Carbonyl compounds base-catalyzed hydration

Fig. 13 Base-catalyzed hydration of a carbonyl compound. Reproduced with permission from ref. 105. Copyright 2000. American Chemical Society.

The mechanistic pattern established by study of hydration and alcohol addition reactions of ketones and aldehydes is followed in a number of other reactions of carbonyl compounds. Reactions at carbonyl centers usually involve a series of addition and elimination steps proceeding through tetrahedral intermediates. These steps can be either acid-catalyzed or base-catalyzed. The rate and products of the reaction are determined by the reactivity of these tetrahedral intermediates. 

Both these methods require equilibrium constants for the microscopic rate determining step, and a detailed mechanism for the reaction. The approaches can be illustrated by base and acid-catalyzed carbonyl hydration. For the base-catalyzed process, the most general mechanism is written as general base catalysis by hydroxide in the case of a relatively unreactive carbonyl compound, the proton transfer is probably complete at the transition state so that the reaction is in effect a simple addition of hydroxide. By MMT this is treated as a two-dimensional reaction proton transfer and C-0 bond formation, and requires two intrinsic barriers, for proton transfer and for C-0 bond formation. By NBT this is a three-dimensional reaction proton transfer, C-0 bond formation, and geometry change at carbon, and all three are taken as having no barrier. 

Several preparative methods exist for the synthesis of 3(2//)-dihydrofuranones. 2,5-Disubstituted or 2,2,5,5-tetrasubstituted 3(2i/)-dihydrofuranones are usually prepared by reaction of sodium or lithium acetylide with a ketone to yield an alkynic alcohol which is then treated with a carbonyl compound in the presence of base to afford alkynic diols. Mercury catalyzed hydration of the resultant diols in the presence of acid affords the furanones in good yields (76JMC709). 

Fig. 12 Mechanisms for base-catalyzed, uncatalyzed, and acid-catalyzed hydration of carbonyl compounds.

Table 8 AG1 for hydration of carbonyl compounds by acid-catalyzed, base-catalyzed, and uncatalyzed mechanisms ...

In the base-catalyzed addition of nitromethane to aldehydes (the Henry reaction5,8), the methanenitronate anion attacks the electron-deficient carbonyl carbon atom. Such derivatives of aldehydes as the hydrates and hemiacetals react readily, owing to the presence of the carbonyl compound in mobile equilibrium, and consequently, aldoses are amenable to the reaction, which generally proceeds rapidly, giving good yields at or below room temperature. Usually, the stoichiometric amount of an alkali is employed for promoting the reactior. and the nitro alcohols are then obtained as nitronate salts and may... 

The COj species in the HT interlayer could be exchanged with OH ions by calcination at 723 K and hydration at room temperature. A spinel phase of Mg-Al mixed oxide obtained after the calcination transforms into the original layered structure during the hydration. This reconstruction is known as the memory effect of HT materials. The reconstructed HT catalyzed the Knoevenagel condensation of various aldehydes with nitriles in the presence of water [119]. The reconstracted HT also showed an aqueous Michael reaction of nitriles with a,p-unsaturated compounds. The layered double-hydroxide-supported diisopropylamine catalyzed the Knoevenagel condensation of aromatic carbonyl compounds with malononitrile or ethyl cyanoacetate [120]. This solid base could be recycled at least four times, and exhibited activity for aldol, Henry, Michael, transesterification, and epoxidation of alkenes. 

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. 

Figure 16.37 contrasts the base-catalyzed reaction of a carbonyl compound in water to give a hydrate with the related formation of a hemiacetal in an alcohol. The hemiacetal is similar to a gem- o, except that the central carbon has an OH and an OR group rather than two OH groups. 

We have been at pains to point out the similarities between these aldol reactions and other addition reactions of carbonyl compounds. Like simple additions, such as hydration, the aldol condensations are series of equilibria. They are affected by structural factors in the same way as the simple reactions. Product formation is unfavorable in base-catalyzed aldol reactions of ketones, just as it is in hydration... 

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