SU1415698A1 - Method of producing 6,8-dichloro-2,3-dihydroquinoline-4-(1n)-on - Google Patents

Abstract

The invention relates to heterocyclic compounds, in particular to the preparation of 6,8-dichloro-2,3-dihydroquinolin-4 (110-one (HHC), which is an intermediate product in the synthesis of medicinal substances. In order to increase the yield of HGH nitrile N- (2-carboxyphenyl) -p-alanine is chlorinated with sulphuryl chloride in a solution of dimethylformamide and acetic acid at 5- The resulting N- (2-Kap6oKCH-4,6-dichlorophenyl) -alanine nitrile when boiling re-, share mass. Formed J-

Description

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ate

ABOUT)

with

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COCH SOzClz C1 90%

C1 H

SOGN

COjH C1 H

ASOC

Ac 2 O 79 °

HC1 / H20 91%

pine

The invention is illustrated by the following examples.

Example 1, Preparation of 6,3-dichloro-2, 3-dngidrokhinolin-4 (1H) -one.

a) Nitrile N- {2-carboxy-4,6-dichlorophenyl) -p-alanine, K 17.1 g (0.09 mol) of N- (2-carboxifenil) -p-alanine nitrile in a mixture 23 ml of dimethylformamide and 14 ml of glacial acetic acid are added dropwise over 1 hour at 5-10 ° C, 17.0 ml (0.21 mol) of sulfuryl chloride, at the same time everything goes into solution by the end of the fusion, continue to stir at 0.5 h and poured into 150 ml of cold water, the precipitated precipitate is filtered off, washed with water, and dried. The yield is 21.0 tons (90%), t, mp, 123-125 ° C (heptane), yellow crystals. Found,%: С А6,4; H 3.3, C. oHgCl N Ocj. Calculated,%: C 46.4; H 3.1,

b) M- (2-Carboxy-4,6-dichlorophenyl) - p-alanine. 46.6 g (0.18 mol) of N- (2-carboxy-4,6-dichlorophenyl) -p-alaine nitrile and alkali solution prepared from

five

0

five

18.8 g (0.47 mol) of caustic soda in 150 MP of water, heated under reflux and stirring for 10 hours, the solution is cooled, filtered and acidified to pH 2, the precipitate is filtered off and washed with water. Yield 40.5 g (81%), m.p. 190-192 ° C (ethyl acetate), yellow crystals.

Found,%: C 42.8; H 3.0; C1 25.2; N 4,8,

C, o HgCl N0.

Calculated Z: C 43.2; H 3.3; C1 25.5; N 5.0.

c) 1-Acetyl-6,8-dichloro-2,3-dihydroquinolin-4 (1H) -one. 34.7 g (0.123 mol) of N- (2-carboxy-4,6 dichlorophenyl) -p-aanine, 24.3 g (0.23 mol) of potassium acetate and 73 ml of acetic anhydride are heated with stirring at 93 -100 ° C for 3 hours, acetic anhydride was distilled off in vacuo, 200 MP of cold water was added to the residue, and the precipitated precipitate was filtered, washed with 3% sodium hydroxide solution, then with water. Yield-2 3.3 g (7.9, OZ) T.nfl.l56-15et (benzene), cream-colored crystals.

0

3t4

Found,%: C 50.8; And 3.3.

WITH,,.

Calculated,%: C 51.2; H 3.5.

d) 6,8-Dichloro-2,3-dngndrokhinolin-4 (1H) -one. 12.9 g (0.05 mol) of 1-acetyl-6,8-dichloro-2,3-dihydroknolyn-A (1H) -one, 40 MP of concentrated hydrochloric acid, 5 or more acetic acid and 2.5 A ml of water is heated with stirring in a boiling water bath for 2 hours, the reaction mixture is cooled, drunk in 100 ml of water, alkalinized to pH 9, filtered off separately with a precipitate, washed with water. Yield 9.8 g (91%), m.p. 145-147 C (heptane). Yellow crystals. UV-Spectrum (ethanol): “about, with 392, 262 nm; Ig b 3,48; 3.82. Literary data: so pl. 142-143 C; UV spectrum (methanol): AMII 395, 255-260, 240 nm; Ig 3.62 3.94, 5.02.

PRI mme R 2. Preparation of 6,8-dichloro-2,3-dihydrochknolyn-4 (1H) -one.

34.7 g (0.125 mol) of L- (2-car15oxy-4,6-dichlorophenyl) -p, -alanine, prepared as indicated in Example 1, 24.5 g (0.25 mol) of freshly melted potassium acetate and 75 ml of vinegar anhydride is heated at 90-95 ° and mixed for 5 hours, then the reaction mass is treated as indicated in example 1. 1-acetyl-6,8-dichloro-2,3-dihydroquinolin-4 (1H) is obtained - it n in the form of cream-colored crystals. Next, a 1-acetylproduct of the obtained 1-acetylproduct is deacetilvented, as described in Example 1. The yield of the desired product is 25.3 g (78.3%), mp. 145-147 C (heptane).

The choice of the optimal temperature for cyclization in the range of EO-SUO C is due to the fact that at a temperature of less than 90 C, a decrease in the product yield occurs, and above 100 ° C, the reaction of the reaction mass is observed, which also leads to a decrease in the yield,

The choice of the optimum temperature for chlorination with sulphuryl chloride (5-10 ° C) is due to the fact that, at a temperature higher, the formation of an impurity is observed in water polyhalide, and at a temperature below 5 ° C,

eight

an impurity of N- (2-Kap-boxy-4-chlorophenl) -p-alamine nitrile is formed.

The technical and economic advantages of the proposed method for the preparation of 6,8-dichloro-2, 3-dihydroquinolin-4 (1H) are as follows:

in the easy availability and low cost of the original (anthranilic acid and acrylonitrile) production

domestic industry on a large scale;

in the possibility of carrying out the process using processes that do not require special equipment and reagents;

in carrying out the process with high yields at all stages;

achieving more than a five-fold increase in the yield of the target product.

Claims (1)

Invention Formula The method of obtaining 6,8-dichlpr-2,3-dihydroquinolin-4 (1H) -one of formula C1 ° five 0 using N-phenyl-p-alanine prodopododnogo, characterized in that, in order to increase the yield of the target product, as a derivative of N-femyl-p-alanine, nitrile N- (2-carboxyphenyl) - p- ala111ga, which is chlorinated by sulphuric chloride n solution of dimethylformaDa and acetic acid at 5-10 ° С, the resulting nitrile M- (2-carboxy-4,6-dichlorophenyl) - alanine is hydrolyzed in a water-alkaline medium at boiling the reaction mass formed by M- (2-carboxy-4,6-dichlorf Shl) - p-alanine cyclized in acetic anhydride in the presence of acetone ata potassium. at 90-100 ° C and the resulting 1-acetyl-6,8-dichloro-2,3-dihydroquinolin-4 (1H) -one is deacetylated by boiling with concentrated hydrochloric acid.