Addition of water to carbonyls

Addition of water to carbonyl compounds acid-catalysed hydration. Preparation of diols... 

Such reactions will not be dealt with (see Vols. 10 and 12). The addition of water to carbonyl compounds, however, deserves mention here. The reaction is reversible, viz. 

There are abundant kinetic data for addition of water to carbonyl compounds either uncatalyzed, acid catalyzed, or base catalyzed. For a considerable number of these reactions the equilibrium constant for hydration is also available and thus an extensive test of NBT is possible [73]. Over the entire range of reactivity for which data are available (from formaldehyde plus hydroxide to NA -dimethylacetamide plus water), the calculated AG values were in good agreement with experiment. At the time this paper was published [73], the rate of uncatalyzed hydrolysis of dimethylacetamide had not been reported. Since then Wolfenden and coworkers [74] have reported a rate constant at elevated temperatures extrapolating to a AG of 32kcal/mol in good agreement with our prediction of 31.11 kcal/mol. 

First stage Formation of the tetrahedral intermediate by nucleophilic addition of water to the carbonyl group... 

The equilibrium constants for addition of alcohols to carbonyl compounds to give hemiacetals or hemiketals show the same response to structural features as the hydration reaction. Equilibrium constants for addition of metiianoHb acetaldehyde in both water and chloroform solution are near 0.8 A/ . The comparable value for addition of water is about 0.02 The overall equilibrium constant for formation of the dimethyl acetal of... 

Aldehyde oxidations occur through intermediate l/l-diols, or hydrates, which are formed by a reversible nucleophilic addition of water to the carbonyl group. Even though formed to only a small extent at equilibrium, the hydrate reacts like any typical primary or secondary alcohol and is oxidized to a carbonyl compound (Section 17.7). 

The acid-catalvzed hydration reaction begins with protonation of the carbonyl oxygen atom, which places a positive charge on oxygen and makes the carbonyl group more electrophilic. Subsequent nucleophilic addition of water to the protonated aldehyde ot ketone then yields a protonated gem diol, which loses H+ to give the neutral product (Figure 19.5). 

Addition of water to the protonated carbonyl compound gives a protonated gem diol intermediate. 

Alternatively one can make use of No Barrier Theory (NBT), which allows calculation of the free energy of activation for such reactions with no need for an empirical intrinsic barrier. This approach treats a real chemical reaction as a result of several simple processes for each of which the energy would be a quadratic function of a suitable reaction coordinate. This allows interpolation of the reaction hypersurface a search for the lowest saddle point gives the free energy of activation. This method has been applied to enolate formation, ketene hydration, carbonyl hydration, decarboxylation, and the addition of water to carbocations. ... 

Mediated by Tin. In 1983, Nokami et al. observed an acceleration of the reaction rate during the allylation of carbonyl compounds with diallyltin dibromide in ether through the addition of water to the reaction mixture.74 In one case, by the use of a 1 1 mixture of ether/water as solvent, benzaldehyde was allylated in 75% yield in 1.5 h, while the same reaction gave only less than 50% yield in a variety of other organic solvents such as ether, benzene, or ethyl acetate, even after a reaction time of 10 h. The reaction was equally successful with a combination of allyl bromide, tin metal, and a catalytic amount of hydrobromic acid. In the latter case, the addition of metallic aluminum powder or foil to the reaction mixture dramatically improved the yield of the product. The use of allyl chloride for such a reaction,... 

Spontaneous hydrolysis of many activated derivatives of carboxylic or carbonic acids involves nucleophilic addition of water to the carbonyl group, assisted by another water molecule which acts as a general base (Johnson, 1967 Mengerand Venkatasubban, 1976). The tetrahedral intermediate then rapidly goes forward to products (Scheme 3). 

Mononuclear ruthenium complexes were found to be superior to carbonyl clusters during a comprehensive comparison of a variety of catalysts in the reduction of acetone [49]. Without solvent, most catalysts were highly selective, although the activity was quite low. The addition of water to the system vastly increased yields, in agreement with Schrock and Osborrfs observations into rhodium-catalyzed hydrogenations (Table 15.9) [41],... 

Figure 6. Schematic representation of the addition of water to the labeled carbonyl in statone pseudosubstrate 6. Labeling of water 2H2 0 or 2h21 0) establishes that water not Asp-32 adds to the carbonyl group (Cf text).

Most of the reactions that we will consider in this chapter involve addition of a proton to a carbon atom or removal of a proton attached to a carbon atom. A frequent metabolic reaction is addition of water to a carbon-carbon double bond that is conjugated with a carbonyl group. This transmits the polarization of the carbonyl group to a position located two carbon atoms further along the chain. 

We already have discussed additions of alcohols and, by analogy, thiols (RSH) to carbonyl compounds (see Section 15-4E). We will not repeat this discussion here except to point out that addition of water to the carbonyl group of an aldehyde is analogous to hemiacetal formation (Section 15-4E) and is catalyzed both by acids and bases ... 

Nucleophilic addition of water to hydrochloric derivatives of pyrimidoben-zoimidazole 300 with the formation of compound 301 was observed by El Ella et al. [167]. The hydrolytic cleavage of dihydrotriazolopyrimidine 302 into aminotriazole 147 and the appropriate unsaturated carbonyl 303 most likely occurs via initial addition of water [174, 175] (Scheme 3.105). 

---