Triphosgene: An efficient catalyst for synthesis of isothiocyanates

Article abstract of DOI:10.1080/00397910801997744

Isothiocyanates are bioactive molecules that show various biological activities such as antifungal and anathematic activities. They play a vital role in the synthesis of various heterocyclic compounds. Various isothiocyanates were prepared in good to high yield using triphosgene. Copyright Taylor & Francis Group, LLC.

Full text of DOI:10.1080/00397910801997744

This article was downloaded by: [Monash University Library]
On: 17 May 2013, At: 04:27
Publisher: Taylor & Francis
Informa Ltd Registered in England and Wales Registered Number: 1072954
Registered office: Mortimer House, 37-41 Mortimer Street, London W1T 3JH,
UK
Synthetic Communications: An
International Journal for Rapid
Communication of Synthetic
Organic Chemistry
Publication details, including instructions for
authors and subscription information:
http://www.tandfonline.com/loi/lsyc20
Triphosgene: An Efficient
Catalyst for Synthesis of
Isothiocyanates
A. C. Chaskar a , S. Yewale a , R. Bhagat a & B. P.
Langi a
a C. K. Thakur Research Center, Navi Mumbai, India
Published online: 12 Jun 2008.
To cite this article: A. C. Chaskar , S. Yewale , R. Bhagat & B. P. Langi (2008):
Triphosgene: An Efficient Catalyst for Synthesis of Isothiocyanates, Synthetic
Communications: An International Journal for Rapid Communication of Synthetic
Organic Chemistry, 38:12, 1972-1975
To link to this article: http://dx.doi.org/10.1080/00397910801997744
PLEASE SCROLL DOWN FOR ARTICLE
Full terms and conditions of use: http://www.tandfonline.com/page/terms-
and-conditions
This article may be used for research, teaching, and private study purposes.
Any substantial or systematic reproduction, redistribution, reselling, loan,
sub-licensing, systematic supply, or distribution in any form to anyone is
expressly forbidden.
The publisher does not give any warranty express or implied or make any
representation that the contents will be complete or accurate or up to
date. The accuracy of any instructions, formulae, and drug doses should be

independently verified with primary sources. The publisher shall not be liable
for any loss, actions, claims, proceedings, demand, or costs or damages
whatsoever or howsoever caused arising directly or indirectly in connection
with or arising out of the use of this material.

Synthetic Communications1, 38: 1972–1975, 2008
Copyright # Taylor & Francis Group, LLC
ISSN: 0039-7911 print/1532-2432 online
DOI: 10.1080/00397910801997744
Triphosgene: An Efficient Catalyst for Synthesis
of Isothiocyanates
A. C. Chaskar, S. Yewale, R. Bhagat, and B. P. Langi
C. K. Thakur Research Center, Navi Mumbai, India
Abstract: Isothiocyanates are bioactive molecules that show various biological
activities such as antifungal and anathematic activities. They play a vital role in
the synthesis of various heterocyclic compounds. Various isothiocyanates were
prepared in good to high yield using triphosgene.
Keywords: Amines; Carbondisulphide; Dithiocarbamate; Isothiocyanates;
Triethylamine; Triphosgene
INTRODUCTION
Isothiocyanates are key constituents in numerous natural products and a
variety of biologically active compounds. They are also used extensively
in organic synthesis.[1]
Isothiocyanates have been used in the synthesis of various hetero-
cyclic compounds,[1] agrochemicals having antifungal and anathematic
activities.[2] Several sesquiterpene isothiocyanates have been isolated
from marine natural products.[3]
Numerous methods have been reported for the synthesis of isothio-
cyanates from amines.[4] Synthesis of isothiocyanates from isocyanides,[5]
organic halides,[6] olefins,[7] aldoximes,[8] and nitriles oxides[9] have also
been reported. However, these methods suffer from low yields and have
isocyanate derivatives.
Received December 28, 2007
Address correspondence to A. C. Chaskar, C. K. Thakur Research Center,
Navi Mumbai, 410206, India. E-mail: achaskar@rediffmail.com
1972

Triphosgene: An Efficient Catalyst for Synthesis
1973
Scheme 1. Synthesis of Isothiocyanate.
RESULTS AND DISCUSSION
Amines were added dropwise to a solution containing methanol, triethy-
lamine, and carbon disulphide at 0–5 ꢀC to form dithiocarbamate salt. In
the case of aniline and higher base-strength amines, precipitation of the
dithiocarbamate began within few minutes, whereas lower base-strength
amines (viz., p-bromoaniline) required several hours under the same con-
ditions for appearance of the dithiocyanates derivatives. The dithiocarba-
mate salt was further treated with triphosgene and chloroform at 0 to
Table 1. Synthesis of isothiocyanates using triphosgene
Sr. no.
Structure
C6H5NCS
Yield (%)
Bp ꢀC
Mp ꢀC
1
2
3
4
5
6
7
8
9
84
82
81
85
86
95
95
106
126
131
130
158
167
146
—
—
—
—
—
—
—
—
—
—
—
—
49
47
69
—
—
o-CH3-C6H4NCS
m-CH3-C6H4NCS
p-CH3-C6H4NCS
o-CH3O-C6H4NCS
p-CH3O-C6H4NCS
p-HO-C6H4NCS
p-Br-C6H4NCS
76
72
p-Cl-C6H4NCS
10
11
12
p-(CH3)2-C6H4NCS
p-CN-C6H4NCS
p-NO2-C6H4NCS
80
No reaction
No reaction
13
84
210
—

1974
A. C. Chaskar et al.
À2 ꢀC with stirring for 4 h. The reaction mixture was quenched by dil.
HCl, and the separated organic layer was washed with water. Chloroform
was distilled out, and the pure isothiocyanate was isolated by high
vacuum distillation (Scheme 1).
CONCLUSION
Various isothiocyanates were prepared in good to high yield using
triphosgene (Table 1). The advantages of the reported process are the
use of a cheap and easily available catalyst, moderate reaction conditions,
easy workup, and better yields.
EXPERIMENTAL
Melting points were taken in open capillaries. The IR spectra were
recorded on a Perkin-Elmer 257 spectrometer using KBr discs. 1H
NMR and 13C NMR spectra in DMSO-d6 were recorded on VXR300-
MHz using TMS as internal standard, and mass spectra were recorded
on Shimadzu GC-MS. The homogeneity of the compounds was described
by thin-layer chromatography (TLC) on silica-gel plates. The spots were
developed in an iodine chamber.
General Procedure for the Synthesis of Isothiocyanates
Methanol and triethylamine were added in a round-bottomed, flask and
cooled to 0 ꢀC. In this solution, carbon disulphide was added, and the
mixture was stirred for 10 min. Then the amine was added dropwise for
20–30 min with constant stirring. After complete precipitation of the
triethylammonium dithiocarbamate salt, the solution was filtered; the
solid was washed with diethyl ether and air dried.
The round-bottomed flask was charged with chloroform and chilled
at 0 to À2 ꢀC. At this temperature, triphosgene was added with stirring
for 10 min. The salt was added portionwise with stirring into this mixture,
and the mixture was stirred for 4 h at 0 ꢀC. The reaction mixture was
quenched by dil. HCl by stirring for 30 min. Two layers were separated,
and the organic layer was washed with water. Excess chloroform was
distilled out, and the pure isothiocyanate product was isolated by high
vacuum distillation or recrystallized from ethanol depending on the
physical state of the compound. All the products were confirmed by
1H NMR, IR, and mass spectroscopy, and data were compared with
the literature report.[4]

Triphosgene: An Efficient Catalyst for Synthesis
ACKNOWLEDGMENT
1975
We acknowledge the financial support from the University of Mumbai
and thank S. T. Gadade, principal, C. K. Thakur College, Navi Mumbai.
REFERENCES
1. (a) Mukerjee, A. K.; Ashare, R. Isothiocyanates in the chemistry of hetero-
cycles. Chem. Rev. 1991, 91, 1–24; (b) Sandler, S. R.; Karo, W. Organic Func-
tional Group Preparations, 2nd ed.; Academic Press: New York, 1983; 359–376.
2. (a) Posner, G. H.; Cho, C.-G.; Green, J. V.; Zhang, Y.; Talalay, P. Design and
synthesis of bifunctional isothiocyanate analogs of sulforaphane: Correlation
between structure and potency as inducers of anticarcinogenic detoxication
enzymes. J. Med. Chem. 1994, 37, 170; (b) Arnold, J. T.; Wilkinson, B. P.;
Sharma, S.; Steele, V. E. Evaluation of chemopreventive agents in different
mechanistic classes using a rat tracheal epithelial cell culture transformation.
Assay Cancer Res. 1995, 55, 537; (c) Lieber, E.; Slutkin, R. Diisothiocyanates
and derivatives. J. Org. Chem. 1962, 27, 2214.
3. (a) He, H.; Faulkner, D. J. A sesquiterpene thiocyanate and three sesquiter-
pene isothiocyanates from the sponge Trachyopsis aplysinoides. J. Org. Chem.
1989, 54, 2511; (b) He, H.; Salva, J.; Catalos, R. F.; Faulkner, D. J. Sesquiter-
pene thiocyanates and isothiocyanates from Axinyssa aplysinoides. J. Org.
Chem. 1992, 57, 3191.
4. (a) Kim, S.; Yi, K. Y. Di-2-pyridyl thionocarbonate: A new reagent for the prep-
aration of isothiocyanates and carbodiimides. Tetrahedron Lett. 1985, 26, 1661;
(b) Hodgkins, J. E.; Reeves, W. P. The modified kaluza synthesis, III: The syn-
thesis of some aromatic isothiocyanates. J. Org. Chem. 1964, 29, 3098; (c) Molina,
P.; Alajarin, M.; Arques, A. Convenient improved syntheses of isocyanates or iso-
thiocyanates from amines. Synthesis 1982, 7, 596; (d) Shibanuma, T.; Shiono, M.;
Mukaiyama, T. A convenient method for the preparation of isothiocyanates
using 2-chloropyridinium salt. Chem. Lett. 1977, 6, 573.
5. (a) Fujiwara, S.; Shin-Ike, T.; Sonoda, N.; Aoki, M.; Okada, K.; Miyoshi, N.;
Kambe, N. Novel selenium catalyzed synthesis of isothiocyanates from isocya-
nides and elemental sulfur. Tetrahedron Lett. 1991, 32, 3503.
6. Kitamura, T.; Kobayashi, S.; Taniguchi, H. Photolysis of vinyl halides: Reaction
of photogenerated vinyl cations with cyanate and thiocyanate ions. J. Org.
Chem. 1990, 55, 1801.
7. (a) Cho, C. G.; Posner, G. H. Alkyl and aryl isothiocyanates as masked primary
amines. Tetrahedron Lett. 1992, 33, 3599; (b) Toshimitsu, A.; Uemura, S.; Okano,
M.; Watanabe, N. Reaction of olefins with a mixture of phenylselenenyl chloride
and mercury (II) thiocyanate: Selective syntheses of b-(phenylseleno) alkyl isothio-
cyanates as precursors of vinylic isothiocyanates. J. Org. Chem. 1983, 48, 5246.
8. Kim, J. N.; Jung, K. S.; Lee, H. J.; Son, J. S. A facile one-pot preparation of
isothiocyanates from aldoximes. Tetrahedron Lett. 1997, 38, 1597.
9. Kim, J. N.; Ryu, E. K. A convenient synthesis of isothiocyanates from nitrile
oxides. Tetrahedron Lett. 1993, 34, 8283.