SU1271861A1 - Method of producing 2,2-dimethyl-3-cyanomethylindenezimidazo/2,1-b/-1,3-oxazolidine - Google Patents

Abstract

The invention approaches the chemistry of heterocyclic compounds, namely, a method for producing a new benzimidazo derivative.

Description

The invention relates to organic chemistry, namely to a new method for producing a new derivative of benzimidazo [2, 1 -b J-1, 3-ox.azolidi-. on - 2,2-dimethyl-3-cyanomethylidene-j benzimidazo [2,1-b] -1,3-oxazolidine, which can be used for the synthesis of biologically active compounds.

The purpose of the invention is to obtain a new derivative of benzimidazo [2,1-b] -1,3-oxazolidine containing a C = C multiple bond between the heterocycle and the side substituent at position 3, which can be used for the synthesis of biologically active connections.

This goal is achieved by the proposed method for producing 2,2-dimethyl-Zcyanomethylidenebenzimidazo [2,1-bl-20

1,3-oxazolidine, which consists in the fact that 2-methyl- (vinyl) thiobenzimidazole is reacted first at room temperature, and then at a temperature of 80-25

100 ° C with 4-hydroxy-4-methyl-2-pentinnitrile in an organic solvent at a molar ratio of 2-methyl (vinyl) thiobenzimidazole and

4-hydroxy-4-methyl-2-pentinnitrile, 30 equal to 1: 2, in the presence of lithium hydroxide in an amount of 5-10% of the total mass of reagents.

Preparation of 2-2-dimethyl-3-cyanomethylidenebenzimidazo [2,1-b] -1, 3-oxaeolidine.

Example 1. Reaction mixture consisting of 0.33 g (2 mmol) 2-methylthiobenzimidazole ·, 0.44 g (4 mmol) 4-hydroxy-4-methyl-2 ~ pentinnitrile and 0.08 g (10%) LiOH in 15 ml of acetonitrile, stirred at room temperature for 6-8 hours, then boiled for 8-10 hours. The solution is passed through a small layer of Al ^ 0 ^ to remove alkali. The solvent was distilled off, the residue was washed with ether to obtain 0.26 g of the target product in the form of a white crystalline substance with a melting point of 190-192 C (hexane with the addition of acetone). 0.1 g of the target product with the same melting point is additionally isolated from the ether. Overall yield 0.36 g, 80%.

Found.%: C 69.35; H 4.90;

N 18.62.

Calculated.%: (1 69.32; H 4.92;

N 18.66.

+

Mass Spectrum: Found 225;

M calculated 225.241,

In the IR spectrum of 2,2-dimethyl-3-cyanomethylidenebenzimidazo [2,1 -b] -1,3oxazolidine, absorption bands are present at 2215 (CN); 3060,1640 (C = CH); 2930 (CH) cm 'and there are no absorption bands characteristic of the OH group (3600 cm ¹ ), SzhC, C = N (2275-2085 cm').

PIR spectrum (CDCl ^; S, 'ppm): 1.75 s (CH ₃ ); 4.61 s (-CHCN); 7.208.40 m (aromatic protons).

PRI me R 2. A mixture of 0.35 g (2 mmol) 2-vinylthiobenzimidazole, 0.44 g (4 mmol) 4-hydroxy-4-methyl2-pentinnitrile and 0.08 g (10%) LiOH in 10 ml of acetonitrile is stirred at room temperature for 8 hours, then refluxed for 10 hours. 0.29 g (65%) of the target product is isolated by a similar treatment, m.p. 190-192 ° C.

Example 3. 0.33 g (2 mmol) 2-methylthiobenzimidazole, 0.44 g (4 mmol) 4-hydroxy ~ 4-methyl ~ 2-pentinnitrile, 0.04 g (5%) LiOH in 15 ml of acetonitrile is stirred at room temperature for 8 h , then refluxed for 10 h. By analogous treatment, 0.27 g (60%) of the target product is isolated with m.p. 190-192 ° C.

PRI me R 4. 0.33 g (2 mmol) 2-methylthiobenzimidazole 0.22 g (2 mmol) 4-hydroxy-4-methyl-2-pentinitrile 0.06 g LiOH in 15 ml of acetonitrile is stirred at room temperature for 8 hours, boil for 10 hours. After similar treatment, the residue is a mixture consisting of the target product and the starting 2-methylthiobenzimidazole. Separation on a column with Al _Q 0 ₃ (eluent - hexane:: benzene: acetone ~ 3: 2: 1) isolate 0.1 g (22% G of the target product, mp 190-192 ° C.

PRI me R 5. 0.33 g (2 mmol) of 2-methylthiobenzimidazole, 0.44 g (4 mmol) of 4-hydroxy-4-methyl-2-pentinnitrile in 10 ml of acetonitrile is incubated for 10 hours at room temperature. The initial reagents are unchanged in the reaction mixture. Adding 0.08 g of LiOH and stirring incubation at room temperature for 10 h without further heating allows isolation of 0.2 g (44%) of the target product by column separation analogously to Example 4, mp. 19О-192 ° С.

Example 6. The reaction mixture containing 0.33 g (2 mmol) of 2-methyl-5 thiobenzimidaeol, 0.44 g- (4 mmol) 4-hydroxy-4-methyl ~ 2-pentinnitrile, 0, 08 g of LiOH in 15 ml of dioxane, stirred at room temperature for 8 hours, then refluxed for 10 hours. Treatment described in Example 1 yields 0.17 g (44%) of the target product, mp. 190-192 ° C.

Claims (2)

The invention relates to organic chemistry, and to a new method of obtaining a new benzimidazo derivative 2, 3-oxazole: vdin — 2,2-dimethyl-3-cyanomethylidene benzkmidazo 2, -Y-1, 3 oxazolidine, which can find a way to synthesize biologically active connections. The purpose of the invention is to obtain a benzimidazo 2, 3-oxazolidine derivative containing a multiple bond between a heterocycle and a side substituent in field 3, which can be used to synthesize biologically active compounds. This goal is achieved by the proposed method of producing 2,2-dimethylcyanomethylidene benzimidazo 2, 3-oxazolidine, which consists in the fact that 2-methyl- (vinyl) thiobenzimidazole is reacted first at room temperature and then at a temperature of 80100 ° C with 4- hydroxy-4-methyl-2-pentine nitrile in an organic solvent medium at a molar ratio of 2-methyl (vinyl) thiobenzimidazole and 4-hydroxy-4-methyl-2-pentennitrnla, equal to: 2, in terms of hydroxy and lithium in the amount 5-10% of the total mass of reagents. Preparation of 2-2-dimethyl-3-cyanometa lidenbenzimidazo 2, 3-oxazo Example 1. A reaction mixture consisting of 0.33 g (2 mmol) 2-methylthiobenzimidazole-0.44 g (4 mmol 4-hydroxy-4 -methyl-2-pentynitrile and 0.08 g (10%) LiOH in 15 ml of acetonitrile, stirred at room temperature for 6-8 hours, then boiled for 8-10 hours. The solution is passed through a small layer of At O to remove alkali. The solvent is distilled off, the residue is taken up in ether and 0.26 g of the expected product is obtained in the form of a white crystalline substance with mp 190-192 ° C (hexane with addition of acetone). From ether and 0.1 g of the desired product with the same melting point is additionally isolated. Total yield is 0.36 g 80%. Found: C 69.35; H 4.90 N 18.62 C ,, H, N, 0. 61 C 69.32; H 4.92; Calculated.% N 18.66. M found 225; Mass spectrum of M calculated 225.241. In the PC spectrum of 2, 2-dimethyl-3-cyanomethylidene benzimidazo 2, 3oxazolidine, there are absorption bands at 2215 (CN); 3060 , 1640 (); 2930 (CH,) media; there are no absorption bands; characteristic for the OH group (3600 cm), CrC, (2275-2085 cm). PMR spectrum (CDC1; S, ppm): 1.75 s (CHJ; 4.61 s (-CHCN); 7.2008, 40 m (aromatic protons), Example 2: Mixture 0.35 g (2 mmol) of 2-vinylthiobenzimidazole, 0.44 g (4 mmol) of 4-hydroxy-4-methyl2-pentennitrile and 0.08 g (10%) of LiOH in 10 ml of acetonitrile is stirred at room temperature for 8 hours, then boil for 10 hours. A similar treatment gives 0.29 g (65%) of the desired product from 190-192 ° C. Example 3: 0.33 g (2 mmol) of 2-methylthiobenzimidazole, 0, 44 g (4 mmol) of 4-hydroxy-4-methyl-2-pentenitrile, 0.04 g (5%) of LiOH in 15 ml of acetonitrile are stirred at room temperature for 8 hours, then boiled for 10 hours. Similarly, 0.27 g (60%) of the desired product was obtained, with a melting point of 190-192 ° C. Example 4: 0.33 g (2 mmol) of 2-methylthiobenzimidazole 0.22 g (2 mmol A) 4-hydroxy-4-methyl-2-peninnitrile 0.06 g of LiOH in 15 ml of acetonitrile is stirred at room temperature for 8 hours and boiled for 10 hours. After a similar treatment, the residue is a mixture of the desired product and the starting material. 2-methylthiobenzimidazole. The separation on a column of c (eluent – hexane:: benzene: aceto n 3: 2: 1) isolated 0.1 g (22%) of the desired product with m.p. . EXAMPLE 5 0.33 g (2 mmol) of 2-methylthiobenzimidazole, 0.44 g (4 mmol) of 4-hydroxy-4-methyl-2-pentennitrile in 10 ml of acetonitrile are kept for 10 hours at room temperature. The starting reagents are unchanged in the reaction mixture. The addition of 0.08 g of LiOH and stirring: at room temperature for 10 hours without further heating allows separation by column, as in Example 4, of 0.2 g (44%) of the desired product with m.p. 190-192S. P. im 6 p. A reaction mixture containing 0.33 g (2 mmol) of 2-methylthiobene-imideaeol, 0.44 g (4 mmol) of 4-hydroxy-4-methyl -1-2-pentennitrile, 0.08 g of LiOH in 15 ml of dioxane, stirred at room temperature for 8 hours, then boiled for 10 hours. The treatment described in Example 1 gave 0.17 g (44%) of the desired product with a mp. 190-192 ° C. Claims 1. Method for preparing 2,2-dimethyl3-cyanomethylidene benzimidazo {2,1-b1I, 3-oxazolidine of the formula, CH-CN on sns wherein 2methyl (vinyl) thiobenzimidazole of the general FORMUL.,, J / SR where R- methyl or vinyl, is reacted with 4-hydrox-4-methyl-2-pentennitrile in an organic solvent medium, first at room temperature and then at a temperature of 80-100 ° C, at a molar ratio of 2-methyl (vinyl) thiobenzimidazole and 4-gndroxy-4-metsh1-2-pentennitrile, equal to 1: 2, in the presence of lithium hydroxide in the amount of 5-10% of the total mass reagents. 2. The method according to item 1, about tl and ch yusch and with the fact that acetonitrile or dioxane is used as an organic solvent.