Facile synthesis of N,N-dialkylselenoamides from amides

Article abstract of DOI:10.1002/hc.10016

The synthesis of the N,N-dialkylselenoamides from amides was discussed. These selenoamides were chlorinated with oxalyl chloride and then they were allowed to react with LiAlHSeH to afford the corresponding N,N-dialkylamides in moderate to good yields. Af

Full text of DOI:10.1002/hc.10016

Heteroatom Chemistry
Volume 13, Number 3, 2002
Facile Synthesis of N,N-Dialkylselenoamides
from Amides
Mamoru Koketsu, Yoshihiro Okayama, Hiroshi Aoki,
and Hideharu Ishihara
Department of Chemistry, Faculty of Engineering, Gifu University, Yanagido 1-1,
Gifu 501-1193, Japan
Received 4 July 2001; revised 14 August 2001
[6]. Previously, bis(dimethylaluminium)selenide has
ABSTRACT: N,N-Dialkylamides were chlorinated
with oxalyl chloride and then allowed to react
with LiAlHSeH to afford the corresponding N,N-
dialkyselenoamides in moderate to good yields. The
N,N-dialkylamides bearing bulky substituent groups
were not converted into the corresponding se-
C
been found to be an excellent reagent for the
conversion of N-substituted formamides to the cor-
responding selenoformamides [4c–4e]. Herein, we
describe a new, efficient method for the syntheses
of N,N-disubstituted selenoamides from the corre-
sponding amides by treatment with oxalyl chloride
and then LiAlHSeH.
lenoamides because of their steric hindrance.
2002
Wiley Periodicals, Inc. Heteroatom Chem 13:195–198,
2002; Published online in Wiley Interscience (www.
interscience.wiley.com). DOI 10.1002/hc.10016
RESULTS AND DISCUSSION
Optimal conditions for the preparation of N,N-
disubstituted selenoarylamides from the corre-
sponding amides were best determined by trial and
error. Direct reaction of amides with LiAlHSeH failed
to produce the corresponding selenoamides at all.
Therefore, we tried the preparation of selenoamides
from amides by combination of chlorinating agents,
such as oxalyl chloride, hydrogen chloride, thionyl
chloride, dichlorotriphenylphosphorane, or phos-
phorus pentachloride, with LiAlHSeH. Finally, the
use of oxalyl chloride and LiAlHSeH was found to
be the optimal procedure for the syntheses of se-
lenoamides from amides as shown in Scheme 1.
A typical procedure in the preparation of an
N,N-disubstituted selenoamide 2 is as follows. Ox-
alyl chloride was added to an anhydrous ether
solution of N,N-dimethylbenzamide (1a). The re-
action mixture was stirred at 0 C for 1 h under
an argon atmosphere and then further stirred at
room temperature for 3 h. LiAlHSeH [7] was
added to the mixture. After the usual workup,
N,N-dimethylselenobenzamide (2a) was obtained as
INTRODUCTION
The syntheses of many selenocarbonyl compounds
have been reported and a recent review details these
studies [1]. Selenoamides have been used as the use-
ful precursors for the synthesis of selenium con-
taining heterocyclic compounds [2] and their reac-
tivity has also become of great interest in recent
years [3]. Several methods for their preparation have
been reported [4]. Generally, the preparation of pri-
mary selenoamides has been achieved by the reac-
tions of nitriles with appropriate selenating reagents
[5], whereas N-substituted selenoamides have been
synthesized by more complicated reactions, includ-
ing the preliminary formation of selenoketene inter-
mediates from allylic alkylnyl selenides or the reac-
tions of Se-alkynyl selenocarboxylates with amines
Correspondence to: Mamoru Koketsu; e-mail: koketsu@cc.gifu-
u.ac.jp.
c
2002 Wiley Periodicals, Inc.
195

196 Koketsu et al.
TABLE 1 Synthesis of Selenoamide
Entry
Product
Yield (%)a
Entry
Product
Yield (%)
1
75
9
54
2
3
4
5
68
61
72
75
10
11
12
13
61
50
0
0
6
7
74
14
0
65
36
15
16
20
8
Trace
aIsolated yield.
yellow crystals in 75% yield. The same reaction con-
ditions with NaHSe [8] did not afford the desired
selenoamide 2. Various kinds of N,N-disubstituted
arylamides 1 were converted into the correspond-
ing N,N-disubstituted selenoarylamides 2 in moder-
ate to good yields under the present reaction condi-
tions (Table 1). However, 2-methylselenobenzamide
was not obtained by the present reaction (entry 12).
Also, neither N,N-diisopropyl nor N,N-diphenylsele-
noamide was obtained because of steric hindrance
(entries 13 and 14). Aliphatic selenoamides could
be obtained only in low yields because of the
SCHEME 1

Facile Synthesis of N,N-Dialkylselenoamides from Amides 197
1H NMR (CDCl3, 400 MHz) ␦ 0.71 (t, J = 7.6 Hz,
3H, CH3), 1.02 (t, J = 7.6 Hz, 3H, CH3), 1.59 (sixtet,
J = 7.6 Hz, 2H, CH2), 1.95 (sixtet, J = 7.6 Hz, 2H,
CH2), 3.34 (t, J = 7.6 Hz, 2H, CH2), 4.14 (t, J = 7.6 Hz,
2H, CH2), 7.18–7.33 (m, 5H, Ar), 13C NMR (CDCl3,
100 MHz) ␦ 10.7, 11.0, 19.1, 21.1, 55.5, 56.6, 123.8,
127.6, 127.7, 146.4, 204.5, 77Se NMR (CDCl3, 76
MHz) ␦ 717.3, MS (CI) m/z = 270 [M+ + 1].
instability of the products (entries 15 and 16).
Also, the synthesis of N-monosubstituted and N,N-
unsubstituted selenoamides failed under the present
conditions because of their instability [5h,9].
The present reaction does offer a new, facile
method for the preparation of many, various N,N-
disubstituted selenoamides from easily available
amides using LiAlHSeH.
N-Ethyl-N-methylselenobenzamide (2d). Yield:
72%. Yellow crystals, IR (KBr) 1514 cm , mp
EXPERIMENTAL
General
1
61.0–62.6 C, 1H NMR (CDCl3, 400 MHz) ␦ 1.18
(t, J = 7.2 Hz, 3H, CH3), 1.42 (t, J = 7.2 Hz, 3H,
CH3), 3.00 (s, 3H, CH3), 3.48 (q, J = 7.2 Hz, 2H,
CH2), 3.62 (s, 3H, CH3), 4.27 (q, J = 7.2 Hz, 2H, CH2),
7.22–7.35 (m, 5H, Ar), 13C NMR (CDCl3, 100 MHz) ␦
10.5, 12.9, 41.5, 44.0, 51.3, 53.1, 123.8, 124.0, 127.8,
127.9, 145.9, 146.1, 203.7, 204.5, 77Se NMR (CDCl3,
76 MHz) ␦ 688.9, 731.4, MS (CI) m/z = 228 [M+ + 1].
LiAlHSeH was prepared in accordance with a pre-
viously described procedure [7]. The 77Se chemical
shifts were expressed in ppm deshielded with respect
to neat Me2Se in CDCl3.
N,N-Dimethylselenobenzamide (2a). Typical
Procedure for 2a–2o. Oxalyl chloride (0.09 ml,
1.0 mmol) was added to stirred solution of
N,N-dimethylbenzamide (0.177 g, 1.0 mmol) in
anhydrous diethyl ether (5 ml) and allowed to
react at 0 C for 1 h under an argon atmosphere.
The mixture was further stirred for 3 h at room
temperature An anhydrous THF solution (25 ml) of
LiAlHSeH (1.2 mmol) was added to the mixture at
room temperature and allowed to react for 3 h. The
mixture was extracted with diethyl ether (100 ml)
and washed with water (100 ml). The organic layer
was dried over sodium sulfate, filtered and evapo-
rated to dryness. The residue was purified by flash
chromatography on silica gel with dichloromethane
to yield 0.16 g (75%) 2a that was obtained by flash
chromatography on silica gel as yellow crystals. IR
N-(Phenylselenocarbonyl)piperidine (2e). Yield:
1
75%. Yellow crystals, IR (KBr) 1509 cm , mp 64.3–
1
66.4 C, H NMR (CDCl3, 400 MHz) ␦ 1.58 (m, 2H,
CH2), 1.77 (m, 2H, CH2), 1.88 (m, 2H, CH2), 3.50 (t,
J = 6.0 Hz, 2H, CH2), 4.49 (t, J = 5.6 Hz, 2H, CH2),
7.23–7.35 (m, 5H, Ar), 13C NMR (CDCl3, 100 MHz) ␦
23.8, 25.4, 26.7, 53.9, 55.0, 124.3, 128.1, 128.2, 146.0,
203.3, 77Se NMR (CDCl3, 76 MHz) ␦ 679.6, MS (CI)
m/z = 254 [M+ + 1].
N-(Phenylselenocarbonyl)pyrrolidine (2f). Yield:
1
74%. Yellow crystals, IR (KBr) 1508 cm , mp 79.7–
1
81.0 C, H NMR (CDCl3, 400 MHz) ␦ 2.02 (quint,
J = 6.8 Hz, 2H, CH2), 2.12 (quint, J = 6.8 Hz, 2H,
CH2), 3.34 (t, J = 6.8 Hz, 2H, CH2), 3.97 (t, J = 6.8 Hz,
2H, CH2), 7.32–7.36 (m, 5H, Ar), 13C NMR (CDCl3,
100 MHz) ␦ 24.6, 26.5, 54.5, 57.1, 124.6, 128.1, 128.5,
146.6, 200.1, 77Se NMR (CDCl3, 76 MHz) ␦ 717.6, MS
(CI) m/z = 240 [M+ + 1].
1
1
(KBr) 1535 cm , mp 80.0–81.4 C, H NMR (CDCl3,
400 MHz) ␦ 3.10 (s, 3H, CH3), 3.70 (s, 3H, CH3),
7.28–7.34 (m, 5H, Ar), 13C NMR (CDCl3, 100 MHz)
␦ 44.7, 47.3, 124.6, 128.1, 128.4, 146.1, 205.3, 77Se
NMR (CDCl3, 76 MHz) ␦ 727.7, MS (CI) m/z = 214
[M+ + 1], Anal. Calcd for C9H11NSe: C, 37.13; H, 3.
81; N, 4.81. Found: C, 37.02; H, 3.66; N, 4.82%.
N,N-Diethyl-4-methoxyselenobenzamide
(2g).
1
Yield: 65%. Yellow crystals, IR (KBr) 1515 cm ,
1
mp 64.3–65.8 C, H NMR(CDCl3, 400 MHz) ␦ 1.09
N,N-Diethylselenobenzamide (2b). Yield: 68%.
Yellow crystals, IR (KBr) 1508 cm , mp 55.2–56.1 C,
1
(t, J = 7.2 Hz, 3H, CH3), 1.36 (t, J = 7.2 Hz, 3H, CH3),
3.40 (q, J = 7.2 Hz, 2H, CH2), 3.72 (s, 3H, CH3), 4.16
(q, J = 7.2 Hz, 2H, CH2), 6.76 (d, J = 8.8 Hz, 2H,
Ar), 7.11 (d, J = 8.8 Hz, 2H, Ar), 13C NMR (CDCl3,
100 MHz) ␦ 11.1, 13.2, 48.1, 49.8, 55.1, 113.1, 125.4,
139.1, 159.1, 203.9, 77Se NMR (CDCl3, 76 MHz) ␦
704.1, MS (CI) m/z = 272 [M+ + 1].
1H NMR (CDCl3, 400 MHz) ␦ 1.15 (t, J = 7.2 Hz,
3H, CH3), 1.44 (t, J = 7.2 Hz, 3H, CH3), 3.44 (q,
J = 7.2 Hz, 2H, CH2), 4.25 (q, J = 7.2 Hz, 2H, CH2),
7.19–7.35 (m, 5H, Ar), 13C NMR (CDCl3, 100 MHz)
␦ 11.2, 13.2, 48.2, 49.7, 123.7, 127.7, 127.9, 146.3,
203.9, 77Se NMR (CDCl3, 76 MHz) ␦ 705.3, MS (CI)
m/z = 242 [M+ + 1], HRMS: m/z = 241.0369, calcd.
for C11H15NSe, found 241.0368.
N,N-Diethylselenonicotinamide
(2h). Yield:
1
36%. Yellow oil, IR(neat) 1506 cm , 1H NMR
(CDCl3, 400 MHz) ␦ 1.12 (t, J = 7.2 Hz, 3H, CH3),
1.39 (t, J = 7.2 Hz, 3H, CH3), 3.38 (q, J = 7.2 Hz,
N,N-Dipropylselenobenzamide (2c). Yield: 61%.
Yellow crystals, IR (KBr) 1508 cm , mp 40.9–42.3 C,
1

198 Koketsu et al.
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2H, CH2), 4.17 (q, J = 7.2 Hz, 2H, CH2), 7.21 (dd,
J = 4.8, 7.8 Hz, 1H, Ar), 7.52 (dt, J = 1.4, 7.8 Hz, 1H,
Ar), 8.42 (d, J = 1.4 Hz, 1H, Ar ), 8.46 (dd, J = 1.4,
4.8 Hz, 1H, Ar), 13C NMR (CDCl3, 100 MHz) ␦ 11.1,
13.3, 48.5, 50.0, 122.7, 131.4, 142.2, 143.8, 148.7,
200.0, 77Se NMR (CDCl3, 76 MHz) ␦ 769.0, MS (CI)
m/z = 243 [M+ + 1].
N,N-Diethyl-2-selenonaphthylamide (2i). Yield:
1
54%. Yellow crystals, IR (KBr) 1509 cm , mp 97.1–
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97.8 C, 1H NMR (CDCl3, 400 MHz) ␦ 1.13 (t, J = 7.2
Hz, 3H, CH3), 1.47 (t, J = 7.2 Hz, 3H, CH3), 3.44
(q, J = 7.2 Hz, 2H, CH2), 4.27 (q, J = 7.2 Hz, 2H,
CH2), 7.34 (dd, J = 1.6, 8.4 Hz, 1H, Ar), 7.44–7.49 (m,
2H, Ar), 7.65 (s, 1H, Ar ), 7.77–7.81 (m, 3H, Ar),13C
NMR (CDCl3, 100 MHz) ␦11.2, 13.3, 48.3, 49.7, 122.0,
122.3, 126.3, 126.5, 127.5, 127.8, 128.0, 132.3, 132.4,
143.5, 203.8, 77Se NMR (CDCl3, 76 MHz) ␦ 716.5, MS
(CI) m/z = 292 [M+ + 1].
N,N-Diethyl-4-methylselenobenzamide (2j). Yield:
1
61%. Yellow crystals, IR (KBr) 1509 cm , mp
1
89.8–91.0 C, H NMR (CDCl3, 400 MHz) ␦ 1.16 (t,
J = 7.2 Hz, 3H, CH3), 1.45 (t, J = 7.2 Hz, 3H, CH3),
2.34 (s, 3H,CH3), 3.46 (q, J = 7.2 Hz, 2H, CH2), 4.25
(q, J = 7.2 Hz, 2H, CH2), 7.13 (s, 4H, Ar), 13C NMR
(CDCl3, 100 MHz) ␦ 11.3, 13.4, 21.4, 48.3, 49.9,
123.9, 128.7, 137.9, 143.9, 204.6, 77Se NMR (CDCl3,
76 MHz) ␦ 704.5, MS (CI) m/z = 257 [M+ + 1].
N,N-Diethyl-3-methylselenobenzamide (2k). Yield:
1
50%. Yellow crystals, IR (KBr) 1508 cm , mp
1
79.8–81.9 C, H NMR (CDCl3, 400 MHz) ␦ 1.16 (t,
J = 7.2 Hz, 3H, CH3), 1.45 (t, J = 7.2 Hz, 3H, CH3),
2.34 (s, 3H, CH3), 3.44 (q, J = 7.2 Hz, 2H, CH2), 4.25
(q, J = 7.2 Hz, 2H, CH2), 7.01 (d, J = 7.6 Hz, 1H, Ar),
7.04 (s, 1H, Ar), 7.09 (d, J = 7.6 Hz, 1H, Ar), 7.22 (t,
J = 7.6 Hz, 1H, Ar), 13C NMR (CDCl3, 100 MHz) ␦
11.4, 13.4, 21.4, 48.3, 49.8, 120.9, 124.5, 128.0, 128.7,
137.9, 146.5, 204.5, 77Se NMR (CDCl3, 76 MHz) ␦
698.0, MS (CI) m/z = 257 [M+ + 1], Anal. Calcd for
C12H17NSe: C, 56.69; H, 6.74; N, 5.51. Found: C,
56.49; H, 6.74; N, 5.51%.
N,N-Diethylselenoacetoamide (2o). Yield: 16%.
1
1
Brown oil, IR (neat) 1519 cm , H NMR (CDCl3,
400 MHz) ␦1.26–1.38 (m, 6H, CH3), 2.71 (s, 3H, CH3),
3.61 (q, J = 7.2 Hz, 2H, CH2), 4.13 (q, J = 7.2 Hz, 2H,
CH2), 13C NMR (CDCl3, 100 MHz) ␦ 11.2, 12.5, 36.4,
46.9, 52.0, 201.1, 77Se NMR (CDCl3, 76 MHz) ␦ 589.6,
MS (CI) m/z = 180 [M+ + 1].
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