SYNTHESIS OF CYCLOHEXANE DERIVATIVES USEFUL AS SENSATES IN CONSUMER PRODUCTS

摘要

The present invention provides synthetic routes for preparing various isomers of cyclohexane-based coolants, such as menthyl esters and menthanecarboxamide derivatives, in particular those substituted at the amide nitrogen, for example with an aromatic ring or aryl moiety. Such structures have high cooling potency and long lasting sensory effect, which make them useful in a wide variety of consumer products. One synthetic route involves a copper catalyzed coupling of a primary menthanecarboxamide with an aryl halide, such reaction working best in the presence of potassium phosphate and water. Using this synthetic route, specific isomers can be prepared including the menthanecarboxamide isomer having the same configuration as l-menthol and new isomers such as a neoisomer having opposite stereochemistry at the carboxamide (C-1) position. The neoisomer unexpectedly has potent and long lasting cooling effect. Preparation schemes for neoisomers of other menthyl derivatives which are useful as coolants, including esters, ethers, carboxy esters and other N-substituted carboxamides are also provided.

主权项

1. A process for preparing specific isomers of menthane derivatives comprising
(a) derivatizing a starting menthane alcohol to a sulfonate ester or other leaving group, (b) reacting a menthane alcohol derivative from step (a) with sodium cyanide to obtain a menthane nitrile having opposite stereochemistry at the C-1 position from the starting menthane alcohol and (c) derivatizing the menthane nitrile obtained in step (b) by
(i) subjecting the menthane nitrile to hydrolysis conditions comprising hydrogen peroxide and dimethyl sulfoxide to obtain a menthane carboxamide having the same stereochemistry as the nitrile, or(ii) subjecting the menthane nitrile to hydrolysis conditions comprising hydrogen bromide to obtain a menthane carboxylic acid having the same stereochemistry as the nitrile, or(iii) subjecting a (1S,2S,5R)-menthane nitrile to hydrolysis conditions comprising potassium hydroxide to obtain a (1R,2S,5R)-menthane carboxylic acid.