A Large-Scale Low-Cost Preparation of N-Benzylhydroxylamine Hydrochloride

Abstract

A high-yielding, practical two-step procedure for the preparation of N-benzylhydroxylamine starting from dibenzylamine is described­. As specified in the detailed protocol, the reaction can be conveniently carried out on a > 0.5 mol laboratory scale.

Key words

N-benzylhydroxylamine - N-benzylnitrones - 1,3-dipolar cycloaddition - secondary amine oxidation - nitrone hydrolysis

References

• 1a Inouye Y. Hara J. Kakisawa H. Chem. Lett.  1980,  1407 
• 1b Nguyen TB. Martel A. Dhal R. Dujardin G. J. Org. Chem.  2008,  73:  2621 
• 1c Dondoni A. Franco S. Junquera F. Merchan F. Merino P. Tejero T. Synth. Commun.  1994,  24:  2537 
• 2a Winterfeldt E. Krohn W. Stracke H. Chem. Ber.  1969,  102:  2346 
• 2b Nguyen TB. Martel A. Dhal R. Dujardin G. Org. Lett.  2008,  10:  4493 
• 3a Nguyen TB. Gaulon C. Chapin T. Tardy S. Tatibouet A. Rollin P. Dhal R. Martel A. Dujardin G. Synlett  2006,  3255 
• 3b Nguyen TB. Martel A. Dhal R. Dujardin G. Synlett  2008,  2041 
• 3c Nguyen TB. Vuong TMH. Martel A. Dhal R. Dujardin G. Tetrahedron: Asymmetry  2008,  19:  2084 
• 3d Nguyen TB. Martel A. Dhal R. Dujardin G. Synlett  2009,  in press 
• 4 Jones LW. Sneed MC. J. Am. Chem. Soc.  1917,  39:  677 
• 5 Feuer H. Vincent BF. Bartlett RS. J. Org. Chem.  1965,  30:  2877 
• 6 Nakajima M. Anselme JP. J. Org. Chem.  1983,  48:  1444 
• 7a Murahashi SI. Mitsui H. Shiota T. Tsuda T. Watanabe S. J. Org. Chem.  1990,  55:  1736 
• 7b Murahashi S.-I. Shiota T. Imada Y. Org. Synth. Coll. Vol. 9   Wiley; New York: 1998.  p.632 
• 8 Murahashi S.-I. Shiota T. Tetrahedron Lett.  1987,  28:  2383 
• 9 Goti A. Cardona A. Soldaini G. Org. Synth.  2005,  81:  204 
• 10 Murray RW. Singh M. J. Org. Chem.  1990,  55:  2954 
• 11 Zajac WW. Walters TR. Darcy MG. J. Org. Chem.  1988,  53:  5856 
• 14a Tokuyama H. Kuboyama T. Amano A. Yamashita T. Fukuyama T. Synthesis  2000,  1299 
• 14b Tokuyama H. Kuboyama T. Fukuyama T. Org. Synth.  2003,  80:  207 
• 14c Coskun N. Parlar A. Synth. Commun.  2005,  35:  2445 
• 15 Inouye Y. Watanabe S. Kakisawa H. Bull. Chem. Soc. Jpn.  1979,  52:  3763 

12

The cost of the tungstate catalyst, used at a 2 mol%, is approximately 60 ı/mol.

13

Evaporation of the solvent (MeOH) at reduced pressure in the presence of large quantities of aqueous H₂O₂, as described in reference 7.