Tetramethyl-cyclopropane carboxylic acid

The Faworski-rearrangement of a-halocyclobutanones provides a very attractive and in practice, often particularly useful method [488-491], since it usually utilizes readily available acid chlorides and olefins as precursors. Not only the commercially important (fenpropathrin) tetramethyl cyclopropane carboxylic acid 247 as in Reaction scheme 169, but many others, particularly higher alkyl-substituted cyclopropane carboxylic acids are preferentially prepared in this way (Reaction scheme 170). 

Hydrolysis of the pyrethroids may occur prior to hydroxylation. For dichloro groups (i.e., cyfluthrin, cypermethrin and permethrin) on the isobutenyl group, hydrolysis of the trans-isomers is the major route, and is followed by hydroxylation of one of the gem-dimethyls, the aromatic rings, and hydrolysis of the hydroxylated esters. The cis-isomers are not as readily hydrolyzed as the tran -isomers and are metabolized mainly by hydroxylation. Metabolism of the dibromo derivative of cypermethrin, deltamethrin, is similar to other pyrethroids (i.e., cyfluthrin, cypermethrin, and permethrin) that possess the dichloro group. Type 11 pyrethroid compounds containing cyano groups (i.e., cyfluthrin, cypermethrin, deltamethrin, fenvalerate, fenpropathrin, and fluvalinate) yield cyanohydrins (benzeneacetonitrile, a-hydroxy-3-phenoxy-) upon hydrolysis, which decompose to an aldehyde, SCN ion, and 2-iminothia-zolidine-4-carboxylic acid (TTCA). Chrysanthemic acid or derivatives were not used in the synthesis of fenvalerate and fluvalinate. The acids (i.e., benzeneacetic acid, 4-chloro-a-(l-methylethyl) and DL-valine, Af-[2-chloro-4-(trifluoromethyl) phenyl]-) were liberated from their esters and further oxidized/conjugated prior to elimination. Fenpropathrin is the oifly pyrethroid that contains 2,2,3,3-tetramethyl cyclopropane-carboxylic acid. The gem-dimethyl is hydroxylated prior to or after hydrolysis of the ester and is oxidized further to a carboxylic acid prior to elimination. 

Cyclopropane carboxylic acid, 2,2,3,3-tetramethyl cyano(3-phenoxyphenyI)methyl ester Fenpropathrin , Danitol ... 

The four-membered ring-system 250 is formed transiently in the next sequence (Reaction scheme 174), which looks like a technical process to produce the tetramethyl cyclopropane carboxylic 247 acid for fenpropathrin [496]. 

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