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The reaction of sulfoxides with hydrogen chloride
Pergsmon Press.
Tetrahedron Letters NO. 38, pIl3553 - 3555, 1971.
Printed in Great Britain.
THE REACTION OF SULFOXIDES WITH HYDROCKN CHLORIDE R. 8. Rynbrandt Diabetes Research, The Upjohn Company, Kalamazoo, Michigan 49001 (Received in USA 6 July 1971;
received in UK for publication 24 Augnst 1971)
The reversible formation of sulfodichloride intermediates (&,)has been proposed to explain the
RlR2SO
+
2HCl&lR2SC123
(Eq. 1)
+ Ii20 1 s
racemization of optically active sulfoxides by hydrogen chloride in organic solvents (Eq. 1).
1,2
Mislow' h8S suggested that the symmetrization of the sulfodichloride may be the result of its being either a slightly distorted trigonal bipyramid
with a plane of symmetry or a set of rapRecently Allegra and co-workersJ
idly interconverting enantiomeric chlorosulfonium chlorides.
have suggested that loss of chirality of t may arise from rapid , reversible dissociation to the achiral sulfide and chlorine (Eq. 2). RlR2SC12, Sulfodichlorides
RlR2S
+
(Eq. 2)
Cl2
(chlorosulfonium chlorides) are also intermediates in the chlorination of sul-
fides to afford a-chlorosulfides
(Eq. 3).495
If sulfodichlorides are indeed intermediates in -HCl
RlCH2-S-R2
b
(Eq.
11
R W-S-R2
3)
Cl
the hydrogen chloride catalyzed racemization of sulfoxides, they should lead to the same products, a-chlorosulfides,
that are observed in the chlorination of sulfides.
This mode of reac-
tion should be facilitated by removal of water, forctig the equilibrima to the right (Eq. 4). 0
I
RlCH2-S-R2
(Eq. 4)
H2°
c12
+
RlCH2-S-R2 RlPI-S-R2 Cl
+
IpC1
Indeed, treatment of methyl P-tolyl sulfoxide6 with HCl in CH2C12, with removal of H20, afforded a 77% yield of the a-chlorosulfide, chloromethyl R-tolyl sulfide (2).
3553
In 8
3554
No. 38
-CH3
HCl-Et*o-CB2C12 Molecular Sieve?
similar manner TWO
was converted into chloromethyl methyl sulfide (2) in 73X yield.
P
cH3-s-cH3
>
CH3-s-CH2c1
3 The formation of a-chlorosulfides from sulfoxides on treatment with BCl lends support to the intermediacy of sulfodichlorides in the racemisation of sulfoxides -and provides a convenient
method for the conversion of certain sulfoxides into a-chlorosulfides,
of synthetic intermediates.
an important class
7
The selectivity of this reaction closely parallels that observed in the chlorination of sulfides.
Bijhme and Gran' have shown that chlorination of chloromethylmethyl
dichloromethyl methyl sulfide (2) as the only isolated product.
sulfide afforded
Preferential formation of 2
also resulted on treatment of chloromethyl methyl sulfoxide with ECl. P CB3-s-CH2c1
HCl-Et20-CH2C12
CH3-S-CHC12
+
C1CH2-S-CH2C1
Molecular Sieve 5 "r
I 95:5g
B&me
and Gran isolated I-chloroethyl methyl sulfide (z) as the only product in the chlorination
of ethyl methyl sulfide.l'
Preferential formation of ,$ also resulted on treatment of ethyl
methyl sulfoxide with HCl.
P
CB~-S-CH~CB~
>
CH3-S-yHCH3
+
C1CH2-S-CH2CH3
Cl
The general procedure used in the above reactions can be illustrated by the following specific example.
Chloromethyl P-Tolyl Sulfide (2). -- A stirred mixture of methyl B-tolyl sulfoxide (18 g; 0.117 mole), CH2C12 (300 ml), and 3A molecular sieves (20 g) was treated dropwise with a saturated solution of HCl in Et20.
After stirring at room temperature for an additional two hours, the
No. 38
3555
solution was decanted from the molecular sieves.
The solvent was removed on a rotary evaporator
and the residue was vacuum distilled to afford 15.6 g (77% yield) of 4, bp, 88'10.2 ma.
It was noted that in all cases the reaction mixtures developed a faint yellow color reminiscent of C12.
This would be in accord with the before mentioned suggestion of Allegra and co-workers'
and the recent equilibrium studies of Wilson and Chang.
12
REFERENCES AND FOOTNOTES 1.
K. Mislow, T. Simmons, J. T. Melillo aad A. L. Ternay, Jr., --J. Amer. Chew. e., (1964).
2.
K. Mislow, w.
3.
G. Allegra, G. E. Wilson, Jr., E. Benedetti, C. Pedone and R. Albert, J_. -Amer. Chem. =., E, 4002 (1970).
4.
H. Bkkane, 8. Fischer and R. Frank, &.,
5.
W. E. Lawson and T. P. Dawson, --J. Amer. Chem. &.,
6.
All compounds described in this publication have been previously reported.
7.
H. Gross and E. Hoft, e.
8.
Ii. B&me
9.
The reaction mixture was analyzed by nmr using authentic samples of 2 and k for comparison.
Chem. Progr., g,
and H. J. Gran, &.,
_., Chem
g,
1452
217 (1967).
x.
@,3, 54 (1949).
Ed. Ens.,
%,
3119 (1927).
&, 335 (1967).
J&L, 133 (1953).
10.
H. B&me
11.
The reaction mixture was analyzed by nmr according to the procedure of D. L. Tuleen and T. B. Stephens, J. a. e., a, 31 (1969).
12.
G. E. Wilson, Jr., and M. M. Y. Chang, Tetrahedron Letters, 1971, 875.
and H. J. Gran, &.,
m,
68 (1952).
Tetrahedron Letters NO. 38, pIl3553 - 3555, 1971.
Printed in Great Britain.
THE REACTION OF SULFOXIDES WITH HYDROCKN CHLORIDE R. 8. Rynbrandt Diabetes Research, The Upjohn Company, Kalamazoo, Michigan 49001 (Received in USA 6 July 1971;
received in UK for publication 24 Augnst 1971)
The reversible formation of sulfodichloride intermediates (&,)has been proposed to explain the
RlR2SO
+
2HCl&lR2SC123
(Eq. 1)
+ Ii20 1 s
racemization of optically active sulfoxides by hydrogen chloride in organic solvents (Eq. 1).
1,2
Mislow' h8S suggested that the symmetrization of the sulfodichloride may be the result of its being either a slightly distorted trigonal bipyramid
with a plane of symmetry or a set of rapRecently Allegra and co-workersJ
idly interconverting enantiomeric chlorosulfonium chlorides.
have suggested that loss of chirality of t may arise from rapid , reversible dissociation to the achiral sulfide and chlorine (Eq. 2). RlR2SC12, Sulfodichlorides
RlR2S
+
(Eq. 2)
Cl2
(chlorosulfonium chlorides) are also intermediates in the chlorination of sul-
fides to afford a-chlorosulfides
(Eq. 3).495
If sulfodichlorides are indeed intermediates in -HCl
RlCH2-S-R2
b
(Eq.
11
R W-S-R2
3)
Cl
the hydrogen chloride catalyzed racemization of sulfoxides, they should lead to the same products, a-chlorosulfides,
that are observed in the chlorination of sulfides.
This mode of reac-
tion should be facilitated by removal of water, forctig the equilibrima to the right (Eq. 4). 0
I
RlCH2-S-R2
(Eq. 4)
H2°
c12
+
RlCH2-S-R2 RlPI-S-R2 Cl
+
IpC1
Indeed, treatment of methyl P-tolyl sulfoxide6 with HCl in CH2C12, with removal of H20, afforded a 77% yield of the a-chlorosulfide, chloromethyl R-tolyl sulfide (2).
3553
In 8
3554
No. 38
-CH3
HCl-Et*o-CB2C12 Molecular Sieve?
similar manner TWO
was converted into chloromethyl methyl sulfide (2) in 73X yield.
P
cH3-s-cH3
>
CH3-s-CH2c1
3 The formation of a-chlorosulfides from sulfoxides on treatment with BCl lends support to the intermediacy of sulfodichlorides in the racemisation of sulfoxides -and provides a convenient
method for the conversion of certain sulfoxides into a-chlorosulfides,
of synthetic intermediates.
an important class
7
The selectivity of this reaction closely parallels that observed in the chlorination of sulfides.
Bijhme and Gran' have shown that chlorination of chloromethylmethyl
dichloromethyl methyl sulfide (2) as the only isolated product.
sulfide afforded
Preferential formation of 2
also resulted on treatment of chloromethyl methyl sulfoxide with ECl. P CB3-s-CH2c1
HCl-Et20-CH2C12
CH3-S-CHC12
+
C1CH2-S-CH2C1
Molecular Sieve 5 "r
I 95:5g
B&me
and Gran isolated I-chloroethyl methyl sulfide (z) as the only product in the chlorination
of ethyl methyl sulfide.l'
Preferential formation of ,$ also resulted on treatment of ethyl
methyl sulfoxide with HCl.
P
CB~-S-CH~CB~
>
CH3-S-yHCH3
+
C1CH2-S-CH2CH3
Cl
The general procedure used in the above reactions can be illustrated by the following specific example.
Chloromethyl P-Tolyl Sulfide (2). -- A stirred mixture of methyl B-tolyl sulfoxide (18 g; 0.117 mole), CH2C12 (300 ml), and 3A molecular sieves (20 g) was treated dropwise with a saturated solution of HCl in Et20.
After stirring at room temperature for an additional two hours, the
No. 38
3555
solution was decanted from the molecular sieves.
The solvent was removed on a rotary evaporator
and the residue was vacuum distilled to afford 15.6 g (77% yield) of 4, bp, 88'10.2 ma.
It was noted that in all cases the reaction mixtures developed a faint yellow color reminiscent of C12.
This would be in accord with the before mentioned suggestion of Allegra and co-workers'
and the recent equilibrium studies of Wilson and Chang.
12
REFERENCES AND FOOTNOTES 1.
K. Mislow, T. Simmons, J. T. Melillo aad A. L. Ternay, Jr., --J. Amer. Chew. e., (1964).
2.
K. Mislow, w.
3.
G. Allegra, G. E. Wilson, Jr., E. Benedetti, C. Pedone and R. Albert, J_. -Amer. Chem. =., E, 4002 (1970).
4.
H. Bkkane, 8. Fischer and R. Frank, &.,
5.
W. E. Lawson and T. P. Dawson, --J. Amer. Chem. &.,
6.
All compounds described in this publication have been previously reported.
7.
H. Gross and E. Hoft, e.
8.
Ii. B&me
9.
The reaction mixture was analyzed by nmr using authentic samples of 2 and k for comparison.
Chem. Progr., g,
and H. J. Gran, &.,
_., Chem
g,
1452
217 (1967).
x.
@,3, 54 (1949).
Ed. Ens.,
%,
3119 (1927).
&, 335 (1967).
J&L, 133 (1953).
10.
H. B&me
11.
The reaction mixture was analyzed by nmr according to the procedure of D. L. Tuleen and T. B. Stephens, J. a. e., a, 31 (1969).
12.
G. E. Wilson, Jr., and M. M. Y. Chang, Tetrahedron Letters, 1971, 875.
and H. J. Gran, &.,
m,
68 (1952).