An efficient procedure for the synthesis of 18O-labelled methanesulfinyl chloride

Article abstract of DOI:10.1002/jlcr.734

A new procedure for the synthesis of methanesulfinyl chloride is described which involves chlorination of dimethyl disulfide with sulfuryl chloride in the presence of hexamethyldisiloxane. The use of ¹⁸O-labelled hexamethyldisiloxane in this reaction results in the formation of ¹⁸O-labelled methanesulfinyl chloride. Copyright

Full text of DOI:10.1002/jlcr.734

JOURNAL OF LABELLED COMPOUNDS AND RADIOPHARMACEUTICALS
J Label Compd Radiopharm 2003; 46: 1001–1005.
Published online in Wiley InterScience (www.interscience.wiley.com). DOI: 10.1002/jlcr.734
Research Article
An efficient procedure for the synthesis of
O-labelled methanesulfinyl chloride
18
J o! zef Drabowicz, Bogdan Bujnicki and Marian Mikolajczyk*
Center of Molecular and Macromolecular Studies, Polish Academy of Sciences,
Department of Heteroorganic Chemistry, 90-363 L o! dz, Sienkiewicza 112,
Poland
Summary
A new procedure for the synthesis of methanesulfinyl chloride is described
which involves chlorination of dimethyl disulfide with sulfuryl chloride in the
1
presence of hexamethyldisiloxane. The use of O-labelled hexamethyldisilox-
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1
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ane in this reaction results in the formation of O-labelled methanesulfinyl
chloride. Copyright # 2003 John Wiley & Sons, Ltd.
Key Words: oxygen-18; methanesulfinyl chloride; hexamethyldisiloxane;
dimethyl disulfide; oxidative chlorination
Introduction
Sulfinyl chlorides are commonly used as substrates for the preparation
of racemic and optically active sulfinyl derivatives such as sulfinates,
1
thiosulfinates, sulfinamides and sulfoxides. Among various sulfinyl
chlorides, methanesulfinyl chloride 1, the parent member of the
aliphatic chloride family, plays a key role. This is due to the fact that
starting from this chloride one can prepare a series of racemic alkyl
methyl and aryl methyl sulfoxides as well as their optically active
analogues. The latter have been very often applied as key substrates for
*Correspondence to: M. Mikolajczyk, Center of Molecular and Macromolecular Studies, Polish
Academy of Sciences, Department of Heteroorganic Chemistry, 90-363 L o! dz, Sienkiewicza 112,
Poland. E-mail: marmikol@bilbo.cbmm.lodz.pl
Copyright # 2003 John Wiley & Sons, Ltd.
Received 2 April 2003
Revised 7 May 2003
Accepted 26 May 2003

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J. DRABOWICZ ET AL.
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the asymmetric carbon–carbon or carbon–heteroatom bond formation.
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Moreover, methyl aryl sulfoxides labelled with oxygen O have been
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frequently used as model compounds in many mechanistic studies.
Therefore, it is obvious that an easy access to methanesulfinyl chloride 1
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labelled with
preparation of
derivatives.
O-isotope should allow convenient and efficient
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O-labelled methyl sulfoxides and other sulfinyl
Although in the chemical literature one can find a few useful
procedures for the preparation of non-labelled methanesulfinyl chloride
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, there is no protocol which describes an effective synthesis of this
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chloride labelled with the O-isotope. In this context, it is of interest to
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note that the procedures used for the preparation of O-arenesulfinyl
chlorides, involving the reaction of labelled arenesulfinic acids with
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thionyl chloride, are less suitable for the synthesis of O-1, owing to
the physico-chemical properties of this chloride and its precursor
methanesulfinic acid.
Results and discussion
In a previous study we developed the preparation of sulfinyl chlorides
through the oxidative chlorination of sulfenyl derivatives with the
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trimethylsilyl acetate/sulfuryl chloride system. Moreover, we found
that hexamethyldisiloxane acts as the chloride anion acceptor in
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the reaction of sulfinyl chlorides with chlorosulfites. As a continuation
of these studies, we wish to disclose herein a new method for the
synthesis of methanesulfinyl chloride 1 which is best suitable for
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the preparation of its O-analogue. It consists of the treatment
of dimethyl disulfide 2 with sulfuryl chloride in the presence of
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hexamethyldisiloxane 3 or its O-analogue. In the case of a large scale
preparation the trimethylchlorosilane formed can be reused for
the preparation of hexamethyldisiloxane. Hexamethyldisiloxane 3
serves in this reaction as the oxygen donor and chloride anion acceptor.
The conversion of dimethyl disulfide 2 into methanesulfinyl chloride
1 (Equation (1)), occurs at temperatures between ꢀ108C and 258C
in less than 1 h after addition of sulfuryl chloride to a mixture of
dimethyl disulfide 2 and hexamethyldisiloxane 3. The yield of the crude
1
product is quantitative ( H-NMR assay) and the pure sulfinyl chloride
is isolated in >90% yield by simple distillation of the residue after
removal of the highly volatile trimethylchlorosilane. This procedure has
Copyright # 2003 John Wiley & Sons, Ltd.
J Label Compd Radiopharm 2003; 46: 1001–1005

AN EFFICIENT PROCEDURE
1003
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already been patented.
(
MeS) + 2 (Me Si) O + 3 SO Cl
2 MeS Cl + 4 Me SiCl + 3 SO
2
3
2
2
2
3
2
2
3
O
ð1Þ
1
1
When O-labelled hexamethyldisiloxane 3 was used in this reaction,
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1
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O-labelled methanesulfinyl chloride O-1, was obtained in 70% yield
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and with 92.5% O-content (MS assay) (Equation (2)).
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(
Me Si)2 O
3
SO Cl2
2
(MeS)2
MeS Cl
ð2Þ
2
18O
18
O-1
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The required O-3 was easily prepared in the reaction of trimethyl-
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chlorosilane and O-water (Equation (3)).
18
2
18
2
Me SiCl +H
O
(Me Si)2 O + 2 HCl
3
3
ð3Þ
18
O-3
Although the mechanistic details of the reaction under discussion
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were not investigated, almost full transfer of
O-isotope from
hexamethyldisiloxane 3 to sulfur may be most reasonably explained
by the sequence of events depicted in Scheme 1.
MeSCl
+
MeSOSiMe
3
SO Cl
(Me Si) O, 3
3 2
2
2
2
SO Cl
1
2
2
-
Me SiCl
- Me SiCl
3
3
MeSCl Cl
2
MeS OSiMe Cl
3
Cl
A
Scheme 1.
In the first step, dimethyl disulfide 2 undergoes chlorination with
sulfuryl chloride to methanesulfenyl chloride and/or to methyldichlor-
osulfonium chloride as an exhaustive chlorination product. Methane-
sulfenyl chloride reacts then with hexamethyldisiloxane 3 to give
trimethylsilyl methanesulfenate which upon treatment with sulfuryl
chloride forms the sulfonium salt A as a key intermediate. This salt may
Copyright # 2003 John Wiley & Sons, Ltd.
J Label Compd Radiopharm 2003; 46: 1001–1005

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J. DRABOWICZ ET AL.
be directly formed from methyldichlorosulfonium chloride and 3. In the
final step, elimination of trimethylsilyl chloride from A gives methane-
sulfinyl chloride 1.
In our attempts to extend the above procedure to the preparation of
aliphatic sulfinyl chlorides containing longer carbon chains we have
noted that in the reaction of diethyl and di-n-propyl disulfides with
sulfuryl chloride in the presence of hexamethyldisiloxane the corre-
sponding sulfinyl chlorides were also formed as the main reaction
1
products ( H-NMR analysis of the crude reaction products). However,
due to the presence of many sulfur containing by-products their
complete purification by distillation could not be achieved.
Experimental
Methanesulfinyl chloride 1
To a mixture of dimethyl disulfide 2 (4.7 g, 0.05 mol) and hexamethyl-
disiloxane 3 (16.2 g, 0.1 mol) cooled to ꢀ108C, sulfuryl chloride (20.5 g,
0
.15 mol) was added dropwise with stirring over a course of 30 min.
After completing the addition, the reaction mixture was allowed to
reach room temperature over 45 min. After removal of the last traces of
sulfur dioxide and the whole of the trimethylchlorosilane below room
temperature, the residue was distilled on a water pump to give pure
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d
chloride 1: yield 9 g (92%); b.p. 58–608C/26 mmHg; Lit.
b.p.
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58C/40 mmHg; H–NMR (CDCl ) d=3.37 (s).
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O-hexamethyldisiloxane O-3
A round-bottom flask protected from moisture by a standard calcium
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chloride tube was charged with O-water (0.55 g, 0.03 mol; O–content
4.1%) and trimethylchlorosilane (10.8 g, 0.1 mol). The heterogeneous
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mixture was efficiently stirred at room temperature until it became
homogeneous. After removal of hydrogen chloride the residue was
distilled with a Vigreux column to give 4.57 g (94%) of the pure siloxane
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O-3; bp 1018C/760 mmHg; 21.8% O-content; Lit. for non-labelled
bp 98.58C/760 mmHg.
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O-methanesulfinyl Chloride O-1
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To a mixture of dimethyl disulfide 2 (0.198 g, 2 mmol) and O-
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hexamethyldisiloxane O-3 (0.650 g, 4 mmol, O-content 21.8%),
Copyright # 2003 John Wiley & Sons, Ltd.
J Label Compd Radiopharm 2003; 46: 1001–1005

AN EFFICIENT PROCEDURE
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which was cooled to ꢀ108C, sulfuryl chloride (0.81 g, 6 mmol) was
added dropwise over a course of 30 min. After completing the addition,
the reaction mixture was stirred at this temperature for an additional
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0 min and then allowed to reach room temperature over the next
5 min.After removal of the last traces of sulfur dioxide and the whole
of the trimethylchlorosilane below room temperature the residue was
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distilled on a water pump to give pure sulfinyl chloride O-1; 0.305 g
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1
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1
(
72%); b.p. 56-598C/26 mmHg; O-content 20.1% (MS assay); H-
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d
NMR (CDCl ) d = 3.37 (s); Lit. for non-labelled b.p. 558C/40 mmHg.
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References
1
. Patai S, Rappoport Z (eds), The Chemistry of Sulfinic Acids, Esters and their
Derivatives. Wiley: New York, 1990, chapters 8, 11, 12, 18, 19 and 20.
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Copyright # 2003 John Wiley & Sons, Ltd.
J Label Compd Radiopharm 2003; 46: 1001–1005