JPH0971560A - Production of n-(1-(2,4-dichlorophenyl)ethyl)-2-cyano-3,3-dimethylbutaneamide - Google Patents

Abstract

PROBLEM TO BE SOLVED: To industrially and readily obtain a compound having excellent control effect against plant disease at a high yield. SOLUTION: The objective N-[1-(2,4-dichlorophenyl)ethyl]-2-cyano-3,3- dimethylbutaneamide is obtained by reacting 1mol of a 2-4C alkyl ester of α-cyano-tert-butylacetic acid (a racemic modification or an optically active substance is also useful) with 0.9-1.2mol of 1-(2,4-dichlorophenyl)ethylamine (a racemic modification or an optically active substance is also useful) without a solvent or in a solvent such as xylene preferably at 130-220 deg.C for usually 0.5-24 hrs. An alkyl ester using in the reaction is obtained by reacting a 2-4C alkyl ester of 2-cyano-3-methyl-butenoic acid with a methylmagnesium halide in the presence of copper catalyst.

Description

Detailed Description of the Invention

[0001]

TECHNICAL FIELD The present invention relates to N- [1- (2,4-
Dichlorophenyl) ethyl] -2-cyano-3,3-dimethylbutanamide.

2. Description of the Related Art
It is described in JP-A-2-76846 that [1- (2,4-dichlorophenyl) ethyl] -2-cyano-3,3-dimethylbutanamide has an excellent plant disease control effect. An industrially advantageous method for producing the compound has been desired.

[0002]

In view of the above situation, the inventors of the present invention industrially prepared N- [1- (2,4-dichlorophenyl) ethyl] -2-cyano-3,3-dimethylbutanamide. As a result of diligently studying the method of manufacturing,
α-Cyano-tert-butylacetic acid (2-cyano-3,3-
C ₂ -C ₄ alkyl esters of dimethyl butanoic acid) and 1
-(2,4-dichlorophenyl) ethylamine and 13
By reacting at 0 to 250 ° C., N- [1- (2,
4-Dichlorophenyl) ethyl] -2-cyano-3,3-
It has been found that dimethylbutanamide can be easily produced in high yield, and in particular, it can be produced by using a C ₂ -C ₄ alkyl ester of α-cyano-tert-butylacetic acid and (R) -1- (2,4).
-Dichlorophenyl) ethylamine, 130-25
By reacting at 0 ° C., N-[(R) -1- (2,4-dichlorophenyl) ethyl] -2-cyano-3,3-dimethylbutanamide, which has a particularly excellent plant disease controlling effect, is industrially available. The inventors have completed the present invention by finding that they can be advantageously manufactured even on a scale.

That is, the present invention relates to a C ₂ -C ₄ alkyl (eg ethyl, n-propyl, isopropyl, n-butyl, isobutyl etc.) ester of α-cyano-tert-butylacetic acid and 1- (2,4). N- [1- (2,4-dichlorophenyl) ethyl] -characterized by reacting with -dichlorophenyl) ethylamine at 130 to 250 ° C.
A method for producing 2-cyano-3,3-dimethylbutanamide (hereinafter referred to as compound 1) (hereinafter referred to as production method 1 of the present invention), and C of α-cyano-tert-butylacetic acid.
₂ -C ₄ alkyl ester and a (R) -1- (2,4- dichlorophenyl) ethylamine, which comprises reacting at 130 to 250 ° C., N - [(R) -1- (2,
4-Dichlorophenyl) ethyl] -2-cyano-3,3-
A method for obtaining dimethylbutanamide (hereinafter referred to as compound 1a) (hereinafter referred to as production method 2 of the present invention) is provided.

[0004]

BEST MODE FOR CARRYING OUT THE INVENTION First, the production method 1 of the present invention will be described. The reaction is carried out with C ₂ of α-cyano-tert-butylacetic acid.
To C ₄ alkyl ester (which may be racemic or optically active) and 1- (2,4-dichlorophenyl) ethylamine (which may be racemic or optically active) without solvent Or, in a solvent, at a reaction temperature of 130 to 250 ° C, preferably 130 to 220 ° C, usually 0.5 to 24
It can be carried out by reacting for a time. The amount of reactants used is C _{2 of} α-cyano-tert-butylacetic acid.
-C ₄ alkyl ester 1 1- moles (2,4-dichlorophenyl) ethylamine is usually a proportion of 0.9 to 1.2 mol. The solvent used as necessary is not particularly limited as long as it is inert in the reaction and has a boiling point of about 130 to 250 ° C., for example, a hydrocarbon solvent such as xylene, cumene, mesitylene, chlorobenzene, Examples thereof include halogenated aromatic hydrocarbon solvents such as dichlorobenzene, ether solvents such as diglyme and triglyme, or a mixture thereof. After completion of the reaction, the reaction solution is usually subjected to a crystallization operation such as cooling to room temperature, and the resulting crystals are collected by filtration, and a suitable solvent (organic solvent such as methanol, ethanol, isopropanol, hexane, monochlorobenzene, water or The compound 1 to be sought can be isolated by washing with a mixed solvent thereof), drying, and further purification by recrystallization or the like if necessary.

Next, the manufacturing method 2 of the present invention will be described. The reaction of α- cyano -tert- butyl acetate C ₂ -C ₄
Alkyl ester (whether racemic or optically active) and (R) -1- (2,4-dichlorophenyl)
Ethylamine (optical purity 100% ee (enantiomeric e
xcess), and may be, for example, an optically active substance rich in (R) -form with an optical purity of 75% ee or higher. ) And with or without a solvent at 130 to 250 ° C., preferably 1
It can be carried out at a reaction temperature of 30 to 220 ° C. and usually for 0.5 to 24 hours. The amount of reactants used for C ₂ -C ₄ alkyl 1 mole of α- cyano -tert- butyl acetate (R) -1- (2,4- dichlorophenyl) ethylamine is usually 0.9 to 1. It is a ratio of 2 mol. The solvent used as necessary is not particularly limited as long as it is inert in the reaction and has a boiling point of 130 to 250 ° C. or higher.
Examples thereof include hydrocarbon solvents such as xylene, cumene and mesitylene, halogenated aromatic hydrocarbon solvents such as chlorobenzene and dichlorobenzene, ether solvents such as diglyme and triglyme, or a mixture thereof. After completion of the reaction, the reaction solution is usually subjected to a crystallization operation such as cooling to room temperature, and the resulting crystals are collected by filtration, and a suitable solvent (organic solvent such as methanol, ethanol, isopropanol, hexane, monochlorobenzene, water or The compound 1a to be obtained can be obtained by washing with a mixed solvent thereof) and then drying. Further, in order to improve the properties of the crystal, the crystal can be taken out by the following crystallization operation. That is, while keeping the reaction solution after completion of the reaction in which the organic solvent has been distilled off as necessary at about 130 to 170 ° C., an organic solvent that is azeotropic with water such as monochlorobenzene and dichlorobenzene is added thereto and dissolved, Then add the solution to 70 ~
Cool to about 100 ° C and keep the same temperature. On the other hand, in a separate container equipped with a thermometer, a cooling pipe for condensing the distillate and a stirrer, water, if necessary, a small amount of acid (hydrochloric acid, sulfuric acid, etc.) and a small amount of seed crystals are charged, and the temperature is about 100 ° C After the temperature was raised to the above temperature, a solution (7
Slowly add (0 to 100 ° C). When the organic solvent is azeotropically distilled with water, the crystals of the compound 1a are almost simultaneously precipitated. The aqueous slurry of the compound 1a thus obtained is slowly cooled to about 20 to 40 ° C., and then the crystals are collected by filtration, washed with water, and dried to give the compound 1a crystallinity with good filterability. It can be obtained as a powder.

The usefulness of the production method 2 of the present invention will be described below. Compound 1 contains 1 on the acid side and 1 on the amine side, respectively.
Since there are two asymmetric carbons, there are a total of four optical isomers, namely (acid side, amine side), in order of X1 form (R, R),
There are X2 bodies (S, S), Y1 bodies (R, S) and Y2 bodies (S, R), and there are two diastereomers in total, namely the X body (racemic body: X1 body and X2 body, etc.). Amount mixture) and Y form (racemic form: Y1 form and Y2 form equivalent mixture) exist, but as shown in the reference example below, the present inventors have shown that Y2 form and X1 form have plant disease controlling activity. It was found that the Y2 form had a much higher plant disease controlling activity than the X1 form, that is, the Y form had a far stronger plant disease controlling activity than the X form. However, when compound 1 derived from a racemic amine was obtained on an industrial scale, when it was attempted to be taken out by crystallization, X-form, which had a weak plant disease controlling activity, was preferentially crystallized out of the above two types of diastereomers. Moreover, it was found that the diastereomer ratio is easily affected by various factors such as heat and is not always constant (difficult to control). Therefore, as a result of various studies, it was unexpectedly found that the compound 1a (optically active form) derived from an optically active amine (for example, an optical isomer rich in R form having an optical purity of 75% ee or higher) was X1.
It was found that the isomer and the Y2 isomer crystallized in almost equal amounts, and that this diastereomer ratio did not change and was not affected by factors such as heat under normal operating conditions, leading to the production method 2 of the present invention. is there.

The C ₂ -C ₄ alkyl ester of α-cyano-tert-butylacetic acid used as the starting compound in the present invention is described in, for example, J. Am. Chem. Soc.
72 , 4791 (1950) and the like, but can be efficiently obtained by the following production method a of raw materials. 1- (2,4-dichlorophenyl) ethylamine is, for example, Organic ReactionVol 5,
It can be produced by the method described in JP-A Nos. 301-330 (1949) and JP-A-2-306942.

(Production Method a) 2-Cyano-3-methyi
Lu-2-butenoic acid C₂ ~ C_Four Alkyl ester and meth
With rumagnesium halide in the presence of copper catalyst
To give C of α-cyano-tert-butylacetic acid
₂ ~ C_Four A method for obtaining an alkyl ester. Below is the raw material
The construction method a will be described in detail. 2-cyano-3-used
C of methyl-2-butenoic acid₂ ~ C_Four With alkyl ester
For example, 2-cyano-3-methyl-2-butenoic acid
Ethyl, 2-cyano-3-methyl-2-butenoic acid n-type
Ropil, isop-2-cyano-3-methyl-2-butenoate
Ropil, 2-cyano-3-methyl-2-butenoic acid n-bu
Chill, isobutyl 2-cyano-3-methyl-2-butenoate
Le etc. Methyl magnesium hara used
As the id, methyl magnesium chloride (CH_Three 
MgCl), methyl magnesium bromide (CH_Three M
gBr), methylmagnesium iodide (CH_Three M
gI), which are commercially available products or
Alternatively, magnesium and methyl halide may be
Can be prepared accordingly. As a copper catalyst,
Usually, monovalent copper salts or divalent copper salts are used.
As an example, for example, copper (I) chloride [CuCl], copper bromide
(I) [CuBr], copper (I) iodide [CuI], copper chloride
(II) [CuCl₂], Copper (II) bromide [CuB
r₂] Or copper (II) iodide [CuI₂]
You. The reaction is usually carried out in an organic solvent and the organic solvent used
As the medium, for example, tetrahydrofuran (hereinafter, TH
Write F. ), Diethyl ether, dibutyl ether, etc.
Ether solvents, toluene, xylene, benzene, etc.
Aromatic hydrocarbon solvent, ether solvent and aromatic hydrocarbon solvent
And the like. The reaction temperature is usually 10 to 60
C, reaction time is usually 0.5-10 hours,
The amount of the reactant that can be added is 2-cyano-3-methyl-2-
Butenoic acid C₂ ~ C _Four 1 mol of alkyl ester
Cylmagnesium halide is usually in a proportion of 1 to 2 mol, 2
-Cyano-3-methyl-2-butenoic acid C₂ ~ C_Four Al
Copper catalyst is usually 0.0005 to 1 part by weight of kill ester.
.About.0.1 part by weight. The reaction liquid after the reaction is usually
For example, treat with water, ammonium chloride water, dilute sulfuric acid water, etc.
After that, the organic layer is concentrated and, if necessary, further purified by distillation.
By performing the operation, the desired α-cyano-ter
C of t-butylacetic acid₂ ~ C_Four Isolate the alkyl ester
Can be

The C ₂ -C of 2-cyano-3-methyl-2-butenoic acid which is the raw material used in the raw material production method a
_{The 4-} alkyl ester can be efficiently produced by the following production method b of raw materials. (Manufacturing method b of raw material) C _{2 to} C ₄ of acetone and cyanoacetic acid
A method for obtaining a C ₂ -C ₄ alkyl ester of 2-cyano-3-methyl-2-butenoic acid by reacting an alkyl ester with n-hexane as a main solvent in the presence of a catalyst. Hereinafter, the raw material manufacturing method b will be described in detail. Examples of the C ₂ -C ₄ alkyl ester of cyanoacetic acid used include ethyl cyanoacetate and cyanoacetic acid n-
Examples thereof include propyl, isopropyl cyanoacetate, n-butyl cyanoacetate, isobutyl cyanoacetate, and the like, which are commercially available or can be produced by a conventional method. As the catalyst, aniline and carboxylic acid which may be substituted are usually used. Examples of the substituent in the optionally substituted aniline include a hydroxyl group, a methyl group and a methoxy group, and examples of the optionally substituted aniline include aminophenol (p-aminophenol, o-amino). Examples thereof include phenol, m-aminophenol), toluidine (p-toluidine, o-toluidine, m-toluidine). Examples of carboxylic acids include, for example, lower (eg C
₁ -C ₄₎ fatty acids (e.g., acetic acid, formic acid, and propionic acid) and benzoic acid. As a reaction solvent, n-hexane is used as a main solvent, and more specifically, the ratio of n-hexane to the total solvent is usually 50 to 100% by weight.
Examples of the reaction solvent that can be used as a mixture with n-hexane include aromatic hydrocarbon solvents such as toluene and xylene. Reaction temperature is usually 50
The reaction time is usually 5 to 20 hours, and the reaction is usually carried out while removing water produced during the reaction. The amount of the reaction agent used in the reaction is usually 1 to 4 mol of acetone and 0.001 to 0.2 mol of the catalyst for 1 mol of the C ₂ -C ₄ alkyl ester of cyanoacetic acid (substituted). The aniline which may be used is usually in the proportion of 0.001 to 0.1 mol; the carboxylic acid is usually in the proportion of 0.01 to 0.2 mol). The reaction solution after the reaction is usually concentrated under reduced pressure or atmospheric pressure and distilled as it is, or dissolved in a solvent such as ethyl acetate, toluene, xylene and washed with water, and the solution is concentrated under reduced pressure to remove the solvent, and if necessary. By further performing a purification operation such as distillation, the desired 2-cyano-3-methyl-2
- the butenoic acid C ₂ -C ₄ alkyl ester can be isolated.

[0010]

The present invention will be described in more detail with reference to the following examples, but the present invention is not limited to these examples. (Method A) Biguryuu type rectification column, a four-necked flask equipped with a thermometer and a mechanical stirrer (RS)-.alpha.-cyano -tert- butyl acetate C ₂ -C ₄ alkyl esters and 1- (2,4 A predetermined amount of -dichlorophenyl) ethylamine was charged. 180-1 after heating up to 180 ° C
At 90 ° C, distilling the produced alcohol, 5-1
The reaction was performed for 0 hours. After completion of the reaction, the reaction mixture was cooled to room temperature, the generated crystals were collected by filtration and washed twice with n-hexane. The desired crystal 1 was obtained by drying the obtained crystal under reduced pressure. (Method B) helicoil packed with the seminal Tome搭(20 cm), a four-necked flask equipped with a thermometer and a mechanical stirrer (RS)-.alpha.-cyano -tert- butyl acetate C ₂ -C ₄
Charge a predetermined amount of alkyl ester and 1- (2,4-dichlorophenyl) ethylamine, and add 50 ml of a predetermined solvent.
Was added. This solution was heated and refluxed for 8 to 20 hours while distilling the produced alcohol together with the solvent (about 30 ml). After completion of the reaction, the mixture was cooled to room temperature and n-hexane 5 was added.
0 ml was added, and the resulting crystals were collected by filtration and washed twice with n-hexane. The desired crystal 1 was obtained by drying the obtained crystal under reduced pressure.

The yield of compound 1 (racemic compound) is shown in Table 1, and the yield of compound 1a (optically active compound) is shown in Table 2. In addition, as a reference comparative example, the above method A or method B
Table 1 shows an example of the case where a methyl ester of α-cyano-tert-butylacetic acid is used in place of the C ₂ -C ₄ alkyl ester of α-cyano-tert-butylacetic acid.

[Table 1] * 1. Alkyl of (RS) -α-cyano-tert-butylacetate alkyl (Me is methyl, Et is ethyl, and Bu is n-butyl). * 2. Alkyl (RS) -α-cyano-tert-butylacetate. * 3. (RS) -1- (2,4-dichlorophenyl) ethylamine. * 4. Ratio calculated by area comparison method by high performance liquid chromatogram analysis [High performance liquid chromatography (HPLC) analysis conditions are as follows; Equipment: Hitachi L-6200 Column: SUMIPAX YMC-GEL SIL 120A (5 μm, diameter 4 mm x 25 cm in length) Mobile phase: n-hexane / ethanol / trifluoroacetic acid = 240: 10: 1 Detection: UV 254 nm]

[0012]

[Table 2] * 1. Alkyl of (RS) -α-cyano-tert-butylacetate alkyl (Et represents ethyl, Bu represents n-butyl, respectively). * 2. (RS) -α-cyano-tert-butyl acetate alkyl. * 3. Optically active 1- (2,4-dichlorophenyl) ethylamine rich in (R) -form. * 4. Calculate the ratio by the area comparison method by high performance liquid chromatogram analysis [The analysis conditions of high performance liquid chromatography (HPLC) are as follows; Equipment: Hitachi L-6200 Column: SUMIPAX YMC-GEL SIL + SUMICHIRAL OA-4700 (5 μm, diameter 4 mm × length 25 cm) (5 μm, diameter 4.6 mm × length 25 cm) Mobile phase: n-hexane / ethanol / trifluoroacetic acid = 240: 10: 1 Detection: UV 254 nm] * 5. Optical purity (R) -1- (2,4-dichlorophenyl) ethylamine with 99.8% ee or more was used. * 6. (R) -1- (2,4-dichlorophenyl) ethylamine having an optical purity of 84% ee was used. * 7. (R) -1- (2,4-dichlorophenyl) ethylamine having an optical purity of 76% ee was used. * 8. X2 / Y1 = <0.1 / <0.1 * 9. X2 / Y1 = <0.1 / <0.1 * 10. X2 / Y1 = <0.1 / <0.1 * 11 X2 / Y1 = 4/4 * 12. X2 / Y1 = 6/6 Example 10 (RS) -α-cyano-tert- in a four-necked flask equipped with a Vigreux type rectification column, a thermometer and a mechanical stirrer.
17.93 g (0.105 mol) of ethyl butyl acetate was charged and the temperature was raised to 190 ° C. There (R) -1-
(2,4-dichlorophenyl) ethylamine (optical purity 9
20.0 g (0.105 mol) of 2.4% ee) was added dropwise at the same temperature over 2 hours. Furthermore, the reaction was carried out at the same temperature for 17 hours while distilling the produced alcohol. After the reaction is completed, the reaction mixture is cooled to 140-150 ° C,
91.9 g of monochlorobenzene was added thereto. Then, the solution was cooled to 80 to 90 ° C. and kept at the same temperature. On the other hand, 215 g of water, 1.14 g of 35% hydrochloric acid water and 0.03 g of seed crystals were charged into another four-necked flask equipped with a thermometer, a Liebig condenser for condensing the distillate and a mechanical stirrer, and 97- After the temperature was raised to 100 ° C., the above-mentioned monochlorobenzene solution (which was kept at about 80 ° C.) was added dropwise thereto at the same temperature over 2 hours and 15 minutes. When water and monochlorobenzene were azeotropically distilled and the monochlorobenzene was distilled off, crystals of compound 1a were precipitated almost at the same time, and a water slurry of compound 1a was obtained. The slurry was cooled to 25 ° C. over 2 hours and then stirred at the same temperature for 30 minutes. The crystals were collected by filtration and washed once with 100 ml of water. The obtained crystal was dried under reduced pressure to obtain 30.0 g of compound 1a. (Yield 91.2%, optical isomer ratio X1 body: X2 body:
Y1 body: Y2 body = 47.2: 1.9: 1.8: 49.
1)

Reference Example Each of the optical isomers (X1, X2, Y1 and Y2) of racemic compound 1 was fractionated and purified by high performance liquid chromatography (HPLC) according to the following method to obtain the plant disease (rice). The results of examining the blast control activity are summarized in Table 3. (1) HPLC preparative HPLC preparative conditions are as follows; Device: Hitachi L-6200 Column: SUMIPAX YMC-GEL SIL + SUMICHIRAL OA-4700 (5 μm, diameter 4 mm × length 25 cm) (5 μm, diameter 4.6mm ×
Mobile phase: n-hexane / ethanol / trifluoroacetic acid = 240: 10: 1 Detection: UV 254 nm] X1, X2, Y1, Y2 were eluted in this order. The absolute structure (R / S) of each was determined by the X-ray structural analysis of the X1 body and the Y body (Y1 + Y2). (2) Test example A plastic pot was filled with sandy loam soil, and rice (Kinki 33
No.) was sowed and grown in a greenhouse for 20 days. Then, the reagent solution prepared in a wettable powder (obtained by thoroughly pulverizing and mixing 50 parts of compound 1, 3 parts of calcium ligninsulfonate, 2 parts of sodium lauryl sulfate and 45 parts of synthetic hydrous silicon oxide) with water was used as a reagent. It was diluted to a predetermined concentration and foliage sprayed so that it adhered sufficiently to the rice leaf surface. After spraying, the plants were air-dried, and a spore suspension of blast fungus was sprayed and inoculated. After the inoculation, the plants were left at 28 ° C. in the dark and humid for 4 days, and then the control efficacy was investigated. In addition, the control efficacy is "5", 10% if the disease state of the test plant at the time of the survey, that is, the microflora of leaves, stems, etc. “4” if the degree is recognized, “3” if about 30% is recognized, “2”, 7 if about 50% is recognized.
If about 0% is found, it is evaluated as “1”, and if there is no difference with the disease state when the compound is not tested, it is evaluated as “0” and evaluated in 6 levels, 5, 4, 3, respectively.
Shown as 2,1,0.

[0014]

[Table 3] *. Display the absolute structure of each asymmetric carbon in the order of (acid side, amine side).

Next, a production example of the raw material production method a will be described. Production Example of Raw Material a-1 To a solution of methylmagnesium chloride prepared from 119 g of methyl chloride, 49.6 g of magnesium and 509 g of THF, copper (I) iodide 6.
After adding 0 g, a solution of 240 g of ethyl 2-cyano-3-methyl-2-butenoate in 480 g of toluene was added dropwise at the same temperature over about 1 hour. After the dropping was completed, the reaction was further performed at the same temperature for 1 hour. 20-30 reaction mixture
After cooling to ℃, 20% ammonium chloride water 174
Poured into 2 g at 10-20 ° C. After standing at room temperature and liquid separation, the aqueous layer was extracted twice with 480 ml of ethyl acetate, and the organic layers were combined and washed twice with 480 g of saturated saline. The organic layer was dried over anhydrous magnesium sulfate and then concentrated under reduced pressure, and the residue was distilled as it was (boiling point of main fraction: 80-86).
(° C / 12 to 15 mmHg) to obtain the desired product. The yield of ethyl α-cyano-tert-butyl acetate after distillation is 249.
The yield was 94%.

Table 4 collectively shows the results of the reaction in Production Example a-1 of Raw Material except that the kind or amount of the catalyst was changed. The yield in the table represents the ratio of 2-cyano-3-methyl-2-butenoic acid to alkyl ester.

[Table 4] * 1. Weight ratio. * 2. Amount of catalyst (parts by weight) relative to 1 part by weight of alkyl ester of 2-cyano-3-methyl-2-butenoic acid. * 3. Alkyl of alkyl ester of 2-cyano-3-methyl-2-butenoic acid. * 4. Yield after distillation. Raw Material Production Example a-7 Methyl chloride 24.2 g, magnesium 11.7 g
And a solution of methylmagnesium chloride prepared from 121 g of THF at 15-25 ° C.
After adding 0.6 g, 2-cyano-3-methyl-2-
A solution of 61.3 g of ethyl butenoate in 61 g of toluene was added dropwise at the same temperature over about 3 hours. After completion of dropping
Further, the reaction was carried out at the same temperature for 2 hours. The reaction mixture was cooled and then poured into 173 g of a 15% sulfuric acid aqueous solution at 5 to 15 ° C. The mixture was heated to 50 to 60 ° C., allowed to stand at the same temperature, and separated. The aqueous layer was extracted once with 31 g of toluene, and the organic layers were combined and washed successively with 67 g of 5% aqueous sodium hydrogen carbonate solution and 31 g of water. The organic layers were combined and subjected to gas chromatography analysis using di-n-propyl phthalate as an internal standard. As a result, α-cyano-
The yield of tert-butyl ethyl acetate is 65 g, and the yield is 9
It was 6%. Production Example of Raw Material a-8 Copper (II) chloride 3.0 in place of copper (II) chloride 0.6 g
The same operation as in Example 9 was repeated except that g was used.
As a result, the amount of ethyl α-cyano-tert-butyl acetate was 64 g, and the yield was 95%.

Next, a production example of the raw material production method b will be described.
The reaction rate is a value calculated by the following equation.

[Equation 1] Gas chromatographic (GC) analysis conditions; Shimadzu GC-7A, column: 10% DEXSIL 300GC, diameter 3 mm
× Length 1 m UNIPORT HP 100 to 200 mesh Column temperature: Temperature was raised to 70 to 150 ° C. at a rate of 5 ° C./min. Production example of raw material b-1 Ethyl cyanoacetate 50.0 g, acetone 51.34 g, acetic acid
1.99 g, p-aminophenol 0.24 g and n-hexane 41 ml were charged, and the mixture was heated under reflux for 9 hours while azeotropically removing water produced during the reaction. When analyzed by gas chromatography, the reaction rate of ethyl cyanoacetate was 99%. After completion of the reaction, the reaction solution is concentrated under reduced pressure to give hexane,
After removing acetic acid and unreacted acetone, the residue was rectified as it was under reduced pressure of 20 mmHg using a 30 cm rectification column packed with a helicoil, and fractions at 110 to 113 ° C. were collected. The yield of ethyl 2-cyano-3-methyl-2-butenoate after distillation was 63.6 g, and the yield was 94%.

Reaction was carried out in the same manner as in Raw Material Production Example b-1, except that the type of reaction solvent, the type of catalyst, the type of alkyl of the alkyl ester of cyanoacetic acid, or the reaction time was changed. The results of the above are summarized in Table 5. The yield in the table represents the ratio of cyanoacetic acid to alkyl ester.

[Table 5] * 1. Alkyl of alkyl ester of cyanoacetic acid (Et represents ethyl and Bu represents butyl). * 2. Yield after distillation. * 3. Weight ratio. * 4. C: p-aminophenol and acetic acid * 5. D: p-toluidine and acetic acid * 6. E: p-aminophenol and benzoic acid * 7. F: p-aminophenol and propionic acid

[0019]

INDUSTRIAL APPLICABILITY According to the present invention, N- [1- (2,4-dichlorophenyl) ethyl] -2-cyano-3,3-dimethylbutanamide having an excellent plant disease controlling effect is industrially advantageous. It can be manufactured.

Claims (4)

[Claims] C ₂ -C according to claim 1] α- cyano -tert- butyl acetate
_4- alkyl ester and 1- (2,4-dichlorophenyl)
N- [1- (2,4-dichlorophenyl), characterized by reacting with ethylamine at 130 to 250 ° C.
Method for producing ethyl] -2-cyano-3,3-dimethylbutanamide. C ₂ -C of wherein α- cyano -tert- butyl acetate
N-[(R) -1- (2,4-dichlorophenyl), characterized in that ₄ alkyl ester and (R) -1- (2,4-dichlorophenyl) ethylamine are reacted at 130 to 250 ° C. Method for producing ethyl] -2-cyano-3,3-dimethylbutanamide. 3. An α-cyano-obtained by reacting a C ₂ -C ₄ alkyl ester of 2-cyano-3-methyl-2-butenoic acid with a methylmagnesium halide in the presence of a copper catalyst.
The method according to claim 1 or 2, wherein a C ₂ -C ₄ alkyl ester of tert-butylacetic acid is used. 4. Acetone and a C ₂ -C ₄ alkyl ester of cyanoacetic acid are reacted with n-hexane as a main solvent in the presence of a catalyst to give a C _{2 of} 2-cyano-3-methyl-2-butenoic acid. -C ₄ alkyl ester give, the 2-cyano -
C of α-cyano-tert-butylacetic acid obtained by reacting a C ₂ -C ₄ alkyl ester of 3-methyl-2-butenoic acid with methylmagnesium halide in the presence of a copper catalyst.
Using ₂ -C ₄ alkyl esters, according to claim 1 or 2
Production method as described.