Steric effects hydration reactions

The production of H2 in the radiolysis of water has been extensively re-examined in recent years [8], Previous studies had assumed that the main mechanism for H2 production was due to radical reactions of the hydrated electron and H atoms. Selected scavenger studies have shown that the precursor to the hydrated electron is also the precursor to H2. The majority of H2 production in the track of heavy ions is due to dissociative combination reactions between the precursor to the hydrated electron and the molecular water cation. Dissociative electron attachment reactions may also play some role in y-ray and fast electron radiolysis. The radiation chemical yield, G-value, of H2 is 0.45 molecule/100 eV at about 1 microsecond in the radiolysis of water with y-rays. This value may be different in the radiolysis of adsorbed water because of its dissociation at the surface, steric effects, or transport of energy through the interface. 

The equiiibrium constants for addition of alcohols to carbonyl compounds to give hemiacetals show the same response to structural features as the hydration reaction. Equilibrium constants for addition of methanol to acetaldehyde in both water and chloroform solution are near 0.8 The structural effects of the alcohol group have been examined. " Steric effects result in an order of CH3 C2H5 > (CH3)2CH > (013)30 for acetaldehyde hemiacetals. EWG substituents in the alcohol disfavor hemiacetal formation and this trend is believed to reflect the decreasing n tt hyperconjugation (anomeric effect, see Topic 1.2) as the substituents become more electron withdrawing. 

Workentin et al. have recently reported the results of an extensive laser flash photolysis investigation of the reactions of the cation radicals of 9-phenyl- and 9,10-diphenylanthracene (PA and DPA, respectively) with amines. Primary amines react with both cation radicals via nucleophilic addition with rate constants which reflect both the amine basicity and a steric requirement for bond formation. Steric effects are more pronounced for addition of DPA " vs. PA ", presumably due to the presence of substituents at both the 9- and 10-position. Tertiary amines and anilines react with PA " and DPA " via electron transfer with rate constants which correlate with amine ionization potentials. Rate constants for nucleophilic addition of primary amines are faster in acetonitrile than in acetonitrile/water solution. The rate-retarding effect of water is attributed to an equilibrium between the fiee amine (reactive) and hydrated amine (unreactive). The beneficial effect of water on preparative ET-sen itized photoamination may reflect its role as a catalyst for the proton transfer processes which follow C-N bond formation (Scheme 2). Hydration of the amine also should render it less reactive in primary and secondary electron transfer processes which can compete with the formation of the arene cation radical. 

Steric effects may play a role in the regiochemistry of the reaction as well. While the oxymercuration-demercuration reaction is generally considered to give only Markovnikov hydration, as shown by predominant formation of 43, this regioselectivity is not absolute. For example, methoxymercuration of 3,3-dimethyl-l-butene produced 2% of 3,3-dimethylbutyl methyl ether (44, equation 9.42). ... 

Figure 19.1 Steric Effects on the Equilibrium of Hydration Reactions...

An example the spectrum of quinazoline is unexpectedly displaced to much shorter wavelengths when the solution is acidified (Fig. 2.3) also the p Ta is 3.51 (an equilibrium value) instead of 1.9, the p/Ca for totally anhydrous species, determined in rapid-reaction apparatus (Bunting and Perrin, 1967). Covalent hydration is largely suppressed if a methyl-group is present on the carbon atom which is attacked by the OH-group of water. This effect has been shown to be due to a steric effect reinforced by induction (Albert et ah, 1961). Thanks to this, 4-methylquinazoline shows a normal spectral shift on acidification (Fig. 2.4), and has a pKa of 2.52 in agreement with calculations. 

Studies on covalent hydration of N-heterocycles (67AG(E)919,76AHC(20)117) have revealed the diagnostic value of alkyl substituents in structural assignments due to their steric hindrance effects in addition reactions. C-Methyl substituents are therefore also considered as molecular probes to solve fine-structural problems in the pteridine field. The derivatives... 

The approach taken above estimates the effect of the metal by simply considering its electrostatic effect (subjected, of course, to the correct steric constraint as dictated by the metal van der Waals parameters). To examine the validity of this approach for other systems let s consider the reaction of the enzyme carbonic anhydrase, whose active site is shown in Fig. 8.6. The reaction of this enzyme involves the hydration of C02, which can be described as (Ref. 5)... 

Benzotriazine (8, R = H), for example, can be isolated as a reasonably stable, colorless crystalline solid, but it reacts rapidly in solution with water to give o-aminobenzaldehyde, presumably by initial covalent hydration to give 98, which decomposes to o-aminobenzaldehyde via the triazene 99. Reaction of 8, R = H, with other nucleophiles also occurs readily, while 4-substituted 1,2,3-benzo-triazines react similarly but more slowly, as expected, owing to a combination of steric and electronic effects. 

Theoretical studies have been done in order to understand this behavior difference. Semiempirical calculations (AMI, MNDO) of formation energy (of the hemithio-ketal-hemiketal interconversion) have shown that hemithioketals are less stable than the corresponding hemiketal (from 10 to 15 kcal/mol). This difference can be due to steric factors, connected to the respective sizes of sulfur and oxygen. Stereoelectronic factors can also be evoked stabilization that is brought about by the anomeric effect is a priori more important for a gem-dihydroxylated compound than for the hemi-thioketal. Moreover, at the kinetic level, displacement of the water molecule of the inhibitor (under aqueous conditions, the inhibitor is hydrated) by the thiol of the enzyme is a slow and disfavored reaction. In contrast, the same reaction is favored with the hydroxyl of a serine. Experimentally, equilibrium occurs very slowly with the enzyme as well as with model molecules. ... 

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