JPS60226874A - Production of 2-aklyl-substituted aminothiophene compound - Google Patents

Abstract

PURPOSE:To obtain the titled compond useful as an intermediate of novel dye, especially as an intermediate of coupler or agricultural or pharmaceutical chemicals, in high yield, by using a 2-aminothiophene compound and a halogenated compound as raw materials, and reacting the components in a solvent in the presence of an acid acceptor. CONSTITUTION:The objective compound of formula III [R<1> is lower alkyl, allyl, benzyl, phenetyl, group of formula II (R<3> is lower alkyl; Y is lower alkylene) or -Y-CN; R<2> is H or R<1>; R is H, (substituted) lower alkyl, phenyl or heterocyclic group; Z is cyano, lower alkoxycarbonyl, or nitro] can be prepared by reacting the 2-aminothiophene compound of formula I with one or two halogenated compounds of formula X-R<1> (X is halogen), in a solvent preferably N,N-dimethylformamide, etc., in the presence of an acid acceptor such as K2CO3, soda ash, etc. at 20-80 deg.C. The reaction can be accelerated by adding 0.001-1.0mol of KI or NaI based on 1mol of the halogenated compound.

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention relates to a method for producing 2-alkyl-substituted aminothiophene compounds.

More specifically, general formula (II) (in the formula (IQ, R represents a hydrogen atom, an optionally substituted lower alkyl group, a phenyl group, a heterocycle,
2 represents a cyan group, a lower alkoxycarbonyl group, or a nitro group. ) to the 2-aminothiophenes represented by the general formula (formula (g), X is a halogen atom, and R1 is a lower alkyl group, an allyl group, a benzyl group, a phenethyl group, or -Y-COR3, -Y- CN++ (where R3 is a lower alkyl group and Y represents a lower alkylene group). , the general formula (1
) (In formula (I), R, Z are the formula ([0 in (7) R, Z,!
: Same L) Teashi, and R1 is the same as R1 in the formula (to), R2 is a hydrogen atom, or the same as R1 in the formula (to), and R1 and H2 are each different. You can leave it there. ) The present invention relates to a method for producing a 2-alkyl-substituted aminothiophene compound represented by the following formula.

The 2-alkyl-substituted aminothiophenes produced according to the present invention can be used as intermediates, especially couplers, for new dyes.
It is also a useful compound as an intermediate for agricultural medicines.

The anocarboxylic acid ester or malonitrile represented by the general formula (II), which is the starting material of the present invention, can be obtained by the reaction of the following formula.

H8-CH2C-R+ NC-CH2Z1 0! Bamboo NC-CH2-CN The 2-aminothiophenes represented by the above general formula (It) are unstable to heat and alkali compounds under alkylation conditions, and also contain a cyan group, alkoxycarbonyl group, etc. at the 3-position. Because it has an electron-withdrawing group, the activity of the amine group at the 2-position is low, and it does not attract much attention in terms of synthetic chemistry.
Moreover, it could not be obtained with a satisfactory yield.

Therefore, the present inventors have intensively studied the alkylation reaction of a compound of formula (It) with a compound of formula (g), and as a result, have arrived at the present invention.

In the method of the present invention, formula (II) to be alkylated
Examples of the substituted or unsubstituted lower alkyl group represented by R in the compound include substituted alkyls such as methyl, ethoxycarbonylalkyl, cyanomethyl, and chloromethyl. Examples of substituted or unsubstituted phenyl groups include phenyl, alkylphenyl, nitrophenyl, chlorophenyl, alkoxyphenyl, etc.
Examples of substituted or unsubstituted heterocycles include thiazole ring, inthiazole ring, oxazole ring, isoxazole ring, thiophene ring, thiadiazole ring, imidazole ring, piracy 1i% Hillff-/L'3J% hendithiazole term, Examples include a benzisothiazole ring or a nitro, chloro, bromo, alkyl, or alkoxy substituted product thereof.

Examples of the lower alkoxycarbonyl group represented by 2 include methoxycarbonyl, ethoxycarbonyl,
Branched or straight chain propoxycarbonyl, methoxycarbonyl, bethoxycarbonyl, hexyloxycarbonyl and the like can be mentioned.

The formula (to) to which these formula (II) compounds are alkylated
Examples of the lower delkyl group of the halogenated compound R1 represented by are methyl, ethyl, branched or straight chain propyl, butyl, pentyl, hexyl and the like. Also, R1 is -
Examples of the Y-CN group include cyanomethyl, cyanoethyl, etc., and examples of the -Y-COR3 group in R1 include methoxycarbonylmethyl, ethoxycarbonylmethyl, propoxycarbonylmethyl, butoxycarbonylmethyl, methoxycarbonylethyl, ethoxycarbonylethyl, Examples include fropoxycarbonylethyl and butoxycarbonylethyl.

In the method of the present invention, the reaction between the 2-aminothiophenes represented by the general formula (IQ) and the halogenated compound represented by the general formula (g) is carried out in an organic solvent in the presence of a deoxidizing agent,
As a reaction solvent, N,N-dimethylformamide,
Examples include cellosolves, such as methyl cellosolve and ethyl cellosolve, and alcohols, such as methanol, ethanol, gropanol, butanol, dimethyl sulfoxide, and preferably N,N-dimethylformamide. The amount of solvent is 0 for 2-aminothiophenes.
1.5 to 20 times, preferably 1 to 10 times. Examples of the deoxidizing agent include potassium carbonate, soda ash, caustic soda, caustic potash, sodium acetate, and magnesium oxide, with potassium carbonate or soda ash being particularly preferred. In addition, the reaction temperature is 20 to 200°C,
The temperature is preferably 40 to 80°C, and the molar ratio of the aminothiophenes to the halogenated compound is O, S to 10.0 mol, preferably 1.0 to 6.0 mol. During the reaction, the reaction will be rapid if potassium iodide or sodium iodide is used in a molar ratio of o, o o i to 1.0 mol, preferably 0,005 to 0.1 mol, to the halogenated compound. proceed.

The sample can be directly subjected to the coupling reaction.

Next, the present invention will be explained in more detail with reference to Examples, but the present invention is not limited to the Examples unless the gist of the invention is exceeded.

"Example center part" and "%" refer to "parts by weight" and 1
% by weight.

[Example-1] 200 parts of N,N-dimethylformamide, 124 parts of 2-amino-3-cyano-thiophene, 27 parts of potassium carbonate
6 parts and 10 parts of potassium iodide were added. 310 parts of allyl chloride was added at room temperature, and the mixture was reacted at 70°C for 4 hours. After cooling to room temperature, it was discharged into 1000 parts of methanol, and the precipitated salts were separated. Methanol was distilled off under reduced pressure, and the remaining liquid was analyzed by liquid chromatography to obtain 194 parts of 2-(N,N-diallyl)amino-3-cyanothiophene (yield 95%). was found to be generated. The residual liquid was separated by column chromatography, and the elemental analysis values of the purified product were as shown below, which agreed well with the calculated values.

[Example-2] 157 parts of 2-amino-3-methoxycarbonylthiophene, 77 parts of soda ash, and 20 parts of potassium iodide were added to 200 parts of N,N-dimethylformamide. 205 parts of n-butyl bromide was added at room temperature, and the mixture was reacted at 70°C for 3 hours. After cooling to room temperature, 100 parts of methanol was added, and the precipitated salts were filtered out. Liquid chromatography revealed that 203 parts (yield: 95%) of 2-(n-butylamino)-3-methoxycarbonylthiophene was present in the reaction solution. After methanol was distilled off under reduced pressure, the product was separated and purified by column chromatography and subjected to elemental analysis. As a result, the digit values agreed well with the calculated values as shown in the table below.

[Example-3] 19 parts of 2-amino-3-ethoxycarbonyl-4-methylthiophene was added to 400 parts of N,N-dimethylformamide.
9 parts, 106 parts of soda ash, and 20 parts of potassium iodide were added. Add 122 parts of monochloroethyl acetate at 50°C,
The reaction was carried out at 70°C for 3 hours. After cooling to room temperature, the mixture was separated and purified by column chromatography to obtain 256 parts (yield: 94%) of 2-(ethoxycarbonylmethyl)amino-3-ethoxycarbonyl-4-methylthiophene. The elemental analysis values for this compound are shown in the table below, and were in good agreement with the calculated values.

[Example-4] In place of monochloroethyl acetate in Example-3, 83 parts of chloroacetonitrile was used to react, and 190 parts of 2-(cyanmethyl)amino-3-ethoxycarbonyl-4-methylthiophene (yield 85%). The elemental analysis values are shown in the table below and were in good agreement with the calculated values.

[Example-5] In place of butyl bromide in Example-2, benzyl chloride 139
A solution containing 230 parts (yield 93%) of 2-benzylamino-3-methoxycarbonylthiophene was obtained. The elemental analysis of the product purified by column chromatography was in good agreement with the calculated values as shown in the table below.

[Example-6] 200 parts of N,,N-dimethylformamide, 138 parts of 2-amino-3-cyano-4-methylthiophene, 75.9 parts of potassium carbonate, 10 parts of potassium iodide, and β-phenylethyl bromide 203 parts were added and reacted at 70°C for 3 hours. After cooling to room temperature, 153 parts of allyl chloride, 138 parts of potassium carbonate and 20 parts of potassium iodide were added to give 50-7.
The reaction was carried out at 0°C for 5 hours. After cooling to room temperature, separation by column chromatography revealed that 169 parts of 2(N-phenylethyl-N-allylamino)-3-cyano-4-methylthiophene, 2-(N,N-diallylamino)-
21 parts of 3-cyano-4-methylthiophore, and U
35 parts of 2-(NN-cyphenylethylamino)-3-cyano-4-methylthiophene were obtained. In addition, the elemental analysis values for each compound are shown in the table below, which agrees well with the calculated values.

2-(N-phenylethyl-N-allylamino)-3-
Cyano-4-methylthiophene 2-(NN-diallylamino)-3-cyano-4-methylthiophene 2- (N,N-cy(phenylethyl)amine 3
-Cyano-4-methylthiophene [Example 7] A reaction was carried out in the same manner as in Example 2, using 400 parts of ethyl cellosolve instead of 200 parts of N,N-dimethylformamide in Example 2. 16 o parts of 2-(n-butylamino)-3-methoxycarbonylthiophene (yield 7s%)
was gotten.

Claims (5)

[Claims] (1) General formula (ID (Formula (It)), R represents a hydrogen atom, an optionally substituted lower alkyl group, a phenyl group, a heterocycle, and 2 represents a cyan group, a lower alkoxycarbonyl group, a nitro 2-aminothiophenes represented by
General formula (g)
-COR3, 1 -Y-CN. However, R3 represents a lower alkyl group, and Y represents a lower alkylene group. ) is reacted with one or two halogenated compounds represented by formula (I) in a solvent in the presence of a deoxidizing agent.
) (In formula (1), R and Z are the same as oR and Z in formula (IN), and R1 is the same as R1 in formula (g), and R2
is a hydrogen atom, which is the same as R1 in formula (g), R
11R2 may be different from each other. ) A method for producing a 2-alkyl-substituted aminothiophene compound. (2) The method according to claim 0, wherein the reaction solvent is dimethylformamide. (3) The method according to claim (1), wherein the reaction temperature is 20 to 80°C. (4) Potassium iodide or sodium iodide, formula (to)
0.001 to 1.
The method according to claim (1), wherein the reaction is carried out by adding 0 molar ratio. (5) The method according to claim (1), wherein the deoxidizing agent is potassium carbonate or soda ash.