CHE 232-001

Facts and Skills to Master for the Third Exam

The third exam will cover Klein Chapters 1–19, plus sections 22.10–11 and 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 second exam.

You should be able to predict the product of the following reactions ("ketohyde" means "ketone or aldehyde"):

• electrophilic aromatic substitution^* of an aromatic compound with:
• HNO₃;
• Cl₂, FeCl₃;
• Br₂, FeBr₃;
• alkyl or acyl halide, AlCl₃;
• ArC(=O)R + Zn, H⁺ or N₂H₄, then aq. NaOH, Δ;
• a nitroaromatic (ArNO₂) with SnCl₂, aq. HCl or H₂, Pd/C;
• an aniline (ArNH₂) with NaNO₂ and HCl,^* then nucleophilic aromatic substitution of ArN₂⁺ with:
• CuCl, CuBr, CuCN, or aq. Cu₂O;
• KI, KBF₄, or H₃PO₂;
• nucleophilic aromatic substitution of an aryl halide with:
• RC≡CH and Pd(0)–phosphine catalyst, base;
• RSnMe₃ and Pd(0)–phosphine catalyst;
• C(sp²)–B(OH)₂ and Pd(0)–phosphine catalyst, base;
• alcohol or 1° or 2° amine and Pd(0)–phosphine catalyst, base;
• CO, MeOH or EtOH, Pd(0)–phosphine catalyst, base;
• nucleophilic aromatic substitution of an electron-poor aryl halide with a simple nucleophile such as an alkoxide or amine;^*
• an aromatic compound with Li in liquid NH₃ and t-BuOH;
• ArCHR₂ + KMnO₄;
• RBr + Mg [and remember ROH + PBr₃ → RBr, as does alkene + HBr ± O₂];
• ketohyde or ester + RMgBr or RLi^*
• ketohyde or ester + LiAlH₄^*
• ketohyde + NaBH₄
• 1° or 2° alcohol + PCC
• 1° or 2° alcohol or ketohyde + aq. CrO₃, H⁺
• ketohyde + alcohol or 1,2-diol under acidic or basic conditions^*
• ketohyde + 1° or 2° amine under acidic or basic conditions in the presence of:^*
• nothing else
• NaBH₃CN
• NaCN, then aq. NaOH
• ketohyde + Ph₃P=CR₂
• ketone + mCPBA, H^+*

You should be able to draw the mechanisms of the reactions above that are marked with an asterisk, including those electrophilic aromatic substitution reactions that may result in rearrangements and including biological examples of reactions involving ketohydes, alcohols, and amines.

You should be able to design a synthesis of a target compound from simpler starting materials using any of the reactions above. The new disconnections we have learned are:

• between an aromatic C and an adjacent:
• CN or other C(sp)
• C(=O)R, CO₂R, or other C(sp²)
• C(sp³)
• NH₂, or substituted N
• OH, or substituted O
• between an alcohol C and an adjacent C
• the N–C and C–H bonds in an amine with an N–C(sp³)–H group
• the N–C and C–CO₂H bonds in an α-amino acid
• down the middle of a double bond with cis stereochemistry or no stereochemistry
• excising the noncarbonyl O from an ester

• ArNO₂ → ArNH₂ → aryl halides or ArOH or ArH
• ArCHR₂ or ArCN or ArCO₂Me → ArCO₂H
• arene → 1,4-cyclohexadiene
• among ketohydes, hemiacetals, acetals, imines, and enamines;
• among 1° alcohols, aldehydes, and esters
• among 2° alcohols and ketones

You should understand and be able to explain the factors that make aromatic substituents activators or deactivators and ortho–para or meta directors.

You should understand and be able to explain how Pd catalysis enables many aryl halide substitution reactions to proceed.

You should understand and be able to explain factors that affect the equilibrium between ketohyde + alcohol, hemiacetal, and acetal, or between ketohyde + amine, imine, and enamine.

You should understand and be able to explain why some carbonyl compounds are higher or lower in energy than others.

You should understand and be able to explain factors that affect the equilibrium between ketohyde + alcohol, hemiacetal, and acetal, or between ketohyde + amine, imine, and enamine.

This page was last updated April 1, 2019.