New preparative procedure for the synthesis of chloroalkyl sulfides

Article abstract of DOI:10.1023/A:1022540002086

Reaction of thiols with dihaloalkanes in the system hydrazine hydrate-base leads to alkyl(chloroalkyl) sulfides with different positions of the chlorine atom with respect to sulfur. The developed one-step procedure for the synthesis of such unsymmetrical sulfides is most suitable for arenethiols and alkanethiols having a long polymethylene chain. The reaction mechanism is discussed.

Full text of DOI:10.1023/A:1022540002086

Russian Journal of Organic Chemistry, Vol. 38, No. 10, 2002, pp. 1445 1448. Translated from Zhurnal Organicheskoi Khimii, Vol. 38, No. 10, 2002,
pp. 1498 1501.
Original Russian Text Copyright
2002 by Russavskaya, Korchevin, Alekminskaya, Sukhomazova, Levanova, Deryagina.
New Preparative Procedure
for the Synthesis of Chloroalkyl Sulfides*
N. V. Russavskaya, N. A. Korchevin, O. V. Alekminskaya, E. N. Sukhomazova,
E. P. Levanova, and E. N. Deryagina
Favorskii Irkutsk Institute of Chemistry, Siberian Division, Russian Academy of Sciences,
ul. Favorskogo 1, Irkutsk, 664033 Russia
fax: (3952)356046; e-mail: admin@irioch.irk.ru
Received January 8, 2002
Abstract Reaction of thiols with dihaloalkanes in the system hydrazine hydrate base leads to alkyl(chloro-
alkyl) sulfides with different positions of the chlorine atom with respect to sulfur. The developed one-step
procedure for the synthesis of such unsymmetrical sulfides is most suitable for arenethiols and alkanethiols
having a long polymethylene chain. The reaction mechanism is discussed.
Chloroalkyl sulfides are used as pesticides [1] and
intermediate products in organic synthesis [2, 3].
-Chloroalkyl sulfides available by the Bohme reac-
tion or its modifications were studied to the greatest
extent [4]. -Chloroalkyl sulfides were also studied
in sufficient detail; they are usually prepared from
sulfur dichloride or sulfenyl chlorides and unsaturated
compounds [5, 6]. Chloroalkyl sulfides with a longer
alkyl chain are synthesized in two steps from thiols
and chlorohydrins with subsequent replacement of
the OH group by chlorine by the action of sulfuryl
chloride [7].
We recently studied the reaction of dihaloalkanes
with thiolate ions RS generated by reductive splitting
of organic disulfides in the system hydrazine hydrate
alkali, which resulted in formation of bis(alkylthio)-
alkanes [8]. In most cases, intermediate unsymmetrical
sulfides having one chlorine atom were not detected.
These were obtained only from diaryl disulfides. In
continuation of our studies on reactions of thiolate
ions with polyelectrophiles, we examined the behavior
of various thiols I toward dihaloalkanes II in the
system hydrazine hydrate alkali. This system prevents
oxidation to disulfides of thiolate ions generated from
thiols. It was surprising that, unlike disulfides, thiols I
reacted with dihalogen derivatives II to give unsym-
metrical chlorine-containing sulfides III even when
____________
the amount of dihaloalkane II was less than stoichio-
metric. In some cases, sulfides III were the major
products (Scheme 1). Simultaneously, bis-sulfide
derivatives IV were formed. The reaction conditions
and yields of the products are given in Table 1.
Scheme 1.
(1)
(2)
(3)
I, R = Et (a), Pr (b), Bu (c), Ph (d), 2-thienyl (e); II, n = 2,
X = Y = Cl (a), Br (b); n = 3, X = Br, Y = Cl (c); n = 5,
X = Y = Cl (d), Br (e); III (Y = Cl), IV, n = 2, R = Et (a),
Pr (b), Bu (c), Ph (d), 2-thienyl (e); n = 3, R = Pr (g);
n = 5, R = Pr (h).
It is seen that the yield of chloro sulfides III from
the same dihaloalkane increases as the alkyl chain in
the alkanethiol becomes longer: Ia < Ib < Ic. This
may be due to decrease of the solubility of the corre-
sponding sulfide III in hydrazine hydrate, which
changes in the same order. In a similar way (cf. [8]),
we can explain the behavior of arenethiols Id and Ie
in reactions (1) (3). Reaction (3) is hampered by
withdrawal of sulfides III to the organic phase.
*
This study was financially supported by the Russian Founda-
tion for Basic Research (project nos. 00-03-32810a and
01-03-06136).
1070-4280/02/3810-1445$27.00 2002 MAIK Nauka/Interperiodica

1446
RUSSAVSKAYA et al.
Table 1. Reactions of thiols with dihaloalkanes
(presumably, through hydrogen bonding N H SR).
Reduction of one disulfide molecule R2S2 with
hydrazine hydrate in the presence of alkali gives two
thiolate ions RS which may be solvated by one
hydrazine molecule, thus forming bridged complex V
whose structure is shown above. Complex V is likely
to be stabilized by additional coordination of the
nitrogen atom to potassium cation.
The reaction of dihalogen derivative II with one
thiolate moiety in complex V gives unsymmetrical
sulfide III in which the remaining chlorine atom
appears spatially close to the sulfur atom of the other
thiolate moiety in complex V. Such orientation is
favorable for the subsequent fast replacement of the
second chlorine atom and formation of bis-sulfide IV.
Amount, mol
Yield,a
%
RSH X(CH2)nY
RSH KOH X(CH2)nY III
IV
Ia
Ia
Ia
Ib
Ib
Ib
Ib
Ib
Ib
Ic
Ic
Ic
Id
Ie
IIa
IIa
IIa
IIa
IIb
IIc
IIc
IId
IIe
IIa
IIa
IIb
IIa
IIa
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1.5
1.5
1.0
1.5
1.2
1.5
1.3
1.5
1.5
1.2
1.5
1.5
1.5
1.5
0.5
1.0
0.5
0.5
0.5
0.5
1.0
0.5
0.5
0.5
0.5
1.0
0.5
0.5
2
6
2
45
68
41
12
78
10
36
72
84 Traces
19
32
48
10
76
Thiolate ions generated from thiols according to
reaction (1) (Scheme 1) are independent species. They
also form solvate complexes with hydrazine, but these
complexes have no bridged structure.
76 Traces
88
12
36
87 Traces
a
The yields were calculated on the initial thiol on the basis of
GLC data.
In all cases, the bromine atoms in dibromoalkanes
are replaced completely. From dibromo derivatives
IIb and IIe we obtained only bis-sulfides IV, and
mixed 1-bromo-3-chloropropane (IIc) gave rise to
unsymmetrical sulfide IIIg having only the chlorine
atom. These results support the previous observation
that bromoalkanes react more effectively with organic
chalcogenide ions (RS , RSe , RTe ). On the other
hand, chloroalkanes react more rapidly than analogous
bromoalkanes with unsubstituted chalcogenide ions
(S2 , Se2 , Te2 ) [9, 10].
A question arises as to why thiolate ions generated
by reductive splitting of dialkyl disulfides react with
dichloroalkanes mainly with replacement of both
chlorine atoms and formation of the corresponding
bis-sulfides, while those generated from thiols under
similar conditions are capable of replacing only one
chlorine atom to give in many cases chloroalkyl
sulfides as the major products. Most probably, hydra-
zine participates in formation of solvate complexes
with thiolate ions generated from disulfides or thiols
In this case, the reaction of complex VI with di-
haloalkane leads primarily to unsymmetrical sulfide
III. The possibility for the latter to react with another
thiolate ion is controlled by diffusion factor, reactant
concentrations, and solubility of sulfide III in hydra-
zine hydrate.
When a dihaloalkane has a long polymethylene
chain, it reacts with complex VI at a higher rate and
at both independent halogen atoms (as with mono-
haloalkanes). Therefore, the corresponding unsym-
metrical sulfide is formed in the reaction of propane-
thiol (I) with 1,2-dichloroethane in a greater yield
than in the reaction with 1,5-dichloropentane (IId
(Table 1). In the latter case, unsymmetrical sulfide
IIIh has a longer tail (as compared to sulfide IIIb),
at which the attack of another thiolate ion is more
facile (diffusion factor).
Thus the reaction of thiols with difunctional elec-
trophiles in the system hydrazine hydrate base may
be regarded as a convenient preparative route to alkyl
chloroalkyl sulfides with different positions of the
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 38 No. 10 2002

NEW PREPARATIVE PROCEDURE
1447
Table 2. Boiling points, elemental analyses, and 1H NMR spectra of compounds IIIb IIIe, IIIg, IIIh, IVa IVd,
IVg, and IVh
Found, %
Calculated, %
Comp.
no.
bp,
(p, mm)
C
Formula
Reference
C
H
S
Cl
C
H
S
Cl
IIIb
IIIc
IIId
IIIe
IIIg
IIIh
IVa
IVb
IVc
IVd
IVg
IVh
75 (25)
90 (5)
100 (7)
110 (5)
43.42
47.13
55.45
40.15
8.06 23.40 25.75
8.63 21.40 23.04
5.31 19.03 20.03
3.78 35.96 20.11
8.71 20.54 23.12
9.43 18.04 19.43
9.65 43.14
C5H11ClS
C6H13ClS
C8H9ClS
C6H7ClS2
C6H13ClS
C8H17ClS
C6H14S2
C8H18S2
C10H22S2
C14H14S2
C9H20S2
C11H24S2
43.17
47.21
55.63
40.34
47.21
53.18
48.00
7.91 23.02 25.90
8.52 20.98 23.28
5.22 18.55 20.58
3.92 35.85 19.89
8.52 20.98 23.28
9.42 17.53 19.67
9.33 42.67
[7]
[1]
[1]
85 87 (17) 46.94
105 (10)
115 (35)
104 (5)
140 (5)
65 (3)
53.62
47.61
53.77
[1]
[1]
9.98 36.25
53.93 10.11 35.96
58.25 10.68 31.07
68.29
56.25 10.42 33.33
60.00 10.91 29.09
58.07 10.43 30.32
68.85 5.95 25.56
56.11 10.47 33.18
60.14 10.98 28.87
5.69 26.02
180 (5)
130 (3)
Comp.
no.
1H NMR spectrum, , ppm
IIIb
IIIc
IIId
IIIe
IIIg
IIIh
IVa
IVb
IVc
IVd
IVg
IVh
0.99 t (CH3), 1.62 m (CCH2C), 2.54 t (ClCH2S), 2.85 t (SCH2CCl), 3.62 t (CH2Cl)
0.93 t (CH3), 1.40 m (CCH2C), 1.56 m (CH3CCH2), 2.54 t (CCCCH2S), 2.81 t (SCH2CCl), 3.58 t (CH2Cl)
3.2 t (CH2S), 3.57 t (CH2Cl), 7.26 m (Harom
)
3.01 t (CH2S), 3.61 t (CH2Cl), 6.90 7.38 m (thienyl)
0.98 t (CH3), 1.58 m (CCH2C), 2.06 m (CCH2CCl), 2.49 t (CCCH2S), 2.65 t (SCH2CCCl), 3.64 t (CH2Cl)
0.98 t (CH3), 1.54 m (CH2), 1.78 m (CH2CCl), 2.48 t (CH2S), 3.42 t (CH2Cl)
1.25 t (CH3), 2.52 q (CCH2S), 2.72 s (SCH2CH2S)
0.98 t (CH3), 1.60 m (CCH2C), 2.51 t (CCCH2S), 2.70 s (SCH2CH2S)
0.91 t (CH3), 1.41 m (CCH2C), 1.58 m (CH3CCH2), 2.54 t (CCCCH2S), 2.70 s (SCH2CH2S)
3.06 s (SCH2CH2S), 7.26 s (Harom
)
0.98 t (CH3), 1.54 m (CCH2C), 2.50 m (CH2S)
0.98 t (CH3), 1.50 m (CCH2CC), 1.58 m (CCH2C, SCCH2CCH2CS)
chlorine atom with respect to sulfur. The proposed
one-step procedure for preparation of sulfides III is
most suitable for arenethiols and long-chain alkane-
thiols. All the products were isolated from the reaction
mixtures by fractional distillation under reduced
pressure; their boiling points, elemental analyses,
an LKhM-80 chromatograph (2000 3-mm column
packed with 5% of XE-60 on Chromaton N-AW-
HMDS, carrier gas helium, linear oven temperature
programming at a rate of 12 deg/min). Gas chromato-
graphic mass spectrometric analysis was performed
using a Hewlett Packard HP 5972A mass-selective
detector (PONA capillary column, 50 m 0.2 mm
0.5 m, carrier gas helium, linear temperature prog-
ramming at a rate of 12 deg/min).
Reaction of thiols I with dihaloalkanes II.
A four-necked flask equipped with a stirrer, reflux
condenser, thermometer, and adapter for loading the
reactants was charged with required amounts of alkali,
hydrazine hydrate, and appropriate thiol (see Table 1).
The mixture was vigorously stirred for 1 h, a required
1
and H NMR spectra are given in Table 2. Some
compounds were synthesized for the first time.
EXPERIMENTAL
1
The H NMR spectra were recorded on a Bruker
DPX-400 spectrometer (400 MHz) in CDCl3 using
HMDS as internal reference. The progress of reactions
and the purity of products were monitored by GLC on
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 38 No. 10 2002

1448
RUSSAVSKAYA et al.
amount of dihaloalkane was added, the mixture was
heated to 50 C, kept for 2 h at that temperature, and
cooled, and the organic phase was separated and dried
over CaCl2. The product yields were calculated from
the GLC data (Table 1). The products were isolated
by vacuum distillation. Compound IVe was isolated
by recrysallization from ethanol. Ethyl 2-chloroethyl
sulfide (IIIa) was identified solely on the basis of
the GC MS data: m/z 124 (M+, 35Cl). The other prod-
ucts are characterized in Table 2.
4. Turchaninova, L.P., Korchevin, N.A., Shipov, A.G.,
Deryagina, E.N., Baukov, Yu.I., and Voron-
kov, M.G., Zh. Obshch. Khim., 1989, vol. 59, no. 3,
pp. 722 723.
5. Pokonova, Yu.V., Galoidsul’fidy (Halogenated Sul-
fides), Leningrad: Leningr. Gos. Univ., 1977, p. 81.
6. Poluchenie i svoistva organicheskikh soedinenii sery
(Synthesis and Properties of Organic Sulfur Com-
pounds), Belen’kii, L.I., Ed., Moscow: Khimiya,
1998, p. 53.
7. Kabachnik, M.I. and Godovikov, N.N., Zh. Obshch.
Khim., 1963, vol. 63, no. 6, pp. 1941 1945.
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