CS266896B1 - Ν, Ν-disubstituted N- [2- (3-cyano-4,5,6,7-tetrahydrobenzo [b] thienyl) / thiocarbamic acid amides and process for their preparation - Google Patents

Abstract

The solution relates to N,N-disubstituted amides of N-/2-(3-cyano-4,5,6,7-tetrahydrobenzo[b]thienyl)/thiocarbamic acid of general formula I, where X represents a morpholino-, piperidino-, diethylamino-, dibutylamino-, bis(2-hydroxyethyl)amino group and a method for their preparation by reacting 2-isothiocyanato-3-cyano-4,5,6,7-tetrahydrobenzo[bthiophene with a secondary amine in a dichloromethane-petroleum ether environment, or in methanol at room temperature. The substances of general formula I are used for the synthesis of substituted 5,6,7,8-tetrahydrobenzo[b]thieno[2,3-d]pyrimidines with applications in pharmacy and agriculture.

Description

The invention relates to N- [2- (3-cyano-4,5,6,7-tetrahydrobenzo [b] thienyl)] thiocarbamic acid β, β-disubstituted amides of the general formula I,

wherein X is morpholino, piperidino, diethylamino, dibutylamino, bis (2-hydroxyethyl) amino and a process for their preparation by reacting 2-isothiocyanato-3-cyano-4,5,6,7-tetrahydrobenzo [b] thiophene with secondary amines in a dichloromethane-petroleum ether medium or in methanol at room temperature.

The compounds of the formula I and the process for their preparation have not yet been described. It is known that related N-phenylthiocarbamoylamides can be prepared by reacting phenylisothiocyanate with primary and secondary amines in organic solvents in a yield of 65-95% (Houben-Weyl, Methoden der organischen Chemie, Volume IX, 4th Edition, Georg Thieme Verlag Stuttgart 1955, p. 890).

It has now been found that by reacting 2-isothiocyanato-3-cyano-4,5,6,7-tetrahydrobenzo [b] thiophene with a secondary amine of formula II

XH (II), where X is as defined above, N, N-disubstituted N- [2- (3-cyano-4,5,6,7-tetrahydrobenzo [b]) can be prepared in dichloromethane-petroleum ether or in methanol. thienyl)] thiocarbamic acid of formula I in a yield of 76-92%.

Example 1

To a solution of 2-isothiocyanato-3-cyano-4,5,6,7-tetrahydrobenzo [b] thiophene (11 g, 0.05 mol) in 75 cm 3 of dichloromethane-petroleum ether (1: 2) was added dropwise at room temperature. , 1 g (0.055 mol) of diethylamine. After standing for 90 minutes, the mixture was concentrated to half volume, the crystals were filtered off with suction and recrystallized from ethanol.

The product is a yellow crystalline substance, m.p. 99-101 ° C. Yield of N- [2- (3-cyano-4,5,6,7-tetrahydrobenzo [b] thienyl)] thiocarbamic acid diethylamide 13.5 g (92%). IR spectrum (KBr tablet): v (NH) 3,300, v (CN) 2,210, v (C = C) 1,590, v (NHCS) 1,480, 1,240, v (CH) 2,950, 2,890, 2,860 cmT

Example 2

To a solution of 11 g (0.05 mol) of 2-isothiocyanato-3-cyano-4,5,6,7-tetrahydrobenzo [b] thiophene in 100 cm 3 of a mixture of dichloromethane and petroleum ether (1: 3) was added dropwise at room temperature 4.3 g (0.05 mol) of morpholine in 20 cm 3 of dichloromethane. After standing for 120 minutes, the crystals were filtered off with suction, washed with petroleum ether and dried in vacuo.

The product forms yellow crystals, m.p. 169170 ° C. Yield of N- [2- (3-cyano-4,5,6,7-tetrahydrobenzo [b] thienyl)] thiocarbamic acid morpholine 14.2 g (92.4%). IR spectrum (KBr tablet): V (NH) 3 250, v (CN) 2 200, V (CC) I 580, V (NHCS) I 475, 1 230, V (Cil) 2 950, 2 900, 2 870 , v (COC) 1 120 cm '.

Example 3

To a solution of 11 g (0.05 mol) of 2-isothiocyanato-3-cyano-4,5,6,7-tetrahydrobenzo [b] thiophene in 80 cm 3 of dichloromethane-petroleum ether (2: 3) was added dropwise 4.3 g (0 .05 moles) of piperidine. After standing for 2 hours, 50 cm ^{3 of} petroleum ether were added, the crystals were filtered off with suction, washed with petroleum ether and dried in vacuo.

The product is a light yellow crystalline substance, m.p. 151-153 ° C. Yield of piperidine N- [2- (3-cyano-4,5,6,7-tetrahydrobenzofb] thienyl) / thiocarbamic acid 13.9 g (91%) · IR spectrum (KBr tablet): v (NH) 3,400, V ( CN) 2,200, v (C = C) 1,590, v (NHCS) 1,480, 1,240, v (CH) 2,950, 2,920, 2,860 cm ^-1 .

Example 4 g (0.05 mol) of 2-isothiocyanato-3-cyano-4,5,6,7-tetrahydrobenzo [b] thiophene were dissolved in 80 cm ³ of dichloromethane-petroleum ether (2: 3). 6.5 g (0.05 mol) of dibutylamine were added to the solution, after standing for 90 minutes the mixture was concentrated to one third volume, 50 cm ^{3 of} petroleum ether were added and the crystals were filtered off with suction. The product was recrystallized from cyclohexane to give pale yellow crystals, m.p. 78-79 ° C. Yield of N- [2- (3-cyano-4,5,6,7-tetrahydrobenzo [b] thienyl)] thiocarbamic acid dibutylamide 13.3 g (76.1%). IR spectrum (KBr tablet): v (NH) 3,300, v (CN) 2,210, V (C = C) 1,590, V (NHCS) 1,480, 1,250, v (CH) 2,950, 2,900, 2,880 cm -1.

Example 1 and d 5

4.5 g (0.02 mol) of 2-isothiocyanato-3-cyano-4,5,6,7-tetrahydrobenzo [b] thiophene and 2.1 g (0.02 mol) of diethanolamine were dissolved in 50 cm ^{3 of methanol.} . After standing for 150 minutes, the solvent was evaporated and the residue was recrystallized from aqueous ethanol (activated carbon added).

The product forms yellowish crystals, m.p. 126-129 ° C. Yield of N- (2- (3-cyano-4,5,6,7-tetrahydrobenzo [b] thienyl)] thiocarbamic acid bis (2-hydroxyethyl) amide 5.8 g (89.1%). IR spectrum (KBr tablet): v (NH) 3,350, v (CN) 2,210, V (C = C) 1,600, V (NHCS) 1,490, 1,260, v (CH) 2,950, 2,900, 2,850, V (C-0) 1,050, v (OH) 3,620 cm- ¹ .

N- [2- (3-Cyano-4,5,6,7-tetrahydrobenzo [b] thienyl)] thiocarbamic acid β, β-disubstituted amides can be used to synthesize substituted 5,6,7,8-tetrahydrobenzo [b] thienylbenzoic acids. ] thieno [2,3-d] pyrimidines for pharmaceutical and agricultural applications.

Claims (2)

OBJECT OF THE INVENTION I. N- [2- (3-Cyano-4,5,6,7-tetrahydro-benzo [b] thienyl)] - thiocarbamic acid β, β-disubstituted amides of the formula I wherein X is morpholino, piperidino, diethylamino, dibutylamino, bis (2-hydroxyethyl) amino. 2. A process for the preparation of N- [2- (3-cyano-4,5,6,7-tetrahydrobenzo [b] thienyl)] thiocarbamic acid N, N-disubstituted amides of the general formula I according to item 1, characterized in that reacting 2-isothiocyanato-3-cyano-4,5,6,7-tetrahydrobenzo [b] thiophene with a secondary amine of formula II, XH (II) wherein X is as defined in 1 at room temperature in dichloromethane-petroleum ether or in methanol.