Chapter 15 Benzene and Aromaticity ⢠Aromatic: class of ...
Chapter 15 Benzene and Aromaticity Aromatic: class of compounds that contain 6-membered benzene-like rings with 3 double bonds Alkyl-sub benzenes are sometimes referred to as arenes; named in diff ways: o Smaller than the ring, arene is named as an alkyl-sub benzene o Larger than the ring, phenyl-sub alkane o Benzyl for group 15.3 Aromaticity and the Huckel 4n+2 rule Benzene is cyclic and conjugated Benzene is unusually stable Planar and has the shape of a regular hexagon. All C are sp2 hybridized Benzene undergoes substitution reactions that retain the cyclic conjugation Resonance hybrid Huckel 4n+2 rule: a molecule is aromatic only if it has a planar, monocyclic system of conjugation and contains a total of 4n+2 pi electrons, where n is an integer Planar, conjugated molecules with 4n pi electrons are said to be antiaromatic because delocalization of their pi electrons would lead to their destabilization 15.4 Aromatic Ions For aromaticity, a molecule must be cyclic, conjugated and have 4n+2 pi electrons
Cyclopentadiene is one of the most acidic hydrocarbons because the anion formed by loss of H is so stable Cycloheptatrienyl is extraordinarily stable 15.5 Aromatic heterocycles: pyridine and Pyrrole Heterocycle: cyclic compound that contains atoms of 2 or more elements in its ring, usually N, O, S
Pyridine Each of the 5 sp2 hybridized C has a p orbital perpendicular to the plane of the ring and each p orbital contains 1 pi electron N atom is also sp2 hybridized and has 1 electron in a p orbital N lone pair are in an sp2 orbital in the plane of the ring and are not part of the aromatic pi system Pyrrole and imidazole 5-membered heterocycles, have 6 pi electrons and are aromatic Each of the 4 sp2-hybridized C contributes 1 pi electron and the sp2-hybridized N atom contributes the two from its lone pair, which occupies a p orbital
N atoms have diff roles depending on the structure of the molecule
Chapter 16 – Chemistry of Benzene: Electrophilic Aromatic Substitution Electrophilic aromatic substitution: an electrophile reacts with an aromatic ring and substitutes for one of the H 16.1 – Electrophlic Aromatic Substitution Reactions: Bromination
For bromination of benzene to take place, a catalyst such as FeBr3 is needed The catalyst makes the Br2 molecule more electrophilic by polarizing it -> FeBr4 – Br+ species ~ Br+ The polarized Br2 molecule then reacts with the nu benzene ring to yield a nonaromatic carbocation intermediate that is doubly allylic and has 3 resonance forms The intermediate is much less stable than benzene -> endergonic reaction -> high Ea and slow The carbocation intermediate loses H+ from the Br-bearing C to give a substitution product When substitution occurs, the stability of the aromatic ring is retained -> exergonic
16.2 – Other Aromatic Substitutions Aromatic Nitration Electrophile is nitronium ion NO2+, which is generated from HNO3 by protonation and loss of water
Aromatic Sulfonation Reactive nu is either HSO3+ or neutral SO3, depending on reaction conditions Readily reversible Favoured in strong acid but desulfonation is favoured in hot, dilute aqueous acid
Halogenation
16.3 Alkylation and Acylation of Aromatic Rings: The Friedel-Crafts Reaction o Alkylation: the introduction of an alkyl group onto the benzene ring; Friedel-Crafts reaction o Treating aromatic compound with an alkyl chloride, RCl, in the presence of AlCl3 to generate a carbocation electrophil, R+. o AlCl3 catalyzes the reaction by helping the alkyl halide to dissociate in much the same way that FeBr3
Several limitations: 1. Only alkyl halides can be used o Aryl and vinylic carbocations are too high in E 2. Don’t succeed on aromatic rings that are substituted either by a strongly electron-withdrawing group or by an amino group
3. Polyalkylation: often difficult to stop the reaction after a single substitution o High yield of monoalkylation product obtained only when a large excess of benzene is used
4. Skeletal rearrangement of the alkyl carbocation electrophile sometimes occurs during reaction, particularly when a primary alkyl halide is used o Acylated by reaction with a carboxylic acid chloride, RCOCL, in the presence of AlCl3
o o o
Mechanism similar to alkylation Same limitations An acyl cation is stabilized by interaction of the vacant orbital on C with lone-pair electrons on the neighbouring O o No rearrangement occurs
o acylations never occur more than once on a ring because the product acylbenzene is less reactive than the nonacylated starting material
16.4 Substituent Effects in Substituted Aromatic Rings o A substituent already present on the ring has 2 effects 1. Substituents affect the reactivity of the aromatic ring o Some activate -> more reactive than benzene o Some deactivate -> less reactive than benzene 2. Substituents affect the orientation of the reaction\ o Ortho, meta, para are not usually formed in equal amounts o Nature of the substituent already present on ring determines the position 3 groups: 1. Ortho and para directing activators 2. Ortho and para deactivators o Halogens 3. Meta directing deactivators Inductive effect: withdrawal or donation of electrons through a sigma bond due to electronegativity o Halogens, OH, carbonyl, cyano, nitro Resonance effect: withdrawal or donation of electrons through a pi bond due to overlap of a p orbital on the substituent with a p orbital on the aromatic ring o Pi electrons flow from the rings to the substituents, leaving a + charge in the ring o Halogen, OH, alkoxyl (-OR), NH substituents donate electrons to the ring by resonance o Lone pair electrons flow from the substituents to the ring, placing a – charge in the ring Inductive and resonance effects don’t necessarily act in the same direction; eg. halogens o Stronger of the two dominates 16.5 An Explanation of Substituents Effects Activating groups: o Donate electrons to the ring -> ring more electron rich, stabilizing the carbocation intermediate, lowering Ea for its formation o Hydroxyl, alkoxyl, amino groups are because of their strong electron-donating resonance effect outweights their weaker electron withdrawing inductive effect o Alkyl groups have a strong electron inductive effect Deactivating groups: o Withdraw electrons from the ring -> ring more electron poor, destabilizing the intermediate, raising the Ea for its formation o Carbonyl, cyano, and nitro because of both electron withdrawing resonance and inductive effects o Halogens are deactivating because their stronger electron withdrawing inductive effect outweighs their weaker electron donating resonance effects
Ortho- and para- directing activators: alkyl groups ortho and para are more stabilized than the meta Ortho and para has a resonance form that places the + charge directly on the methylsubstituted C, where it is in the tertiary position and can best be stabilized by the electron-donating inductive effect of the methyl group
Ortho- and para- directing activators: OH and NH2 strong, electron donating resonance effect that outweighs a weaker electron withdrawing inductive effect only ortho and para have resonance forms in which the + charge is stabilized by donation of an electron pair from O
Ortho- and para- directing deactivators: halogens halogen can stabilize the + charge from ortho and para because of electrondonating resonance effect although weak stronger electron withdrawing inductive which outweighs their weaker electron donating resonance effect
Meta-directing deactivators electron withdrawing inductive and resonance effects that are felt mostly in ortho and para position -> less stable
16.6 Trisubstituted Benzenes: Additivity of Effects 1. If the directing effects of the 2 groups reinforce each other, the situation is straight forward
2. If the directing effects of the 2 oppose each other, the more powerful activating group has the dominant influence, but mixtures often result 3. Further substitution rarely occurs between the 2 groups in a meta disubstituted compound because this site is too hindered. Aromatic rings with 3 adjacent substituents must therefore be prepared by some other route, usually by substitution of an orthodisubstituted compound
16.7 Nucleophlic Aromatic Substitution
Aryl halides that have electron withdrawing substituents can also undergo nucleophilic aromatic substitution The nu first adds to the electron-deficient aryl halide, forming a resonance-stabilized negatively charged intermediate called a Meisenheimer complex Halide ion is then eliminated in the second step Occurs only if the aromatic ring has an electron withdrawing substituent in a position ortho or para to the leaving group More such substiuents, the faster the reaction Only ortho and para electron withdrawing substituents stabilize the anion intermediate through resonance
electrophilic substitutions are favoured by electron-donating substituents, which stabilize the carbocation intermediate Nu substitutions are favoured by electron withdrawing substituents which stabilize the carbocation intermediate The electron withdrawing groups activate nu substitution Ortho-para directors in nu Electro replace H in ring Nu replace a LG
16.8 Benzyne
16.9
When a bromobenzene is treated with KNH2 in the presence of a diene such as furan, a Diels-Alder reaction occurs, implying that the symmetrical intermediate is a benzyne, formed by elimination of HBr from bromobenzene Benzyne in water gives a phenol
Oxidation of Aromatic Compounds
Benzene is inert to strong oxidizing agents Presence of the aromatic ring has a dramatic effect on alkyl side chains: react rapidly -> COOH Involves reaction of CH bonds at the position next to the aromatic ring to form intermediate benzylic rads
Bromination of Alkylbenzene Side Chains Occurs at benzylic position because benzylic radical intermediate is stabilized by reson. Does not give mixtures
16.10 Reduction of Aromatic Compounds Catalytic hydrogenation of Aromatic Rings Possible to reduce an alkene double bond selectively in presence of an aromatic ring
Reduction of Aryl Alkyl Ketones Aryl alkyl ketone prepared by Friedel-Crafts acylation of an aromatic ring can be converted into an alkylbenzene by catalytic hydrogenation over a palladium catalyst
Conversion of a carbonyl group into a methylene group is limited to aryl alkyl ketones Reduction of aryl alkyl ketones is not compatible with the presence of a nitro substituent on the aromatic ring because a nitro group is reduced to an amino group under the reaction conditions
Cyclopentadiene is one of the most acidic hydrocarbons because the anion formed by loss of H is so stable Cycloheptatrienyl is extraordinarily stable 15.5 Aromatic heterocycles: pyridine and Pyrrole Heterocycle: cyclic compound that contains atoms of 2 or more elements in its ring, usually N, O, S
Pyridine Each of the 5 sp2 hybridized C has a p orbital perpendicular to the plane of the ring and each p orbital contains 1 pi electron N atom is also sp2 hybridized and has 1 electron in a p orbital N lone pair are in an sp2 orbital in the plane of the ring and are not part of the aromatic pi system Pyrrole and imidazole 5-membered heterocycles, have 6 pi electrons and are aromatic Each of the 4 sp2-hybridized C contributes 1 pi electron and the sp2-hybridized N atom contributes the two from its lone pair, which occupies a p orbital
N atoms have diff roles depending on the structure of the molecule
Chapter 16 – Chemistry of Benzene: Electrophilic Aromatic Substitution Electrophilic aromatic substitution: an electrophile reacts with an aromatic ring and substitutes for one of the H 16.1 – Electrophlic Aromatic Substitution Reactions: Bromination
For bromination of benzene to take place, a catalyst such as FeBr3 is needed The catalyst makes the Br2 molecule more electrophilic by polarizing it -> FeBr4 – Br+ species ~ Br+ The polarized Br2 molecule then reacts with the nu benzene ring to yield a nonaromatic carbocation intermediate that is doubly allylic and has 3 resonance forms The intermediate is much less stable than benzene -> endergonic reaction -> high Ea and slow The carbocation intermediate loses H+ from the Br-bearing C to give a substitution product When substitution occurs, the stability of the aromatic ring is retained -> exergonic
16.2 – Other Aromatic Substitutions Aromatic Nitration Electrophile is nitronium ion NO2+, which is generated from HNO3 by protonation and loss of water
Aromatic Sulfonation Reactive nu is either HSO3+ or neutral SO3, depending on reaction conditions Readily reversible Favoured in strong acid but desulfonation is favoured in hot, dilute aqueous acid
Halogenation
16.3 Alkylation and Acylation of Aromatic Rings: The Friedel-Crafts Reaction o Alkylation: the introduction of an alkyl group onto the benzene ring; Friedel-Crafts reaction o Treating aromatic compound with an alkyl chloride, RCl, in the presence of AlCl3 to generate a carbocation electrophil, R+. o AlCl3 catalyzes the reaction by helping the alkyl halide to dissociate in much the same way that FeBr3
Several limitations: 1. Only alkyl halides can be used o Aryl and vinylic carbocations are too high in E 2. Don’t succeed on aromatic rings that are substituted either by a strongly electron-withdrawing group or by an amino group
3. Polyalkylation: often difficult to stop the reaction after a single substitution o High yield of monoalkylation product obtained only when a large excess of benzene is used
4. Skeletal rearrangement of the alkyl carbocation electrophile sometimes occurs during reaction, particularly when a primary alkyl halide is used o Acylated by reaction with a carboxylic acid chloride, RCOCL, in the presence of AlCl3
o o o
Mechanism similar to alkylation Same limitations An acyl cation is stabilized by interaction of the vacant orbital on C with lone-pair electrons on the neighbouring O o No rearrangement occurs
o acylations never occur more than once on a ring because the product acylbenzene is less reactive than the nonacylated starting material
16.4 Substituent Effects in Substituted Aromatic Rings o A substituent already present on the ring has 2 effects 1. Substituents affect the reactivity of the aromatic ring o Some activate -> more reactive than benzene o Some deactivate -> less reactive than benzene 2. Substituents affect the orientation of the reaction\ o Ortho, meta, para are not usually formed in equal amounts o Nature of the substituent already present on ring determines the position 3 groups: 1. Ortho and para directing activators 2. Ortho and para deactivators o Halogens 3. Meta directing deactivators Inductive effect: withdrawal or donation of electrons through a sigma bond due to electronegativity o Halogens, OH, carbonyl, cyano, nitro Resonance effect: withdrawal or donation of electrons through a pi bond due to overlap of a p orbital on the substituent with a p orbital on the aromatic ring o Pi electrons flow from the rings to the substituents, leaving a + charge in the ring o Halogen, OH, alkoxyl (-OR), NH substituents donate electrons to the ring by resonance o Lone pair electrons flow from the substituents to the ring, placing a – charge in the ring Inductive and resonance effects don’t necessarily act in the same direction; eg. halogens o Stronger of the two dominates 16.5 An Explanation of Substituents Effects Activating groups: o Donate electrons to the ring -> ring more electron rich, stabilizing the carbocation intermediate, lowering Ea for its formation o Hydroxyl, alkoxyl, amino groups are because of their strong electron-donating resonance effect outweights their weaker electron withdrawing inductive effect o Alkyl groups have a strong electron inductive effect Deactivating groups: o Withdraw electrons from the ring -> ring more electron poor, destabilizing the intermediate, raising the Ea for its formation o Carbonyl, cyano, and nitro because of both electron withdrawing resonance and inductive effects o Halogens are deactivating because their stronger electron withdrawing inductive effect outweighs their weaker electron donating resonance effects
Ortho- and para- directing activators: alkyl groups ortho and para are more stabilized than the meta Ortho and para has a resonance form that places the + charge directly on the methylsubstituted C, where it is in the tertiary position and can best be stabilized by the electron-donating inductive effect of the methyl group
Ortho- and para- directing activators: OH and NH2 strong, electron donating resonance effect that outweighs a weaker electron withdrawing inductive effect only ortho and para have resonance forms in which the + charge is stabilized by donation of an electron pair from O
Ortho- and para- directing deactivators: halogens halogen can stabilize the + charge from ortho and para because of electrondonating resonance effect although weak stronger electron withdrawing inductive which outweighs their weaker electron donating resonance effect
Meta-directing deactivators electron withdrawing inductive and resonance effects that are felt mostly in ortho and para position -> less stable
16.6 Trisubstituted Benzenes: Additivity of Effects 1. If the directing effects of the 2 groups reinforce each other, the situation is straight forward
2. If the directing effects of the 2 oppose each other, the more powerful activating group has the dominant influence, but mixtures often result 3. Further substitution rarely occurs between the 2 groups in a meta disubstituted compound because this site is too hindered. Aromatic rings with 3 adjacent substituents must therefore be prepared by some other route, usually by substitution of an orthodisubstituted compound
16.7 Nucleophlic Aromatic Substitution
Aryl halides that have electron withdrawing substituents can also undergo nucleophilic aromatic substitution The nu first adds to the electron-deficient aryl halide, forming a resonance-stabilized negatively charged intermediate called a Meisenheimer complex Halide ion is then eliminated in the second step Occurs only if the aromatic ring has an electron withdrawing substituent in a position ortho or para to the leaving group More such substiuents, the faster the reaction Only ortho and para electron withdrawing substituents stabilize the anion intermediate through resonance
electrophilic substitutions are favoured by electron-donating substituents, which stabilize the carbocation intermediate Nu substitutions are favoured by electron withdrawing substituents which stabilize the carbocation intermediate The electron withdrawing groups activate nu substitution Ortho-para directors in nu Electro replace H in ring Nu replace a LG
16.8 Benzyne
16.9
When a bromobenzene is treated with KNH2 in the presence of a diene such as furan, a Diels-Alder reaction occurs, implying that the symmetrical intermediate is a benzyne, formed by elimination of HBr from bromobenzene Benzyne in water gives a phenol
Oxidation of Aromatic Compounds
Benzene is inert to strong oxidizing agents Presence of the aromatic ring has a dramatic effect on alkyl side chains: react rapidly -> COOH Involves reaction of CH bonds at the position next to the aromatic ring to form intermediate benzylic rads
Bromination of Alkylbenzene Side Chains Occurs at benzylic position because benzylic radical intermediate is stabilized by reson. Does not give mixtures
16.10 Reduction of Aromatic Compounds Catalytic hydrogenation of Aromatic Rings Possible to reduce an alkene double bond selectively in presence of an aromatic ring
Reduction of Aryl Alkyl Ketones Aryl alkyl ketone prepared by Friedel-Crafts acylation of an aromatic ring can be converted into an alkylbenzene by catalytic hydrogenation over a palladium catalyst
Conversion of a carbonyl group into a methylene group is limited to aryl alkyl ketones Reduction of aryl alkyl ketones is not compatible with the presence of a nitro substituent on the aromatic ring because a nitro group is reduced to an amino group under the reaction conditions
