Patent Watch

January 17, 2011

Make a key fragrance compound economically. Timberone (4) has a woody, amberlike odor and is valued in the fragrance industry for manufacturing perfumes and cosmetics. Inventors W. Bonrath and J. Schuetz state that existing methods for preparing 4 require raw materials that are not readily available and that an alternative synthesis is desirable.

Their method begins with commercially available citral (1), which undergoes an aldol condensation with 2-pentanone. This reaction is carried out with a supported base as the catalyst. The preferred catalyst is 20–30 wt% calcium and 24–32 wt% sodium on silica with a surface area of <200 m2/g. The catalyst preparation is not described, but it is based on World Patent WO0187812 (K. G. James, 2001).

The reaction gives a mixture of E- and Z-isomers of compound 2, isolated in 66–88% yield. The mixture is used in the acid-catalyzed cyclization step in hexane solvent to give 3. The preferred acids contain sulfur: MeSO3H gives the highest yield (87% by GC); H2SO4 and CF3CO2H can also be used. When H3PO4 is used, the yield is 56%, but no solvent is needed.

The reaction scheme shows 3 as the 1-cyclohexene isomer, but the 2-cyclohexene isomer is also formed. The isomer ratio depends on the acid used; sulfur acids give more of the 1-cyclohexene isomer. For example, H2SO4 gives 99% 1-cyclohexene, and H3PO4 gives 85.4% 2-cyclohexene. The mixture is not separated, but it is hydrogenated using a Pd/C catalyst at room temperature and 1 bar. A mixture of diastereomers of 4 is formed in 91.2% isolated yield.

The patent provides 1H and 13C NMR data for all compounds. The process uses a readily available raw material and is therefore economically more attractive than alternatives. (DSM IP Assets B.V. [Heerlen, The Netherlands]. US Patent 7,842,841, Nov. 30, 2010; Keith Turner)

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