Aldehydes hydrate equilibrium

The rate of attack of water upon the tri-/>-anisylmethyl cation is unaffected by binding of this cation to anionic micelles of sodium dodecyl sulfate (SDS) (Bunton and Huang, 1972) and equilibrium constants for aldehyde hydration are only slightly reduced by binding to micelles (Albrizzio and Cordes, 1979). These observations are also consistent with substrate binding at a wet micellar surface rather than in the interior of the micelle. 

Mechanistic questions in the hydration-dehydration equilibrium center around the acid-base relationships and the precise sequence of events in the addition or elimination of the water molecule. Investigations have relied primarily on kinetics of aldehyde hydration to elucidate the mechanistic details ... 

Jones oxidation is generally not useful for the transformation of primary alcohols into aldehydes. This is due to the equilibrium of the aldehydes with the corresponding hydrates in the aqueous media, leading to the subsequent oxidation of the aldehyde hydrates into carboxylic acids. In fact, kinetic studies support the assumption that chromic acid oxidizes aldehydes into carboxylic acids via the corresponding aldehyde hydrates.5... 

The situation for the ordinary Hammett a values based on measurements of the dissociation constants is unsatisfactory. The experimental results do not seem to be very reproducible as between one set of authors and another18. The value of am appears to be about 0.40, and that of op to be about 0.5 (see also Hansch and coworkers86). These are certainly in the region expected for CHO rather than CH(OH)2, so it may well be that the hydration equilibrium is more in favour of CHO in aromatic aldehydes than in compounds in which the group is attached to a saturated carbon atom. 

While checking a sample of 2,5-anhydromannose-6-P for fructose-6-P by incubating it with phosphofructokinase and MgATP, we discovered that this aldehyde, which is sterically hindered from forming an internal hemiacetal, induced an ATPase activity (6). Since aldehyde hydration shows a large inverse equilibrium isotope effect of 0.73 when the hydrogen on the carbonyl carbon is replaced by deuterium (7,8), 2,5-anhydroman-nose-6-P-l-d will be 60% hydrated, compared to 52% hydration of the unlabeled aldehyde. If the free aldehyde were the activator, 48% of the unlabeled and 40% of the deuterated compound would be active, and a normal deuterium isotope effect of 0.48/0.40 = 1.2 would be seen on V/K (the apparent first order rate constant) for the activator, while if the hydrate were the active form, an inverse isotope effect of 0.52/0.60 = 0.87 would be seen. The observed value of 1.23 0.03 showed that the free aldehyde and not the hydrate was the activator (6). 

Ruthenium tetroxide oxidizes an alcohol to furnish an aldehyde. However, the oxidation does not stop at this stage. As soon as the corresponding aldehyde hydrate has been formed from the aldehyde at equilibrium—which is ensured by the high water content in the reaction mixture—the oxidation continues to form the carboxylic acid (example Figure 17.12). Mecha-... 

These stability effects are apparent in the equilibrium constants for hydration of ketones and aldehydes. Ketones have values of Keq of about 10-4 to 10-2. For most aldehydes, the equilibrium constant for hydration is close to 1. Formaldehyde, with no alkyl groups bonded to the carbonyl carbon, has a hydration equilibrium constant of about 40. Strongly electron-withdrawing substituents on the alkyl group of a ketone or aldehyde also destabilize the carbonyl group and favor the hydrate. Chloral (trichloroacetaldehyde) has an electron-withdrawing trichloromethyl group that favors the hydrate. Chloral forms a stable, crystalline hydrate that became famous in the movies as knockout drops or a Mickey Finn. 

The concentrations of hydrate and aldehyde at equilibrium in water may be determined by measuring the UV absorption of known concentrations of aldehyde in water and comparing these with the absorptions in a solvent such as cyclohexane where no hydrate formation is possible. Such experiments reveal that the equilibrium constant for this reaction in water at 25 °C is approximately 0.5 so that there is about twice as much aldehyde as hydrate in the equilibrium mixture. The corresponding value for AG° is -8.314 x 298 x ln(0.5) = +1.7 kj mol-1. In other words, the solution of the hydrate in water is 1.7 kj mol-1 higher in energy than the solution of the aldehyde in water. 

In a similar manner, 2-propanol is oxidized to 2-propanone and cyclobutanol to cyclobu-tanone. N-Methylmorpholine-N-oxide (NMO) or oxygen may be used to reoxidize the expensive TPAP catalyst. The water formed in the reaction is removed by molecular sieves, which prevents further oxidation of the aldehyde to the carboxylic acid. The presence of water increases an equilibrium concentration of the aldehyde hydrate, which can undergo further oxidation to carboxylic acid. The oxidation of 7.21 with TPAP in the presence of NMO gave 7.22 in good yield. ... 

I The intermediate is the chromate ester of the aldehyde hydrate RCH(OH)2 it seems likely at the ester is formed from the hydrate, which exists in equilibrium with the alde-hydA ih that case, what we are dealing with is essentially oxidation of a special kind of alcohol—a gem dxoh... 

In aqueous systems the reaction between the aldehyde hydrate and oxygen is fast, so high yields of the carboxyhc acid are formed as the equilibrium between the aldehyde and the hydrate is pulled to the hydrate as it is removed from the system by forming the acid with oxygen. 

The N.M.R. spectrum obtained depends on the position of the chloral —chloral hydrate equilibrium. Chloral gives a simple spectrum (CDClj), the aldehyde proton absorbing at 69.1. Chloral hydrate, however, consistently gives a peak at 9.1, plus other peaks whose positions are more variable, for hydroxyl absorptions are greatly influenced by temperature and concentration (see fig.3) ... 

In the equilibrium above, the hydrate is higher in energy than the aldehyde at equilibrium there is more aldehyde than hydrate, and the equilibrium constant is therefore less than 1. Whenever this is the case (i.e. the equilibrium lies to the side of the reactants, rather than the... 

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. 

Aldehyde Hydrates yem-DiolS Dissolving an aldehyde such as acetaldehyde in water causes the establishment of an equilibrium between the aldehyde and its hydrate. 

PCC does not oxidize aldehydes further because the PCC reagent is not used in water but rather in an organic solvent, usually CH2CI2. Without water, the product aldehyde is not in equilibrium with the aldehyde hydrate. Recall that only an —OH of an aldehyde hydrate is susceptible to further oxidation by Cr(VI), not an aldehyde carbonyl. Both PCC and H2Cr04 can be used for the oxidation of a T alcohol to a ketone. 

Aldehyde Hydrates ffem-Diols Dissolving an aldehyde such as acetaldehyde in water causes the establishment of an equilibrium between the aldehyde and its hydrate. This hydrate is in actuality a 1,1-diol, called a geminal diol (or simply a gm-diol). 

As these equations indicate, hydrations of aldehydes and ketones are reversible. The equilibrium lies to the left for ketones and to the right for formaldehyde and aldehydes bearing inductively electron-withdrawing substituents. For ordinary aldehydes, the equilibrium constant approaches unity. 

Table 17 3 compares the equilibrium constants for hydration of some simple aldehydes and ketones The position of equilibrium depends on what groups are attached to C=0 and how they affect its steric and electronic environment Both effects con tribute but the electronic effect controls A hydr more than the steric effect... 

Equilibrium Constants (AChydr) and Relative Rates of Hydration of Some Aldehydes and Ketones... 

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... 

The exceptions are formaldehyde, which is nearly completely hydrated in aqueous solution, and aldehydes and ketones with highly electronegative substituents, such as trichloroacetaldehyde and hexafluoroacetone. The data given in Table 8.1 illustrate that the equilibrium constant for hydration decreases with increasing alkyl substitution. 

Althoi h the equilibrium constant for hydration is unfavorable, the equilibrium between an aldehyde or ketone and its hydrate is established rapidly and can be detected by isotopic exchange, using water labeled with 0, for example ... 

As with resoles, we can use a three-phase model to discuss formation of a novolac. Whereas the resole is activated through the phenol, activation in novolacs occurs with protonation of the aldehyde as depicted in Scheme 12. The reader will note that the starting material for the methylolation has been depicted in hydrated form. The equilibrium level of dissolved formaldehyde gas in a 50% aqueous solution is on the order of one part in 10,000. Thus, the hydrated form is prevalent. Whereas protonation of the hydrate would be expected to promote dehydration, we do not mean to imply that the dehydrated cation is the primary reacting species, though it seems possible. 

Electronic and steric effects operate in the sane duection. Both cause the equilibrium constants for hydration of aldehydes to be greater than those of ketones. 

The study of structure and reactivity of tertiary heterocyclic enamines is associated with the problem of equilibrium of the cyclic enamine form (70) and the tautomeric hydration products 173,174) quaternary hydroxide (71), pseudo base (so-called carbinolamine) (72) and an opened form of amino aldehyde or amino ketone (73). 

The addition of water across carbon-carbon double bonds, a reaction thoroughly investigated by Lucas and Taft, requires strong activation and is catalyzed by hydrogen ions and hydroxyl ions. Addition of water across the 0= =0 bond of aldehydes has also been studied kinetically. Whereas chloral and formaldehyde are largely hydrated (at equilibrium in dilute aqueous solution), acetaldehyde and other... 

Occasionally it happens that the oxo compound, produced by oxidation, forms a hydrate which is further oxidized to a dihydroxy compound. Attention must be given to the possibility (so far unreported) that when the hydrated species is in equilibrium with a trace of the ring-opened structure a sufficiently fast oxidation rate of the amino-aldehyde (i.e. the acyclic structure) could lead to the incorrect conclusion that the original material was not cyclic. 

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). 

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