Ester hydrolysis base-promote

Esters undergo base-promoted hydrolysis as well as acid hydrolysis. 

Acid-Catalyzed Hydrolysis. In acid-catalyzed ester hydrolysis the species that undergoes the rate-determining step is the protonated ester (Fig. 13.10). When the molecule is in this protonated form, the enhanced depletion of electrons near the central carbon promotes the approach of an electron-rich oxygen of a water molecule. Hence, the hydrolysis rate depends on the fraction of compound molecules that are protonated. This fraction, in turn, depends on how strong a base the ester function is. If we define an acidity constant (see Chapter 8) for the protonated species... 

The reaction typically gives 60% to 70% of the maximum yield. The reaction is a reversible process. An ester reacting with water, giving the carboxylic acid and alcohol, is called hydrolysis it is acid catalyzed. The base-promoted decomposition of esters yields an alcohol and a salt of the carboxylic acid this process is called saponification. 

Saponification is the base-promoted hydrolysis of the ester linkages in fats and oils (review Section 21-7B). One of the products is soap, and the word saponification is derived from the Latin word saponis, meaning soap. Saponification was discovered before 500 b.c., when people found that a curdy material resulted when animal fat was heated with wood ashes. Alkaline substances in the ashes promote hydrolysis of the ester linkages of the fat. Soap is currently made by boiling animal fat or vegetable oil with a solution of sodium hydroxide. The following reaction shows formation of soap from tristearin, a component of beef fat. 

Base-promoted hydrolysis of an ester. Originally used to describe the hydrolysis of fats to make soap. (p. 1206)... 

For GC analysis, the salts of the lowest molecular weight acids present in ozonation products subjected to base-promoted hydrolysis have been converted to their benzyl esters by reaction with benzyl bromide (Bonnet et al. 1989). The salts of all acids produced have commonly been converted to the free acids, usually with the aid of a cation exchange resin. The acids have then been converted to methyl esters by reaction with diazomethane (Bonnet et al. 1989) or, more often, have been converted to trimethylsilyl (TMS) esters (Matsumoto et al. 1986, Taneda et al. 1989, Habu et al. 1990). Trimethylsilylation has the major advantage that alcoholic and phenolic hydroxyl groups are simultaneously converted to TMS ethers, thus greatly facilitating GC analysis. 

Q I Mechanism 22.9 Base-Promoted Hydrolysis of an Ester to a Carboxylic Acid... 

Hydrolysis is base promoted, not base catalyzed, because the base ( OH) is the nucleophile that adds to the ester and forms part of the product. It participates in the reaction and is not regenerated later. 

Base promotes hydrolysis of esters by providing the strongly nucleophilic reagent OH. This reaction is essentially irreversible, since a resonance-stabilized... 

An acid promoted hydrolysis is usually slower than a similar base promoted hydrolysis. In some cases, as with a z-butyl ester, however, acid catalyzed hydrolyses are preferred. With the Z-butyl ester, sometimes a reducing agent such as formic acid or triethylsilane is added to scavenge the carbocation. 

Differential Solvation of Reactants and Transition States. It should always be kept in mind that solvent effects can modify the energy of both the reactants and the transition state. It is the difference in the solvation that is the basis for changes in activation energies and reaction rates. Thus, although it is common to discuss solvent effects solely in terms of reactant solvation or transition state solvation, this is an oversimplification. A case that illustrates this point is the base-promoted hydrolysis of esters by hydroxide ion. 

Taft proposed a substituent constant, polar effect of alkyl substituents in aliphatic systems. This method is based on the assumption that resonance is unimportant in aliphatic systems and that steric effects are the same for ester hydrolysis whether in acid or base, so only the polar effect of the substituent is different under the two reaction conditions. The value of a for a substituent, R, was based on the rate constants for acid-catalyzed and base-promoted hydrolysis of the ester RCO2R relative to those for CH3CO2R. A factor of 2.48 was used to relate cr values to the Hammett cr values. Thus,... 

For a detailed discussion of the kinetics of the base-promoted hydrolysis of esters, see Johnson, S. L. Adv. Phys. Org. Chem. 1967, 5, 237. 

Base-promoted hydrolysis is called saponification, from the Latin word sapo, for soap (see Section 23.2C). Refluxing an ester with aqueous sodium hydroxide, for example, produces an alcohol and the sodium salt of the acid ... 

The carboxylate ion is very unreactive toward nucleophilic substitution because it is negatively charged. Base-promoted hydrolysis of an ester, as a result, is an essentially irreversible reaction. 

The mechanism for base-promoted hydrolysis of an ester also involves a nucleophilic addition—elimination at the acyl carbon. 

The alkoxyl group of the ester and the alkoxide must be the same so as to avoid transesterification (which occurs with alkoxides by the same mechanism as base-promoted ester hydrolysis Section 17.7B). Ethyl esters and methyl esters, as it turns out, are the most common ester reactants in these types of syntheses. Therefore, we use sodium ethoxide when... 

Acid-Catalyzed Esterification 790 Base-Promoted Hydrolysis of an Ester 793 DCC-Promoted Amide Synthesis 798 Acidic Hydrolysis of an Amide 799 Basic Hydrolysis of an Amide 799 Acidic Hydrolysis of a Nitrile 801 Basic Hydrolysis of a Nitrile 801... 

At the molecular level, saponification corresponds to base-promoted hydrolysis of the ester groups in triglycerides (Section 14.3C). The resulting soaps contain mainly the sodium salts of palmitic, stearic, and oleic acids from tallow and the sodium salts of lauric and myristic... 

Another FGI that gives carboxylic acid products is the hydrolysis of carboxylic acid derivatives, such as esters and nitriles. Such hydrolysis reactions can either be acid catalyzed (H3O+) or base promoted (1. NaOH, H2O 2. H3O ) and involve an acyl substitution mechanism (addition-elimination) that replaces any acyl leaving group with a hydroxyl group. The synthesis of carboxylic acids via nitriles is especially noteworthy since the introduction of the cyano group via Sn2 with CN involves the formation of a new C-C bond (adds one new carbon to the alkyl halide carbon chain). 

The mechanism involves a Michael reaction followed by a Dieckmann reaction (intramolecular Claisen), all base promoted. Loss of the ester group begins with an add-catalyzed hydrolysis, followed by decarboxylation of the resulting carboxylic acid. Finally, a Robinson annulation with methyl vinyl ketone affords the final product. 

---