Esters from carboxylate anions

Although a carboxylate anion is only a relatively modest nucleophile (see Section 6.1.2), it is possible to exploit an Sn2 reaction to prepare esters from carboxylic acids as an alternative to the usual esterification methods (see Section 7.9). Such methods might be useful, depending upon the nature and availability of starting materials. 

Methylsulfinyl enolates are more recently developed d -reagents. They are readily prepared from carboxylic esters and dimsyl anion. Methanesulfenic acid can be eliminated thermally after the condensation has taken place. An example is found in Bartlett s Brefeldin synthesis (P.A. Bartlett. 1978). 

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... 

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). 

The reaction product with monoethanolamine acts as a thickening agent [41,101] and with alcohols as an emollient [40]. Also reaction products with amino acids and oligo- or polypeptides for use in cosmetic formulations are known [43]. Sorbitan esters from ether carboxylates are described as emulsifiers or mild surfactants in cosmetic formulations [39] and alkyl ether carboxylic acid taurides as nonirritant anionic surfactants for cosmetic cleaners in particular [44]. Using unsaturated ether carboxylates it is possible to make viscous formulations based on combinations of unsaturated and saturated ether carboxylates [111]. Highly purified alkyl ether carboxylates based on alcohol ethoxylates with low free alcohol content have also been described [112]. 

Two methods for converting carboxylic acids to esters fall into the mechanistic group under discussion the reaction of carboxylic acids with diazo compounds, especially diazomethane and alkylation of carboxylate anions by halides or sulfonates. The esterification of carboxylic acids with diazomethane is a very fast and clean reaction.41 The alkylating agent is the extremely reactive methyldiazonium ion, which is generated by proton transfer from the carboxylic acid to diazomethane. The collapse of the resulting ion pair with loss of nitrogen is extremely rapid. 

Carboxylate anions derived from somewhat stronger acids, such as p-nilrobcnzoic acid and chloroacetic acid, seem to be particularly useful in this Mitsunobu inversion reaction.53 Inversion can also be carried out on sulfonate esters using cesium carboxy-lates and DMAP as a catalyst in toluene.54 The effect of the DMAP seems to involve complexation and solubilization of the cesium salts. 

Primary and secondary alcohols are oxidized slowly at low temperatures by benzyltriethylammonium permanganate in dichloromethane primary alcohols produce methylene esters (60-70%), resulting from reaction of the initially formed carboxylate anion with the solvent, with minor amounts of the chloromethyl esters and the carboxylic acids. Secondary alcohols are oxidized (75-95%) to ketones [34] the yields compare favourably with those obtained using potassium permanganate on a solid support. 1,5-Diols are oxidized by potassium permanganate under phase-transfer catalytic conditions to yield 8,8-disubstituted-8-valerolactones [35] (Scheme 10.1). 

From the point of view of the synthesis of dissonant systems the most important finding reported by Reissig [19c] is the opening of cyclopropanes by fluoride ion-induced desilylation to give carboxylic ester stabilised "homoenolate" anions, from which a series of 4-oxoalkanoic esters (21a ). with a 1,4-D relationship, were prepared (Table 5.6) ... 

Molecules having two reactive centers that are noninteracting or only weakly interacting, such as the carboxylate anions in malonate or succinate, are not considered to be ambident. The term bifunctional should be used to describe these compounds. If a molecule contains more than two interacting centers, the terms polydent or multident should be used. Examples of such nucleophiles include anions derived from malonic esters, /3-keto esters, /8-diketones, as well as phenoxide ions. 

Theme 2 recognizes carboxylic acids or bioisosteres of them. There is, however, a gradation of properties of this Motif that range from charged anionic carboxylate-like to uncharged ester-like with an intermediate... 

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