Lewis acid catalysed Cyclyzation of Amino alcohol and Cyanoester

SyntheticPage 490

DOI:

10.1039/SP490

Submitted: March 28, 2011, published: April 1, 2011

Authors

Abir Kumar Pal (abirchem2@yahoo.com)

A contribution from

Dr. Reddys Laboratory, India

Chemicals

2-amino-5-chlorobenzyl alcohol (Alfa-Aesar)
Methyl 2-cyanobenzoate (see Referance)
BF₃.Et₂O (SRL) (48-50% BF₃)
Dichloromethane

Procedure

A mixture of 2-amino-5-chlorobenzyl alcohol (250 mg, 1.6 mmol) , methyl 2-cyanobenzoate (260mg, 1.6 mmol) and BF₃.Et₂O (2.5 ml, 48-50% BF₃) was heated at 75-80° C under nitrogen atmosphere for 10-12 h. The reaction was monitored by TLC (neat DCM). The reaction mass was quenched in 10% sodium carbonate solution and extracted with DCM (10 x 2 ml). The crude product was purified by column chromatography (using 230-400 mesh silica gel) using dichloromethane (neat) to yield the pure product as a yellowish solid (250 mg, 58% yield).

Author Comments

The reaction was performed in trifluoroacetic acid (TFA) instead of BF₃- Et₂O giving 40% yield.
(The reaction is neat reaction where BF₃-Et₂O or TFA using as solvent.)

Data

1H NMR (CDCl3, 400MHz): 8.046 (1H,d); 7.919 (1H,d); 7.66~ 7.75(2H,m); 7.425 (1H,d); 7.303 (1H,d); 7.17 (1H,s); 4.969 (2H,s)
Mass (M+H): 269.10

Lead Reference

Kshirsagar, U. A.; Argade, N. P. Tetrahedron, 2009, 65, 5244; doi:10.1016/j.tet.2009.04.088
Eguchi, S.; Takeuchi, H., Chem. Comm., 1989, 602; doi:10.1039/C39890000602
Martinez-Viturro, C. M.; Dominguez, D.,Tet. Lett., 2007, 48, 1023; doi:10.1016/j.tetlet.2006.11.168
Kametani, J. Heterocyclic Chem., 1971, 8, 1071; doi:10.1002/jhet.5570080638

Other References

Preparation of Methyl-2-cyano benzoate: Jin, F.; Confalone, P. N. Tet. Lett., 2000, 41, 3271; doi:10.1016/S0040-4039(00)00384-1
Sakamoto, T.; Ohsawa, K., J. Chem Soc., Perkin Trans. 1, 1999, 16, 2323; doi:10.1039/a903345i
Srivastava, R. R.; Zych, A. J.; Jenkins, D. M.; Wang, H.-J.; Chen, Z.-J.; Fairfax, D. J. Synth. Comm., 2007, 37, 431; doi:10.1080/00397910601039044
Chattopadhyay, K.; Dey, R; Ranu, B. C. Tet. Lett., 2009, 50, 3164; doi:10.1016/j.tetlet.2009.01.027

Get structure file (.cdx)

Keywords

amines, esters, heterocyclic compounds