Equilibrium constants for hydration

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... 

A striking example of an electronic effect on carbonyl group stability and its rela tion to the equilibrium constant for hydration is seen m the case of hexafluoroacetone In contrast to the almost negligible hydration of acetone hexafluoroacetone is completely hydrated... 

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 ... 

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. 

Exercise 16-17 The equilibrium constants for hydration are especially large for methanal, trichloroethanal, cyclopropanone, and compounds with the grouping —COCOCO—. Explain. 

Equilibrium constants for hydration and hemiacetal fonnation have been calculated for representative highly fluorinated ketones.5 Both reactions were substantially more favourable in cyclic than acyclic systems. 

In addition to carbocations, extensive measurements of pK s of oxygen and nitrogen protonated bases have been undertaken, including pK s of proto-nated ketones.65,74 As described below, these lead indirectly to p fR values for a-hydroxycarbocations if the equilibrium constants for hydration of the ketones are known. 

For such unstable carbocations, an alternative approach to pAR can be developed, by recognizing the relationship that exists between pATR and pAa implied in Equation (15) (p. 30). For carbocations with [3-hydrogen atoms, loss of a proton normally yields an alkene. Then, as discussed by Richard, pATR and pAa form two arms of a thermodynamic cycle, of which the third is the equilibrium constant for hydration of the alkene, pAH2o, as already indicated in Scheme 1. The relationship between these equilibrium constants is shown for the t-butyl cation in Scheme 4. In the scheme the equilibria are... 

The pifas for C-protonation of the phenols and phenoxide ions are compared with values for the unsubstituted aromatic molecules in Table 3. The focus on pKn rather than pAR is because the equilibrium constants for hydration of the keto tautomers of the phenols have not been measured or estimated. The values of Ap and ApKf show the magnitude of the oxygen substituent effects relative to the parent aromatic molecules. Again the substituent effects are large, and much larger for O (more then 20 log units) than OH ( 10 log units). At first, it is surprising that the effects are so similar for the benzene, naphthalene, and anthracene. Once more this arises because the pWa reflects the stability of... 

B-5. Rank the following in order of increasing value of the equilibrium constant for hydration, Khyi (smallest value first). 

An important example of this effect is the decrease in equilibrium constants for ketones as compared to aldehydes. The replacement of the aldehyde hydrogen of acetaldehyde (K = 1.3) with a methyl group, to produce acetone (K = 2 X 10-3), results in a decrease in the equilibrium constant for hydration by a factor of approximately 1000. The inductive effect of the electron-donating alkyl group also helps shift the equilibrium for ketones toward the reactant. 

Table 18.1 Some Equilibrium Constants for Hydrate Formation...

Formaldehyde has a large equilibrium constant for hydrate formation because it has no bulky, electron-donating alkyl 2 X I03 groups. It is more than 99.9% in the hydrated form in... 

Explain which compound has the larger equilibrium constant for hydrate formation ... 

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. 

Carbonyl often exists as gem-diol (hydrate) in a aqueous solution (R— CO—R + H2O. R—C(0H)2—R ). The nucleophile (hydroxide ion, HO—) in a base-catalyzed reaction is much more powerful than a water molecule, the nucleophile in neutral media. Aldehydes react faster than ketones because equilibrium constants for hydration are more favorable for aldehydes than they are for ketones. Aldehydes [CO(R )(H)] also react readily with amines (primary amines form an imine or Schiff bases R—N=C(R )(H) -1- H2O while secondary amines form an enamine (must have an aldehyde with hydrogen on alpha carbon). 

Equilibrium constants for hydrations of hexafluoroacetone and acetone in water clearly reveal a big difference in hydration equilibrium constants between both ketones, as shown in Scheme 1.14 [4]. Likewise, calculated heats of hydration of fluoroacetones and fluoroac-etaldehyde indicate that the energy gain for hydration increases with the increasing number of fluorine substituents, as shown in Table 1.21 [5]. 

Aldol addition reactions of ketones are rarely successful, since they are usually endoergonic. For example, the base-mediated aldolization of acetone provides only a few percent of the aldol, diacetone alcohol (equation 26). However, the conversion may be accomplished in 75% yield by refluxing acetone under a Soxhlet extractor containing calcium or barium hydroxide. - On the other hand, di-methoxyacetone dimerizes under basic conditions to the aldol, with an equilibrium constant significantly greater than unity (K = 10 dm mol equation 27). The difference in equilibrium constants of equations (26) and (27) parallels the equilibrium constants for hydration of the two ketones, and results from the inductive effect of the methoxy groups. 

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