Catalysis general-base

All the bases except hydroxide ion (SB) come under the common name general base. When the basicity of a GB is defined in terms of proton basicity, then it is 

If a reaction process is highly sensitive to [HO], the value of [HO] into the reaction mixture is generally controlled by the use of buffers. A buffer solution contains both the GB and GBH+, and experimentally attainable pH range provided by a particular buffer depends on the pK of general acid (GBH+) of buffer components. As both HO and GB have the ability to donate a pair of electrons to an electrophihc center, it is logical to believe that if the rate of a reaction is affected by [HO], then it may be also affected by [GB]. However, if the basicity of GB is much lower than that of hydroxide ion, the effect of [GB] on the reaction rate may not be detected in competition to that of the hydroxide ion. The relative effectiveness of the effects of HO and GB on reaction rate depends on both their relative basicity as well as concentration into the reaction mixture. 

3 parallels that of the corresponding aryl carboxylates [22]. Thus kH2o/o20 for ca- 

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Small amounts of salt-like addition products (85) formed by reaction on the ring nitrogen may be present in the medium. (Scheme 60) but. as the equilibrium is shifted by further reaction on the exocyclic nitrogen, the only observed products are exocyclic acylation products (87) (130. 243. 244). Challis (245) reviewed the general features of acylation reactions these are intervention of tetrahedral intermediates, general base catalysis, nucleophilic catalysis. Each of these features should operate in aminothiazoles reactivity. 

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 formation of oximes, hydrazones, and related imine derivatives is usually catalyzed by both general acids and general bases. General base catalysis of dehydration of the tetrahedral intermediate involves nitrogen deprotonation concerted with elimination of hydroxide ion. ... 

Aminolysis of esters often reveals general base catalysis and, in particular, a contribution to the reaction rate fi om terms that are second-order in the amine. The general base is believed to function by deprotonating the zwitterionic tetrahedral intermediate. Deprotonation of the nitrogen facilitates breakdown of the tetrahedral intermediate, since the increased electron density at nitrogen favors expulsion of an anion ... 

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. 

General base catalysis is catalysis by a Br nsted base acting by accepting a proton. The halogenation of ketones, a reaction discussed in Section 5.3, is general base 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. 

Finally we should note that the demonstration of a Br nsted relationship does not constitute proof that general acid or general base catalysis is occurring. Because of the problem of kinetic equivalence of rate terms, we may not be able unequivocally to distinguish between these possibilities ... 

There is also the possibility of mistaking nucleophilic catalysis for general base catalysis. Table 6-4 outlines some experimental techniques for distinguishing between these possibilities. 

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. 

FIGURE 16.12 Catalysis of nitrophenylacetate hydrolysis by imidazole—an example of general base catalysis. Proton transfer to imidazole in the transition state facilitates hydroxyl attack on the substrate carbonyl carbon. 

The first unequivocal evidence for the AE + DE mechanism came in three papers by Zollinger (1955 a-c) dealing with general base catalysis and primary kinetic hydrogen isotope effects in azo coupling reactions of various types. Three classes of reactions were identified i) reactions with no isotope effects (ArH/A D - 1.0) and no general base catalysis, ii) others with large isotope effects (k /k — 6.5) and (practically) linear base catalysis, and iii) intermediate cases with isotope effects of around 3.0 and less-than-linear base catalysis. 

The original investigations on the general base catalysis of azo coupling reactions were made with nucleophilic substrates in which the reacting carbon atom was... 

A true intramolecular proton transfer in the second step of an azo coupling reaction was found by Snyckers and Zollinger (1970a, 1970b) in the reaction of the 8-(2 -pyridyl)-2-naphthoxide ion (with the transition state 12.151). This compound shows neither a kinetic deuterium isotope effect nor general base catalysis, in contrast to the sterically similar 8-phenyl-2-naphthoxide ion. Obviously the heterocyclic nitrogen atom is the proton acceptor. 

There are two cases in which the general base catalysis observed for an azo coupling reaction is due not to a rate-limiting proton transfer from the o-complex (Scheme 12-66) but to deprotonation of the coupling component when the species involved in the substitution is formed. These reactions are shown in Schemes 12-71 H I... 

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