Proton loss catalysis

Proton electrochemical gradient. 6,714 Proton exchange amine ligands, 2, 24 Proton loss catalysis... 

Keto-enol tautomerism of carbon) ] compounds is catalyzed by both acids and bases. Acid catalysis occurs by protonation of the carbonyl oxygen atom to give an intermediate cation that Joses H+ from its a carbon to yield a neutral enol (Figure 22.1). This proton loss from the cation intermediate is similar to what occurs during an El reaction when a carbocation loses H+ to form an alkene (Section 11.10). 

Now that we have determined that the intermediate in electrophilic aromatic substitution is usually a a complex (see, however, p. 394), let us return to a consideration of Reaction 7.76. Two factors probably combine to cause the observed isotope effect and base catalysis. First, the strong electron-donating groups stabilize the intermediate 76 (Equation 7.77) and make departure of the proton more difficult than proton loss in many other electrophilic substitutions. [Remember, however, that k1 < k2 (see p. 386).] Second, steric interactions between the large diazonium group and the nearby substituents increase the rate... 

There have been a number of studies of the reaction of diazoacetic ester in aprotic solvents, mainly with carboxylic acids (Bronsted and Bell, 1931 Hartman et al., 1946 and references cited). However, the information available hardly justifies conclusions about the mechanism. Addition of relatively basic phenols causes an acceleration in rate which can be interpreted in terms of nucleophilic catalysis of a rate-determining displacement of nitrogen, but the kinetic order in acid varies between one and two. Formally, a mixed order would result if proton loss from the diazonium ion was effected by carboxylate ions alone, while the less discriminating displacement of nitrogen involved competition between anions and unionized molecules. However, there are examples of high or mixed orders in other acid-catalysed reactions (Bronsted and Bell, 1931 Bell, 1941 1959) and in all probability large medium effects play a role. 

Catalysis of Electrophilic Reactions by Proton Loss from a Coordinated Ligand... 

Scheme 9.36. A representation of (Brpnsted) acid catalysis of nucleophilic addition to the carbonyi of an aidehyde or ketone in which the oxygen is not lost. H-Nu is a nucleophile that is capable of proton loss to consummate the reaction B-H is a generalized (Br0nsted) acid. The use of a Lewis acid is not shown.

In terms of the final loss of aniline after ring closure, the fact that reactions using EtsN and BU3N, (ammonium ion as proton source) occurred at the same rate as the reactions with methoxide base (MeOH as proton source) suggested a lack of general acid catalysis. Also, it was found that varying the amount of available acid did not change the rate of cyclization appreciably. ... 

Chromanoxylium cation 4 preferably adds nucleophiles in 8a-position producing 8a-substituted tocopherones 6, similar in structure to those obtained by radical recombination between C-8a of chromanoxyl 2 and coreacting radicals (Fig. 6.4). Addition of a hydroxyl ion to 4, for instance, results in a 8a-hydroxy-tocopherone, which in a subsequent step gives the /zara-tocopherylquinone (7), the main (and in most cases, the only) product of two-electron oxidation of tocopherol in aqueous media. A second interesting reaction of chromanoxylium cation 4 is the loss of aproton at C-5a, producing the o-QM 3. This reaction is mostly carried out starting from tocopherones 6 or /zora-tocopherylquinone (7) under acidic catalysis, so that chromanoxylium 4 is produced in the first step, followed by proton elimination from C-5a. In the overall reaction of a tocopherone 6, a [ 1,4] -elimination has occurred. The central species in the oxidation chemistry of a-tocopherol is the o-QM 3, which is discussed in detail subsequently. 

Since the substituted hydroquinones and quinone dioximes are better electron donors than hexamethylbenzene (as established by cyclic voltammetric studies), donor-induced disproportionation (to generate NO+ NOf) is even more favored. Furthermore, either two successive one-electron oxidations of hydro-quinone (or quinone dioxime) by NO + followed by the loss of two protons from the dication or two sequential oxidation/deprotonation steps complete the oxidative transformation in equation (97). Importantly, the ready aerial oxidation of NO to NO provides the basis for the nitrogen oxide catalysis of hydroquinone (or quinone dioxime) autoxidation as summarized in Scheme 26. 

The similarity in the rate laws does not allow a clear choice to be made between mechanisms, but Mechanism A is required in H20 by the observation of general base catalysis. However, the relative stability of the (red) T° intermediate in Me2SO (this is dependent on the nature of the AA side chain, cf. Section III,C) in the absence of proton-ated amine makes us prefer Mechanism B for reaction in this solvent, since the solvent is unable to assist the departure of MeOH. The similar catalytic rate constants found for B = imidazole, Af-methylimidazole (26) suggest that transfer of the proton from T+ to the alcohol function remains stepwise (i.e., via T°) since N-methylimidazole cannot carry out a concerted transfer. Such general acid-catalyzed loss of MeOH from T° supports a suggestion made many years ago by Burnett and Davies relating to purely organic esters (62). 

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