Chamras Chemistry 106 Lecture otes xamination 2 Materials Chapter 16: Aromatic Compounds Benzene, the Most Commonly Known Aromatic Compound: The aromatic nature of benzene stabilizes it 36 kcal.mol 1. Bond rder = 1.5 Bond Length = 1.4 Å R Δ R 84.92 kcal.mol 1 56.63 kcal.mol 1 49.07 kcal.mol 1 28.34 kcal.mol 1 1
Aromatic Compounds: Definition: rganic compounds containing a continuous, cyclic array of π-electrons resulting in their overall stabilization. xamples: Benzene, cyclopropenyl cation. Geometric Property of Aromatic Systems: Planar Geometries. M s of the π-system for Benzene 2
Circle Mneumonics Method To determine the relative energies of molecular orbitals for π-systems of the cyclic conjugated molecules: (As seen above for benzene) xample: Cyclobutadiene: xample: Cyclopropenium cation: 3
xample: Cyclopropenyl anion: uckel s Rule 1. In a continuous cyclic array of π-electrons, the combination [4n+2] results in aromatic properties (overall stabilization), when {n= a whole number} 2. In a continuous cyclic array of π-electrons, the combination [4n] results in anti-aromatic properties (overall destabilization), when {n= a whole number} ***T: In case the π-system is not continuous, the compound is classified as nonaromatic. 4
Practicing the uckel s Rule: xercise: Label each structure shown below as A (aromatic), AA (anti-aromatic), or A (non-aromatic). 5
Remember the acronyms: omenclature of Benzene Derivatives phenyl fragment -> Ph (aryl fragment -> Ar) ø benzyl fragment Mono-substituted Benzene Derivatives: Me 2 2 Cl Cl 6
Di-substitution Patterns in benzene Derivatives: Common: IUPAC: omenclature in Di-substituted Benzenes: Br C Br 2 Cl 7
Spectroscopic Remarks: IR: C!a)!Stretch!m! 3000+ cm 1 C C!!b) Stretch!mw! 1630 cm 1 1 MR: 6.5 7.5 ppm A Variety of Splitting Patterns Decoupled 13 C MR: C 120 150 ppm Suggested Problems: 27, 28, 32, 36, 43a, 43b, 50. 8
Chapter 17: Reactions of Aromatic Compounds a) AS: lectrophilic Aromatic Substitution b) AS: ucleophilic Aromatic Substitution c) Reactions of Phenols AS: lectrophilic Aromatic Substitution General quation: + General Mechanism: Arenium Ion + Step 1 A Sigma Complex Step 2 9
itration of Benzene quation: 3, 2 S 4 2 Mechanism: 1. Generation of + : + = 2 + (Role of 3 & 2 S 4 ) 2. Addition of + : 3. limination of + : 10
nergy Diagram for AS Reactions alogenation of Benzene General quation: X MX 3, X 2 Role of MX 3 : xample: Br FeBr 3, Br 2 11
Mechanism: Summary of alogenation Details alogenation Type Commonly Applied Conditions Chlorination AlCl 3, Cl 2 Bromination FeBr 3, Br 2 Iodination 3 (A strong oxidizing acid to oxidize I 2 into I + ), I 2 12
Sulfonation of Benzene quation: 2 S 4, S 3 S A Reversible Reaction Fuming Sulfuric Acid: 7% S 3 in 2 S 4 lectrophile: S 3 Mechanism: 13
quation: Desulfonation S +, eat Deuteration of Benzene quation: D 2 S 4, D 2 D Mechanism: exa-deuterobenzene Synthesis D D D 2 S 4, D 2 (Large xcess) D D 14 D D
AS on Substituted Aromatic Compounds ffects of the Substituents on the Rates of AS Reactions: 1. Activation 2. Deactivation ffects of the Substituents on the rientations of AS Reactions: 1. rtho-para Directing. 2. Meta Directing. Mechanisms for Activation & Deactivation: 1. Induction (I) 2. Resonance (R) Consider the Intermediate in an AS Reaction: 1. To stabilize this intermediate, the + charge should be dispersed. If substituent Y helps spread the charge, then the intermediate is stabilized (Lowered in its energetic content) n the other hand, if the substituent intensifies the + charge, the intermediate will become less stable (higher in its energetic content). Y 15
2. This stabilization / destabilization effect affects the energetics of the reaction as shown below. More specifically, it affects the activation energy for the first step (the RDS). Substituted With Deactivating Group Substituted With Activating Group Unsubstituted Reaction Progress Therefore: 1. Substituents that stabilize the CC+ intermediate end up activating the ring. The AS takes place with a faster rate. 2. Substituents that destabilize the CC+ intermediate end up deactivating the ring. The AS takes place with a slower rate. 16
Classification of Substituents in lectrophilic Aromatic Substitution Reactions ffect on Rate Substitutent ffect on rientation 2 (amino) R (alkylamino) Very strongly activating +R (+R prevails over I) R R (dialkylamino) Activating Strongly activating +R (+R prevails over I) (hydroxyl) C R (acylamino) R (alkoxy) C R (acyloxy) ortho, para-directing +I R (alkyl) Activating +R (aryl) +R C C R (alkenyl) (hydrogen, standard of comparison) Deactivating I controls rate +R controls orientation X (X = F, Cl, Br, I = halogen) ortho, para-directing I C 2 X (halomethyl) C C R (formyl) (acyl) Deactivating Strongly deactivating I, R C C C (carboxylic acid) R (ester) Cl (acyl chloride) meta-directing C (cyano) Very strongly deactivating I I, R S (sulfonic acid) CF 3 (trifluoromethyl) (nitro) 17 Definitions: +I = electron-donating via induction I = electron-withdrawing via induction +R = electron-donating via resonance R = electron-withdrawing via resonance
Mechanistic xamples of the ffects of the Substituents: 2 a) Br 2, FeBr 3 2 b) Br 2, FeBr 3 18
rientation of. A. Substitution for the Substituted Aromatic Compounds: Regioselectivity: 1. All the DG s result in ortho/para substitution. These are called ortho/para-directors. 2. All the WG s (with the exception of halogens and halomethyl) result in meta substitution. These are called meta-directors. ************************************************************************ xample: The effect of Amino group as a very strong DG, ortho, para-director: Possible Substitutions Para rtho Meta Para-Substitution 19
rtho-substitution Meta-Substitution xample 2: The effect of itro group as a very strong WG, meta-director: Possible Substitutions Para rtho Meta 20
Para-Substitution rtho-substitution Meta-Substitution 21
xample 3: The effect of chloro group as an WG, ortho, para-director: Possible Substitutions Cl Cl Cl Cl Para rtho Meta Para-Substitution Cl rtho-substitution Cl 22
Meta-Substitution Cl rientation of Substitution in Rings with More Than ne Substituent: 1. The simplest case: All available substitution sites are equivalent: xample: 2. If the available substituents reinforce each other: xample: Br 2, FeBr 3 2 23
3. More complicated cases: xample: Br Br C 3 C Cl xample: C 3 3, 2 S 4 3 C xample: C 3 3 C 3, 2 S 4 24
More AS Reactions: 1. Friedel Crafts Alkylation of Benzene: (1877) General quation: RX, AlX 3 R 0 o C xample: + Cl AlCl 3 Reaction Mechanism: 25
Variations to the riginal FC Alkylation: Generation of CC+ could be achieved differently. xamples: + + 2. Friedel Crafts Acylation: Acyl Group: General quation: R X R AlX 3, CS 2, eat 26
xample: R R R Cl AlCl 3, eat + Mechanism: **************************************************************************** Problems with FC Alkylation: 1. Works with activated systems only. 2. Rearrangements of the CC+ will yield multiple products. 3. Multiple alkylations occur, since the product is more active. Is there a better alternative? YS!: FC Acylation, followed by Reduction 27
Friedel Crafts Acylation / Reduction of Benzene:.as a more desirable alternative to F.C Alklyation. Reaction Scheme: FC Acylation R Reduction C 2 R *Reduction Types mployed for Aryl Ketones: a) Clemmensen: Zn (g), Cl Also employed for aldehydes. b) Wolff Kilshner: 2 2, K or a, high-boiling alcohol (solvent), example: triethylene glycol, heat (175 o C). Also employed for aldehydes. Important Points on the Regioselective Synthesis of Disubstituted Aromatic Compounds Close attention must be paid to: 1. The directing effect, and 2. The activating/deactivating nature of the substituents. xamples: a) Synthetic Target = Suggested Synthetic Pathway: Br 28
b) Synthetic Target = Suggested Synthetic Pathway: Br 2 c) Synthetic Target = Suggested Synthetic Pathway: 29
ucleophilic Aromatic Substitution xample: Cl 2 a + 2 100 o C Mechanism: 30
Birch Reduction quation: a, 3 (l) C 3 benzene 1,4-cyclohexadiene Remember: Sodium-liquid ammonia reductions convert alkynes into trans-alkenes. With the methanol added, it is possible to reduce benzene into the non-conjugated 1,4-cyclohexadiene. Mechanism: Radical-Ionic single e transfer a a 3 C 3 C a single e transfer a + 3 C a + 3 C a 31
Side-Chain xidation of Benzene Derivatives xample: 1. KMn 4 (aq), 100 o C 2. + 32