AbstractThe main marine message in perfumery is projected by Calone 1951® (7‐methyl‐2H‐1,5‐benzodioxepin‐3(4H)‐one). Kraft (Givaudan) and Gaudin (Firmenich) further maximized the marine fragrance molecular membership by extending the carbon chain of the 7‐Me group. Our research targeted the polar group of the benzodioxepinone parent compound to investigate how this region of molecular makeup resonates with the dominant marine fragrance of the Calone 1951® structure. The olfactory evaluation of analogues prepared by chemical modification or removal of the CO group resulted in the introduction of aldehydic, sweet and floral‐fruity notes with a diluted/diminished potency of the marine odor. To further analyze the olfactory properties of benzodioxepinones containing a diverse range of aromatic ring substituents, a novel synthesis route was developed. We found that a 7‐alkyl group in Calone 1951® was essential for the maintenance of the significant marine odor characteristic, and our studies support the concept that the odorant structure occupying the hydrophobic binding pocket adjacent to the aromatic ring‐binding site of the olfactory receptor is pivotal in the design and discovery of more potent and characteristic marine fragrances. How the structure of benzodioxepinones connects to marine sea‐breeze fragrances is our continuing challenging research focus at the chemistry‐biology interface.