1-Menthyl esters

It will be noted that the experiments with sodium nitrate confii m the results of Charabot and Hubert, both as regards the increase in menthyl esters and the decrease in menthone in the essential oil. 

Standnikow has prepared several of the esters of menthol by heating magnesium iodo-mentholate with the esters of ethyl alcohol. For example, with ethyl acetate, propionate, and benzoate the corresponding menthyl esters were obtained. These bodies have the following boiling-points —... 

Preparation of enantiomerically pure sulfmate esters has most often been accomplished by making menthyl esters of arenesulfinic acids, particularly of p-toluenesulfinic acid. This... 

The preparation of enantiomerically enriched a-ketosulphoxides 272 was also based on a kinetic resolution involving the reaction of the carbanion 273 derived from racemic aryl methyl sulphoxides with a deficiency of optically active carboxylic esters 274334, (equation 151). The degree of stereoselectivity in this reaction is strongly dependent on the nature of both the group R and the chiral residue R in 274. Thus, the a-ketosulphoxide formed in the reaction with menthyl esters had an optical yield of 1.3% for R = Et. In the... 

Hydrostannation of chiral menthyl esters of substituted acrylic acids proceeds stereoselectiveiy, providing a route to optically active alkyl-... 

Although menthyl esters, especially 19, are most often used to prepare sulfoxides, esters derived from optically active alcohols other than menthol have been prepared . Ridley and Smal prepared arenesulfmic esters of 1,2 5,6-di-O-cyclohexylidene-a-D-glucofuranose. Unfortunately, these diastereomers were oils, except for the mesityl derivative, with the major epimer having configuration R at sulfur and so they offered no advantage over the menthyl esters. Separation of the epimers by chromatography failed. 

Compound (+ )-(53) has been made from one of the diastereomers of the (—)-menthyl ester of 3-(p-anisylmethyl-l-naphthylstannyl)propionic acid, (54) ([a]p°° — 24) which could be obtained from the mixture of diastereomers because it is much less soluble in -pentane at low temperature than the other one. Their separation could be followed by NMR, both diastereomers differing by the position of their methoxy signal. The pure less soluble diastereomer (54) reacts with methylmagnesium iodide to give a tetraorganotin compound containing only one chiral center, the asymmetric tin atom 36> 87>. 

Asymmetric synthesis of 2,5-dimethyl-2,4-hexadiene (28) and /-menthyl diazoacetate (29) with chiral copper complexes (30) was successfully conducted by Aratani et al. [13] to afford the (1 A)-chrysanthem ic acid /-menthyl ester (31) in high optical and chemical yield. Since this finding, a lot of chiral copper complexes have been reported and applied to the asymmetric synthesis of (IR)-chrysanthemate. However, these copper complexes required more than 1 mol% of the catalyst and the cis/trans ratio still remains unsatisfactory. Moreover, /-menthyl ester was crucial for the high enantioselectivity. Given an industrial production of... 

This sequence was obviously not amenable to a synthesis of optically active a-allokainic acid given the fact that an aminomalonate group was necessary. After unfruitful assays with menthyl esters, the Swiss group was rewarded by the discovery that the phenylmenthyl group (180) brings sufficient asymmetry to the reaction intermediate to afford products with a high percentage of favorable diastereoisomer (Scheme 35) (181). 

Aratani et al. (21) subsequently found that the use of chiral menthyl diazoacetate esters led to higher trans/cis ratios and improved facial selectivity. A number of bulky diazoesters provided high enantioselectivity in the cyclopropanation reaction, but trans selectivity was highest with /-menthyl esters, Eq. 6. It seems clear from these and subsequent studies that the menthyl group is used because of its bulk and ready availability. The chirality present in the ester has a negligible effect on facial selectivity in the cyclopropanation reaction. Slow addition of diazoester is required (7 h at ambient temperature) for high yields presumably to suppress the formation of fumarate byproducts. 

Menthyl chloroformate, chiral derivatizing reagent, 6 76t Menthyl esters, 24 524 Menthyl pyrrolidone carboxylate, 24 525 Menthyl salicylate, 24 524 physical properties of, 22 14t Menthyl valerate, 24 524 Mentoring, of technical service personnel, 24 346-347... 

The kinetic resolution using a chiral zirconocene-imido complex 286 took place with high enantioselectivity to result in chiral allenes 287 (up to 98% ee) (Scheme 4.74) [116]. However, a potential drawback of these methods is irreversible consumption of half of the allene even if complete recovery of the desired enantiomer is possible. Dynamic kinetic resolutions avoid this disadvantage in the enantiomer-differentiating reactions. Node et al. transformed a di-(-)-L-menthyl ester of racemic allene-l,3-dicarboxylate [(S)- and (RJ-288] to the corresponding chiral allene dicarbox-ylate (R)-288 by an epimerization-crystallization method with the assistance of a catalytic amount of Et3N (Scheme 4.75) [117]. 

The appropriate alkyl 2-bromomethylpropenoate (l mol) TEBA-Cl (2.3 g, 10 mmol), and /-BuO,H (90%, 110 g, l.l mol) in CH2Cl2 (150 ml) are stirred at -10°C. Powdered KOH (56 mg, l. I mol) is added portionwise such that the reaction temperature does not exceed -5°C. On complete addition of the hydroxide, the mixture is stirred at -5°C for 30 min and then allowed to come to room temperature and stirred for a further I h. The mixture is filtered and evaporated under reduced pressure. n-C,H12 (200 mi) is added to the residue and the organic solution is filtered, washed with H20 (100 ml), dried (MgS04), and evaporated to yield the peroxide (ethyl ester, 92% menthyl ester, 85% /-butyl ester, 45%). 

Even more complex potential prodrugs of indomethacin were examined, namely its limonenyl, perillyl, bomyl, and menthyl esters, i. e., terpenoid derivatives [21]. These highly lipophilic esters showed rapid enzymatic hydrolysis, and the limonenyl prodrug assayed in humans had an interesting delayed and sustained cutaneous anti-inflammatory activity. 

In 1958 Herbrandson and Cusano (103) prepared menthyl esters of p-iodobenzenesulfinic acid 62. Darwish and McLearen (104) described the synthesis and separation of diastereomeric esters 63 from optically active a-methylbenzyl alchols. Similarly, methane-sulfinyl chloride 64 was found to react with cholesterol to give a... 

In extension of this work, the synthesis of enantiomeric and diastereomeric sulfinimidamides was also described. Treatment of the diastereomerically pure menthyl ester 90 with the lithium salt of AT-methylaniline was found to give the corresponding sulfinimidamide... 

Andersen (75,76), as well as Mislow (221), discovered that the ORD curves of alkyl aryl sulfoxides show a strong Cotton effect in the region below 250 nm. An extensive study by Mislow and his coworkers (47) led to the following empirical rules, correlating the sign of the Cotton effect with the absolute configurations of chiral dialkyl, alkyl aryl, and diaryl sulfoxides, as well as menthyl esters of aromatic sulfinic acids ... 

Mandelic acid with a 13 - 20 % enantiomeric excess of the (R)-isomer has been obtained from reduction of phenylglycolic acid in aqueous alcohol buffers containing strychnine in low concentration. The optical yield depends upon pH and is highest (20 - 24 %) at pH 0 or 9.2 and at low current density. In the pH range 2-4, the optical yield drops to 2-8% [42]. The higher result compares well with the maximum value of 20% excess R-isomer found from reduction of (-)-menthyl phenylglycolate in aqueous buffers where the (-)-menthyl ester is the only chiral reagent present [43 ]. 

Similarly, 291, which has a homochiral menthyl ester group (R), gave the cycloadducts 292 and 293 (181). 

The most commonly applied ot,p-unsaturated ester auxiliary is the menthol group. It is inexpensive and easy to handle. Several different menthyl 2-alkenoates (157), in particular acrylates, have been applied in 1,3-dipolar cycloaddition reactions (Scheme 12.51). The major drawback of the menthyl ester auxiliary in 1,3-dipolar cycloadditions are the poor selectivities often associated with these reactions, except for reactions with azomethine ylides. 

The (17 )-menthyl ester of mandelic acid 8 has been deprotonated to form the enediolate 9 which was preferentially alkylated to give the (7 )-product 10 in 32% yield and with 50% diastereoselectivity116. 

The chemically induced asymmetric photocyclization of the l-(—)-menthyl ester shows a striking temperature dependence 76), a completely reversed ratio is obtained at low temperature. When the chiral group is placed at C(ll) of the benzo[c]phen-anthryl group (77) the effect is of the same order (about 5 % diastereomeric excess) as when the same group is placed at the paraposition of the phenyl group, or when... 

Optically pure (M)-(—)-2-formylhexahelicene (76, R = 2-formyl), prepared from the corresponding resolved (—)-carboxy-menthyl ester, was used as a common precursor for the photochemical synthesis of optically pure (M)-[8]-, (M)-[9]-, (M)-... 

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. 

Menthol from Dementholized Cornmint Oil. Dementholized cornmint oil, from which (-)-menthol has been removed by crystallization and which still contains 40-50% free menthol, can be reused for producing (-)-menthol. The fairly large quantity of (-)-menthone in the oil (30-50%) is hydrogenated to form a mixture of mainly (-)-menthol and (+)-neomenthol the (-)-menthyl esters present (chiefly (-)-menthyl acetate) are saponified. Additional (—)-menthol is then separated from other components by crystallization, distillation, or via the boric acid esters. 

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