Esters hydrolysis using aqueous base

Example of Ester Hydrolysis Using Aqueous Base... 

Difluoroethanol is prepared by the mercuric oxide cataly2ed hydrolysis of 2-bromo-l,l-difluoroethane with carboxyHc acid esters and alkaH metal hydroxides ia water (27). Its chemical reactions are similar to those of most alcohols. It can be oxidi2ed to difluoroacetic acid [381-73-7] (28) it forms alkoxides with alkaH and alkaline-earth metals (29) with alkoxides of other alcohols it forms mixed ethers such as 2,2-difluoroethyl methyl ether [461-57-4], bp 47°C, or 2,2-difluoroethyl ethyl ether [82907-09-3], bp 66°C (29). 2,2-Difluoroethyl difluoromethyl ether [32778-16-8], made from the alcohol and chlorodifluoromethane ia aqueous base, has been iavestigated as an inhalation anesthetic (30,31) as have several ethers made by addition of the alcohol to various fluoroalkenes (32,33). Methacrylate esters of the alcohol are useful as a sheathing material for polymers ia optical appHcations (34). The alcohol has also been reported to be useful as a working fluid ia heat pumps (35). The alcohol is available ia research quantities for ca 6/g (1992). 

Alkaline nitration with alkoxide bases and nitrate esters was first explored by Endres and Wislicenus who synthesized phenylnitromethane by treating ethyl phenylacetate with potassium ethoxide in ethanol, followed by addition of ethyl nitrate and hydrolysis-decarboxylation of the resulting a-nitroester with aqueous acid. Phenylnitromethane is synthesized in a similar way via alkaline nitration of benzyl cyanide, followed by treatment of the resulting a -nitronitrile with aqueous base. ° Wieland and co-workers used alkali metal alkoxides and nitrate esters for the nitration of cyclic ketones but the yields and purity of product are often poor. ° ... 

It then remains to remove protecting groups and release the product from the support. All of these tasks, except for the removal of the dimethoxytrityl group, are achieved by use of a single deprotection reagent, aqueous base (ammonia). The cyanoethyl groups are lost from the phosphates by base-catalysed elimination, and amide protection of the bases is removed by base-catalysed hydrolysis. The latter process also achieves hydrolysis of the succinate ester link to the support. 

In aqueous solution, protons (actually present as hy-dronium ions) or hydroxide ions are the catalysts most commonly used for nonenzymatic reactions. The way in which acid or base catalysts work in ester hydrolysis is illustrated in Figure 10b and c. As a result of the electronegativity of... 

While esters are much more easily hydrolyzed than amides, traditional saponification suffers from the fact that most esters are not soluble in aqueous base and so the rate of the hydrolysis is limited by the solubility, not by the reactivity. This limitation is overcome by the use of lithium hydroxide in aqueous THF, the reagent of choice for basic hydrolysis of esters. Methyl and ethyl esters are cleaved readily by this combination as most esters are soluble in this solvent mixture. 

Perhaps the oldest example of ester hydrolysis is the process called saponification. It is the hydrolysis of a triglyceride (fat) with an aqueous base such as sodium hydroxide (NaOH). During the process, glycerol, also commercially named glycerin, is formed, and the fatty acids react with the base, converting them to salts. These salts are called soaps, commonly used in households. 

Esters, as has already been seen, are formed by the combination of alcohols and acids with the elimination of water. The reverse reaction, which is one of hydrolysis, can also occur under certain conditions, such as the presence of acid or alkali in an aqueous base. Not all esters are equally susceptible to this type of breakdown, but it only requires the formation of traces of a free acid such as butyric acid, totally to spoil a compound. Even an acetate such as linalyl acetate can cause problems by giving rise to free acetic acid. In alkaline media progressive breakdown of the ester may occur as the acid becomes neutralized. In products where this is likely to be a problem terpinyl acetate is often used to replace linalyl acetate. 

Base-catalysed hydrolysis using alkali metal hydroxides or carbonates in aqueous methanol or THF remains the commonest method for cleaving simple esters limited mainly by the stability of the substrate to the basic conditions. In more complex substrates, lithium hydroxide in a mixture of THF-methanol-P O (2 2 1) is the base of choice.1-3 In a synthesis of Lepicidin A, Evans and Black4 accomplished the hydrolysis of a methyl ester with lithium hydroxide in aqueous /err-butyl alcohol at 35 °C [Scheme 6.1). Destannylation that accompanied hydrolysis with other solvents was not observed nor was harm inflicted on the TIPS and TES ethers. In a synthesis of cydoisodityrosine derivatives, Boger and co-workers attempted to hydrolyse methyl ester 2 1 [Scheme 6.2] with 1-3 equivalents of lithium hydroxide in a mixture of THF-methanol-HaO (3 1 1) at room temperature, but the desired hydrolysis was accompanied by scission of the tripeptide side chain from the ring system. However, when the reaction was conducted in the presence of the more nucleophilic lithium hydroperoxide, the desired hydrolysis was achieved in 97% yield without racemisation. 

When treated with concentrated alkali, acetoacetic ester is converted into two moles of sodium acetate, (a) Outline all steps in a likely mechanism for this reaction. (Hint See Sec. 21.11 and Problem 5.8, p. 170.) (b) Substituted acetoacetic esters also undergo this reaction. Outline the steps in a general synthetic route from acetoacetic ester to carboxylic acids, (c) Outline the steps in the synthesis of 2-hexanone via acetoacetic ester. What acids will be formed as by-products Outline a procedure for purification of the desired ketone. (Remember that the alkylation is carried out in alcohol that NaBr is formed that aqueous base is used for hydrolysis and that ethyl alcohol is a product of the hydrolysis.)... 

Polymer-supported equivalents of the widely used organic base 4-(dimethylamino)pyridine (DMAP) were soon developed, but many of their reported applications are as a stoichiometric base. Resin 37 (Scheme 10.10), containing a polyethylene imine) matrix was the first supported system to be prepared. Those materials were more efficient catalysts than DMAP itself, under the same conditions, for the hydrolysis of p-riilropheriyl esters in aqueous solution [175, 176],... 

Hydrolysis of esters may also be carried out with hot aqueous base, such as aqueous NaOH. Hydrolysis of esters in aqueous base is often called saponification, a reference to the use of this reaction in the manufacture of soaps (Section 19.2A). Each mole of ester hydrolyzed requires 1 mole of base, as shown in the following balanced equation ... 

Qaisen condensations, like the aldol reaction, require a base. Aqueous bases, such as NaOH, however, carmot be used in Claisen condensations because they would bring about hydrolysis of the ester (saponification. Section 14.3C) instead. Rather, the bases most commonly used in Claisen condensations are nonaqueous bases, such as sodium ethoxide in ethanol and sodium methoxide in methanol. Furthermore, to prevent transesterification (Section 14.4C), the alkyl group (—R) of the base should match the R group in the alkoxyl portion (— OR) of the ester. 

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