Preparation of N,N-unsubstituted selenoureas and thioureas from cyanamides

Article abstract of DOI:10.1016/S0040-4039(01)01251-5

Reaction of cyanamides with LiAlHSeH and LiAlHSH in the presence of HCl in diethyl ether provided the corresponding N,N-unsubstituted selenoureas and thioureas in moderate to high yields, respectively.

Full text of DOI:10.1016/S0040-4039(01)01251-5

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 42 (2001) 6333–6335
Preparation of N,N-unsubstituted selenoureas and thioureas from
cyanamides
Mamoru Koketsu,* Yoshihisa Fukuta and Hideharu Ishihara*
Department of Chemistry, Faculty of Engineering, Gifu University, Gifu 501-1193, Japan
Received 28 June 2001; revised 10 July 2001; accepted 13 July 2001
Abstract—Reaction of cyanamides with LiAlHSeH and LiAlHSH in the presence of HCl in diethyl ether provided the
corresponding N,N-unsubstituted selenoureas and thioureas in moderate to high yields, respectively. © 2001 Elsevier Science Ltd.
All rights reserved.
The syntheses of many selenocarbonyl compounds have
been reported and the recent reviews detail the studies.1
Selenoureas are used as the precursors for the syntheses
of selenium–nitrogen heterocyclic compounds2 and
their activities have received increasing attentions.3
There is only a few reports of preparation of N,N-
unsubstituted selenourea by the reaction of hydrogen
selenide with cyanamide.2d The preparation of N,N-
unsubstituted selenourea without using poisonous
hydrogen selenide has rarely been reported.1b In this
study, we investigated the synthesis of N,N-unsubsti-
tuted selenourea using LiAlHSeH.4 Herein, we report
the facile preparation of N,N-unsubstituted selenoureas
and thioureas by the reaction of cyanamides with the
introduction reagent of selenium and sulfur.
cyanamides was of importance. The combination of
LiAlHSeH with phosphorus oxychloride, oxalyl chlo-
ride or hydrogen chloride in diethyl ether was examined
for the chlorination of cyanamides and the synthesis of
urea. Previously, we have confirmed N,N-disubstituted
selenourea can be obtained by the reaction of the
corresponding amide with LiAlHSeH and oxalyl chlo-
ride.8 However, in the present reaction, only the combi-
nation with hydrogen chloride in diethyl ether gave a
satisfactory result. The formation of N,N-unsubstituted
selenourea and thiourea could be explained by the
possible mechanism presented in Scheme 2.
The reaction of chloro(methylthio)iminonium salt chlo-
ride, prepared by the reaction of methyl thiocyanate 7
with hydrogen chloride in ether, with LiAlHSeH
afforded S-methyl selenothiocarbamate 8 in a 51%
yield (Table 1, entry 9, Scheme 3).9
In a typical procedure, 1N HCl (2 equiv.) in diethyl
ether was added to N,N-dimethylcyanamide 1a (1
equiv.) of THF solution. The reaction mixture became
a milky white suspension from colorless solution in less
than 30 seconds and then was stirred at 0°C for 2 h.
The compound 2 was formed in situ.5 Subsequently,
LiAlHSeH 3 (1 equiv.)4,6 was added to the reaction
mixture. The reaction mixture was further stirred at
0°C for 3 h. After usual workup, 5a was obtained in a
70% yield as a yellow crystal7 (Scheme 1). The results of
reactions of various cyanamides 1 with LiAlHSeH 3 or
LiAlHSH 4 are summarized in Table 1. The reactions
of cyanamides 1 with 3 gave the corresponding N,N-
unsubstituted selenoureas in 70–91% yields. Similarly,
the reactions using LiAlHSH 4 gave the corresponding
N,N-unsubstituted thioureas in 52–89% yields. In the
present reaction, the selection of chlorinating reagent of
In conclusion, LiAlHSeH and LiAlHSH, as an intro-
duction reagent of selenium and sulfur atom, reacted
with 2 giving the corresponding N,N-unsubstituted sele-
noureas and N,N-unsubstituted thioureas, respectively.
R
R
R
R
HCl in Et2O (2 equiv)
N
C
NH2Cl
N
C
N
THF/0°C/2 h
Cl
1
2
E
LiALHEH (3 or 4)
THF/0°C/3 h
R
N
NH2
R
E = Se (3) or S (4)
Scheme 1.
5 or 6
* Coresponding author.
0040-4039/01/$ - see front matter © 2001 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(01)01251-5

6334
M. Koketsu et al. / Tetrahedron Letters 42 (2001) 6333–6335
Table 1. Syntheses of N,N-unsubstituted selenoureas, N,N-unsubstituted thioureas and S-methyl selenocarbamate
References
R
LiAlHEH (3 or 4)
1. (a) Klayman, D. L.; Shine, R. J. J. Org. Chem. 1969, 34,
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Pergamon Press: Oxford, 1991; Vol. 6, p. 461; (c) Ogawa,
A.; Sonoda, N. Rev. Heteroatom Chem. 1994, 10, 43; (d)
Guziec, Jr., F. S.; Guziec, L. J. In Comprehensive Organic
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Meth-Cohn, O.; Rees, C. W., Eds.; Pergamon Press:
Oxford, 1995; Vol. 6, p. 587; (e) Dell, C. P. In Comprehen-
sive Organic Functional Group Transformations; Katritzky,
A. R.; Meth-Cohn, O.; Rees, C. W., Eds.; Pergamon:
Oxford, 1995; Vol. 5, p. 565; (f) Krief, A. In Comprehen-
sive Organometallic Chemistry; Abel, W. W.; Stone, F. G.
A.; Wilkinson, G., Eds.; Pergamon: Oxford, 1995; Vol. 11,
N
C
NH2Cl
R
Cl
E = Se or S
2
E
H
E
R
R
-HCl
N
NH2
NH2Cl
N
C
R
R
5 or 6
Scheme 2.
p. 515; (g) Organoselenium Chemistry:
A Practical
Approach; Back, T. G., Ed.; Oxford University Press: UK,
1999; (h) Murai, T.; Kato, S. In Organoselenium Chem-
istry. Modern Developments in Organic Synthesis; Wirth,
T., Ed.; Springer, 2000; p. 177.
HCl in Et2O (2 equiv)
CH3S
Se
C
NH2Cl
CH3S
C
N
THF/0°C/2 h
Cl
7
2. (a) Maslankiewicz, A.; Skrzypek, L.; Niedbala, A. Pol. J.
Chem. 1996, 70, 54; (b) Lai, L.-Li; Reid, D. H. Heteroat.
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Maleki, A. J. Heterocyclic Chem. 1999, 36, 901; (d) Diet-
mar, K.; Horst, H. Phosphorus Sulfur Silicon Relat. Elem.
LiAlHSeH 3
CH3S
NH2
THF/0°C/12 h
8
&
1999, 152, 169; (e) Sibor, J.; Zurek, D.; Humpa, O.;
Pazdera, P. Molecules 2000, 5, 37.
Scheme 3.

M. Koketsu et al. / Tetrahedron Letters 42 (2001) 6333–6335
6335
3. (a) Fregona, D.; Graziani, R.; Faraglia, G.; Caselato, U.;
Sitran, S. Polyhedron 1996, 15, 2523; (b) Boyle, P. D.;
Cross, W. I.; Godfrey, S. M.; McAuliffe, C. A.; Pritchard,
R. G.; Teat, S. J. J. Chem. Soc., Dalton Trans. 1 1999,
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Chem. Soc., Dalton Trans. 1999, 4245.
(6H, t, J=6.8 Hz, CH3), 3.49 (2H, br s, CH2), 3.97 (2H, br
s, CH2), 6.48 (2H, br s, NH), 13C NMR (CDCl3): l 12.2,
42.9, 51.1, 176.6, 77Se NMR (CDCl3): l 209.8, MS (CI)
m/z=181 [M++1], HRMS (EI) calcd for C5H12N2Se
180.0165, found 180.0147. 1-Selenocarbamoylpiperidine
5d: Mp 145.0–146.2°C; IR (KBr) 3303, 3169, 1522 cm−1
,
4. Ishihara, H.; Koketsu, M.; Fukuta, Y.; Nada, F. J. Am.
1H NMR (DMSO-d6): l 1.47 (4H, m, CH2), 1.59 (2H, m,
CH2), 3.76 (4H, br s, CH2), 7.75 (2H, br s, NH), 13C NMR
(DMSO-d6): l 23.6, 25.3, 176.0, 77Se NMR (DMSO-d6): l
218.5, MS (CI) m/z=193 [M++1]. HRMS (EI) calcd for
C6H12N2Se 192.0165, found 192.01499. N,N-Diethyl-
thiourea 6b: Mp 99.2–100.6°C; IR (KBr) 3376, 3192, 1522
Chem. Soc., in press.
5. Intermediate 2a was isolated quantitatively. 1H NMR
(CDCl3): l 3.40 (3H, s, CH3), 3.76 (3H, s, CH3), 10.65
(1H, br s, NH), 11.14 (1H, br s, NH), 13C NMR (CDCl3):
l 42.8, 43.0, 195.9, MS (CI): m/z=107 [M++1-HCl].
6. The preparation of LiAlHSeH 2: to a solution of selenium
powder (0.80 g, 10.0 mmol) in dry THF (100 mL) was
added lithium aluminium hydride 1 (0.38 g, 10.0 mmol) at
0°C under an argon atmosphere. The mixture was stirred
for 30 min. The black selenium powder was consumed in
less than 10 min. The reaction mixture became a heteroge-
neous grayish suspension. The 2 is formed in situ and is
then ready for further reaction.
cm−1 1H NMR (DMSO-d6): l 1.06 (6H, t, J=6.8 Hz,
,
CH3), 3.53 (4H, br s, CH2), 7.10 (2H, br s, NH), 13C NMR
(DMSO-d6): l 12.6, 44.5, 179.8, MS (CI) m/z=133 [M++
1]. 1-Thiocarbamoylpiperidine 6d: Mp 127.4–129.1°C; IR
(KBr) 3334, 3188, 1510 cm−1, 1H NMR (DMSO-d6): l 1.45
(4H, m, CH2), 1.56 (2H, m, CH2), 3.69 (4H, br s, CH2),
7.25 (2H, br s, NH), 13C NMR (DMSO-d6): l 23.7, 25.3,
48.2, 180.2, MS (CI) m/z=145 [M++1].
7. Spectral data of selected compounds. N,N-Dimethylsele-
nourea 5a: Mp 172.2–172.8°C; IR (KBr) 3366, 3162, 1551
8. Koketsu, M.; Okayama, Y.; Aoki, H.; Ishihara, H. Het-
eroatom Chem., submitted.
1
cm−1, H NMR (CDCl3): l 3.18 (6H, br s, CH2), 7.60 (2H,
9. S-Methyl selenothiocarbamate 8: Mp 58.9–59.5°C; IR
br s, NH), 13C NMR (CDCl3): l 37.9, 45.3, 177.7, 77Se
NMR (CDCl3): l 230.4, MS (CI) m/z=153 [M++1],
HRMS (EI) calcd for C3H8N2Se 151.98522, found
151.98346. N,N-Diethylselenourea 5b: Mp 121.8–122.7°C;
IR (KBr) 3340, 3176, 1534 cm−1, 1H NMR (CDCl3): l 1.27
(KBr) 3275, 3122, 1636 cm−1 1H NMR (acetone-d6): l
,
2.61 (3H, s, CH3), 9.19 (1H, br s, NH), 9.53 (1H, br s,
NH), 13C NMR (aceton-d6): l 22.0, 204.9, 77Se NMR
(acetone-d6): l 554.2, MS (CI): m/z=156 [M++1], HRMS
(EI) calcd for C2H5NSSe 154.93076, found 154.93083.
.