DD146952A1 - PROCESS FOR THE PREPARATION OF SUBSTITUTED 3-AMINO-4-CYAN-5-PHENYLTHIOPHENESE - Google Patents

Abstract

Title compounds IV, which can be used as intermediates for dyes, are prepared according to the invention by reacting beta-chloro-a-cyano-cinnamic acid nitriles I either with oxomercaptans II or in one stage successively with Na 2 S and halogen compounds III.

Description

167

Title of the invention

Pb.enylthioph.enen method for preparation of substituted 3- ^A -mino 4-cyano ~ .5- "

Int.Cl. C 07 D, 333/26

 Field of application of the invention

The invention relates to a process for the preparation of substituted 3-amino-4-cyano-5-phenylthiophenes. Such compounds can gain importance as intermediates for dyes »

Characteristic of the known technical solutions

It is known that the title compounds according to Pharmazeut, Zentralhalle 1Q2., 348 (1968) and Arch.Pharm. 301 ,, 601 (1968) can produce a thioacylation of malononitrile "But once it requires dithiosäureester and on the other hand Methy! Mercaptan is released. Another method for preparing the title compounds is according to J.prakt. Chem. 315 * 497 (1973) on the Reaction of Oxathiolium Salts with Malononitrile Although this process, starting from benzaldehyde, also comprises only 3 stages, only 3-aminothiophenes with a benzoyl group can be prepared in the second position. Also known is the preparation of related 3-amino ~ 4-cyano-thiophenes according to Liebigs Ann.Ghem, (SJjffi, 90 (1962) and • US-Pat. 3,507,874 (1970), CA 21, 14672 (1970) or Canad. J. Cheia 4J3, 1372 (1971), dedcch contain these 3-aminothiophenes

in the 5-position alkylmercapto or arylamino groups as substituents. The according to F.P. 1 211 620 (1958) producible, related 3-aminothiophenes do not contain 4-cyano group.

Object of the invention

The aim of the invention is to prepare substituted 3-amino-4-cyano-5-phenylthiophene in a simple manner.

Explanation of the essence of the invention

The object of the invention is to produce new as well as already known substituted in 2-position 3-amino-4-cyano-5-ph.enylthioph.ene by a simple process. According to the invention the object is achieved in that B- C hloz-oC-cyano cinnamonitriles of the formula I,

C = C - CN. I.

Il

Cl CN.

wherein R represents a hydrogen or halogen atom or a nitro group, in the presence of bases with mercapto compounds of the formula II,

HS-CH ₂ -R II

in which R represents a carboxyl, carbalkoxy, formyl or acyl group, or by reacting the β-chloro- / cyanimiditrile I in one stage first with sodium sulfide (Na ₂ S) and then with halogen compounds of the formula III,

Cl-CH ₂ -R Uli

wherein R is a nitrile, Carbalkoxyrι carboxy, carbamido, nitro or acyl group, are reacted; Ethanol is preferably suitable as the solvent. This results in both cases, the 2-substituted Q- Cyanthiophene of formula IV,. ···. '''''

rv

wherein R is a hydrogen or halogen atom or a nitro group

Pe and R may be a carboxyl, carbalkoxy, carbamido, nitrile, formyl, nitro or acyl group.

The starting material I is prepared by chlorination of Benzylidenmalonitrilen at 160 ⁰ C in a step according to a prescription from the dissertation K. SCHOLItBERG, TU Dresden 1963 and the diploma thesis E, SCHIITLER, TU Dresden 1972,

embodiments

Example 1: 3-Amino-5-phenyl-4-cyanthiophene-2-carboxylic acid ethyl ester

a) A mixture of 0.01 raol ß-chloro-cyan-cinnamonitrile, 20 ml absol. Ethanol, 0.01 mol of thioglycolic acid ester and 2j8 g of dry, powdered potassium carbonate is stirred for 0.5 hrs. At room temperature and then 0.5 hr. In the boiling water bath. After cooling, dilute with 50-100 ml of water and filtered off with suction. Yield Q $ _t% mp. 114-116 ⁰ C (from ethanol).

b) 0.011 mol of Fa ₂ S · 5 H ₂ O are dissolved in 10 ml of water. With ice-cooling and stirring, a solution of 0.01 mol of β-chloro-cyanocinnamonitrile in 20 ml of ethanol is added dropwise thereto. 'After 30 min. After stirring for 30 min at room temperature, 1.4 g of potassium carbonate are added and the mixture is heated under gentle reflux for 30 min., After cooling, it is stirred into 80 ml of cold water and suction filtered. yield 65% _s mp. 113-115 ⁰ C (from ethanol),

Example 2: Amino-phenyl-cyanothiophene-2-carboxylic acid (potassium salt)

A solution of 1.5 g 8Oproz. Thioglycolic acid i = n 5 ml of ethanol is neutralized with 8 ml of 2N ethanolic KOH. Thereafter, while stirring and cooling with 0.01 mol ß-chloro - <^ T-cyanzimtsäurenitril, dissolved in a little ethanol. After 30 min. Stirring at room temperature is followed by addition of 10 ml of 2N ethanolic KDH and refluxing for 1 hour. After cooling and crystallization has ended, the mixture is filtered off with suction. Yield 86 %, mp 289-292 ⁰ C (from propanol).

(The free acid, mp 172-174 ⁰ C, obtained after dissolving the salt in water and acidify).

Example 3 * 2-Nitro-3-amino-5-phenylthiophene-4-carbonitrile

A solution of 2 g Na.pS · 5 · HPO * ^Ώ ^ ⁰ ^ ^m ^ ^ater, is slowly under ice-cooling and stirring, with a solution of 0.01 mol ß ~ chloro - cyano-cinnamic acid in 20 ml of ethanol - </ and allowed to stand for 30 minutes. At -5 to -15 ° C is added dropwise with stirring slowly 0.012 mol of bromonitromethane. It is then · 30 min. stirred at room temperature. It is then diluted with approx. 80 ml of water and filtered with suction. Yield 55%> mp _c 225-227 ⁰ C

(If the reaction mixture is no longer significantly alkaline before dilution with water, the mixture is heated for a further 15 minutes on the water bath with the addition of 0.01 mol of KpCOo).

Example 4: 3-amino-5-phenyl-2,4-dicyanothiophene

A solution of 1.8 g of Na 2 .5H 2 O in 10 ml of water is added with 0.01 mol of β-chloro-cyano-cinnamonitrile, dissolved in 20 ml of ethanol, while cooling with ice. After 30 min. Are standing with stirring and ice cooling 0.012 mol of chloroacetonitrile, diluted with a little ethanol, added dropwise. After 30 min. stirred at room temperature, it adds 0.01 mol KpCOo and heated for 40 min. under reflux. After cooling, it is diluted with 80-100 ml of water and filtered with suction. Yield 61%, mp. 159-162 ⁰ C (from ethanol). ·

Example 5 J 3 ~ amino-5-p'-phenyl-2-acetyl-4-cyano mophen η

a) According to Example 4 four de η in place of chloroacetonitrile 0.012 mol chloroacetone implemented. Yield 90%, mp. 174-176 ° C (from ethanol).

b) A mixture of 0.01 mol ß-chloro-c ^ -cyan-cinnamonitrile, 0.01 mol of mercaptoacetone (used as a dimer) and 20 ml of ethanol is mixed with 0.02 mol KoCOo, 30 min. at room temperature and then the same time at 50 ⁰ C stirred. After cooling, diluted with 80-1Ό0 ml V / asser and aspirated. Yield 6.0%, mp 176-178 ⁰ C (from ethanol).

Example 6: 3-Amino-5-phenyl-2-benzoyl- ^i! l-cyanothiophene

Following the procedure given in Example 4, instead of chloroacetonitrile, 0.012 mol of phenacyl bromide or chloride are reacted. Yield 80%, mp. 209-212 ⁰ C (from glacial acetic acid).

Example 7J 3-Amino-5- (o-nitrophenyl) -2,4-dicyanothiophene

Following the procedure given in Example 4, instead of β-chloro-, cyano-cinnamonitrile, 0.01 mol of β-chloro-cyano- (o-nitro) -cinnamonitrile is reacted. Yield 52%, mp 214-216 ⁰ C (from verd. Ethanol).

Example 8: 3-Amino-5- (o-nitrophenyl) -4-cyanthiophene-2-carboxylic acid ethyl ester

To a solution of 0.01 mol of β-chloro-c-cyano (o-nitro) -cinnamic acid nitrile and 0.01 mol of thioglycolic acid ester in 30 ml of ethanol are added 0.02 mol of potassium carbonate. The mixture is first 30 min. at room temperature and then stirred for 15 min * in a boiling water bath. After obtaining diluted with 100 ml of water and aspirated. Yield 70%, mp. 169-171 ⁰ O (from ethanol). , ,

Example 9 * 3 ~ amino - ^ - phenyl - ^ - formylthiophene - 4 - carbonitrile

To a Geraisch of O _S O 1 mol ß-Ohlor - ^ - cyano-cinnamic acid nitrile -OjOI mol mercaptoacetaldehyde (used as a dimer) and 15 dl ethanol are added dropwise with stirring and cooling 0.02 mol Triethylaniin "The precipitated product is filtered off, yield 50 % _f Scbmp. 207-208 ° G (from ethanol).

Claims (3)

Process for the preparation of substituted 3-amino-1-cyantliophenes, characterized in that β-chloro-cyano-cinnamonitriles of the formula I 1 GN wherein R represents a hydrogen or halogen atom or a nitro group, either with mercapto compounds of formula II R-CH ₂ - SH II or their dimers wherein R is a carboxyl, carbalkoxy, carbamoyl, acyl or Formy! group, in a solvent at -15 to 80 ^0C in the presence of bases, or in one stage successively with sodium sulfide (Na ^ S ) and halogen compounds of the formula ΪΙΪ, R - CHp - III wherein R is a nitrile, carboxy, carbalkoxy, carbamido, nitro or acyl group means in a solvent with the addition of bases as a cyclizing agent are reacted, wherein the in Substituted 2-position 3-amino-5-phenyl - ^ - cyanothiophenes of the formula ID /, rv j '-vorin R' form a hydrogen or Tialoge.natom or. a. Nitro group and R 1 represents a nitrile, carboxyl, carbalkoxy, carbamido-5-nitro, acyl or formyl group,