Synthesis and Odor of Aliphatic Musks: Discovery of a New Class of Odorants

Abstract

Abstract To find new aliphatic musks, we synthesized the propionates of 2‐[1′‐(3′′,3′′‐dimethylcyclohex‐1′′‐enyl)ethoxy]‐2‐methylpropanol ( 8 ), of 2‐[1′‐(5′′,5′′‐dimethylcyclohex‐1′′‐enyl)ethoxy]‐2‐methylpropanol ( 11 ), of hydroxyacetic acid 1‐(3′,3′‐dimethylcyclohex‐1′‐enyl)ethyl ester ( 12 ), and of hydroxyacetic acid 1‐(5′,5′‐dimethylcyclohex‐1′‐enyl)ethyl ester ( 13 ) starting from 1‐(3′,3′‐dimethylcyclohex‐1′‐enyl)ethanone ( 5 ) and 1‐ethynyl‐3,3‐dimethylcyclohexanol ( 9 ). We found that the 3,3‐dimethylcyclohexenyl derivatives 8 (odor threshold 0.2 ng/air) and 12 (odor threshold 0.6 ng/air) are superior musk odorants, and, thus, we constructed 1,2,4‐trimethylpent‐2‐enyloxy analogues as seco versions. The synthesis of the esters 17 − 26 commenced with a Wittig−Horner− Emmons reaction of isobutyric aldehyde ( 14 ), followed by saponification, alkylation with methyllithium, LAH reduction, etherification with isobutylene oxide, and Steglich esterification. (2′′ E )‐2′‐Methyl‐2′‐(1′′,2′′,4′′‐trimethylpent‐2′′‐enyloxy)propyl cyclopropanecarboxylate [(2′′ E )‐ 19 ], which has a powerful and sweet musk odor and slightly fruity nuances, was found to be a typical representative of this new class of musk odorants, was subjected to conformational analysis. In addition, we report the synthesis and olfactory properties of the related ketones 28 − 30 , the 2‐methyl‐2‐(1′,4′,4′‐trimethylpent‐2′‐enyloxy)propyl esters 31 − 33 , and the 2‐(1′,4′‐dimethylpent‐2′‐enyloxy)‐2‐methylpropyl esters 35 and 36 . (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004)