CS276128B6 - 1-Substituted 3- (2-cyanophenyl) thiourea and a process for the preparation thereof - Google Patents

Abstract

The invention relates to 1-substituted 3-(2-cyanophenyl)thioureas of the general formula I, where R is 4-bromophenyl, 4-chlorophenyl, 4-tolyl, 4-methoxyphenyl, 4-hydroxyphenyl, cyclohexyl, isopropyl, tert, butyl, anilinoacetate and a method for their preparation by the reaction of 2-isothiocyanatobenzonitrile with primary amines in a dichloromethane-petroleum ether environment at a temperature of 0 to 20 °C. The substances of the general formula I are used for the synthesis of N,N'-disubstituted or N,N,N'-trisubstituted N"-(2-cyanophenyl)-guanidines and for the preparation of 3- or 4-substituted quinazolines, which are used in pharmacy and agriculture for their physiological effects.

Description

The invention relates to 1-substituted-3- (2-cyanophenyl) thioureas of formula I.

wherein R is 4-bromophenyl, 4-chlorophenyl, 4-tolyl, 4-methoxyphenyl, 4-hydroxyphenyl, cyclohexyl, isopropyl, tert, butyl, anilino and a process for their preparation by reaction of 2-isothiocyanatobenzonitrile ^{9 with} primary amines in dichloromethane-petroleum ether at 0 to 20 ° C.

The compounds of the formula I and the process for their preparation have not yet been described. It is known from the literature that the related 1-phenyl-3- (2-cyanophenyl) thiourea can be prepared either by reacting phenyl isothloocyanate with aniline in the absence of solvent at 50-2 ° C for 20 hours in 85% (+) yield or by reaction 2 -isothiocyanatobenzonitrile with aniline at room temperature in a mixture of dichloromethane and petroleum ether (1: 1) in a yield of 98% (* Taylor EC, Ravindranathan RV. 3. Org. Chem. 27 (1962) 2622; Pazdera P., Ondráček 0., PV 1747-88; Pazdera P., Nováček E., Ondráček 0., Chemical Rumors, in press).

It has now been found that compounds of formula I can be prepared by reacting 2-isothiocyanatobenzonitrile with primary amines in dichloromethane-petroleum ether at 0-20 ° C in 78-96% yield.

Example 1

To a solution of 2-isothiocyanatobenzonitrile (8 g, 0.05 mol) in 100 cm of dichloromethane-petroleum ether (1: 1) at 20 ° C was added a solution of 4-bromoaniline (8.6 g, 0.05 mol) in 50 cm dichloromethane. The mixture was stirred at 20 DEG C. for 4 hours, then the crystals were filtered off with suction, washed with dichloromethane and dried in vacuo.

White crystals, m.p. 239-241 ° C.

Yield of 1- (4-bromophenyl) -3- (cyanophenyl) thiourea 15.8 g (95.2%). IR spectrum (KBr tablet): δ (NH) 3,270, 3,190.7 (CN) 2,230.7 (CC.) 1,600, 1,590, 1,490.1 450.7 (NHCS) 1,550.1 ^ΛΓ

230 cm.

Example 2

2-Isothiocyanatobenzonitrile (8 g, 0.05 mol) was dissolved in 100 cm 3 with dichloromethane-petroleum ether (1: 1). A solution of 4-toluidine (5.4 g, 0.05 mol) in 50 cm 3 of dichloromethane was added dropwise with stirring at 0 ° C. After 3 hours of reaction, the product was filtered off with suction and washed with dichloromethane.

White crystals, m.p. 181-183 ° C. <,

Yield of 1- (4-tolyl) -3- (2-cyanophenyl) thiourea 12.6 g (94%). IR spectrum (KBr tablet): 7 (NH) 3 280, 3 190, 7 (CN) 2 230, 7 ( ^{c> c} _Ar ) ¹ 595, ¹ 490, ¹ 450, δ '(NHCS) 1 555, 1 230 cm ¹ . Example 3

To a solution of 8 g (0.05 mol) of 2-isothiocyanatobenzonitrile in 100 cm 3 of dichloromethane-petroleum ether (1: 1) at 0 ° C was added dropwise a solution of 4-anisidine (6.2 g, 0.05 mol) in 3. cm of dichloromethane. After 2 hours of reaction, the crystals were filtered off with suction, washed with dichloromethane and dried.

White crystalline substance, m.p. 204-206 ° C.

Yield of 1- (4-methoxyphenyl) -3- (2-cyanophenyl) thiourea 13.6 g (96.1%).

IR spectrum (KBr tablet): 7 (NH) 3250, 3180, 7 (CN) 2240, 7 ^{(C 1} * ^C _Ar) ^{1600, 1590, 1460,} 7 (NHCS) 1550, 1220 cm ¹ .

Example 4

2-Isothiocyanatobenzonitrile (8 g, 0.05 mol) dissolved in 100 cm 3 of dichloromethane-petroleum ether (1: 1) was added dropwise at 20 ° C with stirring to an emulsion containing in 10 cm 3 3.5 g (0.05 mol) of a target , butylamine. After stirring for 60 minutes, the product was filtered off with suction, washed with dichloromethane and dried.

y

CS 276128 B6 2

White crystals, m.p. 163-164 ° C.

Yield 1-tert. butyl 3- (2-cyanophenyl) thiourea 9.1 g (76.1%). IR spectrum (KBr tablet) μ (NH) 3 230, 3 190, 7 (CN) 2-220, 7 ( ^{c c} _Ar ) 1 605, 1 585, 1 450, 7 (NHCS) 1 540, 1 205, μ (CH) 2 980, 2 880 cm ^-1 . ,

Example 5.

To a solution of 2-isothiocyanatobenzonitrile (8 g, 0.05 mol) in 100 cm 3 of dichloromethane-petroleum ether (1: 2) at 0 ° C was added dropwise isopropylamine (2.9 g, 0.05 mol) dissolved in 10 cm 3 of dichloromethane . After 2 hours of reaction, the product was filtered off with suction, washed with dichloromethane and dried.

White crystalline substance, m.p. 156-158 ° C.

Yield of 1-isopropyl-3- (2-cyanophenyl) thiourea 9.8 g (90%), IR spectrum (KBr tablet): 7 (NH) 3 280, 3 190, 7 (CN) 2 240, 7 ( ^c " ^C _Ar) ¹⁶⁰⁰ · ¹ 580 · ¹⁴⁷⁰ (NHCS) 1550, 1210, 7 (CH) 2980, 2950 cm ^-1.

Example 6 o 2-Isothiocyanatobenzonitrile (8 g, 0.05 mol) was dissolved in 100 cm 3 of dichloromethane-petroleum ether (1: 1) and 5 g (0.05 mol) of cyclohexylamine were added dropwise at 0 ° C. After

After stirring for 120 minutes, 50 cm 3 of petroleum ether are added, the product is filtered off with suction and washed with dichloromethane.

White crystals, m.p. 171-173 ° C.

Yield of 1-cyclohexyl-3- (2-cyanophenyl) thiourea 11.9 g (92%). IR spectrum (KBr tablet): δ (NH) 3,280, 3,200, 7 (CN) 2,240.7 (C _{1 -C Ar} ) 1,600, 1,500, 1,450.7 (NHCS) 1,560, 1,220, 7 (CH) 2 950, 2 860 cm ^-1 .

Example 7

To a solution of 8 g (0.05 mol) of 2-isothiocyanatobenzonitrile in 75 cm 3 of dichloromethane-petroleum ether (1: 1) was added dropwise at 0 ° C a solution of 5.4 g (0.05 mol) of phenylhydrazine 3 in 50 cm 3 of dichloromethane. After stirring for 60 minutes, the product was filtered off with suction, washed with dichloromethane and dried.

White crystalline substance, m.p. 191-193 ° C.

Yield of 1-anilino-3- (2-cyanophenyl) thiourea 12.1 g (90%). IR spectrum (KBr tablet): δ (NH) 3,300, 3,24, 3,150,7 (CN) 2,230.7 (C = C _Ar ) 1,600, 1,585, 1,450.7 * (NHCS) 1,540 , 1,210 cm ¹ .

The 1-substituted 3- (2-cyanophenyl) thioureas of the formula I are used, on the one hand, for the synthesis of Ν, Ν'-disubstituted, reap. N, N, N * -trisubstituted N- (2-cyanophenyl) guanidineO, on the one hand for the preparation of 3- and 4-eubstituted quinazolines, which for their physiological effects find application mainly in pharmacology and agriculture.

Claims (2)

PATENT CLAIMS 1-Substituted 3- (2-cyanophenyl) thioureas of the general formula I jMC (I) 3 CS 276128 86 wherein R is 4-bromophenyl, 4-chlorophenyl, 4-tolyl, 4-methoxyphenyl, 4-hydroxyphenyl, cyclohexyl. isopropyl, tert. butyl, anilino. 2. A process for the preparation of 1-substituted 3- (2-cyanophenyl) thioureas of the formula I as claimed in claim 2, wherein 2-isothiocyanatobenzonitrile is reacted with a primary amine of the formula II. r-nh ₂ (Π). wherein R is as defined above, at a temperature of 0 to 20 ° C in a dichloromethane-petroleum ether environment.