CHE 232-001

Facts and Skills to Master for the Fourth Exam

The fourth exam will cover Klein Chapters 1–22 plus section 23.5–6. The following guidelines are not meant to be complete or comprehensive lists of the information you are expected to know.

You are expected to have command of all the material covered on the third exam.

You should be able to predict the product, including the correct regiochemistry, of the following reactions:

• RCO₂H + SOCl₂
• RCOCl or RCO₂COR + alcohol (with or without base) or 1° or 2° amine
• RCO₂H + small or tethered alcohol, cat. acid, Δ
• RCOX (X = Cl, O₂CR, SR, OR, or NR₂) or RCN + aqueous acid or base
• RCO₂H + 1° or 2° amine + DCC
• RCONH₂ + SOCl₂
• simple ketone, ester, amide, or nitrile + 1 equivalent LDA, then RI
• simple ketone + excess RBr or RI, excess moderate base
• 1,3-dicarbonyl + 1 equivalent moderate base, then RBr
• β-carbonyl or α-cyano ester + aq. LiI, DMSO, Δ
• β-carbonyl or α-cyano ester + aq. acid or base, then acid, Δ
• simple ketone, aldehyde, acyl anhydride, or acyl chloride + Br₂ or Cl₂
• simple ketone, ester, amide, or nitrile + 1 equivalent LDA, then aldehyde or ketone
• simple ketone or aldehyde + simple ketone or aldehyde, catalytic moderate base or acid
• simple ketone or ester + ester, 1 equivalent moderate base, Δ, then aqueous workup or RBr
• 1,3-dicarbonyl + α,β-unsaturated carbonyl, catalytic moderate base

You should be able to draw mechanisms that involve all of the above reactions. (Note that the mechanism for elimination of H₂O from an aldol under acidic conditions proceeds through the enol, and that the mechanism for the Claisen or Dieckmann reaction must include deprotonation of the product 1,3-dicarbonyl to be considered correct.)

You should be able to design a synthesis of a target compound from simpler starting materials using any of the reactions above as well as reactions that we studied earlier in the semester and in CHE 230.

You should understand and be able to explain why the course of alkylation of ketones changes when one uses LDA versus a moderate base.

You should understand and be able to explain why it is sometimes necessary to use a 1,3-dicarbonyl compound as a nucleophile in a synthesis instead of a simple carbonyl compound.

You should understand and be able to explain what factors allow a mixed aldol or mixed Claisen condensation to be selective for a single product.

You should understand and be able to explain under what circumstances the equilibrium for an aldol or Claisen condensation favors the starting materials, or when retro-aldol or retro-Claisen condensations are favored.

You should understand and be able to explain why Claisen and Dieckmann condensations and aldol reactions that are followed by dehydration require that the nucleophile have two H atoms on the α-carbon.