Synthesis of N,N-disubstituted selenoamides by O/Se-exchange with selenium-Lawesson's reagent

Article abstract of DOI:10.1016/S0040-4039(03)01690-3

The selenium analogue of Lawesson's reagent, [PhP(Se)(μ-Se)] ₂ is an effective reagent for synthesizing N,N-disubstituted selenoamides. The reaction is carried out under mild conditions (room temperature) and affords the selenoamide in higher y

Full text of DOI:10.1016/S0040-4039(03)01690-3

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 44 (2003) 6911–6913
Synthesis of N,N-disubstituted selenoamides by O/Se-exchange
with selenium–Lawesson’s reagent
John Bethke,a Konstantin Karaghiosoffb,* and Ludger A. Wessjohanna,*
aLeibniz-Institute of Plant Biochemistry, Weinberg 3, 06120 Halle (Saale), Germany
bDepartment of Chemistry, Ludwig-Maximilians-University Munich, Butenandtstraße 5-13 (D), 81377 Munich, Germany
Received 28 May 2003; revised 4 July 2003; accepted 5 July 2003
Abstract—The selenium analogue of Lawesson’s reagent, [PhP(Se)(m-Se)]2 is an effective reagent for synthesizing N,N-disubsti-
tuted selenoamides. The reaction is carried out under mild conditions (room temperature) and affords the selenoamide in higher
yield than using other selenation reagents.
© 2003 Elsevier Ltd. All rights reserved.
Selenoamides are well known in preparative organic
chemistry. Publications on this topic reach back to the
beginning of the last century and many different
reagents for the introduction of selenium were used.1 In
contrast to the homologous thioamides, however, the
synthesis of selenoamides is still a challenge, due to the
lack of suitable, readily obtainable, and easy to handle
selenating reagents. Here we report a general and
highly effecient synthesis of N,N-disubstituted
selenoamides using the novel selenating reagent 1,3-di-
selena-2,4-diphosphetane-2,4-diselenide (2, Fig. 1).2,3
amides 17–21 are isolated in yields up to 85% (Table 1).
This method is of general applicability and can be
extended to the synthesis of various N,N-dialkylsubsti-
tuted selenoamides (22–28) having an alkyl or aryl
substituent at the selenocarbonyl group. As expected,
the reactivity of the amides decreases with increasing
chain length and bulkiness of the substituents at nitro-
Compound 2 represents a selenium analogue of the
well-known sulfur transfer reagent
1 (Lawesson’s
reagent) and is easily prepared by reaction of (PhP)5
with 10 equiv. of grey selenium.4 Its ability to act as a
selenium transfer reagent by means of an O/Se-
exchange was initially reported by one of us,5 and the
group of J. D. Woollins.6
Figure 1. Lawesson’s reagent 1 and the selenium analogue 2.
Reaction of the formamides 3–7 with the selenide 2 in
a 4:1 molar ratio in benzene at ambient temperature
results in an O/Se-exchange at the carbonyl carbon
atom with formation of the selenoformamides 17–21
(Scheme 1). The reaction proceeds smoothly and is
complete within a maximum of 20 h. The selenoform-
Keywords: selenoamides; O/Se-exchange; selenium–Lawesson’s
reagent; selenium-NMR.
* Corresponding author. Tel.: +49-345-5582-1301; fax: +49-345-5582-
1309; e-mail: wessjohann@ipb-halle.de
Scheme 1. Syntheses of selenoamides using 2.
0040-4039/$ - see front matter © 2003 Elsevier Ltd. All rights reserved.
doi:10.1016/S0040-4039(03)01690-3

6912
J. Bethke et al. / Tetrahedron Letters 44 (2003) 6911–6913
Table 1. Selenoamides prepared by O/Se-exchange with reagent 219
Carboxamide
Selenoamide
R
R1
R2
Yield (%)
Mp (°C, uncorr.)
l
77Se20
3
4
5
6
7
8
9
10
11
12
13
14
15
16
1710
1811
1910
2012
2112
2213
2314
24
H
H
H
H
H
Me
Me
Me
Me
Et
Ph
4-MeOC6H4
n=1
n=2
Me
Et
iPr
Me
Ph
Me
Et
iPr
Me
Me
Et
Me
Et
82
77
75
85
59
66
29
21
48
57
72
66
74
61
609.5a
568.8a
586.3a
768.8a
879.4a
627.4b
592.9c
597.9c
659.3c
578.2c
771.0a
718.4a
376.4b
538.9c
iPr
Ph
Ph
Me
Et
iPr
Ph
Me
Et
87–88
–
105
70
25
2613
2715
2816
2917
3018
–
Me
Me
Me
Me
–
–
30
45
a Measured in C6D6.
b Measured in CD2Cl2.
c Measured in CDCl3.
Acknowledgements
gen, which results in longer reaction times and some-
what lower yields. Cyclic selenoamides, e.g. 29 and 30,
can be prepared starting from the corresponding lac-
tams 15 and 16 by the same procedure.
We thank the Deutsche Forschungsgemeinschaft for
financial support.
In all investigated reactions, all four selenium atoms of
the diselenide 2 are transferred to the organic com-
pound. Thus, in its selenium-transfer ability 2 is more
effective than Lawesson’s reagent in its sulfur-transfer
ability, where only half of the sulfur atoms are used
to generate the thioamide. The main phosphorus con-
taining by-product (> 80%) is the 2,4,6-triphenyl-
1,3,5,2,4,6-trioxatriphosphinane-2,4,6-trioxide, which is
readily identified by its 31P NMR spectrum (A2B type
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2
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209.7 for other carboxamides) in the 13C NMR spec-
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for the signal of the formamide proton (l=10.3–11.7)
1
2
in the H NMR spectrum with JSeH in the range of
7–10 Hz. The a-CH-protons of the higher selenoamides
synthesized appear between 2.4 and 3.1 ppm.
In conclusion, the selenation of amides using a selenium
analogue of Lawesson’s reagent, the 1,3-diselena-2,4-
diphosphetane-2,4-diselenide 2, provides a general and
straightforward route to N,N-disubstituted selenoform-
amides and selenoamides. The easy availability of
selenoamides by this route stimulates a systematic study
of their chemical properties. Further chemistry of 2 and
of other analogues of Lawesson’s reagent is under
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J. Bethke et al. / Tetrahedron Letters 44 (2003) 6911–6913
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NMR (CDCl3, 300 MHz): 3.62 (s, 3H, CH3), 3.26 (s, 3H,
CH3), 2.69 (s, 3H, CH3) ppm. 13C NMR (CDCl3, 75.5
MHz): 202.7 (CꢀSe), 48.7 (CH3), 42.7 (CH3), 37.2 (CH3)
ppm. 77Se NMR (CD2Cl2, 95.4 MHz): 627.4 ppm. GC–
+
’
MS (70 eV): m/z 151 (M , 100%), 107 (32%), MS (ESI):
151.99662. Anal. calcd for C4H9NSe (150.08): C, 32.01;
H, 6.04; N, 9.33. Found: C, 31.98; H, 5.91; N, 8.93%. 24:
1H NMR (CDCl3, 300 MHz): 6.35–6.16 (m, 1H), 4.24–
4.04 (m, 1H), 2.89 (s, 3H, CH3), 1.46 (d, J=6.6 Hz, 6H,
CH3), 1.27 (d, J=5.9 Hz, 6H, CH3) ppm. 13C NMR
(CDCl3, 75.5 MHz): 202.8 (CꢀSe), 60.4 (NCH), 50.1
(NCH), 37.4 (CH3), 22.0 (CH3), 19.1 (CH3) ppm. 77Se
NMR (CDCl3, 95.4 MHz): 597.9 ppm. GC–MS (70 eV):
m/z 207 (M , 46%), 123 (43%), 58 (100%). MS (ESI):
16. Yoshifuji, M.; Higeta, N.; An, D.-L.; Toyota, K. Chem.
Lett. 1998, 1, 17–18.
17. Takikawa, Y.; Watanabe, H.; Sasaki, R.; Shimada, K.
+
’
208.05959; calcd: 208.0599. 25: 1H NMR (CDCl3, 300
MHz): 7.51–7.37 (m, 3H, arom. H), 7.22–7.16 (m, 2H,
arom. H), 3.85 (s, 3H, CH3), 2.43 (s, 3H, CH3) ppm. 13C
NMR (CDCl3, 75.5 MHz): 205.1 (CꢀSe), 145.6 (C-i),
129.9 (C-m), 128.6 (C-p), 124.3 (C-o), 49.9 (NCH3), 38.4
Bull. Chem. Soc. Jpn. 1994, 67, 876–878.
18. Michael, J. P.; Reid, H. D.; Rose, G. B.; Speirs, A. R. J.
Chem. Soc., Chem. Commun. 1988, 1494–1496.
19. General procedure: To a suspension of reagent 2 (0.53 g,
1 mmol) in 3–5 ml benzene the corresponding carbox-
amide (4 mmol) is added. The resulting mixture is stirred
for 12–20 h at room temperature, while 2 dissolves com-
pletely. From the resulting clear yellow–green solution
the solvent is evaporated in vacuo and the residue is
subjected to vacuum distillation [10−1 mbar and 90–150°C
Kugelrohr apparatus temperature (Bu¨chi)] or chro-
matographed on dried (!) silica gel with CH2Cl2.
(CH3) ppm. 77Se NMR (CDCl3, 95.4 MHz): 659.3 ppm.
+
’
GC–MS (70 eV): m/z 213 (M , 31%), 91 (38%), 56
(100%). MS (ESI): 214.01217; calcd: 214.0129. 30: 1H
NMR (CDCl3, 300 MHz): 3.58 (s, 3H, NCH3), 3.42 (t,
J=6.2 Hz, 2H, NCH2), 3.04 (t, J=6.2 Hz, 2H, CH2),
1.96 (quint, J=6.2 Hz, 2H, CH2), 1.70 (quint, J=6.2 Hz,
2H, CH2) ppm. 13C NMR (CDCl3, 75.5 MHz): 202.4
(CꢀSe), 53.8 (NCH2), 47.5 (NCH3), 45.1 (CH2), 22.9
(CH2), 20.4 (CH2) ppm. 77Se NMR (CDCl3, 95.4 MHz):
1
20. Spectral data for some typical selenoamides:17: H NMR
+
’
538.9 ppm. GC–MS (70 eV): m/z 177 (M , 91%), 68
(C6D6, 270.17 MHz): 10.32 (s, 1H, CHꢀSe), 2.73 (s, 3H,
CH3), 2.07 (s, 3H, CH3) ppm. 13C{1H} NMR (C6D6,
67.94 MHz): 191.3 (CHꢀSe), 47.9 (CH3), 40.9 (CH3)
(100%). MS (ESI): 178.01214. Anal. calcd for C6H11NSe
(176.12): C, 40.92; H, 6.30; N, 7.95. Found: C, 40.88; H,
6.21; N, 7.63%.
1
ppm. 77Se NMR (C6D6, 51.39 MHz): 609.5 ppm. 22: H