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.