Synthesis of calone derivatives

Abstract

Greater than 900 named fragrances are currently produced worldwide, either through synthetic pathways or by isolation from natural essential oils. The demand for synthetic fragrances in perfumery, cosmetics, and food flavors exceeds by 5-6 times the use of natural products.Herein we present results from a study of transformations of 7-methyl-2H-benzo[b][1,5]dioxepin-3(4H)-one (calone). Calone (1) or watermelon ketone was isolated from watermelon rind and is a valuable fragrance for preparing fresh, marine, and ozone aromas. Up to 25% of the worldwide assortment of modern perfumery contains calone. Calone, being an important indicator of marine aroma, contains in its molecule a constrained reaction center, the carbonyl. Performing reactions at this group enables the two methylenes immediately adjacent to the O atoms and the aromatic ring to be preserved. This is a potential feature of the marine aroma [1].Reaction of 1 with malonic acid dinitrile and cyanoacetic acid ethyl ester in the presence of piperidine and acetic acid formed the condensation products 2-(7-methyl-2H-benzo[b][1,5]dioxepin-3(4H)-ylidene)malononitrile (2) and ethyl-2-cyano-2-(7-methyl-2H-benzo[b][1,5]dioxepin-3(4H)-ylidene)acetates 3a and 3b. Malononitrile 2 with a symmetric substituent is the only reaction product whereas addition of ethyl cyanoacetate forms the cis-(3a) and trans-isomers (3b) in a 1:2 ratio. This was confirmed by PMR spectroscopy.

Occurrence of Marine Ingredients in Fragrance: Update on the State of Knowledge

“…Recently, olfactophore models, developed in analogy with pharmacophore models, are increasingly used in SAR studies. They provide, through the description of the relative spatial arrangement of osmophoric and hydrophobic groups, information on the geometry of the olfactory receptors and the types of interaction with the molecules [201][202][203]. Consequently, the olfactophore models allow the generation of a new candidate's odorants molecules without having the receptor's structure.…”

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

“…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.…”

“…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). Olfactory receptors were discovered by Buck and Axel, [12][13][14] but despite this important breakthrough, the mechanisms of odorant receptor interaction are yet to be understood.…”

Novel synthesis of 2H-1,5-benzoxathiepin-3(4H)-one and 5H-4,1-benzoxathiepin-3(2H)-one derivatives and chemical properties evaluation

“…Moreover, 2H-1,5-benzoxathiepin-3(4H)-one is an isoster of calone (watermelon ketone) that was isolated from watermelon rind and is a valuable fragrance for preparing fresh, marine, and ozone aromas [15].…”