Anhydride intermediate

AijAT-dicyclohexylcarhodiimide (DCC) also leads to essentially quantitative conversion of amic acids to isoimides, rather than imides (30,31). Combinations of trifluoroacetic anhydride—triethjlarnine and ethyl chi oroform a te—triethyl amine also result in high yields of isoimides (30). A kinetic study on model compounds has revealed that isoimides and imides are formed via a mixed anhydride intermediate (12) that is formed by the acylation of the carboxylic group of amic acid (8). 

Fig. 2. Cyclization of amic acid to imides or isoimides via (12). Formation of the mixed anhydride intermediate (12) is shown in text.

More recent processes involving the oxidation of butane to a maleic anhydride intermediate, using both fixed-bed and fluidized-bed processes, have been commercialized. The maleic anhydride is subsequently hydrolyzed to maleic acid or esterified in the presence of methanol to dimethyl maleate, which can be reduced to BDO in the presence of hydrogen and catalyst. These processes are attractive due to the low cost of the butane feedstock. The method of choice to make BDO is often dictated by the local availability of the desired chemical feedstock. 

On the alloy surface the reaction proceeded both via the anhydride and formate intermediates (117). As the copper concentration was increased, the formate species dominated the reaction, until at 63% copper the CO/COj ratio was less than 0.1. This change was due to the decrease in the amount of anhydride formed with increasing copper and the corresponding increase in formate. Since only the anhydride decomposition produced CO, the relative amount of anhydride formed could be determined as a function of surface composition. This relationship is shown in Fig. 21 the anhydride concentration fell as the fourth power of the nickel concentration, suggesting the requirement of four nickel atoms for its stabilization. This value agreed with the earlier determination for the saturation density of anhydride intermediates on Ni(llO) (99). 

The decomposition of acetic acid was studied by TRPS in order to determine the similarities of its surface reactivity to formic acid. Reactions on Fe(100) (95), Ni(llO) 118), and Cu/Ni(110) (100) alloys were studied. On Ni(l 10) acetic acid adsorbed at 300 K with a sticking probability near unity to form the anhydride intermediate and release HjO. The decomposition of this intermediate proceeded by the two-dimensional autocatalytic process observed for formic acid to yield CO2,, CO, and surface carbon. The rate... 

Following earlier studies of the oxidation of formic and oxalic acids by pyridinium fluoro-, chloro-, and bromo-chromates, Banerji and co-workers have smdied the kinetics of oxidation of these acids by 2, 2Tbipyridinium chlorochromate (BPCC) to C02. The formation constant of the initially formed BPCC-formic acid complex shows little dependence on the solvent, whilst a more variable rate constant for its decomposition to products correlates well with the cation-solvating power. This indicates the formation of an electron-deficient carbon centre in the transition state, possibly due to hydride transfer in an anhydride intermediate HCOO—Cr(=0)(0H)(Cl)—O—bpyH. A cyclic intermediate complex, in which oxalic acid acts as a bidentate ligand, is proposed to account for the unfavourable entropy term observed in the oxidation of this acid. 

Lipscomb has commented that glutamic acid-245 might act either as a general base or a nucleophile. The available mechanistic information has been reviewed by Kaiser and Kaiser (1972), who postulated that the carboxylate anion of glutamic acid-245 acts as a nucleophile forming an anhydride intermediate [equation (29)]. The divergent D2O solvent isotope effects, =... 

The pH-rate constant profile for hydrolysis of phthalamic acid showed participation by the undissociated carboxyl group, and an anhydride intermediate was detected (Bender, 1957 Bender et al., 1958b). Hydrolysis was 10 times faster than in the case of p-carboxybenzamide. A four-center mechanism [58] was postulated. 

In 1993, another immunoassay for the detection of monensin was developed but, unfortunately, was never applied to biological material (91). Quite recently a competitive ELISA and a compatible extraction procedure suitable for screening monensin in poultry liver samples was described (92). In this assay, a polyclonal antiserum raised against a monensin-transferrin conjugate and prepared via an acid anhydride intermediate (93) was used. Significant cross-reactivity with other polyethers commonly used by the broiler industry, such as maduramicin, lasalocid, salinomycin, and narasin, was not found. A detection limit of 3 ppb could be readily attained when liver samples were submitted to extraction with aqueous acetonitrile, partitioning between aqueous sodium hydroxide solution and a hexane-diethyl either mixture, evaporation of the organic phase, and reconstitution in ethanol/sodium acetate solution. 

One possible mechanism for the hydrolysis of peptides or esters by carboxypeptidase A involves two steps with an anhydride (acyl-enzyme) intermediate.418 In the first step, the zinc(II) activates the substrate carbonyl group towards nucleophilic attack by a glutamate residue, resulting in the production of a mixed anhydride (127). Breakdown of the anhydride intermediate is rate determining with some substrates.419 An understanding of the chemistry of metal ion effects in anhydride hydrolysis is therefore of fundamental importance in regard to the mechanism of action of the enzyme. Until recently there have been few studies of metal ion-catalysed anhydride solvolysis. 

The rearrangement of the /V-phosphinoyl-O-sulfonylhydroxylarninc (268) (with 57% enrichment with one 180 atom in the SO2 group) to the sulfonamide (269) (43.7% enriched with one 180 atom) occurs with Bu NH2 in dichloromethane via the phosphonamidic-sulfonic anhydride intermediate (270).245 The rearrangement of the O-phosphinoyl compound (271) with /-butoxide gives the phosphonamidic-phosphinic... 

Thus, the collapse of the tetrahedral adduct to the mixed anhydride intermediate is determined purely by rotation around a single C-0 bond of the tetrahedral species formed after substrate binding. The above authors have suggested that the torsional distortion of the substrate by the sites of secondary recognition provides the mechanical driving force that causes the required bond rotation to convert 50 into 51. This interpretation is supported by inspection of molecular models. 

The same authors have also pointed out that the experimental results of others suggest that, with peptide substrates, the kinetics are different as the formation of the mixed anhydride intermediate is rate determining. 

Conformer 50 has the proper electron pair orientation to break down to give either the free ester substrate and the enzyme (cf 49) or the mixed anhydride intermediate 52. The former process is however highly favored over, the latter because (a) a carboxylate group is a much better leaving group than an alkoxy group and (b) the electron pair of an alkoxy group (RO—) is... 

Reactions between a representative range of alkyl- and aryl-amines and of aliphatic and aromatic acids showed that the direct formation of amides from primary amines and carboxylic acids without catalyst occurs under relatively low-temperature conditions (Scheme 1). The best result obtained was a 60% yield of N-bcnzyl-4-phenylbutan-amide from benzylamine and 4-phenylbutanoic acid. For all these reactions, an anhydride intermediate was proposed. Boric and boronic acid-based catalysts improved the reaction, especially for the less reactive aromatic acids, and initial results indicated that bifunctional catalysts showed even greater potential. Again, anhydride intermediates were proposed, in these cases mixed anhydrides of carboxylic acids and arylboronic acids, e.g. (I).1... 

The reaction of phthalic anhydride with 1,3,4,6-tetra-0-acetyl-2-amino-2-deoxy-D-glucose leads to the formation of the expected A-phthaloyl amide or phthalamic acid. Furthermore, intramolecular condensation occurs, presumably by way of a mixed anhydride intermediate, on treating this with ethyl chloroformate, thereby forming an A,A-phthaloyl imide, 1,3,4,6-tetra-0-acetyl-2-deoxy-2-phthalimido-D-glucose.105 106 The 2-amino-2-deoxy-D-glucose derivative can be regenerated by the action of hydrazine.69 107... 

Deslongchamps (1983) conducted his analysis in terms of mechanism (i), assuming that there was a covalent anhydride intermediate and that the substrate carbonyl was coordinated to the active-site Zn2 +. Subsequent work has shown these assumptions to be questionable. 

The X-ray structures of enzyme and enzyme-inhibitor complexes permit the anhydride intermediate only in the case of carboxypeptidase, not in the case of thermolysin, since in this enzyme the catalytic Glu-143 is too far away from the substrate carbonyl (Lipscomb, 1983). The proposal that carboxypeptidase works via an anhydride intermediate thus requires the supposition that two very similar enzymes work by different mechanisms. 

A more serious objection is that the evidence for an anhydride intermediate is based upon observation of a transient phase during the hydrolysis of an ester intermediate under cryoenzymological conditions, i.e. at low temperature and in the presence of an organic cosolvent (Makinen et al., 1979). No evidence was obtained by these workers as to the molecular nature of the transient, but subsequently Hoffman et al. (1983) examined the system by multichannel resonance Raman spectroscopy. The characteristic carbonyl stretching frequency of an anhydride should have been detected by their experiments, but was not. Kuo and Makinen (1985), however, re-... 

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