Regiospecific iodocyclization of S-allyl dithiocarbamates: synthesis of 2-imino-1,3-dithiolane and 2-iminium-1,3-dithiolane derivatives

Article abstract of DOI:10.1016/j.tetlet.2009.03.127

4-Alkyl-2-imino-1,3-dithiolanes and 4-alkyl-2-iminium-1,3-dithiolanes were prepared in excellent yields with complete regiospecificity under mild conditions by the iodocyclization of S-allyl dithiocarbamates. Dehydrohalogenation of the 4-alkyl-2-imino-1,3

Full text of DOI:10.1016/j.tetlet.2009.03.127

Tetrahedron Letters 50 (2009) 2747–2749
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Tetrahedron Letters
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Regiospecific iodocyclization of S-allyl dithiocarbamates: synthesis
of 2-imino-1,3-dithiolane and 2-iminium-1,3-dithiolane derivatives
Azim Ziyaei Halimehjani a, Hajar Maleki b, Mohammad R. Saidi b,
*
a Faculty of Chemistry, Tarbiat Moallem University, 49 Mofateh St., Tehran, Iran
b Department of Chemistry, Sharif University of Technology, PO Box 11465-9516, Tehran, Iran
a r t i c l e i n f o
a b s t r a c t
Article history:
4-Alkyl-2-imino-1,3-dithiolanes and 4-alkyl-2-iminium-1,3-dithiolanes were prepared in excellent
yields with complete regiospecificity under mild conditions by the iodocyclization of S-allyl dithiocarba-
mates. Dehydrohalogenation of the 4-alkyl-2-imino-1,3-dithiolanes gave 4-alkylidene-2-imino-1,3-dith-
iolanes in excellent yields.
Received 16 October 2008
Revised 8 February 2009
Accepted 17 March 2009
Available online 21 March 2009
Ó 2009 Elsevier Ltd. All rights reserved.
The synthesis of compounds that protect crop plants from the
action of herbicides without reducing the herbicidal effectiveness
against weeds would be beneficial. It is well documented that 2-
imino-1,3-dithiolane and 2-iminium-1,3-dithiolane derivatives
are safe agents.1 A variety of methods are available in the literature
for the preparation of these biologically active compounds. Imino
dithiolanes can be prepared from the reaction of vic-dithiocyanates
in refluxing hydrochloric acid,2 by the reaction of vic-dithiols and
cyanogen chloride,3 acid-catalyzed cyclization of propargyl, allylic,
or b-hydroxy alkyl esters of dithiocarbamic acids,4 and by photol-
ysis of chlorinated S-allyl dithiocarbamate compounds.1a,b Unfor-
tunately, difficulties are encountered due to the physical nature
of the starting materials. The drawbacks of using vic-dithiols, the
toxicity of cyanogen chloride, the corrosive character of mineral
acids, and low yield of products are some limitations of these
processes.
Iodocyclization of an unsaturated C–C bond with a wide variety
of nucleophiles, including N, O, Se, and S, has been studied5 exten-
sively and it has become a powerful tool for the construction of
various heterocycles.
In previous work, we reported a simple, one-pot, and green
method for the synthesis of dithiocarbamates from amines, CS2,
and different nucleophile acceptors, such as alkyl halides, activated
olefins, and epoxides under solvent-free and aqueous conditions.6
The starting S-allyl dithiocarbamate can be prepared from the reac-
tion of an amine, carbon disulfide, and allyl chloride in water as
outlined in Scheme 1.
S
R1
H2O
r.t.
Cl
N
R2
S
R1R2NH + CS2
1o or 2o amine
+
1
Scheme 1. One-pot synthesis of allyl dithiocarbamates in water.
the electrophile to give the corresponding 4-alkyl-2-imino-1,3-
dithiolanes and 4-alkyl-2-iminium-1,3-dithiolanes in excellent
yields (Scheme 2).
After synthesizing the starting dithiocarbamates, we optimized
the reaction conditions for the key iodocyclization by changing the
number of equivalents of I2, the solvent, and the temperature for
the reaction of dithiocarbamate 1 with I2. Next, the reactions of
different S-allyl dithiocarbamates with iodine were investigated
under our optimized conditions. The results are summarized in
Tables 1 and 2.7,8 The reaction of S-allyl dithiocarbamates based
on primary amines was strongly influenced by the substituent
present on the allyl group. S-Allyl dithiocarbamates gave excellent
yields of 2-imino-1,3 dithiolanes (Table 1, entries 1–6). The reac-
tion of (Z)- or (E)-S-(2-butenyl)dithiocarbamate with iodine gave
S
R
I2 / CH2Cl2
r.t.
S
I
HN
R
S
N
2
S
S
In continuation of our interest in finding new and efficient meth-
ods for the synthesis of novel dithiocarbamate derivatives and the
use of these intermediates in organic transformations, we report
the iodocyclization of S-allyl dithiocarbamates using I2 or NIS as
S
R
R
I2 / CH2Cl2
r.t.
I
+
R
N
N
R
S
-
3
S
I
R = alkyl or phenyl
* Corresponding author. Tel.: +98 2614551023.
E-mail address: saidi@sharif.edu (M.R. Saidi).
Scheme 2. Synthesis of 2-imino and 2-iminium-1,3-dithiolanes from dithiocarba-
mates.
0040-4039/$ - see front matter Ó 2009 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2009.03.127

2748
A. Z. Halimehjani et al. / Tetrahedron Letters 50 (2009) 2747–2749
Table 1
Table 2
Synthesis of 2-imino-1,3-dithiolanes from dithiocarbamates
Synthesis of 2-iminium-1,3-dithiolanes from dithiocarbamates
Entry
1
Dithiocarbamate
Product
Yielda,b (%)
95
Entry
1
Dithiocarbamate
Producta,a,b
S
S
S
S
S
S
I
+
N
I
N
N
S
3a
N
S
Ph
-
2a
Ph
I
H
S
S
S
S
S
+
I
I
O
N
2
3
4
5
6
7
8
9
N
2
3
4
5
6
100
100
90
N
S
3b
-
2b
S
N
S
I
O
H
S
S
S
S
S
S
+
I
S
I
N
N
N
N
S
3c
-
2c
I
S
S
N
S
H
S
+
N
I
S
I
N
S
S
-
3d
I
2d
N
S
S
S
H
S
+
N
I
S
S
I
3e
N
-
S
S
N
N
S
I
95
N
H
S
S
S
2e
S
+
I
N
N
S
I
3f
-
90
S
I
2f
N
H
S
S
S
S
+
N
I
I
O
N
S
S
S
S
-
3g
I
O
S
7
<10c
N
N
S
S
2g
H
S
S
S
S
+
N
I
N
S
a
Reaction conditions: dithiocarbamate (1 mmol), I2 (1.5 mmol), rt, and CH2Cl2
3h
-
I
(5 mL).
S
b
c
Isolated yield.
+
N
I
NIS as the electrophile.
N
S
S
-
3i
I
a very low yield of product (entry 7). Even the use of NIS failed to
deliver the desired product 2g in an acceptable yield. The reaction
shows complete regiospecificity for the five-membered ring. The
1H and 13C NMR spectra show 1:1 mixtures of E/Z stereoisomers
of 2-imino-1,3 dithiolanes, 2.
S
+
N
I
10
N
S
3j
-
S
I
a
Reaction conditions: dithiocarbamate (1 mmol), I2 (1.5 mmol), rt, and CH2Cl2
(5 mL).
The reaction of S-allyldithiocarbamate prepared from secondary
b
Isolated yield was quantitative in each case.
amines with I2 was not influenced by the substitution on the c-car-
bon and gave excellent yields of the five-membered 2-iminium-
1,3-dithiolanes 3 with complete regiospecificity, (Scheme 2 and
Table 2). The structures of the products were elucidated from their
IR, 1H, and 13C NMR spectra, and by elemental analysis.
The presence of iodine in the products allowed further structural
elaboration via dehydrohalogenation using DBU.9 For example,
when compound 2a was treated with DBU, the corresponding 4-
methylidene-2-imino-1,3-dithiolane, 4, was obtained in excellent
yield (Scheme 3).10
S
S
S
I
DBU/CH2Cl2
r.t., 96%
N
N
S
2a
4
Scheme 3. Synthesis of 2-imino-4-methylidene-1,3-dithiolane by dehydrohalo-
According to the literature,5b,11 the CH2I group in five-mem-
bered compounds is observed at 4–8 ppm in 13C NMR, while the
–CHI group in six-membered compounds appears above 14 ppm.
The 13C NMR spectra of the products given in Tables 1 and 2 are
completely in agreement with the formation of five-membered
rings. Also, 1H NMR spectra indicated that dehydrohalogenation re-
sulted in the formation of an exocyclic double bond and no endo-
cyclic double bond. The DEPT spectrum showed three peaks for the
CH2 groups in compound 4, which is in agreement with the five-
membered ring. The NMR spectra (at 298 K) showed the presence
of an E/Z (1:1) mixture of compound 4 due to the C@N double
bond. Only one isomer was observed at temperatures above
320 K because of the rapid interconversion of E and Z isomers.
In conclusion, we have reported a new route for the iodocycliza-
tion reaction of S-allyl dithiocarbamates to give five-membered
genation.
2-imino- and 2-iminium-1,3-dithiolane derivatives with complete
regiospecificity. Treatment of 2-imino-1,3-dithiolane 2a with DBU
led to the formation of a 2-imino-4-methylidene-1,3-dithiolane.
The procedure is simple and gives excellent yields of potentially
biologically significant products.
Acknowledgments
We are grateful to the research council of Sharif University of
Technology for financial support. We also thank the Faculty of
Chemistry of Tarbiat Moallem University for supporting this work.

A. Z. Halimehjani et al. / Tetrahedron Letters 50 (2009) 2747–2749
2749
164.6; E/Z (1:1) mixture of 2d: 1H NMR (500 MHz, CDCl3): d (ppm) 3.44–3.59
(m, 2H), 3.60–3.81 (m, 6H), 4.15 (m, 1H), 4.21 (m, 1H), 6.92–6.97 (m, 4H), 7.14
(m, 2H), 7.33–7.37 (m, 4H). 13C NMR (125.7 MHz, CDCl3): d (ppm) 6.1 and 6.5,
39.5 and 42.1, 50.8 and 54.0, 120.5 and 120.6, 125.2 and 125.3, 129.4 and 129.5,
152.0 and 152.1, 167.2 and 167.8.
References and notes
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Abstr. 1965, 63, 11577a.; (f) Lovell, J. B. U.S. Patent 3,197,365, 1965; Chem. Abstr.
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8. General procedure for the synthesis of 2-iminium-1,3-dithiolanes: In a round-
bottomed flask equipped with
a
magnetic stirrer, were added S-
allyldithiocarbamate (1 mmol), I2 (1.5 mmol), and CH2Cl2 (10 mL). The
mixture was stirred for 4 h at room temperature. After completion of the
reaction, the solvent was evaporated in vacuo and the residue was triturated
with diethyl ether to afford the products as yellow-brown precipitates.
Filtration and washing of the precipitate with diethyl ether (three times)
gave the pure products. Selected spectroscopic data: 3b: IR (KBr) 1632 cmÀ1
;
1H NMR (500 MHz, CDCl3): d (ppm) 3.85–3.91 (m, 2H), 4.03 (m, 4H), 4.18 (m,
4H), 4.39 (m, 2H), 5.10 (m, 1H). 13C NMR (125.7 MHz, CDCl3): d (ppm) 3.9, 44.5,
56.9, 57.2, 58.3, 65.4, 65.4, 196.2; Anal. Calcd for C8H13I2NOS2: C, 21.00; H,
4. (a) Kennard, K. C.; Vanallan, J. A. J. Org. Chem. 1959, 24, 470–473; (b) Lies, T. A.
U.S. Patent 3,389,148, 1968.; Chem. Abstr. 1968, 69, 77268a.; (c) Levy, S. D. U.S.
Patent 3,364,231, 1968; Chem. Asbtr. 1968, 69, 2950h.
2.84; N, 3.06. Found: C, 20.7; H, 2.49; N, 3.10. 3e: IR (KBr) 1626 cmÀ1 1H NMR
;
(500 MHz, CDCl3): d (ppm) 3.79 (s, 6H), 3.84–3.93 (m, 2H), 4.34 (dd, 1H, J=
12.78, 4.28 Hz), 4.41 (dd, 1H, J= 12.78, 5.17 Hz), 5.09 (m, 1H); 13C NMR
(125.7 MHz, CDCl3): d (ppm) 4.7, 45.5, 48.8, 49.1, 59.4, 194.2; Anal. Calcd for
C6H11I2NS2: C, 17.35; H, 2.65; N, 3.37. Found: C, 17.16; H, 2.42; N, 3.41. 3f: IR
5. (a) Arimitsu, S.; Jacobsen, J. M.; Hammond, G. B. J. Org. Chem. 2008, 73, 2886–
2889; (b) Butters, M.; Elliott, M. C.; Hill-Cousins, J.; Paine, J. S.; Walker, J. K. E.
Org. Lett. 2007, 9, 3635–3638; (c) Hessian, K. O.; Flynn, B. L. Org. Lett. 2006, 8,
243–246; (d) Yao, T.; Yue, D.; Larock, R. C. J. Org. Chem. 2005, 70, 9985–9989;
(e) Kang, S. H.; Lee, S. B.; Park, C. M. J. Am. Chem. Soc. 2003, 125, 15748–15749.
6. (a) Azizi, N.; Aryanasab, F.; Saidi, M. R. Org. Lett. 2006, 8, 5275–5277; (b) Azizi,
N.; Aryanasab, F.; Torkiyan, L.; Ziyaei, A.; Saidi, M. R. J. Org. Chem. 2006, 71,
3634–3635; (c) Ziyaei, A.; Saidi, M. R. Can. J. Chem. 2006, 84, 1515–1519; (d)
Azizi, N.; Ebrahimi, F.; Akbari, E.; Aryanasab, F.; Saidi, M. R. Synlett 2007, 2797–
2800; (e) Azizi, N.; Pourhasan, B.; Aryanasab, F.; Saidi, M. R. Synlett 2007, 1239–
1242.
(KBr) 1630 cmÀ1 1H NMR (500 MHz, CDCl3): d (ppm) 1.88 (m, 2H), 2.02 (m,
;
4H), 2.09 (d, 3H, J= 6.76 Hz), 3.89–3.95 (m, 2H), 4.15–4.18 (m, 4H), 4.37 (dd, 1H,
J= 12.75, 4.36 Hz), 4.42 (dd, 1H, J=12.75, 5.27 Hz). 13C NMR (125.7 MHz, CDCl3):
d (ppm) 14.5, 22.4, 25.9, 26.0, 26.1, 48.8, 58.3, 59.4, 68.3, 190.6. Anal. Calcd for
C10H17I2NS2: C, 25.60; H, 3.62; N, 2.98. Found: C, 25.87; H, 3.52; N, 3.09.
9. Garud, D. R.; Makimura, M.; Ando, H.; Ishihara, H.; Koketsu, M. Tetrahedron Lett.
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10. Synthesis of compound 4 by dehydrohalogenation of 2a: DBU (1.5 mmol) was
added to a solution of 2a (1 mmol) in CH2Cl2 (5 mL), and the resulting mixture
was stirred for 1 h at rt. The product was extracted with CH2Cl2 (2 Â 10 mL).
The combined organic layers were washed with water and brine and were
dried over sodium sulfate, filtered, and evaporated in vacuo. The residue was
pure enough to give satisfactory spectroscopic data. E/Z (1:1) mixture of 4: IR
7. General procedure for the synthesis of 2-imino-1,3-dithiolanes: In
a round-
bottomed flask equipped with magnetic stirrer, S-allyl dithiocarbamate
a
(1 mmol), I2 (1.5 mmol), and CH2Cl2 (5 mL) were added. The mixture was
stirred at room temperature until conversion of the starting material was
complete (TLC). The reaction mixture was diluted with CH2Cl2 and was washed
with aqueous Na2S2O3 solution. (10 mL, 1 M). The organic phase was washed
with brine, dried over Na2SO4, filtered, and evaporated in vacuo. In most cases,
pure products were obtained. If needed, further purification was carried out by
column chromatography on silica gel, using a 2:8 ratio of ethyl acetate and
petroleum ether as eluent. Selected spectroscopic data: E/Z (1:1) mixture of 2c:
1H NMR (500 MHz, CDCl3): d (ppm) 1.25–1.35 (m, 10H), 1.48 (m, 2H), 1.78 (m,
8H), 3.15 (m, 2H), 3.45–3.69 (m, 6H), 3.78 (m, 2H), 4.08 (m, 1H) and 4.29 (m,
1H). 13C NMR (125.7 MHz, CDCl3): d (ppm) 6.5 and 7.0, 25.0 and 25.1, 25.9 and
26.0, 33.2 and 33.3, 39.0 and 41.8, 50.3 and 53.7, 69.1 and 69.2, 164.5 and
(KBr) 1654 cmÀ1 1H NMR (500 MHz, CDCl3): d (ppm) 4.03 (s, 2H) and 4.20 (s,
;
2H), 4.50 (s, 2H) and 4.53 (s, 2H), 5.25 (s, 2H) and 5.39 (s, 1H) and 5.41 (s, 1H),
7.15–7.32 (m, 10H).13C NMR (125.7 MHz, CDCl3): d (ppm) 39.8 and 43.0, 61.7
and 62.8, 110.2 and 111.1, 127.4 and 127.5, 128.1 and 128.2, 128.8 and 128.9,
138.8 and 139.0, 141.7 and 143.5, 164.3 and 165.3.
11. (a) Mancini, F.; Piazza, M. G.; Trombini, C. J. Org. Chem. 1991, 56, 4246–4252;
(b) Sabat, M.; Liebaria, A.; Molins, E.; Miravitlles, C.; Delgado, A. J. Org. Chem.
2000, 65, 4826–4829.