Marine fragrances, particularly Calone 1951(¼ 7-methyl-2H-1,5-benzodioxepin-3(4H)-one; 1) has carved a minor but distinct niche in the broad field of fragrance chemistry. By focusing on the polar structure fragment of the benzodioxepinone parent compound, we set out to determine the molecular influence on the dominant marine note attributed to the Calone 1951 structure. A selection of one-step modifications of the ketone 1 resulted in a range of odor-active conformers with diverse olfactory attributes. The synthesis of a range of benzodioxepine analogues, i.e., of 3 -11, is presented alongside olfactory evaluation (Tables 2 and 3). Removal of the carbonyl group of 1 and increasing the size of the aliphatic ring portion (see 6 and 7) introduced sweetness and a predominant loss of the marine character.

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®, 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).

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