Facile synthesis of coumarinyl isothiocyanate from amino coumarin

Article abstract of DOI:10.1080/00397910902916080

One-pot conversion of amino coumarin to corresponding coumarinyl isothiocyanate using carbon disulfide, iodine, and pyridine is described. In this reaction, pyridine acts as a solvent as well as a catalyst to give coumarinyl isothiocyanate. Excellent yield, short reaction time, and mild reaction conditions make this method a useful synthetic procedure for one-pot preparation of coumarinyl isothiocyanate.

Full text of DOI:10.1080/00397910902916080

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Facile Synthesis of Coumarinyl
Isothiocyanate from Amino Coumarin
Sagar A. Mayekar a , Atul C. Chaskar a & Vinata V. Mulwad a
a Department of Chemistry, Institute of Science, Mumbai, India
Version of record first published: 09 Dec 2009.
To cite this article: Sagar A. Mayekar, Atul C. Chaskar & Vinata V. Mulwad (2009): Facile Synthesis of
Coumarinyl Isothiocyanate from Amino Coumarin, Synthetic Communications: An International Journal
for Rapid Communication of Synthetic Organic Chemistry, 40:1, 46-51
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Synthetic Communications1, 40: 46–51, 2010
Copyright # Taylor & Francis Group, LLC
ISSN: 0039-7911 print=1532-2432 online
DOI: 10.1080/00397910902916080
FACILE SYNTHESIS OF COUMARINYL
ISOTHIOCYANATE FROM AMINO COUMARIN
Sagar A. Mayekar, Atul C. Chaskar, and Vinata V. Mulwad
Department of Chemistry, Institute of Science, Mumbai, India
One-pot conversion of amino coumarin to corresponding coumarinyl isothiocyanate using
carbon disulfide, iodine, and pyridine is described. In this reaction, pyridine acts as a solvent
as well as a catalyst to give coumarinyl isothiocyanate. Excellent yield, short reaction time,
and mild reaction conditions make this method a useful synthetic procedure for one-pot
preparation of coumarinyl isothiocyanate.
Keywords: Amino coumarin; coumarinyl isothiocyanate; iodine; pyridine; pyridinium hydroiodide
Coumarins constitute an important class of benzopyrones, exhibiting a broad
range of biological activities such as anticoagulant,[1] antimicrobial,[2] antibacter-
ial,[3] anticancer,[4] and anti-HIV activity[5]. The interesting biological activities
of the coumarins make them attractive targets in organic synthesis. Similarly, iso-
thiocyanates constitute an important class of compounds in organic chemistry.[6]
The attraction of isothiocyanate as synthons is obviously due to its diverse
reactions and easy availability. It undergoes nucleophilic addition reactions,
cycloaddition to unsaturated systems, Diels–Alder reaction, and reaction with
bifunctional compounds to yield heterocyclic derivatives.[7] Isothiocyanates have
found application in the agrochemical and pharmaceutical industries.[8] They have
attracted attention as potent and selective inhibitors of carcinogenesis in various
animal models.[9]
In view of these observations and in continuation of our work on
coumarin-based heterocycles,[10,11] it was of interest to synthesize new chemical enti-
ties incorporating the two active pharmacophores (namely, coumarin and isothio-
cyanate) in a single molecular framework using aminocoumarin as a basic
building block.
Isothiocyanate can be prepared by various procedures.[12–14] The choice of
method for the preparation of the isothiocyanate depends on the starting com-
pound, which is suitable for the required type of isothiocyanate. From primary
amines, isothiocyanates can be obtained either directly by the action of some sul-
fur compounds (e.g., thiophosgene, dithiocarbamoyl chloride, trichloromethyl
Received January 13, 2009.
Address correspondence to Vinata V. Mulwad, Department of Chemistry, Institute of Science, 15
Madam Cama Road, Mumbai 400032, India. E-mail: vinata_mulwad@hotmail.com
46

FACILE SYNTHESIS OF COUMARINYL ISOTHIOCYANATE
47
sulfide, etc.) or by converting them into suitable intermediate (dithiocarbamates,
dithiocarbazates, thioureas, etc.), which are then decomposed to isothiocyanates
by reaction with various agents. However, these methods are not useful for
amino coumarin, because these methods require highly basic condition and give
poor yields. Also, some of these reagents are hazardous and toxic. Moreover,
many of these recently developed methods require harsh reaction conditions
and have limitations for their applications. Dey and Seshadri[15] synthesized cou-
marinyl isothiocyanate using dicoumarinylthiocarbamide, which decomposed to
isothiocyanates by reaction with acetic anhydride. When used to synthesize iso-
thiocyanates, this method gave poor yields and hence is little used. Development
of a facile synthetic procedure for the preparation of coumarinyl isothiocyanate
is therefore important.
We have developed and report here a facile method for generating a single
isothiocyanate group on a coumarin using iodine as a catalyst under mild con-
ditions (Scheme 1). The use of molecular iodine in organic synthesis has been
known for a long time. In recent years, molecular iodine has received consider-
able attention as an inexpensive, non-toxic, and readily available catalyst for
various organic transformations[16] under mild and convenient conditions
to afford the corresponding products in excellent yields with high selectivity.
In the exploratory studies, the reaction of amino coumarin with carbon disul-
fide in the presence of iodine and pyridine at 0ꢀC was carried out in different solvents
(Table 1). It should be noted that in this proposed reaction, 1 mol of amino coumarin
requires 1 mol of iodine and 2 mol of pyridine and yields 1 mol of coumarinyl isothio-
cyanate and 2 mol of pyridinium hydroiodide. In this reaction, coumarinyl thiourea
is formed as a by-product in a minor amount. The catalyst exhibited high activity in
all the solvents explored, and in every case, good to excellent yields were observed.
Based on this study, pyridine was selected as the solvent for further examination of
this process. Iodine was used as a catalyst to eliminate the hydrogen sulfide to form
hydrogen iodide, and the simultaneous use of pyridine combined immediately with
Scheme 1. Coumarinyl isothiocyanate (2a–h) from amino coumarin (1a–h).

48
S. A. MAYEKAR, A. C. CHASKAR, AND V. V. MULWAD
Table 1. Effect of solvent on the synthesis of coumarinyl isothiocyanate
Reaction
time (h)
Yield
(%)
Entry
Solvent
1
2
3
4
5
Pyridine
THF
3.0
3.0
3.0
3.0
3.0
89
62
45
56
51
Toluene
1,4-Dioxane
CH3CN
the liberated hydrogen iodide to form pyridinium hydroiodide and sulphur.[17] A sol-
ution of iodine in carbon disulfide was added dropwise to a suspension of amino
coumarin in pyridine at 0ꢀC.[18] The contents were stirred for 3.0 h giving coumarinyl
isothiocyanate (2a–h) in moderate to good yield (Table 2).
EXPERIMENTAL
Melting points were taken in open capillaries and are uncorrected. Purity of the
compounds was checked by thin-layer chromatography (TLC). Infrared (IR) spectra
(vmax in cmꢁ1) were recorded on a Perkin Elmer Fourier transform (FT)–IR instru-
ment. NMR (1H and 13C) were measured with a on 300-MHz Jeol NMR AL300
instrument using tetramethylsilane (TMS) as standard and CDCl3 as a solvent,
and mass spectra were determined on a Shimadzu GC-MS QP-2010 instrument.
Typical Procedure
A solution of iodine (10 mmol) in 20 ml of carbon disulfide was added dropwise
to a suspension of amino coumarin (10 mmol) in 15 ml of pyridine at 0ꢀC. The con-
tents were stirred for 3.0 h. A white solid separated out. The reaction mixture was
distilled until all traces of carbon disulfide and pyridine had been driven out. Treat-
ment of the residue with diluted HCl renderd soluble any unaffected amine and pyri-
dine, and it was purified using column chromatography with hexane and ethyl
acetate (90:10) as eluent.
Representative Spectral Data
6-Isothiocyanato-7-methyl-benzopyran-2-one (2a). IR (KBr): 3076, 3030,
2957, 2079, 1726, 1624, 1131, 1103, 887 cmꢁ1. 1H NMR: d 7.60 (d, 1H, J ¼ 9 Hz, C4-
H), 7.33 (s, 1H, C5-H), 7.19 (s, 1H, C8-H), 6.41 (d, 1H, J ¼ 9 Hz, C3-H), 2.48 (s, 3H,
C7-CH3). 13C NMR: d 160.0, 152.3, 142.0, 139.6, 136.8, 127.2, 124.4, 118.7, 117.5,
117.1, 18.9. Mass (m=z %): Mþ 217 (100), 189 (37), 160 (40), 131 (22), 117 (15),
102 (42), 89 (27), 77 (75), 63 (48).
6-Isothiocyanato-4,7-dimethyl-benzopyran-2-one (2b). IR (KBr) 3082,
1
3046, 2962, 2114, 1734, 1620, 1261, 1095, 1024, 872, 801 cmꢁ1. H NMR: d 7.33
(s, 1H, C5-H), 7.11 (s, 1H, C8-H), 6.22 (s, 1H, C3-H), 2.40 (s, 3H, C7-CH3), 2.33

FACILE SYNTHESIS OF COUMARINYL ISOTHIOCYANATE
49
Table 2. Synthesis of coumarinyl isothiocyanate (2a–h) from amino coumarin (1a–h)
Entry
a
Substrate (1)
Product (2)
Yield (%)
Mp (ꢀC)
192–94
89
b
c
84
77
230–32
165–68
d
e
88
69
184–86
115–17
f
71
85
80
165–68
174–76
177–79
g
h
(s, 3H, C4-CH3). 13C NMR: d 160.1, 151.8, 151.2, 139.5, 136.5, 127.1, 121.6, 118.9,
118.8, 115.5, 18.8, 18.6. Mass (m=z %): Mþ 231 (100), 202 (44), 188 (10), 170 (18),
145 (15), 115 (21), 102 (8).

50
S. A. MAYEKAR, A. C. CHASKAR, AND V. V. MULWAD
6-Isothiocyanato-7-methoxy-4-methyl-benzopyran-2-one (2c). IR (KBr)
1
3071, 2965, 2089, 1718, 1632, 1549, 1344, 1313, 1244, 1177, 1107, 850 cmꢁ1. H
NMR: d 7.65 (s, 1H, C8-H), 7.58 (s, 1H, C5-H), 6.35 (s, 1H, C3-H), 3.91 (s, 3H,
C7-OCH3), 2.49 (s, 3H, C4-CH3).
6-Isothiocyanato-benzopyran-2-one (2d). IR (KBr) 3085, 3063, 2084,
1
1721, 1618, 1562, 1179, 1106, 888, 821 cmꢁ1. H NMR: d 7.64 (d, 1H, J ¼ 9 Hz,
C4-H), 7.24–7.40 (m, 3H, C5, C7 & C8-H), 6.48 (d, 1H, J ¼ 9 Hz, C3-H). Mass
(m=z %): Mþ 203 (100), 175 (48), 146 (12), 117 (8), 103 (6), 89 (13).
3-Isothiocyanato-benzopyran-2-one (2e). IR (KBr) 3057, 2952, 2010,
1
1725, 1624, 1450, 1129, 1112, 771, 758 cmꢁ1. H NMR: d 7.25–7.56 (m, 5H). Mass
(m=z %): Mþ 203 (100), 175 (44), 146 (19), 120 (38), 103 (11), 87 (10), 63 (14).
3-Isothiocyanato-7-methoxy-4-methyl-benzopyran-2-one (2f). IR (KBr)
1
3082, 2916, 2008, 1720, 1614, 1554, 1380, 1303, 1253, 1150, 1067, 859 cmꢁ1. H
NMR: d 7.48 (d, 1H, J ¼ 9 Hz, C6-H), 6.90 (d, 1H, J ¼ 9 Hz, C5-H), 6.85 (s, 1H,
C8-H), 3.89 (s, 3H, C7-OCH3), 2.48 (s, 3H, C4-CH3). Mass (m=z %): Mþ 247
(100), 232 (7), 219 (11), 204 (62), 148 (7), 116 (17), 89 (20), 63 (9).
6-Isothiocyanato-4,7,8-trimethyl-benzopyran-2-one (2g). IR (KBr) 3051,
1
2963, 2137, 1738, 1560, 1386, 1260, 1096, 1020, 883, 803 cmꢁ1. H NMR: d 7.33
(s, 1H, C5-H), 6.30 (s, 1H, C3-H), 2.40 (m, 9H, C4,C7, C8-CH3). 13C NMR: d
160.0, 151.6, 150.0, 137.4, 135.5, 126.6, 119.3, 119.2, 118.2, 115.2, 18.6, 15.8, 12.3.
Mass (m=z %): Mþ 245 (100), 216 (30), 202 (18), 184 (21), 174 (9), 159 (16), 128
(14), 115 (22), 108 (11), 91 (16), 77 (20).
7-Isothiocyanato-4-methyl-benzopyran-2-one (2h). IR (KBr): 3076, 3030,
2957, 2079, 1726, 1624, 1131, 1103, 887 cmꢁ1. 1H NMR: d 7.04–7.14 (m, 2H, C8-H &
C6-H), 7.53 (d, 1H, J ¼ 9 Hz, C5-H), 6.16 (s, 1H, C3-H), 2.32 (s, 3H, C4-CH3).
ACKNOWLEDGMENT
Authors are thankful to the director, Institute of Science, for providing the
necessary facility.
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