Of -£-P-santalol

As an example of the synthesis of p-santalol, we will look at that of Erman and Kretschmar, since it also illustrates two interesting points of general relevance. The overall scheme is shown in Figure 6.8. 

Scheme 15.12 Synthesis of the pheromone 2.6-dimethyl-1.5-heptadiene-3-n1 acetate. Scheme 15.13 Synthesis of p-santalol.

The piincipal component, t7t-a-santalol (65), has contioveisial odoi piopeities t7t-P-santalol (66) contributes most to the odor of sandalwood. A number of trace constituents have been characterized, two of which (76) [59300-43-5J and (77) [63569-02-8] ate worthy of mention for their very clean sandalwood notes (38). 

The Prins reaction with formaldehyde, acetic acid, acetic anhydride, and camphene gives the useful alcohol, 8-acetoxymethyl camphene, which has a patchouli-like odor (83). Oxidation of the alcohol to the corresponding aldehyde also gives a useful iatermediate compound, which is used to synthesize the sandalwood compound dihydo- P-santalol. 

OC-Santalol. Sandalwood oil is comprised of mainly (90%) a- and P-santalol, which gives the oil the woody, tenacious sandalwood odor. An impure a-santalol [115-71 -9] (100) can be isolated by the distillation of the oil. P-Santalol [77-42-9] (101) is also isolated but ia much smaller amounts. The price of sandalwood oil, E. Indian, ia 1995 was 286/kg, and the oil from Indonesia was 187/kg (69). The high price of these oils has created the need to synthesize new materials with the sandalwood odor. The terpenophenols are manufactured by condensation of camphene with phenoHc compounds followed by hydrogenation to the cycloaUphatic alcohols (194). 

An important step toward the correct identification of the sex pheromone of P. americana was the identification of several phytochemicals, such as bomyl acetate and santalol, that stimulated courtship behavior in males (Bowers and Bodenstein, 1971 see p. 196). Some years later, Tahara etal. (1975) and Kitamuta et al. (1976) reported that germacrene-D, extracted from composite plant species, stimulated sexual behavior in males of P. americana and the Japanese cockroach Periplaneta japonica Karny. Persoons etal. (1974, 1976) determined, on the basis... 

Two additional minor components of East Indian sandalwood oil have been identified as trans-fi-santalol (111) (cf. Vol 11, ref. 48) and e/n-cw-p-santalol (112).71 New syntheses in this area include those of cw-p-santalol (113) (Scheme 9),72... 

The way in which the santalols are drawn in Figure 6.1, is used to make clear their relationship to tricyclene and camphene. Often the structures will be drawn in a different way. For example, Figure 6.2 shows two different ways of drawing a-santalol. The first, (6.1), is the way in which it is shown in Figure 6.1. The other, (6.7), is often used to illustrate the close similarity in overall shape between a-santalol and P-santalol (6.8), a feature which is less obvious in the structures, (6.1) and... 

Cleavage of the C-3-C-4 bond of farnesane and connection of new bonds from C-2 to C-4, C-3 to C-7 and C-1 to C-4 lead to bicyclic p-santalane, which is another basic skeleton of substances found in sandalwood. Examples are (-)-p-santalene and (-)-( -p-santalol with a pleasant woody, slightly urinary odor used in perfumes and detergents... 

An example of monocyclic sesquiterpenic alcohols is (-l-)-o(-bisabolol (8-24). It occurs in citrus essential oils along with other sesquiterpenic alcohols, and represents the major component of the essential oil of chamomile flowers (Matricaria chamomilla, Asteraceae). a-Bisabolol (0.26%) and other sesquiterpenoids, such as monocyclic sesquiterpenic alcohol (Z)-lanceol (1.7%), bicyclic sesquiterpenic alcohol (Z)-a-essential components of white sandalwood oil (Santalum album, Santa-laceae) used in perfumery, cosmetics and aromatherapy. (Z)-Lanceol is also a component of sage species (Salvia spp., Lamiaceae) essential oil. Sesquiterpenic bicyclic alcohol (-F)-P-nootkatol is the precursor of ketone (-F)-nootkatone, an important component of grapefruit essential oil. Trivial and systematic names of the main sesquiterpenic alcohols are listed in Table 8.7. 

Electrophilic species, other than a proton, can be used, thus adding to the synthetic utility of this variation. One such example is the end-game solution to the total synthesis of a-santalol 61. ° The advanced intermediate 60 was treated with ylide 16. Formation of the P-oxido ylide with -BuLi and addition of formaldehyde provided a one-step procedure for alkene formation and elaboration to 61. 

The same synthetic route was applied to the preparation of the tricyclic sesquiterpene santalol 235). The reaction of the tricyclic aldehyde 435 with ethylidene-triphenylphosphorane and paraformaldehyde 205 gives the a,P-unsaturated alcohol 436, elimination of phosphorus being probably directed by the thermodynamical stability of 436 235) (Scheme 76). 

PROP Mixture of a- and p-isomers from acetylation of santalol. Colorless to sidy yellow liquid sandalwood odor. D 0.980, refr index 1.488-1.491, flash p 212°F. Sol in ale insol in water. 

Definition Mixt. of a- and p-isomers from acetylation of santalol... 

Christenson P A, Secord N, Wills B J 1981 Identification of trans->ff-santalol and epi-cis-yff-san-talol in East Indian sandalwood oil. Phytochemistry 20 1139-1141... 

Daramwar Pa.P., Srivastava P.L., Priyadarshinia B., Thulasiram H.V. Preparative separation of a- and P-santalenes and (Z)-a- and (Z)-fS-santalols using silver nitrate-impregnated silica gel medium pressure liquid chromatography and analysis of sandalwood oil. Analyst, 137 4564-4570 (2012). 

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