SU1027166A1 - Process for preparing 1,2-polymethyleneketocyanoazaheterocycles - Google Patents

Description

The invention relates to the preparation of heterocyclic compounds, specifically to the preparation of 1,2g polymethylene ketocyane aaheterocycles, which can be used as biologically active preparations or intermediates in their synthesis. A known method for producing 8,9,10 11-tetrahydro-8-keto-7 Cyanoazepino (1,2-a) quinoline, which consists in treating a solution of 6E-halogenacyl quinoline in dimethylformamide with an ethereal solution of diazomethane. The yield of the target product is I. The disadvantages of this method are the necessity of using highly toxic explosive diazomethane as a reagent, as well as a low yield of the target product. The purpose of the invention is to increase the yield and expand the range of target products, as well as increase process safety. The abovementioned goal is achieved by the fact that according to the method for producing 1,2-polymethylene ketocyanoazaheterocycles of the formula where A is n 1,2 ,. concluding that (l) -halogen acylase heterocycles of the general formula (a /, 0HH2) where A and n have given X-C1, Bg values, are treated with organic bases at boiling of the reaction mass .. Moreover, the reaction is carried out in a medium organic solvent. The proposed method allows to obtain 8,9,10,11-tetrahydro-8-keto-7-cyanoazepino (1,2-a) quinoline with a yield of 67-95, as well as a number of new 1,2-polymethylene ketocyanoazheterocycles. The use of organic solvents makes it possible to increase the yield and the purity of the target products. In the LPR spectra of condensed pyridones, there are two triplets of protons of methylene groups in region 3, and 5.0 ppm, and in spectra of condensed azepinones, three multiplets in region 2.1 (m ), (t), i, ppm (t). The IR spectra contain absorption bands of nitrile (2220-2200 cm) and the conjugated keto group in the range of 1625-1620 cm. The UV spectra differ sharply from the spectra of the initial {h} -haloacyl derivatives of formula (II). The structure of the compounds of the formula (O is confirmed by chemical transformations in reactions with hydrazines, aromatic aldehydes, hydroxylamine, nitrous acid. EXAMPLE 1. 8,9,10,11-Tetragahydro-8-keto-7-Cyanoazepino (1,2-a). Quinoline. A mixture of 8.1 g of Z-oxo-2- (2-quinoline) -6-chlorohexanenitrile, 6.3 ml of triethylamine in 13 ml of dimethylformamide is boiled for 30 minutes. Cool and dilute 200 ml of water, dry for 30 minutes in a ki; at the top of the bath, cool and filter the crystals. Yield: 6.7 g (95) 8,9,10,11-tetrahydro-8-keto-7-cyano-g azepine (1 , 2-a) quinoline, mp. 178 C (from isopropanol). Nye deno,%: C 76.3; AND 5.3; N11.8. C | d H12 Calculated,%: C 76.25; H 5I; N 11.9. Example 2. 8.9,10,11- Tetrahydro-8-keto-7-cyanoazepino (1,2-a) quinoline is prepared as in Example 1, using an equivalent amount of N-methylpyrrolidine instead of triethylamine. Output 87. Example 3. 8,9,1,0,11-Tetrahydro -8-keto-7-cyanoazepinrhinolinol is obtained analogously to 1 using instead of triethylamine an equivalent amount of N-methylpiperidine. Output

n p and mep 4. 8,9fl07l1-TeTpahydro-8-keto-7-cyanoazepino (1,2-a) quinoline.

2.53 g of 3 oxo-2- (2-quinoline) -6-chlorogeananitrile are boiled in 15 ml of triethyl | for 1 hour. Remove excess triethylamine under vacuum and treat the residue with 50 mL of water. The precipitate is filtered off, washed with water, dried and recrystallized from isopropanol. Yield: 8,9,10,11-tetrahydro-8-keto-7-cyanoazepino (1,2-a) chymoline 67%.

Example 5.8,9, 10-trihydro-8-keto-7 Cyanopyrido (1,2-a) quinoline is obtained from 3 oxo-2 (2-quinoline) -3-bromopentannitrile in analogy to Example 1. Exit: 9.1, so pl. 266 ° C (from isopopanol).

Found,% С 75.9j Н, 6; N 12.8,

C 4 . Calculated,%: C 75.7; H t, 5;

N t2,6.

Example 6. 8,9,10-Tpihydro-8-keto-7-cyanonirido (1, 2-a) quinoline is obtained from 3-oxo-2- (2-quinoli / -5-. -Chloropentannitrile analogously to example 1. Output 88, mp 266 ° C.

PRI me R. 7. 7,8,9,10-Tetrahydro-7-keto-6-cyanoazepino (1,2-a) benzimidazole derived from 5.92 g of Soxo-2- {1-netilbenzimidazol-2-yl) -6-hlrrhekeannitrile and 3.3 ml of triethylamine in 20 ml of dioxane at reflux for 1 hour. The reaction mixture is then evaporated in vacuo and 100 ml of water and 0.5 ml of acetic acid are added, on. heat in a water bath for 15 minutes, cool and filter 1.9 g (37) of the desired product. M.p. 197 ° C (from i-propanol).

Found,% N 17.4 (

0 С, 4Н ,, ЫЗО

Calculated,%: N 17,56.

Example 8. 6,7,8,9 - Tetrahydro-9-keto-10-cyanoazepino- (1,2-f) 5-phenanthidine.

A mixture of 1.13 g of 3 oxo-2- (6-phenanthrydinyl) -6-chlorhexanenitrile, 0.55 ml of triethylamine in 5 ml of benzene is boiled for 8 hours, evaporated in vacuo and the residue 0 is washed with water on a filter, dried and recrystallized from -propanol. Yield 6,7,8,9, -tetrahydro-9-keto-1O-cyanoazepino (1,2-f) phenanthridine 0.56 g (57%) So pl. 171 C (from i-pro5 panola);

Found,%: N 9, b7

C, 9H, 4N20

Calculated,%: N 9.78.

Thus, in the scheme of the proposed method there are no poisonous and explosive substances, in addition, it is possible to obtain a wide range of target products.

Claims (2)

1. METHOD FOR PRODUCING 1,2-POLYMETHYLENE KETOcyan0AZaHETEROcyclo0B of the general formula η -. 1,2, characterized in that, in order to increase the yield and expand the assortment of target products, as well as improve the safety of the process, (D-halogenacyl- <£ -cyanomethylaseheterocycles of the general formula, I where A and η have the given meanings; x - CI, Br, is subjected to treatment with organic bases at the boiling of the reaction mass. 2. The method according to claim 1, characterized in that the reaction is carried out in an environment of an organic solvent. SU .1027166 1 -1027166 2