Synthesis 2005(4): 639-643  
DOI: 10.1055/s-2004-837302
© Georg Thieme Verlag Stuttgart · New York

Unexpected Smiles Rearrangement During Borane Reduction of 2-Aryloxy-2-methylpropionamides

Hans-Peter Buchstaller*, Uwe Anlauf
Merck KGaA, Medicinal Chemistry Research Laboratories, Frankfurter Str. 250, 64271 Darmstadt, Germany
Fax: +49(6151)723129; e-Mail:;
Further Information

Publication History

Received 22 October 2004
Publication Date:
22 December 2004 (online)


2-Nitrophenols spontaneously rearrange during alkyl­ation with 2-bromo-2-methylpropionamide in the presence of cesium carbonate in acetonitrile to the corresponding 2-hydroxy-2-methyl-N-(2-nitrophenyl)propionamides. Upon reduction of 2-aryloxy-2-methylpropionamides, which were obtained from 2-nitrophenols in three steps, with borane dimethyl sulfide complex in THF, a Smiles rearrangement was observed as well leading to 2-methyl-1-phenyl­aminopropan-2-ols. Both approaches give access to valuable 2-nitro substituted aniline derivatives.


  • 1 Weidner JJ. Weintraub PM. Schnettler RA. Peet NP. Tetrahedron  1997,  53:  6303 
  • 2 Geen GR. Mann IS. Valerie Mullane M. Tetrahedron  1998,  54:  9875 
  • 3 Duranti E. Bonifazi P. Salvatori A. Balsamini C. Peruzzi G. Cantoni O. Farmaco, Ed. Sci.  1983,  38:  664 
  • 4 Bayles R. Johnson MC. Maisey RF. Turner RW. Synthesis  1977,  33 
  • 5 Matsumoto Y. Tsuzuki R. Matsuhisa A. Takayama K. Yoden T. Uchida W. Asano M. Fujita S. Yanagisawa I. Fujikura T. Chem. Pharm. Bull.  1996,  44:  103