Menthol structure

In Problem 4 25 you were asked to draw the preferred conformation of menthol on the basis of the information that menthol is the most stable stereoisomer of 2 isopropyl 5 methylcyclo hexanol We can now completely descnbe (—) menthol structurally by noting that it has the R con figuration at the hydroxyl substituted carbon... 

Since the introduction of WS-3, many other coolants have appeared on the market, mostly based on the menthol structure and, in fact, synthesized from menthol. These are shown in Fig. 8.45. Three menthyl esters are produced. The lactate (201) is made by Symrise and sold under the trade name Frescolat ML, while the succinate (202) is available from Advanced Biotech as Koolada. Menthyl pyrrohdone carboxylate (203) is sold by Quest as Questice. Questice serves as a sustained release precursor for menthol, the ester function being cleaved by lipases. It therefore finds use in cosmetics since the release rate is affected by the moisture levels in the skin. Thus as the body tries to lose heat, e.g., on exercise, Questice provides the desirable sensation of cooling. Some higher menthyl esters have been patented as coolants by Firmenich (259). Two menthyl ethers are also of interest as coolants. The mono- ether of propylene glycol (204) has been added to the FEMA/GRAS list and the monoglyceryl ether (205) is sold as... 

The molecule below is menthol, with the stereochemistry omitted (see Section 4-7). (a) Identify all stereocenters in menthol, (b) How many stereoisomers exist for the menthol structure (c) Draw aU the stereoisomers of menthol, and identify all pairs of enantiomers. 

Lewis acids, results in the formation of isopulegol (43) with greater than 98% diastereoselectivity isopulegol (43), wherein all of the ring substituents are equatorially oriented, arises naturally from a chairlike transition state structure in which the C-3 methyl group, the coordinated C-l aldehyde carbonyl, and the A6,7 double bond are all equatorial (see 48). A low-temperature crystallization raises the chemical and enantiomeric purity of isopulegol (43) close to 100%. Finally, hydrogenation of the double bond in 43 completes the synthesis of (-)-menthol (1). 

In y-alkoxyfuranones the acetal functionality is ideally suited for the introduction of a chiral auxiliary simultaneously high 71-face selectivity may be obtained due to the relatively rigid structure that is present. With ( + )- or (—(-menthol as auxiliaries it is possible to obtain both (5S)- or (5/ )-y-menthyloxy-2(5//)-furanones in an enantiomerically pure form293. When the auxiliary acts as a bulky substituent, as in the case with the 1-menthyloxy group, the addition of enolates occurs trans to the y-alkoxy substituent. The chiral auxiliary is readily removed by hydrolysis and various optically active lactones, protected amino acids and hydroxy acids are accessible in this way294-29s-400. 

In 1990, Choudary [139] reported that titanium-pillared montmorillonites modified with tartrates are very selective solid catalysts for the Sharpless epoxidation, as well as for the oxidation of aromatic sulfides [140], Unfortunately, this research has not been reproduced by other authors. Therefore, a more classical strategy to modify different metal oxides with histidine was used by Moriguchi et al. [141], The catalyst showed a modest e.s. for the solvolysis of activated amino acid esters. Starting from these discoveries, Morihara et al. [142] created in 1993 the so-called molecular footprints on the surface of an Al-doped silica gel using an amino acid derivative as chiral template molecule. After removal of the template, the catalyst showed low but significant e.s. for the hydrolysis of a structurally related anhydride. On the same fines, Cativiela and coworkers [143] treated silica or alumina with diethylaluminum chloride and menthol. The resulting modified material catalyzed Diels-Alder reaction between cyclopentadiene and methacrolein with modest e.s. (30% e.e.). As mentioned in the Introduction, all these catalysts are not yet practically important but rather they demonstrate that amorphous metal oxides can be modified successfully. 

TEMPO has been structurally modified to bring about new selectivities. Highly efficient anionic water-soluble TEME<), oil-in-water nanoemulsion containing TEME for oxidation of alcohols and a waste-free system were developed. Especially, the sterically less crowded azabicyclo-Af-oxyls oxidized /-menthol to Z-menthone with much higher efficiencies than TEME O (equation 23). ... 

Y. Chapleur, B. Castro, and B. Gross, Synth. Comm., 1977, 7, 143 the azide is poorly named and based upon an incorrect structure for (—)-menthol. 

The sweet taste and olfactory responses to a variety of stimuli are examples of chemical senses that utilize protein receptors for initial detection of the stimulus. Most bitter compounds have a hydrophobic component which enables their direct interaction with the cell membrane however, some evidence suggests a protein receptor mechanism. The cooling sensation is treated as a chemesthetic sense, where stimulation takes place at the basal membrane. However, compounds that evoke this response have very specific structural limitations, and most are related to menthol. For purposes of discussion, bitter and cooling sensations will be discussed under generalized receptor mechanisms. 

Cooling, The cooling sensation of menthol-related compounds is different from simple evaporative cooling or cooling from dissolution, as experienced with xylitol, and has a very specific structure-activity relationship. Menthol is the primary cooling agent used in commercial products, for its unique flavor sensation either... 

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... 

Exercise 30-6 Reduction of the ketone group of (—)-menthone, which has its alkyl groups trans to one another, gives two products, known as (—(-menthol and (+)-neomenthol. These two substances differ considerably in their reactions. (+)-Neomenthol undergoes dehydration either in methanoic acid or when treated with phosphorus pentachloride, whereas (—(-menthol gives a methanoate ester with methanoic acid and a chloride with phosphorus pentachloride. What is the relationship between neomenthol and menthol, and why do they behave differently with methanoic acid and phosphorus pentachloride What is the likely structure of the menthene from dehydration of neomenthol (Review Sections 8-8D, 12-3D, and 12-5.)... 

In other systems, a particular structure may be found as a mixture of diastereoisomers. Peppermint (Mentha x piperita Labiatae/Lamiaceae) typically produces (—)-menthol, with smaller amounts of the stereoisomers (+)-neomenthol, (+)-isomenthol, and (+)-neoisomenthol, covering four of the possible eight stereoisomers (Figure 5.16). Oils from various Mentha species also contain significant amounts of ketones, e.g. (—)-menthone, (+)-isomenthone, (—)-piperitone, or (+)-pulegone. The metabolic relationship of... 

Because menthol is the most stable stereoisomer of this constitution, all three of its substituents must be equatorial. We therefore draw the chair form of the preceding structure, which has the hydroxyl group equatorial and up, placing isopropyl and methyl groups so as to preserve the R configuration at C-l. 

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