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M. Rahman et al. / Tetrahedron Letters 51 (2010) 2896–2899
Table 1 (continued)
Entry
Substrate
Product
Time (min)
60
Yielda (%)
60
Ref.b
14
13
14
NH2
NHCHO
60
60
60
85
14
7
NH2
NHCHO
NH2
NHCHO
15
NH2
NH2
NHCHO
NHCHO
16
17
60c
60
85
80
7
7
HO
HO
NH2
NHCHO
a
Isolated yield.
Reported in the literature.
2-equiv w.r.t. amine.
b
c
NH2
NHPh
Ph NCHO
(0%)
NHCHO
+
HCOOH (1 equiv.)
80 oC, 25 min
+
(1 equiv.)
(1 equiv.)
CH2NH2
(85 %)
CHO
CH2NHCH2Ph
CH2NHCHO
CH2NCH2Ph
HCOOH (1 equiv.)
+
+
80 oC, 60 min
(1 equiv.)
(1 equiv.)
(0%)
(85 %)
Scheme 2.
to those for aromatic amines. The procedure is equally effective for
secondary amine (entries 10, 11, and 12). Only piperidine, morpho-
line, and 4-nitroaniline took little higher 3, 5, and 8 h, respectively.
The results are summarized in Table 1.
Department of Science and Technology (DST) for financial support
(Grant No. SR/FTP/CS/107/2006). We are thankful to DST-Funding
for Infrastructure in Science and Technology (FIST) and Special
Assistance Program (SAP)-University Grants Commission (UGC).
The difference in the reactivity of amines shows chemoselectiv-
ity of this method, as shown in Scheme 2. Thus when a mixture of
primary amine and secondary amine was exposed to formic acid
(1 equiv), it produced the product based on primary amine
selectively.
References and notes
1. Hartinez, J.; Laur, J. Synthesis 1982, 979.
2. (a) Kobayashi, K.; Nagato, S.; Kawakita, M.; Morikawa, O.; Konishi, H. Chem.
Lett. 1995, 575; (b) Chen, B. C.; Bednarz, M. S.; Zhao, R.; Sundeen, J. E.; Chen, P.;
Shen, Z.; Skoumbourdis, A. P.; Barrish, J. C. Tetrahedron Lett. 2000, 41, 5453.
3. Kobayashi, S.; Nishio, K. J. Org. Chem. 1994, 59, 6620.
4. Kobayashi, S.; Yasuda, M.; Hachiya, I. Chem. Lett. 1996, 407.
5. Downie, I. M.; Earle, M. J.; Heaney, H.; Shuhaibar, K. F. Tetrahedron 1993, 49,
4015.
6. Han, Y.; Cai, L. Tetrahedron Lett. 1997, 38, 5423.
7. Blicke, F. F.; Lu, C.-J. J. Am. Chem. Soc. 1952, 74, 3933.
8. Waki, J.; Meinhofer, J. J. Org. Chem. 1977, 42, 2019.
9. Chen, F. M. F.; Benoiton, N. L. Synthesis 1979, 709.
10. Jung, H. S.; Ahn, J. H.; Park, S. K.; Choi, J. K. Bull. Korean Chem. Soc. 2002, 23, 149.
11. Reddy, P. G.; Kumar, G. D. K.; Bhaskaran, S. Tetrahedron 2000, 41, 9149.
12. Luca, L. D.; Giacomelli, G.; Porcheddu, A.; Salaris, M. Synlett 2004, 2570.
13. (a) Mihara, M.; Ishino, Y.; Minakara, S.; Komatsu, M. Synthesis 2003, 2317; (b)
Hosseini-Sarvari, M.; Sharghi, H. J. Org. Chem. 2008, 71, 6652; (c) Das, B.;
Krishnaiah, M.; Balasubramanyam, P.; Veeranjaneyulu, B.; Nandan kumar, D.
Tetrahedron Lett. 2008, 49, 2225; (d) Firouzabadi, H.; Iranpoor, N.; Farahi, S. J.
Mol. Catal. A: Chem. 2008, 289, 61; (e) Niknam, K.; Saberi, D. Tetrahedron Lett.
2009, 50, 5210.
No organic or aqueous solvents were used except for the extrac-
tion of crude product and purification.
In conclusion, we have developed a remarkably simple and
highly efficient methodology for the N-formylation of amine with
moderate to good yields. Operational simplicity, solvent and cata-
lyst-free media, mild reaction conditions, environmentally friendly
reaction conditions, the compatibility with various functional
groups are the advantages of the present procedure. To the best
of our knowledge, this is the first report of N-formylation with for-
mic acid without any catalyst and solvent. We believe that this will
present a better and more practical alternative to the existing
methodologies for the N-formylation of amines.
Acknowledgments
14. Chandra Shekhar, A.; Ravi Kumar, A.; Sathaiah, G.; Luke Paul, V.; Sridhar, M.;
Shanthan Rao, P. Tetrahedron Lett. 2009, 50, 7099.
15. (a) Yale, H. L. J. Org. Chem. 1971, 36, 3238; (b) Kisfaludy, L.; Laszlo, O. Synthesis
A.M is pleased to acknowledge the financial support of CSIR
(Ref. No. 01(2251)/08/EMR-II dated 21-05-2008) A.H. is thankful
1987, 510; (c) Duezek, W.; Deutsch, J.; Vieth, S.; Niclas, H. J. Synthesis 1996, 37.