Phosphorus Pentasulfide Mediated Conversion of Primary Carbamates into Thiols

Article abstract of DOI:10.1055/s-0036-1589026

In this paper, we report a method for the conversion of primary carbamates into thiols in the presence of phosphorus pentasulfide (P ₂ S ₅) in refluxing toluene. Presently, no method exists in the literature for conversion of carbamates into thiols and, to the best of our knowledge, it is the first report for this type of conversion. This method presents an indirect route for the conversion of alcohols into thiols via their carbamate derivatives that may be useful in the total synthesis of compounds containing a thiol functionality.

Full text of DOI:10.1055/s-0036-1589026

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© Georg Thieme Verlag Stuttgart · New York
2017, 28, A–C
letter
A
en
C. K. Maurya, P. K. Gupta
Letter
Synlett
Phosphorus Pentasulfide Mediated Conversion of Primary Carba-
mates into Thiols
Chandra Kant Maurya
Pradeep Kumar Gupta*
S
P
S
P
S
P
S
S
S
S
S
P
S
Defence Research & Development Establishment (DRDE),
Jhansi Road, Gwalior (MP)-474002, India
pkgupta@drde.drdo.in
S
O
S
SH
R
R
R
S
NH2
O
NH2
toluene
reflux
pr_14@rediffmail.com
15 examples
up to 79% yield
R = alkyl, benzyl, aryl
Received: 14.03.2017
Accepted after revision: 09.04.2017
Published online: 02.05.2017
synthesis for numerous applications.7 The synthetic proto-
col described in this paper makes use of this reagent to pro-
vide an efficient and single-step procedure for the direct
conversion of carbamates into thiols (Scheme 1).
DOI: 10.1055/s-0036-1589026; Art ID: st-2017-d0186-l
Abstract In this paper, we report a method for the conversion of pri-
mary carbamates into thiols in the presence of phosphorus pentasul-
fide (P2S5) in refluxing toluene. Presently, no method exists in the litera-
ture for conversion of carbamates into thiols and, to the best of our
knowledge, it is the first report for this type of conversion. This method
presents an indirect route for the conversion of alcohols into thiols via
their carbamate derivatives that may be useful in the total synthesis of
compounds containing a thiol functionality.
O
P2S5
SH
R
R
O
NH2
R = alkyl, benzyl, aryl
Scheme 1 Conversion of primary carbamate into thiol
Initially, for the reaction optimization, benzyl carba-
mate (Scheme 1, R = Bn) was chosen as the model substrate
and reacted with P2S5 in different organic solvents (Table 1).
Although, the reaction proceeded in a range of solvents in-
cluding benzene, toluene, THF, and dichloromethane, the
best results in terms of reaction time and yields were ob-
tained in toluene. It was also observed that substoichiomet-
ric amounts of reagent and reaction at room temperature
resulted in low product yield or incomplete reaction. In fact,
an excess of thionating reagent at refluxing temperature
was required for reaction completion. Importantly, the re-
Key words carbamate, phosphorus pentasulfide, thiocarbamate,
dithiocarbamate, thiol
Thiols constitute an important group of sulfur-contain-
ing compounds. Thiols have a distinct odor and are often
used as gas odorants in industrial applications.1 They occur
naturally as flavouring compounds in several fruits and
spices2 and are found in a variety of enzymes at their active
sites.3 Thiols are produced naturally by the wood-pulping
industry, manure and sewer systems,4 and by the break-
down of sulfur-containing amino acids and lignin.5 For the
laboratory synthesis of thiols, various methods utilizing al-
cohols, alkyl halides, alkenes as substrate have been report-
ed.6 However, the immense importance of thiols still leaves
scope for further investigations in this area and, in this con-
text, we herein describe a new and efficient method for the
preparation of thiols from primary carbamates. During our
efforts in thionating the carbamates with P2S5, by analogy
with the thionation of carbonyl compounds, we found that
the reaction, instead of furnishing the desired thiocarba-
mates, gave the corresponding thiols. An extensive litera-
ture survey revealed that no synthetic method has been re-
ported for conversion of carbamates into the corresponding
thiols. Phosphorus pentasulfide (P2S5), a commercially
available reagent, has widely been employed in organic
Table 1 Effect of Reaction Medium and Reagents on Conversion of
Benzyl Carbamate into Benzyl Thiol
Entry
Solvent
Reagent
Time (h)
Yield (%)
1
2
3
4
5
6
THF
P2S5
2.5
2.5
3.0
3.0
4.0
4.0
35
30
45
75
–
CH2Cl2
benzene
toluene
toluene
toluene
P2S5
P2S5
P2S5
Lawesson’s reagent
PSCl3
–
© Georg Thieme Verlag Stuttgart · New York — Synlett 2017, 28, A–C

B
C. K. Maurya, P. K. Gupta
Letter
Synlett
S
P
S
P
S
P
S
S
P
S
P
S
S
P
S
P
S
S
P
S
S
P
S
S
+
S
O
R
S
S
S
S
S
S
O
H2N
O R
P
S
R
P
S
S
S
S
S
S
O
P
S
O
O
S
R
NH2
NH2
O
S
P2S5
R
SH
H2N
R
H2N
S R
H2N
S
O
Scheme 2 Plausible mechanism for reaction between carbamate and P2S5
action gave the thiol as the major product with no disulfide
formation. Interestingly, no reaction of the carbamate was
observed with other thionating agents such Lawesson’s re-
agent and PSCl3 and, in those cases, starting material was
recovered.
known to undergo acid-mediated cleavage to thiols.11
Hence, the thiols could be formed by the acid-mediated
cleavage of both S-thiocarbamate and dithiocarbamate in-
termediates.
In summary, the method described in this paper pres-
ents an efficient and direct route for the conversion of pri-
mary carbamates into thiols.12 In this way, it provides an al-
ternate route for converting alcohols into the thiols through
their carbamate derivatives.
To study the scope and limitations of this conversion, a
variety of carbamates (Scheme 2, Table 2) were treated with
P2S5 in refluxing toluene to yield the corresponding thiols in
good to moderate yields. The results indicate that the reac-
tion rates were more susceptible to substituent effect in
comparison to the product yields. Simple short-chain car-
bamates reacted rapidly to give the corresponding thiols.
Increasing the alkyl chain length decreased both rate and
yield of the reaction (Table 2, entries 2 vs. 5), presumably
due to steric effects. In comparison to the alkyl substrates,
the benzyl derivative reacted sluggishly possibly due to ste-
ric hindrance by the benzene ring and this was further evi-
dent by the longer reaction time required by 3-phenoxy-
benzyl carbamate (Table 2, entry 8). In the case of benzyl
carbamates, the presence of electron-donating groups such
as methyl and methoxy groups on the phenyl ring (Table 2,
entries 6 and 7) caused reaction-rate acceleration while
electron-withdrawing halogen substituents diminished the
rate of reaction. Aryl carbamates were also suitable sub-
strates and gave the corresponding thiols in good yields.
A possible mechanism for reaction between carbamate
and P2S5 is proposed to involve initial thionation of the car-
bamate carbonyl group to give the corresponding O-thio-
carbamate that subsequently undergoes Newman–Kwart
rearrangement to the corresponding S-thiocarbamate.8 Fur-
ther thionation of the latter with P2S5 gives a dithiocarba-
mate derivative9 that, in the presence of acid, decomposes
to give the corresponding thiol. To support the intermedia-
cy of the S-thiocarbamate in the reaction, benzyl S-thiocar-
bamate was separately synthesized and reacted with P2S5 in
refluxing toluene to form the corresponding thiol. Further-
more, involvement of the dithiocarbamate was indicated
indirectly by treating the thiocyanate with P2S5 in refluxing
toluene to obtain the thiol. It is thought that the thiocya-
nate, by analogy with the thionation of nitriles to thioam-
ides with P2S5,10 will also furnish the dithiocarbamate that
will ultimately give the corresponding thiol through acid-
mediated cleavage. Additionally, S-thiocarbamates are also
a
Table 2 Conversion of Carbamates into Thiols with P2S5
Entry Reactant
Time Product
(h)
Yield
(%)b
O
SH
1
3
75
O
O
NH2
2
3
4
5
2
2
2
78
76
72
71
SH
O
NH2
O
SH
SH
O
O
NH2
O
NH2
O
3
Br (CH2)9 SH
Br (CH2)9
O
NH2
O
SH
6
7
8
2.5
77
79
74
O
NH2
O
O
SH
SH
2.25
8
O
NH2
MeO
PhO
MeO
PhO
O
NH2
© Georg Thieme Verlag Stuttgart · New York — Synlett 2017, 28, A–C

C
C. K. Maurya, P. K. Gupta
Letter
Synlett
References and Notes
Entry Reactant
Time Product
(h)
Yield
(%)b
(1) Leonardos, G.; Kendall, D.; Barnard, N. J. Air Pollut. Control Assoc.
1969, 19, 91.
O
Br
Br
SH
(2) Maga, J. A.; Katz, I. Crit. Rev. Food Sci. Nutr. 1976, 7, 147.
(3) Mercurio, S. D.; Combs, G. F. Jr. J. Nutr. 1987, 117, 880.
(4) Krouse, H. R.; McCready, R. G. L. In Biogeochemical Cycling of
Mineral-Forming Elements; Trudinger, P. A.; Swine, D. J., Eds.;
Elsevier: Amsterdam, 1979, 401.
(5) (a) Loveluck, J. E.; Maggs, R. J.; Rasmussen, R. A. Nature (London,
U.K.) 1972, 237, 452. (b) Sivela, S.; Sundman, V. Arch. Microbiol.
1975, 103, 303. (c) Banwart, W. L.; Bremner, J. M. Soil Biol. Bio-
chem. 1976, 8, 439.
(6) Wardell, J. L. In The Chemistry of the Thiols Group; Patai, Ed.;
Wiley: New York, 1974, 1, 16.
(7) Ozturk, T.; Ertas, E.; Mert, O. Chem. Rev. 2010, 110, 3419.
(8) Alam, A. R. M.; Inaloo, I. D.; Kleinpeter, E. J. Mol. Str. 2012, 1024,
156.
9
5
71
72
72
O
NH2
O
SH
10
4.5
6
O
NH2
F
F
O
SH
11
O
NH2
O
Cl
Cl
SH
12
5
71
73
O
NH2
(9) Berezin, A. A.; Koutentis, P. A.; Manos, M. J. Tetrahedron 2011,
67, 5437.
Br
Br
(10) Kaboudin, B.; Elhamifar, D. Synthesis 2006, 224.
(11) Werner, E. A. J. Chem. Soc., Trans. 1890, 57, 283.
(12) Conversion of Carbamate into Thiol – Typical Procedure
In a three-neck round-bottom flask, to a solution of carbamate
(10 mmol) in toluene (25 mL), P2S5 (3.33 g, 15 mmol) was
added, and the resulting suspension was heated to reflux until
complete consumption of the starting material (TLC). After the
reaction was complete, the reaction mixture was quenched by
careful addition of water (10 mL), extracted with EtOAc (3 × 10
mL). The organic phase was dried over Na2SO4, filtered, and
evaporated under reduced pressure to obtain the crude product
that was purified by flash chromatography (hexane–EtOAc) to
give the pure thiol.
O
SH
O
NH2
13
4.5
O2N
O2N
O
14
4
4
69
67
SH
O
NH2
O
15
O2N
SH
O2N
O
NH2
a Reaction conditions: carbamate (10 mmol), P2S5 (15 mmol), toluene (25
mL).10
3-Phenoxybenzyl Thiol
b Known compounds were identified by comparison with authentic thiols.
Oil, yield 74%. 1H NMR (400 MHz, CDCl3): δ = 7.24–7.34 (m, 3 H),
6.87–7.10 (m, 6 H), 3.87 (d, 3JH–H = 4.0 Hz, 2 H), 1.75 (t, 3JH–H = 4.0
Hz, 1 H). 13CNMR (100 MHz, CDCl3): δ = 28.70, 117.29, 118.34,
119.01, 122.77, 123.37, 129.76, 129.92, 143.11, 156.94, 157.50.
ESI-HRMS: m/z calcd for C13H12OS [M + Na]+: 239.0609; found:
239.0611
Acknowledgment
The authors thank Dr Lokendra Singh, Director, DRDE, Gwalior and Dr.
D. K. Dubey, Head, Synthetic Chemistry Division for their support and
encouragement.
© Georg Thieme Verlag Stuttgart · New York — Synlett 2017, 28, A–C