Catalysis, continued nucleophilic

The term acid catalysis is often taken to mean proton catalysis ( specific acid catalysis ) in contrast to general acid catalysis. In this sense, acid-catalyzed hydrolysis begins with protonation of the carbonyl O-atom, which renders the carbonyl C-atom more susceptible to nucleophilic attack. The reaction continues as depicted in Fig. 7. l.a (Pathway a) with hydration of the car-bonium ion to form a tetrahedral intermediate. This is followed by acyl cleavage (heterolytic cleavage of the acyl-0 bond). Pathway b presents an mechanism that can be observed in the presence of concentrated inorganic acids, but which appears irrelevant to hydrolysis under physiological conditions. The same is true for another mechanism of alkyl cleavage not shown in Fig. 7.Fa. All mechanisms of proton-catalyzed ester hydrolysis are reversible. 

Typical phase transfer catalysis in liquid-liquid systems combines processes in which Na+ or K+ salts of inorganic and organic anions derived from strong adds (phenolates, thiolates, carboxylates, etc.) are continuously transferred from aqueous (often alkaline) solutions to the organic phase by the phase transfer catalysts. Applications include nucleophilic substitution, addition, elimination, oxidation, and reduction reactions. 

Rate coefficients of hydrolysis and other nucleophilic reactions of epoxides have been measured by various authors (49, 150—154]. The data are reviewed insofar as they are of interest with respect to acid—base catalysis. Measurements have been done mainly by the dilatometric method or by continuous titration of the base formed in the reaction. Table 9 contains rate coefficients, referring to rate eqn. (44), and... 

The catalytic mechanism of the pyrimidine-5 methylation in nucleic acids is more complex as it involves covalent catalysis. The mechanism is common for numerous DNA/RNA cytosine and uracil MTases as well as for thymidylate synthase (although the latter uses tetrahydrofolic acid as the methyl donor) and has been studied in detail in several systems (50). Here, the cytosine-5 methylation in DNA is presented as an example (see Fig. 4a). The C5-position of cytosine, which is part of an aromatic ring, does not carry sufficient nucleophilicity for a direct methyl group transfer. The continuity of the aromatic system is disrupted by a nucleophilic attack of thiolate (from a conserved... 

GBUERAL BASE AND NUCLEOPHILIC CATALYSIS 246 Table 1—continued... 

Fig. 10.4 (continued) tide bond cleavage. In the cysteine (and also serine and threonine) proteases, the nucleophile is the protease type amino acid (in this case cysteine) which forms a covalent bond with the carbon atom of the bond to be cleaved (covalent catalysis) in contrast to the metalloprotei-nases and aspartic proteases which use an activated water molecule to attack the carbon atom to be cleaved (noncovalent catalysis). In covalent catalysis, a nearby histidine residue normally functions as a base to activate the mechanism, whereas in noncovalent catalysis, the protease type serves as an acid and base, with an ancillary histidine (aspartate proteases) or aspartate or glutamate residue acting as the nucleophile (Fig. 8.2b) (Modified from Fig. 9.18 in Berg., et al., Biochemistry, 5th Ed. 2002, W.H. Freeman Co., New York)...

Besides the typical (normal) PTC reactions involving nucleophilic reactant anions and cationic catalyst, it is reasonable to believe that the PTC technique can be applied to reactions involving electrophilic reactant cations such as aryldiazonium and carbonium cations and anionic catalysts. In such reversed phase transfer catalysis (RPTC), a cationic reactant in the aqueous phase is continuously transferred into the organic phase in the form of a lipophilic ion pair with a lipophilic, non-nucleophilic anionic catalyst, and reacts with the second reactant in the organic phase. 

Interest has continued in the wider general synthetic applicability of tertiary phosphines in the nucleophilic catalysis of carbon-carbon bond... 

There is little effect of micelles upon the rate of an intramolecular nucleophilic reaction. Micelles of hexadecyltrimethylammonium bromide catalyse, by factors of 10 —10, the arenesulphinate anion-induced hydrolysis of 4-tolylsulphonyl-methyl perchlorate. There is no relationship between the rate acceleration and hydro-phobicity of the sulphinate anion and catalysis is attributed to the concentration of the reactants in the micellar phase.The rate constants for the reaction of nucleophiles with carbonium ions and those for the addition of cyanide ion to the A -alkylpyridinium ions are similar in the micellar and aqueous phases, and the rate enhancement is due to the concentration of reactants in the micellar pseudophase. Similarly, although micellar catalysed dephosphorylation by nucleophiles may show rate enhancements of up to 4 x 10 -fold, the second-order rate constants may be slightly smaller in the micellar pseudophase lowing to its lower polarity. However, the reaction of fluoride ion with 4-nitrophenyldiphenyl phosphate is very rapid in micelles of cetyltrimethylammonium fluoride, but the rate constant continues to increase when the substrate is fully bound with increasing cetyltrimethylammonium fluoride or sodium fluoride. The failure of the micellar pseudophase model is also apparent in the reaction of hydroxide ion with 2,4-dinitrochlorobenzene. It is suggested that reaction occurs between reactants in the aqueous and micellar pseudophases and also between hydroxide ion in water and substrate in the micelle. ... 

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