Mechanisms methanol carboxylation

In brief, with this mechanism the carboxylate group of Glu-270 acts as a general base to deliver nucleophilic water to the carbonyl. In the presence of methanol the first step would simply reverse. Consequently, only a second deprotonation could drive the reaction in the forward direction, and this proton transfer might well involve the hydroxyl group of Tyr-248 as a bridge between the OH and the N of the amide bond to be cleaved. This proposal has the advantage of giving a justification for the induced-fit effect mentioned earlier in this section. 

Evidence in support of the mechanism shown in figure 21.4 comes from isotope-labeling experiments. When 180-labeled methanol reacts with benzoic acid, the methyl benzoate produced is found to be l80-labeled but the water produced is uniabeled. Thus, it is the C-OH bond of the carboxylic acid that is broken during the reaction rather than the CO—H bond and the RO-H bond of the alcohol that is broken rather than the R-OH bond. 

The ionization of (E)-diazo methyl ethers is catalyzed by the general acid mechanism, as shown by Broxton and Stray (1980, 1982) using acetic acid and six other aliphatic and aromatic carboxylic acids. The observation of general acid catalysis is evidence that proton transfer occurs in the rate-determining part of the reaction (Scheme 6-5). The Bronsted a value is 0.32, which indicates that in the transition state the proton is still closer to the carboxylic acid than to the oxygen atom of the methanol to be formed. If the benzene ring of the diazo ether (Ar in Scheme 6-5) contains a carboxy group in the 2-position, intramolecular acid catalysis is observed (Broxton and McLeish, 1983). 

Methyl 2-furoate was dimethoxylated using methanol in sulfuric acid to give methyl-2,5-dihydro-2,5dimethoxy-2-furan carboxylate [70]. The reaction mechanism at the electrodes is not completely known. However, the anodic reaction is said to be the oxidation of methanol. A two-electron process is assumed and hydrogen production is observed at the cathode. 

Solutions of Ru3(CO)i2 in carboxylic acids are active catalysts for hydrogenation of carbon monoxide at low pressures (below 340 atm). Methanol is the major product (obtained as its ester), and smaller amounts of ethylene glycol diester are also formed. At 340 atm and 260°C a combined rate to these products of 8.3 x 10 3 turnovers s-1 was observed in acetic acid solvent. Similar rates to methanol are obtainable in other polar solvents, but ethylene glycol is not observed under these conditions except in the presence of carboxylic acids. Studies of this reaction, including infrared measurements under reaction conditions, were carried out to determine the nature of the catalyst and the mechanism of glycol formation. A reaction scheme is proposed in which the function of the carboxylic acid is to assist in converting a coordinated formaldehyde intermediate into a glycol precursor. 

The general mechanism for the (La3 + (-OCH3))2-catalyzed concerted process is given in Scheme 6 in which, for the sake of visual clarity, we have omitted the methanols of solvation on each La3+ as well as any associated counterions. As was proposed for the carboxylate esters, a methoxy group bound between two La3+ ions will not be sufficiently nucleophilic to attack the phosphate,60 so we propose that the... 

Before we turn to "mechanisms" let us repeat how a catalyst works. We can reflux carboxylic acids and alcohols and nothing happens until we add traces of mineral acid that catalyse esterification. We can store ethene in cylinders for ages (until the cylinders have rusted away) without the formation of polyethylene, although the formation of the latter is exothermic by more than 80 kjoule/mol. We can heat methanol and carbon monoxide at 250 °C and 600 bar without acetic acid being formed. After we have added the catalyst the desired products are obtained at a high rate. 

Aluminum porphyrins with alkoxide, carboxylate, or enolate can also activate CO2, some catalytically. For example, Al(TPP)OMe (prepared from Al(TPP)Et with methanol) can bring about the catalytic formation of cyclic carbonate or polycarbonate from CO2 and epoxide [Eq. (6)], ° - and Al(TPP)OAc catalyzes the formation of carbamic esters from CO2, dialkylamines, and epoxide. Neither of the reactions requires activation by visible light, in contrast to the reactions involving the alkylaluminum precursors. Another key difference is that the ethyl group in Al(TPP)Et remains in the propionate product after CO2 insertion, whereas the methoxide or acetate precursors in the other reactions do not, indicating that quite different mechanisms are possibly operating in these processes. Most of this chemistry has been followed via spectroscopic (IR and H NMR) observation of the aluminum porphyrin species, and by organic product analysis, and relatively little is known about the details of the CO2 activation steps. 

The stmcture of pyochelin (for a detailed bibliography, see (57)), a secondary siderophore of Pseudomonas aeruginosa and of Burkholderia cepacia was established (75) as 2-(2-o-hydroxyphenyl-2-thiazolin -yl)-3-methylthiazolidine-4-carboxylic acid. It consists of a mixture of two easily interconvertible stereoisomers (pyochelin I and II) differing in the configuration of C-2". They can be separated by chromatography, but in methanolic solution (not in DMSO) the equilibrium (ca. 3 1) is restored quickly. For a discussion of the mechanism of isomerization, see (57, 577). 

Sulfuric acid can form ester derivatives with alcohols, though since it is a dibasic acid (pAla — 3, 2) it can form both mono- and di-esters. Thus, acid-catalysed reaction of methanol with sulfuric acid gives initially methyl hydrogen sulfate, and with a second mole of alcohol the diester dimethyl sulfate. Though not shown here, the mechanism will be analogous to the acid-catalysed formation of carboxylic acid esters (see Section 7.9). 

Aspartame is relatively unstable in solution, undergoing cyclisation by intramolecular self-aminolysis at pH values in excess of 2.0 [91]. This follows nucleophilic attack of the free base N-terminal amino group on the phenylalanine carboxyl group resulting in the formation of 3-methylenecarboxyl-6-benzyl-2, 5-diketopiperazine (DKP). The DKP further hydrolyses to L-aspartyl-L-phenyl-alanine and to L-phenylalanine-L-aspartate [92]. Grant and co-workers [93] have extensively investigated the solid-state stability of aspartame. At elevated temperatures, dehydration followed by loss of methanol and the resultant cyclisation to DKP were observed. The solid-state reaction mechanism was described as Prout-Tompkins kinetics (via nucleation control mechanism). 

Likewise, a study on the bromination of these compounds also indicated that the 1,3-addition was 100% syn stercospecific.10 Interestingly, 3-phenylbicyclo[1.1.0]butane-l-carbonitrile, from which a relatively stable benzylic cation can be formed, yielded a mixture of cis- and /ram-products.10 An electron-transfer mechanism has been proposed for these reactions.10 A recent investigation on perchloric acid catalyzed methanol addition to 3-methylbicyclo[1.1.0]butane-1-carbonitrile and methyl 3-mcthylbicyclo[1.1.0]butane-l-carboxylate, however, showed that mixtures of irons- and cA-cyclobutanes were generated, with the m-isomers predominating.11... 

The metal carboxylate insertion mechanism has also been demonstrated in the dicobaltoctacarbonyl-catalyzed carbomethoxylation of butadiene to methyl 3-pentenoate.66,72 The reaction of independently synthesized cobalt-carboxylate complex (19) with butadiene (Scheme 8) produced ii3-cobalt complex (20) via the insertion reaction. Reaction of (20) with cobalt hydride gives the product. The pyridine-CO catalyst promotes the reaction of methanol with dicobalt octacarbonyl to give (19) and HCo(CO)4. 

The transition metal carboxylate mechanism (Scheme 10), illustrated with palladium, requires the generation of this type of complex in the initial steps. This can occur by the alcoholysis of dicobalt octacarbonyl (Scheme 6) or by, for example, the reaction of methanol with a palladium(II) carbonyl (equa-... 

Deng and co-workers have also applied the cinchona derivatives to the kinetic resolution of protected a-amino acid N-carboxyanhydrides 51 [48]. A variety of alkyl and aryl-substituted amino acids may be prepared with high se-lectivities (krei=23-170, see Scheme 10). Hydrolysis of the starting material, in the presence of the product and catalyst, followed by extractive workup allows for recovery of ester, carboxylic acid, and catalyst. The catalyst may be recycled with little effect on selectivity (run 1, krei=114 run 2, krei=104). The reaction exhibits first-order dependence on methanol and catalyst and a kinetic isotope effect (A MeOH/ MeOD=l-3). The authors postulate that this is most consistent with a mechanism wherein rate-determining attack of alcohol is facilitated by (DHQD)2AQN acting as a general base. 5-Alkyl 1,3-dioxolanes 52 may also... 

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