SU582766A3 - Method of preparing 3-quinolinecarboxylic acid derivatives or their salts - Google Patents

Description

(54) A METHOD FOR OBTAINING DERIVATIVES OF 3-QUINOLINE-CARBIC ACID or their SALTS derivatives of 3-quinolinecarboxylic acid in an acidic medium in the presence of potassium nitrate at low temperatures. Reduction of the compound of the general formula (H) to the compound of the general formula (I) can be carried out by a number of other methods, for example using CHCTeNM zinc-hydrochloric acid. The reduction over the palladium catalyst is carried out in an acidic medium, preferably in the presence of acetic or hydrochloric acid, at atmospheric or elevated pressure. The alkylation is carried out using dimethyl sulfate or triethyl phosphate in the presence of an acid acceptor. The alkylating agent in this reaction may also be the reaction medium. The reaction is carried out at an elevated temperature, preferably at the boiling point of the reaction mixture. As salts of the compound of general formula C), alkali and alkaline earth metal salts and salts with organic amines are preferred. Example. 7.83 g (0.03 mol) of ethyl-1-4-dihydro-4-oxo-6,7-methylenedioxyquinoline-3-carboxylate is dissolved in 34.5 g (0.33 mol) of concentrated sulfuric acid, the solution is cooled before and then slowly mix them in small portions with 3.70 g (0.031 mol) of potassium nitrate, and the temperature of the mixture should not be higher. The exothermic reaction is maintained by cooling and, by adjusting the Lodachi rate of the substance, potassium nitrate is added for 30 minutes. Then it was mixed at another 1 hour, heated to a temperature of the com- bination, mixed again for another 10 hours, and the red oil obtained was poured into 300 ml of ice-water to obtain a yellow powder; which is filtered down to a neutral reaction and treated with alcohol. 8.35 g (91%) of ethyl-1,4-dihydro-4-6 x-5-nitro-biT-methylNG dyuksihinolinii-3-carboxylate are obtained in the form of a colourant in the color of substances that do not yet melt. By recrystallization from dimethylformamide, light yellow crystals with m.p. vye Found% C in 3.31; N9.30 jjHjjjN J O. & 1%: C 50.98; H 3.29; K 9.15. IR spectrum (in KBg}: 3155 (NH); 1702 (ester); 1641b (C – O); 1558 (MO) 1270 and 1032 (C – O – C) cmH Example 2: 12, 24 g (0.04 MSph of ethyl-1,4-dihydro-4-oxo-5-nitro-b, 7-methylenedioxyquinoline-3-carboxylate in a mixture with 300 ml of acetic acid and 100 ml of concentrated hydrochloric acid are hydrogenated in the presence of 2 , 0 g of palladium on activated carbon. After absorbing the theoretical amount of hydrogen, the catalyst is removed and the filtrate is evaporated in a vacuum. The solid yellow residue is added to 100 ml of water and the suspension is brought to neutrality with a dilute sodium hydroxide solution. The soluble portion is filtered and washed with water to give 9.6 g (85.5%) of a greenish-yellow product that does not melt. After recrystallization from dimethylformamide, ethyl 1, 4-dihydro-4-oxo-5-amino-6 is obtained , 7-methylenedioxyquinoline-3-carboxylate in the form of sand-colored crystals. Found: C 56.58; H 4.39; N 10.09. CisH.jHaOs. Calculated,%: 56.53; II 4 , 39 N 10.14. IR spectrum (in KBr): 3470 and 3300 (NHj); 3180 (KN); 1705 (ester C-0); 1665 {C-0); 1300, 1180 and 1072 (C-O-C) cmH Example 3. A. 11.62 g {0.05 mol) 6,7-methylenedioxy-4-quinoline-3-carboxylic acid is dissolved with stirring in 57 g ( 0.55 mol) of concentrated sulfuric acid, the solution is cooled to AISI is mixed in small portions with 5.55 g (0.01 mol) of potassium nitrate, maintaining the temperature at. The mixture is then stirred for 1 hour at low temperature, warmed to room temperature and stirred for another 10 hours. The resulting viscous red oil is poured into 500 ml of ice water to give a yellow powder, which is filtered, dried with water and treated with alcohol. 12.7 g (92.4%) of yellow 1,4-dihydro-4-oxo-5-nitro-b, 7-methylenedioxyquinoline-3-carboxylic acid are obtained, which is melted at. After recrystallization from dimethylformamide, it is also not possible to determine the melting point, as the product absorbs 1 mole of methyl formamide and the adduct decomposes at. B. 1,4-dihydro-4-oxo-5-iitro-b, 7 methylenedioxyquinolin-3-carboxylic acid is also prepared by hydrogenation of TIL-1,4-dihydro-4-oxo-5-nitro-6,7methylenedioxyxynslin-3- carboxyl .at. 4.6 g (0.015 mol) of ethyl 1,4-digiro-4-oxo-5-nitro-6, 7-methylenedioxy-3-carboxonate is heated in mixtures with 100 ml of 5% caustic bag of meat 15 ml 96% Alcohol for 1 hour in a water bath. The mixture is then clarified with activated charcoal and the filtrate is filtered. The filtrate is acidified with 5% hydrochloric acid to pH 2. The precipitated precipitates are filtered, washed with water and 3.2 g (76.8%) of 1,4-dihydro-4-oxo are obtained. b-nitro-b, 7-methylenedicisquinoline-3-carboxylic acid, which does not melt at. The product according to spectrometry data and analysis of thin-layer chromatography is identical to the product obtained by analogy with item A. Found,% g C 47.335 H 2.27 H 10.03

SiiHgN O ,.

Calculated,% s With 47.48; H 2.17

M 10.08

IR spectrum (XBg); 1725 (acids) g 1648 (C-0) 1550 (NOj) i 1270 and 1062 (t C – O – C) cm

PMR spectrum, ff (1 H.NaOB) 8.57 (1, S, 2H) s 7.02 (1, S, ZI) - 6.04 (2, S,) m, d

PRI me R 4. 2.76 g (0.01 mol) of ethyl 1,4-digdro-4-amino-6,7-methylenedioxyquinoline-3-carboxylate is heated in a mixture with 80 ml of 5% caustic potassium and 10 ml of alcohol for 1 hour in boiling water buya, the solution is all substance. The solution is clarified with activated carbon. It is filtered off with suction and acidified with 5% hydrochloric acid to pH 2. The precipitated precipitate is filtered off, and water is added until neutral and 2.3 g (92.8%) of yellow 1,4-DIHYDRO-4- is obtained. OXO-5-5MIIO-6, 7-methylenedioxyquinopin-3-carboxylic acid, which does not melt at. Found,%: C 53.17; "3.40 K 11.11,

CuHeNaOs.

Calculated,%: C 53.23; H 3.25i H 11.29.

IR spectrum (in -KVg): 3455, 3390 (UH); 3350 (NO; 1968 (MF acids) 1662 (b 0); 1292 and 1050 (@ -0-fl) cmC

HMR spectrum (iH.RdOD): 8.42 (1, u2H), 6.58 {I, a, ZN), 5.96 (2, “-,) ppm

Example 5. 52.24 g (0.2 mol of Sf-ethyl-1,4-digidro-4-oxo-6,7-methylenedioxyquinoline 3-carboxylic acid is dissolved with stirring in 230 ml (2.2 ml) mole) with concentrated sulfuric acid. The solution is then slightly heated. After 50 minutes, a temio-colored, viscous, oily solution is obtained, which is cooled to Oc and diluted: in small portions with 30, 3g (0.3 mol) of potassium nitrate, adjusting the rate of addition that the temperature did not rise above with constant cooling. Then the mixture was stirred for 1 hour and 15 hours at room temperature.

Dark red oily solution pouring out: t in 2000 ml of ice water, are vigorously stirred and a yellow powder is obtained, which is filtered off with suction and washed with water to obtain 54.5 g (89%) of N-ethyl-1, 4-DIGIDRO-4-OXO -5-NITRO-6,7-methylenedioxyquinoline-3-carboxylic acid, T.Sh1. (different). After recrystallization from dimethylforma n. M.d. 325C. ,

Found,% s C50.75; H 3.12; M9.17

 NaO.

Calculated,% С 50.98 N. 3.29

M 9.15,

UV spectrum (ethanol) s maximum at 317 and 217 of them.

IR spectrum (in KBG) S 1730 (e- &acid); 1646 (i € -e) 1558 (. Fifta); 1278 and 1052 ((Gf.OtC) cmH

1 H NMR spectrum (1N. NdOD) f 8.12 (1, s 2H) j 8.10 (1, 5S, 3H), 55 (2,% „0-CH" -0), 4.16 (2, a, CHe), 1.42 (2, t, CHj) m, d „

P p and M ep 6. 21.44 g (0.07 mol K-ethyl-1,4-cyhydro-4-oxo-5-nitro-6, 7-methylenioxyquinoline-3-car6anoic acid is suspended in a mixture of 525 ps acetic acid acids and 175 MP of concentrated hydrochloric acid and then hydrogenated at atmospheric pressure in the presence of 4 g of palladium on carbon.After the absorption of hydrogen is completed, the solution is filtered into 3000 ml of water, immediately separating the product, which is filtered, washed with water until neutral, yields 16, 6 g (86%) (yellow H.-ethyl-1, 4-dihydro-4-oxo-5-amino-6, 7-methylenedioxyquinoline-3-carboxylic acid Torazl. After recrystallized brilliant yellow crystals of T.ros.292-294 ° C (Rael) are obtained from dimethylformathmnst.

Found,% 8 C 56.31 H 4.27g M 10, -20.

Ci4 HigiKaSg.

calculated,%: C 56,52; H 4.38; N 10.14,

UV Spectrum (ethanol) maximum at 358, 277 and 265 nm.

IR spectrum (in RBr) j 3475 and 3340 (HNg); 1762 (Cb acid); 1664 (d-0); 1310 and 1042 (C-O-C) see

Mass spectrum: 276 (M, 100%), 258 (M 18.5%), 232 (M 44.22%), 231 (M 45.12%), 218 (M 58.1.5%), 207 (M 72.13%), 203 (M 73.20%).

PRI me R 7. 5.52 g (0.02 mol) of 4-etyl-1,4-dihydro-4-oxo-5-amino-6, 7-methylenediamine-3-carboxylic acid are suspended in 60 ml acetic anhydride and mixed with 1.6 g (0.02 mol) of anhydrous sodium acetate. The mixture is boiled in an ZOmin oil bath, and the substance slowly goes into solution. After that, the solvent is evaporated in vacuo, the residue is skewed