Lower based catalysis

Gold-based catalysis has attracted considerable attention in recent years. A gold-catalyzed aziridination reaction has recently been reported <06JOC5876>. A series of gold catalysts were examined for their ability to catalyze the aziridination of styrene with p-nitrophenylsulfonamide (NsNH2). Styrene and phenyl-substituted styrenes provided the N-nosyl aziridines in good to excellent yields. Cinnamate however provided the aziridine product in only 25% yield. The use of other sulfonamides (e.g. tosyl, trichloroethyl) gave much lower yields of the aziridine product. 

Okamura and Nakatani [65] revealed that the cycloaddition of 3-hydroxy-2-py-rone 107 with electron deficient dienophiles such as simple a,p-unsaturated aldehydes form the endo adduct under base catalysis. The reaction proceeds under NEtj, but demonstrates superior selectivity with Cinchona alkaloids. More recently, Deng et al. [66], through use of modified Cinchona alkaloids, expanded the dienophile pool in the Diels-Alder reaction of 3-hydroxy-2-pyrone 107 with a,p-unsaturated ketones. The mechanistic insight reveals that the bifunctional Cinchona alkaloid catalyst, via multiple hydrogen bonding, raises the HOMO of the 2-pyrone while lowering the LUMO of the dienophile with simultaneous stereocontrol over the substrates (Scheme 22). 

In general acid catalysis, the reaction rate increases because the transition state for the reaction is lowered by proton transfer from a Bronsted acid in general base catalysis, the reaction rate increases by virtue of proton abstraction by a Bronsted base. 

Industrial processes tend to favor base catalysis, since they have lower activation energies allowing the reactions to be carried out near or just above room temperature (5). Further, the carbonate or caustic bases are relatively inexpensive and easily separated with the glycerin product. 

The pH-rate profile for the action of the enzyme shows a typical pH maximum, with sharply lower rates at either higher or lower pH than the optimum these facts suggest that both an acidic and a basic group are required for activity (Herries, 1960). The two essential histidine residues could serve as these groups if, in the active site, one were protonated and the other present in its basic form. The simultaneous acid-base catalysis would parallel that of the model system (discussed below) of Swain and J. F. Brown. The essential lysine, which binds phosphate, presumably serves to bind a phosphate residue of the ribonucleic acid. These facts led Mathias and coworkers to propose the mechanism for the action of ribonuclease that is shown in (13) (Findlay et al., 1961). 

Additional catalytic mechanisms employed by enzymes include general acid-base catalysis, covalent catalysis, and metal ion catalysis. Catalysis often involves transient covalent interactions between the substrate and the enzyme, or group transfers to and from the enzyme, so as to provide a new, lower-energy reaction path. 

Stoichiometry (28) is followed under neutral or in alkaline aqueous conditions and (29) in concentrated mineral acids. In acid solution reaction (28) is powerfully inhibited and in the absence of general acids or bases the rate of hydrolysis is a function of pH. At pH >5.0 the reaction is first-order in OH but below this value there is a region where the rate of hydrolysis is largely independent of pH followed by a region where the rate falls as [H30+] increases. The kinetic data at various temperatures both with pure water and buffer solutions, the solvent isotope effect and the rate increase of the 4-chloro derivative ( 2-fold) are compatible with the interpretation of the hydrolysis in terms of two mechanisms. These are a dominant bimolecular reaction between hydroxide ion and acyl cyanide at pH >5.0 and a dominant water reaction at lower pH, the latter susceptible to general base catalysis and inhibition by acids. The data at pH <5.0 can be rationalised by a carbonyl addition intermediate and are compatible with a two-step, but not one-step, cyclic mechanism for hydration. Benzoyl cyanide is more reactive towards water than benzoyl fluoride, but less reactive than benzoyl chloride and anhydride, an unexpected result since HCN has a smaller dissociation constant than HF or RC02H. There are no grounds, however, to suspect that an ionisation mechanism is involved. 

The lower effective concentrations found in intramolecular base catalysis are due to the loose transition states of these reactions. In nucleophilic reactions, the nucleophile and the electrophile are fairly rigidly aligned so that there is a large entropy loss. In general-base or -acid catalysis, there is considerable spatial freedom in the transition state. The position of the catalyst is not as closely defined as in nucleophilic catalysis. There is consequently a smaller loss in entropy in general-base catalysis, so that the intramolecular reactions are not favored as much as their nucleophilic counterparts. 

Data presented suggest that acid-base catalysis is of major importance in the hydrolytic action of pepsin. The pK of the beat carboxyl group of aspartate is around 4 in the free acid and may very well be lower in the protein molecule due to neighboring group effects. A pH optimum near the pK of aspartic acid suggests that the ability of aspartate to accept and donate protons is of major importance in its mode of action. 

In conclusion, it now appears that the cause of base catalysis in the aminolysis of aromatic substrates may not be of common origin. Further investigations of the mode of decomposition of these zwitterionic intermediates and the analogous o-complexes are clearly desirable. DMSO will remain central to these studies (Fendler et al., 1975b), due to the possibility of isolation of such complexes in this medium. It now appears that DMSO may also be valuable for studies of electrophilic catalysis, since its use tends to avoid ion pairing effects which complicate kinetic studies in aprotic media of lower dielectric constant. The problem of ion pairing is considered further in the following section. 

This type of catalysis, which is available to any base, not only strong bases, is called general base catalysis and will be discussed more in Chapters 41 and 50. It does not speed the reaction up very much but it does lower the energy of the transition state leading to the tetrahedral intermediate since that intermediate is first formed as a neutral compound instead of a dipolar species. Here is the mechanism for the uncatalysed reaction. 

---