Musk synthesis

CifiHjoO. A yellow liquid b.p. 330°C. The perfume base obtained from the scent glands of the Tibetan musk deer also available by synthesis. 

Ambrettohde is obtained from hibiscus and has a musk like odor Its preparation from a compound A is outlined in the table that follows Write structural formulas ignonng stereochem istry for compounds B through G in this synthesis Hint Zinc as used in step 4 converts vici nal dibromides to alkenes )... 

Further important industrial applications of olefin metathesis include the synthesis of 3,3-dimethyl-l-butene ( neohexene , intermediate for the production of musk perfume) from ethene and 2,4,4-trimethyl-2-pentene, the manufacture of a,co-dienes from ethene and cycloalkenes (reversed RCM), and the ROMP of cyclooctene and norbomene to Vestenamer and Norsorex , respectively. 

The classical scent of the sea is afforded by ambergris, which is also the best fixative for perfumes. Once secured from whales, ambergris can now be legally provided by chemical synthesis (Science whaling 2000). Other fixatives are obtained from land animals, such as castoreum, civet, and musk. The first one is a phenolic substance and the latter two macrocyclic ketones that have stimulated the earfy methodologies for the synthesis of macrocyclic conqjoimds... 

In addition to its role as an intermediate in cholesterol biosynthesis, isopentenyl pyrophosphate is the activated precursor of a huge array of biomolecules with diverse biological roles (Fig. 21-48). They include vitamins A, E, and K plant pigments such as carotene and the phytol chain of chlorophyll natural rubber many essential oils (such as the fragrant principles of lemon oil, eucalyptus, and musk) insect juvenile hormone, which controls metamorphosis dolichols, which serve as lipid-soluble carriers in complex polysaccharide synthesis and ubiquinone and plastoquinone, electron carriers in mitochondria and chloroplasts. Collectively, these molecules are called isoprenoids. More than... 

RUZICKA, LEOPOLD (1887-1976). A chemist who won the Nobel prize in 1939 with Adolf Friedrich Johann Butenandt. His work involved research in organic synthesis including polymethylenes and higher terpenes. He was the first chemist to synthesize musk, androsterone. and testosterone from cholesterol. His medical degree was awarded at the University of Basel, Switzerland, although he was born in Croatia and educated partially in Germany. 

Otherwise, in general construction the perfume follows closely that of a classical oriental, with citrus oils (making up some 25%), lavender, sandalwood, patchouli, vanillin, coumarin, castoreum, and rose. The general sweetness of the perfume is further enhanced by the choice of musk materials, Galaxolide (5%), Tonalid, ethylene brassylate, and musk ketone, as well as by the use of Cashmeran, an intensely sweet fruity musk material associated with the synthesis of Galaxolide. 

A variation of the Schmidt type reaction is the rearrangement of an azidocyc-loalkane, which is formed from the addition of hydrazoic acid to an cycloalkene. This reaction was used in the synthesis of muscopyridine (II/U4), a base isolated from the perfume gland of the musk deer [85]. In this context the reaction of II/115 as a model compound under the conditions of the Schmidt reaction gave a mixture of two compounds which after dehydrogenation yielded 11/116 and 11/117. The mechanism can be explained in terms of the migration of different bonds in the precursor. 

It is the pungent aroma that makes up the base-note of musk fragrances. Before chemists had determined its structure and devised a laboratory synthesis the only source of musk was the musk deer, now rare for this very reason. Muscone s skeleton is a 13-mcmbered ring of carbon atoms. 

These ketones are important intermediates in the synthesis of fragrances of the musk type, of UV absorbents and of pharmaceuticals such as paracetamol, ibuprofen, S-naproxen. Thus, in the processes of ibuprofen synthesis (9), the first classical step is the acetylation of isobutylbenzene with acetic anhydride in presence of HF (Hoechst process) or of A1C13 (Boots process) ... 

The pioneering woik of Ohloff in this field is shown by his historic paper on the synthesis of both (118) and (119). Inter alia, the bicyclic tosylate (121) provides, by Grob fragmentation, the unsaturated ketone (122), which also has a strong musk odour. 

Hesse has described an exaltolide (cyclopentadecanolide) (134 Scheme 42) synthesis starting from the readily available 2-cyanocyclododecanone (130). The latter is converted to the quaternary ammonium salt (131), which undergoes fragmentation under mild conditions to provide the lactone (133) via the lactole anion (132). The methylene compound (133) exhibits similar musk odor, as does (134). 

Pure meto-cresol has been used for manufacture of synthetic musk— musk ambrette, used as a fixative to perfumes, for manufacture of synthetic Thymol and Menthol amd also leather preservative p-chloro-meto-cresol, synthetic pyre-throids, and lastly for manufacture of 2,3,6-trimethylphe-nol—an intermediate for vitamin E. o-Cresol has been used for manufacture of Coumarin and some derivatives which are employed in perfumery as fixative. o-Cresol has also been used for making Novolac and epoxy resins and also for the herbicides based on di-nitro-oAt/io-cresol, etc. In sum, individual cresols have been very successfully converted to important intermediates in the organic chemical synthesis. It is expected that further development work will lead to synthesis of many more organic chemicals of vital importance. While new chemicals using individual cresols are in the pipeline... 

The second largest macrocylic musk, in tonnage terms, is cyclopenta-decanolide. Its synthesis is shown in Scheme 4.48. The key starting... 

C. Fehr, J. Galindo, R. Haubrichs, and R. Perret, Hell. Chim. Acta., 72, 1537 (1989). New Aromatic Musk Adherent Design and Synthesis. 

Olefin metathesis has been used by a number of workers to produce macrocyclic musks. One of the earliest examples is Mol s synthesis of civetone from methyl oleate. This takes advantage of the ideally placed double bond in the starting oleic acid. Unfortunately, the ds-geometry of the olefin is lost on metathesis and a mixture of isomers results. Furthermore, almost half of the weight of the starting material is lost as the unwanted 9-octadecene. Dieckmann cyclisation of the metathetical diester, followed by hydrolysis and decarboxylation, gives a mixture of E- and Z-civetone. The synthesis is shown in Figure 4.59. 

In the field of fine chemistry, the Phillips neohexene process was an early commercial application of olefin metathesis [20]. Neohexene (3,3-dimethyl-l-butene) is an important intermediate in the synthesis of musk perfume. The Phillips neohexene process is based on ethenolysis of an isobutene dimer consisting of a mixture of 2,4,4-trimethyl-2-pentene and 2,4,4-trimethyl-1-pentene. Ethenolysis of the former yields the desired product (Eq. 6). 

Grubbs catalyst 86a efficiently produced 16- or 21-membered lactone 90a-c in good yields (Scheme 14) [59], The method was further applied to the synthesis of (4-)-12-methyl-13-tridecanolide (91), a minor musk-odor component. Lasiodiplo-din (94) was efficiently synthesized via the formation of 12-membered lactone 93 by RCM of 92 with 86a as the key step [60]. Schrock catalyst 85 was successfully applied to the synthesis of fluvirucin Bi (Sch 38516) (97). Reaction of the fully functionalized diene 95 with 85 afforded macrolactam 96 as a single (Z)-olefin [61]. RCM has been also utilized in the total synthesis of epothilones (5) (Section... 

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