title: Synthesis of mono- and difluoronaphthoic acids.
abstract: Aryl carboxamides are useful structural units found in several biologically active compounds. Unlike their benzoic acid counterparts, fluorinated versions of naphthoic acids are relatively unknown. In connection with a recent project, we needed viable syntheses of several mono- and difluorinated naphthoic acids. Herein we describe the synthesis of 5-, 6-, 7-, and 8-fluoro-1-naphthalenecarboxylic acids and 5,7-, 5,8-, 6,7-, and 4,5-difluoro-1-naphthalenecarboxylic acids. The 5-fluoro derivative 1was obtained from the corresponding 5-bromo compound via electrophilic fluorination of the lithio-intermediate. The rest of the monofluoro (2, 3, and 4) and the difluoro acids (5, 6, and 7) were prepared by a new, general route which entailed the elaboration of commercial fluorinated phenylacetic acids to 2-(fluoroaryl)glutaric acids with differential ester groups; selective hydrolysis to a mono acid, intramolecular Friedel-Crafts cyclization, and aromatization furnished the target structures. An alternative process to assemble a naphthalene skeleton is also presented for the difluoro acids 5 and 6. Finally, 4,5-difluoro-1-naphthalenecarboxylic acid (8) was prepared expeditiously from 1,8-diaminonaphthalene by adapting classical reactions.
authors.affiliation: Chemical Research, Schering-Plough Research Institute, 2015, Galloping Hill Road, K-15-2B-2800, Kenilworth, New Jersey 07033-0539, USA. jarayam.tagat@spcorp.com
authors.forename: Jayaram R
authors.initials: JR
authors.lastname: Tagat
authors.forename: Stuart W
authors.initials: SW
authors.lastname: McCombie
authors.forename: Dennis V
authors.initials: DV
authors.lastname: Nazareno
authors.forename: Craig D
authors.initials: CD
authors.lastname: Boyle
authors.forename: Joseph A
authors.initials: JA
authors.lastname: Kozlowski
authors.forename: Samuel
authors.initials: S
authors.lastname: Chackalamannil
authors.forename: Hubert
authors.initials: H
authors.lastname: Josien
authors.forename: Yuguang
authors.initials: Y
authors.lastname: Wang
authors.forename: Guowei
authors.initials: G
authors.lastname: Zhou