Synthesis of Anti‐Inflammatory α‐Arylalkanoic Acids by 1,2‐Aryl Shift. New Synthetic Methods (42)

Abstract

I I a-Arylalkanoic acids have acquired importance as anti-inflammatory agents and are now in great demand on the pharmaceutical front. Hence, the need has arisen for new and improved, economical synthetic procedures suitable for their preparation and manufacture on an industrial scale. For many years the synthetic approach to this class of compounds was restricted to the Willgerodt and Darzen reactions. More recently, several methods have been developed which are based on the 1,2-aryl shift in acetals of a-functionalized alkyl aryl ketones. This new approach starts from the oxythallation of alkyl aryl ketones first described by Taylor and McKillop in 1971. Asymmetric syntheses of some important arylalkanoic acids have also been developed on this basis. The highly toxic thallium salts may be replaced, inter alia, by catalytically effective metal salts.

Electrocatalytic reduction of arylethyl chlorides at silver cathodes in the presence of carbon dioxide: Synthesis of 2-arylpropanoic acids

“…Some of the most important NSAIDs are 2-arylpropanoic acids such as naproxen and ibuprofen and several methods have been proposed for their preparation [3][4][5]. Nevertheless, the conventional methods of synthesis on which most industrial processes are based make use of several dangerous or toxic reagents such as cyanides, very strong bases, Grignard reagents, etc.…”

Oxidative rearrangement of aryl ethyl ketones to alkyl 2-arylpropanoates by lead(IV) acetate

“…(1; R' = H, Me, But, Ph, Br) with lead(iv) acetate in trialkyl orthoformate in the presence of acid catalyst is found to give alkyl esters of 2-arylpropanoic acids (2) in good to excellent yields via 1,2-aryl migration in (1). Hydrolysis of (2) leads to the corresponding acids, some of which are important pharmaceutical compounds. The rate of aryl migration increases when the substituent R' is an electron-releasing group such as methyl, isobutyl, or phenyl.…”

Preparation of enantiopure (R)-flurbiprofen catalyzed by a newly isolatedBacillus cereusC71

“…The 2-arylpropanoic acids, also known as Profens, are an important class of non-steroidal anti-inflammatory compounds (NSAIDS) (Giordano et al 1984;Zhang et al 2005). The anti-inflammatory activity of Profens is mainly due to the S-enantiomer (Shen et al 1972;Lotsch et al 1995).…”