Carboxylic acid anhydrides hydrolysis

FIGURE 20 3 An acid cat alyzes the hydrolysis of a carboxylic acid anhydride by increasing the rate of the first stage of the mecha nism The faster the tetra hedral intermediate is formed the faster the rate of hydrolysis... 

Carboxylic acid derivative (Section 20.1) Compound that yields a carboxylic acid on hydrolysis. Carboxylic acid derivatives include acyl chlorides, acid anhydrides, esters, and amides. 

RGURE 8-40 The phosphate ester and phosphoanhydride bonds of ATP. Hydrolysis of an anhydride bond yields more energy than hydrolysis of the ester. A carboxylic acid anhydride and carboxylic acid ester are shown for comparison. 

A cyclization reaction involving the sulfonamide 267 finalized an efficient synthetic approach to the COX-inhihitor 268 after subsequent simultaneous ester hydrolysis and detosylation (Equation 82) <2003JOC4104>. Indoles have also been prepared by reaction of (2-aminobenzyl)triphenylphosphonium salts with carboxylic acid anhydrides in the presence of a base <2002TL2885>. Exposure of o-(benzoylamino)benzonitriles to a-bromoketones under basic conditions gives 3-aminoindole derivatives <2001BML2169>. 

Although ATP reacts readily in enzyme-catalyzed reactions, it reacts quite slowly in the absence of an enzyme. For example, carboxylic acid anhydrides hydrolyze in a matter of minutes, but ATP takes several weeks to hydrolyze. The low rate of ATP hydrolysis is important because it allows ATP to exist in the cell until it is needed for an enzyme-catalyzed reaction. 

In many cases, side reactions are liable to occur during the ROMP of these monomers, for example, esterification and trans-esterification when the ROMP of carboxylic acids, anhydrides, or esters are carried out in solvents containing alcohols, or hydrolysis when carried out in water (Drent 1991 Lu 1993a, 1994). Retro-Diels-Alder reactions can also be a problem. Thus, although 199 is cleanly polymerized to high conversion by [Ru(H20)6](0Ts)2 under mild conditions (55°C), its endo-isomer fails to polymerize because the retro-Diels-Alder reaction produces N-methylmaleimide, which complexes with the catalyst and puts it out of action. The exo-N-phenyl analogue is likewise unable to polymerize (Hillmyer 1992). 

Carboxylic acid anhydrides also undergo hydrolysis ... 

Hydrolysis (Section 20 6) Acid anhydrides react with water to yield two carboxylic acid func tions Cyclic anhydrides yield di carboxylic acids... 

Hydrolysis of aspirin in H2 0 leads to no incorporation of into the product salicylic acid, ruling out the anhydride as an intermediate and thereby excluding mechanism 1. The general acid catalysis of mechanism III can be ruled out on the basis of failure of other nucleophiles to show evidence for general acid catalysis by the neighboring carboxylic acid group. Because there is no reason to believe hydroxide should be special in this way, mechanism III is eliminated. Thus, mechanism II, general base catalysis of hydroxide-ion attack, is believed to be the correct description of the hydrolysis of aspirin. 

Small amounts of water present will lead to partial hydrolysis of the acyl chloride to give the carboxylic acid 7, which then may further react with the acyl chloride to give a carboxylic anhydride 8 ... 

To set the stage for the crucial aza-Robinson annulation, a reaction in which the nucleophilic character of the newly introduced thiolactam function is expected to play an important role, it is necessary to manipulate the methyl propionate side chain in 19. To this end, alkaline hydrolysis of the methyl ester in 19, followed by treatment of the resulting carboxylic acid with isobutyl chlorofor-mate, provides a mixed anhydride. The latter substance is a reactive acylating agent that combines smoothly with diazomethane to give diazo ketone 12 (77 % overall yield from 19). 

Attention has been drawn to the potential of phosphoric acid anhydrides of nucleoside 5 -carboxylic acids (14) as specific reagents for investigating the binding sites of enzymes. For example, (14 B = adenosine) inactivates adenylosuccinate lyase from E. coli almost completely, but has little effect on rabbit muscle AMP deaminase. The rate of hydrolysis of (14) is considerably faster than that of acetyl phosphate, suggesting intramolecular assistance by the 3 -hydroxyl group or the 3-nitrogen atom. 

For the mechanism of azolide hydrolysis under specific conditions like, for example, in micelles,[24] in the presence of cycloamyloses,[25] or transition metals,[26] see the references noted and the literature cited therein. Thorough investigation of the hydrolysis of azolides is certainly important for studying the reactivity of those compounds in chemical and biochemical systems.[27] On the other hand, from the point of view of synthetic chemistry, interest is centred instead on die potential for chemical transformations e.g., alcoholysis to esters, aminolysis to amides or peptides, acylation of carboxylic acids to anhydrides and of peroxides to peroxycarboxylic acids, as well as certain C-acylations and a variety of other preparative applications. 

Almost every major structural class discussed to date has featured at least one nonsteroidal antiinflammatory carboxylic acid. It is thus perhaps not surprising to find a dibenzoheterocycle serving as the nucleus for one of these agents, furobufen (34). Straightforward Friedel-Crafts acylation of dibenzo-furan (33) with succinic anhydride affords a mixture of 2- and 3-acylated products, with the latter predominating. The mixture is esterified with methanol, and the methyl ester of the 3-isomer is separated by fractional crystallization. Hydrolysis back to the... 

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