Microwave assisted synthesis of the fragrant compound Calone 1951®

An innovative synthesis pathway to benzodioxanes: the peculiar reactivity of glycerol carbonate and catechol

“…This compound, however, is a valuable product because it is a reactive intermediate for the synthesis of methylbenzodioxepinone-based compounds (trade name "calone" or "calone 1951"): molecules, which are renowned in the fragrance industry for their distinct marine scent. 28 The suggested reaction mechanism is shown in Scheme 4. One of the catechol acidic hydroxyl groups is deprotonated by the basic catalyst; the catecholate anion (a "softer" nucleophile than aliphatic analogues due to the resonance of the negative charge on the aromatic ring) is able to perform the nucleophilic attack on the more available "soft" electrophilic site of GlyC, leading to the formation of an unstable intermediate, which rapidly undergoes decarboxylation followed by an intramolecular condensation which, in the end, leads either to the desired HMB (Scheme 4, pathway i, a) or to its isomer (pathway i, b), and water as the co-product.…”

Marine Fragrance Chemistry

“…This implies that the hydrophobic alkyl groups in the olfactophore space surrounding the aromatic ring resonate marinefragrance character and intensity. We have briefly investigated the conformational structures of Calone 1951 and related compounds [6]. For Calone 1951, Gaudin et al calculated that the pseudo-twist boat conformation (0 kcal/mol; Fig.…”

“…Improvements in yield and purity were obtained when the Williamson ether synthesis step was assisted by microwave irradiation [6], especially when electron-withdrawing groups were present. The basepromoted condensation of an ester containing a-H-atoms with another molecule of the same sort forming a b-keto ester is the Claisen condensation.…”