2,5-dioxo-3-pyrroline-1-acetanilide fungicidal agents and method for the preparation thereof

Abstract

2,5-Dioxo-3-pyrroline-1-acetanilide compounds which are effective for the control or prevention of phytopathogenic fungi are described. A method for the fungicidal use of said compounds, fungicidal compositions containing said compounds and a method for the preparation of said compounds are also presented.

Description

BACKGROUND OF THE INVENTION

Phytopathogenic fungi are the causal agents for many diseases which infect and destroy crops. Even with the wide variety of fungicides available today to combat this problem diseases caused by fungi still abound. Accordingly, there is an ongoing search in the art to create new and more effective fungicides and methods for controlling or preventing fungal infestations.

It is therefore an object of the present invention to provide 2,5-dioxo-3-pyrroline-1-acetanilide compounds that are highly effective for controlling or preventing phytopathogenic fungal infestations in agronomic crops, both growing and harvested.

SUMMARY OF THE INVENTION

The present invention describes 2,5-dioxo-3-pyrroline-1-acetanilide compounds that are useful in the control or prevention of phytopathogenic fungi, the causal agents for diseases infecting agronomic crops, both growing and harvested.

2,5-Dioxo-3-pyrroline-1-acetanilide compounds of the present invention which are useful for the protection of plants from the effects of plant pathogenic fungi, have the structural formula I ##STR1## wherein

R is hydrogen, halogen, or C.sub.1 -C.sub.4 alkyl optionally substituted with halogen;

R.sub.1 is hydrogen, C.sub.1 -C.sub.10 alkyl optionally substituted with C.sub.1 -C.sub.9 alkoxy or halogen, C.sub.3 -C.sub.6 cycloalkyl, C.sub.2 -C.sub.10 alkylthioalkyl, C.sub.4 -C.sub.10 cycloalkylalkyl, or phenyl or C.sub.7 -C.sub.10 phenylalkyl optionally substituted

with one to three halogen atoms, C.sub.1 -C.sub.4 alkoxy groups, nitro groups, cyano groups, or C.sub.1 -C.sub.4 alkyl groups optionally substituted with halogen;

R.sub.2 is hydrogen, or C.sub.1 -C.sub.6 alkyl optionally substituted with C.sub.1 -C.sub.5 alkoxy;

L, M, Q, W and Z are each independently hydrogen, C.sub.1 -C.sub.6 alkyl optionally substituted with C.sub.1 -C.sub.4 alkoxy or halogen, C.sub.1 -C.sub.4 alkoxy, C.sub.3 -C.sub.6 cycloalkyl, C.sub.2 -C.sub.6 alkenyl, C.sub.5 -C.sub.6 cycloalkenyl, C.sub.2 -C.sub.6 alkynyl,

halogen,

nitro,

cyano,

CO.sub.2 R.sub.3, or

phenyl or phenoxy optionally substituted with one to three C.sub.1 -C.sub.4 alkoxy groups, halogen atoms, nitro groups, cyano groups, or C.sub.1 -C.sub.4 alkyl groups optionally substituted with halogen, with the proviso that at most only one of L, M, Q, W or Z may be phenyl or phenoxy;

R.sub.3 is C.sub.1 -C.sub.4 alkyl; and when R.sub.1 is a substituent other than hydrogen, the optical isomers thereof; and with the proviso that when R.sub.1 is sec-propyl and R is hydrogen or methyl, then at least one of L, M, Q, W, or Z must be other than hydrogen.

DETAILED DESCRIPTION OF THE INVENTION

A more preferred group of 2,5-dioxo-3-pyrroline-1-acetanilide compounds of formula I described above are those in which

R is hydrogen or halogen;

R.sub.1 is hydrogen, C.sub.1 -C.sub.10 alkyl, or C.sub.7 -C.sub.10 phenyl alkyl optionally substituted on the phenyl ring with one to three halogen atoms, C.sub.1 -C.sub.4 alkoxy groups, nitro groups, cyano groups, or C.sub.1 -C.sub.4 alkyl groups optionally substituted with halogen;

R.sub.2 is hydrogen or C.sub.1 -C.sub.6 alkyl;

L, M, Q, W and Z are each independently hydrogen, C.sub.1 -C.sub.6 alkyl optionally substituted with C.sub.1 -C.sub.4 alkoxy or halogen, C.sub.1 -C.sub.4 alkoxy, C.sub.3 -C.sub.6 cycloalkyl, halogen, nitro, cyano, CO.sub.2 R.sub.3, or phenyl or phenoxy optionally substituted with one to three C.sub.1 -C.sub.4 alkoxy groups, halogen atoms, nitro groups, cyano groups, or C.sub.1 -C.sub.4 alkyl groups optionally substituted with halogen with the proviso that at most only one of L, M, Q, W, or Z may be phenyl or phenoxy;

R.sub.3 is C.sub.1 -C.sub.4 alkyl; and with the proviso that when R.sub.1 is sec-propyl and R is hydrogen, then at least one of L, M, Q, W, or Z must be other than hydrogen.

A most preferred group of formula I compounds especially useful in the control or prevention of phytopathogenic fungi are those in which

R is hydrogen;

R.sub.1 is hydrogen, C.sub.1 -C.sub.10 alkyl, or C.sub.7 -C.sub.10 phenylalkyl optionally substituted on the phenyl ring with one to three halogen atoms;

R.sub.2 is hydrogen or C.sub.1 -C.sub.6 alkyl;

L, M, Q, W and Z are each independently hydrogen, C.sub.1 -C.sub.6 alkyl optionally substituted with C.sub.1 -C.sub.4 alkoxy or halogen, C.sub.1 -C.sub.4 alkoxy, C.sub.3 -C.sub.6 cycloalkyl, halogen, nitro, cyano, CO.sub.2 R.sub.3, phenyl or phenoxy; and

R.sub.3 is C.sub.1 -C.sub.4 alkyl.

By the term halogen we intend an atom selected from the group consisting of F, Cl, Br and I.

The present invention also provides a method for controlling or preventing phytopathogenic fungi by applying to the locus of the fungi a fungicidally effective amount of a compound having the structural formula I ##STR2## wherein

R is hydrogen, halogen, or C.sub.1 -C.sub.4 alkyl optionally substituted with halogen;

R.sub.1 is hydrogen, C.sub.7 -C.sub.10 alkyl optionally substituted with C.sub.1 -C.sub.9 alkoxy or halogen, C.sub.3 -C.sub.6 cycloalkyl, C.sub.2 -C.sub.10 alkylthioalkyl, C.sub.4 -C.sub.10 cycloalkylalkyl, or phenyl or C.sub.7 -C.sub.10 phenylalkyl optionally substituted with one to three halogen atoms, C.sub.1 -C.sub.4 alkoxy groups, nitro groups, cyano groups, or C.sub.1 -C.sub.4 alkyl groups optionally substituted with halogen;

R.sub.2 is hydrogen, or C.sub.1 -C.sub.6 alkyly optionally substituted with C.sub.1 -C.sub.5 alkoxy;

L, M, Q, W and Z are each independently hydrogen, C.sub.1 -C.sub.6 alkyl optionally substituted with C.sub.1 -C.sub.4 alkoxy or halogen, C.sub.1 -C.sub.4 alkoxy, C.sub.3 -C.sub.6 cycloalkyl, C.sub.2 -C.sub.6 alkenyl, C.sub.5 -C.sub.6 cycloalkenyl, C.sub.2 -C.sub.6 alkynyl,

halogen,

nitro,

cyano,

CO.sub.2 R.sub.3, or

phenyl or phenoxy optionally substituted with one to three C.sub.1 -C.sub.4 alkoxy groups, halogen atoms, nitro groups, cyano groups, or C.sub.1 -C.sub.4 alkyl groups optionally substituted with halogen, with the proviso that at most only one of

L, M, Q, W or Z may be phenyl or phenoxy;

R.sub.3 is C.sub.1 -C.sub.4 alkyl; and when R.sub.1 is a substituent other than hydrogen, the optical isomers thereof; and with the proviso that when R.sub.1 is sec-propyl and R is hydrogen or methyl, then at least one of L, M, Q, W, or Z must be other than hydrogen.

A more preferred method for controlling or preventing phytopathogenic fungi is that in which R is hydrogen or halogen;

R.sub.1 is hydrogen,

C.sub.1 -C.sub.10 alkyl, or

C.sub.7 -C.sub.10 phenyl alkyl optionally substituted on the phenyl ring with one to three halogen atoms, C.sub.1 -C.sub.4 alkoxy groups, nitro groups, cyano groups, or C.sub.1 -C.sub.4 alkyl groups optionally substituted with halogen;

R.sub.2 is hydrogen or C.sub.1 -C.sub.6 alkyl; L, M, Q, W and Z are each independently hydrogen, C.sub.1 -C.sub.6 alkyl optionally substituted with C.sub.1 -C.sub.4 alkoxy or halogen, C.sub.1 -C.sub.4 alkoxy, C.sub.3 -C.sub.6 cycloalkyl,

halogen,

nitro,

cyano,

CO.sub.2 R.sub.3, or phenyl or phenoxy optionally substituted with one to three C.sub.1 -C.sub.4 alkoxy groups,

halogen atoms,

nitro groups,

cyano groups, or

C.sub.1 -C.sub.4 alkyl groups optionally substituted with halogen with the proviso that at most only one of L, M, Q, W, or Z may be phenyl or phenoxy;

R.sub.3 is C.sub.1 -C.sub.4 alkyl; and with the proviso that when R.sub.1 is sec-propyl and R is hydrogen, then at least one of L, M, Q, W, or Z must be other than hydrogen.

A most preferred method for controlling or preventing phytopathogenic fungi is that in which

R is hydrogen;

R.sub.1 is hydrogen, C.sub.1 -C.sub.10 alkyl, or C.sub.7 -C.sub.10 phenylalkyl optionally substituted on the phenyl ring with one to three halogen atoms;

R.sub.2 is hydrogen or C.sub.1 -C.sub.6 alkyl;

L, M, Q, W and Z are each independently hydrogen, C.sub.1 -C.sub.6 alkyl optionally substituted with C.sub.1 -C.sub.4 alkoxy or halogen, C.sub.1 -C.sub.4 alkoxy, C.sub.3 -C.sub.6 cycloalkyl, halogen, nitro, cyano, CO.sub.2 R.sub.3, phenyl or phenoxy; and

R.sub.3 is C.sub.1 -C.sub.4 alkyl.

The present invention also provides antifungal compositions which include an inert solid or liquid diluent and a compound having the structural formula I described above, except that when R.sub.1 is sec-propyl and R is hydrogen or methyl, then L, M, Q, W and Z may all be hydrogen.

A 2,5-dioxo-3-pyrroline-1-acetanilide compound of formula I may be prepared by reacting an amino acid having the structural formula II ##STR3## wherein

R.sub.1 is hydrogen, C.sub.1 -C.sub.10 alkyl optionally substituted with C.sub.1 -C.sub.9 alkoxy or halogen, C.sub.3 -C.sub.6 cycloalkyl, C.sub.2 -C.sub.10 alkylthioalkyl, C.sub.4 -C.sub.10 cycloalkylalkyl, or phenyl or C.sub.7 -C.sub.10 phenylalkyl optionally substituted with one to three halogen atoms, C.sub.1 -C.sub.4 alkoxy groups, nitro groups, cyano groups, or C.sub.1 -C.sub.4 alkyl groups optionally substituted with halogen;

when R.sub.1 is a substituent other than hydrogen, the optical isomers thereof; with at least one molar equivalent of a maleic anhydride of structure III ##STR4## wherein R is hydrogen, halogen or C.sub.1 -C.sub.4 alkyl optionally substituted with halogen and at least one molar equivalent of an acid in the presence of an inert organic solvent to form a N-(carboxymethyl)maleamic acid intermediate of formula IV ##STR5## wherein R and R.sub.1 are as described above. The formula IV N-(carboxymethyl)maleamic acid is reacted with at least two molar equivalents of an organic base in the presence of an inert organic solvent. Water is concurrently removed from the reaction mixture via azeotropic distillation, molecular sieves, calcium hydride or the like to form the corresponding 2,5-dioxo-3-pyrroline-1-acetate. The acetate is reacted with at least one molar equivalent of a mineral acid to form the 2,5-dioxo-3-pyrroline-1-acetic acid of formula V ##STR6## wherein R and R.sub.1 are as described above. The formula V acetic acid is reacted with at least one molar equivalent of a formula VI aniline ##STR7## wherein L, M, Q, W, Z and R.sub.2 are as described above for formula I and at least one molar equivalent of a coupling agent in the presence of an inert organic solvent to form the desired 2,5-dioxo-3-pyrroline-1-acetanilide compound of formula I. The above reaction scheme is shown below in flow diagram I: ##STR8##

Acids suitable for use in the above reaction scheme include acids such as acetic acid, formic acid, hydrochloric acid, oxalic acid and the like.

Mineral acids useful in the above reaction scheme include mineral acids such as sulfuric acid, hydrochloric acid, nitric acid and the like.

Coupling agents suitable for use in the above reaction include coupling agents such as a p-nitrophenol ester, an N-hydroxysuccinimide, 1-(3-dimenthylaminopropyl)-3-ethyl carbodiimide, dicyclohexylcarbodiimide, an ethyl chloroformate/triethylamine mixture and the like.

A 2,5-dioxo-3-pyrroline-1-acetanilide compound of formula I may also be prepared by reacting the above-prepared formula V 2,5-dioxo-3-pyrroline-1-acetic acid with at least one molar equivalent of thionyl chloride in the presence of an inert aromatic solvent to form the corresponding acid chloride and reacting the acid chloride with at least one molar equivalent of a formula VI aniline and at least one molar equivalent of an organic base in the presence of an inert organic solvent to form the desired compound of formula I. The above reaction scheme is shown below in flow diagram II: ##STR9##

Organic bases suitable for use in the above reaction schemes include organic bases such as C.sub.1 -C.sub.4 trialkylamines, pyridine, dimethylaminopyridine and the like.

Compounds of formula I wherein R.sub.2 is C.sub.1 -C.sub.6 alkyl optionally substituted with C.sub.1 -C.sub.5 alkoxy may be prepared from their formula I precursor wherein R.sub.2 is hydrogen by reacting said precursor with the appropriate alkylhalide in the presence of a base as shown in flow diagram III: ##STR10## wherein R.sub.2 is C.sub.1 -C.sub.6 alkyl optionally substituted with C.sub.1 -C.sub.5 alkoxy and X is halogen.

The compounds of the present invention are effective for controlling or preventing the growth of phytopathogenic fungi in the presence of growing or harvested plants when applied to said plants at fungicidally effective rates. This will vary somewhat with the virulence of the pathogen in question and with other factors such as the environment in which treatment is conducted. These compounds are especially useful for the control of Plasmpara viticola, the causal agent of grape downy mildew. Certain compounds of the invention may not only be employed to control fungi that have infected plants, but also may be applied to healthy plants or seeds or to the soil in which the plant is to be grown in order to prevent infestation.

To protect plants from phytopathogenic fungi, the compounds of formula I are applied to the foliage of the plant, to the seed of the plants, or to the soil in which the plant grows or is to be grown, in the form of a liquid, preferably in aqueous spray, or dust, or granular formulation. Solutions or suspensions containing from about 20 ppm to about 1,000 ppm, and preferably 50 ppm to 500 ppm, of formula I compounds are generally effective for this use.

The compounds of the invention may be formulated as emulsifiable concentrates, flowable concentrates, or wettable powders which are diluted with water or other suitable polar solvent, generally in situ, and then applied as a dilute spray. Said compounds may also be formulated in dry compacted granules, granular formulations, dusts, dust concentrates, suspension concentrates, microemulsions and the like all of which lend themselves to seed, soil, water and/or foliage applications to provide the requisite plant protection. Such formulations include the compounds of the invention admixed with inert, solid or liquid diluents.

For example, wettable powders, dusts, and dust concentrate formulations can be prepared by grinding and blending together about 25% to about 85% by weight of formula I compounds and about 75% to about 15% by weight of a solid diluent such as bentonite, diatomaceous earth, kaolin, attapulgite, or the like, 1% to 5% by weight of a dispersing agent such as sodium lignosulfonate, and about 1% to 5% by weight of a nonionic surfactant, such as octylphenoxy polyethoxy ethanol, nonylphenoxy polyethoxy ethanol or the like.

A typical flowable liquid can be prepared by admixing about 30% to 90% by weight of a gelling agent such as bentonite, 2% to 5% by weight of a dispersing agent such as sodium lignosulfonate, about 1% by weight of polyethyleneglycol, and about 40% to 60% by weight of water.

A typical emulsifiable concentrate can be prepared by dissolving about 15% to 70% by weight of the active ingredient in about 85% to 30% by weight of a solvent such as isophorone, toluene, butyl cellosolve, methyl acetate, propylene glycol monomethyl ether, or the like and dispersing therein about 1% to 5% by weight of a nonionic surfactant such as an alkylphenoxy polyethoxy alcohol.

It is understood that the compounds of the present invention can be applied singly or in combination with one or more other fungicidal compounds, such application being made either by combination of the fungicidal compounds or their formulations in a common container prior to use or by sequential application of the active fungicidal compounds or their formulations to the host crop or its environment. Compounds suitable for combination with the compounds of this invention are suggested by, but not limited to, the following: 4,6-dinitro-o-cresol, benalaxyl, benomyl, captafol, captan, carbendazim, chlorothalonil, copper, cymoxanil, dichlobutrazole, dichlofluanid, diethofencarb, difenconazole, dimethomorph, diniconazole, dinocap, dithianon, fenarimol, fentin acetate, ferbam, flusilazole, folpet, fosetyl, hexaconazole, imazalil, iprodione, mancopper mancozeb, maneb, mepronil, mercuric oxide, metalaxyl, metiram, myclobutanil, nuarimol, ofurace, oxadixyl, penconazole, pencyuron, phosphorous acid, procymidone, propineb, pyrifenox, quintozene, sodium arsenite, sulphur, thiabendazole, thiophanate methyl, thiram, tolclophos-methyl, triadimefon, triadimenol, triforine, vinclozolin, zineb, and ziram.

In order to facilitate a further understanding of the invention, the following examples are presented primarily for the purpose of illustrating more specific details thereof. The invention is not to be deemed limited thereby except as defined in the claims.

EXAMPLE 1

Preparation of L-N-(.alpha.-Carboxyphenethyl)maleamic acid ##STR11##

To a suspension of L-phenylalanine (5.1 g, 0.031 mol) dispersed in a mixture of acetic acid and acetone is added a solution of maleic anhydride (3.03 g, 0.031 mol) in acetone. The reaction mixture is heated at about 50.degree. C. for 21/2 hours, cooled to room temperature and poured into a mixture of hexane and ethyl acetate. The resultant mixture is filtered to give the title product as a white solid (7.4 g, mp 133.degree. C.), identified by .sup.1 HNMR, CIMS and IR analyses.

Following the above procedure and using the appropriately substituted glycine and the appropriately substituted maleic anhydride, the formula IV compounds in table I are obtained.

TABLE I______________________________________ ##STR12##R R.sub.1 mp .degree.C. Isomer______________________________________H CH.sub.2 C.sub.6 H.sub.5 136-140 D, LH -p-ClC.sub.6 H.sub.5 CH.sub.2 139 D, LH .sub.-- mClC.sub.6 H.sub.5 CH.sub.2 132-134 D, LH -o-ClC.sub.6 H.sub.5 CH.sub.2 124 D, LBr H 114 --H H 187 --H CH(CH.sub.3).sub.2 140 D, LH CH(CH.sub.3).sub.2 142 LH CH(CH.sub.3).sub.2 142 DH CH.sub.3 143 D, LH CH.sub.3 145 LH CH.sub.2 CH(CH.sub.3).sub.2 164 D, LH CH.sub.2 CH(CH.sub.3).sub.2 141 LH CH(CH.sub.3)CH.sub.2 CH.sub.3 oil L______________________________________

EXAMPLE 2

Preparation of L-2,5-Dioxo-.alpha.-benzyl-3-pyrroline-1-acetic acid ##STR13##

A suspension of L-N-(.alpha.-carboxyphenethyl)maleamic acid (7.0 g, 0.027 mol) in toluene is treated with triethylamine (8.1 mL, 0.0532 mol), refluxed for 2 hours using a Dean-Stark trap, cooled to room temperature and concentrated in vacuo to give a yellow oil residue. The residue is dissolved in ethyl acetate and treated with 1N Hydrochloric acid. The mixture is separated, the organic phase is dried over anhydrous sodium sulfate and concentrated in vacuo to yield the title product as a white solid (4.56 g, mp 87.degree. C.), indentified by .sup.1 HNMR, CIMS and IR analyses.

Following the above procedure, and using the appropriately substituted maleamic acid, the following formula V compounds are obtained and shown in Table II.

TABLE II______________________________________ ##STR14##R R.sub.1 mp .degree.C. Isomer______________________________________H CH.sub.2 C.sub.6 H.sub.5 87-90 D, LH -p-ClC.sub.6 H.sub.5 CH.sub.2 145 D, LH .sub.-- mClC.sub.6 H.sub.5 CH.sub.2 151 D, LH -o-ClC.sub.6 H.sub.5 CH.sub.2 130-134 D, LBr H 134 --H H 113 --H CH(CH.sub.3).sub.2 87 D, LH CH(CH.sub.3).sub.2 89 LH CH(CH.sub.3).sub.2 oil DH CH.sub.3 97 D, LH CH.sub.3 98 LH CH.sub.2 CH(CH.sub.3).sub.2 102 D, LH CH.sub.2 CH(CH.sub.3).sub.2 87-90 LH CH(CH.sub.3)CH.sub.2 CH.sub.3 oil L______________________________________

EXAMPLES 3-107

Preparation of L-2,5-Dioxo-.alpha.-benzyl-4'-chloro-3-pyrroline-1-acetanilide ##STR15##

To a solution of L-2,5-dioxo-.alpha.-benzyl-3-pyrroline-1-acetic acid (1.5 g, 0.006 mol) in tetrahydrofuran is added a solution of dicyclohexylcarbodiimide (1.38 g, 0.0066 mol) in tetrahydrofuran at room temperature under nitrogen. After stirring for 1 hour, the reaction mixture is treated with a solution of p-chloroaniline (0.78 g, 0.006 mol) in tetrahydrofuran, stirred for 4 hours, filtered and the filtrate is concentrated in vacuo to give a brown oil. Flash chromatography on silica gel (hexane/ethyl acetate - 70/30) gives the title product as a pale yellow solid (2.0 g, mp 189.5.degree. C.), identified by .sup.1 HNMR, CIMS and IR analyses.

Following the above procedure and using the appropriately substituted 2,5-dioxo-3-pyrroline-1-acetic acid and appropriately substituted aniline, the following formula I compounds in table III are obtained.

TABLE III__________________________________________________________________________ ##STR16##Example R R.sub.1 R.sub.2 L M Q W Z mp .degree.C. Isomer__________________________________________________________________________4 H CH.sub.2 C.sub.6 H.sub.5 H H H H H H yellow oil L5 H CH.sub.2 C.sub.6 H.sub.5 H H H OCH.sub.3 H H 119 L6 H CH.sub.2 C.sub.6 H.sub.5 H H Cl H Cl H 158 L7 H CH.sub.2 C.sub.6 H.sub.5 H OCH.sub.3 H H OCH.sub.3 H brown oil L8 H CH.sub.2 C.sub.6 H.sub.5 H OCH.sub.3 H OCH.sub.3 H H oil L9 H CH.sub.2 C.sub.6 H.sub.5 H H H cyclohexyl H H 190 L10 H CH.sub.2 C.sub.6 H.sub.5 H NO.sub.2 H OCH.sub.3 H H orange oil L11 H CH.sub.2 C.sub.6 H.sub.5 H CH.sub.3 H CH.sub.3 H H 142-143 L12 H CH.sub.2 C.sub.6 H.sub.5 H CH.sub.3 H H H CH.sub.3 153-155 L13 H CH.sub.2 C.sub.6 H.sub.5 H F H F H H 126 L14 H CH.sub.2 C.sub.6 H.sub.5 H Br H Br H H yellow oil L15 H CH.sub.2 C.sub.6 H.sub.5 H H F H F H 121 L16 H CH.sub.2 C.sub.6 H.sub.5 H H H OC.sub.6 H.sub.5 H H 140 L17 H CH.sub.2 C.sub.6 H.sub.5 H Cl Cl H H H 164 L18 H CH.sub.2 C.sub.6 H.sub.5 H Cl H Cl H H yellow oil L19 H CH.sub.2 C.sub.6 H.sub.5 H Cl H H Cl H yellow oil L20 H CH.sub.2 C.sub.6 H.sub.5 H H H F H H 144 L21 H CH.sub.2 C.sub.6 H.sub.5 H H H CF.sub.3 H H 169 L22 H CH.sub.2 C.sub.6 H.sub.5 H H H C(CH.sub.3).sub.3 H H 145 L23 H CH.sub.2 C.sub.6 H.sub.5 H H H CH(CH.sub.3).sub.2 H H 136 L24 H CH.sub.2 C.sub.6 H.sub.5 H H H CH.sub.2 CH.sub.3 H H 132 L25 H CH.sub.2 C.sub.6 H.sub.5 H H H CN H H 147 L26 H CH.sub.2 C.sub.6 H.sub.5 H H OCH.sub.3 OCH.sub.3 H H 121 L27 H CH.sub.2 C.sub.6 H.sub.5 H H OCH.sub.3 H OCH.sub.3 H 128 L28 H CH.sub.2 C.sub.6 H.sub.5 H CH.sub.3 H F H H 137 L29 H CH.sub.2 C.sub.6 H.sub.5 H CH.sub.3 H Cl H H 143 L30 H CH.sub.2 C.sub.6 H.sub.5 H CH.sub.3 H H H H yellow oil L31 H CH.sub.2 C.sub.6 H.sub.5 H H H Cl H H 187 D, L32 H CH.sub.2 C.sub.6 H.sub.5 H H H CH.sub.3 H H 200-202 D, L33 H CH.sub.2 C.sub.6 H.sub.5 H H H F H H 181-183 D, L34 H CH.sub.2 C.sub.6 H.sub.5 H Cl H Cl H H 193 D, L35 H CH.sub.2 C.sub.6 H.sub.5 H CH.sub.3 H CH.sub.3 H H 140-143 D, L36 H -p-ClC.sub.6 H.sub.5 CH.sub.2 H H H Cl H H 194-196 D, L37 H -p-ClC.sub.6 H.sub.5 CH.sub.2 H H H CH.sub.3 H H 201-202 D, L38 H -p-ClC.sub.6 H.sub.5 CH.sub.2 H Cl H Cl H H yellow oil D, L39 H -p-ClC.sub.6 H.sub.5 CH.sub.2 H Br H Br H H 244-246 D, L40 H -p-ClC.sub.6 H.sub.5 CH.sub.2 H CH.sub.3 H CH.sub.3 H H 172.6 D, L41 H -p-ClC.sub.6 H.sub.5 CH.sub.2 H F H F H H 147-148 D, L42 H .sub.-- mClC.sub.6 H.sub.5 CH.sub.2 H H H Cl H H 194 D, L43 H .sub.-- mClC.sub.6 H.sub.5 CH.sub.2 H H H CH.sub.3 H H 204-207 D, L44 H .sub.-- mClC.sub.6 H.sub.5 CH.sub.2 H Cl H Cl H H 197-199 D, L45 H .sub.-- mClC.sub.6 H.sub.5 CH.sub.2 H CH.sub.3 H CH.sub.3 H H 174-176 D, L46 H .sub.-- mClC.sub.6 H.sub.5 CH.sub.2 H F H F H H 155-157 D, L47 H -o-ClC.sub.6 H.sub.5 CH.sub.2 H H H Cl H H 191 D, L48 H -o-ClC.sub.6 H.sub.5 CH.sub.2 H H H CH.sub.3 H H 199 D, L49 H -o-ClC.sub.6 H.sub.5 CH.sub.2 H H H F H H 194-196 D, L50 H -o-ClC.sub.6 H.sub.5 CH.sub.2 H Cl H Cl H H 201-203 D, L51 H -o-ClC.sub.6 H.sub.5 CH.sub.2 H CH.sub.3 H CH.sub.3 H H yellow oil D, L52 H -o-ClC.sub.6 H.sub.5 CH.sub.2 H F H F H H 145 D, L53 Br H H H H Cl H H 162-163 --54 H H H H H Cl H H 127 --55 H H H H H OCH.sub.3 H H 114 --56 H H H H H OCH.sub.3 H OCH.sub.3 168.1 --57 H H H H OCH.sub.3 H H OCH.sub.3 164.2 --58 H H H H OCH.sub.3 OCH.sub.3 OCH.sub.3 H 153-154 --59 H CH(CH.sub.3).sub.2 H H OCH.sub.3 H H OCH.sub.3 141.3 D, L60 H CH(CH.sub.3).sub.2 H H H H H H 105 D, L61 H CH(CH.sub.3).sub.2 H H H H H H yellow oil L62 H CH(CH.sub.3).sub.2 H H H Cl H H yellow oil L63 H CH(CH.sub. 3).sub.2 H H H OCH.sub.3 H H yellow oil L64 H CH(CH.sub.3).sub.2 H H H OCH.sub.3 H OCH.sub.3 144.4 L65 H CH(CH.sub.3).sub.2 H H OCH.sub.3 H H OCH.sub.3 oil L66 H CH(CH.sub.3).sub.2 H H H OCH.sub.3 OCH.sub.3 H 141 L67 H CH(CH.sub.3).sub.2 H H OCH.sub.3 OCH.sub.3 OCH.sub.3 H 154 L68 H CH(CH.sub.3).sub.2 H H H H H H yellow oil D69 H CH(CH.sub.3).sub.2 H H H Cl H H yellow oil D70 H CH.sub.3 H H H H H H yellow solid D, L71 H CH.sub.3 H H H Cl H H yellow oil D, L72 H CH.sub.3 H H Cl H Cl H 126 D, L73 H CH.sub.3 H H H OCH.sub.3 H OCH.sub.3 124.2 L74 H CH.sub.3 H H OCH.sub.3 H H OCH.sub.3 117.5 L75 H CH.sub.3 H H H H H H oil L76 H CH.sub.3 H H H Cl H H oil L77 H CH.sub.3 H H H OCH.sub.3 H H yellow oil L78 H CH.sub.2 CH(CH.sub.3).sub.2 H H H H H H 138.9 D, L79 H CH.sub.2 CH(CH.sub.3).sub.2 H H H Cl H H 171 D, L80 H CH.sub.2 CH(CH.sub.3).sub.2 H H H H H H 144.4 L81 H CH.sub.2 CH(CH.sub.3).sub.2 H Cl H H Cl H 131 L82 H CH.sub.2 CH(CH.sub.3).sub.2 H Cl Cl H H H 88.6 L83 H CH.sub.2 CH(CH.sub.3).sub.2 H H H OCH.sub.3 H OCH.sub.3 yellow oil L84 H CH.sub.2 CH(CH.sub.3).sub.2 H H OCH.sub.3 H H OCH.sub.3 semi-solid L85 H CH.sub.2 CH(CH.sub.3).sub.2 H H OCH.sub.3 OCH.sub.3 OCH.sub.3 H 105.4 L86 H CH.sub.2 CH(CH.sub.3).sub.2 H CH.sub.3 H CH.sub.3 H H 124 L87 H CH.sub.2 CH(CH.sub.3).sub.2 H CH.sub.3 H CH.sub.3 CH.sub.3 H 138.2 L88 H CH.sub.2 CH(CH.sub.3).sub.2 H F H F H H 118 L89 H CH.sub.2 CH(CH.sub.3).sub.2 H Br H Br H H oil L90 H CH.sub.2 CH(CH.sub.3).sub.2 H CH.sub.3 H OCH.sub.3 H H orange oil L91 H CH.sub.2 CH(CH.sub.3).sub.2 H F H F H F oil L92 H CH.sub.2 CH(CH.sub.3).sub.2 H CH.sub.3 H H H CH.sub.3 144.9 L93 H CH.sub.2 CH(CH.sub.3).sub.2 H NO.sub.2 H OCH.sub.3 H H orange oil L94 H CH.sub.2 CH(CH.sub.3).sub.2 H OCH.sub.3 H NO.sub.2 H H 188.3 L95 H CH.sub.2 CH(CH.sub.3).sub.2 H H H cyclohexyl H H 174.4 L96 H CH.sub.2 CH(CH.sub.3).sub.2 H H OCH.sub.3 H OCH.sub.3 H yellow solid L97 H CH(CH.sub.3)CH.sub.2 CH.sub.3 H H H Cl H H 127.7 L98 H CH(CH.sub.3)CH.sub.2 CH.sub.3 H H H CH.sub.3 H H yellow oil L99 H CH(CH.sub.3)CH.sub.2 CH.sub.3 H H H F H H 123.5 L100 H CH(CH.sub. 3)CH.sub.2 CH.sub.3 H F H F H H yellow oil L101 H CH.sub.2 CH.sub.2 CH.sub.3 H H H F H H 91.9 L102 H CH.sub.2 CH.sub.2 CH.sub.3 H Cl H Cl H H yellow oil L103 H CH.sub.2 CH.sub.2 CH.sub.3 H H H CH.sub.3 H H yellow oil L104 H CH.sub.2 CH.sub.2 CH.sub.3 H H H Cl H H 128.7 L105 H CH.sub.2 CH.sub.2 CH.sub.3 H CH.sub.3 H CH.sub.3 H H yellow oil L106 H CH.sub.2 C.sub.6 H.sub.5 CH.sub.3 H H CO.sub.2 CH.sub.3 H H 182 L107 H CH.sub.2 C.sub.6 H.sub.5 CH.sub.3 H H CH.sub.3 H H 171 L__________________________________________________________________________

EXAMPLE 108

Preparation of DL-2,5-Dioxo-.alpha.-methyl-3-pyrroline-1-acet-p-anisidide ##STR17##

Triethylamine (1.36 mL, 0.0091 mol) and ethyl chloroformate are added dropwise to a solution of DL-2,5-dioxo-.alpha.-methyl-3-pyrroline-1-acetic acid (1.5 g, 0.0089 mol) in tetrahydrofuran under nitrogen at 0.degree. C. The reaction mixture is stirred for 10 minutes, treated with p-anisidine (1.09 g, 0.0089 mol), stirred for an additional 2 hours and filtered. Flash chromatography of the filtrate on silica gel (hexane/ethyl acetate - 80/20) gives the title product as a yellow solid (0.74 g, 49%, mp 124.degree. C.), identified by .sup.1 HNMR, CIMS and IR analyses.

EXAMPLES 109-118

Preparation of DL-2,5-Dioxo-.alpha.-methyl-2',4'-dichloro-3-pyrroline-1-acetanilide ##STR18##

A suspension of DL-2,5-dioxo-.alpha.-methyl-3-pyrroline-1-acetic acid (1.5 g, 0.0086 mol) in toluene is treated with thionyl chloride (1.28 mL, 0.0176 mol), warmed to 50.degree. C., stirred for 21/2 hours, cooled and concentrated in vacuo to yield a yellow oil. The oil is dissolved in methylene chloride and added to a solution of 2,4-dichloroaniline (1.54 g, 0.0086 mol) and triethylamine (1.32 mL, 0.0094 mol) in methylene chloride under nitrogen at 0.degree. C. The reaction mixture is stirred for 1 hour at room temperature and concentrated in vacuo to give a residue. The residue is flash chromatographed using hexane/ethyl acetate (80/20) as eluent on silica gel to give the title compound as a pale yellow solid (0.94 g, 35%, mp 131.degree. C.), identified by .sup.1 HNMR, CIMS and IR analysis.

Following the procedure of Example 109, and substituting the appropriate pyrroline-1-acetic acid compound and appropriate aniline, the following formula I compounds in table IV are obtained.

TABLE IV______________________________________ ##STR19##Example R.sub.1 L M Q W Z mp .degree.C. Isomer______________________________________110 CH.sub.3 Cl Cl H H H 130 D, L111 CH.sub.3 Cl H H Cl H 130 D, L112 H H H H H H 104 --113 H Cl H Cl H H 136 --114 H Cl H H Cl H 135 --115 H Cl H H H Cl 133 --116 H Cl Cl H H H 134 --117 CH(CH.sub.3).sub.2 H H Cl H H 118 D, L118 CH(CH.sub.3).sub.2 H H OCH.sub.3 H H 158 D, L______________________________________

EXAMPLES 119-129

Preparation of DL-2,5-Dioxo-.alpha.-isobutyl-3',5'-dichloro-3-pyrroline-1-acetanilide ##STR20##

1-(3-Dimethylaminopropyl)-3-ethyl-carbodiimide (3.5 g, 0.0182 mol) is added to a suspension of DL-2,5-dioxo-.alpha.-isobutyl-3-pyrroline-1-acetic acid (3.5 g, 0.0166 mol) in tetrahydrofuran. The reaction mixture is stirred for 30 minutes, treated with 3,5-dichloroaniline (2.69 g, 0.0166 mol) under ntirogen, stirred at room temperature for 12 hours and poured into water. The mixture is extracted with methylene chloride. The extracts are combined and concentrated in vacuo to give a residue. Flash chromatography using hexane/ethyl acetate (80/20) as eluent on silica gel of the residue yields the title compound as a pale yellow solid (0.97 g, 16%, mp 150.5.degree. C.), identified by .sup.1 HNMR, CIMS and IR analysis.

Using the above procedure and substituting the appropriate aniline, the following formula I compounds in table V are obtained.

TABLE V______________________________________ ##STR21##Example L M Q W Z mp .degree.C. Isomer______________________________________120 H H Cl H H 169.9 L121 H H OCH.sub.3 H H 114.5 L122 H H OCH.sub.3 H H 101.9 D, L123 H Cl H Cl H 155.4 L124 H H H Cl Cl 97.5 D, L125 H Cl H H Cl 115.9 D, L126 H H Cl Cl H 168.5 D, L127 H H Cl H Cl 96.5 L128 H H Cl H Cl 119.4 D, L129 H H Cl Cl H 205.5 L______________________________________

EXAMPLE 130

Preparation of L-.alpha.-benzyl-4'-chloro-N-methyl-2,5-dioxo-3-pyrroline-1-acetanilide ##STR22##

A solution of L-2,5-dioxo-.alpha.-benzyl-4'-chloro-3-pyrroline-1-acetanilide (1.0 g, 0.0028 mol) in tetrahydrofuran is added dropwise to a suspension of sodium hydride (0.11 g, 60% pure, 0.0045 mol) in tetrahydrofuran with stirring under nitrogen at 0.degree. C. After stirring for 1 hour, the reaction mixture is treated with methyl iodide (0.8 g, 0.0056 mol), and stirred for 16 hours and filtered. The filtrate is concentrated in vacuo to give a yellow oil. Flash chromatography of the yellow oil using silica gel and hexane/ethyl acetate (80:20) as eluant gives the title product as a pale yellow solid (0.55 g, mp 181.degree. C.), identified by .sup.1 HNMR, CIMS and IR analysis.

EXAMPLE 131

Evaluation of test compounds as fungicidal agents

Compounds are dissolved in acetone, diluted to the desired concentration with water and surfactant and sprayed onto the test plants. After drying, the test plants are treated with fungal inoculum. When disease symptom development is optimal plants are rated for disease control. Inoculated untreated plants, solvent/surfactant treated plants and plants treated with a reference standard are used for comparison.

______________________________________Test OrganismsHEADER COMMON NAME SCIENTIFIC NAME______________________________________AS Apple scab Venturia inaequalisGDM Grape downy mildew Plasmopara viticolaPB Pepper botrytis Botrytis cinereaRB Rice blast Pyricularia oryzaeSBC Sugar beet cercospora Cercospora beticolaTLB Tomato late blight Phytophthora infestansWLR Wheat leaf rust Puccinia recondita f. sp. triticiWPM Wheat powdery mildew Erysiphe graminis f. sp. tritici______________________________________

Compounds are rated for control of each disease according to the rating scale shown below

______________________________________Rating % Control of Disease______________________________________0 01 1-142 15-293 30-444 45-595 60-746 75-897 90-958 96-999 100______________________________________

The results are reported in table VI.

TABLE VI__________________________________________________________________________ AS GDM PB RB SBC TLB WLR WPMExample No. (400) (400) (100) (400) (400) (400) (400) (400) (400) (PPM)__________________________________________________________________________ 3 0 9 8 0 0 0 6 6 0 4 0 0 0 0 4 8 0 0 5 0 7 4 0 0 5 5 5 0 6 6 9 9 0 0 4 2 5 0 7 5 9 7 4 6 2 0 7 0 8 0 8 6 6 0 4 0 7 4 9 0 9 0 0 0 0 0 010 6 9 6 4 0 0 0 7 011 7 9 6 6 4 0 4 7 012 0 9 7 4 0 0 6 0 013 0 9 8 4 0 0 6 0 014 7 9 9 7 0 0 0 4 015 7 9 9 4 0 0 0 6 016 7 9 9 0 0 7 4 017 8 9 9 0 7 7 0 4 018 6 9 9 0 8 7 0 0 019 7 9 9 0 9 0 0 0 020 9 9 9 0 7 7 8 0 021 7 9 9 0 0 0 0 0 022 9 9 9 0 7 6 0 0 023 9 9 9 0 7 7 0 0 024 8 9 9 7 7 7 0 7 025 8 9 9 0 7 7 0 7 026 6 8 2 7 0 0 0 027 7 7 0 7 0 0 0 028 0 9 8 0 0 0 2 0 029 7 9 7 7 0 0 2 4 030 0 7 0 0 0 4 5 0 031 0 6 0 4 4 0 032 0 6 0 0 4 0 033 7 5 0 0 0 4 0 034 7 9 9 6 0 0 4 035 7 9 8 4 0 0 6 036 0 9 8 0 0 0 6 0 037 4 9 9 0 0 0 0 0 038 8 9 9 0 0 5 4 4 039 7 9 8 0 0 6 0 0 040 0 9 9 0 0 6 4 0 041 8 8 7 0 0 0 6 0 042 6 9 9 4 0 6 4 0 043 8 9 9 0 0 7 0 0 044 7 9 9 4 0 6 4 0 045 6 9 6 8 0 7 0 7 046 4 9 8 6 0 0 0 7 047 4 9 9 0 0 4 2 0 048 4 9 9 0 0 0 6 0 049 0 9 9 0 0 4 7 0 050 7 9 9 0 0 0 0 0 051 7 9 7 7 0 7 0 0 052 3 9 9 0 0 4 0 0 053 0 8 8 0 0 0 7 7 054 6 0 2 7 6 6 6 055 0 3 0 9 4 0 5 256 0 8 7 4 6 6 0 7 057 0 9 6 7 4 5 7 6 258 0 8 4 6 5 6 7 059 0 7 3 7 4 5 3 6 060 4 2 5 9 1 5 461 0 6 0 0 0 4 0 4 062 4 8 0 0 0 0 0 6 063 0 6 7 0 0 0 0 6 064 0 9 4 3 4 6 4 7 065 6 9 6 7 4 6 0 7 066 0 5 3 3 7 6 0 7 067 0 0 4 4 6 5 4 7 068 5 9 8 4 0 5 0 7 069 3 9 7 4 0 0 0 6 070 0 8 4 0 7 2 5 7 271 0 7 5 1 7 0 6 2 072 6 8 8 0 0 7 7 5 073 0 0 5 4 6 4 6 174 5 8 4 3 4 4 0 7 075 0 9 3 0 7 0 6 3 076 3 0 0 0 7 6 7 077 0 4 0 0 0 7 0 0 078 7 7 7 0 6 0 0 6 079 7 8 7 0 0 0 0 5 080 7 9 8 4 0 0 4 6 081 6 0 0 0 0 0 0 0 082 9 9 8 7 4 7 6 7 083 4 8 6 4 6 4 0 7 084 3 7 6 0 6 5 0 7 085 0 0 0 0 0 0 4 8 386 0 9 8 0 6 6 6 9 087 8 9 9 0 7 0 6 7 088 7 9 7 0 8 7 0 7 089 9 9 8 0 7 7 8 7 090 0 0 0 0 0 4 6 091 0 9 9 4 0 0 0 7 092 7 9 9 0 6 0 4 6 093 0 9 8 0 6 0 0 4 094 7 9 8 6 4 0 0 0 095 7 9 9 0 0 0 4 0 096 6 0 6 0 0 0 0 0 097 7 9 9 9 4 7 4 0 098 6 9 8 0 6 0 5 8 099 9 9 7 7 8 8 0 0 0100 7 9 7 0 9 8 0 8 0101 0 4 0 7 0 0 8 0102 0 9 8 0 4 0 0 6 0103 0 6 0 0 0 0 8 0104 0 8 8 0 0 0 0 5 0105 6 9 0 0 8 7 0 0 0106 0 8 0 5 0 5 4 2107 4 5 0 0 6 6 6 0108 0 4 0 0 0 2 5 0109 3 7 6 0 7 4 7 0110 0 9 3 8 0 5 8 5 0111 6 0 5 0 5 7 6 0112 0 0 0 0 4 0 4 0113 0 9 6 5 7 6 4 1 0114 5 9 7 0 0 0 2 0 0115 0 9 3 0 0 3 0 2 0116 0 0 6 0 3 0 3 0117 6 9 7 5 5 7 8 6 0118 0 7 3 0 6 6 0 5 0119 7 0 0 0 4 0 6 0120 1 0 0 4 0 0 4 0121 1 0 0 0 4 0 4 0122 0 3 1 0 0 0 0 0123 7 0 0 6 4 0 6 1124 7 9 7 8 6 5 4 7 0125 6 0 0 6 6 0 5 0126 4 0 0 4 6 0 5 0127 8 9 9 8 0 0 0 6 0128 8 9 9 0 6 0 3 0 0129 7 6 0 0 0 0 0 0130 0 7 7 0 8 4 0 0 0__________________________________________________________________________

Claims

1. A method for the preparation of a 2,5-dioxo-3-pyrroline-1-acetic acid compound having the structural formula ##STR23## wherein R is hydrogen, halogen or C.sub.1 -C.sub.4 alkyl optionally substituted with halogen;

R.sub.1 is hydrogen,

C.sub.1 -C.sub.10 alkyl optionally substituted with C.sub.1 -C.sub.9 alkoxy or halogen,

C.sub.3 -C.sub.6 cycloalkyl,

C.sub.2 -C.sub.10 alkylthioalkyl,

C.sub.4 -C.sub.10 cycloalkylalkyl, or phenyl or C.sub.7 -C.sub.10 phenylalkyl optionally substituted

with one to three halogen atoms, C.sub.1 -C.sub.4 alkoxy groups, nitro groups, cyano groups, or C.sub.1 -C.sub.4 alkyl groups optionally substituted with halogen;

when R.sub.1 is a substituent other than hydrogen, the optical isomers thereof which comprises reacting an amino acid compound having the structural formula ##STR24## wherein R.sub.1 is as described above with at least one molar equivalent of a maleic anhydride compound having the structural formula ##STR25## wherein R is as described above in the presence of a carboxylic acid and a polar solvent to form a N-(carboxymethyl)maleamic acid compound having the structural formula ##STR26## wherein R and R.sup.1 are as described above and heating the N-(carboxymethyl)maleamic acid compound in the presence of at least two molar equivalents of an amine base and an azeotropic organic solvent with the azeotropic removal of water to form the corresponding 2,5-dioxo-3-pyrroline-1-acetate and admixing the 2,5-dioxo-3-pyrroline-1-acetate with at least one molar equivalent of an aqueous mineral acid to form said 2,5-dioxo-3-pyrroline-1-acetic acid compound.

2. The method according to claim 1 wherein the carboxylic acid is acetic acid, formic acid, propionic acid or butyric acid.

3. The method according to claim 2 wherein the carboxylic acid is acetic acid.

4. The method according to claim 1 wherein the polar solvent is acetone, methyl isobutyl acetone, or acetonitrile.

5. The method according to claim 4 wherein the polar solvent is acetone.

6. The method according to claim 1 wherein the amine base is a secondary amine base, tertiary amine base or an aromatic amine base.

7. The method according to claim 6 wherein the amine base is a tertiary amine base.

8. The method according to claim 7 wherein the amine base is triethylamine.

9. The method according to claim 1 wherein the azeotropic organic solvent is benzene, toulene, or xylene.

10. The method according to claim 9 wherein the azeotropic organic solvent is toulene.

11. The method according to claim 1 wherein the aqueous mineral acid is aqueous hydrochloric acid.