A clay-mediated eco-friendly thiocyanation of indoles and carbazoles

Article abstract of DOI:10.1016/j.tetlet.2003.09.032

Indoles 1a-f and carbazoles 3a-c on treatment with ammonium thiocyanate on montmorillonite K10 clay at 80°C furnished the corresponding 3-thiocyanato derivatives 2a-f and 4a-c in good to high yields. Skatole 5 furnished the dimeric oxindole 6, which resulted from autoxidation.

Full text of DOI:10.1016/j.tetlet.2003.09.032

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 44 (2003) 8131–8133
A clay-mediated eco-friendly thiocyanation of indoles and
carbazoles
Manas Chakrabarty* and Sandipan Sarkar
Department of Chemistry, Bose Institute, 93/1, A.P.C. Road, Kolkata 700009, India
Received 21 July 2003; revised 14 August 2003; accepted 3 September 2003
Abstract—Indoles 1a–f and carbazoles 3a–c on treatment with ammonium thiocyanate on montmorillonite K10 clay at 80°C
furnished the corresponding 3-thiocyanato derivatives 2a–f and 4a–c in good to high yields. Skatole 5 furnished the dimeric
oxindole 6, which resulted from autoxidation.
© 2003 Elsevier Ltd. All rights reserved.
Thiocyanation of arenes and heteroarenes is a very
useful reaction in organic synthesis since it constitutes a
direct method for the introduction of sulphur into aryl
rings and the thiocyanate group can be converted into
other sulphur-bearing functionalities.1 Thiocyanations
have earlier been achieved utilising varied reagents and
conditions,2,3 most of which are cumbersome and utilise
toxic metal thiocyanates and reagents. Thiocyanation of
indoles has been achieved only three times using
bromine and potassium thiocyanate (only for indole),3a
N-thiocyanatosuccinimide3b (only for 5-methoxy-2-
methylindole, forming two bisthiocyanates) and ammo-
nium thiocyanate in the presence of ceric ammonium
nitrate in methanol.3c In continuation of our interests in
exploring the potential of montmorillonite K10 clay and
in the solvent-free reactions and synthesis of heteroaro-
matics,4 we have now developed a solvent-free method
for the thiocyanation of indoles and carbazoles using
ammonium thiocyanate and montmorillonite K10 clay.
Initially, a solution of indole 1a and 3 equiv. of ammo-
nium thiocyanate in the required minimum volume of
methanol was adsorbed on montmorillonite K10 clay
and the solvent was allowed to evaporate off at room
temperature. The reaction mixture was kept at 80°C in
an oven until completion of the reaction. Leaching of
the clay with dichloromethane furnished 3-thiocyana-
toindole 2a3a,c in a very good yield. This method was
applied to a number of other 3-unsubstituted indoles
1b–f and the reaction succeeded in all cases.5 The indole
Scheme 1.
Keywords: thiocyanation; indoles; carbazoles; montmorillonite clay; ammonium thiocyanate.
* Corresponding author. Fax: +91-33-2350-6790; e-mail: chakmanas@yahoo.co.in
0040-4039/$ - see front matter © 2003 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2003.09.032

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M. Chakrabarty, S. Sarkar / Tetrahedron Letters 44 (2003) 8131–8133
Table 1. Thiocyanation of indoles (1a–f) and carbazoles (3a–c) with NH4SCN (3 equiv.) on montmorillonite K10 clay at
80°C
Entry
Substratea
X
R
R%
Product
Time (h)
Yield (%)b
1
2
3
4
5
6
7
8
1a
1b
1c
1d
1e
1f
H
H
H
Br
OMe
NO2
H
–
–
H
H
Me
H
H
H
Ac
H
Me
H
–
H
Me
H
H
H
H
H
H
H
Me
–
2a3a,c (Lit.3a mp 76.5–78°C)
2
3
2.5
2
2
4
24
8
10
8
85
92
89
80
90
89
–
72
65
80
45
2b3c
2c3c
2d
2e
2f6
1gc
3a
3b
3c
5
–
4a7
9
10
11
4b
4c
–
–
68 (Lit. mp 222–224°C)
48
a 1 mmol of substrates was used.
b Isolated yields. No attempt was made to optimise the yields.
c No reaction took place.
Scheme 2.
1f required a somewhat longer period to furnish 2f,6
which is clearly due to the electron-withdrawing effect
of the nitro group. This effect was confirmed when
N-acetylindole 1g failed to undergo thiocyanation even
after a prolonged period. The reaction was then
extended to carbazoles 3a–c when the 3-thiocyanatocar-
bazoles 4a–c7 were obtained in good yields. The reac-
tions are shown in Scheme 1 and the results in Table 1.
The isolation of the products involved an easy work-up,
as in case of indole itself.
tans, sulphonic acids, sulfides, disulfides, thiocarbonic
acid amides, etc., this eco-friendly thiocyanation proce-
dure can be employed for synthesising sulphur-bearing
condensed indoles and carbazoles.
Acknowledgements
The authors sincerely thank the Director, the Bose
Institute for laboratory facilities, the CSIR, Govern-
ment of India for providing a fellowship (S.S.), Mr. B.
Majumder, NMR Laboratory, Mr. J. Chatterjee, RSIC,
and Mr. P. Dey, Microanalytical Laboratory, all of
Bose Institute, for recording the spectra.
Skatole (5) behaved differently. Similar treatment
required the unusually long period of 48 h for comple-
tion and furnished the dimer 6, instead of the expected
2-thiocyanato derivative (Scheme 2). This dimer may be
considered to have been formed by the autoxidation of
5, since skatole alone, when similarly adsorbed on
montmorillonite K10 clay and heated at 80°C, fur-
nished 6 as the only product. This dimer has been
reported earlier having been formed from skatole and
N-chlorosuccinimide.8
References
1. (a) Wood, J. L. In Organic Reactions; Adams, R., Ed.;
John Wiley and Sons: New York, 1946; p. 240; (b) Guy,
R. G. In The Chemistry of Cyanates and their Thio Deriva-
tives; Patai, S., Ed.; John Wiley and Sons: New York,
1977; Part 2, p. 819.
2. (a) So¨derback, E. Acta. Chem. Scand. 1954, 8, 1851; (b)
Angus, A. B.; Bacon, R. G. R. J. Chem. Soc. 1958, 774; (c)
Uemura, S.; Uchida, S.; Okano, M.; Ichikawa, K. Bull.
Chem. Soc. Jpn. 1973, 46, 3254; (d) Uemura, S.; Onoe, A.;
Okazaki, H.; Okano, M. Bull. Chem. Soc. Jpn. 1975, 48,
619; (e) Kita, Y.; Takada, T.; Mihara, S.; Whelan, B. A.;
To conclude, we have developed the first solvent-free
protocol for a simple but effective thiocyanation of
indoles and carbazoles, which is mild, clean, does not
employ any toxic reagent and furnishes the thio-
cyanates in good to high yields following a simple
isolation procedure. Indoles and carbazoles constitute
core units of numerous biologically active compounds.
Since the thiocyanates can be converted into mercap-

M. Chakrabarty, S. Sarkar / Tetrahedron Letters 44 (2003) 8131–8133
8133
1
Tohma, H. J. Org. Chem. 1995, 60, 7144; (f) Khazei, A.;
Alizadeh, A.; Vaghei, R. G. Molecules 2001, 6, 253.
3. (a) Grant, M. S.; Snyder, H. R. J. Am. Chem. Soc. 1960,
82, 2742; (b) Toste, F. D.; Stefano, V. D.; Still, I. W. J.
Synth. Commun. 1995, 25, 1277; (c) Nair, V.; George, T.
G.; Nair, L. G.; Panicker, S. B. Tetrahedron Lett. 1999, 40,
1195.
4. (a) Chakrabarty, M.; Ghosh, N.; Basak, R.; Harigaya, Y.
Tetrahedron Lett. 2002, 43, 4075; (b) Chakrabarty, M.;
Sarkar, S. Tetrahedron Lett. 2002, 43, 1351.
5. General procedure for thiocyanation: A solution of indoles/
carbazoles (1 mmol) and NH4SCN (3 mmol) in MeOH (2
ml) was adsorbed on montmorillonite K10 clay (2 g) and
the methanol was allowed to evaporate off at room tem-
perature when the clay turned reddish brown in colour.
The clay with substrates adsorbed was kept at 80°C until
completion of the reaction (TLC). The clay was then
leached with CH2Cl2 (3×10 ml) and the products were
purified by crystallisation. Of the products, only 2a–c and
6 are known. All products were identified by IR, LR
EI-MS, elemental analysis, H (500 MHz), 13C (125 MHz)
and DEPT 135 NMR spectra.
6. 2f: Yellow fluffy flakes, mp 210–212°C (CH2Cl2); IR
(Nujol): 3370, 2163 (SCN), 1527 and 1328 (NO2), 1083,
738 cm−1; H NMR (DMSO-d6): l 12.61 (1H, br s), 8.52
1
(1H, d, J=2 Hz), 8.26 (1H, s), 8.12 (1H, dd, J=9, 2 Hz),
7.70 (1H, d, J=9 Hz); 13C NMR: l 143.0, 140.3, 127.7,
112.7, 94.0 (all C), 137.9, 119.0, 115.2, 114.5 (all CH); MS:
m/z 219 (M+; 100%), 173 (65), 146 (54), 119 (26).
7. 4a: Pale yellow needles, mp 98–100°C (CH2Cl2–petroleum
ether); IR (Nujol): 3416, 2150 (SCN), 1600, 758 cm−1; H
1
NMR (DMSO-d6): l 8.34 (1H, br s), 8.24 (1H, s), 8.02
(1H, d, J=8 Hz), 7.54 (1H, dd, J=8.5, 1.5 Hz), 7.48 (1H,
d, J=8 Hz), 7.45 (1H, t, J=8 Hz), 7.39 (1H, d, J=8.5
Hz), 7.29 (1H, t, J=7.5 Hz); 13C NMR: l 140.5, 140.3,
125.2, 122.5, 113.0, 112.5 (all C), 130.0, 127.5, 125.6, 121.0,
120.8, 112.7, 111.4 (all CH); MS: m/z 224 (M+; 100%), 197
(16), 191 (47).
8. Powers, J. C. J. Org. Chem. 1966, 31, 2627.