Conception, Characterization and Correlation of New Marine Odorants

Abstract

Via a synthetic sequence consisting of PPA‐mediated Friedel−Crafts acylation of veratrol (8), Clemmensen reduction, demethylation with TMSI, Williamson ether synthesis employing 3‐chloro‐2‐(chloromethyl)prop‐1‐ene and in‐situ ruthenium tetroxide oxidation, numerous substituted benzo[b][1,4]dioxepinones 15−27 and 2,3‐dihydro‐1H‐5,9‐dioxacyclohepta[f]indenones 7, 13 and 14 were prepared to study their odor−structure correlation. In the course of these studies, we discovered the extremely powerful new marine odorant 7‐(3′‐methylbutyl)benzo[b][1,4]dioxepin‐3‐one (16). On the basis of the measured odor threshold data, an olfactophore model was constructed that rationalizes the observed odor intensities, and indicates an aliphatic hydrophobe at a distance of 6.3 Å from the centre of the aromatic‐ring binding site. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003)

Synthesis and Qualitative Olfactory Evaluation of Benzodioxepine Analogues

“…The marine tonality remains detectable upon removal of the carbonyl group, and in addition, more dominant accords begin to arise such as aldehydic, sweet, and floral-fruity. Most notable is the transition from a potent odor (0.031 ng/l) [11] to a significantly weaker odor for both structures 3 and 4. It seems the olfactory receptor binding pocket is quite specifically delineated for a ketone on the adjoining dioxepin ether ring, with an sp 2 to sp 3 conversion perhaps contributing to the potent-to-weak alteration of the odor intensity.…”

Crossing the Boundaries between Marine and Muguet: Discovery of Unusual Lily‐of‐the‐Valley Odorants Devoid of Aldehyde Functions

“…Both methoxy ethers were then cleaved by action of the boron tribromide dimethyl sulfide complex in toluene at 95° to provide the corresponding pyrocatechol 25 in 78% yield after chromatographic purification. Instead of the commercial synthesis of Calone 1951 ( 10 ) by Williamson etherification with two equivalents of methyl bromoacetate, Dieckmann condensation, hydrolysis and decarboxylation as described in the original patent by Beereboom , Cameron , and Stephens , the benzannulated 1,4‐dioxepane ring was constructed by double Williamson etherification using the bifunctional building block 3‐chloro‐2‐(chloromethyl)prop‐1‐ene as developed in the discovery of Azurone (7‐isopentyl‐2 H ‐1,5‐benzodioxepin‐3(4 H )‐one) . Thus, slow addition of a 1:1 mixture of the pyrocatechol 25 and 3‐chloro‐2‐(chloromethyl)prop‐1‐ene in dioxane to a refluxing suspension of two equivalents of potassium carbonate in diethyl ketone afforded the 6‐cyclopropyl‐3‐methylene‐3,4‐dihydro‐2 H ‐benzo[ b ][1,4]dioxepine ( 26 ) in 59% yield after chromatographic purification.…”

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

“…1 H NMR: δ = 3.37 (d, J = 7.0 Hz, 2 H), 3.83 (s, 3 H), 3.89 (s, 3 H), 5.06-5.14 (m, 2 H), 5.95 (m, 1 H), 6.76 (dd, J = 7.9, 2.0 Hz, 1 H), 6.79 (d, J = 2.0 Hz, 1 H), 7.03 (d, J = 7.9 Hz, 1 H) ppm. 1 H NMR: δ = 3.37 (d, J = 7.0 Hz, 2 H), 3.83 (s, 3 H), 3.89 (s, 3 H), 5.06-5.14 (m, 2 H), 5.95 (m, 1 H), 6.76 (dd, J = 7.9, 2.0 Hz, 1 H), 6.79 (d, J = 2.0 Hz, 1 H), 7.03 (d, J = 7.9 Hz, 1 H) ppm.…”

“…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).…”