SU1220570A3 - Method of producing derivatives of quinoxalyndioxide - Google Patents

Description

This invention relates to an improved process for the preparation of quinoxalinedioxide derivatives, which are bactericidal agents and have the property of increasing the weight of animals.

The purpose of the invention is to intensify the process and expand the range of target compounds.

Example 1. To a solution of 21.2 (0.2 mol) of benzaldehyde in 200 ml of water containing 2 ml of concentrated hydrochloric acid, a solution of 18.0 g (0.2 mol of methyl carbazate in 50 ml of water) is added in portions at room temperature. After about 10 minutes, a white-colored suspension is formed. After another 10 minutes, a solution of 38.0 g (0.2 mol) of 2-formylchinoxalin-1,4-dioxide in 400 ml of hot water is added in portions to 400 ml of hot water, after which the reaction mixture is kept for 20 minutes in an iodine bath with a temperature of 95 -. The precipitate and yellow-colored crystals are precipitated Allically, the prokukt is filtered off in a hot standing and washed with a small amount of ethyl alcohol.

Yield 45.0 g (85.8%) of methyl- (2-quin-oxalinylmethylene) -carbamate-S, oxide. T. pl. 258-259 s (with decomposition).

Example 2. 42 g (0.5 mol) of cyclopentanone and 45 g (0.5 mol) of methyl carbazate are reacted for 1 hour in 200 ml of ethyl alcohol in the presence of 1 ml of acetic acid. The color of the precipitate formed (white color, b5-67 s) is filtered off, then it is dissolved in 250 ml of methyl alcohol and mixed with a solution of 118 g (0.5 mol) 2 formylchioxalindimethyl acetal-1,4-dioxide in water containing 35 ml of hydrochloric acid, and carried out the reaction for 25 minutes at 80 ° Yellow-colored methyl- (2-quinoxalinylmethylene) -carbazate-N, N dioxide precipitated from the mixture while it is still hot. The product is filtered and washed. The consumption of 101 g (79%). T. pl. 259-260 0 (with diff.).

Example 3. 5.7 g (0.11 mol of 98% hydrazine hydrate added in portions to a solution of 9.9 g (0.11 mol of dimethyl carbonate in 25 ml of methyl alcohol. The reaction mixture is stirred

wag

2 hours at room temperature, then methyl alcohol and traces of unreacted hydrazine are distilled off. The residue is stirred

with a solution of 12.2 g (0.1 mol) of salicylic aldehyde in 30 ml of ethyl alcohol and stirring is continued for about 0, 5 h in the presence of 0.5 ml of acetic acid. Received

Azomethine derivative has

mp, 169-171 C. The product is stirred for 1 hour with 19 g (0.1 mol) of 2-formyl-oxaline-1,4-dioxide in water acidified with hydrochloric acid.

at 20-25 s. The resulting yellow-colored methyl- (2-quinoxalinyl-methylene) -carbazate-N, N-dioxide is filtered and washed. Output

16.8 g (78.8%). M.p. 260-261 ° C

(with different).

Example 4. The azomethine derivative obtained by the method described in example 3, from 10.8 g (0.1 mol) pyridine-2-aldehyde, by analogy with the method described in example 3, is reacted with 2 -formyl-quinoxaline-1,4-dioxide for 90 min. As a result, with a yield of 80%, methyl- (2-quinoxalin-ylmethylene) -carbazate-N, M-dioxide are obtained.

Mp 257-259 C (with decomposition).

Example 5. An azomethrin probe produced by the method described in Example 3, with 8.6 g (0.1 mol) of midazolidone- (2), is reacted with 19 g (0.1 mol) of 2-formylchinoxalin-1.4 dioxide at 35-40 C for 40 min, as a result of which methyl- (2-quinoxalinylmethylene) -carba 44 is obtained

sat-N, N-dioxide with a yield of 93%, So pl. 260-261 ° C (with decomp.).

Example 6. A solution of 19 g (0.1 mol) of 2-formyl-quinoxalin-1,4-oxide in 250 ml of a 1% aqueous solution of hydrochloric acid is added in portions in a hot state to a solution of 10.1 g (0.1 mol ), acetaldehyde semicarbazone in 70 ml

ethyl alcohol. After heating the reaction mixture at b.p. (80 ° C) for 1 h, the yellow colored precipitate is filtered off in a hot state and washed with ethyl acetate.

alcohol, resulting in a gain of 22 g (80%) quinoxaline- (2-aldehyde) - semicarbazone-N, N-dioxide. T. pl. 288-290 ° C.

Example 7. In carrying out the method corresponding to example 6, from 5.9 g (0.1 mol) of acetaldehydoxime and 19 g (0.1 mol) of 2-formsh quinoxaline-1,4-dioxide at 55-60 ° C in Within 45 minutes, 2-quinoxalinyl-aldoxime-1,4-dioxide is obtained with a yield of 91%, mp. 248-249 ° C.

Example 8. Starting from 16.2 g (O, 1 mol) of benzaldehyde aminoguanidine and by carrying out the method by analogy with Example 6 with and a reaction time of 1 hour, 90% (2-quinoxalinylmethyl) -amino-guanidine-N is obtained with a code of N-dioxide. M.p. 286 С

Example 9. Starting from 18.8 g (O, 1 mol) of cyclohexanonephenylhydrazone and by carrying out the method in accordance with Example 6 at 80 ° C and a reaction time of 1 hour, (2-quinoxalinylmethylene) -phenylhydrazine-N is obtained in 82% yield N-dioxide. T. pl. .

Example 10. 22.6 g (0.1 mol of trimethoxybenzoic acid hydrazide) are added to a solution of 10.6 g (O, 1 mol) of benzaldehyde in 200 ml of water containing 8 ml of concentrated hydrochloric acid. The mixture is stirred for 15 minutes at room temperature then the resulting azomethine derivative is reacted with 19 g (0.1 mol) of 2-formyl quinoxalin-1,4-dioxide. The reaction mixture is stirred for 30 minutes in a water bath at 95-100 C. The resulting orange-yellow colored 2- (3, 4, 5-trimethoxy-benzoyl) -hydrazonoformalyl quinoxalin-1,4-dioxide filtering are hot and washed with ethyl alcohol, duct.

Yield 38.8 g (97.4%) pro- ess. Pcs. .

Example 11. When carrying out the reaction by the method described in 1; Reamer 10, from an azomethine derivative obtained from 10.6 g (0.1 mol of benzaldehyde and 21.4 g (0.1 mol) of lauric acid hydrazide, and 19 g (0.1 mol) of 2-formylquinoxaline-1,4-dioxide at 65-70 s and a reaction time of 55 min. get 33.2 g (88.7%) of 2-laurinoylhydrazonoformylxinoxalin-1,4-dioxide, having mp 233

Example 12. The reaction of the azomethine derivative obtained from 10.6 g (0.1 mol) of benzaldehyde and 15.0 g (0.1 mol)

-

1220570

phenylacetic acid hydrazide, with 19 g (0.1 mol) of 2-formylquinoxalin-1,4-dioxide, and

By analogy with that described in Example 10 at 85-90 0 and a reaction time of 40 minutes, 31.8 g (8.4%) of 2- (fench1 acetals) -hydrazino-formyl-quinoxalin-1,4-dioxide, m.p. which 25b with. Example 13. As a result of the reaction of the azomethine derivative obtained from 20.0 g (0.1 mol) of 1-naphthylacetic acid hydrazide and 10.6 g (0.1 mol) of benzaldegnd, with 19 g (0.1 mol) of 2- formylquinoxaline-1,4-dioxide by the method described in example 10, at 90-95 ° C and a reaction time of 35 minutes, 33.4 g (89.9%) of 2- (1-naphthyl-acetyl) -hydra-formoforhinoquinoxalin-1,4 dioxide with so pl. 247 C.

Example 14. As a result of the reaction of a Schiff base, obtained from 10.6 g (0.1 mol) of benzaldehyde and 15.2 g (0.1 mol) of p-hydroxybenzoic acid hydrazide, with 2-formyl-quinoxaline-1 , 4-dioxide by the method described in example 10, at 95-100 ° C for 25 missions, 30.8 g (93%) of 2- (p-hydroxybenzoyl) -hydrazone-formsine-quinoxalin-1,4-dioxide with m.p. . 308 ° C.

Example 15. As a result of the reaction of a Schiff base obtained from 15.1 g (0.1 mol) of p-benzoic acid hydrazide and 10.6 g (0.1 mol) of benzaldehyde, from 19 g (0.1 mol) of 2- formylquinoxaline-1,4-dioxide by the method described in example 10, with EZ-SHO C and a reaction time of 25 minutes, 28.5 g (83.2%) of 2- (p-aminobenzoyl) -hydrazonoformsh1-hinoxin-1-1 are obtained , 4-dioxide with so pl. 291- 292 C.

Example 16. Starting from 22.2 g (0.1 mol) of benzaldehyde nicotinoyl hydrazone and by carrying out the method by analogy with that described in example 10, at 95-1 hours of reaction time of 20 minutes, g (85.4%) 2- (nicotinol) -hydrazonoformylquinoxaline-1,4-dioxide having m.p. 270 C.

Example 17. Starting from 22.2 g (0.1 mol) of benzaldehyde isonicotinoyl-hydrazone and when performing

ba by analogy; ii with described in example 10 at 90–9 5 5 C and reaction time 35 minutes, get 29, O g (93.8%) 2 (from nicotinoyl) -hydrazoan formylcholine saline-1,4-dioxide with t .gsh 268 C.

Example 18. Starting from 19.6 g (O, 1 mol) acetaldehyde- (p-chlorobenzoyl) -hydrazone and when carrying out the method by analogy with that described in example 10 at 95-100 ° C and a reaction time of 30 minutes, 32 are obtained 2 g (94%) of 2- (p-chlorobenzoyl) -hydrazone-formyl-quinoxalic-1,4-dioxide, having so pl. , 173-274 ° C.

Example 19. Starting from 29.2 g (0.1 mol) of decanaldehyde-furan-2-carbonylhydrazone and when carried out by the scientific-research institute of the method, by analogy with example 11 at 95-100 ° C and a reaction time of 30 min, 2- (2-furanoyl) is obtained - hydrazonoformalinoxaline-1,4-dioxyd with a yield of 94%, having so pl. 261

Example 20. Starting from 26.6 g (0.1 mol) of benzaldehyde- (3-nitro-benzoyl) -hydrazone and when carrying out the reaction as described in example 10 at 95-100 ° C and reaction time 30 minutes, 32 are obtained , 6 g (92%) of 2- (3-nitrobenzoyl) -hydrazo-formyl-quinoxalin-1,4-dioxide. T. pl. 289-290 ° C.

Example 21. Starting from 25.6 g of (O, 1 mol) benzaldehyde- (5-nitrofuranoyl-2) -hydrazone and when performing the method described in Example 10, at 95-100 ° C and a reaction time of 30 min. 84% yield, 2- (5-iitro-2-furanach1) -hydrazonoformylquinoxalin-1,4-dioxide is obtained. T. pl. 265 ° C

Example 22. Starting from 17.8 g (0.1 mol) of acetaldehyde- (o-oxybenzoyl) -hydrazone and by carrying out the method by analogy with the described in Example 10 at 95-100 ° C and a reaction time of 20 minutes, 2- (salicyloyl) hydrazonoformylquinoxalin-1, 4-dioxide. Output 83%, T, pl. .

Example 23. Starting from 27.1 g (O, 1 mol) of benzaldehyde capronoyl hydrazone and by carrying out the method as described in Example 10 at 95–100 ° C for 25 min, 2- (caprinos1) -hydrazono formylquinoxaline-1,4-dioxide. Yield 88%, mp. 237-238 s.

Example 24. Starting from 22.1 g (0.1 mol) of acetone- (p-nitrobenzoyl) -hydrazone and by carrying out the method by analogy with that described in example 10 at 95-100 C for 15 minutes, 2- (p- nitrobenzoyl-hydrazonoformylquinoxalin-1,4-dioxide. Yield 91.8%, t, pl 275-276 ° С

Example 25. Starting from benzaldehyde-beta-phenylpropionyl hydrazone and by carrying out the method by analogy with that described in example 10 with 95-100 C and a reaction time of 25 m, 2- (beta-phenylpropionyl) -hydrazonoformylquinoxalin-1,4-dioxide c is obtained yield 91%. T. pl. 241 ° C.

Example 26. Starting from benzaldehyde stearinoyl hydrazone and by carrying out the method by analogy with that described in example 10 at 95-100 ° C and a reaction time of 30 minutes, 2- (stearinoyl) -hydrazonoformal-quinoxaline-1,4-dioxide is obtained with a yield of 76% T. pl. .

Example 27. Starting from benzaldegidanisoylhydrazone and by carrying out the method by analogy with that described in example 10 at 80-85 ° C and a reaction time of 45 minutes, 2- (anisoyl) -hydrazonoformilhinoksalin-1,4-dioxide is obtained with a yield of 80.3 % T. pl. .

Example 28. Starting from cyclopentanone-piperidino-4-carbonyl hydrazone and by carrying out the method by analogy with that described in example 10 at 75-80 C and a reaction time of 50 minutes, is obtained with a yield of 76% 2- (piperidino-4-carbonyl ) -hydrazonoformylquinoxalin-1,4-dioxide. T. pl. 185-188

Example 29. Starting from benzaldegido- (2-hydroxy-3-naphthoyl) -hydrazone and by carrying out the method by analogy with that described in example 10 at 95 ° C and a reaction time of 30 minutes, 2- (2 -oxy-3 -naphtoyl) -hydra zonoformalkinoksalin-1. 4-dioxide with a yield of 97%, so pl. 260 S.

Example 30. Starting from benzaldehyde-benzoyl hydrazone and by carrying out the method by analogy with that described in example 10, 2- (benzoyl) -hydrazonoformylquinoxesin-1,4-dioxide is obtained at a yield of 84.62% with a reaction time of 90 minutes.

T. pl. 278 C.

Example 31. Starting from benzaldehyde-heptanyl hydrazone and by carrying out the method by analogy with that described in example 1 at 100 C and a reaction time of 20 minutes, 87.2% of 2- (heptanoyl) -hydrazonoformilhinoksalin-1, 4-dioxide is obtained in a yield of 87.2%. T. pl. 241 ° C.

The table shows the temperature and time conditions for the reaction.

Table continuation

Claims (1)

METHOD FOR PRODUCING CHINOXALINDIOXIDE DERIVATIVES of the general formula where Q is NHCOOR ₃ (R ₃ - C, -C ₆ -alkyl); - NH-CO-NHj, - OH, - NHC0R ₄ (R ₄ C, | -C ₅ ~ alkyl), by the interaction of a quinoxalindioxide derivative and an azomethine derivative in a solvent medium, characterized in that, in order to intensify the process and expand the range of target compounds , a compound of the formula ί is used as a quinoxalindioxide derivative I about a as an azomethine derivative - a compound of the formula C-N-Q, where Q has the indicated meanings; R _(- C4 ~ C ₄ alkyl, phenyl, hydroxyphenyl, pyridyl; R ₂ is hydrogen or Cj-Cd alkyl; R _{t and} II ₂ together with the adjacent carbon atom mean a cycloalkylidene group with 5-6 carbon atoms or a 1,5-diazacyclopentene-2-yne group, and the process is carried out at 18-100 ° C for 15-90 minutes. SU <., 1220570