SYNTHESIS AND OLFACTIVE PROPERTIES OF 11-OXAHEXADECANOLIDE CHEMICAL CONSTITUTION AND ODOUR IV. SYNTHESIS AND OLFACTIVE PROPERTIES OF 11-OXAHEXADECANOLIDE M. H. KLOUWEN, Dr. Phil., J. G. J. KOK, and A. H. RUYS* Presented at the Symposium on Perfumery, organised by the Society, at Cheltenham, Glos., on ldth November 1962. The oilactive l•rol•er•ies of •he syn•hesisetl 10-, 11-, 12-, 13- aml 14- oxahexatlecanolitles are considered. The crystalline 11-oxahexatlecanolkle is fountl •o be equal in character and otlour in•ensi•r •o l•en•atlecanoli{le, while •he o•er liquid oxalac•ones are all weaker. Previous conclusions on •he correlation be•veen s•ruch•re and otlour are Ul•Se• by •his l•henomenon. INTRODUCTION MUSK COMPOUNDS are almost always required to complete a perfume com- position. Beyond the introduction of musk odour other factors also play an important part because most commercial musk odorants possess positive fixative and exaltating properties. The importance of this group of compounds is emphasised by numerous publications in this field. Many aspects of these characteristic substances have been discussed in original articles and reviews dealing with synthesis, application, oilactive properties and physiological data. Even a few psychological effects have been described, e.g. Cardinal Richelieu did not feel inclined to work when he missed the odour of musk in his study. The commercial importance of musk odorants probably accounts for the fact that far more research findings are being published in this field than in other subjects of research. Musks are found in different classes of organic compounds and they have been classified by Mignat • as follows: 1. Macrocyclic compounds. 2. Steroids. 3. Benzene derivatives- (a) nitrated benzene compounds, (b) non-nitrated benzene compounds, (c) indane derivatives, (d) tetraline derivatives. 4. Other compounds. *N.V. Chemische Fabriek "Naarden", Naarden, Netherlands.

20 JOURNAL OF THE SOCIETY OF COSMETIC CHEMISTS We do not propose to enter into details of this classification but are restricting ourselves to the macrocyclic series, and especially to the macrocyclic lactones. The well-known and valued pentadecanolide occupies a very special place in this group. From an olfactory point of view it is one of the most important components of the essential oil of Angelica archangelica L2. Pentadecanolide possesses a very strong musk odour with a flowery note. Ruzicka and Stoll 3 already synthesized pentadecano- lide in 1928 developments until 1962 have been reviewed by us 4. Research on other macrocyclic lactones started very soon after the 1928 discovery of pentadecanolide because the synthesis was difficult and expensive. This led to the preparation of oxalactones, resembling pentadecanolide in character, but weaker in odour intensity. The oxahexadecanolides in the group of macrocyclic oxalactones have the most interesting olfactive properties. Figure 1 A Stuart model of 11-oxahexadecanolide. Figure oe 11-oxahexadecanolide crystals. Only a few oxahexadecanolides have been described in the literature, viz. 6-, 10-, 12- and 13-oxahexadecanolide. We planned to synthesize all isomeric oxahexadecanolides as we expected a definite insight into the correlation between structure and odour, and we have already succeeded in preparing 10-, 11-, 12-, 13- and 14-oxahexadecanolide. Although we do not possess the data of all oxahexadecanolides, we will now deal with the synthesis and olfactive properties of the mentioned five isomers, because one of these lactones, 11-oxahexadecanolide, is equal in character and odour intensity to pentadecanolide (superior among macrocyclic lactones up to now). It is a remarkable fact that these two compounds also show a definite similarity in appearance, being crystalline with an almost identical melting point (35 ø and 37ø). All other known oxahexadecanolides are liquids at room temperature. Correlations between structure and odour will be discussed below because 11-oxahexadecanolide showed surprising olfactive propertie½.