Carboxylate anion, basicity

Esters are hydrolyzed in aqueous base to form carboxylate anions. Basic hydrolysis of an ester is called saponification. 

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... 

Since the inception of our work Jere, Miller and Jackson have published kinetic and stereochemical data on the hydrogenation of alanine (19). Important in their analysis is the observation that amino acids must be in their protonated form to undergo facile hydrogenation since reduction of carboxylate anions is significantly more endothermic than protonated acids (19). Control of pH is important for two reasons at neutral pH amino acids exist as zwitterions and the resultant hydrogenation products are basic. For these reasons a full equivalent of phosphoric acid (or similar acid) is required to obtain high yields. 

Methyl esters undergo trans-esterification with the quaternary ammonium salts at high temperature and the reaction has been used with some effect for the preparation of, for example, n-butyl esters by heating the methyl ester with tetra-n-butylammo-nium chloride at 140°C [31]. Optimum yields (>75%) are obtained in HMPA or in the absence of a solvent. A two-step (one-pot) trans-esterification under phase-transfer catalysed conditions in which the carboxylate anion generated by initially hydrolysis of the ester is alkylated has been reported for Schiff s bases of a-amino acids [32] and for A-alkoxycarbonylmethyl [1-lactams [33]. Direct trans-esterification of methyl and ethyl esters with alcohols under basic catalytic conditions occurs in good yield in the presence of Aliquat [34, 35]. 

Imidoyl esters (Scheme 3.7) are obtained readily when the appropriate imidoyl chloride is reacted with an alcohol or phenol under basic conditions in the presence of phase-transfer catalysts [71]. The reaction with thiophenol yields the corresponding thioimidoyl ester. Diaroyl amides are produced by the analogous reaction of the imidoyl chloride and carboxylate anions. In this reaction, the initially formed carboxylic ester undergoes a 1,3-migration to produce the amide. 

During the degradation the keto-carbonyl groups increased in amount as obtained by attenuated total reflectance (ATR)-FTIR. In the basic environment a growing peak corresponding to carboxylate anion is observed (13). 

We can appreciate that ionization of the carboxylie acid is affected by the electron-withdrawing inductive effect of the ammonium residue hence the increased acidity when compared with an alkanoic acid. Similarly, loss of a proton from the ammonium cation of the zwitterion is influenced by the electron-donating inductive effect from the carboxylate anion, which should make the amino group more basic than a typical amine. That this is not the case is thought to be a solvation effect (compare simple amines). 

When the reaction condition is too warm or basic, the oxidation proceeds further to generate two carboxylate anions, which on acidification yield two carboxylic acids. 

Bruice and Schmir (3) have shown that for a series of imidazole derivatives, klm depends on the base strength of the catalyst and since pKA is an approximate measure of base strength, the value of klm should increase with increase in pKA. Table I shows that this is indeed the case. Imidazole, pKA = 7.08, has a catalytic constant eight times larger than that of benzimidazole, pKA = 5.53. Bronsted and Guggenheim (2) have obtained a linear relationship between log k/ and pKA for a series of carboxylic acids in the pKA range of 2 to 5, where kB is the carboxvlate anion basic catalytic constant for the mutarotation of glucose and Ka is the acid dissociation constant of the acid. Our results for imidazole and benzimidazole fit fairly well into the Bronsted plot. 

The enthalpy and entropy of complex formation between Zn11 and picolinate and dipicolinate anions in aqueous solution have been determined by calorimetry and from formation constant data. The greater stability of the dipicolinate complex compared to the picolinate complex reflects an entropy effect, and Ais actually less favourable. These anions are well known to have a low basicity to H+ compared to their complexing ability to metals. In the present case, this probably reflects the coplanarity of the carboxylate anions and the pyridine ring, so that the oxygen atoms are in a favourable position to coordinate.800... 

Basic Hydrolysis. Throughout most of history, soap was manufactured by boiling an ester with aqueous alkali. In this reaction, known as saponification, the ester is hydrolyzed with a stoichiometric amount of alkali. The irreversible formation of carboxylate anion drives the reaction to completion. 

A classic example of ester hydrolysis is demonstrated with aspirin. Aspirin hydrolyzes under acidic and basic conditions to yield acetic and salicylic acid (Fig. 2) (6). Aspirin easily hydrolyzes because it is an activated ester (i.e., the leaving group, carboxylate anion, can readily stabilize the anionic charge). An additional API example that undergoes ester hydrolysis is cyclandelate (7). 

First the carboxylic acid 10 reacts with the amino group of the amino acid L-serine methyl ester 44. This reaction is carried out with DCC 45 and DMAP 46 as activators of the carboxyl group.20,21 With the basic DMAP 46 as the catalyst, a proton transfer between the carboxylic acid 10 and the diimide 45 yields the carboxylate anion 47 which undergoes nucleophilic addition to the protonated diimide 48. This activated ester 49 is readily attacked by the amino group of L-serine methyl ester 44 as a nucleophile. 

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