Nucleophiles specific base-general acid mechanisms

The mechanism shown in Scheme 3 envisions an association by hydrogen bonding between the catalyst and the carbonyl compound, followed by rate-determining attack of the nucleophile (HaO) and simultaneous transfer of the proton. The rate of this step will depend on the nature and concentration of HA, and the mechanism is consistent with general catalysis. It should be noted that the reverse process consists of a specific acid plus a general base catalysis. A possible general base catalysis mechanism is shown in Scheme 4. The reverse is a specific base plus a general acid catalysis. 

The experimental evidence favors the conclusion that in addition of nucleophiles to carbonyl groups the observed catalysis is true general acid catalysis. Table 8.2 presents selected data a decreases with increasing nucleophilicity of the addend. More specific techniques applicable to particular reactions lead to the same conclusion.27 For hydration, Mechanism I of Scheme 5, with true general acid catalysis in the forward direction and specific acid plus general base catalysis in the reverse direction, thus appears to be the most reasonable one. 

The kinetic ambiguity registered between general acid and specific acid-general base mechanisms in carbonyl addition reactions with nucleophiles (Scheme 17) is a classic mechanistic problem. ... 

In Chapter 12 (p. 263) we pointed out that even weak bases—too weak to deprotonate a nucleophile by the mechanism we have just described for SBC—can still act as catalysts. Such catalysts are known as general base catalysts, and are the promoters of a parallel kind of acid-base catalysis called general rather than specific. General base catalysis, abbreviated GBC, depends not only on pH (i.e. the concentration of hydroxide ion) but also on the concentration of other bases too. General acid catalysis, abbreviated GAC, likewise depends not only on pH (i.e. the concentration of H3O+) but also on the concentration of other undissociated acids HA. General acid-base catalysis is a milder kind of catalysis and is characteristic of reactions catalysed by enzymes in the metabolism of living things. 

The chemistry involved in the formation of mesoporous silica thin films is qualitatively well understood. However, specific reaction mechanisms of the individual steps are still debated. In addition, owing to the complexity of the sol-gel reaction pathways and cooperative self-assembly, full kinetic models have not been developed. From the time of mixing, hydrolysis reactions, condensation reactions, protonation and deprotonation, dynamic exchange with solution nucleophiles, complexation with solution ions and surfactants, and self-assembly, all occur in parallel and are discussed here. Although the sol-gel reactions involved may be acid or base catalyzed, mesoporous silica film formation is carried out under acidic conditions, as silica species are metastable and the relative rates of hydrolysis and condensation reactions lead to interconnected structures as opposed to the stable sols produced at higher pH. Silicon alkoxides are the primary silica source (tetramethyl orthosilicate, tetraethyl orthosilicate, tetrapropyl orthosilicate, etc.) and are abbreviated TMOS, TEOS, and TPOS, respectively. Starting from the alkoxide, Si(OR)4, in ROH and H2O solution, some of the general reactions are ... 

The reactions of carboxylic acids and their derivatives are summarized here. Many (but not all) of the reactions in this summary are acyl substitution reactions (they are principally the reactions referenced to Sections 17.5 and beyond). As you use this summary, you will find it helpful to also review Section 17.4, which presents the general nucleophilic addition-elimination mechanism for acyl substitution. It is instructive to relate aspects of the specific acyl substitution reactions below to this general mechanism. In some cases proton transfer steps are also involved, such as to make a leaving group more suitable by prior protonation or to transfer a proton to a stronger base at some point in a reaction, but in all acyl substitution the essential nucleophilic addition-elimination steps are identifiable. 

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