M. I. Ansari et al. / Tetrahedron Letters 53 (2012) 2063–2065
2065
Table 3
Ministry of Health & Family Welfare is highly acknowledged and
all are also grateful to SAIF-CDRI for spectroscopic analysis of the
compounds.
N-formylation of secondary amines
Entry
Amine
N-formaldehyde
Time
(min)
Yielda
(%)
Supplementary data
O
O
N
NH
1
2
30
40
91
94
O
Supplementary data associated with this article can be found, in
N
N
N
NH
O
References and notes
N
NH
3
4
25
20
86
74
O
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74, 5967.
NH
N
O
H
N
O
N
5
6
30
30
72
70
H3C
H3C
N
NH
O
a
Isolated yield.
10. Chen, B. C.; Bednarz, M. S.; Zhao, R.; Sundeen, J. E.; Chen, P.; Shen, Z.;
Skoumbourdis, A. P.; Barrish, A. P. Tetrahedron Lett. 2000, 41, 5453.
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Table 4
Comparison of N-formylation with other silica supported protic acids
Entry
Catalyst
Time (min)
Yield (%)
1
2
3
4
HClO4–SiO2
H2SO4–SiO2
HBF4–SiO2
TFA–SiO2
15
35
40
20
96
55
50
48
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Table 5
The catalytic activity of HClO4–SiO2 in the model reaction with aniline
Entry
No. of cycles
Yield (%)
1
2
3
4
1
2
3
4
96
90
85
65
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by simple filtration, washed (2–3 times) with diethyl ether, and
dried at 80 °C under vacuum for 2 h. The recovered catalyst was
reused for N-formylation without any significant loss of activity
upto three cycles. However, reuse of the catalyst in the fourth cycle
results in considerably reduced yields, may be due to the poisoning
of the surface of the catalyst8 (Table 5).
24. Angelis, A. D.; Flego, C.; Ingallina, P.; Montanari, L.; Clerici, M. G.; Carati, C.;
Perego, C. Catal. Today 2001, 65, 363.
25. Preparation of HClO4–SiO2 Catalyst5: Perchloric acid (1.25 g, 12.5 mmol, 70% aq.
solution) was added to a suspension of silica-gel (230–400 mesh, 23.75 g) in
Et2O (70.0 mL) and the mixture was stirred for 30 min. The residue obtained on
the removal of excess solvent was heated at 100 °C for 72 h under vacuum to
furnish silica supported perchloric acid as a free flowing powder (1 g silica gel
contains 0.5 mmol of HClO4). General procedure of N-formylation—To a mixture
of 2-bromoaniline (0.11 ml, 1 mmol) and formic acid (0.12 ml, 3 mmol) in a
10 ml round bottomed flask was added HClO4–SiO2 (50 mg, 0.025 mmol). The
reaction mixture was stirred at room temperature for 25 min. On completion,
the mixture was diluted with diethyl ether and filtered to remove the solid
catalyst. The filtrate was washed with sat. solution of NaHCO3 (5 ml  3),
water, and dried over anhy. Na2SO4. The solvent was evaporated and the crude
residue was purified by column chromatography to give a colourless solid,
yield 94%, mp: 89 °C, IR (KBr): 3297, 1666 (C@O), 1536, 1435, 1401, 1293,
740 cmÀ1 ESIMS, m/z: 199.97; 1H NMR (300 MHz, DMSO) d 9.71 (br s, s, 1H,
NH), 8.35 (s, 1H, CHO), 8.01 (d, J = 7.5, 1H), 7.65 (d, J = 6.97, 1H), 7.37 (t, J = 7.66,
1H), 7.09 (t, J = 6.97, 1H), 13C, 50 MHz (DMSO): 162.5, 160.3, 135.4, 133.1,
128.1, 126.1, 124.3, 124.0, 114.4.
In conclusion, we have developed a highly efficient and solvent-
free HClO4–SiO2 catalyzed method for the N-formylation of primary
aromatic and secondary amines at room temperature. Excellent
chemoselectivity was observed with substrates having phenolic
OH, providing N-formamide as the sole product. This protocol can
be used to generate a diverse range of primary and secondary for-
mamides in excellent yields. The catalyst is completely recoverable
and the efficiency of the catalyst remains unaltered even after three
to four cycles.
Acknowledgements
The authors, M. I.A, M. K.H, N. Y. and P.K. G are thankful to CSIR
New Delhi, for SRF & JRF fellowships. Financial assistance from