Organic 1: Nucleophilic addition to the carbonyl group

Question 1

what does ⇒ mean

Answer 1

can be made from

Question 2

2 main steps of nucleophilic addition to C=O?

Answer 2

1. Nucleophilic addition to carbonyl
2. Protonation of resulting anion

Question 3

Why is the C in C=O attacked rather than O?

Answer 3

• C & O in carbonyl are sp2
• So O lone pairs are in sp2 orbitals perpendicular to pi system
• Largest pi* coefficient is on C
• So strongest interaction with nucleophile is with C

(Incomplete explanation: large carbonyl dipole & electrostatic attraction between carbon & nucleophile)

Question 4

Why is the 107^o angle of attack most favourable?

(Burgi-Dunitz trajectory)

Answer 4

• In-plane approach, 180^o → no net interaction due to equal degrees of constructive & destructive interference
• Directly above, 90^o → no net overlap for same reason
• From this alone, ideal angle would be 135^o to align with C=O pi* & therefore give maximum overlap
• But angle is decreased to 107 by repulsion of nucleophile from electrons in filled pi bonding MO

Question 5

Reactions of aldehydes/ketones with hydride

• Why can’t H^- directly be used to nucleophilically attack / reduce C=O?
• What source of hydride is used?

Answer 5

• H^- acts as a base, preferentially reacting with H-X rather than C=O, because the filled H^- is orbital is better-matched in size to H’s contribution to the sigma* MO in H-X than to C’s more diffuse contribution to the pi* (LUMO) of the C=O group
• Source of hydride is NaBH₄, sodium borohydride (rather than a metal hydride)

Note: NaBH4 is ionic so it’s BH4- which attacks.

Question 6

Reactions of aldehydes/ketones with hydride

Draw the mechanism for the reduction of a generalised ketone by sodium borohydride.

Answer 6

Question 7

Reactions of aldehydes/ketones with hydride

Explain how the BH₃ produced above can cause reduction of more reagent molecules. Use a mechanism.

Answer 7

• BH3 is Sp2 hybridised. Has an empty p-orbital, so is a Lewis acid
• Reacts rapidly with either the oxyanion intermediate or a solvent molecule → tetravalent boron anion produced
• Can react again, transferring another hydride as below (could transfer all 4 Hs, but is rarely this efficient)
• So reaction (in water/alcoholic solution) gives good yield

Question 9

What is the functional group R-O-C-O-R?

Why is it different from ethers?

Answer 9

Acetal

Different since the lp on one O can attack into its C-O bond, then the other C-O bond breaks by attacking into its O. So acetal can cause the bond to cleave, forming R-O^-, which can then be protonated etc