Synthesis of benzodioxepinone analogues via a novel synthetic route with qualitative olfactory evaluation

Britta Drevermann, Anthony Lingham, Helmut Martin Huegel, Philip Marriott

Research output: Contribution to journalArticleResearchpeer-review

11 Citations (Scopus)

Abstract

Marine odorants represent a minor yet diverse class of substances within the fragrance industry, of which 7-methyl-2H-1,5-benzodioxepin-3(4H)-one (1) is commercially known as Calone 1951 (R), a synthetic first in the area of marine-fragrance chemistry To determine the extent to which the characteristic marine odor of Calone 1951 (R) corresponds to the substitution at the benzo portion of the molecule, a variety of aromatic substituents were incorporated into the benzodioxepi none structure (Scheme 1, Table 3). In light of the difficulty experienced in applying patented literature to deriving the analogues 12-18, particularly those with electron-withdrawing substituents, an alternative synthetic scheme was implemented for the construction of all analogues in favorable yields (Scheme 4, Table 3). Formation of the hydroxy-protected dihalo alkylating agent 24 via epoxide cleavage of epichlorohydrin (Scheme 3) allowed etherification favoring dihalo displacement and subsequent intramolecular ring closure (-> 26a-g). THP Deprotection followed by oxidation of the alcohols 27a-g to the ketones 12-18 provided a general pathway to the benzodioxepi none products. The influence of the substituent nature on odor activity revealed a diverse scope of olfactory character (Table 4).
Original languageEnglish
Pages (from-to)1006 - 1027
Number of pages22
JournalHelvetica Chimica Acta
Volume90
Issue number5
DOIs
Publication statusPublished - 2007
Externally publishedYes

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