Reaction with carboxylic acid salts

As one of the most reactive groups of carboxylic acid derivatives, acyl halides are very useful substrates for the preparation of the other classes of derivatives. For example, anhydrides may be synthesized by the reaction of carboxylic acid salts with an acyl halide. In this reaction, the carboxylate anion acts as the nucleophile, eventually displacing the halide leaving group. 

Fig. 13.10. Formation of carboxylate enolates ("carboxylic acid dianions") by reaction of carboxylic acid salts with strong bases.

For the reaction of TDI with a polyether triol, bismuth or lead compounds can also be used. However, tin catalysts are preferred mainly because of their slight odor and the low amounts required to achieve high reaction rates. Carboxylic acid salts of calcium, cobalt, lead, manganese, zinc, and zirconium are employed as cocatalysts with tertiary amines, tin compounds, and tin—amine combinations. Carboxylic acid salts reduce cure time of rigid foam products. Organic mercury compounds are used in cast elastomers and in RIM systems to extend cream time, ie, the time between mixing of all ingredients and the onset of creamy appearance. 

Introduction. The object of this experiment is to illustrate a number of general reactions of carboxylic acids. Salt formation is a characteristic property of the carboxyl group. The salts of the alkali metals as a rule are soluble. The higher, sparingly soluble, fatty acids form salts which give colloidal dispersions. The soluble salts are prepared by neutralization of the acid with alkali, or by boiling with an excess of the metallic carbonate and evaporating the solution. 

Reductive alkylation of N-methylacridinium (87) occurs when it is irradiated with carboxylic acid salts. The reaction is thought to proceed by electron transfer from the carboxylate to the excited acrldinium ring followed by decarboxylation of RCOO coupling of the alkyl radical produced with the acridinyl radical then gives (88). A very similar sequence probably occurs in a reaction proposed as a synthetic procedure for decarboxylation of carboxylic acids.In this case an aza-aromatic compound such as acridine is irradiated with a carboxylic acid in benzene in the presence of tert-butyl thiol. The authors propose that a hydrogen bonded acridine-acid complex is excited and that adiabatic proton transfer is followed by electron transfer. This produces RCOO which decarboxylates, and reduction of the alkyl radical then ensues. The major fate of the acridine is coupling to (89) if the reaction is perfonned in the absence of oxygen. 

The biomimetic phosphoric acid mixed anhydride concept stimulated further search for activating reagents that produce derivatives of acylamino acids (and peptides) in more simple ways than the ones mentioned earlier in the Chapter (on p. 78) An interesting attempt in this direction is the so called Bates reagent [47] which on reaction with carboxylic acids yields acyloxyphosphonium salts. 

Amines (Chapter 5, Part VI, and Chapter 10) are basic.Thus, their reactions with carboxylic acids produce the corresponding salts rather than amides (Equation 9.97). Although it is possible for some amine salts of carboxylic acids to be converted to the corresponding amides by heating them to high temperatures (pyrolysis), the fragile nature of many compounds prohibits such drastic treatment. 

The general reaction of acyl halides with carboxylic acid salts may be written as in Eq. (7). 

Adipic acid, 219.2 g (1.5 mol), and 77.6 g (1.25 mol) of 1,2-ethanediol are weighed into a 500-mL glass reactor equipped with a mechanical stirrer, a nitrogen inlet, and a distillation head connected to a condenser and a receiver fiask. The reactor is placed in a salt bath preheated at 180°C and the temperature is dien raised gradually to 220°C (see note at end of procedure) until the greater part of water has been removed (3 h). The reactor is cooled down to 160°C and vacuum is applied slowly to ca. 0.07 mbar (30 min). Temperature is ramped to 220°C (see note below) at a rate of l°C/min and reaction is continued for an additional 90 min. At the end of reaction, the carboxylic acid endgroup content is close to 1.90 mol/kg. No purification of final polyester is carried out. 

Although, the enzymatic reaction of esters with amines or ammonia have been well documented, the corresponding aminolysis with carboxylic acids are rarer, because of the tendency of the reactants to form unreactive salts. For this reason some different strategies have been used to avoid this problem. Normally, this reaction has been used for the preparation of amides of industrial interest, for instance, one of the most important amides used in the polymer industry like oleamide has been produced by enzymatic amidation of oleic acid with ammonia and CALB in different organic solvents [10]. 

Unsymmetrical as well as symmetrical anhydrides are often prepared by the treatment of an acyl halide with a carboxylic acid salt. The compound C0CI2 has been used as a catalyst. If a metallic salt is used, Na , K , or Ag are the most common cations, but more often pyridine or another tertiary amine is added to the free acid and the salt thus formed is treated with the acyl halide. Mixed formic anhydrides are prepared from sodium formate and an aryl halide, by use of a solid-phase copolymer of pyridine-l-oxide. Symmetrical anhydrides can be prepared by reaction of the acyl halide with aqueous NaOH or NaHCOa under phase-transfer conditions, or with sodium bicarbonate with ultrasound. 

The rigid, planar pyridine analog 111 was isolated in low yield by first hydrolyzing the known (67) pyridine diethyl phosphonate 109 to the corresponding free acid 110 followed by permanganate oxidation (2). An alternative synthesis of 111 has recently been reported (68). Alkylation of pyridine-2-carboxylate -oxide with dimethylsulfate and subsequent reaction with the sodium salt of diethyl phosphite gave the triester 112, which was readily converted to 111. 

As noted in the preceding section, one of the most general methods of synthesis of esters is by reaction of alcohols with an acyl chloride or other activated carboxylic acid derivative. Section 3.2.5 dealt with two other important methods, namely, reactions with diazoalkanes and reactions of carboxylate salts with alkyl halides or sulfonate esters. There is also the acid-catalyzed reaction of carboxylic acids with alcohols, which is called the Fischer esterification. 

Alternatively, esterification of carboxylic acid can be carried out in aqueous media by reacting carboxylic acid salts with alkyl halides through nucleophilic substitutions (Eq. 9.10).20 The reaction rate of alkyl halides with alkali metal salts of carboxylic acids to give esters increases with the increasing concentration of catalyst, halide, and solvent polarity and is reduced by water. Various thymyl ethers and esters can be synthesized by the reactions of thymol with alkyl halides and acid chlorides, respectively, in aqueous medium under microwave irradiation (Eq. 9.11).21 Such an esterification reaction of poly(methacrylic acid) can be performed readily with alkyl halides using DBU in aqueous solutions, although the rate of the reaction decreases with increasing water content.22... 

It has been shown that reaction of carboxylic acids with benzyl halides, which does not occur when heated conventionally, could be performed efficiently under the action of MW irradiation in the presence of a quaternary ammonium salt as a catalyst (Eq. 3) [15]. Typical results are given in Tab. 5.3. 

Miscellaneous Reactions.—A full report has appeared of the reactions of carbon dioxide and carbon disulphide with tervalent phosphorus aryl esters and amines the products are ureas and thioureas, respectively.74 The suggested mechanism, previously invoked for similar reactions of carboxylic acids, involves the N-phosphonium salt (97). 

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