Esterification, azeotropic

Allyl esters are synthesized by the azeotropic esterification of amino acids with allyl alcohol in the presence of TosOH or by reaction of N -protected amino acid cesium salts with allyl bromide.P °l They are also available from N -protected amino acids by treatment with allyl alcohol/DCC in or with diallyl dicarbonate in THF with DMAP as cat-... 

Of great importance in peptide chemistry are the f-butyl, benzyl and substituted benzyl es-ters. 226 They are more stable to acids than the corresponding urethanes. Benzyl and substituted benzyl esters can be prepared by azeotropic esterification with the respective benzyl alcohol, by activating the carboxy group, e.g. with dicyclohexylcarbodiimide (DCC) or by reacting a carboxylate with a benzyl halide (Scheme 65). The latter 5N2-type ester formation is particularly efficient if cesium carbox-ylates are employed. Under the conditions required for this reaction the racemization of a-chiral car-... 

As has already been detailed for the allyloxycarbonyl (Aloe) moiety, allyl esters also proved to be very versatile and useful carboxy-protecting groups. They can be easily constructed by azeotropic esterification or nucleophilic displacement on allylic halides. For the cleavage of these esters lithium di-methylcuprate can be used. However, a much milder method is found in the Rh -catalyzed isomerization of the allyl moiety to a propenyl ester which immediately hydrolyzes under the reaction conditions (Scheme 67). Even milder is the Pd°-catalyzed allyl transfer to morpholine as an accepting nucleophile. The removal of allyl ester protection has earlier been used in particular in -lactam anti-... 

Continuous removal of the product water by azeotropic distillation after addition of a carrier such as benzene, toluene, xylene, or a halogenated aliphatic solvent leads to rapid esterification ( azeotropic esterification ) and usually also to high yields. The course of the reaction can be followed directly from the amount of water liberated the apparatus used for this purpose (a water separator) is well known. 

Azeotropic esterification, applied to the acid-catalysed reaction, permits a considerable saving in mineral acid. Mineral acids can then be replaced by aliphatic or aromatic sulfonic acids, and decomposition is then reduced. Secondary as well as primary alcohols can be converted into esters by azeotropic esterification, but in general not tertiary alcohols. 

Methyl esters of carboxylic acids cannot be prepared by the usual method of azeotropic esterification. In a process for production of methyl esters, Clinton and Laskowski803 heated a carboxylic acid with methanol for 6-15 h in the presence of methylene dichloride or 1,2-dichloroethane and with sulfuric acid as catalyst, without removing the product water then they separated the organic phase containing the ester, washed it with sodium hydrogen carbonate solution, and worked it up as usual. 

When either or both the acid and the alcohol are volatile, the reaction may be carried to completion by distilling out the water produced in the reaction, usually as an azeotrope. The azeotrope can be water with one of the components of the reaction mixture or with an inert solvent which is insoluble in water. Generally, an azeotrope is selected which has a toiling point below 100 C and which condenses into two phases. The butyl alcohols and their higher homologues form azeotropes with water which behave in this manner, as do the inert solvents btozene, toluene, chloroform, ethylene dichloride, and carton tetrachloride. When methyl, ethyl, or propyl alcohol is used in an azeotropic esterification, one of the inert solvents can be used to produce a two-phase distillate. 

The apparatus used for azeotropic esterification includes a receiver in which the phases separate. The nonaqueous phase automatically returhs to the esterification vessel by an overflow, while the aqueouis phase is with drawn from the bottom of the receiver. 

Novel mixtures of optical isomers of natural and kosher styrallyl alcohol (a-phenylethyl alcohol), and their corresponding acetate esters of styrallyl alcohol (a-phenylethyl acetate) were prepared by multiple fermentation processes and an azeotropic esterification reaction. In the first step, natural acetophenone was produced by bioconversion of cinnamic acid by Pseudomonas sp. (P), Comanonas sp, and Arthrobacter sp. 6). In the first microbial oxidation process, the side chain of cinnamic acid was oxidized to the ketone to form acetophenone that was transiently accumulated in the fermentation broth (P). The current commercial fermentation process yielded >5g/L of acetophenone in the fermentation broth following 2 days of incubation using Arthrobacter sp. The resulting acetophenone was recovered and purified from the fermentation broth by solvent extraction followed by fractional distillation. Acetophenone itself can be used in creating flavor formulations and in enhancement of aroma and taste or both. 

In view of the diversity in the synthesis of pyrethroid ester components it is small wonder, that the final step of formation of the actual insecticidal ester may be accomphshed in many ways. Often, novel methods were needed to make it possible on a larger technical scale. Classical methods like azeotropic esterification of free acid [767] or reaction of acid chloride with simple alcohols, in many cases preferably in the absence of any auxiliary additional reagent or solvent [768], mostly proceeds in a textbook-like manner. 

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