Cedrenes

Review Problem 17 Design a synthesis for TM 206, an intermediate in Crandall and Lewton s biogenetically patterned synthesis of cedrene ( J. Amer. Chem. Soc.. 1969, 91, 2127). 

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. 

Cyclic sesquiterpenes having the cedrene skeleton have also been isolated. When R = COOH, this stmcture (11) has been named sheUoflc acid. 

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. 

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. 

Acetyl cedrene (95) is obtained by the acetylation of the hydrocarbon fraction, a-cedrene [469-61-4] (91). The product has a woody, warm-ambergris, and musk odor, and many types of products are available (189). 

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) ... 

Semmler considers /3-gurjunene to resemble the tricyclic sesquiterpene, cedrene, so that it is doubtful whether it is bicyclic or tricyclic. 

Cedrene is the naturally occurring sesquiterpene of cedar wood oil of which it forms the principal constituent. It is a tricyclic compound having the following characters —... 

The above figures are for the purest specimen of natural cedrene which has been prepared. 

Semmler and Hoffmann have examined this sesquiterpene in considerable detail. It was dissolved in acetone and oxidised with potassium permanganate, and the indifferent products thus obtained were separated by fractional distillation. Cedrene glycol, Cj Hj O, was obtained to the extent of 12 to 15 per cent. it crystallises from acetone in prisms, melting at 160°. 

When cedrene was oxidised with permanganate, there were chiefly formed products of an acid nature, from which a cedrene keto acid, CjjHj Oa, was isolated, which boiled at 215° to 222° (11 mm. press.). Its semicarbazone melts at 245° and its oxime at 60°. 

When cedrene is oxidised by chromic acid, in acetic acid solution, a mixture of two ketones is obtained, of which the principal is a body to which the name cedrone has been assigned. Cedrone has the following characters —... 

By the reduction of cedrone by means of sodium and alcohol, there is formed dihydro-isocedrol, CijH gO, boiling at 148° to 151° C. under a pressure of 9-5 mm. When cedrene is heated at 180° to 210° C. with hydriodic acid and red phosphorus, and the product formed is reduced by sodium and alcohol, a body Cj Hjg is obtained, which Semmler describes by the name dihydro-cedrene It boils at 116° to 122° C. under 12 mm. pressure its specific gravity is 0-9052 at 15° C. 

Although the constitution of cedrene is not understood, Semmler and Hoffmann consider that the following complexes are present in the various bodies described —... 

Semmler and Risse have studied the oxidation of cedrene by means of ozone. They obtained the keto-acid, Cj Hj Oj, which on further oxidation either by means of bromine or nitric acid yields a dicarboxylic acid. 

C,4H2204, melting at 182 5. The formation of this cedrene-dicarboxylic acid serves for the detection of cedrene in essential oils. It is sufficient if the fraction to be examined be oxidised by permanganate or ozone, and the acid obtained (boiling-point at 10 mm. = 200° to 220° C.) be then oxidised further, either by an alkaline solution of bromine or by nitric acid. Even very small proportions of cedrene have definitely led to the obtaining of this acid melting at 182 5° C. 

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 —... 

No crystalline halogen derivatives of cedrene have been prepared, only liquid compounds being obtained when the sesquiterpene is treated by the usual processes. 

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 —... 

When pseudocedrol is heated in a sealed tube at 235° it yields a mixture of dihydrocedrene, CjgH2g, and cedrene, C16H24-... 

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 —... 

By the action of phosphorus pentachloride, cedrenol yields cedrenyl chloride, CisHggCl, which, when reduced by sodium and alcohol yields cedrene. 

The second chemotype (their Type 1) had, in addition to the Type 0 array, substantial amounts of a-longipinene [297] and an unidentified sesquiterpene alcohol. The third chemotype (their Type 2) was distinguished by the presence of, among other compounds, cedrene isomers, [a-cedrene is shown as 298], and large amounts of the isomeric sesquiterpene alcohols a-acorenol [294] and its P-isomer [295]. The acora-diene isomers [295 and 296] were also identified. Some geographic patterning was observed in the Type 0 chemotype when the data were subjected to numerical analysis a trend in the reduction of caryophyllene content was revealed in a west to east direction. The data sets for Types 1 and 2 were too small to allow for similar analysis. 

In a similar way, a-cedrene has been synthesized by the same group [35]. Moreover, these authors have also developed a further access to modhephene (3-70) using a free-radical 6-mdo-/5 - exo-do rn i rio cyclization of a dieneyne [36]. 

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