A Simple Route to N,N-Disubstituted Selenoureas from N,N-Disubstituted Cyanamides

Article abstract of DOI:10.1055/s-2003-44349

N,N-Disubstituted selenoureas 4 can be obtained in satisfactory yields by addition of an acid to a mixture of freshly prepared sodium selenide and N,N-disubstituted cyanamides 5.

Full text of DOI:10.1055/s-2003-44349

SHORT PAPER
15
A Simple Route to N,N-Disubstituted Selenoureas from N,N-Disubstituted
Cyanamides
A
S
imple Route to
i
N
,N-
D
e
isubstitute
t
Selen
m
oureas ar Keil,a Horst Hartmann*b
a
Sensient Imaging Technologies GmbH, SynTec Division, ChemiePark Bitterfeld-Wolfen, Arial A; Emil-Fischer-Strasse 3, 06766
Wolfen, Germany
b
Fachbereich Chemie, Fachhochschule Merseburg, Geusaer Str., 06217 Merseburg, Germany
Fax +49(3461)462192; E-mail: Horst.Hartmann@cui.fh-merseburg.de
Received 11 August 2003; revised 22 October 2003
R3
R3
O
Abstract: N,N-Disubstituted selenoureas 4 can be obtained in satis-
factory yields by addition of an acid to a mixture of freshly prepared
sodium selenide and N,N-disubstituted cyanamides 5.
R1
R2
H
H
6
N
O
Cl
N=C=X
N
C
X
7,8
Key words: N,N-disubstituted selenoureas, N,N-disubstituted cy-
anamides, nucleophilic substitution, selenium
1, 2
+ R1R2NH
heat
R3
NH2
In analogy to N,N-disubstituted thioureas 3,1 N,N-disubsti-
tuted selenoureas 4 are versatile starting materials for the
preparation of different types of heterocycles. For in-
stance, they can be used for the synthesis of N,N-disubsti-
tuted 2-aminoselenazoles.2 Recently, these compounds
have received a special interest as starting materials for a
variety of functional dyes useful for, e.g. measuring the
solvent polarity,3–5 manufacturing electrophotographic
data recording systems,6,7 or for preparing compounds ab-
sorbing infrared radiation.8
HN
O
+ H2O, H+
R1
R2
N
X
N
X
R2
R1
3, 4
9, 10
4
NR1R2
+ M2X, H+
a
b
c
d
e
f
NMe2
NEt2
NBn2
morpholino
pyrrolidino
piperidino
X
N
1, 3, 7, 9
2, 4, 8, 10
S
Se
R1
C
N
R2
5
Scheme 1
Compared to their N,N-disubstituted sulfur analogues 3,
N,N-disubstituted selenoureas 4 can not be prepared by
heating the corresponding ammonium selenocyanates 2.2
Similarly, they can not also be prepared, analogous to
their sulfur analogues 3,9 by hydrolysis of acylselenoureas
9 which are available by reaction of alkali or ammonium
selenocyanides 2 with acyl chlorides 6 and subsequent re-
action of the primarily formed acyl isoselenocyanates 8
with amines10 (Scheme 1). The N,N-disubstituted sele-
noureas 4 can be prepared, however, from N,N-disubstitut-
ed thioureas 3 via their alkyl derivatives,11 or from N,N-
disubstituted cyanamides 5 by reaction with dihydro-
genselenide that has been generated from Al2Se3 by hy-
drolysis.2 Although both methods seem, at first glance,
rather simple they require the use of an extremely toxic re-
agent.
a mineral acid, like hydrochloric acid, to a mixture of the
components. Instead of the acid, a suitable ammonium
salt, such as pyridinium hydrochloride, can also be used.
The reaction has some analogies to the reported prepara-
tion of selenobenzamides from benzonitriles13–15 as well
as to the preparation of N,N-disubstituted selenoureas 4
from N,N-disubstituted cyanamides and LiAlSeH.16
For obtaining a satisfactory yield of the N,N-disubstituted
selenoureas 4, it is recommendable to let the reaction mix-
ture stand overnight after the addition of acid. The prod-
ucts formed can be isolated by usual work-up (see
experimental).
Melting points were determined by means of a Differential Scan-
ning Calorimeter (Mettler, Toledo) with a heating rate of 5 °C/min.
The NMR spectra were recorded with a Varian Gemini 300 MHz
spectrometer. The elemental analyses were estimated by means of a
Now, we have found a more simple method for obtaining
N,N-disubstituted selenoureas 4. It also starts from N,N-
disubstituted cyanamides, and proceeds by the use of
Na2Se or NaHSe avoiding the free gaseous H2Se LECO analyser CHNS 932.
(Scheme 1). These reagents can be prepared, as generally
N,N-Disubstituted Selenoureas 4; General Procedure
known, very simply from elemental selenium by reaction
with sodium borohydride.12 For carrying out the reaction,
it is only necessary to add slowly an equivalent amount of
Method A: Under inert gas conditions, NaBH4 (8.1 g, 215 mmol)
was slowly added to a cooled and stirred mixture of elemental Se
(15.8 g, 200 mmol) in EtOH (200 mL). After decolourisation of the
reaction mixture, a N,N-disubstituted cyanamide 5 (100 mmol), fol-
lowed by pyridine hydrochloride (46.2 g, 400 mmol), were added
slowly and the mixture was stirred overnight. The reaction was
quenched by addition of H2O (500 mL) and the product formed was
extracted with CH2Cl2 (300 mL). The CH2Cl2 solution was dried
SYNTHESIS 2004, No. 1, pp 0015–0016
x
x
.
x
x
.2
0
0
3
Advanced online publication: 19.11.2003
DOI: 10.1055/s-2003-44349; Art ID: T08803SS.pdf
© Georg Thieme Verlag Stuttgart · New York

16
D. Keil, H. Hartmann
SHORT PAPER
and the solvent evaporated in vacuo to give a crystalline product. It
was recrystallised from toluene under N2.
References
(1) (a) Liebscher, J. In Methoden der organischen Chemie
(Houben-Weyl), Vol. E8b; Schaumann, E., Ed.; Thieme:
Stuttgart, 1994, 1. (b) Kikelj, D.; Urleb, U. In Science of
Synthesis, Vol. 11; Schaumann, E., Ed.; Thieme: Stuttgart,
2002, 627.
(2) Keil, D.; Hartmann, H. Phosphorus, Sulfur Silicon Relat.
Elem. 1999, 152, 169; and references cited therein.
(3) Hartmann, H.; Eckert, K.; Schröder, A. Angew. Chem. Int.
Ed. 2000, 39, 556.
(4) Keil, D.; Hartmann, H.; Zug, I.; Schröder, A. J. Prakt. Chem.
2000, 342, 169.
(5) Zug, I.; Hartmann, H. Z. Naturforsch., B: Chem. Sci. 2002,
57, in press.
Method B (In Analogy to Ref.13): A N,N-disubstituted cyanamide 5
(100 mmol) was added to a freshly prepared solution of NaSe (200
mmol) in EtOH (200 mL) under an inert gas atmosphere. After add-
ing pyridine (32.4 mL, 400 mmol), aq 2 M HCl (100 mL) was slow-
ly added to the boiling mixture over a period of 4 h. The reaction
mixture was quenched by addition of H2O (500 mL) and worked up
as before.
N,N-Dimethylselenourea (4a)
Yield: 50–55%; mp 174 °C (Lit.2 mp 173 °C).
13C NMR (DMSO-d6): = 177.9 (CSe).
(6) Keil, D.; Hartmann, H. Dyes Pigm. 2000, 44, 149.
(7) Keil, D.; Hartmann, H. High-Tech Chemie 1992-1997;
Firmenschrift Syntec GmbH: Wolfen, 1997.
(8) Keil, D.; Flaig, R.; Schröder, A.; Hartmann, H. Dyes Pigm.
2001, 50, 67.
(9) Hartmann, H.; Reuther, I. J. Prakt. Chem. 1973, 315, 144.
(10) Zhou, Y.; Linden, A.; Heimgartner, H. Helv. Chim. Acta
2000, 83, 539.
N,N-Diethylselenourea (4b)
Yield 40–45%; mp 122 °C (Lit.2 mp 121 °C).
13C NMR (CDCl3): = 177.1 (CSe).
N,N-Dibenzylselenourea (4c)
Yield: 45–50%; mp 141 °C (Lit.2 mp 139 °C).
13C NMR (CDCl3): = 181.6 (CSe).
(11) Douglas, I. B. J. Am. Chem. Soc. 1937, 59, 740.
(12) Klayman, D. L.; Griffin, T. S. J. Am. Chem. Soc. 1973, 95,
197.
(13) Lai, L.-L.; Reid, D. H. Synthesis 1993, 870.
(14) Ruan, M.-D.; Zhang, P.-F.; Tao, Y.; Fan, W.-F. Synth.
Commun. 1996, 26, 2617.
(15) Geisler, K.; Jacobs, A.; Künzler, A.; Mathes, M.; Girrleit, I.;
Zimmerman, B.; Bulka, E.; Pfeiffer, W.-D.; Langer, P.
Synlett 2002, 1983.
N-(Selenocarbamido)morpholine (4d)
Yield 30–35%; mp 201 °C (Lit.2 mp 195 °C).
13C NMR (DMSO-d6): = 178.2 (CSe).
N-(Selenocarbamido)pyrrolidine (4e)
Yield: 49–50%; mp 213 °C (Lit.2 mp 212 °C).
13C NMR (CDCl3): = 173.7 (CSe).
(16) Koketsu, M.; Fukuta, Y.; Ishihara, H. Tetrahedron Lett.
2001, 42, 6333.
N-(Selenocarbamido)piperidine (4f)
Yield: 35–40%; mp 147 °C (Lit.2 mp 147 °C).
13C NMR (CDCl3): = 177.8 (CSe).
Synthesis 2004, No. 1, 15–16 © Thieme Stuttgart · New York