The method of obtaining 2', 3', 4', 5'-tetrabenzyl-5-acetyl-1,5 - dihydroquinoline

 

(57) Abstract:

Describes how to obtain 2', 3', 4', 5'-tetrabenzyl-5-acetyl-1,5-dihydroquinoline by dibenzoylmethane 3, 2', 3', 4', 5'-pentamethylpiperidine education 2', 3', 4', 5'-tetramethylaniline, which is subjected to reductive acetylation in the presence of 3 - 5% palladium on aluminium oxide without separation from the reaction medium. Predlogennyi method makes it possible to increase the yield of the target product by more than 25% and to simplify the technology of its receipt.

The invention relates to organic chemistry, in particular to a method of obtaining 2', 3', 4',5'-tetrabenzyl-5-acetyl-1,5-dihydroquinoline (benzoflavone), and can be used in pharmaceutical industry and medicine.

A method of obtaining benzoflavone by restoring 2',3',4', 5'-tetramethylrhodamine (I) of zinc dust in the environment of acetic acid and acetic anhydride in boiling with the release of 85.7% [1]. (Copyright certificate 413148, 1974).

The disadvantage of this method is the complexity of its reproduction on an industrial scale, because the allocation of the target product provides for flushing of hot acetic acid, the distillation in vacuum acetic to the Tadei selection of product.

A method of obtaining benzoflavone by restoring 3,2',3',4', 5'-pentamethylpiperidine (II) with hydrogen in the presence of 3 - 5% Pd/C at 25 - 30 MPa. and 125 - 130oC for 3.5 hours with a yield of 80%. (Chemistry, Biochemistry, and pharmacology of vitamin B2and its derivatives. // Collected works. - M., 1988, S. 9. - [2]).

The disadvantage of this method is the relatively low output of benzoflavone and complexity of the production technology, due to the high process temperature and high pressure, in addition, the product contains impurities of isoalloxazine patterns.

There is also known a method of obtaining benzoflavone by dibenzoylmethane II by boiling in acetic acid medium with the formation of I (yield 86%) and subsequent hydrogenation of the latter with hydrogen in the presence of Pd/C in the medium of acetic acid and acetic anhydride in an autoclave at 25 - 30oC for 10 hours. The output of benzoflavone 80% [2]. (Chemistry, Biochemistry, and pharmacology of vitamin B2and its derivatives. // Collected works. - M., 1988, S. 8).

The disadvantage of this method is the necessity of selection 2',3',4',5'-tetramethylaniline, which complicates the process, as well as a low output. The total yield of benzoflavone after PE output and simplification of technology for benzoflavone.

This is achieved by a method of obtaining benzoflavone by dibenzopyrene II education 2',3',4',5'-tetramethylrhodamine with subsequent reductive acetylation of the latter in the presence of a catalyst, the hallmark of which is used as a catalyst 3 - 5% palladium on aluminium oxide and conducting the reaction of reductive acetylation without the isolation of intermediate I.

Carrying out the reaction of reductive acetylation without the isolation of intermediate 2', 3', 4',5'-tetramethylrhodamine technology simplifies the process, and use as catalyst 3 - 5% Pd/Al2O3allows to increase the output of benzoflavone to 95%, and reduce the time for recovery of acetylation of up to 2 hours, which also simplifies the process.

The essence of the method consists in the following: heated 3,2',3',4',5'-pentamethylenebis in a mixture of acetic acid and acetic anhydride, taken in the ratio of 1:1-1:2 at 100 - 120oC for 1 to 4 hours, cooled to 20 to 25oC, was added a catalytic amount of 3 - 5% Pd/Al2O3and with vigorous stirring miss hydrogen at 50 - 80oC for 1 to 8 cha the water, the precipitate is filtered off, washed until neutral wash water, dried at 50 - 55oC without light. The output of benzoflavone 93,78 - 95,5%.

Example:

A mixture of 16 g 3,2',3',4',5'-pentamethylpiperidine, 160 ml of acetic acid and 160 ml of acetic anhydride is heated under stirring at 110oC for 2 hours, then the mixture is cooled to 20oC add 0.32 g of 5% Pd/Al2O3and with vigorous stirring miss hydrogen gas. The reaction mixture is heated under stirring at 70oC for 2 hours. At the end of the separate hydrogenation catalyst, the reaction solution was poured with stirring into 2 liters of distilled water. The residue is washed until the pH of wash water (pH 5-6), and then dried. Yield 14 g (93,78%).

The quality of the drug with VFS N 42-2002-95.

The moisture content of 1.97%; the product contains 98.4% of C47H40N4O11in terms of anhydrous substance, practically insoluble in water, easily soluble in chloroform and acetone, sparingly soluble in 95% alcohol; UV spectrum has a maximum absorption at 3062 nm, a minimum at 2902 nm; sulphate ash of 1 g of the drug - 0,11%.

The use of the proposed and is by reducing the number of process steps, as well as reducing the time of hydrogenation of from 10 to 2 hours.

Used books

1. Author's certificate N 413148, 1974, BI N 4.

2. Chemistry, Biochemistry and pharmacology of vitamin B2and its derivatives. // Collected works. - M., 1988.

The method of obtaining 2', 3', 4', 5' - tetrabenzyl-5-acetyl-1,5-dihydroquinoline by dibenzoylmethane 3, 2', 3', 4', 5' - pentamethylpiperidine with subsequent reductive acetylation of the obtained 2', 3', 4', 5' - tetramethyldisilane in the presence of a catalyst, wherein the catalyst used 3 - 5% palladium on aluminum oxide, and the reaction of reductive acetylation carried out without the isolation of intermediate 2', 3', 4', 5' - tetramethyldisilane.

 

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