Synthesis of Benzodioxepinone Analogues via a Novel Synthetic Route with Qualitative Olfactory Evaluation

✍ Scribed by Britta Drevermann; Anthony R. Lingham; Helmut M. Hügel; Philip J. Marriott

• Publisher: John Wiley and Sons
• Year: 2007
• Tongue: German
• Weight: 274 KB
• Volume: 90
• Category: Article
• ISSN: 0018-019X
• DOI: 10.1002/hlca.200790085

✦ Synopsis

Abstract

Marine odorants represent a minor yet diverse class of substances within the fragrance industry, of which 7‐methyl‐2__H__‐1,5‐benzodioxepin‐3(4__H__)‐one (1) is commercially known as Calone 1951^®^, a synthetic first in the area of marine‐fragrance chemistry. To determine the extent to which the characteristic marine odor of Calone 1951^®^ corresponds to the substitution at the benzo portion of the molecule, a variety of aromatic substituents were incorporated into the benzodioxepinone 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 benzodioxepinone products. The influence of the substituent nature on odor activity revealed a diverse scope of olfactory character (Table 4).