Menthol esterification

It is thus apparent that at the commencement of vegetation of the peppermint the oil is rich in menthol, hut only a small amount is present in the esterified condition. Menthone only exists in small quantity. As the green parts of the plant develope, the proportion of esterified menthol increases, as has heen found to be the case with other alcohols. This esterification, however, only takes place in the leaves, and when the essential oil extends towards the flowering tops, it becomes poorer in esters. 

These observations throw light on the mechanism which governs the transformation in the plant of the compounds belonging to the menthol group. This alcohol being produced simultaneously with the green parts of the plant, is partially esterified in the leaves the esterification here... 

By this method, for example, the absolute configurations of the following compounds were established (-)-2-phenylbutyric acid,[48] (-)-hydratropic acid,[48] (+)-0-acetyl-mandelic acid,t48] (-)-2-(7/-carbazolyl)propionic acid,t48] (+)-1 -phenylethanol,[48] (-)-menthol,t48] (+)-1 -phenylethylamine,[48] and 1-alanine ethylester.[48] The determination of the absolute configuration of bacteriochlorophylles c, d and e was made possible by the esterification of the phaeophorbides by CDI to imidazolides.[49]... 

Esterification of p-toluenesulfinic acid with (- )-menthol gives a mixture of two diastereomers, which equilibrate to the pure (-)-menthyl (S)-p-toluenesulfinate diastereomer in the presence of hydrochloric acid (80% yield). The report includes an improved procedure for reaction of 1 with CH,MgI to give (R)-( + )-methyl p-tolyl sulfoxide.1... 

Azides [e.g. (+)-neomenthyl azide no physical data reported] are formed efficiently by inversion, from the corresponding alcohols and diphenylphosphoryl azide, in the presence of triphenylphosphine and diethyl azodicarboxylate [which has also been used for esterification with inversion (Vol. 5, p. 334) for a related esterification of (—)-menthol see ref. 119] a conceptually similar synthesis also yields (+)-neomenthyl azide. Cyanoselenenylation of aldehydes and of alcohols has been reported thus treatment of geraniol with o-nitrophenyl seleno-cyanide-Bu sP-THF yields the selenide (19) which can be converted into the... 

In particular, substrates like terpene alcohols are often used with Candida rugosa with very high enantiomeric excesses and at high yields. Lee et al. could increase significantly the maximum reaction velocity of this lipase in AOT-based reverse micelles and obtained conversions up to 70% during the esterification of diterpenes alcohols (geraniol, menthol, citronellol) [130]. 

Hexane Enantioselective esterification of Menthol with several anhydrides [128]... 

Chemical Properties. Hydrogenation of menthols yields / -menthane oxidation with chromic acid or catalytic dehydrogenation yields menthones. Dehydration under mild conditions yields 3-/ -menthene as the main product. Reaction with carboxylic acids or their derivatives yields menthyl esters, which are used mainly as aroma substances and in pharmaceutical preparations and formulations. The esterification of menthols with benzoic acid is used on an industrial scale in the resolution of racemic menthol. 

Occurs in essential oils. It is synthesized by esterification of racemic menthol. Its odor is crisper and less fruity than that of (—)-menthyl acetate. It is used for essential oil compositions and occasionally in household perfumery. 

Fontes et al. (1998b) studied the enantioselectivity of cutinase and found that it was very selective toward one enantiomer with an enantiomeric excess of almost 100%. They found that the enantioselectivity was very sensitive to changes in water content. Bornscheuer et al. (1992) studied hydrolysis, esterification, and transesterification in carbon dioxide to try to find the best method for producing enantiomerically pure substances in carbon dioxide. They found that the thermodynamically favored hydrolysis led to higher enantiomeric excess with less enzyme in the shortest time. Michor et al. (1996b) also examined more than one system to determine a better route to product and found that while the transesterification of -menthol was fast and resulted in high enantiomeric excess, resolution of -citronellol was not feasible. The reaction rate for the reaction of -citronellol was 10-20 times of that of -menthol, but was not selective. 

In the case of lipases and esterases, chiral recognitions are not so strict. Both enantiomers were incorporated to the enzyme to form the substrate-enzyme complex. However, the slow reacting enantiomer lacked the necessary hydrogen-bonding interaction, for example in the hydrolysis of menthol acetate, between the substrate menthol and the enzyme histidine group for the reaction to proceed further (Figure 3(b)).2 3 The explanation was also supported by the observation in the esterification reaction of 1-phenylethanol by lipases.4 Km values of the slow and fast reacting... 

Amino acylations.1 This salt is far more reactive, particularly for O-acylation, than N,N -carbonyldiimidazole. Thus it effects esterification of N-Cbz protected amino acids with even hindered alcohols such as /-menthol in 98% yield without need of a base and, consequently, free from racemization. It also can effect coupling of amino acids in high yields and without racemization. 

Crude i-menthol is, obtained similarly from the strongly levorotatory fractions of the ester. It may be purified by esterification with d-menthoxyacetyl chloride and crystallization of the resulting mixture of esters. The i-alcohol-d-acid ester is then readily purified since it is the less soluble and also the more abundant component. Various other methods for purifying the partially active 1-menthol also may be used if desired. See references in Table III, p. 408). 

A typical procedure is a follows An esterification solution was prepared by dissolving 3.5 g(+)-menthol,0.12 g DCC, 3 mg 4-dimethylaminopyridine (4-DMAP), and 3 mg 4-DMAP-HCI in one mL dry CH2CI2. For the analysis of a product sample, about 0.05mg of the compound in about 10 microliter dichloromethane is mixed well with 10(0.1 esterification solution at ambient temperature for 30 minutes. The final solution was analyzed on a Varian 370 GC with a 25-meter Chirasil-L-Val column at 195°C isothermally. Excellent baseline separations of the diasteromers are usually obtained. A calibration with naproxen of known optical purity is carried out before using this method for analysis. 

Esterification with alcohols in the presence of pyridine was used by Felder et al. [36]. Water produced in the reaction mixture is bound by the addition of N,N -dicyclohexyl-carbodiimide (Scheme 4.8). The acid (ca. 10 mequiv.) is dissolved in 25 ml of alcohol and 4 ml of pyridine and an excess of dicyclohexylcarbodiimide (12 mequiv.) are added (even more if the sample is not dry). The amount of pyridine can also be larger and it then acts as a solvent, e.g., if the alcohol used is solid (menthol). The mixture is then stirred at room temperature only with some higher alcohols or acids must the mixture be heated at 40—80°C for 30—120 min. If a precipitate of N,N -dicyclohexylurea is produced in the reaction, it is allowed to sediment and, after adding an internal standard,... 

Kinetic Resolution by Direct Esterification. This is the least common strategy for kinetic resolution and is most commonly executed on racemic alcohols with carboxylic acids in organic solvents. Reports include several alicyclic secondary alcohols such as menthol and various aliphatic secondary alcohols. Kinetic resolution of a variety of racemic saturated, unsaturated, and a-substituted carboxylic acids has also been effected by direct esterification with various alcohols. ... 

Preparative Methods obtained by reaction of (—)-menthol with p-toluenesulfinyl chloride. This esterification showed no particular stereoselectivity, giving an equal amount of the two sulfinate diastereomers. In order to avoid a chromatographic separation, it is possible to epimerize these sulfinate esters in acidic medium and displace the resulting equilibrium towards the less soluble isomer, (—)-menthyl (5)-p-toluenesulfinate, in 80% yield (eq 1). This procedure was later extended to large scale preparation. ... 

The GC separation of enantiomeric d- and L-amino acids with nonchiral phases requires their conversion to diastereomeric derivatives. The second asymmetric center in the molecule ( ) arises after esterification by optically active alcohols [2-BuOH, 2-AmOH, pinacolol, (-)-menthol, etc.] or NH2 group acylation by chiral reagents e.g., a-methoxy-a-trifiuoromethylphenylacetyl chloride [MTPAC (IV)], A-trifiuoroacetyl-L-prolyl chloride [N-TFA-L-Pro-Cl (V)], A-trifiuoroacetyl-thiazolidine-4-carbonyl chloride (VI), etc. ... 

The best way to prepare large quantities of optically active sulfoxides makes use of optically active menthyl sulfinate. By esterification of p-toluenesulflnic acid with 1-menthol, a mixture of dia-stereoisomeric menthyl sulfinates is obtained. This esterification reaction shows no particular stereoselectivity and therefore a mixture of the two diastereoisomeric esters was obtained. However, it is possible to equilibrate these diastereoisomers in acidic media and to shift the equilibrium towards the... 

Use Menthol and camphor substitute, antifoaming agent, hydraulic fluids and textile soaps, odor masking, esterification agent, pharmaceuticals, wax additive, printing inks. 

Insoluble in water, soluble in most organic solvents made by esterification of menthol and salicyclic acid. 

The esterase EPIO was highly selective for esterification of the L-isomer. Supercritical CO2 was the solvent for the reaction and for the postreaction separation of the acetate from the unreacted D-menthol. 

Yuan Y, Bai S, Sun Y (2006) Comparison of Upase-catalysed enantioselective esterification of (9)-menthol in ionic liquids and organic solvents. Food Chem 97 324-330... 

Diastereoselective [2+2] photocycloaddition of a polymer-supported cyclic chiral enone with ethylene has been reported (Scheme 12.33) [43]. The auxiliary was derived from (-)-8-(p-methoxyphenyl) menthol (87). Protection of the secondary alcohol and demethylation were carried out to give (-)-8-(p-hydroxyphenyl)menthyl acetate (88). An alkyl linker was introduced and finally loaded to poly (ethylene glycol) grafted Wang resin. Deprotection of the alcohol functionality was followed by esterification with cyclohexen-3-one-l-carboxylic acid to provide the chiral enone 89. The photochemical reaction with ethylene was performed by irradiating with light (k > 280 nm). Trifluoroacetic acid (TFA) or aqueous hydrolysis with... 

The first approach to this problem was to attach the chiral auxiliary to the diene by a vinylogous trans-esterification reaction of chiral alcohols with the 3-alkoxy enones (Scheme 21). This reaction was used to construct a variety of chiral dienes including the menthol and phenmenthol dienes (55a) and (55b) by transesterification followed by enol silylation using the Simchen procedure (RsSiOTf taN). However, these dienes exhibit poor diastereofacial selectivity despite the precedent for high stereochemical control in homo Diels-Alder reactions by the use of similar auxiliaries on a,P-unsaturated enones. ... 

The material is prepared by esterification of menthol with lactic acid. 

Menthol [(—)-l] has been used as a chiral ligand for aluminum in Lewis acid catalyzed Diels-Alder reactions with surprising success2 (Section D.l.6.1.1.1.2.2.1). The major part of its application is as a chiral auxiliary, by the formation of esters or ethers. Esters with carboxylic acids may be formed by any convenient esterification technique. Esters with saturated carboxylic acids have been used for the formation of enolates by deprotonation and subsequent addition or alkylation reactions (Sections D.l.1.1.3.1. and D.l.5.2.3.), and with unsaturated acids as chiral dienes or dienophiles in Diels-Alder reactions (Section D. 1.6.1.1.1.), as chiral dipolarophiles in 1,3-dipolar cycloadditions (Section D.l.6.1.2.1.), as chiral partners in /(-lactam formation by [2 + 2] cycloaddition with chlorosulfonyl isocyanate (SectionD.l.6.1.3.), as sources for chiral alkenes in cyclopropanations (Section D.l.6.1.5.). and in the synthesis of chiral allenes (Section B.I.). Several esters have also been prepared by indirect techniques, e.g.,... 

The chiral alcohols are mainly employed as esters or enol ethers. Esters with carboxylic acids can be obtained by any convenient esterification technique. Dienol ethers were obtained by transetherification with the ethyl enol ether of a 1,3-diketone, followed by Wittig reaction8 silyldienol ethers were obtained by the method of Danishefsky11-12 and simple enol ethers by mercury-catalyzed transetherification13. Esters and enol ethers have been used as chiral dienophiles or dienes in diastereoselective Diels-Alder reactions (Section D. 1.6.1.1.1.1.). (R)-l-Phenylethanol [(R)-4] has been used for enantioselective protonation (Section C.) and the (S)-enantiomer as chiral leaving group in phenol ethers for the synthesis of binaphthols (Section B.2.) the phenol ethers are prepared as described for menthol in the preceding section. (S)-2-Octanol [(S)-2] has found applications in the synthesis of chiral allenes (Section B.I.). 

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