1. Reactions of a-Hydrogens:Condensation Reactions Chapter 21 WWU -- Chemistry

2. 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

3. ALSO DO: • Summary • Problems

4. 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

5. 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.

6. Keto-Enol Tautomerism

7. 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.

8. 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.

9. 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.

10. Keto-Enol Tautomerism in 1,3-Dicarbonyl Compounds

11. 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.

12. Some Representative Enol Percents

13. More Representative Enol Percents

14. 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!

15. 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)

16. Acidity of a-Hydrogens: The Reason

17. 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.

18. Base-Promoted Halogenation of Ketones

19. The experimental rate law is: Rate = k[ketone][OH-] Note that the rate law does not contain bromine! Base-Promoted Halogenation of Ketones

20. Mechanism Note that the first step is rate-determining

21. Example

22. But... • The halogenation is difficult to stop at the mono-substitution stage. • Often, poly-halogenated products are formed in this reaction.

23. With an excess of bromine:

24. 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.

25. Example

26. 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.

27. Alkylation of a Ketone

28. … and the “strong base” is: Best Choice

29. Mechanism

30. 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.

31. Example

32. Here’s something different: