Hydrophobic rate acceleration

The rate acceleration imposed by 0-cyclodextrin was explained in terms of a microsolvent effect 6> The inclusion of the substrate within the hydrophobic cavity of cyclodextrin simulates the changes in solvation which accompany the transfer of the substrate from water to an organic solvent. Uekama et al.109) have analyzed the substituent effect on the alkaline hydrolysis of 7-substituted coumarins (4) in the... 

Density functional theory study of aqueous-phase rate acceleration and endo/exo selectivity of the butadiene and acrolein Diels-Alder reaction72 shows that approximately 50% of the rate acceleration and endo/exo selectivity is attributed to hydrogen bonding and the remainder to bulk-phase effects, including enforced hydrophobic interactions and cosolvent effects. This appears to be supported by the experimental results of Engberts where a pseudothermodynamic analysis of the rate acceleration in water relative to 1-propanol and 1-propanol-water mixtures indicates that hydrogen-bond stabilization of the polarized activated complex and the decrease of the hydrophobic surface area of the reactants during the activation process are the two main causes of the rate enhancement in water.13... 

An ab initio MO calculation by Jorgensen revealed enhanced hydrogen bonding of a water molecule to the transition states for the Diels-Alder reactions of cyclopentadiene with methyl vinyl ketone and acrylonitrile, which indicates that the observed rate accelerations for Diels-Alder reactions in aqueous solution arise from the hydrogenbonding effect in addition to a relatively constant hydrophobic term.7,76 Ab initio calculation using a self-consistent reaction field continuum model shows that electronic and nuclear polarization effects in solution are crucial to explain the stereoselectivity of nonsymmetrical... 

Murakami and Kondo (1975) reported that the cationic micelle is quite effective for the pyridoxal-catalyzed elimination of S-phenylcysteine. The significant rate acceleration was explained by the binding of the Schiff s base to the micelle phase, followed by the efficient proton abstraction by hydroxide ion at the micelle surface. According to Gani et al. (1978), mixed micelles of CTAB and dodecylamine hydrochloride are good models for the site accommodating pyridoxal 5 -phosphate in glycogen phosphorylase, since the micelles can imitate well the formation of SchifT s bases in hydrophobic environments. 

The ease of formation of hydrophobic ion pairs, and hence the rate acceleration, will be determined by the hydrophobic and electrostatic interactions between the anionic and cationic species. Lapinte and Viout (1974) found that the nucleophilic order OH- > CN > C6H50- in water was completely reversed in CTAB micelles hydrophobic phenoxide ion is activated better by the micelle. The micellar binding of phenols and phenoxides was determined by Bunton and Sepulveda (1979). Similarly, hydrophobic hydroxamates are activated much better than their hydrophilic counterparts. In the same vein, the extent of activation correlates approximately with the hydrophobic nature of aqueous aggregates as estimated by Amax of methyl orange (Table 7) and of picrate ion (Bougoin et al., 1975 Shinkai et al., 1978f Table 5). 

While widespread investigations on rate accelerations in Diels-Alder reactions by additives were highly successful, the effect of these additives on the selectivities of [4 + 2]-cycloadditions in water has not received much attention. Scattered reports on this aspect point to an increase in endo/exo selectivity by additives, due to an increase in the hydrophobic interactions209. 

Several factors have been invoked to explain the aqueous rate acceleration aggregation of the reactants leading to micellar catalysis, effects connected with the internal pressure of the solvent, polarity of the solvent, H-bonding interactions with the solvent, and hydrophobic interactions (A y < 0). The initial literature was rather controversial, and there was a strong need for a systematic study using physical-organic techniques. 

The pseudothermodynamic analysis of solvent elfects in 1-PrOH-water mixtures over the whole composition range (shown in Figure 7.3) depicts a combination of thermodynamic transfer parameters for diene and dienophile with isobaric activation parameters that allows for a distinction between solvent elfects on reactants (initial state) and on the activated complex. The results clearly indicate that the aqueous rate accelerations are heavily dominated by initial-state solvation effects. It can be concluded that for Diels-Alder reactions in water the causes of the acceleration involve stabilization of the activated complex by enforced hydrophobic interactions and by hydrogen bonding to water (Table 7.1, Figure 7.4). °... 

It may be noted that sucrose solutions enhanced exhibit hydrophobic effects, leading to increased rate accelerations of such reactions as the Diels-Alder and related processes.363... 

The ability of micelles or related aggregates to alter reaction rates and selectivity has been an area of active research for the past several decades. Reactants are partitioned into the aggregates by coulombic and hydrophobic interactions the observed rate accelerations are largely a result of the increased localization of the reactants and also of the typical physicochemical properties of the micellar environment, which are significantly different from those of the bulk solvents. This unique ability of the aggregate systems has therefore prompted several scientists to employ micellar media for catalytically carrying out specific reactions. 

The energy barrier to isomerization is lowered when substrates are transferred either to acidic or organic solutions. In acidic solution, rate acceleration occurs because an alternate, low-energy pathway is provided by protonation to produce a substrate in which the C-O bond is more ketonelike and the C-N bond more aminelike, thereby destroying resonance stabilization. In organic solutions, rate acceleration occurs as a result of transferring the substrate from a nonpolar transition state to a hydrophobic environment. We will see below that enzymatic strategies for catalysis may exploit both of these chemical mechanisms. 

The Diels-Alder cycloaddition reaction of 2,6-dimethyl-1,4-benzoquinone with methyl (ii)-3,5-hexadienoate, carried out in toluene as solvent, gives only traces of the cycloadduct shown in Eq. (5-160), even after seven days. However, when the solvent is changed to water and sodium ( )-3,5-hexadienoate is used as the diene, 77 cmol/mol of the desired cycloadduct is obtained after one hour and esterification with diazomethane [714] f Again, hydrophobic interactions between diene and dienophile in the aqueous medium seem to be responsible for this remarkable and synthetically useful rate acceleration. 

Polymer acids or polyanions can catalyze the acid hydrolyss of esters, amides, and ethers. This is because the local proton concentration in the polymer domain is hi r than that in the bulk phase. The rate acceleration caused by this effect is moderate. However, when substrate molecules are attracted to the polymer molecule by electrostatic and hydrophobic forces, the catalytic efficiency increases (up to ca. 100 fold compared with mineral acids). Similar results were obtained for the alkali hydrolysis in the presence of polycations. 

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