Water deprotonation

The pinacol rearrangement is a dehydration of an alcohol that results in an unexpected product. When hot sulfuric acid is added to an alcohol, the expected product of dehydration is an alkene. However, if the alcohol is a vicinal diol, the product will be a ketone or aldehyde. The reaction follows the mechanism shown, below. The first hydroxyl group is protonated and removed by the acid to form a carboca-tion in an expected dehydration step. Now, a methyl group may move to fonn an even more stable carbocation. This new carbocation exhibits resonance as shown. Resonance Structure 2 is favored because all tire atoms have an octet of electrons. The water deprotonates Resonance Structure 2, forming pinacolone and regenerating the acid catalyst. 

Figure 9.27. Kinetics of Water Deprotonation. The kinetics of deprotonation and protonation of the zinc-bound water molecule in carbonic anhydrase.

Although addition of a nucleophile to a tt radical cation seems to be a straightforward process, several mechanistic scenarios [284] (e.g. the disproportionation, complexation, and half-regeneration pathways) that depend on the reactants need to be considered [285]. It has, moreover, been stressed that for protic nucleophiles such as alcohols and water, deprotonation of the primary adduct is important [286]. As a consequence, the rational design of bond-forming reactions requires deeper understanding of mechanistic matters. 

Fig. 8. Model for the period-of-four oscillation of manganese oxidation, net charge formation, and water deprotonation. The S-state cycle is driven by four photons initiating electron transfer from P680 to Q, with P680 being stepwise reduced by tyrosine Yz. indicates pH-independent net charge of an S-state. "50,260 ns" indicates biphasic kinetics. Figure from Schlodder and Witt (1999) Stoichiometry of proton reiease from the cataiytic center in photosynthetic water oxidation. J Biol Chem 274 30391.

Figure 9.25 Mechanism of carbonic anhydrase. The zinc-bound hydroxide mechanism for the hydration of carbon dioxide reveals one aspect of metal ion catalysis. The reaction proceeds in four steps (1) water deprotonation (2) carbon dioxide binding (3) nucleophilic attack of hydroxide on carbon dioxide and (4) displacement of bicarbonate ion by water.

The acidity constant for water deprotonation in cis (NH3)2Pt(Cl)(H2O) is unknown and needs to be estimated. For three examples ( ) I note that the pKa value for deprotonation from an aquo-chloro complex is about the average of the successive pKi and pK2 values from the corresponding diaquo complex. Thus from the average of the pKi and pK2 values in the preceding paragraph I estimate for cis (NH3)2Pt(Cl)(H2O) that pKa = 6.3. This values is identical to that reached in reference by a similar argument. 

Additional solvent molecules (water) deprotonate the alkyloxonium ion. 

Acid-catalyzed tautomerization of an aldehyde (see Chapter 11) gives an enol as the starting point. Protonation of the alcohol attached to the (i-carbon makes it a good leaving group. In the second step, a lone pair on the enol OH is used as an electron source to expel the water. Deprotonation of the carbonyl yields the final product in a last step. 

The tetrahedral intermediate formed from the acid has more options, because it has one OR and two OH groups. Protonation of the OR simply takes us back along the path to the starting acid. Protonation of one of the OH groups leads to an intermediate that can lose water, deprotonate, and give the ester (Rg. 17.23). In excess alcohol, the reaction is driven in this direction. 

Water deprotonates the intermediate, giving the neutral hydrate addition product and regenerating the acid catalyst H30". ... 

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