Catalysis general-acid

The reaction is said to be subject to general acid catalysis because adds in general, not just H, catalyze the reaction. If more than one add is available to transfer protons, then the rate is a summation of the individual rates from the acid catalysis of all of the acids present (equation 7.42).  

The second process leading to general acid catalysis involves fast initial proton transfer from AH to S (equation 7.43), followed by rate-limiting 

Bunnett (reference 91, p. 317) noted that it is doubtful whether any major chemical phenomena have been blessed with names more confusing than specific oxonium ion catalysis and general acid catalysis.  

A similar treatment for base-catalyzed reactions can be used to develop corresponding equations for specific base catalysis. Again, the terms specific hydroxide ion catalysis in water or specific lyate ion catalysis in another solvent (e.g., CHsO in methanol) may be used for greater precision. (See reference 91.) 

In the latter case, the proton transfer may be concerted with some other bonding change in the substrate. For example, see Capon, B. Nimmo, K, /. Chem. Soc. Perkin Trans. 2 1975,1113. 

In the presence of acidic media, organic molecules can undergo a wide range of transformations. The specific case of electrophilic aromatic substitution catalysed by acids, i.e. Friedel-Crafts catalysis, will be discussed at length in a later section. However, the diversity of industrial reactions 

Many typical acid promoted reactions involve the use of strong Brons-ted acids which, whilst cheap and effective, cause considerable handling problems due to their intensely corrosive nature. These problems can be surmounted if solid acids are used. Solid acids such as zeolites have been used for many years in the petrochemical industry, but their use in the fine chemical industry is not yet widespread. The following section will outline two classes of solid acids, and present a few of their applications. 

This is obviously a situation where shape selectivity is required, and the steric constrains of the pores in a zeolite framework can be utilised effectively. The use of K-zeolite L in dichloromethane at 40°C will selectively produce the required isomer in 96% yield, compared to a disappointing 9% selectivity for iron(III) chloride under the same conditions [12]. Being heterogeneous, the zeolite can be recovered and reused via simple filtration. 

Other liquid phase applications of zeolites on the laboratory scale have been reported, including a shape selective /7flr -acylation of toluene with carboxylic acids [15], and the production of 4,4 -diisopropylbiphenyl from biphenyl and propene is catalysed by the naturally occurring zeolite, mor-denite [16]. The latter reaction shows similar pore-imposed selectivity to the chlorination of biphenyl mentioned above. 

Nucleophilic participation by the neighbouring acetamido-group in the substrate has also been postulated, but substrates lacking this group have been developed which give enzymatic rates (Raftery and Rand-Meir, 1968). It is therefore not necessary to invoke such participation to explain the rates attained with the enzyme. 

The binding site of lysozyme will accommodate six hexose residues (A-F). The carboxyl groups of glutamic acid-35 and aspartic-52 are located between sites D and E. The lactyl groups at C-3 of the NAM residues cannot fit in sites A, C, and E. Therefore NAM residues must be located at sites B and D. Cleavage occurs at the reducing end of the NAM residue in site D (the bond being broken is between residues D and E). 

In addition to x-ray elucidation of the structure of the crystalline enzyme, the structure of a crystalline complex of lysozyme and tri(N-acetylglucosamine) was determined (Phillips, 1966). The trisaccharide occupied sites A, B, and C. Assuming that binding of a hexamer (adding hexose residues D, E, and F) would not change the conformation of the enzyme, the conformations of the substrate at 

At the time the mechanism shown in [60] was proposed it was not known whether it was even chemically reasonable. Bimolecular general acid catalysis involving proton transfer in the transition state [equation (45)] had never been observed in the hydrolysis of glycosides or simple acetals. Bronsted and Wynne-Jones (1929) had 

Prior to 1967 acetal hydrolysis had been found to be a specific-acid catalysed reaction with the accepted mechanism [equation (46)] involving fast pre-equilibrium protonation of the acetal by hydronium ion, followed by unimolecular rate-determining decomposition of the protonated intermediate to an alcohol and a resonance stabilized carbonium ion (Cordes, 1967). An A-l mechanism was supported by an extremely large body of evidence, but it appeared unlikely that such a mechanism could explain the 

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The sulfonated resin is a close analogue of -toluenesulfonic acid in terms of stmcture and catalyst performance. In the presence of excess water, the SO H groups are dissociated, and specific acid catalysis takes place in the swelled resin just as it takes place in an aqueous solution. When the catalyst is used with weakly polar reactants or with concentrations of polar reactants that are too low to cause dissociation of the acid groups, general acid catalysis prevails and water is a strong reaction inhibitor (63). 

The role that acid and base catalysts play can be quantitatively studied by kinetic techniques. It is possible to recognize several distinct types of catalysis by acids and bases. The term specie acid catalysis is used when the reaction rate is dependent on the equilibrium for protonation of the reactant. This type of catalysis is independent of the concentration and specific structure of the various proton donors present in solution. Specific acid catalysis is governed by the hydrogen-ion concentration (pH) of the solution. For example, for a series of reactions in an aqueous buffer system, flie rate of flie reaction would be a fimetion of the pH, but not of the concentration or identity of the acidic and basic components of the buffer. The kinetic expression for any such reaction will include a term for hydrogen-ion concentration, [H+]. The term general acid catalysis is used when the nature and concentration of proton donors present in solution affect the reaction rate. The kinetic expression for such a reaction will include a term for each of the potential proton donors that acts as a catalyst. The terms specific base catalysis and general base catalysis apply in the same way to base-catalyzed reactions. 

The experimental detection of general acid catafysis is done by rate measurements at constant pH but differing buffer concentration. Because under these circumstances [H+] is constant but the weak acid component(s) of the buffer (HA, HA, etc.) changes, the observation of a change in rate is evidence of general acid catalysis. If the rate remains constant, the reaction exhibits specific acid catalysis. Similarly, general base-catalyzed reactions show a dependence of the rate on the concentration and identity of the basic constituents of the buffer system. 

Several situations can lead to the observation of general acid catalysis. General acid catalysis can occur as a result of hydrogen bonding between the reactant R and a proton donor D—H to form a reactive complex D—H—R which then reacts with a substance Z ... 

Under these circumstances, a distinct contribution to the overall rate will be seen for each potential hydrogen-bond donor D—H. General acid catalysis is also observed when a ratedetermining proton transfer occurs fiom acids other than the solvated proton ... 

A kinetic expression which is equivalent to that for general acid catalysis also occurs if a prior equilibrium between reactant and the acids is followed by rate-controlling proton transfer. Each individual conjugate base will appear in the overall rate expression ... 

Notice that specific acid catalysis describes a situation in which the reactant is in equilibrium with regard to proton transfer, and proton transfer is not rate-determining. On the other hand, each case that leads to general acid catalysis involves proton transfer in the rate-determining step. Because of these differences, the study of rates as a function of pH and buffer concentrations can permit conclusions about the nature of proton-transfer processes and their relationship to the rate-determining step in a reaction. 

Alkenes lacking phenyl substituents appear to react by a similar mechanism. Both the observation of general acid catalysis and the kinetic evidence of a solvent isotope effect are consistent with rate-limiting protonation with simple alkenes such as 2-metlQ lpropene and 2,3-dimethyl-2-butene. 

In agreement with expectation for a rate-determining proton transfer, the reaction shows general acid catalysis. Base-catalyzed ketonization occurs by C-protonation of the enolate. 

Both specific acid catalysis and general acid catalysis can be observed. (Review Section 4.8 for the discussion of specific and general acid catalysis.)... 

Scheme 8.1. Acetals and Ketals That Exhibit General Acid Catalysis in Hydrolysis...

There is an intermediate mechanism between these extremes. This is a general acid catalysis in which the proton transfer and the C—O bond rupture occur as a concerted process. The concerted process need not be perfectly synchronous that is, proton transfer might be more complete at the transition state than C—O rupture, or vice versa. These ideas are represented in a three-dimensional energy diagram in Fig. 8.1. 

General acid catalysis of the breakdown of the carbinolamine intermediate occurs by assistance of the expulsion of water. 

The transition state for the rapid hydrolysis of the monoanion has been depicted as involving an intramolecular general acid catalysis by the carboxylic acid group, with participation by the anionic carboxylate group, which becomes bound at the developing electrophilic center... 

A mixed acetal of benzaldehyde, methanol, and salicylic acid has also been studied. It, too, shows a marked rate enhancement attributable to intramolecular general acid catalysis ... 

Hydrolysis of aspirin in H2 0 leads to no incorporation of into the product salicylic acid, ruling out the anhydride as an intermediate and thereby excluding mechanism 1. The general acid catalysis of mechanism III can be ruled out on the basis of failure of other nucleophiles to show evidence for general acid catalysis by the neighboring carboxylic acid group. Because there is no reason to believe hydroxide should be special in this way, mechanism III is eliminated. Thus, mechanism II, general base catalysis of hydroxide-ion attack, is believed to be the correct description of the hydrolysis of aspirin. 

The relative importance of the potential catalytic mechanisms depends on pH, which also determines the concentration of the other participating species such as water, hydronium ion, and hydroxide ion. At low pH, the general acid catalysis mechanism dominates, and comparison with analogous systems in which the intramolecular proton transfer is not available suggests that the intramolecular catalysis results in a 25- to 100-fold rate enhancement At neutral pH, the intramolecular general base catalysis mechanism begins to operate. It is estimated that the catalytic effect for this mechanism is a factor of about 10. Although the nucleophilic catalysis mechanism was not observed in the parent compound, it occurred in certain substituted derivatives. 

The acid-catalyzed hydrolysis of 2-alkoxy-2-phenyl-l,3-dioxolanes has been studied. The initial step is rate-determining under eertain eonditions and is deseribed by the rate law given below, whieh reveals general acid catalysis. 

Derive the general expression for the observed rate constant for hydrolysis of A as a function of pH. Assume, as is the case experimentally, that intramolecular general acid catalysis completely outweighs intermolecular catalysis by hydronium ion in the pH range of interest. Does the form of your expression agree with the pH rate profile given for this reaction in Fig. 8.6 (p. 489) ... 

General acid catalysis is a catalysis by a Br(4nsted acid (other than the lyonium ion) acting by donating a proton. The addition of thiols to the carbonyl group is general acid catalyzed. ... 

The rate equation for this reaction is expected to be v = A [RCOOR [MeNH2], but it is possible for terms like A [RCOOR ][MeNH2] or A "[RCOOR ] [MeNH2j[MeNH3 ] to be present. The k term could be a general base catalysis or nucleophilic attack, the k" term, general acid catalysis of nucleophilic attack. 

I, pp. 162-8 jencks PP- uses the selectivity—reactivity relationship between Br nsted slopes and nucleophilic reactivity to distinguish between general acid catalysis and specific acid—general base catalysis. 

On the basis of the above, the rate acceleration afforded by lysozyme appears to be due to (a) general acid catalysis by Glu (b) distortion of the sugar ring at the D site, which may stabilize the carbonium ion and the transition state) and (c) electrostatic stabilization of the carbonium ion by nearby Asp. The overall for lysozyme is about 0.5/sec, which is quite slow (Table... 

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. ... 

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