Efficient thiocyanation of indoles using para-toluene sulfonic acid

Article abstract of DOI:10.1080/00397910902883744

Treatment of indoles with ammonium thiocyanate in the presence of para-toluene sulfonic acid afforded the corresponding 3-thiocyano indoles at room temperature in excellent yields.

Full text of DOI:10.1080/00397910902883744

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Efficient Thiocyanation of Indoles Using
Para-Toluene Sulfonic Acid
a
a
Biswanath Das & Avula Satya Kumar
a
Organic Chemistry Division I, Indian Institute of Chemical
Technology, Hyderabad, Andhra Pradesh, India
Version of record first published: 06 Jan 2010.
To cite this article: Biswanath Das & Avula Satya Kumar (2010): Efficient Thiocyanation of Indoles
Using Para-Toluene Sulfonic Acid, Synthetic Communications: An International Journal for Rapid
Communication of Synthetic Organic Chemistry, 40:3, 337-341
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1
Synthetic Communications , 40: 337–341, 2010
Copyright # Taylor & Francis Group, LLC
ISSN: 0039-7911 print=1532-2432 online
DOI: 10.1080/00397910902883744
EFFICIENT THIOCYANATION OF INDOLES
USING PARA-TOLUENE SULFONIC ACID
Biswanath Das and Avula Satya Kumar
Organic Chemistry Division I, Indian Institute of Chemical Technology,
Hyderabad, Andhra Pradesh, India
Treatment of indoles with ammonium thiocyanate in the presence of para-toluene sulfonic
acid afforded the corresponding 3-thiocyano indoles at room temperature in excellent yields.
Keywords: Ammonium thiocyanate; indoles; para-toluene sulfonic acid; regioselectivity; thiocyanation
INTRODUCTION
Thiocyanation of aromatic and heteroaromatic compounds is a useful reaction
in organic synthesis because this reaction initiates the direct introduction of sulfur
[
1,2]
into the molecules.
for the synthesis of sulfur-containing heterocycles. The thiocyanate group can
Aryl and heteroaryl thiocyanates are important intermediates
[
3]
[
4,5]
also be converted into other sulfur-bearing groups.
been prepared earlier using different reagents under various conditions.
Aryl thiocyanates have
1–7]
[
However, only a limited number of reagents [such as N-halosuccinamides (N-
chlorosuccinimide, NCS and N-bromosuccinimide, NBS), ceric ammonium nitrate
(CAN), K10 clay, oxone, and halogens (Br and I )] have been reported for thiocya-
nation of indoles.
2 2
[8–12]
Many of the methods utilizing these reagents suffer from vari-
ous drawbacks such as the use of excess amounts of strong oxiding agents and toxic
metal thiocyanates, unsatisfactory yields, and high temperatures.
RESULTS AND DISCUSSION
[13–16]
In continuation of our work
on the development of useful synthetic meth-
odologies, we observed that the thiocyanation of indoles can efficiently be carried
out by treatment with ammonium thiocyanate in the presence of para-tolune sulfonic
acid (p-TSA) at room temperature (Scheme 1).
Various indoles were converted into the corresponding 3-thiocyano analogs by
following this method (Table 1). The derivatives of indoles with substituents in the
Received December 27, 2008.
Address correspondence to Biswanath Das, Organic Chemistry Division I, Indian Institute of
Chemical Technology, Uppal Road, Hyderabad 500 007, Andhra Pradesh, India. E-mail: biswanathdas@
yahoo.com
3
37

338
B. DAS AND A. S. KUMAR
Scheme 1. Thiocyanation of indoles using para-toluene sulfonic acid.
aromatic ring as well as 2-methyl indole and N-methyl indole were applied equally.
In each case, only the monothiocyanation product was formed. The reaction was
completed within 30–45 min, and the yields were good (85–91%). Indoles containing
electron-donating as well as electron-withdrawing groups smoothly underwent the
conversion. The reaction is highly regioselective, forming 3-thiocyano derivaties as
the products. The structures of the thiocyanates were established from their spectral
[
1
infrared (IR), H NMR, and mass (MS)] and analytical data.
CONCLUSION
In conclusion, we have developed a simple and efficient method for
high-yielding regioselective thiocyanation of indoles by treatment with ammonium
thiocyanate using para-tolune sulfonic acid at room temperature.
EXPERIMENTAL
General Procedure for the Synthesis of b-Amino Ketones
p-TSA (0.2 mmol) was added to a solution of indole (1 mmol) and NH SCN
4
(1.6 mmol) in methanol (MeOH, 5 mL), and the mixture was stirred at room tem-
perature. The reaction was monitored by thin-layer cromotography (TLC). After
completion, the reaction was quenched with aqueous saturated NaHCO solution,
3
and the mixture was extracted with EtOAc (3 ꢀ 10 mL). The extract was con-
centrated, and the residue was purified by column chromatography (silica gel,
hexane–EtOAc) to obtain pure thiocyanate.
1
The spectroscopic ( H NMR and MS) and analytical data of the new
compounds are given here.
Compound 2e (Table 1)
ꢁ
1 1
IR (KBr): tmax 3414, 2155, 1647, 1457 cm ; H NMR (CDCl , 200 MHz):
3
d 10.82 (1H, brs), 7.64 (2H, brs), 7.43 (1H, d, J ¼ 8.0 Hz), 7.20 (1H, dd, J ¼ 8.0 Hz);
þ
ESI-MS: m=z 231, 233 [M þ Na] . Anal. calcd. for C H ClN S: C, 51.80; H, 2.40; N,
9
5
2
1
3.43%. Found: C, 51.68; H, 2.49; N, 13.36%.

EFFICIENT THIOCYANATION OF INDOLES
339
Isolated yield (%)
88
a
Table 1. Synthesis of 3-thiocyano indoles using p-TSA
No.
a
Indole 1
Product 2
Time (min)
45
40
b
c
86
87
87
40
40
d
e
f
40
45
30
91
89
86
g
h
30
40
85
88
i
a 1
The structures of the products were settled from their spectral (IR, H NMR, and MS) data.

340
B. DAS AND A. S. KUMAR
Compound 2f (Table 1)
IR (KBr): tmax 3348, 2158, 1631, 1511, 1449 cm
00 MHz): d 8.62 (1H, brs), 7.65 (1H, m), 7.48 (1H, d, J ¼ 1.5 Hz), 7.14–7.01 (2H, m);
ꢁ
1
1
;
H NMR (CDCl3,
2
þ
ESI-MS: m=z 215 [M þ Na] . Anal. calcd. for C H FN S: C, 56.25; H, 2.60; N,
9
5
2
1
4.58%. Found: C, 56.32; H, 2.54; N, 14.51%.
ACKNOWLEDGMENTS
The authors thank the Council of Scientific and Industrial Research and the
University Grants Commission, New Delhi, India, for financial assistance.
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