To acid anhydrides

Section 20 4 Acyl chlorides are converted to acid anhydrides esters and amides by nucleophilic acyl substitution... 

The first example in Table 20.2 introduces a new aspect of nucleophilic acyl substitution that applies not only to acid anhydrides but also to acyl chlorides, thioesters, esters, and amides. Nucleophilic acyl substitutions can be catalyzed by acids. 

Barker, R.D. et al., Risk factors for sensitisation and respiratory symptoms among workers exposed to acid anhydrides a cohort study, Occup. Environ. Med., 55, 684, 1998. 

Triethyl- and triphenylphosphine have been used for deoxygenation not only of hydroperoxides to alcohols but also of dialkyl peroxides to ethers, of diacyl peroxides to acid anhydrides, of peroxy acids and their esters to acids or esters, respectively, and of endoperoxides to oxides [290] in good to excellent yields. The deoxygenation of ascaridole to l-methyl-4-isopropyl-l,4-oxido-2-cyclohexene [290] was later challenged the product is claimed to be p-cymene instead [668]). 

An enzymatic reaction intermediate formed by phospho-ryl transfer to a carboxyl group on an enzyme. Acyl-phosphates are structurally analogous to acid anhydrides (R—CO —O —CO—R ), and they are thermodynamically less stable than either of the two phosphoanhydride bonds in ATP. This is evident by the fact that the acetate kinase reaction (ADP + acetyl-phosphate = ATP + acetate) favors ATP formation with an equilibrium constant of about 3,000. Acetyl-phosphate can be chemically synthesized by reacting orthophosphate with acetic anhydride. 

Bi(0Tf)3-xH20 proved to be a superior catalyst than BiCl3 for FC acylation (Schemes 7 and 8). Its activity as a Lewis acid is restricted to acid anhydrides since with acid chlorides Bi(0Tf)3-xH20 leads to ligand exchange reactions in which mixed anhydrides (RCOOTf, see path a in Scheme 8) are the active acylating... 

Acid chlorides are the most reactive carboxylic acid derivatives, and easily converted to acid anhydrides, esters and amides via nucleophilic acyl substitutions (see Section 5.5.5). Acid chlorides are sufficiently reactive with H2O, and quite readily hydrolysed to carboxylic acid (see Section 5.6.1). 

Acid chlorides can be converted to acid anhydrides, esters, or amides. These reactions are possible because acid chlorides are the most reactive of the four carboxylic acid derivatives. Nucleophilic substitutions of the other acid derivatives are more limited because they are less reactive. For example, acid anhydrides can be used to synthesise esters and amides, but cannot be used to synthesise acid chlorides. 

Thus, acid chlorides can be converted to acid anhydride, esters, and amides (Fig.I). Hydrochloric acid is released in all these reactions and this may lead to side reactions. Therefore, pyridine or sodium hydroxide may be added so as to mop up the hydrochloric acid (Fig.J). 

The preparation of the acid derivatives is organized according to their precursors. The synthetic method of choice in a particular case will depend on a number of factors of which the presence of other functional groups in the molecule under study is not the least important. The methods will be evaluated with respect to their scope of application. The chemistry of acid halides has been reviewed. Methods of preparation are treated in Houben-WeyP as well as in other reference books. This applies also to acid anhydrides and a-ketonitriles. ... 

A procedure which converts carboxylic acids under very mild conditions to acid anhydrides was discovered in the reaction of 2 equiv. of acid with carbon tetrachloride in the presence of 1 equiv. of hexa-methylphosphoramide and 1 equiv. of triethylamine in THF at -70 °C (equation 26). The anhydride of cyclopropanecarboxylic acid is, for example, formed in 76% yield. The reaction can be modified in the sense that preformed chlorotrisdimethylaminophosphonium perchlorate is used as reagent. At room temperature acids arc transformed into anhydrides in very good yield according to equation (27). The latter reagent can be applied successfully to the coupling of amino acids to form peptides. 

The use of imidazolides in organic synthesis has been propagated by Staab and coworkers." " Acid anhydrides can also be prepared with carbonyldiimidazolide. The reaction of a carboxylic acid with this reagent leads to acid anhydride if the transacylation equilibrium (equation 35) can be shifted to the side of the anhydride. This is possible either if the acid is used in twofold excess and forms an insoluble salt with the liberated imidazole or if trifluoro- or trichloro-acetylimidazolide is taken as the reagent. Symmetrical acid anhydrides can be obtained in a number of cases in good yield according to equation (36). 20... 

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. 

Table 10 Conversion of Carboxylic Acids to Acid Anhydrides with a Copolymer of 4-Vinylpyridine...

Several other metal salts have been proposed to react with acid halides to give acid anhydrides in good yield. Thus, thallium carboxylates in etheral suspension may be treated with acid halides to lead to acid anhydrides in high yield. The method has the advantage that thallium chloride can be separated by filtration and the product is isolated after evaporation of the solvent. Another synthetic possibility exists in the desulfurization of thioesters with mercury(II) carboxylates. Mercuiy(II) carboxylates can also be reacted with triethyl phosphite or tri-n-butylphosphine to provide acid anhydrides in yields of 60-80%. Another possibility is offered by the reaction of 1 mol of iV,Af-dicyclohexylthiourea and 2 mol of silver or mercury(II) carboxylates. Mixed carboxylatocarbamato anhydrides follow from the room temperature reaction of iV, -dialkylcarbamato metal derivatives with acid chlorides. Either Na, Cu", Ti" or V" are employed. ... 

Direct catalytic oxidative carbonylation to form acid anhydrides was achieved with arylmercuiy acetate. Palladium(II) salts are taken as catalysts. Aromatic compounds such as benzene, toluene, anisole, furan, thiophene and naphthalene can be converted catalytically with palladium(II) acetate and an excess of 1,2-dibromoethane to acid anhydrides in yields of 30- %. 

Cullis, P. M., Arnold, J. R. P., Clarke, M., Howell, R., DeMira, M., Naylor, M., Nicholls, D. On the mechanism of peracid oxidation of -diketones to acid anhydrides an oxygen-17 and oxygen-18 isotope study. J. Chem. Soc., Chem. Common. 1987, 1088-1089. 

BERNSTEIN, D.I., GALLAGHER, J.S., D SOUZA, L. BERNSTEIN, I.L. (1984) Heterogeneity of specific-IgE responses in workers sensitized to acid anhydride compounds. Journal of Allergy and Clinical Immunology, 74, 794—801. 

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