CZ20004901A3 - Process for preparing amides - Google Patents

Abstract

Intermediates for the preparation of phenylalkanoic acid amides having excellent germicidal effects, a method of preparation intermediates and a process for preparing starting materials for preparation intermediates. Specifically, the process for preparing amides IV characterized by reacting nitrile I with an acid to form oxazolinone II by intramolecular cyclization and this reaction oxazolinone II and carboxylic compound III in the presence of base.

Description

Technical field

The present invention relates to an amide which is an important intermediate in the preparation of a phenylalkanoic acid amide useful as a fungicide, a process for its preparation, a process for the preparation of an oxazolinone compound which is a starting material used in the preparation of this amide phenylalkanoic acids from this amide.

BACKGROUND OF THE INVENTION

It is known that some phenylalkanoic acid amides are useful as active fungicides (e.g. JP-A-9-48750 and Japanese Patent Application No. 10-296078), but no method for preparing these phenylalkanoic acid amides from oxazolinone compounds is known.

It is generally known to prepare oxazolinone compounds comprising subjecting an amino acid whose amino group is protected by an acyl group to dehydration cyclization (Protective Groups in Organic Synthesis, p. 223, John Wiley & Sons, 1981). In addition, a method is known which comprises the preparation of oxazolinone from acylated aminonitrile using oxalyl chloride or chlorooxoacetate [Tetrahedron, 40. 2395-2404 (1984)]. However, these methods have the disadvantages that it is difficult to obtain the corresponding amino acid or it is impossible to prepare the intended oxazolinone compound on an industrial scale at low cost.

The present invention aims to provide important

«·

intermediates used in the preparation of phenylalkanoic acid amides which exhibit excellent fungicidal action, and novel and simple processes for preparing these intermediates or starting materials used in the preparation of these intermediates.

The essence of the invention

The present inventor has made considerable efforts to solve the above-described object. As a result, the inventor has surprisingly found that an amide, which is an important intermediate for the preparation of phenylalkanoic acid amide, can be readily prepared by reacting an oxazolinone compound with a carboxylic compound (e.g., malonic polyester) in the presence of a base. The present inventor also finds that this oxazolinone compound can be obtained in a simple manner by reacting a readily available nitrile with an acid. The invention is practiced on the basis of the above findings.

The best embodiment of the invention

A detailed description of the invention follows.

The present invention provides the individual inventions described in the following paragraphs [1] to (6).

[1] A process for preparing an amide of formula

in which

R is alkyl, cycloalkyl, haloalkyl, aryl, substituted aryl, arylalkyl, substituted arylalkyl (aryl) - (alkoxy) alkyl or (substituted aryl) - (alkoxy) alkyl,

R ¹ and R ² are independently alkyl, cycloalkyl, haloalkyl, arylalkyl, substituted arylalkyl, aryl, substituted aryl or hydrogen, and these groups may be linked to each other to form a ring together with a carbon atom, to which they are attached, and

R ³ is an alkyl group, a cycloalkyl group, a haloalkyl group, an arylalkyl group, a substituted arylalkyl group, an aryl group, a substituted aryl group or a hydrogen atom which comprises the reaction of a nitrile of the formula · ·

in which

R, R ^x and R ² are as defined above, with an acid obtaining an intramolecular ring closure to form an oxazolinone compound of formula

R-

in which

R, R ^x and R ² are as defined above, and reacting this oxazolinone compound with a carboxylic acid.

4443 4 «4» 44

44444 4,444 4 4 «4444 44 4

444 44 44 44 44 444

in which

Y is a hydrogen atom, a carboxyl group, or a salt of a carboxyl group; and

R ³ is as defined above in the presence of a base.

[2] A process for preparing an oxazolinone compound of the formula

in which

R is an alkyl group, a cycloalkyl group, a haloalkyl group, or a haloalkyl group. 00 000000 0 000 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0000 0 0 0 · 0 · 0 00 0 · 00 00 * aryl, aryl, substituted aryl, arylalkyl, substituted arylalkyl, (aryl) - (alkoxy) alkyl or (substituted aryl) - (alkoxy) alkyl, and

R ¹ and R ² are independently alkyl, cycloalkyl, haloalkyl, arylalkyl, substituted arylalkyl, aryl, substituted aryl or hydrogen, and the two groups may be linked to each other to form a ring together with a carbon atom to which they are attached, comprising reacting a nitrile of the general formula

in which

R, R ¹ and R ² are as defined above, with an acid having intramolecular ring closure.

[3] A process for preparing an amide of formula

in which

R is alkyl, cycloalkyl, haloalkyl, aryl, substituted aryl, arylalkyl, substituted arylalkyl, (aryl) - (alkoxy) alkyl or (substituted aryl) - (alkoxy) alkyl,

R ¹ and R ² are independently alkyl, cycloalkyl, haloalkyl, arylalkyl, substituted arylalkyl, aryl, substituted aryl or hydrogen, and the two groups may be linked to each other to form a ring together with a carbon atom to which they join, and

R ³ is an alkyl, cycloalkyl, haloalkyl, arylalkyl, substituted arylalkyl, aryl, substituted aryl or hydrogen atom;

4444 44 4 4444

444 44 4 44 4 • 44444 4,444 4 4

4,444,444

444 44 44 44 44 444 comprising reacting an oxazolinone compound of the general formula

in which

R ¹ , R ¹ and R ² are as defined above, with the carboxyl compound of the formula 'COOR ³ ' wherein:

Y is a hydrogen atom, a carboxyl group, or a salt of a carboxyl group, and

R ³ is as defined above in the presence of a base.

[4] A process for preparing a ketone of formula

in which

R ¹ and R ² are independently alkyl, cycloalkyl, haloalkyl, arylalkyl, substituted arylalkyl, aryl, substituted aryl, or hydrogen and can be taken together to form a ring together with a carbon atom, to which they join, and

R ⁴ is alkylcarbonyl, cycloalkylcarbonyl, haloalkylcarbonyl, arylcarbonyl, substituted arylcarbonyl, arylalkylcarbonyl, substituted arylalkylcarbonyl, (aryl) - (alkoxy) alkylcarbonyl, (substituted aryl) - (alkoxy) alkylcarbonyl hydrogen, comprising reacting an amide of formula

in which

R is alkyl, cycloalkyl, haloalkyl, aryl, substituted aryl, arylalkyl, substituted arylalkyl, (aryl) - (alkoxy) alkyl or (substituted aryl) - (alkoxy) alkyl,

R ¹ and R ² are as defined above and

R ³ is alkyl, cycloalkyl, haloalkyl, arylalkyl, substituted arylalkyl, aryl, substituted aryl or hydrogen with an acid or base in the presence of water.

[5] The amide preparation process described in [1] or [3] above, wherein the base is selected from alkali metal bases, alkaline earth metal bases, organic amines and pyridines.

9 9

[6] Acid amide of general formula

in which

R ⁵ is alkyl, cycloalkyl, haloalkyl, arylalkyl, substituted arylalkyl, (aryl) - (alkoxy) alkyl or (substituted aryl) - (alkoxy) alkyl, and

R ¹ and R ² are independently alkyl, cycloalkyl, haloalkyl, arylalkyl, substituted arylalkyl, aryl, substituted aryl or hydrogen, and the two groups may be taken together to form a ring together with a carbon atom, to which they join,

R ³ is an alkyl group, a cycloalkyl group, a haloalkyl group, an arylalkyl group, a substituted aryalkyl group, an aryl group, a substituted aryl group or a hydrogen atom.

• ·· »* * * 9 • • ···· • ·· F · • · • iri · • • • · · • · • · ·· • • * « • · ·· • 9 «· ··

The following is a description of the invention according to paragraph [1] above.

In the invention according to paragraph [1], the nitrile of the general formula is first reacted

with an intramolecular ring closure acid that provides an oxazolinone compound of formula

(This method corresponds to the invention described in paragraph [2] above).

The nitrile used as starting material in this method that • η «« · ···· ···· ·· · · · · »* - * j ^e j · ^e j · d • 4" 49 94 4 4 «« The present invention may be any compound that corresponds to the general formula depicted above. In this general formula

R is a straight or branched chain alkyl group having 1 to 6 carbon atoms (hereinafter, carbon atoms, for example, 1 to 6 carbon atoms are described as C1-C6), such as methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, tert-butyl, n-pentyl, n-hexyl or the like, straight or branched C1-C6 haloalkyl such as trifluoromethyl, chloromethyl, dichloromethyl, trichloromethyl a group or the like, a C3-C6 cycloalkyl group such as a cyclopropyl group, a cyclobutyl group, a cyclopentyl group, a cyclohexyl group or the like, an aryl group such as a phenyl group, a naphthyl group or the like, halogen-, C1-C6 alkyl- or C1- C6-alkoxy-substituted aryl such as 2-chlorophenyl, 4-chlorophenyl, 4-methylphenyl, 4-methoxyphenyl or the like, aryl (C 1 -C 6 alkyl) such as phenylmethyl, 1-phenylethyl or the like, halogen-, C 1 -C 6 alkylo- or C 1 -C 6 alkoxy-substituted aryl (C 1 -C 6 alkyl) such as 1- (4-chlorophenyl) ethyl, 1- (4-methylphenyl) ethyl,

1- (4-methoxyphenyl) ethyl or the like, (aryl) - (C1-C6 alkoxy) - (C1-C6 alkyl) group in which the alkyl group is substituted with an aryl group (for example a phenyl group or a naphthyl group) and a C1- C6 alkoxy (e.g., methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, isobutoxy, n-pentyloxy or n-hexyloxy) such as 1-phenyl-1-methoxymethyl or the like, or (substituted aryl) -C6 alkoxy) - (C1-C6 alkyl) group, ve

which is an alkyl group substituted with a halogen-, C1-C6 alkyl- or C1-C6 alkoxy-substituted aryl group (e.g. 2-chlorophenyl, 4-chlorophenyl, 2-fluorophenyl, 4-fluorophenyl, 4-methoxyphenyl, 4-methylphenyl or 2-methylphenyl) and C 1 -C 6 alkoxy (e.g., methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, isobutoxy, n-pentyloxy or n-hexyloxy) such as 1- (4-chlorophenyl) a methoxymethyl group or the like.

R ¹ and R ² are independently C 1 -C 6 straight or branched chain alkyl groups such as methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, tert-butyl , n-pentyl, n-hexyl or the like, straight or branched C1-C6 haloalkyl such as trifluoromethyl, chloromethyl, dichloromethyl, trichloromethyl or the like, C3-C6 cycloalkyl such as cyclopropyl , cyclobutyl, cyclopentyl, cyclohexyl or the like, aryl (C1-C6 alkyl) group such as phenylmethyl, 1-phenylethyl or the like, halogen-, C1-C6 alkyl- or C1-C6 alkoxy-substituted aryl (C1- A C 6 alkyl group such as a 1- (4-chlorophenyl) ethyl group, a 1- (2-chlorophenyl) ethyl group,

1- (4-methylphenyl) ethyl, 1- (4-methoxyphenyl) ethyl or the like, aryl group such as phenyl, naphthyl or the like, halogen-, C1-C6 alkyl- or C1-C6 alkoxy-substituted aryl , such as 2-chlorophenyl, 4-chlorophenyl,

4-methylphenyl, 4-methoxyphenyl or the like or a hydrogen atom. R @ ¹ and R @ ² may be taken together with 15

forming a C3-CS ring together with the carbon atom to which they are attached.

Specific examples of the nitrile having these substituents of the above formula are: N- (1-cyano-1-methylpropyl) acetamide,

N- (1-cyano-1,2-dimethylpropyl) acetamide,

N- (1-cyano-1,2-dimethylpropyl) benzamide,

4-chloro-N- (1-cyano-1,2-dimethylpropyl) benzamide,

4-methyl-N- (1-cyano-1,2-dimethylpropyl) benzamide,

2- (4-chlorophenyl) -N- (1-cyano-1,2-dimethylpropyl) propanamide,

N- (1-cyano-1,2-dimethylpropyl) -2,2,2-trifluoroacetamide,

N- (1-cyano-1,2-dimethylpropyl) cyclopropanamide,

N- (1-cyano-1,2-dimethylpropyl) benzamide,

N- (1-cyano-1,2-dimethylpropyl) -4-chlorobenzamide,

N- (1-cyano-1,2-dimethylpropyl) -4-methoxybenzamide,

N- (1-cyano-1,2-dimethylpropyl) phenylacetamide,

2- (4-chlorophenyl) -N- (1-cyano-1,2-dimethylpropyl) acetamide,

2- (4-methoxyphenyl) -N- (1-cyano-1,2-dimethylpropyl) acetamide,

N- (1-cyano-1-trifluoromethyl-2-methylpropyl) acetamide,

N- (1-cyano-1-phenylpropyl) acetamide

N- [1-cyano-1- (4-chlorophenyl) propyl] acetamide,

N- [1-cyano-1- (4-methoxyphenyl) propyl] acetamide,

N- (1-cyano-1-benzylpropyl) acetamide

N- [1 - {(4-chlorophenyl) methyl} -1-cyanopropyl] acetamide,

N- [1 - {(4-methoxyphenyl) methyl} -1-cyanopropyl] acetamide,

N- (1-cyano-1-cyclopropylethyl) acetamide; and 2- (4-chlorophenyl) -N- (1-cyano-1,2-dimethylpropyl) -2-methoxyacetamide.

Some of the nitriles of the above formula are generally known compounds and otherwise can be prepared, for example, from the corresponding acid halide and aminonitrile,

9 9

9 9 9 ·

9 9 99 9 9 · · 9

-ι / - · · 9 9 · · 9 999 9 «± O 9 9 9999« 9 9

99, 99 99 99 99 999, for example, as described in Organic Synthesis Collective Volume V, p. 336 (1973).

As the acid used in the process of the invention (for intramolecular ring closure reaction), for example, mineral acids such as hydrochloric acid, sulfuric acid and the like, carboxylic acids such as formic acid, acetic acid and the like and acidic ion exchangers such as Amberlist and the like. A combination of two or more types of these acids may be used, but sulfuric acid is preferably used. The amount of acid used may be in such a range that the oxazolinone compound to be prepared does not decompose, but is, for example, 0.1 to 2 moles, preferably 0.5 to 1 moles, per 1 mol of the nitrile of the general formula shown above.

This reaction is carried out in a conventional manner using a solvent. Suitable solvents include, for example, acetic acid esters such as methyl acetate, ethyl acetate, propyl acetate and the like, nitriles such as acetonitrile and the like, ethers such as tetrahydrofuran, dioxane, diethyl ether and the like, aromatic hydrocarbons such as toluene, xylene, chlorobenzene and the like, aliphatic hydrocarbons such as hexane, cyclohexane and the like, aprotic polar solvents such as dimethyl formamide, dimethylacetamide and the like, halogenated aliphatic hydrocarbons such as chloroform, dichloromethane and the like, ethylene glycols such as polyethylene glycol 400 (PEG 400) and similarly, and aliphatic carboxylic acids such as glacial acetic acid and the like. These solvents may be used singly or as mixed solvents containing any proportions of two or more solvents. The amount of solvent used may be such as to allow sufficient mixing, and may be, for example, 0.5

1 to 3 liters, preferably 1 to 3 liters per 1 mol of the nitrile of the general formula shown above.

When the reaction is carried out in the presence of water in an amount of 0.0005 to 1 mol, preferably 0.1 to 1 mol, per 1 mol of the nitrile of the general formula shown above, the yield of the intended product is sometimes high.

The reaction temperature can be selected from -20 ° C to the reflux temperature of the solvent used, but is preferably 0 to 80 ° C. There is no particular limitation on the reaction time, but preferably it is 0.5-12 hours.

Specific examples of the oxazolinone compounds of the above-described general formula obtained as described above may be contemplated

4-Isopropyl-2,4-dimethyl-1,3-oxazol-5-one;

- isopropyl-4-methyl-2-phenyl-1,3-oxazol-5-one,

2- [1- (4-chlorophenyl) ethyl] -4-isopropyl-4-methyl-1,3-oxazol-5-one;

4-ethyl-4-methyl-2-trifluoromethyl-1,3-oxazol-5-one,

- cyclohexyl-4-isobutyl-4-methyl-1,3-oxazol-5-one,

4,4-diethyl-2-pentyl-1,3-oxazol-5-one;

2- (2-chlorophenyl) -4-isopropyl-4-methyl-1,3-oxazol-5-one, 4-benzyl-2,4-dimethyl-1,3-oxazol-5-one,

4- (4-chlorobenzyl) -2,4-dimethyl-1,3-oxazol-5-one;

4- (4-Methoxybenzyl) -2,4-dimethyl-1,3-oxazol-5-one;

4- (4-methylbenzyl) -2,4-dimethyl-1,3-oxazol-5-one and 2- [1- (4-chlorophenyl) -1-methoxymethyl] -4-isopropyl-4-methyl-1, 3-Oxazol-5-one.

Some of these oxazolinone compounds are known compounds or can be prepared by the reaction described above.

- 18 · - ··· · · · · · · · · · · · ·

and in addition using the corresponding amino acid and carboxylic acid halide as starting materials according to the method described, for example, in Bulletin de la Societe Chimique de France, p. 543 (1958).

In the invention described in paragraph [1] above, an oxazolinone compound of the general formula

ΕΚ i

then reacted with a carboxylic compound of formula

COOR ³ in the presence of a base to provide an amide of formula

(this reaction corresponds to the invention described in paragraph [3] above) ·

In the carboxyl compound of the above-represented formula

R ³ is a straight or branched C 1 -C 6 alkyl group such as methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, tert-butyl, n-pentyl, n-hexyl or the like, C3-C6 cycloalkyl, such as cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl or the like, straight or branched C1-C6 haloalkyl such as trifluoromethyl, chloromethyl, 2- fluoroethyl or the like, aryl group such as phenyl, naphthyl or the like, halogen-, C 1 -C 6 alkyl- or C 1 -C 6 alkoxy-substituted aryl group such as 2-chlorophenyl, 4-chlorophenyl, 2-fluorophenyl a group, 4-fluorophenyl, 4-methoxyphenyl, 4-methylphenyl,

2-methylphenyl or the like, aryl (C 1 -C 6 alkyl) · · · »· · · φ · φ · φ · φ ·« · «·« · · · · · A halo, C 1 -C 6 alkyl- or C 1 -C 6 alkoxy-substituted aryl (C 1 -C 6 alkyl) group, such as 1- (4-chlorophenyl); ethyl, 1- (2-chlorophenyl) ethyl, 1- (4-methylphenyl) ethyl, 1- (4-methoxyphenyl) ethyl or the like, or a hydrogen atom.

Y is a hydrogen atom, a carboxyl group or a salt of a carboxyl group. Examples of such salts include alkali metal salts (e.g., sodium or potassium), alkaline earth metals (e.g., calcium or barium), amines (e.g., triethylamine or diethylamine), and pyridines (e.g., pyridine).

Particular examples of the carboxyl compound represented by the general formula above and useful in the present invention may be methyl acetate, ethyl acetate, propyl acetate, butyl acetate, mono-methyl-malonate, mono-ethyl-malonate, mono-tert-butylbutalonate, dithriethylamine malonic acid, ethylmalonate, monocal isopropyl imalonate and malonic acid.

The carboxylic compound represented by the general formula above is a known compound or can be prepared in a known manner, for example, from the corresponding malonic acid diester and base as described in, for example, Journal Organic Chemistry, p. 2536 (1980).

The reaction between the oxazolinone compound of the above formula and the carboxyl compound of the above formula is carried out at any molar ratio of the two compounds. However, the carboxyl compound represented by the above-described formula, for example, usually uses an amount of 0.5 to 3 moles, preferably 1 to 2 moles.

• ·· • · · · • · * · 99 9 9 9 • • · 9 9 9 9 • ··· «· · 9 9 • 9 9 _ · · • · · · · 9 9 9 9 9 9 9 9 • 9 9 » 9 9 9 9

per mole of oxazolinone compound according to the above general formula.

This reaction is usually carried out using a solvent. As the solvent usable in this reaction, for example, acetic esters such as methyl acetate, ethyl acetate, propyl acetate and the like, nitriles such as acetonitrile and the like, ethers such as tetrahydrofuran, dioxane, diethyl ether and the like, aromatic hydrocarbons such as toluene, xylene, chlorobenzene and the like, aprotic polar solvents such as dimethylformamide, dimethylacetamide and the like, halogenated hydrocarbons such as chloroform, dichloromethane and the like, pyridines such as pyridine and the like. These solvents may be used singly or as mixed solvents representing any proportions of two or more solvents. An amount of solvent that allows sufficient agitation of the reaction mixture may be used and may be, for example, 1 to 5 liters, preferably 1 to 3 liters, per 1 mol of the oxazolinone compound of the general formula shown above.

The reaction is carried out in the presence of a base. As the base, for example, alkali metal bases such as sodium hydride, potassium hydride, potassium carbonate, sodium amide, lithium diisopropylamide (LDA) and the like, alkaline earth metal salts such as magnesium ethoxide and the like, organic amines such as is triethylamine, 1,8-diazabicyclo [5.4.0] -7-undecene (DBU) and the like; and pyridines such as dimethylaminopyridine (DMAP) and the like. There is no particular restriction on the amount of base used, provided that this amount does not hinder the reaction, but is, for example, normally 0.1 to 3 mol, preferably 0.1 to 2 mol, per 1 mol of the oxazolinone compound of the formula shown above.

«·· ·· ·· · · ··

9 ·· 9 9 9 9 9 9

999 99 99 999 9

999 99 99 99 9 · 999

This base can be used in combination with a Lewis acid such as magnesium chloride, zinc chloride, boron trifluoride or the like. There is no particular limitation on the amount of Lewis acid used in combination so long as this amount does not hinder the reaction, but is 0.1 to 3 mol, preferably 0.1 to 2 mol, per 1 mol of the oxazolinone compound of the formula shown above.

The reaction temperature can be, for example, from -78 ° C to the reflux temperature of the solvent used, and is preferably from 0 to 100 ° C. There is no particular limitation on the reaction time, but is preferably 1 to 24 hours.

The following is a description of the invention described in paragraph [4] above.

The invention described in paragraph [4] involves the reaction of an amide of the general formula

with an acid or base in the presence of water in which hydrolysis and decarboxylation occur to give the ketone according to the following general formula.

• ·· • 44 4 4 4 4 4 4444 4 44 4 4 4 4 4 4 444 4 4 4 4 4 4 4 4 -4 4 4 4 4 4 4 • 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4

In the amide of the above formula and the ketone of the above formula, R, R ¹ , R ² and R ^{3 have the} same meaning as in the description of the invention according to paragraph [1] above.

In the ketone of the formula shown above, R ⁴ is a straight or branched chain carbonyl group such as acetyl, propionyl, butyryl, valeryl, hexanoyl, pivaloyl and the like, (C 3 -C 6 cycloalkyl) ) a carbonyl group such as a cyclopropylcarbonyl group, a cyclobutylcarbonyl group, a cyclopentylcarbonyl group, a cyclohexylcarbonyl group or the like, a straight or branched (C1-C6 haloalkyl) carbonyl group such as a trifluoroacetyl group, a chloroacetyl group,

3-fluoropropionyl or the like, arylcarbonyl, such as benzoyl or the like, halogen-

C 1 -C 6 alkyl- or C 1 -C 6 alkoxy-substituted arylcarbonyl such as 2-chlorobenzoyl, 4-fluorobenzoyl, 2-methylbenzoyl, 4-methoxybenzoyl or the like, aryl (C 1 -C 6 alkyl) carbonyl such as phenylacetyl group or the like, halogen-, ·· ·· «·

24.w ..

C 1 -C 6 alkyl or C 1 -C 6 alkoxy-substituted aryl (C 1 -C 6) alkylcarbonyl such as 2-chlorophenylacetyl, 4-methylphenylacetyl, 4-methoxyphenylacetyl, 1- (4-chlorophenyl) propionyl or the like, (aryl (C1-C6 alkoxy) (C1-C6 alkyl) carbonyl, in which the alkyl group is substituted with an aryl group (for example a phenyl or naphthyl group) and a C1-C6 alkoxy group (for example methoxy, ethoxy, n-propoxy, isopropoxy, n -butoxy, isobutoxy, n-pentyloxy or n-hexyloxy) such as (1-phenyl-1-methoxy) methylcarbonyl or the like, (substituted aryl) (C1-C6 alkoxy) (C1-C6 alkyl) carbonyl, in which is an alkyl group substituted by a halogen-, C1-C6 alkyl- or C1-C6 alkoxy-substituted aryl group (e.g. 2-chlorophenyl, 4-chlorophenyl, 2-fluorophenyl,

4-fluorophenyl, 4-methoxyphenyl,

4-methylphenyl or 2-methylphenyl) and C 1 -C 6 alkoxy (e.g., methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, isobutoxy, n-pentyloxy or n-hexyloxy-1- (4-) -, such as [[4-]) chlorophenyl) -1-methoxy] methylcarbonyl or the like or a hydrogen atom.

In the process of the invention, the hydrolysis and decarboxylation of the amide in the presence of water is carried out using an acid or a base. As the acid useful in this reaction, for example, mineral acids such as hydrochloric acid, sulfuric acid and the like, acetic acids such as acetic acid, trifluoroacetic acid and the like, sulfonic acids such as p-toluenesulfonic acid and the like, acidic ion exchangers, like Amberlist and the like. Bases useful in this reaction include, for example, hydro25

• 00 0 0 0 0 00 0 0000 0 0 0 0 0 0 0 • 000 0 0 0 0 0 0 0 • 0 0 0 0 0 0 0 0 · 0 0 00 0 0 0 0 0 0

alkali metal oxides such as sodium hydroxide, potassium hydroxide and the like, alkali metal carbonates such as sodium carbonate, potassium carbonate and the like, alkaline earth metal hydroxides such as barium hydroxide and the like, organic amines such as 1,8-diazabicyclo [5.4.0] -7-undecene (DBU) and the like, pyridines such as dimethylaminopyridine (DMAP) and the like, and alcoholates such as sodium methoxide and the like. The reaction is preferably carried out using a mineral acid, particularly preferably hydrochloric acid or sulfuric acid. In the decomposition reaction, the amount of acid or base is not limited as long as it does not decompose the formed ketone of the formula shown above, but is generally between 0.001 to 10 moles, preferably 0.1 to 5 moles, per 1 mol of amide of the above formula.

The reaction is carried out in the presence of water. The amount of water used may be 1 mol (18 ml) or more per 1 mol of the amide of the general formula shown above and is, for example, usually 1 to 5,000 mol (90 liters), preferably 1 to 1,000 mol. When the reaction is carried out using an acid, the amount of water is preferably such that the pH of the reaction mixture is about 4 or less, although this value may vary depending on the type and amount of acid used.

The reaction proceeds well without the use of any solvent, but can be carried out using a solvent. The solvent usable in this decomposition reaction may be any solvent that does not interfere with the reaction. As the solvent, for example, aromatic hydrocarbons such as toluene, xylene, chlorobenzene and the like, acetic esters such as methyl acetate, ethyl acetate, butyl acetate and the like, alcohols such as methanol, ethanol, n-propanol, isopropanol and the like, aprotic polar solvents such as • · · 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 Is dimethylformamide, dimethylacetamide and the like, ether solvents such as diethyl ether, tetrahydrofuran, dioxane, monoglyme, diglyme and the like, aliphatic hydrocarbons such as pentane, n-hexane and the like, nitriles, such as acetonitrile and the like, ketones such as acetone, ethyl (methyl) ketone, isobutyl (methyl) ketone and the like, polyethylene glycols such as polyethylene glycol (PEG) 400 and the like, and water. These solvents may be used singly or as mixed solvents containing any proportions of two or more solvents. The amount of solvent used may be such as to allow sufficient stirring of the reaction mixture, but is typically 0.5 to 5 liters, preferably 1 to 3 liters, per 1 mol of the amide of the above formula.

The reaction temperature is, for example, -20 ° C to the reflux temperature of the solvent used, but preferably 0 to 80 ° C.

There is no particular limitation on the reaction time, but this time is preferably 0.5 to 12 h.

In this reaction, a suitable choice of conditions may even produce a ketone compound of the formula shown above in which R ⁴ is a hydrogen atom, or a compound in which R ⁴ is a substituent other than a hydrogen atom, or a compound in which R ⁴ is a different substituent from the hydrogen atom and after subjecting the compound to isolation and purification to allow further decomposition as necessary to give a compound wherein R ⁴ is a hydrogen atom.

In this reaction, it is considered that R ³ is first hydrolyzed in the reaction system to form a compound in which R ³ is a hydrogen atom (or a salt thereof) as an intermediate, and subsequently the compound (or a salt thereof) is rapidly subjected to de27

99 99 9900 99 9

9999 98 9 9999

9 9 9 9 9

99999 9,999 9 9 • · 9 9 9 9 9 9 9

999 9 · 9 99 99 99 · carboxylation under reaction conditions. It is contemplated that, depending on the reaction conditions used, the amide bond is even hydrolyzed and decomposition proceeds to give a compound in which R ⁴ is a hydrogen atom.

The following is a description of the invention according to paragraph [6].

The invention described in paragraph [6] above provides an acid amide of the above-represented formula. This acid amide can be prepared as described in paragraph [1] above.

In the above general formula

^R is C1-C6 alkyl group, a linear or branched, such as methyl group, ethyl group, n-propyl, isopropyl, n-butyl, sec-butyl, tert-butyl, n-pentyl, n-hexyl or the like, C3-C6 cycloalkyl, such as cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl or the like, straight or branched C1-C6 haloalkyl such as trifluoromethyl, chloromethyl, 2- fluoroethyl or the like, aryl (C1-C6 alkyl) group such as phenylmethyl, 1-phenylethyl or the like, halogen-, C1-C6 alkyl- or C1-C6 alkoxy-substituted aryl (C1-C6 alkyl) group such as 1- (4-chlorophenyl) ethyl, 1- (4-methylphenyl) ethyl, 1- (4-methoxyphenyl) ethyl or the like, (aryl) (C1-C6 alkoxy) (C1-C6 alkyl) group, in which is an alkyl group an aryl-substituted pin (e.g., phenyl or naphthyl) and a C1-C6 alkoxy (e.g., methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy group);

9 9 9 9 9

999 999 9999 · _9 9 9 9 9 9 9 9 9

999 99 99 99 999, isobutoxy, n-pentyloxy or n-hexyl oxy), such as 1-phenyl-1-methoxymethyl or the like, or (substituted aryl) (C1-C6 alkoxy) (C1- (C 6 alkyl) group in which the alkyl group is substituted by a halogen-, C 1 -C 6 alkyl- or C 1 -C 6 alkoxy-substituted aryl group (e.g. 2-chlorophenyl, 4-chlorophenyl, 2-fluorophenyl, 4-fluorophenyl, -methoxyphenyl,

4-methylphenyl or 2-methylphenyl and C1-C6 alkoxy (e.g., methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, isobutoxy, n-pentyloxy or n-hexyloxy) such as 1- (4) -1-methoxymethyl or the like.

R ¹ , R ^a and R ³ are defined as above in paragraph [1].

The acid amide described by the general formula above includes compounds having one or more asymmetric carbon atoms in the molecule and which form enantiomers or diastereomers. The compound of the invention includes all such pure isomers and mixtures thereof (e.g., racemic modifications) in any proportions.

Examples of the compound of the present invention are shown in Table 1. However, the compound of the present invention is not limited to these examples and includes all compounds of the general formula described above.

The abbreviations in Table 1 have the following meanings.

Me: methyl group

Et: ethyl group

- 29. • *> «€ ·· ♦ · ·» 9

9 9 9 9 9 9 9 99 99

9 9

9 9

99 i-Pr: isopropyl group c-Pr: cyclopropyl group t-Bu: tert-butyl group c-Hex: cyclohexyl group

Ph: phenyl

4-Cl-Ph: 4-chlorophenyl

Bn: benzyl group

4-Cl-Bn: 4-chlorobenzyl

1- (4-Cl-Ph) -Et: 1- (4-chlorophenyl) ethyl 6D 9 9 9 9 9 9 9 9

Table 1

Merge- '. ninna no. R ¹ R ² R ³ R ³  Temperature ; melting point (° C) 1 Me Me Me Me 2 Me Et Me Me 3 Et Et Me Me 4 Me i-Pr Et Me 71.0-73.0 5 Me i-Pr t-Bu Me 6 Me i-Pr Et 1- (4-Cl-Ph) -Et 92.5-99.7 7 Me i-Pr Bn 1- (4-Cl-Ph) -Et 8 Me i-Pr Me 1- (4-Cl-Ph) -Et 104 _« 0 ~ 110 _from 0 9 Me i-Pr t-Bu 1- (4-Cl-Ph) -Et 10 cf ₃ Me Ph 4-Cl-Bn 11 c-Pr Me 4-Cl-Ph cf ₃ 12 Ph Me 4-Cl-Bn c-Hex 13 4-Cl-Ph Me c-Hex Me 14 Bn Me CH ₂ CF ₃ Me 15 Dec 4-Cl-Bn Me Et Me 16 Me i-Pr i-Pr 1- (4-Cl-Ph) -Et 110.4-112.8 17 Me i-Pr Et 4-Cl-Bn 96.3-98.3 18 Me i-Pr Et 4-Cl _and-CH3 0-Bn 19 Dec Me i-Pr H 1- (4-Cl-Ph) -Et 161 ^ 8-164.8

· · © © © © © © © © © © © © © © © © © © © ©

Below is an example of a reaction scheme for preparing a phenylalkanoic acid amide, which may be a fungicide, from an oxazolinone compound of the above-described general formula to form the ketone intermediate shown by the above-described general formula.

As the scheme above shows, the methods of the invention (described in paragraphs [1] to [5] above) and the compound of the invention (described in paragraph [6] above) are very useful in the preparation of phenylalkanoic acid amides, which are the active ingredient of a fungicide .

DETAILED DESCRIPTION OF THE INVENTION

Methods for preparing the products of this invention are further specifically described by way of example.

Example 1 (invention described in paragraph [2] above)

Preparation of 2-phenyl-4-isopropyl-4-methyl-1,3-oxazol-5-one ml of glacial acetic acid, 3.92 g (0.038 mol) of concentrated sulfuric acid and 0.36 g (0 2.0 mol of water was added to 8.6 g (0.04 mol) of N- (1-cyano-1,2-dimethylpropyl) benzamide. The mixture was stirred at 80 ° C for 2 h to effect the reaction. After completion of the reaction, the reaction mixture was cooled. 100 ml of water and 100 ml of ethyl acetate were added to separate the layers. The organic layer was washed with saturated aqueous sodium bicarbonate solution and saturated aqueous sodium chloride solution and evaporated to give 7.2 g (0.033 mol) of 2-phenyl-4-isopropyl-4-methyl-1,3-oxazol-5-one (yield 83%).

Example 2 (invention described in paragraph [2] above)

Preparation of 2- [1- (4-chlorophenyl) ethyl] -4-isopropyl-4-methyl-1,3-oxazol-5-one ml of glacial acetic acid, 1.96 g (0.019 mol) of concentrated sulfuric acid 36 g (0.02 mol) of water was added to 5.56 g (0.02 mol) of 2- (4-chlorophenyl) -N- (1-cyano-1,2-dimethylpropyl) propanamide. The mixture was stirred at 60 ° C for 2 h to effect the reaction. After completion of the reaction, the reaction mixture was cooled. 400 ml of water and 400 ml of ethyl acetate were added to separate the layers. The organic layer was washed with a saturated aqueous sodium bicarbonate solution and a saturated aqueous sodium chloride solution and evaporated to give 5.58 g of 2- [1- (4-chlorophenyl) ethyl] -4-isopropyl-4-methyl-1,3-oxazole- Of 5-one (yield 100%).

Example 3 (invention described in paragraph [2] above)

Preparation of 2- [1- (4-chlorophenyl) ethyl] -4-isopropyl-4-methyl-1,3-oxazol-5-one 4 · 4 · 4 · 4 · 4 · 4 · 4 · 4 4 4 4 4

450 ml of toluene, 45 g (0.44 mol) of concentrated sulfuric acid and 45 ml of glacial acetic acid are added to 126.7 g (0.45 mol) of 2- (4-chlorophenyl) -N- (1-cyano-1). (2-dimethylpropyl) propanamide. The mixture was refluxed for 4 h with heating to effect the reaction. After completion of the reaction, the reaction mixture was cooled and added dropwise to a solution of 18.2 g (0.45 mol) of sodium hydroxide dissolved in 300 ml of water. The organic layer was separated, washed with saturated aqueous sodium bicarbonate solution and water and evaporated to give 125 g (0.448 mol) of 2- [1- (4-chlorophenyl) ethyl] -4-isopropyl-4-methyl-1,3-oxazole- Of 5-one (yield 99.6%).

Example 4 (invention described in paragraph [3] above)

Preparation of ethyl 4- (2- (4-chlorophenyl) propanoylamino) -4,5-dimethyl-3-oxohexanoate

0.73 g (0.00722 mol) of triethylamine and 0.41 g (0.0043 mol) of magnesium chloride were added at room temperature to a solution of 0.73 g (0.043 mol) of monocalcium ethyl malonate dissolved in 10 ml of acetonitrile and the mixture was spinal cord. 0.8 g (0.00287 mol) of 2- [1- (4-chlorophenyl) ethyl] -4-isopropyl-4-methyl-1,3-oxazo-5-one is added. The mixture was stirred at 60 ° C for 5 h to effect the reaction. After completion of the reaction, the reaction mixture was cooled. 50 ml of water and dilute hydrochloric acid are added thereto to adjust the pH of the mixture to 4 or less.

The mixture was subjected to extraction with ethyl acetate. The organic layer was washed with saturated aqueous sodium bicarbonate solution and saturated aqueous sodium chloride solution, then dried over anhydrous sodium sulfate and evaporated. The concentrate was subjected to column chromatography separation to give 0.5 g (0.00136 mol) of ethyl (4- [2- (4-chlorophenyl) propanoylamino] 34-9). · * · · · ·

999 98 · 9 · 9 9

9 · 9 «« ·· · 99 ···

-4,5-dimethyl-3-oxohexanoate) (yield 48%).

Example 5 (invention described in paragraph [3] above)

Preparation of ethyl [4,5-dimethyl-3-oxo-4- (benzoylamino) hexanoate]

1.06 g (0.01 mol) of triethylamine and 0.85 g (0.01 mol) of magnesium chloride are added at room temperature to a solution of 0.85 g (0.005 mol) of monocalcium ethyl malonate dissolved in 10 ml of acetonitrile and then spinal cord. To this was added 1.1 g (0.005 mol) of 2-phenyl-4-isopropyl-4-methyl-1,3-oxazol-5-one. The mixture was stirred at 60 ° C for 8 h to effect the reaction. After completion of the reaction, the reaction mixture was cooled. 50 ml of water and dilute hydrochloric acid are added thereto to adjust the pH of the mixture to 4 or less. The mixture was subjected to extraction with ethyl acetate. The organic layer was washed with saturated aqueous sodium bicarbonate solution and saturated aqueous sodium chloride solution, then dried over anhydrous sodium sulfate and evaporated. The concentrate was subjected to column chromatography to give 0.4 g (0.00131 mol) of ethyl [4,5-dimethyl-3-oxo-4- (benzoylamino) hexanoate] (26% yield).

Example 6 (invention described in paragraph [3] above)

Preparation of ethyl [4- (acetylamino) -4,5-dimethyl-3-oxohexanoate]

0.91 g (0.01 mol) of triethylamine and 0.43 g (0.0045 mol) of magnesium chloride are added at room temperature to a solution of 0.76 g (0.0045 mol) of monocalcium ethyl malonate dissolved in 10 ml of acetonitrile with ethyl acetate. followed by stirring. 0.47 g (0.003 mol) of 2-methyl-4-isopropyl-4-methyl-1,3-oxazol-5-one is added. The mixture was stirred at 65 ° C for 10 h for 35

4 4 · • · • 4 4 4 « 4 · • · · 4 • • • • ··· * · • • • · 4 4 4 • · • ·· · · • • »· • · • » • • 4 4 4 ♦ 4 *

creep reaction. After completion of the reaction, the reaction mixture was cooled. 50 ml of water and dilute hydrochloric acid are added thereto to adjust the pH of the mixture to 4 or less. The mixture was subjected to extraction with ethyl acetate. The organic layer was washed with saturated aqueous sodium bicarbonate solution and saturated aqueous sodium chloride solution, then dried over anhydrous sodium sulfate and evaporated. The concentrate was subjected to column chromatography to give 0.2 g (0.00081 mol) of ethyl [4- (acetylamino) -4,5-dimethyl-3-oxohexanoate] (yield 27%).

Example 7 (invention described in paragraph [3] above)

Preparation of methyl (4- [2- (4-chlorophenyl) propanoylamino] -4,5-dimethyl-3-oxohexanoate)

4.6 g (0.029 mol) of monocalcium methyl malonate, 7.5 ml of toluene and 10 ml of dimethylformamide are placed in a reaction vessel. The mixture was cooled to 10 ° C. 3.0 g (0.032 mol) of magnesium chloride and 2.1 g (0.021 mol) of triethylamine are added, followed by stirring. A solution of 5.6 g (0.020 mol) of 2- (1- (4-chlorophenyl) ethyl] -4-isopropyl-4-methyl-1,3-oxazol-5-one dissolved in 2.5 ml of toluene is added dropwise. The mixture was stirred at 80 ° C for 20 h to effect the reaction, after the reaction was cooled, 20 ml of water and 4.4 g sulfuric acid were added followed by stirring at 50 ° C for 1 h. Toluene (30 ml) was added and the layers were separated at 50 DEG C. The toluene layer was washed with saturated aqueous sodium bicarbonate solution and saturated aqueous sodium chloride solution and evaporated to give the crude crystals which were recrystallized from n-hexane to give 1.2 g (0.1 g). Methyl (4- [2- (4-chlorophenyl) propanoylamino] -4,5-dimethyl-3-oxohexanoate) (17% yield).

© © β β β © © © © © © © © © © © © © © © © © © © ©

Example 8 (invention described above in paragraph [3])

Preparation of ethyl 4- (2- (4-chlorophenyl) propanoylamino) -4,5-dimethyl-3-oxohexanoate

51.0 g (0.3 mol) of monocalcium ethyl malonate, 100 ml of toluene and 100 ml of dimethylformamide are placed in a reaction vessel. The mixture was cooled to 10 ° C. 20.9 g (0.22 mol) of magnesium chloride and 22.2 g (0.22 mol) of triethylamine are added and the mixture is then stirred. 56.0 g (0.2 mol) of 2- (1- (4-chlorophenyl) ethyl) -4-isopropyl-4-methyl-1,3-oxazol-5-one are added and the mixture is stirred at 80 ° The reaction mixture was cooled, 200 ml of water and 44 g of sulfuric acid were added thereto, followed by stirring at 50 ° C for 1 h, and extracted with 300 ml of toluene. Wash with saturated aqueous sodium bicarbonate solution and saturated aqueous sodium chloride solution and evaporate to give 62.5 g (0.17 mol) of ethyl (4- [2- (4-chlorophenyl) propanoylamino] -4,5-dimethyl-3). -oxohexanoate) (yield 85%).

Example 9 (invention described in paragraph [3] above)

Preparation of isopropyl - (4- [2- (4-chlorophenyl) propanoylamino] -4,5-dimethyl-3-oxohexanoate)

5.52 g (0.03 mol) of monocalcium isopropyl malonate, 15 ml of toluene and 12 ml of dimethylformamide are placed in a reaction vessel. The mixture was cooled to 10 ° C. 2.1 g (0.022 mol) of magnesium chloride and 2.2 g (0.022 mol) of triethylamine were added thereto, followed by stirring. 5.6 g (0.02 mol) of 2- [1- (4-chlorophenyl) ethyl] -4-isopropyl-4-methyl-1,3-oxazol-5-one are added. The mixture was stirred at 80 ° C for 20 h

• · · 9 · 4 • · • 4 · 4 4 • 4 4 9 9 9 • • 4 9 4 4 • 4 4 ’4 • 4 9 • 4 * 4 * 4 * 9 4 • 4 • · 9 9 4 4

to effect the reaction. After completion of the reaction, the reaction mixture was cooled. 20 ml of water and 4 g of sulfuric acid are added, followed by stirring at 50 ° C for 1 h. Extraction is carried out with 30 ml of toluene. The toluene layer was washed with a saturated aqueous solution of sodium bicarbonate and a saturated aqueous solution of sodium chloride and evaporated to give 3.8 g (0.01 mol) of isopropyl- (4- [2- (4-chlorophenyl) propanoylamino] -4,5-dimethyl 3-oxohexanoate) (yield 50%, mp 110.4-112.8 ° C).

Example 10 (invention described in paragraph [3] above)

Preparation of ethyl (4 - [(4-chlorophenyl) acetylamino] -5-methyl-3-oxohexanonate)

5.11 g (0.03 mol) of monocalcium ethyl malonate, 20 ml of toluene and 15 ml of dimethylformamide are placed in a reaction vessel. The mixture was cooled to 10 ° C. Add 2.1 g (0.022 mol) of magnesium chloride and 2.22 g (0.022 mol) of triethylamine followed by stirring. 5.3 g (0.02 mol) of (4-chlorobenzyl) -4-isopropyl-4-methyl-1,3-oxazol-5-one are added. The mixture was stirred at 80 ° C for 5 h to effect the reaction. After completion of the reaction, the reaction mixture was cooled. Add 40 ml of water and 4 g of sulfuric acid followed by stirring at 50 ° C for 1 h. Extract with 100 ml of toluene. The toluene layer was washed with a saturated aqueous solution of sodium bicarbonate and a saturated aqueous solution of sodium chloride, and evaporated to give 5.0 g (0.014 mol) of ethyl 4 - [(4-chlorophenyl) acetylamino] -5-methyl-3-oxohexanonate) ( 70% yield).

Example 11 (invention described in paragraph [4] above)

0 0 0 99 · · 0 · 0

00000 0 «00« 0 0 0

000 00 00 00 00 00

Preparation of 3-amino-3,4-dimethylpentan-2-one ml of 10% hydrochloric acid was added to 0.5 g (0.00205 mol) of ethyl [4- (acetylamino) -4,5-dimethyl-3-oxohexanoate]. ]. The mixture was refluxed for 1 h. The reaction mixture was analyzed by gas chromatography to verify the formation of N-acetyl-1-isopropyl-1-methyl-2-oxopropanamide.

To the reaction mixture was added 10 mL of concentrated hydrochloric acid, followed by refluxing for 6 h with heating to effect the reaction. After completion of the reaction, the reaction mixture is washed with toluene to remove the neutral components. The pH of the aqueous layer was adjusted to 12 or above using aqueous sodium hydroxide solution and this solution was subjected to extraction with ethyl acetate. The organic layer was evaporated to give 0.2 g (0.00155 mol) of 3-amino-3,4-dimethylpentan-2-one (yield 76%).

Example 12 (invention described in paragraph [4] above)

Preparation of 2- (4-chlorophenyl) -N- [1-methyl-1- (methylethyl) -2-oxopropyl] propanamide ml of 3 N hydrochloric acid solution was added to 0.2 g (0.000544 mol) of ethyl (4 [2- (chlorophenyl) propanoylamino] -4,5-dimethyl-3-oxohexanoate). The mixture was refluxed for 3 h. The reaction mixture was analyzed by gas chromatography to verify the formation of 2- (4-chlorophenyl) -N- [1-methyl-1- (methylethyl) -2-oxopropyl] propanamide (100% conversion). ).

Example 13 (invention described in paragraph [4] above)

Preparation of 2- (4-Chlorophenyl) -N- [1-methyl-1- (methylethyl) -239-> fφφφφ •φ methyφφφφ) 4 φφφφφφφφφφφφφ φφ φφ • φ φφφ

-oxopropyl] propanamide

57.5 g (0.156 mol) of ethyl 4- [2- (4-chlorophenyl) propanoylamino] -4,5-dimethyl-3-oxohexanoate), 156 ml of 2-propanol, 62.4 ml are charged to the reaction vessel. water and 15.6 ml of concentrated sulfuric acid. The mixture was refluxed for 7 h to effect the reaction. After completion of the reaction, the reaction mixture was cooled to 60 ° C. 446 ml of water was added for further cooling. The mixture was neutralized with 23% aqueous sodium hydroxide solution. The precipitated crystals were collected by filtration to give 41.5 g (0.14 mol) of 2- (4-chlorophenyl) -N- [1-methyl-1- (methylethyl) -2-oxopropyl] propanamide (yield 90%).

Example 14 (invention described in paragraph [4] above)

Preparation of N- [1-methyl-1- (methylethyl) -2-oxopropyl] - (4-chlorophenyl) acetamide

2.5 g (0.007 mol) of ethyl 4 - [(4-chlorophenyl) acetylamino] -4,5-dimethyl-3-oxohexanoate, 7 ml of 2-isopropanol, 8 ml of water and 0.7 ml are placed in a reaction vessel. The reaction mixture is cooled to room temperature, 20 ml of water are added, the mixture is neutralized with 23% aqueous sodium hydroxide solution, and the precipitated crystals are separated. filtration to give 2.37 g (0.0067 mol) of N- [1-methyl-1- (methylethyl) -2-oxopropyl] - (4-chlorophenyl) acetamide (yield 96.3%).

Industrial use

According to the present invention there is provided an amide which is a useful intermediate in the preparation of a phenylalkanoic acid amide useful as a fungicide, a process for the preparation of the amide, a process for the preparation of the oxazolinone compound starting from the amide, and a process for the preparation an intermediate in the preparation of the phenylalkanoic acid amide from the amide described above.

Claims (7)

PATENT CLAIMS A process for preparing an amide of the general formula wherein: R is alkyl, cycloalkyl, haloalkyl, aryl, substituted aryl, arylalkyl, substituted arylalkyl (aryl) - (alkoxy) alkyl or (substituted aryl) - (alkoxy) alkyl, R ¹ and R ² are independently alkyl, cycloalkyl, haloalkyl, arylalkyl, substituted arylalkyl, aryl, substituted aryl or hydrogen, and these groups may be linked to each other to form a ring together with a carbon atom, to to which they are attached and R ³ is alkyl, cycloalkyl, haloalkyl, arylalkyl, substituted AND Φ · · φ φ φ φ φ φ φ φ φ φ φ φ · φ φ · · · An arylalkyl group, an aryl group, a substituted aryl group or a hydrogen atom, characterized in that it comprises the reaction of a nitrile of the general formula in which: R, R ¹ and R ² are as defined above, with an acid to achieve intramolecular ring closure to form an oxazolinone compound of formula R- ‘0 * ·· »9 9 9 9 9 • 999 9 • · 9 9 9 • · 9,999 9 • • 9 ♦ · • 9 · 9 • 9 9 9 « 9 ·· 9 · ·· • ♦ in which R, R ¹ and R ² are as defined above, and reacting this oxazolinone compound with a carboxylic compound of the formula 'COOR ³ ' wherein: Y is a hydrogen atom, a carboxyl group, or a salt of a carboxyl group; and R ³ has the same definition as above in the presence of a base. 2. A process for preparing an oxazolinone compound of the formula 44 44 4444 44 44 4 44 44 444 4 4 ·· 443 44 * 4 4 4 4444 444 44444 44 44 44 444 in which R is alkyl, cycloalkyl, haloalkyl, aryl, substituted aryl, arylalkyl, substituted arylalkyl, (aryl) - (alkoxy) alkyl or (substituted aryl) - (alkoxy) alkyl, and R ¹ and R ² are independently alkyl, cycloalkyl, haloalkyl, arylalkyl, substituted arylalkyl, aryl, substituted aryl or hydrogen, and the two groups may be linked to each other to form a ring together with a carbon atom to which they are attached, characterized by a nitrile of the formula: in which R, R ¹ and R ³ are as defined above, with an acid to achieve intramolecular ring closure. A process for the preparation of an amide of the formula is an alkyl group, a cycloalkyl group, a haloalkyl group in which * 99 • 9 · 9 • 9 9 • 9 9 9 9 9 99 9 9 9 9,999 9 9 9 9 9 9 9 9 9 9 9 9 9 9 • 9 99 9 9 99 9 9 an aryl group, an aryl group, a substituted aryl group, an arylalkyl group, a substituted arylalkyl group, an (aryl) - (alkoxy) alkyl group, or a (substituted aryl) - (alkoxy) alkyl group, R ³ and R ² are independently alkyl, cycloalkyl, haloalkyl, arylalkyl, substituted arylalkyl, aryl, substituted aryl or hydrogen, and the two groups may be linked to each other to form a ring together with the atom the carbon to which they are attached; and R ³ is an alkyl group, a cycloalkyl group, a haloalkyl group, an arylalkyl group, a substituted arylalkyl group, an aryl group, a substituted aryl group or a hydrogen atom, comprising reacting an oxazolinone compound of the general formula wherein: · · «« * * · · · · '' · · · · · · · · · · · · · · · · · · · R ¹ , R ¹ and R ² are as defined above with a carboxyl compound of the general formula COOR ³ in which Y is a hydrogen atom, a carboxyl group, or a salt of a carboxyl group, and R ³ is as defined above in the presence of a base. 4. A method for the preparation of a ketone of the general formula 9 9 9 9 9 9 9,999,999 9,999 9 9 9 9 9 9 999 99 99 99 99 999 in which R ¹ and R ² are independently alkyl, cycloalkyl, haloalkyl, arylalkyl, substituted arylalkyl, aryl, substituted aryl, substituted aryl or hydrogen and may be linked to each other to form a ring together with a carbon atom to which they join, and R ⁴ is alkylcarbonyl, cycloalkylcarbonyl, haloalkylcarbonyl, arylcarbonyl, substituted arylcarbonyl, arylalkylcarbonyl, substituted arylalkylcarbonyl, (aryl) - (alkoxy) alkylcarbonyl, (substituted aryl) - (alkoxy) alkylcarbonyl, or characterized in that it comprises the reaction of an amide of the general formula in which: 9999 99 9 9 9 9 9 9 9 9 9 999 9 9 99 99 99 99 9 99 99 99 R is alkyl, cycloalkyl, haloalkyl, aryl, substituted aryl, arylalkyl, substituted arylalkyl, (aryl) - (alkoxy) alkyl or (substituted aryl) - (alkoxy) alkyl, R ¹ and R ² are as defined above and R ³ is alkyl, cycloalkyl, haloalkyl, arylalkyl, substituted arylalkyl, aryl, substituted aryl or hydrogen with an acid or base in the presence of water. The process for preparing an amide described in claim 1 or 3, characterized in that the base is selected from alkali metal bases, alkaline earth metal bases, organic amines and pyridines. 6. The acid amide of the formula R '* © © © © © © © © 9 9 9 9 9 9 9 9 9 9 9 9 9 in which ^R is alkyl, cycloalkyl, haloalkyl, aralkyl, substituted aralkyl, (aryl) - (alkoxy) alkyl or (substituted aryl) - (alkoxy) alkyl, and R ¹ and R ² are independently alkyl, cycloalkyl, haloalkyl, arylalkyl, substituted arylalkyl, aryl, substituted aryl or hydrogen, and the two groups may be taken together to form a ring together with a carbon atom, to which they join, R ³ is an alkyl group, a cycloalkyl group, a haloalkyl group, an arylalkyl group, a substituted aryalkyl group, an aryl group, a substituted aryl group or a hydrogen atom.