Mechanisms of Acid-Base Catalyzed Reactions

It is important to ask why acids catalyze some reactions, that is, how the proton donor enters the mechanism. Also, we shall explore why some reactions show specific catalysis and others general. 

A simple scheme illustrates some of the possibilities. In it, A is the substrate, P the product, and BH+ the catalyst. The reactions are 

The ratio of [BH+]/[B] is controlled by the equilibrium condition, and so the rate law becomes 

The reaction shows only specific acid catalysis under this condition. Even if acids other than H+ are present, they will alter the velocity only insofar as they change [H+]. That is, the concentration of the reactive species, [AH1 ], depends only upon [H+], irrespective of the acids that supply it. 

Similar treatments of base catalysis are left as an exercise (Problem 10-13). There is for specific base catalysis an additional mechanism, known as nucleophilic catalysis. 

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Investigation of the mechanisms of acid- base catalyzed reactions 3.1 TYPES OF MECHANISM AND NOMENCLATURE... 

Survey of mechanisms of acid—base catalyzed reactions 5.1 MECHANISMS OF ACID CATALYSIS... 

While Baker and Gaunt postulate that the mechanism of the base-catalyzed reaction of isocyanates and alcohols involves the attack of the isocyanate-base complex by the alcohol, according to Iwakura and Okada the higher acidity of the active hydrogen containing compounds changes... 

As in the case of the base-catalyzed reaction, the thermodynamically most stable alkene is the one predominantly formed. However, the acid-catalyzed reaction is much less synthetically useful because carbocations give rise to many side products. If the substrate has several possible locations for a double bond, mixtures of all possible isomers are usually obtained. Isomerization of 1-decene, for example, gives a mixture that contains not only 1-decene and cis- and franj-2-decene but also the cis and trans isomers of 3-, 4-, and 5-decene as well as branched alkenes resulting from rearrangement of carbocations. It is true that the most stable alkenes predominate, but many of them have stabilities that are close together. Acid-catalyzed migration of triple bonds (with allene intermediates) can be accomplished if very strong acids (e.g., HF—PF5) are used. If the mechanism is the same as that for double bonds, vinyl cations are intermediates. 

As catalyzed reactions are multistep processes, kinetic studies must be concerned with the exploration of the mechanism and the evaluation of the rate-determining step. The methods of finding the rate-determining step are particularly well developed for acid-base catalyzed reactions [3, 4]. They will be extensively discussed in this article. 

The complex then reacts with the alcohol in a manner similar to that postulated by the Baker mechanism for the base-catalyzed reaction. The kinetics involving this square root law is not valid for the cupric acetate-or zinc naphthenate-catalyzed reaction of these tertiary isocyanates. It seems that metal salts of strong acids and of weak acids conform to different mechanisms. 

The mechanism is presumed to involve a pathway related to those proposed for other base-catalyzed reactions of isocyanoacetates with Michael acceptors. Thus base-induced formation of enolate 9 is followed by Michael addition to the nitroalkene and cyclization of nitronate 10 to furnish 11 after protonation. Loss of nitrous acid and aromatization affords pyrrole ester 12. 

Active Figure 21.8 MECHANISM Mechanism of acid-catalyzed ester hydrolysis. The forward reaction is a hydrolysis the back-reaction is a Fischer esterification and is thus the reverse of Figure 21.4. Sign in afwww.thomsonedu.com to see a simulation based on this figure and to take a short quiz. 

Metal-catalyzed hydrophosphination has been explored with only a few metals and with a limited array of substrates. Although these reactions usually proceed more quickly and with improved selectivity than their uncatalyzed counterparts, their potential for organic synthesis has not yet been exploited fully because of some drawbacks to the known reactions. The selectivity of Pt-catalyzed reactions is not sufficiently high in many cases, and only activated substrates can be used. Lanthanide-catalyzed reactions have been reported only for intramolecular cases and also sulfer from the formation of by-products. Recent studies of the mechanisms of these reactions may lead to improved selectivity and rate profiles. Further work on asymmetric hydrophosphination can be expected, since it is unlikely that good stereocontrol can be obtained in radical or acid/base-catalyzed processes. 

Therefore, the base-catalyzed reaction of isobutylene yields the same dimer as the acid-catalyzed reaction although the mechanisms are completely different. Since olefin isomerizations are also catalyzed under these conditions, an equilibrium distribution of products is expected for example, the reaction of isobutylene yields 78% of 2,4,4-trimethyl-l-pentene and 22% of 2.4,4-trimethyl-2-pentene. 

In another DFT study devoted to the reaction mechanism of FeIV=0-catalyzed hydroxylation of L-Phe, the gas-phase cluster model was based on the X-ray crystal structure of the catalytic domain of hPAH containing ferric iron (hPAH-Fe111) (PDBid 1PAH (97)) (119). The water molecule distal to His290 was replaced by the oxo-ligand and only ligands of the first coordination sphere were included in the model. The amino acid residues were truncated in the model to include the side chains only. This model was also used as the QM part in a QM/MM study of the hydroxylation of L-Phe. In the latter study, the MM part included the complete catalytic domain (119). 

Neutral Hydrolysis. We finish our discussion of the major hydrolysis mechanisms of carboxylic acid esters by looking at the neutral (pH independent) reaction at the carbonyl carbon. From the reaction scheme given in Fig. 13.12, we see that, very similar to what we have postulated for the base-catalyzed reaction, the dissociation... 

Note that the reaction at the phosphorus atom is postulated to occur by an SN2 (no intermediate formed) rather than by an addition mechanism such as we encountered with carboxylic acid derivatives (Kirby and Warren, 1967). As we learned in Section 13.2, for attack at a saturated carbon atom, OH- is a better nucleophile than H20 by about a factor of 104 (Table 13.2). Toward phosphorus, which is a harder electrophilic center (see Box 13.1), however, the relative nucleophilicity increases dramatically. For triphenyl phosphate, for example, OH- is about 108 times stronger than H20 as a nucleophile (Barnard et al., 1961). Note that in the case of triphenyl phosphate, no substitution may occur at the carbon bound to the oxygen of the alcohol moiety, and therefore, neutral hydrolysis is much less important as compared to the other cases (see /NB values in Table 13.12). Consequently, the base-catalyzed reaction generally occurs at the phosphorus atom leading to the dissociation of the alcohol moiety that is the best leaving group (P-0 cleavage), as is illustrated by the reaction of parathion with OH ... 

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