Flavor-Base - 10th Edition is Here NEW - A new version to the world's most extensive database on flavoring materials and food additives - Click HERE

Beverage-Master 2011 - NEW - A new version with enhanced features for Excel 2007 & 2010. The world's leading program for beverage development.

Juice-Master 2011 - NEW - A new version with enhanced features for Excel 2007 & 2010. The leading program for development of juice containing beverages.

(+)-delta-3-Carenc from Western U.S. turpentine provides another monoterpeiie raw material for the potential production of (-)-menthol. Catalytic isomerization provides the needed (+)-delta-2-carene required for either of two alternate synthetic routes. In one approach, reaction of (+)-2-carelie with peracid yields (+)-cis-2,8-p-menthadien-l-ol via the intermediate cis-2-carene epoxide. Allylic displacements with acetic or formic acid in a buffered solution affords a mixture of cis- and trans-piperitenyl acetates (or formates) which on hydrolysis give (+)-cis- and (-)-trans-piperitenol. These isomeric alcohols are separated by fractional distillation and the cis-isomer is recycled by the same buffered carboxylic acid system used above to mixed cis & trans piperitenyl esters. In this manner pure (-)-trans-piperitenol is obtained with minimum losses due to (+)-cis isomer formation. The
(-)-trans-piperitenol is desired here so as to be able to selectively obtain (-)-menthol directly on hydrogenation. Hydrogenation over Pd/C affords better thin 70% (-)-menthol along with some undesired (-)-isomenthol. Efficient fractional distillation gives (-)-menthol of good purity. Unfortunately, the (-)-isomenthol obtained in the last step of this synthesis is of the opposite optical series, but since this can be catalytically converted to racemic menthol under strong catalytic conditions this by-product is still salable.

A second route, developed by Hercules, Inc., involves pyrolysis of (+)-delta-2-carene to (+)trans-2,8-p-menthadiene with generation of an asymmetric center at C-1 which is carried through the remainder of the synthesis. Isomerization of this 2,8-menthadiene to (+)-2,4(8)-p-menthadiene can be accomplished either catalytically in the presence of strong bases (e.g., potassium t-butoxide) or via hydrochlorination-dehydrochlorination. Treatment of (+)-2,4(8)-p-menthadiene with hydrogen chloride affords 8-chloro-3-p-menthene which can be reacted with sodium acetate and acetic acid to give mixed (cis/trans) pulegol esters via allylic displacements. Hydrolysis affords (-)-cis and (+)-trans-pulegol. Because the absolute configuration of C-1 is fixed in this system, reduction of either pulegol isomer provides menthol isomers which can be readily equilibrated to predominently (-)-menthol. More specifically, reduction of (-)-cis-pulegol affords (-)-menthol and (+)-neoisomentliol, while (+)-trans-pulegol gives (+)-isomentliol and (+)-neomenthol. Purification of equilibrated menthol isomers is carried out by fractional distillation and crystallization of menthol derivatives. This latter process is intrinsically one of the most attractive potential routes to (-)-menthol developed to date but was never commercialized.

1. Leffingwell, J.C. & R.E. Shackelford, Laevo-Menthol - Syntheses and organoleptic properties, Cosmetics and Perfumery, 89(6), 69-89, 1974

2. Hopp, R., Menthol: its origins, chemistry, physiology and toxicological properties, Rec. Adv. Tobacco Science, Vol. 19, 3-46 (1993).