyridyl 2-ClPh 0 H H H H H 262 5-Cl-2-pyridyl Ph 0 H H H H H 263 5-Cl-2-pyridyl 2-FPh 0 H H H H H 264 5-Cl-2-pyridyl 2-ClPh 0 H H H H H 265 2-Cl-3-pyridyl Ph 0 H H H H H 266 2-Cl-3-pyridyl 2-FPh 0 H H H H H 267 2-Cl-3-pyridyl 4-FPh 0 H H H H H 268 2-Cl-3-pyridyl 2,4-F.sub.2Ph 0 H H H H H 142-143 269 2-Cl-3-pyridyl 2-ClPh 0 H H H H H 270 2-Cl-3-pyridyl 4-ClPh 0 H H H H H 140-145 271 2-Cl-3-pyridyl 2,4-Cl.sub.2Ph 0 H H H H H 272 3-Cl-2-pyridyl Ph 0 H H H H H 273 3-Cl-2-pyridyl 2-FPh 0 H H H H H 274 3-Cl-2-pyridyl 4-FPh 0 H H H H H 275 3-Cl-2-pyridyl 2,4-F.sub.2Ph 0 H H H H H 276 3-Cl-2-pyridyl 2-ClPh 0 H H H H H 277 3-Cl-2-pyridyl 4-ClPh 0 H H H H H 278 3-Cl-2-pyrid yl 2,4-Cl.sub.2Ph 0 H H H H H 279 6-Cl-3-pyridyl Ph 0 H H H H H 280 6-Cl-3-pyridyl 2-FPh 0 H H H H H 281 6-Cl-3-pyridyl 4-FPh 0 H H H H H 282 6-Cl-3-pyridyl 2,4-F.sub.2Ph 0 H H H H H 283 6-Cl-3-pyridyl 2-ClPh 0 H H H H H 284 6-Cl-3-pyridyl 4-ClPh 0 H H H H H 285 6-Cl-3-pyridyl 2,4-Cl.sub.2Ph 0 H H H H H 286 Ph 4-FPh 0 H CH.sub.3 H H H 108-111 287 Ph 4-FPh 0 H F H H H 288 Ph 4-FPh 0 H Cl H H H 289 Ph 4-FPh 0 H Br H H H 2 90 Ph 4-FPh 0 (CH.sub.2).sub.2 H H H 291 Ph 4-FPh 0 H Ph H H H (oil).sup. g 292 Ph 4-FPh 0 CH.sub.3 CH.sub.3 H H H 293 Ph 4-FPh 0 F F H H H 294 Ph 4-FPh 0 Cl Cl H H H 295 4-FPh 4-FPh 0 H CH.sub.3 H H H 296 4-FPh 4-FPh 0 H F H H H 297 4-FPh 4-FPh 0 H Cl H H H 298 4-FPh 4-FPh 0 H Br H H H 299 4-FPh 4-FPh 0 (CH.sub.2).sub.2 H H H 300 4-FPh 4-FPh 0 CH.sub.3 CH.sub.3 H H H 301 4-FPh 4-FPh 0 F F H H H 302 4-FPh 4-FPh 0 Cl Cl H H H 303 4-ClPh 2,4-Cl.sub.2Ph 0 H CH.sub.3 H H H 304 4-ClPh 2,4-Cl.sub.2Ph 0 H F H H H 305 4-ClPh 2,4-Cl.sub.2Ph 0 H Cl H H H 306 4-ClPh 2,4-Cl.sub.2Ph 0 H Br H H H 307 4-ClPh 2,4-Cl.sub.2Ph 0 (CH.sub.2).sub.2 H H H 308 4-ClPh 2 ,4-Cl.sub.2Ph 0 CH.sub.3 CH.sub.3 H H H 309 4-ClPh 2,4-Cl.sub.2Ph 0 F F H H H 310 4-ClPh 2,4-Cl.sub.2Ph 0 Cl Cl H H H 311 2-ClPh 4-ClPh 0 H CH.sub.3 H H H 312 2-ClPh 4-ClPh 0 H F H H H 313 2-ClPh 4-ClPh 0 H Cl H H H 314 2-ClPh 4-ClPh 0 H Br H H H 315 2-ClPh 4-ClPh 0 (CH.sub.2).sub.2 H H H 316 2-ClPh 4-ClPh 0 CH.sub.3 CH.sub.3 H H H 317 2-ClPh 4-ClPh 0 F F H H H 318 2-ClPh 4-ClPh 0 Cl Cl H H H 319 4-FPh 4-FPh 0 H C.sub.2 H.sub.5 H H H 320 4-FPh 4-FPh 0 H -i-C.sub.3 H.sub.7 H H H 321 4-FPh 4-FPh 0 H -n-C.sub.4 H.sub.9 H H H 322 4-FPh 4-FPh 0 H Ph H H H 323 4-FPh 4-FPh 0 CH.sub.3 .sub.-t-C.sub.4 H.sub.9 H H H 324 4-FPh 4-FPh 0 CH.sub.3 Ph H H H 325 4-FPh 4-FPh 0 H I H H H 326 4-FPh 4-FPh 0 CH.sub.3 F H H H 327 4-FPh 4-FPh 0 CH.sub.3 Cl H H H 328 4-FPh 4-FPh 0 Br Br H H H 329 4-FPh 4-FPh 0 (CH.sub.2).sub.3 H H H 330 4-FPh 4-FPh 0 (CH.sub.2).s ub.4 H H H 331 4-FPh 4-FPh 0 (CH.sub.2).sub.5 H H H 332 4-FPh 4-FPh 0 (CH.sub.2).sub.6 H H H 333 4-CH.sub.3Ph 4-FPh 0 H CH.sub.3 H H H 334 P 4-Fh 4-FPh 1 H CH.sub.3 H H H 335 4-ClPh 4-FPh 4 H CH.sub.3 H H H 336 -n-C.sub.4 F.sub.9 4-FPh 0 H CH.sub.3 H H H 337 (CH.sub.3).sub.2 N 4-FPh 1 H CH.sub.3 H H H 338 5-Cl-thio- 4-FPh 0 H CH.sub.3 H H H phen-2-yl 339 2-Cl-thio- 4-FPh 0 H CH.sub.3 H H H phen-3-yl 340 1-imida- 4-FPh 0 H CH.sub.3 H H H zoyl 341 1,2,4-tria- 4-FPh 0 H CH.sub.3 H H H zol-1-yl 342 5-chloro-2- 4-FPh 0 H CH.sub.3 H H H pyridyl 343 4-FPh -n-C.sub.4 H.sub.9 0 H CH.sub.3 H H H 344 4-FPh .sub.-t-C.sub.4 H.sub.9 0 H CH.sub.3 H H H 345 4-FPh -n-C.sub.4 F.sub.9 0 H CH.sub.3 H H H 346 4-CH.sub.3Ph 4-FPh 0 H F H H H 347 4-FPh 4-FPh 1 H F H H H 348 4-ClPh P 4-Fh 4 H F H H H 349 -n-C.sub.4 F.sub.9 4-FPh 0 H F H H H 350 (CH.sub.3).sub.2 N 4-FPh 1 H F H H H 351 5-Cl- 4-FPh 0 H F H H H thiophen- 2-yl 352 2-Cl- 4-FPh 0 H F H H H thiophen- 2-yl 353 1-imida- 4-FPh 0 H F H H H zoyl 354 1,2,4- 4-FPh 0 H F H H H triazol- 1-yl 355 5-Cl-2- 4-FPh 0 H F H H H pyridyl 356 4-FPh -n-C.sub.4 H.sub.9 0 H F H H H 357 4-FPh .sub.-t-C.sub.4 H.sub.9 0 H F H H H 358 4-FPh -n-C.sub.4 F.sub.9 0 H F H H H 359 4-FPh 4-FPh 0 H H CH.sub.3 H H (oil).sup.h 360 4-FPh 4-FPh 0 H H CH.sub.2 CHCH.sub.2 H H (oil).sup.i 361 4-FPh 4-FPh 0 H H COCH.sub.3 H H (oil).sup.j 362 4-FPh 4-FPh 0 H H CO.sub.2 CH.sub.3 H H 363 4-FPh 4-FPh 0 H H CONHCH.sub.3 H H 164-167 364 4-FPh 4-FPh 0 H H CONH--nBu H H 365 4-FPh 4-FPh 0 H H CONHPh H H 366 4-FPh 4-FPh 0 H H CONH- H H (4-FPh) 367 4-FPh 4-FPh 0 H H CON(CH.sub.3).sub.2 H H 368 2-ClPh 4-ClPh 0 H H CH.sub.3 H H 369 2-ClPh 4-ClPh 0 H H CH.sub.2 CHCH.sub.2 H H 370 2-ClPh 4-ClPh 0 H H COCH.sub.3 H H 371 2-ClPh 4-ClPh 0 H H CO.sub.2 CH.sub.3 H H 372 2-ClPh 4-ClPh 0 H H CONHCH.sub.3 H H 373 2-ClPh 4-ClPh 0 H H CONH--nBu H H 374 2-ClPh 4-ClPh 0 H H CONHPh H H 375 2-ClPh 4-ClPh 0 H H CONH- H H (4-FPh) 376 2-ClPh 4-ClPh 0 H H CON(CH.sub.3).sub.2 H H 377 4-ClPh 2,4-Cl.sub.2Ph 0 H H CH.sub.3 H H 378 4-ClPh 2,4-Cl.sub.2Ph 0 H H CH.sub.2 CHCH.sub.2 H H 379 4-ClPh 2,4-Cl.sub.2Ph 0 H H COCH.sub.3 H H 380 4-ClPh 2,4-Cl.sub. 2Ph 0 H H CO.sub.2 CH.sub.3 H H 381 4-ClPh 2,4-Cl.sub.2Ph 0 H H CONHCH.sub.3 H H 382 4-ClPh 2,4-Cl.sub.2Ph 0 H H CONH--nBu H H 383 4-ClPh 2,4-Cl.sub.2Ph 0 H H CONHPh H H 384 4-ClPh 2,4-Cl.sub.2Ph 0 H H CONH(4-FPh) H H 385 4-ClPh 2,4-Cl.sub.2Ph 0 H H CON(CH.sub.3).sub.2 H H 386 Ph 4-FPh 0 H H CH.sub.3 H H 387 Ph 4-FPh 0 H H CH.sub.2 CHCH.sub.2 H H 388 Ph 4-FPh 0 H H COCH.sub.3 H H 389 Ph 4-FPh 0 H H CO.sub.2 CH.sub.3 H H 390 Ph 4-FPh 0 H H CONHCH.sub.3 H H 391 Ph 4-FPh 0 H H CONH--nBu H H 392 Ph 4-FPh 0 H H CONHPh H H 393 Ph 4-FPh 0 H H CONH(4-FPh) H H 394 Ph 4-F Ph 0 H H CON(CH.sub.3).sub.2 H H 395 4-FPh 4-FPh 0 H H C.sub.2 H.sub.5 H H 396 P 4-Fh 4-FPh 0 H H -i-C.sub.3 H.sub.7 H H 397 4-FPh 4-FPh 0 H H -n-C.sub.4 H.sub.9 H H 398 4-FPh 4-FPh 0 H H COC.sub.2 H.sub.5 H H 399 4-FPh 4-FPh 0 H H CO-.sub.-tC.sub.4 H.sub.9 H H 400 4-FPh 4-FPh 0 H H COPh H H 401 4-FPh 4-FPh 0 H H COCH.sub.2 Ph H H 402 4-FPh 4-FPh 0 H H CONH.sub.2 H H 403 4-FPh 4-FPh 0 H H CONH--iC.sub.3 H.sub.7 H H 404 4-FPh 4-FPh 0 H H CONHCH.sub.2 Ph H H 405 4-FPh 4-FPh 0 H H CON(CH.sub.3)Ph H H 406 4-FPh 4-FPh 0 H H CONH(4-ClPh) H H 407 4-FPh 4-FPh 0 H H CONH(4-CH.sub.3Ph) H H 408 4-F Ph 4-FPh 0 H H CONH(4-CH.sub.3Ph) H H 409 4-FPh 4-FPh 0 H H CONH(3-CF.sub.3Ph) H H 410 4-FPh 4-FPh 0 H H CONH(4-NO.sub.2Ph) H H 411 4-FPh 4-FPh 0 H H CONH(2-CH.sub.3Ph) H H 412 4-FPh 4-FPh 0 H H CONH(2,4-F .sub.2Ph) H H 413 4-FPh 4-FPh 0 H H CONH(2,4-Cl.sub.2Ph) H H 414 4-FPh 4-FPh 0 H H CO.sub.2 C.sub.2 H.sub.5 H H 415 4-FPh 4-FPh 0 H H CO.sub.2 --nC.sub.4 H.sub.9 H H 416 4-FPh 4-FPh 0 H H CO.sub.2 -.sub.-tC.sub.4 H.sub.9 H H 417 4-FPh 4-FPh 0 H H CO.sub.2 CH.sub.2 Ph H H 418 4-FPh 4-FPh 0 H H CO.sub.2 Ph H H 419 4-FPh 4-FPh 0 H H CF.sub.2 H H H 420 4-FPh 4-FPh 0 H H CH.sub.2 CF.sub.3 H H 421 4-FPh 4-FPh 0 H H CH.sub.2 CH.sub.2 CH.sub.2 F H H 422 4-FPh 4-FPh 0 H H CH.sub.2 CH.sub.2 CH.sub.2 CH.sub.2 Cl H H 423 Ph 2,4-F.sub.2Ph 0 H H CH.sub.2CCH H H 424 Ph 4-ClPh 0 H H CH.sub.2CCH H H 425 4-FPh 2-FPh 0 H H CH.sub.2CCH H H 426 4-FPh P 4-Fh 0 H H CH.sub.2CCH H H (HCl salt 184-187) 427 4-FPh 2,4-F.sub.2Ph 0 H H CH.sub.2CCH H H 428 4-FPh 2-ClPh 0 H H CC CH.sub.2H H H 429 2-ClPh 2,4-F.sub.2Ph 0 H H CH.sub.2C CH H H 68-70 430 2-ClPh 4-ClPh 0 H H CH.sub.2CCH H H 108-111 431 4-ClPh 2-FPh 0 H H CH.sub.2CCH H H 432 4-ClPh 2,4-F.sub.2Ph0 H H CH.sub.2CCH H H 433 4-FPh 4-FPh 1 H H H H H 434 4-FPh 4-FPh 2 H H H H H 435 4-FPh 4-FPh 3 H H H H H 436 4-FPh 4-FPh 4 H H H H H 437 2-ClPh 4-ClPh 1 H H H H H 438 2-ClPh 4-ClPh 2 H H H H H 439 2-ClPh 4-ClPh 3 H H H H H 440 2-ClPh 4-ClPh 4 H H H H H 441 4-ClPh 2,4-Cl.sub.2Ph 1 H H H H H 442 4-ClPh 2,4-Cl.sub.2Ph 2 H H H H H 443 4-ClPh 2,4-Cl.sub.2Ph 3 H H H H H 444 4-ClPh 2,4-Cl.sub.2Ph 4 H H H H H 445 Ph 4-FPh 1 H H H H H 446 Ph 4-FPh 2 H H H H H 447 OH 4-ClPh 1 H H H H H (oil).sup.k 448 OH Ph 1 H H H H H 94-100 449 OH 2,4-Cl.sub.2Ph 1 H H H H H 166-168 450 OH 4-FPh 1 H H H H H 115-116 451 OH 4-BrPh 1 H H H H H (foam).sup.1 452 OH 4-PhPh 1 H H H H H 140-143 453 (CH.sub.3).sub.2 N 2,4-Cl.sub.2Ph 1 H H H H H 104-107 454 (CH.sub.3).sub.2 N 4-FPh 1 H H H H H (oil).sup.m 455 (CH.sub.3).sub.2 N 4-BrPh 1 H H H H H (oil).sup.n 456 (CH.sub.3).sub.2 N 4-PhPh 1 H H H H H (oil).sup.o 457 1-imidazoyl P 4-Fh 1 H H H H H 458 1-imidazoyl 4-FPh 2 H H H H H 459 1-imidazoyl 4-FPh 3 H H H H H 460 1-imidazoyl 4-FPh 4 H H H H H 461 1H-1,2,4- 4-FPh 1 H H H H H triazol-1-yl 462 1H-1,2,4- 4-FPh 2 H H H H H triazol-1-yl 463 1H-1,2,4- 4-FPh 3 H H H H H triazol-1-yl 464 1H-1,2,4- 4-FPh 4 H H H H H triazol-1-yl 465 1H-1,2,4- 2,4-Cl.sub.2Ph 1 H H H H H triazol-1-yl 466 1H-1,2,4- 2,4-Cl.sub.2Ph 2 H H H H H triazol-1-yl 467 1-imidazoyl 2,4-Cl.sub.2Ph 1 H H H H H 468 1-piperidyl Ph 1 H H H H H 469 1-piperidyl 2-FPh 1 H H H H H 470 1-piperidyl 4-FPh 1 H H H H H 471 1-piperidyl 2,4-F.sub.2Ph 1 H H H H H 472 1-piperidyl 2-ClPh 1 H H H H H 473 1-piperidyl 4-ClPh 1 H H H H H 474 1-piperidyl 2,4-Cl.sub.2Ph 1 H H H H H 475 2,6-(CH.sub.3).sub.2 -1-morpholinyl Ph 1 H H H H H 476 2,6-(CH.sub.3).sub.2 -1-morpholinyl 2-FPh 1 H H H H H 477 2,6-(CH.sub.3 ).sub.2 -1-morpholinyl 4-FPh 1 H H H H H 97-99 478 2,6-(CH.sub.3).sub.2 -1-morpholinyl 2,4-F.sub.2Ph 1 H H H H H 479 2,6-(CH.sub.3).sub.2 -1-morpholinyl 2-ClPh 1 H H H H H 480 2,6-(CH.sub.3).sub.2 -1-morpholinyl 4-ClPh 1 H H H H H 481 2,6-(CH.sub.3).sub.2 -1-morpholinyl 2,4-Cl.sub.2Ph 1 H H H H H 482 4-CH.sub.3 -1-piperazinyl Ph 1 H H H H H 483 4-CH.sub.3 -1-piperazinyl 2-FPh 1 H H H H H 484 4-CH.sub.3 -1-piperazinyl 4-FPh 1 H H H H H 485 4-CH.sub.3 -1-piperazinyl 2,4-F.sub.2Ph 1 H H H H H 486 4-CH.sub.3 -1-piperazinyl 2-ClPh 1 H H H H H 487 4-CH.sub.3 -1-piperazinyl 4-ClPh 1 H H H H H 488 4-CH.sub.3 -1-piperazinyl 2,4-Cl.sub.2Ph 1 H H H H H 489 4--n-Bu-1-piperazinyl Ph 1 H H H H H 490 4--n-Bu-1-piperazinyl 2-FPh 1 H H H H H 491 4--n-Bu-1-pip erazinyl 4-FPh 1 H H H H H 492 4- -n-Bu-1-piperazinyl 2,4-F.sub.2Ph 1 H H H H H 493 4--n-Bu-1-piperazinyl 2-ClPh 1 H H H H H 494 4--n-Bu-1-pipera zinyl 4-ClPh 1 H H H H H 495 4--n-Bu-1-piperazinyl 2,4-Cl.sub.2Ph 1 H H H H H 496 4-acetyl-1-piperazinyl Ph 1 H H H H H 497 4-acetyl-1-piperaziny l 2-FPh 1 H H H H H 498 4-acetyl-1-piperazinyl 4-FPh 1 H H H H H 499 4-acetyl-1-piperazinyl 2,4-F.sub.2Ph 1 H H H H H 500 4-acetyl-1-piperazin yl 2-ClPh 1 H H H H H 501 4-acetyl-1-piperazinyl 4-ClPh 1 H H H H H 502 4-acetyl-1-piperazinyl 2,4-Cl.sub.2Ph 1 H H H H H 503 2-(2-pyridyl)-Ph 4-FPh 0 H H H H H 504 2-(3-pyridyl)-Ph 4-FPh 0 H H H H H 505 2-(4-pyridyl )-Ph 4-FPh 0 H H H H H 506 3-(2-pyridyl)-Ph 4-FPh 0 H H H H H 507 3-(3-pyridyl)-Ph 4-FPh 0 H H H H H 508 3-(4-pyridyl)-Ph 4-FPh 0 H H H H H 509 4-(2-pyridyl)-Ph 4-FPh 0 H H H H H 510 4-(3-pyridyl)-Ph 4-FPh 0 H H H H H 511 4-(4-pyridyl)-Ph 4-FPh 0 H H H H H 512 2-(1H-1,2,4-triazol-1- yl)-Ph 4-FPh 0 H H H H H 513 3-(1H-1,2,4-triazol-1-yl)-Ph 4-FPh 0 H H H H H 514 4-(1H-1,2,4-triazol-1-yl)-Ph 4-FPh 0 H H H H H 515 2-(imidazol-1- yl)-Ph 4-FPh 0 H H H H H 516 3-(imidazol-1-yl)-Ph 4-FPh 0 H H H H H 517 4-(imidazol-1-yl)-Ph 4-FPh 0 H H H H H 518 2-(4-methylpiperazin-1-yl)-Ph 4-FPh 0 H H H H H 519 3-(4-methylpiperazin-1-yl)-Ph 4-FPh 0 H H H H H 520 4-(4-methylpiperazin-1-yl)-Ph 4-FPh 0 H H H H H 521 2-(4-acetylpipera zin-1-yl)-Ph 4-FPh 0 H H H H H 522 3-(4-acetylpiperazin-1-yl)-Ph 4-FPh 0 H H H H H 523 4-(4-acetylpiperazin-1-yl)-Ph 4-FPh 0 H H H H H 524 2-(2-pyridyl)-Ph 2,4-F.sub.2Ph 0 H H H H H 525 2-(3-pyridyl)-Ph 2,4-F.sub .2Ph 0 H H H H H 526 2-(4-pyridyl)-Ph 2,4-F.sub.2Ph 0 H H H H H 527 3-(2-pyridyl)-Ph 2,4-F.sub.2Ph 0 H H H H H 528 3-(3-pyridyl)-Ph 2,4-F.sub .2Ph 0 H H H H H (Foam).sup.am 529 3-(4-pyridyl)-Ph 2,4-F.sub.2Ph 0 H H H H H 530 4-(2-pyridyl)-Ph 2,4-F.sub.2Ph 0 H H H H H 531 4-(3-pyridyl)-Ph 2,4-F.sub.2Ph 0 H H H H H (Foam).sup.an 532 4-(4-pyridyl)-Ph 2,4-F.sub.2P h 0 H H H H H 533 2-(1H-1,2,4-triazol-1-yl)-Ph 2,4-F.sub.2Ph 0 H H H H H 534 3-(1H-1,2,4-triazol-1-yl)-Ph 2,4-F.sub.2Ph 0 H H H H H 535 4-(1H-1,2, 4-triazol-1-yl)-Ph 2,4-F.sub.2Ph 0 H H H H H 536 2-(imidazol-1-yl)-Ph 2,4-F.sub.2Ph 0 H H H H H 537 3-(imidazol-1-yl)-Ph 2,4-F.sub.2Ph 0 H H H H H 538 4-(imidazol-1-yl)-Ph 2,4-F.sub.2Ph 0 H H H H H 539 2-(4-methylpip erazin-2-yl)-Ph 2,4-F.sub.2Ph 0 H H H H H 540 3-(4-methylpiperazin-2-yl)- Ph 2,4-F.sub.2Ph 0 H H H H H 541 4-(4-methylpiperazin-2-yl)-Ph 2,4-F.sub. 2Ph 0 H H H H H 542 2-(4-acetylpiperazin-1-yl)-Ph 2,4-F.sub.2Ph 0 H H H H H 543 3-(4-acetylpiperazin-1-yl)-Ph 2,4-F.sub.2Ph 0 H H H H H 544 4-(4-acetylpiperazin-1-yl)-Ph 2,4-F.sub.2Ph 0 H H H H H 545 2-Cl-3-(3-pyr idyl)-Ph 2,4-F.sub.2Ph 0 H H H H H 546 2-(2-pyridyl)-Ph 4-ClPh 0 H H H H H 547 2-(3-pyridyl)-Ph 4-ClPh 0 H H H H H 548 2-(4-pyridyl)-Ph 4-ClPh 0 H H H H H 549 3-(2-pyridyl)-Ph 4-ClPh 0 H H H H H 550 3-(3-pyridyl)-Ph 4-ClPh 0 H H H H H 551 3-(4-pyridyl)-Ph 4-ClPh 0 H H H H H 552 4-(2-pyrid yl)-Ph 4-ClPh 0 H H H H H 553 4-(3-pyridyl)-Ph 4-ClPh 0 H H H H H 554 4-(4-pyridyl)-Ph 4-ClPh 0 H H H H H 555 2-(1H-1,2,4-triazol-1-yl)-Ph P 4-Clh 0 H H H H H 556 3-(1H-1,2,4-triazol-1-yl)-Ph 4-ClPh 0 H H H H H 557 4-(1H-1,2,4-triazol-1-yl)-Ph 4-ClPh 0 H H H H H 558 2-(imidazol-1-yl) -Ph 4-ClPh 0 H H H H H 559 3-(imidazol-1-yl)-Ph 4-ClPh 0 H H H H H 560 4-(imidazol-1-yl)-Ph 4-ClPh 0 H H H H H 561 2-(4-methylpiperazin-1-yl)-Ph 4-ClPh 0 H H H H H 562 3-(4-methylpiperazin-1-yl)-Ph 4-ClPh 0 H H H H H 563 4-(4-methylpiperazin-1-yl)-Ph 4-ClPh 0 H H H H H 564 2-(4-acetylpiper azin-1-yl)-Ph 4-ClPh 0 H H H H H 565 3-(4-acetylpiperazin-1-yl)-Ph 4-ClPh 0 H H H H H 566 4-(4-acetylpiperazin-1-yl)-Ph 4-ClPh 0 H H H H H 567 2-Cl-3-(3-pyridyl)-Ph 4-ClPh 0 H H H H H 568 2-(2-pyridyl)-Ph 2,4-Cl.sub.2Ph 0 H H H H H 569 2-(3-pyridyl)-Ph 2,4-Cl.sub.2Ph 0 H H H H H 570 2-(4-pyridyl)-Ph 2,4-Cl.sub.2Ph 0 H H H H H 571 3-(2-pyridyl)-Ph 2,4-Cl.sub.2Ph 0 H H H H H 572 3-(3-pyridyl)-Ph 2,4-Cl.sub.2Ph 0 H H H H H 573 3-(4-pyridyl)-Ph 2,4-Cl.sub.2Ph 0 H H H H H 574 4-(2-pyridyl)-Ph 2,4-Cl.sub.2Ph 0 H H H H H 575 4-(3-pyridyl)-Ph 2,4-Cl.sub.2Ph 0 H H H H H 576 4-(4-pyridyl)-Ph 2,4-Cl.sub.2Ph 0 H H H H H 577 2-(1H-1,2,4-triazol -1-yl)-Ph 2,4-Cl.sub.2Ph 0 H H H H H 578 3-(1H-1,2,4-triazol-1-yl)-Ph 2,4-Cl.sub.2Ph 0 H H H H H 579 4-(1H-1,2,4-triazol-1-yl)-Ph 2,4-Cl.sub.2P h 0 H H H H H 580 2-(imidazol-1-yl)-Ph 2,4-Cl.sub.2Ph 0 H H H H H 581 3-(imidazol-1-yl)-Ph 2,4-Cl.sub.2Ph 0 H H H H H 582 4-(imidazol-1-yl)-Ph 2,4-Cl.sub.2Ph 0 H H H H H 583 2-(4-methylpiperazin-1-yl)-Ph 2,4-Cl.sub.2P h 0 H H H H H 584 3-(4-methylpiperazin-1-yl)-Ph 2,4-Cl.sub.2Ph 0 H H H H H 585 4-(4-methylpiperazin-1-yl)-Ph 2,4-Cl.sub.2Ph 0 H H H H H 586 2-(4-acetylpiperazin-1-yl)-Ph 2,4-Cl.sub.2Ph 0 H H H H H 587 3-(4-acetylp iperazin-1-yl)-Ph 2,4-Cl.sub.2Ph 0 H H H H H 588 4-(4-acetylpiperazin-1-y l)-Ph 2,4-Cl.sub.2Ph 0 H H H H H 589 2-Cl-3-(3-pyridyl)-Ph 2,4-Cl.sub.2Ph 0 H H H H H 590 3-(morpholin-1-yl)-Ph 2,4-F.sub.2Ph 0 H H H H H 591 3-(2,6-dimethyl- 2,4-F.sub.2Ph 0 H H H H H morpholin-1-yl)-Ph 592 4-(-n-butyl-piperazin-1-yl)-Ph 2,4-F.sub.2Ph 0 H H H H H 593 4-(piperidin -1-yl)-Ph 2,4-F.sub.2Ph 0 H H H H H 594 Ph 2-FPh 0 H H H H H (oil).sup.p (HCl salt 190-195) 595 Ph 3-FPh 0 H H H H H 596 Ph P 2-Clh 0 H H H H H 78-80 597 Ph 3-ClPh 0 H H H H H 598 Ph 4-BrPh 0 H H H H H 92-95 599 Ph 4-IPh 0 H H H H H 600 Ph 3,4-F.sub.2Ph 0 H H H H H 601 Ph 3,4-Cl.sub.2Ph 0 H H H H H 602 Ph 2,6-Cl.sub.2Ph 0 H H H H H 603 Ph 3,5-Cl.sub.2Ph 0 H H H H H 142-144 604 Ph 2-Cl-(4-F)Ph 0 H H H H H 605 Ph 3-Cl-(4-F)Ph 0 H H H H H 119-124 (dec.) 606 Ph 2,4,6-Cl.sub.3P h 0 H H H H H 607 Ph 2-F-(4-Cl)Ph 0 H H H H H 608 Ph Ph 0 H H H H H 130-133 609 Ph 4-CH.sub.3Ph 0 H H H H H 610 Ph 3-CH.sub.3Ph 0 H H H H H 611 Ph 2-CH.sub.3Ph 0 H H H H H 160.5-163 612 Ph 2-CF.sub.3Ph 0 H H H H H 613 Ph 3-CF.sub.3Ph 0 H H H H H 614 Ph 2-Cl-3-thienyl 0 H H H H H 615 Ph 2-F-(4-CF.sub.3)Ph 0 H H H H H 616 Ph 4-CH.sub.3 OPh 0 H H H H H 617 Ph 5-Cl-2-pyridyl 0 H H H H H 618 Ph 5-Cl-2-thienyl 0 H H H H H 88-90 619 Ph .sub.-s-C.sub.4 H.sub.9 0 H H H H H 620 2-ClPh 2-FPh 0 H H H H H 118-119 621 2-ClPh 3-FPh 0 H H H H H 622 2-ClPh 2-ClPh 0 H H H H H 149-150 623 2-ClPh 3-ClPh 0 H H H H H 624 2-ClPh 4-BrPh 0 H H H H H 151-152 625 2-ClPh 4-IPh 0 H H H H H 626 2-ClPh 3,4-F.sub.2Ph 0 H H H H H 627 2-ClPh 3,4-Cl.sub.2Ph 0 H H H H H 122-123.5 628 2-ClPh 2,6-Cl.sub.2P h 0 H H H H H 629 2-ClPh 2-Cl-(4-F)Ph 0 H H H H H 630 2-ClPh 2,4,6-Cl.sub .3Ph 0 H H H H H 631 2-ClPh 2-F-(4-Cl)Ph 0 H H H H H 632 2-ClPh Ph 0 H H H H H 633 2-ClPh 4-CH.sub.3Ph 0 H H H H H 634 2-ClPh 3-CH.sub.3Ph 0 H H H H H 635 2-ClPh 2-CH.sub.3Ph 0 H H H H H 636 2-ClPh 2-CF.sub.3Ph 0 H H H H H 637 2-ClPh 3-CF.sub.3Ph 0 H H H H H 638 2-ClPh 2-F-(4-CF.sub.3)Ph 0 H H H H H 639 2-ClPh 4-CH.sub.3 OPh 0 H H H H H 640 2-ClPh 5-Cl-2-pyridyl 0 H H H H H 641 2-ClPh 5-Cl-2-thienyl 0 H H H H H (oil).sup.v 642 2-ClPh 2-Cl-3-thienyl 0 H H H H H 643 2-ClPh .sub.-s-C.sub.4 H.sub.9 0 H H H H H 644 4-FPh 2-FPh 0 H H H H H 96-97 645 4-FPh 3-FPh 0 H H H H H 646 4-FPh 2-ClPh 0 H H H H H 116-119 647 4-FPh 3-ClPh 0 H H H H H 648 4-FPh 4-BrPh 0 H H H H H 114-116 649 4-FPh 4-IPh 0 H H H H H 650 4-FPh 3,4-F.sub.2Ph 0 H H H H H 651 4-FPh 3,4-Cl.sub.2Ph 0 H H H H H 98-99 652 4-FPh 2,6-Cl.sub.2Ph 0 H H H H H 653 4-FPh 2-Cl-(4-F)Ph 0 H H H H H 128-130 654 4-FPh 2,4,6-Cl.sub .3Ph 0 H H H H H 655 4-FPh 2-F-(4-Cl)Ph 0 H H H H H 656 4-FPh Ph 0 H H H H H 124-125 657 4-FPh 4-PhPh 0 H H H H H 116-119 658 4-FPh 4-CH.sub.3Ph 0 H H H H H 145-147 659 4-FPh 2-CH.sub.3Ph 0 H H H H H 145-149 660 4-FPh 2-CF.sub.3Ph 0 H H H H H 661 4-FPh 3-CF.sub.3Ph 0 H H H H H 121-122 662 4-FPh 2-F-(4-CF.sub.3)Ph 0 H H H H H 663 4-FPh 4-CH.sub.3 OPh 0 H H H H H 112-114 664 4-FPh 5-Cl-2-pyridyl 0 H H H H H 665 4-FPh 5-Cl-2-thienyl 0 H H H H H 114-115 666 4-FPh 2-Cl-3-thienyl 0 H H H H H 667 4-FPh .sub. -i-C.sub.3 H.sub.7 0 H H H H H 74-75 668 4-FPh C.sub.2 H.sub.5 0 H H H H H (oil).sup.q 669 4-ClPh 2-FPh 0 H H H H H 130-131 670 4-ClPh 3-FPh 0 H H H H H 671 4-ClPh 2-ClPh 0 H H H H H 137-139 672 4-ClPh 3-ClPh 0 H H H H H 673 4-ClPh 4-BrPh 0 H H H H H 121-123 674 4-ClPh 4-IPh 0 H H H H H 675 4-ClPh 3,4-Cl.sub.2Ph 0 H H H H H 107-198 676 4-ClPh 2,6-Cl.sub.2Ph 0 H H H H H 677 4-ClPh 2-Cl-(4-F)Ph 0 H H H H H 678 4-ClPh 2,4,6-Cl.sub.3Ph 0 H H H H H 679 4-ClPh 2-F-(4-Cl)Ph 0 H H H H H 680 4-ClPh Ph 0 H H H H H 681 4-ClPh 4-CH.sub.3Ph 0 H H H H H 682 4-ClPh 3-CH.sub.3Ph 0 H H H H H 683 4-ClPh 2-CH.sub.3 Ph 0 H H H H H 684 4-ClPh 2-CF.sub.3Ph 0 H H H H H 685 4-ClPh 3-CF.sub.3Ph 0 H H H H H 103-104 686 4-ClPh 2-F-(4-CF.sub.3)Ph 0 H H H H H 687 4-ClPh 4-CH.sub.3 P Oh 0 H H H H H 688 4-ClPh 5-Cl-2-pyridyl 0 H H H H H 689 4-ClPh 5-Cl-2-th ienyl 0 H H H H H (oil).sup.w 690 4-ClPh 2-Cl-3-thienyl 0 H H H H H 691 4-ClPh .sub.-s-C.sub.4 H.sub.9 0 H H H H H 692 4-FPh ##STR32## 0 H H H H H 693 4-FPh .sub.-t-butyl 0 H H H H H 694 4-FPh -n-hexyl 0 H H H H H 695 4-FPh -n-heptyl 0 H H H H H 696 4-FPh 2,4-(CH.sub.3).sub.2Ph 0 H H H H H 148-149 697 4-FPh C.sub.6 F.sub.13 0 H H H H H 698 4-FPh C.sub.8 F.sub.17 0 H H H H H 699 4-FPh 4-pyridyl 0 H H H H H 175-178 700 4-FPh 2-pyridyl 0 H H H H H 701 4-FPh 2-thienyl 0 H H H H H 702 4-FPh n 4---BuPh 0 H H H H H 703 4-FPh 4--n-BuOPh 0 H H H H H 704 4-FPh 5-CF.sub. 3 -pyrid- 0 H H H H H 2-yl 705 4-FPh 5-MeSO.sub.2 -2- 0 H H H H H thienyl 706 4-C.sub.2 H.sub.5Ph 4-FPh 0 H H H H H 707 4-(-n-BuO)Ph 4-FPh 0 H H H H H 708 2-CH.sub.3 SO.sub.2 - 4-FPh 0 H H H H H imidazol-1-yl 709 5-CH.sub.3 -1,2,4- 4-FPh 0 H H H H H triazol-1-yl 710 C.sub.6 F.sub.13 4-FPh 0 H H H H H 711 C.sub.8 F.sub.17 4-FPh 0 H H H H H 712 2-Cl-3-(3-pyridyl)-Ph 4-FPh 0 H H H H H 713 2-CF.sub.3 -imidazol-1-yl P 4-Fh 0 H H H H H 714 4-(.sub.-i-PrO)Ph 4-FPh 0 H H H H H 715 4-IPh 4-FPh 0 H H H H H 716 3,4-F.sub.2Ph 4-FPh 0 H H H H H 717 3,4-Cl.sub.2Ph 4-FPh 0 H H H H H 718 2,6-Cl.sub.2Ph 4-FPh 0 H H H H H 719 2-Cl-(4-F)Ph 4-FPh 0 H H H H H 720 2,4,6-Cl.sub.3Ph 4-FPh 0 H H H H H 721 4-CH.sub.3Ph 4-FPh 0 H H H H H 119-120 722 3-CH.sub.3Ph 4-FPh 0 H H H H 723 2-CH.sub.3P h 4-FPh 0 H H H H H 181-184 724 2-CF.sub.3Ph 4-FPh 0 H H H H H 110-112 725 3-CF.sub.3Ph 4-FPh 0 H H H H H 106-108 726 4-CH.sub.3 OPh 4-FPh 0 H H H H H 109-111 727 2,3-Cl.sub.2Ph4-FPh 0 H H H H H 728 3,5-Cl.sub.2Ph 4-FPh 0 H H H H H 729 2,5-Cl.sub.2Ph 4-FPh 0 H H H H H 730 3-BrPh 4-FPh 0 H H H H H 91-93 731 4-EtOPh 4-FPh 0 H H H H H 732 2,4-(CH.sub.3).sub.2P h 4-FPh 0 H H H H H 733 2,4,6-(CH.sub.3).sub.3Ph 4-FPh 0 H H H H H 734 4-PhPh 4-FPh 0 H H H H H 735 5-Cl-2-thienyl 4-FPh 0 H H H H H 736 2-Cl-3-thienyl 4-FPh 0 H H H H H 737 1-imidazoyl 4-FPh 0 H H H H H 738 1H-1,2,4-triazoyl 4-FPh 0 H H H H H 739 2-pyridyl 4-FPh 0 H H H H H 740 5-Cl-pyridyl-2-yl 4-FPh 0 H H H H H 741 3-pyridyl 4-FPh 0 H H H H H 742 4-pyridyl 4-FPh 0 H H H H H 743 -n-C.sub.4 F.sub.9 4-FPh 0 H H H H H 744 4-IPh 2,4-Cl.sub.2Ph 0 H H H H H 745 3,4-F.sub. 2Ph 2,4-Cl.sub.2Ph 0 H H H H H 746 3,4-Cl.sub.2Ph 2,4-Cl.sub.2Ph 0 H H H H H 747 2,6-Cl.sub.2Ph 2,4-Cl.sub.2Ph 0 H H H H H 748 2-Cl-(4-F)Ph 2,4-Cl.sub.2Ph 0 H H H H H 749 2,4,6-Cl.sub.3Ph 2,4-Cl.sub.2Ph 0 H H H H H 750 4-CH.sub.3Ph 2,4-Cl.sub.2Ph 0 H H H H H 751 3-CH.sub.3Ph 2,4-Cl.sub.2Ph 0 H H H H H 752 2-CH.sub.3Ph 2,4-Cl.sub.2Ph 0 H H H H H 753 2-CF.sub.3Ph 2,4-Cl.sub.2P h 0 H H H H H 133-137 754 3-CF.sub.3Ph 2,4-Cl.sub.2Ph 0 H H H H H 77-84 755 4-CH.sub.3 OPh 2,4-Cl.sub.2Ph 0 H H H H H 756 2,3-Cl.sub.2Ph 2,4-Cl.sub.2Ph 0 H H H H H 757 3,5-Cl.sub.2Ph 2,4-Cl.sub.2Ph 0 H H H H H 758 2,5-Cl.sub.2Ph 2,4-Cl.sub.2Ph 0 H H H H H 759 3-BrPh 2,4-Cl.sub.2Ph 0 H H H H H 171-173 760 4-EtO Ph 2,4-Cl.sub.2Ph 0 H H H H H 761 2,4-(CH.s ub.3).sub.2Ph 2,4-Cl.sub.2Ph 0 H H H H H 762 2,4,6-(CH.sub.3).sub.3Ph 2,4-Cl.sub.2Ph 0 H H H H H 763 4-PhPh 2,4-Cl.sub.2Ph 0 H H H H H 764 5-Cl-2-thienyl 2,4-Cl.sub.2Ph 0 H H H H H 765 2-Cl-3-thienyl 2,4-Cl.sub.2P h 0 H H H H H 766 1-imidazoyl 2,4-Cl.sub.2Ph 0 H H H H H 767 1H-1,2,4-tri azoyl-1-yl 2,4-Cl.sub.2Ph 0 H H H H H 768 2-pyridyl 2,4-Cl.sub.2Ph 0 H H H H H 769 5-Cl-pyrid-2-yl 2,4-Cl.sub.2Ph 0 H H H H H 770 3-pyridyl 2,4-Cl.sub.2Ph 0 H H H H H 771 4-pyridyl 2,4-Cl.sub.2Ph 0 H H H H H 772 n --C.sub.4 F.sub.9 2,4-Cl.sub.2Ph 0 H H H H H 773 4-IPh 4-ClPh 0 H H H H H 774 3,4-F.sub.2Ph 4-ClPh 0 H H H H H 775 3,4-Cl.sub.2Ph 4-ClPh 0 H H H H H 776 2,6-Cl.sub.2Ph 4-ClPh 0 H H H H H 777 2-Cl-(4-F)Ph 4-ClPh 0 H H H H H 778 2,4,6-Cl.sub.3Ph 4-ClPh 0 H H H H H 779 4-CH.sub.3Ph 4-ClPh 0 H H H H H 780 3-CH.sub.3Ph 4-ClPh 0 H H H H H 781 2-CH.sub.3Ph 4-ClPh 0 H H H H H 782 2-CF.sub.3Ph 4-ClPh 0 H H H H H 43-49 783 3-CF.sub.3Ph P 4-Clh 0 H H H H H 109-112 784 4-CH.sub.3 OPh 4-ClPh 0 H H H H H 111-113 785 2,3-Cl.sub.2Ph 4-ClPh 0 H H H H H 786 3,5-Cl.sub.2Ph 4-ClPh 0 H H H H H 787 2,5-Cl.sub.2Ph 4-ClPh 0 H H H H H 788 3-BrPh 4-ClPh 0 H H H H H 119-121 789 4-EtOPh 4-ClPh 0 H H H H H 790 2,4-(CH.sub.3).sub.2Ph 4-ClPh 0 H H H H H 791 2,4,6-(CH.sub.3).sub.3Ph 4-ClPh 0 H H H H H 792 4-PhPh 4-ClPh 0 H H H H H 793 5-Cl-2-thienyl 4-ClPh 0 H H H H H 794 2-Cl-3-thien yl 4-ClPh 0 H H H H H 795 1-imidazoyl 4-ClPh 0 H H H H H 796 1H-1,2,4-tri azoyl-1-yl 4-ClPh 0 H H H H H 797 2-pyridyl 4-ClPh 0 H H H H H 798 5-Cl-pyrid-2-yl 4-ClPh 0 H H H H H 799 3-pyridyl 4-ClPh 0 H H H H H 800 4-pyridyl 4-ClPh 0 H H H H H (oil).sup.af 801 -n-C.sub.4 F.sub.9 4-ClPh 0 H H H H H 802 4-IPh 2,4-F.sub.2Ph 0 H H H H H 803 3,4-F.sub.2Ph 2,4-F.sub.2Ph 0 H H H H H 804 3,4-Cl.sub.2Ph 2,4-F.sub.2Ph 0 H H H H H 805 2,6-Cl.sub.2Ph 2,4-F.sub.2Ph 0 H H H H H 806 2-Cl-(4-F)Ph 2,4-F.sub.2P h 0 H H H H H 807 2,4,6-Cl.sub.3Ph 2,4-F.sub.2Ph 0 H H H H H 808 4-CH.sub.3Ph 2,4-F.sub.2Ph 0 H H H H H 129-130.5 809 3-CH.sub.3Ph 2,4-F.sub.2Ph 0 H H H H H 810 2-CH.sub.3Ph 2,4-F.sub.2Ph 0 H H H H H 811 2-CF.sub.3Ph 2,4-F.sub.2Ph 0 H H H H H 113-116 812 3-CF.sub.3Ph 2,4-F.sub .2Ph 0 H H H H H 123-124 813 4-CH.sub.3 OPh 2,4-F.sub.2Ph 0 H H H H H 88-89 814 2,3-Cl.sub.2Ph 2,4-F.sub.2Ph 0 H H H H H 815 3,5-Cl.sub.2Ph 2,4-F.sub.2Ph 0 H H H H H 173-175 816 2,5-Cl.sub.2Ph 2,4-F.sub.2Ph 0 H H H H H 817 3-BrPh 2,4-F.sub.2Ph 0 H H H H H 103-107 818 4-EtOPh 2,4-F.sub. 2Ph 0 H H H H H 819 2,4-(CH.sub.3).sub.2Ph 2,4-F.sub.2Ph 0 H H H H H 820 2,4,6-(CH.sub.3).sub.3Ph 2,4-F.sub.2Ph 0 H H H H H 821 4-PhPh 2,4-F.sub.2P h 0 H H H H H 822 5-Cl-2-thienyl 2,4-F.sub.2Ph 0 H H H H H 823 2-Cl-3-thi enyl 2,4-F.sub.2Ph 0 H H H H H 824 1-imidazoyl 2,4-F.sub.2Ph 0 H H H H H 825 1H-1,2,4-triazoyl-1-yl 2,4-F.sub.2Ph 0 H H H H H 826 2-pyridyl 2,4-F.sub.2Ph 0 H H H H H 827 5-Cl-pyrid-2-yl 2,4-F.sub.2Ph 0 H H H H H 828 3-pyridyl 2,4-F.sub.2Ph 0 H H H H H 829 4-pyridyl 2,4-F.sub.2Ph 0 H H H H H 830 -n-C.sub.4 F.sub.9 2,4-F.sub.2Ph 0 H H H H H 831 2-FPh 4-BrPh 0 H H H H H 832 3-FPh 4-BrPh 0 H H H H H 833 3-ClPh 4-BrPh 0 H H H H H 834 4-BrPh 4-BrPh 0 H H H H H 835 2,4-F.sub.2Ph 4-BrPh 0 H H H H H 836 2,4-Cl.sub.2Ph 4-BrPh 0 H H H H H 837 2-CF.sub.3Ph 4-BrPh 0 H H H H H 838 3-CF.sub.3Ph 4-BrPh 0 H H H H H 839 4-CF.sub.3Ph 4-BrPh 0 H H H H H 840 2-FPh 4-IPh 0 H H H H H 841 3-F Ph 4-IPh 0 H H H H H 842 3-ClPh P 4-Ih 0 H H H H H 843 4-BrPh 4-IPh 0 H H H H H 844 2,4-F.sub.2Ph 4-IPh 0 H H H H H 845 2,4-Cl.sub.2Ph 4-IPh 0 H H H H H 846 2-CF.sub.3Ph 4-IPh 0 H H H H H 847 3-CF.sub.3Ph 4-IPh 0 H H H H H 848 4-CF.sub.3Ph 4-IPh 0 H H H H H 849 2-FPh 2-CH.sub.3Ph 0 H H H H H 850 3-FPh 2-CH.sub.3Ph 0 H H H H H 851 3-ClPh 2-CH.sub.3Ph 0 H H H H H 852 4-BrPh 2-CH.sub.3Ph 0 H H H H H 853 2,4-F.sub.2Ph 2-CH.sub.3Ph 0 H H H H H 854 2,4-Cl.sub.2Ph 2-CH.sub.3Ph 0 H H H H H 855 2-CF.sub.3Ph 2-CH.sub.3Ph 0 H H H H H 856 3-CF.sub.3Ph 2-CH.sub.3Ph 0 H H H H H 857 4-CF.sub.3Ph 2-CH.sub.3Ph 0 H H H H H 858 4-(4-FPh)Ph 4-FPh 0 H H H H H 859 4-(2-ClPh)Ph 4-ClPh 0 H H H H H 860 3-(3-CF.sub.3Ph)Ph 2,4-F.sub.2Ph 0 H H H H H 861 3-(2,4-F.sub.2P h)Ph 2,4-Cl.sub.2Ph 0 H H H H H 862 2,4-F.sub.2Ph 4-CH.sub.3Ph 0 H H H H H 863 4-CH.sub.3Ph 4-CH.sub.3Ph 0 H H H H H 178-181.5 864 2-CF.sub.3Ph 4-CH.sub.3Ph 0 H H H H H 865 3-CF.sub.3Ph 4-CH.sub.3Ph 0 H H H H H 866 4-CF.sub.3Ph 4-CH.sub.3Ph 0 H H H H H 867 2-FPh 4-CH.sub.3 OPh 0 H H H H H 868 3-FPh 4-CH.sub.3 OPh 0 H H H H H 869 3-ClPh 4-CH.sub.3 OPh 0 H H H H H 870 4-BrPh 4-CH.sub.3 OPh 0 H H H H H 871 2,4-F.sub.2Ph 4-CH.sub.3 OPh 0 H H H H H 872 2,4-Cl.sub.2Ph 4-CH.sub.3 OPh 0 H H H H H 873 2-CF.sub.3Ph 4-CH.sub.3 OPh 0 H H H H H 874 3-CF.sub.3Ph 4-CH.sub.3 OPh 0 H H H H H 875 4-CF.sub.3Ph 4-CH.sub.3 OPh 0 H H H H H 876 Ph 2-CH.sub.3 OPh 0 H H H H H 877 2-FPh 2-CH.sub.3 P Oh 0 H H H H H 878 3-FPh 2-CH.sub.3 OPh 0 H H H H H 879 4-FPh 2-CH.sub.3 OPh 0 H H H H H 56-70 (138-139.5 .H.sub.2 C.sub.2 O.sub.4) 880 2,4-F.sub.2Ph 2-CH.sub.3 OPh 0 H H H H H 881 2-ClPh 2-CH.sub.3 OPh 0 H H H H H 882 3-ClPh 2-CH.sub.3 OPh 0 H H H H H 883 P 4-Clh 2-CH.sub.3 OPh 0 H H H H H 884 2,4-Cl.sub.2Ph 2-CH.sub.3 OPh 0 H H H H H 885 4-BrPh 2-CH.sub.3 OPh 0 H H H H H 886 2-CF.sub.3Ph 2-CH.sub.3 P Oh 0 H H H H H 887 3-CF.sub.3Ph 2-CH.sub.3 P OPh 0 H H H H H 888 4-CF.sub.3h 2-CH.sub.3 OPh 0 H H H H H 889 Ph 4-CF.sub.3 OPh 0 H H H H H 890 2-FPh 4-CF.sub.3 OPh 0 H H H H H 891 3-FPh 4-CF.sub.3 OPh 0 H H H H H 892 4-FPh 4-CF.sub.3 OPh 0 H H H H H 893 2,4-F.sub.2Ph 4-CF.sub.3 OPh 0 H H H H H 894 2-ClPh 4-CF.sub.3 OPh 0 H H H H H 895 3-ClPh 4-CF.sub.3 OPh 0 H H H H H 896 4-ClPh 4-CF.sub.3 OPh 0 H H H H H 897 2,4-Cl.sub.2Ph 4-CF.sub.3 OPh 0 H H H H H 898 4-BrPh 4-CF.sub.3 OPh 0 H H H H H 899 2-CF.sub.3Ph 4-CF.sub.3 OPh 0 H H H H H 900 3-CF.sub.3Ph 4-CF.sub.3 OPh 0 H H H H H 901 4-CF.sub.3Ph 4-CF.sub.3 P Oh 0 H H H H H 902 2-FPh 3,4-Cl.sub.2Ph 0 H H H H H 903 3-FPh 3,4-Cl.sub. 2Ph 0 H H H H H 904 2,4-F.sub.2Ph 3,4-Cl.sub.2Ph 0 H H H H H 905 3-ClPh 3,4-Cl.sub.2Ph 0 H H H H H 110-111 906 2,4-Cl.sub.2Ph 3,4-Cl.sub.2Ph 0 H H H H H 907 4-BrPh 3,4-Cl.sub.2Ph 0 H H H H H 908 2-CF.sub.3Ph 3,4-Cl.sub .2Ph 0 H H H H H 909 3-CF.sub.3Ph 3,4-Cl.sub.2Ph 0 H H H H H 910 4-CF.sub.3Ph 3,4-Cl.sub.2Ph 0 H H H H H 911 Ph 2,5-F.sub.2Ph 0 H H H H H 912 2-FPh 2,5-F.sub.2Ph 0 H H H H H 913 3-FPh 2,5-F.sub.2Ph 0 H H H H H 914 4-FPh 2,5-F.sub.2Ph 0 H H H H H 915 2,4-F.sub.2Ph 2,5-F.sub.2Ph 0 H H H H H 916 2-ClPh 2,5-F.sub.2 Ph 0 H H H H H 917 3-ClPh 2,5-F.sub.2Ph 0 H H H H H 918 4-ClPh 2,5-F.sub.2Ph 0 H H H H H 919 2,4-Cl.sub.2Ph 2,5-F.sub.2Ph 0 H H H H H 920 4-BrPh 2,5-F.sub.2Ph 0 H H H H H 921 2-CF.sub.3Ph 2,5-F.sub.2Ph 0 H H H H H 922 3-CF.sub.3Ph 2,5-F.sub.2Ph 0 H H H H H 923 4-CF.sub.3Ph 2,5-F.sub.2Ph 0 H H H H H 924 Ph 2,5-Cl.sub.2P h 0 H H H H H 925 2-FPh 2,5-Cl.sub.2Ph 0 H H H H H 926 3-FPh 2,5-Cl.sub.2P h 0 H H H H H 927 4-FPh 2,5-Cl.sub.2Ph 0 H H H H H 928 2,4-F.sub.2Ph 2,5-Cl.sub.2Ph 0 H H H H H 929 2-ClPh 2,5-Cl.sub.2Ph 0 H H H H H 930 P 3-Clh 2,5-Cl.sub.2Ph 0 H H H H H 931 4-ClPh 2,5-Cl.sub.2Ph 0 H H H H H 932 2,4-Cl.sub.2Ph 2,5-Cl.sub.2Ph 0 H H H H H 933 4-BrPh 2,5-Cl.sub.2Ph 0 H H H H H 934 2-CF.sub.3Ph 2,5-Cl.sub.2Ph 0 H H H H H 935 3-CF.sub.3Ph 2,5-Cl.sub.2Ph 0 H H H H H 936 4-CF.sub.3Ph 2,5-Cl.sub.2Ph 0 H H H H H 937 Ph 2,4,6-F.sub.3Ph 0 H H H H H 938 2-FPh 2,4,6-F.sub.3Ph 0 H H H H H 939 3-FPh 2,4,6-F.sub.3Ph 0 H H H H H 940 4-FPh 2,4,6-F.sub.3Ph 0 H H H H H 941 2,4-F.sub.2Ph 2,4,6-F.sub.3Ph 0 H H H H H 942 2-ClPh 2,4,6-F.sub. 3Ph 0 H H H H H 943 3-ClPh 2,4,6-F.sub.3Ph 0 H H H H H 944 4-ClPh 2,4,6-F.sub.3Ph 0 H H H H H 945 2,4-Cl.sub.2Ph 2,4,6-F.sub.3Ph 0 H H H H H 946 4-BrPh 2,4,6-F.sub.3Ph 0 H H H H H 947 2-CF.sub.3Ph 2,4,6-F.sub.3Ph 0 H H H H H 948 3-CF.sub.3Ph 2,4,6-F.sub.3Ph 0 H H H H H 949 4-CF.sub.3P h 2,4,6-F.sub.3Ph 0 H H H H H 950 Ph 2,4,5-F.sub.3Ph 0 H H H H H 951 2-FPh 2,4,5-F.sub.3Ph 0 H H H H H 952 3-FPh 2,4,5-F.sub.3Ph 0 H H H H H 953 4-FPh 2,4,5-F.sub.3Ph 0 H H H H H 954 2,4-F.sub.2Ph 2,4,5-F.sub.3Ph 0 H H H H H 955 2-ClPh 2,4,5-F.sub.3Ph 0 H H H H H 956 3-ClPh 2,4,5-F.sub .3Ph 0 H H H H H 957 4-ClPh 2,4,5-F.sub.3Ph 0 H H H H H 958 2,4-Cl.sub.2P h 2,4,5-F.sub.3Ph 0 H H H H H 959 4-BrPh 2,4,5-F.sub.3Ph 0 H H H H H 960 2-CF.sub.3Ph 2,4,5-F.sub.3Ph 0 H H H H H 961 3-CF.sub.3Ph 2,4,5-F.sub.3Ph 0 H H H H H 962 4-CF.sub.3Ph 2,4,5-F.sub.3Ph 0 H H H H H 963 2-FPh 2-Cl-4-FPh 0 H H H H H 964 3-FPh 2-Cl-4-FPh 0 H H H H H 965 4-FPh 2-Cl-4-FPh 0 H H H H H 966 3-ClPh 2-Cl-4-FPh 0 H H H H H 967 2,4-Cl.sub.2P h 2-Cl-4-FPh 0 H H H H H 968 4-BrPh 2-Cl-4-FPh 0 H H H H H 969 2-CF.sub.3P h 2-Cl-4-FPh 0 H H H H H 970 3-CF.sub.3Ph 2-Cl-4-FPh 0 H H H H H 971 4-CF.sub.3Ph 2-Cl-4-FPh 0 H H H H H 972 Ph 4-F-1-naphthyl 0 H H H H H 973 2-FPh 1-naphthyl 0 H H H H H 974 3-FPh 1-naphthyl 0 H H H H H 975 P 4-Fh 1-naphthyl 0 H H H H H 976 2,4-F.sub.2Ph 1-naphthyl 0 H H H H H 977 2-ClPh 1-naphthyl 0 H H H H H 978 3-ClPh 1-naphthyl 0 H H H H H 979 4-ClPh 1-naphthyl 0 H H H H H 980 2,4-Cl.sub.2Ph 1-naphthyl 0 H H H H H 981 4-BrPh 1-naphthyl 0 H H H H H 982 2-CF.sub.3Ph 1-naphthyl 0 H H H H H 983 3-CF.sub.3Ph 1-naphthyl 0 H H H H H 984 4-CF.sub.3Ph 1-naphthyl 0 H H H H H 985 Ph 6-Cl-2-naphthyl 0 H H H H H 986 2-FPh 2-naphthyl 0 H H H H H 987 3-FPh 2-naphthyl 0 H H H H H 988 4-FPh 2-naphthyl 0 H H H H H 989 2,4-F.sub.2Ph 2-naphthyl 0 H H H H H 990 2-ClPh 2-naphthyl 0 H H H H H 991 3-ClPh 2-naphthyl 0 H H H H H 992 4-ClPh 2-naphthyl 0 H H H H H 993 2,4,-Cl.sub.2Ph 2-naphthyl 0 H H H H H 994 4-BrPh 2-naphthyl 0 H H H H H 995 2-CF.sub.3Ph 2-naphthyl 0 H H H H H 996 3-CF.sub.3Ph 2-naphthyl 0 H H H H H 997 4-CF.sub.3Ph 2-naphthyl 0 H H H H H 998 Ph PhCH.sub.2 0 H H H H H 999 2-FPh PhCH.sub.2 0 H H H H H 1000 3-FPh PhCH.sub.2 0 H H H H H 1001 4-FPh PhCH.sub.2 0 H H H H H 1002 2,4-F.sub.2Ph PhCH.sub.2 0 H H H H H 1003 2-ClPh PhCH.sub.2 0 H H H H H 1004 3-ClPh PhCH.sub.2 0 H H H H H 1005 4-ClPh PhCH.sub.2 0 H H H H H 1006 2,4-Cl.sub.2Ph PhCH.sub.2 0 H H H H H 1007 4-BrPh PhCH.sub.2 0 H H H H H 1008 2-CF.sub.3Ph PhCH.sub.2 0 H H H H H 1009 3-CF.sub.3Ph PhCH.sub.2 0 H H H H H 1010 4-CF.sub.3Ph PhCH.sub.2 0 H H H H H 1011 Ph PhCH(CH.sub.3) 0 H H H H H 1012 2-FPh PhCH(CH.sub.3) 0 H H H H H 1013 3-FPh PhCH(CH.sub.3) 0 H H H H H 1014 4-FPh PhCH(CH.sub.3) 0 H H H H H 1015 2,4-F.sub.2Ph PhCH(CH.sub. 3) 0 H H H H H 1016 2-ClPh PhCH(CH.sub.3) 0 H H H H H 1017 3-ClPh PhCH(CH.sub.3) 0 H H H H H 1018 4-ClPh PhCH(CH.sub.3) 0 H H H H H 1019 2,4-Cl.sub.2Ph PhCH(CH.sub.3) 0 H H H H H 1020 4-BrPh PhCH(CH.sub.3) 0 H H H H H 1021 2-CF.sub.3Ph PhCH(CH.sub.3) 0 H H H H H 1022 3-CF.sub.3Ph PhCH(CH.sub.3) 0 H H H H H 1023 4-CF.sub.3Ph PhCH(CH.sub.3) 0 H H H H H 1024 Ph PhC(CH.sub.3).sub.2 0 H H H H H 1025 2-FPh PhC(CH.sub.3).sub.2 0 H H H H H 1026 3-FPh PhC(CH.sub.3).sub.2 0 H H H H H 1027 4-FPh PhC(CH.su b.3).sub.2 0 H H H H H 1028 2,4-F.sub.2Ph PhC(CH.sub.3).sub.2 0 H H H H H 1029 2-ClPh PhC(CH.sub.3).sub.2 0 H H H H H 1030 3-ClPH PhC(CH.sub.3).s ub.2 0 H H H H H 1031 4-ClPh PhC(CH.sub.3).sub.2 0 H H H H H 1032 2,4-Cl.sub.2Ph PhC(CH.sub.3).sub.2 0 H H H H H 1033 4-BrPh PhC(CH.sub.3). sub.2 0 H H H H H 1034 2-CF.sub.3Ph PhC(CH.sub.3).sub.2 0 H H H H H 1035 3-CF.sub.3Ph PhC(CH.sub.3).sub.2 0 H H H H H 1036 4-CF.sub.3Ph PhC(CH.sub.3).sub.2 0 H H H H H 1037 Ph 4-Cl-PhC(CH.sub.3).sub.2 0 H H H H H 1038 2-FPh 4-Cl-PhC(CH.sub.3).sub.2 0 H H H H H 1039 3-FPh 4-Cl-PhC(C H.sub.3).sub.2 0 H H H H H 1040 4-FPh 4-Cl-PhC(CH.sub.3).sub.2 0 H H H H H (oil).sup.x 1041 2,4-F.sub.2Ph 4-Cl-PhC(CH.sub.3).sub.2 0 H H H H H 1042 2-ClPh 4-Cl-PhC(CH.sub.3).sub.2 0 H H H H H 1043 3-ClPh 4-Cl-PhC(CH. sub.3).sub.2 0 H H H H H 1044 4-ClPh 4-Cl-PhC(CH.sub.3).sub.2 0 H H H H H 1045 2,4-Cl.sub.2Ph 4-Cl-PhC(CH.sub.3).sub.2 0 H H H H H 1046 4-BrPh 4-Cl-PhC(CH.sub.3).sub.2 0 H H H H H 1047 2-CF.sub.3Ph 4-Cl-PhC(CH.sub. 3).sub.2 0 H H H H H 1048 3-CF.sub.3Ph 4-Cl-PhC(CH.sub.3).sub.2 0 H H H H H 1049 4-CF.sub.3Ph 4-Cl-PhC(CH.sub.3).sub.2 0 H H H H H 1050 Ph 2-thienyl 0 H H H H H 127-129 1051 2-FPh 2-thienyl 0 H H H H H 1052 3-FPh 2-thienyl 0 H H H H H 1053 4-FPh 2-thienyl 0 H H H H H 125-134 1054 2,4-F.sub.2Ph 2-thienyl 0 H H H H H 1055 2-ClPh 2-thienyl 0 H H H H H 1056 3-ClPh 2-thienyl 0 H H H H H 110 1057 4-ClPh 2-thienyl 0 H H H H H 141-143 1058 2,4-Cl.sub.2Ph 2-thienyl 0 H H H H H (oil).sup.y 1059 P 4-Brh 2-thienyl 0 H H H H H 1060 2-CF.sub.3Ph 2-thienyl 0 H H H H H 1061 3-CF.sub.3Ph 2-thienyl 0 H H H H H 1062 4-CF.sub.3Ph 2-thienyl 0 H H H H H 1063 Ph 3-thienyl 0 H H H H H 1064 2-FPh 3-thienyl 0 H H H H H 1065 P 3-Fh 3-thienyl 0 H H H H H 1066 4-FPh 3-thienyl 0 H H H H H 1067 2,4-F.sub.2Ph 3-thienyl 0 H H H H H 1068 2-ClPh 3-thienyl 0 H H H H H 1069 3-ClPh 3-thienyl 0 H H H H H 1070 4-ClPh 3-thienyl 0 H H H H H 1071 2,4-Cl.sub.2Ph 3-thienyl 0 H H H H H 1072 4-BrPh 3-thienyl 0 H H H H H 1073 2-CF.sub.3Ph 3-thienyl 0 H H H H H 1074 3-CF.sub.3Ph 3-thienyl 0 H H H H H 1075 4-CF.sub.3Ph 3-thienyl 0 H H H H H 1076 2-FPh 2-Cl-3-thienyl 0 H H H H H 1077 3-FPh 2-Cl-3-thienyl 0 H H H H H 1078 2,4-F.sub.2Ph 2-Cl-3-thienyl 0 H H H H H 1079 3-ClPh 2-Cl-3-thienyl 0 H H H H H 1080 2,4-Cl.sub.2Ph 2-Cl-3-thienyl 0 H H H H H 1081 4-BrPh 2-Cl-3-thienyl 0 H H H H H 1082 2-CF.sub.3Ph 2-Cl-3-thienyl 0 H H H H H 1083 3-CF.sub.3Ph 2-Cl-3-thienyl 0 H H H H H 1084 4-CF.sub.3Ph 2-Cl-3-thienyl 0 H H H H H 1085 2-FPh 5-Cl-2-thienyl 0 H H H H H 1086 3-FPh 5-Cl-2-thienyl 0 H H H H H 1087 2,4-F.sub.2Ph 5-Cl-2-thienyl 0 H H H H H 1088 3-ClPh 5-Cl-2-thie nyl 0 H H H H H 111-112 1089 2,4-Cl.sub.2Ph 5-Cl-2-thienyl 0 H H H H H 103-106 1090 4-BrPh 5-Cl-2-thienyl 0 H H H H H 1091 2-CF.sub.3Ph 5-Cl-2-thienyl 0 H H H H H 1092 3-CF.sub.3Ph 5-Cl-2-thienyl 0 H H H H H (oil).sup.z 1093 4-CF.sub.3Ph 5-Cl-2-thienyl 0 H H H H H 1094 Ph 2,5-Cl.sub.2 -3-thienyl 0 H H H H H (oil).sup.aa 1095 2-FPh 2,5-Cl.sub.2 -3-thienyl 0 H H H H H 1096 3-FPh 2,5-Cl.sub.2 -3-thienyl 0 H H H H H 1097 4-FPh 2,5-Cl.sub.2 -3-thienyl 0 H H H H H 60-62 1098 2,4-F.sub.2Ph 2,5-Cl.sub.2 -3-thienyl 0 H H H H H 1099 2-ClPh 2,5-Cl.sub.2 -3-thienyl 0 H H H H H (oil).sup.ab 1100 3-ClPh 2,5-Cl.sub.2 -3-thienyl 0 H H H H H 54-57 1101 4-ClPh 2,5-Cl.sub.2 -3-thienyl 0 H H H H H (oil).sup.ac 1102 2,4-Cl.sub.2Ph 2,5-Cl.sub.2 -3-thienyl 0 H H H H H (oil).sup.ad 1103 P 4-Brh 2,5-Cl.sub.2 -3-thienyl 0 H H H H H 1104 2-CF.sub.3Ph 2,5-Cl.sub.2 -3-thienyl 0 H H H H H 1105 3-CF.sub.3Ph 2,5-Cl.sub.2 -3-thienyl 0 H H H H H (oil).sup.ae 1106 4-CF.sub.3Ph 2,5-Cl.sub.2 -3-thienyl 0 H H H H H 1107 Ph 5-bromo-2-thienyl 0 H H H H H 1108 2-FPh 5-bromo-2-thienyl 0 H H H H H 1109 3-FPh 5-bromo-2-thienyl 0 H H H H H 1110 4-FPh 5-bromo-2-thien yl 0 H H H H H 1111 2,4-F.sub.2Ph 5-bromo-2-thienyl 0 H H H H H 1112 P 2-Clh 5-bromo-2-thienyl 0 H H H H H 1113 3-ClPh 5-bromo-2-thienyl 0 H H H H H 1114 4-ClPh 5-bromo-2-thienyl 0 H H H H H 1115 2,4-Cl.sub.2Ph 5-bromo-2-thienyl 0 H H H H H 1116 4-BrPh 5-bromo-2-thienyl 0 H H H H H 1117 2-CF.sub.3Ph 5-bromo-2-thienyl 0 H H H H H 1118 3-CF.sub.3Ph 5-bromo-2-thienyl 0 H H H H H 1119 4-CF.sub.3Ph 5-bromo-2-thienyl 0 H H H H H 1120 Ph 2-pyridyl 0 H H H H H 1121 2-FPh 2-pyridyl 0 H H H H H 1122 3-FPh 2-pyridyl 0 H H H H H 1123 2,4-F.sub.2Ph 2-pyridyl 0 H H H H H 1124 2-ClPh 2-pyridyl 0 H H H H H 1125 3-ClPh 2-pyridyl 0 H H H H H 1126 4-ClPh 2-pyridyl 0 H H H H H 1127 2,4-Cl.sub.2Ph 2-pyridyl 0 H H H H H 1128 4-BrPh 2-pyridyl 0 H H H H H 1129 2-CF.sub.3Ph 2-pyridyl 0 H H H H H 1130 3-CF.sub.3Ph 2-pyridyl 0 H H H H H 1131 4-CF.sub.3Ph 2-pyridyl 0 H H H H H 1132 Ph 3-pyridyl 0 H H H H H 1133 2-FPh 3-pyridyl 0 H H H H H 1134 3-FPh 3-pyridyl 0 H H H H H 1135 4-FPh 3-pyridyl 0 H H H H H 1136 2,4-F.sub.2Ph 3-pyridyl 0 H H H H H 1137 2-ClPh 3-pyridyl 0 H H H H H 1138 3-ClPh 3-pyridyl 0 H H H H H 1139 4-ClPh 3-pyridyl 0 H H H H H 1140 2,4-Cl.sub.2Ph 3-pyridyl 0 H H H H H 1141 4-BrPh 3-pyridyl 0 H H H H H 1142 2-CF.sub.3Ph 3-pyridyl 0 H H H H H 1143 3-CF.sub.3Ph 3-pyridyl 0 H H H H H 1144 4-CF.sub.3Ph 3-pyridyl 0 H H H H H 1145 Ph 4-pyridyl 0 H H H H H 1146 2-FPh 4-pyridyl 0 H H H H H 1147 3-FPh 4-pyridyl 0 H H H H H 1148 2,4-F.sub.2Ph 4-pyridyl 0 H H H H H 1149 2-ClPh 4-pyridyl 0 H H H H H 1150 3-ClPh 4-pyridyl 0 H H H H H 1151 4-ClPh 4-pyridyl 0 H H H H H 1152 2,4-Cl.sub.2Ph 4-pyridyl 0 H H H H H 1153 4-BrPh 4-pyridyl 0 H H H H H 1154 2-CF.sub.3Ph 4-pyridyl 0 H H H H H 1155 3-CF.sub.3Ph 4-pyridyl 0 H H H H H 1156 4-CF.sub.3Ph 4-pyridyl 0 H H H H H 1157 Ph 2-Cl-3-pyrid yl 0 H H H H H 1158 2-FPh 2-Cl-3-pyridyl 0 H H H H H 1159 3-FPh 2-Cl-3-py ridyl 0 H H H H H 1160 4-FPh 2-Cl-3-pyridyl 0 H H H H H 1161 2,4-F.sub.2P h 2-Cl-3-pyridyl 0 H H H H H 1162 2-ClPh 2-Cl-3-pyridyl 0 H H H H H 1163 3-ClPh 2-Cl-3-pyridyl 0 H H H H H 1164 4-ClPh 2-Cl-3-pyridyl 0 H H H H H 1165 2,4-Cl.sub.2Ph 2-Cl-3-pyridyl 0 H H H H H 1166 4-BrPh 2-Cl-3-pyridyl 0 H H H H H 1167 2-CF.sub.3Ph 2-Cl-3-pyridyl 0 H H H H H 1168 3-CF.sub.3P h 2-Cl-3-pyridyl 0 H H H H H 1169 4-CF.sub.3Ph 2-Cl-3-pyridyl 0 H H H H H 1170 Ph 3-Cl-2-pyridyl 0 H H H H H 1171 2-FPh 3-Cl-2-pyridyl 0 H H H H H 1172 3-FPh 3-Cl-2-pyridyl 0 H H H H H 1173 4-FPh 3-Cl-2-pyridyl 0 H H H H H 1174 2,4-F.sub.2Ph 3-Cl-2-pyridyl 0 H H H H H 1175 2-ClPh 3-Cl-2-py ridyl 0 H H H H H 1176 3-ClPh 3-Cl-2-pyridyl 0 H H H H H 1177 4-ClPh 3-Cl-2-pyridyl 0 H H H H H 1178 2,4-Cl.sub.2Ph 3-Cl-2-pyridyl 0 H H H H H 1179 4-BrPh 3-Cl-2-pyridyl 0 H H H H H 1180 2-CF.sub.3Ph 3-Cl-2-pyridyl 0 H H H H H 1181 3-CF.sub.3Ph 3-Cl-2-pyridyl 0 H H H H H 1182 4-CF.sub.3P h 3-Cl-2-pyridyl 0 H H H H H 1183 2-FPh 5-Cl-2-pyridyl 0 H H H H H 1184 3-FPh 5-Cl-2-pyridyl 0 H H H H H 1185 2,4-FPh 5-Cl-2-pyridyl 0 H H H H H 1186 3-ClPh 5-Cl-2-pyridyl 0 H H H H H 1187 2,4-Cl.sub.2Ph 5-Cl-2-pyridyl 0 H H H H H 1188 4-BrPh 5-Cl-2-pyridyl 0 H H H H H 1189 2-CF.sub.3Ph 5-Cl-2-pyridyl 0 H H H H H 1190 3-CF.sub.3Ph 5-Cl-2-pyridyl 0 H H H H H 1191 4-CF.sub.3Ph 5-Cl-2-pyridyl 0 H H H H H 1192 Ph 6-Cl-3-pyridyl 0 H H H H H 1193 2-FPh 6-Cl-3-pyridyl 0 H H H H H 1194 3-FPh 6-Cl-3-pyridyl 0 H H H H H 1195 4-FPh 6-Cl-3-pyridyl 0 H H H H H 1196 2,4-F.sub.2Ph 6-Cl-3-pyridyl 0 H H H H H 1197 2-ClPh 6-Cl-3-pyridyl 0 H H H H H 1198 3-ClPh 6-Cl-3-pyridyl 0 H H H H H 1199 4-ClPh 6-Cl-3-pyridyl 0 H H H H H 1200 2,4-Cl.sub.2Ph 6-Cl-3-pyridyl 0 H H H H H 1201 4-BrPh 6-Cl-3-pyridyl 0 H H H H H 1202 2-CF.sub.3Ph 6-Cl-3-pyridyl 0 H H H H H 1203 3-CF.sub.3P h 6-Cl-3-pyridyl 0 H H H H H 1204 4-CF.sub.3Ph 6-Cl-3-pyridyl 0 H H H H H 1205 2-thienyl 2-thienyl 0 H H H H H 1206 3-thienyl 2-thienyl 0 H H H H H 1207 2-Cl-3-thienyl 2-thienyl 0 H H H H H 1208 5-Cl-2-thienyl 2-thienyl 0 H H H H H 1209 2,5-Cl.sub.2 -3-thienyl 2-thienyl 0 H H H H H 1210 2-thienyl 3-thienyl 0 H H H H H 1211 3-thienyl 3-thienyl 0 H H H H H 1212 2-Cl-3-thienyl 3-thienyl 0 H H H H H 1213 5-Cl-2-thienyl 3-thienyl 0 H H H H H 1214 2,5-Cl.sub.2 -3-thienyl 3-thienyl 0 H H H H H 1215 2-thienyl 2-Cl-3-thienyl 0 H H H H H 1216 3-thienyl 2-Cl-3-thienyl 0 H H H H H 1217 2-Cl-3-thienyl 2-Cl-3-thienyl 0 H H H H H 1218 5-Cl-2-thienyl 2-Cl-3-thienyl 0 H H H H H 1219 2,5-Cl.sub.2 -3-thienyl 2-Cl-3-thienyl 0 H H H H H 1220 2-thienyl 5-Cl-3-thienyl 0 H H H H H 1221 3-thienyl 5-Cl-3-thienyl 0 H H H H H 1222 2-Cl-3-thienyl 5-Cl-3-thienyl 0 H H H H H 1223 5-Cl-2-thienyl 5-Cl-3-thienyl 0 H H H H H 1224 2,5-Cl.sub.2 -3-thienyl 5-Cl-3-thienyl 0 H H H H H 1225 2-thienyl 2,5-Cl.sub.2 -3-thienyl 0 H H H H H 1226 3-thienyl 2,5-Cl.sub.2 -3-thienyl 0 H H H H H 1227 2-Cl-3-thienyl 2,5-Cl.sub.2 -3-thienyl 0 H H H H H 1228 5-Cl-2-thienyl 2,5-Cl.sub.2 -3-thienyl 0 H H H H H 1229 2,5-Cl.sub.2 -3-thienyl 2,5-Cl.sub.2 -3-thienyl 0 H H H H H 1230 thienyl 5-F-2-thienyl 0 H H H H H 1231 3-pyridyl 5-Cl-2-pyridyl 0 H H H H H 1232 5-Cl-2-pyridyl 5-Cl-2-pyridyl 0 H H H H H 1233 4-pyridyl 5-Cl-2-pyridyl 0 H H H H H 1234 2-Cl-3-pyridyl 5-Cl-2-pyridyl 0 H H H H H 1235 2-pyridyl 5-Cl-2-pyridyl 0 H H H H H 1236 4-F Ph 4-FPh 0 H H H C.sub.2 H.sub.5 H 1237 4-FPh 4-FPh 0 H H H -n-C.sub.3 H.sub.7 H 1238 4-FPh 4-FPh 0 H H H -n-C.sub.4 H.sub.9 H 1239 4-FPh 4-FPh 0 H H H -i-C.sub.3 H.sub.7 H 1240 4-FPh 4-FPh 0 H H H .sub.-s-C.sub.4 H.sub.9 H 1241 2-ClPh 4-ClPh 0 H H H C.sub.2 H.sub.5 H 1242 2-ClPh 4-ClPh 0 H H H n --C.sub.3 H.sub.7 H 1243 2-ClPh 4-ClPh 0 H H H -n-C.sub.4 H.sub.9 H 1244 2-ClPh 4-ClPh 0 H H H -i-C.sub.3 H.sub.7 H 1245 2-ClPh 4-ClPh 0 H H H .sub.-s-C.sub.4 H.sub.9 H 1246 4-ClPh 2,4-Cl.sub.2Ph 0 H H H C.sub.2 H.sub.5 H 1247 4-ClPh 2,4-Cl.sub.2Ph 0 H H H - n-C.sub.3 H.sub.7 H 1248 4-ClPh 2,4-Cl.sub.2Ph 0 H H H -n-C.sub.4 H.sub.9 H 1249 4-ClPh 2,4-Cl.sub.2Ph 0 H H H -i-C.sub.3 H.sub.7 H 1250 4-ClPh 2,4-Cl.sub.2Ph 0 H H H .sub.-s-C.sub.4 H.sub.9 H 1251 Ph 4-FPh 0 H H H C.sub.2 H.sub.5 H 1252 Ph 4-FPh 0 H H H -n-C.sub.3 H.sub.7 H 1253 Ph 4-FPh 0 H H H -n-C.sub.4 H.sub.9 H 1254 Ph 4-FPh 0 H H H -i-C.sub.3 H.sub.7 H 1255 Ph 4-FPh 0 H H H .sub.-s-C.sub.4 H.sub.9 H 1256 4-FPh 4-FPh 0 H H H CH.sub.3 H 1257 4-FPh 4-FPh 0 H H H CH.sub.3 CH.sub.3 1258 4-FPh 4-FPh 0 H H H F H 166-167 1259 4-FPh 4-FPh 0 H H H F CH.sub.3 1260 4-FPh 4-F Ph 0 H H H F F 145-147 1261 4-ClPh 2,4-Cl.sub.2Ph 0 H H H CH.sub.3 H 1262 4-ClPh 2,4-Cl.sub.2Ph 0 H H H CH.sub.3 CH.sub.3 1263 P 4-Clh 2,4-Cl.sub.2Ph 0 H H H F H 1264 4-ClPh 2,4-Cl.sub.2Ph 0 H H H F CH.sub.3 1265 4-ClPh 2,4-Cl.sub.2Ph 0 H H H F F 1266 2-ClPh 4-ClPh 0 H H H CH.sub.3 H 1267 2-ClPh 4-ClPh 0 H H H CH.sub.3 CH.sub.3 1268 2-ClPh 4-ClPh 0 H H H F H 1269 2-ClPh 4-ClPh 0 H H H F CH.sub.3 1270 2-ClPh P 4-Clh 0 H H H F F 1271 Ph 4-FPh 0 H H H CH.sub.3 H 1272 Ph 4-FPh 0 H H H CH.sub.3 CH.sub.3 1273 Ph 4-FPh 0 H H H F H 1274 Ph 4-FPh 0 H H H F CH.sub.3 1275 Ph 4-FPh 0 H H H F F 1997 Ph 4-.sub.-t-BuPh 0 H H H H H 112-114 1998 4-FPh 2,6-F.sub.2Ph 0 H H H H H 110-116 1999 4-FPh 3-CH.sub. 3 -4-ClPh 0 H H H H H 127.5-129 2000 4-FPh 4-.sub.-t-BuPh 0 H H H H H 105-107 2001 4-FPh 4-CNPh 0 H H H H H 137-139 2002 4-FPh CF.sub.3 0 H H H H H (oil).sup.ag 2003 2-CF.sub.3Ph 3-CF.sub.3Ph 0 H H H H H (oil).sup.a h 2004 4-CH.sub.3Ph 2-FPh 0 H H H H H 115-118 2005 4-CH.sub.3Ph 2-Cl-4-FP h 0 H H H H H 111-116 2006 Ph 2,4-F.sub.2Ph 0 H H CH.sub.3 H H 67-72 2007 Ph 4-ClPh 0 H H CH.sub.3 H H 110.5-111 2008 4-FPh 2-FPh 0 H H CH.sub.3 H H 67-72 2009 4-FPh 2,4-F.sub.2Ph 0 H H CH.sub.3 H H (oil).sup. ai 2010 2-Cl-3-pyridyl, 4-ClPh 0 H H H H H (HCl salt).sup.aj N-oxide 2011 4-Cl-3-pyridyl 2,4-F.sub.2Ph 0 H H H H H (oil).sup.ak 2012 4-Cl-3-py ridyl 4-ClPh 0 H H H H H 172-174 2013 4-Cl-3-pyridyl 2,4-Cl.sub.2Ph 0 H H H H H (oil).sup.al 2014 4-CH.sub.3 S-3-l 4-ClPh 0 H H H H H 138-140 pyridyl 2015 2-Cl-4-pyridyl 4-ClPh 0 H H H H H (2HCl salt 170-175) 2016 2-CH.sub.3Ph 2-Cl-4-FPh 0 H H H H H .sup.a NMR: (CDCl.sub.3) .delta. 4.70(q, J=14Hz, 2H), 4.90(s, 1H), 5.40(s, 1H), 5.55(s, 1H), 6.8-7.0(m, 4H), 7.2-7.4(m, 4H), 7.8(bs, 2H). .sup.b NMR: (CDCl.sub.3) .delta. 4.8(q, 2H), 5.2(s, 1H), 5.3(s, 1H), 5.6(s, 1H), 6.9-7.6(m, 8H), 7.8(s, 1H), 8.1(s, 1H). .sup.c NMR: (CDCl.sub .3) .delta. 4.70(q, J=13Hz, 2H), 4.85(s, 1H), 5.35(s, 1H), 5.55(s, 1H), 6.85-7.4(m, 8H), 7.7(s, H), 7.9(s, 1H). .sup.d NMR: (CDCl.sub.3) .delta. 4.60(q, J=12Hz, 2H), 5.0(s, 1H), 5.40(s, 1H), 5.55(s, 1H), 6.8(1/2 of ABq, J=10Hz, 2H), 7.00(m, 2H), 7.3(1/2 of ABq, J=10Hz, 2H), 7.45(m, 2H), 7.80(s, 1H), 7.85(s, 1H). .sup.e NMR: (CDCl.sub.3) .delta. 4.6, 4.8(ABq, J=14Hz, 2H), 4.9(br s, 3H), 5.3(s, 1H), 5.6(s, 1H), 6.8(d, 1H), 7.0(m, 3H), 7.4(m, 3H), 7.8(s, 1H), 7.9(s, 1H). .sup.f NMR: (CDCl.sub.3) .delta. 1.3(s, 9H), 4.7(q, 2H), 4.6(s, 1H), 5.0(s, 1H), 5.4(s, 1H), 6.8-7.4(9H), 7.8(s, 1H). .sup.g NMR: (CDCl.sub.3) .delta. 4.7, 4.8(ABq, J=12Hz), 2H), 6.7-7.5(m, 14H), 7.9(s, 1H), 8.0(s, 1H). .sup.h NMR: (CDCl.sub.3) .delta. 3.45(s, 3H), 4.75(ABq, J=18Hz, 14Hz, 2H), 4.6(m, 2H), 6.8-7.0(m, 4H), 7.05-7.25(m, 4H), 8.0(s, 1H), 8.25(s, 1H). .sup.i NMR: (CDCl.sub.3) .delta. 4.0(dd, 14, 4Hz, 1H), 4.3(dd, 14, 4Hz, 1H), 4.6(d, 13Hz, 1H), 4.9(d, 13Hz, 1H), 5.1(d, 1H), 5.3(d, 1H), 5.55(s, 1H), 5.60 (s, 1H), 5.85(m, 1H), 6.8-7.0(m, 4H), 7.05-7.2(m, 4H), 8.05(s, 1H), 8.25(s, 1H). .sup.j NMR: (CDCl.sub.3) .delta. 1.90(s, 3H), 4.80(1/2 of ABq, J=14Hz, 1H), 5.65(1/2 of ABq, J=14Hz, 1H), 5.55(s, 1H), 5.60(s, 1H), 6.75-7.0(m, 4H), 7.0-7.2(t, 2H), 7.25-7.4(m, 2H), 7.35(s, 1H), 7.85(s, 1H). .sup.k NMR: (CDCl.sub.3) .delta. 4.03, 4.11(ABq, J=11Hz, 2H), 4.25(s, 1H, 0H), 4.39(s, 1H, 0H), 4.54, 4.81(ABq, J=14Hz, 2H), 5.31, 5.33(2 sharp s, 1H each), 7.25-7.40(m, 4H), 7.71(s, 1H), 8.03(s, 1H). .sup.l NMR: (CDCl.sub.3) .delta. 2.03(s, 1H, 0H), 4.0-4.2(m, 2H), 4.57, 4.85(ABq, J=15Hz, 2H), 5.3-5.35(m, 2H), 5.7-5.9(broad s, 1H, 0H), 7.3-7.6(m, 4H), 7.75(s, 1H), 8.11(s, 1H). .sup.m NMR: (CDCl.sub.3) .delta. 2.10(s, 6H), 2.52, 3.03(ABq, J=12Hz, 2H), 4.41, 4.78(ABq, J=15Hz, 2H), 5.19(s, 1H), 5.50(s, 1H), 6.9-7.2(m, 2H), 7.4-7.6(m, 2H), 7.80(s, 1H), 8.36(s, 1H). .sup.n NMR: (CDCl.sub.3) .delta. 2.11(s, 6H), 2.61, 3.11(ABq, J=12Hz, 2H), 4.50, 4.90(ABq, J=13Hz, 2H), 5.13(s, 1H), 5.50(s, 1H), 7.50(s, 4H), 7.86(s, 1H), 8.14(s, 1H). .sup.o NMR: (CDCl.sub .3) .delta. 2.13(s, 3H), 2.19(s, 3H), 2.5-3.1(m, 2H), 4.44, 485(ABq, J=14Hz, 2H), 5.0-5.5(m, 2H), 7.3-7.8(m, 9H), 7.97(s, 1H), 8.32(s, 1H, 0H), 8.50(s, 1H). .sup.p NMR: (CDCl.sub.3) .delta. 4.6(d, 1/2 of ABq, 1H), 4.9(d, 1/2 of ABq, 1H), 5.0(s, 1H), 5.3(two s, 2H), 6.9-7.6(m, 9H), 7.8(two s, 2H). .sup.q NMR: (CDCl.sub.3) .delta. 1.0(t, 3H), 1.2(s, 1H), 1.6(m, 2H), 4.2(ABq, 2H), 5.1(s, 1H), 5.4(s, 1H), 6.9-7.1(m, 4H), 7.9(s, 1H), 8.0(s, 1H). .sup.r NMR: (CDCl.sub.3) .delta. 4.6(AB, 2H), 4.6(d, 1H), 5.3(s, 1H), 5.5(s, 1H), 7.2(m, 1H), 7.6(m, 7H), 7.7(m, 1H), 7.7(s, 1H), 7.8(s, 1H). .sup.s NMR: (CDCl.sub.3) .delta. 4.6(1/2 of AB, J=13, 1H), 5.0(1/2 of AB, J=13, 1H), 5.2(s, 1H), 5.3(s, 1H), 5.4(s, 1H), 7.0(m, 2H), 7.2(m, 1H), 7.4(m, 5H), 7.8(s, 1H), 7.82(s, 1H). .sup.t NMR: (CDCl.sub.3) .delta. 4.6(1/2 ABq, 1H), 5.3(s), 5.4(1/2 of ABq + s + br, 4H total), 7.1(m, 1H), 7.3(m, 1H), 7.5(m, 5H), 7.8(s, 2H). .sup.u NMR: (CDCl.sub.3) .delta. 4.4(1/2 of AB, 1H), 5.7(1/2 of AB, 1H), 5.1(s, 1H), 5.3(s, 1H), 5.4(s, 1H), 7.2(m, 3H), 7.3(m, 2H), 7.4(d, 1H), 7.6(m, 1H), 7.7(s, 1H), 7.9(s, 1H). .sup.v NMR: (CDCl.sub.3) .delta. 4.4(s, 2H), 4.8(s, 1H), 5.1(s, 1H), 5.5(s, 1H), 6.3(d, 1H) 6.5(d, 1H) 6.8-7.2(m, 4H), 7.6(s, 1H), 7.7(s, 1H). .sup.w NMR: (CDCl.sub.3) .delta. 4.7(dd, 2H), 5.4(s, 1H), 5.6(s, 1H), 6.7(d, 1H), 7.0(d, 1H), 7.2(m), 8.0(s, 1H), 8.2(s, 1H). .sup.x NMR: (CDCl.sub.3) .delta. 1.6(two s, 6H total), 4.3(1/2 of ABq, 1H), 4.6(1/2 of ABq, 1H), 5.0(d, 1H), 5.2(d, 1H), 5.3(s, 1H), 6.7-7.6(m, 8H), 7.9(s, 1H), 8.1(s, 1H). .sup.y NMR: (CDCl.sub.3) .delta. 4.7(s, 2H), 5.3(s, 1H), 5.8(s, 1H), 6.9(m, 3H), 7.1(m, 1H), 7.2(m, 1H), 7.4(s, 1H), 7.9(s, 1H), 8.1(s, 1H). .sup.z NMR: (CDCl.sub.3) .delta. 4.6(dd, 2H), 5.2(s, 1H), 5.4(s, 1H), 5.6(s, 1H), 6.7(d, 1H), 6.8(d, 1H), 7.4-7.6(m, 4H), 7.9(s, 1H), 7.9(s, 1H). .sup.aa NMR: (CDCl.sub.3) .delta. 4.6(d, 1H), 5.0(d, 1H), 5.2(s, 1H), 5.34(s, 1H), 5.4(s, 1H), 6.8(s, 1H), 7.2(m, 5H), 7.9(s, 2H). .sup.ab NMR: (CDCl.sub.3) .delta. 4.4(d, 1H), 5.3(d, 1H), 5.3(s, 1H), 5.6(s, 1H), 6.8(s, 1H), 7.2-7.4(m, 4H), 7.8(s, 1H), 8.1(s, 1H). .sup.ac NMR: (CDCl.sub.3) .delta. 4.6(d, 1H), 5.1(d, 1H), 5.3(s, 1H), 5.35(s, 1H), 5.45(s, 1H), 6.8(s, 1H), 7.2(m, 4H), 7.9(s, 1H), 8.1(s, 1H). .sup.ad NMR: (CDCl.sub.3) .delta. 4.6(d, 1H), 5.3(d, 1H), 5.3(s, 1H), 5.6(s, 1H), 6.8(s, 1H), 7.2(m, 2H), 7.4(s, 1H), 7.9(s, 1H), 8.1(s, 1H). .sup.af NMR: (CDCl.sub.3) .delta. 4.7(bs, 1H), 4.9(bs, 1H), 5.33(2s, 2H), 6.75(d, 2H), 7.12(m, 4H), 7.45(s, 1H), 7.83(s, 1H), 8.00(s, 1H), 8.33(d, 2H). .sup.ag NMR: (CDCl.sub.3) .delta. 4.6(s, 2H), 5.4(s, 1H), 5.5(s, 1H), 5.8(s, 1H), 6.8-7.0(m, 3H), 7.3-7.4(m, 1H), 8.0, 8.1(two s, 2H). .sup.ah NMR: (CDCl.sub.3) .delta. 4.6(ABq, 2H), 5.2(s, OH), 5.3(s, 1H), 5.4(s, 1H), 7.1-7.7(m, 8H), 7.7(s, 1H), 7.8(s, 1H). .sup.ai NMR: (CDCl.sub.3) .delta. 3.6(s, 3H), 4.7-5.0(ABq, 2H), 5.4(s, 1H), 5.7(s, 1H), 6.6-7.2(m), 7.7(s, 1H), 7.8(s, 1H). .sup.aj NMR: (free base, CDCl.sub.3) .delta. 4.77(s, 2H), 5.27(s, 1H), 5.33(s, 1H), 5.73(s, 1H), 6.72(d, 1H), 7.00(t, 1H), 7.32(ABq, 4H), 7.77(s, 1H), 8.13(s, 1H), 8.18(d, 1H). .sup.ak NMR: (CDCl.sub.3) .delta. 4.63(d, 1H), 5.03(d, 1H), 5.30(s, 1H), 5.42(s, 1H), 5.50(s, 1H), 6.75(m, 2H), 7.23(d, 1H), 7.43(q, 1H), 7.67(dd, 1H), 7.83(s, 1H), 7.88(s, 1H), 8.28(d, 1H). .sup.al NMR: (CDCl.sub.3) .delta. 4.67(d, 1H), 5.40(s, 1H), 5.46(s, 1H), 5.45(d, 2H), 7.00-7.27(m, 3H), 7.43(d, 1H), 7.67-7.83(m, 3H), 8.33(d, 1H). .sup.am NMR: (CDCl.sub.3) .delta. 4.7(1/2 of ABq, 1H), 5.0(1/2 of ABq, 1H), 5.3(s, 2H), 6.0(s, 1H), 6.8(m, 2H), 7.3-7.6(m, 6H), 7.7(s, 1H), 7.8(d, 1H), 8.0(s, 1H), 8.6(d, 1H), 8.7(s, 1H). .sup.an NMR: (CDCl.sub.3) .delta. 4.6(1/2 of ABq, 1H), 5.0(1/2 of ABq, 1H), 5.2-5.3(three s, 3H), 6.8(m, 2H), 7.5(m, 6H), 7.8(m, 3H), 8.6(d, 1H), 8.8(s, 1H).
EXAMPLES 1276 and 1276a
Preparation of the (S)-enantiomer of Example 49
The compound of Example 49 (1.5 g) and 1.5 g of l-.alpha.-bromocamphor-.pi.-sulfuric acid was dissolved in 75 ml of acetonitrile and refluxed for 2 hours. The solution was allowed to cool to ambient temperature and stand for 14 hours. Filtration of the resulting solids followed by recrystallization from an additional portion of acetonitrile, yielded 1.28 g of white solid, mp 216.degree.-217.degree.; [.alpha.].sub.25.sup.D =104.degree. (C=1; DMSO).
The acetonitrile can be evaporated to yield the adduct having a (+)- rotation (Example 1276a). This compound can be recrystallized from an ether/acetone mixture to yield a solid, that on treatment with aqueous NaHCO.sub.3 yields material identical by NMR to that of Example 49.
The solid was suspended in 50 ml of saturated NaHCO.sub.3 solution and stirrred vigorously until the evolution of gas ceased (1-2 hours). The mixture was extracted twice with 50 ml of CHCl.sub.3. The organic layers were combined, washed with brine, dried over Na.sub.2 SO.sub.4 and the solvent removed in vacuo. This yielded 750 mg of a white solid (Example 1276) having an 'H NMR identical to that of the compound of Example 49, mp=82.degree.-83.degree.; [.alpha.].sub.25.sup.D =-62.degree. (C=1; CHCl.sub.3).
These compounds and other compounds which were resolved as described above are shown in Table 2.
TABLE 2__________________________________________________________________________ ##STR33##Ex.No. A B n R R.sup.1 R.sup.2 R.sup.3 R.sup.4 M.P. .degree.C. [.alpha.].sub.D.sup.25__________________________________________________________________________1276 ##STR34## ##STR35## 0 H H H H H 82-83 -62.degree.1276a.sup.(1) ##STR36## ##STR37## 0 H H H H H 83-84 +60.degree.1277.sup.(2) ##STR38## ##STR39## 0 H H H H H 60-61 (HCl salt 181-184) -67.degree.1277a.sup.(1), (2) ##STR40## ##STR41## 0 H H H H H 60-62 +66.degree.__________________________________________________________________________ *denotes chiral center .sup.(1) = substitute d.alpha.-bromocamphor-.pi.-sulfonic acid .sup.(2) = use a 3 parts ether 1 part acetone mixture as solvent.
EXAMPLE 1278
Preparation of 2-(4-fluorophenyl)-3-phenyl-1-(5-mercapto-1H-1,2,4-triazol-1-yl) -3-buten-1-ol
To a solution of 1.24 g (0.004 mol) of 2-(4-fluorophenyl)-3-phenyl-1-(1H-1,2,4-triazol -1-yl)-3-buten-2-ol in 15 mL of THF at -70.degree. was added 5.2 mL (0.008 mol) of a 1.55 M solution of n-butyllithium in hexanes over 5 minutes. After 30 minutes, 0.13 g (0.004 mol) of sulfur was added and the reaction mixture was allowed to warm to room temperature over 1 h, then quenched with 8 mL of 1N HCl. After pouring into saturated NH.sub.4 Cl, the mixture was extracted with 2 x ether and the combined organic layers were washed with brine, dried over Na.sub.2 SO.sub.4 and evaporated. The crude product was purified by flash chromatography using 2:13:85 methanol/ether/methylene chloride to give 0.85 g of the title compound, m.p. 54.degree.-58.degree.; NMR (CDCl.sub.3).delta.4.7 (ABq, 2H), 5.0 (s, 1H, OH), 5.3 (s, 1H, vinyl), 5.5 (s, 1H, vinyl), 7.0 (m, 4H), 7.2 (m, 3H), 7.5 (m, 2H), 7.7 (s, 1H, triazole proton), 12.5 (brs, 1H, SH), IR (methylene chloride) 3500-3000 (br), 1590, 1500, 1465, 1230, 1162, 1109, 825 cm.sup.-1 ; MS: highest m/e b 341.
The compounds shown in Table 3 were prepared or can be prepared by the methods described above.
TABLE 3*__________________________________________________________________________ ##STR42##Ex.No. A B R R.sup.1 R.sup.2 R.sup.4 Q M.P. .degree.C.__________________________________________________________________________1278 Ph 4-F-Ph H H H H SH 54-581279 Ph Ph H H H H SH1280 Ph 2-F-Ph H H H H SH1281 Ph 2-Cl-Ph H H H H SH1282 Ph 4-Cl-Ph H H H H SH1283 Ph 2,4-F.sub.2 -Ph H H H H SH1284 Ph 2,4-Cl.sub.2 -Ph H H H H SH1285 2-F-Ph Ph H H H H SH1286 2-F-Ph 2-F-Ph H H H H SH1287 2-F-Ph 4-F-Ph H H H H SH1288 2-F-Ph 2-Cl-Ph H H H H SH1289 2-F-Ph 4-Cl-Ph H H H H SH1290 2-F-Ph 2,4-F.sub.2 -Ph H H H H SH1291 2-F-Ph 2,4-Cl.sub.2 -Ph H H H H SH1292 3-F-Ph Ph H H H H SH1293 3-F-Ph 2-F-Ph H H H H SH1294 3-F-Ph 4-F-Ph H H H H SH1295 3-F-Ph 2-Cl-Ph H H H H SH1296 3-F-Ph 4-Cl-Ph H H H H SH1297 3-F-Ph 2,4-F.sub.2 -Ph H H H H SH1298 3-F-Ph 2,4-Cl.sub.2 -Ph H H H H SH1299 4-F-Ph Ph H H H H SH1300 4-F-Ph 2-F-Ph H H H H SH 144.5-1481301 4-F-Ph 4-F-Ph H H H H SH1302 4-F-Ph 2-Cl-Ph H H H H SH1303 4-F-Ph 4-Cl-Ph H H H H SH1304 4-F-Ph 2,4-F.sub.2 -Ph H H H H SH (foam).sup.a1305 4-F-Ph 2,4-Cl.sub.2 -Ph H H H H SH1306 2-Cl-Ph Ph H H H H SH1307 2-Cl-Ph 2-F-Ph H H H H SH1308 2-Cl-Ph 4-F-Ph H H H H SH1309 2-Cl-Ph 2-Cl-Ph H H H H SH1310 2-Cl-Ph 4-Cl-Ph H H H H SH1311 2-Cl-Ph 2,4-F.sub. 2 -Ph H H H H SH1312 2-Cl-Ph 2,4-Cl.sub.2 -Ph H H H H SH1313 3-Cl-Ph Ph H H H H SH1314 3-Cl-Ph 2-F-Ph H H H H SH1315 3-Cl-Ph 4-F-Ph H H H H SH1316 3-Cl-Ph 2-Cl-Ph H H H H SH1317 3-Cl-Ph 4-Cl-Ph H H H H SH1318 3-Cl-Ph 2,4-F.sub.2 -Ph H H H H SH1319 3-Cl-Ph 2,4-Cl.sub.2 -Ph H H H H SH1320 4-Cl-Ph Ph H H H H SH1321 4-Cl-Ph 2-F-Ph H H H H SH1322 4-Cl-Ph 4-F-Ph H H H H SH1323 4-Cl-Ph 2-Cl-Ph H H H H SH1324 4-Cl-Ph 4-Cl-Ph H H H H SH1325 4-Cl-Ph 2,4-F.sub.2 -Ph H H H H SH1326 4-Cl-Ph 2,4-Cl.sub.2 -Ph H H H H SH1327 2-CF.sub.3 -Ph Ph H H H H SH1328 2-CF.sub.3 -Ph 2-F-Ph H H H H SH1329 2-CF.sub.3 -Ph 4-F-Ph H H H H SH1330 2-CF.sub.3 -Ph 2-Cl-Ph H H H H SH1331 2-CF.sub.3 -Ph 4-Cl-Ph H H H H SH1332 2-CF.sub.3 -Ph 2,4-F.sub.2 -Ph H H H H SH1333 2-CF.sub.3 -Ph 2,4-Cl.sub.2 -Ph H H H H SH1334 4-CF.sub.3 -Ph Ph H H H H SH1335 4-CF.sub.3 -Ph 2-F-Ph H H H H SH1336 4-CF.sub.3 -Ph 4-F-Ph H H H H SH1337 4-CF.sub.3 -Ph 2-Cl-Ph H H H H SH1338 4-CF.sub.3 -Ph 4-Cl-Ph H H H H SH1339 4-CF.sub.3 -Ph 2,4-F.sub.2 -Ph H H H H SH1340 4-CF.sub.3 -Ph 2,4-Cl.sub.2 -Ph H H H H SH1341 2,4-F.sub.2 -Ph Ph H H H H SH1342 2,4-F.sub.2 -Ph 2-F-Ph H H H H SH1343 2,4-F.sub.2 -Ph 4-F-Ph H H H H SH1344 2,4-F.sub.2 -Ph 2-Cl-Ph H H H H SH1345 2,4-F.sub.2 -Ph 4-Cl-Ph H H H H SH1346 2,4-F.sub.2 -Ph 2,4-F.sub.2 -Ph H H H H SH1347 2,4-F.sub.2 -Ph 2,4-Cl.sub.2 -Ph H H H H SH1348 2,4-Cl.sub.2 -Ph Ph H H H H SH1349 2,4-Cl.sub.2 -Ph 2-F-Ph H H H H SH1350 2,4-Cl.sub.2 -Ph 4-F-Ph H H H H SH1351 2,4-Cl.sub.2 -Ph 2-Cl-Ph H H H H SH1352 2,4-Cl.sub.2 -Ph 4-Cl-Ph H H H H SH1353 2,4-Cl.sub.2 -Ph 2,4-F.sub.2 -Ph H H H H SH1354 2,4-Cl.sub.2 -Ph 2,4-Cl.sub.2 -Ph H H H H SH1355 Ph Ph H H H H I1356 Ph 2-F-Ph H H H H I1357 Ph 4-F-Ph H H H H I1358 Ph 2-Cl-Ph H H H H I1359 Ph 4-Cl-Ph H H H H I1360 Ph 2,4-F.sub.2 -Ph H H H H I1361 Ph 2,4-Cl.sub.2 -Ph H H H H I1362 2-F-Ph Ph H H H H I1363 2-F-Ph 2-F-Ph H H H H I1364 2-F-Ph 4-F-Ph H H H H I1365 2-F-Ph 2-Cl-Ph H H H H I1366 2-F-Ph 4-Cl-Ph H H H H I1367 2-F-Ph 2,4-F.sub.2 -Ph H H H H I1368 2-F-Ph 2,4-Cl.sub.2 -Ph H H H H I1369 3-F-Ph Ph H H H H I1370 3-F-Ph 2-F-Ph H H H H I1371 3-F-Ph 4-F-Ph H H H H I1372 3-F-Ph 2-Cl-Ph H H H H I1373 3-F-Ph 4-Cl-Ph H H H H I1374 3-F-Ph 2,4-F.sub.2 -Ph H H H H I1375 3-F-Ph 2,4-Cl.sub.2 -Ph H H H H I1376 4-F-Ph Ph H H H H I1377 4-F-Ph 2-F-Ph H H H H I 96-97.51378 4-F-Ph 4-F-Ph H H H H I1379 4-F-Ph 2-Cl-Ph H H H H I1380 4-F-Ph 4-Cl-Ph H H H H I1381 4-F-Ph 2,4-F.sub.2 -Ph H H H H I (foam).sup.b1382 4-F-Ph 2,4-Cl.sub.2 -Ph H H H H I1383 2-Cl-Ph Ph H H H H I1384 2-Cl-Ph 2-F-Ph H H H H I1385 2-Cl-Ph 4-F-Ph H H H H I1386 2-Cl-Ph 2-Cl-Ph H H H H I1387 2-Cl-Ph 4-Cl-Ph H H H H I1388 2-Cl-Ph 2,4-F.sub.2 -Ph H H H H I1389 2-Cl-Ph 2,4-Cl.sub.2 -Ph H H H H I1390 3-Cl-Ph Ph H H H H I1391 3-Cl-Ph 2-F-Ph H H H H I1392 3-Cl-Ph 4-F-Ph H H H H I1393 3-Cl-Ph 2-Cl-Ph H H H H I1394 3-Cl-Ph 4-Cl-Ph H H H H I1395 3-Cl-Ph 2,4-F.sub.2 -Ph H H H H I1396 3-Cl-Ph 2,4-Cl.sub.2 -Ph H H H H I1397 4-Cl-Ph Ph H H H H I1398 4-Cl-Ph 2-F-Ph H H H H I1399 4-Cl-Ph 4-F-Ph H H H H I1400 4-Cl-Ph 2-Cl-Ph H H H H I1401 4-Cl-Ph 4-Cl-Ph H H H H I1402 4-Cl-Ph 2,4-F.sub.2 -Ph H H H H I1403 4-Cl-Ph 2,4-Cl.sub.2 -Ph H H H H I1404 2-CF.sub.3 -Ph Ph H H H H I1405 2-CF.sub.3 -Ph 2-F-Ph H H H H I1406 2-CF.sub.3 -Ph 4-F-Ph H H H H I1407 2-CF.sub.3 -Ph 2-Cl-Ph H H H H I1408 2-CF.sub.3 -Ph 4-Cl-Ph H H H H I1409 2-CF.sub.3 -Ph 2,4-F.sub.2 -Ph H H H H I1410 2-CF.sub.3 -Ph 2,4-Cl.sub.2 -Ph H H H H I1411 4-CF.sub.3 -Ph Ph H H H H I1412 4-CF.sub.3 -Ph 2-F-Ph H H H H I1413 4-CF.sub.3 -Ph 4-F-Ph H H H H I1414 4-CF.sub.3 -Ph 2-Cl-Ph H H H H I1415 4-CF.sub.3 -Ph 4-Cl-Ph H H H H I1416 4-CF.sub.3 -Ph 2,4-F.sub.2 -Ph H H H H I1417 4-CF.sub.3 -Ph 2,4-Cl.sub.2 -Ph H H H H I1418 2,4-F.sub.2 -Ph Ph H H H H I1419 2,4-F.sub.2 -Ph 2-F-Ph H H H H I1420 2,4-F.sub.2 -Ph 4-F-Ph H H H H I1421 2,4-F.sub.2 -Ph 2-Cl-Ph H H H H I1422 2,4-F.sub.2 -Ph 4-Cl-Ph H H H H I1423 2,4-F.sub.2 -Ph 2,4-F.sub.2 -Ph H H H H I1424 2,4-F.sub.2 -Ph 2,4-Cl.sub.2 -Ph H H H H I1425 2,4-Cl.sub.2 -Ph Ph H H H H I1426 2,4-Cl.sub.2 -Ph 2-F-Ph H H H H I1427 2,4-Cl.sub.2 -Ph 4-F-Ph H H H H I1428 2,4-Cl.sub.2 -Ph 2-Cl-Ph H H H H I1429 2,4-Cl.sub.2 -Ph 4-Cl-Ph H H H H I1430 2,4-Cl.sub.2 -Ph 2,4-F.sub.2 -Ph H H H H I1431 2,4-Cl.sub.2 -Ph 2,4-Cl.sub.2 -Ph H H H H I1432 Ph 2,4-F.sub.2 -Ph H H H H SS1433 4-F-Ph 2-F-Ph H H H H SS1434 4-F-Ph 2,4-F.sub.2 -Ph H H H H SS1435 Ph 2,4-F.sub.2 -Ph H H H H SSCH.sub.31436 4-F-Ph 2-F-Ph H H H H SSCH.sub.31437 4-F-Ph 2,4-F.sub.2 -Ph H H H H SSCH.sub.31438 Ph 2,4-F.sub.2 -Ph H H H H ##STR43##1439 4-F-Ph 2-F-Ph H H H H ##STR44##1440 4-F-Ph 2,4-F.sub.2 -Ph H H H H ##STR45##1441 Ph 2,4-F.sub.2 -Ph H H H H ##STR46##1442 4-F-Ph 2-F-Ph H H H H ##STR47##1443 4-F-Ph 2,4-F.sub.2 -Ph H H H H ##STR48##1444 Ph 2,4-F.sub.2 -Ph H H H H Cl1445 4-F-Ph 2-F-Ph H H H H Cl1446 4-F-Ph 2,4-F.sub.2 -Ph H H H H Cl1447 Ph 2,4-F.sub.2 -Ph H H H H CHO1448 4-F-Ph 2-F-Ph H H H H CHO1449 4-F-Ph 2,4-F.sub.2 -Ph H H H H CHO1450 Ph 2,4-F.sub.2 -Ph H H H H SCH.sub.2 CN1451 4-F-Ph 2-F-Ph H H H H SCH.sub.2 CN oil.sup.c1452 4-F-Ph 2,4-F.sub.2 -Ph H H H H SCH.sub.2 CN1453 Ph 2,4-F.sub.2 -Ph H H H H SCH.sub.2 SCN1454 4-F-Ph 2-F-Ph H H H H SCH.sub.2 SCN1455 4-F-Ph 2,4-F.sub.2 -Ph H H H H SCH.sub.2 SCN1456 Ph 2,4-F.sub.2 -Ph H H H H SCCl.sub.31457 4-F-Ph 2-F-Ph H H H H SCCl.sub.31458 4-F-Ph 2,4-F.sub.2 -Ph H H H H SCCl.sub.31459 Ph 4-F-Ph H H H H S- .sub.- n-Bu semi-solid.sup.d1460 4-F-Ph 2-F-Ph H H H H F1461 4-F-Ph 2-F-Ph H H H H Br1462 4-F-Ph 2-F-Ph H H H H ##STR49##1463 4-F-Ph 2-F-Ph H H H H ##STR50##1464 4-F-Ph 2-F-Ph H H H H ##STR51##1465 4-F-Ph 2-F-Ph H H H H ##STR52##1466 4-F-Ph 2-F-Ph H H H H SCF.sub.2 H1467 4-F-Ph 2-F-Ph H H H H SCF.sub.2 CF.sub.2 H1468* 4-F-Ph 2-F-Ph H H H H ##STR53## (oil).sup.e1469* 4-F-Ph 2-F-Ph H H H H ##STR54## (oil).sup.f1470 4-F-Ph 2-F-Ph H H H H ##STR55##1471 4-F-Ph 2-F-Ph H H H H ##STR56##1472 4-F-Ph 2-F-Ph H H H H ##STR57##1473 4-F-Ph 2-F-Ph H H H H ##STR58##1474 4-F-Ph 2-F-Ph H H H H ##STR59##1475 4-F-Ph 2-F-Ph H H H H ##STR60##1476 4-F-Ph 2-F-Ph H H H H ##STR61##1477 4-F-Ph 2-F-Ph H H H H ##STR62##1478 4-F-Ph 2-F-Ph H H H H ##STR63##1479 4-F-Ph 2-F-Ph H H H H ##STR64##1480 4-F-Ph 2-F-Ph H H H H ##STR65##1481 4-F-Ph 2-F-Ph H H H H ##STR66##1482 4-F-Ph 2-F-Ph H H H H ##STR67##1483 4-F-Ph 2-F-Ph H H H H SCN1484 4-F-Ph 2-F-Ph H H H H SSCH.sub.2 Ph1485 4-F-Ph 2-F-Ph H H H H SS-allyl1486 4-F-Ph 2-F-Ph H H H H SSPh__________________________________________________________________________ *All compounds in this table are compounds in which E is a bond except 1468 and 1469 in which E is an oxygen atom. .sup.a NMR: (CDCl.sub.3) .delta. 4.9(s, 2H); 5.1(s, 1H); 5.2(s, 1H); 5.3(s, 1H); 6.7(m, 2H); 6.9(m, 2H); 7.2(m, 2H); 7.5(m, 1H); 7.6(s, 1H); 12.2(brs, 1H). .sup.b NMR: (CDCl.sub.3) .delta. 4.7(ABq, 2H); 5.3(s, 2H); 5.8(s, 1H); 6.7(m, 2H); 6.9(m, 2H); 7.3(m, 2H); 7.5(m, 1H); 7.8(s, 1H). .sup.c NMR: (CDCl.sub.3) .delta. 3.8(ABq, 2H); 4.7(ABq, 2H); 5.2(s, 1H); 5.3(two s, 2H); 6.9-7.2(m, 4H); 7.2-7.4(m, 3H); 7.5(m, 1H); 7.8(s, 1H). .sup.d NMR: (CDCl.sub.3) .delta. 0.92(t, 3H); 1.4-1.7(m, 4H); 3.1(t, 2H); 4.5(ABq, 2H); 5.4(two s, 2H); 5.8(s, 1H); 7.0(m, 4H); 7.2(m, 3H); 7.5(m, 2H); 7.8(s, 1H). .sup.e NMR: (CDCl.sub.3) .delta. 2.7-3.5(m, 2H); 4.3(s, 1H); 4.4(m, 2H); 5.2(m, 2H); 6.8-7.4(m, 8H), 7.9(m, 1H). .sup.f NMR: (CDCl.sub.3) .delta. 2.7-3.4(m, 2H); 4.2(d, 1H); 4.5(ABq, 2H) 5.3(m, 2H); 6.8-7.4(m, 8H); 7.9(d, 1H).
EXAMPLE 1487
Preparation of 2,3-bis(4-fluorophenyl)-1-(1H-1,2,4-triazol-1-yl)-3,4-epoxy-2-butanol
2,3-Bis(4-fluorophenyl)-1-(1H-1,2,4-triazol-1-yl)-3-butene-2-ol (1.0 g) was dissolved in 50 ml of anhydrous benzene and stirred under nitrogen. To this solution was added 0.012 g of vanadium acetonylacetonate. The solution was then refluxed and tert-butyl hydroperoxide (0.44 g dissolved in 5 ml of anhydrous benzene) was added dropwise over 10 minutes. The reaction was refluxed for one additional hour and then cooled to ambient temperature. The benzene was removed in vacuo and the residue chromatographed on silica gel (2% MeOH/CH.sub.2 Cl.sub.2). This yielded a total of 650 mg of diastereomeric products in a 3:1 ratio. Further chromatography resulted in the separation of the diastereomers. The major isomer was a waxy white solid. NMR (CDCl.sub.3 /TMS).delta.2.60 (d, J=6 Hz, 1H); 3.48 (d, J=6 Hz, 1H); 4.70 (q, J=7 Hz, 2H), 5.25 (s, 1H); 6.8-7.3 (m, 8H); 7.55 (s, 1H); 7.90 (s, 1H).
The minor isomer was an amorphous white solid. NMR (CDCl.sub.3 /TMS).delta.2.55 (d, J=6H, 1H); 2.75 (d, J=6 Hz, 1H); 4.80 (q, J=7 Hz); 5.0 (s, 1H); 6.85-7.10 (m, 4H); 7.15-7.45 (m, 4H); 7.80 (s, 1H); 8.05 (s, 1H).
The epoxides shown in Table 4 were prepared or can be prepared by the method described in Example 1487.
TABLE 4__________________________________________________________________________ ##STR68##Ex. No. A B n R R.sup.1 R.sup.2 R.sup.3 R.sup.4 M.P.__________________________________________________________________________ .degree.C.1487 4-F-Ph 4-F-Ph 0 H H H H H 53-551488 4-F-Ph 2,4-Cl.sub.2 -Ph 0 H H H H H1489 4-F-Ph 4-Cl-Ph 0 H H H H H1490 4-F-Ph 2,4-F.sub.2 -Ph 0 H H H H H (semi-solid).sup.a1491 4-F-Ph 4-CF.sub.3 -Ph 0 H H H H H1492 4-F-Ph 2-F-Ph 0 H H H H H (110-119)1493 4-F-Ph 2-Cl-Ph 0 H H H H H1494 4-F-Ph -n-C.sub.4 F.sub.9 0 H H H H H1495 3-F-Ph 4-F-Ph 0 H H H H H1496 3-F-Ph 2,4-Cl.sub.2 -Ph 0 H H H H H1497 3-F-Ph 4-Cl-Ph 0 H H H H H1498 3-F-Ph 2,4-F.sub.2 -Ph 0 H H H H H1499 3-F-Ph 4-CF.sub.3 -Ph 0 H H H H H1500 3-F-Ph 2-F-Ph 0 H H H H H1501 3-F-Ph 2-Cl-Ph 0 H H H H H1502 3-F-Ph -n-C.sub.4 F.sub.9 0 H H H H H1503 4-Cl-Ph 4-F-Ph 0 H H H H H1504 4-Cl-Ph 2,4-Cl.sub.2 -Ph 0 H H H H H1505 4-Cl-Ph 4-Cl-Ph 0 H H H H H1506 4-Cl-Ph 2,4-F.sub.2 -Ph 0 H H H H H1507 4-Cl-Ph 4-CF.sub.3 -Ph 0 H H H H H1508 4-Cl-Ph 2-F-Ph 0 H H H H H1509 4-Cl-Ph 2-Cl-Ph 0 H H H H H1510 4-Cl-Ph -n-C.sub.4 F.sub.9 0 H H H H H1511 2-Cl-Ph 4-F-Ph 0 H H H H H1512 2-Cl-Ph 2,4-Cl.sub.2 -Ph 0 H H H H H1513 2-Cl-Ph 4-Cl-Ph 0 H H H H H 149-150 Low R.sub.f isomer 141-143 High R.sub.f isomer1514 2-Cl-Ph 2,4-F.sub.2 -Ph 0 H H H H H 138-140 Isomer A 152-156 Isomer B1515 2-Cl-Ph 4-CF.sub.3 -Ph 0 H H H H H1516 2-Cl-Ph 2-F-Ph 0 H H H H H1517 2-Cl-Ph 2-Cl-Ph 0 H H H H H1518 2-Cl-Ph -n-C.sub.4 F.sub.9 0 H H H H H1519 3-Cl-Ph 4-F-Ph 0 H H H H H1520 3-Cl-Ph 2,4-Cl.sub.2 -Ph 0 H H H H H1521 3-Cl-Ph 4-Cl-Ph 0 H H H H H1522 3-Cl-Ph 2,4-F.sub.2 -Ph 0 H H H H H1523 3-Cl-Ph 4-CF.sub.3 -Ph 0 H H H H H1524 3-Cl-Ph 2-F-Ph 0 H H H H H1525 3-Cl-Ph 2-Cl-Ph 0 H H H H H1526 3-Cl-Ph -n-C.sub.4 F.sub.9 0 H H H H H1527 Ph 4-F-Ph 0 H H H H H 88-941528 Ph 2,4-Cl.sub.2 -Ph 0 H H H H H1529 Ph 4-Cl-Ph 0 H H H H H 156-1581530 Ph 2,4-F.sub.2 -Ph 0 H H H H H 87-90 Low R.sub.f isomer 148-150 High R.sub.f isomer1531 Ph 4-CF.sub.3 -Ph 0 H H H H H1532 Ph 2-F-Ph 0 H H H H H1533 Ph 2-Cl-Ph 0 H H H H H1534 Ph -n-C.sub.4 F.sub.9 0 H H H H H1535 4-CF.sub.3 -Ph 4-F-Ph 0 H H H H H1536 4-CF.sub.3 -Ph 2,4-Cl.sub.2 -Ph 0 H H H H H1537 4-CF.sub.3 -Ph 4-Cl-Ph 0 H H H H H1538 4-CF.sub.3 -Ph 2,4-F.sub.2 -Ph 0 H H H H H1539 4-CF.sub.3 -Ph 4-CF.sub.3 -Ph 0 H H H H H1540 4-CF.sub.3 -Ph 2-F-Ph 0 H H H H H1541 4-CF.sub.3 -Ph 2-Cl-Ph 0 H H H H H1542 4-CF.sub.3 -Ph -n-C.sub.4 F.sub.9 0 H H H H H1543 4-Br-Ph 4-F-Ph 0 H H H H H1544 4-Br-Ph 2,4-Cl.sub.2 -Ph 0 H H H H H1545 4-Br-Ph 4-Cl-Ph 0 H H H H H1546 4-Br-Ph 2,4-F.sub.2 -Ph 0 H H H H H1547 4-Br-Ph 4-CF.sub.3 -Ph 0 H H H H H1548 4-Br-Ph 2-F-Ph 0 H H H H H1549 4-Br-Ph 2-Cl-Ph 0 H H H H H1550 4-Br-Ph -n-C.sub.4 F.sub.9 0 H H H H H1551 2,4-Cl.sub.2 -Ph 4-F-Ph 0 H H H H H1552 2,4-Cl.sub.2 -Ph 2,4-Cl.sub.2 -Ph 0 H H H H H1553 2,4-Cl.sub.2 -Ph 4-Cl-Ph 0 H H H H H1554 2,4-Cl.sub.2 -Ph 2,4-F.sub.2 -Ph 0 H H H H H1555 2,4-Cl.sub.2 -Ph 4-CF.sub.3 -Ph 0 H H H H H1556 2,4-Cl.sub.2 -Ph 2-F-Ph 0 H H H H H1557 2,4-Cl.sub.2 -Ph 2-Cl-Ph 0 H H H H H1558 2,4-Cl.sub.2 -Ph -n-C.sub.4 F.sub.9 0 H H H H H1559 2-F-Ph 4-F-Ph 0 H H H H H1560 2-F-Ph 2,4-Cl.sub.2 -Ph 0 H H H H H1561 2-F-Ph 4-Cl-Ph 0 H H H H H1562 2-F-Ph 2,4-F.sub.2 -Ph 0 H H H H H1563 2-F-Ph 4-CF.sub.3 -Ph 0 H H H H H1564 2-F-Ph 2-F-Ph 0 H H H H H1565 2-F-Ph 2-Cl-Ph 0 H H H H H1566 2-F-Ph -n-C.sub.4 F.sub.9 0 H H H H H1567 2,4-F.sub.2 -Ph 4-F-Ph 0 H H H H H1568 2,4-F.sub.2 -Ph 2,4-Cl.sub.2 Ph 0 H H H H H1569 2,4-F.sub.2 -Ph 4-Cl-Ph 0 H H H H H1570 2,4-F.sub.2 -Ph 2,4-F.sub.2 -Ph 0 H H H H H1571 2,4-F.sub.2 -Ph 4-CF.sub.3 -Ph 0 H H H H H1572 2,4-F.sub.2 -Ph 2-F-Ph 0 H H H H H1573 2,4-F.sub.2 -Ph 2-Cl-Ph 0 H H H H H1574 2,4-F.sub.2 -Ph -n-C.sub.4 F.sub.9 0 H H H H H1575 Ph 4-F-Ph 0 H CH.sub.3 H H H1576 Ph 4-F-Ph 0 (CH.sub.2).sub.2 H H H1577 Ph 4-F-Ph 0 CH.sub.3 CH.sub.3 H H H1578 4-F-Ph 4-F-Ph 0 H CH.sub.3 H H H1579 4-F-Ph 4-F-Ph 0 (CH.sub.2).sub.2 H H H1580 4-F-Ph 4-F-Ph 0 CH.sub.3 CH.sub.3 H H H1581 4-Cl-Ph 2,4-Cl.sub.2 -Ph 0 H CH.sub.3 H H H1582 4-Cl-Ph 2,4-Cl.sub.2 -Ph 0 (CH.sub.2).sub.2 H H H1583 4-Cl-Ph 2,4-Cl.sub.2 -Ph 0 CH.sub.3 CH.sub.3 H H H1584 2-Cl-Ph 4-Cl-Ph 0 H CH.sub.3 H H H1585 2-Cl-Ph 4-Cl-Ph 0 (CH.sub.2).sub.2 H H H1586 2-Cl-Ph 4-Cl-Ph 0 CH.sub.3 CH.sub.3 H H H1587 4-F-Ph 4-F-Ph 0 H C.sub.2 H.sub.5 H H H1588 4-F-Ph 4-F-Ph 0 H .sub.-i-C.sub.3 H.sub.7 H H H1589 4-F-Ph 4-F-Ph 0 H -n-C.sub.4 H.sub.9 H H H1590 4-F-Ph 4-F-Ph 0 H Ph H H H1591 4-F-Ph 4-F-Ph 0 H .sub.-t-C.sub.4 H.sub.9 H H H1592 4-F-Ph 4-F-Ph 0 H Ph H H H1593 4-F-Ph 4-F-Ph 0 CH.sub.3 .sub.-t-C.sub.4 H.sub.9 H H H1594 4-F-Ph 4-F-Ph 0 CH.sub.3 Ph H H H1595 4-F-Ph 4-F-Ph 0 (CH.sub.2).sub.3 H H H1596 4-F-Ph 4-F-Ph 0 (CH.sub.2).sub.4 H H H1597 4-F-Ph 4-F-Ph 0 (CH.sub.2).sub.5 H H H1598 4-F-Ph 4-F-Ph 0 (CH.sub.2).sub.6 H H H1599 4-CH.sub.3 -Ph 4-F-Ph 0 H CH.sub.3 H H H1600 4-F-Ph 4-F-Ph 1 H CH.sub.3 H H H1601 4-Cl-Ph 4-F-Ph 4 H CH.sub.3 H H H1602 -n-C.sub.4 F.sub.9 4-F-Ph 0 H CH.sub.3 H H H1603 (CH.sub.3).sub.2 N 4-F-Ph 1 H CH.sub.3 H H H1604 5-Cl-2-thienyl 4-F-Ph 0 H CH.sub.3 H H H1605 2-Cl-3-thienyl 4-F-Ph 0 H CH.sub.3 H H H1606 1-imidazoyl 4-F-Ph 0 H CH.sub.3 H H H1607 4-F-Ph 4-F-Ph 0 H H CH.sub.3 H H1608 4-F-Ph 4-F-Ph 0 H H CH.sub.2 CHCH.sub.2 H H1609 4-F-Ph 4-F-Ph 0 H H COCH.sub.3 H H1610 4-F-Ph 4-F-Ph 0 H H CO.sub.2 CH.sub.3 H H1611 4-CF.sub.3 O-Ph 4-F-Ph 0 H H H H H1612 2-Cl-Ph 4-Cl-Ph 0 H H CH.sub.3 H H1613 2-Cl-Ph 4-Cl-Ph 0 H H CH.sub.2 CHCH.sub.2 H H1614 2-Cl-Ph 4-Cl-Ph 0 H H COCH.sub.3 H H1615 2-Cl-Ph 4-Cl-Ph 0 H H CO.sub.2 CH.sub.3 H H1616 4-Cl-Ph 2,4-Cl.sub.2 -Ph 0 H H CH.sub.3 H H1617 4-Cl-Ph 2,4-Cl.sub.2 -Ph 0 H H CH.sub.2 CHCH.sub.2 H H1618 4-Cl-Ph 2,4-Cl.sub.2 -Ph 0 H H COCH.sub.3 H H1619 4-Cl-Ph 2,4-Cl.sub.2 -Ph 0 H H CO.sub.2 CH.sub.3 H H1620 Ph 4-F-Ph 0 H H CH.sub.3 H H1621 Ph 4-F-Ph 0 H H CH.sub.2 CHCH.sub.2 H H1622 Ph 4-F-Ph 0 H H COCH.sub.3 H H1623 Ph 4-F-Ph 0 H H CO.sub.2 CH.sub.3 H H1624 OH 2,4-Cl.sub.2 -Ph 2 H H H H H1625 OH 2,4-Cl.sub.2 -Ph 3 H H H H H1626 OH 2,4-Cl.sub.2 -Ph 4 H H H H H1627 1-imidazoyl 2,4-Cl.sub.2 -Ph 1 H H H H H1628 1-imidazoyl 2,4-Cl.sub.2 -Ph 2 H H H H H1629 1-imidazoyl 4-F-Ph 3 H H H H H1630 1-imidazoyl 4-F-Ph 4 H H H H H1631 1H-1,2,4-triazoyl-1-yl 4-F-Ph 1 H H H H H1632 1H-1,2,4-triazoyl-1-yl 4-F-Ph 2 H H H H H1633 1H-1,2,4-triazoyl-1-yl 4-F-Ph 3 H H H H H1634 1H-1,2,4-triazoyl-1-yl 4-F-Ph 4 H H H H H1635 1H-1,2,4-triazoyl-1-yl 2,4-Cl.sub.2 -Ph 1 H H H H H1636 Ph 2,5-F.sub.2 -Ph 0 H H H H H1637 Ph 3-F-Ph 0 H H H H H1638 Ph 2,5-Cl.sub.2 -Ph 0 H H H H H1639 Ph 3-Cl-Ph 0 H H H H H1640 Ph 4-Br-Ph 0 H H H H H1641 Ph 4-I-Ph 0 H H H H H1642 Ph 3,4-F.sub.2 -Ph 0 H H H H H1643 Ph 3,4-Cl.sub.2 -Ph 0 H H H H H1644 Ph 2,6-Cl.sub.2 -Ph 0 H H H H H1645 Ph 2-Cl-(4-F)-Ph 0 H H H H H1646 Ph 2,4,6-Cl.sub.3 -Ph 0 H H H H H1647 Ph 2-F-(4-Cl)-Ph 0 H H H H H1648 Ph Ph 0 H H H H H1649 Ph 4-CH.sub.3 -Ph 0 H H H H H1650 Ph 3-CH.sub.3 -Ph 0 H H H H H1651 Ph 2-CH.sub.3 -Ph 0 H H H H H1652 Ph 2-CF.sub.3 -Ph 0 H H H H H1653 Ph 3-CF.sub.3 -Ph 0 H H H H H1654 Ph 2-F-(4-CF.sub.3)-Ph 0 H H H H H1655 Ph 4-CH.sub.3 O-Ph 0 H H H H H1656 Ph 5-Cl-2-pyridyl 0 H H H H H1657 Ph 5-Cl-2-thienyl 0 H H H H H1658 Ph 2-Cl-3-thienyl 0 H H H H H1659 Ph .sub.-s-C.sub.4 H.sub.9 0 H H H H H1660 2-Cl-Ph 2,5-F.sub.2 -Ph 0 H H H H H1661 2-Cl-Ph 3-F-Ph 0 H H H H H1662 2-Cl-Ph 2,5-Cl.sub.2 -Ph 0 H H H H H1663 2-Cl-Ph 3-Cl-Ph 0 H H H H H1664 2-Cl-Ph 4-Br-Ph 0 H H H H H1665 2-Cl-Ph 4-I-Ph 0 H H H H H1666 2-Cl-Ph 3,4-F.sub.2 -Ph 0 H H H H H1667 2-Cl-Ph 3,4-Cl.sub.2 -Ph 0 H H H H H1668 2-Cl-Ph 2,6-Cl.sub.2 -Ph 0 H H H H H1669 2-Cl-Ph 2-Cl-(4-F)-Ph 0 H H H H H1670 2-Cl-Ph 2,4,6-Cl.sub.3 -Ph 0 H H H H H1671 2-Cl-Ph 2-F-(4-Cl)-Ph 0 H H H H H1672 2-Cl-Ph Ph 0 H H H H H1673 2-Cl-Ph 4-CH.sub.3 -Ph 0 H H H H H1674 2-Cl-Ph 3-CH.sub.3 -Ph 0 H H H H H1675 2-Cl-Ph 2-CH.sub.3 -Ph 0 H H H H H1676 2-Cl-Ph 2-CF.sub.3 -Ph 0 H H H H H1677 2-Cl-Ph 3-CF.sub.3 -Ph 0 H H H H H1678 2-Cl-Ph 2-F-(4-CF.sub.3)-Ph 0 H H H H H1679 2-Cl-Ph 4-CH.sub.3 O-Ph 0 H H H H H1680 2-Cl-Ph 5-Cl-2-pyridyl 0 H H H H H1681 2-Cl-Ph 5-Cl-2-thienyl 0 H H H H H1682 2-Cl-Ph 2-Cl-3-thienyl 0 H H H H H1683 3-Cl-Ph 2,5-F.sub.2 -Ph 0 H H H H H1684 3-Cl-Ph 2,5-Cl.sub.2 -Ph 0 H H H H H1685 4-F-Ph 2,5-F.sub.2 -Ph 0 H H H H H1686 4-F-Ph 3-F-Ph 0 H H H H H1687 4-F-Ph 2,5-Cl.sub.2 -Ph 0 H H H H H1688 4-F-Ph 3-Cl-Ph 0 H H H H H1689 4-F-Ph 4-Br-Ph 0 H H H H H1690 4-F-Ph 4-I-Ph 0 H H H H H1691 4-F-Ph 3,4-F.sub.2 -Ph 0 H H H H H1692 4-F-Ph 3,4-Cl.sub.2 -Ph 0 H H H H H1693 4-F-Ph 2,6-Cl.sub.2 -Ph 0 H H H H H1694 4-F-Ph 2-Cl-(4-F)-Ph 0 H H H H H1695 4-F-Ph 2,4,6-Cl.sub.3 -Ph 0 H H H H H1696 4-F-Ph 2-F-(4-Cl)-Ph 0 H H H H H1697 4-F-Ph Ph 0 H H H H H1698 4-F-Ph 4-CH.sub.3 -Ph 0 H H H H H1699 4-F-Ph 3-CH.sub.3 -Ph 0 H H H H H1700 4-F-Ph 2-CH.sub.3 -Ph 0 H H H H H1701 4-F-Ph 2-CF.sub.3 -Ph 0 H H H H H1702 4-F-Ph 3-CF.sub.3 -Ph 0 H H H H H1703 4-F-Ph 2-F-(4-CF.sub.3)-Ph 0 H H H H H1704 4-F-Ph 4-CH.sub.3 O-Ph 0 H H H H H1705 4-F-Ph 5-Cl-2-prridyl 0 H H H H H1706 4-F-Ph 2-Cl-3-thienyl 0 H H H H H1707 4-F-Ph 5-Cl-2-thienyl 0 H H H H H1708 3-F-Ph 2,5-Cl.sub.2 -Ph 0 H H H H H1709 3-F-Ph 2,5-F.sub.2 -Ph 0 H H H H H1710 4-Cl-Ph 2,5-F.sub.2 -Ph 0 H H H H H1711 4-Cl-Ph 3-F-Ph 0 H H H H H1712 4-Cl-Ph 2,5-Cl.sub.2 -Ph 0 H H H H H1713 4-Cl-Ph 3-Cl-Ph 0 H H H H H1714 4-Cl-Ph 4-Br-Ph 0 H H H H H1715 4-Cl-Ph 4-I-Ph 0 H H H H H1716 4-Cl-Ph 3,4-F.sub.2 -Ph 0 H H H H H1717 4-Cl-Ph 3,4-Cl.sub.2 -Ph 0 H H H H H1718 4-Cl-Ph 2,6-Cl.sub.2 -Ph 0 H H H H H1719 4-Cl-Ph 2-Cl-(4-F)-Ph 0 H H H H H1720 4-Cl-Ph 2,4,6-Cl.sub.3 -Ph 0 H H H H H1721 4-Cl-Ph 2-F-(4-Cl)-Ph 0 H H H H H1722 4-Cl-Ph Ph 0 H H H H H1723 4-Cl-Ph 4-CH.sub.3 -Ph 0 H H H H H1724 4-Cl-Ph 3-CH.sub.3 -Ph 0 H H H H H1725 4-Cl-Ph 2-CH.sub.3 -Ph 0 H H H H H1726 4-Cl-Ph 2-CF.sub.3 -Ph 0 H H H H H1727 4-Cl-Ph 3-CF.sub.3 -Ph 0 H H H H H1728 4-Cl-Ph 2-F-(4-CF.sub.3)-Ph 0 H H H H H1729 4-Cl-Ph 4-CH.sub.3 O-Ph 0 H H H H H1730 4-Cl-Ph 5-Cl-2-pyridyl 0 H H H H H1731 4-Cl-Ph 5-Cl-2-thienyl 0 H H H H H1732 4-Cl-Ph 2-Cl-3-thienyl 0 H H H H H1733 4-Cl-Ph ##STR69## 0 H H H H H1734 4-Cl-Ph .sub.-t-butyl 0 H H H H H1735 4-Cl-Ph -n-hexyl 0 H H H H H1736 4-Cl-Ph - n-heptyl 0 H H H H H1737 4-Cl-Ph -n-octyl 0 H H H H H1738 4-Cl-Ph C.sub.8 F.sub.17 0 H H H H H1739 4-Cl-Ph C.sub.6 F.sub.13 0 H H H H H1740 4-Cl-Ph 4-pyridyl 0 H H H H H1741 4-Cl-Ph 2-pyridyl 0 H H H H H1742 4-Cl-Ph 2-thienyl 0 H H H H H1743 4-Cl-Ph 4- -n-Bu-Ph 0 H H H H H1744 4-Cl-Ph 4- -n-BuO-Ph 0 H H H H H1745 4-Cl-Ph 5-CF.sub.3 -2-pyridyl 0 H H H H H1746 4-Cl-Ph 5-CH.sub.3 SO.sub.2 -2-thienyl 0 H H H H H1747 4-C.sub.2 H.sub.5 -Ph 4-F-Ph 0 H H H H H1748 4-( -n-BuO)-Ph 4-F-Ph 0 H H H H H1749 2-CH.sub.3 SO.sub.2 -imidazol-1-yl 4-F-Ph 0 H H H H H1750 5-CH.sub.3 S-1,2,4-triazol-1-yl 4-F-Ph 0 H H H H H1751 C.sub.6 F.sub.13 4-F-Ph 0 H H H H H1752 C.sub.8 F.sub.17 4-F-Ph 0 H H H H H1753 3-CH.sub.3 O-Ph 4-F-Ph 0 H H H H H1754 2-CF.sub.3 -imidazol-1-yl 4-F-Ph 0 H H H H H1755 4-( .sub.-i-C.sub.3 H.sub.7 O)-Ph 4-F-Ph 0 H H H H H1756 4-I-Ph 4-F-Ph 0 H H H H H1757 3,4-F.sub.2 -Ph 4-F-Ph 0 H H H H H1758 3,4-Cl.sub.2 -Ph 4-F-Ph 0 H H H H H1759 2,6-Cl.sub.2 -Ph 4-F-Ph 0 H H H H H1760 2-Cl-(4-F)-Ph 4-F-Ph 0 H H H H H1761 2,4,6-Cl.sub.3 -Ph 4-F-Ph 0 H H H H H1762 4-CH.sub.3 -Ph 4-F-Ph 0 H H H H H1763 3-CH.sub.3 -Ph 4-F-Ph 0 H H H H H1764 2-CH.sub.3 -Ph 4-F-Ph 0 H H H H H1765 2-CF.sub.3 -Ph 4-F-Ph 0 H H H H H1766 3-CF.sub.3 -Ph 4-F-Ph 0 H H H H H1767 4-CH.sub.3 O-Ph 4-F-Ph 0 H H H H H1768 2,3-Cl.sub.2 -Ph 4-F-Ph 0 H H H H H1769 3,5-Cl.sub.2 -Ph 4-F-Ph 0 H H H H H1770 2,5-Cl.sub.2 -Ph 4-F-Ph 0 H H H H H1771 3-Br-Ph 4-F-Ph 0 H H H H H1772 4-C.sub.2 H.sub.5 O-Ph 4-F-Ph 0 H H H H H1773 2,4-(CH.sub.3).sub.2 -Ph 4-F-Ph 0 H H H H H1774 2,4,6-(CH.sub.3).sub.3 -Ph 4-F-Ph 0 H H H H H1775 4-Ph-Ph 4-F-Ph 0 H H H H H1776 5-Cl-2-thienyl 4-F-Ph 0 H H H H H1777 2-Cl-3-thienyl 4-F-Ph 0 H H H H H1778 1-imidazoyl 4-F-Ph 0 H H H H H1779 1H-1,2,4-triazoyl-1-yl 4-F-Ph 0 H H H H H1780 2-pyridyl 4-F-Ph 0 H H H H H1781 5-Cl-2-pyridyl 4-F-Ph 0 H H H H H1782 3-pyridyl 4-F-Ph 0 H H H H H1783 4-pyridyl 4-F-Ph 0 H H H H H1784 -n-C.sub.4 F.sub.9 4-F-Ph 0 H H H H H1785 4-I-Ph 2,4-Cl.sub.2 -Ph 0 H H H H H1786 3,4-F.sub.2 -Ph 2,4-Cl.sub.2 -Ph 0 H H H H H1787 3,4-Cl.sub.2 -Ph 2,4-Cl.sub.2 -Ph 0 H H H H H1788 2,6-Cl.sub.2 -Ph 2,4-Cl.sub.2 -Ph 0 H H H H H1789 2-Cl-(4-F)-Ph 2,4-Cl.sub.2 -Ph 0 H H H H H1790 2,4,6-Cl.sub.3 -Ph 2,4-Cl.sub.2 -Ph 0 H H H H H1791 4-CH.sub.3 -Ph 2,4-Cl.sub.2 -Ph 0 H H H H H1792 3-CH.sub.3 -Ph 2,4-Cl.sub.2 -Ph 0 H H H H H1793 2-CH.sub.3 -Ph 2,4-Cl.sub.2 -Ph 0 H H H H H1794 2-CF.sub.3 -Ph 2,4-Cl.sub.2 -Ph 0 H H H H H1795 3-CF.sub.3 -Ph 2,4-Cl.sub.2 -Ph 0 H H H H H1796 4-CH.sub.3 O-Ph 2,4-Cl.sub.2 -Ph 0 H H H H H1797 2,3-Cl.sub.2 -Ph 2,4-Cl.sub.2 -Ph 0 H H H H H1798 3,5-Cl.sub.2 -Ph 2,4-Cl.sub.2 -Ph 0 H H H H H1799 2,5-Cl.sub.2 -Ph 2,4-Cl.sub.2 -Ph 0 H H H H H1800 3-Br-Ph 2,4-Cl.sub.2 -Ph 0 H H H H H1801 4-C.sub.2 H.sub.5 O-Ph 2,4-Cl.sub.2 -Ph 0 H H H H H1802 2,4-(CH.sub.3).sub.2 -Ph 2,4-Cl.sub.2 -Ph 0 H H H H H1803 2,4,6-(CH.sub.3).sub.3 -Ph 2,4-Cl.sub.2 -Ph 0 H H H H H1804 4-Ph-Ph 2,4-Cl.sub.2 -Ph 0 H H H H H1805 5-Cl-2-thienyl 2,4-Cl.sub.2 -Ph 0 H H H H H1806 2-Cl-3-thienyl 2,4-Cl.sub.2 -Ph 0 H H H H H1807 1-imidazoyl 2,4-Cl.sub.2 -Ph 0 H H H H H1808 1H-1,2,4-triazoyl-1-yl 2,4-Cl.sub.2 -Ph 0 H H H H H1809 2-pyridyl 2,4-Cl.sub.2 -Ph 0 H H H H H1810 5-Cl-2-pyridyl 2,4-Cl.sub.2 -Ph 0 H H H H H1811 3-pyridyl 2,4-Cl.sub.2 -Ph 0 H H H H H1812 4-pyridyl 2,4-Cl.sub.2 -Ph 0 H H H H H1813 -n-C.sub.4 H.sub.9 2,4-Cl.sub.2 -Ph 0 H H H H H1814 4-I-Ph 4-Cl-Ph 0 H H H H H1815 3,4-F.sub.2 -Ph 4-Cl-Ph 0 H H H H H1816 3,4-Cl.sub.2 -Ph 4-Cl-Ph 0 H H H H H1817 2,6-Cl.sub.2 -Ph 4-Cl-Ph 0 H H H H H1818 2-Cl-(4-F)-Ph 4-Cl-Ph 0 H H H H H1819 2,4,6-Cl.sub.3 -Ph 4-Cl-Ph 0 H H H H H1820 4-CH.sub.3 -Ph 4-Cl-Ph 0 H H H H H1821 3-CH.sub.3 -Ph 4-Cl-Ph 0 H H H H H1822 2-CH.sub.3 -Ph 4-Cl-Ph 0 H H H H H1823 2-CF.sub.3 -Ph 4-Cl-Ph 0 H H H H H1824 3-CF.sub.3 -Ph 4-Cl-Ph 0 H H H H H1825 4-CH.sub.3 O-Ph 4-Cl-Ph 0 H H H H H1826 2,3-Cl.sub.2 -Ph 4-Cl-Ph 0 H H H H H1827 3,5-Cl.sub.2 -Ph 4-Cl-Ph 0 H H H H H1828 2,5-Cl.sub.2 -Ph 4-Cl-Ph 0 H H H H H1829 3-Br-Ph 4-Cl-Ph 0 H H H H H1830 4-EtO-Ph 4-Cl-Ph 0 H H H H H1831 2,4-(CH.sub.3).sub.2 -Ph 4-Cl-Ph 0 H H H H H1832 2,4,6-(CH.sub.3).sub.3 -Ph 4-Cl-Ph 0 H H H H H1833 4-Ph-Ph 4-Cl-Ph 0 H H H H H1834 5-Cl-2-thienyl 4-Cl-Ph 0 H H H H H1835 2-Cl-3-thienyl 4-Cl-Ph 0 H H H H H1836 1-imidazoyl 4-Cl-Ph 0 H H H H H1837 1H-1,2,4-triazoyl-1-yl 4-Cl-Ph 0 H H H H H1838 2-pyridyl 4-Cl-Ph 0 H H H H H1839 5-Cl-2-pyridyl 4-Cl-Ph 0 H H H H H1840 3-pyridyl 4-Cl-Ph 0 H H H H H1841 4-pyridyl 4-Cl-Ph 0 H H H H H1842 - n-C.sub.4 F.sub.9 4-Cl-Ph 0 H H H H H1843 4-I-Ph 2,4-F.sub.2 -Ph 0 H H H H H1844 3,4-F.sub.2 -Ph 2,4-F.sub.2 -Ph 0 H H H H H1845 3,4-Cl.sub.2 -Ph 2,4-F.sub.2 -Ph 0 H H H H H1846 2,6-Cl.sub.2 -Ph 2,4-F.sub.2 -Ph 0 H H H H H1847 2-Cl-(4-F)-Ph 2,4-F.sub.2 -Ph 0 H H H H H1848 2,4,6-Cl.sub.3 -Ph 2,4-F.sub.2 -Ph 0 H H H H H1849 4-CH.sub.3 -Ph 2,4-F.sub.2 -Ph 0 H H H H H1850 3-CH.sub.3 -Ph 2,4-F.sub.2 -Ph 0 H H H H H1851 2-CH.sub.3 -Ph 2,4-F.sub.2 -Ph 0 H H H H H1852 2-CF.sub.3 -Ph 2,4-F.sub.2 -Ph 0 H H H H H1853 3-CF.sub.3 -Ph 2,4-F.sub.2 -Ph 0 H H H H H1854 4-CH.sub.3 O-Ph 2,4-F.sub.2 -Ph 0 H H H H H1855 2,3-Cl.sub.2 -Ph 2,4-F.sub.2 -Ph 0 H H H H H1856 3,5-Cl.sub.2 -Ph 2,4-F.sub.2 -Ph 0 H H H H H1857 2,5-Cl.sub.2 -Ph 2,4-F.sub.2 -Ph 0 H H H H H1858 3-Br-Ph 2,4-F.sub.2 -Ph 0 H H H H H1859 4-C.sub.2 H.sub.5 O-Ph 2,4-F.sub.2 -Ph 0 H H H H H1860 2,4-(CH.sub.3).sub.2 -Ph 2,4-F.sub.2 -Ph 0 H H H H H1861 2,4,6-(CH.sub.3).sub.3 -Ph 2,4-F.sub.2 -Ph 0 H H H H H1862 4-Ph-Ph 2,4-F.sub.2 -Ph 0 H H H H H1863 5-Cl-2-thienyl 2,4-F.sub.2 -Ph 0 H H H H H1864 2-Cl-3-thienyl 2,4-F.sub.2 -Ph 0 H H H H H1865 1-imidazoyl 2,4-F.sub.2 -Ph 0 H H H H H1866 1H-1,2,4-triazoyl-1-yl 2,4-F.sub.2 -Ph 0 H H H H H1867 2-pyridyl 2,4-F.sub.2 -Ph 0 H H H H H1868 5-Cl-2-pyridyl 2,4-F.sub.2 -Ph 0 H H H H H1869 3-pyridyl 2,4-F.sub.2 -Ph 0 H H H H H1870 4-pyridyl 2,4-F.sub.2 -Ph 0 H H H H H1871 -n-C.sub.4 F.sub.9 2,4-F.sub.2 -Ph 0 H H H H H1872 4-F-Ph 4-F-Ph 0 H H H CH.sub.3 H1873 4-F-Ph 4-F-Ph 0 H H H CH.sub.3 CH.sub.31874 4-F-Ph 4-F-Ph 0 H H H F H1875 4-F-Ph 4-F-Ph 0 H H H F CH.sub.31876 4-F-Ph 4-F-Ph 0 H H H F F1877 4-Cl-Ph 2,4-Cl.sub.2 -Ph 0 H H H CH.sub.3 H1878 4-Cl-Ph 2,4-Cl.sub.2 -Ph 0 H H H CH.sub.3 CH.sub.31879 4-Cl-Ph 2,4-Cl.sub.2 -Ph 0 H H H F H1880 4-Cl-Ph 2,4-Cl.sub.2 -Ph 0 H H H F CH.sub.31881 4-Cl-Ph 2,4-Cl.sub.2 -Ph 0 H H H F F1882 2-Cl-Ph 4-Cl-Ph 0 H H H CH.sub.3 H1883 2-Cl-Ph 4-Cl-Ph 0 H H H CH.sub.3 CH.sub.31884 2-Cl-Ph 4-Cl-Ph 0 H H H F H1885 2-Cl-Ph 4-Cl-Ph 0 H H H F CH.sub.31886 2-Cl-Ph 4-Cl-Ph 0 H H H F F1887 Ph 4-F-Ph 0 H H H CH.sub.3 H1888 Ph 4-F-Ph 0 H H H CH.sub.3 CH.sub.31889 Ph 4-F-Ph 0 H H H F H1890 Ph 4-F-Ph 0 H H H F CH.sub.31891 Ph 4-F-Ph 0 H H H F F__________________________________________________________________________ .sup.a NMR: (CDCl.sub.3) .delta. 2.7 (m, 2H), 4.4 (1/2 of ABq, J= 12, 1H) 4.9 (1/2 of ABq, J=12, 1H), 5.0 (br s, 1H), OH), 6.7 (m, 2H), 7.0 (m, 2H) 7.4 (m, 3H), 7.8 (s, 1H), 8.0 (s, 1H).
EXAMPLE 1930
2-(2,4-Difluorophenyl)-3-(2-chlorophenyl)-1-(1H-1,2,4-imidazol-1-yl) -3-buten-2-ol
A mixture of 10.2 g (0.035 mol) of 2-(2,4-difluorophenyl)-2-[1-(2-chlorophenyl)ethenyl]oxirane; 6.20 g (0.091 mol) of imidazole and 12.44 g (0.091 mol) of potassium carbonate in 100 mL of DMSO was heated overnight at 100.degree., then cooled and poured into 800 mL of H.sub.2 O. The aqueous mixture was extracted with 4.times.500 mL Et.sub.2 O, and the organic extracts were washed with water (2.times.) and brine, dried over MgSO.sub.4 and evaporated to give 7.8 g of a yellow-brown solid. Flash chromatography and trituration with Et.sub.2 O gave 4.0 g of a white powder, mp 139.degree.-142.degree.: NMR: (CDCl.sub.3).delta.3.9 (br, OH), 4.2 (1/2 of ABq, 1H), 4.7 (1/2 of ABq, 1H, CH.sub.2 -imidazole), 5.3 (s, 1H, vinyl), 5.5 (s, 1H, vinyl), 6.7 (m, 4H), 7.0-7.5 (m, 6H); IR (nujol) 3400-2600 (br), 1614, 1512, 1501, 1111, 1075, 852, 819, 768, 743, 623 cm.sup.-1.
The compounds shown in Table 4A were prepared or can be prepared by the methods described above.
TABLE 4A__________________________________________________________________________ ##STR70##Ex.No. A B n R R.sup.1 R.sup.2 R.sup.3 R.sup.4 M.P. .degree.C.__________________________________________________________________________1892 Ph Ph 0 H H H H1893 Ph 2-FPh 0 H H H H1894 Ph 4-FPh 0 H H H H (oil).sup.a1895 Ph 2,4-F.sub.2 Ph 0 H H H H 157-1581896 Ph 2-ClPh 0 H H H H1897 Ph 4-ClPh 0 H H H H1898 Ph 2,4-Cl.sub.2 Ph 0 H H H H1899 2-FPh Ph 0 H H H H1900 2-FPh 2-FPh 0 H H H H1901 2-FPh 4-FPh 0 H H H H1902 2-FPh 2,4-F.sub.2 Ph 0 H H H H1903 2-FPh 2-ClPh 0 H H H H1904 2-FPh 4-ClPh 0 H H H H1905 2-FPh 2,4-Cl.sub.2 Ph 0 H H H H1906 3-FPh Ph 0 H H H H1907 3-FPh 2-FPh 0 H H H H1908 3-FPh 4-FPh 0 H H H H1909 3-FPh 2,4-F.sub.2 Ph 0 H H H H1910 3-FPh 2-ClPh 0 H H H H1911 3-FPh 4-ClPh 0 H H H H1912 3-FPh 2,4-Cl.sub.2 Ph 0 H H H H1913 4-FPh Ph 0 H H H H1914 4-FPh 2-FPh 0 H H H H 159-1601915 4-FPh 4-FPh 0 H H H H 175-1771916 4-FPh 2,4-F.sub.2 Ph 0 H H H H 194-1971917 4-FPh 2-ClPh 0 H H H H1918 4-FPh 4-ClPh 0 H H H H1919 4-FPh 2,4-Cl.sub.2 Ph 0 H H H H 200-215 (60% pure)1920 2,4-F.sub.2 Ph Ph 0 H H H H1921 2,4-F.sub.2 Ph 2-FPh 0 H H H H1922 2,4-F.sub.2 Ph 4-FPh 0 H H H H1923 2,4-F.sub.2 Ph 2,4-F.sub.2 Ph 0 H H H H1924 2,4-F.sub.2 Ph 2-ClPh 0 H H H H1925 2,4-F.sub.2 Ph 4-ClPh 0 H H H H1926 2,4-F.sub.2 Ph 2,4-Cl.sub.2 Ph 0 H H H H1927 2-ClPh Ph 0 H H H H1928 2-ClPh 2-FPh 0 H H H H1929 2-ClPh 4-FPh 0 H H H H1930 2-ClPh 2,4-F.sub.2 Ph 0 H H H H 139-142 (HCl salt 215-217)1931 2-ClPh 2-ClPh 0 H H H H1932 2-ClPh 4-ClPh 0 H H H H 160-162 (HCl salt 170-173)1933 2-ClPh 2,4-Cl.sub.2 Ph 0 H H H H1934 3-ClPh Ph 0 H H H H H1935 3-ClPh 2-FPh 0 H H H H H1936 3-ClPh 4-FPh 0 H H H H H1937 3-ClPh 2,4-F.sub.2 Ph 0 H H H H H1938 3-ClPh 2-ClPh 0 H H H H H1939 3-ClPh 4-ClPh 0 H H H H H1940 3-ClPh 2,4-Cl.sub.2 Ph 0 H H H H H1941 4-ClPh Ph 0 H H H H H1942 4-ClPh 2-FPh 0 H H H H H1943 4-ClPh 4-FPh 0 H H H H H1944 4-ClPh 2,4-F.sub.2Ph 0 H H H H H1945 4-ClPh 2-ClPh 0 H H H H H1946 4-ClPh 4-ClPh 0 H H H H H 179-1811947 4-ClPh 2,4-Cl.sub.2 Ph 0 H H H H H1948 2,4-Cl.sub.2Ph Ph 0 H H H H H1949 2,4-Cl.sub.2 Ph 2-FPh 0 H H H H H1950 2,4-Cl.sub.2 Ph 4-FPh 0 H H H H H1951 2,4-Cl.sub.2 Ph 2,4-F.sub.2Ph 0 H H H H H1952 2,4-Cl.sub.2 Ph 2-ClPh 0 H H H H H1953 2,4-Cl.sub.2 Ph 4-ClPh 0 H H H H H1954 2,4-Cl.sub.2 Ph 2,4-Cl.sub.2 Ph 0 H H H H H1955 2-BrPh Ph 0 H H H H H1956 2-BrPh 2-FPh 0 H H H H H1957 2-BrPh 4-FPh 0 H H H H H1958 2-BrPh 2,4-F.sub.2 Ph 0 H H H H H1959 2-BrPh 2-ClPh 0 H H H H H1960 2-BrPh 4-ClPh 0 H H H H H1961 2-BrPh 2,4-Cl.sub.2 Ph 0 H H H H H1962 3-BrPh Ph 0 H H H H H1963 3-BrPh 2-FPh 0 H H H H H1964 3-BrPh 4-FPh 0 H H H H H1965 3-BrPh 2,4-F.sub.2 Ph 0 H H H H H1966 3-BrPh 2-ClPh 0 H H H H H1967 3-BrPh 4-ClPh 0 H H H H H1968 3-BrPh 2,4-Cl.sub.2 Ph 0 H H H H H1969 4-BrPh Ph 0 H H H H H1970 4-BrPh 2-FPh 0 H H H H H1971 4-BrPh 4-FPh 0 H H H H H1972 4-BrPh 2,4-F.sub.2 Ph 0 H H H H H1973 4-BrPh 2-ClPh 0 H H H H H1974 4-BrPh 4-ClPh 0 H H H H H1975 4-BrPh 2,4-Cl.sub.2 Ph 0 H H H H H1976 2-CF.sub.3 Ph Ph 0 H H H H H 177-1791977 2-CF.sub.3 Ph 2-FPh 0 H H H H H 185-1871978 2-CF.sub.3 Ph 4-FPh 0 H H H H H 170-1721979 2-CF.sub.3 Ph 2,4-F.sub.2 Ph 0 H H H H H1980 2-CF.sub.3 Ph 2-ClPh 0 H H H H H1981 2-CF.sub.3 Ph 4-ClPh 0 H H H H H 159-1611982 2-CF.sub.3 Ph 2,4-Cl.sub.2 Ph 0 H H H H H1983 3-CF.sub.3 Ph Ph 0 H H H H H1984 3-CF.sub.3 Ph 2-FPh 0 H H H H H1985 3-CF.sub.3 Ph 4-FPh 0 H H H H H1986 3-CF.sub.3 Ph 2,4-F.sub.2 Ph 0 H H H H H1987 3-CF.sub.3 Ph 2-ClPh 0 H H H H H1988 3-CF.sub.3 Ph 4-ClPh 0 H H H H H1989 3-CF.sub.3 Ph 2,4-Cl.sub.2 Ph 0 H H H H H1990 4-CF.sub.3 Ph Ph 0 H H H H H1991 4-CF.sub.3 Ph 2-FPh 0 H H H H H1992 4-CF.sub.3 Ph 4-FPh 0 H H H H H1993 4-CF.sub.3 Ph 2,4-F.sub.2 Ph 0 H H H H H1994 4-CF.sub.3 Ph 2-ClPh 0 H H H H H1995 4-CF.sub.3 Ph 4-ClPh 0 H H H H H1996 4-CF.sub.3 Ph 2,4-Cl.sub.2 Ph 0 H H H H H__________________________________________________________________________ .sup.a NMR: (CDCl.sub.3) .delta. 4.5(ABq, 2H), 4.8(br s, 1H), 5.5(two s, 2H), 6.7(s, 1H), 6.9(s, 1H), 7.0-7.6(m, 10H)
Pharmaceutical Utility
In vitro activity (Table 5) is expressed in terms of the minimal inhibitory concentration (MIC) of the test compound which inhibits the growth of yeasts and fungi.
The target organisms, Candida albicans ATCC 11651 and Aspergillus funigatus ATCC 28214 are standardized, [V. Bezjak, J. Clinical Micro., 21 509-512 (1984)] to a concentration of 10.sup.7 organisms/ml and maintained at -70.degree. until use. Test compounds are solubilized in dimethyl sulfoxide (DMSO) and diluted in Eagle's Minimum Essential Medium (EMEM) broth to achieve a final concentration of 200 .mu.g/ml. Stock solutions of standard antifungal agents are stored at -70.degree. and diluted in EMEM as required.
The in vitro assay utilizes a microtiter broth dilution technique [L. Polonelli and G. Morace, Mycopathologia, 86, 21-28 (1984)] and C. Hughes, et. al. Antimicrob. Ag. and Chemo., 25, 560-562 (1984)]. Test compounds are serially diluted in EMEM to give graded concentrations ranging from 100 to 0.4 .mu.g/ml. The appropriate wells are inoculated with the required organism (C. albicans at 1.times.10.sup.4 organisms/ml and A. fumigatus at 5.times.10.sup.5 organisms/ml) and the assay incubated at 30.degree. for 24 hours. The extent of fungal growth is determined at an optical density equal to 540 nm using a scanning spectrophotometer (Flow.RTM. MCC) and MIC values, representing the minimal concentration of a compound which inhibited growth, are determined, [V. Grenta, et al. Antimicrob. Ag. and Chemo., 22, 151-153 (1982)].
The in vivo activity of test compounds is based on the percent (%) survival of infected animals receiving test or standard agent compared to that in an infected untreated group (Table 6). The in vivo assays are chronic systemic infections lethal to mice within 7 days post infection, [J. Barnes, et al. Lab Investigation, 49 460-467 (1963), and T. Rogers and E. Balish, Infection and Immunity, 14 33-38 (1976)].
Candida albicans ATCC 11651, from a frozen stock culture (10.sup.9 organisms/ml) maintained at -70 .degree., is diluted in saline to 1.times.10.sup.7 organisms/ml and 0.2 ml inoculated intravenously (caudal vein) into 20.0 gm CF-1 female mice (Charles River).
Test compounds are routinely solubilized in 0.25% (w/v) methylcellulose (Methocel.RTM.) but for those compounds difficult to solubilize 10% (w/v) Emulophor.RTM. (EL620 GAF Corp.) is used. The standard antifungal agents, amphotericin B (Fungizone.RTM.) in water and ketoconazole (Nizoral.RTM.) in Methocel.RTM. are administered at 1.0 mg/kg/day and 150 mg/kg/day, respectively.
In a primary assay, mice (10 per group) are infected with C. albicans, and receive test compounds at 50 or 150 mg/kg/day via the subcutaneous route. Animals are dosed with the test compound at 1 and 6 hour post-infection and then once daily for the next three days. Survival of mice in each group is recorded for 21 days.
Compounds which protect .gtoreq.70% of the infected animals for 14 days at a dose 150 mg/kg/day or less are viewed as active.
TABLE 5______________________________________In Vitro Antifungal Results ##STR71##Example MIC values (.mu.g/ml)Number C. albicans A. fumigatus______________________________________1 .ltoreq.0.01 6.31 HCl salt 0.05 12.52 .ltoreq.0.4 1.63 .ltoreq.0.4 504 0.03 0.86 1.6 2510 1.6 2515 0.1 5016 0.03 6.317 0.03 12.525 1.6 2526 .ltoreq.0.4 12.526 HCl salt 0.03 0.427 .ltoreq.0.4 12.528 0.03 1.632 .ltoreq.0.4 1.633 0.03 0.0334 0.03 3.234 HCl salt 0.03 1.635 0.03 0.135 HCl salt 0.03 .ltoreq.0.239 0.4 2540 0.4 3.241 0.4 5042 0.03 6.347 0.03 1.649 0.03 12.550 0.1 0.851 0.03 3.252 0.03 0.452 HCl salt 0.03 0.465 0.2 10067 0.03 10085 .ltoreq.0.4 12.594 0.4 5099 0.05 6.3100 0.03 3.2101 0.03 12.5114 0.4 50117 0.4 100163 0.03 12.5164 0.03 1.6170 1.6 100177 3.2 >100208 1.6 50286 0.4 25291 0.2 100359 0.4 50360 0.8 100361 0.8 25363 100 100447 3.2 N.T.449 .ltoreq.0.4 N.T.450 >100 N.T.451 12.5 N.T.452 >100 N.T.453 1.6 >100454 100 >100455 25 N.T.477 >100 N.T.594 0.8 0.8594 HCl salt 0.03 0.4596 0.05 0.4603 0.1 >100605 0.2 100608 0.4 6.3620 0.03 0.05622 0.03 0.1627 0.03 25644 0.03 0.4646 0.03 0.4651 0.8 100656 .ltoreq.0.4 12.5657 0.4 100661 1.6 100667 6.3 25668 0.4 50669 0.03 0.8671 0.03 0.2675 0.1 25685 0.8 100699 50 100721 0.4 12.5724 0.4 0.4726 0.8 6.3815 0.03 >100905 0.04 1001258 1.6 >1001260 0.8 >1001276 0.03 1.61276a 3.2 1001277 0.03 6.31277 HCl salt 0.03 3.21277a 6.3 1001278 .ltoreq.0.4 >1001300 .ltoreq.0.4 6.31377 1.6 1001451 >100 >1001459 >100 >1001487 0.4 6.31527 0.4 6.3Standards*Amphotericin B 0.33 .+-. 0.2 1.4 .+-. 0.5Nystatin 1.3 .+-. 0 3.0 .+-. 1.05-Fluorocytosine 0.14 .+-. 0.1 5.7 .+-. 4.0Ketoconazole .ltoreq.0.1 11.0 .+-. 5.0Miconazole .ltoreq.0.1 1.3 .+-. 0______________________________________ *MIC values of the standard drugs are the mean of five determinations .+-. Standard deviation
TABLE 6______________________________________In Vivo Antifungal Results% Survival (150 mg/kg per day)Primary AssayEx. DaysNo. 7 14 21______________________________________ 1 100 100 80 2 100 100 80 3 100 100 60 4 100 50 N.T. 6 50 10 0 10 20 10 0 15 100 90 60 16 100 100 100 17 100 90 70 25 100 100 50 26 100 100 100 26 salt 100 90 80 27 100 100 100 28 100 90 N.T. 32 100 90 50 33 100 100 100 34 100 100 100 34 salt 100 100 100 35 100 100 90 35 sat 100 100 70 39 100 80 N.T. 40 100 100 N.T. 41 100 100 N.T. 42 80 80 50 47 90 80 30 49 100 90 60 50 100 90 50 51 100 100 80 52 100 100 90 52 salt 100 100 90 55 100 70 50 65 100 70 50 67 100 100 100 85 100 80 70 94 100 40 10 99 100 100 40 100 100 50 30 101 100 90 60 114 70 10 10 117 60 0 0 163 90 60 40 164 100 80 70 208 0 0 0 286 100 50 20 359 100 80 80 360 100 60 40 361 100 100 90 363 10 0 0 453 60 40 30 594 70 10 0 596 70 60 40 603 10 0 0 608 100 70 20 620 100 100 90 622 100 100 100 627 0 0 0 644 80 70 50 646 100 100 70 651 100 50 20 656 100 90 40 657 0 0 0 661 50 20 0 667 10 0 0 668 70 10 0 669 100 100 100 671 100 100 60 675 100 60 0 685 30 10 0 721 100 30 30 724 100 90 40 725 90 90 40 726 100 80 10 905 80 50 201276 100 70 501276a 0 0 01277 100 100 901277a 80 0 01278 0 0 01487 100 100 701527 100 70 20StandardsAmphotericin B 100 100 100Ketoconazole 100 80 50______________________________________ N.T.: Not Tested
DOSAGE FORMS
The antimycotic agents of this invention can be administered by any means that effects contact of the active ingredient with the agent's site of action in the body. The compounds can be administered by any conventional means available for use in conjunction with pharmaceuticals, either as individual therapeutic agents or in a combination of therapeutic agents. They can be administered alone, but are generally administered with a pharmaceutical carrier selected on the basis of the chosen route of administration and standard pharmaceutical practice.
The dosage administered will, of course, vary depending on the use and known factors such as the pharmacodynamic characteristics of the particular agent, and its mode and route of administration: age, health, and weight of the recipient; nature and extent of symptoms, kind of concurrent treatment, frequency of treatment, and the effect desired.
Dosage forms (combinations) suitable for administration contain from about 200 milligrams to about 2000 milligrams of active ingredient per unit. In these pharmaceutical compositions, the active ingredient will ordinarily be present in an amount of about 0.5-95% by weight based on the total weight of the composition. For use in the treatment of said diseases, a daily dose of active ingredient can be about 10 to 50 milligrams per kilogram of body weight.
The composition of the invention may be in a conventional pharmaceutical form suitable for oral administration, for example a tablet, a capsule, an emulsion or an aqueous or oily solution or suspension, or suitable for topical application, for example a cream, ointment or gel. It can also be administered parenterally in sterile liquid dosage forms.
Gelatin capsules contain the active ingredient and powdered carriers, such as lactose, starch, cellulose derivatives, magnesium stearate, stearic acid and the like. Similar diluents can be used to make compressed tablets. Both tablets and capsules can be manufactured as sustained release products to provide for continuous release of medication over a period of hours. Compressed tablets can be sugar coated or film coated to mask any unpleasant taste and protect the tablet from the atmosphere, or enteric coated for selective disintegration in the gastrintestinal tract.
The pharmaceutical compositions which are ointments, creams and gels can, for example, contain the usual diluents, e.g. animal and vegetable fats, waxes, paraffins, starch, tragacanth, cellulose derivatives, polyethylene glycols, silicones, bentonites, silicic acid, talc and zinc oxide or mixtures of these substances.
In general, water, a suitable oil, saline, aqueous dextrose (glucose), and related sugar solutions and glycols such as propylene glycol or polyethylene glycols are suitable carriers for parenteral solutions. Solutions for parenteral administration preferably contain a water soluble salt of the active ingredient, suitable stabilising agents, and if necessary, buffer substances. Antioxidising agents such as sodium bisulfite, sodium sulfite, or ascorbic acid, either alone or combined, are suitable stabilising agents.
All the pharmaceutical compositions according to the invention can also contain coloring and flavoring to increase patient acceptance.
Also used are citric acid and its salts and sodium EDTA. In addition, parenteral solutions can contain preservatives, such as benzalkonium chloride, methyl or propyl-paraben, and chlorobutanol.
Suitable pharmaceutical carriers are described in Remington's Pharmaceutical Sciences, A. Osol, a standard reference text in this field.
Useful pharmaceutical dosage forms for administration of the compounds of this invention can be illustrated as follows:
Capsules
A large number of unit capsules are prepared by filling standard two-piece hard gelatin capsules each with 100 milligrams of powdered active ingredient, 150 milligrams of lactose, 50 milligrams of cellulose, and 6 milligrams of magnesium stearate.
Soft Gelatin Capsules
A mixture of active ingredients in a digestable oil such as soybean oil, cottonseed oil or olive oil is prepared and injected by means of a positive displacement pump into gelatin to form soft gelatin capsules containing 100 milligrams of the active ingredient. The capsules are washed and dried.
Tablets
A large number of tables are prepared by conventional procedures so that the dosage unit is 100 milligrams of active ingredient, 0.2 milligrams of colloidal silicon dioxide, 5 milligrams of magnesium stearate, 275 milligrams of microcrystalline cellulose, 11 milligrams of starch and 98.8 milligrams of lactose. Appropriate coatings may be applied to increase palatability of delay absorption.
Injectable
A parenteral composition suitable for administration by injection is prepared by stirring 1.5% by weight of active ingredient in 10% by volume propylene glycol. The solution is made to volume with water for injection and sterilized.
Suspension
An aqueous suspension is prepared for oral administration so that each 5 milliliters contain 100 milligrams of finely divided active ingredient, 100 milligrams of sodium carboxymethyl cellulose, 5 milligrams of sodium benzoate, 1.0 grams of sorbitol solution, U.S.P., and 0.025 milliliters of vanillin.
Cream
A cream for topical application is prepared by incorporating 100 milligrams of the finely pulverized active ingredient in 5 grams of a cream base which comprises 40% white petrolatum, 3% microcrystalline wax, 10% lanolin, 5% Span.RTM.20, 0.3% Tween.RTM.20 and 41.7% water.
Agricultural Formulations
The compounds of this invention when used for agricultural purposes will generally be used in formulation with a liquid or solid diluent or with an organic solvent. Useful formulations of the compounds of Formula I can be prepared in conventional ways. They include dusts, granules, pellets, solutions, emulsions, wettable powders, emulsifiable concentrates and the like. Many of these may be applied directly. Sprayable formulations can be extended in suitable media and used at spray volumes of from about one to several hundred liters per hectare. High strength compositions are primarily used as intermediates for further formulation. The formulations, broadly, contain about 1% to 99% by weight of active ingredient(s) and at least one of (a) about 0.1% to 35% surfactant(s) and (b) about 5% to 99% solid or liquid inert diluent(s). More specifically, they will contain these ingredients in the following approximate proportions:
______________________________________ Percent by Weight Active Ingredient Diluent(s) Surfactant(s)______________________________________Wettable Powders 20-90 0-74 1-10Oil Suspensions, 5-0 40-95 0--35Emulsions, Solutions,(including EmulsifiableConcentrates)Aqueous Suspensions 10-50 40-84 1-20Dusts 1-25 70-99 0-5Granules and Pellets 1-95 5-99 0-15High Strength 90-99 0-10 0-2Compositions______________________________________
Lower or higher levels of active ingredient can, of course, be present depending on the intended use and the physical properties of the compound. Higher ratios of surfactant to active ingredient are sometimes desirable, and are achieved by incorporation into the formulation or by tank mixing.
Typical solid diluents are described in Watkins, et al., "Handbook of Insecticide Dust Diluents and Carriers", 2nd Ed., Dorland Books, Caldwell, N.J. The more absorptive diluents are preferred for the wettable powders and the denser ones for dusts. Typical liquid diluents and solvents are described in Marsden, "Solvents Guide," 2nd Ed., Interscience, New York, 1950. Solubility under 0.1% is preferred for suspension concentrates; solution concentrates are preferably stable against phase separation at 0.degree. C. "McCutcheon's Detergents and Emulsifiers Annual", MC Publishing Corp., Ridgewood, N.J., as well as Sisely and Wood, "Encyclopedia of Surface Active Agents", Chemical Publ. Co. Inc., New York, 1964, list surfactants and recommended uses. All formulations can contain minor amounts of additives to reduce foam, caking, corrosion, microbiological growth, etc. Preferably, ingredients should be approved by the U.S. Environmental Protection Agency for the use intended.
The methods of making such compositions are well known. Solutions are prepared by simply mixing the ingredients. Fine solid compositions are made by blending and, usually, grinding as in a hammer or fluid energy mill. Suspensions are prepared by wet milling (see, for example, Littler, U.S. Pat. No. 3,060,084). Granules and pellets may be made by spraying the active material upon preformed granular carriers or by agglomeration techniques. See. J. E. Browing, "Agglomeration", Chemical Engineering, Dec. 4, 1967, pp. 147ff. and "Perry's Chemical Engineer's Handbook", 4th Edn., McGraw-Hill, New York, 1963, pp. 8-59ff.
For further information regarding the art of formulation, see for example:
H. M. Loux, U.S. Pat. No. 3,235,361, Feb. 15, 1966, Col. 6, Line 16 through Col. 7, Line 19 and Examples 10 through 41.
R. W. Luckenbaugh, U.S. Pat. No. 3,309,192, Mar. 14, 1967, Col. 5, Line 43 through Col. 7, Line 62 and Examples 8, 12, 15, 39, 41, 52, 53, 58, 132, 138-140, 162-164, 166, 167, 169-192.
H. Gysin and E. Knusli, U.S. Pat. No. 2,891,855, June 23, 1959, Col. 3, Line 66 through Col. 5, Line 17 and Examples 1-4.
G. C. Klingman, "Weed Control as a Science", John Wiley and Sons, Inc., New York, 1961, pp. 81-96.
J. D. Fryer and S. A. Evans, "Weed Control Handbook", 5th Edn. Blackwell Scientific Publications, Oxford, 1968, pp. 101-103.
Examples of useful formulations of compounds of the present invention are as follows.
______________________________________Wettable Powder______________________________________2-(2,4-difluorophenyl)-3-(4-fluorophenyl)-1-(1H-1,2,4- 80%triazol-1-yl)-3-buten-1-ol; and the (S) enantiomerthereofsodium alkylnaphthalenesulfonate 2%sodium ligninsulfonate 2%synthetic amorphous silica 3%kaolinite 13%______________________________________
The ingredients are blended, hammer-milled, reblended and packaged.
______________________________________Granule______________________________________wettable powder of above example 15%gypsum 69%potassium sulfate 16%______________________________________
The ingredients are blended in a rotating or fluid bed mixer and water sprayed on to accomplish granulation. When most of the material has reached the desired range of 1.0 to 0.42 mm. (U.S.S. No. 18 to 40 sieves), the granules are removed, dried, and screened. Oversize material is crushed to produce additional material in the desired range.
______________________________________High Strength Concentrate______________________________________2-(2-fluorophenyl)-3-(4-fluorophenyl)-1-(1H-1,2,4- 98.5%triazol-1-yl)-3-buten-2-ol; and the (S) enantiomerthereofsilica aerogel 0.5%synthetic amorphous fine silica 1.0%______________________________________
The ingredients are blended and ground in a hammer-mill to produce a high strength concentrate essentially all passing a U.S.S. No. 50 sieve (0.3 mm openings). This material may then be formulated in a variety of ways.
______________________________________Aqueous Suspension______________________________________2-(2,4-difluorophenyl)-3-phenyl-1-(1H-1,2,4- 25%triazol-1-yl)-3-buten-2-ol; and the (S)enantiomer thereofhydrated attapulgite 3%crude calcium ligninsulfonate 10%sodium dihydrogen phosphate 0.5water 61.5%______________________________________
The ingredients are ground together in a ball, sand, or roller mill until the solid particles have been reduced to diameters under 10 microns.
______________________________________Solution______________________________________2-(2,4-difluorophenyl)-3-(4-chlorophenyl)-1-(1H- 30%1,2,4-triazol-1-yl)-3-buten-2-ol; and the (S)enantiomer thereofdimethylformamide 70%______________________________________
The ingredients are combined and stirred to produce a solution, which can be used for low volume applications.
______________________________________Emulsifiable Concentrate______________________________________2-(2,4-difluorophenyl)-3-(4-fluorophenyl)-1-(1H- 15%1,2,4-triazol-1-yl)-3-buten-2-ol; and the (S)enantiomer thereofblend of calcium sulfonates 25%and nonionic surfactantsxylene 60%______________________________________
The ingredients are combined and stirred until the active is dissolved. A fine screen filter is included in packaging operation to insure the absence of any extraneous undissolved material in the product.
Utility
The compounds of this invention are useful as plant disease control agents. They are effective in controlling a broad spectrum of plant diseases, particularly foliar pathogens of ornamental, vegetable, field, cereal and fruit crops, such as Puccinia recondita, Erysiphe cichoracearum, Erysiphe graminis, Venturia inaequalis, Cercospora arachidicola, and Monilinia fructicola, Rhizoctonia solani, Pyricularia oryzae, Botrytis cinerea, Pseudocercosporella herpotrichlorides, and Cercosporidium personatum. They also control seed pathogens.
Disease control is ordinarily accomplished by applying an effective amount of the compound either pre- or post-infection to the portion of the plant to be protected, such as the roots, stems, foliage, fruit, seeds, tubers or bulbs, or to the media (soil or sand) in which the plants to be protected are growing. The compound may also be applied to the seed from which the plants to be protected are to be grown.
Rates of application for these compounds can be influenced by many factors of the environment and should be determined under actual use conditions. Foliage can normally be protected when treated at a rate of from less than 1 g/ha to 5000 g/ha of active ingredient. Plants growing in soil treated at a concentration from 0.1 to about 20 kg/ha can be protected from disease. Seed and seedlings can normally be protected when seed is treated at a rate of from 0.06 to about 3 grams per kilogram of seed.
The compounds of this invention can be mixed with fungicides, bactericides, acaricides, nematicides, insecticides, or other biologically active compounds in order to achieve desired results with a minimum expenditure of time, effort and material. Amounts of these biologically active materials added for each part by weight of the composition of this invention may vary from 0.05 to 25 parts by weight. Suitable agents of this type are well-known to those skilled in the art. Some are listed below:
Fungicides
methyl 2-benzimidazolecarbamate (carbendazim)
tetramethylthiuram disulfide (thiuram)
n-dodecylguanidine acetate (dodine)
manganese ethylenebisdithiocarbamate (maneb)
1,4-dichloro-2,5-dimethoxybenzene (chloroneb)methyl
1-(butylcarbamoy)-2-benzimidazolecarbamate (benomyl)
2-cyano-N-ethylcarbamoyl-2-methoxyiminoacetamide (cymoxanil)
N-trichloromethylthiotetrahydrophthalamide (captan)
N-trichloromethylthiophthalimide (folpet)
dimethyl 4,4'-(o-phenylene)bis(3-thioallophanate)(thiophanate-methyl)
2-(thiazol-4-yl)benzimidazole (thiabendazole)
aluminum tris(O-ethyl phosphonate)(phosethyl aluminum) tetrachloroisophthalonitrile (chlorothalonil)
2,6-dichloro-4-nitroaniline (dichloran) N-(2,6-dimethylphenyl)-N-(methoxyacetyl)alanine methyl ester (metalaxyl)
cris-N-[1,2,2,2-tetrachloroethyl)thio]cyclohex-4-ene-1,2-dicarbioximide (captafol)
3-(3,5-dichlorophenyl)-N-(1-methylethyl)-2,4-dioxo-1-imidazolidine carboxamide (iprodione)
3-(3,5-dichlorophenyl)-5-ethenyl-5-methyl-2,4-oxazolidinedione (vinclozolin)
kasugamycin
O-ethyl-S,S-diphenylphosphorodithioate (edifenphos)
4-(3-(4-(1,1-dimethyl-ethyl)phenyl)-2-methyl)propyl-2,6-dimethylmorpholine (Fenpropimorph)
4-(3-4(1,1-dimethyl-ethyl)phenyl)-2-methyl)propylpiperidine (Fenpropidine)
Bactericides
tribasic copper sulfate
streptomycin sulfate
oxytetracycline
Acaricides
senecioic acid, ester with 2-sec-butyl-4,6-dinitrophenol (binapacryl)
6-methyl-1,3-dithiolo[2,3-B]quinonolin-2-one (oxythiioquinox)
2,2,2-trichlor-1,1-bis(4-chlorophenyl)ethanol(dicofol)
bis(pentachloro-2,4-cyclopentadien-1-yl)(dienochlor)
tricyclohexyltin hydroxide (cyhexatin)
hexakis(2-methyl-2-phenylpropyl)distannoxane (fenbutin oxide)
Nematicides
2-[diethoxyphosphinylimino]-1,3-diethietane (fosthietan)
S-methyl-1-(dimethylcarbamoyl)-N-(methylcarbamoyloxy)thioformimidate(oxamyl
S-methyl-1-carbamoyl-N-(methylcarbamoyloxy)thioformimidate
N-isopropylphosphoramidic acid, O-ethyl-O'-[4-(methylthio)-m-tolyl]diester (fenamiphos)
Insecticides
3-hydroxy-N-methylcrotonamide(dimethylphosphate)ester (monocrotophos)
methylcarbamic acid, ester with 2,3-dihydro-2,2-dimethyl-7-benzofuranol (carbofuran)
O-[2,4,5-trichloro-.alpha.-(chloromethyl)benzyl]phosphoric acid, O',O'-dimethyl ester (tetrachlorvinphos)
2-mercaptosuccinic acid, diethyl ester, S-ester with thionophosphoric acid, dimethyl ester (malathion)
phosphorothioic acid, O,O-dimethyl, O-p-nitrophenyl ester (methyl parathion)
methylcarbamic acid, ester with .alpha.naphthol (carbaryl)
methyl N-[[(methylamino)carbonyl]oxy]ethanimidothioate (methomyl)
N'-(4-chloro-o-tolyl)-N,N-dimethylformamidine (chlordimeform)
O,O-diethyl-0-(2-isopropyl-4-methyl-6-pyrimidyl)phosphorothioate (diazinon)
octachlorocamphene (toxaphene)
O-ethyl O-p-nitrophenyl phenylphosphonothioate (EPN)
cyano(3-phenoxyphenyl)-methyl 4-chloro-.alpha.-(1-methylethyl)benzeneacetate (fenvalerate)
(3-phenoxyphenyl)methyl (.+-.)-cis,trans-3-(2,2-dichloroethenyl)-2,2-dimethylcyclopropanecarboxylate (permethrin)
dimethyl N,N'-[thiobis(N-methylimmo)carbonyloxy]]bis[ethanimidothioate] (thiodicarb)
phosphorothiolothionic acid, O-ethyl-O-[4-(methylthio)phenyl]-S-n-propyl ester (sulprofos)
.alpha.-cyano-3-phenoxybenzyl 3-(2,2-dichlorovinyl)-2,2-dimethylcyclopropane carboxylate (cypermethrin)
cyano(3-phenoxyphenyl)methyl 4-(difluoromethoxy)-.alpha.-(methylethyl)benzeneacetate (flucythrinate)
O,O-dimethyl-O-(3,5,6-trichloro-2-pyridyl)phosphorothioate (chlorpyrifos)
O,O-dimethyl-S-[(4-oxo-1,2,3-benzotriazin-3-(4H)-yl)methyl]phosphorodithioate (azinphos-methyl)
5,6-dimethyl-2-dimethylamino-4-pyrimidinyl dimethyl carbamate (pirimicarb)
S-(N-formyl-N-methylcarbamoylmethyl)-O,O-dimethyl phosphorodithioate (formothion)
S-2-(ethylthioethyl)-O,O-dimethyl phosphiorothioate (demeton-S-methyl)
.alpha.-cyano-3-phenoxybenzyl cis-3-(2,2-dibromovinyl)-2,2-dimethylcyclopropane carboxylate (deltamethrin)
cyano(3-phenoxyphenyl)methyl ester of N-(2-chloro-4-trifluoromethylphenyl)alanine (fluvalinate)
Test results indicate that the compounds of the present invention are also active preemergent or postemergent herbicides or plant growth regulants. Some of them have utility for broad-spectrum pre- and/or post emergence weed control in areas where complete control of all vegetation is desired, such as around industrial storage areas, parking lots, drive-in theaters, around billboards, highway and railroad structures. Other compounds have utility for selective weed control in crops such as rice, wheat, barley, corn, soybeans, sugarbeets and cotton. Some of the compounds are useful as selective herbicides for rice. They may be used either in direct seeded or transplanted rice. Alternatively, the subject compounds are useful to modify plant growth.
The rates of application for the compounds of the invention are determined by a number of factors, including their use as plant growth modifiers or as herbicides, the crop species involved, the types of weeds to be controlled, weather and climate, formulations selected, mode of application, amount of foliage present, etc. In general terms, the subject compounds should be applied at levels of around 0.050 to 20 kg/ha, the lower rates being suggested for use on lighter soils and/or those having a low organic matter content, for plant growth modification or for situations where only short-term persistance is required, such as a herbicide for fallow land.
The compounds of the invention may be used in combination with any other commercial herbicide, non-limiting examples of which are those below:
______________________________________ Chemical Name______________________________________Common Nameacifluorfen 5-[2-chloro-4-(trifluoromethyl)- phenoxy]-2-nitrobenzoic acidacrolein acroleinalachlor 2-chloro-2',6',-diethyl-N- (methoxymethyl)-acetanilideametryn 2-(ethylamino)-4-(isopropylamino)-6- methylthio)- .sub.- s-triazineamitrole 3-amino- .sub.- s-triazoleAMS ammonium sulfamateasulam methyl sulfanilylcarbamateatrazine 2-chloro-4-(ethylamino)-6- (isopropylamino)- .sub.- s-triazinebarban 4-chloro-2-butynyl .sub.-- m- chlorocarbanilatebenefin N-butyl-N-ethyl-.alpha.,.alpha.,.alpha.-trifluoro-2,6- dinitro- -p-toluidinebensulide O,O-diisopropyl phosphorodithioate S-ester with N-(2-mercaptoethyl)- benzenesulfonamidebentazon 3-isopropyl-1H-2,1,3- benzothiadiazin-4(3H)-one 2,2- dioxidebenzipram 3,5-dimethyl-N-(1-methylethyl)-N- (phenylmethyl)benzamidebenzoylprop N-benzoyl-N-(3,4-dichlorophenyl)-DL- alainebifenox methyl 5-(2,4-dichlorophenoxy)-2- nitrobenzoatebromacil 5-bromo-3-sec-butyl-6-methyluracilbromoxynil 3,5-dibromo-4-hydroxybenzonitrilebutachlor N-(butoxymethyl)-2-chloro-2',6'- diethylacetanilidebutam 2,2-dimethyl-N-(1-methylethyl)-N- (phenylmethyl)propanamidebuthidazole 3-[5-(1,1-dimethylethyl)-1,3,4- thiadiazol-2-yl]-4-hydroxy-1- methyl-2-imidazolidinonebutralin 4-(1,1-dimethylethyl)-N-(1-methyl- propyl)-2,6-dinitrobenzenaminebutylate S-ethyl-diisobutylthiocarbamatecacodylic acid hydroxydimethylarsine oxidecarbetamide D-N-ethyllactamide carbanilate (ester)CDAA N-N-diallyl-2-chloroacetamideCDEC 2-chloroallyl diethyldithiocarbamatechlorbromuron 3-(4-bromo-3-chlorophenyl)-1- methoxy-1-methylureachloroxuron 3-[ -p-( -p-chlorophenoxy)phenyl]-1,1- dimethylureachlorpropham isoproyl .sub.-- m-chlorocarbanilatechlorsulfuron 2-chloro-N-[(4-methoxy-6-methyl- 1,3,5-triazin-2-yl)amino- carbonyl]benzene-sulfonamidechlortoluron N'-(3-chloro-4-methylphenyl-N',N'- dimehylureacisanilide cis-2,5-dimethyl-N-phenyl-1- pyrrolidine-carboxamideCMA calcium methanearsonatecyanazine 2-[[4-chloro-6-(ethylamino)- .sub.- s- triazin-2-yl]amino]-2- methylpropionitrilecycloate S-ethyl N-ethylthiocyclohexane- carbamatecycluron 3-cyclooctyl-1,1-dimethylureacyperquat 1-methyl-4-phenylpyridiniumcyprazine 2-chloro-4-(cyclopropylamino)-6- (isopropylamino)- .sub.- s-triazinecyprazole N-[5-(2-chloro-1,1-dimethylethyl)- 1,3,4-thiadiazol-2-yl] cyclopropanecarboxamidecypromid 3',4'-dichlorocyclopropanecar- boxanilidedalapon 2,2-dichloropropionic aciddazomet tetrahydro-3,5-dimethyl-2H-1,3,5- thiadiazine-2-thioneDCPA dimethyl tetrachloroterephthalatedesmetryn 2-(isopropylamino)-4-(methylamino)- 6-methylthio)- .sub.- s-triazinediallate S-(2,3-dichloroallyl)diisopropyl- thiocarbamatedicamba 3,6-dichloro- -o-anisic aciddichlobenil 2,6-dichlorobenzonitriledichlorprop 2-(2,4-dichlorophenoxy)propionic aciddiclofop 2-[4-(2,4-dichlorophenoxy)phenoxyl]- propanoic aciddiethatyl N-(chloroacetyl)-N-(2,6- diethylphenyl)-glycinedifenzoquat 1,2-dimethyl-3,5-diphenyl-1H- pyrazoliumdinitramine N.sup.4,N.sup. 4 -diethyl-.alpha.,.alpha.,.alpha.-trifluoro-3 ,5- dinitrotoluene-2,4-diaminedinoseb 2-sec-butyl-4,6-dinitrophenoldiphenamide N,N-dimethyl-2,2-diphenylacetamidedipropetryn 2-(ethylthio)-4,6-bis(isopropyl- amino)- .sub.- s-triazinediquat 6,7-dihydrodipyrido[1,2-.alpha.:2',1',-c]- pyrazinediium iondiuron 3-(3,4-dichlorophenyl)-1,1- dimethylureaDSMA disodium methanearsonateendothall 7-oxabicyclo[2.2.1]heptane-2,3- dicarboxylic aciderbon 2-(2,4,5-trichlorophenoxy)ethyl 2.2- dichloropropionateethafluralin N-ethyl-N-(2-methyl-2-propenyl)-2,6- dinitro-4-(trifluoromethyl)- benzenamineethofumesate (.+-.)-2-ethoxy-2,3-dihydro-3,3- dimethyl-5-benzofuranyl methanesulfonatefenac (2,3,6-trichlorophenyl)acetic acidfenoxaprop ethyl 2-(4-(6-chloro-2-benzoxazolyl- oxy)phenoxy)propanoatefenuron 1,1-dimethyl-3-phenylureafenuron TCA 1,2-dimethyl-3-phenylurea mono(trichloroacetate)flamprop N-benzoyl-N-(3-chloro-4- fluorophenyl)-DL-anilinefluchloralin N-(2-chloroethyl)-2,6-dinitro-N- propyl-4-(trifluoromethyl)anilinefluometuron 1,1-dimethyl-3-(.alpha.,.alpha.,.alpha.-trifluoro- .sub.-- m- tolyl)-ureafluorodifen -p-nitrophenyl .alpha.,.alpha.,.alpha.-trifluoro-2- nitro- -p-tolyl etherfluridone 1-methyl-3-phenyl-5-[3-(trifluoro- methyl)phenyl]-4-(1H)-pyridinonefomesafen 5-(2-chloro-4-trifluoromethyl- phenoxy)-N-methylsulfonyl-2- nitrobenzamidefosamine ethyl hydrogen (aminocarbonyl)- phosphonateglyphosate N-(phosphonomehyl)glycinehexaflurate potasium hexafluoroarsenatehexazinone 3-cyclohexyl-6-(dimethylamino)-1- methyl-1,3,5-triazine-2,4(1H, 3H)- dioneimazaquin 2-(4,5-dihydro-4-methyl-4-(l-methyl- ethyl)-5-oxo-1H-imidazol-2-yl)-3- quinolinecarboxylic acidioxynil 4-hydroxy-3,5-diiodobenzonitrileisopropalin 2,6-dinitro-N,N-dipropylcumidinekarbutilate tert-butylcarbamic acid ester with 3-( .sub.-- m-hydroxyphenyl)-1,1- dimethylurealactofen 1'-(carboethoxy)ethyl-5-(2-chloro-4- (trifluoromethyl)phenoxy)-2- nitrobenzoatelenacil 3-cyclohexyl-6,7-dihydro-1H- cyclopentapyrimidine-2,4(3H,5H)- dionelinuron 3-(3,4-dichlorophenyl)-1-methoxy-1- methylureaMAA methanearsonic acidMAMA monoammonium methanearsonateMCPA [(4-chloro- -o-tolyl)oxy]acetic acidMCPB 4-[(4-chloro- -o-tolyl)oxy]butyric acidmecoprop 2-[(4-chloro- -o-tolyl)oxy]propionic acidmefluidide N-(2,4-dimethyl-5- [[(trifluoromethyl)- sulfonyl]amino]phenyl]acetamidemethalpropalin N-(2-methyl-2-propenyl)-2.6-dinitro- N-propyl-4-(trifluoromethyl)- benzenamidemethabenzthiazuron 1,3-dimethyl-3-(2-benzothiazolyl) ureametham sodium methyldithiocarbamatemethazole 2-(3,4-dichlorophenyl)-4-methyl- 1,2,4-oxadiazolidine-3,5-dionemethoxuron N'-(3-chloro-4-methoxyphenyl)N,N- dimethylureametolachlor 2-chloro-N-(2-ethyl-6-methylphenyl)- N-(2-methoxy-1-methylethyl)- acetamidemetribuzin 4-amino-6-tert-butyl-3-(methylthio)- as-triazine-5(4H)-onemetsulfuron methyl 2-[[(4-methoxy-6-methyl-1,3,5- triazine-2-yl)aminocarbonyl]amino- sulfonyl]benzoic acid, methyl estermolinate S-ethyl hexahydro-1H-azepine-1- carbothioatemonolinuron 3-( -p-chlorophenyl)-1-methoxy-1- methylureamonuron 3-( -p-chlorophenyl)-1,1-dimethylureamonuron TCA 3-( -p-chlorophenyl)-1,1-dimethylurea mono(trichloroacetate)MSMA monosodium methanearsonatenapropamide 2-.alpha.-naphthoxy)-N,N- diethylpropionamidenaptalam N-1-naphthylphthalamic acidneburon l-butyl-3-(3,4-dichlorophenyl)-1- methylureanitralin 4-(methylsulfonyl)-2,6-dinitro-N,N- dipropylanilinenitrofen 2,4-dichlorophenyl -p-nitrophenyl ethernitrofluorofen 2-chloro-1-(4-nitrophenoxy)-4- (trifluoromethyl)benzenenorea 3-(hexahydro-4.7-methanoindan-5-yl)- 1.1-dimethylureanorflurazon 4-chloro-5-(methylamino)-2-(.alpha.,.alpha.,.alpha.- trifluoro- .sub.-- m-tolyl)-3(2H)- pyridazinoneoryzalin 3,4-dinito-N,N-dipropylsulfanilamideoxadiazon 2-tert-butyl-4-(2,4-dichloro-5- isopropoxyphenyl).DELTA..sup.2 -1,3,4- oxadiazolin-5-oneoxyfluorfen 2-chloro-1-(3-ethoxy-4-nitro- phenoxy)-4-(trifluoro- methyl)benzeneparaquat 1,1'-dimethyl-4,4'-bipyridinium ionPBA chlorinated benzoic acidpendimethalin N-(1-ethylpropyl)-3,4-dimethyl-2,6- dinitrobenzenamineperfluidone 1,1,1-trifluoro-N-[2-methyl-4- (phenylsulfonyl)phenyl]methane- sulfonamidepicloram 4-amino-3,5,6-trichloropicolinic acidprocyazine 2-[[4-chloro-6-(cyclopropylamino)- 1,3,5-triazine-2-yl]amino]-2- methylpropanenitrileprofluralin N-(cyclopropylmethyl)-.alpha.,.alpha.,.alpha.- trifluoro-2,6-dinitro-N-propyl- -p- toluidineprometon 2.4-bis(isopropylamino)-6-methoxy- .sub.- s- triazineprometryn 2,4-bis(isopropylamino)-6- (methylthio)- .sub.- s-triazinepronamide 3,5-dichloro N-(1,1-dimethyl-2- propyn-yl)enzamidepropachlor 2-chloro-N-isopropylacetanilidepropanil 3',4'-dichloroprionalidepropazine 2-chloro-4,6-bis(isopropylamino)- .sub.- s- triazinepropham isopropyl carbanilateprosulfalin N-[[4-(dipropylamino)-3,5- dinitrophenyl]sulfonyl]-S,S- dimethylsulfilimineprynachlor 2-chloro-N-(1-methyl-2- propynyl)acetanilidequinofop ethyl 2-[4-(6-chloroquinoxalin-2-yloxy)- phenoxypropanoic acid, ethyl estersecbumeton N-ethyl-6-methoxy-N'(1- methylpropyl)-1,3,5-triazine-2,4- diaminesethoxydim 2-[1-(ethoxyimino)butyl]-5-[2- (ethylthio)propyl]-3-hydroxy-2- cyclohexene-1-onesiduron 1-(2-methylcyclohexyl)-3-phenylureasimazine 2-chloro-4,6-bis(ethylamino)- .sub.- s- triazinesimetryn 2,4-bis(ethylamino)-6-(methylthio)- .sub.- s-triazinesupriox 2-[1-(2,5-dimethylphenyl)- ethylsulfonyl]-pyridine-N-oxideTCA trichloroacetic acidtebuthiuron N-[5-(1,1-dimethylethyl)-1,3,4- thiadiazol-2-yl]-N,N'-dimethylureaterbacil 3-tert-butyl-5-chloro-6-methyluracilterbuchlor N-(butoxymethyl)-2-chloro-N-[2-(1.1- dimethylethyl)-6-methylphenyl]- aceamideterbuthylazine 2-(tert-butylamino)-4-chloro-6- (ethylamino)- .sub.- s-triazineterbutol 2,6-di-tert-butyl- -p-tolyl methylcarbamateterbutryn 2-(tert-butylamino)-4-(ethylamino)- 6-(methylthio)- .sub.- s-triazinetetrafluron N,N-dimethyl-N'-[3-(1,1,2,2- tetrafluoroethoxy)phenyl]ureathiobencarb S-[(4-chlorophenyl)methyl] diethylcarbamothioatetriallate S-(2,3,3-trichloroallyl)- diisopropylthiocarbamatetrifluralin .alpha.,.alpha.,.alpha.-tifluoro-2,6-dinitro-N,N propyl- -p-toluidinetrimeturon 1-( -p-chlorophenyl)-2,3,3- trimethylpseudoureavernolate S-propyl dipropylthiocarbamae ethyl 5-[2-chloro-4-(trifluoromethyl)- phenoxy]-2-nitrobenzoic acid2,3,6-TBA 2,3,6-trichlorobenzoic acid2,4-D (2,4-dichlorophenoxy)acetic acid2,4-DB 4-(2,4-dichlorophenoxy)butyric acid2,4-DEP tris[2-(2,4-dichlorophenoxy)ethyl] phosphiteTrade Name orCode Number"Cinch" exo-1-methyl-4-(1-methylethyl)-2-[2- methylphenyl)methoxy]7- oxabicyclo[2.2.1] heptaneAC 263,499 2-[4,5-dihydro-4-methyl-4-(1-methyl- ethyl)-5-oxo-1H-imidazol-2-yl]-5- ethyl-3-pyridinecarboxylic acidHarmony .TM. 3-[[(4-methoxy-6-methyl-1,3-5- triazin-2-yl)aminocarbonyl]amino- sulfonyl]-2-thiophenecarboxylic acid, methyl eserPPG-1013 5-(2-chloro-4-(trifluoromethyl)- phenoxy)propanoic acid, methyl esterFMC 57020 2-(2'-chlorophenyl)methyl-4,4- dimethyl-3-isoxazolidinoneAC 222,293 6-(4-isopropyl-4-methyl-5-oxo-2- imidazolin-2-yl)- .sub.-- m-toluic acid,methyl ester and 6-(4- isopropyl-4-methyl-5-oxo-2- imidazolin-2-yl- -p-toluic acid, methyl ester______________________________________
The herbicidal properties of the subject compounds were discovered in a number of greenhouse tests. The test procedures and results follow.
This invention is further illustrated by the following examples.
EXAMPLE A
The test compounds were dissolved in acetone in an amount equal to 6% of the final volume and then suspended at a concentration of 100 or 20 ppm in purified water containing 250 ppm of the surfactant TREM 014 (polyhydric alcohol esters). This suspension was sprayed to the point of run-off on apple seedings. The following day plants were inoculated with a spore suspension of Venturia inaequalis, the casual agent of apple scab, and incubated in a saturated humidity chamber at 20.degree. C. for 24 hours and then in a growth chamber at 22.degree. C. for 11 days, when disease ratings were made.
EXAMPLE B
The test compounds were dissolved in acetone in an amount equal to 6% of the final volume and then suspended at a concentration of 100 or 20 ppm in purified water containing 250 ppm of the surfactant TREM 014 (polyhydric alcohol esters). This suspension was sprayed to the point of run-off on peanut seedlings. The following day plants were inoculated with a spore suspension of Cercosporidium personatum, the casual agent of Peanut Late Leafspot, and incubated in a saturated humidity chamber at 22.degree. C. for 24 hours, then in a high humidity chamber at 27.degree. C. for 7 days, and then in a growth chamber at 29.degree. C. for 7 days, when disease ratings were made.
EXAMPLE C
The test compounds were dissolved in acetone in an amount equal to 6% of the final volume and then suspended at a concentration of 100 or 20 ppm in purified water containing 250 ppm of the surfactant TREM 014 (polyhydric alcohol esters). This suspension was sprayed to the point of run-off on broad bean seedlings. The following day plants were inoculated with a spore suspension of Botrytis cinerea, the causal agent of beam grey mold, and incubated in a saturated humidity chamber at 20.degree. C. for 24 hours when disease ratings were made.
EXAMPLE D
The test compounds were dissolved in acetone in an amount equal to 6% of the final volume and then suspended at a concentration of 100 or 20 ppm in purified water containing 250 ppm of the surfactant TREM 014 (polyhydric alcohol esters). This suspension was sprayed to the point of run-off on wheat seedlings. The following day plants were inoculated with a spore dust of Erysiphe graminis f. sp. tritici, the causal agent of wheat powdery mildew, and incubated in a growth chamber at 20.degree. C. for 6 days, when disease ratings were made.
EXAMPLE E
The test compounds were dissolved in acetone in an amount equal to 6% of the final volume and then suspended at a concentration of 100 or 20 ppm in purified water containing 250 ppm of the surfactant TREM 014 (polyhydric alcohol esters). This suspension was sprayed to the point of run-off on rice seedlings. The following day plants were inoculated with a spore suspension of Pyricularia oryzae, the causal agent of rice blast, and incubated in a saturated humidity chamber at 27.degree. C. for 24 hours and then in a growth chamber at 29.degree. C. for 4 days, when disease ratings were made.
EXAMPLE F
The test compounds were dissolved in acetone in an amount equal to 6% of the final volume and then suspended at a concentration of 100 or 20 ppm in purified water containing 250 ppm of the surfactant TREM 014 (polyhydric alcohol esters). This suspension was sprayed to the point of run-off on rice seedlings. The following day plants were inoculated with a spore suspension of Rhizoctonia solani, the causal agent of rice sheath blight, and incubated in a saturated humidity chamber at 27.degree. C. for 48 hours and then in a growth chamber at 29.degree. C. for 4 days, when disease ratings were made.
EXAMPLE G
The test compounds were dissolved in acetone in an amount equal to 6% of the final volume and then suspended at a concentration of 100 or 20 ppm in purified water containing 250 ppm of the surfactant TREM 014 (polyhydric alcohol esters). This suspension was sprayed to the point of run-off on wheat seedlings. The following day plants were inoculated with a spore suspension of Puccinia recondita, the causal agent of wheat leaf rust, and incubated in a saturated humidity chamber at 20.degree. C. for 24 hours and then in a growth chamber at 20.degree. C. for 8 days, when disease ratings were made.
EXAMPLE H
The test compounds were dissolved in acetone in an amount equal to 6% of the final volume and then suspended at a concentration of 100 or 20 ppm in purified water containing 250 ppm of the surfactant TREM 014 (polyhydric alcohol esters). This suspension was sprayed to the point of run-off on tomato seedlings. The following day plants were inoculated with a spore suspension of Phytophthora infestans, the causal agent of tomato late light, and incubated in a saturated humidity chamber at 20.degree. C. for 24 hours and then in a growth chamber at 20.degree. C. for 5 days, when disease ratings were made.
EXAMPLE I
The test compounds were dissolved in acetone in an amount equal to 6% of the final volume and then suspended at a concentration of 100 or 20 ppm in purified water containing 250 ppm of the surfactant TREM 014 (polyhydric alcohol esters). This suspension was sprayed to the point of run-off on grape seedlings. The following day plants were inoculated with a spore suspension of Plasmorpara viticola, the causal agent of grade downy mildew, and incubated in a saturated humidity chamber at 20.degree. C. for 24 hours, then in a growth chamber at 20.degree. C. for 7 days and then held in a saturated humidity chamber at 20.degree. C. for 24 hours, when disease ratings were made.
EXAMPLE J
The test compounds were dissolved in acetone so that 1 ml of solution yielded a concentration of 0.5 kilogram/hectare when added to cucumber seeds and soil in pots. Seeds and soil were then inoculated with a mixture of sand, cereal and mycelium of the fungus Pythium aphanadermatum, causal agent of cucumber damping off, and incubated in a growth chamber at 30.degree. C. for 14 days. Disease ratings were then made.
EXAMPLE K
The test compounds were dissolved in acetone so that 1 ml of solution yielded a concentration of 0.5 kilogram/hectare when added to cotton seeds and soil in pots. Seeds and soil were then inoculated with a mixture of sand, cereal and mycelium of the fungus Rhizoctonia solani, causal agent of cotton blight, and incubated in a growth chamber at 30.degree. C. for 14 days. Disease ratings were then made.
EXAMPLE L
The test compounds were dissolved in acetone so that 1 ml of solution yielded a concentration of 0.5 kilogram/hectare when added to cucumber seeds and soil in pots. Seeds and soil were then inoculated with a mixture of sand, cereal and mycelium of the fungus Fusarium oxysporum f. sp. cucumerinum, causal agent of cucumber wilt, and incubated in a growth chamber at 20.degree. C. for 14 days. Disease ratings were then made.
EXAMPLE M
The test compounds were dissolved in acetone so that 1 ml of solution yielded a concentration of 0.5 kilogram/hectare when added to lima bean seeds and soil in pots. Seeds and soil were then inoculated with a mixture of sand, cereal and mycelium of the fungus Sclerotium rolfsii, causal agent of southern blight, and incubated in a growth chamber at 30.degree. C. for 14 days. Disease ratings were then made.
Results for Examples A-M are given in Table 7. In this table, a rating of 100 indicates 100% disease control and a rating of 0 indicates no disease control relative to the controls. A -- entry indicates that no test was performed with the specified compound. A P entry indicates that disease control was not measured due to phytoxicity.
TABLE 7__________________________________________________________________________Ex. Rate Ex. Ex. Ex. Ex. Ex. Ex. Ex. Ex. Ex. Rate Ex. Ex. Ex. Ex.No. (PPM) A B C D E F G H I (kg/ha) J K L M__________________________________________________________________________ 1 100 62 100 81 98 90 97 100 0 12 5 0 P 0 P 2 100 62 100 93 98 95 100 100 0 99 5 0 P 0 P 3 100 100 100 93 93 5 93 100 0 0 5 0 0 P P 4 100 100 100 88 100 96 100 100 0 81 5 0 0 P 0 6 100 0 82 84 98 0 0 96 23 0 5 0 0 P 0 10 100 0 76 52 63 0 17 64 0 0 5 0 0 0 0 15 100 100 100 99 100 1 93 100 26 0 5 0 P 0 P 16 100 -- -- 46 -- 0 0 -- 0 23 5 0 0 P 0 20 74 99 27 67 0 0 100 -- -- 17 100 -- -- 89 -- 0 81 -- 0 42 5 0 0 P 0 20 80 100 57 95 0 0 100 -- -- 25 100 100 100 96 91 31 48 97 0 0 5 0 P P 35 26 100 100 100 96 86 31 61 97 23 86 5 0 25 25 35 27 100 62 100 88 98 95 100 100 24 84 5 0 0 0 0 28 100 89 100 88 98 81 100 100 0 6 5 0 0 0 0 32 100 100 100 98 95 97 33 100 0 98 5 0 0 P P 33 100 -- -- 56 -- 0 60 -- 0 24 5 0 0 0 0 20 47 99 37 89 0 29 100 -- -- 34 100 69 100 94 60 86 16 66 0 0 5 0 0 0 0 35 100 100 100 96 100 0 100 96 0 26 5 0 0 0 0 39 100 89 97 96 98 7 100 100 0 81 5 0 0 0 0 40 100 19 100 80 91 7 61 96 0 0 5 0 0 0 0 41 100 100 100 96 98 7 97 100 0 100 5 0 0 0 0 42 100 -- -- 100 100 31 41 -- 0 23 5 -- -- -- -- 20 29 100 38 98 15 0 100 -- -- 47 100 -- -- 89 -- 31 47 -- 0 25 5 -- -- -- -- 20 93 100 26 98 15 0 100 -- -- 49 100 89 100 62 100 76 96 100 0 0 5 0 P 0 P 50 100 100 100 98 95 86 93 100 0 46 5 0 P 0 P 51 100 100 100 96 100 0 100 100 0 0 5 P P P P 52 100 100 100 95 94 93 81 100 0 0 5 0 P 0 0 65 100 34 96 94 85 30 62 100 0 0 5 0 0 0 0 67 100 -- -- 75 -- 0 68 -- 2 1 5 0 0 0 0 20 58 99 60 85 0 35 89 -- -- 94 100 86 61 96 98 78 36 100 0 0 5 0 0 P P 99 100 100 100 89 83 98 61 100 0 83 5 0 0 P P 100 100 100 100 96 83 95 80 100 0 83 5 P 0 P 0 101 100 100 100 94 83 0 80 100 0 100 5 0 0 P 0 163 100 -- -- 95 -- 5 0 -- 0 0 5 -- -- -- -- 20 0 81 58 23 5 0 99 -- -- 164 100 -- -- 84 -- 15 0 -- 8 0 5 -- -- -- -- 20 82 100 57 88 5 0 100 -- -- 170 100 -- -- 20 -- 10 0 -- 0 0 5 -- -- -- -- 20 19 69 32 95 0 100 -- -- 177 100 -- -- 26 -- 10 0 -- 0 0 5 -- -- -- -- 20 82 26 50 46 0 0 100 -- -- 208 100 84 37 83 76 4 61 97 0 74 5 0 0 0 0 291 100 -- -- 81 -- 1 0 -- 24 78 5 -- -- -- -- 20 32 26 6 83 1 0 73 -- -- 359 100 72 100 83 95 88 62 100 0 0 5 0 0 0 0 360 100 88 100 71 86 74 49 93 0 0 5 0 0 0 0 361 100 -- -- 46 -- 1 0 -- 27 9 5 -- -- -- -- 20 43 26 29 33 1 0 100 -- -- 363 100 0 49 92 28 0 0 38 0 0 5 0 0 0 0 447 100 -- 0 24 46 46 0 30 0 24 5 0 0 0 0 448 100 -- 0 54 -- 0 42 16 0 0 5 -- -- -- -- 449 100 71 0 24 0 76 13 30 0 51 5 0 0 0 0 450 100 -- 0 54 11 46 34 30 0 51 5 0 0 0 0 451 100 16 100 72 0 0 0 0 0 0 5 0 0 0 0 452 100 36 0 54 46 0 67 30 0 0 5 0 0 0 0 453 100 55 32 75 94 0 0 100 0 0 5 0 0 0 0 454 100 0 0 0 22 0 0 0 0 0 5 -- -- -- -- 455 100 64 65 0 12 0 0 43 0 0 5 0 0 0 0 456 100 82 0 58 53 98 0 96 9 0 5 0 0 0 0 477 100 95 100 76 100 48 48 100 0 0 5 P P P P 594 100 86 100 93 77 2 -- 100 0 79 5 0 60 100 50 596 100 -- -- 89 -- 0 0 -- 0 25 5 -- -- -- -- 20 91 95 35 94 0 0 100 -- -- 603 100 44 97 91 69 0 -- 95 0 0 5 0 0 0 0 605 100 70 99 32 81 0 -- 100 0 0 5 0 0 0 0 608 100 87 100 98 98 4 81 100 0 0 5 0 0 P P 618 100 100 100 98 89 0 -- 100 0 0 5 0 80 80 P 620 100 100 100 96 98 51 100 100 0 0 5 0 0 P 0 622 100 100 100 84 99 0 100 100 0 26 5 0 0 P 0 627 100 -- -- 38 -- 0 14 -- 0 61 5 -- -- -- -- 20 31 70 19 81 0 0 99 -- -- 644 100 100 100 94 100 100 100 100 23 0 5 0 0 P P 646 100 100 100 95 98 97 61 100 0 99 5 100 0 0 0 651 100 -- -- 42 -- 0 62 -- 0 46 5 0 0 0 0 20 67 0 7 67 0 0 100 -- -- 656 100 93 100 88 97 0 50 100 0 20 5 0 P P P 657 100 62 100 81 98 49 97 100 24 37 5 0 0 0 0 661 100 -- -- 56 -- 0 70 -- 5 85 5 -- -- -- -- 20 81 79 61 62 0 10 100 -- -- 663 100 42 100 95 99 57 36 100 0 39 5 -- -- -- -- 667 100 -- -- 4 -- 0 0 -- 0 10 5 0 0 0 0 20 13 14 7 39 0 0 0 -- -- 668 100 -- -- 76 -- 1 0 -- 22 31 5 -- -- -- -- 20 65 17 31 31 1 0 100 -- -- 669 100 100 100 90 100 96 100 100 0 0 5 0 0 P 0 671 100 100 100 92 94 84 100 100 0 84 5 0 P P 0 675 100 -- -- 30 -- 0 62 -- 0 69 5 -- -- -- -- 20 40 0 42 44 0 0 16 -- -- 685 100 -- -- 0 -- 0 29 -- -- -- 5 -- -- -- -- 20 57 66 28 67 -- 15 100 -- -- 721 100 73 89 95 94 18 100 100 0 0 5 P P P P 724 100 100 100 95 100 63 100 100 0 0 5 0 P P P 726 100 -- -- -- -- 0 0 -- 0 38 5 0 20 0 0 20 75 0 23 81 0 0 100 -- -- 815 100 40 98 0 62 2 -- 97 0 65 5 0 0 0 0 905 100 -- -- 19 -- 0 37 -- 0 87 5 0 0 0 0 20 7 0 15 47 0 0 16 -- --1276 100 100 -- 96 100 1 97 100 0 0 5 0 P 0 P 20 93 100 86 100 1 52 100 -- --1276a 100 -- -- 53 -- 1 0 -- 16 22 5 -- -- -- -- 20 42 26 33 88 1 0 100 -- --1277 100 9 65 0 0 0 0 39 0 25 5 0 0 0 01277a 100 -- -- 36 -- 1 52 -- 8 31 5 -- -- -- -- 20 58 74 24 95 1 0 100 -- --1278 100 100 100 87 85 17 36 100 0 16 5 0 0 01300 100 100 100 93 92 58 81 100 0 0 5 0 0 0 01304 100 100 100 97 100 78 88 100 0 18 5 0 0 0 01377 100 100 100 96 92 58 100 100 0 44 5 0 P 0 P1381 100 100 100 97 98 51 73 100 0 78 5 0 50 0 01451 100 86 84 48 77 2 -- 93 0 79 5 0 0 0 01459 100 72 70 65 31 17 0 65 0 74 5 0 0 0 01468 100 40 0 0 77 2 -- 93 0 46 5 0 60 0 01469 100 68 84 81 77 2 -- 100 24 89 5 0 80 70 01527 100 0 100 93 100 -- 35 100 0 0 5 0 P 0 P__________________________________________________________________________
TEST A
Seeds of crabgrass (i Digitaria spp.), barnyardgrass (Echinochloa crusgalli), giant foxtail (Setaria faberii), wild oats (Avena fatua), cheatgrass (Bromus secalinus), velvetleaf (Abutilon theophrasti), morningglory (Ipomoea spp.), cocklebur (Xanthium pensylvanicum), sorghum, corn, soybean, sugarbeet, cotton, rice, wheat, barley and purple nutsedge (Cyperus rotundus) tubers were planted and treated preemergence with the test chemicals dissolved in a non-phytotoxic solvent. At the same time, these crop and weed species were treated with a soil/foliage application. At the time of treatment, the plants ranged in height from 2 to 18 cm. Treated plants and controls were maintained in a greenhouse for sixteen days, after which all species were compared to controls and visually rated for response to treatment. The ratings, summarized in Table A, are based on a numerical scale extending from 0=no injury, to 10=complete kill. The accompanying descriptive symbols have the following meanings:
C=chlorosis/necrosis;
B=burn;
D=defoliation;
E=emergence inhibition;
G=growth retardation;
H=formative effect;
U=unusual pigmentation;
X=axillary simulation;
S=albinism; and
Y=abscised buds or flowers.
TABLE A__________________________________________________________________________POSTEMERGENCE CMPD 52 CMPD 56 CMPD 52 (salt) CMPD 56 (salt) CMPD 57 CMPD 58 CMPD 59 CMPD__________________________________________________________________________ 61RATE = KG/HA 0.1 0.4 0.4 0.4 0.4 0.4 0.4 0.4 0.4COKER COTTON 2H 2H 0 7P,9G 4H 10P,9G 10P,9G 0 2HCULT MORNINGLRY 2C,4H 3C,6H 0 4C,9G 3C,7G 5C,9G 2C,3G 3C,5H 3C,COCKLEBUR 0 2C 0 3H,8G 2C 1H 2C,8H 0 1CPURPLE NUTSEDGE 0 -- 0 0 5G 0 0 0LARGE CRABGRASS 0 3C,6G 0 4G 0 9C 2C,8H 0 0BARNYARDGRASS 0 0 0 5G 0 7H 0 0 0WILD OATS 0 2C,4G 0 0 0 0 0 0 0ERA WHEAT 0 0 0 0 0 0 0 0 0G4646 CORN 0 0 0 0 0 0 0 0 0WILLMS SOYBEANS 0 1C 0 3C,8G 1C 4C,9G 4C,9G 1C,1H 3HRICE DRY SEEDED 0 1C 0 0 0 0 0 0 0G522 SORGHUM 0 0 0 0 0 0 0 0 0CHEAT GRASS 0 0 0 0USH11 SUGARBEET 0 4G 0 5H,5I 2H 4H,5I 3H,7G 4H 3HVELVETLEAF 3G 2C,5G 0 7G 2G 4C,9G 2C,8G 0 3C,5GGIANT FOXTAIL 0 2C,5G 0 0 0 9G 0 0 0KLAGES BARLEY 0 0 0 0 0 0 0 0 0DOWNY BROME 0 0 0 0 0__________________________________________________________________________ CMPD 66 CMPD 67 CMPD 99 CMPD 101 CMPD 106 CMPD 107 CMPD 108 CMPD__________________________________________________________________________ 208RATE = KG/HA 0.4 0.4 0.4 0.4 0.4 0.4 0.4 0.4COKER COTTON 10P,9G 10P,9G 5H 9G,10P 4G 10P,8G 6H 0CULT MORNINGLRY 5C,9G 2C,2G 2C,4H 5C,9H 2C,8G 5C,9G 3C,6G 2C,5HCOCKLEBUR 2C,5H 2C,5G 4C,7H 3C,6H 2C,2H 3C,5G 2C,2H 2CPURPLE NUTSEDGE 0 0 0 0 5G 0 0 5GLARGE CRABGRASS 0 4G 9G 7G 2G 0 0 0BARNYARDGRASS 0 0 0 0 5H 7H 0 0WILD OATS 0 0 0 0 0 0 0 0ERA WHEAT 0 0 0 0 0 0 0 0G4646 CORN 0 0 0 0 0 0 0 0WILLMS SOYBEANS 3C,4H 1C,4H 3C,5H 2C,4H 2C,5G 5C,9G 2C,7G 2C,2HRICE DRY SEEDED 0 0 0 0 0 2C,5G 0 0G522 SORGHUM 0 0 0 0 0 0 0 0CHEAT GRASS 0 0 0 0 0 0USH11 SUGARBEET 8H,5I 7H,5I 7H 6H 5G 0 3C,6G 6HVELVETLEAF 3G 2C,5G 8G 9H 3C,7G 3C,6G 2C,5G 8GGIANT FOXTAIL 0 0 0 0 0 0 0 0KLAGES BARLEY 0 0 0 0 0 0 0 0DOWNY BROME 0 0__________________________________________________________________________ CMPD 594 CMPD 594 CMPD 596 CMPD 598 CMPD 603 CMPD 605 CMPD 611 CMPD__________________________________________________________________________ 618RATE = KG/HA 0.4 0.4 0.4 0.4 0.4 0.4 0.4 2COKER COTTON 4G 3G 0 8G 0 0 7G &P,9GCULT MORNINGLRY 6G 2C,2H 2C 0 3B 2B 0 0COCKLEBUR 2C 0 1C 2C 1B 1B 1H 1HPURPLE NUTSEDGE 0 0 3G 0 0 0 0LARGE CRABGRASS 2G 2G 0 2G 0 0 5G 8GBARNYARDGRASS 0 0 0 0 0 0 2C 0WILD OATS 0 0 0 2G 0 0 0 0ERA WHEAT 0 0 0 3G 0 0 0 0G4646 CORN 0 2G 0 0 0 0 0 0WILLMS SOYBEANS 2B,3H 2C,3H 2C 2C,2H 0 1C 2C,4H 2C,4GRICE DRY SEEDED 3G 0 0 0 0 0 0 0G522 SORGHUM 0 0 0 0 0 0 0 0CHEAT GRASS 0 0 0 0 0 0 0 0USH11 SUGARBEET 0 3G 1H 4G,5I 0 0 0 5HVELVETLEAF 2C 0 1C 0 1B 0 0 2C,7GGIANT FOXTAIL 0 2G 0 3G 0 0 0 8GKLAGES BARLEY 0 0 0 0 0 0 0 0__________________________________________________________________________ CMPD 620 CMPD 624 CMPD 627 CMPD 644 CMPD 644 CMPD 646 CMPD__________________________________________________________________________ 648RATE = KG/HA 0.4 2 0.4 0.4 2 0.1 0.4 0.4 0.4COKER COTTON 3H 10P,9G 2H,9G 1C 5G 2C,7G 9G,10P 9P,9GCULT MORNINGLRY 2C,5G 3C,8G 2C,3H 2C,6G 6C,9G 3C,3G 3C,5G 3C,8G 1CCOCKLEBUR 2C,2H 3C,9G 2C,5H 2C 5C,8H 0 2C 2C 2CPURPLE NUTSEDGE 0 5G 0 0 8G,5X 0 0 0 0LARGE CRABGRASS 9G 2C,9G 9C 0 3C,9G 0 0 6G 0BARNYARDGRASS 2H 3C,9H 6H 0 5C,9H 0 0 0 0WILD OATS 0 0 0 0 3C,6G 0 0 0 0ERA WHEAT 0 0 2G 0 4C,8G 0 0 0 0G4646 CORN 3C,3H 3C,7H 0 0 3C,6H 0 0 0 0WILLMS SOYBEANS 3C,8G 4C,9G 3C,8H 1H 9C 2C,2H 2C,5H 5C,8H 2CRICE DRY SEEDED 2C,4G 2C,8G 0 0 3C,8G 0 1C 0 0G522 SORGHUM 2C 2C,3H 0 0 3C,9H 0 0 0 0CHEAT GRASS 0 8G 0 0 2C,8G 0 0USH11 SUGARBEET 3H 8H 7H,5I 2H 5G,5I 2G 7G 4H 4G,5IVELVETLEAF 3C,5H 2C,9G 1C 0 9G 3G 2C,6G 2C,3G 2C,5GGIANT FOXTAIL 2C,7H 9G 2C,9G 0 3C,9G 0 2C,3G 0 0KLAGES BARLEY 0 0 0 0 2C,9G 0 0 0 0DOWNY BROME 0 0__________________________________________________________________________ CMPD 651 CMPD 653 CMPD 656 CMPD 658 CMPD 659 CMPD 661 CMPD 669 CMPD__________________________________________________________________________ 673RATE = KG/HA 0.4 0.4 0.4 0.4 0.4 0.4 2 0.4COKER COTTON 0 10P,9G 7G 0 0 1C,3H 3C,7H 10P,9GCULT MORNINGLRY 2C 2C 2C,3H 0 3C,6G 1C 6C,9G 2C,1HCOCKLEBUR 1C 2C,5G 2C 0 2C, 1C 3C,7G 2C,3HPURPLE NUTSEDGE 0 2G 0 0 0 4G 0LARGE CRABGRASS 0 5C,9G 2G 0 0 0 2G 3C,3GBARNYARDGRASS 0 0 0 0 0 0 5C,9G 0WILD OATS 0 0 0 0 0 0 2C,4G 0ERA WHEAT 0 0 0 0 0 0 2G 0G4646 CORN 2G 2G 0 0 0 0 0 0WILLMS SOYBEANS 1C 3C,7G 2C 0 3C 1H 5C,9G 1C,1HRICE DRY SEEDED 0 0 0 0 0 0 0 0G522 SORGHUM 0 0 0 0 0 0 2G 0CHEAT GRASS 0 0 0 0 0 0 3G 0USH11 SUGARBEET 1H 2C,7H 4H 0 0 4H 5G,5I 8H,5IVELVETLEAF 0 1C 8G 2C,5G 1C 6G 1CGIANT FOXTAIL 0 2C,7H 0 0 0 0 2G 9HKLAGES BARLEY 0 0 0 0 0 0 2G 0__________________________________________________________________________ CMPD 675 CMPD 721 CMPD 724 CMPD 724 CMPD 726 CMPD 753 CMPD 754 CMPD__________________________________________________________________________ 782RATE = KG/HA 0.4 0.4 0.4 0.4 0.4 0.4 0.4 0.4COKER COTTON 0 5G 6G 10P,9G 4H 10P,9G 2H 10P,9GCULT MORNINGLRY 1C 3C,6H 3C,5H 5C,9G 3C,7G 4C,9G 5C,9G 5C,9GCOCKLEBUR 0 2C 3C,4H 3C,9H 1C,2H 2C,6G 2C,3H 8GPURPLE NUTSEDGE 0 0 2C,8H 0 0 0 0 0LARGE CRABGRASS 0 0 9G 5G 0 4C,9G 0 5C,9GBARNYARDGRASS 0 0 2C,3H 7G 0 5H 0 7HWILD OATS 0 0 0 0 0 0 0 0ERA WHEAT 0 0 0 2G 0 0 0 0G4646 CORN 0 0 0 0 2G 0 0 0WILLMS SOYBEANS 1C 2C 4C,8H 3C,9G 2H 9C 2C,3H 8GRICE DRY SEEDED 0 0 5G 0 0 0 0 0G522 SORGHUM 0 0 0 0 0 2G 0 0CHEAT GRASS 0 0 0 0 0 0 0USH11 SUGARBEET 1C 3H 7H 3H 3H 8H 7G 7H,5IVELVETLEAF 0 6G 9H 3C,9G 0 3C,8G 3G 8GGIANT FOXTAIL 0 0 9G 9G 5G 2C,9G 0 7GKLAGES BARLEY 0 0 0 0 0 0 0 0DOWNY BROME 0__________________________________________________________________________ CMPD 784 CMPD 810 CMPD 811 CMPD 815 CMPD 863 CMPD 879 CMPD 905 CMPD__________________________________________________________________________ 1276RATE = KG/HA 0.4 0.4 0.4 0.4 2 0.4 0.4 0.4 0.4COKER COTTON 10P,9G 0 10P,9G 9G,10P 2B 2C,6G 0 0 4HCULT MORNINGLRY 3H 2C,5G 5C,9G 3C,9H 0 1C,2G 1C,2H 2C 2C,4HCOCKLEBUR 2H 8G 3H,8G 2C,4H 0 2C 1C 0 2CPURPLE NUTSEDGE 0 0 0 0 0 0 0 0LARGE CRABGRASS 6H 5G 9C 0 1B 0 3G 0 0BARNYARDGRASS 0 2G 3C,9G 0 1B 0 0 0 0WILD OATS 0 0 0 0 0 0 0 0 0ERA WHEAT 0 0 0 0 0 0 0 0 0G4646 CORN 0 0 0 0 1B 0 0 0 0WILLMS SOYBEANS 2C,5H 5G 3C,9G 0 2B 2C 2H,5G 0 2C,6HRICE DRY SEEDED 0 0 0 0 0 0 2G 0 0G522 SORGHUM 0 0 0 0 0 0 0 0 0CHEAT GRASS 0 0 0 0 0 0 0 0 0USH11 SUGARBEET 7H 4G 6H,5I 0 1B 0 3G 0 2HVELVETLEAF 2H 8G 4C,9G 0 2B 2C 2G 0 8GGIANT FOXTAIL 2G 2G 9G 0 1B 0 0 0 0KLAGES BARLEY 0 0 0 0 0 0 0 0 0__________________________________________________________________________ CMPD 1276 (salt) CMPD 1276A CMPD 1277 CMPD 1278 CMPD 1279 CMPD 1280 CMPD__________________________________________________________________________ 1377RATE = KG/HA 0.4 0.4 0.4 0.4 0.4 0.4 0.4 2COKER COTTON 9G,10P 7G 3H,6G 0 10P,9G 7G 9G,10P 9G,10PCULT MORNINGLRY 2C,3G 1C 2C,3G 1C 5C,9G 2H 2C,6H 4C,9HCOCKLEBUR 3C 1C 2C,7G 1C 5H 4H 2C,3H 4C,9HPURPLE NUTSEDGE 0 0 0 0 0 -- 4GLARGE CRABGRASS 0 0 4G 4G 3C,5G 9H 0 4C,9GBARNYARDGRASS 0 0 1C 0 2G 5H 2G 5C,9HWILD OATS 0 0 0 0 0 0 0 0ERA WHEAT 0 0 0 0 0 0 0 0G4646 CORN 0 0 0 0 0 0 0 0WILLMS SOYBEANS 3C 2H,6G 1C,1H 0 3C,5G 5C,9G 3C,5H 3C,6HRICE DRY SEEDED 0 0 0 0 0 0 0 0G522 SORGHUM 0 2G 0 0 0 2G 0 0CHEAT GRASS 0 0 0 0 0 0 0 2GUSH11 SUGARBEET 0 3H 1H 1H 7H,5I 8H 6H,5I 7H,5IVELVETLEAF 2C,4G 2C 0 0 3C,7G 7H 2C,3H 3C,7HGIANT FOXTAIL 0 0 3G 0 0 9H 0 3C,9HKLAGES BARLEY 0 0 0 0 0 0 0 0__________________________________________________________________________ CMPD 1381 CMPD 1304 CMPD 1 CMPD 4 CMPD 9 CMPD 11 CMPD__________________________________________________________________________ 13RATE = KG/HA 0.4 2 0.4 2 0.4 0.4 0.1 0.4 2 0.4COKER COTTON 3G 10P,9G 5H 10P,9G 3H 3C,9H 3H 3H 10P,9G 6HCULT MORNINGLRY 3C,5G 2C,8H 3C,7G 2C,7G 1C,1H 4C,8H 3C,4H 3C,6G 4C,9G 4C,8GCOCKLEBUR 2C 2C,7H 2C,4G 8H 1C,3G 3C,8H 0 3C,6G 3C,9G 3C,3HPURPLE NUTSEDGE 0 2C,5G 0 8G 0 5G 0 9G 7G 0LARGE CRABGRASS 2G 4C,9G 3C,7G 3C,9G 0 9G 0 3G 9C 0BARNYARDGRASS 2H 9H 5H 9H 0 2C,8H 0 0 5C,9G 0WILD OATS 0 2G 0 2G 0 0 0 0 7G 0ERA WHEAT 0 2G 0 4G 0 0 0 0 8G 0G4646 CORN 0 3G 0 3G 2G 2G 0 0 7H 0WILLMS SOYBEANS 2C,4G 2C,8G 2C,5G 2C,6G 2C,3H 4C,8G 1C,1H 2C,4H 4C,9G 3C,5GRICE DRY SEEDED 0 8G 0 7G 0 5G 0 1C 3C,7G 0G522 SORGHUM 0 9H 0 7G 0 5G 0 0 3C,8H 2GCHEAT GRASS -- 2G -- 5G 0 5G 7GUSH11 SUGARBEET 5G 9H 2H 7H,5I 8G 6H 3G 3G 9H,5I 7GVELVETLEAF 0 9G 0 9G 0 2C,8H -- 4G 3C,9G 2CGIANT FOXTAIL 0 9G 0 9H 0 9G 0 2C,2G 9G 3GKLAGES BARLEY 0 2G 0 3G 0 0 0 0 5G 0DOWNY BROME 0 -- 0 -- 0 0 0__________________________________________________________________________ CMPD 15 CMPD 16 CMPD 17 CMPD 18 CMPD 23 CMPD 33 CMPD 34 CMPD__________________________________________________________________________ 34RATE = KG/HA 0.4 0.4 0.4 0.4 0.4 0.4 0.4 0.4COKER COTTON 7G 8G 3H 7G,5I 2H 10P,9G 10P,8G 8P,8GCULT MORNINGLRY 2C,4H 4C,9G 3C,4G 2C 2C,3H 2C,5G 3C,10P 5C,9GCOCKLEBUR 2C 2C,6G 2C,5G 2C,3G 1C,1H 3C,4H 2C,2H 2C,2HPURPLE NUTSEDGE 0 0 0 0 0 0 0 0LARGE CRABGRASS 0 8G 3C,7G 3G 5C,9G 3G 0BARNYARDGRASS 3G 0 0 9H 0 0 0 0WILD OATS 0 0 0 0 0 0 0 0ERA WHEAT 0 0 0 0 0 0 0 0G4646 CORN 0 0 0 0 0 2G 0 0WILLMS SOYBEANS 3C,5H 2C,2H 1C,2H 3C,5G 1C,1H 4C,9G 4C,9G 2C,3HRICE DRY SEEDED 0 2C 1C 0 0 0 2G 0G522 SORGHUM 0 0 0 0 0 0 0 0CHEAT GRASS 0 0 0 0 0 0USH11 SUGARBEET 5H 2G 7H 3G,5I 4H 8H,5I 7H 3GVELVETLEAF 6G 6G 0 2C,5G 0 3C,8G 5C,8G 3C,8GGIANT FOXTAIL 0 7G 3G 5G 2G 9G 0 0KLAGES BARLEY 0 0 0 0 0 0 0 0DOWNY BROME 3G 0__________________________________________________________________________ CMPD 35 CMPD 35 CMPD 35 CMPD 35 CMPD 34 CMPD 35 (salt) (salt) (salt) (salt) CMPD 39 CMPD__________________________________________________________________________ 42RATE = KG/HA 0.4 0.4 2 2 0.4 0.4 0.4 0.4 0.4COKER COTTON 4G 10P,9G 10P,9G 10P,9G 3H 0 9P,8G 8G,10P 1CCULT MORNINGLRY 0 10P,9G 4C,9G 5C,9G 3C,8G 0 2C,2H 2C 2CCOCKLEBUR 2C,3H 2C,5G 3C,8G 4C,9H 2C,1H 0 2C,2H 2C 3CPURPLE NUTSEDGE 0 2G 8G 8G 0 0 0 0 0LARGE CRABGRASS 5G 2C,9G 3C,9G 3C,9G 0 0 0 0 0BARNYARDGRASS 5H 2C,8H 4C,9H 5C,9G 0 0 5H 0 0WILD OATS 0 0 1C 0 0 0 0 0 0ERA WHEAT 0 0 0 0 0 0 0 0 0G4646 CORN 0 1C,3H 3C,7H 3C,7H 2H 0 2G 0 0WILLMS SOYBEANS 4C,7G 10P,9G 3C,9G 4C,9G 3C,9G 2G 9G,5I 2C 1HRICE DRY SEEDED 0 1C 3C,9G 4G 0 0 0 0 0G522 SORGHUM 0 0 3C,9H 7G 0 0 0 0 0CHEAT GRASS 0 5G 4G 0 0 0USH11 SUGARBEET 6G 5H 2C,8H 3H,7G 7G 2G 4H 4H 3HVELVETLEAF 5C,9G 4C,8G 4C,9G 7C,9G 3C,5G 0 3C,8H 4H 5CGIANT FOXTAIL 0 8H 9G 3C,9G 2G 0 0 0 2GKLAGES BARLEY 0 0 1C 6G 0 0 0 0 0DOWNY BROME 0 0 0__________________________________________________________________________ CMPD 47 CMPD CMPD__________________________________________________________________________ 52 RATE = KG/HA 0.4 2 2 COKER COTTON 10P,8G 1C,6H 3H,8G CULT MORNINGLRY 1C 5G 5C,9G COCKLEBUR 1C 2C,7H 3C,9H PURPLE NUTSEDGE 0 0 LARGE CRABGRASS 0 2C,9G 3C,9G BARNYARDGRASS 0 2C,7G 5C,9G WILD OATS 0 2C,2G 2C,4G ERA WHEAT 0 2C,3G 2C,6G G4646 CORN 2G 2C,6H 2C,6G WILLMS SOYBEANS 2C,2H 3C,7H 4C,9G RICE DRY SEEDED 0 2C,5G 2C,6G G522 SORGHUM 0 0 9H CHEAT GRASS 0 5G 2C,6G USH11 SUGARBEET 0 7G 3H,7G VELVETLEAF 0 4G 7C,9G GIANT FOXTAIL 0 2C,7G 1C,9G KLAGES BARLEY 0 0 6G__________________________________________________________________________PREEMERGENCE CMPD 52 CMPD 52 CMPD 56 CMPD 56 CMPD 57 CMPD 58 CMPD 59 CMPD__________________________________________________________________________ 61RATE = KG/HA 0.1 0.4 0.4 0.4 0.4 0.4 0.4 0.4 0.4COKER COTTON -- 2G 0 5G 0 7G 8G 0 0CULT MORNINGLRY 0 8H 0 4C,9G 0 4C,9G 8G 0 0COCKLEBUR 2G 2C,2G 0 2G 0 0 3G 0 0PURPLE NUTSEDGE 0 0 0 5G 0 0 0 0 0LARGE CRABGRASS 2C,7H 4C,9H 0 4C,9G 9G 4C,9G 9G 0 0BARNYARDGRASS 0 9C 5G 7C,9H 0 9C 4C,9G 0 0WILD OATS 0 0 0 0 0 0 0 0 0ERA WHEAT 0 8G 0 0 0 2G 0 0 0G4646 CORN 0 0 0 0 0 2G 3G 0 0WILLMS SOYBEANS 0 0 0 7G 0 3C,9G 4G 0 0RICE DRY SEEDED 0 0 0 0 0 0 0 0 0G522 SORGHUM 0 8G 0 7G 0 8G 7G 0 0CHEAT GRASS 0 5G 9G 3GUSH11 SUGARBEET 0 5H 0 6G 3H 7H 9G 0 0VELVETLEAF 0 4C,8H 0 4C,9G 0 5C,9G 5G 0 0GIANT FOXTAIL 3C,9H 9H 0 9H 4C,9G 9H 3C,9G 0 7GKLAGES BARLEY 0 0 0 0 0 2G 0 0 0DOWNY BROME 2G 3C,8G 0 0 0__________________________________________________________________________ CMPD 66 CMPD 67 CMPD 99 CMPD 101 CMPD 106 CMPD 107 CMPD 108 CMPD__________________________________________________________________________ 208RATE = KG/HA 0.4 0.4 0.4 0.4 0.4 0.4 0.4 0.4COKER COTTON 0 0 0 0 0 3G 0 0CULT MORNINGLRY 0 0 8H 2C,9H 0 5C,9G 3H 0COCKLEBUR 0 0 0 0 0 0 0 0PURPLE NUTSEDGE 0 0 0 0 0 0 10E 0LARGE CRABGRASS 2C,9G 7G 2C,9G 2G 4C,9H 5C,9G 9G 0BARNYARDGRASS 0 3G 2G 2G 0 9H 0 0WILD OATS 0 0 0 0 0 0 0 0ERA WHEAT 0 0 0 0 0 0 0 0G4646 CORN 0 0 0 0 0 0 0 0WILLMS SOYBEANS 0 1H 0 0 2G 0 0 0RICE DRY SEEDED 0 0 0 0 0 0 0 0G522 SORGHUM 0 0 0 0 0 2H 0 0CHEAT GRASS 0 3G 0 0 0 0USH11 SUGARBEET 5G 7G 3H 0 3H 3H 0 2HVELVETLEAF 2G 0 0 0 0 5G 0 0GIANT FOXTAIL 3G 5G 2C,9H 7G 3C,9G 3C,9G 8H 0KLAGES BARLEY 0 0 0 0 3G 0 0 0DOWNY BROME 0 0__________________________________________________________________________ CMPD 594 CMPD 594 CMPD 596 CMPD 598 CMPD 603 CMPD 605 CMPD 611 CMPD__________________________________________________________________________ 618RATE = KG/HA 0.4 0.4 0.4 0.4 0.4 0.4 0.4 2COKER COTTON 0 3G 3G 0 0 0 0 4GCULT MORNINGLRY 0 0 0 0 0 0 0 2HCOCKLEBUR 0 0 2G 2G 0 0 0PURPLE NUTSEDGE 0 0 10E 0 0 0 0 &ELARGE CRABGRASS 9G 2U,9G 9H 3C,9G 0 3G 8G 8HBARNYARDGRASS 4C,8H 2C,8G 3C,7H 2G 0 0 2C,6G 5C,9HWILD OATS 0 3G 0 0 0 0 0 0ERA WHEAT 0 0 0 0 0 0 0 3GG4646 CORN 0 2G 2G 0 0 0 0 3GWILLMS SOYBEANS 0 0 0 0 0 0 0 0RICE DRY SEEDED 0 4G 0 0 0 0 2GG522 SORGHUM 0 3G 2C,9H 0 0 0 0CHEAT GRASS 2G 3G 0 0 0 0 2GUSH11 SUGARBEET 2G 4G 3G 7F 0 0 0 7GVELVETLEAF 4G 5G 2G 0 0 0 5GGIANT FOXTAIL 9G 3C,9G 9H 0 0 3C,8G 9HKLAGES BARLEY 0 0 0 0 0 0 0 0__________________________________________________________________________ CMPD 620 CMPD 624 CMPD 627 CMPD 644 CMPD 646 CMPD__________________________________________________________________________ 648RATE = KG/HA 0.4 2 0.4 0.4 0.1 0.4 0.4 0.4COKER COTTON 9G 9G 0 0 9G 0 0 0 0CULT MORNINGLRY 2C,8G 9G 2G 0 9G 0 2C 0 0COCKLEBUR 3C,7G 2H 2G 3C,7G 0 0 0 0PURPLE NUTSEDGE 5G 0 0 0 10 10E 10E 0 0LARGE CRABGRASS 9H 9H 9H 0 9H 3C,7H 5C,9H 9G 3C,8GBARNYARDGRASS 2C,5H 7C,9H 8H 0 9C 0 5C,9H 0 0WILD OATS 0 0 0 0 4C,8G 0 2C,5G 0 0ERA WHEAT 0 0 0 0 9G 0 0 0 0G4646 CORN 0 1H 0 0 2C,8H 0 0 0 2GWILLMS SOYBEANS 7G 8G 0 0 8G 0 0 3H 0RICE DRY SEEDED 3G 2G 2G 0 6G 0 0 0 0G522 SORGHUM 9G 9G 0 0 3C,9G 0 4G 0 0CHEAT GRASS 0 2G 0 0 7G 0 2GUSH11 SUGARBEET 8H 9H 8H 0 9G 0 6H 5H 7HVELVETLEAF 6G 9H 8G 0 6C,9G 0 2C 2G 4GGIANT FOXTAIL 9H 9H 9H 0 9H 3C,9H 5C,9H 9H 2C,9GKLAGES BARLEY 0 0 0 0 3G 0 0 0 3GDOWNY BROME 0 3C,5G__________________________________________________________________________ CMPD 651 CMPD 653 CMPD 656 CMPD 658 CMPD 659 CMPD 661 CMPD 669 CMPD__________________________________________________________________________ 673RATE = KG/HA 0.4 0.4 0.4 0.4 0.4 0.4 2 0.4COKER COTTON 0 5G 0 0 3G 0 8G 0CULT MORNINGLRY 0 2C,5G 0 0 1C 0 5C,9H 0COCKLEBUR 0 2H 0 2G 0 0 0PURPLE NUTSEDGE 0 0 2G 6G 10E 0 3G 0LARGE CRABGRASS 0 9C 5C,9H 9H 3C,9G 5G 9H 9HBARNYARDGRASS 0 3C,9G 0 5G 2C,5G 0 9C 4HWILD OATS 0 0 0 0 0 0 2C 0ERA WHEAT 0 2G 0 0 0 0 0 2GG4646 CORN 0 0 0 4G 0 0 2C,5H 2GWILLMS SOYBEANS 0 0 0 2G 0 0 8G 0RICE DRY SEEDED 0 0 0 0 0 0 0 0G522 SORGHUM 0 7G 0 0 0 0 9G 0CHEAT GRASS 0 8G 0 0 0 0 0 3GUSH11 SUGARBEET 0 8H 2H 0 0 5G 8G 6HVELVETLEAF 0 5C,9G 0 0 7G 0 4C,8G 0GIANT FOXTAIL 0 5C,9H 4C,9H 7H 3C,9H 3G 9H 2C,8GKLAGES BARLEY 0 0 0 0 0 0 0 2G__________________________________________________________________________ CMPD 675 CMPD 721 CMPD 724 CMPD 724 CMPD 726 CMPD 753 CMPD 754 CMPD__________________________________________________________________________ 782RATE = KG/HA 0.4 0.4 0.4 0.4 0.4 0.4 0.4 0.4COKER COTTON 0 0 0 8G 0 3G 0 0CULT MORNINGLRY 0 3H 2C,8H 9C 0 9G 0 3C,9HCOCKLEBUR 0 0 0 2G 3H 0 0PURPLE NUTSEDGE 0 0 0 0 0 9G 0 0LARGE CRABGRASS 0 7G 2C,9H 4C,9H 7G 9G 8G 3C,9GBARNYARDGRASS 0 0 5C,9H 5C,9H 3C,6G 8G 2H 2C,9HWILD OATS 0 0 0 0 0 0 0 0ERA WHEAT 0 0 0 0 0 0 0 0G4646 CORN 0 0 0 0 2G 0 0 0WILLMS SOYBEANS 0 0 0 6G 0 3G 0 3GRICE DRY SEEDED 0 0 0 0 0 0 0 0G522 SORGHUM 0 0 0 6G 0 5G 0 6GCHEAT GRASS 0 0 0 8G 0 0 0USH11 SUGARBEET 0 2C,3H 5H 8G 2H 8H 3G 9GVELVETLEAF 0 2G 9G 4C,9G 0 4G 0 2C,8GGIANT FOXTAIL 0 7G 3C,9H 9H 2C,9H 3C,9G 7G 9HKLAGES BARLEY 0 0 0 0 0 0 0 0DOWNY BROME 0__________________________________________________________________________ CMPD 784 CMPD 810 CMPD 811 CMPD 815 CMPD 863 CMPD 879 CMPD 905 CMPD__________________________________________________________________________ 1276RATE = KG/HA 0.4 0.4 0.4 0.4 2 0.4 0.4 0.4 0.4COKER COTTON 0 0 9G 0 0 5G 0 0 0CULT MORNINGLRY 1H 0 9C 0 0 0 0 0 0COCKLEBUR 0 2G 0 2G 0 0PURPLE NUTSEDGE 5G 0 10E 0 0 4G 8G 0 0LARGE CRABGRASS 9H 9H 5C,9H 9G 0 4G 9H 0 4C,9HBARNYARDGRASS 0 4C,9H 7C,9H 0 0 3G 4C,8H 0 4C,8HWILD OATS 0 2G 0 0 0 2G 0 0 0ERA WHEAT 0 2G 0 0 0 0 0 0 0G4646 CORN 0 0 2G 0 0 0 2G 0 0WILLMS SOYBEANS 0 0 7G 0 0 0 2G 0 0RICE DRY SEEDED 0 0 0 0 0 0 0 0 0G522 SORGHUM 2G 0 8G 0 0 0 0 0 0CHEAT GRASS 0 3G 5G 0 0 2G 2G 0 0USH11 SUGARBEET 5G 9G 8G 0 0 0 5H 0 2HVELVETLEAF 4G 3G 2C,9G 3G 0 0 4G 0 0GIANT FOXTAIL 3G 9H 9H 2G 0 8G 9H 0 4C,9HKLAGES BARLEY 0 0 2G 0 0 0 0 0 0__________________________________________________________________________ CMPD 1276 CMPD 1276A CMPD 1277 CMPD 1278 CMPD 1279 CMPD 1280 CMPD__________________________________________________________________________ 1377RATE = KG/HA 0.4 0.4 0.4 0.4 0.4 0.4 0.4 2COKER COTTON 0 0 0 0 0 2G 0 7GCULT MORNINGLRY 1C,3G 0 0 0 0 2H 2C 2C,3GCOCKLEBUR 0 0 0 0 0 0 0 2GPURPLE NUTSEDGE 8G 10E 0 0 0 0 0 9GLARGE CRABGRASS 7G 0 5C,9G 0 7G 9H 4C,8H 5C,9HBARNYARDGRASS 0 0 3C,8H 0 2G 3G 2G 10CWILD OATS 0 0 0 0 0 0 0 0ERA WHEAT 0 0 0 0 0 0 0 0G4646 CORN 0 0 2G 0 0 0 0 0WILLMS SOYBEANS 0 0 0 0 0 0 0 5GRICE DRY SEEDED 2G 0 0 0 0 0 0 0G522 SORGHUM 0 0 0 0 0 0 0 2C,6GCHEAT GRASS 0 0 0 0 0 0 0 0USH11 SUGARBEET 7G 6G 7H 0 3H 5G 2C,6H 8G,5IVELVETLEAF 4G 8G 3G 0 5G 5G 3G 7GGIANT FOXTAIL 2C,9G 0 3C,9H 2G 8G 9H 3C,9H 4C,9HKLAGES BARLEY 0 0 0 0 0 0 0 0__________________________________________________________________________ CMPD 1381 CMPD 1304 CMPD 1 CMPD 4 CMPD 9 CMPD 11 CMPD__________________________________________________________________________ 13RATE = KG/HA 0.4 2 0.4 2 0.4 0.4 0.1 0.4 2 0.4COKER COTTON 0 8G 0 7G 0 8G 0 5H 9G 0CULT MORNINGLRY 0 7H 0 7G 0 9H 0 1C 9G 0COCKLEBUR 0 3G 0 0 0 0 0 0 2C,8G 0PURPLE NUTSEDGE 0 0 0 3G 5G 0 0 8G 10E 0LARGE CRABGRASS 5C,9G 3C,9G 4C,9H 4C,9G 4C,9G 9C 3C,7H 4C,9H 9H 5C,9GBARNYARDGRASS 3H 5C,9H 0 5C,9H 1C 10C 4C,6H 9C 5C,9H 3C,7GWILD OATS 0 0 0 2G 0 0 0 0 8G 0ERA WHEAT 0 0 0 0 2G 0 0 2G 2C,9G 0G4646 CORN 0 3G 0 5G 0 0 0 2C,2H 3C,8H 3GWILLMS SOYBEANS 0 9G 0 7G 2G 0 0 3C,7H 9G 0RICE DRY SEEDED 0 4G 0 0 3G 0 0 0 0 0G522 SORGHUM 0 7G 3G 9G 0 9H 0 2C,9G 9H 2HCHEAT GRASS -- 0 -- 6G 0 0 3C,8GUSH11 SUGARBEET 2H 8H 0 8H 4H 8H 3H 6H 9H 7HVELVETLEAF 3G 8G 5G 7G 5G 7H 0 5C,9H 9G 9CGIANT FOXTAIL 4C,9H 9H 3C,9H 9H 3C,9H 3C,9H 4C,9H 4C,9H 9H 2C,9GKLAGES BARLEY 0 0 0 0 0 0 0 0 4G 0DOWNY BROME 0 -- 0 -- 0 2C,7G 4G__________________________________________________________________________ CMPD 15 CMPD 16 CMPD 17 CMPD 18 CMPD 23 CMPD 33 CMPD 34 CMPD__________________________________________________________________________ 34RATE = KG/HA 0.4 0.4 0.4 0.4 0.4 0.4 0.4 0.4COKER COTTON 0 5G 0 0 0 8G 0 0CULT MORNINGLRY 0 0 0 1H 0 7G 6G 8GCOCKLEBUR 0 0 0 0 0 2G 0 0PURPLE NUTSEDGE 9G 10E 10E 7G 0 0 0 0LARGE CRABGRASS 3C,9H 8G 9G 10H 9H 8G 3C,9G 4C,9GBARNYARDGRASS 0 5G 3G 5C,9H 3C,6G 2C,8H 5G 5HWILD OATS 0 0 0 0 0 0 0 0ERA WHEAT 0 0 0 7G 0 0 0 0G4646 CORN 0 2G 0 2G 0 0 0 0WILLMS SOYBEANS 0 0 0 0 0 4G 0 0RICE DRY SEEDED 0 2G 0 0 0 2G 0 0G522 SORGHUM 0 0 0 9G 0 5G 1H 0CHEAT GRASS 0 0 0 8G 4G 0USH11 SUGARBEET 0 6G 0 7H 3H 7G 5H 2HVELVETLEAF 6G 5G 2G 7G 3G 2G 7G 5GGIANT FOXTAIL 0 9H 6G 9H 5C,9H 9H 3C,9H 3C,9HKLAGES BARLEY 0 0 0 0 0 0 0 0DOWNY BROME 0 0__________________________________________________________________________ CMPD 34 CMPD 35 CMPD 35 CMPD 35 CMPD 35 CMPD 35 CMPD 39 CMPD__________________________________________________________________________ 42RATE = KG/HA 0.4 0.4 2 2 0.4 0.4 0.4 0.4 0.4COKER COTTON 0 6G 8H 9G 0 8G 0 0CULT MORNINGLRY 2C,8G 8H 9H 3C,9H 8G 0 6G 0 0COCKLEBUR 0 1H 2H 0 0 0 0 0PURPLE NUTSEDGE 0 0 0 3G 0 0 0 0 0LARGE CRABGRASS 4C,9G 9H 10E 10H 3C,9G 0 3C,9G 6G 2C,9GBARNYARDGRASS 3C,8G 6C,9H 7C,9H 9H 7H 0 3C,9G 2G 0WILD OATS 0 0 7G 8G 0 0 2G 0 2GERA WHEAT 0 0 8G 5G 0 0 0 0 0G4646 CORN 2G 0 2C,3H 3G 0 0 0 0 0WILLMS SOYBEANS 0 2G 7G 2C,9G 0 0 9G 0 0RICE DRY SEEDED 0 0 1C 0 0 0 4G 0 0G522 SORGHUM 0 7G 9H 2C,9G 0 0 5G 0 0CHEAT GRASS 0 8G 8G 5G 0 0USH11 SUGARBEET 4H 5H 9H 9G 3H 0 5H 2H 5HVELVETLEAF 5C,8G 8H 9H 9G 5C,9G 0 7G 0 0GIANT FOXTAIL 3C,9G 9H 9H 9H 9H 0 3C,9G 6G 3C,9GKLAGES BARLEY 0 0 0 0 0 0 0 0 0DOWNY BROME 3G 0 0__________________________________________________________________________ CMPD 47 CMPD CMPD__________________________________________________________________________ 52 RATE = KG/HA 0.4 2 2 COKER COTTON 0 5G 9G CULT MORNINGLRY 0 9H 5C,9H COCKLEBUR 0 1C,2G PURPLE NUTSEDGE 0 0 LARGE CRABGRASS 9G 10H BARNYARDGRASS 1H 3C,9H WILD OATS 0 2G 2C,8G ERA WHEAT 0 0 4C,9G G4646 CORN 3G 0 3C,8H WILLMS SOYBEANS 0 0 9G,5I RICE DRY SEEDED 0 0 8G G522 SORGHUM 0 2C,9G 9G CHEAT GRASS 0 3G 9G USH11 SUGARBEET 4H 9H 9G VELVETLEAF 0 9H 9G GIANT FOXTAIL 3C,9H 3C,9H 10H KLAGES BARLEY 0 0 7G__________________________________________________________________________
TEST B
Postemergence
Three round pans (25 cm diameter by 12.5 cm deep) were filled with Sassafras sandy loam soil. One pan was planted with nutsedge (Cyperus rotundus) tubers, crabgrass (Digitaria sanguilalis), sicklepod (Cassia obtusifolia), jimsonweed (Datura stramonium), velvetleaf (Abutilon theophrasti), lambsquarters (Chenopodium album), rice (Oryza sativa), and teaweed (Sida spinosa). The second pot was planted with green foxtail (Setaria viridis), cocklebur (Xanthium pensylvanicum), morningglory (Ipomoea hederacea), cotton (Gossypium hirsutum), johnsongrass (Sorghum halepense), barnyardgrass (Echinochloa crusgalli), corn (Zea mays), soybean (Glycine max), and giant foxtail (Setaria faberi). The third pot was planted with wheat (Triticum aestivum), barley (Hordeum vulgare), wild buckwheat (Polygonum convolvulus L.), cheatgrass (Bromus secalinus L.), sugarbeet (Beta vulgaris), wild oat (Avena fatua L.), common chickweed (Stellaria media), blackgrass (Alopecurus myosuroides), and rape (Brassica napus). The plants were grown for approximately fourteen days, then sprayed postemergence with the chemicals dissolved in a nonphytotoxic solvent.
Premergence
Three round pans (25 cm diameter by 12.5 cm deep) were filled with Sassafras sandy loam soil. One pan was planted with nutsedge tubers, crabgrass, sicklepod, jimsonweed, velvetleaf, lambsquarters, rice and teaweed. The second port was planted with green foxtail, cocklebur, morningglory cotton, johnsongrass, barnyardgrass, corn, soybean, and giant foxtail. The third pot was planted with wheat, barley, wild buckwheat, cheatgrass, sugarbeet, wild oat, viola, blackgrass, and rape. The three pans were sprayed preemergence with the chemicals dissolved in a nonphytotoxic solvent.
Treated plants and controls were maintained in the greenhouse for approximately 24 days, then all rated plants were compared to controls and visually rated for plant response.
Response ratings are based on a scale of 0 to 100 where 0=no effect, and 100=complete control. A dash (-) response means no test.
Response ratings are contained in Table B.
TABLE B__________________________________________________________________________ CMPD 51 CMPD 669 CMPD 35 CMPD 52RATE = G/HA 0250 0125 0062 2000 1000 0500 0250 0500 0250 2000 1000 0250 0062 2000 1000 0250__________________________________________________________________________POSTGIANT FOXTAIL -- 0 0 -- 50 30 0 100 90 -- 80 70 30 -- 70 50VELVETLEAF 30 0 0 80 50 30 0 100 70 100 90 70 50 90 70 50USH11 SUGARBEET -- 30 0 -- 80 70 50 70 50 -- 70 60 50 -- 70 50LARGE CRABGRASS 0 0 0 80 70 50 30 100 50 100 100 90 30 100 90 90PRICKLY SIDA 30 0 0 90 70 50 30 100 90 100 90 70 50 90 80 70JIMSONWEED 0 0 0 60 40 20 0 60 20 90 70 50 0 90 70 50RICE DRY SEEDED 0 0 0 0 0 0 0 30 10 60 30 0 0 60 40 0COCKLEBUR 30 0 0 60 30 0 0 30 -- 90 70 50 30 90 60 30COKER COTTON 20 0 0 70 50 30 0 90 70 50 40 30 20 50 40 30WILLMS SOYBEANS -- 0 0 -- 40 0 0 80 60 -- 80 60 20 -- 30 0BARNYARDGRASS 0 0 0 70 50 30 0 100 80 80 60 30 0 80 60 30WILD OATS -- 0 0 -- 0 0 0 50 0 -- 30 0 0 -- 30 0IVY MORNINGLORY 30 0 0 100 70 50 30 20 0 70 60 50 30 90 70 50ERA WHEAT -- 0 0 -- 0 0 0 10 0 -- 0 0 0 -- 50 30SICKLEPOD 0 0 0 80 30 0 0 50 30 90 70 50 30 70 40 30JOHNSONGRASS 0 0 0 30 0 0 0 100 100 90 70 50 30 90 70 50PURPLE NUTSEDGE 0 0 0 30 0 0 0 80 -- 30 0 0 0 50 30 0G4646 CORN -- 0 0 -- 0 0 0 0 0 -- 40 0 0 -- 40 0WILD BUCKWHEAT -- 0 0 -- 70 60 50 -- 0 -- 70 50 30 -- 70 50BLACKGRASS -- 0 0 -- 50 30 0 90 60 -- 50 30 0 -- 70 50ALTEX RAPE -- 0 0 -- 50 30 0 80 60 -- 80 50 30 -- 50 30KLAGES BARLEY -- 0 0 -- 0 0 0 0 0 -- 0 0 0 -- 30 0GREEN FOXTAIL 30 0 0 80 50 30 0 100 90 90 80 60 30 90 70 50CHEAT GRASS -- 0 0 -- 0 0 0 -- 0 0 0 -- 50 30FIELD VIOLET -- 0 0 -- 0 0 0 -- 0 0 0 -- 50 30LAMBSQUARTER 70 60 50 90 80 70 60 100 80 100 100 70 50 90 80 70CHICKWEED SPP. 80 20DOWNY BROME 40 20__________________________________________________________________________ CMPD 52 CMPD 18 CMPD 35 CMPD 33 CMPD 35 CMPD 1381RATE = G/HA 0062 0500 0250 0250 0500 0250 0125 0500 0250 0125 0062 0250 0125 0062__________________________________________________________________________POSTGIANT FOXTAIL 30 30 0 80 30 0 0 0 0 0 -- 60 30 0VELVETLEAF 30 80 50 70 90 70 60 90 70 50 30 0 0 0USH11 SUGARBEET 30 60 50 60 90 80 70 50 30 0 -- 70 50 30LARGE CRABGRASS 50 30 20 80 70 60 50 70 50 60 30 0 0 0PRICKLY SIDA 50 70 50 80 70 60 50 90 60 30 0 0 0 0JIMSONWEED 30 40 0 50 90 70 50 30 20 0 0 60 50 30RICE DRY SEEDED 0 40 30 0 0 0 0 0 0 0 0 0 0 0COCKLEBUR 0 40 20 30 30 20 0 30 0 0 0 50 30 0COKER COTTON 0 60 40 90 30 30 30 60 40 30 0 50 30 0WILLMS SOYBEANS 0 30 30 30 60 50 40 60 40 30 -- 30 0 0BARNYARDGRASS 0 10 10 90 0 0 0 0 0 0 0 0 0 0WILD OATS 0 30 0 0 30 0 0 0 0 0 -- 0 0 0IVY MORNINGLORY 30 30 20 70 80 70 50 50 30 0 0 50 30 0ERA WHEAT 0 0 0 0 0 0 0 0 0 0 -- 0 0 0SICKLEPOD 0 40 20 20 50 30 20 50 30 0 0 30 0 0JOHNSONGRASS 0 40 0 90 0 0 0 50 30 0 0 30 0 0PURPLE NUTSEDGE 0 30 0 0 0 0 0 60 30 0 0 30 0 0G4646 CORN 0 0 0 0 0 0 0 0 0 0 -- 30 0 0WILD BUCKWHEAT 30 40 -- 50 60 30 0 80 50 30 -- 50 30 0BLACKGRASS 30 40 0 40 30 0 0 50 30 0 -- 70 50 30ALTEX RAPE 0 100 80 50 70 50 30 30 0 0 -- 30 0 0KLAGES BARLEY 0 10 0 0 0 0 0 0 0 0 -- 0 0 0GREEN FOXTAIL 30 40 0 80 30 0 0 50 30 0 0 30 0 0CHEAT GRASS 0 30 10 0 0 0 0 0 0 -- 0 0 0FIELD VIOLET 0 90 60 30LAMBSQUARTER 50 100 50 60 80 70 50 50 30 0 0 0 0 0CHICKWEED SPP. 50 0 0 60 30 0 -- 0 0 0DOWNY BROME 0__________________________________________________________________________ CMPD 1304 CMPD 810 CMPD 9 CMPD 107 CMPD 13RATE = G/HA 0250 0125 0062 0500 0250 0125 0062 0500 0250 0125 0500 0250 0125 0250 0125__________________________________________________________________________POSTGIANT FOXTAIL 0 0 0 80 20 0 0 80 50 30 60 20 0 20 0VELVETLEAF 100 70 30 60 30 20 0 70 40 -- 80 80 70 70 60USH11 SUGARBEET 30 0 0 20 20 0 -- 90 50 40 90 90 80 80 40LARGE CRABGRASS 0 0 0 40 20 0 0 30 20 0 30 30 -- 0 0PRICKLY SIDA 50 30 0 30 20 0 0 70 60 30 100 90 80 60 40JIMSONWEED 60 30 0 30 20 0 0 50 30 30 90 50 30 40 30RICE DRY SEEDED 0 0 0 30 0 0 0 30 0 0 10 0 0 0 0COCKLEBUR 50 30 0 30 20 0 0 40 40 30 50 40 20 30 0COKER COTTON 50 30 0 30 20 10 10 80 60 30 90 70 60 90 80WILLMS SOYBEANS 30 0 0 80 30 0 0 30 20 0 -- 60 0 40 0BARNYARDGRASS 0 0 0 30 20 0 0 100 90 30 100 80 70 20 0WILD OATS 0 0 0 30 20 0 -- 30 20 10 20 20 -- 30 0IVY MORNINGLORY 30 0 0 0 0 0 0 50 -- 0 100 90 60 70 40ERA WHEAT 0 0 0 20 0 0 0 0 0 0 0 0 0 10 0SICKLEPOD 50 30 0 20 0 0 0 70 60 60 90 40 20 40 20JOHNSONGRASS 0 0 0 20 0 0 0 50 30 0 0 0 0 0 0PURPLE NUTSEDGE 70 50 30 0 0 0 0 -- 0 0 70 70 0 0 0G4646 CORN 0 0 0 30 20 0 0 0 0 0 0 0 0 0 0WILD BUCKWHEAT 60 30 0 0 0 0 0 60 40 30 90 70 70 50 30BLACKGRASS 30 0 0 80 30 20 -- 70 10 0 70 40 0 80 30ALTEX RAPE 0 0 0 80 30 20 -- 60 40 0 70 60 60 30 0KLAGES BARLEY 0 0 0 30 20 0 -- 0 0 0 0 0 0 0 0GREEN FOXTAIL 0 0 0 30 20 0 0 100 70 30 80 40 30 40 0CHEAT GRASS 0 0 0 --LAMBSQUARTER 80 50 0 80 70 30 0 -- 90 50 80 80 60 50 --CHICKWEED SPP. 60 30 0 80 20 0 -- 70 70 30 80 50 40 50 0DOWNY BROME 0 0 0 0 0 0 0 0 0 0 0__________________________________________________________________________ CMPD 51 CMPD 669 CMPD 35RATE = G/HA 1000 0500 0250 0125 0062 2000 1000 0500 0250 0500 0125 2000 1000 0250 0062__________________________________________________________________________PREGIANT FOXTAIL 100 100 90 60 30 100 100 100 100 100 100 100 100 100 90VELVETLEAF 80 50 30 0 0 50 30 0 0 100 90 90 80 70 60USH11 SUGARBEET 80 70 60 50 30 70 50 30 0 90 20 60 40 30 0LARGE CRABGRASS 100 90 70 50 30 100 100 90 80 100 100 100 100 100 100PRICKLY SIDA 90 80 70 50 30 90 70 50 30 100 100 90 80 70 60JIMSONWEED 80 60 40 30 0 70 50 40 30 70 50 100 90 80 60RICE DRY SEEDED 0 0 0 0 0 0 0 0 0 10 0 0 0 0 0COCKLEBUR 50 30 0 0 0 40 20 0 0 20 0 50 40 30 0COKER COTTON 0 0 0 0 0 0 0 0 0 100 20 80 70 60 30WILLMS SOYBEANS 0 0 0 0 0 0 0 0 0 10 0 90 80 30 0BARNYARDGRASS 100 80 50 30 0 100 100 50 30 100 60 100 100 100 60WILD OATS 0 0 0 0 0 0 0 0 0 40 20 0 0 0 0IVY MORNINGLORY 0 0 0 0 0 40 0 0 0 0 0 80 60 40 0ERA WHEAT 0 0 0 0 0 0 0 0 0 20 0 0 0 0 0SICKLEPOD 60 30 0 0 0 30 0 0 0 50 0 90 70 30 0JOHNSONGRASS 90 70 50 30 0 90 80 50 30 100 50 100 100 90 70PURPLE NUTSEDGE 0 0 0 0 0 0 0 0 0 50 0 0 0 0 0G4646 CORN 0 0 0 0 0 0 0 0 0 40 10 60 40 20 0WILD BUCKWHEAT 60 30 0 0 0 70 50 30 0 100 30 80 70 50 30BLACKGRASS 60 30 0 0 0 70 50 30 0 100 80 90 80 60 30ALTEX RAPE 70 60 50 30 0 70 50 30 0 80 40 90 70 50 30KLAGES BARLEY 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0GREEN FOXTAIL 100 100 90 70 50 100 100 100 100 100 100 100 100 100 100CHEAT GRASS 0 0 0 0 0 30 0 0 0 60 30 0 0FIELD VIOLET 90 70 50 30 0 80 30 0 0 80 70 50 30LAMBSQUARTER 100 100 90 80 70 90 70 50 100 90 100 100 90 80CHICKWEED SPP. 40 --DOWNY BROME 80 40__________________________________________________________________________ CMPD 52 CMPD 18 CMPD 33 CMPD 35RATE = G/HA 2000 1000 0250 0062 0500 0250 0125 0062 0500 0250 0125 0250 0125 0062 0500 0250__________________________________________________________________________PREGIANT FOXTAIL 100 100 90 60 100 100 90 30 100 90 80 100 100 100 100 100VELVETLEAF 90 70 50 30 70 20 -- -- 90 80 70 -- 90 30 90 80USH11 SUGARBEET 80 50 30 0 50 30 20 -- 80 50 30 50 20 0 70 50LARGE CRABGRASS 100 100 100 80 100 100 100 50 90 70 50 100 100 60 100 100PRICKLY SIDA 90 80 80 70 90 90 80 50 60 30 0 -- 70 60 70 60JIMSONWEED 100 100 70 50 70 20 0 0 70 50 30 0 0 0 40 40RICE DRY SEEDED 50 30 0 0 10 0 0 0 0 0 0 30 10 0 10 10COCKLEBUR 100 100 50 30 20 0 0 0 30 0 0 0 -- 0 30 30COKER COTTON 80 60 20 0 10 0 0 -- 30 0 0 50 20 0 60 10WILLMS SOYBEANS 80 60 0 0 10 0 0 0 0 0 0 40 10 0 10 10BARNYARDGRASS 100 100 80 30 100 60 20 0 100 90 80 80 30 10 100 90WILD OATS 30 20 0 0 30 0 -- -- 0 0 0 10 0 0 40 30IVY MORNINGLORY 80 60 40 0 40 30 30 0 60 40 20 50 40 40 20 0ERA WHEAT 50 30 0 0 10 0 0 0 0 0 0 0 -- 0 20 20SICKLEPOD 90 60 30 0 100 50 30 0 50 30 0 90 40 30 30 20JOHNSONGRASS 100 90 80 50 100 50 30 0 50 30 0 70 10 0 90 80PURPLE NUTSEDGE 70 30 0 0 90 60 30 0 0 0 0 0 0 0 100 20G4646 CORN 60 30 0 0 10 10 10 0 0 0 0 0 0 0 0 0WILD BUCKWHEAT 80 50 30 0 50 30 30 0 0 0 0 40 0 -- 50 30BLACKGRASS 90 70 50 30 90 80 80 30 30 0 0 50 -- 10 60 40ALTEX RAPE 70 40 20 0 30 20 20 -- 90 80 70 40 40 30 80 80KLAGES BARLEY 30 20 0 0 30 30 20 10 0 0 0 10 0 0 20 0GREEN FOXTAIL 100 100 90 70 100 100 100 30 100 90 80 100 100 70 100 100CHEAT GRASS 70 50 30 0 40 20 20 20 0 0 0 40 30FIELD VIOLET 100 90 30 0 70 50 30LAMBSQUARTER 100 100 90 80 100 90 80 60 100 100 100 100 70 60 100 90CHICKWEED SPP. 50 20 -- -- 40 30 0 30 0DOWNY BROME 30 10 0__________________________________________________________________________ CMPD 35 CMPD 1381 CMPD 1304 CMPD 810 CMPD 9RATE = G/HA 0125 0062 0250 0125 0062 0250 0125 0062 0500 0250 0125 0062 0500 0250 0125 0062__________________________________________________________________________PREGIANT FOXTAIL 100 90 100 100 90 100 100 70 50 40 20 0 100 100 100 40VELVETLEAF 60 50 0 0 0 30 0 0 50 40 20 0 100 70 40 20USH11 SUGARBEET 40 0 90 70 50 50 30 0 40 30 30 20 90 70 60 40LARGE CRABGRASS 100 100 100 100 100 100 90 80 100 90 90 20 100 100 100 100PRICKLY SIDA 60 50 30 0 0 70 50 30 60 50 30 20 90 50 10 0JIMSONWEED 20 0 50 30 0 30 0 0 50 40 30 30 80 50 30 30RICE DRY SEEDED 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0COCKLEBUR 0 0 50 30 0 50 30 0 30 20 0 0 30 0 0 0COKER COTTON 0 0 30 30 30 0 0 0 0 0 0 0 30 10 -- 0WILLMS SOYBEANS 0 0 0 0 0 0 0 0 20 0 0 0 10 0 0 0BARNYARDGRASS 40 30 80 50 30 70 30 0 100 90 70 40 100 100 30 0WILD OATS 20 0 50 30 0 50 30 0 20 0 0 0 0 0 0 0IVY MORNINGLORY 0 0 60 30 0 0 0 0 30 20 0 0 20 0 0 0ERA WHEAT 10 0 30 0 0 30 0 0 20 0 0 0 0 0 0 0SICKLEPOD 0 0 0 0 0 0 0 0 0 0 0 0 50 20 0 0JOHNSONGRASS 40 40 70 30 0 40 0 0 50 40 30 20 100 90 50 40PURPLE NUTSEDGE 0 0 30 0 0 0 0 0 0 0 0 0 0 0 0 0G4646 CORN 0 0 0 0 0 0 0 0 30 20 0 0 10 0 0 0WILD BUCKWHEAT 0 0 0 0 0 70 50 30 30 0 0 0 80 50 30 0BLACKGRASS 40 30 50 40 30 50 30 0 70 30 20 0 90 50 20 0ALTEX RAPE 70 30 70 50 30 0 0 0 30 20 0 0 90 70 50 30KLAGES BARLEY 0 0 0 0 0 0 0 0 30 0 0 0 0 0 0 0GREEN FOXTAIL 100 600 100 100 80 100 100 70 100 100 100 90 100 100 100 40CHEAT GRASS 0 0 30 0 0 40 30 20 0LAMBSQUARTER 80 80 70 50 30 50 30 0 90 80 50 40 100 100 90 80CHICKWEED SPP. 0 0 70 50 30 0 0 0 30 0 0 0 40 10 0 0DOWNY BROME 0 0 0 40 20 0 0__________________________________________________________________________ CMPD 107 CMPD 13 RATE = G/HA 0500 0250 0125 0062 0250 0125 0062__________________________________________________________________________ PRE GIANT FOXTAIL 100 100 90 70 100 90 40 VELVETLEAF 80 40 30 20 40 20 0 USH11 SUGARBEET 90 80 60 10 90 80 50 LARGE CRABGRASS 100 100 100 100 100 100 100 PRICKLY SIDA 80 80 70 0 90 60 40 JIMSONWEED 50 40 20 0 50 30 0 RICE DRY SEEDED 0 0 0 0 0 0 0 COCKLEBUR 10 0 0 0 20 0 0 COKER COTTON 10 0 0 0 0 0 0 WILLMS SOYBEANS 0 0 0 0 0 0 0 BARNYARDGRASS 100 90 40 0 90 40 0 WILD OATS 30 0 0 0 0 0 0 IVY MORNINGLORY 50 30 0 0 0 0 0 ERA WHEAT 0 0 0 0 20 0 0 SICKLEPOD 80 40 -- 0 30 0 0 JOHNSONGRASS 100 90 40 20 60 50 30 PURPLE NUTSEDGE 30 -- 0 0 0 0 0 G4646 CORN 10 0 0 0 0 0 0 WILD BUCKWHEAT 70 60 50 20 80 40 30 BLACKGRASS 70 50 30 10 40 30 10 ALTEX RAPE 70 60 60 40 70 60 50 KLAGES BARLEY 0 0 0 0 0 0 0 GREEN FOXTAIL 100 100 100 90 100 50 20 LAMBSQUARTER 100 90 90 80 100 90 80 CHICKWEED SPP. 70 40 0 0 30 0 0 DOWNY BROME 0 0 0 0 20 0 0__________________________________________________________________________
TEST C
Sixteen cm diameter Airlite plastic pots were partially filled with Tama silt loam soil and the soil saturated with water. Japonica and Indica rice seedlings a the 2.0 to 2.5 leaf stage were transplanted into 1/3 of the pots. Into another third of the pots were transplanted seedling or sprouted tubers of water plantain (Alisma trivale), Scripus (Scirpus paludosus), Cyperus (Cyperus esculentus), and arrowhead (Sagittaria spp.). The remaining pots were planted with barnyardgrass (Echinochloa crusgalli) seeds and sprouted tubes of water chestnut (Eleocharis spp.). These weeds all represent major rice weeds or genera of weeds important in rice. Three to four days after planting, the water level was raised to 3 cm (about 1200 ml/pot) and maintained a this level throughout the test. Chemical treatments were applied directly to the paddy water, within 24 hours of raising the water, after being formulated in a nonphytotoxic solvent. The pots were maintained in the greenhouse. Rates of application and plant response ratings made 21 days after treatment are summarized in Table C.
TABLE C__________________________________________________________________________ CMPD 669 CMPD 18 CMPD 1381RATE .times. G/HA 1000 0500 0250 0125 0064 1000 0500 0250 0125 0064 1000 0500 0250 0125 0064__________________________________________________________________________BARNYARDGRASS 100 90 98 98 90 60 40 0 0 0 100 100 60 55 55WATERCHESTNUT 0 0 0 0 0 50 40 0 0 0 0 0 0 0 0ARROWHEAD 0 0 0 0 0 35 20 0 0 0 0 0 0 0 0SCIRPUS 30 0 0 0 0 0 0 0 0 0 30 0 0 0 0YELLOW NUTSEDGE 80 60 0 0 0 50 40 0 0 0WATER PLAINTAIN 0 0 0 0 0 40 20 0 0 0 0 0 0 0 0RICE JAP EFF 0 0 0 0 0 70 50 0 0 0 60 40 20 0 0RICE INDICA EFF 0 0 0 0 0 50 30 0 0 0 60 40 20 0 0__________________________________________________________________________ CMPD 35 CMPD 50 CMPD 1304RATE .times. G/HA 1000 0500 0250 0125 0064 1000 0500 0250 0125 0064 1000 0500 0250 0125 0064__________________________________________________________________________BARNYARDGRASS 95 100 80 100 70 70 70 60 0 0 100 98 100 100 85WATERCHESTNUT 0 0 60 40 60 0 0 0 0 0 50 0 0 0 0ARROWHEAD 95 50 40 0 0 50 30 0 0 0 30 0 0 0 0SCIRPUS 50 0 0 0 0 0 0 0 0 0 80 70 65 0 0YELLOW NUTSEDGE 100 95 60 0 0 50 30 0 0 0 0 0 0 0 0WATER PLAINTAIN 60 40 40 0 0 0 0 0 0 0 65 0 0 0 0RICE JAP EFF 20 0 0 0 0 70 60 30 0 0 40 0 0 0 0RICE INDICA EFF 20 0 0 0 0 80 70 30 40 0 40 0 0 0 0__________________________________________________________________________ CMPD 33 CMPD 107RATE .times. G/HA 1000 0500 0250 0125 0064 1000 0500 0250 0125 0064__________________________________________________________________________BARNYARDGRASS 95 70 80 10 0 80 90 40 0 0WATERCHESTNUT 0 0 0 0 0 30 60 40 0 0ARROWHEAD 0 0 0 0 0 70 95 0 0 0SCIRPUS 0 0 0 0 0 80 80 60 0 0YELLOW NUTSEDGE 40 0 0 0 0 95 30 50 0 0WATER PLAINTAIN 0 0 0 0 0 80 60 0 0 0RICE JAP EFF 60 30 0 0 0 50 40 30 0 0RICE INDICA EFF 70 30 0 0 0 50 40 30 0 0__________________________________________________________________________ CMPD 35 RATE .times. G/HA 2000 0500 0125 0032__________________________________________________________________________ RICE JAP TOL 50 50 20 0 RICE INDICA TOL 60 55 55 0__________________________________________________________________________
TEST D
The Corn and Sorghum Herbicide Test included the following species in both the preemergence and postemergence evaluations:
______________________________________ SPECIESCategory Common Name Scientific Name______________________________________Crops Corn Zea mays Soybean Glycine max Sorghum Sorghum bicolorGrasses Green foxtail Setaria viridis Giant foxtail Setaria faberii Johnsongrass Sorghum halepense Barnyardgrass Echinochloa crus-galli Fall panicum Panicum dichotomiflorum Crabgrass Digitaria sanguinalis Nutsedge Cyperus rotundusBroadleaves Cocklebur Xanthium pensylvanicum Morningglory Ipomoea hederacea Velvetleaf Abutilon theophrasti Jimsonweed Datura stramonium Lambsquarters Chenopodium album Pigweed Amaranthus retroflexus Smartweed Polygonum persicaris______________________________________
Postemergence
Postemergence plantings were grown in Sassafras sandy loam soil. Corn and soybeans were grown in separate 25 diameter containers. Sorghum and the seven grass weed species were grown in two 18 cm diameter containers, 4 species per container. The seven broadleaf weed species were also grown in two 18 cm diameter containers, 4 species in one container, 3 species in the second container. One additional planting of corn in an 18 cm diameter container was made. One additional planting of corn in an 18 cm diameter container was made. The soil surface of this additional container of corn was covered with the absorbent, perlite, before spray treatment so that test chemicals would enter the plant only via the foliage. The plants were grown 10-21 days, dependent upon the species and then sprayed postemergence with the test chemicals dissolved in a nonphytotoxic solvent.
Postemergence
Preemergence plantings were grown in fertilized Tama silt loam soil. These plantings are identical to those described in the postemergence section, with the exception of the corn planting having perlite covering the soil surface. These plantings were made the day of or the day before spraying the test chemicals dissolved in a nonphytotoxic solvent.
Evaluation
Treated plants and controls were maintained in the greenhouse for 2 to 4 weeks. Visual planting response ratings were made on a percentage scale of 0 to 100 in comparison with a control where 0=no injury, and 100=death.
The results are shown in Table D.
TABLE D__________________________________________________________________________ CMPD 50 CMPD 33 CMPD 35__________________________________________________________________________RATE GM/HA 0500 0250 0125 0064 1000 0500 0250 0500 0250 0125 0064__________________________________________________________________________PREEMERGENCEG4646 CORN 0 0 0 0 0 0 0 0 0 0 0WILLMS SOYBEANS 20 0 0 0 0 0 0 0 0 0 0GREEN FOXTAIL 85 50 30 0 0 0 0 100 80 70 30GIANT FOXTAIL 85 75 65 20 0 0 0 100 80 50 0FALL PANICUM 95 60 35 20 0 0 0 100 80 50 0LARGE CRABGRASS 100 100 75 40 0 0 0 100 95 70 50BARNYARDGRASS 45 20 0 0 0 0 0 100 40 60 0JOHNSONGRASS 95 90 70 35 0 0 0 100 100 30 30G522 SORGHUM 0 0 0 0 0 0 0 0 0 0 0PURPLE NUTSEDGE 30 0 0 0 0 0 0 50 0 0 --VELVETLEAF 65 40 25 0 0 0 0 100 100 70 60COCKLEBUR 25 0 0 0 0 0 0 20 0 0 0LADY SMARTWEED 40 20 0 0 0 0 0 100 50 30 0LAMBSQUARTER 90 75 35 0 0 0 0 80 60 30 30REDROOT PIGWEED 100 85 40 0 0 0 0 98 50 0 0IVY MORNINGLORY 65 40 30 0 0 0 0 30 0 0 0JIMSONWEED 70 50 25 0 0 0 0 30 80 0 0__________________________________________________________________________RATE GM/HA 0500 0250 1000 0500 0250 0500 0250__________________________________________________________________________POSTEMERGENCEG4646 CORN 20 0 0 0 0 0 0WILLMS SOYBEANS 65 35 0 0 0 30 10GREEN FOXTAIL 0 0 0 0 0 40 0GIANT FOXTAIL 0 0 0 0 0 60 0FALL PANICUM 35 20 0 0 0LARGE CRABGRASS 100 70 0 0 0 30 30BARNYARDGRASS 0 0 0 0 0 60 40JOHNSONGRASS 40 20 0 0 0 50 0G522 SORGHUM 0 0 0 0 0 50 0PURPLE NUTSEDGE 0 0 0 0 0 0 0VELVETLEAF 25 0 0 0 0 90 60COCKLEBUR 40 25 0 0 0 30 0LADY SMARTWEED 40 30 0 0 0 50 50LAMBSQUARTER 80 65 0 0 0 20 0REDROOT PIGWEED 95 65 0 0 0 70 30IVY MORNINGLORY 60 20 0 0 0 30 20JIMSONWEED 45 20 0 0 0 20 20PERLITE CORN 0 0 0 0 0 0 0__________________________________________________________________________
TEST E
Seeds of the following crops and weeds are sown into 15 cm pots containing Sassafras sandy loam soil: wheat (Triticum aestivum cv. Park), barley (Hordeum vulgare cv. Bonanza), sugarbeet (Beta vulgaris cv. USH-11), rapeseed (Brassica napus cv. Jet Neuf), black nightshade (Solanum nigrum), chickweed (Stellaria media), lambsquarter (Chenopodium album), Galium aparine, knotweed (Polygonum aviculare), Kochia scoparia, Matricaria indora, redroot pigweed (Amaranthus retroflexus), smartweed (Polygonum persicaria), speedwell (Veronica persica), wild buckwheat (Polygonum convolvulus), wild mustard (Brassica spp.), wild radish (Raphanus raphanistrum), annual bluegrass (PO annua), annual ryegrass (Lolium multiflorum), blackgrass (Alopercurus mysuroides), greed foxtail (Setaria viridis), and wild oats (Avena fatua). Compounds are formulated in a nonphytotoxic solvent and applied to the plants as a foliar spray or applied to the soil surface. Plants are treated at two stages: preemergence, or postemergence when the sugarbeets are at the 2-3 true leaf stage. Plants are grown in a temperature-controlled greenhouse for the duration of the test.
Weed control and crop injury are evaluated visually at 3-4 weeks after compound application, using a scale of 0 to 100%, where 0=no injury and 100=complete death of the plant. All plants are rated with respect to untreated plants (checks) grown in the greenhouse under identical conditions to the treated plants.
TABLE E__________________________________________________________________________ CMPD 51 CMPD 644 CMPD 52 CMPD 4RATE GM/HA 0500 0250 0125 0064 0500 0250 0125 0064 0500 0250 0125 0064 0500 0250 0125 0064__________________________________________________________________________POSTEMERGENCEPARK WHEAT 0 0 0 0 40 30 20 0 50 40 30 30 50 30 10 0BONANZA BARLEY 0 0 0 0 40 20 20 0 40 20 20 0 60 40 30 20BLACK NIGHTSHAD 60 40 0 0 20 10 0 0 70 10 0 0 90 70 30 10CMN CHICKWEED 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0LAMBSQUARTER 40 20 0 0 40 20 0 0 10 0 0 0 70 20 20 0CTCHWD BEDSTRAW 50 0 0 0 30 30 30 0 100 70 80 20 100 80 20 20KOCHIA 0 0 0 0 70 50 0 0 70 0 0 0 90 70 30 0SNTLS CHAMOMILE 60 40 20 0 90 50 50 20 85 50 50 20 85 70 50 30REDROOT PIGWEED 90 60 50 30 60 50 50 50 90 90 50 0 90 90 40 20LADY SMARTWEED 100 100 100 0PERSN SPEEDWELL 40 20 0 0 80 40 20 0 90 60 30 40 100 100 70 20WILD BUCKWHEAT 0 0 0 0 0 0 0 0 30 0 0 0 70 40 0 0MUSTARD SPP. 30 30 30 0 50 50 20 20 50 20 0 0 80 40 40 20WILD RADISH 60 30 30 0 80 50 30 20 80 50 10 10 90 80 60 20ANN. BLUEGRASS 50 20 0 0 80 50 50 20 70 60 40 30 60 40 20 0ITALN. RYEGRASS 0 20 20 0 40 50 20 0 80 50 20 0 80 30 0 0BLACKGRASS 0 0 0 0 50 30 0 0 60 20 0 0 50 20 20 0GREEN FOXTAIL 0 0 0 0 50 50 30 30 75 40 0 0 80 20 20 0WILD OATS 0 0 0 0 20 20 0 0 30 20 0 0 30 0 0 0JET RAPE 20 0 0 0 30 0 0 0 40 20 0 0 30 20 20 0__________________________________________________________________________ CMPD 51 CMPD 644 CMPD 52 CMPD CMPD 107 RATE GM/HA 0500 0500 0250 0500 0250__________________________________________________________________________ PREEMERGENCE PARK WHEAT 0 30 70 80 30 BONANZA BARLEY 30 50 70 80 30 BLACK NIGHTSHAD 100 0 100 100 80 CMN CHICKWEED 0 20 0 0 0 LAMBSQUARTER 100 85 100 100 90 CTCHWD BEDSTRAW 0 0 100 100 0 KOCHIA 70 100 0 100 70 SNTLS CHAMOMILE 100 100 100 100 70 REDROOT PIGWEED 70 80 100 100 100 LADY SMARTWEED 100 PERSN SPEEDWELL 20 50 100 90 100 WILD BUCKWHEAT 0 30 20 40 0 MUSTARD SPP. 0 0 50 50 20 WILD RADISH 0 0 50 50 60 ANN. BLUEGRASS 20 80 100 100 20 ITALN. RYEGRASS 0 0 70 70 0 BLACKGRASS 0 20 20 90 20 GREEN FOXTAIL 100 100 100 100 100 WILD OATS 20 20 70 90 0 JET RAPE 0 20 20 40 30__________________________________________________________________________
TEST F
Weed species were planted 3 or 4 per 15-cm diameter pot in Sassafras sandy loam (pH 6.8; 1% OM). Cotton was planted separately in the same sized pot. Postemergence plantings were made 12-16 days prior to treating so plants were in the 2- to 3-leaf stage (5-12 cm tall). Preemergence plantings were made the day before treating. Compounds were sprayed in a suitable non-phytotoxic solvent at 374 1/ha, then after 3 weeks of growth in a greenhouse, plant responses were visually rated on a percent scale where 0=no injury and 100=plant death. The following species were included:
______________________________________ PlantingCommon Name Latin Name Depth (cm)______________________________________Cotton (Coker 315) Gossypium hirsutum 2Barnyardgrass Echinochloa crus-galli 1Bermudagrass Cynodon dactylon 1Broadleaf signalgrass Brachiaria platyphylla 1Crabgrass Digitaria sanguinalis 1Fall panicum Panicum dichotomiflorum 1Goosegrass Eleusine indica 1Johnsongrass Sorghum halepense 1Nutsedge Cyperus rotundus 3Cocklebur Xanthium pensylvanicum 3Ivy leaf morningglory Ipomoea hederacea 3Lambsquarters Chenopodium album 1Pigweed Amaranthus retroflexus 1Prickly sida Sida spinosa 1Purslane Portulaca oleracea 1Sicklepod Cassia obtusifolia 3Smartweed Polygonum persicaria 1Velvetleaf Abutilon theophrasti 3Ground cherry Physalis heterophylla 1______________________________________
The results are shown in Table F.
TABLE F______________________________________ CMPD 4RATE GM/HA 0500 0250 0125 0064 0032______________________________________PREEMERGENCECOKER COTTON 0 0 0 0 0REDROOT PIGWEED 100 100 60 70 50LAMBSQUARTER 70 60 20 20 0VELVETLEAF 30 0 0 0 0PRICKLY SIDA 90 100 0 0 0SICKLEPOD 0 0 0 0 0COCKLEBUR 0 0 0 0 0CMN PURSLANE 80 30 30 20 0IVY MORNINGLORY 0 0 0 0 0GOOSEGRASS 100 100 100 80 80BERMUDAGRASS 100 100 95 20 0BARNYARDGRASS 95 0 0 0 0JOHNSONGRASS 50 50 20 0 0FALL PANICUM 100 100 90 90 90LARGE CRABGRASS 100 100 100 20 0BRDLF SGNLGRASS 30 0 0 0 0PURPLE NUTSEDGE 0 0 0 0 0LADY SMARTWEED 20 20 0 0 0GROUND CHERRY 0 0 0 0 0______________________________________
Claims
  • 1. A compound having the formula: ##STR72## or a pharmaceutically or agriculturally suitable salt thereof wherein E is an oxygen atom with the proviso that R, R.sup.1 are not halogen;
  • A is perfluoroalkyl of 1-8 carbon atoms, N(CH.sub.3).sub.2, OH, naphthyl optionally substituted with a total of 1-3 substituents each of which is independently selected from halogen and CH.sub.3, ##STR73## optionally substituted with 1 or 2 methyl groups, phenyl optionally substituted with a total of 1-3 substituents each of which is independently selected from:
  • halogen, alkyl of 1-4 carbon atoms, haloalkyl of 1-4 carbon atoms, alkoxy of 1-4 carbon atoms, and with no more than one group selected from:
  • haloalkoxy of 1-4 carbon atoms, CN, CO.sub.2 R.sup.14, CH.dbd.NOR.sup.14, S(O).sub.m R.sup.5, R.sup.6, 2-, 3-, or 4-pyridyl or an N-oxide thereof, imidazol-1-yl, 1,2,4-triazol-1-yl, and ##STR74## optionally substituted with 1 or 2 methyl groups, or a heterocycle selected from imidazol-1-yl, 1,2,4-triazol-1-yl, 2- or 3-thienyl, and 2-, 3-, or 4-pyridyl or an N-oxide thereof optionally substituted with one or two substituents each of which is independently selected from:
  • halogen, alkyl of 1-4 carbon atoms, alkoxy of 1-4 carbon atoms, haloalkoxy of 1-4 carbon atoms, CF.sub.3, and S(O).sub.m R.sup.5 ;
  • B is alkyl of 1-8 carbon atoms, naphthyl, biphenyl, ##STR75## perfluoroalkyl of 1-8 carbon atoms, phenyl optionally substituted with 1-3 substituents each of which is independently selected from:
  • halogen, alkyl of 1-4 carbon atoms, haloalkyl of 1-4 carbon atoms, alkoxy of 1-4 carbon atoms, and with no more than one group selected from haloalkoxy of 1-4 carbon atoms, CN, CO.sub.2 R.sup.14, CH.dbd.NOR.sup.14, S(O).sub.m R.sup.5, 2-, 3-, 4-pyridyl or an N oxide thereof,
  • benzyl optionally substituted on the phenyl ring with halogen or alkyl of 1-4 carbon atoms, or optionally .alpha.-substituted with 1 or 2 methyl groups, or
  • a heterocycle selected from 2- or 3-thienyl, and 2-, 3-, or 4-pyridyl optionally substituted with one or two substituents each of which is independently selected from:
  • halogen, alkyl of 1-4 carbon atoms, haloalkoxy of 1-4 carbon atoms, CF.sub.3 or S(O).sub.m R.sup.5 ;
  • Q is H, halogen, S(O).sub.m R.sup.11, ##STR76## CO.sub.2 R.sup.13, SCN, SSR.sup.12, or SH or its corresponding disulfide, provided however that when Q is other than H, then n is O, R, R.sup.1, and R.sup.4 are independently H or CH.sub.3, R.sup.3 is H, and A and B are each phenyl optionally substituted with from 1-3 substituents each of which is independently halogen, CH.sub.3, CF.sub.3, OCH.sub.3 or S(O).sub.m R.sup.5 ;
  • L is N;
  • n is 0-4 with the proviso that when A is ##STR77## N(CH.sub.3).sub.2, or OH, then n is other than O; m each occurrence is 0, 1 or 2;
  • X is C, NR.sup.10, or O;
  • R and R.sup.1 independently are H, alkyl or 1-4 carbon atoms, halogen or phenyl, or taken together form cycloalkyl of 3-7 carbon atoms;
  • R.sup.2 is H, allyl, propargyl, alkyl of 1-4 carbon atoms, ##STR78## or haloalkyl of 1-4 carbon atoms; R.sup.3 and R.sup.4 independently are H, F, or alkyl or 1-4 carbon atoms;
  • R.sup.5 is alkyl of 1-4 carbon atoms;
  • R.sup.6 is phenyl optionally substituted with a total of 1-3 substituents each of which is independently selected from halogen and CF.sub.3 ;
  • R.sup.7 is alkyl of 1-4 carbon atoms, phenyl, or benzyl;
  • R.sup.8 and R.sup.9 independently are H, alkyl of 1-4 carbon atoms, phenyl or benzyl;
  • R.sup.10 is H, alkyl of 1-4 carbon atoms, or acetyl;
  • R.sup.11 is alkyl of 1-4 carbon atoms, haloalkyl of 1-4 carbon atoms, CH.sub.2 CN, CH.sub.2 SCN, CH(CH.sub.3)CN, CH.sub.2 CO.sub.2 CH.sub.3, or CH.sub.2 CO.sub.2 CH.sub.2 CH.sub.3 ;
  • R.sup.12 is alkyl of 1-4 carbon atoms, allyl, phenyl optionally substituted with 1-2 substituents each of which is independently halogen, CH.sub.3, or OCH.sub.3 ;
  • R.sup.13 is H, or alkyl of 1-4 carbon atoms; and
  • R.sup.14 is alkyl of 1-4 carbon atoms.
  • 2. A compound of claim 1 wherein n is 0 or 1.
  • 3. A compound of claim 1 wherein R.sup.3 and R.sup.4 are each independently H, CH.sub.3 or F.
  • 4. A compound of claim 1 wherein n is 0 or 1, and R.sup.3 and R.sup.4 are each independently H, CH.sub.3 or F.
  • 5. A compound of claim 4 wherein A and B independently are phenyl optionally substituted with from 1-3 substituents each of which is halogen, alkoxy of 1-4 carbon atoms, alkyl of 1-4 carbon atoms, S(O).sub.m R.sup.5 or haloalkyl of 1-4 carbon atoms.
  • 6. A compound of claim 4 wherein R and R.sup.1 independently are H or CH.sub.3.
  • 7. A compound of claim 4 wherein n is 0.
  • 8. A compound of claim 4 wherein R and R.sup.2 is H, alkyl of 1-4 carbon atoms, allyl or propargyl.
  • 9. A compound of claim 4 wherein Q is H, I or SH.
  • 10. A compound of claim 4 wherein R and R.sup.1 independently are H or CH.sub.3, R.sup.2 is H, alkyl of 1-4 carbon atoms, allyl or propargyl, n is O, Q is H, I or SH, and A and B independently are phenyl optionally substituted with from 1-3 substituents each of which is halogen, alkoxy of 1-4 carbon atoms, alkyl of 1-4 carbon atoms, S(O).sub.m R.sup.5, or haloalkyl of 1-4 carbon atoms.
  • 11. A compound of claim 10 wherein R, R.sup.1, R.sup.2, R.sup.3, R.sup.4 and Q are all H.
  • 12. A compound of claim 10 wherein A and B independently are phenyl optionally substituted with from 1-3 halogen atoms, CH.sub.3, OCH.sub.3, CF.sub.3 or SCH.sub.3.
  • 13. A compound of claim 10 wherein R, R.sup.1, R.sup.2, R.sup.3, R.sup.4 and Q are all H, and A and B independently are phenyl optionally substituted with 1-3 halogen atoms, CH.sub.3, OCH.sub.3, CF.sub.3 or SCH.sub.3.
  • 14. The compound of claim 1 which is 2-(4-fluorophenyl)-3-phenyl-1-(1H-1,2,4-triazol-1-yl) -3,4-epoxy-2-butanol, or a salt thereof.
  • 15. The compound of claim 1 which is 2,3-bis(4-fluorophenyl)-1-(1H-1,2,4-triazol-1-yl) -3,4-epoxy-2-butanol, or a salt thereof.
  • 16. The compound of claim 1 which is 2-(2,4-dichlorophenyl)-3-(4-chlorophenyl)-1-(1H-1,2,4-triazol-1-yl)-3,4-epoxy-2-butanol, or a salt thereof.
  • 17. The compound of claim 1 which is 2-(2,4-difluorophenyl)-3-(2-chlorophenyl)-1-(1H-1,2,4-triazol-1-yl)-3,4-epoxy-2-butanol, or a salt thereof.
  • 18. The compound of claim 1 which is 2-(4-chlorophenyl)-3-(2-chlorophenyl)-1-(1H-1,2,4-triazol-1-yl)-3,4-epoxy-2-butanol, or a salt thereof.
  • 19. A pharmaceutical composition comprising a suitable pharmaceutical carrier and a therapeutically effective amount of a compound of claim 1.
  • 20. A pharmaceutical composition comprising a suitable pharmaceutical carrier and a therapeutically effective amount of a compound of claim 2.
  • 21. A pharmaceutical composition comprising a suitable pharmaceutical carrier and a therapeutically effective amount of a compound of claim 3.
  • 22. A pharmaceutical composition comprising a suitable pharmaceutical carrier and a therapeutically effective amount of a compound of claim 4.
  • 23. A pharmaceutical composition comprising a suitable pharmaceutical carrier and a therapeutically effective amount of a compound of claim 5.
  • 24. A pharmaceutical composition comprising a suitable pharmaceutical carrier and a therapeutically effective amount of a compound of claim 6.
  • 25. A pharmaceutical composition comprising a suitable pharmaceutical carrier and a therapeutically effective amount of a compound of claim 7.
  • 26. A pharmaceutical composition comprising a suitable pharmaceutical carrier and a therapeutically effective amount of a compound of claim 8.
  • 27. A pharmaceutical composition comprising a suitable pharmaceutical carrier and a therapeutically effective amount of a compound of claim 9.
  • 28. A pharmaceutical composition comprising a suitable pharmaceutical carrier and a therapeutically effective amount of a compound of claim 10.
  • 29. A pharmaceutical composition comprising a suitable pharmaceutical carrier and a therapeutically effective amount of a compound of claim 11.
  • 30. A pharmaceutical composition comprising a suitable pharmaceutical carrier and a therapeutically effective amount of a compound of claim 12.
  • 31. A pharmaceutical composition comprising a suitable pharmaceutical carrier and a therapeutically effective amount of a compound of claim 13.
  • 32. A pharmaceutical composition comprising a suitable pharmaceutical carrier and a therapeutically effective amount of the compound of claim 14.
  • 33. A pharmaceutical composition comprising a suitable pharmaceutical carrier and a therapeutically effective amount of a compound of claim 15.
  • 34. A pharmaceutical composition comprising a suitable pharmaceutical carrier and a therapeutically effective amount of the compound of claim 16.
  • 35. A pharmaceutical composition comprising a suitable pharmaceutical carrier and a therapeutically effective amount of the compound of claim 17.
  • 36. A pharmaceutical composition comprising a suitable pharmaceutical carrier and a therapeutically effective amount of the compound of claim 18.
  • 37. A agricultural composition for controlling a plant fungus disease which comprises an effective amount of a compound of claim 1 and at least one of the following: surfactant, solid or liquid inert diluent.
Parent Case Info

This is a division of application Ser. No. 07/134,261, filed Dec. 17, 1987, which is a continuation-in-part of application Ser. No. 042,541, filed Apr. 29, 1987 (now abandoned, which in turn is a continuation-in-part of application Ser. No. 877,525, filed June 23, 1986 (now abandoned).

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Number Name Date Kind
4427673 Kramer et al. Jan 1984
4507140 Sugavaran Mar 1985
4530922 Moberg Jul 1985
4623654 Parry et al. Nov 1986
4654332 Parry et al. Mar 1987
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Number Date Country
542110 May 1981 AUX
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0097425 Jan 1984 EPX
117578 Feb 1984 EPX
0143384 Jun 1985 EPX
3018865 Nov 1981 DEX
3314548 Oct 1984 DEX
2146987 May 1985 GBX
Non-Patent Literature Citations (4)
Entry
Chem. Abstracts, vol. 102, No. 13, Apr. 1, 1985, Columbus, Ohio, U.S.A.
Chem. Abstracts, vol. 104, No. 13, Mar. 31, 1986, Columbus, Ohio, U.S.A.
Chem. Abstracts, vol. 84, No. 13, Mar. 29, 1976, Columbus, Ohio, U.S.A.
Chem. Abstracts, vol. 99, No. 15, Oct. 10, 1983, Columbus, Ohio U.S.A.
Divisions (1)
Number Date Country
Parent 134261 Dec 1987
Continuation in Parts (2)
Number Date Country
Parent 42541 Apr 1987
Parent 877525 Jun 1986