Efficient one-pot synthesis of unsymmetrical 2-thioparabanic acids from oxalyl chloride, benzoyl isothiocyanate, and primary amines

Article abstract of DOI:10.1055/s-2008-1077872

An efficient synthesis of unsymmetrical 2-thioparabanic acids is described via a three-component reaction between benzoyl isothiocyanate and primary amines in the presence of oxalyl chloride. Thieme Stuttgart.

Full text of DOI:10.1055/s-2008-1077872

LETTER
1633
Efficient One-Pot Synthesis of Unsymmetrical 2-Thioparabanic Acids from
Oxalyl Chloride, Benzoyl Isothiocyanate, and Primary Amines
One-Pot
s
Synthesis
s
of
U
nsym
a
metrical 2-Thiop
Y
arabanic
A
cids avari,* Sanaz Souri, Mehdi Sirouspour
Chemistry Department, Tarbiat Modares University, P.O. Box 14115-175, Tehran 18716, Iran
Fax +98(21)88006544; E-mail: yavarisa@modares.ac.ir
Received 21 April 2008
S
Abstract: An efficient synthesis of unsymmetrical 2-thioparabanic
acids is described via a three-component reaction between benzoyl
isothiocyanate and primary amines in the presence of oxalyl chlo-
ride.
O
O
S
R
CH2Cl2
r.t.
C
Cl
N
NH
O
+
+
RNH2
Ph
N
Cl
O
O
1
2
3
4
Key word: oxalyl chloride, primary amines, 2-thioparabanic acid,
multicomponent reaction
Yield (%)
1, 4
R
a
Bn
78
75
76
80
b
c
d
4-MeC6H4CH2
4-MeOC6H4CH2
2-ClC6H4CH2
Multicomponent reactions (MCRs) are economically and
environmentally advantageous because multistep synthe-
ses produce considerable amounts of waste mainly due to
complex isolation procedures often involving expensive,
toxic, and hazardous solvents after each step. MCRs are
perfectly suited for combinatorial library syntheses, thus
are finding increasing use in the discovery process for
new drugs and agrochemicals.1–7
e
f
g
4-ClC6H4CH2
t-Bu
1-naphthylmethyl
83
74
90
Scheme 1
O
NR
O
O
S
3
Ph
N
S
The reaction of oxalyl chloride with 1,3-disubstituted
ureas to produce parabanic acids is well known.8–10 The
preparation of 1,3-diisopropyl-2-thioparabanic acid has
been reported via the reaction of 1,3-diisopropylthiourea
with oxalyl chloride in refluxing benzene. The reaction
occurs by attack of oxalyl chloride on the sulfur atom of
the thiourea to form the isomeric iminothiazolidine-4,5-
dione, which gradually forms on standing, or more rapidly
on heating, a yellow solid identified as the 2-thioparaban-
ic acid.11
R
H
1 + 2
Ph
N
N
Cl
– HCl
H
H
O
6
5
NR
O
S
O
H2O
– PhCOOH
N
N
Ph
S
4
Ph
NR
O
O
O
O
7
8
As part of our current studies on the development of new
routes in heterocyclic synthesis,12–15 we report herein an
efficient one-pot synthesis of unsymmetrical 2-thiopara-
banic acids16 from primary amines, benzoyl isothiocyan-
ate, and oxalyl chloride (Scheme 1).
Scheme 2
spectra of 4b–g are similar to those for 4a except for the
alkyl moiety, which showed characteristic resonances in
appropriate regions of the spectrum.
The structures of compounds 4a–g were apparent from
A tentative mechanism for this transformation is proposed
in Scheme 2. It is conceivable that the initial event is the
formation of the substituted thiourea 5 from the amine and
benzoyl isothiocyanate, which is subsequently attacked
by oxalyl chloride to produce 6. Intermediate 6 undergoes
cyclization to produce 7, which undergoes isomerization
to yield 8. Compound 4 is apparently formed by addition
of adventitious water to 8, followed by elimination of ben-
zoic acid.
their mass spectra, which displayed in each case the mo-
1
lecular ion peak at the appropriate m/z values. The H
NMR and 13C NMR spectroscopic data, as well as IR
spectra, are in agreement with the proposed structures.
1
The H NMR spectrum of 4a in CDCl3 showed two sin-
glets for methylene (d = 5.10 ppm) and NH (d = 11.71
ppm) protons, along with a multiplet (d = 7.28–7.48 ppm)
for the aromatic protons. The 13C NMR spectrum of 4a ex-
hibited eight signals in agreement with the proposed struc-
ture. Partial assignments of these resonances are given in
In conclusion, we have described a convenient route to
unsymmetrical 2-thioparabanic acids from oxalyl chloride
and benzoyl isothiocyanate in the presence of primary
amines. The advantage of the present procedure is that the
reaction is performed under neutral conditions by simple
1
the experimental section.16 The H NMR and 13C NMR
SYNLETT 2008, No. 11, pp 1633–1634
x
x
.x
x
.2
0
0
8
Advanced online publication: 11.06.2008
DOI: 10.1055/s-2008-1077872; Art ID: D12808ST
© Georg Thieme Verlag Stuttgart · New York

1634
I. Yavari et al.
LETTER
(12) Yavari, I.; Souri, S. Synlett 2007, 2969.
(13) Moradi, L. Helv. Chim. Acta 2006, 89, 1942.
(14) Yavari, I.; Sabbaghan, M.; Hossaini, Z. Synlett 2006, 2501.
(15) Yavari, I.; Ghazanfarpour-Darjani, M.; Sabbaghan, M.;
Hossaini, Z.; Hosseini, N. Synlett 2008, 889.
mixing of the starting materials. The procedure described
here provides an acceptable one-pot method for the prep-
aration of functionalized 2-thioparabanic acids.
(16) 1-Benzyl-2-thioxodihydro-1H-imidazole-4,5-dione (4a)
To a stirred solution of benzoyl isothiocyanate (0.32 g, 2
mmol) and benzylamine (0.20 g, 2 mmol) in CH2Cl2 (10 mL)
was added oxalyl chloride (0.25 g, 2 mmol) at r.t. The
reaction mixture was then stirred for 12 h. The solvent was
removed under reduced pressure and the viscous residue was
purified by flash column chromatography on SiO2 (Merck
230–400 mesh) using hexane–EtOAc as eluent to give 4a as
yellow powder; mp 151–153 °C, yield 0.30 g (70%). IR
(KBr): nmax = 3220, 1764, 1735, 1666, 1441, 1340 cm–1.
1H NMR (500 MHz, CDCl3): d = 5.10 (2 H, s, NCH2), 7.28
(1 H, d, 3J = 7.1 Hz, CH), 7.32 (2 H, t, 3J = 7.6 Hz, CH), 7.41
(2 H, d, 3J = 7.3 Hz, CH), 11.71 (1 H, br s, NH) ppm.
13C NMR (125 MHz, CDCl3): d = 45.0 (NCH2), 128.6 (CH),
129.0 (CH), 129.2 (CH), 136.2 (CH), 156.8 (C=O), 157.3
(C=O), 182.7 (C=S) ppm. MS: m/z (%) = 222 (4) [M+ + 2],
221 (10) [M+ + 1], 220 (64) [M+], 91 (26), 77 (60), 59 (20),
45 (60). Anal. Calcd (%) for C10H8N2O2S (220.24): C, 54.53;
H, 3.66; N, 12.72. Found: C, 54.41; H, 3.70; N, 12.65.
References and Notes
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28, 1805.
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Synlett 2008, No. 11, 1633–1634 © Thieme Stuttgart · New York