DD263055A1 - PROCESS FOR PRODUCING SUBSTITUTED 3-AMINO-5-PHENYL-THIOPHENE - Google Patents

Abstract

The invention relates to a process for preparing substituted 3-amino-5-phenylthiophenes. These compounds, which can be used as intermediates, are made accessible by a simple process according to the invention by reacting a-chlorocinnamic acid nitriles with acceptor-substituted methanethiols in alcoholic solution and in the presence of potassium hydroxide or potassium carbonate.

Description

    - 1 -

Title of the invention

Process for the preparation of substituted 3-anino-5-phen; ylthiophenes. -. ,

Field of application of the invention

The invention relates to a process for the preparation of substituted 3-amino-5-phenyl-thiophenes. These compounds can gain importance as intermediates.

Characteristic of the known technical solutions

It is known that 3-Ami "^ o-5-pben3" 1-thiophene-2-carboxylic acid. esters of β-Chldrziintsäurenitril and thioglycol ester in the presence of sodium alkoxide according to Synthesis 19 & 4 , 274 can be prepared. The 3-amino-5-phen; yl-thiophene-2-carboxylic acid ethyl ester is according to J.prakt. Chem. 325 , 87β (1983) also been prepared from cc-Olilorzimtsäurenitril and Thioglykolsäureester. However, this also requires the relatively expensive sodium tetrachlorate, which is prepared separately. In particular, however, nothing is said about how 3-amino-5-phenyl-thiophene can be prepared from α-or β-chlorocinnamonitrile with other acceptor groups in 2-position. -

Object of the invention.

The aim of the invention is to produce ^ -Amino - ^ - phenyl-thiophenes in a simple manner.

n.

Statement of the invention

The object of the invention is to produce 3-amino-5-phenyl-thiophenes having functional electron acceptor groups in the 2-position and bypassing sodium alkoxide by a simple and novel process.

According to the invention the object is achieved in that 3-amino-5-pheny! -Thiophene of the general formula I,

wherein R and R represent a hydrogen or each a halogen atom, an alkyl, alkoxy or litro group and R " ^{1 represents} an alkoxycarbonyl, carbamido !, acyl, Iormyl or p-Uitrophenylgruppe prepared by α -Chlorzimtsäurenitrile the general! Formula II with acceptor-substituted

12

Methanethiols of the general formula III in which R, R and

3 R have the meaning given above,

II HS-GH ₂ -R ³ IH

be reacted in alcoholic solution and in the presence of potassium hydroxide or potassium carbonate.

The process dispenses with the use of ITatriumaIkoholat and replaced by potash or potassium hydroxide solution. As a result, new, previously unknown 3-amino-5-phenylthiophenes are made accessible with functional groups in the 2-position. The required cc-Chlorzimtsäurenitrile

\ J .1

- 3 are after J.prakt. Chem. 325 »876 (1983) easily representable.

embodiments

Example 1 3-Amino-2-formyl-5-phenylthiophene

A solution of 20 mmol of mercaptoacetaldehyde in 50 ml of ethanol is mixed with 20 mmol of a-chlorocinnamonitrile. At 2O-25 ° C, 10 ml of 4N KOH are added. Bach 4-5 hours is slowly diluted with 100 ml of water, filtered off with suction and washed with water and ethanol. If the reaction product is greasy, it is triturated with ethanol. Yield 43 y ₀ , mp 15 9-161 ° after recrystallization from Sssigester.

Example 2.

3-Ämino-2- (p-nitrophenyl) -5-phenyl-thiophene

To a solution of 20 mmol p-lTitrobenzylmercaptan in 60 ml of ethanol are added 20 mmol a-chlorocinnamonitrile and 10 ml of 4N KOH, Liach 5-6 hrs. The reaction mixture is stirred into 200 ml of water and the precipitate was filtered off with suction and washed with water. Yield 82 %, mp 153-156 ⁰ C after recrystallization from glacial acetic acid.

Example 3 Ethyl 3-amino-5-phenyl-thiophene-2-carboxylate

20 mmol of α-Chlorzimtsäurenitril be in 50 ml. Abs. Dissolved ethanol, treated with 20 mmol of thioglycolic acid ethyl ester and 6 g of potassium carbonate and stirred at .20-25 ⁰ C for 3 hrs. The reaction mixture is stirred into 3OO ml of water and the precipitate is filtered off with suction. Yield 45 %, mp 1O3-1O5 ° C after recrystallization from ethanol.

Example 4

3-amino-5- (p-methyl-phenyl) -thiophene-2-carboxylic acid ethyl! Ester

10 mmol of α-chloro-4-methyl-cinnamonitrile are dissolved in 20 ml of abs. Ethanol dissolved. Jan gives 10 mmol of thioglycolic acid ester and 3 g

Potassium carbonate added and stirred for 4 hrs. At 2O-25 ° C. Thereafter, it is intended to stir in 100 ml of water, the precipitate is filtered off with suction and washed with water. Yield 65%, - F. 60-61 ⁰ G after recrystallization from ethanol / water.

Example 5

3-linino-5-phenyl-thiophene-2-carbo amide ::

To a .Lösung of 10 mmpl α-chlorocinnamic acid nitrile and 10 mmol Thioglykolsäyeamid in 25 'ml of ethanol are added 10 ml of 4N KOH,! La after 12 hrs the Reaktionsgeraisch is stirred into 100 ml of water, the precipitate sucked off and washed with water. Yield 50 %, mp 208-210 ⁰ G after recrystallization from ethanol. When using 3 g KpGO-, in place of K the yield 59

in place of the KOH and eight hours of stirring at 20 ⁰ G.

Example 6 · 2-Acetyl-3-amino-5-phenyl-thiophene. , ,

To a mixture of 10 mmol mercaptoacetone and 10 mmol of a * -Chlorzimtsäurenitril in 25 ml of ethanol are added at room temperature with stirring 10 ml of 4N KOH. It is stirred for 5 hours and the reaction mixture is then added to about 200 ml of ice / water. After completion of crystallization is filtered off with suction. Yield 49 / e »m. 134-136 after recrystallization from ethanol. When using 3 g K ₀ GO ₀

ο ri

in place of KOH and stirring for 2 hours at 60G

the yield is 41%. , · "

Example 7 "

3-amino thiophene-2-benzoyl-5-phenyl-

10 mmol of benzoyl mercaptan and 10 mmol of α-chlorocinnamononitrile in 20 ml of ethanol are mixed at room temperature while stirring with 10 ml of 4N KOH. Stirring is continued for 5 hours and the reaction mixture is then added to approx. 150 ml of ice / water. .Each crystallization is sucked off. Yield 45 5 $, F. 143-145 ⁰ G after recrystallization from ethanol.

Claims (2)

- 5 - Claim '. 1. Process for the preparation of substituted 3-amino-5-phenylthiophenes of general formula I, wherein R and R is a hydrogen or a halogen = 3 atom, an alkyl, alkoxy or thio group and 'R represents an alkoxycarbonyl, oarbamido, acyl, pormyl or p-nitro = phenyl group, characterized in that a-chlorocinnamonitriles of the general formula II II with acceptor-substituted Kethanthiolen of the general formula III,. , " , HS-CH ₂ -R ³ 12 3 in which R, R and E ^ have the abovementioned meaning, be reacted in alcoholic or aqueous-alcoholic solution and in the presence of a base. 2. The method according to claim 1, characterized in that preferably used as bases potassium hydroxide or potassium carbonate v / earth.