SU1085978A1 - Process for preparing 5-alkyl-1,3-diheterocycloalanes - Google Patents

Abstract

A METHOD FOR OBTAINING 5-ALKYL-1, 3-DIGETEROCYCLO ALKANES of the formula R where R is lower alkyl; X is oxygen or lower alkylimino; Y is lower alkylimino; by the interaction of a 5-alkyl-5-nitro-1,3 diheterocycloalkane of the formula R 02N where R, X and Y have the indicated meanings,. with the basic sodium compound, characterized in that, in order to increase the yield of the target product 3, sodium thioethylate is taken as the basic sodium compound, with a molar ratio of the compound of formula (s) to sodium thioethylate 1:

Description

OS O1

The invention relates to an improved method for producing 5-alkyl-1,3-diheterocycloalkanes of the formula (1) where R is lower alkyl; X - oxygen or lower alkylimy - lower alkylimino, which can be used as biologically active compounds. A known method for the preparation of 1,3,5-trimethylhexahylopyrimidine of the formula CH, which consists in the fact that 1,3, -trimethyl-5-nitrohexahydropyrim, qi is reacted with sodium methoxide in methanol at a molar ratio of reagents 1: 4 at 130 68% l. I The disadvantage of the method is the relatively low yield of the desired product. A known general method for the preparation of compounds of formula (1) is that the corresponding 5-alkyl-5-nitro-1,3-diheterocycloal can be of the formula (II) where R, X and Y have the indicated meanings, is subjected to the reduction of alcohol. rub 2. The specific conditions for carrying out the method are not given; it is stated only that the yield of the target products is 50-70%. The disadvantage of this method is the relatively low yield of the target products. The purpose of the invention is to increase the yield of the target product. The goal is achieved according to the method of producing 3-alkyl-1, 3-diheterocycloalkanes of formula (i), which is that 5-alkyl-5-nitro-1,3-diheterocycloal cannons of (P) where R, K, and Y have the indicated values, are reacted with sodium thioethylate, with a molar ratio of the compound of formula (II) to sodium thioethylate 1; (1.1-2), respectively, in dimethylformamide at 100-120 ° C. According to the proposed method, the corresponding 5-alkyl-5-nitro-1,3-diheterocycloalkane is placed in a reactor equipped with a reflux condenser, a thermometer, a capillary to supply argon, sodium thiostilate is added at a molar ratio of 5-alkyl 5-nitro-1, 3 - diheterocycloalkane; . Sodium thioethate is 1: (1.1-2.0) j dimethylformamide and heated for 30 minutes at 100-120 ° C, then the reaction mixture is diluted with water and extracted with benzene, benzene is distilled off and the end product is isolated by distillation. Example 1. In a glass reactor equipped with a reflux condenser, a thermometer, a capillary for argon supply, 17.3 g (O, 1 mol) of 1, 3, 5-trimethyl-5-nitrohexahyropyrimidine, 9.2 g (0 , 11 Mole) sodium thioethylate, 50 ml of dimethylformamide and heated for 30 minutes at 120 ° C. Then 50 ml of water are added to the reaction mixture and the organic layer is extracted with benzene 4 times in 30 ml each. The benzene is distilled off and the desired 1,3,5-trimethyl hexahydropyrimidine (1a) is isolated by distillation. 11.4 g of product are obtained (yield 89%), b.p. . 1.4739. NMR-H spectrum (in S, MD: 0.68 (d, ZN, CH3) 2.17 (s., 6H, 2HCHs) 2.05 (m, 4H, MSN) 2.98 (m, 2H, NCHjN). Example 2 Analogously to example 1, use 17.3 g (OD mol) 1.3 f 5-trimethyl-5-nitrohexahyropyrimidine, 12.6 g (0.15 mol) of sodium thioethylate, Reaction time 40 min at 110 ° C, 11.6 g of product are isolated (yield 91% j, Example 3. Analogously to example 1, use 17.3 (0.1 mol) 1, 3,5-T | Eimethyl 5-nitrohexahyropyrimidine , 16.8 g (0.2 mol) of sodium thioethylate. The reaction time is 35 minutes at. 10.6 g of product is isolated (yield 83%). Example 4. As in Example 1, use 17.3 g (0.1 mol) 1 p 3, 5 - trimethyl-5-nitrohexahyropia Yin, 21 g (0.25 mol) of sodium thioethyla. The reaction time is 30 minutes, 10.9 g of product (85%) is recovered, Example 5, 17.3 (0.1 mol), 3 , 5-trimethyl-5 mitrohexahydropiimcdine, 5p9 g (O, .07 stranded) sodium tkogilat. Reaction time 40 min at 120 C. 8.7 g of product are isolated (yield 64%). Example 6. In a similar manner to Example 1, use 17, 3 g (0.1 mol) 1,3,5-trimethyl-5-nitrohexahylopyrimidine, 9.2 g (0.11 mol) of sodium thioethyl and sodium. The reaction time is 50 minutes at 80 ° C. 8.6 g of product are recovered (yield 67%). Example 7. In a similar manner to Example 1, 17.3 g (0.1 mol) of 1,3,5-trimethyl-5-nitrohexahydropyridine, 12.6 g (0.15 mol) of sodium thioethylate, are used. The reaction time is 15 min at. 7.95 g of product was isolated (yield 62%). Example 8. Similarly to Example 1, 16 g (0.1 mol) of 3,5-dimethyl-5-nitro-1,3-tetrahydrooxazine, 9.2 g (OD1 mol) sodium thioethylate, reaction time 30 min at. 9.9 g of 3,5-limethyl-1, 3-tetrahydrooxazine (1b) were isolated. Yield 86%. Bp 108 ° C, n D lHSSS. NMR-H spectrum (in CCl4) S, ppm: 0.66 (d, 3N, CH); 0.73-0.91 (m.1N, CH); 2.30 (s, ЗН, СНзК) - 2.01-2.46 (m, 2Н cycle); 2.56-3.58 (m, 2H-CH2-0 cycle), 3.76 (1H), 4.13 (Me), 2H,. Example 9. Analogously to Example 1, 16 g (0.1 mol) of 3,5-dimethyl-5-nitro-1,3-tetrahydrooxazine, 12.6 g (0.15 mol) of sodium sodium thioethylate, were used, the reaction time was 40 minutes at , 10.2 g of product are recovered (yield 89%). Example 10. Analogously to example 1, use 16 g (0.1 mol) of 3,5-dimethyl-5-nitro-1,3-tetrahydrooxazine, 16.8 g (0.2 mol) of naui. The reaction time is 35 min at 9.3 g of product is isolated (yield 81%). Example 11. In a similar manner to Example 1, 16 g (0.1 mol) of 3,5-dimethyl-5-nitro-1, 3-tetragi-cycrooxazine, 21 g (0.25 mol) of sodium thioethylate lat are used. The reaction time is 30 minutes at 130 ° C, 9.55 g of product are isolated. (yield 83%). Example 12. Analogously to Example 1, 16 g (0.1 mol) of 3,5-dimethyl-5-nitro-1,3-tetrahydrooxazine, 5.9 g (0.07 mol) of sodium thioethylate were used. The reaction time is 40 minutes at; 7 g of product are isolated (yield 61%). Example 13. Analogously to Example 1, 16 g (0.1 mol) of 3,5-dimethyl-5-nitro-1,3-tetrahydrooxazine, 9.2 g (0.11 mol) of sodium thioethylate were used. The reaction time is 50 minutes at, 7.5 g of product is isolated (yield 65%), Example 14. In analogy to example 1, 16 g (0.1 mol) of 3,5-dimethyl-5-nitro-1,3-tetrahydrooxazine are used, 12.6 g (0.15 mol) of sodium thioethyl. The reaction time is 15 minutes at 110 s. 7 g of product were recovered (yield 61%). The effect of the reaction conditions on the yield of the target products is presented in the table. As follows from the analysis of experimental data, the optimal ratio (molar) of the reagents is 1,3,5-trimethyl-5-nitro-hexahydropyrimidine (3,5-dimethyl-1,3-tetrahydrooxazine): sodium thioethylate is 1; (1,1) -2) respectively. The yield of the reaction 30-40 min, the reaction temperature 100-120 ° C. The yield of the target product in optimal conditions is 83-91% (compound 1a); 81.89% (compound 16). Under conditions beyond the specified limits, the product yield does not exceed 65-67%. The advantage of the proposed method is that it allows an increase in the yield of 5-alkyl-1,3-diheterocycloalkanes to 80-90%.

1D

1.5 2.0 2.5

120

: 0.7

80 I 1.1

110 "1.5

Table continuation

61 65

12 13 14

64 6.7 61

62

Claims (1)

METHOD FOR PRODUCING 5-ALKyl- -1,3-DIGETEROCYCLOalkanes of the formula Χχ / Ύ where R is lower alkyl; X is oxygen or lower alkylimino; Y is lower alkylimino; the interaction of 5-alkyl-5-nitro ~ 1,3-diheterocycloalkane of the formula 0, N R where r, ;; and γ - have the indicated values. with a basic sodium compound, characterized in that, in order to increase the yield of the target product, sodium thioethylate is taken as the main sodium compound, with a molar ratio of the compound of formula (II) to sodium thioethylate 1:: (1,1- 2), respectively, and the process is carried out in a medium of dimethylformamide at 100-120 ° C.