WO1993022299A1

WO1993022299A1 - Fungicidal oxazolidinones

Info

Publication number: WO1993022299A1
Application number: PCT/US1993/002797
Authority: WO
Inventors: Carlton Lane Campbell
Original assignee: E.I. Du Pont De Nemours And Company
Priority date: 1992-04-24
Filing date: 1993-03-25
Publication date: 1993-11-11
Also published as: EP0637301A1; MX9302388A

Abstract

Oxazolidinoe compounds useful as fungicides of formula (I) wherein A is O or NH; R3 is optionally substituted phenyl; R?1 and R4¿ are each H or alkyl; and R2 is one of formula (A), (B) or (C), are disclosed.

Description

TITLE

FUNGICIDAL OXAZOLIDNONES BACKGROUND OF THE INVENTION

This invention relates to particular oxazolidinone compounds useful as fungicides, agriculturally suitable compositions containing such compounds, and methods of use of such compounds or compositions as fungicides in crop plants.

WO90/12791 is drawn to the use of fungicidal compounds of Formula i

wherein:

A is O orNR⁴; and

W is O or S.

WO90/12791 generically discloses compounds of Formula i wherein R² is phenyl substituted with benzyloxy and the phenyl of the benzyloxy is optionally substituted. WO90/12791 specifically discloses a compound of Formula i wherein W is O, A is NH, R¹ is methyl, R³ is phenyl, and R² is 4-benzyloxy-phenyl. This compound is not within the scope of the instant application.

PCT Application US92/01224 discloses fungicidal compounds of

Formula ii

wherein:

A is S or N-E-J;

W is O, S or N-Q-G;

E is a direct bond, O, or NR¹⁴; and

J is H, alkyl, phenyl, etc.

US92/01224 generically discloses compounds wherein A is NH and R² is phenyl substituted with benzyloxy or phenoxymethyl. US92/01224 specifically discloses several compounds wherein A is NH, W is O, R¹ is methyl, R³ is phenyl, R⁴ is H, and R² is phenyl substituted with benzyloxy or phenoxymethyl, and said benzyloxy and phenoxymethyl groups are substituted on the phenyl ring. Compounds specifically disclosed in US92/01224 are not within the scope of the instant application.

SUMMARY OF THE INVENTION

This invention comprises compounds of Formula I including all geometric and stereoisomers, agricultural compositions containing them and the use of the compounds or said compositions as fungicides. The compounds of Formula I are:

wherein:

A is O or NH;

R¹ is H; methyl; or ethyl;

R³ is phenyl optionally substituted with R⁵;

R⁴ is H or methyl;

R⁵ is F; Cl; or C₁-C₄ alkyl; and

R² is selected from the group consisting of substituents of Formulae A, B and C: ,

and

such that:

X is CHR⁶Q or QCH₂;

Q is O or S;

G is a phenyl, naphthalenyl, pyridinyl, furanyl, thienyl, indolyl,

N-methylindolyl, benzo[b]furanyl, benzo[b]thienyl, quinolinyl, isoquinolinyl, pyrrolyl, N-methylpyirolyl or N-ethylpyrrolyl each optionally substituted with R⁷, R⁸, or R⁷ and R⁸; such that the point of attachment to X is a carbon atom of G;

T is CH or N;

U is O; S; NH; or NCH₃;

R⁶ is H; methyl; or ethyl;

R⁷ is halogen; C₁-C₆ alkyl; C₂-C₆ alkenyl; C₁-C₆ haloalkyl; C₁-C₄

alkylthio; allylthio; allyloxy; C₁-C₄ haloalkoxy; cyano;

carbomethoxy; carboethoxy; phenoxy; nitro; amino; C₁-C₆ alkoxy; or dimethylamino;

R⁸ is F; Cl; Br; C₁-C₃ alkyl; or trifluoromethyl;

R⁹ is H or F;

R¹⁰ is hydrogen; halogen; C₁-C₆ alkyl; C₂-C₆ alkenyl; C₁-C₆ haloalkyl;

C₁-C₄ alkylthio; allylthio; allyloxy; C₁-C₄ haloalkoxy; cyano;

carbomethoxy; carboethoxy; phenoxy; nitro; amino; C₁-C₆ alkoxy; or dimethylamino; or when G is an optionally substituted phenyl ring, and:

(i) when R⁷ and R⁸ are bonded to adjacent carbons, then R⁷ and R⁸ can be taken together to form R⁷-R⁸ which is CH₂CH₂W, WCH₂CH₂, or WCH₂CH₂CH₂; or

(ii) when R⁸ is bonded to C-2 of G, and X is CHR⁶Q, then R⁸ and

R⁶ can be taken together to form R⁸-R⁶ which is ZCH₂CH₂, ZCH₂CH₂CH₂, ZCH=CH, CH₂ZCH₂, ZCH₂, or CH=CH; or (iii) when R⁹ is bonded to C-3 of the phenyl ring, and X is CHR⁶Q, then R⁶ and R⁹ can be taken together to form R⁶-R⁹ which is CH₂J, or CH₂; or

(iv) when R⁸ is bonded to C-2 of G, and R⁹ is bonded to C-3 of the phenyl ring, then R⁸ and R⁹ can be taken together to form R⁸-R⁹ which is CH₂, CH(CH₃), or CH₂CH₂;

J, W, and Z are each independently CH₂, O, or S;

provided that

(i) when A is O, R¹ is methyl, R² is a substituent of Formula A, R³ is phenyl, X is CH₂O and R⁴ and R⁹ are H, then G is other than unsubstituted phenyl; and

(ii) when A is NH, Q is O, R¹ is methyl, R² is a substituent of

Formula A, R³ is phenyl, and R⁴, and R⁶ are H, then G is other than optionally substituted phenyl.

DETAILED DESCRIPTION OF THE INVENTION

In the above recitations, the term "alkyl", used either alone or in compound words such as "alkylthio" or "haloalkyl" denotes straight-chain or branched alkyl; e.g., methyl, ethyl, n-propyl, t-propyl, or the different butyl, pentyl or hexyl isomers. "Alkenyl" denotes straightchain or branched alkenes; e.g. 1-propenyl, 2-propenyl, 3-propenyl and the different butenyl, pentenyl and hexenyl isomers. "Alkenyl" also denotes polyenes such as 13-hexadiene and 2,4,6-heptatriene. "Alkylthio" denotes branched or straight-chain alkylthio moieties; e.g. methylthio, ethylthio, and the different propylthio, butylthio, pentylthio and hexylthio isomers. "Alkoxy" denotes, for example, methoxy, ethoxy, n-propyloxy, isopropyloxy and the different butoxy, pentoxy and hexyloxy isomers. The term "halogen", either alone or in compound words such as "haloalkyl", denotes fluorine, chlorine, bromine or iodine. Further, when used in compound words such as "haloalkyl", said alkyl may be partially or fully substituted with halogen atoms which may be the same or different. Examples of "haloalkyl" include F₃C, ClCH₂, CF₃CH₂ and CF₃CF₂. Examples of "haloalkoxy" include CF₃O, CCl₃CH₂O, CF₂HCH₂CH₂O and CF₃CH₂O. The total number of carbon atoms in a substituent group is indicated by the "C_i-C_j" prefix where i and j are numbers from 1 to 6. For example, C₁-C₃ alkylsulfonyl designates methylsulfonyl through propylsulfonyl; C₂ alkoxyalkoxy designates CH₃OCH₂O; C₃ alkoxyalkoxy designates, for example, CH₃OCH₂CH₂O or CH₃CH₂OCH₂O; and C₄ alkoxyalkoxy designates the various isomers of an alkoxy group substituted with a second alkoxy group containing a total of 4 carbon atoms, examples including CH₃CH₂CH₂OCH₂O, and CH₃CH₂OCH₂CH₂O.

Preferred compounds, compositions containing them, and methods of their use for reasons of better activity and/or ease of synthesis are:

Preferred 1. Compounds of Formula I above wherein:

R² is a substituent of Formula A and X is CHR⁶Q;

G is phenyl optionally substituted with R⁷ or with R⁷ and R⁸;

1-naphthalenyl; or 2-naphthalenyl;

R⁷ is C₂-C₅ alkenyl; C₁-C₅ haloalkyl; C₁-C₄ alkylthio; allylthio; allyloxy; C₁-C₄ haloalkoxy; cyano; carbomethoxy;

carboethoxy; or dimethylamino; or

when R⁷ and R⁸ are bonded to adjacent carbons, they can be taken together to form -CH₂CH₂CH₂- or -CH₂CH₂CH₂CH₂-; and provided that

(i) when A is O, Q is O, and R⁶ is H, then R⁷ is other than CF₃ or MeS; and

(ii) when A is NH, Q is O, and R⁶ is H, then R⁷ is other than CF₃, cyano or CF₃O.

Preferred 2. Compounds of Formula I above wherein:

R¹ is methyl;

R² is a substituent of Formula A;

R³ is phenyl;

R⁴ is H;

R⁹ is H; and

G is a phenyl, naphthalenyl, pyridinyl. or furanyl, each optionally substituted with R⁷, R⁸, or R⁷ and R⁸.

Preferred 3. Compounds of Preferred 2 wherein: X is CHR⁶Q;

Q is O;

R⁶ is H or methyl; and

G is a phenyl optionally substituted with R⁷, R⁸, or R⁷ and R⁸. Specifically preferred for greatest fungicidal activity and/or ease of synthesis are:

5-methyl-5-((4-(2-methylphenyl)methoxy)phenyl)-3-phenylamino-2,4- oxazolidinedione;

5-methyl-5-((4-(3-methylphenyl)methoxy)phenyl)-3-phenylamino-2,4- oxazolidinedione; and

5-methyl-5 -(1-phenylethoxy)phenyl)-3-phenylamino-2,4- oxazolidinedione.

It is recognized that some reagents and reaction conditions described below for preparing compounds of Formula I may not be compatible with some functionalities claimed for R¹, R², R³, R⁴ and A. In these cases, the incorporation of protection/deprotection sequences into the synthesis may be necessary in order to obtain the desired products. The cases in which protecting groups are necessary, and which protecting group to use, will be apparent to one skilled in chemical synthesis.

In the following description of the preparation of compounds of Formula I, compounds denoted as Formula la and lb are various subsets of the compounds of Formula I, and all substituents for Formula Ia and Ib are as defined above for Formula I.

Compounds of Formula I may exist as one or more stereoisomers. The various stereoisomers include enantiomers, diastereomers and geometric isomers. One skilled in the art will appreciate that one stereoisomer may be the more active. One skilled in the art knows how to separate said enantiomers, diastereomers, and geometric isomers. Accordingly, the present invention comprises racemic mixtures, individual stereoisomers, and optically active mixtures of compounds of Formula I.

The compounds of Formula I can be prepared as described below in Equations 1-5.

Several methods are taught in the literature for the preparation of

2,4-oxazolidinediones of Formula la (Equations 1 and 2). Geffken et al.

(WO90/12791) disclose the preparation of la by treating dioxazinediones of Formula 1 with a substituted hydrazine of Formula 2 as illustrated in Method 1, Equation 1. The preparation of the starting dioxazinediones 1 is also described therein. WO 90/12791 also describes the desulfurization of 2-thioxo-4- oxazolidinones of Formula 3 to yield 2,4-oxazolidinediones la as shown in

Method 2, Equation 1. Suitable desulfurizing agents include aqueous OXONE^® (KHSO₅) and aqueous silver nitrate.

Equation 1

Substituted hydrazines of Formula 2 are either commercially available or can be prepared by literature methods (J. Timberlake; J. Stowell; The Chemistry of the Hydrazo, Azo, and Azoxy Groups (S. Patai, Ed.) John Wiley and Sons, Ltd., London (1975), p 69; Demers, J. P.; Klaubert, D. J.; Tetrahedron Lett. (1987), 4933.

2-Thioxo-4-oxazolidinones of Formula 3 can be prepared by one or both of the methods described in detail in the literature (Geffken, D.; Z. Naturforsch, (1983), 38b, 1008; Geffken, D.; Arch. Pharm., (1982), 315, 802; WO90/12791 and U.S. 4,957,933).

In addition, compounds of Formula Ia can be prepared by the methods outlined in Equation 2. These procedures involve treatment of a

2-hydroxycarboxylic acid ester of Formula 4 with a carbonylating agent of Formula 6 to produce compounds of Formula 5, followed by conversion of 5 to la by treatment with a substituted hydrazine 2. In Equation 2, U can be chlorine, 1-imidazolyl, or other suitable leaving group. The ester group containing Z in compounds of Formula 4 can be alkyl (C₁-C₄), alkenyl (C₃-C₄), cycloalkyl (C₃-C₁₂ ), cycloalkylalkyl (C₆-C₇), alkoxyalkyl (C₂-C₄), and phenylmethyl.

Preferred for ease of synthesis and lower expense are esters in which Z is C₁-C₄ alkyl.

Equation 2

y

Z=C₁-C₄ alkyl, C₃-C₄ alkenyl, C₃-C₁₂ cycloalkylal C₆-C₇ cycloalkylalkyl, C₂-C₄ alkoxyalkyl, PhCH₂ The 2-hydroxycarboxylic acid esters of Formula 4 can be prepared by a number of methods known in the literature.

(1) They can be formed from the corresponding 2-hydroxycarboxylic acids by esterification as is well known in the literature. The 2-hydroxycarboxylic acids can be prepared from ketones or aldehydes by formation of cyanohydrins, then hydrolysis, as is also known. For example, Org. Syntheses. Coll. Vol. 4, 58 (1968) teaches the preparation of atrolactic acid from acetophenone. (2) The esters can also be synthesized from aldehyde and ketone cyanohydrins by treatment with alcohols in the presence of HCl to afford the iminoether hydrochlorides, followed by hydrolysis.

(3) A third method known for preparing 2-hydroxycarboxylic acids and esters involves treating 2-keto-acids or 2-keto-esters with nucleophilic-organometallic reagents such as Grignard reagents, and alkyl- and aryl-lithium reagents. For example, R. G. Salomon et al. teaches the preparation of some esters of Formula 4 by the addition of aryl-Grignard reagents to pyruvate esters (J. Org. Chem. (1982), 47, 4692). Similarly, some 2-hydroxycarboxylic acids may be prepared by the regioselective nucleophilic addition of an aryl organometallic reagent to the metal salt (e.g., sodium salt) of pyruvic acid. (4) Another method described in the literature for preparing some 2-aryl-2-hydroxyesters and acids is by acylation of aromatic rings with activated carbonyl compounds in the presence of a protic or Lewis acid. Aromatic substrates capable of undergoing reactions of this type are benzene, diphenyl ether, furan and other aromatic compounds known to be of sufficient reactivity to undergo Friedel-Crafts-type reactions. In the case ofmono-substituted benzene derivatives, the acylation occurs preferentially, but not necessarily exclusively, para to the point of attachment of the substituent. For example, see Org. Syntheses, Coll. Vol.3, 326, (1955), Salomon et al., J. Org. Chem., (1982), 47, 4692, and U.S.4,922,010.

Carbonyl compounds known to undergo this reaction include pyruvate esters and acids, glyoxylate esters and acids, and diesters of oxomalonates. The acids used in the acylation reaction can either be protic in nature, for example, a mixture of acetic and sulfuric acid, or a Lewis acid such as aluminum chloride, tin tetrachloride, titanium tetrachloride, or other Lewis acid known to effect Friedel-Crafts-type reactions. The acid can be used either catalytically or in excess. In some cases, the acid may react destructively with the carbonyl substrate and excess carbonyl compound must be used.

The acylation can be conducted neat or in a solvent known by one skilled in the art to be suitable for Friedel-Crafts reactions, for example, methylene chloride, carbon disulfide, and nitrobenzene. The reaction may be conducted from -50 to 100°C. The specific choice of acid, solvent, temperature, and reaction time will depend on the carbonyl and aromatic substrates to be reacted. The compounds of Formula 5 can be prepared by the method illustrated in Step 1, Equation 2. For the preparation of the compounds of Formula 5a (U=Cl), the alcohols of Formula 4 are dissolved in an inert solvent such as methylene chloride or 1-chlorobutane, and treated with a tertiaty-amine base such as triethylamine, pyridine, and N,N-diisopropylethylamine, at a temperature from -60 to +30°C. To this mixture is added phosgene (6a) to provide chloroformates of Formula 5a. The phosgene can be added as a gas or dissolved in a inert solvent such as toluene and added in solution. When the reaction of Step 1 is complete, the resulting mixture is poured into a water-immiscible solvent and washed with dilute aqueous mineral acid, water, and brine. The organic liquid phase is dried and evaporated to yield products of Formula 5a.

The compounds represented by Formula 5b (U = 1-imidazolyl) can be prepared using 1,1'-carbonyldiimidazole (CDI, 6b) as described below. The alcohols of Formula 4 are dissolved in an inert solvent in which the CDI has sufficient solubility at the reaction temperature. Methylene chloride,

1-chlorobutane and toluene are three of many suitable inert solvents. The CDI is added as a solid or as a solution in an inert solvent at temperatures from 0 to 100°C.

When the reaction is complete, the resulting mixture is poured into a water-immiscible solvent and washed successively with dilute mineral acid, water, and brine. The organic liquid phase of this mixture is separated, dried, and evaporated to isolate the product.

In some cases, isolation of compounds of Formula 5 is not necessary. For example, after the formation of 5 is complete, the compounds can be treated in situ with a hydrazine of Formula 2 as described below for Step 2.

Furthermore, the use of pure, isolated CDI is not necessary in the synthesis of 5b described in Equation 2, Step 1. The CDI can be first prepared, for example by treatment of a solution of imidazole in an inert solvent with phosgene as described by Staab and Wendel (Org. Syntheses. Coll. Vol.5, 201, (1973)), and then treated in situ with alcohols 4 to afford 5b.

As illustrated in Step 2 of Equation 2, compounds of Formula 5 can be dissolved in an inert solvent such as methylene chloride, 1-chlorobutane, or THF and treated with a hydrazine of Formula 2 at a temperature from 0 to 80°C.

When U is Cl as shown in Formula 5a, about one equivalent of a tertiary-amine base such as triethylamine, N,N-diethylaniline, N,N-diisopropylethylamine, or a second equivalent of a hydrazine 2 can be added. When U=1-imidazole as in Formula 5b, about one equivalent of a carboxylic acid can be added to accelerate the reaction. Suitable carboxylic acids include acetic acid, pivalic acid, and benzoic acid.

Upon completion of the reaction of Step 2, the product of Formula la can be isolated by evaporation of the aforementioned inert solvent, and purified by dissolving the residue in a water-immiscible solvent such as ether or methylene chloride, washing with mineral acid, aqueous base, and water, drying, and evaporating the extraction solvent. Crystallization or chromatography can be utilized for additional purification if desired.

For reasons of higher yields and lower expense, the methods of preparing compounds of Formula la from compounds of Formula 5b (U = 1-imidazolyl) are preferred to the methods of preparing la from 5a.

4-Imino-2-oxazolid-nones of Formula lb can be prepared by sequential conversion of cyanohydrins of Formula 7 to their respective chloroformates of Formula 8 or O-(-midazolylcarbonyl) derivatives of Formula 9, treatment of a compound 8 or 9 with a substituted hydrazine which produces the carbazates of Formula 109, then cyclization of a caibazate 10 to the product of Formula lb. This sequence is schematically illustrated in Equation 3.

Equation 3

The (9-(imidazolylcarbonyl) derivatives of Formula 9 will be the intermediates of choice over the chloroformates of Formula 8 for those cyanohydrins 7 which fail to react, or react only poorly, with phosgene. The cyanohydrins which react poorly with phosgene tend to be those derived from electron-rich-aryl alkyl ketones. Methodology for preparation of ketone cyanohydrins is well known to those skilled in the art. See, for example, Org.

Syntheses, Coll. Vol.4, 58, (1968) which teaches the preparation of acetophenone cyanohydrin, and Gassman et al. in Tetrahedron Lett. (1978), 3773, which teaches a general method for preparation of trimethylsilyl cyanohydrins.

Conversion of cyanohydrins to chloroformates is generally accomplished by mixing the cyanohydrin with phosgene and an acid acceptor in an inert solvent. Typical acid acceptors include the tertiary-amine bases (such as pyridine, N,N-dimethylaniline, N,N-diethylamline). Typical inert solvents include the aromatic hydrocarbons (such as benzene, toluene, xylenes), ethers (such as THF, dioxane, diethyl ether), and chlorinated hydrocarbons (such as methylene chloride, chloroform). Temperatures are typically -20 to +40°C. The chloroformates can be used directly in solution or be isolated by filtration of the reaction mixture and evaporation of the solvent from the filtrate; further purification can be accomplished by dissolution of the chloroformate in an inert, water-immiscible solvent (such as ether, benzene, toluene, xylenes, ethyl acetate, methylene chloride, chloroform, 1-chlorobutane), washing the solution with cold, dilute mineral acid, cold water, drying the solution, and evaporation of the solvent. Conversion of cyanohydrins to their chloroformates is known in the literature (e.g., N. Kondratenko et al., Probl. Poluch. Poluprod. Prom. Org. Sin., Akad, Nauk SSSR, Otd. Obshch. Tekh. Khim. (1967), 60-63; Chem. Abs., (1968), 68, 12441m).

Conversion of cyanohydrins to their O-imidazolyl carbonates can be accomplished by mixing the cyanohydrin with 1,1'-carbonyldiimidazole (CDI) in an inert solvent until the reaction is substantially complete [optionally the CDI can be generated in situ from phosgene and imidazole as described by Staab and Wendel, Org. Synthesis Coll. Vol.5, 201, (1973)]. The progress of the reaction can be conveniently followed by thin-layer chromatography, or by noting evolution of CO₂ (or lack thereof) on treatment of a sample of the reaction mixture with water, which reacts quickly with any unreacted CDI. Depending on the particular substrates, temperature, and concentration of reactants in solution, the reaction is generally over within a few minutes to a few days; typical times are about 2 h to an overnight period. Suitable inert solvents include those mentioned above for preparation of the chloroformates. Reaction temperatures can vary from about -20°C up to the boiling point of the solvent, with ambient temperatures preferred for convenience. The reaction mixtures can be used directly for the next step (reaction with a substituted hydrazine), or the intermediate O-(imidazolylcarbonyl) compounds can be purified and even isolated prior to use. For purification and isolation the solvent in the reaction mixture is evaporated (if water-immiscible), and the residue is treated with cold water and water-immiscible solvent (e.g., diethyl ether, benzene, toluene, 1-chlorobutane, methylene chloride, chloroform, ethyl acetate); the layers are separated, and the organic layer is dried and evaporated to the

(9-(imidazolylcarbonyl) compound.

Conversion of the cyanohydrin chloroformates to the carbazates comprises mixing the chloroformate with a substituted hydrazine in an inert solvent, with either some of a substituted hydrazine or an added tertiary-amine base [e.g., pyridine, N,N-diethylaniline, N,N-dimethylaniline, triethylamine. (N,N-diisopropyl)ethylamine] acting as an acid acceptor. Suitable solvents include those suitable for preparation of the chloroformate. The reaction is generally rapid and complete within a few minutes in the usual temperature range (about -20°C to ambient). If desired, the intermediate carbazate can be isolated by evaporating the solvent in vacuo (if water-immiscible) and washing a solution of the residue in a water-immiscible solvent [such as mentioned for the preparation of an O-(imidazolylcarbonyl) compound] with dilute mineral acid and water, drying, and evaporation of the solvent. If the carbazate does not spontaneously cyclize to the 4-imino-2-oxazolidinone within an acceptable time, cyclization can be effected by treatment of a solution of the carbazate in an inert solvent (e.g., toluene, benzene, 1-chlorobutane, THF, chloroform) with imidazole or atertiary-amine base [e.g., triethylamine, (N,N-diisopropyl)ethylamine, pyridine] and optionally heating the mixture up to the boiling point of the solvent; for example, cyclization is typically effected by boiling a toluene solution of the carbazate in the presence of triethylamine at reflux for 2 h.

Conversion of an O-(imidazolylcarbonyl) derivative to a carbazate (which generally cyclizes spontaneously to the 4-imino-2-oxazolidinone under the influence of the liberated imidazole) is effected by mixing an O-(imidazolylcarbonyl) derivative with a substituted hydrazine in an inert solvent (such as those mentioned for preparation of the chloroformate). Reaction is generally complete within a few minutes to an hour. Purification of the products can be effected by washing the reaction mixtures (if a water-immiscible solvent was used) with water, drying, and evaporation of the solvent. If cyclization of a carbazate to a 4-imino-2-oxazolidinone is incomplete, it can be effected as described above. If cyclization is substantially complete, then the product has been obtained. As noted in the Examples, the infrared spectrum of the carbazate shows absorption around 1738 cm^-1; for the 4-imino-2-oxazolidinone the corresponding figure is around 1800 cm^-1.

Ease of isolation of the imino compound of Formula Ib can sometimes be enhanced by conversion of it to a salt, for example by addition of a strong acid HX, wherein HX is HBr, HCl, HI, HNO₃, H₂SO₄, H₃PO₄, or an organic acid such as alkyl- and arylsulfonic acids, to a solution of compound lb in an inert organic solvent (such as those mentioned for preparation of the chloroformate above). Crystallization of the salt of Formula Ib-HX can then often be effected from the same or different organic solvent, or the salt can be recovered by evaporation of the solvent. Some of the imine salts offer advantage of formulation or enhanced fungicidal activity over the free-base forms.

Additionally, compounds of Formula Ib-HX can be converted to the corresponding 2,4-oxazolidinedione of Formula la by reaction with water;

typically the salt (or lb plus an acid) is mixed with water, optionally in the presence of a cosolvent (e.g., acetone, butanone, THF) and optionally heated until conversion to the 4-oxo compound la is substantially complete (Equation 4). The 4-oxo compound can be isolated in the usual ways, such as by filtration or evaporation of the reaction mixture, or by extraction of the product into an organic solvent and evaporation of that solvent.

Equation 4

One skilled in the art will recognize that a substituent residing on R² may be incompatible with the conditions in the methods described above for the preparation of the 2-hydroxyester functionality. In some instances, the constraction of the R² unit after the introduction of the hydroxy ester moiety may be desirable. For example, the formation of the bridge linking G with the R⁹-substituted phenyl ring may be synthesized with the hydroxyester

functionalities already in place (Equation 5).

Equation 5

Z = C₁-C₄ alkyl, C₁-C₄ alkenyl, benzyl

LG=Cl, Br, I, OMs, OTs The formation of ethers and thioethers is well known in the chemical literature. The classical method for the preparation of ethers, the Williamson ether synthesis, involves reaction of an alkoxide, such as alkoxides derived from compounds of Formulae 11 and 15, with an electrophile, such as compounds of Formulae 12 and 14, in an inert solvent. The same methodology can be used to form thioethers. A variety of electrophiles of Formulae 12 and 14 are commercially available or can be prepared by known methods (e.g., see

Hudlicky, M.; Hudlicky, T. In The Chemistry of Functional Groups, Patai, S; Rappoport, Z., Eds.; Supplement D, Pt 2; pp 1021-1172). For example, a chemoselective O-alkylation of a compound of Formula 11 in Method 1 (Q = O) is accomplished by heating a mixture of a compound of Formula 11 with an optionally substituted arylmethyl halide (LG = Cl, Br, or I) of Formula 12 and a base (e.g., potassium carbonate) in an inert solvent.

One skilled in the art will recognize that the use of protecting groups may be necessary in order to prepare the hydroxyesters of Formulae 11 and 14. For example in the case of compounds of Formula 11 , a protecting group may be necessary to mask the acidic proton on Q during the introduction of the hydroxyester group. A trialkylsilyl protecting group is preferred in this regard when Q = O (see Synthesis, (1982), 817 and Tetrahedron Lett. (1979), 3981).

The methods described in the following Examples further describe the nature of the invention. THF = tetrahydrofuran, Et₂O = diethyl ether,

EtOAc = ethyl acetate, DMF = dimethyl formamide, EtI = iodoethane,

HO Ac = acetic acid. EXAMPLE 1

(a) Preparation of 2-(4-(t-butyldimethylsilyloxy)phenyl)lactic acid

A round-bottom flask equipped with a magnetic stirbar, addition funnel, condenser and an N₂ inlet was charged with Mg (90 mg) and the apparatus was dried under a N₂ flow. Once cooled to room temperature, THF (1 mL) was added to the flask along with I₂ (1 mg) and BrCH₂CH₂Br (2 drops). To the flask was then added 2 mL of a solution of 4-(t-butyldimethyl-silyloxy)bromobenzene (1.0 g, 3.48 mmol) in THF (12 mL) and the I₂ color was discharged within 3-5 min. The remainder of the halide solution was added over a 5 min. period and the resulting mixture was stirred and heated at reflux for 4 h. The flask was cooled to 0°C, sodium pyruvate (420 mg, 3.83 mmol) was added in a single portion, and the resulting mixture was stirred vigorously overnight. The resulting solid mass was broken-up, suspended in Et₂O (50 mL) and collected by vacuum filtration. The filter cake was washed with Et₂O (2 × 25 mL), allowed to air dry and was then transferred to a flask and suspended in H₂O (10 mL). After stirring for 15 min., con. HCl (0.7 mL) was added along with EtOAc (25 mL) and the mixture was stirred until the phases cleared. The phases were separated and the aqueous phase was extracted with EtOAc (2 × 25 mL). All organic phases were washed with H₂O (2 × 20 mL), brine (2 × 25 mL), combined and dried (Na₂SO₄). Solvents were evaporated in vacuo to afford the title compound as a light yellow, dense oil, 660 mg (66%); ¹H NMR (CDCl₃): 57.45-7.4 (d,2H), 6.84-6.8 (d,2H), 1.81 (s,3H), 0.98 (s,9H), 0.19 (s,6H).

(b) Preparation of Ethyl 2-(4-(t-butyldimethylsilyloxy)phenyl)lactate

To a solution of 2-(4-t-butyldimethylsilyloxy)phenyl-lactic acid (2.14 g, 7.23 mmol) in dry DMF was added N,N-diisopropylethylamine (2.26 g,

14.46 mmol) and EtI (2.26 g, 14.46 mmol) and the resulting mixture was stirred at room temperature overnight. The mixture was diluted with Et₂O (100 mL) and washed with H₂O (4 × 40 mL), 1N aq. HCl (2 × 10 mL), saturated aq. NaHCO₃ (1 × 30 mL) and brine (1 × 50 mL). The aqueous washes were extracted with Et₂O (1 × 50 mL) and the Et₂O phases were combined, dried (MgSO₄) and concentrated in vacuo to afford a clear yellow oil, 2.32 g. The product was purified by column chromatography on silica gel to yield the tide compound as a clear, colorless oil, 1.36 g; ¹H NMR (CDCl₃): δ 7.39 (d,2H), 6.80 (d,2H), 4.24-4.20 (m,2H), 3.74 (s,1H), 1.75 (s,3H), 1.25 (t,3H), 0.98 (s,9H), 0.19 (s,6H). (c) Preparation of Ethyl 2-(4-hydroxyphenyl)lactate

To a solution of ethyl 2-(4-(t-butyldimethyl-silyloxy)phenyl)lactate (14.0 g, 44.7 mmol) in CH₃CN (225 mL) was added 47% aq. HF (5 mL) and the resulting mixture was stirred overnight. The solvent volume was reduced to approximately 150 mL by rotary-evaporation and then the acid was quenched by the addition of saturated aq. NaHCO₃ (160 mL). Precipitated solids were dissolved by the addition of H₂O (50 mL) and the reaction mixture was extracted with Et₂O (3 × 150 mL). The extracts were washed with H₂O (2 × 150 mL), brine

(2 × 150 mL), combined and dried (MgSO₄). Evaporation of solvents in vacuo yielded crude material as an orange oil which was subjected to column

chromatography on silica gel eluting with 10% EtOAc/hexane to afford pure tide compound as a dense, orange oil, 7.1 grams (75%); IR (neat): 3408, 2983, 2939, 1892, 1724, 1514, 1444, 1255 cm^-1; ¹H NMR (CDCl₃): δ 7.36 (d,2H), 6.77 (d,2H), 6.35 (bs, 1H), 4.28-4.08 (m,2H), 3.95 (s, 1H), 1.76 (s,3H), 1.24 (t,3H).

(d) Preparation of Ethyl 2-(4-(2-methylbenzyloxy)phenyl)lactate

A mixture of ethyl 2-(4-hydroxyphenyl)lactate (1.0 g, 4.7 mmol), powdered K₂CO₃ (6.3 g, 47 mmol) and 2-methylbenzylbromide (870 mg, 4.7 mmol) in dry acetone (35 mL) was heated at a gentle reflux for 4 h at which time analysis by thin layer chromatography indicated no starting material remained. The mixture was diluted with Et₂O (75 mL) and washed with H₂O (2 × 50 mL) and brine (2 × 50 mL). The aqueous washes were extracted with Et₂O (75 mL) and the ether phases were combined, dried (MgSO₄) and concentrated under reduced pressure to afford the tide compound as a yellow solid, 1.41 g, (95%); ¹H NMR (CDCl₃): δ 7-52 (d,2H), 7.44-7.40 (m,1H), 7.26 (s,3H), 7.00 (d,2H), 5.05 (s,2H), 4.28-4.21 (m,2H), 3.87 (s,1H), 2.40 (s,3H), 1.80 (s,3H), 1.27 (t,3H).

(e) Preparation of 5-Methyl-5-(4-((2-methylphenyl)methoxy)-phenyl)-3- (phenylamino)-2,4-oxazolidinedione

To a solution of euiyl2-(4-(2-methylbenzyloxy)-phenyl)lactate (1.41 g, 4.5 mmol) in CH₂Cl₂ (10 mL) was added 1,1'-carbonyldiimidazole (1.33 g, 8.2 mmol) and the resulting mixture was heated at reflux for 3 h. Analysis by ti-tin layer chromatography indicated all starting material had been consumed. The mixture was diluted with Et₂O (100 mL) and washed widi H₂O (2 × 50 mL) and brine (2 × 50 mL). The aqueous washes were extracted with Et₂O

(1 × 75 mL) and the organics were combined and dried (MgSO₄). Solvent was removed in vacuo to yield an oily residue which was dissolved in CH₂Cl₂ (10 mL), treated with PhNHNH₂ (680 mg, 6.3 mmol) and HOAc (0.48 mL, 8.2 mmol) and stirred at room temperature overnight. The solution was then diluted with ether (150 mL) and washed with 1N aq. HCl (2 × 50 mL), saturated aq. NaHCO₃ (2 × 50 mL) and brine (2 × 50 mL). The aqueous washes were extracted widi ether (1 × 150 mL) and the organics were combined and dried (MgSO₄). Evaporation of solvent in vacuo yielded an orange solid, 1.5 g, which was purified by column chromatography (15 g of silica gel eluted with 5% EtOAc/hexane (10 × 15 mL), 15% EtOAc/hexane (10 × 15 mL), 20%

EtOAc/hexane (10 × 15 mL), 25% EtOAc/hexane (10 × 15 mL)) to afford the tide compound as an offwhite solid, 1.13 g; (63%); m.p. 121-125°C; IR (mineral oil): 3259, 1833, 1751, 1605, 1514, 1461, 1377 cm^-1; ¹H NMR (CDCl₃): δ 7.56 (d,2H), 7.34-7.30 (m,6H), 7.15-7.00 (m,3H), 6.78 (d,2H), 6.06 (s,1H), 5.03 (s,2H), 2.41 (s,3H), 1.98 (s,3H).

EXAMPLE 2

(a) Preparation of Ethyl 2-(4-(l-phenylethoxy)phenyl)lactate

A mixture of ethyl 2-(4-hydroxyphenyl)lactate (1.0 g, 4.7 mmol), powdered K₂CO₃ (6.3 g, 47 mmol) and (1-bromoethyl)benzene (880 mg, 4.7 mmol) in dry acetone (35 mL) was heated at a gentle reflux for 4 h at which time analysis by thin layer chromatography indicated no starting material remained. The mixture was diluted with Et₂O (100 mL) and washed with H₂O (2 × 50 mL) and brine (2 x 50 mL). The aqueous washes were extracted with Et₂O (100 mL) and the ether phases were combined, dried (MgSO₄) and concentrated under reduced pressure to afford me tide compound as a clear yellow oil, 1.3 g, (88%); IR (neat): 3507, 2980, 1726, 1608, 1583, 1450, 1244 cm ^-1; ¹H NMR (CDCl₃):

δ 7.36-7.30 (m,6H), 7.25-7.22 (t,1H), 6.81 (d,2H), 5.30-5.26 (m,1H), 4.23-4.13 (m,2H), 3.70 (s,1H), 1.70 (s,3H), 1.62 (d,3H), 1.24-1.21 (m,3H).

(b) Preparation of 5-Methyl-5-(4-(1-phenylethoxy)phenyl)-3-phenylamino-

2,4-oxazolidinedione

To a solution of ethyl 2-(4-(1-phenylethoxy)phenyl)lactate

(1.21 g, 4.1 mmol) in CH₂Cl₂ (10 mL) was added 1,1'-carbonyldiimidazole

(1.21 g, 7.4 mmole) and the resulting mixture was heated at reflux for 5 h. Thin layer chromatography indicated all starting material had been consumed. The mixture was diluted with Et₂O (100 mL) and washed with H₂O (2 × 50 mL) and brine (2 × 50 mL). The aqueous washes were extracted with Et₂O (1 × 75 mL) and the organics were combined and dried (MgSO₄). Solvent was removed in vacuo to yield a gummy, orange solid which was dissolved in CH₂Cl₂ (10 mL) treated with PhNHNH₂ (730 mg, 7.9 mmol) and HOAc (0.43 mL, 7.4 mmol) and stirred at room temperature for 60 h. The solution was then diluted with Et₂O (100 mL) and washed with 1N aqueous HCl (2 × 50 mL), saturated aqueous NaHCO₃ (2 × 50 mL) and brine (2 × 50 mL). The aqueous washes were extracted with Et₂O (1 × 100 mL) and the organics were combined and dried (MgSO₄). Evaporation of solvent in vacuo afforded a light brown solid, 410 mg, m.p. 119-122°C. IR (mineral oil): 3276, 1835, 1753, 1607, 1245 cm^-1; ¹H NMR (CDCl₃): δ 7.39-6.70 (m,14H), 5.98 (s,1H), 5.33-5.29 (m,1H), 1.92 (s,3H), 1.64 (dJ=6.4Hz,3H).

EXAMPLE 3

Preparation of 4-Imino-5-methyl-5-[4-[2-(methylphenyl)methoxy]phenyl]- 3- phenylamino-2-oxazoIidinone hydrobromide To a stirred solution of 4'-hydroxyacetophenone (25.9 g) and α- bromo-o-xylene (25.5 mL) in acetone (200 mL) was added potassium carbonate (13.2 g), and the mixture was boiled under reflux for 16 h, filtered, and the filtrate evaporated to a white solid. The solid was mixed with ethyl acetate and water, the layers separated, and the organic solution washed with water and saturated brine and dried (MgSO₄). The filtered solution was evaporated to a white solid, which was recrystallized from ethyl acetate, providing 33.5 g of

1-[4-[2-(methylphenyl)methoxy]phenyl]ethanone as a white solid,

m.p.98-100°C. Anal. Calcd for C₁₆H₁₆O₂: C 79.97; H 6.71; Anal. Fd: C 79.62, H 6.74.

To a solution of the above-obtained ketone product (31.4 g) in methylene chloride (150 mL) was added zinc iodide (0.5 g); the mixture was set into a water bath, trimethylsilyl cyanide (18.5 mL) added, and the mixture stirred overnight. Thin-layer chromatography on silica gel (5:1 chloroform/hexane, v/v, eluent) showed the ketone had been completely consumed. The mixture was washed with water (2X) and saturated brine, dried (MgSO₄), and the filtered solution evaporated to a yellow oil (44.6 g), the trimethylsilyl cyanohydrin of the starting ketone.

To a solution of the trimethylsilyl cyanohydrin (58 g) in THF (75 mL) was added cone, hydrochloric acid (40 mL), and the mixture evaporated in vacuum to an orangish turbid liquid. The mixture was mixed with water and benzene. The benzene solution was washed with water and saturated brine, dried (MgSO₄), and the filtered solution evaporated to an orangish crystalline solid, the cyanohydrin of 1-[4-[2-(methylphenyl)methoxy]phenyl]ethanone, which was used directly in the next reaction step.

The cyanohydrin was dissolved in THF (200 mL), treated with

1,1'-carbonyldiimidazole, the mixture stirred overnight, and evaporated to a yellow grease. The grease was dissolved in butyl chloride and the solution washed with ice-cold water (2X) and cold saturated brine, dried (MgSO₄), and the filtered solution evaporated to an oil (64.2 g); the IR spectrum of the oil showed strong absorption at 1773 cm^-1, due to the carbonyl group of the imidazolylcarbonyl derivative of the cyanohydrin.

To a solution of the above imidazolylcarbonyl derivative (53.5 g) in THF (150 mL) was slowly added phenylhydrazine (14.5 mL) with icebath cooling. The mixture was stirred overnight, then boiled under reflux for one hour, and evaporated to a red oil. The oil was dissolved in butyl chloride and the solution washed with water (3X), saturated sodium bicarbonate solution and saturated brine, dried (MgSO₄), and the filtered solution evaporated to a red oil. A portion of the oil was chromatographed on silica gel (5:1 chlorofoim/ethyl acetate, v/v, eluent), providing a yellow grease. An ether solution of the grease was treated with a solution of HBr in acetic acid, precipitating the tide product as an off-white solid, m.p. 115-120°C, dec. The IR spectrum (mineral oil mull) showed absorption at 1711 (imino salt) and 1834 cm^-1 (carbonyl of the 4-imino-2-oxazolidinone ring). Anal. Calcd for C₂₄H₂₃N₃ .HBr. C 59.76; H 5.01; N 8.71; Br 16.57. Anal. Fd: C 58.55; H 5.05; N 8.47; Br 16.81. Specific compounds mat can be made by this invention are described in the

Tables which follow. These are intended to be only exemplary, and are not all-inclusive. Formulae denoted as Formula Ic through Iq are various subsets of the compounds of Formula I and all substituents are as defined above for Formula I.

Using the procedures outiined in Schemes 1-5 and the Examples, the compounds of Tables 1-14 can be prepared. The following are a list of abbreviations and their definitions used in the Tables which follow. Unless indicated otherwise, alkyl, alkenyl, and alkynyl radicals are the normal isomers. For example, "pentyl" implies the w-pentyl isomer. The numbering system for heterocyclic groups is defined in the following way. First, hetero atoms contained in the ring are given the lowest possible numbers using the accepted rules of heterocycle numbering. Then, the point of attachment of the radical is the position assigned the highest priority. For example, the attached group at C-3 in 6-MeOC(=O)-3-pyridyl is higherpriority than the MeOC(=O) substituent. t - is tertiary OMe - is methoxy

s - is secondary SMe - is methylthio

n - is normal SEt - is ethylthio

i - is iso NO₂ - is nitro

Me -is methyl CN - is cyano

Et - is ethyl

Ph - is phenyl

Compounds of this invention will generally be used in formulation with an agriculturally suitable composition. The fungicidal compositions of the present invention comprise an effective amount of at least one compound of Formula I as defined above and at least one of (a) a surfactant, (b) an organic solvent, and (c) at least one solid or liquid diluent. Useful formulations can be prepared in conventional ways. They include dusts, granules, pellets, solutions, suspensions, emulsions, wettable powders, emulsifiable concentrates, dry flowables and the like. Sprayable formulations can be extended in suitable media and used at spray volumes from about one to several hundred liters per hectare. High strength compositions are primarily used as intermediates for further formulation. The formulations will typically contain effective amounts of active ingredient, diluent and surfactant within the following approximate ranges which add up 100 weight percent.

Weight Percent

Active

Ineredient Diluent Surfactant

Wettable Powders 25-90 0-74 1-10

Oil Suspensions, Emulsions, 5-50 40-95 0-15 Solutions, (including Emulsifiable

Concentrates)

Dusts 1-25 70-99 0-5

Granules, Baits and Pellets 0.01-99 5-99.99 0-15

High Strength Compositions 90-99 0-10 0-2

Typical solid diluents are described in Watkins, et al., Handbook of Insecticide Dust Diluents and Carriers, 2nd Ed., Dorland Books, Caldwell, New Jersey. Typical liquid diluents and solvents are described in Marsden, Solvents Guide, 2nd Ed., Interscience, New York, (1950). McCutcheon's Detergents and Emulsifiers Annual, Allured Publ. Corp., Ridgewood, New Jersey, as well as Sisely and Wood, Encyclopedia of Surface Active Agents, Chemical Publ. Co., Inc., New York, (1964), list surfactants and recommended uses. All formulations can contain minor amounts of additives to reduce foam, caking, corrosion, microbiological growth, etc.

Methods for formulating such compositions are well known. Solutions are prepared by simply mixing the ingredients. Fine solid compositions are made by blending and, usually, grinding as in a hammer mill or fluid energy mill. Water-dispersible granules can be produced be agglomerating a fine powder

composition; see for example, Cross et al., Pesticide Formulations, Washington, D.C., (1988), pp 251-259. Suspensions are prepared by wet-milling; see, for example, U.S.3,060,084. Granules and pellets can be made by spraying the active material upon preformed granular carriers or by agglomeration techniques. See Browning, "Agglomeration". Chemical Engineering, December 4, 1967, pp 147-148, Perry's Chemical Engineer's Handbook, 4th Ed., McGraw-Hill, New York, (1963), pp 8-57 and following, and WO 91/13546. Pellets can be prepared as described in U.S. 4,172,714. Water-dispersible and water-soluble granules can be prepared as taught in DE 3,246,493.

For further information regarding the art of formulation, see U.S.

3,235,361, Col. 6, line 16 through Col. 7, line 19 and Examples 10 through 41; U.S. 3,309,192, Col. 5, line 43 through Col. 7, line 62 and Examples 8, 12, 15, 39, 41, 52, 53, 58, 132, 138-140, 162-164, 166, 167 and 169-182; U.S.

2,891,855, Col. 3, line 66 through Col. 5, line 17 and Examples 1-4; Klingman, Weed Control as a Science, John Wiley and Sons, Inc., New York, (1961), pp 81-96; and Hance et al., Weed Control Handbook, 8th Ed., Blackwell Scientific Publications, Oxford, (1989).

In the following Examples, all percentages are by weight and all formulations are worked up in conventional ways. Compound numbers refer to Index Table A hereinafter.

Example A

Wettable Powder

Compound 3 65.0% dodecylphenol polyethylene glycol ether 2.0% sodium ligninsulfonate 4.0% sodium silicoaluminate 6.0% montmorillonite (calcined) 23.0%.

Example B

Granule

Compound 3 10.0% attapulgite granules (low volative

matter, 0.71/0.30 mm; U.S.S. No.

25-50 sieves) 90.0%.

Example C

Extruded Pellet

Compound 3 25.0% anhydrous sodium sulfate 10.0% crude calcium ligninsulfonate 5.0% sodium alkylnaphthalenesulfonate 1.0% calcium/magnesium bentonite 59.0%. Example D

Emulsifable Concentrate

Compound 3 20.0% blend of oil soluble sulfonates

and poly oxyethylene ethers 10.0% isophorone 70.0%.

The compounds of this invention are useful as plant disease control agents. The present invention therefore further comprises a method for controlling plant diseases caused by fungal plant pathogens comprising applying to the plant or portion thereof to be protected, or to the plant seed or seedling to be protected, an effective amount of a compound of Formula I as defined above or a fungicidal composition containing said compound. The compounds and compositions of this invention provide control of diseases caused by a broad spectrum of fungal plant pathogens in the Basidiomycete, Ascomycete, Oomycete and Deuteromycete classes. They are effective in controlling a broad spectrum of plant diseases, particularly foliar pathogens of ornamental, vegetable, field, cereal, and fruit crops. These pathogens include Plasmopara viticola, Phytophthora infestans, Peronospora tabacina, Pseudoperonospora cubensis, Pythium aphanidermatum, Alternaria brassicae, Septoria nodorum, Cercosporidiumpersonatum,

Cercospora arachidicola, Pseudocercosporella herpotrichoides, Cercospora beticola, Botrytis cinerea, Monilinia fructicola, Pyricularia oryzae, Podosphaera leucotricha, Venturia inaequalis, Erysiphe graminis, Uncinula necatur, Puccinia recondita, Puccinia graminis, Hemileia vastatrix, Puccinia striiformis, Puccinia arachidis, Rhizoctonia solani, Sphaerotheca fuliginea, Fusarium oxysporum, Verticillium dahliae, Pythium aphanidermatum, Phytophthora megasperma and other generea and species closely related to these pathogens.

Compounds of this invention can also be mixed with one or more other insecticides, fungicides, nematocides, bactericides, acaricides, semiochemicals, repellents, attractants, pheromones, feeding stimulants or other biologically active compounds to form a multi-component pesticide giving an even broader spectrum of agricultural protection. Examples of other agricultural protectants with which compounds of this invention can be formulated are: insecticides such as monocrotophos, carbofuran, tetrachlorvinphos, malathion, parathion— methyl, methomyl, chlordimeform, diazinon, deltamethrin, oxamyl, fenvalerate, esfenvalerate, permethrin, profenofos, sulprofos, triflumuron, difiubenzuron, methoprene, buprofezin, thiodicarb, acephate, azinphosmethyl, chlorpyrifos, dimethoate, fipronil, flufenprox, fonophos, isofenphos, methidathion, methamidophos, phosmet, phosphamidon, phosalone, pirimicarb, phorate, terbufos, trichlorfon, methoxychlor, bifenthrin, biphenate, cyfiuthrin, fenpropathrin, fluvalinate, flucythrinate, tralomethrin, metaldehyde and rotenone; fungicides such as carbendazim, thiuram, dodine, maneb, chloroneb, benomyl, cymoxanil, fenpropidine, fenpropimorph, triadimefon, captan, thiophanate-methyl, thiabendazole, phosethyl-A1, chlorothalonil, dichloran, metalaxyl, captafol, iprodione, oxadixyl, vinclozolin, kasugamycin, myclobutanil, tebuconazole, difenoconazole, diniconazole, fluquinconazole, ipconazole, metconazole, penconazole, propiconazole, uniconzole, flutriafol, prochloraz, pyrifenox, fenarimol, triadimenol, diclobutrazol, copper oxychloride, furalaxyl, folpet, flusilazol, blasticidin S, diclomezine, edifenphos, isoprothiolane, iprobenfos, mepronil, neo-asozin, pencycuron, probenazole, pyroquilon, tricyclazole, validamycin, and flutolanil; nematocides such as aldoxycarb, fenamiphos and fosthietan; bactericides such as oxytetracyline, streptomycin and tribasic copper sulfate; acaricides such as binapacryl, oxythioquinox, chlorobenzilate, dicofol, dienochlor, cyhexatin, hexythiazox, amitraz, propargite, tebufenpyrad and fenbutatin oxide; and biological agents such as Bacillus thuringiensis, baculovirus and avermectin B.

In certain instances, combinations with other fungicides having a similar spectrum of control but a different mode of action will be particularly

advantageous for resistance management.

Plant disease control is ordinarily accomplished by applying an effective amount of a compound of this invention either pre— or post— infection, to the portion of the plant to be protected such as the roots, stems, foliage, fruit, seeds, tubers or bulbs, or to the media (soil or sand) in which the plants to be protected are growing. The compounds can also be applied to the seed to protect the seed and seedling.

Rates of application for these compounds can be influenced by many factors of the environment and should be determined under actual use conditions.

Foliage can normally be protected when treated at a rate of from less than 1 g/ha to 5,000 g/ha of active ingredient. Seed and seedlings can normally be protected when seed is treated at a rate of from 0.1 to 10 g per kilogram of seed.

The following Tests demonstrate the control efficacy of compounds of this invention on specific pathogens. The pathogen control protection afforded by the compounds is not limited, however, to these species. See Index Table A for compound descriptions.

Test compounds were first dissolved in acetone in an amount equal to 3% of the final volume and then suspended at a concentration of 200 ppm in purified water containing 250 ppm of the surfactant Trem^® 014 (polyhydric alcohol esters). The resulting test suspensions were then used in the following tests.

TESTA

The test suspension was sprayed to the point of run-off on wheat seedlings. The following day the seedlings were inoculated with a spore suspension of Puccinia recondita (the causal agent of wheat leaf rust) and incubated in a saturated atmosphere at 20°C for 24 h, and then moved to a growth chamber at 20°C for 6 days, after which disease ratings were made.

TESTB

The test suspension was sprayed to the point of run-off on rice seedlings. The following day the seedlings were inoculated with a spore suspension of Pyricularia oryzae (the causal agent of rice blast) and incubated in a saturated atmosphere at 27°C for 24 h, and then moved to a growth chamber at 30°C for 5 days, after which disease ratings were made.

TEST C

The test suspension was sprayed to the point of run-off on tomato seedlings.

The following day the seedlings were inoculated with a spore suspension of Phytophthora infestans (the causal agent of potato and tomato late blight) and incubated in a saturated atmosphere at 20°C for 24 h, and then moved to a growth chamber at 20°C for 5 days, after which disease ratings were made.

TEST D

The test suspension was sprayed to the point of run-off on potato seedlings. The following day the seedlings were inoculated with a spore suspension of Phytophthora infestans (the causal agent of potato and tomato late blight) and incubated in a saturated atmosphere at 20°C for 24 h, and then moved to a growth chamber at 20°C for 5 days, after which disease ratings were made.

TEST E

The test suspension was sprayed to the point of run-off on grape seedlings. The following day the seedlings were inoculated with a spore suspension of Plasmopara viticola (the causal agent of grape downy mildew) and incubated in a saturated atmosphere at 20°C for 24 h, moved to a growth chamber at 20°C for 6 days, and then incubated in a saturated atmosphere at 20°C for 24 h, after which disease ratings were made.

Table 15

Cmpd. Test Test Test Test Test

No. A B C D E

1 98 27 52 9 100*

2 98 27 90* 43 100*

3 100* 49* 90* 100* 100*

4 100* 27* 99* 98* 100*

5 72 0 52* 53 100*

6 88* 100* 23* 65 100*

7 85 100* 47 78 100*

8 100* 19* 93* 95* 100*

9 98 0 93* 53 100*

10 98 0* 93* 100 100*

11 97* 0 86* 80 100*

12 99* 31* 60* 86 100*

13 84* 0 60 100 100*

14 100* 31* 96* 83 100*

15 97* 52* 74* 98 100*

16 90* 24* 85* 80 100*

17 95* 24* 97* 76 100*

18 98* 24* 20* 41* 100*

19 96* 24* 20* 15 100*

20 100* 84 99 100 100* 21 99* 24* 61* 54* 100*

22 93 24* 85 69 100*

23 94 24* 20* 100 100*

24 100 99 96 100 100*

25 88 0 73* 55* 97*

26 96 35 73 29 98*

27 96 60 58 96 100*

28 99 0 84 81 100*

29 100 82 99 100 100*

* = The compound was sprayed at a concentration of 40 ppm.

Claims

What is claimed is:

1. A compound of Formula I

wherein:

A is O or NH;

R¹ is H; methyl; or ethyl;

R³ is phenyl optionally substituted with R⁵;

R⁴ is H or methyl;

R⁵ is F; Cl; or C₁-C₄ alkyl; and

R² is selected from the group consisting of substituents of Formulae A, B and C:

,

and

such that:

X is CHR⁶Q or QCH₂;

Q is O or S; G is a phenyl, naphthalenyl, pyridinyl, furanyl, thienyl, indolyl,

T is CH or N;

U is O; S; NH; or NCH₃;

R⁶ is H; methyl; or ethyl;

alkylthio; allylthio; allyloxy; C₁-C₄ haloalkoxy; cyano;

R⁸ is F; Cl; Br; C₁-C₃ alkyl; or trifluoromethyl;

R⁹ is H or F;

C₁-C₄ alkylthio; allylthio; allyloxy; C₁-C₄ haloalkoxy; cyano;

carbomethoxy; carboethoxy; phenoxy; nitro; amino; C₁-C₆ alkoxy; or dimethylamino; or

when G is an optionally substituted phenyl ring, and:

(ii) when R⁸ is bonded to C-2 of G, and X is CHR⁶Q, then R⁸ and R⁶ can be taken together to form R⁸-R⁶ which is ZCH₂CH₂, ZCH₂CH₂CH₂, ZCH=CH, CH₂ZCH₂, ZCH₂, or CH=CH; or

(iii) when R⁹ is bonded to C-3 of the phenyl ring, and X is CHR⁶Q, then R⁶ and R⁹ can be taken together to form R⁶-R⁹ which is CH₂J, or CH₂; or

(iv) when R⁸ is bonded to C-2 of G, and R⁹ is bonded to C-3 of the phenyl ring, then R⁸ and R⁹ can be taken together to form

R⁸-R⁹ which is CH₂, CH(CH₃), or CH₂CH₂;

J, W, and Z are each independently CH₂, O, or S;

provided that (i) when A is O, R¹ is methyl, R² is a substituent of Formula A, R³ is phenyl, X is CH₂O and R⁴ and R⁹ are H, then G is other than unsubstituted phenyl; and

(ii) when A is NH, Q is O, R¹ is methyl, R² is a substituent of Formula A, R³ is phenyl, and R⁴, and R⁶ are H, then G is other than optionally substituted phenyl.

2. A compound of Claim 1, wherein

R² is a substituent of Formula A and X is CHR⁶Q;

G is phenyl optionally substituted with R⁷ or with R⁷ and R⁸;

1-naphthalenyl; or 2-naphthalenyl;

carboethoxy; or dimethylamino; or

(ϋ) when A is NH, Q is O, and R⁶ is H, then R⁷ is other than CF₃, cyano or CF₃O.

3. A compound of Claim 1, wherein

R¹ is methyl;

R² is a substituent of Formula A;

R³ is phenyl;

R⁴ is H;

R⁹ is H; and

G is a phenyl, naphthalenyl, pyridinyl, or furanyl, each optionally substituted with R⁷, R⁸, or R⁷ and R⁸.

4. A compound of Claim 3 , wherein

X is CHR⁶Q;

Q is O;

R⁶ is H or methyl; and G is a phenyl optionally substituted with R⁷, R⁸, or R⁷ and R⁸.

5. A compound of Claim 4 which is:

5-methyl-5-(4-(1-phenylethoxy)phenyl)-3-phenylamino-2,4- oxazolidinedione.

6. A fungicidal composition comprising an effective amount of a compound of Formula I

wherein:

A is O orNH;

R¹ is H; methyl; or ethyl;

R³ is phenyl optionally substituted with R⁵;

R⁴ is H or methyl;

R⁵ is F; Cl; or C₁-C₄ alkyl; and

,

and

such that:

X is CHR⁶Q or QCH₂;

Q is O or S;

G is a phenyl, naphthalenyl, pyridinyl, furanyl, thienyl, indolyl,

N-methylindolyl, benzo[b]furanyl, benzo[b]thienyl, quinolinyl, isoquinolinyl, pyrrolyl, N-methylpyrrolyl or N-ethylpyrrolyl each optionally substituted with R⁷, R⁸, or R⁷ andR⁸; such that the point of attachment to X is a carbon atom of G;

T is CH or N;

U is O; S; NH; or NCH₃;

R⁶ is H; methyl; or ethyl;

alkylthio; allylthio; allyloxy; C₁-C₄ haloalkoxy; cyano;

R⁸ is F; CI; Br, C₁-C₃ alkyl; or trifluoromethyl;

R⁹ is H or F;

C₁-C₄ alkylthio; allylthio; allyloxy; C₁-C₄ haloalkoxy; cyano;

when G is an optionally substituted phenyl ring, and: (i) when R⁷ and R⁸ are bonded to adjacent carbons, then R⁷ and R⁸ can be taken together to form R⁷-R⁸ which is CH₂CH₂W, WCH₂CH₂, or WCH₂CH₂CH₂; or

(ϋ) when R⁸ is bonded to C-2 of G, and X is CHR⁶Q, then R⁸ and R⁶ can be taken together to form R⁸-R⁶ which is ZCH₂CH₂,

ZCH₂CH₂CH₂, ZCH=CH, CH₂ZCH₂, ZCH₂, or CH=CH; or (iii) when R⁹ is bonded to C-3 of the phenyl ring, and X is CHR⁶Q, then R⁶ and R⁹ can be taken together to form R⁶-R⁹ which is CH₂J, or CH₂; or

J, W, and Z are each independently CH₂, O, or S;

provided that

(ii) when A is NH, Q is O, R¹ is methyl, R² is a substituent of

Formula A, R³ is phenyl, and R⁴, and R⁶ are H, then G is other than optionally substituted phenyl;

and at least one of (a) a surfactant, (b) an organic solvent, and (c) at least one solid or liquid diluent.

7. A method for controlling plant diseases caused by fungal plant pathogens comprising applying to the plant or portion thereof to be protected, or to the plant seed or seedling to be protected, an effective amount of a compound of Formula I.

wherein:

A is O or NH; R¹ is H; methyl; or ethyl;

R³ is phenyl optionally substituted with R⁵;

R⁴ is H or methyl;

R⁵ is F; Cl; or C₁-C₄ alkyl; and

,

and

such that:

X is CHR⁶Q or QCH₂;

Q is O or S;

G is a phenyl, naphthalenyl, pyridinyl, furanyl, thienyl, indolyl,

N-methylindolyl, benzo[b]furanyl, benzo[b]thienyl, quinolinyl, isoquinolinyl, pyrrolyl, N-methylpyrrolyl or N-ethylpyrrolyl each optionally substituted with R⁷, R⁸, or R⁷ and R⁸; such that the point of attachment to X is a carbon atom of G;

T is CH or N;

U is O; S;NH; or NCH₃;

R⁶ is H; methyl; or ethyl;

alkylthio; allylthio; allyloxy; C₁-C₄ haloalkoxy; cyano;

R⁸ is F; Cl; Br; C₁-C₃ alkyl; or trifluoromethyl; R⁹ is H or F;

C₁-C₄ alkylthio; allylthio; allyloxy; C₁-C₄ haloalkoxy; cyano;

when G is an optionally substituted phenyl ring, and:

(ii) when R⁸ is bonded to C-2 of G, and X is CHR⁶Q, then R⁸ and

J, W, and Z are each independently CH₂, O, or S;

provided that

(ii) when A is NH, Q is O, R¹ is methyl, R² is a substituent of

8. A method for controlling plant diseases caused by fungal plant pathogens comprising applying to the plant or portion thereof to be protected, or to the plant seed or seedling to be protected, an effective amount of a composition comprising a compound of Formula I of Claim 7 and at least one of (a) a surfactant, (b) an organic solvent, and (c) at least one solid or liquid diluent.

9) The method of Claim 7, wherein the fungal plant pathogens are caused by the plant pathogens Phytophthora infestans and Plasmopara viticola.