Orgo 2 Exam 2 Reactions

RMgBr, then H3O+

Grignard addition • Adds R to carbonyl → alcohol

• Aldehyde → 2° alcohol; ketone → 3° alcohol

• Mech: R− attacks C=O → alkoxide → H3O+ protonates

• Limitation: destroyed by water/alcohols/acids/amines

RMgBr excess + ester, then H3O+

Grignard to ester

• Adds twice → 3° alcohol

• Two identical R groups added

• Mech: R attacks C=O → OR leaves → ketone → R attacks again → alcohol

• Needs excess Grignard

NaBH4, MeOH/H2O

Mild carbonyl reduction

• Aldehyde → 1° alcohol

• Ketone → 2° alcohol

• Mech: H− attacks C=O → alkoxide → protonation

• Usually does not reduce esters/acids

LiAlH4, then H3O+

Strong reduction

• Aldehydes/ketones → alcohols

• Esters/acids → 1° alcohols

• Mech: H− attack → leaving group if possible → second H− attack → acid workup

• Must add H3O+ second

H2, Pd/C or Pt or Ni

Catalytic hydrogenation

• Aldehydes → primary alcohols

• Ketones → secondary alcohols

• Mech:H₂ adds across C=O on metal surface → C=O becomes C–OH

• Important: Less commonly used for carbonyls than NaBH₄ or LiAlH₄; can also reduce alkenes/alkynes if present.

KMnO4, heat, then H3O+

Benzylic oxidation

• Alkylbenzene → benzoic acid

• Needs at least one benzylic H

• No benzylic H = no reaction

• Mech memory: oxidizes side chain all the way to CO2H

NBS, hv or Δ

Benzylic/allylic bromination

• Br replaces benzylic/allylic H

• Avoids direct alkene bromination

• Mech: Br radical abstracts H → resonance radical → Br transfer

Na/NH3(l), ROH

Birch reduction

• Benzene → 1,4-cyclohexadiene

• Partial reduction, not full hydrogenation

• Mech: e− → radical anion → H+ → e− → H+

Br2/FeBr3 or Cl2/FeCl3

Aromatic halogenation

• Adds Br or Cl to benzene

• EAS reaction

• Mech: make X+ → benzene attacks → sigma complex → deprotonation

HNO3/H2SO4

Nitration

• Adds NO2 to benzene

• NO2 = strong deactivator, meta director

• Mech: make NO2+ → benzene attacks → sigma complex → deprotonation

SO3/H2SO4

Sulfonation

• Adds SO3H to benzene

• Reversible with dilute acid/water + heat • SO3H = meta director

• Mech: benzene attacks SO3 → sigma complex → deprotonation

R-Cl / AlCl3

Friedel-Crafts alkylation

• Adds alkyl group to benzene

• Problems: rearrangements + overalkylation

• Fails on strongly deactivated rings

• Mech: make carbocation → benzene attacks → deprotonation

RCOCl / AlCl3

Friedel-Crafts acylation

• Adds acyl group → aryl ketone • No rearrangement

• Usually no overreaction

• Mech: acylium ion forms → benzene attacks → deprotonation

Zn(Hg), HCl

Clemmensen reduction

• C=O → CH2

• Acidic conditions

• Good after FC acylation

• Mech memory: carbonyl gets fully deoxygenated

H2NNH2, KOH, heat

Wolff-Kishner reduction

• C=O → CH2

• Basic conditions

• Use if acid-sensitive

• Mech: hydrazone forms → base/heat kicks out N2 → CH2

Sn/HCl or Fe/HCl or H2/Pd

Nitro reduction

• Ar-NO2 → Ar-NH2

• NO2 meta director becomes NH2 ortho/para director

• Mech memory: stepwise reduction of N-O bonds

Strong Nu− + aryl halide with o/p NO2

SNAr

• Replaces halide on benzene with Nu

• Needs EWG ortho/para to leaving group

• Meta EWG does not stabilize enough

• Mech: Nu attacks → Meisenheimer intermediate → LG leaves

Diene + dienophile, Δ

Diels-Alder [4+2]

• Makes cyclohexene

• Diene must be s-cis

• EWG on dienophile helps

• Endo usually favored

• Mech: concerted π arrows around 6-membered ring

Thermal electrocyclic

Thermal ring opening/closing

• 4π thermal = conrotatory

• 6π thermal = disrotatory

• Use ground-state HOMO

• Mech: terminal p orbitals rotate to overlap

Photochemical electrocyclic, hv

Light-driven ring opening/closing

• 4π photo = disrotatory

• 6π photo = conrotary

• Use excited HOMO = old LUMO

• Mech: light promotes e− → terminal overlap changes

Cope rearrangement, Δ

[3,3] sigmatropic

• 1,5-diene rearranges

• All C-C bonds shift concertedly

• Mech: 6-membered cyclic TS; three arrows around

Claisen rearrangement, Δ

[3,3] sigmatropic

• Allyl vinyl ether → carbonyl compound

• Mech: 6-membered cyclic TS → enol → carbonyl tautomer

Aldehyde/ketone + H2O, H+ or OH−

Hydration

• C=O → gem-diol

• Aldehydes hydrate more than ketones

• Equilibrium reaction

• Mech: add water/OH to C=O → proton transfers

HCN or NaCN/HCl

Cyanohydrin formation

• Adds CN and OH to same carbon

• Forms new C-C bond

• Racemic if new stereocenter

• Mech: CN− attacks C=O → alkoxide → protonation

ROH, H+

Acetal formation

• Carbonyl + alcohol → acetal

• Protects aldehydes/ketones

• Removed by aqueous acid

• Mech: protonate C=O → ROH attacks → hemiacetal → OR replaces OH

Diol, H+

Cyclic acetal formation

• Carbonyl → cyclic acetal

• Protecting group

• Stable to base/nucleophiles

• Removed with H3O+

1° amine, mild acid

Imine formation

• Aldehyde/ketone → C=N-R

• Needs mild acid

• Too much acid kills amine nucleophile

• Mech: amine attacks → carbinolamine → water leaves

2° amine, mild acid

Enamine formation

• Aldehyde/ketone → enamine

• Needs alpha H • Mech: amine attacks → iminium → lose alpha H → C=C-NR2

NH2OH, H+

Oxime formation

• C=O → C=N-OH

• Condensation reaction

• Mech: N attacks C=O → proton transfers → water leaves

H2NNH2, H+

Hydrazone formation

• C=O → C=N-NH2

• Pre-step for Wolff-Kishner

• Mech: hydrazine attacks → carbinolamine → water leaves