2.4.6- Trimethylbenzoate esters

Trimethylbenzoate (Mesitoate) Ester 34. Methyl Carbonate 36. 2,2,2-Trichloroethyl Carbonate 39. Allyl Carbonate... 

Usually, in situ preparation in Barbier-type carbonyl additions are carried out with the bromides or chlorides even sterically blocked carboxylates, such as 2,4,6-trimethylbenzoic acid esters, can be used successfully15. The reactions are accelerated by ultrasound16,17. 

The other mechanism involving acyl cleavage is the AacI mechanism. This is rare, being found only where R is very bulky, so that bimolecular attack is sterically hindered, and only in ionizing solvents. The mechanism has been demonstrated for esters of 2,4,6-trimethylbenzoic acid (mesitoic acid). This acid depresses the freezing point of sulfuric acid four times as much as would be predicted from its molecular weight, which is evidence for the equilibrium... 

Exactly the same considerations apply to the esterification of hindered acids (182) in the reverse direction. It will be noticed that this mechanism requires protonation on the less favoured (cf. p. 240) hydroxyl oxygen atom (185) to allow the formation of the acyl carbocationic intermediate (184). Apart from a number of R3C types, a very well known example is 2,4,6-trimethylbenzoic (mesitoic) acid (186), which will not esterify under ordinary acid-catalysis conditions—and nor will its esters (187) hydrolyse. Dissolving acid or ester in cone. H2S04 and pouring this solution into told alcohol or water, respectively, is. found to effect essentially quantitative esterification or hydrolysis as required the reaction proceeds via the acyl cation (188) ... 

The kinetics of the acid-catalyzed esterification reaction of 2,4,6-trimethylbenzoic acid in i-PrOH under microwave irradiation have been investigated [84], A simple and practical technique for MW-assisted synthesis of esters has been reported wherein the reactions are conducted either on solid mineral supports or by using a phase transfer catalyst (PTC) in the absence of organic solvents [85], The esterification of enols with acetic anhydride and iodine has also been recorded [86],... 

Saponification of esters of 2,4,6-trimethylbenzoic acid with potassium hydroxide complex of dicyclohexyl-1 S-crown-fi0,4... 

Pedersen (1) noted that the sterically hindered esters of 2, 4, 6-trimethylbenzoic acid, although resistant to saponification by KOH in hydroxylic solvents, are saponified by the KOH complex of dicyclohexyl-18-crown-6 in aromatic hydrocarbons. 

The important reactions of protonated acids and esters were deduced many years ago, largely on the basis of the anomalous cryoscopic behaviour of a few compounds. Treffers and Hammett5, while extending the work of Hantzsch4 on cryoscopic measuremnets in concentrated sulphuric acid, found that 2,4,6-trimethylbenzoic acid gives an / -value of 4, twice the usual figure. The only reasonable interpretation of this result was in terms of an ionization, as proposed by Hantzsch to account for the similar behaviour of triphenylcarbinol, viz. 

Trimethylbenzoic acid has two methyl groups ortho to the carboxylic acid functional group. These bulky methyl groups block the approach of the alcohol and prevent esterification from occurring under Fischer esterification conditions. A possible route to the methyl ester ... 

The reaction fails when highly sterically hindered substrates are used. From t-butanol and 1-phenylcyclohexane-l-carboxylic acid or 2,4,6-trimethylbenzoic acid, respectively, only the dianhydrides of the carboxylic acids are obtained. Better yields of the thiolesters are obtained by first reacting the carboxylic acid with 1-hydroxybenzotriazole in the presence of DCC, followed by reaction with the thioalcohol. A number of sugar esters are obtained in a similar manner. The use of DCC in the polycondensation of aliphatic dicar-boxylic acids and diols is also reported. These polyester are biodegradable surface active compounds. ... 

The most remarkable property of cyclic polyethers is their ability to form complexes with metal salts, which are soluble in organic solvents. These complexes show enhanced reactivity. Thus sterically hindered esters of 2,4,6-trimethylbenzoic acid which resist saponification by potassium hydroxide in hydroxylic solvents can be hydrolyzed by the... 

Changes in the steric requirements of the benzoic acid component of the ester did suggest a strong influence on the reactivity the reactions of ethylmagnesium bromide with the ethylesters of benzoic acid, o-methylbenzoic acid, and 2,4,6-trimethylbenzoic acid had relative rates of 1000 30 1. An interesting series studied in the same paper consisted of the... 

If such an equilibrium exists, it can indeed be assumed that reaction occurs only when the proton is on the ethereal oxygen atom. That addition does take place at the ethereal oxygen in certain cases has been shown unequivocally with the methyl ester Of 2,4,6-trimethylbenzoic acid. This compound gives a fivefold freezing point depression in sulfuric acid,2 which can mean only that dissociation has occurred, probably according to the equation ... 

II. Unimolecular Acid-Catalyzed Reactions Involving Acyl-Oxygen Fission. At least one instance is known in which decomposition of the protonated complex does not seem to depend upon the attack of water or an alcohol molecule. It is the formation or hydrolysis of esters of 2,4,6-trimethylbenzoic acid in sulfuric acid solution. Since cryoscopic studies have shown that the acid gives a molar freezing point depression of four (p. 39), and the ester five (p. 225), we must conclude that decomposition of the protonated complex to the acyl carbonium ion 0... 

R —C ) has already occurred. This conclusion is supported by the observations that a freshly prepared solution of methyl 2,4,6-trimethyl-benzoate gave a quantitative yield of 2,4,6-trimethylbenzoic acid on being poured into ice water.11 A similar solution of the acid gave a 78 per cent yield of the ester when poured into methanol.12 The equations are ... 

Esterification. Carboxylic acids are converted into their ethyl esters when heated with an excess of the reagent. Even hindered acids such as 2,4,6-trimethylbenzoic acid are esterified. An acid catalyst usually is not necessary and may be deleterious however, esterification of nicotinic acid and of hippuric acid was accomplished with p-toluenesulfonic acid in dimethylformamide. 

Trimethylbenzoate (Mesitoate) Ester 2,4,6-Me3C6H2C02R (Chart 2) Formation... 

SYNTHESIS OF THE METHYL ESTER OF N-tert-BUTOXYCARBONYL-(Z)-[P-(2,3,7-TRIMETHYLBENZO[6]THIEN-6-YLJDEHYDROAMINOBUTYRIC ACID... 

Esterification. DCC has seen little use for esterification because of variable yields, which are satisfactory only in the case of phenols and thiophenols. Pyridine exerts a favorable effect the more effective acylation catalyst DMAP is more useful. With this catalyst, esters and thioesters can be obtained generally in yields of 60-95 7 . Even the hindered 2,4,6-trimethylbenzoic acid can be converted in this way into the methyl ester in yield. However, the method is subject to steric effects for example, adamantqnecarboxylic acid does not react with r-butyl alcohol under these conditions. 

Posner and colleagues have recently made use of a [3,3]-sigmatropic rearrangement of an a,P-unsaturated sulfoxide as part of a regiospecific conversion of allylic alcohols into two-carbon-extended conjugated dienoate esters [233]. For example, reaction of allyl alcohol (291) with the sulfinyl orthoester (292) and a catalytic amount of 2,46-trimethylbenzoic acid in dichloromethane at 100°C produced ethyl pentadienoate (295) in 75% yield. The reaction is believed to... 

This mechanism is the basis for a useful method of hydrolyzing esters that are very severely sterically hindered, such as esters of 2,4,6-trimethylbenzoic acid. The ester is dissolved in strong sulfuric acid, and then quenched into water. Hydrolysis occurs via the acylium ion. 

Zeolites have been employed to shift the equilibrium in transesterifica-tions by absorbing smaller molecules [57]. For example, the methyl ester of benzoic acid can be converted into the tertiary-butyl ester by refluxing in tertiary-butanol in the presence of zeolite 5A. Selective esterification of sterically hindered carboxylic acids with alkyl chloroformates over silica bound hexaalkylguanidinium chloride achieves high yields [58]. For example, benzyl 2,4,6-trimethylbenzoate was synthesised from the carboxylic acid and benzyl chloroformate in 96% yield at 120°C. 

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