Carboxylation anion intermediates

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... 

Carboxylate anions can also serve as nucleophilic catalysts. In this case, an anhydride is the reactive intermediate ... 

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... 

First, the acid anhydride is produced by the reaction of the free acid with DCC. NucleophiUc attack by 4-pyrroUdinonepyridine on the anhydride results in the corresponding, highly reactive acylpyridinium carboxylate this leads to the formation of cellulose ester, plus a carboxylate anion. The latter imdergoes a DCC-mediated condensation with a fresh molecule of acid to produce another molecule of anhydride. N,N-carbonyldiimidazole (CDl) may substitute DCC for acid activation, the intermediate being N-acyhmidazol,... 

The intermediate N-acylpyridinium salt is highly stabilized by the electron donating ability of the dimethylamino group. The increased stability of the N-acylpyridinium ion has been postulated to lead to increased separation of the ion pair resulting in an easier attack by the nucleophile with general base catalysis provided by the loosely bound carboxylate anion. Dialkylamino-pyridines have been shown to be excellent catalysts for acylation (of amines, alcohols, phenols, enolates), tritylation, silylation, lactonization, phosphonylation, and carbomylation and as transfer agents of cyano, arylsulfonyl, and arylsulfinyl groups (lj-3 ). 

Loss of C02 from carboxylate anions (41) is believed to involve a carbanion intermediate (42) that subsequently acquires a proton from solvent, or other source ... 

The cyclopropanone intermediate (81) undergoes subsequent addition of eOH, followed by ring-opening to yield the more stable of the two possible carbanions (83, benzyl > primary), followed by proton exchange to yield the rearranged carboxylate anion end-product (84). 

Although the reaction could proceed via intermediate 14 or 15, the authors favour a mechanism where the formation of 14 is rate-determining because the displacement of the acetate at Pb by carboxylate anions is known to be rapid. The large negative AS (—34 e.u./mol) observed for the oxidation reaction is consistent with formation of the pseudo-cyclic intermediate 14. Also, the small Hammett p value of 0.4 determined for a series of meta- and para-substituted mandelic acids indicates that there is very little charge development on the benzyl carbon in the transition state of the rate-determining step. This is also consistent with the proposed mechanism. 

DR. TAUBE With unstable intermediates, there is the problem of competing rates. My guess is that, if you could keep the carboxylate anion long enough, it would reduce CIO.. The... 

In a related study, the oxidation-reduction sequence was carried out in the presence of an olefin (Scheme 21). Two products were formed. The major product resulted from the net reduction of the carboxylic acid to an aldehyde. The minor product resulted from trapping of the radical anion intermediate generated from the reduction reaction by the olefin. It should be noted that, in the absence of a trapping group, the acid can be selectively reduced to the aldehyde without any over-reduction. Although not in the scope of this review, this is a very useful transformation in its own right [35]. At this time, the yields of the cyclized products from the cyclization reaction of the radical anion with the olefin remain low. 

Lipscomb has commented that glutamic acid-245 might act either as a general base or a nucleophile. The available mechanistic information has been reviewed by Kaiser and Kaiser (1972), who postulated that the carboxylate anion of glutamic acid-245 acts as a nucleophile forming an anhydride intermediate [equation (29)]. The divergent D2O solvent isotope effects, =... 

Capon et al. considered three possible mechanisms [equation (47)] for hydrolysis of o-methoxymethoxybenzoic acid. Mechanisms (a) and (b) involve nucleophilic attack by the carboxylate anion on the protonated acetal, and mechanism (c) proceeds with intramolecular gener2il acid catalysis. Capon was able to rule out mechanisms (a) and (b) since the synthetically prepared intermediate in (a) is stable under the reaction conditions. That in (b) leads to products at... 

Pyridine has another useful attribnte, in that it behaves as a nncleophilic catalyst, forming an intermediate acylpyridinium ion, which then reacts with the nucleophile. Pyridine is more nucleophilic than the carboxylate anion, and the acylpyridinium ion has an excellent leaving group (pATa pyridinium 5.2). The reaction thus becomes a double nucleophilic substitution. 

The initial reaction is effectively the same as with an aldehyde or ketone, in that hydride is transferred from the reducing agent, and that the tetrahedral anionic intermediate then complexes with the Lewis acid aluminium hydride. However, the typical reactivity of the carboxylic acid derivatives arises because of the presence of a leaving group. 

The carboxylate anion has two strongly coupled C—O bonds with bond strengths intermediate between C=0 and C—O. 

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