WWU -- Chemistry Reactions of  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 through Section SKIP: Sections 21.5 through 21.6 Sections through Sections through 21.21

WWU -- Chemistry ALSO DO: Summary Problems

WWU -- Chemistry Problem Assignment In-Text Problems: 21-1 through through through End-of-Chapter Problems: 1 through through 24

WWU -- Chemistry 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-enol tautomerism.

WWU -- Chemistry Keto-Enol Tautomerism

WWU -- Chemistry 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 about 75 kJ/mole.

WWU -- Chemistry Keto-Enol Tautomerism From this energy, one calculates an equilibrium constant for enolization: 6.3 x Clearly, for most aldehydes and ketones, the ability to form an enol is an extremely minor property.

WWU -- Chemistry 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.

WWU -- Chemistry Keto-Enol Tautomerism in 1,3- Dicarbonyl Compounds

WWU -- Chemistry 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.

WWU -- Chemistry Some Representative Enol Percents

WWU -- Chemistry More Representative Enol Percents

WWU -- Chemistry 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!

WWU -- Chemistry Acidity of  -Hydrogens Review material in Chapter 7, Section 7.7 The acidity of a hydrogen attached to the  -carbon of a carbonyl compound is much higher than the acidity of a typical C-H hydrogen. pK a values range from about 19 to 20 (compared with 48 to 50)

WWU -- Chemistry Acidity of  -Hydrogens: The Reason

WWU -- Chemistry Acidity of  -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  -carbon of the enolate ion bears substantial negative charge.

WWU -- Chemistry Base-Promoted Halogenation of Ketones

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

WWU -- Chemistry Mechanism Note that the first step is rate- determining

WWU -- Chemistry Example

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

WWU -- Chemistry With an excess of bromine:

WWU -- Chemistry 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 Br 2, forming the brominated product. In the acid-catalyzed mechanism, mono- substitution is the predominant result.

WWU -- Chemistry Example

WWU -- Chemistry Alkylation of Enolate Ions In the presence of a very strong base, the  -hydrogen of an aldehyde or ketone can be replaced by an alkyl group. Once again, the strong base removes an  -hydrogen to form an enolate ion. The enolate ion, acting as a nucleophile, participates in an S N 2 substitution with an alkyl halide.

WWU -- Chemistry Alkylation of a Ketone

WWU -- Chemistry … and the “strong base” is: Best Choice

WWU -- Chemistry Mechanism

WWU -- Chemistry Alkylation of Enolate Ions Remember that enamines can also react with alkyl halides to give similar products. Review Chapter 16, Section See also Chapter 21, Section 21.8.

WWU -- Chemistry Example

WWU -- Chemistry Here’s something different: