Carbonyl compounds acid-catalyzed hydration

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

Fig. 15 Acid-catalyzed hydration of a carbonyl compound. Reproduced with permission from ref. 105. Copyright 2000. American Chemical Society.

FIGURE 16.25 A comparison of the acid-catalyzed hydration reactions of (a) an alkene and (b) a carbonyl compound. 

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. 

Si. rra(pentafluorophenyl)boron was found to be an efficient, air-stable, and water-tolerant Lewis-acid catalyst for the allylation reaction of allylsilanes with aldehydes.167 Sc(OTf)3-catalyzed allylations of hydrates of a-keto aldehydes, glyoxylates and activated aromatic aldehydes with allyltrimethylsilane in H2O-CH3CN were examined. a-Keto and a-ester homoallylic alcohols and aromatic homoallylic alcohols were obtained in good to excellent yields.168 Allylation reactions of carbonyl compounds such as aldehydes and reactive ketones using allyltrimethoxysilane in aqueous media proceeded smoothly in the presence of 5 mol% of a CdF2-terpyridine complex (Eq. 8.71).169... 

At lower acidities the iV-nitrobenzamides and /V-methyl-.V-nitrobenzamides have a hydrolysis mechanism that is not acid-catalyzed for these cases plots of log kv - log h2o are linear, as for the acyhmidazoles discussed above. N-Nitroacetamide also hydrolyzes in this way.291 The proposed mechanism is given in Scheme 17, written for TV-nitroacetamide if the hydration shown is a pre-equilibrium (this is a carbonyl compound with a strong electron-withdrawing group attached, so this is likely), only one water molecule will appear in the rate expression (the difference between 3 and 2), as observed.287 Some evidence for hydroxide-catalyzed processes at the very lowest acidities was also found for some of these compounds.287... 

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). 

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

CO2 promotes the reaction of unreactive nitrile groups at moderate pH but cannot be truly considered as a catalyst since it is not released at the end of the reaction (unless the hydantoin undergoes further hydrolysis) unlike carbonyl compounds in a-aminonitrile hydration (Sect. 2.1.3). However, hydantoins can be considered as AA precursors through a two-step hydrolysis. The first step leads to an N-carbamoyl amino acid (CAA). The rate of this HCT-catalyzed step has been examined by Taillades and co-workers [43], extending the earlier work of Blagoeva et al. [49]. 

There are many examples of acid catalyzed carbonyl addition reactions, such as formation of hydrates (R2C(OH)2), hemiacetals, hemiketals, cyanohydrins, bisulfite compounds, azomethines, oximes, hydrazones, etc. These important reactions are discussed in Vol. 11. 

Methyl and methylene groups adjacent to carbonyl groups are easily oxidized to carbonyls to yield a-keto aldehydes or a-diketones. The reagent of choice is selenium dioxide or selenious acid. The reaction is catalyzed by acids and by acetate ion and proceeds through transition states involving enols of the carbonyl compounds [518]. The oxidation is carried out by refluxing the ketone with about 1.1 mol of selenium dioxide in water, dilute acetic acid, dioxane, or aqueous dioxane [517]. The byproduct, black selenium, is filtered off, but small amounts of red selenium sometimes remain in a colloidal form and cannot be removed even by distillation of the product. Shaking the product with mercury [523] or Raney nickel [524] takes care of the residual selenium. The a-dicarbonyl compounds are yellow oils that avidly react with water to form white crystalline hydrates (equations 407 and 408). 

Two examples of monocyclic 1,3,4-oxadiazepines have been reported. The fully unsaturated compounds have, however, not been isolated, although the photolysis of pyrimidine. iV-oxides is known to involve such oxadiazepines as unisolable intermediates <69TL4899>. 2-Benzoylpropene or 2-benzoylpropanol condensed with hydrazine hydrate and an appropriate carboxylic acid to form the hydrazone esters (133), which were converted into the 6,7-dihydro-l,3,4-oxadiazepines (134) (30 72% yields) by intramolecular attack of the amino group to the ester carbonyl, followed by acid-catalyzed loss of water (Scheme 23) <84S342>. 

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. 

The reactivity of carbon-carbon double bonds toward acid-catalyzed addition of water is strongly increased by electron-releasing groups, and the reaction of vinyl ethers with water in acidic solution has been extensively studied. With these substrates, the initial addition products are unstable and decompose to carbonyl compounds and alcohol. Nevertheless, the hydration is rate-determining, and so the kinetic results pertain to this step. The mechanistic features that have been... 

In the acid-catalyzed reactions, water can be lost from the hydrate, hemiacetai, and carbinoiamine to give new, resonance-stabilized intermediates. In the hydrate, this results only in reformation of the original carbonyl group, but new compounds can be produced in the other two cases. The carbinolamines... 

Imines and enamines are hydrolyzed under acidic conditions back to the carbonyl compound and the amine. Aldehydes and ketones undergo acid-catalyzed addition of water to form hydrates. Electron-donating and bulky substituents decrease the percentage of hydrate present at equilibrium. Most hydrates are too unstable to be isolated. 

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