Mechanism aldehyde hydration

Hydration of aldehydes and ketones is a rapid reaction quickly reaching equilibrium but faster in acid or base than in neutral solution Thus instead of a single mechanism for hydration we 11 look at two mechanisms one for basic and the other for acidic solution... 

Aldehydes can be oxidized to carboxylic acids by both Mn(VII) and Cr(VI). Fairly detailed mechanistic studies have been carried out for Cr(VI). A chromate ester of the aldehyde hydrate is believed to be formed, and this species decomposes in the rate-determining step by a mechanism similar to the one that operates in alcohol oxidations.209... 

The feasibility of some of these radical pathways has been examined using Marcus theory to obtain rate constants for comparison with the experimental data (Eberson, 1984). For some relevant anions, including hydroxide, methoxide, t-butoxide, the anion of benzaldehyde hydrate and di-2-propyl-amide, the necessary E°(RO-/RO) values are available or can be estimated with sufficient accuracy. For the reaction of t-butoxide with benzophenone in THF, or the benzaldehyde hydrate anion with benzaldehyde in aqueous dioxan, direct electron transfers between the anion and the neutral are not feasible the calculated rate constants are orders of magnitude too low to be compatible with the observed reduction rates. Any radicals observed in these reactions must arise by some other more complex mechanism. The behaviour of an aromatic aldehyde hydrate dianion has not been examined in this way, but MNDO calculation (Rzepa and Miller, 1985) suggests that such a species could easily transfer either a single electron or a hydrogen atom to an accepting aldehyde. 

Fig. 6.34. Chemoselective reduction of free carboxylic acids to aldehydes. Intermediate B yields, upon hydrolysis, initially an aldehyde hydrate, which dehydrates to the aldehyde spontaneously (mechanism Section 7.2.1).

FIGURE 17.4 The mechanism of hydration of an aldehyde or ketone in basic solution. Hydroxide ion is a catalyst it is consumed in the first step, and regenerated in the second. 

Two mechanisms for the NAD -dependent oxidation of an alcohol to a carboxylate have been characterized in enzymatic reactions. In the first mechanism, an active-site cysteine plays a crucial role in the reaction. A hydride is transferred to NAD from the alcohol substrate to generate an aldehyde intermediate, then the cysteine thiolate attacks the aldehyde to form a thiohemiacetal intermediate. The thiohemiacetal is oxidized by the second NAD" " to form a thioester, which is hydrolyzed to generate the carboxylate product. The second mechanism is similar to the first, except that the aldehyde undergoes hydration instead of thiohemiacetal formation. The aldehyde hydrate is oxidized by NAD" " to form the observed product. This reaction proceeds... 

Step 6 is the final step in the cellulose-to-lactic acid cascade, involving the isomerization of the 2-keto-hemi-acetal (here pyruvic aldehyde hydrate) into a 2-hydroxy-carboxyhc acid. This reaction is known to proceed in basic media following a Cannizzaro reaction with 1,2-hydride shift [111], Under mild conditions, Lewis acids are able to catalyze this vital step, which can also be seen as an Meerwein-Ponndorf-Verley reduction reaction mechanism. The 1,2-hydride shift has been demonstrated with deuterium labeled solvents [110, 112], Attack of the solvent molecule (water or alcohol) on pymvic aldehyde (step 5) and the hydride shift (step 6) might occur in a concerted mechanism, but the presence of the hemiacetal in ethanol has been demonstrated for pyruvic aldehyde with chromatography by Li et al. [113] andfor4-methoxyethylglyoxal with in situ CNMRby Dusselier et al. (see Sect. 7) [114]. 

You might ask how an aldehyde can be oxidized by this mechanism, since an aldehyde does not contain a hydroxyl group to participate as shown above. The answer lies in whether the aldehyde reaction mixture includes water or not. In the presence of water, an aldehyde can form an aldehyde hydrate (by an addition reaction that we shall study in Chapter 16). 

The carbon of an aldehyde hydrate has both a hydroxyl group and the hydrogen atom required for elimination thus when water is present, an aldehyde can be oxidized by the mechanism shown above. Although the aldehyde hydrate may be present in low equilibrium concentration, those molecules in the hydrate form can be oxidized, drawing the reaction ultimately toward oxidation of all of aldehyde molecules to the corresponding carboxylic acid via LeChatelier s principle. 

Oxidation of a Primary Alcohol to a Carboxylic Acid (Section 10.8A) A primary alcohol is oxidized to a carboxylic acid by chromic acid. The mechanism involves initial formation of an alkyl chromate intermediate, followed by reaction with base to remove a proton, generating the carbonyl group of an aldehyde and simultaneously reducing the chromium(VI) to chromium(IV). An initially formed aldehyde adds water, generating an aldehyde hydrate, which is oxidized according to the same mechanism to give the carboxylic acid. 

The aldehyde initially formed from the 1° alcohol (produced by a mechanism similar to the one we have just given) reacts with water to form an aldehyde hydrate. The aldehyde hydrate can then react with HCr04 (and H+) to form a chromate ester, and this can then be oxidized to the carboxylic acid. In the absence of water (i.e., using PCC in CH2CI2), the aldehyde hydrate does not form therefore, further oxidation does not take place. 

Oxidation of aliphatic aldehydes by benzyltrimethylammonium chlorobromate to the corresponding carboxylic acid proceeds via the transfer of a hydride ion from the aldehyde hydrate to the oxidant. The oxidation of aUyl alcohol with potassium bromate in the presence of osmium(Vin) catalyst in aqueous acidic medium is first order in bromate, Os(Vni) and substrate, but inverse fractional order in H+ the stoichiometry of the reaction is 2 3 (oxidantsubstrate). The active species of oxidant and catalyst in the reaction were understood to be BrOs and H2OSO5, respectively, which form a complex. Autocatalysis by Br, one of the products, was observed, and attributed to complex formation between Br and osmium(VIII). First-order kinetics each in BrOs, Ru(VI), and substrate were observed for the ruthenium(VI)-catalyzed oxidation of cyclopentanol by alkaline KBrOs containing Hg(OAc)2. A zero-order dependence on HO concentration was observed and a suitable mechanism was postulated. The oxidation reaction of aniUne blue (AB+) with bromate at low pH exhibits interesting non-linear phenomena. The depletion of AB+ in the presence of excess of bromate and acid occurs at a distinctly slow rate, followed by a very rapid reaction. A 12-step reaction mechanism, consistent with the reaction dynamics, has been proposed. The novel cyclohexane-l,4-dione-bromate-acid system has been shown to exhibit a rapid oscillatory redox reaction superimposed on a slower... 

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