PL169661B1 - Method for producing methanesulfinyl chloride - Google Patents

Abstract

. A method for producing methanesulfinyl chloride containing an oxygen atom 160 or 180, characterized in that dimethyl disulfide is oxidatively chlorinated with sulfuryl chloride in the presence of hexamethyldisiloxane as an oxygen carrier 160 or 18O, at a temperature of -10 to 25°C.

Description

The present invention relates to a process for the preparation of methanesulfinyl chloride containing ¹⁶ O or 1O oxygen. Metanosulfinylowy chloride containing in the molecule an oxygen atom ^rt O is used as a primary substrate in the synthesis of optically active racemjcznych and metanosulfmianów O-alkyl and O-aryl. These esters in turn serve as starting products for the synthesis of racemic and optically active methyl alkyl and methyl aryl sulfoxides. The reactions of this chloride with cholesterol or diacetonoglucose produce diastereomeric sulfinates which have been used in the synthesis of a number of optically active methyl alkyl and methyl aryl sulfoxides with very high optical purities. Methanesulfinyl chloride is also used as a substrate in the synthesis of other methanesulfinic acid derivatives, such as sulfinamides and thiosulfinates.

The availability of methanesulfinyl chloride containing an oxygen atom of? O should enable highly efficient syntheses of the above-mentioned methanesulfinic acid derivatives labeled with an oxygen atom of? O.

In the chemical literature, there are several practical procedures for the synthesis of methanesulfinyl chloride containing the oxygen atom ^n6O , while there is no method allowing for the convenient and highly efficient preparation of the analogue labeled with oxygen ^ ^O.

Methanesulfinyl chloride containing an oxygen atom of ¹⁶ O is obtained by oxidative chlorination reactions of sulfenyl derivatives such as methyl mercaptan, dimethyl disulfide or S-methyl thioacetate in the presence of acetic acid anhydride or acetic acid as an oxygen carrier of 20 O. Chlorine gas is used as the chlorinating agent (IBDouglass, BS Farrah, EG Thomas, J.Org.Chem. 32, 3645, (I967); MKKee, IBDouglass, Org.Prep.Proced. Int, 2, 235, (1970)) or sulluryl chloride ((.ίί.Υοιιη, R.Hemman Teetaaeebon Irett., 27, 493, (1986); Synthesis, 72, (1987); WMHiUrr, K.Schenk, Oiem.Ber.1 111, 2070, (7878 Depending on the combination of chlorinating agent and oxygen donor, the existing preparation procedures used for the synthesis of methanesulfinyl chloride are schematically described by equations 4, 5, 6, 7, 8 and 9.

2MeSH + 2 (MeCO) 2O + 4Cl ₂ (SOiCb) (4)

2MeSOCl + 4MeCOCl + 2HCl (4So2)

MeSSMe + 2 (MeCO) 2O + 3Cb (SO2C12) - (5)

2MeSOCl + 4MeCOCl + (3SO2)

Me (CO) SMe + (MeCO ^ O + 2CL (SO2Cl2) - (6)

MeSOCl + 3MeCOCl + (2SO ₂ )

MeSH MeCO ₂ H + + 2C22 (SO2Cl2) - (7)

MeSOCl + MeCOCl + 2HC1 (2SO2)

MeSSMe- + 2MeCO2H + 3Cb (SO2CI2) - (8)

2MeSOCl + MeCOCl + 2HC1 (3SO ₂ )

2Me (CO) SMe + 2MeCO ₂ H + 3C1 ₂ (SOaCh) - (9)

2MeSOCl + MeCOCl + 2HC1 (3S <0 ₂ )

169 661

The methods known so far for the synthesis of oxygen-labeled ¹⁸ O sulfinyl chlorides allowed theoretically to incorporate a maximum of 50% of ^I8 O oxygen into the sulfinyl group (J. Drabowicz, S. Oae, Tetrahedron 34, 63, (1978); O.Itoh, T.Numata, T .Yoshimura, S.Oae, Bull.Chem.Soc.Jpn., 56, 266, (1983)) and could not be used for the synthesis of methanesulfinyl chloride ¹⁸ O due to the physicochemical properties of this chloride and its precursor methanesulfinic acid and O , ^ O.

The method of producing meta ^^ and ^^^^^^^^^, according to the invention, consists in subjecting oxidative chlorination of dimethyl disulfide with sulfuryl chloride in the presence of hexamethyldisiloxane as an oxygen carrier * & O or ^ O at -10 to 25 ° C.

The reaction in the process of the invention is described by Equation 1. It is carried out in less than one hour after the addition of sulfuryl chloride to the mixture of dimethyl disulfide and hexamethyldisiloxane.

MeSSMe + 2Me3SiOSiMe ₃ + 3SO2Cl2 - (1)

2MeSOCl + 4Me3SiCl + 3SO2

Based on the1H-NMR spectrum analysis of the reaction mixture (Equation 1), the yield of methanesulfinyl chloride is quantitative.

When using diethyl and di-n-propyl disulfides as starting materials, the corresponding sulfinyl chlorides are also the main reaction products. However, they are accompanied by significant amounts of other sulfur-containing products that prevent the isolation of pure sulfinyl chlorides.

Since hexamethyldisiloxane is obtained in high yield by reacting trimethylchlorosilane with water, an oxygen-labeled analogue is obtained by reaction with water of 2 O as described by Equation 2.

2Me3SiCl + H2 ^ O - Me3Si-'8O-SiMe3 + 2HC1 (2)

The hexamethyldisiloxane thus obtained, containing 21.76% of oxygen? O, is preferably used for the synthesis of oxygen-labeled methanesulfinyl chloride. The content of this isotope in the obtained in the process according to the invention, according to the equation 3 of methanesulfinyl chloride, was 20.13%. This result shows that the reaction proceeds with 92.5% oxygen ™ O incorporation from the hexamethyldisiloxane molecule to the methanesulfinyl chloride being formed.

MeSSMe + 2Me3Si-'8O-SiMe3 + 3SO2CI2 - (3)

2MeS '8OCl + 4Me3SiCl + 3SO2

This is the first example of a conversion allowing theoretically to incorporate 100% oxygen into the sulfinyl moiety. The hitherto known methods allowed for up to 50% incorporation of oxygen O to ^U sulfinyl group could not be used.

Non-limiting examples of the invention are presented below.

Example I. Synthesis of ¹⁶ O methanesulfinyl chloride.

20.5 g (0.15 mol) of sulfuryl chloride was added dropwise at -10 ° C to a mixture containing 4.7 g (0.05 mol) of dimethyl disulfide and 16.2 g (0.1 mol) of hexamethyldisiloxane minutes. Stirring was continued at this temperature for 30 minutes and the reaction mixture was allowed to reach room temperature in 45 minutes. After removing the residual sulfur dioxide and all trimethylsilyl chloride below room temperature, the residue was distilled on a water pump to give 9.0 g of the product as a light yellow oil. Tw = 58-60 ° C / 2666 Pa, the reaction yield was 92%,. 1-NMR (CDCl 2)? = 3.37 ppm (s, 3H).

Example II. Synthesis of methanesulfinyl chloride ^U O.

1. Synthesis of hexamethylsiloxane labeled with 1θ oxygen isotope.

In a round bottom flask protected against moisture, 0.555 g (0.03 mol) of water with an oxygen content of 24.1% and 10.8 g (0.1 mol) of trimethylsilyl chloride (3 fold molar excess) were placed. The mixture was stirred vigorously at room temperature until the reaction mixture was homogenous. After degassing the hydrogen chloride, it was distilled on a distillation column to obtain 4.57 g of hexamethyl4

169 661 disiloksanu oxygen isotope content equal to about ^l8% 21.76 _T = 101 ° C / 101308Pa, the reaction yield was 94% and the percentage incorporation of oxygen ^'8 0 = 9O%.

2. Synthesis of methane sulfinyl chloride labeled with oxygen isotope 2 O.

A mixture of 198 mg (2 mmol) of dimethyl disulfide, and 650 mg (4 mmol) of hexamethyldisiloxane ^U O content of oxygen isotope ¹⁸ O equal to 21.76% was placed in a round bottom flask and cooled to -10 ° C. Then 810 mg (6 mmol) of sulfuryl chloride were added dropwise over 15-30 minutes, and stirring was carried out at this temperature for a further 30 minutes. The next 45 minutes was stirred while the temperature was raised from -10 ° C to room temperature. After removing the residual sulfur dioxide and all of the trimethylsilyl chloride at a temperature below room temperature, the residue was microdistilled on a water pump to obtain 305 mg of methanesulfinyl chloride.

The yield was 72%, bp = 56-59 ° C / 2666Pa. The content of the oxygen 2 O isotope in the product was

20.135. The percentage of oxygen ¹⁸ O incorporation into the sulfinyl moiety is 92.5%.

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Claims (2)

Patent claims 1. Method for the production of methanesulfinyl chloride containing an oxygen atom of ¹⁶ 0 or ¹⁸ 0, characterized by subjecting dimethyl disulfide to oxidative chlorination with sulfuryl chloride in the presence of hexamethyldisiloxane as an oxygen carrier ^] 60 or ^{) 8} 0, at a temperature of -10 to 25 ° C C. 2. The method according to p. 1, characterized in that use is made, hexamethyl meant oxygen ^I8 0, obtained by reaction of trimethylchlorosilane with water, oxygen labeled ^I8 0.