CS207299B1 - 6-benzoylamino-2-sek-butylthiobenzothiazol - Google Patents

Description

The present invention provides 6-benzoylamino-2-secbutylthiobenzothiazole.

The starting material for the synthesis of said compound, 6-amino-2-sec-butylthiobenzothiazole, is active against both typical and atypical tuberculous mycobacteria [Sidóová, E., Odlerová, Ž., Volná, F. and Blóckinger, G., Chem. Rumors, 33, 830 (1979)].

We have now discovered that the hitherto unknown compounds of formula L-CO-NH \ g of ^Z-8-CH

0H _and CH ₃ CH _with the antimycobacterial effective against typical tuberculous mycobacteria Mycobacterium (M.) tuberculosis H ₃₇ 1U, and the atypical tuberculous mycobacteria M. kansasii and M. avium.

At the same time, three processes for the preparation of said compound on the basis of 6-amino-2-mercaptobenzothiazole derivatives respectively were identified. its tautomeric form

6-amino-2-benzotiazolíntiónu.

Procedure A is carried out by alkylation of the potassium salt of 6-benzoylamino-2-mercaptobenzothiazole, resulting from the dissolution of 6-benzoylamino-2-benzothiazolinothione in a potassium hydroxide solution. Process B is carried out by reaction between benzoic anhydride and 6-amino-2-sec-butylthiobenzothiazole. Process C consists of acylating 6-amino-2-sec-butylthiobenzothiazole with benzoyl chloride in the presence of an equivalent amount of N, N-diethylaniline.

The following examples illustrate but do not limit the preparation and properties of the compound of the invention.

Example 1

Preparation of 6-benzoylamino-2-sec-butylthiobenzothiazole (according to Procedure A)

6-Benzoylamino-2-benzothiazolinothione (8.8 g, 0.03 mol) was dissolved in a mixture of potassium hydroxide (2.0 g, 0.036 mol), water (25 ml) and ethanol (75 ml). Freshly distilled sec-butyl iodide (6.6 g, 0.036 mol) was added to the mixture. The reaction mixture was heated to boiling and after 5 minutes boiling it was decolourised with charcoal and filtered through a heated funnel. After cooling to 5 ° C, it fell out

207 299 from a solution of crystalline 6-benzoylamino-2-sec-butylthiobenzothiazole with 1.1.147-149.5 ° C in the amount of

7.4 g (72.2%).

The sample was recrystallized from 5: 1 ethyl alcohol-water using activated carbon. The product was obtained in the form of yellowish flakes with 1.1. 148.5-150.5 ° C.

M.H .: 342.48

For C ₁₈ H ₁₈ N ₂ OS ₂ calculated: C 63.13 H 5.30 N 8, 18 S 18, 72% found: 62.99 5.36 8.03 18.67

Example 2

Preparation of 6-benzoylamino-2-sec-butylthiobenzothiazole (according to Procedure B)

A mixture of 6-amino-2-sec-butylthiobenzothiazole (7.15 g, 0.03 mol) and benzoic anhydride (22.6 g, 0.10 mol) was melted in a sand bath and kept in a molten state for 10 minutes. After cooling to the comminuted melt, a 5% potassium hydroxide solution (200 mL) was added. After dissolving the benzoic acid and decanting its potassium salt solution, a dark sticky residue remained, which was recrystallized from 5: 1 ethyl alcohol-water using activated carbon. 6-Benzoylamino-2-sec-butylthiobenzothiazole, identical to the compound of Example 1, was obtained in an amount of

7.15 g (69.8%) in the form of yellowish scales with 1.1.

148.5-150.5 ° C, whose mixed melting point with the compound of Example 1 did not give depression.

Example 3

Preparation of 6-benzoylamino-2-sec-butylthiobenzothiazole (according to Procedure C)

A mixture of 6-amino-2-sec-butylthiobenzothiazole (4.75 g, 0.02 mol), benzoyl chloride (2.80 g, 0.02 mol), N, N-diethylaniline (3.00 g, 0.02 mol) ) and benzene (25 mL) was refluxed for 30 minutes. After the benzene was distilled off under reduced pressure, a 5: 1 mixture of ethanol and water (150 ml) was added to the distillation residue, the solution was decolorized with charcoal at boiling and, after filtration, ice water (500 g) was added. The precipitated product was washed first with 0.5% hydrochloric acid (500 ml) and then with water (500 ml) and finally recrystallized from a 5: 1 mixture of ethanol and water using activated carbon. 6-Benzoylamino-2-sec-butylthiobenzothiazole, identical to that of Examples 1 and 2, was obtained in an amount of 4.7 g in the form of flakes of cream color, m.p. t.

148.5-150.5 ° C, whose mixed melting point with the compound of Examples 1 and 2 does not give depression.

Example 4

The antimycobacterial activity of a compound of the invention compared to that of known antituberculotics

substance MIC versus Mycobacterium tuberculosis H ₃₇ Rv can- chassis avium Compound of the Invention 5 5 25 isoniazid 1 10 10 ethionamide 1 10 25

MIC = minimum inhibitory concentration in / zg / ml. Antimycobacterial efficacy against tuberculous mycobacteria was monitored in the liquid Granule soil by the dilution test. Dimethylsulfoxide was used as solvent. The final concentration of substances in the soil was 1, 5, 10, 25, 50, 100 and 200 µg / ml.

Significantly, the compound of the present invention, by its activity against atypical tuberculous mycobacteria of M. kansasii, already at a concentration of 5 μg / ml, is twice as high as the most well-known established preparations of Izoniazid and Etionamide. tuberculosis H ^ Ry and at a concentration of 25 μg / ml against atypical tuberculous mycobacteria M. avium. *

The compound of the invention may be used as an active ingredient of antimycobacterial preparations, or as an intermediate for further syntheses.

Claims (4)

OBJECT OF THE INVENTION 1. 6-Benzoylamino-2-sec-butylthiobenzothiazole of the formula 2. A process for the preparation of a compound according to claim 1, which comprises reacting the potassium salt of 6-benzoylamino-2-mercaptobenzothiazole with secbutyl iodide in a 3: 1 mixture of ethanol-water at boiling. 3. A process for the preparation of a compound according to claim 1, which comprises reacting 6-amino-2-sec-butylthiobenzothiazole with benzoic anhydride in the melt. 4. A process for the preparation of a compound according to claim 1, which comprises reacting 6-amino-2 sec-butylthiobenzothiazole with benzoyl chloride in the presence of an equivalent amount of N, N-diethynyline in benzene at boiling.