SU413679A3 - - Google Patents

Description

one

The invention relates to a process for the preparation of new compounds - derivatives of 3-carbalkoxy-1-thiaisochroman-1, 1-Dioxide of formula I

(

(I)

i 0-R,

where RI and R2 is lower alkyl;

Rs is a hydrogen atom or lower alkyl;

RI is an aliphatic hydrocarbon residue, unsubstituted or substituted by a halogen atom or a benzene, or tetrahydrofuryl residue, or a cycloalkyl residue.

These compounds have valuable pharmacological properties.

The method is based on the reactions known in organic chemistry for the preparation of carboxylic acid halides by acid action with an inorganic acid halide, such as thionyl chloride, and the synthesis of carboxylic esters by the esterification of their acid halides.

The proposed method is that the carboxylic acid derivative of the formula P

2

Cilo-- r

h

COOH

(eleven)

S- 0 0

where Ri, R2 H Rs have the indicated meanings, is reacted with an inorganic acid halide, for example with chloride, formed the acid anhydride of a carboxylic acid derivative of the formula I, and is etherfied with an alcohol of the formula P1 R.-OI (111),

RI has the indicated meanings, and the desired product is usually obtained by conventional preparations. Lateralization of esterification of the halide anhydride of the carboxylic acid derivative of forrid And, for example, the mules are preliminarily removed by excess of the halide ion by inorganic distillation.

acid.

The resulting compounds of formula I precipitate in pure form either already during the process of heating or during the cooling of the reaction mixture.

Example 1. A mixture of 2.9 g of 3-carboxy-6, 7-dimethoxy-1-thiaisochroman-1,1-dioxide and 10 g of thionyl chloride is boiled in a water bath for 8 hours with a refrigerator.

After distillation of the excess thionylchoporide from the reaction mixture, the crude 3-chlorocarbonyl-6,7-dimethoxy-1-thiaisochroman-1, 1-dioxide is esterified with 60 ml of methanol and the mixture is heated for 1-2 hours at a tempered area. The precipitated 3-carbomethox-6, 7-dimethoxy-1-thiaisochroman-1,1-dioxide after cooling the reaction mixture is sucked off, washed with methanol and dried, m.p. 211-214 ° C. Yield 2.8 g, which is 92.7% of theory.

Example 2. 3-chlorocarbonyl-6,7-dimethoxy1-thiaisochromium-1, 1-dioxide, obtained analogously to example 1 of 5.8 g of 3-carboxy-6,7-dimethoxy-1-thiaisochroman-1, 1 dioxide and 20 g thionyl chloride, mixed with 120 ml. metaiol and 2-3 drops of triethylamine and stir the mixture for 2 hours at room temperature. The precipitated 3-carbmethoxy-6,7-dimethoxy-thiaisochroman-1,1-dioxide is filtered off, washed with water, then with methanol and dried, so it is. 211-214 ° C. The output of 5.9 g (97.5% of theory).

Example 3. 3-chlorocarbonyl-6,7-dimethoxy1-thiaisochroman-1, 1-dioxide, obtained analogously to example 1 of 5.8 g of 3-carboxy-6,7-dimethoxy-1-thiaisochroman-1, 1-dioxide and 20 g of thionyl chloride, mixed with 120 ml of methanol, 0.2 g of triethylamine hydrochloride and stirred the mixture for 2 hours at room temperature. 3-carbomethoxy-6,7-methoxy-1-thiaisochroman-1, 1-dioxide filter is precipitated, washed, washed with water and then with methanol, and dried; m 211-213 ° C. The output of 5.8 g (95.9% of theory).

Example 4. 3-chlorocarbonyl-6,7-dimethoxy1-thiaisochroman-1, 1-dioxide, prepared analogously to example 1 of 5.8 g of 3-rboxy-6,7-di-methoxy-1-thiaisochromat-1.1 -dioxide and 20 g of thionyl chloride, mixed with 80 ml of acetone, 2.4 g of 3-chloropropanol-1 and 2 g of triethylamine. Stir the reaction mixture for 2 hours at room temperature. The triethylamine hydrochloride precipitated is filtered off, and the pulp is washed with acetone and acetone agonists.

kO | filtrates are concentrated in vacuo. The residue obtained (7.9 g) is recrystallized from methanol; t. wop 114.5-116 ° C. Mol weight 364.8. Output 5.5 g (75.3% of theory).

Found,%: C 46.24; H 4.69; S 8.79; C1 9.62.

C ,, P | 7S1075.

Calcium,%: C, 46.15; H 4.70; S 8.79; C1 9.72.

Subject invention

Method for producing derivatives of 3-carbalkoxy-1-thiaisochroman-1, 1-dioxides of formula 1

nn

-Ch ..: o

SG

(I)

0-r.

about

S

 ABOUT

where RI and R2 is lower alkyl;

Rs is a hydrogen atom or lower alkyl;

R.) - an aliphatic hydrocarbon residue, an unsubstituted or mixed with a halogen atom or a benzene, or a tetrahydrofuryl residue, or a cycloalkyl residue, and with the fact that the carboxylic acid derivative of the formula II

Rio

(eleven)

- where Ri, Ra and Hz have the indicated values, undergo interaction with an inorganic acid halide, for example with thionyl chloride, to form a carboxylic acid derivative halide of the formula: And is esterified with an alcohol of formula II

R4-OH (1P),

where R: has the indicated meanings, and isolate the target product by conventional techniques.