Claims
- 1. A metal salt complex of the formula: ##STR46## wherein Z is (C.sub.6 -C.sub.14) aryl or (C.sub.6 -C.sub.14) aryl substituted with up to three substituents selected from the group consisting of (C.sub.1 -C.sub.4) alkyl, methoxy, ethoxy, chloro, fluoro, bromo, iodo, nitro, amino and methylthio; R.sup.1 is hydrogen, (C.sub.1 -C.sub.10) alkyl, (C.sub.3 -C.sub.7) cycloalkyl, (C.sub.2 -C.sub.12) alkenyl, (C.sub.5 -C.sub.7) cycloalkenyl, (C.sub.7 -C.sub.9) aralkyl or phenyl, or (C.sub.7 -C.sub.9) aralkyl or phenyl substituted with up to two substituents selected from the group consisting of (C.sub.1 -C.sub.4) alkyl, methoxy, ethoxy, chloro, fluoro, bromo, iodo, nitro, amino and methylthio; R.sup.2 is (C.sub.1 -C.sub.10) alkyl, (C.sub.3 -C.sub.7) cycloalkyl, (C.sub.2 -C.sub.12) alkenyl, (C.sub.5 -C.sub.7) cycloalkenyl, (C.sub.7 -C.sub.9) aralkyl or phenyl or (C.sub.7 -C.sub.9) aralkyl or phenyl substituted with up to two substituents selected from the group consisting of (C.sub.1 -C.sub.4) alkyl, methoxy, ethoxy, chloro, fluoro, bromo, iodo, nitro, amino and methylthio; R.sup.1 and R.sup.2 taken together form (C.sub.3 -C.sub.8) cycloalkyl; A and B are divalent (C.sub.1 -C.sub.5) alkylene groups; X is (C.sub.1 -C.sub.4) alkyl, halogen or nitro; a is 0 to 3; n is 0 or 1; n' is 0 or 1; and n plus n' is 1 or 2; provided that when Z is unsubstituted phenyl, R.sup.1 is hydrogen, A is methylene and n' is 0, then R.sup.2 is (C.sub.4 -C.sub.10) alkyl, (C.sub.3 -C.sub.7) cycloalkyl, (C.sub.2 -C.sub.12) alkenyl, (C.sub.5 -C.sub.7) cycloalkenyl, (C.sub.7 -C.sub.9) aralkyl or phenyl, or (C.sub.7 -C.sub.9) aralkyl or phenyl substituted with up to two substituents selected from the group consisting of (C.sub.1 -C.sub.4) alkyl, methoxy, ethoxy, chloro, fluoro, bromo, iodo, nitro, amino and methylthio; m is 1 to 4; M is a metal salt cation selected from the group consisting of calcium, magnesium, manganese, copper, nickel, zinc, iron, cobalt, tin, cadmium, mercury, chromium, lead and barium; and Y is a solubilizing anion counterion selected from the group consisting of chloride, bromide, iodide, sulfate, bisulfate, phosphate, nitrate, perchlorate, carbonate, bicarbonate, hydrosulfide, hydroxide, acetate, oxalate, malate, and citrate.
- 2. A metal salt complex according to claim 1 wherein n' is 1.
- 3. A metal salt complex according to claim 2 wherein n is 0.
- 4. A metal salt complex according to claim 3 wherein R.sup.1 is hydrogen and a is 0.
- 5. A metal salt complex according to claim 4 wherein Z is phenyl group substituted by up to three substituents selected from the group consisting of chloro, fluoro, bromo, iodo, (C.sub.1 -C.sub.4) alkyl, methoxy, ethoxy, nitro, amino and methylthio.
- 6. A method for controlling phytopathogenic fungi which consists of applying to a plant, to plant seed or to the plant habitat an effective amount of a complex of claim 2.
- 7. A method according to claim 6 wherein the complex is applied to the plant or plant habitat at a rate of from 0.1 to 50 lbs. per acre.
- 8. A method according to claim 6 wherein the complex is applied to the plant seeds at a rate of 0.1 to 20 ounces per hundred pounds of seed.
- 9. A fungicidal composition for controlling phytopathogenic fungi which comprises an agronomically acceptable carrier and, as the active ingredient, an effective amount of a complex of claim 1.
SUMMARY OF THE INVENTION
This application is a continuation-in-part application of U.S. application Ser. No. 547,291, filed Feb. 5, 1975, now abandoned.
The 1-substituted aralkyl imidazoles of this invention possess eradicant fungicidal properties which are unique in that they kill phytophathogenic fungi in infected plant tissues and therefore can be utilized after fungal infection has already occurred. The systemic properties of these compounds are equally unique in that the compounds will move both acropetally and basipetally in plant tissues. Furthermore, these compounds possess protectant properties against phytopathogenic fungi when applied to the plants prior to infection.
This invention is concerned with the preparation and use of 1-substituted aralkyl imidazoles of the formula: ##STR1## wherein Z is a (C.sub.6 -C.sub.14) aryl or a substituted (C.sub.6 -C.sub.14) aryl group; R.sup.1 is a hydrogen atom, a (C.sub.1 -C.sub.10) alkyl group; a (C.sub.2 -C.sub.12) alkenyl group, a (C.sub.7 -C.sub.9) aralkyl or substituted (C.sub.7 -C.sub.9) aralkyl group; a phenyl or substituted phenyl group, a (C.sub.3 -C.sub.7) cycloalkyl group, or a (C.sub.5 -C.sub.7) cycloalkenyl group; R.sup.2 is a (C.sub.1 -C.sub.10) alkyl group, a (C.sub.2 -C.sub.12) alkenyl group, a (C.sub.7 -C.sub.9) aralkyl or substituted (C.sub.7 -C.sub.9) aralkyl group; a phenyl or substituted phenyl group, a (C.sub.3 -C.sub.7) cycloalkyl group, or a (C.sub.5 -C.sub.7) cycloalkenyl group; R.sup.1 and R.sup.2 when taken together form a (C.sub.3 -C.sub.8) cycloalkyl group; A and B are divalent (C.sub.1 -C.sub.5) alkylene groups; X is a (C.sub.1 -C.sub.4) alkyl group, a halogen atom or a nitro group; a is an integer from 0 to 3; n is the integer 0 or 1; n' is the integer 0 or 1; and the sum of n plus n' is equal to 1 or 2; or when Z is an unsubstituted phenyl group, R.sup.1 is a hydrogen atom, A is methylene, and n' is 0, then R.sup.2 is a (C.sub.4 -C.sub.10) alkyl group, a (C.sub.2 -C.sub.12) alkenyl group, a (C.sub.7 -C.sub.9) aralkyl or substituted (C.sub.7 -C.sub.9) aralkyl group, a phenyl or substituted phenyl group, a (C.sub.3 -C.sub.7) cycloalkyl group or a (C.sub.5 -C.sub.7) cycloalkenyl group.
A further embodiment of this invention is the metal salt complexes of the above 1-substituted aralkyl imidazoles having the formula: ##STR2## wherein Z, A, B, R.sup.1, R.sup.2, n, n', X and a are the same as above and M is a metal cation which can be selected from Groups IIA, IVA, VA, IB, IIB, VIB, VIIB and VIII of the Periodic Table. Y is a solubilizing anion counterion and m is 1-4.
In the above description of Z the term "aryl" refers to a phenyl, naphthyl, biphenyl, acenaphthenyl, indanyl, indolyl, pyridyl, pyrimidyl, pyrryl, furyl or thienyl group preferably a phenyl group which can be unsubstituted or substituted with up to three substituents preferably two substituents selected from the group consisting of (C.sub.1 -C.sub.4) alkyl, methoxy, ethoxy, chloro, fluoro, bromo, iodo, nitro, amino, methylthio and the like.
The terms "A" and "B" are divalent alkylene groups of from 1 to 5 carbon atoms which can be branched or straight chained.
The term "alkyl" in the description of R.sup.1 and R.sup.2 above refers to a straight or branched chain alkyl group of from 1 to 10 carbon atoms. The term "alkenyl" refers to a straight or branched chain alkenyl group of from 2 to 12 carbon atoms. The term "cycloalkyl" refers to a cycloalkyl group of from 3 to 7 carbon atoms and the term "cycloalkenyl" refers to a cycloalkenyl group of from 5 to 7 carbon atoms.
The term "aralkyl" refers to an aralkyl group of from 7 to 9 carbon atoms preferably benzyl or phenethyl which can be substituted with up to two substituents selected from the group consisting of (C.sub.1 -C.sub.4) alkyl, methoxy, ethoxy, chloro, fluoro, bromo, iodo, nitro, amino, methylthio and the like.
By the term substituted phenyl as used in the definition of R.sup.1 and R.sup.2 is meant a phenyl group which can be substituted with up to two substituents selected from the group consisting of (C.sub.1 -C.sub.4) alkyl, methoxy, ethoxy, chloro, fluoro, bromo, iodo, nitro, amino, methylthio and the like.
The preferred compounds of this invention are those in which n' in Formulas I and II is one. The more preferred compounds of this invention are those in which n' is 1 and n is 0. The most preferred compounds of this invention are those in which n' is 1, n is 0; R.sup.1 is a hydrogen atom; a is 0; Z is a substituted phenyl group having up to three substituents selected from the group consisting of (C.sub.1 -C.sub.4) alkyl, methoxy, ethoxy, chloro, fluoro, bromo, iodo, nitro, amino and methylthio, and R.sup.2 is an alkyl group of from 4 to 10 carbon atoms, an alkenyl group of from 2 to 12 carbon atoms, an aralkyl group of from 7 to 9 carbon atoms which can be substituted with up to two substituents selected from the group consisting of (C.sub.1 -C.sub.4) alkyl, methoxy, ethoxy, chloro, fluoro, bromo, iodo, nitro, amino and methylthio; a phenyl group which can be substituted with up to two substituents selected from the group consisting of (C.sub.1 -C.sub.4) alkyl, methoxy, ethoxy, chloro, fluoro, bromo, iodo, nitro, amino and methylthio; a cycloalkyl group of from 3 to 7 carbon atoms or a cycloalkenyl group of from 5 to 7 carbon atoms.
Typical compounds encompassed by this invention include:
The compounds of this invention can be prepared by standard methods of synthesis. Typical methods of preparation which can be utilized in the preparation of these compounds include the following general syntheses, the temperatures given unless indicated otherwise are in degrees centigrade.
When the proper acetate derivative (III) is reacted with sodium hydride in tetrahydrofuran or glyme it forms the corresponding sodio salt (IV). The reaction of (IV) with an organic halide affords the ester (V). ##STR3## These esters (V) are converted to the corresponding carbinol derivatives (VI) by a reduction with reagents such as lithium aluminum hydride (LiAlH.sub.4) in ether or bis(2-methoxyethoxy) aluminum hydride in benzene. The subsequent treatment of (VI) with methane sulfonyl chloride in the presence of triethyl amine in an aromatic hydrocarbon solvent such as benzene or toluene provides the sulfonate (VII). Treatment of (VI) with thionyl chloride or phosphorus pentachloride in an aromatic hydrocarbon such as benzene or toluene provides the chloride (VIIa). The reaction of (VII) with excess of an imidazole or (VIIa) with the sodium salt of an imidazole either neat or in the presence of such solvents as benzene, glyme, N,N-dimethylformamide, etc., gives the alkylated imidazole products (VIII).
The 1-(.alpha.-substituted alkyl) imidazoles are synthesized by a different route. ##STR4##
The Grignard reagent (IX) is formed from the reaction of magnesium metal with the appropriate organic chloride in ether. This reagent (IX) subsequently reacted with the desired aldehyde to provide the carbinol derivative (X). The formation of the sulfonate or chloride followed by its reaction with an imidazole or its sodio salt is carried out by the previously described route to give the product (XI).
A malonate synthesis is utilized to provide the starting materials for some other closely related analogues where the methylene chain is extended. ##STR5## The reaction of an alkyl halide (XII) with sodio ethyl malonate in a solvent such as THF or glyme gives the substituted malonate (XIII). A further reaction of (XIII) with first sodium hydride in THF followed by the addition of the appropriate organic halide affords the disubstituted ester (XIV). A basic hydrolysis of (XIV) and a subsequent acidification and decarboxylation gives the mono acid (XV). The reduction of (XV) with LiAlH.sub.4 gives the corresponding carbinol derivative (XVI). The alkylated imidazole product (XVII) is then formed by the usual route.
The methylene chain can be extended from the methane sulfonate (VII) via the preparation of the nitrile (XVIII). ##STR6##
This sulfonate (VII) in DMF is treated with sodium cyanide in DMF to give the nitrile derivative (XVIII). The hydrolysis of (XVIII) in boiling 50% sulfuric acid provides the acid (XIX) which is subsequently reduced with LiAlH.sub.4 to provide the alcohol (XX). The imidazole derivative is then formed via the sulfonate in the usual way or the sulfonate can be recycled through the process for further chain extension.
The synthesis of the phenyl substituted analogue involves a Darzen's reaction. A substituted benzophenone is reacted with ethyl chloroacetate in the presence of sodium hydride to give the glycidic ester (XXI). ##STR7## A hydrolysis and a subsequent decarboxylation of (XXI) gives the diaryl acetaldehyde (XXII). This aldehyde (XXII) is reduced to the corresponding alcohol (XXIII) by LiAlH.sub.4, and it is then converted to the alkylated imidazole product (XXIV) by the usual route.
The Friedel-Craft acylation of a substituted aromatic hydrocarbon with an acyl halide in the presence of aluminum chloride either neat or with a halogenated hydrocarbon provides the desired product (XXV). ##STR8## Treatment of (XXV) with an excess of ethyl chloroacetate and sodium hydride gives the glycidic ester (XXVI) which upon saponification with base and hydrolysis with hot mineral acid followed by decarboxylation gives the aldehyde (XXVII). A Grignard Reaction with an alkyl or aryl magnesium halide yields the alcohol (XXVIII). The formation of the sulfonate followed by its reaction with an imidazole as previously described gives the product XXIX.
When the appropriate sodio alkyl acetate derivative (XXX) prepared as previously described is reacted at elevated temperatures in a solvent such as ether, tetrahydrofuran or dimethylformamide with an iodoalkane the desired trisubstituted acetate (XXXI) is obtained. ##STR9## Reduction of (XXXI) with LiAlH.sub.4 in anhydrous ether gives the alcohol (XXXII). Formation of the sulfonate followed by the imidazole reaction as previously described gives the desired product (XXXIII).
The reduction of a substituted phenylacetic acid (XXXIV) with LiAlH.sub.4 in tetrahydrofuran gives the alcohol (XXXV). ##STR10## Formation of the sulfonate by reaction with an imidazole gives the desired product (XXXVI).
The reaction of chloroacetaldehyde diethylacetal with a substituted aromatic hydrocarbon in the presence of sulfuric acid at room temperature gives the substituted arylethylchloride (XXXVII). The reaction of (XXXVII) with the sodium salt of an imidazole as previously described affords the product (XXXVIII). ##STR11##
When a substituted aromatic hydrocarbon is treated with 1,2-epoxyhexane in the presence of aluminum chloride the rearranged hexanol (XXXIX) is obtained. ##STR12##
Formation of the methane sulfonate followed by the reaction with an imidazole gives the product (XL).
When a benzene substituted with electron donating groups is treated with 1,2-epoxyhexane in the presence of stannic chloride the hexanol (XLI) is obtained. ##STR13##
The imidazole derivative is formed via the above route from the methane sulfonate.
The alkylthio and alkylsulfonyl derivatives are prepared from the aldehyde (XLII). ##STR14## The aldehyde (XLII) is reduced to the alcohol (XLIII) with LiAlH.sub.4. The alcohol (XLIII) is reacted with methane sulfonyl chloride in the presence of triethylamine to form the sulfonate (XLIV). Treatment of the methane sulfonate (XLIV) with sodium cyanide gives the benzyl nitrile derivative (XLV). Alkylation of the nitrile (XLV) via NaH metallation followed by treatment with alkylhalide gives the .alpha.-alkyl benzyl nitrile derivative (XLVI). Hydrolysis of the nitrile (XLVI) with sulfuric acid in an alcoholic solvent gives the .alpha.-alkyl phenylacetic acid ester (XLVII) which upon reduction with LiAlH.sub.4 gives the phenethyl alcohol (XLVIII). The imidazole product is formed via the methane sulfonate as shown above. When the imidazole (XLIX) is oxidize with hydrogen peroxide in acetic acid the alkylsulfonyl (L) is formed. ##STR15##
The nitro substituted phenyl derivatives (LII) are formed by nitration of the unsubstituted or substituted analogs (LI). ##STR16##
The amino substituted phenyl derivatives (LIII) are formed by reduction of the nitro substituted phenyl derivative. ##STR17##
The analogs in which the imidazole rings itself is substituted (LV) are prepared by reacting the appropriate methane sulfonate (LIV) with either an excess of the substituted imidazole or the sodium salt of the imidazole. ##STR18##
The salts of aralkyl imidazole derivatives are prepared by treating an ether solution of the imidazole (LVI) with an equivalent amount of the desired inorganic or organic acid dissolved in ether or alcohol followed by filtration or concentration then filtration to give the desired salt. ##STR19##
The metal complex salts of the aralkyl imidazole derivatives (LVIII) are prepared by the treatment of an alcoholic or aqueous solution of the imidazole (LVI) with a metal salt at temperatures from about 15.degree. to about 60.degree. C.
US Referenced Citations (4)
| Number |
Name |
Date |
Kind |
| 3285921 |
Ortner et al. |
Nov 1966 |
|
| 3647810 |
Bayer et al. |
Mar 1972 |
|
| 3927017 |
Heeres et al. |
Dec 1975 |
|
| 4005083 |
Buchel et al. |
Jan 1977 |
|
Non-Patent Literature Citations (1)
| Entry |
| Garnouskii et al., Chemical Abstracts 65, 11,742f (1966). |
Continuation in Parts (1)
|
Number |
Date |
Country |
| Parent |
547291 |
Feb 1975 |
|
Patent Grant
4105762
