RU2461552C1 - Method of producing 2(3h)-benzothiazolones with carbamate function at c6 - Google Patents

Abstract

FIELD: chemistry.

SUBSTANCE: invention relates to a method of producing methyl-N-(2-oxo-2,3-dihydro-1,3-benzothiazol-6-yl)carbamate of formula

(I) and methyl-N-(5-chloro-2-oxo-2,3-dihydro-1,3-benzothiazol-6-yl)carbamate of formula

(II). The method is realised by holding equimolar amounts of N,N'-dimethoxycarbonyl-1,4-benzoquinone diimine (or 2-chloro-N,N'-dimethoxycarbonyl-1,4-benzoquinone diimine to obtain methyl-N-(5-chloro-2-oxo-2,3-dihydro-1,3-benzothiazol-6-yl)carbamate) and thioacetic acid in methylene chloride for 3 hours at room temperature, filtering the obtained crystalline product, washing said product with diethyl ether and then boiling for 5 hours in ethanol in the presence of concentrated HCl. The obtained mass is poured into ice water. The crystalline product is filtered, washed with water, dried in air and recrystallised from dioxane.

EFFECT: high efficiency of the method.

2 ex

Description

The invention relates to the chemical industry, to products of small-tonnage chemistry, namely 2 (3H) -benzothiazolone with a carbamate function at C ⁶ and some of its derivatives.

Substituted derivatives of 2 (3H) -benzothiazolones have a wide spectrum of biological activity. Among them, compounds with high herbicidal [UK Patent No. 966,496, US Patents No. 4,971,619, No. 4,824,465], antimicrobial [El-Hamouly W.S., Amine K.M., Abbas E.M.H., Abdel-Maguid E.A., Taibah Int. Chem. Conf. - 2009, March 23-25, 2009 Al-Madinah Al-Munawwarach, Saudi Arabia, p. 568-569], analgesic [Şafak C., Erdoğan H., Palaska E., Sunal R., Duru S., J. Med. Chem., 1992, 35, 1296-1299], anti-inflammatory [Doğruer SD, Ünlü S., Şahin MF, Yeşilada E., Il Farmaco, 1998, 53, 80-84], anti-fungicidal [German Patent No. 2,924,712, US Patent No. 4,293,702], growth-regulating [Loos D., Sidoova E., Sutoris V., Molecules, 1999, 4, 81-93] and other types of activity. They also serve as valuable precursors in the synthesis of new functionally substituted compounds.

A number of methods are known for producing 2 (3H) benzothiazolonones: (1) cyclization of 2-aminothiophenols with phosgene, chlorocarbonates [Elderfield RC, Short FW, J. Org. Chem., 1952, 17, 758-763, Erlenmeyer H., Buchmann P., Schenkel H., Helv. Chim. Acta, 1944, 27, 1432] and urea [Fife N.T., Hutchins JEC, Wang MS, J. Am. Chem. Soc., 1975, 97, 5878-5882]; (2) reductive carbonylation of substituted nitrobenzenes using sulfur, carbon monoxide and water in the presence of bases [British Patent No. 966496], (3) cyclization of thiocarbamates, followed by cleavage of the resulting 2-alkoxybenzothiazoles [Fife TN, Hutchins JEC, Wang MS, J. Am. Chem. Soc., 1975. ., Yoshioka H., Bull. Chem. Soc. Jpn., 1983, 53, 1255-1256, Ramazanova P.A., Vagabov M.V., Tarakanova A.V., Akhmedov N.G., Anisimov A.V., Vestn. Mosk. University, 2000, 41, 119-120]; (5) by reacting o-nitrochlorobenzenes with thioglycolic acid followed by cyclocondensation of o-nitrophenylthioacetic acid with acetic anhydride and then deacylation [Elderfield RC, Short FW, J. Org. Chem., 1952, 17, 758-763]; (6) the reaction of 2-aminobenzothiazoles with alkali metal hydroxides in an anhydrous medium and cyclization of the resulting o-mercaptophenylureas [US Patents No. 5,594,145, No. 4,429,134]; (7) by the reaction of thiosalicylic acid with ammonium azide and three equivalents of the DMF-POCl ₃ complex [Sridhar R., Perumal R.T., Synth. Comm., 2004, 34, 735].

The preparation of 3-substituted 2 (3H) benzothiazolones by nitrosation of 3-substituted 2 (3H) iminobenzothiazoles in the xylene-hydrochloric acid system is described (Patent EP No. 0622361 A1).

A method for producing 2 (3H) -benzothiazolone with a carbamate function at C ⁶ (I) and its 5-chloro derivative (II) is proposed, which consists in extracting equimolar amounts of N, N'-dimethoxycarbonyl-1,4-benzoquinondiimine (or 2-chloro N, N'-dimethoxycarbonyl-1,4-benzoquinondiimine) (Maksimova T.N., Velikorodov A.V. ZhORKh. 1986, 22, 1092) and thioacetic acid in methylene chloride for 3 hours at room temperature, filtering the crystalline product, washing it diethyl ether and subsequent boiling for 5 hours in ethanol in the presence of concentrated HCl, pouring the mass into ice w water, filtration of the crystalline product, washing it with water, air dried and recrystallized from dioxane.

The interaction of N, N'-dimethoxycarbonyl-1,4-benzoquinone-diimine (or 2-chloro-N, N'-dimethoxycarbonyl-1,4-benzoquinone-diimine) with thioacetic acid in methylene chloride at room temperature proceeds as a 1,4-addition reaction according to the system conjugated bonds N = CC = C with the formation of products of aromatic structure, which upon boiling in ethanol in the presence of HCl undergo heterocyclization with the formation of compounds (I, II).

Heterocyclization probably occurs through a nucleophilic attack by a nitrogen atom of a carbamate group at a carbonyl carbon atom with elimination of methyl acetate.

The structure of compounds (I, II) was confirmed by IR, ¹ H NMR spectra.

Example 1

аром.). Спектр ЯМР ¹H, δ, м.д.: 3.68 с (3H, NHCO₂ Me), 7.03 д (1H, Н_аром., J 8.7 Гц), 7.27 д (1H, H_аром., J 8.7 Гц), 7.68 с (1H, H_аром.), 9.65 уш. с (1H, NH), 11.73 уш. с (1H, NH). Масс-спектр, m/z (I, %): 226 (5) [М+2], 225 (10) [M+1], 224 (100) [M]⁺, 192 (73.8), 164 (40), 137 (92.5), 125 (20), 119 (12.5), 110 (23.8), 93 (15), 83 (21.3), 79 (47.5), 69 (23.8), 59 (86.3), 52 (78.8). Найдено, %: C 47.98; H 3.55; N 12.28. C₉H₈N₂O₃S. Вычислено, %: C 48.21; H 3.57; N 12.50.Methyl-N- (2-oxo-2,3-dihydro-1,3-benzothiazol-6-yl) carbamate (I). To a solution of 1.1 g (5 mmol) of N, N'-dimethoxycarbonyl-1,4-benzoquinone diimine in 10 ml of methylene chloride was added 0.36 ml (5 mmol) of thioacetic acid and the mixture was kept at room temperature for 3 h. The precipitated crystalline product was filtered off, washed on a filter diethyl ether (5 ml). A mixture of 0.8 g (2.7 mmol) of the above 1,4-addition adduct, 1 ml of concentrated hydrochloric acid in 10 ml of ethanol was boiled for 5 hours, poured into 50 ml of ice water, the precipitate was filtered off, washed with water, dried in air and recrystallized from dioxane. Yield 0.54 g (90%), colorless crystals, mp. 256-258 ° C. IR spectrum, ν, cm ^-1 : 3300-3340 (NH), 2845-3120 (CH), 1725, 1710 (C = O), 1615, 1565, 1535 (

aroma.). ¹ H NMR spectrum, δ, ppm: 3.68 s (3H, NHCO ₂ Me ), 7.03 d (1H, N _arom. , J 8.7 Hz), 7.27 d (1H, H _arom. , J 8.7 Hz), 7.68 s (1H, H _arom. ), 9.65 br. s (1H, NH), 11.73 br. s (1H, NH). Mass spectrum, m / z (I,%): 226 (5) [M + 2], 225 (10) [M + 1], 224 (100) [M] ⁺ , 192 (73.8), 164 (40 ), 137 (92.5), 125 (20), 119 (12.5), 110 (23.8), 93 (15), 83 (21.3), 79 (47.5), 69 (23.8), 59 (86.3), 52 (78.8 ) Found,%: C 47.98; H 3.55; N, 12.28. C ₉ H ₈ N ₂ O ₃ S. Calculated,%: C 48.21; H 3.57; N, 12.50.

Example 2. Methyl - N- (5-chloro-2-oxo-2,3-dihydro-1,3-benzothiazol-6-yl) carbamate (II). To a solution of 1.28 g (5 mmol) of 2-chloro-N, N'-dimethoxycarbonyl-1,4-benzoquinone diimine in 10 ml of methylene chloride was added 0.36 ml (5 mmol) of thioacetic acid and the mixture was kept at room temperature for 3 h. The precipitated crystalline product was filtered off , washed on the filter with diethyl ether (5 ml). A mixture of 0.9 g (2.7 mmol) of the obtained 1,4-addition adduct, 1 ml of concentrated hydrochloric acid in 10 ml of ethanol was boiled for 5 h, poured into 50 ml of ice water, the precipitate was filtered off, washed with water, dried in air and recrystallized from dioxane. Yield 0.6 g (87%), colorless crystals, mp. 242-245 ° C. ¹ H NMR spectrum, δ, ppm: 3.73 s (3H, NHCO ₂ Me ), 7.51 s (1H, H _arom. ), 7.62 s (1H, H _arom. ), 9.13 s (1H, N H CO ₂ Me), 12.01 s (1H, NH). Found,%: C 41.55; H 2.57; N, 10.67. C ₉ H ₇ ClN ₂ O ₃ S. Calculated,%: C 41.70; H 2.70; N, 10.81.

Claims (2)

1. The method of obtaining methyl N- (2-oxo-2,3-dihydro-1,3-benzothiazol-6-yl) carbamate (I), which consists in extracting equimolar amounts of N, N'-dimethoxycarbonyl-1,4- benzoquinondiimine and thioacetic acid in methylene chloride for 3 hours at room temperature, filtering the crystalline product, washing it with diethyl ether and then boiling it for 5 hours in ethanol in the presence of concentrated HCl, pouring the mass into ice water, filtering the crystalline product, washing it with water, air drying and recrystallization from dioxane

2. A method of producing methyl N- (5-chloro-2-oxo-2,3-dihydro-1,3-benzothiazol-6-yl) carbamate (II), which consists in extracting equimolar amounts of 2-chloro-N, N '-dimethoxycarbonyl-1,4-benzoquinone diimine and thioacetic acid in methylene chloride for 3 hours at room temperature, filtering the crystalline product, washing it with diethyl ether and then boiling for 5 hours in ethanol in the presence of concentrated HCl, pouring the mass into ice water, filtering the crystalline product washing it with water, air drying and recrystallization from dioxane