Carboxylic acid esters basic hydrolysis mechanism

The first term, representing acid-"catalyzed" hydrolysis, is important in reactions of carboxylic acid esters but is relatively unimportant in loss of phosphate triesters and is totally absent for the halogenated alkanes and alkenes. Alkaline hydrolysis, the mechanism indicated by the third term in Equation (2), dominates degradation of pentachloroethane and 1,1,2,2-tetrachloroethane, even at pH 7. Carbon tetrachloride, TCA, 2,2-dichloropropane, and other "gem" haloalkanes hydrolyze only by the neutral mechanism (Fells and Molewyn-Hughes, 1958 Molewyn-Hughes, 1953). Monohaloalkanes show alkaline hydrolysis only in basic solutions as concentrated as 0.01-1.0 molar OH- (Mabey and Mill, 1978). In fact, the terms in Equation(2) can be even more complex both elimination and substitution pathways can operate, leading to different products, and a true unimolecular process can result from initial bond breaking in the reactant molecule. 

The basic hydrolysis mechanism (shown next for a primary amide) is similar to that for hydrolysis of an ester. Hydroxide attacks the carbonyl to give a tetrahedral intermediate. Expulsion of an amide ion gives a carboxylic acid, which is quickly deproto-nated to give the salt of the acid and ammonia. 

The familiar substitution reactions of derivatives of carboxylic acids with basic reagents illustrate nucleophihc substitution at aliphatic sp carbons. (Substitution reactions of carboxylic acids, and their derivatives, with acidic reagents are covered in Chapter 4.) The mechanisms of these reactions involve two steps (1) addition of the nucleophile to the carbonyl group and (2) elimination of some other group attached to that carbon. Common examples include the basic hydrolysis and aminolysis of acid chlorides, anhydrides, esters, and amides. 

Basic hydrolysis has been carried out on carboxylic esters labeled with O in the carbonyl group. If this reaction proceeded by the normal Sn2 mechanism, all the 0 would remain in the carbonyl group, even if, in an equilibrium process, some of the carboxylic acid formed went back to the starting material ... 

Quite a few substitution reactions of heteroatom nucleophiles at the carboxyl carbon as well as their mechanisms are discussed in introductory organic chemistry courses. The left and the center columns of Table 6.3 summarize these reactions. Accordingly, we will save ourselves a detailed repetition of all these reactions and only consider ester hydrolysis once more. Section 6.4.1 will not only revisit the acidic and basic ester hydrolysis but will go into much more detail. Beyond that, SN reactions of this type will only be discussed using representative examples, namely ... 

It is more common to hydrolyze esters under basic conditions because the equilibrium is favorable. The mechanism for this process, called saponification, is presented in Figure 19.4. The production of the conjugate base of the carboxylic acid, the car-boxylate anion, which is at the bottom of the reactivity scale, drives the equilibrium in the desired direction. To isolate the carboxylic acid the solution must be acidified after the hydrolysis is complete. Some examples are provided in the following equations. We saw another example of this hydrolysis reaction in Chapter 10, where it was... 

Problem-Solving Strategy Proposing Reaction Mechanisms 1007 Mechanism 21-8 Transesterification 1008 21-7 Hydrolysis of Carboxylic Acid Derivatives 1009 Mechanism 21-9 Saponification of an Ester 1010 Mechanism 21-10 Basic Hydrolysis of an Amide 1012 Mechanism 21-11 Acidic Hydrolysis of an Amide 1012 Mechanism 21-12 Base-Catalyzed Hydrolysis of a Nitrile 1014 21-8 Reduction of Acid Derivatives 1014... 

Amides undergo hydrolysis to yield carboxylic acids plus amine on heating in either aqueous acid or aqueous base. The conditions required for amide hydrolysis are more severe than those required for the hydrolysis of acid chlorides or esters, but the mechanisms are similar. The acidic hydrolysis reaction occurs by nucleophilic addition of water to the protonated amide, followed by loss of ammonia. The basic hydrolysis occurs by nucleophilic addition of OH" to the amide carbonyl group, followed by deproto nation of the -OH group and elimination of amide ion NH2). 

Under basic conditions, the hydroxide ion acts as the nucleophile. For example, the mechanism of hydrolysis of ethyl acetate is shown (in fig.K). However, the mechanism does not stop here. The carboxylic acid which is formed reacts with sodium hydroxide to form a water soluble carboxylate ion [Fig.L (a)]. Moreover, the ethoxide ion that is lost from the molecule is a stronger base than water and undergoes protonation [Fig.L (b)]. The basic hydrolysis of an ester is also called saponification and produces a water soluble carboxylate... 

In base the tetrahedral intermediate is formed in a manner analogous to that proposed for ester saponification. Steps 1 and 2 in Mechanism 19.7 show the formation of the tetrahedral intermediate in the basic hydrolysis of amides. In step 3 the basic amino group of the tetrahedral intermediate abstracts a proton from water, and in step 4 the derived ammonium ion dissociates. Conversion of the carboxylic acid to its corresponding carboxylate anion in step 5 completes the process and renders the overall reaction irreversible. 

Section 19.10 Ester hydrolysis in basic solution is called saponification and proceeds through the same tetrahedral intermediate (Mechanism 19.4) as in acid-catalyzed hydrolysis. Unlike acid-catalyzed hydrolysis, saponification is irreversible because the carboxylic acid is deprotonated under the reaction conditions. 

Esters are less reactive than acid chlorides and anhydrides in addition reactions, but more reactive than amides. Esters can be converted into their parent carboxylic acids under either basic or acidic aqueous conditions in a process called, logically enough, ester hydrolysis. In base, the mechanism is the familiar addition-elimination one (Fig. 18.31). Hydroxide ion attacks the carbonyl group to form a tetrahedral intermediate. Loss of alkoxide then gives the acid, which is rapidly deproto-nated to the carboxylate anion in basic solution. Notice that this reaction, saponification (p. 862), is not catalytic. The hydroxide ion used up in the reaction is not regenerated at the end. To get the carboxylic acid itself, a final acidification step is necessary. 

Buffer catalysis of the hydrolysis of phenyl (311 R = Ph) and methyl (311 R = Me) benzenesulfinates to give the sulfinic acid (312) and alcohol ROH is strongly accelerated by both carboxylate and amine components of the buffer which give Bronsted /i values of approximately unity on separate lines. The carboxylates are about 44 tunes more effective than amines of similar basicity. A concerted. S n2 mechanism with a hypervalent intermediate (313) is proposed for the nucleophilic reaction of these esters.286 The reaction of the thiosulfinate esters (314) with sulfenyl chlorides RSCI and sulfenate esters (315) to give sulfinyl chlorides and disulfides and sulfinate esters and disulfides, respectively, has been studied.287 Hydrolysis of 2-(3-aminophenyl)sulfonyl-ethanol hydrogensulfate gives under different conditions various products such as the ether (316) and the sulfone (317).288... 

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