Organic Reaction Mechanisms and Synthesis
Organic Reaction Mechanisms and Synthesis asks you to decide how a reaction proceeds, why it gives that product, and how to build a target molecule from simple starting materials.
Core rules
- SN2: one concerted step, backside attack, inversion of configuration, rate = k[substrate][nucleophile]. Favoured by methyl and primary halides, strong nucleophiles, polar aprotic solvents.
- SN1: ionisation to a carbocation first, then attack; rate = k[substrate]; racemisation at a chiral centre; favoured by tertiary halides in polar protic solvents.
- E2 competes with SN2 when the base is strong or bulky and the temperature is high; E1 accompanies SN1.
- Carbocation stability: tertiary > secondary > primary > methyl; benzylic and allylic are stabilised by resonance.
- Aromatic substitution: –OH, –NH₂, –OR and –R are ortho/para directors; –NO₂, –COOH, –SO₃H and –CHO are meta directors. Halogens are deactivating but ortho/para directing.
- Synthesis tools: Grignard reagents add to aldehydes, ketones and CO₂; oxidation with KMnO₄ or K₂Cr₂O₇; reduction with LiAlH₄ or H₂/Ni.
Worked example
Nitration of chlorobenzene gives mainly para-nitrochlorobenzene. Chlorine withdraws electron density inductively, so the ring is less reactive than benzene, but it donates by resonance, stabilising the arenium ion at the ortho and para positions. The para product dominates because the ortho positions are sterically hindered by chlorine. Nitrobenzene, by contrast, is meta-directing and far less reactive.
Traps
- Calling halogens activating directors; they deactivate but still direct ortho/para.
- Forgetting the Lewis acid catalyst (FeBr₃, AlCl₃) in Friedel–Crafts reactions.
- Expecting a single inverted product from an SN1 reaction at a chiral centre.