Carboxylic acids carboxylate anions

This difference in behavior for acetic acid in pure water versus water buffered at pH = 7 0 has some important practical consequences Biochemists usually do not talk about acetic acid (or lactic acid or salicylic acid etc) They talk about acetate (and lac tate and salicylate) Why Its because biochemists are concerned with carboxylic acids as they exist in di lute aqueous solution at what is called biological pH Biological fluids are naturally buffered The pH of blood for example is maintained at 7 2 and at this pH carboxylic acids are almost entirely converted to their carboxylate anions... 

Carboxylic acids are weak acids and m the absence of electron attracting substituents have s of approximately 5 Carboxylic acids are much stronger acids than alcohols because of the electron withdrawing power of the carbonyl group (inductive effect) and its ability to delocalize negative charge m the carboxylate anion (resonance effect)... 

The negatively charged oxygen substituent is a powerful electron donor to the carbonyl group Resonance m carboxylate anions is more effective than resonance m carboxylic acids acyl chlorides anhydrides thioesters esters and amides... 

This IS because carboxylic acids are converted to their corresponding carboxylate anions which are stable under the reaction conditions... 

In base the tetrahedral intermediate is formed m a manner analogous to that pro posed for ester saponification Steps 1 and 2 m Figure 20 8 show the formation of the tetrahedral intermediate m the basic hydrolysis of amides In step 3 the basic ammo group of the tetrahedral intermediate abstracts a proton from water and m step 4 the derived ammonium ion dissociates Conversion of the carboxylic acid to its corresponding carboxylate anion m step 5 completes the process and renders the overall reaction irreversible... 

Section 20 17 Like ester hydrolysis amide hydrolysis can be achieved m either aque ous acid or aqueous base The process is irreversible m both media In base the carboxylic acid is converted to the carboxylate anion m acid the amine is protonated to an ammonium ion... 

The carbon-carbon bond forming potential inherent m the Claisen and Dieckmann reac tions has been extensively exploited m organic synthesis Subsequent transformations of the p keto ester products permit the synthesis of other functional groups One of these transformations converts p keto esters to ketones it is based on the fact that p keto acids (not esters ) undergo decarboxylation readily (Section 19 17) Indeed p keto acids and their corresponding carboxylate anions as well lose carbon dioxide so easily that they tend to decarboxylate under the conditions of their formation... 

In most biochemical reactions the pH of the medium is close to 7 At this pH car boxylic acids are nearly completely converted to their conjugate bases Thus it is common practice m biological chemistry to specify the derived carboxylate anion rather than the carboxylic acid itself For example we say that glycolysis leads to lactate by way of pyruvate... 

The actual process of solid phase peptide synthesis outlined m Figure 27 15 begins with the attachment of the C terminal ammo acid to the chloromethylated polymer m step 1 Nucleophilic substitution by the carboxylate anion of an N Boc protected C terminal... 

Step 1 The Boc protected amino acid is anchored to the resin Nucleophilic substitution of the benzylic chloride by the carboxylate anion gives an ester... 

Metal carboxyiates have been considered as nucleophilic agents capable of removing aHyUc chlorine and thereby affording stabilization (143). Typical PVC stabilizers, eg, tin, lead, or cadmium esters, actually promote the degradation of VDC polymers. The metal cations in these compounds are much too acidic to be used with VDC polymers. An effective carboxylate stabilizer must contain a metal cation sufftcientiy acidic to interact with aHyUc chlorine and to facihtate its displacement by the carboxylate anion, but at the same time not acidic enough to strip chlorine from the polymer main chain (144). 

Another example of the effect of resonance is in the relative acidity of carboxylic acids as compared to alcohols. Carboxylic acids derived from saturated hydrocarbons have ipK values near 5, whereas saturated alcohols have pA values in the range 16-18. This implies that the carboxylate anion can accept negative charge more readily than an oxygen on a saturated carbon chain. This can be explained in terms of stabilization of the negative charge by resonance, ... 

In the case of esters, carboxylate anions, amides, and acid chlorides, the tetrahedral adduct may undergo elimination. The elimination forms a ketone, permitting a second addition step to occur. The rate at which breakdown of the tetrahedral adduct occurs is a function of the reactivity of the heteroatom substituent as a leaving group. The order of stability of the... 

The easy liberation of trifluoroethanol from 2,2,2-tnfluoroethyl hydrogen 3,6-di methylphthalate can be accounted for by nng closure to form 3,6 dimethylphthalic anhydride [57] (equation 56) The carboxylate anion is the intermediate needed for nng closure because the rate increases as the pH, while still acidic, increases... 

While carboxylate anions do not add to the imonium function of ketone derived enamines, such as morpholinocyclohexene, when these are combined with carboxylic acids (38), the addition of thiophenol or benzyl mercaptan leads to a-aminothioethers (509,510). 

Finally a proton transfer leads to formation of carboxylate anion 3. Of particular interest is the benzilic acid rearrangement of cyclic diketones such as 4, since it... 

Like other Bronsted-Lowry acids discussed in Section 2.7, carboxylic acids dissociate slightly in dilute aqueous solution to give H30+ and the corresponding carboxylate anions, RC02. The extent of dissociation is given by an acidity constant, Ka. 

Because the dissociation of a carboxylic acid is an equilibrium process, any factor that stabilizes the carboxylate anion relative to undissociated carboxylic acid will drive the equilibrium toward increased dissociation and result in increased acidity. An electron-withdrawing chlorine atom, for instance, makes chloroacetic acid (Ka = 1.4 x 10-3) approximately 80 times as strong as acetic acid introduction of two chlorines makes dichloroacetic acid 3000 times as strong as acetic acid, and introduction of three chlorines makes trichloroacetic acid more than 12,000 times as strong. 

Perhaps the most useful reaction of carboxylic acids is their conversion into esters. There are many methods for accomplishing the transformation, including the S -2 reaction of a carboxylate anion with a primary alkyl halide that we saw in Section 11.3. 

Conversion of Acid Halides into Anhydrides Nucleophilic acyl substitution reaction of an acid chloride with a carboxylate anion gives an acid anhydride. Both symmetrical and unsymmetrical acid anhydrides can be prepared in this way. 

We saw in Sections 20.3 and 24.5 that a carboxyl group is deprotonated and exists as the carboxylate anion at a physiological pH of 7.3, while an amino group is protonated and exists as the ammonium cation. Thus, amino acids exist in aqueous solution primarily in the form of a dipolar ion, or zwitterion (German zwitter, meaning "hybrid"). 

Step 2 of Figure 29.11 Decarboxylation The TPP addition product, which contains an iminium ion j8 to a carboxylate anion, undergoes decarboxylation in much the same way that a jB-keto acid decarboxylates in the acetoacetic ester synthesis (Section 22.7). The C=N+ bond of the pyruvate addition product acts... 

Examples of polyfunctional carboxylic acids esterified by this method are shown in Table I. Yields are uniformly high, with the exception of those cases (maleic and fumaric acids) where some of the product appears to be lost during work-up as a result of water solubility. Even with carboxylic acids containing a second functional group (e.g., amide, nitrile) which can readily react with the oxonium salt, the more nucleophilic carboxylate anion is preferentially alkylated. The examples described in detail above illustrate the esterification of an acid containing a labile acetoxy group, which would not survive other procedures such as the traditional Fischer esterification. 

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