Carboxylic acids, from anhydrides

Three methods are known for the synthesis of acid anhydrides from carboxylic acids by means of azolides ... 

Formation of anhydrides from carboxylic acids or esters... 

Synthesis of esters and anhydrides from carboxylic acids. 

A.7.1 Esterification of Acids using Carbodiimides. The formation of anhydrides from carboxylic acids, thiocarboxylic acids, sulfonic acids and phosphorous acids are discussed in Section 2.4.S.2. In this section only special cases of anhydride formation are described. Mixed anhydrides of amino acids and adenylic acid are produced from the corresponding acids using DCC as the condensation agent. ° Mixed anhydrides not containing amino acids, such as butyryl adenate, adenosine 5 -phosphosulfate and p-nitrophenyl-thymidine-5-phosphate are also obtained. 

Kende has demonstrated that the mixed anhydride from carboxylic acids and diphenylphosphinic chloride would acylate Grignard reagents to afford ketones in moderate to good yield. Tertiary carbinols were not observed unless excess Grignard reagent was added. The intermediate anhydrides were generally isolated and made free of triethylamine hydrochloride before addition of the nucleophile. The reaction shown in equation (52) gave improved yields over the simple addition of methyllithium to the carboxylic acid. ... 

Acid Anhydrides from Carboxylic Acids by Dehydration... 

Acid Anhydrides from Carboxylic Acid Salts and Acid Halides 2.133 Acid Anhydrides by Miscellaneous Methods... 

Table 6 Symmetrical Carboxylic Acid Anhydrides from Carboxylic Acids and Reagents (3) and (4)...

Carbodiimides, in particular dicyclohexylcarbodiimide, have been applied in many syntheses where dehydration had to be performed under mild conditions. It is therefore no surprise that this reagent was also introduced for the synthesis of acid anhydrides from carboxylic acids." " In order to avoid N-acylation the reactions are carried out at low temperature. First 0-acylisoureas are formed, which then react further with free acid to the acid anhydride (equation 34). The reaction has been exploited in particular for the preparation of peptides." )V-alkoxycarbonyl-protected amino acids can be transformed in high yield to the corresponding anhydrides, which themselves are activated acid derivatives and may be converted to peptides. As in many other examples polymer-bound carbodiimides may prove superior sometimes, as the isolation of the products is facilitated. Easy preparation of acid anhydrides is possible in this way." ... 

Another general approach to acid anhydrides from carboxylic acids was developed with esters of cyanuric acid as reagents (equation 37). If the reactions are carried out in solvents like carbon tetrachloride or benzene, the resulting aryl esters of carbaminic acid are insoluble and can be removed by filtration. 

Mixed anhydrides from carboxylic acids (26a) have to be so devised that the desired acyl group is transferred, lliis can be achieved in two ways. The first one is to block the undesired carbonyl position by steric (e.g. 26aa equation 5) or electronic (e.g. 26ab equation 6) deactivation. The second one, as illustrated by (26ac equation 7) is to allow the reversible attack of both carbonyl groups the desired acyl transfer is accomplished by the better leaving group quality of the trifluoroacetate. Specifically, the... 

Carboxylic acid anhydrides from carboxylic acids of N-heterocycIes s. 4, 214 coo-oc... 

Carboxylic acid anhydrides from carboxylic acids COOOC... 

Mixed anhydrides can be obtained by those of the above methods in which acid chlorides are used. Further, formation of anhydrides from carboxylic acids and acetic anhydride involves mixed anhydrides as intermediates, and in some cases these can be isolated, e.g., the mixed formic acetic anhydride.977 This anhydride can replace the unstable formic anhydride itself, for only the reactive formyl group is transferred in its reactions this fact has been utilized in the preparation of numerous formic esters, which in turn can be transformed into esters of tertiary alcohols that are otherwise difficult of access (see page 376). 

C=N- From aminomethyl polystyrene (Scheme Symmetric anhydrides from carboxylic acids. Maffatt oxidation of prim, and sec. alcohols. - -- ... 

Fallacious acetate I triphenylphosphine I sodium salt Carboxylic acid anhydrides from carboxylic acid salts and iodides Carbonylation under mild conditions... 

Potassium chloride Mixed carboxylic acid anhydrides from carboxylic acid chlorides... 

Carbonylation may also be achieved by insertion of carbon monoxide into an existing bond, as for instance in the formation of anhydrides from carboxylic acid esters, of esters from ethers, or acids from alcohols. 

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