A Menthol

AH (A)-menthol is made by synthetic methods. One method involves the cyclization of (+)-citroneIlal (68). Using a mild acid catalyst, (+)-citroneIlal [2385-77-5] undergoes an ene-reaction to produce a mixture of isopulegols (142). Catalytic hydrogenation of the isopulegol mixture gives a mixture of menthol and its isomers. The (A)-menthol is obtained after efficient fractional distillation and the remaining isomers can be equilibrated, usually with sodium menthol ate or aluminum isopropoxide. An equilibrium mixture is obtained, comprised of 62 wt % (A)-menthol, 23 wt % (+)-neomenthol, 12 wt % (+)-isomenthol, and 3 wt % (+)-neoisomenthol. The equilibrium mixture can be distilled to recover additional (+)-mentbol. 

A)-Menthol can also be made synthetically by hydrogenation of thymol [89-83-8], which can be produced by isopropylation of y -cresol with propylene (143,144). 

Optical resolution is another method of producing (—)-mentho1 from racemic materials. (A)-Menthol is treated with optically active resolving agents to separate the (—)-mentho1 from the (+)-menthol, which is further processed by racemization over a nickel catalyst and recycled (156). 

Resolution methods using nonopticaHy active agents are also used by taking advantage of the fact that certain benzoic acid derivatives of (A)-menthol can be inoculated with crystals of one enantiomer to induce immediate crystallization of that enantiomer. Although repeated crystallizations and separations must be done, the technique has been successhil for (—)-mentho1 (157). 

Brimble and coworkers172 reported the asymmetric Diels-Alder reactions between quinones 265 bearing a menthol chiral auxiliary and cyclopentadiene (equation 73). When zinc dichloride or zinc dibromide was employed as the Lewis acid catalyst, the reaction proceeded with complete endo selectivity, but with only moderate diastereofacial selectivity affording 3 1 and 2 1 mixtures of 266 and 267 (dominant diastereomer unknown), respectively. The use of stronger Lewis acids, such as titanium tetrachloride, led to the formation of fragmentation products. Due to the inseparability of the two diastereomeric adducts, it proved impossible to determine which one had been formed in excess. 

A series of cyanoacetic acid derivatives 96 (94TA1435, 95TA255) was used for the introduction of a chiral moiety into position 3 of a pyran ring Oppolzer s sultam (a), (—)-menthol (b), (IS)-endo-(-)-borneol (c), ethyl (S)-(—)-lactate (d), diisopropylidene-o-glucofuranose (e). Both Methods 1 and... 

The enantioselective hydrolysis of racemic menthyl benzoate (industrially key compound) by recombinant Candida rugosa lipase LIPl leads to optically pure l-(-)-menthol ee>99% [21]. This pathway is part of a menthol synthesis developed by the flavour industry. 

N.A. Menthol, menthone, menthyl acetate, camphene, limonene, terpenoids." Treat colds, sore throats, sore mouth. 

The first report of an asymmetric Diels-Alder reaction with chiral Lewis acids (252) was made by Russian chemists in 1976 (253). Koga was probably the first to report a meaningful enantioselective Diels-Alder reaction (Scheme 105) in which the cyclopentadiene-methacro-lein exo adduct was obtained in 72% ee with the aid of 15 mol % of a menthol-modified aluminum chloride (254). The ee is highly dependent on the structures of the substrates, and asymmetric induction has not been observed with methyl acrylate as dienophile. Disproportionation... 

Bach and co-workers developed the axially chiral N-arylthiazolium catalyst 41 bearing a menthol-derived backbone (Fig. 9.6) [45]. Using 20 mol% of this catalyst, they were able to isolate the Stetter product 30 (R = Me) in 75% yield with 50% ee. The low stereoselectivity was ascribed to an atropo-isomerization of the catalyst during the course of the reaction. 

Perillartine, a-syn-oxime of perillaldehyde, is reported to be 2000 times sweeter than sucrose.48 49 Perillaldehyde is a principal volatile oil of Perilla frutescens (L.) Britton (Labiatae) and is reported to be only slightly sweet. Perillartine is used as a replacement for maple syrup and licorice for the sweetening of tobacco in Japan. However, due to its low solubility in water as well as a menthol-licorice off-taste, there is some limitation to its use. 

Krishnaiah, Y. S., and Bhaskar, P. (2004), Studies on the transdermal delivery of nimodipine from a menthol-based TTS in human volunteers, Curr. Drug Deliv., 1(2), 93-102. 

A 40-year-old woman with no personal or family history of asthma had dyspnea, wheezing, and nasal symptoms for 2 years whenever she used toothpaste and/or ingested mint confections. She had no history of aspirin sensitivity, and a challenge test with a menthol solution diluted in alcohol ruled out any possibihty that the asthma had been caused by preservatives, dyes, or other additives. 

Polymers and copolymers of vinylic carbonates and carbamates may find interesting applications as aroma and flavours releasing agents. For example, isopropenyl menthyl carbonate has been patented (Ref. 148) as an useful monomer for the manufacture of a smoking composition comprising an admixture of tobacco and a menthol-release agent. Recently, Harwood et. al (Ref. 149) have published a new preparation of enol carbonates including especially isopropenyl menthyl carbonate by selective O-acylation of ketones sodium... 

The world s biggest application of asymmetric catalysis is Takasago Perfumery s synthesis of (-)-menthol from myrcene (see Sections 2.9 and 3.3.1) with about 1500 t/a (menthol and other chiral terpenic substances). The key step is the isomerization of geranyldiethylamine with an Rh -S-BINAP catalyst to citronellal ( )-enamine (eqs. (17)) (BINAP = 2,2 -bis(diphenylphosphine)-l,l -binaphthyl).The geometry of the double bond is 100% E. 

Few examples have been reported demonstrating enantioselective cyclization methodology. One known example, however, is similar to the diastereoselective cyclization of 175, which uses a menthol-derived chiral auxiliary and a bulky aluminum Lewis acid (see Eq. (13.55)). The enantioselective variant simply utilizes an achiral template 188 in conjunction with a bulky chiral binol-derived aluminum Lewis acid 189 (Eq. (13.59)) [75]. Once again the steric bulk of the chiral aluminum Lewis acid complex favors the s-trans rotamer of the acceptor olefin. Facial selectivity of the radical addition can then be controlled by the chiral Lewis acid. The highest selectivity (48% ee) was achieved with 4 equivalents of chiral Lewis acid, providing a yield of 63%. 

Calculate the percent composition of each of the following compounds (a) menthol, CjgHjpOH (b) carborundum, SiC (c) aspirin, C9Hg04. 

A menthol-based route to grandisol is described by H.-D. Scharf using the [2+2] cycloaddition of ethylene with an enantiomerically pure menthyl-substituted furanone as the photochemical key step. The asymmetric induction of this reaction is relatively poor, the diastereomeric photoproducts, however, can be easily separated. Both enantiomers of grandisol can be synthesized using this methodology. 

Few examples have been reported demonstrating enantioselective cyclization methodology. One known example, however, is similar to the diastereoselective cyclization which uses a menthol-derived chiral auxiliary and a bulky aluminum Lewis acid to impart selective cyclization [30[. The enantioselective variant simply... 

An asymmetric center next to a carbonyl group is not disturbed during the reduction. Thus from (—)-menthone a menthol mixture [71% of (—)-menthol and 29% of neomenthol (cis)] is obtained that can be reoxidized to (—)-menthone 359... 

Heating the sodium salt of pyrrole-2-carboxylic acid with methyl iodide in a sealed tube at 120°C gave the first example of an isopyrrole, formulated9 as 1 or its isomer (2). The same compound, having a menthol- or camphor-like odor, was isolated together with a methylenepyrroline formulated as 3 on treatment of 2,3,4,5-tetramethylpyrrole with methyl iodide and potassium... 

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