SU1414849A1 - 5h-5-oxoimidazobenzothiazines and method of production thereof - Google Patents

Abstract

The invention relates to heterocyclic compounds, in particular, the method of producing 5H-5-oxoimidazo (2,1-b) -1,3-benzothiazines of the general formula R / -, where R is CHg or Rj is H or N02, which can be used in as bioactive preparations and semi products for their synthesis. The goal is to create a method for obtaining a new heterocyclic system. The synthesis of the target products is carried out by the reaction of 4, 5-dimethyl- or 4,5-diphenyl-2-mercaptoimidazole and the o-halobenzoic acid chloride of the general formula CH CR2-CH CH-CX CC (OJC1, where Rj has the indicated values, X is F or C1, in the presence of a tertiary amine when heated in a solvent, and the process is best carried out at 80-115 C and use pyridine as a tertiary amine and solvent. Yield,%: mp. C; gross formula in examples 1-5 : 1) 81,149; - With HfoNiOS; 2) 78, no, no; 3) 85, - 200; CjiHjNjOjS, 4) 90; 261; 5) PP, - 313; CjiH aNjOgS. 2 s, and 2 zp ff. about (/ s

Description

00

with

The invention relates to the field of organic chemistry, specifically to the new heterocyclic system of 5H-5-oxo-imidazo (2,1-in) -1,3-benzothiazines, which can be used in medicine as bioactive drugs or in the medical industry. as intermediates, and the way they are received. 10

The purpose of the invention is the creation of a new heterocyclic system containing a new combination of known types of bonds between imidazole, thiazole and benzene drams.

The goal is achieved by the fact that L, 5-disubstituted 2 mercaptoimidazop is reacted with chloro-nhydride ortho-halogenbenzoic acid. Ota in the presence of a tertiary amine 20 when heated.

Example 1. Preparation of 2,3-di methyl-5-oxoimidazo (.2,1-в) -1,3-benzotiazine.25

1.75 g (.0.01 mol) of 2-chlorobenzoic acid chloride are added to a solution of 1.28 g (.0.01 mol) of 4,5-dimethyl 2-mercaptoimidazole in 30 ml of pyridine, heated at within 3h 30 are cooled, the solvent is removed in vacuo, the residue is treated with 50 ml of water, filtered, washed with water, dried. Yield 1.88 g (81%), mp: 149 ° C (from iso-cropanol)

Found,%: N 12.15; S 13.90.

Calculated,%: N 12.31; S 13.92.

In the PMR spectrum of 2,3-dimethyl-5-oxy-imidazo f2, 1-c} -1, 3-benzothiazine, written in deuterochloroform with TMS as an internal standard, the singlets corresponding to the two methyl groups in the second and the third position of the molecule, lie in strong sweat 45 le at 2.24 and 2.67 ppm respectively. Aromatic protons in the seventh - ninth position of the molecule give a rather complex multiplet at 7.37-7.71 ppm. Unusual position of the single CQ ta at 8.49 ppm (.1H, doublet, J8 Hz), which is explained by the influence of the oxygen atom of the carbonyl group in the fifth position of the molecule, which is in the immediate vicinity of the proton in question, in the sixth position of the molecule, which falls into the region of the screening effect carbonyl group.

Example 2. Preparation of 2,3-dimethyl-5-oxoimidazo (2,1-b) -1,3-benzothiazine.

To a mixture of 1.28 g (0.01 mol) of 4,5-dimethyl-2-mercaptoimidazole and 2.02 g (0.02 mol) of triethylamine in 100 ml of 1,4-dioxane is added a solution of 1.58 g (0.01 ml) of 2-fluorobenzoic acid chloride in 10 ml of 1,4-dioxane, heated at lUO C for 2 hours. Cool, solvent is removed in vacuo, the residue is treated with 50 ml of water, filtered and dried. The yield of 1.8 g (78%).

Example 3. Preparation of 2,3-dimethyl-7-nitro-5-oxoimidazo (2,1-b) -1 -1-benzothiazine.

To a mixture of 1.28 g (0.01 mol) of 4,5-dimethyl-2-mercaptoimidazole and 2.02 g (0.02 mol) of triethylamine in 150 ml of benzene was added a solution of 2.2 g (0.01 mol). mol) 2-chloro-5- -nitrobenzoic acid chloride in 50 ml of benzene, heated at 6 h. Cool, remove solvent in vacuum, treat the residue with 50 ml of species, filter, wash with water and dry. Yield 2.37 g (85%), mp: 200 ° C (from dimethylformamide).

Found,%: N 15.36; S 11.60.

with HgNjOaS

Calculated,%: N 15.41; S 11.7.

In the PMR spectrum of 2,3-dimesh1-7-nitro-5-oxoimidazo (2,1-в) -1,3-benzothiazine, recorded in deuterochloroform with TMS as an internal standard, are singlets. the two methyl groups are at 2.26 and 2.69 MD, the proton in the sixth position of the molecule is shown in the spectrum as a doublet at 9, 3b ppm. (J 2 Hz), the proton in the eighth position of the molecule appears as a doublet of doublets at 8.44 ppm, (.Jo 9 Hz, Ldd 2 Hz), the proton in the ninth position of the molecule appears in the spectrum at 7.78 ppm (doublet, J 9 Hz).

Example 4. Preparation of 2,3-diphenyl-5-oxoimidazo (.2, 1-b) -1,3-benzothiazine.

To a solution of 2.5 g (0.01 mol) of 4,5-diphenyl-2-mercaptoimidazole in 30 ml of pyridine was added 1.58 g (0.01 mol) of 2-fluorobenzoic acid chloride, heated at 115 ° C for 1,5h It is cooled, the solvent is removed in vacuo, the residue is taken up in 50 ml of water, filtered, washed 311414849

watered with water, dried. Yield 3.1 g (90%),

m.p. 261 ° C (from dimethylformamide). Found,%: N 7.81; S 9.08.

and Formula of Invention

Claims (4)

1, 5H-5-Oxo-Imidos 2 (1, 1) -1,3-ben. Thus, the proposed method allows to obtain the desired products in high yields and a small amount of time. Vyisleno,%: N 7, PP; S 9.01. In the PMR spectrum of 2,3-difensh1-5-oxo-imidazo (2,1-в) -1,3-benzothiazine, recorded in deuterodimethylsulfoxide with TMS as the internal standard iQ zohiazines of the formula m, the protons of the phenyl groups in the second and third positions of the molecule appear as a singlet at 7.45 ppm. the protons in the seventh-ninth positions of the pro molecule are in the form of a rather complex multiplet in the region. 7.21-7.90 ppm The proton, which is in the sixth position of the molecule, appears as a doublet at 8.28 ppm. (J 10 Hz). Such a shift in the weak field is due to the disscreening effect of the oxygen atom of the carbonyl group in the same position of the molecule. Example 5. 2,3-Diphenyl-7-nitro-5-oxoimidazo (2,1-b) - 25 -1,3-benzothiazine. To a solution of 2.5 g (0.01 mol) of 4,5-diphenyl-2-mercaptoimidazole in 30 ml of pyridine is added. 2.2 g (0.01 mol) of 2-chloro-5-nitrobenzoic acid hydrochloride, heated at 115 ° C for 1 h. Cooled, the solvent removed in va-. The residue is treated with 50 ml of water, filtered, washed with water and dried. The output of 3.6 g (90%), so pl. (from dimethylformamide) .f. Found,%: N 10.65; S 8,10. 20 where Rf t methyl or phenyl and R2 is a hydrogen atom or a nitro group. 2. The method of obtaining 5H-5-oxoimidazo (2,1-in) -1,3-benzothiazines of the formula where R. is methyl or phenyl and a hydrogen atom or a nitro group, which is 4,5-disubstituted 2-mercaptoimidazole. formulas n SH X-n CaiHfjNjOjS 45 Vyisleno,%: N 10,52; S 8.02. ™ the indicated values, under the supervised PMR spectrum of 2,3-diphenyl-7-nitro-40, interacting with xperanga-i-5-o-co-imidazo (2.11b) -1: 3-benzothia- "ortho-halogenobenzoinic acid forzine, recorded in deuterodimethylsulfoxide with TMS as an internal standard, the protons of the phenyl groups in the second and third positions of the molecule appear as a singlet at 7.48 MD, the protons in the sixth, eighth and ninth positions give a doublet (J 2 Hz), doublet of doublets (Ld 10 Hz, J c4 4 Hz) and doublet (J 10 Hz). In the IR spectra of all bases, recorded in KBr tablets, the absorption band of the carbonyl group is in the 1705-U 1710 cm region. The control of the reaction code and the purity of the final products is carried out by the method of those eluent - chloroform: methanol 9: 1. 50 55 where X is a fluorine or chlorine atom, and R has the indicated values, in the presence of a tertiary amine when heated in a solvent medium. 3. A method according to claim 2, characterized in that the heating is carried out at 80-115 ° C. 4. A method according to claim 2, characterized in that pyridine is taken as the tertiary amine and solvent. and Formula of Invention 1, 5H-5-Oxoimide SO (2, 1-in) -1,3-benzothiazines of the formula where Rf t methyl or phenyl and R2 is a hydrogen atom or a nitro group. 2. The method of obtaining 5H-5-oxoimidazo (2,1-in) -1,3-benzothiazines of the formula f. where R. is methyl or phenyl and a hydrogen atom or a nitro group, which is 4,5-disubstituted 2-mercaptoimidazole. formulas n SH X-n 45 40 40 interaction with xporangida- "° ortho-halobenzoic acid forms 50 55 where X is a fluorine or chlorine atom, and R has the indicated values, in the presence of a tertiary amine when heated in a solvent medium. 3. A method according to claim 2, characterized in that the heating is carried out at 80-115 ° C. 4. A method according to claim 2, characterized in that pyridine is taken as the tertiary amine and solvent.