Perfume and aroma enhancing compounds are widely used as additives in the detergent and food industries. These compounds are used, for example, to augment or enhance the aromas of certain detergent compositions and perfumes, or to enhance the aroma and flavor characteristics of certain food or tobacco products among other products. Compounds with floral, fruity, woody, or other pleasing aroma are particularly desirable.
Many of these compounds have specific molecular features, such as the presence of a cyclic ring and/or a ketone, ester or other carbonyl derivative. For example, many fragrance components may include a substituted cyclohexene structure. These structures include, for example, various ionone isomers, damascone isomers, cyclogeranate isomers, and irone isomers. Other cyclic fragrance compounds are also known.
The damascones, including α-damascone, β-damascone, and δ-damascone are examples of compounds having pleasing floral, fruity aromas used in the perfumery art. The damascone isomers differ in the position of the ring double bond as shown in Scheme 1.
For example, trans,trans-δ-damascone is one of the most widely used fragrance additives in the detergent and food industries. Therefore, the industrial scale production of δ-damascone and other related compounds is of great interest.
The synthesis of damascones typically involves a three-step process: (1) a Diels-Alder cycloaddition of a diene and a dienophile to produce a mixture of cis- and trans-cycloadducts; (2) epimerization of the cis-cycloadduct to the trans-cycloadduct; and (3) an aldol condensation of the trans-cycloadduct using an aldehyde followed by the elimination of water to generate a damascone. These reactions are performed in three separate reaction processes. A process for synthesizing damascone is described in Ayyer et al., Journal of the Chemical Society Perkin Trans., 1975, 1, 1727-1736.
1-(2,6,6-Trimethylcyclohex-3-en-1-yl)-ethanone is a useful compound as an intermediate for the synthesis of the damascones. 1-(2,6,6-Trimethylcyclohex-3-en-1-yl)-ethanone can be readily synthesized by a Diels-Alder reaction between 1,3-pentadiene (piperylene) and mesityl oxide to produce a mixture of cis- and trans-1-(2,6,6-trimethylcyclohex-3-en-1-yl)ethanone. Typically, the cycloadduct from the Diels-Alder cycloaddition is a mixture of cis-1-(2,6,6-trimethylcyclohex-3-en-1-yl)ethanone and trans-1-(2,6,6-trimethylcyclohex-3-en-1-yl)ethanone. Thus, further synthetic transformations are necessary to convert the Diels-Alder cycloadduct to δ-damascone.
The conventional epimerization and aldol condensation processes used to synthesize δ-damascone from the mixture of 1-(2,6,6-trimethylcyclohex-3-en-1-yl)ethanone cycloadducts suffer from low yields and lack of control over the stereochemistry of the products. On the industrial scale, these reactions are problematic because of high reaction dilutions, large volumes of solvents, large reaction vessels, long reaction times, complex workup requirements, several extraction and drying steps, low atom efficiency, and low yields.
Therefore, a more commercially viable production of damascone isomers and other substituted cyclohexene based perfume components is necessary.
USPTO Backgrounds
USPTO Backgrounds