ODOR AND ISOMERISM IN OLFACTIVE CHEMICALS By E. H. EscuN^s, PH.D.* Presened February 25, 1963, Meeting, New England Chapler ABSTRACT This paper describes some typical cases of odor variations as functions of isomeric changes in certain known species of olfactive chemicals. Selected examples are used to illustrate the theoretical and practical importance of the isolation and stereo- specific synthesis of pure odorant compounds. The oilactive evaluation of essential oils, isolates and aromatic chemicals leads quite often to divergent and sometimes conflicting results for the organic chemist working in this field of challenging problems. In- deed, few are the chances of encountering the same absolute odor likeness in different samples of the same essential oil or isolate. Variation due to geographic origin, seasonal changes and different means of extraction, handling and preparation of the essential oils and their related products are chief contributors to odor variance. Major differences in odor found in similar isolates of varying origin have been traced to the presence of different minor constituents originally present in their respective parent oils. The complete removal of these so-called impurities from the isolates is often difficult and seldom even desirable. In other instances, however, odor variations could be related to fluctuations of some specific stereoisomeric oilactive species. With the remarkable progress made in analytical and preparative tech- niques in chemistry, especially in the field of gas-liquid chromatography, it became possible, in the last decade, to prepare isolates and synthetic com- pounds of unusual chemical purity. The use of preparative chromato- graphic columns, equivalent to fractionadng columns having an efficiency of more than thousand plates, afforded for the first time a practi- cal and rapid separation of pure stereoisomers. The availability of chem- icals of reliable structures contributed to a greater measure of objectivity and reliability in their oilactive evaluation. As a result, the study of the relationship between odor and chemical structure advanced a step further and helped, in some instances, to dramatize the effect of isomerism on odor variations. * The Givaudan Corp., Delawanna, N.J. 261

262 JOURNAL OF THE SOCIETY OF COSMETIC CHEMISTS The existence of isomers in aromatic chemicals and their contribution to the oilactive distinctiveness has long been known. The eugenols, safroles, menthols, ionones and many others have been known for quite some time, and their use in the aromatic industry is quite well established. OH O-- k ...!.• Eugenols Saoeroles Menthols Ionones Continuing advances in the gas-liquid chromatographic techniques have made possible the resolution and separation of many pure isomeric species and simultaneously promoted the search for new stereospecific methods of synthesis. Although the nature of the relation between odor perception and chemical structure remains as complex as ever (1), some measure of comfort is taken from the knowledge that real progress can be achieved in this field with research now carried out with absolutely pure oilactive chemicals of known conformation and structure. Some of the odor variations and their relation to isomerism will be reviewed and the synthesis of a number of pure oilactive isomeric species will be described. A few typical examples have been chosen to illustrate the odor differ- ences between isomers and to emphasize their economic importance. The examples include the citronellyl and rhodinyl series (I), the methylionones (II), the irones (III), the Netones ©* (2) (IV), the rosenoxides (V) and the hexenols (VI and VII). R = H,,,HOH, O, HO Acyl. R• -- H, CHa o o --'• (II) (III) (I) (IV) (vi) (wi) (v) * Neronc is a registered trademark of The Givaudan Corp.