A-Geraniol

Synthesis from Linalool. A 96% pure synthetic geraniol prepared by isomerization of linalool has become commercially available. Orthovanadates are used as catalysts, to give a >90% yield of a geraniol nerol mixture [31]. Geraniol of high purity is finally obtained by fractional distillation. 

In Part A geraniol is oxidized to geranial (citral) by Swern s modification of the Moffat oxidation. 1 The stereoisomerlc purity of the product is at least 98%. This procedure is readily conducted on a large-scale and requires only 4 hours time including distillation of oxalyl chloride. The oxidation of geraniol to pure (E)-geranial may also be accomplished by... 

Hydroxylamines can be reduced electrochemically with N—O bond cleavage. This reaction was used in a geraniol synthesis (fragrance material) ... 

A word about the synthesis of the a-series, a-geraniol (73) and a-nerol (74), is warranted because they are often intermediates in the synthesis of 1-hydroxylated compounds (e.g., some diols described below). Weiler has continued his exploitation of the dianion of methyl acetoacetate to this end. Instead of prenylation (Vol. 4, p. 461, Ref. 73) he carried out a similar series of operations by alkylating the dianion with 4-bromo-2-methyl-l-butene, thus arriving at compounds of the a-series via the keto ester 75, methylating the enol phosphate to 76. He also prepared the double methylene isomer 77 (R = COEt) of geranyl propionate from the intermediate 75. The purpose of synthesizing this propionate was to prepare the pheromone of the San Jose scale, Quadraspidiotus pernicious, which is a mixture of the propionates of 73, 74,... 

This synthesis has been adapted to make the natural (5 -isomer of 114, reducing the initially formed aldehyde to (S)-114 with baker s yeast. [This same synthesis has been adapted to make (S)-callosobruchic acid (115), see below]. Julia s synthesis of a-geraniol (73) was also extended to make 114 by hydro-boration. Hydroboration of 73 with diisopinocampheylborane (made from (- )-a-pinene [(-)-116]) gave only a small ee however. A synthesis of ( )-114 started with the reaction of 2-methylpropiolactone and the ethylene acetal of 3-oxobutylmagnesium bromide. The methyl ester of the acid 117 thus prepared was chain-lengthened by reaction with acetylene and rearrangement with a vanadium catalyst of the ynol thereby obtained. The aldehyde 118 was then reduced with lithium aluminum hydride to 114. ... 

SHALIT, M., GUTERMAN, I., VOLPIN, H., BAR, E., TAMARI, T., MENDA, N., ADAM, Z, ZAMIR, D., VAINSTEIN, A., WEISS, D., PICHERSKY, E., LEWINSOHN, E., Volatile ester formation in roses. Identification of an acetyl-coenzyme A. Geraniol/citronellol acetyltransferase in developing rose petals. Plant Phys., 2003,131, 1868-1876. 

The CD complexes are compatible with thermoplastic resins. Mixing a dry pulverized CD eomplex of a perfume, for example, a geraniol aCD complex, with a thermoplastic resin (polyethylene), and molding it, yielded plastic products with a long-lasting (at least 6 months) fragrance. Rapid loss of the perfume by volatility and thermal decomposition can be avoided in this way. 

Fig. 4.4 Retention of stereochemistry in cytochrome P450-catalyzed carbon hydroxylations has been explicitly demonstrated with a variety of substrates, including octane (a), geraniol (b), and testosterone (c)...

Shalit, M., et al. (2003) Volatile ester formation in roses. Identification of an acetyl-coenzyme A Geraniol/citronellol acetylfransferase in developing rose petals. Plant Physiol. 131,... 

Chemical studies on the sex attractant of the boll weevil led to the isolation (454) and identification (38) of four terpenoid compounds. Tumlinson et al. (455) suggested a hypothetical biosynthetic scheme in which all four compounds could be derived from a geraniol-like compound. Hardee (45 showed that male boll weevils required feeding for the synthesis of the attractant substances. Cotton squares proved to be the best diet, but pheromone production was demonstrated on a variety of diets. Mitlin and Hedin (457), using C tracers, obtained evidence... 

C10H13O. B.p. 225-226"C. A terpenic alcohol and a constituent of neroli, petit-grain and bergamot, and of many other essential oils. Nerol has a blander smell than its isomer, geraniol, and is more valuable as a constituent of perfumes. 

Wnte a structural formula or build a molecular model for geraniol showing its stereo chemistry... 

The enzyme catalyzed reactions that lead to geraniol and farnesol (as their pyrophosphate esters) are mechanistically related to the acid catalyzed dimerization of alkenes discussed m Section 6 21 The reaction of an allylic pyrophosphate or a carbo cation with a source of rr electrons is a recurring theme m terpene biosynthesis and is invoked to explain the origin of more complicated structural types Consider for exam pie the formation of cyclic monoterpenes Neryl pyrophosphate formed by an enzyme catalyzed isomerization of the E double bond m geranyl pyrophosphate has the proper geometry to form a six membered ring via intramolecular attack of the double bond on the allylic pyrophosphate unit... 

Uses ndReactions. a-Pinene (8) is useful for synthesizing a wide variety of terpenoids. Hydration to pine oil, acid-catalyzed isomerization to camphene, thermal isomerization to ocimene and aHoocimene, and polymerization to terpene resins are some of its direct uses. Manufacture of linalool, nerol, and geraniol has become an economically important use of a-pinene. 

Another important use of a-pinene is the hydrogenation to i j -pinane (21). One use of the i j -pinane is based on oxidation to cis- and /n j -pinane hydroperoxide and their subsequent catalytic reduction to cis- and /n j -pinanol (22 and 23) in about an 80 20 ratio (53,54). Pyrolysis of the i j -pinanol is an important route to linalool overall the yield of linalool (3) from a-pinene is about 30%. Linalool can be readily isomerized to nerol and geraniol using an ortho vanadate catalyst (55). Because the isomerization is an equiUbrium process, use of borate esters in the process improves the yield of nerol and geraniol to as high as 90% (56). 

The production of myrcene (7) from P-pinene is important commercially for the synthesis of a wide variety of flavor and fragrance materials. Some of those include nerol and geraniol, citroneUol (27) and citral (5). 

Myrcene Manufacture. An important commercial source for mycene is its manufacture by pyrolysis of p-piaene at 550—600°C (87). The thermal isomerization produces a mixture of about 75—77 wt % myrcene, 9% limonene, a small amount of T -limonene [499-97-8] and some decomposition products and dimers. The cmde mixture is usually used without purification for the production of the important alcohols nerol and geraniol. Myrcene may be purified by distillation but every precaution must be taken to prevent polymerization. The use of inhibitors and distillation at reduced pressures and moderate temperatures is recommended. Storage or shipment of myrcene in any purity should also include the addition of a polymerization inhibitor. 

Nerol, geraniol, and linalool, known as the rose alcohols, are found widely in nature. Nerol and geraniol have mild, sweet odors reminiscent of rose flowers. They are manufactured by the hydrochlorination of mycene at the conjugated double bonds when a copper catalyst is used (88,89). 

Uses ndReactions. Nerol (47) and geraniol (48) can be converted to citroneUol (27) by hydrogenation over a copper chromite catalyst (121). In the absence of hydrogen and under reduced pressure, citroneUal is produced (122). If a nickel catalyst is used, a mixture of nerol, geraniol, and citroneUol is obtained and such a mixture is also useful in perfumery. Hydrogenation of both double bonds gives dimethyl octanol, another useful product. 

Acid-catalyzed esterification of nerol and geraniol with acid anhydrides produces the corresponding esters. The acetates and isobutyrates are also avaUable commercial products. U.S. production of neryl acetate [141-12-8] in 1993 was 18 t at a price of 11.56/kg and that of geranyl acetate [105-37-3] was 132 t at a price of 9.86/kg (67). 

Linalool can also be made along with nerol and geraniol via the hydrochlorination of myrcene. After conversion of the chlorides to acetates followed by saponification of the acetates, the mixture of alcohols is obtained. Fractionation of the mixture gives linalool in about 95% purity, but the presence of close boiling impurities prohibits manufacture of a perfiimery-quahty product. 

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