DD240890A1 - PROCESS FOR THE PREPARATION OF N- (THIEN-2-YL) -N '- (ALKOXYCARBONYLARYL-BZW.-ALKYL) -THIOROUS SUBSTANCES - Google Patents

Abstract

The invention relates to a process for the preparation of N- (thien-2-yl) -N- (alkoxycarbonylaryl or alkyl) -thioureas of the general formula I in which R 1 is H, alkyl, phenyl, substituted phenyl, R 2 H, alkyl, R1, R2 are polymethylene, R3 alkoxycarbonyl, R4polymethylene, phenylene, hetarylene, R5 alkyl. These compounds are potential drugs and at the same time serve as an intermediate for the preparation of other potential drugs. The aim of the invention is, starting from 3-alkoxycarbonyl-2-isothiocyanatothiophenen of the general formula II, whereinR1H, alkyl, phenyl, substituted phenyl, R2H, alkyl, R1, R2 polymethylene, R3 alkoxycarbonylbedeuten, N- (thien-2-yl ) -N- (alkoxycarbonylaryl or alkyl) thioureas. The synthesis of the compounds of the general formula I is carried out by reacting the compounds of the general formula II with aminocarboxylic acid esters of the general formula III in an organic solvent.

Description

field of use

The invention relates to a process for the preparation of N- (thien-2-yl) -N '- (alkoxycarbonylaryl- or alkyD-thioureas of the general formula I,

R ¹ = H, alkyl, phenyl, substituted phenyl,

R ² = H, alkyl,

R ¹ , R ² = polymethylene,

R ³ = alkoxycarbonyl,

R ⁴ = polymethylene, phenylene, hetarylene,

R ⁵ = alkyl

mean.

Compounds of general formula I are potential drugs and also serve as an intermediate for the preparation of other potential drugs.

Characteristic of the known technical solution

So far, only those compounds of general formula I have been shown, wherein R ⁴ = methylene. They were obtained by reacting corresponding S-alkoxycarbonyl-isothiocyanatothiophenes with glycine methyl or ethyl ester hydrochloride (HeIv. Chim. Acta 66, 14 & 157,1983). Object of the invention

The aim of the invention is to develop a simple process for the synthesis of N- (thien-2-yl) -N '- {alkoxycarbonylaryl- or -alkyl) thioureas of the general formula I.

The presentation of a number of such substituted thioureas expands the range of potential drugs or interesting intermediates.

Explanation of the essence of the invention

The invention is based on the object, new N- (thien-2-yl) -N '- (alkoxycarbonylaryl- or -alkyl) thioureas of the general formula I,

R ¹ = H, alkyl, phenyl, substituted phenyl,

R ² = H, alkyl,

R ¹ , R ² = polymethylene,

R ³ = alkoxycarbonyl,

R ⁴ = polymethylene, phenylene, hetarylene,

R ⁵ = alkyl

mean to represent.

According to the invention the object is achieved in that S-alkoxycarbonyl ^ -isothiocyanatothiophene of the general formula II,

R ¹ "= H, alkyl, phenyl, substituted phenyl,

R ² = H, alkyl,

R ¹ , R ² = polymethylene,

R ³ = alkoxycarbonyl

mean, with aminocarboxylic acid esters of general formula III,

R ⁴ = polymethylene, phenylene, hetarylene,

R ⁵ = alkyl

mean to be reacted in an organic solvent.

embodiments

The invention will be explained below with reference to two embodiments.

example 1 Preparation of N-IS-ethoxycarbonyl-B-dimethylthien-1-yl-N'-ip-ethoxycarbonyl-phenyl-thiourea, Ci ₉ H ₂₂ N ₂ O ₄ S ₂

2.4 g (10 mmol) of S-ethoxycarbonyl-isothiocyanato-B-dimethylthiophene are stirred with 3.3 g (20 mmol) of p-aminobenzoic acid ethyl ester in 70 ml of benzene at room temperature for 20 h. The resulting product is filtered off and recrystallized several times. If the product does not precipitate out, it is evaporated in vacuo and the residue obtained is recrystallized.

Melting point: 167-169 ° C, yield: 73%.

In an analogous way were shown:

NO-ethoxycarbonyl-B-ethyl-thien ^ -ylJ-N'-ip-ethoxy-carbonyl-phenyl-thiourea, C ₁₉ H ₂₂ N ₂ O ₄ S ₂ (406.5),

Melting point: 176-179 ⁰ C, yield: 63%.

NO-ethoxycarbonyl-B-ethyl-thienyl-Nyl-N'-fp-ethoxycarbonylphenylmethyD-thiourea, C ₂₀ H ₂₄ N ₂ O ₄ S ₂ (420.6),

Melting point: 155-157 ° C, yield: 70%.

N- (ethoxycarbonyl-4,5-dimethylthien-2-yl) -N '- (2-ethoxycarbonylethyl) thiourea, Ci ₅ H ₂₂ N ₂ O ₄ S ₂ (358.5),

Melting point: 98-99 ⁰ C, yield: 61%.

NO-ethoxycarbonyl-α-dimethyl-thien-cy-ND-N'-ii-ethoxycarbonylethyl (thiourea, C ₁₆ H ₂₂ N ₂ O ₄ S ₂ (358.5),

Melting point: 140-142 ⁰ C, yield: 66%.

N-iS-EthoxycarbonylAö ^^ - tetrahydro-benzo / b / ^ -ylJ thien-N'-fp-ethoxycarbonylphenylJ-thiourea, C ₂₁ H ₂₄ N ₂ O ₄ S ₂ (432.6)

Melting point: 166-169 ° C, yield: 81%. '

N-β-ethoxycarbonyl-phenyl-thienyl-Yl-N'-fp-ethoxy-carbonyl-phenyl-thiourea, C ₂₃ H ₂₂ N ₂ O ₂ S ₂ (454.7),

Melting point: 159-161 ° C, yield: 71%.

N- (4-p-chlorophenyl-3-ethoxycarbonylthien-2-yl) -N '- (p -ethoxycarbonylphenyl) -thiourea, C ₂₃ H ₂₁ CIN ₂ O ₄ S ₂ (489.0), m.p .: 182-185 ° C, yield: 61%.

N- (4-p-chlorophenyl-3-ethoxycarbonyl-thien-2-yl) -N '- (p-ethoxycarbonylphenylmethyl (thiourea, C ₂₄ H ₂₃ CIN ₂ O ₄ S ₂ (503.0), Melting point: 164-167 ° C, yield: 76%.

N- (3-ethoxycarbonyl-4,5,6,7-tetrahydrobenzo / b / thien-2-yl) -N '- (2-ethoxycarbonylethyl) thiourea, C ₁₇ H ₂₄ N ₂ O ₄ S ₂ (384.5) .

Melting point: 117-119 ° C, yield: 68%.

NO-ethoxycarbonyl-6-dimethyl-thien-cy-N'-ip-ethoxycarbonyl-phenylmethyl-thiourea, C ₂₀ H ₂₄ N ₂ O ₄ S ₂ (420.6),

Melting point: 238-242 ⁰ C, yield: 61%.

Example 2 Preparation of N _, N'-bis [4- (p-chlorophenyl) -3-ethoxycarbonylthien-2-yl] thiourea,

C ₂₇ H ₂₂ Cl ₂ N ₂ O ₄ S ₃ (605.6)

3.2 g (10 mmol) of 4-p-chlorophenyl-3-ethoxycarbonyl-2-isothiocyanatothiophene are refluxed with 5.7 g (20 mmol) of 2-amino-4-p-chlorophenyl-3-ethoxycarbonylthiophene 6 h in 100 ml of benzene. After cooling, the solvent is distilled off in vacuo and the residue recrystallized.

Melting point: 201-204 ⁰ C, yield: 34%.

In an analogous manner was shown:

NO-ethoxycarbonyl-phenyl-thienyl-N-N'-O-ethoxycarbonyl-B. Ej-tetrahydrobenzo / b / thienyl-thiourea, C ₂₅ H ₂₆ N ₂ O ₄ S ₃ (514.7) .

Melting point: 199-200 ° C, yield: 40%.

Formula I

R ² S ^ S ^ NHCSNB-R ⁴ -GOOR ⁵

R ¹ = H, alkyl, phenyl, substituted phenyl,

R ² = H, alkyl,

R ¹ , R ² = polymethylene,

R ³ = alkoxycarbonyl,

R ⁴ = polymethylene, phenylene, hetarylene,

R ⁵ = alkyl

Formula II

R ¹

R ¹ = H, alkyl, phenyl, substituted phenyl,

R ² = H, alkyl,

R ¹ , R ² = polymethylene,

R ³ = alkoxycarbonyl

Formula III

H ₂ NR ⁴ -COOR ⁵

R ⁴ = polymethylene, phenylene, hetarylene,

R ⁵ = alkyl

Claims (1)

Claim: Process for the preparation of N- (thien-2-yl) -N '- (alkoxycarbonylaryl or -alkyD-thioureas of the general formula I, R ^{1 is} H, alkyl, phenyl, substituted phenyl, R ² = H, alkyl, R ¹ ; R ² = polymethylene, R ³ = alkoxycarbonyl, R ⁴ = polymethylene, phenylene, hetarylene, R ^s = alkyl mean, characterized in that S-alkoxycarbonyl ^ -isothiocyanatothiophene of the general formula II, wherein R ¹ = H, alkyl, phenyl, substituted phenyl, R ² = H, alkyl, R ¹ , R ² = polymethylene, R ³ = alkoxycarbonyl mean, with amino acid esters of general formula III, wherein R ⁴ = polymethylene, phenylene, hetarylene, R ⁵ = alkyl mean to be reacted in an organic solvent.