Step 2: Acyl Transfer Reaction

FORMATION OF TETRAHEDRAL INTERMEDIATE

The pi bond LUMO on the ester carboxyl group will have the highest electron probability density near the carbon atom, due to the low electronegativity of carbon in relation to oxygen. As a result, the highly basic methoxy anion will react with the LUMO of the carbonyl bond through the methoxy group HOMO made up of the high-energy oxygen non-bonding electrons. The pi bond will break and the electrons formerly in the carbonyl pi bond will be transfered to the most electronegative atom nearby, the oxygen on the carbonyl group, to form an oxygen anion. The resulting structure is a tetrahedral intermediate with a negative charge on the oxygen from the former carbonyl group.

LONE-PAIR ASSISTED IONIZATION

Due to the negative charge present on the oxygen anion, the nonbonding electrons will be higher in energy. Thus, the HOMO of the molecule are the nonbonding electrons on the negatively charged oxygen. A pair of non-bonding electrons from the HOMO will attack the LUMO of either the carbon-oxygen bond between the hydroxyl group and the rest of the molecule, or the carbon-oxygen bond between the methoxy group and the remaining portion of the molecule. In either case, the carbon-oxygen sigma antibonding orbital will have electron probability density concentrated around the low-electronegative carbon atom. Since the oxygen non-bonding electrons are near the LUMO carbon, lone-pair assisted ionization will readily occur. Only the addition of the HOMO oxygen non-bonding electrons to the carbon=oxygen sigma bond LUMO attaching the methoxy group to the molecule will drive the reaction forward, and so the oxygen non-bonding electrons will fill the carbon-oxygen holding the methoxy group to the molecule. As a result, the methoxy group will leave, and the carbonyl pi bond will be restored.

DEPROTONATION

The product from lone-paired assisted ionization is sodium methoxide and carboxylic acid. The proton on the carboxylic acid group is highly acidic, since the deprotonated carboxylic acid group is a resonance stabilized anion. Also, the non-bonding electrons on the methoxy anion are high in energy, and so the HOMO of the methoxy anion is high due to the non-stabilized negative charge concentrated on the oxygen atom. Thus, the methoxy anion oxygen atom is highly basic, and so the acidic proton on the carboxylic acid group will readily transfer to the methoxy anion, resulting in methanol and sodium salt of carboxylate.

(There will be an acidic workup which will protonate the carboxylate.)

PROTIP: If the animations do not activate on your computer, then open another slide on the slideshow and go back to the desired slide for a guaranteed, live animation.

University of Michigan Chem 215/216 HH Winter 2014. Nicholas Carducci's Structured Study Group. HTML Project of Callie Chappell, James Lawniczak, Aiman Faruqi, and Ryan Gentil