Proton abstraction reaction, solvent effects

Comparison of reactions 4.9, 4.10, 4.12, 4.13 and 4.15 leads to another important conclusion, viz., in an amphiprotic solvent its own solvonium cation represents the strongest acid possible, and its own anion the strongest base. Even when a very strong foreign acid or base is dissolved, excessive proton donation to and proton abstraction from the solvent molecule yield the respective acid or base this phenomenon is generally known as the levelling effect, which in an amphiprotic solvent takes place on both the acid and the basic... 

To conclude this section on the effect of solvent on a-nucleophilicity, we refer to the current, rather controversial, situation pertaining to gas-phase smdies and the a-effect. As reported in our review on the a-effect and its modulation by solvent the gas-phase reaction of methyl formate with HOO and HO , which proceeds via three competitive pathways proton abstraction, nucleophilic addition to the carbonyl group and Sat2 displacement on the methyl group, showed no enhanced nucleophilic reactivity for HOO relative to This was consistent with gas-phase calculational work... 

The addition of hydroxide ions to substituted benzaldehydes (ArCHO + OH <=> ArCH(0H)0 ) is used to establish J-acidity scales in water-ethanol and water-DMSO mixtures containing sodium hydroxide as a base. The pK-values in such mixtures are linearly correlated with Hammett substituent constants. The independence of reaction constant p of solvent composition confirms that substituted benzaldehydes are suitable J- indicators for hydroxide solutions in water-ethanol and water-DMSO mixtures. Dependence of J- values on sodium hydroxide concentration is only slightly affected by ethanol up to 90 % and at a constant sodium hydroxide concentration shows only small increase between 90 and 98 % ethanol. J- increases more with increasing DMSO concentration, but the effect is much smaller than that of DMSO on H- values based on proton abstraction from aniline. 

If a hydrogen atom is abstracted from an alkane by an alkyl radical, both the initial and final state of the reaction involve neutral species and it is only the transition state where some limited charge separation can be assumed. In the case of a homolytic O—H bond fission, however, the initial state possesses a certain polarity and possible changes in polarity during the reaction depend on both the lifetime of the transition state and the nature of the attacking radical. If the unpaired electron is localized mainly on oxygen in the reactant radical, the polarity of the final state will be close to that of the initial state and any solvent effect will primarily depend on the solvation of the transition state. Solvent effects can then be expected since the electron and proton transfers are not synchronous. 

In the ozonation of tri-n-butylamine at —40°C. with an ozone-nitrogen stream, 1.2 to 1.6 mole equivalents of ozone were absorbed, and the yields of tri-n-butylamine oxide were 53% from chloroform and 6% from pentane solvents. The other products were the side chain oxidation products described by Henbest and Stratford (II). These results eliminate the possibility that the side chain oxidation is an ozone-initiated autoxidation. The mechanism outlined by Reaction 3 explains nicely both the requirement of ozone itself as the oxidizing agent and the solvent effect observed. Solvents such as chloroform would be expected to solvate the ozone-amine adduct (lb) and make the abstraction of the proton in Reaction 3 difficult. Thus, loss of molecular oxygen to give the amine oxide becomes the major reaction (Reaction 2). In pentane solu-... 

Before the structure of the enzyme was determined, chemical modification experiments (using proteolysis and mass spectrometry to identify the modified residue) and site-directed mutagenesis were used to identify Arg 21, Tyr 28, and a His as catalytically important side chains.Substrate and solvent H isotope effects, proton inventory studies, and the pH-dependence of the kinetic parameters and were used to identify the enzyme mechanismas an E]CB elimination reaction proceeding via an enolate intermediate, with the initial proton abstraction as the rate-limiting step. The unusual sharp increase in and above pH 9 was interpreted as the effect of an active-site Arg side chain on the basicity of a His. " ... 

This reaction, similar to the competing reaction of the Myers-Saito Cyclization, proceeds via a biradical intermediate, as supported by the trapping of a biradical intermediate with 1,4-cyclohexadiene and the experimental fact that the change of the polarity of solvent has no effect on the reaction rate and the ratio of products formed, indicating the absence of a zwitterionic intermediate. The proton abstraction by the vinyl radical leads to the formation of fulvene derivatives. An illustration of this reaction is provided here. 

The aliphatic side chains in alanine and leucine have no major influence but branching at the ) -carbon atom in valine and isoleucine can enhance racemization because the combination of electron release and steric hindrance results in reduced coupling rates. The ensuing increase in the life-time of the reactive intermediate provides an extended opportunity for proton abstraction by base. It is obvious from these examples that the effect of individual side chains, the influence of various methods of coupling and the conditions of the peptide bond forming reaction (solvents, concentration, temperature, additives) must be studied in well designed experiments. Several model systems have been proposed for this purpose. 

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