Cedrol and Cedrene

The tricyclic fragrances of cedar wood, cedrene and cedrol, were synthesized by several routes involving cation-olefin cyclization. 

From the intermediate A, cedrene was also made by an alternative route  

Another synthesis of cedrene and of cedrol was achieved via the following sequence (Ref. 2)  

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Important commercial sesquiterpenes mosdy come from essential oils, for example, cedrene and cedrol from cedarwood oil. Many sesquiterpene hydrocarbons and alcohols are important in perfumery as well as being raw materials for synthesis of new fragrance materials. There are probably over 3000 sesquiterpenes that have been isolated and identified in nature. 

It yields a phenylurethane if it is heated almost to boiliog-point with phenyl-isocyanate. This compound melts, at 106° to 107°. On dehydration with phosphoric acid it yields the sesquiterpene cedrene. The relationship between cedrene and cedrol is probably as follows —... 

Cedrene and cedrol are used as fragrances in perfumery and as insect repellants. Acid-catalyzed dehydration of cedrol, the product of a nucleophilic addition of... 

Cedarwood oil, distilled from the wood of Juniperus virginiana. Specific gravity at 15° 0., 0 938-0 960 optical rotation, -35° to -45° refractive index at 20° C., 1 5013-1 5030. The principal constituents are cedrene and cedrol. 

Corey, E. J. Balanson, R. D. Simple synthesis of ( )-cedrene and ( )-cedrol using a synchronous double annulation process Tetrahedron Lett. 1973, 14, 3153-3156. 

Recently, Corey and Balanson reported an ingeniously simple approach to cedrene and cedrol, utilizing a synchronous doubie annulation process. The key step involves direct conversion of the cationic enol ester (B), generated from the readily accessible cyclopropyl ketone (A), to give cedrone. 

Corey, E. J., and R. D. Balanson A Simple Synthesis of ( )-Cedrene and ( )-Cedrol Using a Synchronous Double Annulation Process. Tetrahedron Letters 1973, 3153. 

Ced rwood. Many varieties of cedarwood oil are obtained from different parts of the world. They are produced mainly by steam distillation of chipped heartwood, but some are also produced by solvent extraction. The oils, which vary significantly ia chemical composition, are used ia perfumes as such, but the main uses are as distillation fractions and chemical derivatives. For the latter purposes the most used oils, which are similar ia composition, are from Texas ia the United States (Juniperus mexicand) and from China Cupressusfunebris). The principal constituents of these oils are cedrene [11028-42-5] (4), thujopsene [470-40-6] (5), and cedrol [77-53-2] (6). The first two of these are obtained together by distillation and used mostiy ia the form of acetylated derivatives. Cedrol is used as such and, to a greater extent, as its acetate ester. 

Semmler and Mayer have isolated from the oil of cedar wood an alcohol, pseudocedrol. There also exists in the oil a sesquiterpene alcohol, cedrol. The latter, on dehydration yields cedrene, which is probably identical with, or very closely allied to, natural cedrene, whilst pseudocedrol yields a mixture, when heated in a sealed tube, of cedrene and dihydrocedrene. Dihydrocedrene is a colourless oil having the following characters —... 

Cedrene and Gedrol. Cedarwood oil is one of the essential oils whose production is large and provides a source for synthesizing a number of derivatives. Cedrene (91) and thujopsene (92) are the two main sesquiterpene hydrocarbons found in the oil, along with a number of minor components (187). Cedrol [77-53-2] (93) is the main alcohol component of the oil. 

The major components of the Juniperus wood oils are cedrol, cedrene and thujopsane, and a number of perfume ingredients are made from... 

Two almost simultaneous communications reported the successful syntheses of a-cedrene (123) and cedrol (124). Both syntheses were modelled along a proposed biogenetic scheme, and as such the penultimate goal was the generation of the cation (125) which should, and did, undergo a smooth acid-catalysed cyclisa-tion to a-cedrene. The two pathways to this cation differed in several respects yet practically coincided at the key spiro-dienone ester (126, R = Me and R = Et ). Whereas Crandall and Lawton completed the synthesis by formic acid treatment of the alcohol (127), Corey et al. found that similar treatment of the diol (128) also yielded a-cedrene, albeit in lower yield. Alternatively, the ene-diol (129) was converted into a-cedrene in better yield by formic acid treatment, thermolysis of the derived formates and subsequent lithium-ethylamine reduction of the diene (130). Finally, cedrol (124) was obtained by boron trifluoride cyclisation of the enol-acetate (131), followed by methyl-lithium treatment of the intermediate cedrone. 

The major components of the Cedrus wood oils are cedrol, cedrene and thujopsene, and a number of perfume ingredients are made from these. The most important is acetylated cedarwood. This product is used because it possesses a much stronger cedarwood odour than the natural oil and is available under various trade names such as Lixetone and Vertofix . The acetylation can be carried out using acetyl chloride in the presence of a Lewis acid or by using a Bronsted acid system such as polyphos-phoric acid/acetic anhydride or sulfuric acid/acetic anhydride. The cedrol dehydrates into cedrene under the reaction conditions and so the major component in the product is acetylcedrene. However, the main contributor to the odour of the complex reaction product mixture is the ketone derived from acetylation of thujopsene (Daniker et al., 1972). These reactions are shown in Figure 4.36. 

The isocedrenes are considered to be analogs of the tricyclic sesquiterpene cedrol (2) which has been synthesized by G. Stork. Cedrene and its derivatives, most notably the 9 and 10- oxy derivatives have found applications in the cosmetics field as additives to perfumes, and in other fields as plant growth stimulators. ... 

Production By steam distillation from the wood of the Chinese red pine Chamaecyparis funebris (Cupressaceae). The annual production amounts to ca. 200-3(X) t. CompositionThe main components of all mentioned oils are the sesquiterpene compounds a- cedrene (ca. 10-25%), tIiM/opsene(ca.20-35%),and cedrol(c. 20-40%, in Chinese oil only 10-15%). 

Cedrane derivatives such as (-)-3-cedrene (a-cedrene) and (-l-)-3(15)-cedrene (p-cedrene) are wide-spread among Juniperus species (Cupressaceae). (-)-a-Cedrene (content up to 25%) and (+)-cedrol (content 20-40%) are the chief constituents of the oil of cedar wood used in perfumery and as an insect repellant, obtained from Juniperus virginiana growing in the south-east of USA. (-l-)-Cedrol shapes the... 

According to Semmler cedrenol stands in the same relation towards cedrene as the two primary alcohols of the santalol series towards the sesquiterpenes, Cig 4, the santalanes and as myrtenol and the ginger-grass alcohol stand towards pinene and limonene. The primary CHjOH group in the cedrenol molecule occupies the same position which is occupied by the GH, group in cedrene and in solid cedrol. Hence the relation of cedrene towards cedrol and cedrenol is as follows... 

The main components of these cedarwood oils are a-cedrene [469-61-4] (270), cedrol [77-53-2] (271), and thujopsene [470-40-6 ] (272). The oils also contain a variety of minor components (327). Fractional distillation gives hydrocarbon and alcohol fractions. Cedrene and thujopsene are separated from the former and recrystallization of the latter gives cedrol. A crude alcoholic fraction containing both cedrol and isomers, such as wid-drol (273) together with some ketonic material, is sold as cedrenol. Thujopsene is also isolated from Hiba Wood oil (83). 

The price of Gedarwood oil from Texas in 1995 was 7.70/kg and the price of the oil from Virginia was 15.18/kg (69). Distillation of the oil gives two main fractions, the cedrene or hydrocarbon fraction, and the alcohol fraction consisting of impure cedrol, which when purified by crystallization can be used direcdy in perfumery. Gedrenol is a product comprising a mixture of cedrol and its isomers widdrol and some ketone components. 

In addition to cedrol and pseudocedrol, cedar-wood oil contains a third alcohol, of the formula Cj5H. 40, which has been named cedrenol. This alcohol was isolated by Semmler and Mayer, who found it to exist to the extent of about 3 per cent, in the oil. It is a tricyclic unsaturated alcohol, closely related in constitution to the sesquiterpene cedrene, as shown hy the following formulae —... 

Biosynthetic considerations and the discovery of their co-occurrence with a-cedrene (42) and (+)-zizaene (43) have led to the reformulation of various cedrane derivatives (44 R = Me, CH2OH, CHO, or COzH) found in vetiver oil 76 it is believed that these sesquiterpenoids are formed from the common precursor (45). The metabolites of cedrol found in the urine of rabbits are mainly glucuronides of hydroxylated cedrol derivatives 77 presumably formation of the glucuronide of the tertiary alcohol itself is difficult because of steric hindrance. 

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