Hydrogen bonding catalysis

Bronsted Acid Catalysis. Hydrogen bond catalysis has emerged as a powerful tool to carry out successful enantioselective Michael-type reactions. However, few effective enantioselective approaches are known for the specific addition of nitrogen-centered nucleophiles. First attempt to catalyze aza-Michael... 

Studies on solvent effects on the endo-exo selectivity of Diels-Alder reactions have revealed the importance of hydrogen bonding interactions besides the already mentioned solvophobic interactions and polarity effects. Further evidence of the significance of the former interactions comes from computer simulations" and the analogy with Lewis-acid catalysis which is known to enhance dramatically the endo-exo selectivity (Section 1.2.4). 

The second important influence of the solvent on Lewis acid - Lewis base equilibria concerns the interactions with the Lewis base. Consequently the Lewis addity and, for hard Lewis bases, especially the hydrogen bond donor capacity of tire solvent are important parameters. The electron pair acceptor capacities, quantified by the acceptor number AN, together with the hydrogen bond donor addities. O, of some selected solvents are listed in Table 1.5. Water is among the solvents with the highest AN and, accordingly, interacts strongly witli Lewis bases. This seriously hampers die efficiency of Lewis-acid catalysis in water. 

CS indicated that the enolate of acetyl-CoA is significantly more stable than the enol or a proton-sharing enolic form and thus do not support the proposal that a low barrier hydrogen bond is involved in catalysis in CS. This study demonstrates the practial application of high level QM-MM studies to the elucidation of mechanistic details of an enzymatic reaction that are otherwise unclear. 

Wells, T.N.C., Fersht, A.R. Hydrogen bonding in enzymatic catalysis analyzed by protein engineering. Nature 316 656-657, 1985. 

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 ... 

The hydration reaction has been extensively studied because it is the mechanistic prototype for many reactions at carbonyl centers that involve more complex molecules. For acetaldehyde, the half-life of the exchange reaction is on the order of one minute under neutral conditions but is considerably faster in acidic or basic media. The second-order rate constant for acid-catalyzed hydration of acetaldehyde is on the order of 500 M s . Acid catalysis involves either protonation or hydrogen bonding at the carbonyl oxygen. 

By using imidazole catalysis, it is possible to get a better understanding of the active forms that water takes in enzymatic processes Thus, at low concentrations m the presence of an enzyme, the water may not be fully hydrogen bonded and therefore more reactive [61] The rate of hydrolysis of p-nitrotrifluoroacetanilide in acetonitrile shows a strong dependence on water concentration at low levels in the presence of imidazole The imidazolium complex is the approximate transition state (equation 60)... 

Gerlt, J. A., Kreevoy, M. M., Cleland, W. W., and Frey, P. A., 1997. Understanding enzymic catalysis The importance of short, strong hydrogen bonds. Chemistry and Biology 4 259-267. 

The factors in carboaromatic nucleophilic displacements summarized in this section are likely to be characteristic of heteroaromatic reactions and can be used to rationalize the behavior of azine derivatives. The effect of hydrogen bonding and of complexing with metal compounds in providing various degrees of electrophilic catalysis (cf. Section II, C) would be expected to be more extensive in heteroaromatics. 

The catalytic effect of aromatic nitro groups in the substrate and product or in an added inert nitro compoimd (e.g., w-dinitrobenzene in 18) has been observed in the reaction of 2,4-dinitrochlorobenzene with an amine in chloroform. Hydrogen bonding to benzil or to dimethyl sulfone and sulfoxide also provided catalysis. It is clear that the type of catalysis of proton transfer shown in structure 18 will be more effective when hydrogen bonding is to an azine-nitrogen. 

The rate of reaction of a series of nucleophiles with a single substrate is related to the basicity when the nucleophilic atom is the same and the nucleophiles are closely related in chemical type. Thus, although the rates parallel the basicities of anilines (Tables VII and VIII) as a class and of pyridine bases (Tables VII and VIII) as a class, the less basic anilines are much more reactive. This difference in reactivity is based on a lower energy of activation as is the reactivity sequence piperidine > ammonia > aniline. Further relationships among the nucleophiles found in this work are morpholine vs. piperidine (Table III) methoxide vs. 4-nitrophenoxide (Table II) and alkoxides vs. piperidine (Tables II, III, and VIII). Hydrogen bonding in the transition state and acid catalysis increase the rates of reaction of anilines. Reaction rates of the pyridine bases are decreased by steric hindrance between their alpha hydrogens and the substituents or... 

In the above formulation the proton is transferred in the step in which the intermediate is formed. Such proton transfer is not essential for base catalysis. An alternate mode of catalysis is one in which the transition state for intermediate formation is a hydrogen-bonded complex, e.g. L, but in which this complex collapses to VI and the catalyst rather than to VIII. For such a formulation the only significant intermediate determining the rates would be VI, which would now be formed by the additional steps... 

---