Prototropic reactions

On the other hand, the electron-attracting properties (—I and —M) of the 2-thienyl groups should also facilitate prototropic reactions, where the rate-determining step is the removal of a proton from the a-carbon and which thus is facilitated by electron-attracting sub-... 

It is thus obvious that the 2-thienyl group is both a better electron donator and electron acceptor than the phenyl group, facilitating both nucleophilic and prototropic reactions at the a-methylene carbon. 

When, after a detailed photophysical study, all the characteristics of the ground and excited states prototropic reactions of a molecule are known, in return we have in hand a probe which can quantitatively monitor the pH of its microscopic surrounding. In fact, as a rule, the absorption and the fluorescence spectra of a probe are only measurably dependent on pH over ca. 2 pH units around its pKa-Since probes with a wide range of pKu values—currently from 1 to 9—are available, pH values from 0 to 10 are addressable. For multiple reasons fluorescence measurements are preferred to direct absorption spectra. 

In the last few years more information on excited state pA-values has accumulated and the present review contains extensive reference tables of the experimental results in the literature available up to August 1974. We have confined our attention throughout to Br nsted acids and bases, though work on Lewis acid (donor-acceptor) systems continues (Weller, 1961 Birks, 1970 Ottolenghi, 1973) and may prove directly relevant to a deeper understanding of prototropic reactions, which must often be preceded by the formation of hydrogen-bonded complexes. Such interactions also play a role in solvent effects upon the absorption frequencies of acid and base molecules. 

The Grigg group also studied the tautomerization of oximes to N-H nitrones followed by a dipolar cycloaddition reaction. The well-known H-bonding dimeric association of oximes, in both solution and the solid state, allows for a concerted proton transfer to occur and provides nitrone 56 (Scheme 11) (91TL4007). Another possible pathway involves tautomerization of the oxime to an ene-hydroxylamine (i.e. 57) followed by a 1,4-hydride shift to give nitrone 58. To probe the ene-hydro-xylamine mechanism, deuterated oxime 59 was prepared and heated at 140 °C in xylene. The physical characteristics of the isolated product, however, were consistent with compound 60, suggesting that the 1,2-prototropic reactions does not proceed... 

NB See also Mitomycin C. The prototropic properties of mitomycin and porfiromycin were studied, and Bie dissociation constants for 2 potentially basic groups and one acidic function were established by titration. The kinetics of ttie tautomerization preceding the prototropic reaction in an alkaline medium are also discussed. 

Although the reason for acid or basic catalysis is specially clear in reactions involving the addition or removal of water, the effect is not by any means confined to such reactions. It is very prominent in prototropic reactions such as the enolization of acetone. Here the first step appears to be the acceptance by the acetone of a proton from the acid to give an addition compound which readily isomerizes by a redistribution of charge. The result is a molecule from which any proton acceptor present, including water, will readily remove H+ to leave the enol. The general principle is still the same. 

Although there is no reason why (66) should be generally valid, it is likely to hold approximately for catalysts of similar structure, and this may be why the more complex behaviour represented by (64) has not been observed in prototropic reactions. 

Returning to the general problem of prototropic reactions, the discussion so far has assumed that the two proton transfers take place consecutively, as in Equations (59)-(61). There is another possibility, the... 

There is of course ample evidence that acid-base catalysis in solvents of low dielectric constant does not necessarily involve a concerted process. Such a process cannot operate when catalysis is effected by a single acid or base present in an aprotic solvent, and there are many examples of this, including typical prototropic reactions such as the halogenation of acetone, the racemization and inversion of optically active ketones, and the mutarotation of nitrocamphor. Moreover, in the isomerization of mesityl oxide oxalic ester in chlorobenzene, which depends kinetically on the interconversion of two isomeric enols, the velocity in a solution containing both an amine and an acid is no greater than the sum of the velocities for the two catalysts separately, in contrast to the behaviour found by Swain for the mutarotation reaction. 

Since )8 < 1, this is equivalent to (105), and it is thus understandable that the same type of relation applies to prototropic reactions whether or not there is a pre-equilibrium with the catalyst. 

By making use of these considerations Gutmann and Lindqvist s extended the Bronsted theory by replacing the term prototropic reactions by ionotropic reactions . In general solvent systems are classified as a) cationotropic, h) anionotropic. 

Prototropic reactions involve the transfer of a proton from an acid HX to a base B,... 

Prototropic reactions of simple acids with normal bases are slow only if they are extremely endothermic, i.e., if the acids are extremely weak. Since the reactions follow the BEP principle, one can then use the rates of proton transfer to a given base to estimate relative acidities in the case of acids so weak that normal acid-base equilibria cannot be observed. Streitwieser et al have used this procedure to estimate the pK of a number of hydrocarbons some of their results are shown in Table 5.3. Note the enormous... 

Prototropic reactions are also very endothermic, and consequently slow, if the proton acceptor is a very weak base. Such reactions involve no new principles since a very weak base is the conjugate base of a very strong acid and we have already considered the relation between structure and acid strength. Since reactions of this kind all follow the BEP principle, their... 

Some authors have regarded prototropic reactions as special kinds of process, X being a hydrogen atom. However, hydrogen is not lost as the free ion H and indeed such reactions occur only in the presence of a base that can combine with the proton. The course of the reaction depends critically on the nature of the base. It is therefore better to reserve the designation S l for reactions where the group X is expelled as a neutral molecule [from an initial anion (RX)"] or as a stable cation X. ... 

The Ef,l reaction involves the same intermediate carbonium ion as an Sjyl replacement of Y and its rate is governed by similar considerations. Likewise, the ElcB process involves an initial step analogous to a prototropic reaction (Y replacing hydrogen). Both reactions are of EOg type and the effect of structure on their rates can be predicted in the same way as the rates of S,yl reactions (p. 237) or of deprotonations by base (p. 243). Thus the Effl reaction will be favored by -I, E, and —E substituents a to X and the lcB reaction by -H/, E, or -f substituents a to Y. Indeed, elimination reactions involving a proton a to a powerful -f group such as acyl always take place by the ElcB mechanism, as in the conversion of )S-chloroethyl ketones to vinyl ketones. 

The fluorescence decays and steady-state data (see below) indicated that all the prototropic reactions shown in Scheme 15.12 had to be considered (six rate constants plus three reciprocal Ufetimes). 

Freitas AA, Quina FH, Fernandes AC, Ma anita AL (2010) Picosecond dynamics of the prototropic reactions of 7-hydroxyflavylium photoacids anchored at an anionic micellar surface. J Phys Chem A 114 4188-4196... 

Rather than attempting an exhaustive review of all possible enzymatic proton transfers, which are manifold, we would like to discuss in the following a few well-documented enzymatic mechanisms involving different types of prototropic reactions. Of these, enzymatic amide- and ester-hydrolyses will be treated the most thoroughly, since at the present time they are the most extensively studied and their corresponding non-enzymatic model systems provide the most solid foundation for discussion. These examples will be preceded by a review of experimental techniques often utilized in mechanistic investigations of enzymatic reactions. 

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