Reactions of Carboxylic Acid Anhydrides

One reaction of this type, Friedel-Crafts acylation (Section 12.7), is already famihar to us. 

An acyl cation is an intermediate in Friedel-Crafts acylation reactions. 

Conversions of acid anhydrides to other carboxylic acid derivatives are illustrated in Table 20.3. Since a more highly stabilized carbonyl group must result in order for nucleophilic acyl substimtion to be effective, acid anhydrides are readily converted to carboxylic acids, esters, and amides but not to acyl chlorides. 

Conversion of Acid Anhydrides to Other Carboxylic Acid Derivatives 

Reaction with alcohols (Section 15.8) Acid anhydrides react with alcohols to form esters. The reaction may be carried out in the presence of pyridine or it may be catalyzed by acids. In the example shown, only one acetyl group of acetic anhydride becomes incorporated into the ester the other becomes the acetyl group of an acetic acid molecule. 

Bond cleavage occurs here in an acid anhydride. 

---

Hill, C.A.S. and Hillier, J. (1999). Kinetic studies of the reaction of carboxylic acid anhydrides with wood. Experimental determination and modelling of kinetic profiles. Physical Chemistry and Chemical Physics, 1, 1569-1576. 

Horner, L., Kaiser, P. The course of substitution. XVIII. The reaction of carboxylic acid anhydrides with sulfoxides. Ann. 1959, 626, 19-25. 

P-Diketones. The Nicer we in2 synthesis of /3-diketones (4) involves the reaction of carboxylic acid anhydrides (1) with ketones (2) with boron trifluoride as... 

This chapter covers not only nuclear and extranuclear quinoxahnecarboxylic acids (and anhydrides) but also the carboxylic esters, acyl halides, carboxamides, carbohydrazides, carbonitriles, carbaldehydes, and (ketonic) acyl derivatives of quinoxaline a few related speceis are also included. To avoid repetition, the interconversions of these quinoxaline derivatives are discussed only at the first opportunity thus the esterification of quinoxalinecarboxylic acids in covered as a reaction of carboxylic acids rather than as a preparative route to carboxylic esters, simply because the section on carboxylic acids precedes that on carboxylic esters. To minimize any confusion, appropriate cross-references have been inserted. 

A few of the important reactions carboxylic acids undergo are shown above. Soap is made by reacting sodium or potassium hydroxide with long-chain acids such as C17H35COOH (stearic acid). Acid chlorides and acid anhydrides are more reactive than their corresponding carboxylic acids and are used in the chemical industry to make various acid derivatives. A very important industrial reaction is the reaction of carboxylic acids (or the chlorides or anhydrides) with alcohols to form esters. 

A two-step mechanism must be assumed for this very valuable reaction of carboxylic acids with CDI.[9] Obviously the first step is a nucleophilic attack of the carboxylic acid or —depending on the acidity —the carboxylate ion on the carbonyl group of CDI, leading after elimination of imidazole to a mixed anhydride of imidazole-iV-carboxylic acid and the attacking carboxylic acid. This intermediate must have a very short life-time since it has not been detected down to — 50 °C. Rapid cleavage of CO2 from this mixed anhydride involves exclusively the carbonyl group linked to the imidazole unit If... 

Hill, C.A.S. and Jones, D. (1996a). The dimensional stabilisation of Corsican pine sapwood by reaction with carboxylic acid anhydrides. Holrforschung, 50(5), 457 62. 

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. 

Formation of acid anhydride by the reaction of carboxylic acid with acetic anhydride. 

The most important reactions of carboxylic acids are the conversions to various carboxylic acid derivatives, e.g. acid chlorides, acid anhydrides and esters. Esters are prepared by the reaction of carboxylic acids and alcohols. The reaction is acid catalysed and is known as Fischer esterification (see Section 5.5.5). Acid chlorides are obtained from carboxylic acids by the treatment of thionyl chloride (SOCI2) or oxalyl chloride [(COCl)2], and acid anhydrides are produced from two carboxylic acids. A summary of the conversion of carboxylic acid is presented here. All these conversions involve nucleophilic acyl substitutions (see Section 5.5.5). 

Carboxylic acid anhydrides generally react with sulfur tetrafluoride in the same manner as carboxylic acids to give acid fluorides, then trifluoromethyl derivatives. Various cyclic anhydrides, which are particularly stable under acidic conditions, react without cleavage to give, in a stepwise fashion, difluoro lactones and a,a,a, a -tetrafluoro ethers. Conversely, the corresponding diacids are readily dehydrated by sulfur tetrafluoride to give anhydrides in the first step of the reaction. Therefore, in this section reactions of carboxylic acids and carboxylic acid anhydrides are discussed together. 

This procedure describes the use of pseudoephedrine as a chiral auxiliary for the asymmetric alkylation of carboxylic acid amides. In addition to the low cost and availability in bulk of both enantiomeric forms of the chiral auxiliary, pseudoephedrine, a particular advantage of the method is the facility with which the pseudoephedrine amides are formed. In the case of carboxylic acid anhydrides, the acylation reaction occurs rapidly upon mixing with pseudoephedrine. Because pseudoephedrine amides are frequently crystalline materials, the acylation products are often isolated directly by crystallization, as illustrated in the procedure above. 

In Chapter 2 the DSC technique is discussed in terms of instruments, experimental methods, and ways of analysing the kinetic data. Chapter 3 provides a brief summary of epoxy resin curing reactions. Results of studies on the application of DSC to the cure of epoxy resins are reviewed and discussed in Chapter 4. These results are concerned with the use of carboxylic acid anhydrides, primary and secondary amines, dicyanodiamide, and imidazoles as curing agents. 

Conversions of carboxylic acids to ketones are typically performed in stepwise fashion6 via intermediates such as acid chlorides,7 anhydrides,8 thioesters,9 or N-alkoxy amides,16 or by the direct reaction of carboxylic acids with lithium reagents.11 In this latter method trimethylsiiyl chloride has been shown to be an effective reagent for trapping the tetrahedral alkoxide intermediates and for quenching excess organolithium reagent. 

The reactions of carboxylic acids and anhydrides with epoxy resins have been extensively studied in a variety of investigations, particularly References 27—31. The general reaction of epoxide resins and anhydrides is... 

---