A novel rearrangement of ortho-aryloxy arylcarboxamides

ORGN 615

Yinglin Han, yhan@arqule.com1, Lixin Shen1, Chee-Seng Lee1, Grace Bi1, Steve Couture1, Andrew Bell2, David Hepworth2, Libing Yu1, Ying Zhang, yzhang@arqule.com1, Michele Harris1, and Carmen Baldino1. (1) Chemistry Department, ArQule, Inc, 19 Presidential Way, Woburn, MA 01801, (2) Discovery Chemistry, Sandwich Laboratories, Pfizer Clobal Reseach & Development, Sandwich, Kent, CT13 9NJ, Kent, United Kingdom
During the course of our research, we discovered an unusual rearrangement of ortho-aryloxy arylcarboxamides. It was intriguing to find that heating of ortho-aryloxy N-alkyl benzamides at 120 oC in DMF or N,N-dimethylacetamide resulted in formation of the corresponding ortho-hydroxy N-alkyl-N-aryl derivatives. This rearrangement also occurred with substituted 2-aryloxy N-alkyl-3-pyridine carboxamides, 1, and substituted 4-aryloxy N-alkyl-3-pyridine carboxamides. Electron donating groups on the aryl ring at the meta-position promoted the rearrangement while sterically hindered amides at R3 resulted in slow formation of products. Further details about the proposed mechanism and the impact of the nature of the R groups on the ease of rearrangement will be presented.

 

New Reactions and Methodology
8:00 AM-12:00 PM, Wednesday, 16 March 2005 Convention Center -- Ballroom 20 C-D, Oral

Division of Organic Chemistry

The 229th ACS National Meeting, in San Diego, CA, March 13-17, 2005