CS262022B1 - N- (N-Acylthioureido) cyclic enaminonitrile derlvates; - Google Patents

Abstract

The present invention relates to N- (N-acylthioureido) derivatives of cyclic enaminonitriles of the general formula I wherein R is methyl, phenyl, ethoxy and R is 2-cyanophenyl, 2- (3-cyanoquinolyl), 2- (5 and cyano-1,5,6,7-tetrahydrobenzothienyl) -3- (.beta.-cyanopyrazolyl) and a process for the preparation thereof by reacting cyclic naminontriles with acyl isothiocyanates at < 10-40 DEG C. in acetone. The compounds of formula I are used for the synthesis of condensed pyrimidine and thiazine derivatives. cycles having a broad spectrum of R-OO-NH-CS-NH-R (i) -activating antibacterial, antifolic, herbicidal, antimalarial, antitussive, sedative, hypocholesterolemic, oostocidal contraceptive, or positive maturation effects of crop plants.

Description

The invention relates to N- (N-acylthioureido) cyclic enaminonitrile derivatives of the general formula I

R-CO-NH-CS-NH-R (I) wherein R 1 is phenyl, methyl, ethoxy, and R 2 is 2-cyanophenyl, 2- (3-cyano-4,5,6,7-tetrahydrobenzyl-thienyl) , 2- (3-cyanoquinolyl), 3- (4-cyanopyrazolyl) and a process for their preparation by reaction of cyclic enaminonitriles with acyl isothiocyanate in solution in acetone.

The compounds of formula I and the process for their preparation have not been described. It is known that related N- (N-acylthioureido) derivatives of aliphatic or aromatic amines (acyl being acetyl, benzoyl, ethoxycarbonyl) can be prepared by adding the corresponding amines to the acylisothiocyanates in an aprotic organic solvent in a yield of 70-80% (Houben-Weyl, Methoden der organischen Chemie, Vol. IX, 4th edition, Georg Thieme Verlag, Stuttgart 1955, p. 893).

The N- (N-acylthioureido) derivatives of aliphatic or aromatic amines are used in particular to prepare N-substituted thioureas by alkaline hydrolysis.

It has now been found that by reacting an acylisothiocyanate (acyl means acetyl, benzoyl, ethoxycarbonyl) with cyclic enaminonotriles in an acetone solution at 20-40 ° C, N- (N-acylthioureido) derivatives of cyclic enaminonitriles of formula I can be prepared.

Example 1

A solution of anthranilonitrile (11.8 g, 0.1 mol) in 50 ml of absolute acetone was reacted with 13.1 g (0.1 mol) of ethoxycarbonyl isothiocyanate at 30 ° C for 120 minutes. By cooling the reaction mixture the product crystallizes.

After recrystallization from acetone, 19.1 g (76.8%) of 2- [N- (N-ethoxycarbonylthioureido) 3-benzonitrile was obtained, mp T29-131 ° C. _

IR spectrum (1% in KBr): V (C _Ar- H) 3030, V (NH) 3390,

262 022

14O, V (CN) 2,230.7 (NHCO) ΐ 725, 1,560.7 (NHCS) 1,510, 1,240, V (COOC) 1,200, 1,040 cm ^-1 .

Example 2

A solution of 11.8 g (0.1 mol) anthranilonitrile in 50 ml absolute acetone was treated with 10.1 g (0.1 mol) acetyl isothiocyanate at room temperature for 60 minutes. The product was isolated after cooling the reaction mixture to 5 ° C.

19.6 g (89.3%) of 2- [N- (N-acetylthioureido)] benzonitrile were obtained, m.p. 190-192 ° C (dec.).

IR spectrum (1% in KBr): V (C _Ar- H) 3030, v (NH) 3400,

170.7 (CN) 2,230.7 (NHCO) 1,705, 1,550.7 (NHCS) 1,510, 1,230 cm.

Example 3

To a solution of 8.86 g (0.075 mol) of anthranilonitrile in 30 ml of absolute acetone was added 12.24 g (0.075 mol) of benzoyl isothiocyanate, the mixture was reacted at 40 ° C for 10 minutes. Cooling the reaction mixture to 10 ° C gave 16.92 g (80.2%) of 2- [N- (N-benzoylthioureido)] benzonitrile, m.p. 172-173 ° C.

IR spectrum (1% in KBr): 7 (C _Ar @ + H) 3030.7 (NH) 3390,

140.7 (CN) 2,230.7 (NHCO) 1,660, 1,530.7 (NHCS) 1,510,

240 cm ” ¹ .

Example 4

To a solution of 8.46 g (0.05 mol) of 2-amino-3-cyanquinoline in 250 ml of acetone was added 6.6 g (0.05 mol) of ethoxycarbonylisothiocyanate, the mixture was reacted at 40 ° C for 180 minutes. Concentrating the reaction mixture to half volume gave 10.7 g (71.0%) of 2- {N - (N-ethoxycarbonylthioureido) -3-cyanquinoline, m.p. 175-177 ° C (dec.).

IR spectrum (1% in KBr): 7 (NH) 3,400, 3,150.7 (CN) 2,240.7 (C = N) 1,620.7 (NHCO) 1,725,154 O, V (NHCS) 1 495, 1 215, (COOC) 1 200, 1 040 cm ^-1 .

Example 5

262 022

To a solution of 8.46 g (0.05 mol) of 2-amino-3-cyanquinoline in 250 ml of absolute acetone was added 5.1 g (0.05 mol) of acetyl isothiocyanate, the mixture was reacted at 40 ° C for 180 minutes. evaporation of acetone was concentrated to half volume, cooled to 10 ° C to give 9.74 g (76.1%) of 2- [η- (N-acetylthioureido) -3-cyanquinoline, mp 219-221 ° C.

**** IR spectrum (1% in KBr): V (NH) 3 350, 3 1 30, V (CN) 2 225,? (C = N) 1 620, V (NHCO) 1 660, 1 500 , V (NHCS) 1480, 1210 cm ¹ .

Example 6

To a solution of 10.8 g (0.1 mol) of 3-amino-4-cyanopyrazole in 400 ml of absolute acetone was added 13.1 g (0.1 mol) of ethoxycarbonyl isothiocyanate, the solution was reacted at 25 ° C for 30C minutes. The solution was concentrated by evaporation of 300 ml of solvent to give 15.6 g (65.2%) of 3 - [, N- (N-aethoxycarbonylthioureido) -4-cyanopyrazole. The substance does not melt to 360 ° C.

IR spectrum (1% in KBr): V (pyrazole ring) 1,575, 1,490, V (NH) 3,550, 3,400, 3,210, V (CN) 2,240, V (NHCO) 1,740, 1,535, (NHCS) 1 475, 1 200, V (COOC) 1 215, 1 035 cm ¹ .

Example 7

To a solution of 10.8 g (0.1 mol) of 3-amino-4-cyanopyrazole in 400 ml of absolute acetone was added 10.1 g (0.1 mol) of acetyl isothiocyanate, after 180 minutes of reaction at 30 ° C the evaporation was 300 ml of acetone gave 12.5 g (59.8%) of 3- [n- (N-acetylthioureido)] - 4-cyanopyrazole. The substance does not melt to 360 ° C.

IR spectrum (1 µf in KBr): M (pyrazole ring) 1560, 1490,

V (NH) 3,550, 3,400, 3,180, V (CN) 2,240, V (NHCO) 1,690, 1,535, (NHCS) 1,480, 1,210 cm ^-1 .

Example 8

To a solution of 8.9 g (0.05 mol) of 2-amino-4-cyano-4,5,6,7-tetra-262 022 hydrobenzo-4-thiophene in 40 ml of absolute acetone was added 8.2 g (0.05 mol) of benzoyl isothiocyanate, after 60 minutes of reaction at 20 ° C, 20 ml of acetone was evaporated.

3.7 g (80.4%) of 2- [N- (N-benzoylthioureido)] - 3-cyano-4,5,6,7-tetrahydrobenzo [b] thiophene were obtained, m.p. 220-222 ° C. (with decomposition).

IR spectrum (1% in γ): Ϊ (ΝΗ) 3,400, 3,150, V (CN) 2,210, (NHCO) T 660, 1,540, V (NHCS) 1,520, 1,240 cm ^-1 .

Example 9

To a solution of 8.9 g (0.05 mol) of 2-amino-3-cyano-4,5,6,7-tetrahydro-benzo [b] thiophene in 40 ml of abaolute acetone was added 5.05 g (0.05 mol) of acetyl isothiocyanate, the mixture was reacted at room temperature for 60 minutes.

After evaporation of 20 ml of solvent, 9.76 g of (7011) 2- [N- (N-acetylthioureido)] -3-cyano-4,5,6,7-tetrahydrobenzo [b] thiophene, m.p. C (dec.).

IR spectrum ($ 1 in KBr): V (NH) 3400, 3170.7 (CN) 2220,

V (NHCO) 1,690, 1,540, V (NHCS) 1,525, 1,225 cm ^-1 .

Example 10

To a solution of 8.9 g (0.05 mol) of 2-amino-3-cyano-4,5,6,7-tetrahydrobenzo-4-thiophene in 40 ml of acetone was added 6.55 g (0.05 mol) of ethoxycarbonylieothiocyanate The mixture was reacted for 60 minutes at 25 ° C.

Evaporation with 20 ml of acetone gave 11.4 g (73.8%).

2- [N- (N-ethoxycarbonylthioureido)] - 3-cyano-4,5,6,7-tetrahydrobenzo [b] thiophene, m.p.

IR spectrum (% in KBr): V (NH) 3,380, 3,170, V (CN) 2,220,

V (NHCO) 1,715, 1,540, V (NHCS) 1,520, 1,230.7 (0000) 1,200,

040 cm ¹ .

The N- (N-acylthioureido) cyclic enaminonitrile derivatives of formula (Ie) utilize condensates for the synthesis of the condensates.

The compounds of the present invention have a wide range of applications for their pharmacological and biological effects, e.g., antibacterial, herbicidal, antimalaric, hypocholeaterolemic, postcoital contraceptive, antitussive, ededative, antifolic, or some positive effects on the ripening of crop plants.

Claims (2)

SUBJECT OF THE INVENTION N- (N-Acylthioureido) cyclic enaminonitrile derivatives of general formula I R-CO-NH-CS-NH-Λ (I) wherein R * is methyl, phenyl, ethoxy and R is 2-cyanophenyl, 2- (3-cyanoquinolyl), 2- (3-cyano-4, 5- (6,7-tetrahydrobenzo [b] thienyl), 3- (4-cyanopyrazolyl). 2. A process for the preparation of N- (N-acylthioureido) cyclic enaminonitrile derivatives of the general formula I according to claim 1, characterized in that ae is reacted with an acylisothiocyanate of the general formula II R-CO-NCS (II) / wherein R * is as defined in point t with an amine of formula III r-nh ₂ (III), wherein R is as defined in point 1 in acetone at 20-40 ° C.