Efficient synthesis of selenoureas from the corresponding carbodiimides

Article abstract of DOI:10.1081/SCC-120013001

Selenoureas were synthesized by the reaction of carbodiimides with LiA1HSeH in the presence of hydrogen chloride.

Full text of DOI:10.1081/SCC-120013001

This article was downloaded by: [University of Illinois Chicago]
On: 09 June 2012, At: 23:55
Publisher: Taylor & Francis
Informa Ltd Registered in England and Wales Registered Number: 1072954 Registered office: Mortimer House,
37-41 Mortimer Street, London W1T 3JH, UK
Synthetic Communications: An International Journal
for Rapid Communication of Synthetic Organic
Chemistry
Publication details, including instructions for authors and subscription information:
http://www.tandfonline.com/loi/lsyc20
EFFICIENT SYNTHESIS OF SELENOUREAS FROM THE
CORRESPONDING CARBODIIMIDES
Mamoru Koketsu a , Naotaka Takakura a & Hideharu Ishihara b
a Department of Chemistry, Faculty of Engineering, Gifu University, Gifu, 501-1193, Japan
b Department of Chemistry, Faculty of Engineering, Gifu University, Gifu, 501-1193, Japan
Available online: 16 Aug 2006
To cite this article: Mamoru Koketsu, Naotaka Takakura & Hideharu Ishihara (2002): EFFICIENT SYNTHESIS OF SELENOUREAS
FROM THE CORRESPONDING CARBODIIMIDES, Synthetic Communications: An International Journal for Rapid Communication of
Synthetic Organic Chemistry, 32:19, 3075-3079
To link to this article: http://dx.doi.org/10.1081/SCC-120013001
PLEASE SCROLL DOWN FOR ARTICLE
Full terms and conditions of use: http://www.tandfonline.com/page/terms-and-conditions
This article may be used for research, teaching, and private study purposes. Any substantial or systematic
reproduction, redistribution, reselling, loan, sub-licensing, systematic supply, or distribution in any form to
anyone is expressly forbidden.
The publisher does not give any warranty express or implied or make any representation that the contents
will be complete or accurate or up to date. The accuracy of any instructions, formulae, and drug doses should
be independently verified with primary sources. The publisher shall not be liable for any loss, actions, claims,
proceedings, demand, or costs or damages whatsoever or howsoever caused arising directly or indirectly in
connection with or arising out of the use of this material.

MARCEL DEKKER, INC. • 270 MADISON AVENUE • NEW YORK, NY 10016
©2002 Marcel Dekker, Inc. All rights reserved. This material may not be used or reproduced in any form without the express written permission of Marcel Dekker, Inc.
SYNTHETIC COMMUNICATIONS
Vol. 32, No. 19, pp. 3075–3079, 2002
EFFICIENT SYNTHESIS OF
SELENOUREAS FROM THE
CORRESPONDING CARBODIIMIDES
*
Mamoru Koketsu, Naotaka Takakura,
*
andHideharu Ishihara
Department of Chemistry, Faculty of Engineering,
Gifu University, Gifu 501-1193, Japan
ABSTRACT
Selenoureas were synthesized by the reaction of carbodiimides
with LiAlHSeH in the presence of hydrogen chloride.
Key Words: Selenourea; Carbodiimide; Hydrogen chloride
New synthetic methods for the preparation of selenocarbonyl com-
pounds have been extensively developed.[1] Selenoureas, generally prepared
from the reaction of isoselenocyanate with amine,[2] are useful precursors
for the synthesis of selenium–nitrogen heterocyclic compounds.[3] However,
a facile method for the preparation of selenoureas, in which formation
of unstable isoselenocyanate intermediate is not required, has been desired.
In the present study, we investigated the preparation of various selenoureas
from the corresponding carbodiimides using LiAlHSeH 2. Herein, we report
a new method for preparation of selenoureas by the reaction of carbodi-
imides with LiAlHSeH 2 in the presence of hydrogen chloride (Scheme 1).
*Corresponding authors. E-mail: koketsu@cc.gifu-u.ac.jp
3075
DOI: 10.1081/SCC-120013001
Copyright & 2002 by Marcel Dekker, Inc.
0039-7911 (Print); 1532-2432 (Online)
www.dekker.com

MARCEL DEKKER, INC. • 270 MADISON AVENUE • NEW YORK, NY 10016
©2002 Marcel Dekker, Inc. All rights reserved. This material may not be used or reproduced in any form without the express written permission of Marcel Dekker, Inc.
3076
KOKETSU, TAKAKURA, AND ISHIHARA
Scheme 1.
Table 1. Synthesis of Selenoureas
Carbodiimide (1)
Yield (%)a
(3)
Entry
R
R0
1
2
3
4
5
6
7
4-CH3C6H4
2-CH3C6H4
C6H5
(CH3)2CH
(CH3)3C
(CH3)3C
C6H11
4-CH3C6H4
2-CH3C6H4
C6H5
(CH3)2CH
(CH3)3C
C2H5
93( 3a)
89 (3b)
88 (3c)
90 (3d)
85 (3e)
59 (3f)
56 (3g)
C6H11
aIsolated yield.
1N Hydrogen chloride in diethyl ether was added to N,N0-di-p-tolyl-
carbodiimide 1a in THF at room temperature. The reaction mixture was
stirred at room temperature for 4 h under an argon atmosphere. To the
mixture, an anhydrous THF solution of LiAlHSeH 2[4] was added at 0ꢀC.
The mixture was stirred at 0ꢀC for 1 h under an argon atmosphere. After
standard workup, N,N0-di-p-tolylselenourea 3a was obtained in 93% yield.
Several selenoureas were obtained from the corresponding carbodiimides
1.[5] Both N-aryl- and N-alkyl-selenoureas and also both symmetric and
unsymmetric selenoureas were obtained in moderate to high yields (Table 1).
In the present reaction, chlorination of carbodiimide[6] was important
for obtaining higher yield of 3. Various reaction conditions were tested to
determine the optimal conditions. When the reaction of carbodiimide 1d
with LiAlHSeH 2 was carried out without hydrogen chloride, the yield of
3d was 45%. A BF3-promoted reaction of 1d with LiAlHSeH gave 3d in only
28% yield. When the reaction mixture of 1d and hydrogen chloride was
stirred for only 1 h under similar conditions shown in Sch. 1, the yield
of 3d was 53%. When HCl was added to the mixture of 1d and 2, the
yield of 3d was 62%. Finally, the conditions shown in Sch. 1 gave the highest
yield of 3d (Entry 4, Table 1) . These results would indicate that increasing

MARCEL DEKKER, INC. • 270 MADISON AVENUE • NEW YORK, NY 10016
©2002 Marcel Dekker, Inc. All rights reserved. This material may not be used or reproduced in any form without the express written permission of Marcel Dekker, Inc.
SYNTHESIS OF SELENOUREAS
3077
Scheme 2.
electrophilicity of carbon atom of carbodiimide by chlorination of carbo-
diimide using hydrogen chloride might provide higher yield of selenourea
(Scheme 2).
In previously, 1,3-disubstituted selenoureas have been synthesized
by the reaction with carbodiimides and H2Se,[7] which is highly toxic
and air sensible. In present method, selenoureas 3 were readily synthesized
by reacting carbodiimides 1 with LiAlHSeH 2 in the presence of hydrogen
chloride.
EXPERIMENTAL
Melting points were determined by use of Yanagimoto micromelting
point apparatus and are uncorrected. IR spectra were measured on
Perkin-Elmer 1600 spectrometer. 1H, 13C and 77Se NMR spectra were
recorded on a JEOL-JNM-a400 (400 MHz) spectrometer. Mass spectra
were obtained on Shimadzu 9020-DF mass spectrometer. Tetrahydrofuran
was distilled from benzophenone immediately prior to use.
General Procedure: To a solution of carbodiimide (2 mmol) in 10 mL
anhydrous THF at room temperature under argon was added 1 N dry
hydrogen chloride in diethyl ether (2 mL, 2 mmol). The reaction mixture
was stirred at the same temperature for 4 h. To the mixture was added
an anhydrous THF solution (10 mL) of LiAlHSeH 2[4] (1 mmol) at 0ꢀC.
The resulting mixture was stirred at 0ꢀC for 1 h under argon. The mixture
was extracted with diethyl ether (50 mL) and washed with saturated NaCl
aqueous solution. The organic layer was dried over sodium sulfate and
evaporated. The residue was purified by flash chromatography on silica
gel with diethyl ether : dichloromethane (50 : 1) to give selenourea 3.
N,N 0-Di-p-tolylselenourea 3a: M.p. 180.2–181.2ꢀC (lit.[2b] 176ꢀC); IR
1
(KBr) 1554, 3173 cmÀ1; H NMR (CDCl3) ꢀ 2.33 (6H, s, CH3), 7.17 (4H,
d, J ¼ 8.0 Hz, Ar), 7.23(4H, d, J ¼ 8.0 Hz, Ar), 8.54 (2H, br, NH); 13C NMR

MARCEL DEKKER, INC. • 270 MADISON AVENUE • NEW YORK, NY 10016
©2002 Marcel Dekker, Inc. All rights reserved. This material may not be used or reproduced in any form without the express written permission of Marcel Dekker, Inc.
3078
KOKETSU, TAKAKURA, AND ISHIHARA
(CDCl3) ꢀ 20.9, 125.6, 130.0, 134.7, 137.3, 178.3; 77Se NMR (CDCl3) ꢀ
241.3; MS (CI) m/z ¼ 305 [Mþþ1]; Anal. Calcd. for C15H16N2Se: C,
59.41; H, 5.32; N, 9.24. Found: C, 59.24; H, 5.25; N, 8.94.
N,N 0-Di-o-tolylselenourea 3b: M.p. 159.8–161.1ꢀC (lit.
174ꢀC); IR
[2b]
(KBr) 1529, 3117, 3319 cmÀ1 1H NMR (CDCl3) ꢀ 2.31 (6H, s, CH3),
;
7.26–7.42 (8H, m, Ar), 8.5 (2H, br, NH); 13C NMR (CDCl3) ꢀ 18.0, 127.0,
128.0, 128.6, 131.2, 135.5, 179.4; 77Se NMR (CDCl3) ꢀ 228.1; MS (Cl)
m/z ¼ 305 [Mþþ1].
N,N 0-Diphenylselenourea 3c: M.p. 195.2–197.2ꢀC (lit. 186[2b]
,
192–194ꢀC[8]); IR (KBr) 1560, 3257 cmÀ1; H NMR (CDCl3) ꢀ 7.26–7.36
(10H, m, Ar), 8.2 (2H, br s, NH); 13C NMR (CDCl3) ꢀ 120.6, 125.7,
127.7, 129.2, 179.0; 77Se NMR (CDCl3) ꢀ 140.1; MS (EI) m/z ¼ 276 [Mþ].
N,N 0-Diisopropylselenourea 3d: M.p. 142.6–148.2ꢀC (lit.[9]); IR (KBr)
1570, 3195, 3245 cmÀ1; 1H NMR (CDCl3) ꢀ 1.19 (12H, d, CH3), 4.21 (2H, br
s, CH), 6.1 (2H, br, NH); 13C NMR (CDCl3) ꢀ 22.4, 47.9, 176.2; 77Se NMR
(CDCl3) ꢀ 140.3, MS (EI) m/z ¼ 208 [Mþ]; HRMS Calcd. for C7H16N2Se
208.0478, Found 208.0503; Anal. Calcd. for C7H16N2Se: C, 40.58; H, 7.78;
N, 13.52. Found: C, 40.59; H, 7.78; N, 13.51%.
1
N,N 0-Di-tert-butylselenourea 3e: M.p. 144.8–147.6ꢀC IR (KBr) 1542,
3062, 3258 cmÀ1 1H NMR (CDCl3) ꢀ 1.51 (18H, s, CH3), 6.2 (2H, br,
;
NH); 13C NMR (CDCl3) ꢀ 29.2, 29.4, 54.1, 175.2; 77Se NMR (CDCl3)
ꢀ 262.3; MS (EI) m/z ¼ 236 [Mþ]; HRMS (EI) Calcd. for C9H20N2Se
236.0791, Found 236.0788;
N-tert-Butyl-N 0-ethylselenourea 3f: M.p. 114.8–116.0ꢀC; IR (KBr)
1
1549, 3009, 3238 cmÀ1; H NMR (CDCl3) ꢀ 1.08 (3H, t, CH3), 1.27 (9H, s,
CH3), 3.05 (2H, br s, CH2), 5.94 (1H, br, NH), 6.33 (1H, br, NH);
13C NMR (CDCl3) ꢀ 14.4, 29.3, 43.2, 53.8, 177.4; 77Se NMR (CDCl3) ꢀ
209.6; MS (CI) m/z ¼ 209 [Mþþ1]; HRMS (EI) Calcd. for C7H16N2Se
208.0478, Found 208.0492; Anal. Calcd. for C7H16N2Se: C, 40.58; H, 7.78;
N, 13.52. Found: C, 40.68; H, 7.90; N, 13.47%.
N,N 0-Dicyclohexylselenourea 3g: M.p. 134.6–137.2ꢀC; IR (KBr) 1560,
1
3257 cmÀ1; H NMR (CDCl3) ꢀ 1.15–1.29 (12H, m, C6H11), 1.52–1.83(8H,
m, C6H11), 4.27 (2H, br, CH), 7.46 (2H, br, NH); 13C NMR (CDCl3) ꢀ 24.6,
25.3, 32.6, 34.9, 53.6, 175.8; 77Se NMR (CDCl3) ꢀ 141.5; MS (EI) m/z ¼ 288
[Mþ]; HRMS Calcd. for C13H24N2Se 288.1103, Found 288.1097.
REFERENCES
1. (a) Dell, C.P. Thioamides and Their Selenium and Tellurium Analogues.
In Comprehensive Organic Functional Group Transformations, Katritzky,
A.R., Meth-Cohn, O., Rees, C.W. Eds. Pergamon: Oxford, 1995; Vol. 5,

MARCEL DEKKER, INC. • 270 MADISON AVENUE • NEW YORK, NY 10016
©2002 Marcel Dekker, Inc. All rights reserved. This material may not be used or reproduced in any form without the express written permission of Marcel Dekker, Inc.
SYNTHESIS OF SELENOUREAS
3079
pp. 565–628; (b) Organoselenium Chemistry: APractical Approach
,
Back, T.G., Ed.; Oxford University Press: U.K., 1999; (c) Murai, T.;
Kato, S. Selenocarbonyls. In Organoselenium Chemistry. Modern
Developments in Organic Synthesis, Wirth, T., Ed. Springer Verlag:
2000; pp. 177–199.
2. (a) Sheehan, J.C.; Hlavka, J.J. J. Org. Chem. 1956, 21, 439. (b) Bulka, E.;
Ahlers, K.-D.; Tucek, E. Chem. Ber. 1967, 100, 1459. (c) Sonoda, N.;
Yamamoto, G.; Tsutsumi, S. Bull. Chem. Soc. Jpn. 1972, 45, 2937; (d)
Boccanfuso, A.M.; Griffin, D.W.; Dunlap, R.B.; Odom, J.D. Bioorg.
Chem. 1989, 17, 231; (e) Koketsu, M.; Suzuki, N.; Ishihara, H. J. Org.
Chem. 1999, 64, 6473.
3. (a) Maslankiewicz, A.; Skrzypek, L.; Niedbala, A. Pol. J. Chem. 1996,
70, 54; (b) Keil, D.; Hartmann, H. Phosphorus, Sulfur Silicon Relat.
Elem. 1999, 152, 169; (c) Shafiee, A.; Ebrahimzadeh, M.A.; Maleki, A.
J. Heterocycl. Chem. 1999, 36, 901; (d) Zhou, Y.; Linden, A.;
Heimgartner, H. Helv. Chim. Acta 2000, 83, 1576.
4. Ishihara, H.; Koketsu, M.; Fukuta, Y.; Nada, F. J. Am. Chem. Soc.
2001, 123, 8408.
5. Carbodiimides 1 and LiAlHSeH 2 were prepared according to pre-
viously reported methods. See: for 1; Fell, J.B.; Coppola, G.M. Synth.
Commun. 1995, 25, 43and for 2; ref. 4. Biriefly, to a solution of
selenium powder (0.80 g, 10.0 mmol) in dry THF (100 mL) was
added lithium aluminium hydride (0.38 g, 10.0 mmol) at 0ꢀC under an
argon atmosphere. The mixture was stirred at 0ꢀC for 30 min. The
formed LiAlHSeH 2 is then ready for use in further reaction without
concentration.
6. Jung, F.; Olivier, A.; Boucherot, D. Tetrahedron Lett. 1989, 30, 2379.
7. (a) Zetzche, F.; Pinske, H. Ber. 1941, 74B, 1022; (b) Zingaro, R.A.;
Bennett, F.C.; Hammr, G.W. J. Org. Chem. 1953, 18, 292; (c)
Giudicelli, J.F.; Menin, J.; Najer, H. Bull. Soc. Chim. Fr. 1968, 1099.
8. Warner, J.S. J. Org. Chem. 1963, 28, 1642.
9. (a) Rosenbaum, A.; Kirchberg, H.; Liebnitz, E. J. Prakt. Chem. 1962,
19, 1; (b) Rosenbaum, A. J. Prakt. Chem. 1968, 37, 200.
Received in Japan July 2, 2001

MARCEL DEKKER, INC. • 270 MADISON AVENUE • NEW YORK, NY 10016
©2002 Marcel Dekker, Inc. All rights reserved. This material may not be used or reproduced in any form without the express written permission of Marcel Dekker, Inc.