A simple and efficient thiocyanation of indoles, anilines and keto compounds catalyzed by a polystyrene resin amberlyst-15

Article abstract of DOI:10.2174/157017810791514878

Thiocyanation of various aromatic, heteroaromatic and enolizable ketone compounds has been achieved with ammonium thiocyanate in presence of polystyrene cation exchange resin, Amberlyst-15. All the reactions were carried out in acetonitrile at room temper

Full text of DOI:10.2174/157017810791514878

392
Letters in Organic Chemistry, 2010, 7, 392-395
A Simple and Efficient Thiocyanation of Indoles, Anilines and Keto
Compounds Catalyzed by a Polystyrene Resin Amberlyst-15
Racha Lenin and Rallabandi M. Raju*
Department of Chemistry, Osmania University, Hyderabad, 500007, India
Received December 28, 2008: Revised March 22, 2010: Accepted March 22, 2010
Abstract: Thiocyanation of various aromatic, heteroaromatic and enolizable ketone compounds has been achieved with
ammonium thiocyanate in presence of polystyrene cation exchange resin, Amberlyst-15. All the reactions were carried out
in acetonitrile at room temperature.
Keywords: Indoles, amines, ketones, amberlyst-15, ammonium thiocyanate, pyrrole.
The electrophilic thiocyanation of aromatic, hetero
aromatic and ketone compounds is a direct way for carbon
sulfur bond formation and is a very useful reaction in organic
synthesis [1]. The thiocyanate function is an interesting part
of the molecule, which will be readily transformed into the
other sulfur-bearing functionalities, especially for producing
compounds with pharmaceutical properties [2]. Therefore, it
is important to find new and fast methods for synthesis of
thiocyanate group containing aromatic, hetero aromatic and
keto systems. Various methods have been reported for
thiocyanation using N-thiocyanato succimiunide [3], DDQ
and DDQ-TPP [4], Iodine and Iodine (III) sulfonate [5],
Oxone and potassium peroxydisulfate-copper (II)sulfate [6],
perchlorates in electrolyte medium, CAN and K10-Clay [7],
nBu4NF, CuBr2/Al2O3 and FeCl3 [8]. However, many of these
methods involve the use of a large excess of strong oxidizing
agents and toxic metal thiocyanates resulting in low
conversions due to the formation of complex mixtures of
products. Therefore, the development of a new and efficient
method for the thiocyanation of aromatic, hetero aromatic
and ketone compounds under mild and more convenient
conditions is still needed. In recent years, heterogeneous
catalysts have gained importance due to their reactivity
enhancement as well as from economic and ecological point
of view. A macro reticular sulfonic acid based polystyrene
cation exchange resin, Amberlyst-15, is an inexpensive and
commercially available catalyst, which is very useful for
organic transformations [9].
product 3-thiocyanatoindole (entry a) was obtained in 93%
yield as shown in Scheme 1. Encouraged by this result, we
extended our study for various substituted indoles such as 1-
methyl (entry b), 2-methyl (entry c) and 5-bromoindoles
(entry d), and which were reacted with ammonium
thiocyanate in presence of Amberlyst-15 to obtain the
corresponding derivatives in very good yields.
SCN
Amberlyst 15
+
H4NSCN
CH3CN.r.t
N
H
N
H
Scheme 1.
In a similar manner, aniline was treated with ammonium
thiocyanate in presence of Amberlyst-15. The reaction has
gone to completion within 4 hours at room temperature and
the corresponding product (entry f) was obtained in 85%
yield. In this sequence, pyrrole (entry e) and N, N-
dimethylaniline (entry g) was reacted smoothly to afford the
corresponding thiocyanato derivatives in very good yields. In
the case of aryl amines, the products were obtained with high
para-selectivity.
The same reaction conditions were extended for the ꢀ-
thiocyanation of enolizable ketones. Initially, acetophenone
was studied as
a model substrate with ammonium
thiocyanate using Amberlyst-15 in acetonitrile at room
temperature to afford the corresponding derivative of 1-
phenyl-2-thiocyanatoethanone (entry h) in 89% yield. The
excellent catalytic activity of Amberlyst-15 for the
thiocyanation of acetophenone prompted us to investigate its
use in reactions with other enolizable ketones. Interestingly,
various substituted ketones, such as 2-acetylnaphthalene
(entry i), propiophenone (entry l) and 4-methoxy
acetophenone (entry m) reacted efficiently to afford the
corresponding ꢀ-thiocyanato ketones in excellent yields.
Like acetophenones, cyclic ketones such as 1-tetralone (entry
j), cyclohexanone (entry k) and 2,3-dihydrochromanone
(entry n) were reacted well under similar reaction conditions
to give the ꢀ-ketothionates in very good yields.
In continuation of our interest in developing new
synthetic methodologies [10], we herein report, a simple,
convenient and efficient protocol for the thiocyanation of
aromatic, heteroaromatic and keto compounds with
ammonium thiocyanate using an inexpensive and readily
available catalyst amberlyst-15.
Initially, we studied the thiocyanation of indole as a
model substrate with ammonium thiocyanate in presence of
Amberlyst-15, in acetonitrile. The reaction was completed
within 3 hours at room temperature and the corresponding
*Address correspondence to this author at the Department of Chemistry,
Osmania University, Hyderabad, 500007, India; Tel: +91-40-27018541;
Fax: +91-40-27018541; E-mail: rallabaldimr@yahoo.co.in
The reaction most likely proceeds via the formation of
active thiocyanogen (SCN) from Amberlyst-15 and
1570-1786/10 $55.00+.00
© 2010 Bentham Science Publishers Ltd.

A Simple and Efficient Thiocyanation of Indoles, Anilines
Letters in Organic Chemistry, 2010, Vol. 7, No. 5
393
Table 1. Amberlyst 15 Catalyzed Thiocyanation of Indoles and Ketones with NH4SCN
Substrate
Product
Entry
Reaction Time (H)
Yield (%)
SCN
a
3.0
93
N
H
N
H
SCN
b
c
4.0
3.5
86
89
N
N
Me
Me
SCN
Me
N
H
Me
N
H
Br
Br
SCN
d
e
4.0
3.5
86
82
N
N
H
H
N
H
N
H
SCN
NH2
SCN
NH2
f
4.0
3.0
85
89
Me
N
Me
N
Me
g
Me
NCS
O
O
SCN
h
i
5.0
5.0
4.0
4.5
89
92
90
84
O
O
SCN
O
O
SCN
j
O
O
SCN
k

394 Letters in Organic Chemistry, 2010, Vol. 7, No. 5
Lenin and Raju
(Table 1). Contd…..
Yield (%)
Substrate
Product
Entry
Reaction Time (H)
O
O
l
5.0
86
85
SCN
O
O
SCN
m
n
6.0
6.0
MeO
MeO
O
O
O
O
SCN
88
ammonium thiocyanate. All the products were characterized
by 1H NMR, IR and mass spectroscopic data. This method is
very clean and free from side products. The scope and
generality of this protocol are illustrated with respected to
various indoles, anilines, enolizable ketones and cyclic
ketones and the obtained results are presented in Table 1.
products were identified by their spectroscopy data and
compared with literature reports Ref. [4, 5a, 6a, 6b, 8c].
Spectral Data for all Products
3-Thiocyanato-1H-indole (a)
0
In conclusion, we have demonstrated
a
simple,
Off- white solid, mp, 120-122 C, lit. [8c] 125-127. IR
convenient and efficient protocol for the thiocyanation of
indoles, aromatic anilines and ketone compounds using a
polystyrene cation exchange resin Amberlyst-15 as a
catalyst. The notable features of the protocol are mild
reaction conditions, high conversions, simple experimental
procedure and ease of the isolation of products which make
it useful and an alternative process for the thiocyanation of
indoles, aromatic anilines and ketone compounds at room
temperature.
(KBr): ꢀ 3236, 3051, 2934, 2863, 2148, 1562, 1436, 1412,
1
1374, 1235, 1156, 1092, 938, 861, 738, 660 cm-1.: H NMR
(CDCl3): ꢀ 7.30-7.45 (m, 4H), 7.80 (d, 1H, J = 8.5 Hz), 8.90
(brs, 1H, NH). EIMS m/z (%): 174 (m+ 100), 148 (65), 116
(40), 91(15), 88 (18), 76 (12), 61 (10), 51 (20).
1-Methyl-3-thiocyanato-1H-indole(b) [6a]
0
Brown solid, mp, 82-83 C. IR (KBr): ꢀ 3078, 2961,
2834, 2145, 1518, 1460, 1324, 1243, 1106, 1056, 941, 820,
1
739, 665 cm-1.: H NMR (CDCl3): ꢀ 3.80 (s, 3H), 7.30-7.40
(m, 4H), 7.80 (d, 1H, J = 7.5 Hz). EIMS m/z (%): 188 (m+
100), 173 (34), 162 (25), 146 (55), 130 (20), 114 (32), 91
(23), 76 (15), 51 (30).
EXPERIMENTAL SECTION
General Methods
2-Methyl-3-thiocyanato-1H-indole (c)
Melting points were recorded on Buchi R-535 apparatus
and are uncorrected. IR spectra were recorded on a Perkin-
Elmer FT-IR 240-c spectrophotometer using KBr disk. H
NMR spectra were recorded on Gemini-200 spectrometer in
CDCl3 using TMS as internal standard. Mass spectra were
recorded on a Finnigan MAT 1020 mass spectrometer
operating at 70 eV.
Light yellow solid, mp, 100-101 0C, lit. [8c] 102-103. IR
1
(KBr): ꢀ 3328, 3049, 2979, 2853, 2152, 1580, 1458, 1542,
1409, 1369, 1230, 1162, 1053, 971, 815, 739, 658 cm-1.: H
1
NMR (CDCl3): ꢀ 2.56 (s, 3H), 7.22-7.30 (m, 2H) 7.36 (d,
1H, J = 7.5 Hz), 7.70 (d, 1H, J = 7.5 Hz), 8.42 (brs, 1H,
NH). EIMS m/z (%): 188 (m+ 100), 173 (12), 161 (28), 146
(18), 117 (22), 91 (10), 51 (15).
General Procedure
5-Bromo-3-thiocyanato-1H-indole (d) [6a]
0
To a stirred solution of ammoniumthiocyanate (2mmol)
and indole (1mmol) in acetonitrile the catalyst Amberlyst-15
(1mmol) was added. The resulting reaction mixture was
stirred for appropriate time (Table 1). After completion of
the substrate as indicated by TLC, the reaction mixture was
filtered and the catalyst was washed with solvent (2x10ml).
The combined filtrates were concentrated under reduced
pressure. The crude compound was dissolved in ethyl acetate
and washed with water followed by brine and dried over
Na2SO4. The obtained product was purified by column
chromato-graphy using silica gel 60-120 mesh. All the pure
Yellow solid, mp, 125-126 C. IR (KBr): ꢀ 3326, 3047,
2938, 2850, 2124, 1533, 1451, 1409, 1265, 1105, 1043, 921,
843, 795, 650 cm-1.: 1H NMR (CDCl3): ꢀ 7.30 (d, 1H, J = 8.5
Hz), 7.40 (dd, 1H, J = 8.5 & 1.5 Hz), 7.55 (d, 1H, J = 3.0
Hz), 7.90 (s, 1H), 8.70 (brs, 1H, NH). EIMS m/z (%): 253
(m+ 30), 227 (12), 195 (10), 173 (100), 146 (20), 114 (15),
90 (22), 85 (10), 50 (15).
2-Thiocyanato pyrrole (e) [8c]
Light red oily mass. IR (neat): ꢀ 3392, 2905, 2128, 1465,
1380, 1208, 1120, 1051, 973, 847, 740, 665 cm-1.: 1H NMR

A Simple and Efficient Thiocyanation of Indoles, Anilines
Letters in Organic Chemistry, 2010, Vol. 7, No. 5
395
(CDCl3): ꢀ 6.30 (dd, 1H, J = 6.0 & 2.0 Hz), 6.65 (s, 1H),
6.98 (s, 1H), 8.85 (brs, 1H, NH). EIMS m/z (%): 124 (m+
100), 98 (15), 66 (20), 51 (12), 41 (18).
3H), 4.35 (s, 2H), 6.90-6.98 (m, 2H), 7.60-7.68 (m, 2H).
EIMS m/z (%): 207 (m+ 22), 192 (35), 181 (10), 176 (100),
149 (75), 134 (10), 118 (22), 104 (10), 88 (12), 76 (80), 51
(25).
4-Thiocyanatoaniline (f)
2,3-Dihydro-3-thiocyanatochromen-4-one (n) [6b]
0
White solid, mp, 50-51 C, lit. [8c] 49-51. IR (KBr): ꢀ
3341, 3051, 2925, 2857, 2145, 1633, 1591, 1508, 1467,
Colorless oily mass.IR (KBr): ꢀ 3079, 2930, 2843, 2156,
1648, 1605, 1596, 1506, 1461, 1373, 1239, 1163, 1015, 961,
843, 738, 649 cm-1.: 1H NMR (CDCl3): ꢀ 3.15-3.25 (m, 2H),
4.38-4.45 (m, 1H), 6.90 (d, 1H, J = 9.5 Hz), 7.25-7.35 (m,
2H), 7.50-7.60 (m, 1H). EIMS m/z (%): 205 (m+ 35), 179
(20), 147 (10), 104 (100), 76 (15), 51 (12).
1
1345, 1295, 1172, 1038, 950, 821, 740 cm-1.: H NMR
(CDCl3): ꢀ 3.92 (brs, 2H), 6.62 (d, 2H, J = 8.0 Hz), 7.42 (d,
2H, J = 8.0 Hz). EIMS m/z (%): 150 (m+ 100), 125 (68), 91
(18), 76 (30), 51 (20).
N,N-Dimethyl-4-thiocyanatoaniline (g)
Light red solid, mp, 71-72 0C, lit. [8c] 72-74. IR (KBr): ꢀ
3058, 2963, 2857, 2135, 1586, 1505, 1478, 1370, 1235,
1162, 1078, 981, 805, 743 cm-1.: 1H NMR (CDCl3): ꢀ 3.02
(s, 6H), 6.68 (d, 2H, J = 8.5 Hz), 7.45 (d, 2H, J = 8.5 Hz).
EIMS m/z (%): 178 (m+ 100), 163 (18), 152 (30), 148 (12),
134 (12), 120 (15), 108 (25), 90 (10), 76 (50), 51 (35).
REFERENCES AND NOTES
[1]
Guy, R.G. The Chemistry of Cyanates and their thioderivatives:
Part 2, Chapt. 18, Patai, S: Ed: John Wiles & Sons: New York,
1977, p. 819.
[2]
(a) Wood, J. L. Organic Reactions: Wiles, New York, 1946, Vol. 3,
240. (b) Kelly, T. R.; Kim, M. H.; Cetris, A. D. M. Structure
Correction and Synthesis of the naturally occurring
benzothiazinone BMY 40662. J. Org. Chem., 1993, 58, 5855.
Falck, J. R.; Gao, S.; Prasad, R. N.; Reddy, K. S. Electrophilic ꢁ -
Thiocyanation of chiral and achiral N-acyl imides: a convenient
route to 5- substituted and 5,5-disubsituted 2,4-thiazolidinediones.
Bioorg. Med. Chem. Lett., 2008, 18, 1768.
Iranpoor, N.; Firouzabadi, H.; Nowrouzi, N. Preparation of
thiocyanates and isothiocyanates from alcohols, thiols, trimethyl-
silyl-, and tetrahydropyranyl ethers using triphenylphosphine/2,3-
dichloro-5,6-dicyanobenzoquinone (DDQ)/n-Bu4NSCN system.
Tetrahedron, 2006, 62, 5498.
1-Phenyl-2-thiocyanatoethanone (h) [5a]
0
[3]
[4]
Off-white solid, mp, 78-80 C. IR (KBr): ꢀ 3071, 2953,
2839, 2156, 1628, 1605, 1542, 1415, 1353, 1243, 1171,
1061, 973, 854, 747, 650 cm-1.: 1H NMR (CDCl3): ꢀ 4.85 (s,
2H), 7.60-7.70 (m, 3H), 7.80-7.90 (m, 2H). EIMS m/z (%):
177 (m+ 50), 151 (20), 119 (15), 105 (100), 77 (22), 51 (15).
1-(Naphthalen-6-yl)-2-Thiocyanatoethanone (i)
Light yellow solid, mp, 101-102 0C, lit. [8c] 102-104. IR
[5]
[6]
(a) Yadav, J. S.; Reddy, B. V. S.; Reddy, U. V. S.; Krishna, A. D.
Iodine /MeOH as a novel and versatile reagent system for the
synthesis of ꢁ - ketothiocyanates. Tetrahedron Lett., 2007, 48,
5243. (b) Koser, G. F.; Telu, S.; Laali, K. K. Oxidative-substitution
reactions of polycyclic aromatic hydrocarbons with iodine (III)
sulfonate reagents. Tetrahedron Lett., 2006, 47, 7011.
(a) Wu, G.; Liu, Q.; Sheu, Y.; Wu, W.; Wu, L. Regioselective
thiocyanation of aromatic and heteroaromatic compounds using
ammonium thiocyanate and oxone. Tetrahedron Lett., 2005, 46,
5831. (b) Kumar, A.; Ahamd, P.; Maurya, R. A. Direct ꢁ -
thiocyanation of carbonyl and ꢂ-dicarbonyl compounds using
potassium peroxydisulfate-copper(II). Tetraedron Lett., 2007, 48,
1399. (c) Pezzella, A.; Palma, A.; Iadonisi, A.; Napolitano, A.;
d’Ischia, M. The first entry to 5,6-dihydroxy-3-mercaptoindole, 5-
hydroxy-3-mercaptoindole and their 2-carbomethoxy derivatives
by a mild thiocyanation/reduction methodology. Tetrahedron Lett.,
2007, 48, 3883.
(KBr): ꢀ 3053, 2986, 2847, 2153, 1659, 1620, 1538, 1455,
1
1406, 1347, 1263, 1163, 1056, 981, 826, 734, 667 cm-1.: H
NMR (CDCl3): ꢀ 4.85 (s, 2H), 7.40-7.50 (m, 2H), 7.80-7.90
(m, 4H), 8.40 (s, 1H). EIMS m/z (%): 227 (m+ 65), 201 (22),
169 (100), 127 (18), 102 (15), 76 (25), 51 (30).
3,4-Dihydro-2-thiocyanatonaphthalen-1(2H)-one (j) [5a]
Light yellow oily mass. IR (KBr): ꢀ 3049, 2962, 2838,
2150, 1652, 1618, 1542, 1450, 1408, 1343, 1210, 1103,
1
1016, 931, 812, 739, 652 cm-1.: H NMR (CDCl3): ꢀ 1.90-
2.10 (m, 2H), 2.50-2.65 (m, 2H), 4.30-4.40 (m, 1H), 6.90-
6.98 (m, 2H), 7.40-7.50 (m, 2H). EIMS m/z (%): 203 (m+
100), 177 (15), 143 (35), 104 (75), 76 (20), 51 (10).
[7]
[8]
(a) Chakrabarty, M.; Sarkar, S. A clay-mediated eco-friendly
thiocyanation of indoles and carbazoles. Tetrahedron Lett., 2003,
44, 8131. (b) Nair, V.; George, T. G.; Nair, L. G.; Panicker, S. B. A
direct synthesis of aryl thiocyanates using cerium(IV) ammonium
nitrate. Tetrahedron Lett., 1999, 40, 1195.
(a) Renard, P. Y.; Schwebel, H.; Vayron, P.; Leclerc, E.; Dias, S.;
Mioskowski, C. Optimized access to alkyl thiocyanates.
Tetrahedron Lett., 2001, 42, 8479. (b) Suzuki, Y.; Kodomari, M.
One- pot synthesis using supported reagents system: conversion of
ꢂ-dicarbonyl compounds to ꢁ –thiocyano- ꢂ-dicarbonyl compounds
using CUBr2/Al2O3- KSCN/SiO2. Chem. Lett., 1998, 1091. (c)
Yadav, J. S.; Reddy, B. V. S.; Krishna, A. D.; Reddy, C. S.;
Narsaiah, A. V. Ferric(III) Chloride- promoted electrophilic
thiocyanation of aromatic and heteroaromatic compounds.
Synthesis., 2005, 961.
(a) Yadav, J. S.; Reddy, B. V. S.; Sekar, K. C.; Sekar, D. G.
Amberlyst-15 catalyzed novel synthesis of tetrahydropyranols.
Synthesis, 2001, 885. (b) Kalena, G. P.; Jain, A.; Benerji, A.
Amberlyst 15 catalyzed prenylation of phenols: One –step
synthesis of benzopyrans. Molecules, 1997, 100.
Lenin, R.; Madhusudhan Raju, R. Lanthanum trichloride: an
efficient Lewis acid catalyst for chemo and regioselective
enamination of ꢂ-dicarbonyl compounds. ARKIVOC, 2007, XIII,
204.
2-Thiocyanatocyclohexanone (k) [5a]
Light yellow oily mass. IR (KBr): ꢀ 1678, 1623, 1595,
1538, 1467, 1418, 1326, 1241, 1178, 1095, 1015, 964, 1249,
786, 694, 639 cm-1.: 1H NMR (CDCl3): ꢀ 1.60-1.95 (m, 5H),
2.40-2.80 (m, 3H), 3.95-4.15 (m, 1H). EIMS m/z (%): 155
(m+ 100), 129 (10), 97 (40), 81 (10), 55 (10).
1-Phenyl-2-thiocyanatopropan-1-one (l) [6b]
Light red oil. IR (neat): ꢀ 3078, 2956, 2843, 2146, 1626,
1532, 1405, 1347, 1251, 1132, 1015, 963, 851, 747, 689 cm-
1.: 1H NMR (CDCl3): ꢀ1.23 (t, 3H, J = 6.0 Hz), 4.75 (q, 1H, J
= 6.0 Hz), 7.35-7.45 (m, 3H), 7.76-7.86 (m, 2H). EIMS m/z
(%): 191 (m+ 100), 165 (14), 133 (28), 105 (80), 77 (20), 51
(20).
[9]
1-(4-Methoxyphenyl)-2-thiocyanatoethane (m) [6b]
[10]
Low melting off-white solid. IR (KBr): ꢀ 3051, 2947,
2872, 2150, 1639, 1608, 1542, 1435, 1357, 1233, 1103,
1026, 971, 836, 738, 672 cm-1.: 1H NMR (CDCl3): ꢀ 3.70 (s,