RU2342369C1 - Method of obtaining 5-(1,3,5-dithiazinan-5-sulfanyl)-phenyl) -1,3,5-dithiazinan - Google Patents

Abstract

FIELD: chemistry, pharmacology.

SUBSTANCE: climed invention relates to method of obtaining 5-(4-(1,3,5-dithiazinan-5-sulfanyl)-phenyl)-1,3,5-dithiazinan, which finds application as radio protective, anti-tumor, diuretic means, and selective sorbent, and extragent of noble and precious metals. Essence of method lies in interaction of saturated with hydrogen sulfate water solution of formalin with water solution of n-anylin sulfamide (streptocide) with HCI with molar ratio streptocide: formaldehyde: hydrogen sulfate: HCl=1:6:4:4, at temperature 40°C, constant mixing during 2 hours and with further neutralisation with NaOH solution. Output of target product 5-[4-(1,3,5-dithiazinan-5-sulfanyl)-phenyl]-1,3,5- dithiazinan is 93%.

EFFECT: obtaining 5-(4-(1,3,5-dithiazinan-5-sulfanyl)-phenyl)-1,3,5-dithiazinan with high output.

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Description

The present invention relates to the field of organic chemistry, and in particular to a method for the synthesis of 5- [4- (1,3,5-dithiazinan-5-sulfonyl) phenyl] -1,3,5-dithiazinane of the formula (I):

The presented compound may find application as a modified selective sorbent and extractant of noble and precious metals (Murinov Yu.I., Maistrenko V.N., Afzaletdinova N.G. Extraction of metals by S, N-organic compounds. M: Science. 1993, p. 192), as a pharmacologically active compound (Z. Brzozowski, F. Saczewski and M. Gdaniec. Bioorganic & Medicinal Chemistry, 2003, No. 11, p.3673-3681), as well as an antimicrobial and fungicidal preparation (Chem. Abstr . 1964. - V.60. - No. 5. - P.398).

The synthesis of 5- [4- (1,3,5-dithiazinan-5-sulfonyl) phenyl] -1,3,5-dithiazinane is not described in the literature. From literature references it is known [Collins D., Gray-more JJChem. Soc. - 1958. - P.2893] that N-methylidenecyclohexylamine with H ₂ S and CH ₂ O in the presence of benzaldehyde forms N-cyclohexyl-1,3,5-dithiazinan (II).

The authors suggest that the use of Schiff bases, including benzylidenecyclohexylamine in condensation with H ₂ S and CH ₂ O, leads to target III.

The authors (Khafizova S.R., Akhmetova V.R., Kulakova R.V., Dzhemilev U.M. Izv. AN., Ser. Chem., 2003, No. 8, pp. 1722-1726) developed effective synthesis methods N-aryl-substituted 1,3-thiazetidines, 1,3,5-dithiazinans and 1,3,5-thiadiazinans based on the available reagents - H ₂ S and CH ₂ O during thiomethylation of aniline (IVa), m- (IVb) - and n- (IVc) -toluidines, m- (IVg) -, n- (IVd) -, o- (IVe) -anisidines, o-phenetidine (IVg) and p-xylidine (IVc). The direction of the reaction depends not only on the nature of the amine, but also on the ratio of the starting reagents, the reaction temperature, and the duration of the process.

The above methods cannot be obtained 5- [4- (1,3,5-dithiazinan-5-sulfonyl) phenyl] -1,3,5-dithiazinan.

The objective of the invention is to obtain 5- [4- (1,3,5-dithiazinan-5-sulfonyl) phenyl] -1,3,5-dithiazinane by one-reactor condensation of n-anilinesulfamide (streptocide) with formaldehyde and hydrogen sulfide.

The synthesis of 5- [4- (1,3,5-dithiazinan-5-sulfonyl) phenyl] -1,3,5-dithiazinane by the interaction of an aqueous solution of n-anilinesulfamide (streptocide) with a mixture of hydrogen sulfide - formalin (37%) in the presence of HCl at a molar ratio of streptocid: formaldehyde: hydrogen sulfide: HCl = 1: 6: 4: 4, a temperature of 40 ° C and constant stirring for 2 hours. As a result, with a yield of 93%, 5- [4- (1,3,5-dithiazinan-5-sulfonyl) phenyl] -1,3,5-dithiazinan (I) is formed, which is a crystalline product with mp 148-150 ° C. The reaction proceeds according to the scheme:

The advantages of the proposed method

Based on the proposed method, it is possible to selectively obtain 5- [4- (1,3,5-dithiazinan-5-sulfonyl) phenyl] -1,3,5-dithiazinan, the synthesis of which has not been previously described in the literature. The proposed method is technologically simple, water is used as a solvent, the process does not require energy and toxic waste is not generated.

The method is illustrated by example.

EXAMPLE

At a temperature of 40 ° С, 6 moles of formaldehyde (2.5 ml of a 37% aqueous solution) are placed in a glass reactor equipped with a magnetic stirrer, a reflux condenser, a gas tube, and a dropping funnel, and a formaldehyde solution is saturated with 4 moles of hydrogen sulfide for 1 hour by bubbling. Then, the prepared aqueous solution of n-anilinesulfamide (1 g (1 mol)), pre-mixed with 4 moles of HCl (5.9 ml of 15% dilute acid), was added dropwise into a reactor with saturated formalin hydrogen sulfide and stirred for 2 hours, maintaining the required temperature (40 ° C). Then, the resulting mixture was neutralized with a NaOH solution (9.3 ml of a 10% alkali solution) and, after filtration, crystalline 5- [4- (1,3,5-dithiazinan-5-sulfonyl) phenyl] -1,3,5-dithiazinine was isolated with a yield of 93%.

Spectral characteristics

5- [4- (1,3,5-dithiazinan-5-sulfonyl) phenyl] -1,3,5-dithiazinane

Yield 2.05 g (93%). so pl. 148-150 ° C. IR spectrum, ν / cm ^-1 : 550, 645, 695, 810, 1005, 1090, 1140, 1300, 1395, 1445, 1595, 2900. ¹ H NMR spectrum (δ. Ppm): 3.93 (s , 2H, H ₂ C (2)); 4.26 (s, 2H, CH ₂ (17)), 4.72 (s, 4H, CH ₂ (4, 6)), 5.14 (s, 4H, CH ₂ (15, 19)), 6.73-8.02 (m 4H, Ph). ¹³ C NMR spectrum (δ, ppm): 31.48 (t, C (2)), 33.10 (t, C (17)), 56.05 (t, C (4.6)), 63.40 (t, C (15, 19)), 113.90 (d, C (8,12)), 127.03 (d, C (9, 11)), 127.97 (d, C (10)), 146.59 (d, C (7)) . Calculated (%): C, 37.87; H, 4.24; N, 7.36; S, 42.13. C ₁₂ H ₁₆ N ₂ S ₅ O ₂ . Found (%): C, 37.71; H, 4.53; N, 8.18; S, 43.91.

* - ¹ H, ¹³ C NMR spectra were recorded on a Jeol FX 90Q spectrometer (89.55 and 22.50 MHz), TMS internal standard, DMSO-d ₆ solvent. IR spectra were recorded on a Specord 75 IR spectrometer in suspension in liquid paraffin. Elemental analysis of the samples was determined on an Karlo Erba elemental analyzer, model No. 1106. The maximum error of determination is 2.0% rel. For the obtained compound, the melting temperature determined on the RNMK 80/2617 device is shown.

Claims (1)

The method of obtaining 5- [4- (1,3,5-dithiazinan-5-sulfonyl) phenyl] -1,3,5-dithiazinane of the formula

consisting in the fact that an aqueous solution of formaldehyde saturated with hydrogen sulfide is reacted with an aqueous solution of n-anilinesulfamide (streptocide) in the presence of HCl at a molar ratio of streptocide: formaldehyde: hydrogen sulfide: HCl = 1.6: 4: 4, temperature 40 ° C, constant stirring for 2 hours