Basicity carboxylate ions

As long as the nucleophilic atom is the same the more basic the nucleophile the more reactive it is An alkoxide ion (RO ) is more basic and more nucleophilic than a carboxylate ion (RC02 )... 

Certain functional groups may be protected from reduction by conversion to anions that resist reduction. Such anions include the alkoxides of allylic and benzylic alcohols, phenoxide ions, mercaptide ions, acetylide ions, ketone carbanions, and carboxylate ions. Except for the carboxylate, phenoxide, and mercaptide ions, these anions are sufficiently basic to be proton-ated by an alcohol, so they are useful for protective purposes only in the... 

None of the other reactions so far discussed involve interaction between a pair of charged species. This is but another instance of the electrostatic effect shown by Kirkwood and Westheimer to be responsible for the disparity between the first and second ionization constants of dibasic acids, for the effect of the carboxylate ion on the basicity of an a-amino acid, and for the difference in reactivity of ionic compounds compared with analogous nonionic species in acid- or base-catalyzed reactions. ... 

Because under basic conditions carboxylic acids are deprotonated to the carboxylate ions, which are no longer electrophilic enough that a weak nucleophile like MeO- can attack them. Upon workup the carboxylate is neutralized to give back the carboxylic acid. 

In HO -catalyzed hydrolysis (specific base catalyzed hydrolysis), the tetrahedral intermediate is formed by the addition of a nucleophilic HO ion (Fig. 3.1, Pathway b). This reaction is irreversible for both esters and amides, since the carboxylate ion formed is deprotonated in basic solution and, hence, is not receptive to attack by the nucleophilic alcohol, phenol, or amine. The reactivity of the carboxylic acid derivative toward a particular nucleophile depends on a) the relative electron-donating or -withdrawing power of the substituents on the carbonyl group, and b) the relative ability of the -OR or -NR R" moiety to act as a leaving group. Thus, electronegative substituents accelerate hydrolysis, and esters are more readily hydrolyzed than amides. 

Figure 10-32 shows one common reagent mixture (the Jones reagent — Cr03/H2S0yacetone). Another common procedure is a two-step reaction where basic potassium permanganate oxidizes the aldehyde to a carboxylate ion and the second step involves the acidification of the product to form the carboxylic acid. 

It was seen in the last section that highly basic groups are not readily displaced from carbonyl compounds and from saturated carbon. An extreme example of ihis is the esterification of an alcohol by a carboxylate ion. This would require... 

There are some very basic concepts in chemistry that have proved to be helpful in rationalizing experimental facts, and which have been taught for perhaps the last 50 years, but which have nevertheless been questioned in the last couple decades or so an example is the role of resonance in stabilizing species like carboxylate ions. Some newer concepts, intriguing but not as traditional, have also been scrutinized and questioned an example is homoaromaticity. 

The carboxylate ion remote from the ammonium group is most basic. The product of protonation is... 

The same mechanism is involved in the basic hydrolysis of an amide and also results in the formation of a water soluble carboxylate ion. The leaving group from an amide is initially charged (i.e. R,N ). However, this is a strong base and reacts with water to form a free amine and a hydroxide ion. 

In the basic hydrolysis of esters and amides, the formation of carboxylate ion is irreversible and so serves to drive the reaction to completion. 

Whereas all the alkylations in Figure 2.31 take place in basic or neutral solutions, carboxylic acids can be directly methylated with diazomethane (Figure 2.32). The actual nucleophile (the carboxylate ion) and the actual methylating agent (H3C—N N) are produced from the reaction partners by proton transfer. 

O The strongly basic hydride ion removes the acidic proton from the carboxylic acid. 

In general, we can easily accomplish nucleophilic acyl substitutions that convert more reactive derivatives to less reactive ones. Thus, an acid chloride is easily converted to an anhydride, ester, or amide. An anhydride is easily converted to an ester or an amide. An ester is easily converted to an amide, but an amide can be hydrolyzed only to the acid or the carboxylate ion (in basic conditions). Figure 21-9 graphically summarizes these conversions. Notice that thionyl chloride (SOCI2) converts an acid to its most reactive derivative, the acid chloride (Section 20-15). 

Basic hydrolysis of esters, called saponification, avoids the equilibrium of the Fischer esterification. Hydroxide ion attacks the carbonyl group to give a tetrahedral intermediate. Expulsion of alkoxide ion gives the acid, and a fast proton transfer gives the carboxylate ion and the alcohol. This strongly exothermic proton transfer drives the saponification to completion. A full mole of base is consumed to deprotonate the acid. 

The overall haloform reaction is summarized next. A methyl ketone reacts with a halogen under strongly basic conditions to give a carboxylate ion and a haloform. 

The last compound s p/ n is very low. This is even less basic than a carboxylate ion. 

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