1304
Chemistry Letters 2000
Remarkably Fast Direct Synthesis of Thiols from Alcohols under Mild Conditions
B. P. Bandgar,* V. S. Sadavarte, and L. S. Uppalla
School of Chemical Sciences, Swami Ramanand Teerth Marathwada University, Nanded-431 606, Maharashtra, India.
(Received July 13, 2000; CL-000670)
One pot rapid synthesis of thiols from alcohols via trifluo-
roacetates using polymer supported hydrosulfide in acetonitrile
under mild conditions has been described.
utes at room temperature. The resulting trifluoroacetic acid and
the excess of anhydride were evaporated off and the intermedi-
ate trifluoroacetate was treated in situ with polymer supported
hydrosulfide in acetonitrile at 25 °C to give corresponding thiol
in a very short time in essentially pure form and in good yield.
The results are surnmarized in Table 1.
Thiols are important not only for their use in the synthesis
of organosulfur compounds but also for their roles in cell bio-
chemistry.l Therefore, many synthetic methods have been
developed.2,3 Although direct preparations of thiols from alkyl
halides and metal sulfides would be straightforward, direct
methods give only a moderate yield of thiols accompanying a
considerable amount of dialkyl sulfide.2 Therefore, indirect
methods involving thiourea,2 xanthate2 and thioacetate2 are
commonly utilized for the synthesis of thiols and other indirect
methods have been reported.4–9 These indirect methods usually
give around 80% yield and no dialkyl sulfides or other unde-
sired byproducts; however, intermediates have to be trans-
formed to thiols by hydrolysis with base5–9 or by reduction with
lithium aluminium hydride.10,11 Recently thiols have been pre-
pared in quantitative yield from the corresponding thioacetates2
and alkyl halides.12
Various primary, secondary, tertiary, acyclic and cyclic alco-
hols, diols, benzylic alcohols are converted into corresponding
thiols using trifluoroacetic anhydride and polymer supported
hydrosulfide. Alcohols are selectively converted into thiols with-
out interfering other functional groups such as carbonyl, methoxy,
methylenedioxy, C=C, ester, THP ether, isopropylidenedioxy,
boc, fmoc and phenolic OH. It is worth commenting that second-
ary alcohol in the presence of tertiary alcohol (entry 16), benzyl
alcohol in the presence of primary alcohol (entry 17), benzyl
alcohol in the presence of phenol (entry 18), and secondary alco-
hol in the presence of phenol (entry 19), is converted chemose-
lectively into corresponding thiol. In addition it is interesting to
note that (+) optically active alcohol (entry 14) and (–) optically
active alcohols (entries 4, 15, 17, 19) were converted into (–)
optically active mercaptans and (+) optically active mercaptans
respectively under these reaction conditions indicating that the
reaction involves SN2 mechanism. Optical rotation values of
these alcohols and thiols are shown in Table 1.
We now report for the first time rapid and efficient method
for direct synthesis of thiols from alcohols using trifluoroacetic
anhydride and polymer supported hydrosulfide under mild con-
dition (Scheme 1). It is worth commenting that this method
produces thiols in excellent yields without any trace of dialkyl
sulfide.
Amberlite IRA- 400 (Cl–) was procured from S. D. Fine
Chemicals, Mumbai.
Procedure for preparation of polymer supported hydrosul-
fide: To a solution of NaSH (50 mmol) in distilled water (50
mL), Amberlite IRA 400 (Cl–) (10 g) was added and mixture
was shaken for 1 h. Then resin was filtered and washed with
distilled water, ethanol, ether and then dried under vacuum at
50 °C for 2 h. The capacity of hydrosulfide exchange resin (by
titration method) was found to be 1 mmol/g dry resin.
The synthesis of thiols from alkyl halides and NaSH
always results in the formation of dialkyl sulfidel3 because the
alkyl thiols formed initially further react with excess of alkyl
halide. Alcohols are cheap and easily available compared with
alkyl halides. Attempts to prepare thiols from alcohols via the
corresponding trifluoroacetates with NaSH required longer
reaction time and resulted in poor yields. This is due to low
solubility of NaSH in organic solvents. However alcohols via
trifluoroacetates (which are not isolated as such) on treatment
with polymer supported hydrosulfide under mild condition gave
corresponding thiols in good yield in a very short time. This is
because polymer supported hydrosulfide has more nucleophilic
character than NaSH. The success of this transformation may
also be attributed to the high nucleofugal character of the triflu-
oroacetate moiety in nucleophilic substitution,14 which resem-
bles that of triflates.15
In a typical procedure, to a solution of (–)-menthol (5 mmol)
in dichloromethane (10 mL) was added trifluoroacetic anhydride
(6 mmol). The reaction mixture was stirred for 15 min at room
temperature. The trifluoroacetic acid formed, along with the sol-
vent is then evaporated off and the residue was diluted with ace-
tonitrile (10 mL) which was treated with hydrosulfide supported
resin (6 g, 6 mmol). The reaction mixture was stirred for 5 min
at 25 °C. After completion of the reaction, the resin was filtered
off and washed with dichloromethane (2 × 10 mL). Then,
removal of the solvent under reduced pressure gave (+)-menthyl
mercaptan in almost pure form. Yield = 88%; IR: 2565 cm–1
1
(SH); H NMR (90 MHz, CDCl3) δ 0.82 (d, 3H, CH3), 0.90 (d,
3H, CH3), 0.93 (d, 3H, CH3), 1.52–2.6 (m, 10H), 3.12 (m, 1H);
MS (70 eV): m/z (%) = 172.27 (37) [M+]; C10H20S (172). Anal.
Calcd for : C, 69.66; H, 11.61; S, 18.58%. Found: C, 69.71; H,
11.58; S, 18.61%.
Trifluoroacetylation was carried out in almost quantitative
yield by treatment of the alcohol with an excess of trifluo-
roacetic anhydride. The reaction was complete in a few min-
VSS thanks CSIR, New Delhi. for junior research fellow-
ship.
Copyright © 2000 The Chemical Society of Japan
Bandgar
