Civetone, preparation

The animals are kept in cages, and the fresh secretion is taken from the pouches at regular (about one-week) intervals. Civet is almost liquid with a light yellow color. It darkens when exposed to light and takes on a consistency like salve. In dilutions (e.g., as an alcoholic tincture), civet has a pleasant, sweetish odor. A resinoid prepared by extraction with acetone is a dark brown-red mass [257]. Civetone (see p. 88) is the main odoriferous constituent of civet (2.5-3.4%). Civet contains other macrocyclic ketones such as cyclohexa- and cycloheptadecanone and 6-cw-cycloheptadecenone. Traces of indole and skatole contribute to the animal note [258]. 

The ketones 47-49 can be made in good yield (55-95%) by RCM of the appropriate diallyl compounds using 8 as catalyst234. If the spacing between the two C=C bonds in the reactant is increased to ten bonds, then ADMET polymerization is the preferred reaction at normal concentrations. However, by working at 10-3 M it is possible to favour the RCM of oleon (50), equation 35, to give civetone (51) (musk odour) with a yield of up to 14%235. This method of preparation of 51 has the advantage that the metathesis reaction... 

Similarly cyclododecyne (4) was synthesized from 1,2-dichlorocyclododecane (3)-. Civetone (7), a natural perfume of animal origin, w-as prepared by partial reduction followed by acid hydrolysis of the ketal of the cyclohcptadecyne derivative 6 obtained by dehydrobromination of the dibromo ketal 5. ... 

The first documented synthetic macrocycle was synthesized by Baeyer via the condensation of pyrrole and acetone in the presence of mineral acid (Baeyer, 1886). Other examples, from a historical point of view, are listed in a review by Newkome and coworkers (Newkome et al., 1977). The aliphatic macrocycles were synthesized later as exemplified by Willstatter s synthesis of eight-membered rings (Willstatter and Veraguth, 1905) and Ruzicka s studies of the chemistry of muscone and civetone (Ruzicka, 1926). The synthesis of thiacycloalkanes using the reaction of sodium sulfide with an alkyl dihalide was also investigated early in the twentieth century (Braun and Tcherniac, 1907). A cyclam (cyclic amine) was first synthesized by Alphen (1937). The preparation of the peraza-crowns was first developed by Stetter (1953a,... 

This reaction has general application in the preparation of intermediate to macrocyclic ketones, such as muscone and civetone. ... 

After the development of the modern metathesis catalysts, [185] the synthesis of civetone was one of the first applications of ring-closing metathesis. [186] A Claisen condensation followed by metathesis can be used to prepare civetone, but even under extreme dilution (10" -10 molar), the maximum yield is only 24 %, because of considerable polymer formation. 

As previously stated, mRCM is an important method for the synthesis of large rings (Sect. 3.3). Using cyclometalated catalysts, we are now able to exclusively prepare Z-macrocycles using catalyst 10 via mRCM (>95% Z) [52], Alternatively, by Z-selective ethenolysis, we are able to form the corresponding -isomer with catalyst 9 (>95% E). This was showcased in the synthesis of both - and Z-civetone (17) (Scheme 11), as well as several other macrocyclic musk compounds [51]. 

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