Linalool synthesis

On an industrial scale it was best to introduce the vinyl anion synthon as acetylene and then hydrogenate the alkyne. The unsaturated ketone was chosen as the starting material because its synthesis was already known, linalool synthesis... 

Semikolenov, V., Ilyna, I. and Simakova, I. (2001). Linalool Synthesis from a-Pinene Kinetic Peculiarities of Catalytic Steps, Appl Catal. A Gen., 211, pp. 9-107. 

The methylheptenones are intermediates for the synthesis of linalool (3). A continuous ethynylation with sodium hydroxide and /V-methy1pyrro1idinone has been developed (eq. 3) (29). 

The synthesis of dehydro-hnalool (28) rehes on the basic chemicals acetone and acetjiene. Addition of a metal acetyUde to acetone yields methylbutynol (33). Semihydrogenation affords the alkene (34) which is reacted with /-propenylmethyl ether. A Cope rearrangement of the adduct yields methyUieptenone (35). Addition of a second mole of metal acetyUde to dehydro-linalool (28) is followed by a second Cope rearrangement to yield... 

A one-step synthesis of the triphenylphosphonium salt (81) from linalool or geraniol and triphenylphosphonium bromide, with simultaneous... 

S)-3,7-Dimethyl-2-oxo-6-octene-l,3-diol (39) was recently identified as the aggregation pheromone of the Colorado potato beetle (Leptinotarsa decem-lineata), and synthesized by Oliver et al., starting from (S)-linalool [86]. An improved synthesis of (S)-39 by Mori is shown in Scheme 57 [87]. Enzymatic acetylation of ( )-2,3-epoxynerol (A) with vinyl acetate and lipase PS gave B together with C. The acetate B was converted to a multi-gram quantity of (S)-39 according to Oliver [86]. 

Linalool is an important fragrance and fragrance precursor (esters) with an annual production of over 15 000 t. Some 50% is made by semi-synthesis from a- and / -pinene, the other part is made synthetically starting from isobutene via 6-methylhept-5-en-2-one (9). Addition of an acetylene fragment followed by partial hydrogenation (Pd) leads to linalool. 

Scheme 17. Synthesis of cis- and frans-linalool oxide using bacterial epoxide hydrolase...

Linalool is one of the most widely used fragrant substances in cosmetic and pharmaceutical industry (as a composite of many cosmetics and perfumes and as an intermediate in synthesis of vitamins (A, E)) (1). But natural resources can t supply the growing needs, so the necessity in synthetic LN has been increasing. Therefore the reaction of selective catalytic hydrogenation of DHL to LN is one of the most significant reactions in the chemistry of fragrant substances (2), and the main problem of this research is the development of modern catalytic technology for preparation of linalool. 

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. 

Synthesis from (3-Pinene. For a description of this route, see under Geraniol. Addition of hydrogen chloride to myrcene (obtained from /3-pinene) results in a mixture of geranyl, neryl, and linalyl chlorides. Reaction of this mixture with acetic acid-sodium acetate in the presence of copper(I) chloride gives linalyl acetate in 75-80% yield [37]. Linalool is obtained after saponification. 

Synthesis from 6-Methyl-5-hepten-2-one. The total synthesis of linalool starts with 6-methyl-5-hepten-2-one several large-scale processes have been developed for synthesizing this compound ... 

Industrial synthesis of nerolidol starts with linalool, which is converted into ger-anylacetone by using diketene, ethyl acetoacetate, or isopropenyl methyl ether, analogous to the synthesis of 6-methyl-5-hepten-2-one from 2-methyl-3-buten-2-ol. Addition of acetylene and partial hydrogenation of the resultant dehydroner-olidol produces a mixture of cis- and trans-nerolidol racemates. 

Terpenes important for both fragrances and flavours can be prepared from citral, such as citronellol, linalool, nerolidol, geraniol, farnesol and bisabolol. Citral is also an important starting material for the synthesis of vitamins A and E, carotenoids and other flavour and fragrance compounds like ionones. Most of the /3-ionone synthesised is probably used for vitamin A synthesis. 

Hotrienol was found for the first time in Ho leaf oil as the S enantiomer [7], but has been found since then in many natural sources for instance, the R enantiomer was found in black tea and in green tea. The product can be used in many flavours, such as eldertlower, grape, berry and honey flavours. It can be prepared from linalool obtained from citrus oils or Chinese Ho oils, but most linalool is obtained by synthesis from isoprene from petrochemical sources. 

Recently a practical and convenient synthesis was described starting from linalool via linalyl acetate [8]. It involves the ene-type chlorination of linalyl acetate prepared from linalool which results in the formation of y-chloro-a-linalyl acetate (Scheme 13.8). Dehydrochloronation with lithium bromide and lithium carbonate in dimethylformadide followed by hydrolysis of dehydro-a-linalyl ac-ylate results in hotrienol. 

Scheme 13.8 Chemical synthesis of hotrienol from linalool...

The most important and frequently used terpene esters in flavours are the acetates of nerol, geraniol, citronellol, linalool and isoborneol [12], As discussed before, all these terpene alcohols are available both from renewable resources and from petrochemical origin. Acetic acid can be obtained from renewable resources by pyrolysis of wood as wood vinegar, and also by synthesis from petrochemical origin. 

The raw material, myrcene (15 FF/Kg), is significantly cheaper than linalool (40 FF/Kg), the feedstock in the existing process.54 Furthermore, the intermediate P-ketoesters can be used for the synthesis of pseudoionone a key intermediate for the manufacture of vitamin A (world market for vitamin A 3 000 t/a at a price of 40-50 /kg).54>504... 

The synthesis of tetrahydrofurans through cyclization via epoxide ring opening has been well investigated and has been applied to the preparation of a-bisabolol oxides (69IJC1060) and linalool oxides (77H(6)1365) and by Kishi et al. in the synthesis of lasalocid A (195), where the epoxide pathway resulted in a stereospecific construction of six out of the ten chiral centers (Scheme 93) (78JA2933). 

Scheme 12 RCM of linalool as a first step of the synthesis of the high-density fuel RJ-4 [86]...

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