Investigation of the reaction of dithiocarbamic acid salts with trimethyl orthoformate and styrene epoxide

Article abstract of DOI:10.1016/j.tetlet.2015.11.033

The reaction of dithiocarbamic acid salts with trimethyl orthoformate in the presence of BF₃·OEt₂ was investigated to give 4-(N,N-dialkyldithiocarbamato)-2-dialkyliminio-1,3-dithietane tetrafluoroborates in good yields. Additionally, a one-pot procedure for the synthesis of 2-iminium-1,3-dithiolanes from the BF₃·OEt₂ catalyzed reaction of dithiocarbamic acid salts with styrene epoxide is described.

Full text of DOI:10.1016/j.tetlet.2015.11.033

Accepted Manuscript
Investigation of the reaction of dithiocarbamic acid salts with trimethyl ortho-
formate and styrene epoxide
Azim Ziyaei Halimehjani, Mojtaba Hajilou Shayegan, Shiva Shakori Poshteh,
Vahid Amani, Behrouz Notash, Mohammad M. Hashemi
PII:
S0040-4039(15)30341-5
DOI:
http://dx.doi.org/10.1016/j.tetlet.2015.11.033
TETL 46973
Reference:
To appear in:
Tetrahedron Letters
Received Date:
Revised Date:
Accepted Date:
11 May 2015
20 October 2015
10 November 2015
Please cite this article as: Halimehjani, A.Z., Shayegan, M.H., Poshteh, S.S., Amani, V., Notash, B., Hashemi, M.M.,
Investigation of the reaction of dithiocarbamic acid salts with trimethyl orthoformate and styrene epoxide,
Tetrahedron Letters (2015), doi: http://dx.doi.org/10.1016/j.tetlet.2015.11.033
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1
Tetrahedron Letters
Investigation of the reaction of dithiocarbamic acid salts with trimethyl orthoformate
and styrene epoxide
,
a
b
d
c
Azim Ziyaei Halimehjani,* Mojtaba Hajilou Shayegan, Shiva Shakori Poshteh, Vahid Amani, Behrouz
e
b
Notash, Mohammad M. Hashemi
a
Faculty of Chemistry, Kharazmi University, 49 Mofateh St., Tehran, Iran. Tel.: +98(21)88848949, Fax: +98(21)88820992. Email address: ziyaei@khu.ac.ir
Department of Chemistry, Sharif University of Technology, P.O. Box 11465-9516, Tehran, Iran.
Islamic Azad University, Pharmaceutical Science Branch (IAUPS), No. 99, Yakhchal Gholhak, Shariati, Tehran
Department of Chemistry, Yadegar-e-Imam Khomeini (RAH) Branch, Islamic Azad University, Tehran, Iran.
Chemistry Department, Shahid Beheshti University, G. C., Evin, Tehran 1983963113, Iran.
b
c
d
e
ARTICLE INFO
ABSTRACT
Article history:
Received
Received in revised form
Accepted
The reaction of dithiocarbamic acid salts with trimethyl orthoformate in the presence of
BF .OEt was investigated to give 4-(N,N-dialkyldithiocarbamato)-2-dialkyliminio-1,3-
dithietane tetrafluoroborates in good yields. Additionally, a one-pot procedure for the
synthesis of 2-iminium-1,3-dithiolanes from the BF .OEt catalyzed reaction of
dithiocarbamic acid salts with styrene epoxide is described.
3
2
3
2
Available online
Keywords:
Dithiocarbamate
orthoesters
epoxides
4
-(N,N-Dialkyldithiocarbamato)-2-dialkyliminio-1,3-
dithietane tetrafluoroborate 2-iminium-1,3-
dithiolanes
2
009 Elsevier Ltd. All rights reserved.
The chemistry of dithiocarbamates is well known and has
widespread application in different branches of chemistry,
1
agriculture and medicinal chemistry. Dithiocarbamic acids are
good nucleophiles and react with various electrophiles such as
2
3
4
5
alkyl halides, epoxides, carbonyls, electron-rich alkenes, α,β-
6
7
unsaturated carbonyl compounds, and many others. Although
dithiocarbamic acids are unstable, their esters and complexes are
stable and have found widespread application as intermediates in
8
synthetic organic chemistry, as NO
x
trapping agents in analytical
agents in rubber
manufacturing, radical chain transfer agents in reversible
9
chemistry,
s0ulfur
vulcanization
1
11
addition-fragmentation chain transfer (RAFT) polymerization,
fungicides and pesticides and as drugs.
12
13
Scheme 1. Schumacher's route for the synthesis of 4-(N,N-
dialkyldithiocarbamato)-2-dialkyliminio-l,3-dithietane cations
To the best of our knowledge, the only route for the synthesis
of 4-(N,N-dialkyldithiocarbamato)-2-dialkyliminio-l,3-dithietane
cations was reported by Schumaker and co-workers proceeding
in three steps from dithiocarbamic acid salts (Scheme 1). It was
shown that these compounds underwent ring-opening, ring-
We began our investigation with the one-pot, three-component
reaction of diethylamine, CS and trimethyl orthoformate in
2
1
4
chloroform. At room temperature under catalyst-free conditions,
no product was obtained. According to our previous experience
utilizing the reactions of dithiocarbamic acid salts with carbonyl
closing tautomerism. Herein, we report
a simple, and
straightforward route for the synthesis of 4-(N,N-
dialkyldithiocarbamato)-2-dialkyliminio-l,3-dithietane
4a
compounds in the presence of BF
3 2
.OEt , we next performed the
2
tetrafluoroborate from amines, CS and trimethyl orthoformate.
reaction using BF .OEt as a catalyst, however once again no
3
2
product was obtained. Therefore, an alternative strategy was
pursued. Dithiocarbamic acid salt 1, prepared from the reaction
of diethylamine and CS in CHCl , was added to a solution of
2 3

2
Tetrahedron
.OEt in CHCl at room
3 2 3
trimethyl orthoformate and BF
temperature furnishing 4-(N,N-diethyldithiocarbamato)-2-
diethyliminio-1,3-dithietane tetrafluoroborate 2a in moderate
yield. Performing the reaction with trimethyl orthovalerate and
trimethyl orthobenzoate were not successful, however the
reactions
hexamethyleneamine and piperidine were similar to diethylamine
Scheme 2). The isolated yields are based on trimethyl
with
other
secondary amines
such
as
(
orthoformate.
Fig 1. Molecular structure of 2b with 30% probability
displacement ellipsoids. Selected bond lengths (Å ): C(7)-N(1),
1
1
1
.328 (2); C(7)-S(1), 1.683 (2); C(7)-S(2), 1.774 (2); C(8)-S(2),
.793 (2); C(8)-S(3), 1.832 (2); C(8)-S(4), 1.827 (2); C(9)-N(2),
.288 (2); C(9)-S(3), 1.7314 (19); C(9)-S(4), 1.7432 (19).
The reaction of dithiocarbamic acid salts with epoxides for the
Scheme 2. Synthesis of 4-(N,N-dialkyldithiocarbamato)-2-
dialkyliminio-1,3-dithietane tetrafluoroborates
preparation of β-hydroxy dithiocarbamates has been well
3a,15
documented by our group and others.
The formed β-hydroxy
dithiocarbamates can be converted to 2-iminium-1,3-dithiolanes
via treatment with a strong acid or activation of the hydroxide
group by tosyl chloride, followed by intramolecular ring
1
13
The structures of products 2a-c were confirmed by H and
C
1
NMR spectroscopy and CHN analysis. The H NMR spectra of
the products showed a singlet peak between 5.50-6.00 ppm for
the CH resonance. Three peaks were observed between 3.50-4.20
ppm for the four methylenes attached to the nitrogens; two for
methylenes attached to the dithiocarbamate nitrogen due to the
restricted rotation around the C-N bond and another for both
methylenes attached to the nitrogen in the 2-iminium moiety. The
distinctive carbons of the dithiocarbamate and the iminium
moieties on the dithietane ring were observed between 190.0-
16
closure. In a continuation of our efforts regarding the chemistry
of dithiocarbamates, we examined a straightforward method for
the reaction of dithiocarbamic acids with epoxides to form 2-
iminium-1,3-dithiolanes. For this purpose, diethyldithiocarbamic
acid was reacted with styrene epoxide under the previously
optimized conditions. We observed that 2-iminium-1,3-dithiolane
tetrafluoroborate 3a was obtained in 45% isolated yield. The
reaction with hexamethyleneamine and piperidine were similar to
diethylamine (Scheme 3). The isolated yields are based on
styrene epoxide. These products were only obtained using
styrene epoxide and β-hydroxy dithiocarbamates were obtained
1
95.0 ppm and 185.0-188.0 ppm, respectively. Additionally, a
peak near -153 ppm in the F NMR was assigned to the
tetrafluoroborate anion.
19
A single crystal of 2b was prepared in CHCl
3
, and X-ray
1
using aliphatic epoxides. The H NMR spectra of the products
crystallographic analysis confirmed the proposed structure. An
ORTEP representation is shown in Figure 1 (CCDC no. 1025387;
for details of the crystal structure data and refinement of 2b see
the ESI). Compound 2b crystallized in the monoclinic space
showed a peak between 5.50-6.00 ppm for the benzylic hydrogen
2 2
while the CH N and CH S signals appeared between 3.50-4.50
13
ppm. Additionally, the C of the iminium moiety in the
dithiolane ring of the products was observed between 189-195
group P2
1
/c. Fluorine atoms appeared as disorder in the
13
ppm in the C NMR spectra.
i
tetrafluoroborate anion. The S···B (distance 3.088(5)Å)
interaction and intra and intermolecular C-H···F and C-H···S
hydrogen bonds (Fig. 2 and Table 3 in ESI) were effective in the
stabilization of the crystal structure and formation of a 3D
supramolecular network. The C7-N1 bond distance (1.328 Å)
was much closer to the C=N double bond length (typical C-N and
C=N bond distances are 1.47 and 1.28 Å, respectively) which
indicated that the π electron density was delocalized over the
dithiocarbamate moiety. As shown in Figure 1, the observed
bond distances of C(9)-S(3), 1.7314(19) Å and C(9)-S(4),
1
1
.7432(19) Å, were virtually equal and shorter than C(8)-S(3),
.832(2) Å and C(8)-S(4), 1.827(3) Å due to incorporation of the
sulfur atoms in resonance with the iminium group. The X-ray
crystal analysis also showed that the molecular structure in the
solid state was favorably oriented for rearrangement in solution.
Scheme 3. A direct route for the synthesis of 2-iminium-1,3-
dithiolanes from styrene epoxide

3
2
3
.
.
Azizi, N.; Aryanasab, F.; Saidi, M. R. Org. Lett. 2006, 8, 5275-
277.
3
A single crystal of 3b was prepared in CHCl , and X-
5
ray crystallographic analysis established the proposed structure.
An ORTEP representation is shown in Fig. 2 (CCDC no. 923256;
for details of the crystal structure data and refinement of 3b see
the ESI). Crystallographic analysis showed that compound 3b
crystallizes as both (R) and (S) enantiomers which were located
(a) Ziyaei Halimehjani, A.; Saidi, M. R. Can. J. Chem. 2006, 84,
1515-1519; (b) Azizi, N.; Pourhasan, B.; Aryanasab, F.; Saidi, M.
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.
in
(
a
similar position in the triclinic crystal system
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2
Å) interaction and intra and intermolecular C-H···F and C-H···S
hydrogen bonds (see Fig. 4 and Table 3 in the ESI) were
effective in the stabilization of the crystal structure and the
formation of a 3D supramolecular network. The observed bond
distances of C(6)-S(2), 1.743(7) Å and C(6)-S(1), 1.735(7) Å
were shorter than typical C-S bond lengths (ca. 1.82 Å ), but
longer than C=S double bonds and could be attributed to the
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1
1
1
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2
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In conclusion, for the first time, a simple and
straightforward method for the preparation of 4-(N,N-
dialkyldithiocarbamato)-2-dialkyliminio-l,3-dithietane
tetrafluoroborates from the reaction of dithiocarbamic acid
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Acknowledgment
We are grateful to the Research Council of the Sharif University
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2
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4
Tetrahedron
Weyl Methods of Molecular Transformations Vol. 30:
Acetals:O/N, S/S, S/N, and Higher heteroatom analogues, Thieme
014.
Supplementary Material
2
Supplementary data associated with this article can be found,
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Investigation of the reaction of dithiocarbamic
acid salts with trimethyl orthoformate
and styrene epoxide
Azim Ziyaei Halimehjani, Mojtaba Hajilou Shayegan, Shiva Shakori Poshteh,
Vahid Amani, Behrouz Notash, Mohammad M. Hashemi