Pyridazinone derivatives, preparation thereof, and insecticidal, acaricidal, nematicidal, fungicidal compositions

BACKGROUND OF THE INVENTION
(1) Field of the Invention
This invention relates to novel 3(2H)-pyridazinone derivatives; preparation thereof; insecticidal, acaricidal, nematicidal, fungicidal compositions for agricultural and horticultural uses; and expellent compositions for ticks parasitic on animals; said compositions containing said derivatives as an active ingredient.
(2) Description of the Prior Art:
The present inventors have previously found a part of the 3(2H)-pyridazinone derivatives represented by the following formula (IV) exhibits agricultural and horticultural insecticidal, acaricidal, nematicidal, fungicidal action (refer to European Laid-Open Patent Application Nos. 0088384 and 0134439): ##STR3## (wherein, for example, R' denotes an alkyl; A' denotes a halogen; R.sup.10 and R.sup.11 denote hydrogen atom or a lower alkyl; X' denotes oxygen or sulfur atom; and Y" denotes a lower alkyl, a cycloalkyl, a lower alkoxy, a lower haloalkyl, a lower haloalkoxy or a substituted phenyl).
The present inventors have further conducted researches on pyridazinone derivatives and have found that the compounds of the present invention represented by the general formula (I) given below have an excellent insecticidal, acaricidal, nematicidal and/or fungicidal action. For example, with respect to fungicidal action, the compounds represented by the general formula (IV) are effective against powdery mildew and downy mildew whereas the compounds of the present invention exhibit a strong action against red rust, rice blight and the like in addition to the above mentioned diseases, which clearly shows a wider fungicidal spectrum of the present compounds. Moreover, it was found that the compounds of the present invention have a higher activity than the known compounds represented by the formula (IV) and can effectively contol organisms which are agriculturally and horticulturally harmful even with an extremely low drug concentration. Thus, the present inventors have completed the present invention. These effects are clearly shown by the test examples given below.
SUMMARY OF THE INVENTION
The primary object of the present invention is to offer a 3(2H)-pyridazinone derivative of the general formula (I): ##STR4## wherein R represents a straight or branched chain alkyl having 2 to 6 carbon atoms,
A represents a straight or branched chain alkyl having 1 to 6 carbon atoms or a halogen atom,
X represents --O-- or --S--,
R.sup.1 and R.sup.2 independently of one another represent hydrogen atom or an alkyl having 1 to 3 carbon atoms,
B represents --CH.dbd.CH--, --N.dbd.CH--, --N.dbd.N--, --S--, --O-- or ##STR5## wherein R.sup.3 represents hydrogen or an alkyl having 1 to 3 carbon atoms,
Y represents halogen atom, a straight or branched chain alkyl having 1 to 6 carbon atoms, a cycloalkyl or cycloalkoxy having 3 to 6 carbon atoms; a straight or branched chain alkoxy or alkylthio having 1 to 6 carbon atoms; a straight or branched chain alkylsulfinyl or alkylsulfonyl having 1 to 6 carbon atoms; a haloalkyl or haloalkoxy having 1 to 4 carbon atoms; a haloalkylthio having 1 to 4 carbon atoms, an alkenyloxy having 2 to 4 carbon atoms, trimethylsilyl, an alkoxylcarbonyl having 1 to 4 carbon atoms, dimethylamino, nitro, cyano, ##STR6## wherein Z represents a halogen atom, a straight or branched chain alkyl or alkoxy having 1 to 6 carbon atoms, a cycloalkyl having 3 to 6 carbon atoms, a haloalkyl having 1 to 4 carbon atoms, an alkoxycarbonyl having 1 to 4 carbon atoms or nitro, l is 0 or an integer of 1 to 5, and when l is a number of 2 to 5, Z may be same or different, or
Y represents --O--W,
W represents a group of the formula: ##STR7## in which R.sup.4, R.sup.5 and R.sup.6 independently from each other represent hydrogen atom or an alkyl having 1 to 4 carbon atoms,
R.sup.7 represents hydrogen atom or an alkyl or alkoxyl having 1 to 3 carbon atoms,
R.sup.8 represents a straight or branched chain alkyl having 1 to 6 carbon atoms, a cycloalkyl having 3 to 6 carbon atoms or an alkenyl or alkynyl having 3 to 6 carbon atoms,
E represents --O--, --S--, --SO--, --SO.sub.2 --, ##STR8## wherein R.sup.9 represents a straight or branched chain alkyl having 1 to 4 carbon atoms, or
R.sup.8 and R.sup.9 together may form 5- or 6-membered ring.
m is 0 or an integer of 1 to 3, n is 0 or an integer of 1 to 3, and when n is 2 or 3, Y may be the same or different, with the proviso that when B is --CH.dbd.CH--, n is an integer of 1 to 3 and at least one of Y is --O--W.
Another object of the present invention is to offer a process for producing said 3(2H)-pyridazinone derivative of the general formula (I).
Further object of the invention is to offer insecticidal, acaricidal, nematicidal and fungicidal compositions for agricultural and horticultural uses and expellent compositions for ticks parasitic on animals, which contain as active substances one or more of the 3(2H)-pyridazinone derivatives of the general formula (I).
A still further object of this invention is to provide a method for insecticidal, acaricidal, and/or fungicidal treatment in the agricultural and horiticultural field with the effective amount of a compound of the formula (I).
DETAILED DESCRIPTION OF THE INVENTION
Among the compounds of the present invention, following compounds are preferable in respect to the above-mentioned pest control activities.
Compounds of the general formula (IA): ##STR9## wherein R, A, X, R.sup.1, R.sup.2 and Y have the same meanings as given in formula (I), and n represents an integer of 1 to 3 and at least one of Y represents --O--W, in which W have the meaning as given before.
More preferable compounds are those of the general formula (IB): ##STR10## wherein A represents a halogen or CH.sub.3,
X represents O or S,
R.sup.1 represents hydrogen,
R.sup.2 represents hydrogen or CH.sub.3,
G represents a straight or branched chain alkylene having 1 to 6 carbon atoms,
Q represents a straight or branched chain alkyl having 1 to 6 carbon atoms, and
q is 1 or 2.
Another preferable compounds are those of the general formula (IC): ##STR11## wherein R, A, X, R.sup.1, R.sup.2 and Y have the same meanings as given in formula (I), n is 0 or an integer of 1 to 3, and B represents --N.dbd.CH--, --N.dbd.N--, --S--, --O--, or ##STR12##
Preferable compounds among those of the general formula (IC) are compounds of the general formula (ID): ##STR13## wherein A represents a halogen or CH.sub.3,
X represents O or S,
R.sup.1 represents hydrogen,
R.sup.2 represents hydrogen or CH.sub.3,
U represents a straight or branched chain alkyl having 1 to 6 carbon atoms, ##STR14## in which Hal represents a halogen atom, or a haloalkyl having 1 to 5 carbon atoms or a group of the formula --G--O--Q).sub.q, wherein G, Q and q have the same meanings as mentioned above.
Among others, more preferable compounds are those of the general formula (IE): ##STR15## wherein A represents a halogen or CH.sub.3,
X represents O or S,
R.sup.1 represents hydrogen,
R.sup.2 represents hydrogen or CH.sub.3, and
Y represents a straight or branched chain alkyl having 1 to 6 carbon atoms or a straight or branched chain alkoxy having 1 to 6 carbon atoms.
Specific compounds included in the present invention are, for example, those listed in Tables 1 and 2. The compounds in Tables 1 and 2 are exemplified only for illustrating, but not limiting the present invention.
[In Tables 1 and 2, each symbol Me, Et, Pro, Bu, Pen and Hex means methyl, ethyl, propyl, butyl, pentyl and hexyl, respectively, and t, s and i means tertiary, secondary and iso, respectively].
Among the compounds exemplified in Tables 1 and 2, following compounds are preferred in respect to the pest control activity.
Nos. 7, 15, 45, 68, 71, 81, 403, 415, 424, 504, 511, 513, 517, 521, 524, 527, 533, 535, 538, 553, 554, 555, 582, 612, 616, 661, 664, 667, 671, 675, 844, 857, 872, 997, 998, 999, 1001, 1003, 1004, 1010, 1011, 1042, 1063, 1067, 1081, 1083, 1093, 1055, 1062, 1072 and 1073.
Especially preferable compounds are Nos. 45, 68, 71, 81, 403, 415, 504, 511, 513, 517, 521, 524, 527, 538, 555, 582, 612, 661, 664, 667, 671, 844, 997, 998, 1001, 1003, 1004 1081, 1083, 1062, 1063 and 1072.
In case of the compounds containing asymmetric carbon atoms, optical isomers, i.e. (+)-isomers and (-)-isomers are also included in the present invention.
The compound number in Tables 1 and 2 is referred to also in the production examples, the formulation examples and the test examples, which will be mentioned below.
TABLE 1__________________________________________________________________________ ##STR16## No. R A X R.sup.1 ##STR17## ER.sup.8 (Y).sub.n-1 M.P. (.degree.C.)__________________________________________________________________________1 Et Cl O H 4-OCH.sub.2 OMe H2 Et Br O H 4-OCH.sub.2 OMe H 104.0.about.106.03 i-Pro Cl O H 4-OCH.sub.2 OMe H4 t-Bu Me O H 4-OCH.sub.2 OMe H5 t-Bu Cl O H 4-OCH.sub.2 OMe H 70.0.about.73.06 t-Bu Br O H 4-OCH.sub.2 OMe H7 t-Bu Cl S H 4-OCH.sub.2 OMe H 50.0.about.54.08 t-Bu Br S H 4-OCH.sub.2 OMe H9 Hex Cl S H 4-OCH.sub.2 OMe H10 i-Pro Cl O H 4-OCH.sub.2 OEt H11 i-Pro Br O H 4-OCH.sub.2 OEt H12 s-Bu Cl O H 4-OCH.sub.2 OEt H13 t-Bu Me S H 4-OCH.sub.2 OEt H14 t-Bu Me O H 4-OCH.sub.2 OEt H Oil15 t-Bu Cl S H 4-OCH.sub.2 OEt H Oil16 t-Bu Br O H 4-OCH.sub.2 OEt H Oil17 t-Bu Cl O H 4-OCH.sub.2 OEt H Oil18 t-Bu Cl O H 3-OCH.sub.2 OEt H19 t-Bu Br O H 3-OCH.sub.2 OEt H20 Pen Cl O H 4-OCH.sub.2 OEt H21 Et Cl O H 4-OCH.sub.2 OPro H22 t-Bu Cl O H 4-OCH.sub.2 OPro H23 t-Bu Br O H 4-OCH.sub.2 OPro H24 t-Bu Cl S H 4-OCH.sub.2 OPro H25 t-Bu Cl O H 3-OCH.sub.2 OPro H26 t-Bu Me O H 4-OCH.sub.2 OPro H27 Et Cl O H 4-OCH.sub.2 OBu H28 Et Br O H 4-OcH.sub.2 OBu H29 i-Pro Cl O H 4-OCH.sub.2 OBu H30 t-Bu Me S H 4-OCH.sub.2 OBu H31 t-Bu Cl O H 4-OCH.sub.2 OBu H32 t-Bu Cl S H 4-OCH.sub.2 OBu H33 t-Bu Br O H 4-OCH.sub.2 OBu H34 t-Bu Cl O H 3-OCH.sub.2 OBu H35 t-Bu Br O H 3-OCH.sub.2 OBu H36 t-Bu Cl S H 3-OCH.sub.2 OBu H37 Et Cl O H 4-OC.sub.2 H.sub.4 OMe H 86.7.about.88.438 Et Cl S H 4-OC.sub.2 H.sub.4 OMe 3-F39 t-Bu Me O H 4-OC.sub.2 H.sub.4 OMe H40 t-Bu Me O Me 4-OC.sub.2 H.sub.4 OMe H41 t-Bu Me S H 4-OC.sub.2 H.sub.4 OMe H42 Pro Cl O H 4-OC.sub.2 H.sub.4 OMe H 84.6.about.85.743 i-Pro Cl O H 4-OC.sub.2 H.sub.4 OMe H 102.0.about.104.044 t-Bu Cl O H 4-OC.sub.2 H.sub.4 OMe H 93.5.about.94.345 t-Bu Cl S H 4-OC.sub.2 H.sub.4 OMe H 105.6.about.107.346 t-Bu Cl S Me 4-OC.sub.2 H.sub.4 OMe H47 t-Bu Cl S H 4-OC.sub.2 H.sub.4 OMe 3-Me48 t-Bu Me S H ##STR18## OMe H49 t-Bu Me O H ##STR19## OMe H50 t-Bu Cl O H 3-OC.sub.2 H.sub.4 OMe H51 t-Bu Cl S H 3-OC.sub.2 H.sub.4 OMe H52 Bu Cl O H 4-OC.sub.2 H.sub.4 ##STR20## H53 t-Bu Cl O H 4-OC.sub.2 H.sub.4 ##STR21## H54 t-Bu Cl S H 4-OC.sub.2 H.sub.4 ##STR22## H55 t-Bu Me O H ##STR23## ##STR24## H56 t-Bu Me O H 4-OC.sub.2 H.sub.4 ##STR25## H57 t-Bu Cl O H 4-OC.sub.2 H.sub.4 ##STR26## H58 t-Bu Bu O H 4-OC.sub.2 H.sub.4 ##STR27## H59 t-Bu Cl S H 4-OC.sub.2 H.sub.4 ##STR28## H60 t-Bu Me O H ##STR29## ##STR30## H61 t-Bu Me O H 4-OC.sub.2 H.sub.4 ##STR31## H62 t-Bu Cl O H 2-OC.sub.2 H.sub.4 OMe H63 t-Bu Cl O H 3-OC.sub.2 H.sub.4 OEt H64 t-Bu Me S H 4-OC.sub.2 H.sub.4 OEt H65 t-Bu Me O H 4-OC.sub.2 H.sub.4 OEt H66 Et Cl O H 4-OC.sub.2 H.sub.4 OEt H67 t-Bu Cl S H ##STR32## OEt 3-Et68 t-Bu Cl S H 4-OC.sub.2 H.sub.4 OEt H 50.5.about.52.069 t-Bu Cl S H ##STR33## OEt 3-Proi70 t-Bu Me S H ##STR34## OEt H71 t-Bu Cl O H 4-OC.sub.2 H.sub.4 OEt H 82.0.about.83.072 t-Bu Me O H ##STR35## OEt H73 t-Bu Cl O H 4-OC.sub.2 H.sub.4 OEt 3-Me74 t-Bu Br O H 4-OC.sub.2 H.sub.4 OEt H75 t-Bu Cl O H ##STR36## OEt 3-Et76 Hex Br O H 4-OC.sub.2 H.sub.4 OEt H77 Et Cl O H 4-OC.sub.2 H.sub.4 OPro H 79.9.about.83.778 Et Cl O H 4-OC.sub.2 H.sub.4 OPro 3-Cl 91.0.about.93.579 t-Bu Me O H ##STR37## OPro H80 t-Bu Me O H 4-OC.sub.2 H.sub.4 OPro H81 t-Bu Cl S H 4-OC.sub.2 H.sub.4 OPro H 59.5.about.63.082 t-Bu Cl S H 4-OC.sub.2 H.sub.4 OPro 3-Cl 61.5.about.62.583 t-Bu Br S H 4-OC.sub.2 H.sub.4 OPro H84 t-Bu Br S Et 4-OC.sub.2 H.sub.4 OPro H85 t-Bu Me S H 4-OC.sub.2 H.sub.4 OPro H86 t-Bu Cl O H 4-OC.sub.2 H.sub.4 OPro 3-Et87 t-Bu Cl O H 4-OC.sub.2 H.sub.4 OPro H Oil88 t-Bu Cl O H 4-OC.sub.2 H.sub.4 OPro 3-Cl 66.0.about.68.089 t-Bu Br O H 4-OC.sub.2 H.sub.4 OPro H90 t-Bu Et O H 4-OC.sub.2 H.sub.4 OPro H91 i-Pro Cl O H 4-OC.sub.2 H.sub.4 OPro H 60.3.about.63.592 t-Bu Me O H ##STR38## OPro H93 t-Bu Me S H ##STR39## OPro H94 t-Bu Cl O H ##STR40## OEt 3-Proi95 t-Bu Me S H ##STR41## OPro H96 t-Bu Me O H 4-OC.sub.2 H.sub.4 OPro 3-Me97 t-Bu Pro O H 4-OC.sub.2 H.sub.4 OPro H98 t-Bu Cl O H ##STR42## OProi 3-Et99 t-Bu Hex S H 4-OC.sub.2 H.sub.4 OProi H100 t-Bu Cl S H 4-OC.sub.2 H.sub.4 OProi 3-Me101 t-Bu Me S H 4-OC.sub.2 H.sub.4 OProi H102 t-Bu Me O H 4-OC.sub.2 H.sub.4 OProi H103 t-Bu Cl O H 4-OC.sub.2 H.sub.4 OProi H104 t-Bu Cl S H 4-OC.sub.2 H.sub.4 OProi H105 t-Bu Cl S H ##STR43## OProi 3-Et106 t-Bu Me O H ##STR44## OProi H107 t-Bu Cl O H 4-OC.sub.2 H.sub.4 OProi 3-Me108 t-Bu Cl S Me 4-OC.sub.2 H.sub.4 OProi H109 t-Bu Me S H ##STR45## OProi H110 t-Bu Cl O H 4-OC.sub.2 H.sub.4 OProi 3-Et111 t-Bu Me O H ##STR46## OProi H112 t-Bu Me S H ##STR47## OProi H113 t-Bu Cl S H 3-OC.sub.2 H.sub.4 OProi H114 Et Cl O H 4-OC.sub.2 H.sub.4 OBu H115 Pro Cl O H 4-OC.sub.2 H.sub.4 OBu H116 s-Bu Cl O H 4-OC.sub.2 H.sub.4 OBu H117 t-Bu Me S H 4-OC.sub.2 H.sub.4 OBu H118 t-Bu Me O H 4-OC.sub.2 H.sub.4 OBu H119 t-Bu i-Pro O H 4-OC.sub.2 H.sub.4 OBu H120 t-Bu Cl O H 4-OC.sub.2 H.sub.4 OBu H121 t-Bu Br O H 4-OC.sub.2 H.sub.4 OBu H122 t-Bu Cl S H 4-OC.sub.2 H.sub.4 OBu H123 t-Bu Me O H ##STR48## OBu H124 t-Bu Cl O H 4-OC.sub.2 H.sub.4 OBu 3-F125 t-Bu Me S H ##STR49## OBu H126 t-Bu Cl O H 3-OC.sub.2 H.sub.4 OBu H127 t-Bu Me O H ##STR50## OBu H128 t-Bu Cl S H 3-OC.sub.2 H.sub.4 OBu H129 t-Bu Me S H ##STR51## OBu H130 i-Pen Cl O H 3-OC.sub.2 H.sub.4 OBu H131 Et Cl O H 4-OC.sub.2 H.sub.4 OBui H132 Pro Cl O H 4-OC.sub.2 H.sub.4 OBui H133 t-Bu Cl O H 4-OC.sub.2 H.sub.4 OBui H134 t-Bu Cl S H 4-OC.sub.2 H.sub.4 OBui H135 t-Bu Me S H 4-OC.sub.2 H.sub.4 OBui H136 t-Bu Me O H 4-OC.sub.2 H.sub.4 OBui H137 t-Bu Br O H 4-OC.sub.2 H.sub.4 OBui 3-F138 t-Bu Br O Me 4-OC.sub.2 H.sub.4 OBui 3-Cl139 t-Bu Br S H 4-OC.sub.2 H.sub.4 OBui H140 t-Bu Me O H ##STR52## OBui H141 t-Bu Me S H ##STR53## OBui H142 t-Bu Cl O H 3-OC.sub.2 H.sub.4 OBui H143 Et Cl O H 4-OC.sub.2 H.sub.4 OBus H144 t-Bu Cl O H 4-OC.sub.2 H.sub.4 OBus H145 t-Bu Cl S H 4-OC.sub.2 H.sub.4 OBus H146 t-Bu Cl S Me 4-OC.sub.2 H.sub.4 OBus H147 t-Bu Cl O H 4-OC.sub. 2 H.sub.4 OBus 3-Me148 t-Bu Br O H 4-OC.sub.2 H.sub.4 OBus H149 t-Bu Br S H 4-OC.sub.2 H.sub.4 OBus H150 t-Bu Me O H 3-OC.sub.2 H.sub.4 OBus H151 t-Bu Me S H 3-OC.sub. 2 H.sub.4 OBus H152 i-Pro Cl O H 4-OC.sub.2 H.sub.4 OPen H153 t-Bu Cl O H 4-OC.sub.2 H.sub.4 OPen H154 t-Bu Cl O H 4-OC.sub.2 H.sub.4 OPen 3-Me155 t-Bu Cl O H 4-OC.sub.2 H.sub.4 OPen 3-F156 t-Bu Me O H 4-OC.sub.2 H.sub.4 OPen H157 t-Bu Me S H 4-OC.sub.2 H.sub.4 OPen H158 t-Bu Me S H ##STR54## OPen H159 t-Bu Cl O H 3-OC.sub.2 H.sub.4 OPen H160 Et Cl O H 4-OC.sub.2 H.sub.4 ##STR55## H161 t-Bu Cl O H 4-OC.sub.2 H.sub.4 ##STR56## 3-F162 t-Bu Br O H 4-OC.sub.2 H.sub.4 ##STR57## H163 t-Bu Cl S H 4-OC.sub.2 H.sub.4 ##STR58## H164 t-Bu Cl O H 4-OC.sub.2 H.sub.4 ##STR59## H165 t-Bu Me O H 4-OC.sub.2 H.sub.4 ##STR60## H166 t-Bu Cl O H 3-OC.sub.2 H.sub.4 ##STR61## H167 Pro Cl O H 4-OC.sub.2 H.sub.4 ##STR62## H168 i-Pro Cl S H 4-OC.sub.2 H.sub.4 ##STR63## H169 t-Bu Cl O H 4-OC.sub.2 H.sub.4 ##STR64## H170 t-Bu Cl S H 4-OC.sub.2 H.sub.4 ##STR65## H171 t-Bu Br O H 4-OC.sub.2 H.sub.4 ##STR66## H172 t-Bu Me S H 4-OC.sub.2 H.sub.4 ##STR67## H173 t-Bu Me O H 4-OC.sub.2 H.sub.4 ##STR68## H174 t-Bu Me O H ##STR69## ##STR70## H175 Pro Cl O H 4-OC.sub.2 H.sub.4 OHex H176 t-Bu Cl O H 4-OC.sub.2 H.sub.4 OHex H177 t-Bu Cl S H 4-OC.sub.2 H.sub.4 OHex H178 t-Bu Me O H 4-OC.sub.2 H.sub.4 OHex H179 t-Bu Me S H 4-OC.sub.2 H.sub.4 OHex H180 Et Cl O H 4-OC.sub.2 H.sub.4 OCH.sub.2 CHCH.sub.2 H181 t-Bu Cl O H 4-OC.sub.2 H.sub.4 OCH.sub.2 CHCH.sub.2 H182 t-Bu Cl S H 4-OC.sub.2 H.sub.4 OCH.sub.2 CHCH.sub.2 H183 t-Bu Cl S Me 4-OC.sub.2 H.sub.4 OCH.sub.2 CHCH.sub.2 H184 t-Bu Br O H 4-OC.sub.2 H.sub.4 OCH.sub.2 CHCH.sub.2 H185 t-Bu Me S H 4-OC.sub.2 H.sub.4 OCH.sub.2 CHCH.sub.2 H186 t-Bu Cl O H 4-OC.sub.2 H.sub.4 OCH.sub.2 CHCH.sub.2 H187 t-Bu Me O H 4-OC.sub.2 H.sub.4 OCH.sub.2 CHCH.sub.2 H188 t-Bu Me O H ##STR71## OCH.sub.2 CHCH.sub.2 H189 t-Bu Me S H ##STR72## OCH.sub.2 CHCH.sub.2 H190 t-Bu Cl O H 3-OC.sub.2 H.sub.4 OCH.sub.2 CHCH.sub.2 H191 t-Bu Me O H ##STR73## OCH.sub.2 CHCH.sub.2 H192 t-Bu Me S H ##STR74## OCH.sub.2 CHCH.sub.2 H193 t-Bu Me O H 4-OC(CH.sub.3).sub.2 CH.sub.2 OCH.sub.2 CHCH.sub.2 H194 t-Bu Me O H 4-OC.sub.2 H.sub.4 OCH.sub.2 CHCHCH.sub.3 H195 t-Bu Cl O H 4-OC.sub.2 H.sub.4 OCH.sub.2 CHCHCH.sub.3 H196 t-Bu Cl S H 4-OC.sub.2 H.sub.4 OCH.sub.2 CHCHCH.sub.3 H197 t-Bu Cl O H 4-OC.sub.2 H.sub.4 OCH.sub.2 CHCHCH.sub.3 H198 t-Bu Me O H ##STR75## OCH.sub.2 CHCHCH.sub.3 H199 t-Bu Br S H 4-OC.sub.2 H.sub.4 OCH.sub.2 CHCHCH.sub.3 H200 t-Bu Br S Me 4-OC.sub.2 H.sub.4 OCH.sub.2 CHCHCH.sub.3 H201 t-Bu Me S H 4-OC.sub.2 H.sub.4 OCH.sub.2 CHCHCH.sub.3 H202 t-Bu Cl O H 3-OC.sub.2 H.sub.4 OCH.sub.2 CHCHCH.sub.3 H203 t-Bu Me S H ##STR76## OCH.sub.2 CHCHCH.sub.3 H204 t-Bu Me O H ##STR77## OCH.sub.2 CHCHCH.sub.3 H205 t-Bu Cl O H 4-OCH.sub.2 CH.sub.2 CH.sub.2 ##STR78## H206 t-Bu Cl S H 4-OCH.sub.2 CH.sub.2 CH.sub.2 ##STR79## H207 t-Bu Cl O H 4-OCH.sub.2 CH.sub.2 CH.sub.2 CH.sub.2 ##STR80## H208 Et Cl O H ##STR81## ##STR82## H209 t-Bu Cl O H ##STR83## ##STR84## H210 t-Bu Cl S H ##STR85## ##STR86## H211 t-Bu Cl O H ##STR87## ##STR88## H212 t-Bu Cl S H ##STR89## ##STR90## H213 t-Bu Cl S H 4-OC(CH.sub.3).sub.2 CH.sub.2 ##STR91## H214 t-Bu Cl O H 4-OC(CH.sub.3).sub.2 CH.sub.2 ##STR92## H215 t-Bu Cl O H ##STR93## ##STR94## H216 t-Bu Br O H ##STR95## ##STR96## H217 i-Pro Cl O H ##STR97## ##STR98## H218 t-Bu Cl O H ##STR99## ##STR100## H219 t-Bu Cl S H ##STR101## ##STR102## H220 t-Bu Br O H ##STR103## ##STR104## H221 t-Bu Cl O H ##STR105## ##STR106## H222 t-Bu Cl O H 4-OCH.sub.2 CH.sub.2 CH.sub.2 ##STR107## H223 t-Bu Cl O H 3-OCH.sub.2 CH.sub.2 CH.sub.2 ##STR108## H224 t-Bu Cl O H ##STR109## ##STR110## H225 t-Bu Cl S H ##STR111## ##STR112## H226 t-Bu Br O H ##STR113## ##STR114## H227 t-Bu Cl O H ##STR115## ##STR116## H228 t-Bu Cl O H ##STR117## ##STR118## H229 t-Bu Cl S H ##STR119## ##STR120## H230 Et Cl O H ##STR121## ##STR122## 3-Me231 t-Bu Cl S H ##STR123## ##STR124## H232 t-Bu Cl O H 4-OC(CH.sub.3).sub.2 CH.sub.2 ##STR125## H233 t-Bu Cl S H 4-OC(CH.sub.3).sub.2 CH.sub.2 ##STR126## H234 i-Pro Cl O H ##STR127## ##STR128## H235 t-Bu Cl O H ##STR129## ##STR130## H236 t-Bu Cl S H ##STR131## ##STR132## H237 t-Bu Br O H ##STR133## ##STR134## H238 Et Cl O H 4-OC.sub.2 H.sub.4 OCH.sub.2 C CH H239 Pro Cl O H 4-OC.sub.2 H.sub.4 OCH.sub.2 CCH H240 t-Bu Me O H 4-OC.sub.2 H.sub.4 OCH.sub.2 CCH H241 t-Bu Me S Me 4-OC.sub.2 H.sub.4 OCH.sub.2 CCH H242 t-Bu Cl O H 4-OC.sub.2 H.sub.4 OCH.sub.2 CCH H243 t-Bu Me O H 4-OC(CH.sub.3).sub.2 CH.sub.2 OCH.sub.2 CCH H244 t-Bu Cl O H 4-OC.sub.2 H.sub.4 OCH.sub.2 CCH 3-F245 t-Bu Cl S H 4-OC.sub.2 H.sub.4 OCH.sub.2 CCH H246 t-Bu Me O H ##STR135## OCH.sub.2 CCH H247 t-Bu Me O H ##STR136## OCH.sub.2 CCH H248 t-Bu Cl O H 3-OC.sub.2 H.sub.4 OCH.sub.2 CCH H249 t-Bu Me S H ##STR137## OCH.sub.2 CCH H250 t-Bu Me O H ##STR138## OCH.sub.2 CCH H251 t-Bu Cl O H 4-OC.sub.2 H.sub.4 OCH.sub.2 CCCH.sub.3 H252 t-Bu Cl S H 4-OC.sub.2 H.sub.4 OCH.sub.2 CCCH.sub.3 H253 t-Bu Br O H 4-OC.sub.2 H.sub.4 OCH.sub.2 CCCH.sub.3 H254 t-Bu Me O H 4-OC.sub.2 H.sub.4 ##STR139## H255 t-Bu Et O H 4-OC.sub.2 H.sub.4 ##STR140## H256 t-Bu Cl O H 4-OC.sub.2 H.sub.4 ##STR141## H257 t-Bu Cl S H 4-OC.sub.2 H.sub.4 ##STR142## H258 t-Bu Br O H 4-OC.sub.2 H.sub.4 ##STR143## H259 t-Bu Me O H ##STR144## ##STR145## H260 t-Bu Me O H ##STR146## ##STR147## H261 t-Bu Me O H 4-OC.sub.2 H.sub.4 ##STR148## H262 t-Bu Cl O H 4-OC.sub.2 H.sub.4 ##STR149## H263 t-Bu Br O H 4-OC.sub.2 H.sub.4 ##STR150## H264 t-Bu Me O H ##STR151## ##STR152## H265 t-Bu Cl S H 4-OC.sub.2 H.sub.4 ##STR153## H266 t-Bu Me S H ##STR154## ##STR155## H267 t-Bu Me S H 4-OC.sub.2 H.sub.4 ##STR156## H268 t-Bu Me O H 4-OC.sub.2 H.sub.4 ##STR157## H269 t-Bu Me S H 4-OC.sub.2 H.sub.4 ##STR158## H270 t-Bu Cl O H 4-OC.sub.2 H.sub.4 ##STR159## H271 t-Bu Cl S H 4-OC.sub.2 H.sub.4 ##STR160## H272 t-Bu Br O H 4-OC.sub.2 H.sub.4 ##STR161## H273 t-Bu Et O H 4-OC.sub.2 H.sub.4 ##STR162## H274 t-Bu Me O H ##STR163## ##STR164## H275 t-Bu Me S Me ##STR165## ##STR166## H276 t-Bu Me O H ##STR167## ##STR168## H277 t-Bu Me O H ##STR169## ##STR170## H278 t-Bu Cl S H ##STR171## SMe H279 t-Bu Me O H 4-OC.sub.2 H.sub.4 SMe H280 t-Bu Cl O H 4-OC.sub.2 H.sub.4 SMe 3-Cl281 t-Bu Cl O H 4-OC.sub.2 H.sub.4 SMe H 77.0.about.79.0282 t-Bu Cl S H 4-OC.sub.2 H.sub.4 SMe H283 t-Bu Cl O H ##STR172## SMe H284 Pen Cl O H 4-OC.sub.2 H.sub.4 SMe H285 t-Bu Me S H 4-OC.sub.2 H.sub.4 SMe H286 t-Bu Cl O H 4-OC(CH.sub.3).sub.2 CH.sub.2 SMe H287 t-Bu Me S H ##STR173## SMe H288 t-Bu Me O H ##STR174## SMe H289 Pro Cl O H 4-OC.sub.2 H.sub.4 SEt H290 t-Bu Me O H 4-OC.sub.2 H.sub.4 SEt H291 t-Bu Cl O H 4-OC.sub.2 H.sub.4 SEt H 60.0.about.62.0292 t-Bu Cl S H 4-OC.sub.2 H.sub.4 SEt H293 t-Bu Cl O H ##STR175## SEt H294 t-Bu Me S H 4-OC.sub.2 H.sub.4 SEt H295 t-Bu Cl O H 4-OC.sub.2 H.sub.4 SEt 3-Et296 t-Bu Cl S Me 4-OC.sub.2 H.sub.4 SEt H297 t-Bu Me O H ##STR176## SEt H298 t-Bu Me S H ##STR177## SEt H299 t-Bu Cl S H ##STR178## SEt H300 Et Cl S H 4-OC.sub.2 H.sub.4 SPro H301 t-Bu Me O H 4-OC.sub.2 H.sub.4 SPro H302 t-Bu Cl O H 4-OC.sub.2 H.sub.4 SPro H 66.5.about.67.9303 t-Bu Cl S H 4-OC.sub.2 H.sub.4 SPro H304 t-Bu Br O H 4-OC.sub.2 H.sub.4 SPro H305 t-Bu Me O H ##STR179## SPro H306 t-Bu Me S H 4-OC(CH.sub.3).sub.2 CH.sub.2 SPro H307 t-Bu Cl O H ##STR180## SPro H308 t-Bu Me O H 4-OC.sub.2 H.sub.4 SProi H309 t-Bu Et O H 4-OC.sub.2 H.sub.4 SProi H310 t-Bu Cl O H 4-OC.sub.2 H.sub.4 SProi H 82.0.about.84.5311 t-Bu Cl O H 4-OC.sub.2 H.sub.4 SProi 3-Me312 t-Bu Cl S H 4-OC.sub.2 H.sub.4 SProi H313 t-Bu Cl S H 4-OC.sub.2 H.sub.4 SProi 3-F314 t-Bu Cl O H 4-OC(CH.sub.3).sub.2 CH.sub.2 SProi H315 t-Bu Me O H ##STR181## SProi H316 t-Bu Me S H ##STR182## SProi H317 t-Bu Me O H ##STR183## SProi H318 t-Bu Cl S H 3-OC.sub.2 H.sub.4 SProi H319 t-Bu Me O H 4-OC.sub.2 H.sub.4 SBu H320 t-Bu Pro S H 4-OC.sub.2 H.sub.4 SBu H321 t-Bu Cl O H 4-OC.sub.2 H.sub.4 SBu H 57.0.about.58.0322 t-Bu Cl S H 4-OC.sub.2 H.sub.4 SBu H323 t-Bu Cl O H ##STR184## SBu H324 t-Bu Me O H ##STR185## SBu H325 t-Bu Me S H 4-OC(CH.sub.3).sub.2 CH.sub.2 SBu H326 t-Bu Me O H ##STR186## SBu H327 t-Bu Me S H 4-OC.sub.2 H.sub.4 SPen H328 t-Bu Me O H ##STR187## SPen H329 t-Bu Cl O H 4-OC.sub.2 H.sub.4 SPen H330 t-Bu Cl S H 4-OC.sub.2 H.sub.4 SPen H331 t-Bu Br S H 4-OC.sub.2 H.sub.4 SPen H332 t-Bu Me S H ##STR188## SPen H333 t-Bu Et O H 4-OC.sub.2 H.sub.4 SPen H334 t-Bu Me O H 4-OC.sub.2 H.sub.4 SOMe H335 t-Bu Me O H 4-OC.sub.2 H.sub.4 SO.sub.2 Me H336 t-Bu Cl O H 4-OC.sub.2 H.sub.4 SOMe H337 t-Bu Cl O H 4-OC.sub.2 H.sub.4 SO.sub.2 Me H338 t-Bu Cl S H 4-OC.sub.2 H.sub. 4 SOMe H339 t-Bu Me O H ##STR189## SO.sub.2 Me H340 t-Bu Cl O H ##STR190## SOMe H341 t-Bu Cl O H ##STR191## SO.sub.2 Me H342 t-Bu Me O H 4-OC.sub.2 H.sub.4 SOEt H343 t-Bu Cl S H 4-OC.sub.2 H.sub.4 SO.sub.2 Et H344 t-Bu Cl S H 4-OC.sub.2 H.sub.4 SOEt H345 t-Bu Cl S H 4-OC.sub.2 H.sub.4 SO.sub.2 Et H346 t-Bu Et O H 4-OC.sub.2 H.sub.4 SOEt H347 t-Bu Cl O H 4-OC.sub.2 H.sub.4 SO.sub.2 Et H348 t-Bu Cl O H ##STR192## SOEt H349 t-Bu Me O H ##STR193## SO.sub.2 Et H350 t-Bu Cl O H 4-OC.sub.2 H.sub.4 SOPro H351 t-Bu Cl O H 4-OC.sub.2 H.sub.4 SO.sub.2 Pro H352 t-Bu Cl S H 4-OC.sub.2 H.sub.4 SOPro H353 t-Bu Cl S H 4-OC.sub.2 H.sub.4 SO.sub.2 Pro H354 t-Bu Cl O H ##STR194## SOPro H355 t-Bu Cl O H ##STR195## SO.sub.2 Pro H356 t-Bu Cl O H 4-OC.sub.2 H.sub.4 SOProi H357 t-Bu Cl O H 4-OC.sub.2 H.sub.4 SO.sub.2 Proi H358 t-Bu Cl O H ##STR196## SOProi H359 t-Bu Cl O H ##STR197## SO.sub.2 Proi H360 t-Bu Cl S H 4-OC.sub.2 H.sub.4 SOProi H361 t-Bu Cl S H 4-OC.sub.2 H.sub.4 SO.sub.2 Proi H362 t-Bu Cl O H 4-OC.sub.2 H.sub.4 SOBu H363 t-Bu Cl O H 4-OC.sub.2 H.sub.4 SO.sub.2 Bu H364 t-Bu Me O H 4-OC.sub.2 H.sub.4 SOPen H365 t-Bu Me O H 4-OC.sub.2 H.sub.4 SO.sub.2 Pen H366 i-Pro Cl S H 4-OC.sub.2 H.sub.4 ##STR198## H367 t-Bu Cl O H 4-OC.sub.2 H.sub.4 ##STR199## H 99.0.about.100.8368 t-Bu Br O H 4-OC.sub.2 H.sub.4 ##STR200## H369 t-Bu Cl S H 4-OC.sub.2 H.sub.4 ##STR201## H 89.0.about.90.4370 t-Bu Cl S H ##STR202## ##STR203## H371 t-Bu Me S H 4-OC.sub.2 H.sub.4 ##STR204## H372 t-Bu Me O H 4-OC.sub.2 H.sub.4 ##STR205## H373 t-Bu Cl O H ##STR206## ##STR207## H374 t-Bu Br O H 4-OC.sub.2 H.sub.4 ##STR208## H375 t-Bu Cl S H 4-OC.sub.2 H.sub.4 ##STR209## H376 t-Bu Cl O H 4-OC.sub.2 H.sub.4 ##STR210## H377 t-Bu Me O H 4-OC.sub.2 H.sub.4 ##STR211## H378 t-Bu Cl O H 4-OC(CH.sub.3).sub.2 CH.sub.2 ##STR212## H379 t-Bu Cl O H 4-OC.sub.2 H.sub.4 ##STR213## H380 t-Bu Me S H 4-OC.sub.2 H.sub.4 ##STR214## H381 t-Bu Cl S H 4-OC.sub.2 H.sub.4 ##STR215## H382 t-Bu Pro S H 3-OC.sub.2 H.sub.4 ##STR216## H383 t-Bu Cl O H ##STR217## ##STR218## H384 t-Bu Cl O H 4-OC.sub.2 H.sub.4 ##STR219## H385 t-Bu Cl S H 4-OC.sub.2 H.sub.4 ##STR220## H386 t-Bu Cl O H ##STR221## ##STR222## H387 t-Bu Cl S H ##STR223## ##STR224## H389 t-Bu Me O H 4-OC.sub.2 H.sub.4 ##STR225## H390 Et Cl O H 4-OC.sub.2 H.sub.4 ##STR226## H391 t-Bu Cl O H 4-OC.sub.2 H.sub.4 ##STR227## H Oil392 t-Bu Cl S H 4-OC.sub.2 H.sub.4 ##STR228## H Oil393 t-Bu Br O H 4-OC.sub.2 H.sub.4 ##STR229## H394 t-Bu Cl O H 4-OC.sub.2 H.sub.4 ##STR230## H395 t-Bu Cl S H 4-OC.sub.2 H.sub.4 ##STR231## H396 t-Bu Cl O H ##STR232## ##STR233## H397 t-Bu Cl S H 4-OC.sub.2 H.sub.4 ##STR234## H398 t-Bu Me O H ##STR235## ##STR236## H399 Et Cl S H 4-OCH.sub.2 CH.sub.2 CH.sub.2 OMe H400 Pro Br S Et 4-OCH.sub.2 CH.sub.2 CH.sub.2 OMe Me401 t-Bu Cl O H 4-OCH.sub.2 CH.sub.2 CH.sub.2 OMe 3-F402 t-Bu Cl O H 4-OCH.sub.2 CH.sub.2 CH.sub.2 OMe H 94.0.about.96.0403 t-Bu Cl S H 4-OCH.sub.2 CH.sub.2 CH.sub.2 OMe H 102.0.about.104.0404 t-Bu Et O H 4-OCH.sub.2 CH.sub.2 CH.sub.2 OMe H405 t-Bu Cl S Me 4-OCH.sub.2 CH.sub.2 CH.sub.2 OMe H406 t-Bu Me S H 4-OCH.sub.2 CH.sub.2 CH.sub.2 OMe H407 t-Bu Cl O H 3-OCH.sub.2 CH.sub.2 CH.sub.2 OMe H408 t-Bu Me O H 4-OCH.sub.2 CH.sub.2 CH.sub.2 OMe H409 t-Bu Cl S H 3-OCH.sub.2 CH.sub.2 CH.sub.2 OMe H410 Et Cl S H 4-OCH.sub.2 CH.sub.2 CH.sub.2 OEt H411 Pro Cl O H 4-OCH.sub.2 CH.sub.2 CH.sub.2 OEt 3-Me412 t-Bu Cl O H 4-OCH.sub.2 CH.sub.2 CH.sub.2 OEt 3-F413 t-Bu Cl O H 4-OCH.sub.2 CH.sub.2 CH.sub.2 OEt H 77.0.about.78.0414 t-Bu Br S H 4-OCH.sub.2 CH.sub.2 CH.sub.2 OEt H415 t-Bu Cl S H 4-OCH.sub.2 CH.sub.2 CH.sub.2 OEt H 111.0.about.112.0416 t-Bu Cl S H 3-OCH.sub.2 CH.sub.2 CH.sub.2 OEt H417 t-Bu Cl O H 3-OCH.sub.2 CH.sub.2 CH.sub.2 OEt H418 t-Bu Me S H 4-OCH.sub.2 CH.sub.2 CH.sub.2 OEt H419 t-Bu Me O H 4-OCH.sub.2 CH.sub.2 CH.sub.2 OEt H420 Et Cl O H 4-OCH.sub.2 CH.sub. 2 CH.sub.2 OPro H421 t-Bu Cl O H 4-OCH.sub.2 CH.sub.2 CH.sub.2 OPro H Oil422 t-Bu Br O H 4-OCH.sub.2 CH.sub.2 CH.sub.2 OPro H Oil423 t-Bu Cl O H 4-OCH.sub.2 CH.sub.2 CH.sub.2 OPro 3-F424 t-Bu Cl S H 4-OCH.sub.2 CH.sub.2 CH.sub.2 OPro H 78.5.about.80.0425 t-Bu Cl S Me 4-OCH.sub.2 CH.sub.2 CH.sub.2 OPro H426 t-Bu Cl O H 3-OCH.sub.2 CH.sub.2 CH.sub.2 OPro H427 t-Bu Me O H 4-OCH.sub.2 CH.sub.2 CH.sub.2 OPro H428 t-Bu Cl S H 3-OCH.sub.2 CH.sub.2 CH.sub.2 OPro H429 Bu i-Bu O H 4-OCH.sub.2 CH.sub.2 CH.sub.2 OProi H430 t-Bu Cl S H 4-OCH.sub.2 CH.sub.2 CH.sub.2 OProi H431 t-Bu Cl O H 4-OCH.sub.2 CH.sub.2 CH.sub.2 OProi H432 t-Bu Br O H 4-OCH.sub.2 CH.sub.2 CH.sub.2 OProi H433 t-Bu Me O H 3-OCH.sub.2 CH.sub.2 CH.sub.2 OProi H434 t-Bu Cl S H 3-OCH.sub.2 CH.sub.2 CH.sub.2 OProi H435 t-Bu Me S H 4-OCH.sub.2 CH.sub.2 CH.sub.2 OProi H436 t-Bu Me O H 4-OCH.sub.2 CH.sub.2 CH.sub.2 OProi H437 Pro Cl O H 4-OCH.sub.2 CH.sub.2 CH.sub.2 OBu H438 t-Bu Me S H 4-OCH.sub.2 CH.sub.2 CH.sub.2 OBu H439 t-Bu Cl S H 4-OCH.sub.2 CH.sub.2 CH.sub.2 OBu H440 t-Bu Cl S Me 4-OCH.sub.2 CH.sub.2 CH.sub.2 OBu H441 t-Bu Pen O H 3-OCH.sub.2 CH.sub.2 CH.sub.2 OBu H442 t-Bu Cl S H 3-OCH.sub.2 CH.sub.2 CH.sub.2 OBu H443 t-Bu Cl O H 4-OCH.sub.2 CH.sub.2 CH.sub.2 OBui H444 t-Bu Cl S H 4-OCH.sub.2 CH.sub.2 CH.sub.2 OBui H445 t-Bu Me O H 4-OCH.sub.2 CH.sub.2 CH.sub.2 OBui H446 t-Bu Cl O H 3-OCH.sub.2 CH.sub.2 CH.sub.2 OBui H447 t-Bu Cl S H 3-OCH.sub.2 CH.sub.2 CH.sub.2 OBui H448 t-Bu Cl O H 4-OCH.sub.2 CH.sub.2 CH.sub.2 OBus H449 t-Bu Cl S H 4-OCH.sub.2 CH.sub.2 CH.sub.2 OBus H450 t-Bu Cl S H 3-OCH.sub.2 CH.sub.2 CH.sub.2 OBus H451 t-Bu Cl O H 3-OCH.sub.2 CH.sub.2 CH.sub.2 OBus H452 Et Cl O H 4-OCH.sub.2 CH.sub.2 CH.sub.2 OPen 3-Me453 t-Bu Cl O H 4-OCH.sub.2 CH.sub.2 CH.sub.2 OPen H454 t-Bu Cl O H 3-OCH.sub.2 CH.sub.2 CH.sub.2 OPen H455 t-Bu Cl O H 4-OCH.sub.2 CH.sub.2 CH.sub.2 ##STR237## H456 t-Bu Cl O H 4-OCH.sub.2 CH.sub.2 CH.sub.2 ##STR238## H457 t-Bu Br S H 3-OCH.sub.2 CH.sub.2 CH.sub.2 OHex H458 t-Bu Cl O H 4-OCH.sub.2 CH.sub.2 CH.sub.2 OCH.sub.2 CHCH.sub.2 H459 t-Bu Cl S H 4-OCH.sub.2 CH.sub.2 CH.sub.2 OCH.sub.2 CHCH.sub.2 H460 t-Bu Me O H 4-OCH.sub.2 CH.sub.2 CH.sub.2 OCH.sub.2 CHCH.sub.2 H461 t-Bu Cl O H 3-OCH.sub.2 CH.sub.2 CH.sub.2 OCH.sub.2 CHCH.sub.2 H462 t-Bu Me O H 4-OCH.sub.2 CH.sub.2 CH.sub.2 OCH.sub. 2 CHCHCH.sub.3 H463 t-Bu Cl O H 4-OCH.sub.2 CH.sub.2 CH.sub.2 OCH.sub.2 CHCHCH.sub.3 H464 t-Bu Cl S H 4-OCH.sub.2 CH.sub.2 CH.sub.2 OCH.sub.2 CHCHCH.sub.3 H465 t-Bu Cl O H 3-OCH.sub.2 CH.sub.2 CH.sub.2 OCH.sub.2 CHCHCH.sub.3 H466 Pro Cl O H 4-OCH.sub.2 CH.sub.2 CH.sub.2 OCH.sub.2 CCH H467 t-Bu Cl O H 4-OCH.sub.2 CH.sub.2 CH.sub.2 OCH.sub.2 CCH H468 t-Bu Cl S H 4-OCH.sub.2 CH.sub.2 CH.sub.2 OCH.sub.2 CCH H469 t-Bu Br O H 4-OCH.sub.2 CH.sub.2 CH.sub.2 OCH.sub.2 CCH H470 t-Bu Cl O H 4-OCH.sub.2 CH.sub.2 CH.sub.2 OCH.sub.2 CCCH.sub.3 H471 t-Bu Cl S H 4-OCH.sub.2 CH.sub.2 CH.sub.2 OCH.sub.2 C CCH.sub.3 H472 t-Bu Cl O H 4-OCH.sub.2 CH.sub.2 CH.sub.2 ##STR239## H473 t-Bu Cl S H 4-OCH.sub.2 CH.sub.2 CH.sub.2 ##STR240## H474 t-Bu Br O H 4-OCH.sub.2 CH.sub.2 CH.sub.2 ##STR241## H475 t-Bu Et O H 3-OCH.sub.2 CH.sub.2 CH.sub.2 ##STR242## H476 t-Bu Cl O H 4-OCH.sub.2 CH.sub.2 CH.sub.2 ##STR243## H477 t-Bu Cl S H 4-OCH.sub.2 CH.sub.2 CH.sub.2 ##STR244## H478 t-Bu Cl O H 4-OCH.sub.2 CH.sub.2 CH.sub.2 ##STR245## H479 t-Bu Cl S H 4-OCH.sub.2 CH.sub.2 CH.sub.2 ##STR246## H480 t-Bu Me O H 4-OCH.sub.2 CH.sub.2 CH.sub.2 CH.sub.2 OMe H481 t-Bu Cl O H 4-OCH.sub.2 CH.sub.2 CH.sub.2 CH.sub.2 OMe H482 t-Bu Cl S H 4-OCH.sub.2 CH.sub.2 CH.sub.2 CH.sub.2 OMe H483 t-Bu Cl O H 3-OCH.sub.2 CH.sub.2 CH.sub.2 CH.sub.2 OMe H484 t-Bu Cl O H 4-OCH.sub.2 CH.sub.2 CH.sub.2 CH.sub.2 OEt H485 t-Bu Cl S H 4-OCH.sub.2 CH.sub.2 CH.sub.2 CH.sub.2 OEt H486 t-Bu Br O H 4-OCH.sub.2 CH.sub.2 CH.sub.2 CH.sub.2 OEt H487 t-Bu Cl O H 4-OCH.sub.2 CH.sub.2 CH.sub.2 CH.sub.2 OPro H488 t-Bu Br O H 4-OCH.sub.2 CH.sub.2 CH.sub.2 CH.sub.2 OPro H489 t-Bu Cl S H 4-OCH.sub.2 CH.sub.2 CH.sub.2 CH.sub.2 OPro H490 t-Bu Cl O H 3-OCH.sub.2 CH.sub.2 CH.sub.2 CH.sub.2 OPro H491 t-Bu Cl O H 4-OCH.sub.2 CH.sub.2 CH.sub.2 CH.sub.2 OProi H492 t-Bu Cl S H 4-OCH.sub.2 CH.sub.2 CH.sub.2 CH.sub.2 OProi H493 t-Bu Cl O H 4-OCH.sub.2 CH.sub.2 CH.sub.2 CH.sub.2 OBu H494 t-Bu Cl S H 4-OCH.sub.2 CH.sub.2 CH.sub.2 CH.sub.2 OBu H495 t-Bu Cl O H 4-OCH.sub.2 CH.sub.2 CH.sub.2 CH.sub.2 OBui H496 t-Bu Cl S H 3-OCH.sub.2 CH.sub.2 CH.sub.2 CH.sub.2 OBui H497 t-Bu Cl O H 4-OCH.sub.2 CH.sub.2 CH.sub.2 CH.sub.2 OBus H498 t-Bu Cl S H 3-OCH.sub.2 CH.sub.2 CH.sub.2 CH.sub.2 OBus H499 t-Bu Br O H 3-OCH.sub.2 CH.sub.2 CH.sub. 2 OHex H500 Et Cl O H ##STR247## OMe H 51.0.about.53.0501 i-Pro Cl O H ##STR248## OMe H 115.2.about.116.1502 t-Bu Cl O H ##STR249## OMe H 68.4.about.70.0503 t-Bu Br O H ##STR250## OMe H504 t-Bu Cl S H ##STR251## OMe H 51.0.about.52.0505 t-Bu Br S H ##STR252## OMe H506 t-Bu Cl O H ##STR253## OMe H507 Et Cl O H ##STR254## OEt H508 t-Bu Cl O H ##STR255## OEt 3-Me Oil509 t-Bu Cl S H ##STR256## OEt 3-Me Oil510 t-Bu Cl S Me ##STR257## OEt H511 t-Bu Cl O H ##STR258## OEt H 72.3.about.73.1512 t-Bu Br O H ##STR259## OEt H513 t-Bu Cl S H ##STR260## OEt H 89.2.about.90.2514 t-Bu Cl O H ##STR261## OEt H515 t-Bu Cl S H ##STR262## OEt H Oil516 t-Bu Cl O H ##STR263## OEt H Oil517 t-Bu Cl O H ##STR264## OPro H Oil518 t-Bu Cl O H ##STR265## OPro 3-Me519 t-Bu Br O H ##STR266## OPro H520 t-Bu Br S H ##STR267## OPro H521 t-Bu Cl S H ##STR268## OPro H Oil522 t-Bu Cl S H ##STR269## OPro H Oil523 t-Bu Cl O H ##STR270## OPro H Oil524 t-Bu Cl O H ##STR271## OProi H 60.0.about.62.0525 t-Bu Br O H ##STR272## OProi H526 t-Bu Br S H ##STR273## OProi H527 t-Bu Cl S H ##STR274## OProi H 83.0.about.84.5528 t-Bu Cl S Me ##STR275## OProi H529 t-Bu Cl O H ##STR276## OProi H530 Pro Cl O H ##STR277## OBu H531 t-Bu Cl O H ##STR278## OBu H Oil532 t-Bu Br O H ##STR279## OBu H533 t-Bu Cl S H ##STR280## OBu H Oil534 t-Bu Cl O H ##STR281## OBu H535 t-Bu Cl O H ##STR282## OBui H Oil536 t-Bu Br O H ##STR283## OBui H537 t-Bu Br S H ##STR284## OBui H538 t-Bu Cl S H ##STR285## OBui H Oil539 t-Bu Cl O H ##STR286## OBus H540 t-Bu Br O H ##STR287## OBus H541 t-Bu Cl S H ##STR288## OBus H542 t-Bu Me O H ##STR289## OBus H543 t-Bu Cl O H ##STR290## OPen H544 t-Bu Br O H ##STR291## OPen H545 t-Bu Et O H ##STR292## ##STR293## H546 t-Bu Cl O H ##STR294## ##STR295## H547 t-Bu Cl S H ##STR296## ##STR297## H548 t-Bu Cl S H ##STR298## ##STR299## H549 t-Bu Cl O H ##STR300## ##STR301## H550 t-Bu Me O H ##STR302## ##STR303## H551 t-Bu Br O H ##STR304## OHex H Oil552 t-Bu Cl O H ##STR305## OHex H Oil553 t-Bu Cl S H ##STR306## OHex H Oil554 t-Bu Cl O H ##STR307## OCH.sub.2 CHCH.sub.2 H Oil555 t-Bu Cl S H ##STR308## OCH.sub.2 CHCH.sub.2 H Oil556 t-Bu Br O H ##STR309## OCH.sub.2 CHCH.sub.2 H557 Pro Cl O H ##STR310## OCH.sub.2 CHCHCH.sub.3 H558 t-Bu Cl O H ##STR311## OCH.sub.2 CHCHCH.sub.3 H559 t-Bu Cl S H ##STR312## OCH.sub.2 CHCHCH.sub.3 H560 t-Bu Cl O H ##STR313## OCH.sub.2 CHCHCH.sub.3 H561 t-Bu Cl O H ##STR314## OCH.sub.2 CCH H562 t-Bu Cl S H ##STR315## OCH.sub.2 CCH H563 t-Bu Cl O H ##STR316## OCH.sub.2 CCHCH.sub.3 H564 t-Bu Cl O H ##STR317## ##STR318## H565 t-Bu Cl S H ##STR319## ##STR320## H566 t-Bu Br O H ##STR321## ##STR322## H567 t-Bu Br O H ##STR323## ##STR324## H568 t-Bu Cl O H ##STR325## ##STR326## H569 t-Bu Cl S H ##STR327## ##STR328## H570 t-Bu Cl S H ##STR329## ##STR330## H571 t-Bu Cl O H ##STR331## ##STR332## H572 t-Bu Br S H ##STR333## ##STR334## H573 t-Bu Me O H ##STR335## OMe H574 t-Bu Me S H ##STR336## OMe H575 t-Bu Cl S H ##STR337## OMe H576 t-Bu Cl O H ##STR338## OMe H577 Pro Br S Me ##STR339## OEt H578 t-Bu Et O E ##STR340## OEt H579 t-Bu Cl O H ##STR341## OEt H Oil580 t-Bu Cl S H ##STR342## OEt H581 t-Bu Cl O H ##STR343## OPro H Oil582 t-Bu Cl S H ##STR344## OPro H Oil583 t-Bu Br O H ##STR345## OPro H584 t-Bu Cl O H ##STR346## OPro 3-Me585 t-Bu Me S H ##STR347## OPro H586 t-Bu Me O H ##STR348## OPro H587 t-Bu Br O H ##STR349## OBu H588 t-Bu Cl O H ##STR350## OBu H589 t-Bu Cl O H ##STR351## OBui H590 t-Bu Cl S Me ##STR352## OBui H591 t-Bu Cl O H ##STR353## OPen H592 t-Bu Cl O H ##STR354## OPen H593 t-Bu Cl O H ##STR355## OPen-i H594 t-Bu Cl O H ##STR356## OHex H595 t-Bu Cl O H ##STR357## OCH.sub.2 CHCH.sub.2 H596 t-Bu Cl S H ##STR358## OCH.sub.2 CHCH.sub.2 H597 t-Bu Me O H ##STR359## OCH.sub.2 CHCH.sub.2 H598 t-Bu Br O H ##STR360## OCH.sub.2 CHCHCH.sub.3 H599 t-Bu Cl O H ##STR361## OCH.sub.2 CHCHCH.sub.3 H600 t-Bu Cl O H ##STR362## OCH.sub.2 CCH H601 t-Bu Cl S H ##STR363## OCH.sub.2 CCH H602 t-Bu Br O H ##STR364## OCH.sub.2 CCH H603 t-Bu Cl O H ##STR365## OCH.sub.2 CCCH.sub.3 H604 t-Bu Cl S H ##STR366## OCH.sub.2 C CCH.sub.3 H605 t-Bu Cl S H ##STR367## ##STR368## H606 t-Bu Cl O H ##STR369## ##STR370## H607 t-Bu Cl O H ##STR371## ##STR372## H608 t-Bu Cl O H 4-OC(CH.sub.3).sub.2 CH.sub.2 OMe H609 t-Bu Cl S H 4-OC(CH.sub.3).sub.2 CH.sub.2 OMe H610 Pro Cl O H 4-OC(CH.sub.3).sub.2 CH.sub.2 OEt H611 t-Bu Cl O H 4-OC(CH.sub.3).sub.2 CH.sub.2 OEt H Oil612 t-Bu Cl S H 4-OC(CH.sub.3).sub.2 CH.sub.2 OEt H Oil613 t-Bu Me O H 4-OC(CH.sub.3).sub.2 CH.sub.2 OEt H614 t-Bu Br O H 4-OC(CH.sub.3).sub.2 CH.sub.2 OPro H615 t-Bu Cl O H 4-OC(CH.sub.3).sub.2 CH.sub.2 OPro H Oil616 t-Bu Cl S H 4-OC(CH.sub.3).sub.2 CH.sub.2 OPro H Oil617 Pen Cl O H 4-OC(CH.sub.3 ).sub.2 CH.sub.2 OPro H618 t-Bu Cl O H 4-OC(CH.sub.3).sub.2 CH.sub.2 OProi H619 t-Bu Cl S H 4-OC(CH.sub.3).sub.2 CH.sub.2 OProi H620 t-Bu Cl S H 4-OC(CH.sub.3).sub.2 CH.sub.2 OBu H621 t-Bu Cl O H 4-OC(CH.sub.3).sub.2 CH.sub.2 OBu H622 t-Bu Cl O H 4-OC(CH.sub.3).sub.2 CH.sub.2 OBui H623 t-Bu Cl S H 4-OC(CH.sub.3).sub.2 CH.sub.2 OBui H624 t-Bu Me O H 4-OC(CH.sub.3).sub.2 CH.sub.2 OProi H625 t-Bu Me S H 4-OC(CH.sub.3).sub.2 CH.sub.2 OProi H626 t-Bu Cl O H 4-OC(CH.sub.3).sub.2 CH.sub.2 OCH.sub.2 CCH.sub.2 H627 t-Bu Cl S H 4-OC(CH.sub.3).sub.2 CH.sub.2 OCH.sub.2 CCH.sub.2 H628 t-Bu Cl O H 4-OC(CH.sub.3).sub.2 CH.sub.2 OCH.sub.2 CHCHCH.sub.3 H629 t-Bu Cl O H 4-OC(CH.sub.3).sub.2 CH.sub.2 OCH.sub.2 CCH H630 t-Bu Cl S H 4-OC(CH.sub.3).sub. 2 CH.sub.2 OCH.sub.2 CCH H631 t-Bu Cl S H 4-OC(CH.sub.3).sub.2 CH.sub.2 ##STR373## H632 t-Bu Cl O H 4-OC(CH.sub.3).sub.2 CH.sub.2 ##STR374## H633 t-Bu Cl O H 4-OC(CH.sub.3).sub.2 CH.sub.2 ##STR375## H634 t-Bu Cl S Me 4-OC(CH.sub.3).sub.2 CH.sub.2 ##STR376## H635 t-Bu Cl O H 4-OC(CH.sub.3).sub.2 CH.sub.2 OMe H636 t-Bu Cl S H ##STR377## OMe H637 t-Bu Cl O H ##STR378## OMe H 78.4.about.80.1638 t-Bu Me O H ##STR379## OMe H639 t-Bu Cl S H ##STR380## OMe H Oil640 t-Bu Cl O H ##STR381## OEt H641 t-Bu Cl S H ##STR382## OEt H642 t-Bu Me O H ##STR383## OEt H643 t-Bu Me S H ##STR384## OEt H644 t-Bu Cl O H ##STR385## OPro H645 t-Bu Cl S H ##STR386## OPro H646 t-Bu Me S H ##STR387## OPro H647 t-Bu Cl S H ##STR388## OBu H648 t-Bu Br O H ##STR389## OBui H649 t-Bu Cl S H ##STR390## OBui H650 t-Bu Cl O H ##STR391## OCH.sub.2 CHCH.sub.2 H651 t-Bu Cl S H ##STR392## OCH.sub.2 CHCH.sub.2 H652 t-Bu Me S H ##STR393## OCH.sub.2 CHCH.sub.2 H653 t-Bu Cl O H ##STR394## OCH.sub.2 CCH H654 t-Bu Cl S H ##STR395## OCH.sub.2 CCH H655 t-Bu Me S H ##STR396## OCH.sub.2 CCH H656 t-Bu Cl O H ##STR397## ##STR398## H657 t-Bu Cl O H ##STR399## OCH.sub.2 CCCH.sub.3 H658 i-Pro Cl O H ##STR400## OMe H 128.5.about.129.6659 t-Bu Cl O H ##STR401## OMe H Oil660 t-Bu Br O H ##STR402## OMe H661 t-Bu Cl S H ##STR403## OMe H Oil662 t-Bu Me O H ##STR404## OMe H663 Pro Cl O H ##STR405## OEt H 72.0.about.74.0664 t-Bu Cl O H ##STR406## OEt H Oil665 t-Bu Me O H ##STR407## OEt H666 t-Bu Me S H ##STR408## OEt H667 t-Bu Cl S H ##STR409## OEt H 46.0.about.53.0668 t-Bu Cl O H ##STR410## OPro H Oil669 t-Bu Br O H ##STR411## OPro H670 t-Bu Br S H ##STR412## OPro H671 t-Bu Cl S H ##STR413## OPro H Oil672 Et Cl O H ##STR414## OBu H673 t-Bu Cl O H ##STR415## OBu H Oil674 t-Bu Br O H ##STR416## OBu H675 t-Bu Cl S H ##STR417## OBu H 43.0.about.46.0676 t-Bu Cl S H ##STR418## OBui H677 t-Bu Cl O H ##STR419## OBui H678 t-Bu Cl O H ##STR420## OBus H679 t-Bu Cl S H ##STR421## OBus H680 t-Bu Cl O H ##STR422## OPen H681 t-Bu Cl O H ##STR423## OCH.sub.2 CHCH.sub.2 H682 t-Bu Cl S H ##STR424## OCH.sub.2 CHCH.sub.2 H683 t-Bu Cl O H ##STR425## OCH.sub.2 CHCHCH.sub.3 H684 t-Bu Cl S H ##STR426## OCH.sub.2 CHCHCH.sub.3 H685 t-Bu Cl S H ##STR427## OCH.sub.2 CCH H686 t-Bu Cl O H ##STR428## OCH.sub.2 C CH H687 t-Bu Br O H ##STR429## OCH.sub.2 CCH H688 t-Bu Cl O H ##STR430## ##STR431## H689 t-Bu Cl S H ##STR432## ##STR433## H690 t-Bu Cl S H ##STR434## ##STR435## H691 t-Bu Cl O H ##STR436## ##STR437## H692 t-Bu Cl O H ##STR438## ##STR439## H693 t-Bu Me S H ##STR440## OMe H694 t-Bu Cl S H ##STR441## OMe H695 t-Bu Cl O H ##STR442## OMe H696 t-Bu Br O H ##STR443## OMe H697 t-Bu Cl O H ##STR444## OEt H698 t-Bu Cl S H ##STR445## OEt H699 t-Bu Cl S H ##STR446## OPro H700 t-Bu Cl O H ##STR447## OPro H701 Bu Cl O H ##STR448## OBu 3-Me702 t-Bu Cl O H ##STR449## OBui H703 t-Bu Cl S H ##STR450## OBui H704 t-Bu Cl S H ##STR451## OBus H705 t-Bu Cl S H ##STR452## ##STR453## H706 t-Bu Cl O H ##STR454## ##STR455## H707 t-Bu Cl O H ##STR456## ##STR457## H708 t-Bu Cl S H ##STR458## ##STR459## H709 t-Bu Cl O H ##STR460## ##STR461## H710 Bu Cl O H ##STR462## OCH.sub.2 CHCH.sub.2 H711 t-Bu Cl S H ##STR463## OCH.sub.2 CHCH.sub.2 H712 t-Bu Cl O H ##STR464## OCH.sub.2 CHCHCH.sub.3 H713 t-Bu Br O H ##STR465## OCH.sub.2 CHCHCH.sub.3 H714 t-Bu Cl O H ##STR466## OCH.sub.2 CCH H715 t-Bu Cl S H ##STR467## OCH.sub.2 CCH H716 t-Bu Cl S H ##STR468## OCH.sub.2 CCCH.sub.3 H717 t-Bu Cl O H ##STR469## SOEt H718 t-Bu Cl O H ##STR470## SO.sub.2 Et H719 t-Bu Cl S H ##STR471## OCH.sub.2 CCCH.sub.3 H720 t-Bu Pro S H ##STR472## OMe H721 t-Bu Cl O H ##STR473## OMe H722 t-Bu Cl S H ##STR474## OMe H723 t-Bu Cl O H ##STR475## OEt H724 t-Bu Cl S H ##STR476## OEt H725 t-Bu Cl O H ##STR477## OPro H726 t-Bu Cl S H ##STR478## OPro H727 t-Bu Cl O H ##STR479## OProi H728 t-Bu Cl S H ##STR480## OProi H729 t-Bu Cl O H ##STR481## ##STR482## H730 t-Bu Cl O H ##STR483## ##STR484## H731 t-Bu Cl O H ##STR485## OCH.sub.2 CHCH.sub.2 H732 t-Bu Cl O H ##STR486## SMe H733 t-Bu Cl O H ##STR487## SEt H734 t-Bu Cl S H ##STR488## OProi H735 t-Bu Cl S H ##STR489## OProi 3-F736 t-Bu Cl O H ##STR490## OProi H737 Et Cl S H ##STR491## SMe H738 t-Bu Cl O H ##STR492## SMe H739 t-Bu Cl S H ##STR493## SMe H740 t-Bu Cl O H ##STR494## SEt H741 t-Bu Cl S H ##STR495## SEt H742 t-Bu Cl O H ##STR496## SEt H743 t-Bu Cl O H ##STR497## SPro H744 t-Bu Cl S H ##STR498## SPro H745 t-Bu Cl O H ##STR499## SProi H746 t-Bu Cl S H ##STR500## SProi H747 t-Bu Br O H 4-OC(CH.sub.3).sub.2 CH.sub.2 SProi H748 t-Bu Cl S H ##STR501## SProi H749 Pro Cl O H ##STR502## SBu H750 t-Bu Cl O H ##STR503## SBu H751 t-Bu Cl S H ##STR504## SBu H752 t-Bu Cl S H ##STR505## SBu H753 t-Bu Me O H 4-OCH.sub.2 CH.sub.2 CH.sub.2 SMe H754 t-Bu Cl S H 4-OCH.sub.2 CH.sub.2 CH.sub.2 SMe H755 t-Bu Cl O H 4-OCH.sub.2 CH.sub.2 CH.sub.2 SOMe H756 t-Bu Cl O H 4-OCH.sub.2 CH.sub.2 CH.sub.2 SO.sub.2 Me H757 t-Bu Cl S H 4-OCH.sub.2 CH.sub.2 CH.sub.2 SOMe H758 t-Bu Cl S H 4-OCH.sub.2 CH.sub.2 CH.sub.2 SO.sub.2 Me H759 t-Bu Cl O H 4-OCH.sub.2 CH.sub.2 CH.sub.2 SEt H760 t-Bu Cl O H 4-OCH.sub.2 CH.sub.2 CH.sub.2 SOEt H761 t-Bu Cl O H 4-OCH.sub.2 CH.sub.2 CH.sub.2 SO.sub.2 Et H762 t-Bu Cl S H 4-OCH.sub.2 CH.sub.2 CH.sub.2 SEt H763 t-Bu Cl O H 4-OCH.sub.2 CH.sub.2 CH.sub.2 SPro H764 t-Bu Cl S H 4-OCH.sub.2 CH.sub.2 CH.sub.2 SPro H765 t-Bu Cl O H 4-OCH.sub.2 CH.sub.2 CH.sub.2 SProi H766 t-Bu Cl O H 4-OCH.sub.2 CH.sub.2 CH.sub.2 SOProi H767 t-Bu Cl O H 4-OCH.sub.2 CH.sub.2 CH.sub.2 SO.sub.2 Proi H768 t-Bu Pro S H 4-OCH.sub.2 CH.sub.2 CH.sub.2 SBu H769 t-Bu Cl O H 4-OC.sub.2 H.sub.4 NMe.sub.2 H770 t-Bu Me O H 4-OC.sub.2 H.sub.4 NMe.sub.2 H771 t-Bu Cl S H 4-OC.sub.2 H.sub.4 NMe.sub.2 H772 t-Bu Cl S H ##STR506## NMe.sub.2 H773 t-Bu Cl O H ##STR507## NMe.sub.2 H774 t-Bu Me S H ##STR508## NMe.sub.2 H775 t-Bu Cl S H ##STR509## NMe.sub.2 H776 t-Bu Me O H ##STR510## NMe.sub.2 H777 t-Bu Me S H ##STR511## NMe.sub.2 H778 t-Bu Cl O H ##STR512## NMe.sub.2 H779 t-Bu Cl S H ##STR513## NMe.sub.2 H780 t-Bu Cl O H 4-OCH.sub.2 C(CH.sub.3).sub.2 NMe.sub.2 H781 t-Bu Cl S H 4-OCH.sub.2 C(CH.sub.3).sub.2 NMe.sub.2 H782 t-Bu Cl O H 4-OCH.sub.2 CH.sub.2 CH.sub.2 NMe.sub.2 H783 t-Bu Me S H 4-OCH.sub.2 CH.sub.2 CH.sub.2 NMe.sub.2 H784 t-Bu Cl S H 4-OCH.sub.2 CH.sub.2 CH.sub.2 NMe.sub.2 H785 t-Bu Et O H 4-OCH.sub.2 CH.sub.2 CH.sub.2 NMe.sub.2 H786 t-Bu Cl O H 4-OC.sub.2 H.sub.4 NEt.sub.2 H 55.0.about.56.0787 t-Bu Cl S H 4-OC.sub.2 H.sub.4 NEt.sub.2 H Oil788 t-Bu Br O H 4-OC.sub.2 H.sub.4 NEt.sub.2 H789 t-Bu Cl O Me 4-OC.sub.2 H.sub.4 NEt.sub.2 H Oil790 t-Bu Cl O H 3-OCH.sub.2 CH.sub.2 CH.sub.2 NEt.sub.2 H791 t-Bu Cl O H 4-OCH.sub.2 CH.sub.2 CH.sub.2 NEt.sub.2 H792 t-Bu Cl S H 4-OCH.sub.2 CH.sub.2 CH.sub.2 NEt.sub.2 H793 t-Bu Cl O H ##STR514## NEt.sub.2 H794 t-Bu Cl S H ##STR515## NEt.sub.2 H795 t-Bu Me O H ##STR516## NEt.sub.2 H796 t-Bu Cl O H ##STR517## NEt.sub.2 H797 t-Bu Cl S H ##STR518## NEt.sub.2 H798 t-Bu Cl O H 4-OCH.sub.2 C(CH.sub.3).sub.2 NEt.sub.2 H799 t-Bu Cl S H 4-OCH.sub.2 C(CH.sub.3).sub.2 NEt.sub.2 H800 t-Bu Cl O H 4-OC.sub.2 H.sub.4 NPro.sub.2 H801 t-Bu Cl S H 4-OC.sub.2 H.sub.4 NPro.sub.2 H802 t-Bu Me S H 4-OCH.sub.2 CH.sub.2 CH.sub.2 NPro.sub.2 H803 t-Bu Cl O H 4-OCH.sub. 2 CH.sub.2 CH.sub.2 NPro.sub.2 H804 t-Bu Et S H 4-OCH.sub.2 CH.sub.2 CH.sub.2 NPro.sub.2 H805 t-Bu Cl O H ##STR519## NPro.sub.2 H806 t-Bu Cl S H ##STR520## NPro.sub.2 H807 t-Bu Cl O H ##STR521## NPro.sub.2 H808 t-Bu Cl S H ##STR522## NPro.sub.2 H809 t-Bu Br S H 4-OC.sub.2 H.sub.4 NPro.sub.2 H810 t-Bu Br O H 4-OC.sub.2 H.sub.4 NPro.sub.2 H811 t-Bu Cl O H 4-OC.sub.2 H.sub.4 N(Proi).sub.2 H812 t-Bu Cl O H 4-OCH.sub.2 CH.sub.2 CH.sub.2 N(Proi).sub.2 H813 t-Bu Cl O H ##STR523## N(Proi).sub.2 H814 t-Bu Me S H ##STR524## N(Proi).sub.2 H815 t-Bu Cl O H ##STR525## N(Proi).sub.2 H816 t-Bu Me O H 4-OC.sub.2 H.sub.4 NBu.sub.2 H817 t-Bu Cl O H 4-OC.sub. 2 H.sub.4 NBu.sub.2 H818 t-Bu Cl S H 4-OC.sub.2 H.sub.4 NBu.sub.2 H819 t-Bu Cl O H 4-OCH.sub.2 CH.sub.2 CH.sub.2 NBu.sub.2 H820 t-Bu Cl O H ##STR526## NBu.sub.2 H821 t-Bu Cl S H ##STR527## NBu.sub.2 H822 t-Bu Cl O H ##STR528## NBu.sub.2 H823 t-Bu Cl O H 4-OC.sub.2 H.sub.4 N(Bui).sub.2 H824 t-Bu Cl S H 4-OC.sub.2 H.sub.4 N(Bui).sub.2 H825 t-Bu Cl O H ##STR529## N(Bui).sub.2 H826 t-Bu Cl S H ##STR530## N(Bui).sub.2 H827 t-Bu Me O H 4-OC.sub.2 H.sub.4 ##STR531## H828 t-Bu Cl O H 4-OC.sub.2 H.sub.4 ##STR532## H829 t-Bu Cl S H 4-OC.sub.2 H.sub.4 ##STR533## H830 t-Bu Cl O H 4-OCH.sub.2 CH.sub.2 CH.sub.2 ##STR534## H831 t-Bu Cl O H ##STR535## ##STR536## H832 t-Bu Cl S H ##STR537## ##STR538## H833 t-Bu Cl O H 4-OC.sub.2 H.sub.4 ##STR539## H834 t-Bu Pro S H 4-OC.sub.2 H.sub.4 ##STR540## H835 t-Bu Cl S H ##STR541## ##STR542## H836 t-Bu Cl O H ##STR543## ##STR544## H837 Pro Cl O H ##STR545## OMe H838 t-Bu Cl O H ##STR546## OMe H 98.0.about.101.0839 t-Bu Cl S H ##STR547## OMe H840 t-Bu Me O H ##STR548## OMe H841 t-Bu Me S H ##STR549## OMe H842 Et Cl O H ##STR550## OEt H 84.8.about.86.3843 t-Bu Cl O H ##STR551## OEt H 57.9.about.63.0844 t-Bu Cl S H ##STR552## OEt H Oil845 t-Bu Br O H ##STR553## OEt H846 t-Bu Me O H ##STR554## OEt H847 t-Bu Cl O H ##STR555## OPro H848 t-Bu Cl S H ##STR556## OPro H849 t-Bu Me O H ##STR557## OPro H850 t-Bu Cl O H ##STR558## OPro H__________________________________________________________________________
TABLE 2__________________________________________________________________________ ##STR559## No. R A X R.sup.1 R.sup.2 ##STR560## (.degree.C.)__________________________________________________________________________ m.p.851 Et Cl O H H ##STR561## 105.0.about.106.0852 t-Bu Cl O H H ##STR562## 102.0.about.103.5853 t-Bu Cl O H H ##STR563##854 t-Bu Br O H H ##STR564##855 t-Bu Me O H H ##STR565##856 t-Bu Cl S H H ##STR566##857 t-Bu Cl S H H ##STR567## oil858 t-Bu Cl S Me H ##STR568## oil859 t-Bu Me S H H ##STR569##860 t-Bu Cl S H H ##STR570## oil oil861 Et Cl S H H ##STR571##862 i-Pro Br O H H ##STR572##863 t-Bu Cl O H H ##STR573##864 t-Bu Et S H H ##STR574##865 Et Et O H H ##STR575##866 t-Bu Cl S H H ##STR576##867 t-Bu Me S H H ##STR577##868 t-Bu Pro O H H ##STR578##869 t-Bu Cl S H H ##STR579##870 t-Bu Cl S H H ##STR580## oil871 t-Bu Cl O H H ##STR581##872 t-Bu Me S H H ##STR582## oil m.p.873 t-Bu Me S Me H ##STR583##874 t-Bu Cl S Me H ##STR584##875 t-Bu Cl S H H ##STR585##876 t-Bu Cl S H H ##STR586## oil877 t-Bu Me O H H ##STR587##878 t-Bu Cl S H H ##STR588##879 t-Bu Cl S H H ##STR589##880 t-Bu Cl S H H ##STR590##881 t-Bu Cl S H H ##STR591##882 t-Bu Me S H H ##STR592##883 t-Bu Cl S H H ##STR593## oil884 t-Bu Me O H H ##STR594##885 t-Bu Cl S H H ##STR595## oil886 t-Bu Me S H H ##STR596##887 t-Bu Cl S H H ##STR597##888 t-Bu Cl O H H ##STR598##889 t-Bu Me O H H ##STR599##890 t-Bu Cl S H H ##STR600## oil891 t-Bu Me S H H ##STR601##892 t-Bu Cl S H H ##STR602##893 t-Bu Me S H H ##STR603##894 t-Bu Cl O H H ##STR604##895 Et Cl O H H ##STR605## 168.0.about.168.5896 Et Br O H H ##STR606##897 Pro Cl O H H ##STR607##898 t-Bu Cl S H H ##STR608## 191.5.about.193.0899 Et Cl O H H ##STR609##900 t-Bu Me S H H ##STR610##901 Et Cl O H H ##STR611##902 t-Bu Me S H H ##STR612##903 t-Bu Cl S H H ##STR613##904 t-Bu Cl S H H ##STR614##905 t-Bu Cl O H H ##STR615##906 t-Bu Cl S H H ##STR616##907 t-Bu Cl O H H ##STR617##908 t-Bu Cl S H H ##STR618##909 t-Bu Cl O H H ##STR619##910 t-Bu Cl S H H ##STR620##911 t-Bu Cl S H H ##STR621##912 t-Bu Cl S H H ##STR622##913 t-Bu Cl S H H ##STR623##914 t-Bu Cl S H H ##STR624##915 t-Bu Cl O H H ##STR625##916 t-Bu Cl S H H ##STR626##917 t-Bu Cl S H H ##STR627##918 t-Bu Cl S H H ##STR628##919 t-Bu Cl S H H ##STR629##920 Et Cl O H H ##STR630## 82.0.about.82.5921 t-Bu Cl O H H ##STR631## 123.5.about.124.0922 Pro Me O H H ##STR632##923 Et Br O H H ##STR633##924 t-Bu Br O Me H ##STR634##925 t-Bu Cl O H H ##STR635##926 t-Bu Et O H H ##STR636##927 t-Bu Me O H H ##STR637##928 t-Bu Cl O H H ##STR638##929 Et Cl O H H ##STR639## 96.0.about.97.0930 t-Bu Cl O H H ##STR640## oil931 t-Bu Me S H H ##STR641##932 Et Cl O H H ##STR642##933 C.sub.6 H.sub.13 Cl O Me H ##STR643##934 t-Bu Cl O H H ##STR644##935 i-Bu Cl S H H ##STR645##936 t-Bu Me S H H ##STR646##937 Pro Cl S H H ##STR647##938 Et Cl S H H ##STR648##939 Bu Cl O H H ##STR649##940 Et Cl O H H ##STR650##941 t-Bu Me O H H ##STR651##942 t-C.sub.5 H.sub.11 Cl O H H ##STR652##943 t-Bu Pro O Me H ##STR653##944 t-Bu Cl S H H ##STR654##945 t-Bu Cl O H H ##STR655##946 t-Bu Me O H H ##STR656##947 t-Bu Cl O Me H ##STR657##948 t-Bu Me S H H ##STR658##949 t-Bu Cl S H H ##STR659##950 t-Bu Cl O Me H ##STR660##951 t-Bu Cl S H H ##STR661## 115.5.about.117.5952 i-Pro Cl O H H ##STR662##953 Et Et S H H ##STR663##954 t-Bu Me S H H ##STR664##955 Pro Cl S H H ##STR665##956 Et Cl O H H ##STR666##957 t-Bu Cl S H H ##STR667##958 t-Bu Me O H H ##STR668##959 t-Bu Cl S H H ##STR669##960 t-Bu Me S H H ##STR670##961 t-Bu Me S H H ##STR671##962 t-Bu Cl O Me H ##STR672##963 t-Bu Cl S H H ##STR673## oil964 t-Bu Cl O H H ##STR674## 108.0.about.109.0965 t-Bu Cl S H H ##STR675##966 t-Bu Me O H H ##STR676##967 t-Bu Me S H H ##STR677##968 t-Bu Cl O H H ##STR678##969 t-Bu Cl S H H ##STR679##970 t-Bu Me S H H ##STR680##971 t-Bu Cl S Me H ##STR681##972 t-Bu Me O H H ##STR682##973 t-Bu Cl S H H ##STR683##974 t-Bu Cl S H H ##STR684##975 t-Bu Me O H H ##STR685##976 t-Bu Cl S H H ##STR686##977 t-Bu Cl S H H ##STR687##978 t-Bu Me S H H ##STR688##979 t-Bu Cl S H H ##STR689##980 t-Bu Cl O H H ##STR690##981 t-Bu Cl S H H ##STR691##982 t-Bu Cl O H H ##STR692##983 t-Bu Me O H H ##STR693##984 t-Bu Cl O Me H ##STR694##985 t-Bu Me S H H ##STR695##986 t-Bu Br O H H ##STR696##987 t-Bu Cl S H H ##STR697##988 Et Br S H H ##STR698##989 i-Pro Br O H H ##STR699##990 Et Cl O H H ##STR700##991 t-Bu Cl S H H ##STR701##992 t-Bu Me S H H ##STR702##993 Et Cl O H H ##STR703##994 Pro Cl O H H ##STR704##995 i-Pro Cl O H H ##STR705##996 Bu Cl S H H ##STR706##997 t-Bu Cl S H H ##STR707## 92.0.about.93.5998 t-Bu Me S H H ##STR708## oil999 t-Bu Cl O H H ##STR709## oil1000 t-Bu Cl O Me H ##STR710##1001 t-Bu Cl O H H ##STR711## 104.4.about.106.31002 t-Bu Cl S H H ##STR712##1003 t-Bu Cl S H H ##STR713## 57.0.about.58.01004 t-Bu Me O H H ##STR714## oil1005 t-Bu Me S H H ##STR715##1006 t-Bu Cl O H H ##STR716##1007 t-Bu Cl S H H ##STR717## 78.0.about.82.01008 i-Pro Cl O H H ##STR718## oil1009 t-Bu Cl S H H ##STR719##1010 t-Bu Me O H H ##STR720## oil1011 t-Bu Cl O H H ##STR721## 121.0.about.124.01012 t-Bu Me O H H ##STR722##1013 t-Bu Cl S H H ##STR723##1014 t-Bu Me S H H ##STR724##1015 t-Bu Cl S H H ##STR725##1016 t-Bu Cl S H H ##STR726## m.p.1017 t-Bu Me S H H ##STR727##1018 t-Bu Cl O H H ##STR728##1019 t-Bu Cl S H H ##STR729##1020 t-Bu Me O H H ##STR730##1021 Et Me S H H ##STR731##1022 t-Bu Cl S H H ##STR732##1023 t-Bu Cl O H H ##STR733## 540..about.56.01024 t-Bu Cl S H H ##STR734## 82.0.about.84.01025 t-Bu Cl S H H ##STR735## 124.5.about.126.51026 t-Bu Cl S H H ##STR736## 106.0.about.106.51027 t-Bu Cl S H H ##STR737## oil1028 t-Bu Me S H H ##STR738## Oil1029 t-Bu Cl S H H ##STR739## oil1030 t-Bu Cl O Me H ##STR740##1031 t-Bu Cl S H H ##STR741##1032 t-Bu Me O H H ##STR742##1033 t-Bu Cl S H H ##STR743##1034 t-Bu Me S H H ##STR744##1035 t-Bu Cl S H H ##STR745##1036 t-Bu Cl S Et H ##STR746##1037 t-Bu Me O Pro H ##STR747##1038 t-C.sub.5 H.sub.11 Cl O H H ##STR748##1039 C.sub.6 H.sub.13 Cl S H H ##STR749##1040 t-Bu Cl O H H ##STR750##1041 t-Bu Cl O H H ##STR751## 150.0.about.154.51042 t-Bu Cl S H H ##STR752## 113.0.about.114.01043 t-Bu Me S H H ##STR753##1044 t-Bu Cl O H H ##STR754##1045 t-Bu Cl S H H ##STR755##1046 t-Bu Me O Me H ##STR756##1047 t-Bu Cl O H H ##STR757##1048 t-Bu Me O H H ##STR758##1049 t-Bu Cl S H H ##STR759## 124.0.about.127.51050 t-Bu Cl O H H ##STR760##1051 t-Bu Cl O H H ##STR761##1052 Et Cl O H H ##STR762##1053 t-Bu Cl O H H ##STR763##1054 t-Bu Cl S H H ##STR764##1055 t-Bu Cl S H H ##STR765## 109.0.about.110.01056 t-Bu Cl O H H ##STR766## 102.0.about.103.01057 t-Bu Cl O H H ##STR767##1058 t-Bu Cl O H H ##STR768## 91.3.about.93.31059 Et Cl O H H ##STR769## 139.8.about.140.91060 Et Cl S H H ##STR770## 116.7.about.121.11061 t-Bu Me S H H ##STR771##1062 t-Bu Cl O H H ##STR772## 112.0.about.118.01063 t-Bu Cl S H H ##STR773## 113.0.about.114.01064 t-Bu Cl S H H ##STR774##1065 t-Bu Me S H H ##STR775##1066 t-Bu Cl O H H ##STR776##1067 t-Bu Cl O H H ##STR777## 94.1.about.96.31068 Et Me S H H ##STR778##1069 i-Pro Me S H H ##STR779##1070 i-Pro Cl S H H ##STR780##1071 i-Pro Cl O H H ##STR781##1072 t-Bu Cl S H H ##STR782## 90.1.about.91.41073 t-Bu Cl O H H ##STR783## 87.2.about.89.61074 t-Bu Cl S H H ##STR784##1075 t-Bu Cl O H H ##STR785##1076 t-Bu Cl S H H ##STR786##1077 t-Bu Cl S H H ##STR787##1078 t-Bu Cl S H H ##STR788##1079 t-Bu Cl O H H ##STR789##1080 t-Bu Cl S H H ##STR790##1081 t-Bu Cl S H H ##STR791## 111.2.about.113.31082 Et Cl O H H ##STR792## 136.1.about.137.31083 t-Bu Cl S H H ##STR793## 100.0.about.101.51084 t-Bu Cl S H H ##STR794##1085 t-Bu Cl O H H ##STR795##1086 t-Bu Me O H H ##STR796##1087 t-Bu Me S H H ##STR797##1088 t-Bu Cl O H H ##STR798## 100.9.about.102.31089 t-Bu Br O H H ##STR799##1090 t-Bu Me O H H ##STR800##1091 t-Bu Me S H H ##STR801##1092 t-Bu Cl S H H ##STR802##1093 t-Bu Cl S H H ##STR803## 93.0.about.97.01094 t-Bu Cl O H H ##STR804## oil1095 t-Bu Cl S H H ##STR805## 82.2.about.85.71096 t-Bu Cl O H H ##STR806## 111.2.about.113.31097 t-Bu Cl S H H ##STR807## oil__________________________________________________________________________
The compounds of the present invention may be produced according to the following reaction formulae: ##STR808## wherein R, R.sup.1, R.sup.2, A, B, X, Y and n have the same meanings as given above, X.sup.1 represents a halogen atom, --OH or --SH, and X.sup.2 represents a halogen atom, --OH or --SH, with the proviso that when X.sup.1 represents a halogen atom, X.sup.2 represents --OH or --SH and when X.sup.1 represents --OH or --SH, X.sup.2 represents a halogen atom.
Namely, the invention compound (I) may be produced by reacting one of the raw materials, i.e. a (2H)-pyridazinone derivative of the formula (II) with another raw material, i.e. a compound of the formula (III) in an inert solvent in the presence of a hydrogen halide absorbing agent. Solvents to be used in the present invention are, for example, lower alcohols such as methanol and ethanol; ketones such as acetone and methyl ethyl ketone; hydrocarbons such as benzene and toluene; ethers such as isopropyl ether, tetrahydrofurane and 1,4-dioxane; amides such as N,N-dimethylformamide and hexamethylphosphoric triamide; and halogenated hydrocarbons such as dichloromethane and dichloroethane. If desired, mixed solvents consisting of these solvents with water may be used.
As the hydrogen halide absorbing agent, inorganic bases such as sodium hydride, sodium hydroxide, potassium hydroxide, sodium carbonate, potassium carbonate and sodium hydrogen carbonate, and organic bases such as sodium methoxide, sodium ethoxide, triethylamine and pyridine may be used. If necessary, a tetraammonium salt, for example, tetra-n-butylammonium bromide, triethylbenzylammonium chloride and the like may be added as a catalyst into the reaction system. The reaction temperature may be within a range from room temperature to the boiling point of the solvent used in the reaction. There is no limitation in the proportions between the raw materials, but equimolar ratio or approximately equimolar ratio may be advantageous.
In the following, the process for producing the compounds of the present invention will be concretely explained by working examples and reference examples, but the present invention is not limited to these examples.
REFERENCE EXAMPLE 1
Synthesis of 2-t-butyl-5-chloro-4-methyl-3(2H)-pyridazinone starting material
To a solution of 6.0 g (0.25 mol) of magnesium in 50 ml of dry tetrahydrofuran was added dropwise under stream of nitrogen 35.5 g (0.25 mol) of methyl iodide to prepare a Grignard reagent. After dropwise addition of the methyl iodide, 1000 ml of dry toluene was added thereto. The resulting solution was heated at 60.degree. to 70.degree. C. and additional methyl iodide was added thereto until the magnesium completely disappeared. The Grignard reagent was cooled to room temperature and then added dropwise over 20 minutes with a solution of 22.1 g (0.1 mol) of 2-t-butyl-4,5-dichloro-3(2H)-pyridazinone in 200 ml of dry toluene. After dropwise addition, the resulting mixture was subjected to reaction at room temperature for 1.5 hours. The reaction liquid was poured into a solution of 100 ml of concentrated hydrochloric acid in 900 ml of ice water to effect extraction. The resulting organic layer was washed with 500 ml of a 10% sodium hydroxide solution and then with 500 ml of water, and then dried over anhydrous sodium sulfate. Solvent was distilled off therefrom under reduced pressure to give 17.2 g of a crude product. The crude product was subjected to distillation (boiling point: 60.degree. to 62.degree. C./0.22 mmHg) and then to column chromatography [on silica gel; eluting with hexane-acetone (15:1)] for separation and purification to obtain 4.5 g of 2-t-butyl-5-chloro-4-methyl-3(2H)-pyridazinone.
N.sub.D.sup.10 =1.5238.
NMR (CDCl.sub.3, .delta., TMS): 1.63 (9H, s), 2.23 (3H, s), 7.66 (1H, s).
REFERENCE EXAMPLE 2
Synthesis of 2-t-butyl-5-mercapto-4-methyl-3(2H)-pyridazinone starting material
To 75 ml of ethanol were added 17.0 g (0.085 mol) of 2-t-butyl-5-chloro-4-methyl-3(2H)-pyridazinone and 8.5 g (0.106 mol) of 70% sodium hydrosulfide and the mixture was stirred under reflax for 4 hours. After cooling, the mixture was poured into 300 ml of ice water and extracted with 200 ml of ethyl ether. The ether layer was washed with 100 ml of water, dried over anhydrous sodium sulfate and then freed of solvent by distillation to obtain 16.3 g of a crude product.
NMR (CDCl.sub.3, .delta., TMS): 1.61 (9H, s), 2.23 (3H, s), 7.46 (1H, s).
M/Z: 198 (M.sup.+), 143 (100%).
The compound was used without subjecting to purification as a starting material in the Preparation Examples given below.
REFERENCE EXAMPLE 3
Synthesis of 2-t-butyl-5-hydroxy-4-methyl-3(2H)-pyridazinone starting material
To 30 ml of ethylene glycol were added 20 g (0.01 mol) of 2-t-butyl-5-chloro-4-methyl-3(2H)-pyridazinone and 2.8 g (0.05 mol) of potassium hydroxide and the mixture was stirred at 130.degree. C. for 4 hours. After allowing to cool, the mixture was poured into 200 ml of water and added with 20 ml of 6N hydrochloric acid. The precipitated crystals were gathered by filtration. After drying, the crystals were washed with 30 ml of hot isopropyl ether to obtain 1.7 g of 2-t-butyl-5-hydroxy-4-methyl-3(2H)-pyridazinone, m.p. 236.0.degree..about.239.0.degree. C.
NMR (CDCl.sub.3, .delta., TMS): 1.62 (9H, s), 1.97 (3H, s), 4.63 (1H, s), 7.60 (1H, s).
M/Z: 182 (M.sup.+), 127 (100%).

PREPARATION EXAMPLE 1
Preparation of 2-t-butyl-4-chloro-5-[4-(2-isopropylthioethoxy)-benzyloxy]-3(2H)-pyridazinone (Compound No. 310)
In 15 ml of N,N-dimethylformamide were dissolved 1.2 g of 2-t-butyl-4,5-dichloro-3(2H)-pyridazinone and 1.2 g of p-(2-isopropylthioethoxy)benzyl alcohol, and then 0.31 g of powdery potassium hydroxide was added thereto. The resulting mixture was stirred overnight at room temperature, poured into water, extracted with diethyl ether, washed with water, dried over anhydrous sodium sulfate and then freed of the diethyl ether by distillation under reduced pressure. The resulting solid was recrystallized from n-hexane to obtain 1.2 g of the aimed compound, m.p. 82.0.degree..about.84.5.degree. C.
.sup.1 H-NMR (CDCl.sub.3, .delta., TMS): 1.28 (3H, d, J=6.5 Hz), 1.62 (9H, s), 2.90 (2H, t, J=7.0 Hz), 2.90 (1H, dq, J=6.5 Hz), 4.12 (2H, t, J=7.0 Hz), 5.21 (2H, s), 6.85 (2H, d, J=8.4 Hz), 7.29 (2H, d, J=8.4 Hz), 7.69 (1H, s).
PREPARATION EXAMPLE 2
Preparation of 2-t-butyl-4-chloro-5-[4-(2-ethoxyethoxy)benzyloxy]-3(2H)-pyridazinone (Compound No. 71)
In 10 ml of N,N-dimethylformamide were dissolved 1.0 g of 2-t-butyl-4-chloro-5-hydroxy-3(2H)-pyridazinone and 1.3 g of 4-(2-ethoxyethoxy)-benzyl bromide, and then 1.0 g of anhydrous potassium carbonate was added thereto. The mixture was heated with stirring on an oil bath at 90.degree. to 100.degree. C. for 3 hours, poured into water, extracted with benzene, washed with water and dried over anhydrous sodium sulfate. Benzene was distilled off under reduced pressure and the resulting oil was purified by means of column chromatography (on silica gel, eluting with benzene/ethyl acetate=18/1) and recrystallization (from n-hexane-benzene) to obtain 1.1 g of the aimed compound, m.p. 82.0.degree..about.83.0.degree. C.
.sup.1 H-NMR (CDCl.sub.3, .delta., TMS): 1.23 (3H, t, J=7 Hz), 1.61 (9H, s), 3.57 (2H, q, J=7 Hz), 3.50.about.3.88 (2H, m), 3.98.about.4.36 (2H, m), 5.19 (2H, s), 6.88 (2H, d, J=9 Hz), 7.29 (2H, d, J=9 Hz), 7.68 (1H, s).
PREPARATION EXAMPLE 3
Preparation of 2-t-butyl-4-chloro-5-[4-(2-methoxyethoxy)-benzylthio]-3(2H)-pyridazinone (Compound No. 45)
In 30 ml of 95% ethanol were dissolved 1.5 g of 2-t-butyl-4-chloro-5-mercapto-3(2H)-pyridazinone and 1.85 g of 4-(2-methoxyethoxy)benzyl bromide, and then 0.48 g of anhydrous sodium carbonate was added thereto. The resulting mixture was stirred overnight at room temperature, poured into water, extracted with benzene, washed with water and dried over anhydrous sodium sulfate. Benzene was distilled off under reduced pressure and the resulting solid was recrystallized from n-hexane-benzene to obtain 1.64 g of the aimed compound, m.p. 105.6.degree..about.107.3.degree. C.
.sup.1 H-NMR (CDCl.sub.3, .delta., TMS): 1.60 (9H, s), 3.39 (3H, s), 3.58.about.3.82 (2H, m), 3.96.about.4.20 (2H, m), 4.16 (2H, s), 6.84 (2H, d, J=9 Hz), 7.26 (2H, d, J=9 Hz), 7.56 (1H, s).
PREPARATION EXAMPLE 4
Preparation of 4-bromo-2-ethyl-5-(4-methoxymethoxybenzyloxy)-3(2H)-pyridazinone (Compound No. 2)
In 30 ml of N,N-dimethylformamide were dissolved 1.2 g of 4,5-dibromo-2-ethyl-3(2H)-pyridazinone and 0.88 g of 4-methoxymethoxybenzyl alcohol, and 0.34 g of powdery potassium hydroxide was added thereto. The reaction mixture was stirred overnight at room temperature, poured into water and extracted with benzene. The benzene layer was washed with water, dried over anhydrous sodium sulfate and freed of the benzene by distillation under reduced pressure. The resulting oil was purified by means of TLC [eluting with benzene/ethyl acetate (12/1)] and recrystallization (from benzene/n-hexane) to obtain 450 mg of the aimed compound, m.p. 104.degree..about.106.0.degree. C.
.sup.1 H-NMR (CDCl.sub.3, .delta., TMS): 1.33 (3H, t, J=7 Hz), 3.44 (3H, s), 4.20 (2H, q, J=7 Hz), 5.13 (2H, s), 5.21 (2H, s), 6.99 (2H, d, J=8 Hz), 7.30 (2H, d, J=8 Hz), 7.63 (1H, s).
PREPARATION EXAMPLE 5
Preparation of 4-bromo-2-t-butyl-5-[4-(3-propoxypropoxy)-benzyloxy]-3(2H)-pyridazinone (Compound No. 422)
In 20 ml of N,N-dimethylformamide were dissolved 1.7 g of 4-bromo-2-t-butyl-5-hydroxy-3(2H)-pyridazinone and 2.0 g of 4-(3-propoxypropoxy)-benzyl bromide, and 1.3 g of anhydrous potassium carbonate was added thereto. The resulting mixture was heated under stirring on an oil bath at 80.degree. to 90.degree. C. for 3 hours. Then, procedures similar to those in Preparation Example 2 were carried out to obtain 1.3 g of the aimed compound as an oil.
.sup.1 H-NMR (CDCl.sub.3, .delta., TMS): 0.91 (3H, t, J=6.4 Hz), 1.61 (9H, s), 1.29.about.2.27 (4H, m), 3.37 (2H, t, J=6.4 Hz), 3.56 (2H, t, J=6.4 Hz), 4.05 (2H, t, J=6.4 Hz), 5.20 (2H, s), 6.95 (2H, d, J=8 Hz), 7.30 (2H, d, J=8 Hz), 7.59 (1H, s).
PREPARATION EXAMPLE 6
Preparation of 2-t-butyl-4-chloro-5-(4-methoxymethoxybenzylthio)-3(2H)-pyridazinone (Compound No. 7)
In 10 ml of N,N-dimethylformamide were dissolved 0.94 g of 2-t-butyl-4-chloro-5-mercapto-3(2H)-pyridazinone and 0.8 g of 4-methoxymethoxybenzyl chloride, and then 0.55 g of anhydrous sodium carbonate was added thereto. The mixture was stirred overnight at room temperature. Then, procedures similar to those in Preparation Example 3 were carried out to obtain 520 mg of the aimed compound, m.p. 50.0.degree..about.54.0.degree. C.
.sup.1 H-NMR (CDCl.sub.3, .delta., TMS): 1.60 (9H, s), 3.42 (3H, s), 4.17 (2H, s), 5.10 (2H, s), 6.94 (2H, d, J=8.4 Hz), 7.26 (2H, d, J=8.4 Hz), 7.56 (1H, s).
PREPARATION EXAMPLE 7
Preparation of 2-t-butyl-4-chloro-5-[4-(2-propoxyethoxy)-benzyloxy]-3(2H)-pyridazinone (Compound No. 87)
In 30 ml of N,N-dimethylformamide were dissolved 2.0 g of 2-t-butyl-4-chloro-5-hydroxy-3(2H)-pyridazinone and 3.0 g of 4-(2-propoxyethoxy)-benzyl bromide, and then 2.0 g of anhydrous potassium carbonate was added thereto. The mixture was heated under stirring on an oil bath at 80.degree. to 90.degree. C. for 3 hours. Then, procedures similar to those in Preparation Example 2 were carried out to obtain 1.4 g of the aimed product as an oil.
.sup.1 H-NMR (CDCl.sub.3, .delta., TMS): 0.93 (3H, t, J=6.8 Hz), 1.61 (9H, s), 1.38.about.1.89 (2H, m), 3.48 (2H, t, J=6.4 Hz), 3.65.about.3.91 (2H, m), 3.99.about.4.27 (2H, m), 5.21 (2H, s), 6.91 (2H, d, J=9 Hz), 7.32 (2H, d, J=9 Hz), 7.70 (1H, s).
PREPARATION EXAMPLE 8
Preparation of 2-t-butyl-4-chloro-5-[4-(2-ethoxy-1-methylethoxy)-benzyloxy]-3(2H)-pyridazinone (Compound No. 511)
In 30 ml of N,N-dimethylformamide were dissolved 2.0 g of 2-t-butyl-4-chloro-5-hydroxy-3(2H)-pyridazinone and 3.0 g of 4-(2-ethoxy-1-methylethoxy)-benzyl bromide, and then 1.9 g of anhydrous potassium carbonate was added thereto. The mixture was heated under stirring on an oil bath at 80.degree. to 90.degree. C. for 3 hours. Then, procedures similar to those in Preparation Example 2 were carried out to obtain 1.5 g of the aimed product, m.p. 72.3.degree..about.73.1.degree. C.
.sup.1 H-NMR (CDCl.sub.3, .delta., TMS): 1.18 (3H, t, J=7 Hz), 1.31 (3H, d, J=6 Hz), 1.61 (9H, s), 3.30.about.3.79 (4H, m), 4.38.about.4.72 (1H, m), 5.20 (2H, s), 6.93 (2H, d, J=8.8 Hz), 7.30 (2H, d, J=8.8 Hz), 7.71 (1H, s).
PREPARATION EXAMPLE 9
Preparation of 2-t-butyl-4-chloro-5-[4-(1-methyl-2-propoxyethoxy)-benzyloxy]-3(2H)-pyridazinone (Compound No. 517)
Procedures similar to those in Preparation Example 8 were carried out by using 2.0 g of 2-t-butyl-4-chloro-5-hydroxy-3(2H)-pyridazinone and 3.1 g of 4-(1-methyl-2-propoxyethoxy)-benzyl bromide to obtain 1.43 g of the aimed compound as an oil.
.sup.1 H-NMR (CDCl.sub.3, .delta., TMS): 0.89 (3H, t, J=6.8 Hz), 1.31 (3H, d, J=6 Hz), 1.60 (9H, s), 1.25.about.1.68 (2H, m), 3.27.about.3.68 (4H, m), 4.35.about.4.69 (1H, m), 5.20 (2H, s), 6.91 (2H, d, J=8.4 Hz), 7.29 (2H, d, J=8.4 Hz), 7.71 (1H, s).
PREPARATION EXAMPLE 10
Preparation of 2-t-butyl-4-chloro-5-[4-(2-ethoxy-1-ethylethoxy)-benzyloxy]-3(2H)-pyridazinone (Compound No. 664)
Procedures similar to those in Preparation Example 8 were carried out by using 2.0 g of 2-t-butyl-4-chloro-5-hydroxy-3(2H)-pyridazinone and 3.1 g of 4-(2-ethoxy-1-ethylethoxy)-benzyl bromide to obtain 1.0 g of the aimed compound as an oil.
.sup.1 H-NMR (CDCl.sub.3, .delta., TMS): 0.99 (3H, t, J=7 Hz), 1.17 (3H, t, J=7 Hz), 1.60 (9H, s), 1.39.about.1.88 (2H, m), 3.28.about.3.73 (4H, m), 4.08.about.4.51 (1H, m), 5.19 (2H, s), 6.91 (2H, d, J=8.6 Hz), 7.27 (2H, d, J=8.6 Hz), 7.68 (1H, s).
PREPARATION EXAMPLE 11
Preparation of 2-t-butyl-4-chloro-5-[4-(1-methyl-2-isopropoxyethoxy)-benzyloxy]-3(2H)-pyridazinone (Compound No. 524)
In 15 ml of N,N-dimethylformamide were dissolved 1.0 g of 2-t-butyl-4-chloro-5-hydroxy-3(2H)-pyridazinone and 1.6 g of 4-(1-methyl-2-isopropoxyethoxy)-benzyl bromide, and thereto was added 1.0 g of anhydrous potassium carbonate. The mixture was heated under stirring on an oil bath at 100.degree. to 120.degree. C. for 2 hours. Then, procedures similar to those in Preparation Example 2 were conducted to give 1.2 g of the aimed compound, m.p. 60.0.degree..about.62.0.degree. C.
.sup.1 H-NMR (CDCl.sub.3, .delta., TMS): 1.15 (3H, d, J=6 Hz), 1.27 (3H, t, J=6.4 Hz, 1.63 (9H, s), 3.32.about.3.86 (4H, m), 4.21.about.4.70 (2H, m), 5.20 (2H, s), 6.92 (2H, d, J=8.4 Hz), 7.32 (2H, d, J=8.4 Hz), 7.73 (1H, s).
PREPARATION EXAMPLE 12
Preparation of 2-t-butyl-4-chloro-5-[4-(2-hexyloxy-1-methylethoxy)-benzylthio]-3(2H)-pyridazinone (Compound No. 553)
In 20 ml of N,N-dimethylformamide were dissolved 1.7 g of 2-t-butyl-4-chloro-5-mercapto-3(2H)-pyridazinone and 2.8 g of 4-(2-hexyloxy-1-methylethoxy)-benzyl bromide, and the resulting solution was stirred overnight at room temperature. The crude product which had been obtained similarly to the procedures in Preparation Example 3 was isolated through column chromatography [eluting with benzene/ethyl acetate (18/1)] to give 3.4 g of the aimed product as an oil.
.sup.1 H-NMR (CDCl.sub.3, .delta., TMS): 1.31 (3H, d, J=6 Hz), 0.20.about.1.93 (11H, m), 1.64 (9H, s), 3.28.about.3.70 (4H, m), 4.18 (2H, s), 4.29.about.4.78 (1H, m), 6.87 (2H, d, J=8.6 Hz), 7.27 (2H, d, J=8.4 Hz), 7.59 (1H, s).
PREPARATION EXAMPLE 13
Preparation of 2-t-butyl-4-chloro-5-[4-(2-ethoxypropoxy)benzyloxy]-3(2H)-pyridazinone (Compound No. 579)
In 15 ml of N,N-dimethylformamide were dissolved 1.5 g of 2-t-butyl-4-chloro-5-hydroxy-3(2H)-pyridazinone and 2.2 g of 4-(2-ethoxypropoxy)-benzyl bromide, and the resulting solution was heated under stirring on an oil bath at 80.degree. to 90.degree. C. for 3 hours. Then, similarly to the procedures in Preparation Example 2, 1.1 g of the aimed product was obtained as an oil.
.sup.1 H-NMR (CDCl.sub.3, .delta., TMS): 1.05 1.44 (6H, m), 1.61 (9H, s), 3.62 (2H, t, J=6.4 Hz), 3.83.about.4.12 (3H, m), 5.20 (2H, s), 6.90 (2H, d, J=9 Hz), 7.30 (2H, d, J=9 Hz), 7.69 (1H, s).
PREPARATION EXAMPLE 14
Preparation of 2-t-butyl-4-chloro-5-[4-(1,1-dimethyl-2-propoxyethoxy)-benzyloxy]-3(2H)-pyridazinone (Compound No. 615)
By using 2.0 g of 2-t-butyl-4-chloro-5-hydroxy-3(2H)-pyridazinone and 3.0 g of 4-(1,1-dimethyl-2-propoxyethoxy)benzyl bromide and similarly to the procedures in Preparation Example 13, 2.1 g of the aimed product was obtained as an oil.
.sup.1 H-NMR (CDCl.sub.3, .delta., TMS): 0.94 (3H, t, J=7 Hz), 1.30 (6H, s), 1.62 (9H, s), 1.42.about.1.96 (2H, m), 3.39 (2H, s), 3.44 (2H, t, J=7 Hz), 5.24 (2H, s), 7.02 (2H, d, J=9 Hz), 7.30 (2H, d, J=9 Hz), 7.63 (1H, s).
PREPARATION EXAMPLE 15
Preparation of 2-t-butyl-4-chloro-5-[4-(2-diethylaminoethoxy)-.alpha.-methylbenzyloxy]-3(2H)-pyridazinone (Compound No. 789)
By using 1.0 g of 2-t-butyl-4,5-dichloro-3(2H)-pyridazinone and 1.1 g of 4-(2-diethylaminoethoxy)-.alpha.-methylbenzyl alcohol and similarly to the procedures in Preparation Example 1, a crude product was obtained. The crude product was then purified through column chromatography (eluting with chloroform/methanol=200/5) to obtain 710 mg of the aimed product as an oil.
.sup.1 H-NMR (CDCl.sub.3, .delta., TMS): 1.05 (6H, t, J=7.4 Hz), 1.57 (9H, s), 1.68 (3H, d, J=6 Hz), 2.62 (4H, q, J=7.4 Hz), 2.84 (2H, t, J=6 Hz), 4.01 (2H, t, J=6 Hz), 5.44 (1H, q, J=6 Hz), 6.85 (2H, d, J=9.2 Hz), 7.26 (2H, d, J=9.2 Hz), 7.51 (1H, s).
PREPARATION EXAMPLE 16
Preparation of 2-t-butyl-5-(4-ethoxymethoxybenzyloxy)-4-methyl-3(2H)-pyridazinone (Compound No. 14)
By using 1.0 g of 2-t-butyl-5-hydroxy-4-methyl-3(2H)-pyridazinone, 1.1 g of 4-ethoxymethoxybenzyl chloride and 1.0 g of anhydrous potassium carbonate and similarly to the procedures in Preparation Example 2, 1.1 g of the aimed product was obtained as an oil.
.sup.1 H-NMR (CDCl.sub.3, .delta., TMS): 1.22 (3H, t, J=7 Hz), 1.61 (9H, s), 2.03 (3H, s), 3.73 (2H, q, J=7 Hz), 5.10 (2H, s), 5.21 (2H, s), 7.02 (2H, d, J=9 Hz), 7.29 (2H, d, J=9 Hz), 7.70 (1H, s).
PREPARATION EXAMPLE 17
Preparation of 2-t-butyl-5-{(5-t-butyl-2-thienyl)-methylthio}-4-methyl-3(2H)-pyridazinone (Compound No. 872)
In 20 ml of N,N-dimethylformamide were dissolved 2.0 g of 2-t-butyl-5-mercapto-4-methyl-3(2H)-pyridazinone and 1.9 g of 2-t-butyl-5-chloromethylthiophene, and thereto was added under stirring 1.5 g of potassium carbonate at room temperature. After additional stirring for 8 hours at room temperature, the mixture was poured into 50 ml of water and then extracted twice with 50 ml of benzene. The organic layer was washed with water, dried over anhydrous sodium sulfate and then freed of solvent by distillation under reduced pressure to obtain 3.5 g of a crude product. The crude product was separated and purified through thin layer chromatography (on silica gel; benzene) to give 2.2 g of 2-t-butyl-5-{(5-t-butyl-2-thienyl)-methylthio}-4-methyl-3(2H)-pyridazinone as an oil.
NMR (CDCl.sub.3, .delta., TMS): 1.32 (9H, s), 1.61 (9H, s), 2.14 (3H, s), 4.28 (2H, s), 6.58 (1H, d, J=3 Hz), 6.74 (1H, d, J=3 Hz), 7.64 (1H, s).
PREPARATION EXAMPLE 18
Preparation of 2-t-butyl-4-chloro-5-{(6-propyloxy-3-pyridyl)-methylthio}-3(2H)-pyridazinone (Compound No. 997)
To a solution of 2.2 g of 2-t-butyl-4-chloro-5-mercapto-3(2H)-pyridazinone and 1.9 g of 5-chloromethyl-2-propyloxypyridine in 20 ml of N,N-dimethylformamide was added under stirring 1.5 g of potassium carbonate at room temperature. After additional stirring for 8 hours at room temperature, the mixture was poured into 50 ml of water and then extracted twice with 50 ml of benzene. The organic layer was washed with water, dried over anhydrous sodium sulfate and then freed of solvent by distillation under reduced pressure to obtain 3.7 g of a crude product. The crude product was added with isopropyl ether and recrystallized therefrom to give 3.0 g of 2-t-butyl-4-chloro-5{-(6-propyloxy-3-pyridyl)-methylthio}-3(2H)-pyridazinone, m.p. 92.0.degree..about.93.5.degree. C.
.sup.1 H-NMR (CDCl.sub.3, .delta., TMS): 1.01 (3H, t, J=7 Hz), 1.50.about.2.00 (2H, m), 1.61 (9H, s), 4.21 (2H, s), 4.24 (2H, t, J=7 Hz), 6.84 (1H, d, J=9 Hz), 7.53.about.7.73 (1H, m), 7.66 (1H, s), 8.18 (1H, d, J=2 Hz).
PREPARATION EXAMPLE 19
Preparation of 2-t-butyl-4-chloro-5-{(5-chloro-2-thienyl)-.alpha.-methylmethylthio}-3(2H)-pyridazinone (Compound No. 858)
To a solution of 2.2 g of 2-t-butyl-4-chloro-5-mercapto-3(2H)-pyridazinone and 2.0 g of 2-chloro-5-(1-chloroethyl)thiophene in 20 ml of N,N-dimethylformamide was added under stirring 1.5 g of potassium carbonate at room temperature. After additional stirring for 8 hours at room temperature, the mixture was poured into 50 ml of water and then extracted twice with 50 ml of benzene. The organic layer was washed with water, dried over anhydrous sodium sulfate and then freed of solvent by distillation under reduced pressure to obtain 3.7 g of a crude product. The crude product was separated and purified through column chromatography (on silica gel: benzene) to obtain 2.5 g of 2-t-butyl-4-chloro-5{(5-chloro-2-thienyl)-.alpha.-methyl-methylthio}-3(2H)-pyridazinone as an oil.
NMR (CDCl.sub.3, .delta., TMS): 1.61 (9H, s), 1.75 (3H, d, J=7 Hz), 4.87 (1H, q, J=7 Hz) 6.70 (1H, d, J=3 Hz), 6.85 (1H, d, J=3 Hz), 7.61 (1H, s).
PREPARATION EXAMPLE 20
Preparation of 2-t-butyl-4-chloro-5-[{6-(4-chlorophenoxy)-3-pyridyl}-methyloxy]-3(2H)-pyridazinone (Compound No. 1041)
To 20 ml of N,N-dimethylformamide were added 2.1 g of 2-t-butyl-4-chloro-5-hydroxy-3(2H)-pyridazinone, 2.5 g of 5-chloromethyl-2-(4-chlorophenoxy)-pyridine and 1.5 g of potassium carbonate, and the mixture was stirred at 80.degree. to 90.degree. C. for 2 hours. After cooling, the reaction mixture was poured into 50 ml of water and extracted twice with 50 ml of benzene. The organic layer was washed with water, dried over anhydrous sodium sulfate and then freed of solvent by distillation under reduced pressure to obtain 3.9 g of a crude product. The crude product was added with a mixed solvent of isopropyl ether and 2-propanol and recrystallized therefrom to give 3.3 g of 2-t-butyl-4-chloro-5-[{6-(4-chlorophenoxy)-3-pyridyl}methyloxy]-3(2H)-pyridazinone, m.p. 150.0.degree..about.154.5.degree. C.
NMR (CDCl.sub.3, .delta., TMS): 1.61 (9H, s), 5.21 (2H, s), 6.85.about.7.40 (5H, m), 7.65.about.7.85 (1H, m), 7.72 (1H, s), 8.15 (1H, d, J=2 Hz).
PREPARATION EXAMPLE 21
Preparation of 4-chloro-5[{5-(4-chlorobenzoyl)-2-thienyl}methyloxy]-2-ethyl-3(2H)-pyridazinone (Compound No. 895)
To 20 ml of N,N-dimethylformamide were added 1.9 g of 4-chloro-2-ethyl-5-hydroxy-3(2H)-pyridazinone, 3.2 g of 2-bromomethyl-5-(4-chlorobenzoyl)-thiophene and 1.5 g of potassium carbonate, and the mixture was stirred at 50.degree. to 60.degree. C. for 2 hours. After cooling, the reaction mixture was poured into 50 ml of water and extracted twice with 50 ml of benzene. The organic layer was washed with water, dried over anhydrous sodium sulfate and then freed of solvent by distillation under reduced pressure to obtain 4.0 g of a crude product. The crude product was recrystallized from 2-propanol to obtain 3.1 g of 4-chloro-5-[{5-(4-chlorobenzoyl)-2-thienyl}-methyloxy]-2-ethyl-3(2H)-pyridazinone, m.p. 168.0.degree..about.168.5.degree. C.
NMR (CDCl.sub.3, .delta., TMS): 1.35 (3H, t, J=7 Hz), 4.21 (2H, q, J=7 Hz), 5.67 (2H, s), 7.25.about.7.95 (6H, m), 8.12 (1H, s).
PREPARATION EXAMPLE 22
Preparation of 2-t-butyl-5[{6-(4-fluorobenzyloxy)-3-pyridyl}-methyloxy]-4-methyl-3(2H)-pyridazinone (Compound No. 1010)
To a solution of 2.3 g of 6-(4-fluorobenzyloxy)-3-pyridine methanol in 20 ml of N,N-dimethylformamide was added under stirring at 0.degree. C. 0.5 g of 55% sodium hydride (in mineral oil). After stirring for 30 minutes at room temperature, thereto was added dropwise a solution of 2.0 g of 2-t-butyl-5-chloro-4-methyl-3(2H)-pyridazinone in 5 ml of N,N-dimethylformamide. The reaction mixture was stirred at room temperature for additional 8 hours, poured into 50 ml of ice water and extracted twice with 50 ml of benzene. The organic layer was washed with water, dried over anhydrous sodium sulfate and then freed of solvent by distillation under reduced pressure to give 3.8 g of a crude product. The crude product was separated and purified through thin layer chromatography (on silica gel; benzene) to obtain 2.5 g of 2-t-butyl-5-[{6-(4-fluorobenzyloxy)-3-pyridyl}-methyloxy]-4-methyl-3(2H)-pyridazinone as an oil.
NMR (CDCl.sub.3, .delta., TMS): 1.63 (9H, s), 2.02 (3H, s), 5.09 (2H, s), 5.34 (2H, s), 6.75.about.7.80 (6H, m), 7.78 (1H, s), 8.21 (1H, d, J=2 Hz).
PREPARATION EXAMPLE 23
Preparation of 2-t-butyl-4-chloro-5[{6-(4-fluorobenzyloxy)-3-pyridyl}-methyloxy]-3(2H)-pyridazinone (Compound No. 1011)
To a solution of 2.3 g of 6-(4-fluorobenzyloxy)-3-pyridine methanol in 20 ml of N,N-dimethylformamide was added under stirring at 0.degree. C. 0.5 g of 55% sodium hydride (in mineral oil). After stirring for 30 minutes at room temperature, thereto was added 2.2 g of 2-t-butyl-4,5-dichloro-3(2H)-pyridazinone. The reaction mixture was stirred at room temperature for additional 8 hours, poured into 50 ml of ice water and extracted twice with 50 ml of benzene. The organic layer was washed with water, dried over anhydrous sodium sulfate and then freed of solvent by distillation under reduced pressure to give 4.1 g of a crude product. The crude product was added with isopropyl ether and recrystallized therefrom to obtain 3.2 g of 2-t-butyl-4-chloro-5-[{6-(4-fluorobenzyloxy)-3-pyridyl}-methyloxy]-3(2H)-pyridazinone, m.p. 121.0.degree..about.124.0.degree. C.
NMR (CDCl.sub.3, .delta., TMS): 1.62 (9H, s), 5.25 (2H, s), 5.33 (2H, s), 6.75.about.7.85 (6H, m), 7.89 (1H, s), 8.26 (1H, d, J=2 Hz).
PREPARATION EXAMPLE 24
Preparation of 2-t-butyl-4-chloro-5-[{6-(2,2,3,3-tetrafluoropropyloxy)-3-pyridyl}-methylthio]-3(2H)-pyridazinone (Compound No. 1063)
In 40 ml of acetonitrile were dissolved 2.2 g of 2-t-butyl-4-chloro-5-mercapto-3(2H)-pyridazinone and 2.7 g of 5-chloromethyl-2-(2,2,3,3-tetrafluoropropyloxy)-pyridine, and thereto was added 1.5 g of potassium carbonate. The reaction mixture was stirred overnight at room temperature, poured into water and extracted with benzene. The organic layer was washed with a 5% aqueous solution of sodium hydroxide and then with water, and dried over anhydrous sodium sulfate. Solvent was distilled off under reduced pressure and the resulting crystals were washed with n-hexane to obtain 4.0 g of 2-t-butyl-4-chloro-5-[{6-(2,2,3,3-tetrafluoropropyloxy)-3-pyridyl}-methylthio]-3(2H)-pyridazinone, m.p. 113.0.degree..about.114.0.degree. C.
NMR (CDCl.sub.3, .delta., TMS): 1.60 (9H, s), 4.20 (2H, s), 4.49.about.4.94 (2H, m), 5.94 (1H, t-t, J=52 Hz, 4 Hz), 6.75 (1H, d, J=9 Hz), 7.53 (1H, s), 7.48.about. 7.77 (1H, m), 8.06 (1H, d, J=2 Hz).
PREPARATION EXAMPLE 25
Preparation of 2-t-butyl-4-chloro-5-[{6-(2,2,3,3-tetrafluoropropyloxy)-3-pyridyl}-methyloxy]-3(2H)-pyridazinone (Compound No. 1062)
In 40 ml of N,N-dimethylformamide were dissolved 2.2 g of 2-t-butyl-4,5-dichloro-3(2H)-pyridazinone and 2.5 g of 6-(2,2,3,3-tetrafluoropropyloxy)-3-pyridine methanol, and thereto was added 0.7 g of powdery potassium hydroxide. The reaction mixture was stirred overnight at room temperature and poured into water. Then, procedures similar to those in Preparation Example 24 were conducted to obtain 3.6 g of 2-t-butyl-4-chloro-5-[{6-(2,2,3,3-tetrafluoropropyloxy)-3-pyridyl}-methyloxy]-3(2H)-pyridazinone, m.p. 112.0.degree..about.118.0.degree. C.
NMR (CDCl.sub.3, .delta., TMS): 1.62 (9H, s), 4.52.about.4.97 (2H, m), 5.25 (2H, s), 5.99 (1H, t-t, J=52 Hz, 4 Hz), 6.86 (1H, d, J=9 Hz), 7.58.about.7.88 (1H, m), 7.77 (1H, m), 8.19 (1H, d, J=2 Hz).
PREPARATION EXAMPLE 26
Preparation of 2-t-butyl-4-chloro-5-[{6-(2,2,2-trifluoroethoxy)-3-pyridyl}-methylthio]-3(2H)-pyridazinone (Compound No. 1055)
In 40 ml of methanol were dissolved 2.2 g of 2-t-butyl-4,5-dichloro-3(2H)-pyridazinone and 2.4 g of 5-mercaptomethyl(2,2,2-trifluoro-ethoxy)-pyridine, and thereto was added 1.2 g of sodium carbonate. The reaction mixture was stirred overnight at room temperature and then poured into water. Then, procedures similar to those in Preparation Example 24 were conducted to obtain 3.6 g of 2-t-butyl-4-chloro-5-[{6-(2,2,2-trifluoroethoxy)-3-pyridyl}-methylthio]-3(2H)-pyridazinone, m.p. 109.0.degree..about.110.0.degree. C.
NMR (CDCl.sub.3, .delta., TMS): 1.61 (9H, s), 4.22 (2H, s), 4.73 (2H, q, J=9 Hz), 6.87 (1H, d, J=9 Hz), 7.62 (1H, s), 7.60.about.7.89 (1H, m), 8.15 (1H, d, J=2 Hz).
PREPARATION EXAMPLE 27
Preparation of 2-t-butyl-4-chloro-5-{4-(2-methoxy-1-methyl-ethoxy)-benzylthio}-3(2H)-pyridazinone (Compound No. 504)
In 30 ml of 95% ethanol were dissolved 1.5 g of 2-t-butyl-4-chloro-5-mercapto-3(2H)-pyridazinone and 1.8 g of 4-(2-methoxy-1-methylethoxy)-benzyl bromide, and thereto was added 0.48 g of powdery potassium hydroxide. The reaction mixture was stirred overnight at room temperature. Then, similarly to the procedures in Preparation Example 3, there was obtained 1.2 g of the aimed product, m.p. 51.0.degree..about.52.0.degree. C.
.sup.1 H-NMR (CDCl.sub.3, .delta., TMS): 1.27 (3H, d, J=6 Hz), 1.61 (9H, s), 3.35 (3H, s), 3.44 (2H, t, J=5.6 Hz), 4.17 (2H, s), 4.25.about.4.79 (1H, m), 6.84 (2H, d, J=9 Hz), 7.24 (2H, d, J=9 Hz), 7.59 (1H, s).
PREPARATION EXAMPLE 28
Preparation of 2-t-butyl-4-chloro-5-{4-(2-ethoxy-1-methylethoxy)-benzylthio}-3(2H)-pyridazinone (Compound No. 513)
In 15 ml of N,N-dimethylformamide were dissolved 1.4 g of 2-t-butyl-4-chloro-5-mercapto-3(2H)-pyridazinone and 2.0 g of 4-(2-ethoxy-1-methylethoxy)-benzyl bromide, and thereto was added 1.0 g of anhydrous sodium carbonate. The reaction mixture was stirred overnight at room temperature. Then, similarly to the procedures in Preparation Example 12, there was obtained 2.0 g of the aimed compound, m.p. 89.2.degree..about.90.2.degree. C.
.sup.1 H-NMR (CDCl.sub.3, .delta., TMS): 1.19 (3H, d, J=6.2 Hz), 1.30 (3H, d, J=6 Hz), 1.60 (9H, s), 3.36.about.3.78 (4H, m), 4.20 (2H, s), 4.30.about.4.73 (1H, m), 6.88 (2H, d, J=8.8 Hz), 7.28 (2H, d, J=8.8 Hz), 7.60 (1H, s).
PREPARATION EXAMPLE 29
Preparation of 2-t-butyl-4-chloro-5-{(6-i-propyloxy-3-pyridyl)-methylthio}-3(2H)-pyridazinone (Compound No. 1081)
To a solution of 2.2 g of 2-t-butyl-4-chloro-5-mercapto-3(2H)-pyridazinone and 2.0 g of 5-chloromethyl-2-i-propyloxypyridine in 50 ml of toluene were added 8.8 g of a 5% aqueous solution of sodium hydroxide and 0.2 g of tetra-n-butylammonium bromide, and the mixture was stirred at 40.degree. C. for 5 hours. After termination of the reaction, water was added thereto to remove the aqueous layer. The organic layer was washed with water, dried over anhydrous sodium sulfate and then freed of solvent of distillation under reduced pressure to give 3.7 g of a crude product. The crude product was added with i-propyl ether and recrystallized therefrom to obtain 3.0 g of 2-t-butyl-4-chloro-5-{(6-i-propyloxy-3-pyridyl)-methylthio}-3(2H)-pyridazinone, m.p. 111.2.degree..about.113.3.degree. C.
NMR (CDCl.sub.3, .delta., TMS): 1.34 (6H, d, J=6 Hz), 1.61 (9H, s), 4.17 (2H, s), 5.25 (1H, m), 6.63 (1H, d, J=9 Hz), 7.47.about.7.67 (1H, m), 7.60 (1H, s), 8.09 (1H, d, J=2 Hz).
With respect to the compounds produced according to any one of the methods in Preparation Examples 1 through 29, the melting points thereof are shown in Tables 1 and 2. Among the compounds, those obtained in the form of an oil are identified with .sup.1 H-NMR data in Table 3. The Compound numbers correspond to those in Tables 1 and 2.
TABLE 3______________________________________CompoundNo. .sup.1 H--NMR Data CDCl.sub. 3, .delta. (ppm)______________________________________15 1.22(t,3H), 1.63(s,9H), 3.70(q,2H), 4.20(s,2H), 5.20(s,2H), 6.9-7.4(m,4H), 7.61(s,1H),16 1.20(t,3H), 1.60(s,9H), 3.68(q,2H), 5.19(bs,4H), 6.9-7.4(m,4H), 7.62(s,1H)17 1.21(t,3H), 1.62(s,9H), 3.70(q,2H), 5.20(s,4H), 6.9-7.4 (m,4H), 7.70(s,1H)88 0.96(t,3H), 1.5-1.8(m,2H), 1.62(s,9H), 3.51(t,2H), 3.85(t,2H), 4.21(t,2H), 5.19(s,2H), 6.9-7.4(m,3H), 7.69(s,1H)391 0.8-1.0 (m,3H), 1.2-1.8(m,4H), 1.60(s,9H), 2.35(t,2H), 4.1-4.5(m,4H), 5.21(s,2H), 6.8-7.4(m,4H), 7.70(s,1H)392 0.8-1.0(m,3H), 1.2-1.7(m,4H), 1.61(s,9H), 2.35(t,2H), 4.1-4.6(m,4H), 4.23(s,2H), 6.8-7.4(m,4H), 7.62(s,1H)421 0.90(t,3H), 1.4-2.3(m,4H), 1.59(s,9H), 3.2-3.7(m,4H), 4.03(t,2H), 5.20(s,2H), 6.8-7.4(m,4H), 7.70(s,1H)521 0.90(t,3H), 1.30(d,3H), 1.5-1.8(m,2H), 1.60(s,9H), 3.25(d,2H), 3.4-3.6(m,2H), 4.13(s,2H), 4.3-4.6(m,1H), 6.7-7.3(m,4H), 7.50(s,1H)522 0.90(t,3H), 1.30(d,3H), 1.5-1.8(m,2H), 1.62(s,9H), 3.3-3.6(m,4H), 4.2-4.7(m,1H), 4.30(s,2H), 6.7-7.4(m,4H), 7.58(s,1H)523 0.90(t,3H), 1.28(d,3H), 1.5-1.8(m,2H), 1.62(s,9H), 3.3-3.6(m,4H), 4.3-4.7(m,1H), 5.25(s,2H), 6.7-7.5(m,4H), 7.65(s,1H),531 1.0-1.8(m,8H), 1.65(s,9H), 3.4-3.6(m,4H), 4.3-4.8(m,1H), 5.20(s,2H), 6.9-7.4(m,4H), 7.72(s,1H),533 0.9-1.1(m,3H), 1.2-1.7(m,5H), 1.61(s,9H), 3.4-3.6(m,4H), 4.20(s,2H), 4.3-4.7(m,1H), 6.8-7.4(m,4H), 7.60(s,1H)535 0.86(d,6H), 1.32(d,3H), 1.61(s,9H), 1.7-2.0(m,2H), 3.23(d,2H), 3.4-3.8(m,3H), 4.4-4.7(m,1H), 5.21(s,2H), 6.9-7.3(m,4H), 7.72(s,1H)538 0.90(d,6H), 1.35(d,3H), 1.62(s,9H), 1.7-2.0(m,2H), 3.24(d,2H), 3.3-3.8(m,3H), 4.20(s,2H), 4.4-4.7(m,1H), 6.8-7.4(m,4H), 7.61(s,1H)551 0.8-1.7(m,14H), 1.62(s,9H), 3.3-3.6(m,4H), 4.3-4.7(m,1H), 5.21,(s,2H), 6.8-7.4(m,4H), 7.62(s,1H)552 0.9-1.8(m,14H), 1.61(s,9H), 3.4-3.7(m,4H), 4.4-4.8(m,1H), 5.20(s,2H), 6.9-7.4(m,4H), 7.68(s,1H),554 1.35(d,3H), 1.62(s,9H), 3.5-3.7(m,2H), 4.05(d,2H), 4.4-4.8(m,1H), 5.1-5.4(m,2H), 5.6-6.0(m,1H), 6.8-7.4(m,4H), 7.71(s,1H)555 1.35(d,3H), 1.63(s,9H), 3.5-3.7(m,2H), 4.05(d,2H), 4.21(s,2H), 4.4-4.8(m,1H), 5.0-5.4(m,2H), 5.6-5.9(m,1H), 6.8-7.4(m,2H), 7.60(s,1H)581 0.8-1.1(m,3H), 1.2-1.7(m,5H), 1.63(s,9H), 3.4-4.0(m,5H), 5.21(s,2H), 6.8-7.4(m,4H), 7.73(s,1H)582 0.8-1.1(m,3H), 1.2-1.7(m,5H), 1.60(s,9H), 3.4-4.0(m,5H), 4.19(s,2H), 6.8-7.4(m,4H), 7.58(s,1H),611 1.22(t,3H), 1.31(s,6H), 1.62(s,9H), 3.38(s,2H), 3.56(q,2H), 5.22(s,2H), 6.9-7.4(m,4H), 7.70(s,1H),612 1.22(t,3H), 1.29(s,6H), 1.61(s,9H), 3.37(s,2H), 3.54(q,2H), 4.22(s,2H), 6.9-7.3(m,4H), 7.58(s,1H),616 0.8-1.0(t,3H), 1.30(s,6H), 1.2-1.5(m,2H), 1.61(s,9H), 3.3-3.5(m,4H), 4.21(s,2H), 6.9-7.3(m,4H), 7.59(s,1H),639 1.1-1.4(m,6H), 1.61(s,9H), 1.40(s,3H), 3.3-3.7(m,1H), 4.2-4.6(m,1H), 4.22(s,2H), 6.8-7.4(m,4H), 7.65(s,1H)659 0.99(s,3H), 1.5-1.9(m,2H), 1.60(s,9H), 3.37(s,3H), 3.54(d,2H), 4.1-4.5(m,1H), 5.21(s,2H), 6.9-7.4(m,4H), 7.70(s,1H)661 0.97(s,3H), 1.5-1.9(m,2H), 1.61(s,9H), 3.35(s,3H), 3.52(d,2H), 4.1-4.4(m,1H), 4.19(s,2H), 6.8-7.3(m,4H), 7.56(s,1H)668 0.8-1.2(m,6H), 1.4-1.9(m,4H), 1.62(s,9H), 3.3-3.7(m,4H), 4.2-4.5(m,1H), 5.25(s,2H), 6.9-7.4(m,4H), 7.76(s,1H)671 0.8-1.1(m,6H), 1.4-1.9(m,4H), 1.61(s,9H), 3.3-3.6(m,4H), 4.1-4.5(m,1H), 4.20(s,2H), 6.8-7.4(m,4H), 7.62(s,1H),673 0.8-1.2(m,6H), 1.3-1.9(m,6H), 1.61(s,9H), 3.3-3.6(m,4H), 4.1-4.5(m,1H), 5.20(s,2H), 6.8-7.3(m,4H), 7.72(s,1H),787 1.02(t,6H), 1.59(s,9H), 2.4-2.9(m,6H), 3.98(t,2H) 4.18(s,2H), 6.8-7.3(m,4H), 7.58(s,1H)844 1.21(t,6H), 1.60(s,9H), 3.5-3.8(m,4H), 3.95(d,2H), 4.17(s,2H), 4.78(t,1H), 6.7-7.3(m,4H), 7.52(s,1H)508 1.20(t,3H), 1.33(d,3H), 1.62(s,9H), 2.22(s,3H), 3.39-3.78(m,4H), 4.27-4.77(m,1H), 5.18(s,2H), 6.78-7.29(m,3H), 7.71(s,1H)509 1.19(t,3H), 1.31(d,3H), 1.60(s,9H), 2.19(s,3H), 3.33-3.75(m,4H), 4.15(s,2H), 4.23-4.72(m,1H), 6.72-7.33(m,3H) 7.60(s,1H)515 1.17(t,3H), 1.35(d,3H), 1.61(s,9H), 3.36-3.80(m,4H), 4.25(s,2H), 4.32-4.77(m,1H), 6.73-7.49(m,4H), 7.68(s,1H),516 1.18(t,3H), 1.32(d,3H), 1.61(s,9H), 3.32-3.74(m,4H), 4.34-4.83(m,1H), 5.32(s,2H), 6.79-7.52(m,4H), 7.79(s,1H),857 1.61(s,9H), 4.36(s,2H), 6.70-6.95(m,2H), 7.63(s,1H),858 1.60(s,9H), 1.75(d,J=7 Hz,3H) 4.87(q,J=7 Hz,1H), 6.70(d,J= 3 Hz,1H), 6.83(d,J=3 Hz, 1H), 7.62(s,1H)860 1.62(s,9H), 4.39(s,2H), 6.85(bs,2H), 7.62(s,1H)870 1.33(s,9H), 1.60(s,9H), 4.39(s,2H), 6.60(d, J=3 Hz,1H), 6.83(d,J=3 Hz,1H), 7.67(s,1H)872 1.32(s,9H), 1.61(s,9H), 2.14(s,3H),4.28(s,2H), 6.58(d,J=3 Hz, 1H) 6.74(d,J=3 Hz,2H) 7.64(s,1H)876 0.7-1.05(m,3H), 1.15-1.75(m,4H), 1.58(s,9H), 2.70(t,J=7 Hz,2H 4.38(s,2H), 6.53(d,J=3 Hz,1H) 6.81(d,J=3 Hz,1H) 7.66(s,1H)883 1.00-2.00(m,10H), 1.60(s,9H), 2.35-2.95(m,1H), 4.36(s,2H), 6.57 (d,J=3 Hz,1H), 6.81(d, J=3 Hz,1H) 7.62(s,1H)885 1.60(s,9H), 4.40(s,2H), 6.90-7.55(m,6H), 7.68(s,1H)890 1.58(s,9H, 4.09(s,2H), 4.33(s,2H), 6.56(d,J=4 Hz,1H), 6.71(d,J=4 Hz,1H), 7.00-7.35(m,3H), 7.58(s,1H)930 1.62(s,9H), 3.90(s,2H), 5.07(s,2H), 6.04(s,1H), 7.21(s,1H), 7.35(s,1H), 7.69(s,1H)963 0.80-1.10(m,3H), 1.15-1.90(m,4H), 1.59(s,9H), 2.59(t,J=7 Hz,2H), 4.35(s,2H), 7.25-7.50(m,2H), 7.88(s,1H), 8.46(bs,1H)998 1.00(t,J=7 Hz,3H), 1.50-2.05(m,2H), 1.62(s,9H), 2.12(s,3H), 4.11(s,2H), 4.22(t,J=7 Hz,2H), 6.69(d,J=9 Hz, 1H) 7.50-7.80(m,1H), 7.63(s,1H), 8.07(d,J=2 Hz,1H)999 1.00(t,J=7 Hz,3H) 1.50-2.05(m,2H), 1.62(s,9H), 4.24(t,J=7 Hz,2H), 5.26(s,2H), 6.75(d,J=9 Hz,1H), 7.69(d-d,J=9 Hz,2 Hz,1H), 7.90(s,1H), 8.22(d,J=2 Hz,1H)1010 1.63(s,9H), 2.02(s,3H), 5.09(s,2H), 5.34(s,2H), 6.75-7.80(m,6H), 7.78(s,1H), 8.21(d,J=2 Hz,1H),1027 1.62(s,9H), 4.16(s,2H), 6.75-7.70(m,8H), 7.82(s,1H),1028 1.61(s,9H), 2.11(s,3H), 4.10(s,2H), 6.65-7.61(m,8H) 7.66(s,1H)1029 1.61(s,9H), 4.13(s,2H), 6.72-7.66(m,7H), 7.75(s,1H),1004 0.80-2.06(m,7H), 1.61(s,9H), 2.00(s,3H), 4.28(t,J=6 Hz,2H), 5.06(s,2H), 6.71(d,J=9 Hz,1H), 7.58(d-d,J=9 Hz,2 Hz,1H) 7.71(S,1H) 8.14(d, J=2 Hz,1H),1094 1.60(s,9H), 5.35(s,2H), 7.03(s,1H), 7.30(s,1H), 7.66(s,1H)1097 1.62(s,9H), 4.38(s,2H), 6.82(d,J=4 Hz,1H), 6.91(d,J=4 Hz,1H) 7.60(s,1H)______________________________________
When the compounds according to the present invention are used for insecticidal, acaricidal, nematicidal and/or fungicidal agents for agricultural and horticultural uses or for expellents of ticks parasitic on animals, they are generally mixed with appropriate carriers, for instance, solid carriers such as clay, talc, bentonite or diatomaceous earth, or liquid carriers such as water, alcohols (e.g. methanol and ethanol), aromatic hydrocarbons (e.g. benzene, toluene and xylene), chlorinated hydrocarbons, ethers, ketones, esters (e.g. ethyl acetate), or acid amides (e.g. dimethylformamide). If desired, to these mixtures may be added emulsifier, dipersing agent, suspension agent, penetrating agent, spreader, stabilizer and the like to put them into practical uses in the form of liquid preparation, emulsifiable concentrate, wettable powder, dust, granule, flowable or the like. Moreover, the mixtures may be incorporated with other herbicides, various insecticides, fungicides, plant-growth regulating agents and/or synergists during preparation or application thereof, as necessary.
The amount of the compounds of the invention to be used as an active ingredient is suitably in the range of approximately 0.005 to 50 kg per hectare although it varies depending upon the place and the season where the compounds are applied, manner of application, diseases and insect pests to be applied, cultivated crops to be protected and the like.
In the following, there are shown formulation examples of fungicidal, insecticidal, acaricidal and/or nematicidal compositions and expellent compositions for ticks parasitic on animals, said compositions containing the compounds of the present invention as an active ingredient. These examples are only illustrative and not to restrict the invention. In the following examples, "part" means "part by weight".
______________________________________Formulation Example 1: Emulsifiable concentrates______________________________________Active ingredient 20 partsXylene 55 partsN,N--dimethylformamide 20 partsSolpol 2680 (trade name, a mixture of 5 partsa non-ionic surface-active agentand an anionic surface-active agentmanufactured by Toho Chemicals, Co.,Ltd., Japan)______________________________________
The above components are mixed intimately together to form an emulsifiable concentrate. Upon use, the emulsifiable concentrate is diluted with water up to one fiftieth to one twenty thousandth in concentration and applied at a rate of 0.005 to 50 kg of the active ingredient per hectare.
______________________________________Formulation Example 2: Wettable powders______________________________________Active ingredient 25 partsSiegreit PFP (trade name, a mixture 66 partsof kaolinite and sericitemanufactured by Siegreit MiningIndustries Co., Ltd.)Solpol 5039 (trade name, an anionic 4 partssurface-active agent manufacturedby Toho Chemical Co., Ltd., Japan)Carplex #80 (trade name, white carbon 3 partsmanufactured by Shionogi SeiyakuK.K., Japan)Calcium lignin sulfonate 2 parts______________________________________
The above components are homogeneously mixed together and ground to form a wettable powder. Upon use, the wettable powder is diluted with water up to one fiftieth to one twenty thousandth and applied at a rate of 0.005 to 50 kg of the active ingredient per hectare.
______________________________________Formulation Example 3: Oil solutions______________________________________Active ingredient 10 partsmethylcellosolve 90 parts______________________________________
The above components are homogeneously mixed together to form an oil solution. Upon use, the oil solution is applied at a rate of 0.005 to 50 kg of the active ingredient per hectare.
______________________________________Formulation Example 4: Dusts______________________________________Active ingredient 3.0 partsCarplex #80 (trade name, white carbon 0.5 part.sup.manufactured by Shionogi SeiyakuK.K., Japan)Clay 95.0 partsdi-isopropyl phosphate 1.5 parts______________________________________
The above components are homogeneously mixed together and ground to form a dust. Upon use, the dust is applied at a rate of 0.005 to 50 kg of the active ingredient per hectare.
______________________________________Formulation Example 5: Granules______________________________________Active ingredient 5 partsBentonite 54 partsTalc 40 partsCalcium lignin sulfonate 1 part.sup.______________________________________
The above components are mixed intimately together and ground, incorporated with a small amount of water and mixed together with stirring. The resulting mixture is granulated by means of extrusion-granulator and dried to form granules. Upon use, the granule is applied at a rate of 0.005 to 50 kg of the active ingredient per hectare.
______________________________________Formulation Example 6: Flowables______________________________________Active ingredient 25 partsSolpol 3353 (trade name, a non ionic 10 partssurface-active agent manufacturedby Toho Chemicals, Co., Ltd., Japan)Runox 1000C (trade name, an anionic 0.5 part .sup.surface-active agent manufacturedby Toho Chemicals, Co., Ltd., Japan)1% aqueous solution of Xanthan gum 20 parts(natural high-molecular compound)Water 44.5 parts______________________________________
The above components except the active ingredient are uniformly mixed together to form a solution, and thereto is added the active ingredient. The resulting mixture is throughly stirred, wet-ground by means of sand mill to form a flowable. Upon use, the flowable is diluted up to one fiftieth to one twenty thousandth with water and applied at a rate of 0.005 to 50 kg of the active ingredient per hectare.
The compounds according to the present invention not only exhibit superior insecticidal action on hemiptera insect such as green rice leafhopper (Nephotettix cincticeps), lepidoptera insect such as diamondback moth (Plutella xylostella), Coleoptera and sanitary insect pests such as pale house mosquito (Culex pipiens), but are also useful for expelling mites parasitic on fruits and vegetables such as two-spotted spider mite (Tetranychus urticae), Kanzawa spider mite (Tetranychus kanzawai), Carmine mite (Tetranychus cinnabarinus), citrus red mite (Panonychus citri) and European red mite (Panonychus ulmi), as well as ticks parasitic on animals such as southern cattle tick (Boophilus microplus), cattle tick (Boophilus annulatus), galf coast tick (Amblyomma maculatum), brown-ear tick (Rhipicephalus appendiculatus) and (Haemaphysalis longicornis). The compounds of the present invention are also useful for controlling nematoda such as root-knot nematode (Meloidogyne sp.), root-lesion nematode (Pratylenchus sp.) and cyst nematode. The main features of the compounds of the present invention resides in that the compounds are useful for the prevention or control of blight (or disease) of fruits and vegetables such as powdery mildew, downy mildew, rust, rice blast disease (or rice blight) etc. in addition to having the above mentioned insecticidal, acaricidal and nematicidal actions. Accordingly, the compounds of the present invention are an excellent agricultural drug which enables control of pests and blight (or disease) simultaneously. Moreover, they are excellent as an expellent for ticks parasitic on animals such as domestic animals (e.g. cattle, horse, sheep and pig), domestic fowls, and other animals such as dog, cat, rabbit and the like.
The invention is further explained in detail by way of the following test examples.
TEST EXAMPLE 1
Insecticidal Test on Green Rice Leafhopper (Nephotettix cincticeps)
Stems and leaves of paddy were immersed into a 1000 ppm aqueous emulsion which had been prepared by diluting with water an emulsifiable concentrate containing each compound of the invention for about 10 seconds, and then the stems and leaves were placed into a glass cylinder. After 10 adults of green rice leafhopper which would show resistance to organic phosphorus type insecticides were released, the glass cylinder was covered with a plastic lid having some pores and placed in a thermostatic chamber kept at 25.degree. C. After 96 hours later, the mortality was calculated according to the following equation. Incidentally, the test was repeated twice for each compound. The results are shown in Table 4. ##EQU1##
TEST EXAMPLE 2
Contact Insecticidal Test on 28-spotted Lady Beetle (Henosepilachna vigintioctopunctata)
A leaf of tomato was immersed for about 10 seconds in a 1000 ppm aqueous emulsion which had been prepared by diluting with water an emulsifiable concentrate containing each compound of the invention and then air-dried. The leaf thus treated was placed in a laboratory dish, into which 10 second inster 28-spotted lady beetle larvae were released. The dish was then fitted with a cap provided with pores and then placed in a thermostatic chamber kept at 25.degree. C. The number of the larvae killed was checked after 96 hours and the mortality thereof was calculated according to the equation below. Incidentally, the test was repeated twice for each compound. The test results are shown in Table 4. ##EQU2##
TEST EXAMPLE 3
Acaricidal Test on Kanzawa Spider Mite (T. kanzawai)
A leaf of kidney bean was cut into a round piece of 1.5 cm in diameter by a leaf punch, and then placed on a moistened filter paper on a styrol cup of 7 cm in diameter. Each piece of the leaf was inoculated with 10 Kanzawa Spider Mite nymphs. Half a day after the inoculation, each 2 ml of a 1000 ppm aqueous emulsion which had been prepared by diluting with water an emulsifiable concentrate containing each compound of the invention was applied to each styrol cup by means of a rotary spray tower. After 96 hours, the mortality of the nymph was determined according to the equation below. Incidentally, the test was repeated twice for each compound. The results are shown in Table 4. ##EQU3##
TABLE 4______________________________________Compound Green Rice 28-spottedNo. of the Leafhopper Lady Beetle KanzawaPresent (Nephotettix (Henosepilachna Spider MiteInvention cincticeps) vigintioctopunctata) (T. Kanzawai)______________________________________5 100 100 1007 100 100 10015 100 100 10016 100 100 10017 100 100 10044 100 100 10045 100 100 10068 100 100 10071 100 100 10081 100 100 10087 100 100 100281 100 100 100291 100 100 100302 100 100 100310 100 100 100369 100 100 100402 100 100 100403 100 100 100413 100 100 100415 100 100 100421 100 100 100424 100 100 100663 100 100 100502 100 100 100504 100 100 100508 100 100 100511 100 100 100513 100 100 100517 100 100 100521 100 100 100524 100 100 100527 100 100 100531 100 100 100533 100 100 100551 100 100 100552 100 100 100553 100 100 100579 100 100 100581 100 100 100582 100 100 100611 100 100 100612 100 100 100615 100 100 100616 100 100 100637 100 100 100639 100 100 100659 100 100 100661 100 100 100664 100 100 100667 100 100 100668 100 100 100671 100 100 100673 100 100 100675 100 100 100838 100 100 100843 100 100 100844 100 100 100857 100 100 100858 100 100 100860 100 100 100870 100 100 100872 100 100 100876 100 100 100883 100 100 100885 100 100 100898 100 100 100929 100 100 100930 100 100 100951 100 100 100963 100 100 100964 100 100 100997 100 100 100998 100 100 100999 100 100 1001001 100 100 1001003 100 100 1001004 100 100 1001007 100 100 1001010 100 100 1001011 100 100 1001027 100 100 1001028 100 100 1001029 100 100 1001041 100 100 1001042 100 100 1001055 100 100 1001056 100 100 1001058 100 100 1001062 100 100 1001063 100 100 1001067 100 100 1001081 100 100 1001083 100 100 10082 100 100 10088 100 100 100509 100 100 100535 100 100 100538 100 100 100554 100 100 100555 100 100 100787 100 100 100______________________________________
TEST EXAMPLE 4
Insecticidal Test on Common Cutworm or Cluster Caterpillar (Spodoptera litura)
A leaf of cabbage was immersed in a 1000 ppm aqueous emulsion which had been prepared by diluting with water an emulsifiable concentrate containing each compound of the invention for about 10 seconds, and then air-dried. The leaf thus treated was placed in a laboratory dish, into which second instar common cutworm or cluster caterpillar (Spodoptera litura) larvae were released. The dish was fitted with a cap provided with some pores and then placed in a thermostatic chamber kept at 25.degree. C. The mortality after 7 days was determined according to the equation below. Incidentally, the test was repeated twice for each compound. ##EQU4##
As the results, the following compounds showed a mortality of 100%:
Compound Nos. 45, 403, 415, 424, 504, 513, 521, 533, 639, 667, 671, 857, 858, 860, 870, 872, 876, 883, 885, 963, 964, 997, 998, 999, 1001, 1003, 1004, 1007, 1010, 1011, 1041, 1042, 1055, 1056, 1058, 1062, 1063, 1081 and 1083.
TEST EXAMPLE 5
Nematicidal Test on Root-knot Nematode (Meloidogyne sp.)
Soil contaminated with root-knot nematode was placed in a styrol cup of 8 cm in diameter. A liquid containing 1000 ppm of an active ingredient was prepared by diluting an emulsifiable concentrate containing a compound of the present invention with water. The soil contaminated with nematode and placed in the styrol cup was drenched with each 50 ml of the resulting liquid. After 48 hours, a tomato seedling as an indicator was transplanted into the soil thus treated. Thirty days after the transplantation, the roots of the tomato were washed with water and the root-knot parasitism was checked by observation. Incidentally, the test was repeated twice for each compound. As a result, no root-knot parasitism was observed in the roots of the tomato treated with the following compounds; it was shown that these compounds exhibit a strong nematicidal activity:
Compound Nos. 895, 964, 999 and 1041.
TEST EXAMPLE 6
Test for Controlling Downy Mildew of Cucumber
Employing cucumbers (Cucumis sativus L.: variety Sagamihanjiro) which had been grown for 2 weeks, thereto was sprayed a solution of an emulsifiable concentrate according to the invention which had been adjusted to a predetermined concentration (1000 ppm) at the rate of 20 ml per pot. After each pot was placed for one day in a greenhouse, a suspension of spores of Pseudoperonospora cubensis (the concentration of the spores being such that 15 pieces of the spore can be observed by a 150 magnification microscope) was sprayed to the cucumbers for inoculation. The cucumbers to which the spores of Pseudoperonospora cubensis had been inoculated were left for 24 hours in a room kept at 25.degree. C. with a relative humidity of 100% and then transported to a greenhouse for observation of disease appearance. Seven days after the inoculation, the percentages of the disease appearance were measured. As the results, no disease appearance was observed at all with respect to the following compounds:
Compound Nos. 5, 81, 87, 281, 392, 415, 421, 424, 511, 513, 517, 521, 524, 527, 531, 533, 552, 553, 581, 582, 616, 637, 639, 659, 661, 663, 664, 667, 668, 671, 843, 885, 951, 964, 997, 998, 999, 1010, 1011 and 1041.
TEST EXAMPLE 7
Test for Controlling Powdery Mildew of Cucumber
Employing cucumbers (Cucumis sativus L.: variety Sagamihanjiro) which had been grown in pots for 2 weeks, thereto was sprayed a solution of an emulsifiable concentrate containing a compound of the present invention and which had been adjusted to a predetermined concentration (1000 ppm) at the rate of 20 ml per pot. After each pot was placed for one day in a greenhouse, a suspension of spores of Sphaerotheca fuliginea (the concentration of the spores being such that 25 pieces of the spores can be observed by a 150 magnification microscope) was sprayed to the cucumbers for inoculation. The cucumbers were placed in a greenhouse at 25.degree.-30.degree. C. for observation of disease appearance. Ten days after the inoculation, the percentages of the disease appearance were measured and evaluated. As the results, no disease appearance was observed at all with respect to the following compounds:
Compound Nos. 17, 68, 71, 81, 87, 281, 415, 421, 504, 511, 513, 517, 521, 524, 527, 531, 552, 581, 582, 616, 637, 639, 659, 664 843, 844, 872, 885, 898, 951, 963, 964, 997, 998, 999, 1010, 1011, 1041 and 1042.
TEST EXAMPLE 8
Test for Controlling Leaf Rust of Wheat
To wheats (Norin No. 61, third to fourth leaf-stage) which had been grown in pots of 9 cm in diameter was sprayed a solution of an emulsifiable concentrate containing a compound of the invention and which had been adjusted to a concentration of 1000 ppm at the rate of 20 ml per pot by means of a spray gun. The next day, thereto was sprayed a suspension of Uredospore of Puccinia triticina (the concentration of the suspension being such that 30 pieces of the spores can be observed by a 150 magnification microscope). Each pot was placed in an inoculation box kept at 25.degree. C. with a relative humidity of not lower than 95% for one day and then allowed to stand at room temperature. Ten days after the inoculation, the disease area thus formed was measured and the protective value of each compound was calculated according to the following equation: ##EQU5##
As the results, the following compounds showed a protective value of 100%:
Compound Nos. 424, 504, 517, 533, 637, 885, 951, 964, 997, 998, 999, 1010, 1011, 1041 and 1042.
TEST EXAMPLE 9
Test for Controlling Rice Blight
To rice plants (Nihonbare, third to fourth leaf-stage) which had been grown in pots of 9 cm in diameter was sprayed a solution of an emulsifiable concentrate which contains a compound of the present invention in the concentration of 1000 ppm at the rate of 20 ml per pot by means of a spray gun. The next day, a suspension of spores of Pyricularia oryzae (concentration of the suspension being such that 40 pieces of the spore can be observed by a 150 magnification microscope) was sprayed to the rice plants. Each pot was placed in an inoculation box kept at 25.degree. with a relative humidity of not lower than 95% for one day and thereafter allowed to stand at room temperature. Seven days after the inoculation, the number of the disease appearance formed was measured and the protective value was calculated according to the following equation: ##EQU6##
As the results, the following compounds showed 100% in protective value:
Compound Nos. 16, 17, 281, 517, 611, 885, 951, 964, 997, 998, 999, 1010, 1011, 1029 and 1041.
TEST EXAMPLE 10
Test for Controlling Downy Mildew of Cucumber (Low Concentration Test)
Test was conducted in accordance with Test Example 6 except that the concentration each of the present compound and a control compound was changed to 500, 100 and 50 ppm. The protective value was calculated according to the following equation: ##EQU7##
The results are shown in Table 5. From the results, it can be seen that the present compounds exhibit much higher fungicidal activity than the known control compounds.
TEST EXAMPLE 11
Test for Controlling Powdery Mildew of Cucumber (Low Concentration Test)
Test was conducted in accordance with Test Example 7 except that the concentration each of the present compound and a control compound was changed to 500, 100 and 50 ppm. The protective value was calculated according to the following equation: ##EQU8##
The results are shown in Table 5. From the results, it can be seen that the present compounds exhibit much higher fungicidal activity than the known control compounds.
TEST EXAMPLE 12
Test for Controlling Leaf Rust of Wheat (Low Concentration Test)
Test was conducted in accordance with Test Example 8 except that the concentration each of the present compound and a control compound was changed to 500, 100 and 50 ppm. The protective value was calculated according to the following equation: ##EQU9##
The results are shown in Table 5. From the results, it can be seen that the present compounds exhibit much higher fungicidal activity than the known control compounds.
TEST EXAMPLE 13
Test for Controlling Rice Blight (Low Concentration Test)
Test was conducted in accordance with Test Example 9 except that the concentration each of the present compound and a control compound was changed to 500, 100 and 50 ppm. The protective value was calculated according to the following equation: ##EQU10##
The results are shown in Table 5. From the results, it can be seen that the present compounds exhibit much higher fungicidal activity than the known control compounds.
(a) a compound described in European Laid-open Patent Application No. 0134439 Gazette.
(b) a compound encompassed by the general formula described in European Laid-open Patent Application No. 0088384 Gazette.
As the results of Test Examples 10 through 13, it was shown that the present compounds, compared with the control compounds, are not only markedly increased in activity for controlling each blight but also have a wider spectrum and that the present compounds have an excellent fungicidal activity which enables simultaneous control of downy mildew and powdery mildew of vegetables or powdery mildew and red rust of wheat.
TABLE 5__________________________________________________________________________ ##STR809## Compound A' = N, X = S A' = N, X = O A' = CH, X = S A' = CH, X = O Present Compound Present Compound Reference ReferenceProtective value (%) ppm No. 997 No. 999 Compound 1.sup.a Compound 2.sup.b__________________________________________________________________________Downy mildew of 500 100 100 0 0cucumber 100 100 80 0 0 50 80 50 0 0Powdery mildew of 500 100 100 0 100cucumber 100 100 100 0 70 50 60 80 0 30Leaf rust of 500 100 100 0 80wheat 100 100 100 0 70 50 100 80 0 0Rice Blast ( Pyricularia 500 100 100 80 0oryze) of rice plant 100 100 80 0 0 50 70 40 0 0__________________________________________________________________________
TEST EXAMPLE 14
Insecticidal Test on Green Rice Leafhopper (Nephotettix cincticeps) (Low Concentration Test)
Test was conducted in accordance with Test Example 1 except that the concentration each of the present compound and a control compound was changed to 10 ppm. The results are shown in Table 6.
As the results, it was shown that the present compounds exhibit higher insecticidal activity compared with the known control compounds.
(a) a compound encompassed by the general formula described in European Laid-open Patent Application No. 0088384 Gazette.
Control compound A: ##STR810##
(b) a compound described in European Laid-open Patent Application No. 0134439 Gazette.
Control compound B: ##STR811##
Control compound C: ##STR812##
(c) Compound No. of the present invention
TABLE 6______________________________________ Green Rice Green RiceCompound Leafhopper Compound LeafhopperNo. mortality (%) No. mortality (%)______________________________________Reference 55 511.sup.c 100Compound.sup.aReference 30 521.sup.c 100Compound.sup.bBReference 25 527.sup.c 100Compound.sup.bC68.sup.c 100 611.sup.c 10081.sup.c 100 616.sup.c 100______________________________________
TEST EXAMPLE 15
Acaricidal Test on Kanzawa Spider Mite (T. kanzawai) (Low Concentration Test)
Test was conducted in accordance with Test Example 3 except that the concentration each of the present compound and a control compound was changed to 100 ppm. The results are shown in Table 7.
As the results, it was shown that the present compounds exhibit higher acaricidal activity compared with the known control compounds.
TABLE 7______________________________________ ##STR813##CompoundPresent Compound Reference Compound.sup.aS CHCHYActivity Cl (No. 857) Br (No. 860) Cl Br______________________________________Kanzawa 100 100 50 50Spider Mitemortality(%)______________________________________ .sup.a The compound described in European Laidopen Patent No. 0134439
TEST EXAMPLE 16
Acaricidal Test on Two-Spotted Spider Mite (Tetranychus urticae) (Low Concentration Test)
Test was conducted in accordance with Test Example 3 except that two-spotted spider mite adults were used and that the concentration each of the present compound and a control compound was changed to 100 ppm and 10 ppm. The results are shown in Table 8. As the results, it was shown that the present compounds exhibit much higher acaricidal activity compared with the known control compounds.
TABLE 8______________________________________ Two-spottedReference spider mite Present Two-spotted spiderCompound mortality (%) Compound mite mortality (%)No. 100 ppm 10 ppm No. 100 ppm 10 ppm______________________________________B.sup.a 95 40 504 100 100C.sup.a 100 55 521 100 100D.sup.a 95 35 612 100 100 844 100 100______________________________________ .sup.a The compound described in European Laidopen Patent No. 0134439 ##STR814## Reference Compound B: R' = nC.sub.5 H.sub.11 Reference Compound C: R' = nC.sub.6 H.sub.13 Reference Compound D: R' = nC.sub.4 H.sub.9-
TEST EXAMPLE 17
Residual Action Test on Two-Spotted Spider Mite (Tetranychus urticae)
Emulsifiable concentrates each containing a present compound or a control compound were diluted with water to give a drug solution having a concentration of 100 ppm. The drug solution was sprayed onto an eggplant in the sixth leaf-stage which had been grown in a 1/5000 are pot until the eggplant was drenched therewith. After air-drying, the pot was kept in a greenhouse. Seven days after and twenty eight days after the spraying, a leaf of the eggplant was cut into a round piece of 1.5 cm in diameter by a leaf punch and then placed on a moistened filter paper put on a styrol cup of 7 cm. in diameter. Each piece of the leaf was inoculated with 10 Two-spotted spider mite nymphs. The styrol cup was placed in a thermostatic chamber kept at 25.degree. C. After 96 hours, the mortality of the nymph was checked. The results are shown in Table 9.
As the results, it was shown that the present compounds exhibit superior residual action to the known control compounds.
TABLE 9______________________________________Two spotted spider Two spotted spidermite aftereffective mite aftereffectivemortality (%) mortality (%)Compound after after Compound after afterNo. 7 days 28 days No. 7 days 28 days______________________________________Reference 100 0 513.sup.b 100 100Compound.sup.aReference 100 0 521.sup.b 100 100Compound.sup.aCReference 100 0 612.sup.b 100 100Compound.sup.aD504.sup.b 100 100 661.sup.b 100 100______________________________________ .sup.a The compound described in European LaidOpen Patent No. 0134439 .sup.b The compound No. of the present invention
TEST EXAMPLE 18
Nematicidal Test on Root-Knot Nematode (Meloidogyne sp.)
Soil contaminated with root-knot nematode was placed in a 1/10000 are pot. The present compound was formulated into a 5% dust according to Formulation Example 4, and 300 mg of the dust per pot was intimately mixed with the soil in the pot. The amount of the present compound in the soil corresponds to 30 kg of the compound per hectare. After 48 hours, a tomato seedling as an indicator was transplanted into the soil and kept in a greenhouse. Thirty days after the transplantation, the roots of the tomato were washed with water, and the root-knot parasitism was checked by observation and evaluated according to the following rating:
Rating of root-knot parasitism
0: no root-knot observed at all
1: a few root-knots observed
2: a medium number of root-knots observed
3: many root-knots observed
4: considerably many root-knots observed
The results are shown in Table 10
TABLE 10______________________________________ Root-knot Root-knotCompound No. parasitism Compound No. parasitism______________________________________Reference 2 81.sup.b 0Compound.sup.aReference 2 504.sup.b 0Compound.sup.aCReference 3 513.sup.b 0Compound.sup.aD 7.sup.b 0 533.sup.b 015.sup.b 0 582.sup.b 045.sup.b 0 1072.sup.b 068.sup.b 0 1073.sup.b 0______________________________________ .sup.a The compound described in European Laidopen Patent No. 0134439 .sup.b The compound No. of the present invention

Number	Date	Country	Kind
60-82297	Apr 1985	JPX
61-50859	Mar 1986	JPX

Number	Name	Date
2832780	King	Apr 1958
3137696	Reicheneder et al.	Jun 1964
3346577	Nakagome et al.	Oct 1967
4177273	Bennett	Dec 1979
4571397	Taniguchi et al.	Feb 1986
4576630	Parg et al.	Mar 1986
4663324	Graf et al.	May 1987
4783462	Mutsukado	Nov 1988

Number	Date	Country
78450	May 1983	EPX
0088384	Sep 1983	EPX
0134439	Jun 1984	EPX
135076	Mar 1985	EPX
183212	Jun 1986	EPX
0193853	Sep 1986	EPX
199281	Oct 1986	EPX
3143303	May 1983	DEX
3328770	Feb 1985	DEX
0225039	Jul 1985	DDX
41-2459	Feb 1966	JPX
41-2788	Feb 1966	JPX
42-1302	Jan 1967	JPX
43-11902	May 1968	JPX
43-11903	May 1968	JPX
43-11904	May 1968	JPX
43-11905	May 1968	JPX
43-11906	May 1968	JPX
43-11907	May 1968	JPX
43-11908	May 1968	JPX
43-11909	May 1968	JPX
44-8857	Apr 1969	JPX
44-8858	Apr 1969	JPX
44-8859	Apr 1969	JPX
44-8861	Apr 1969	JPX
44-12421	Jun 1969	JPX
61-130275	Jun 1986	JPX
61-243078	Oct 1986	JPX
61-268672	Nov 1986	JPX

Pyridazinone derivatives, preparation thereof, and insecticidal, acaricidal, nematicidal, fungicidal compositions

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US Referenced Citations (8)

Foreign Referenced Citations (29)

Non-Patent Literature Citations (10)

Entry
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