5692
N. B. Gowda et al. / Tetrahedron Letters 51 (2010) 5690–5693
Table 1 (continued)
Entry
Substrate
CONH2
Time (h)
4.5
Yielda (%)
62
Productb
CONH2
14
15
N
O
N
14
14a
O
N
N
4.5
4.5
79
74
15a
15
16
16a
N
O
CH3
N
CH3
16
a
Yields of isolated products.
b
c
Most of the products are commercially available and were identified by comparison of their NMR and mass spectra with those of authentic samples.
N-Oxides dissolved in water and ethanol (2:1).
N-Oxides dissolved in water and methanol (2:1).
d
When amitriptyline N-oxide35,45 (entry 1) and cyclobenza-
Supplementary data
prine N-oxide (entry 7) were subjected to deoxygenation, com-
plete chemoselective deoxygenation occurred to give good yield
of 1a and 7a. In both the cases, double bond was not affected.
The utility of the method has been extended to the deoxygen-
ation of many pharmacologically active N-oxides. Similarly in en-
try 3, tert-hydroxyl and olefin groups remained intact, and the
reaction gave 92% of the deoxygenated product, 3a. This product
is an intermediate in the synthesis of cyclobenzaprine.37 Trimip-
ramine N-oxide and imipramine N-oxide (entries 2 and 4) were
deoxygenated to the corresponding amines 2a and 4a38 in good
yields. Clomipramine N-oxide (entry 5) was completely reduced
to Clomipramine and the halogen group remained intact. Venla-
faxine N-oxide (entry 6) was deoxygenated to venlafaxine39 with
92% yield. Similarly ether groups and pyridine groups were unaf-
fected during the reduction of Orphenadrine N-oxide (entry 8),
carbinoxamine N-oxide, and doxepin N-oxide41 (entries 9 and
10) to afford the corresponding amines 9a40 and 10a in good
yields. Loperamide N-oxide and ebastine N-oxide (entries 11
and 12) also reacted well to give corresponding reduced product
of 11a42 and 12a. In the case of ebastine (entry 12), keto group
was also reduced. Other aromatic N-oxides36,43,44 (entries 13–16)
were completely reduced to their corresponding amines. The
moderate yields in these examples are due to the partial solubil-
ity of these products in water. This method however failed to
work for triphenyl phosphine oxide and chlorpromazine
sulfoxide.
Supplementary data (spectral data and 1H and 13C NMR of N-
oxides and corresponding products) associated with this article
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Acknowledgments
Authors would like to thank Professor B. G. Shivananda, Prin-
cipal, Al-Ameen College of Pharmacy and management, Visvesw-
arapura Institute of Pharmaceutical Sciences, Bangalore for
providing facilities and constant support. This work was also
generously supported by Mr. Anjan Roy Managing director R.L.
Fine Chem, Bangalore, India. Also we would like to thank Dr.
K. R. Prabhu, Indian Institute of Science, Bangalore, India for use-
ful discussion.
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