Exchange reactions, base catalyzed mechanism

A completely symmetrical system in which the mechanism can be fully described is the ethanolysis of ethyl trifluoroacetate (Johnson, 1964). This exchange reaction is catalyzed by general bases. Ofthemany possible general base-catalyzed schemes listed in Table 1, only two are possible which include a tetrahedral intermediate since the reactants are equal to the products. These two paths are the general base path which involves the anionic tetrahedral intermediate (path A) and the specific... 

The reaction takes place extremely rapidly, and if D2O is present in excess, all the alcohol is converted to ROD. This hydrogen-deuterium exchange can be catalyzed by either acids or bases. If D30 is the catalyst in acid solution and DO the catalyst in base, write reasonable reaction mechanisms for the conversion of ROH to ROD under conditions of (a) acid catalysis and (b) base catalysis. 

Fig. 9.2. Simplified reaction mechanisms in the hydrolytic decomposition of organic nitrites. Pathway a Base-catalyzed hydrolysis with liberation of nitrite. Pathway b Reversible nitro-syl exchange between organic nitrites and alcohols. Pathway c General acid catalysis with concerted mechanism in the acid hydrolysis of organic nitrites.

The V(IV)-H20 exchange is catalyzed by V(V) (Prob. 5(a)). The enhanced reactivity for the base form is observed in dimerization, substitution and redox reactions (below). The mechanism of substitution of remains uncertain. One of the problems is to assess the contribution of the highly reactive VO(OH)+. Rate constants for complexing by VO + are all = lO M s, Ref. 35, consistent with an/ mechanism. By using chelating ligands to tie up... 

This analogy is plausible on energetic grounds, since the decreased base strength of the proton acceptor should be approximately compensated by the increased acid strength of the proton donor. In view of the different species involved, however, it is reasonable to expect appreciable differences in the configurations of the transition states and hence in the activation barriers for the two paths. Therefore, the failure to observe an acid-catalyzed exchange reaction cannot be taken as conclusive evidence in favor of the alternative (hydride ion) mechanism. 

Analogous parahydrogen conversion and deuterium exchange reactions, catalyzed by NH2, have been observed in liquid ammonia (Wilmarth and Dayton, 61). The kinetics are of the same form as those of the OH -cat-alyzed reaction in water and the mechanism is open to similar interpretations. The NH2 -catalyzed reaction is much faster, its rate constant at —50° being 10 times that of the OH -catalyzed reaction at 100°. The assumption of equal frequency factors for the two reactions leads to a calculated activation energy for the NH2 -catalyzed reaction of about 10 kcal. This low value has been attributed to the much greater base strength of NH2 relative to OH . The results provide some support for the hydride ion mechanism. 

The mechanism for the bond cleavages indicated in figure 10.1b was clarified by Ronald Breslow. In one of the earliest applications of nuclear magnetic resonance to biochemical mechanisms, he demonstrated that the proton bonded to C-2 in the thiazolium ring is readily exchangeable with the protons of H20 and deuterons of D20 in a base-catalyzed reaction... 

Because of the simplicity of the chemical systems involved, the reaction mechanism of these base-catalyzed activations of hydrogen should be particularly susceptible to determination. Wilmarth and his coworkers established that the rate of activation is proportional to concentration of base (OH- or NH2-). Although they did not establish that the rate is first order with respect to hydrogen, it is probable that this is so. (Because, in the absence of complications, every exchange reaction is apparently first order during any single experiment, it is necessary to vary the initial concentration to establish the true order.)... 

The one-base mechanism is characterized by the retention of the substrate-derived proton in the product (internal retum).30) With this criterion, reactions catalyzed by a-amino-c-caprolactam racemase,323 amino acid racemase of broad specificity from Pseudomonas striata333 have been considered to proceed through the one-base mechanism. However, such internal returns were not observed in the reactions of alanine racemases from K coli B,33) B. stearothermophilus,263 and S. typhirmaium (DadB and /1/r).263 The internal return should not be observed in the two-base mechanism, because the base catalyzing the protonation to the intermediate probably obtains the proton from the solvent. But the failure of the observation of the internal return can be also explained by the single-base mechanism in which exchange of the proton abstracted from the substrate a-carbon with the solvent is much faster than its transfer to the a-carbanion. Therefore, lack of the internal return does not directly indicate the two-base mechanism of the alanine racemase reaction. 

Replacement of hydrogen in an aromatic ring by lithium is an electrophilic substitution, entry of lithium taking place in the second and fast step of the reaction the reaction mechanism parallels that for base-catalyzed hydrogen exchange. Since the most acidic hydrogen is replaced,... 

Supporting evidence for the mechanism comes from the observation that the bromination and iodination proceed at the same rates. The deuterium exchange is also comparable in absolute rate. Very extensive work with the optically active sec-butyl phenyl ketone, C2H5—CH(CH3)COC6H6, has shown that the acid-catalyzed iodination, bromination, and inversion have identical rates. The base-catalyzed, OD, rates of deuteration and inversion have also been shown to be equal. If the enol and enolate ion can be considered to be planar about the a carbon atom, then these results provide very strong support for the slow enolization step. In fact it is difficult to find any other reasonable interpretation of the data. The enol mechanism is also compatible with the well-known susceptibility of H atoms, in the alpha position to one or more C==0 groups, to substitution reactions. 

The interchange of the stereochemically significant sec-NH proton in (20) (21) (inversion) or (22) — (23) (isomerization) is a base-catalyzed process and takes place via a deprotonation-protonation mechanism. This interchange is one of the simplest types of reaction of a coordinated ligand , and proton exchange rates have been measured for quite a number of inert transition metal-amine complexes. With suitable central metals (Pt ) or ligands,the deprotonated intermediates can be isolated and characterized. Other reactions of coordinated amine ligands will be considered in Section 7. 

When a base catalyzed reaction with proton transfer in the first step is carried out in D20 solution, the substrate exchanges its acidic hydrogen with the deuterium of the solvent before the reaction takes place if the mechanism is fast pre-equilibrium proton transfer with subsequent slow step. If, on the other hand, hydrogen exchange does not occur prior to the reaction, it may be concluded that proton transfer is the rate-determining step. 

The reaction of acylimidazoles with imidazole is subject to both imidazole and imidazolium ion catalysis (Fife, 1965). The latter reaction is no doubt due to the imidazole-catalyzed hydration of acetylimidazolium ion, as in 18, and fully analogous to the N-methylimidazole-catalyzed hydrolysis of N-acetyl,N -methylimidazolium ion. The mechanism of the former reaction is undefined at the present time, since no 0 exchange studies have been performed with acylimidazoles in more alkaline solution where imidazole catalysis occurs. The leaving group, the imidazole anion, is quite basic (piC = 14-5) therefore it is possible that general base-catalyzed decomposition of the neutral tetrahedral intermediate (24) or general acid-assisted decomposition of the anionic tetrahedral intermediate (25) may occur. The general base-catalyzed alkaline hydrolysis of amides most probably occurs by the... 

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