Aromatic Compounds •Aromaticity Repetition •Electrophilic aromatic subst. •Nucleophilic aromatic subst. (McM 7th ed, 16.7) •Benzyne (McM 7th ed, 16.8) •Reduction of aromatics (McM 7th ed, 16.10)

Alchohols, Phenols, Ethers •Phenols (McM 7th ed, 17.9) •Oxidation of alcoholes and phenols (McM 7th ed, 17.7, 17.10) •Protection groups (7th ed, 17.8) •Cleavage of ethers (McM 7th ed, 18.3)

MO orbitals benzene - aromaticity

antibonding Energy

non-bonding

6 p orbitals

Degenerate orbitals node 2 at same energy level bonding

1,3,5-hexatriene Benzene only bonding MO shown Criteria for Aromaticity (Hückel) •(Monocyclic) ring •Planar •No of -electrons in conjugation 4n+2 (n: 0, 1, 2,....)

Benzene: The 3 bonding MOs are filled Filled shell of MOs (cf. filled shell of atomic orbitals nobel gasses)

antibonding Energy Less than 6 -electrons: Half-filled orbital(s) - radical character

non-bonding

6 p orbitals More than 6: Electron in antibonding orbitals

Degenerate orbitals node bonding Unstable, high-enegy species 2 at same energy level

Ex. of an anti-aromatic compound - Cyclobutadiene

Energy antibonding

non-bonding

4 p orbitals

bonding

antibonding

non-bonding

Aromatic heterocyclic compds., see chapt. 28 bonding Frost circles / Frost devices (not in McM)

How to find rel. energies of MO for planar, cyclic, fully conjug. compds. (aromatic compds?) No math. involved

Benzene Energy

3 antibonding MO (2 degenerate)

3 bonding MO (2 degenerate)

Hexagon inside circle Vertex (corner) down

Molecular orbitals

Level of a non-bionding MO

Energy 6 electrons in 3 bonding MO

Energy Benzene Cyclobutadiene 4 electrons 6 electrons

Diradical

Cyclopentadienyl anion Cyclopropenium cation 6 !"electrons 2 !"electrons

All electrons in the bonding MO All electrons in the bonding MO Tropylium cation 6 !"electrons Cyclooctatetraene 8 !"electrons

All electrons in the bonding MO Diradical Electrophilic Aromatic Substitution and Substituent Effects

E E E E Base E H H H

Aromaticity broken Resonanse satb. cationic intermediate End product aromatic

1. step ! 1. step in E-fil add. to alkene

•Halogenation (bromination) •Nitration R R •Sulfonation E •Alkylation (Friedel Craft) E •Acylation (Friedel Craft) R influence: •Reactivity •Regiochemistry

Regiochemistry in E-fil aromatic subst of disubst. benzene derivs.

OCH3 o/p directing OCH3 * * * * E

CN m-directing CN

OCH3 o/p directing OCH3 * * E * *

CH3 o/p-directing CH3 Resonance effects more powerfull than inductive effects

OCH3 o/p directing OCH3 OCH3 E * * * * +

OCH2CH3 OCH CH * * OCH2CH3 2 3 E o/p-directing

Sterical hindrance

Synth of trisubst. benzene deriv. - Planning of a good reaction sequence Nucleophilic Aromatic Substitution

E-fil Ar subst

R R

+ E E + H

Nucleophile

Nu-fil Ar subst

X Nu

+ Nu + X

Electrophile

X = Leaving group

More common on -difficient heterocycles, see chapt 28

Not like SN2 (or SN1)

Nu-fil Ar subst

X Nu

+ Nu + X

Electrophile

X = Leaving group

Nu X X 2 2 ! SN1, not on sp C ! SN2, not on sp C

(but NB! diazotation, amine chapt.) Mechanisms:

X Nu X X X Nu •SNAr Nu Nu Nu

•SN1: Via diazonium salts (See amine chapter)

•Benzyne

•(SRN1: Involves radicals) •(VNS: Vicarious nucl. Subst.)

•SNAr

X X X X Nu Nu Nu Nu Nu EWG EWG EWG EWG EWG

Only on electron defficient arenes (EWG o/p to X, Anion stabilizing effect)

(Aromatic heterocycles)

1st step rate limiting (Aromaticity broken)

X=F>Cl>Br>I •Benzyne

H H Br NH 2 NH3 NH3 NH2

c.f. E2 Br ±H

“Triple bond” between sp2 C Br p-p overlap 2 2 H sp -sp overlap - weak bond Benzynes unstable / reactive intermed.

Br NH2 * NH H NH2 * 2 * * NH3 + c.f. E2 Br

14 Reactivity of benzynes: * C •Adds nucleophiles •Dienophile in Diels Alder react.

Reduction of aromatics

H / Pt Aromatic rings reduced by some Pt-cat 2 and high pressure 130 atm

Selective red. of side chain functional groups

O H2 / Pd H2 / Pd

NO2 H2 / Pd NH2

Partial reduction - Birch red. (not in McM)

Na / NH3 (l) ROH Mech. see http://en.wikipedia.org/wiki/Birch_reduction Phenols

OH

Acidity OH pKa = 10.2 OH O O O O CH3

OH pKa = 10.0 pKa = 7.15

NO2 CH3OH: pKa = 15.5

E-fil Ar subst: Activating, o / p directing

Oxidation of alcohols and phenols

Selective oxidation to aldehyde ex. PCC H O O R C OH C C R H R OH CrO Cl H 3 N Primary alcohol Aldehyde Carboksylic acid H

R' O R' R C OH C R C OH C-H bonds broken R R' (not C-C) H R' Secondary alcohol ketone tertiary alcohol

Phenol O OH (KSO3)2NO OH (Fremy's salt) SnCl2, H2O radical mech. O OH 1,4-benzoquinone 1,4-hydroquinone

OH O HO

O

R-H BHT R stable radical !-Tocoferol (antioxidant, food etc) (Vitamin E) Protecting groups (PG) in organic synthesis A C

B B

C A

and / or D D Solutions A C C

B

A A C

PG B PG

Examples

Protection of ROH

acidic basic

Mg Mg-Br Br HO XMgO HO

Me3SiCl Base

Mg "E+" Si Br Si E O Si MgBr O O even more stable (acid / base): acid or selective - cleavage F Si O E HO cleaved by fluoride Protection of aldehydes / ketones

O O OH O OH LiAlH4 NaBH4 O O HO ???

O

HO

O O cat. H+ O acetal HO OH O O O O

LiAlH4

O + O H3O O HO HO

•Two extra steps •The protecting group curse

Acidic cleavage of ethers

Cleavage by SN2 mech (Ethers as prot. groups)

H-X X + O O OH X H Attack on least sterically shielded C leaving group Prim and sec alkyls

Cleavage by SN1 / EI mechanisms E1

H-X + O O OH H SN1 X

tert, allylic benzylic alkyls (stable carbocations)

R R O O OH SN2/SN1/EI depending on R etc H