RU2034833C1 - Process for preparing bis-2-chloroethylsulfoxide - Google Patents

Abstract

FIELD: organic chemistry. SUBSTANCE: the product: bis-(2- chloroethyl) sulfoxide having the empirical formula: C₄H₈C₁₂OS, m p 180 C; the yield is 100 % . Reagent 1: bis (2- chloroethyl) sulfide. Reagent 2: 35% aqueous solution of hydrogen peroxide. Reaction conditions: 75-100 C. EFFECT: improved preparation process.

Description

CH₂CH₂Cl
Сульфоксиды в настоящее время используются и широко исследуются как реагенты для гидрометаллургии [Никитин Ю.Е. Муринов Ю.И. Усп. хим. 1975. т. 45, N 12, с. 2233-2252] специальные комплексообразователи [Розен А.М. Муринов Ю.И. Никитин Ю.Е. Радиохимия, 1970, т. 12, N 2, с. 355-361] биологически активные вещества для медицины и сельского хозяйства [Gusarova N.K. Voronkov M.G. Trofimov B.A. Sulfur Reports. 1989. v. 9. N 2. p. 95-146; Трофимов Б.А. Никольская А. Н. Гусарова Н.К. и др. Хим.-фарм. журн. 1987, N 1, с. 26-30; Мельников Н. Н. Пестициды. Химия, технология и применение. М. Химия, 1987, 712 с]
Особое место среди этих соединений занимают функциональные сульфоксиды, в частности, целевой бис(2-хлорэтил)сульфоксид, синтез которого встречает известные трудности.The invention relates to the chemistry of organosulfur compounds, namely to an improved method for producing bis (2-chloroethyl) sulfoxide of the formula
ClCH ₂ CH

CH ₂ CH ₂ Cl
Sulfoxides are currently used and widely studied as reagents for hydrometallurgy [Yu. E. Nikitin Murinov Yu.I. Usp. Chem. 1975.Vol. 45, No. 12, p. 2233-2252] special complexing agents [Rosen A.M. Murinov Yu.I. Nikitin Yu.E. Radiochemistry, 1970, v. 12, N 2, p. 355-361] biologically active substances for medicine and agriculture [Gusarova NK Voronkov MG Trofimov BA Sulfur Reports. 1989. v. 9. N 2. p. 95-146; Trofimov B.A. Nikolskaya A.N. Gusarova N.K. and other Chem.-farm. journal 1987, N 1, p. 26-30; Melnikov N.N. Pesticides. Chemistry, technology and application. M. Chemistry, 1987, 712 s]
Functional sulfoxides occupy a special place among these compounds, in particular, the target bis (2-chloroethyl) sulfoxide, the synthesis of which meets certain difficulties.

 It should also be emphasized that the development of a technologically advanced method for producing bis (2-chloroethyl) sulfide (mustard) sulfoxide 1 is currently gaining worldwide importance due to the urgent need for the speedy processing of chemical poisonous substances into practically valuable, safe intermediates and materials.

 Describes a method for producing sulfoxide 1 by oxidation of bis (2-chloroethyl) sulfide (II) with ozone [C.C. Price, O.H. Bullitt. J. Org. Chem. 1947. v. 12. R. 238-248] The reaction proceeds in an organic solvent (cellosolve) at room temperature. The yield of the target sulfoxide I 53%. The degree of conversion of sulfide II was not reported in the work, although this process parameter is fundamentally significant.

In the cited work [CCPrice, OHBullitt. J. Org. Chem. 1947. V. 12. P 238-48] authors also provides a method of oxidation of sulfide II sodium hypochlorite in methanol at 20 ^C. The yield of sulfoxide I in this case 57%
The disadvantages of these methods for the synthesis of sulfoxide I include the low yield of the target product, as well as the use of organic solvents in the process, which requires additional costs for their isolation and purification.

S(O)

N

NO₂ [Yu-Chu Yang, L. L. Szafraneci, W.T.Beaudry. J.Org.Chem. 1990. 55. 3664-3666] Реакция протекает при комнатной температуре в присутствии двукратного молярного избытка N-сульфонилоксазиридина III и заканчивается через несколько минут (контроль с помощью спектроскопии ЯМР ¹³С). Несмотря на положительные стороны этого метода (мягкие условия, количественный выход сульфоксида I, 100%-ная конверсия исходного сульфида II), данные условия не могут быть приняты как универсальные и технологичные, поскольку требуют использования значительных количеств труднодоступного экзотического окислителя III.Known is a selective and practically quantitative method for producing sulfoxide I by oxidation of bis (2-chloroethyl) sulfide with derivatives of N-sulfonyloxyaziridine, for example, compound III

S (o)

N

NO ₂ [Yu-Chu Yang, LL Szafraneci, WTBeaudry. J. Org. Chem. 1990. 55. 3664-3666] The reaction proceeds at room temperature in the presence of a twofold molar excess of N-sulfonyloxyaziridine III and ends in a few minutes (control using ¹³ C NMR spectroscopy). Despite the positive aspects of this method (mild conditions, quantitative yield of sulfoxide I, 100% conversion of the starting sulfide II), these conditions cannot be accepted as universal and technologically advanced, since they require the use of significant amounts of hard-to-reach exotic oxidizing agent III.

The possibility of producing sulfoxide I by the action of dimethyl sulfoxide on sulfide II was also shown [Hsu Fu-Lian, Szafranek LL Beaudry WT Yang Vu-Chu. J. Org. Chem. 1990. V. 55. P. 4153] Under the proposed conditions (25 ^° C, 30 days), the yield of sulfoxide I and the conversion of the initial sulfide II of the order of 30%
An effective and selective emulsion method for the oxidation of bis (2-chloroethyl) sulfide to sulfoxide I with sodium hypochlorite in a hydrocarbon system (cyclohexane or hexadecane 3-4%), water (60-82%), 1-butanol (10-12%) has recently been described ), stabilizer (4% sodium dodecyl sulfate or 24% polyoxyethylene ether) [Menger FM Elrington ARJAm.Chem. Soc. 1990. V. 112. N 22. P. 8201] The disadvantages of this method include the need to use organic solvents and additives in this process and, as a consequence, the need for additional stages of their isolation and purification.

The prototype of the invention is a method for the synthesis of sulfoxide I by selective oxidation of bis (2-chloroethyl) sulfide with an equimolar amount of concentrated (93-98%) hydrogen peroxide. The reaction is carried out at room temperature for 17 hours using significant amounts (9-fold excess by volume) of an organic solvent (a mixture of ethanol and xylene in a ratio of 2: 1, respectively). Yield of sulfoxide I 70% [Takenouchi Osamu, Kamiya Novuyuki, Okavara Makoto. J. Chem. Soc. Jap. Ind. Chem. Soc. 1971. V. 74. N 6. P 1169 (RKhKhim. 1971. 24 G 338)]
The disadvantages of the prototype are.

 The relatively low (70%) yield of sulfoxide I, and, consequently, the incomplete conversion of bis (2-chloroethyl) sulfide.

 The need to use concentrated hydrogen peroxide and significant amounts of organic solvents in the process, which is an explosive mixture.

 The need for regeneration and purification (in particular, from the initial mustard gas) of organic solvents.

 The purpose of the invention is the improvement of the method for producing bis (2-chloroethyl) sulfoxide is to increase the yield of the target product and the degree of conversion of the starting bis (2-chloroethyl) sulfide.

This goal is achieved by carrying out the reaction of bis (2-chloroethyl) sulfide with a diluted (30-35%) aqueous solution of hydrogen peroxide at 75-100 ^about C.

H₂SCH₂CH₂Cl

ClCH₂C

CH₂CH₂Cl
В лучших условиях (температура 90-97^оС, время нагрева 1 ч, 30-35%-ный водный раствор перекиси водорода) выход сульфоксида I количественный при полной конверсии исходного сульфида II.Clch

H ₂ SCH ₂ CH ₂ Cl

ClCH ₂ C

CH ₂ CH ₂ Cl
In the best conditions (temperature 90-97 ^{° C,} the heating time of 1 hour, 30-35% aqueous solution of hydrogen peroxide) quantitative yield sulfoxide I with complete conversion of starting sulfide II.

Stirring the reaction mixture at 80-85 ^{° C} resulted in a slight decrease in both yield (98%) of the desired sulfoxide I, and conversion of sulphide II (98%). Increasing the processing temperature to 100-110 ^C is also impractical, firstly, from the viewpoint of increasing energy costs, and, secondly, at this temperature the reaction mixture along with a basic compound I (yield 95%) appear minor amount of a product partial hydrolysis of 2-hydroxy-2'-chlorodiethyl sulfoxide (IY).

In the oxidation reaction of sulfide II, it is advisable to use a 30-35% aqueous solution of hydrogen peroxide. The use of less concentrated (25-27%) aqueous solutions of H ₂ O ₂ reduces the selectivity of this reaction due to the formation of insignificant amounts (3-5%) of hydroxysulfoxide IY. The use of a 40% aqueous hydrogen peroxide solution does not lead to an improvement in the performance of the sulfoxide I synthesis process.

 The proposed method for producing bis (2-chloroethyl) sulfoxide has the following advantages.

 The quantitative yield of the target product.

 Quantitative conversion of the starting sulfide II.

 Available large-capacity feedstock.

 The simplicity of the technological design of the process, implemented using standard chemical equipment.

The proposed method for producing bis (2-chloroethyl) sulfoxide differs from the well-known [Takenouchi Osamu, Kamiya Novuyuki. Okavara Makoto. J. Chem. Soc. Jap. Ind. Chem. Soc. 1971. V. 74. N 6. P. 1169 (RZhKhim. 1971. 24 G 338)] in that in order to increase the yield of the target product and the degree of conversion of the starting sulfide II, as well as to simplify the process technology, the oxidation reaction of sulfide II spend 30-35% aqueous solution of hydrogen peroxide when heated (75-100 ^about C) instead of used in the prototype 93-98% hydrogen peroxide and room temperature.

 Thus, the developed effective, non-waste, environmentally friendly method for producing a low-toxic, non-skin-absorbing sulfoxide I opens up real possibilities for the processing of highly toxic sulfide II (mustard gas) into a promising reactive sinton and intermediate for the synthesis of practically useful materials.

Example 1 To a 4 ml (5.1 g, 3.2 mmol) bis (2-chloroethyl) sulfide was added dropwise a 33% aqueous solution of hydrogen peroxide. The reaction mixture was stirred at 90-97 ^{° C} for 1 hour, cooled, dried in vacuo to give 5.6 g (100% yield) of bis (2-chloroethyl) sulfoxide, colorless crystals. so pl. 108 ^about S.

NMR spectrum ( ¹ H; ¹³ C), δ, CDCl ₃ : 3.14 m (CH ₂ S = O), 3.94 t (CH ₂ Cl); 36.55 and 55.35 (O = SCH ₂ CH ₂ Cl).

IR Spectrum, cm ^-1 : 1040 (ν S = O).

 Found C, 27.52; H 4.52; Cl 40.30; S 18.11.

C ₄ H ₈ Cl ₂ OS. M ⁺ . 174.

 Calculated, C 27.44; H 4.61; Cl 40.50; S 18.32.

PRI me R 2. To 4 ml (5.1 g, 3.2 mmol) of bis (2-chloroethyl) sulfide was added dropwise a 33% aqueous solution of hydrogen peroxide. The reaction mixture was stirred at 80-85 ^{° C} for 1 hour, cooled, dried in vacuo to give 5.6 g of product containing According to PMR spectrum the expected sulfoxide except I (yield 98%) 2% of the starting bis (2-chloroethyl) sulfide to which the following signals belong in the spectrum: δ, ppm CDCl ₃ : 2.90 t (CH ₂ S) and 3.65 (CH ₂ Cl). Sulfide II was also identified in the reaction mixture by GLC and TLC.

Example 3. To 4 ml (5.1 g, 3.2 mmol) of bis (2-chloroethyl) sulfide was added dropwise a 33% aqueous solution of hydrogen peroxide. The reaction mixture was stirred at 75-80 ^{° C} for 1 hour, cooled, dried in vacuo to give 5.6 g of product containing 96% sulphoxide 1 and 4% of the starting bis (2-chloroethyl) sulphide (TMR data, GLC, TLC).

Example 4. To 4 ml (5.1 g, 3.2 mmol) of bis (2-chloroethyl) sulfide was added dropwise a 30% aqueous solution of hydrogen peroxide. The reaction mixture was stirred at 90-97 ^{° C} for 1 hour, cooled, dried in vacuo to give 5.6 g (100% yield) of bis (2-chloroethyl) sulphide.

Example 5. To 4 ml (5.1 g, 3.2 mmol) of bis (2-chloroethyl) sulfide was added dropwise a 35% aqueous solution of hydrogen peroxide. The reaction mixture was stirred at 90-97 ^{° C} for 1 hour, cooled, dried in vacuo to give 5.6 g (100% yield) of bis (2-chloroethyl) sulphide.

Example 6. To 4 ml (5.1 g, 3.2 mmol) of bis (2-chloroethyl) sulfide was added dropwise a 25% aqueous solution of hydrogen peroxide. The reaction mixture was stirred at 90-97 ^{° C} for 1 hour, cooled, dried in vacuo to give 5.6 g of product containing 95% sulphoxide 1 and 5% gidroksisulfoksida IY.

PRI me R 7. To 4 ml (5.1 g, 3.2 mmol) of bis (2-chloroethyl) sulfide was added dropwise a 40% aqueous solution of hydrogen peroxide. The reaction mixture was stirred at 90-97 ^{° C} for 1 hour, cooled, dried in vacuo to give 5.6 g (100% yield) of bis (2-chloroethyl) sulphide.

 Analytical chromatographic analysis was performed on an LKhM-8MD chromatograph, 3000 x 3 mm column, Chromaton N-AW-HMDS solid phase, DC-550 or XE-60 liquid phase, helium carrier gas).

 For TLC analysis, we used: KIESELGEL-60 sorbent (F 254), an eluent of a mixture of hexane and chloroform in a weight ratio of 10: 3, UV developer (254 nm).

NMR ( ¹ H and ¹³ C) spectra were recorded on a JEOL FX-900 spectrometer (22.49 Hz). IR spectra were recorded on a Specord 75-IR spectrometer.

Claims (1)

METHOD FOR PRODUCING BIS (2-CHLOROETHYL) SULPHOXIDE by oxidation of bis (2-chloroethyl) sulfide with hydrogen peroxide, characterized in that the process is carried out with a 30-35% aqueous solution of hydrogen peroxide at 75-100 ^o C.