5534
L. D. S. Yadav et al. / Tetrahedron Letters 50 (2009) 5532–5535
Table 2
3 to nitriles 1 with BDMS is favorable in acetonitrile, which is in
Conversion of aldoximes to nitriles with BDMSa
conformity with the solvent effect earlier observed with PPh3/
CCl4 system.13b
Br
S
CH3CN
Br
R
CN +
DMSO
2HBr
+
R
CH NOH +
In conclusion, bromodimethylsulfonium bromide (BDMS) has
been employed here for the first time as a mild and efficient re-
agent for the conversion of the wide range of aldoximes and pri-
mary amides to the corresponding nitriles. The method offers a
useful alternative to the existing methodologies, as it is simple,
high yielding and requires no added base or catalyst. The present
work has opened up a new aspect of the synthetic utility of BDMS.
rt
BDMS
2
1
Entry
R
Nitrileb
Time (h)
Conv.c (%)
Yieldd,e (%)
2a
2b
2c
2d
2e
2f
2g
2h
2i
Ph
1a
1b
1c
1d
1e
1f
1g
1h
1i
5.5
4
3
5
6
4
3
4
4.5
4
>99
98
>99
96
98
97
97
90
93
89
94
91
96
89
92
88
90
76
81
78
84
87
4-MeOC6H4
3,4,5-(MeO)3C6H2
4-ClC6H4
4-NO2C6H4
4-MeC6H4
C6H5CH@CH
CH3(CH2)2
CH3(CH2)3
C6H5(CH2)2
2-Furyl
Acknowledgment
We sincerely thank SAIF, Punjab University, Chandigarh, for
providing microanalyses and spectra.
2j
2k
2l
1j
1k
1l
6
3
92
>99
2-Thienyl
References and notes
a
See Ref. 31a for general procedure.
All are known compounds.32
Conversion (%) of 2 as determined by GC analysis with diphenyl or naphthalene
1. (a) Smith, M.; March, J. Advanced Organic Chemistry: Reactions, Mechanisms and
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2001, 31, 431.
b
c
as an internal standard.
d
Products were characterized by comparison of their mp or bp, TLC, IR, and 1H
NMR data with those of authentic samples.
e
Yields of the isolated pure compounds.
Table 3
Conversion of primary amides into nitriles with BDMSa
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Br
CH3CN
Br
S
R
CN + DMSO
2HBr
+
+
R
CONH2
reflux
BDMS
1
3
Entry
R
Nitrileb
Time (h)
Conv.c (%)
Yieldd,e (%)
3a
3b
3c
3d
3e
3f
Ph
1a
1b
1d
1e
1m
1n
1o
1p
2
2
3
4
2
3.5
3
>99
96
96
95
>99
92
91
86
89
90
94
78
80
87
4-MeOC6H4
4-ClC6H4
4-NO2C6H4
3,4-(MeO)2C6H3
C6H5CH2
3g
3h
Cyclohexyl
CH3(CH2)6
94
94
4
a
See Ref. 31b for general procedure.
All are known compounds.32
Conversion (%) of 3 as determined by GC analysis with diphenyl or naphthalene
b
c
6. Yamaguchi, K.; Mizuno, N. Angew. Chem., Int. Ed. 2003, 42, 1480.
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Srinivas, R.; Yadav, J. S. Synth. Commun. 2000, 30, 4507.
as an internal standard.
Products were characterized by comparison of their mp or bp, TLC, IR, and 1H
NMR data with those of authentic samples.
d
e
Yields of the isolated pure compounds.
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A mechanistic rationale for the preparation of nitriles 1 from
aldoximes 2 and primary amides 3 is depicted in Scheme 2. It is
easily conceivable that the aldoxime 2 and primary amide 3 are
initially coupled with BDMS to form an active O-derivative inter-
mediate 4 or 5, respectively, which in turn undergo bromide an-
ion-induced elimination to deliver the corresponding nitriles 1
along with DMSO and HBr. The aldoximes 2 were converted to ni-
triles 1 at rt but primary amides 3 required reflux temperature
probably due to demand of high energy for the breakage of more
strong C–O bond involved during elimination process in primary
amide-derived O-intermediate 5 than that of N–O bond breakage
operated in aldoxime-derived O-intermediate 4. Moreover, among
the solvents tested (CH3CN, DCM, THF, and 1,4-dioxane), the trans-
formation of primary amide to nitriles took place only in CH3CN.
This suggests that in CH3CN the equilibrium concentration of tau-
tomer 30 is enough to attack BDMS to afford the corresponding ni-
trile 1 (Scheme 2), whereas in THF or 1,4-dioxane it is too low to
bring about the reaction. Thus, the conversion of primary amides
16. (a) Sahu, S.; Patel, S.; Mishra, B. K. Synth. Commun. 2005, 35, 3123; (b) Isobe, T. J.
Org. Chem. 1999, 64, 6984.