Reactions of a-Hydrogens:Condensation Reactions Chapter 21 WWU -- Chemistry
Assignment for Chapter 21 • DO: • Sections 21.0 through 21.4 • Sections 21.7 through 21.9 • Sections 21.12 through 21.17 • Section 21.22 • SKIP: • Sections 21.5 through 21.6 • Sections 21.10 through 21.11 • Sections 21.18 through 21.21
ALSO DO: • Summary • Problems
Problem Assignment • In-Text Problems: • 21-1 through 21-9 • 21-12 through 21-17 • 21-25 through 21-45 • End-of-Chapter Problems: • 1 through 11 • 13 through 24
Tautomerism • Compounds whose structures differ markedly in the arrangement of atoms, but which exist in equilibrium, are called tautomers. • Most often, tautomers are species that differ by the position of a hydrogen atom and which exist in equilibrium. • The best-known example is keto-enoltautomerism.
Keto-Enol Tautomerism • In general, the equilibrium favors the keto form very dramatically. • If one calculates the relative energies of the keto and enol forms, one concludes that the formation of enol from keto should be endothermic by about75 kJ/mole.
Keto-Enol Tautomerism • From this energy, one calculates an equilibrium constant for enolization: 6.3 x 10-14 • Clearly, for most aldehydes and ketones, the ability to form an enol is an extremely minor property.
Keto-Enol Tautomerism • In the case of 1,3-dicarbonyl compounds, however, the equilibrium may shift to favor the enol form, since a stabilized, hydrogen-bonded structure is now possible.
Keto-Enol Tautomerism in 1,3-Dicarbonyl Compounds • The equilibrium lies substantially to the right. • In simple ketones, such a hydrogen-bonded structure cannot form, and the percentage of enol found in an equilibrium mixture is very small. • The following tables illustrate some typical enol percentages. Notice the difference between simple ketones and dicarbonyl compounds.
One last comment on this... • You may recognize some structural similarities between enols and enamines. • Whenever an enol form can exist, it has the potential to be a nucleophile!
Acidity of a-Hydrogens • Review material in Chapter 7, Section 7.7 • The acidity of a hydrogen attached to the a-carbon of a carbonyl compound is much higher than the acidity of a typical C-H hydrogen. • pKa values range from about 19 to 20 (compared with 48 to 50)
Acidity of a-Hydrogens • Resonance stabilization of the enolate ion shifts the equilibrium to the right, thereby making the C-H bond more acidic. • Once formed, the enolate ion is capable of reacting as a nucleophile. The a-carbon of the enolate ion bears substantial negative charge.
The experimental rate law is: Rate = k[ketone][OH-] Note that the rate law does not contain bromine! Base-Promoted Halogenation of Ketones
Mechanism Note that the first step is rate-determining
But... • The halogenation is difficult to stop at the mono-substitution stage. • Often, poly-halogenated products are formed in this reaction.
There is also an acid-catalyzed halogenation reaction, which operates through the formation of the enol form of the ketone (recall that the enol is nucleophilic). • Once formed, the enol displaces bromide ion from Br2, forming the brominated product. • In the acid-catalyzed mechanism, mono-substitution is the predominant result.
Alkylation of Enolate Ions • In the presence of a very strong base, the a-hydrogen of an aldehyde or ketone can be replaced by an alkyl group. • Once again, the strong base removes an a-hydrogen to form an enolate ion. • The enolate ion, acting as a nucleophile, participates in an SN2 substitution with an alkyl halide.
… and the “strong base” is: Best Choice
Alkylation of Enolate Ions • Remember that enamines can also react with alkyl halides to give similar products. • Review Chapter 16, Section 16.13. • See also Chapter 21, Section 21.8.