JPH03218347A - Carboxylic acid amide derivative and its preparation - Google Patents

Abstract

NEW MATERIAL:A compound of formula I [R is alkyl, alkenyl or cycloalkyl capable of having a substituent (e.g. phenyl, halogen, lower alkoxycarbonyl, etc.,), e.g. aryl capable of having a substituent (e.g. halogen, lower alkyl, nitro, phenyl, etc.,); R<1> is H, CH2Y (Y is cyano, acyl, alkoxycarbonyl, etc.,); (n) is 1 or 2]. EXAMPLE:N-[Cyano(phenylthio)methyl]-2-methoxycarbonylacetoamide. USE:A starting raw material for medically or agricultural-chemically active compounds, dyes, perfumes, polymers, etc., such as an amide derivative represented by EP-135304-A and having antimicrobial and herbicidal activities. PREPARATION:For example, an aminoacetonitrile derivative of formula II is subjected to a reaction with a compound of formula III {Z is halogen, OH or formula III [r<1> is lower alkyl, R<1>; but when R<1> is H, Z is formula IV (r<2> is lower alkyl)]} to provide the compound of formula I.

Description

Detailed Description of the Invention [Field of Industrial Application] The present invention relates to a novel carboxylic acid amide derivative of aminoacetonitrile. It relates to a compound substituted with a group or an oxidized form thereof.

The carboxylic acid amide derivative of the present invention is, for example, EP-1
3 5 3.0 It can be used as a starting material for medicinal and agricultural active compounds such as amide derivatives having bactericidal and herbicidal activity shown in 4-A, as well as dyes, perfumes, polymers, and the like.

[Conventional technology]

Conventionally, in order to produce carboxylic acid amides of α-substituted aminoacetonitrile, aminoacetonitrile is converted into a carboxylic acid amide by an appropriate method. It was then produced by halogenating the methylene group at the α-position and carrying out a substitution reaction with a nucleophile, thiol. The sulfur oxidized product was produced by further oxidizing with a suitable oxidizing agent.

[Problems to be solved by the present invention]

An object of the present invention is to provide a new and stable carboxylic acid amide derivative of aminoacetonitrile that can be easily synthesized from an aminoacetonitrile derivative and can be used as a starting material for various organic compounds, and an inexpensive method for synthesizing the same. .

[Means to solve the problem]

(1) The present invention is based on the general formula CN RS (0)nCHNHCOR'...--(1
) [wherein R is (substituted with a phenyl group, a halogen atom, a lower alkoxycarbonyl group, a lower alkoxyalkylthio group, a hydroxyl group, a mercapto group, a cycloalkyl group, or an oxygen-containing heterocyclic group, which may have a substituent) an alkyl group, an alkenyl group, a cycloalkyl group (which may have a halogen atom, a lower alkyl group, a nitro group, a phenyl group which may have a substituent, or a phenoxy group which may have a substituent) R1 is a hydrogen atom or -CH2Y, Y is a cyano group, an alkoxycarponyl group, R2S(0)
m (R 2 is an alkyl group or phenyl group which may have a substituent, mho, 1.2), a halogen atom or an alkoxyl group. ] and a method for producing the same.

The compound of the present invention can be produced according to the following reaction formula.

■． Production method (al (II) CI[) (I) [wherein Rs R' and n have the same meanings as above, Z
represents a halogen atom, a hydroxy group, or a general formula O 11 r'C-0- (wherein r1 is a lower alkyl group or R1
shows. , ), provided that when R1 is a hydrogen atom, Z represents 0 l1 r2C-0- (r": lower alkyl group).

] The reaction is carried out in an organic solvent in the presence of a base in the case of an acid halide in which Z is a halogen atom or in the case of an acid anhydride in which Z is represented by the general formula r'C-0- or 0 11 r2C-〇-1, in which Z is a hydroxy group. In the case of carboxylic acid, the reaction is carried out at 0 to 50° C. for 10 minutes to several 10 hours in the presence of a condensing agent such as dicyclohexylcarbodiimide (DCC).

Examples of the organic solvent used include hydrocarbons such as benzene and toluene, nitriles such as acetonitrile, and halogenated hydrocarbons such as dichloromethane and chloroform.

Examples of bases include inorganic bases such as sodium carbonate, triethylamine, pyridine, diazabicycloundecene (D
Organic bases such as BU) can be used.

The molar ratio is 1 to 1.5 mol in the case of an acid halide or acid anhydride, 1 to 1 in the case of a carboxylic acid, per 1 mol of the aminoacetonitrile derivative represented by the general formula [■].
3 mol, and the base or condensing agent is approximately equimolar to the acid halide or acid anhydride 7 or carboxylic acid to be reacted.

C}+2 CII) IJV) (I') The reaction is carried out in an organic solvent at a temperature from 0° C. to the boiling point of the solvent used for 10 minutes to several 10 hours.

As the organic solvent used, the same ones as in the case of production method (a) can be mentioned.

3. Production method (C) A compound in which n is 1 or 2 in the general formula [■] can also be obtained by oxidizing a corresponding compound in which n is O.

CI') (I') (wherein,
n' represents 1 or 2. ) The oxidation reaction is carried out under normal oxidation conditions, i.e., in a solvent at a temperature of 0 to 70
The reaction is carried out at ℃ for 10 minutes to several tens of hours under atmospheric pressure.

The solvent used is the same as in production method (a), as well as
8 Alcohols such as tanol, acetic acid, water, etc. can be used.

Oxidizing agents include hydrogen peroxide, peracids, hydrogen peroxide and tungsten or vanadium catalysts, human peroxide, ozone, oxygen and transition metal catalysts, potassium peroxosulfate, potassium permanganate, chromic acid, and hypochlorite. Sodium chlorate, metaperiodic acid, etc. can be used.

Regardless of the manufacturing method (a), (b), or (C), the desired product can be obtained by performing a normal post-treatment after the reaction is completed.

Incidentally, the raw material compound represented by the general formula [■] can be easily produced, for example, according to the following reaction formula.

C.N. [II) 〔Example〕 Next, the present invention will be explained in more detail with reference to Examples.

Example 1, (Compound No. 4) PhSC}IN+{2CN? hSCHNHCOCH2CO■Me 2-phenylthio-2-aminoacetonitrile16.
19. g was dissolved in 50 ml of chloroform, and 8.6 g of pyridine (Pyr) was added. After cooling on ice, 18.2 g of methyl malonyl chloride was added. 1 hour later water 10
01 dl was poured into the solution and extracted three times with 30-ml of chloroform. The extracts were combined, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. N-(cyano(phenylthio)methyl)-2-methoxycarbonylacetamide 2 was separated by column chromatography using silica gel, and pale yellow crystals were obtained.
2.23 g was obtained. Further recrystallization from benzene gave colorless crystals. Yield 85.3% mp 89 -90°C Example 2 (Compound No. 15) CN 2-(4-chlorophenylthio)-2-aminoacetonitrile 0.666 g and phenylsulfonylacetic acid 0.6
84 g was dissolved in 31 nl of dichloromethane.

Cool on ice and dicyclohexylcarbodiimide (DCC)
0.711 g was added. After reacting for 3 hours, the mixture was further left in the refrigerator overnight. Dichloromethane was distilled off, and 30% of ethyl acetate was added and filtered. Add the filtrate to 10% citric acid water,
The mixture was washed with water, 4% aqueous sodium bicarbonate, and then water, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. Separated by column chromatography using silica gel, yellow crystals of N-C cyano(4-chlorophenylthio)methyl]-
1.128 g of 2-phenylsulfonylacetamide was obtained. Further recrystallization from ethyl acetate and hexane gave colorless crystals.

Yield 88.4% mp 156-157°C Example 3 (
Compound number 26) CN PhC}lx! icHNHcOc}+20Me1 1 1.164 g of 2-(phenylmethyl)thio-2-aminoacetonitrile in dichloromethane 3 Td! dissolved in
0.686 g of pyridine (Pyr) was added.

Under water cooling, methoxyacetic anhydride 1. 382 g was added.

After reacting for 1 hour, it was concentrated under reduced pressure. Ethyl acetate (20%) was added, and the liquid was washed with 10% citric acid solution, water, 4% sodium bicarbonate solution, and then water, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. N-[cyano(phenylmethylthio)methyl]-2-methoxyacetamide F was separated by column chromatography using silica gel, and yellow crystals were obtained.
1. 533 g was obtained. Further recrystallization from benzene and hexane gave pale yellow needle crystals.

Yield 93.7% mp, 78 -79°C Example 4 (Compound No. 30) EtSC}INH2 CN BtSCHNl{COCHzSPh 2-Ethylthio2 Aminoacetonitrile 1 2 0.448 g was dissolved in chloroform 10-, and pyridine ( 0.31 g of P y r ) was added. After cooling on ice, 1.08 g of phenylthioacetyl chloride was added. 2
After 0 minutes, water 1 (W) was poured, and the mixture was extracted twice with dichloromethane 10. The extracts were combined, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. Crystalline N-[cyano(ethylthio)methyl]2-phenylthioacetamide 0.
960 g was obtained. Further recrystallization from benzene gave colorless crystals.

Yield 93.3% mp 66 -67°C Example 5 (Compound No. 35) 2-Cyclohexylthio-2-aminoacetonitrile 0
．． 457 g and 0.326 g of cyanoacetic acid were dissolved in 3d dichloromethane. After cooling on ice, 0.554 g of dicyclohexycarbodiimide (DCC) was added. 2
．． After reacting for 5 hours, the mixture was further left in the refrigerator overnight. Dichloromethane was distilled off, and 30% of ethyl acetate was added and filtered. The filtrate was washed with lθ% citric acid solution, water, 4% sodium bicarbonate solution, and then water, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. Separation by column chromatography using silica gel yielded 0.524 g of N-(cyano(cyclohexylthio)methyl)-2-cyanoacetamide as a yellow oil.Furthermore, it was recrystallized from benzene and hexane to obtain pale yellow crystals. Obtained.

Yield 82.5% mp 93 -94°C Example 6 (Compound No. 2) CHz 17 g of 2-phenylthio-2-aminoacetonitrile was dissolved in 1 nl of benzene 120, and diketene l was dissolved at room temperature.
lg was added. The temperature was raised to about 60°C and the reaction was carried out for 5 hours. 60 mm of water was poured into the mixture and extracted twice with 40 mm of benzene. The extracts were combined, dried over anhydrous magnesium sulfate, and then concentrated under reduced pressure. 9. Separate by column chromatography using silica gel to obtain colorless crystals. Obtained 42 g.

Yield 32.7% mp 62.5 -646C Example 7
(Compound No. 44) CN N-Ccyano(4-chlorophenylthio)methyl]-2
-0.276 g of chloroacetamide was dissolved in 10 mj of dichloromethane. Cool on ice and add m-chloroperbenzoic acid (
0.238 g of 80% content MCPBA') was added. After reacting for 15 minutes, the colorless crystals of If-
[Cyano(4-chlorophenylsulfinyl)methyl]
0.270 g of -2-chloroacetamide was obtained. Further recrystallization from ethyl acetate and hexane gave colorless crystals.

Yield 93.0% mp 98-101°C 15 Example 8 (Compound No. 54) 0.251 g of N-[cyano(phenylmethylthio)methyl]2-methoxyacetamide was dissolved in dichloromethane 8
- dissolved in Cool on ice and add m-chloroperbenzoic acid (80%
Content, MCPBA) 0.667 g was added. After reacting for 9 hours, the mixture was further left in the refrigerator overnight. The product was directly separated by column chromatography using silica gel to obtain 0.232 g of colorless crystals of N[cyano(phenylmethylsulfonyl)methyl]-2-methoxyacetamide. Further recrystallization from dichloromethane and benzene gave colorless crystals.

Yield 82.0% mp 163-165°C Representative examples of the compounds of the present invention produced in the same manner as in the above examples are listed in Tables 1 and 2.

- 1 6 (Note 1) A is acid chloride (Z=C I), B is carboxylic acid (Z
C represents acid anhydride (Z=R'CO2), D represents diketene, and E represents production using acetic acid and formic acid.

OH), Table 2 (Note 2) A indicates oxidation using MCPBA, B indicates oxidation using hydrogen peroxide and sodium tungstate, and C indicates oxidation using metaperiodic acid.

〔Effect of the invention〕

The production method of the present invention uses an aminoacetonitrile derivative represented by the general formula [■] that can be easily obtained from hydrogen cyanide, and the desired carboxylic acid amide derivative of aminoacetonitrile represented by the general formula (I) is produced in one step. It can be obtained in good yield and is an industrially excellent production method.

Claims (3)

[Claims] (1) General formula▲There are mathematical formulas, chemical formulas, tables, etc.▼・・・・・・・・・
[I] [In the formula, R is (a phenyl group which may have a substituent,
halogen atom, lower alkoxycarbonyl group, lower alkoxycarbonylalkylthio group, hydroxyl group, mercapto group, cycloalkyl group or oxygen-containing heterocyclic group) alkyl group, alkenyl group,
Cycloalkyl group, (halogen atom, lower alkyl group,
An aryl group (which may be substituted with a nitro group, a phenyl group which may have a substituent, or a phenoxy group which may have a substituent) or a heterocyclic group containing an oxygen atom or a sulfur atom, R^1 is a hydrogen atom or -CH_2Y, Y is a cyano group, acyl group, alkoxycarbonyl group, R
^2S(O)m (R^2 is an alkyl group or a phenyl group which may have a substituent, m: 0, 1, 2), a halogen atom or an alkoxyl group. ] Carboxylic acid amide derivative represented by. (2) General formula ▲ Numerical formula, chemical formula, table, etc. ▼ [II] [In the formula, R and n have the same meanings as above. ) and the general formula Z-CO-R^
1 [II] [In the formula, R^1 has the same meaning as above, Z is a halogen atom, a hydroxy group, or a general formula ▲ Numerical formula, chemical formula, table, etc. ▼ (In the formula, r^1 is lower alkyl group or R^1), however, when R^1 is a hydrogen atom, Z indicates ▲There are mathematical formulas, chemical formulas, tables, etc.▼ (r^2: lower alkyl group). ] General formula ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼ [ I ] (In the formula, R, R^1 and n have the same meanings as above.)
A method for producing a carboxylic acid amide derivative represented by (3) General formula ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼ [II] (In the formula, R and n have the same meanings as above.) Characterized by reacting an aminoacetonitrile derivative with diketene. A method for producing an acetoacetamide derivative represented by the general formula ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼ [ I ′] (In the formula, R and n have the same meanings as above.)