Reversible proton addition

The specifically generated 2-methyl-1-phenylcyclopropyl (186) and l-methyl-2-phenylallyl anions (187) were also shown to exist as stable, non-interconverting isomers. However, in the presence of H2O 187 is converted to the 1-methyl-1-phenylallyl anion (188) by reversible proton addition and re-abstraction. 

In solution, reversible proton addition occurs at all positions, being by far the fastest at the nitrogen, and about twice as fast at C-2 as at C-3. In the gas phase, mild acids like C4H9 and NH4 protonate pyrrole only on carbon and with a larger proton affinity at C-2 than at C-37 Thermodynamically, the stablest cation is the 2//-pyrrolium ion, formed by protonation at C-2 and observed p/faH values for pyrroles are for these... 

The NH group lends to pyrrole the functionality of a base as weU as that of an acid [99]. The basicity of pyrrole is very weak (pfQ, = —3.8 for the conjugated acid) compared to cyclic aliphatic amines (e.g., pyrrolidine, pfQ, = +11.3). This large difference is due to incorporation of the nonbonding N-electron pair into the 6it-electron system of pyrrole. In principle, reversible proton addition to pyrrole may occur at all positions, but leads to cations of different thermodynamic stability ... 

The driving force for the hydrogenolysis is the aromatization in cooperation with the particular nature of the side chain stabilizing the intermediate (crypto) allylic or benzylic cation. The reaction starts with a reversible proton addition to the carbonyl function and proceeds via addition of a hydride ion to an allylic carbon atom. Concurrently or subsequently the double bond in the side chain is hydrogenated (Fig. 12). 

Reversible electron addition to the enone forms the radical anion. Rate determining protonation of the radical anion occurs on oxygen to afford an allylic free radical [Eq. (4b) which undergoes rapid reduction to an allylic carbanion [Eq. (4c)]. Rapid protonation of this ion is followed by proton removal from the oxygen of the neutral enol to afford the enolate ion [Eq. (4c)]. 

The equilibrium ratios of enolates for several ketone-enolate systems are also shown in Scheme 1.1. Equilibrium among the various enolates of a ketone can be established by the presence of an excess of ketone, which permits reversible proton transfer. Equilibration is also favored by the presence of dissociating additives such as HMPA. The composition of the equilibrium enolate mixture is usually more closely balanced than for kinetically controlled conditions. In general, the more highly substituted enolate is the preferred isomer, but if the alkyl groups are sufficiently branched as to interfere with solvation, there can be exceptions. This factor, along with CH3/CH3 steric repulsion, presumably accounts for the stability of the less-substituted enolate from 3-methyl-2-butanone (Entry 3). 

We would expect the C=0 linkage, by analogy with C=C (p. 178), to undergo addition reactions but whereas polar attack on the latter is normally initiated only by electrophiles, attack on the former— because of its bipolar nature—could be initiated either by electrophilic attack of X or X on oxygen or by nucleophilic attack of Y or Yt on carbon (radical-induced addition reactions of carbonyl compounds are rare). In practice, initial electrophilic attack on oxygen is of little significance except where the electrophile is an acid (or a Lewis acid), when rapid, reversible protonation may be a prelude to slow, rate-limiting attack by a nucleophile on carbon, to complete the addition, i.e. the addition is then acid-catalysed. 

Fig. 5 Logarithmic plots of rate-equilibrium data for the formation and reaction of ring-substituted 1-phenylethyl carbocations X-[6+] in 50/50 (v/v) trifluoroethanol/water at 25°C (data from Table 2). Correlation of first-order rate constants hoh for the addition of water to X-[6+] (Y) and second-order rate constants ( h)so1v for the microscopic reverse specific-acid-catalyzed cleavage of X-[6]-OH to form X-[6+] ( ) with the equilibrium constants KR for nucleophilic addition of water to X-[6+]. Correlation of first-order rate constants kp for deprotonation of X-[6+] ( ) and second-order rate constants ( hW for the microscopic reverse protonation of X-[7] by hydronium ion ( ) with the equilibrium constants Xaik for deprotonation of X-[6+]. The points at which equal rate constants are observed for reaction in the forward and reverse directions (log ATeq = 0) are indicated by arrows.

Because most species will release energy when a proton is added, the proton addition enthalpy is negative. The proton affinity is the heat associated with the reverse process, the removal of the proton,... 

Upon addition of a solution of sulfuric acid in D20 the reaction of A-acetoxy-A-alkoxyamides obeys pseudo-unimolecular kinetics consistent with a rapid reversible protonation of the substrate followed by a slow decomposition to acetic acid and products according to Scheme 5. Here k is the unimolecular or pseudo unimolecular rate constant and K the pre-equilibrium constant for protonation of 25c. Since under these conditions water (D20) was in a relatively small excess compared with dilute aqueous solutions, the rate expression could be represented by the following equation ... 

In addition, the NMR technique provides kinetic measurements for reversible proton transfers that are fast and occur on the NMR time scale (i.e., for processes... 

It was found that the 15-membered macrocyclic complexes were significantly less acidic. Similar reversible protonations have been shown to occur in related macrocyclic complexes36 37 and this work has been developed by Busch into a major study of ligand reactions,38 which are summarized in equations (16)—(19). It is significant that these reactions include not only typical substitution reactions such as acylation and nitration (equations 16 and 19), but also nucleophilic addition to isocyanates (equation 17) and to a, 3-unsaturated esters (equation 18). 

Ignoring any ionization in the side chain R it can be seen from the data in Table 1 that all amino acids undergo two reversible proton ionizations steps (equation 1). Consequently, depending upon the solution pH, the amino acids can coordinate through either or both of the amino (NH2) or carboxyl (C02 ) groups in aqueous media. In addition those with polar R groups, e.g. Asp, Cys, His, Glu, Pen, offer additional coordinating sites. 

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