LETTER
Conversion of Thiols to Alkyl Halides by Triphenylphosphine/N-Halosuccinimides
1177
Scheme 2
Similar elimination reaction also occurs in the reaction of In conclusion, the use of triphenylphosphine and N-halo-
cyclohexylmercatptane with other reagents such as Ph P/ succinimide is a simple, mild and efficient method for the
3
1
4
Br2.
conversion of thiols to alkyl halides. Availability of the re-
agents, easy work up, high yields, operation at room tem-
perature and possibility of formation of chlorides,
bromides and also iodides make this method a general and
useful method for this transformation.
Since 2,4,4,6-tetrabromo-2,5-cyclohexadienone in the
presence of Ph P has been used for the conversion of al-
cohols to alkyl bromides, we decided to study the possi-
bility of using this compound instead of NBS for
conversion of thiols to alkyl bromides. When we treated
3
1
5
1
-butanthiol with PPh /2,4,4,6-tetrabromo-2, 5-cyclo-
3
Experimental
hexadienone using the same molar ratio as Ph P/NBS in
3
All products are known compounds. NMR spectra were recorded on
a Brucker Advanced DPX-250 spectrophotometer. GC spectra were
recorded on a shimadzu GC-14A.
dichloromethane at room temperature, 1-bromobutane
was obtained in 76% yield after 12h. This result shows
that the use of NBS (Table 2, entry 9) is more efficient
than 2,4,4,6-tetrabromo-2,5-cyclohexadienone as the
source of electrophilic bromine for this reaction.
Typical procedure for conversion of 1-dodecanethiol to 1-bromo-
dodecane:
To a flask containing NBS (1.4 mmol) in anhyd CH Cl (10 ml) was
2
2
added PPh3 (1.6 mmol). The reaction is exothermic and required
to be kept at room temperature. To this mixture, 1-dodecanethiol
We continued this study by using the combination of
Ph P/NCS for conversion of thiols to their alkyl chlorides.
3
(1 mmol) was added and the reaction mixture was stirred at room
The reactions of thiols with this reagent were found to oc-
temperature. After completion of the reaction (13 h) on the basis of
GC analysis, the solvent was evaporated. Column chromatography
of the crude mixture on silica gel using n-pentane as eluent gave
cur much faster than the reactions with Ph P/NBS and the
3
corresponding alkyl chlorides were obtained in high
yields (Table 2, entries 2,5,10,13). Indeed benzyl mercap- 1-bromododecane in 80% yield.
tane was immediately converted to benzyl chloride with
this reagent in high yield. (Table 2, entry 2).
Acknowledgement
4
In comparison with PPh /CCl , this reagent is more effi-
3
4
We gratefully acknowledge the partial support of this work by Shir-
az University Research Council.
cient for the conversion of thiols to alkyl chlorides, since
when we used PPh /CCl for the conversion of benzylm-
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4
ercaptane, 1-butanthiol and 1-dodecanthiol to their corre-
sponding chlorides at room temperature, the reactions References and Notes
were not successful and their chlorides were obtained in
(
1) G. A. Wiley, R. L. Hershkowitz, B. M. Rein, B. C. Chung. J.
Am. Chem. Soc. 1964, 86, 964.
3
-6% yields after 10 h. We also tried the reaction of ben-
4
zyl thiol with Ph P/CCl at 50-55 °C, but again the ob-
(2) J. P. Schaefer, J. G. Higgins, P.K. Shenoy Org. Syn. 1968, 48,
3
4
tained yield was very low and only 18% was obtained
instead of the reported 85%.
51.
(
(
3) A. K. Bose, B. Lal, Tetrahedron Lett. 1973, 40, 3937.
4) R. G. Wiess, E. I. Snyder, Chem. Commun. 1968, 1358.
The use Ph P/CX is only limited for the conversion of
3
4
(5) (a) C. R. Harison, P. Hodge, B.J. Hunt, E. Khoshdel, G.
Richardson, J. Org. Chem. 1983, 48, 3721. (b) D. L. J. Clive,
C. V. Denyer, J. Chem. Soc., Chem. Commun. 1972, 773.
RSH to RX; (X = Cl, Br), we therefore extended the appli-
cability of the present method for conversion of thiols to
(
1
c) I. W. J. Still, G. W. Kutney, D. McLean, J. Org. Chem.
982, 47, 560.
their alkyl iodides by using the combination of Ph P/NIS.
3
The conversions were found to occur in dichloromethane
at room temperature to produce alkyl iodides in good
yields. The results of this conversion are shown in Table
(
(
(
(
6) J. B. Lee, T. J. Nolan, Can. J. Chem. 1966, 44, 1331.
7) J.Hooz, S. S. H. Giliani, Can. J. Chem. 1968, 46, 86.
8) S. Trippet, J. Chem. Soc. 1962, 2337.
2
, entries 3, 6 and 8.
9) (a) A. J. Burns, J. I. G. Cadogan, J. Chem. Soc. 1963, 5788.
(
b) O. Sugimato, M. Mori, K. Tanji, Tetrahedron Lett. 1999,
40, 7477.
10) (a) M. J Dagani, (Ethyl Corp), U.S. 3, 624,159 (Cl.260/
06.5P;C07f), 30 Nov 1971, Appl. 09 Apr 1969; 3pp; Chem.
The reaction pathway could be similar to that reported for
the conversion of alcohols with the intermediacy of a
quaternary phosphonium salt 1, which cleaves to give the
desired triphenylphosphinesulfide with concomitant for-
3
(
6
Abstr. 1972, 76, p 46304z. (b) S. Oae, H. Togo, Synthesis
1981, 373.
mation of an alkyl halide and succinimide in a S 2 type re-
N
-
action with X (Scheme 2).
(11) M. F. Abd El-wahab, M. Z. Barecat, Monatsh. Chem. 1957,
8, 692-701.
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Synlett 2001, No. 7, 1176–1178 ISSN 0936-5214 © Thieme Stuttgart · New York