Topics for Exam III

Chapter 19-Carboxylic Acids

Decarboxylation of malonates (same reaction covered in chapter 21)

Chapter 20-Nucleophilic Acyl Substitution (NAS)

Topics:
Rationalizing reactivity of carboxylic acid derivatives based on electrophilicity of carbonyl.

Synthesis of anhydrides, amides (and lactams), and esters (and lactones) via strong nucleophiles
under basic/anionic conditions

Synthesis of anhydrides, amides, and esters via strong nucleophiles under acidic conditions.
e.g. Fisher esterification.

Reactions of esters and nitriles with organometallics: Grignard/organolithim + ester yield

tertiary alcohol. LiAlH4 + ester yields primary alcohol. Grignard/organolithium + Nitrile yields
Ketone.

Multi-step synthesis: be able to use NAS in multistep syntheses. Note 2301 conditions:
alcohols can be converted in alkyl halides (SOCl2 or PBr3) and Carboxylic acids can be converted
into Acid Chlorides via SOCl2.

Mechanisms:
Be able to draw a general mechanism for NAS under either basic or acidic conditions
E.g. Hydrolysis or synthesis of esters, hydrolysis or synthesis of amides, hydrolysis of nitriles

Chapter 21:
-Rationalize acidity of alpha hydrogens in carbonyl containing compounds

-Enolate alkylation. Also be able to predict products for kinetic and thermodynamic enolates

-Aldol addition and aldol condensation reaction. Be able to predict products, or starting
materials for Self-crossed and intramolecular (5 or 6 mem rings!) reactions

-Halogenation under neutral, acidic, or basic conditions

-Claisen crossed, self, and intramolecular (5 or 6 mem rings!) Be able to predict products, or
starting materials

- Be able to predict products, or starting materials for Malonic ester and Acetoacetic ester
synthesis

-Conjugate addition reactions will not be covered on this exam.

Mechanism:
You should be able to show a mechanisms for Aldol and Claisen reactions and enolate alkylation
as well as enol tautomerization.