Synthesis and Qualitative Olfactory Evaluation of Benzodioxepine Analogues

Abstract

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.

Structure–Activity Relationships in the Domain of Odorants Having Marine Notes

“…For example, it is interesting to observe that Calone 1951 ® (carbonyl group in the benzenic plane for the preferred conformation) is described as strongly marine and ozone, whereas its carba-analogue, in which the two cyclic oxygen atoms are replaced by carbon www.eurjoc.org atoms (carbonyl out of the benzenic plane for preferred conformation), is described as a Lilial ® -like odor. As a first comment, we fully confirm the results obtained by Hügel and co-workers [7] for alcohol 8a and the correspond-ing acetate 9c. [6] The generation of the olfactophore model of Calone 1951 ® was performed by using the program Phase.…”

“…A large number of the molecules investigated in this work can be superimposed on the main structural features of Calone 1951 ® . These results round off the series described by Hügel and coworkers [7] concerning Calone 1951 ® analogues with a substituent at position 3 of the benzodioxepine ring, and confirm that the carbonyl group is definitely the best functional group for this skeleton. For example, in mol- Figure 6.…”

“…This domain was later revisited, [2][3][4][5][6][7][8][9][10][11] and now compounds such as Transluzone (1b), Aldolone ® (1c), and Azurone ® (1d) are produced on a ton scale by Firmenich and Givaudan, and used in fine fragrance as well as in body-and home-care products (e.g., shower products, air fresheners, and powder detergents).…”

“…To evaluate the odors of these compounds, we have thus synthesized a series of molecules 5-7 ( Figure 4) in which W represents various hydrogen-bond acceptors (the main topic of two recent studies published by Hügel and co-workers [7] and Kozlov et al [11] ). Modifying the spacer between the aromatic ring and the functional group could also provide interesting new perspectives.…”

Marine Fragrance Chemistry

“…Our qualitative olfactory data [4] [5] shown in Table 2 is consistent with previous findings that many odorants contain a polar group as anchor to a similar site on the olfactory receptor with the rest of the structure residing in and sensing a hydrophobic receptor…”