Marine fragrance chemistry : synthesis, olfactory characterisation and structure-odour-relationships of benzodioxepinone analogues

摘要

Calone 1951® (7-methyl-2H-1,5-benzodioxepin-3(4H)-one) is renowned in the fragrance industry for its distinct marine odour and offers an interesting molecular framework for structure-odour-relationship (SOR) research. Limited olfactory reports on 7-membered benzodioxepine analogues with modification influenced by functionality, polarity, and ring size, prompted us to construct a range of aromatic and C-3 substituted structures for olfactory evaluation. Incorporation of a diverse range of functionality contributes valuable information on the molecular aspects that determine the archetypal marine character of Calone 1951®. Here we present the preparation of Calone 1951® analogues including spectroscopic and olfactory details to contribute to the sparse marine fragrance arena. In these studies pertaining to the odour properties of benzodioxepinone systems, we considered the mod ification of substitution and functionality on the aromatic ring in the context of qualitative olfactory analysis. Application of the patented Williamson and Dieckmann reaction pathways resulted in construction of the benzodioxepinone molecule. Preparation of aryl-substituted benzodioxepinones required introduction of an alternate broadly applicable synthetic pathway due to the diverse nature of the introduced substituents. Limitations of the patented approach led to incorporation of a simple but novel methodology applied to the same range of substituted catechol reagents for synthesis of the benzodioxepinone skeleton and an overview of comparable yields. Single-step mechanisms were also successfully applied to contribute to the repertoire of benzodioxepin(on)e structures prepared for olfactory analysis. Semi-empirical models of the synthesised data set were generated and evaluated in light of previous research undertaken by Archer and Claret and related to the olfactory characteristics of each compound. Evaluation of the models with corresponding olfactory information revealed that functionality and ring size contribute significantly to the conformation adopted by the benzodioxepinone species and therefore the olfactory character of the molecule. It is evident from our observations that aromatic ring substitution and functional alteration of the cyclic ketone modifies the perceived odour of Calone 1951®. Structural modification overall led to a decrease in odour potency. The presence of the aromatic methyl substituent in Calone 1951® reinforces, but is not critical for, the marine tonality. Modification of the ketone of Calone 1951® led to significant deviation in character from the prototypical marine odour.