Benzenes & Aromatic Compounds 1
Structure of Benzene H H C C C H C 6 H 6 H C C C H H A cyclic conjugate molecule Benzene is a colourless odourless liquid, boiling at 80 o C and melting at 5 o C. It is a suspected carcinogen. Benzene and its derivatives are said to be aromatic compounds 2
Resonance Structure = 1.5 bonds on average Rearrange the bonding electrons Delocalisation, Resonance-stabilise molecules, so make them less reactive Delocalised or Conjugated System p-bonding electrons can move within the molecule 3
Aromatic compounds have the following characteristics: 1. Aromatic compounds are cyclic, planar and conjugated. 2. Aromatic compounds react with electrophiles to give substitution products, in which cyclic conjugation is restrained. 3. Must contain 4n2π electrons (where n = 0, 1, 2,...) Hückel Rule n = 1, 6π electrons Naphthalene Anthracene Phenanthrene 10 π 14 π 4
An Interesting Aromatic Compound 5
Selected drugs that contain a benzene rings 6
Monosubstituted Benzenes Br CH 3 O N O bromobenzene vinylbenzene methylbenzene (toluene) H N H OH HO O nitrobenzene aminobenzene (aniline) hydroxybenzene (phenol) Benzenecarboxylic acid (benzoic acid) 7
Disubstituted Benzenes Prefixes ortho- (o) metha- (m) para-(p) 8
Polysubstituted Benzenes 9
Reaction of Aromatic Compounds 10
Electrophilic Aromatic Substitution The characteristic reaction of aromatic compounds is substitution by a wide variety of electrophilic reagents- electrophilic aromatic substitution. 11
Examples of Electrophilic Aromatic Substitution Reactions X 2, FeX 3 X = Cl, Br HONO 2 H 2 SO 4 X Halogenation NO 2 Nitration SO 3 H 2 SO 4 SO 3 HSulfonation RCl R Friedel-Crafts AlCl 3 Alkylation O RCCl AlCl 3 = O C = R Friedel-Crafts Acylation These reactions are commonly used synthetic procedures for modifying arenes. They proceed by a general mechanism initiated by addition of an electrophile E to the aromatic π-system, forming a nonaromatic carbocation intermediate called an arenium ion. 12
Mechanism: Electrophilic Aromatic Substitution Step 1 : Electrophilic attack: Slow, Rate Determining Step 13
Mechanism: Electrophilic Aromatic Substitution Step 2 : Fast Step is the loss of a proton 14
Halogenation Halogenation requires a Lewis acid catalyst to form the electrophile. Cl 2, AlCl 3 Cl Br 2, FeBr 3 Br 15
Mechanism: Halogenation Br-Br FeBr 3 Br Br FeBr 3 Bromine-FeBr 3 complex Br Br Br FeBr3 H FeBr 4 Br H Br FeBr 4 HBr FeBr 3 Regenerate the catalyst so only a small amount is required 16
Aromatic Compounds are resonance stabilized. This gives them added stability. They undergo Electrophilic Substitution Reactions. Upon substitution, the fast step is the loss of a proton to regenerate aromaticity H Br H Br H Br double-headed arrows 17
---rapid re-aromatization Nitration of Benzene HNO 3, H 2 SO 4 NO 2 Aromatic rings can be nitrated by reaction with a mixture of concentrate nitric and sulfuric acids. The electrophile in this reaction is the nitronium ion, NO 2, which is generated from HNO 3 by protonation and loss of water. O O H O S O H O S O O O H HO NO 2 O NO 2 NO 2 H 2 O H H 2 H 18
Mechanism: Nitration _ O O N O electrophilic attack N slow O electrophile = _ O N O O 2 N H O O N - H fast = NO 2 19
Sulfonation of Benzene Sulfonation of Benzene Benzene reacts with fuming sulfuric acid (concentrated sulfuric acid plus added SO 3, the actual electrophile) to give benzenesulfonic acid.. O.. Fuming H 2 SO SO 4 3 H S=O O 25 o C = = Sulfur trioxide Benzenesulfonic acid In concentrated sulfuric acid alone, an equilibrium-limited supply of SO 3 effects slow sulfonation. (1) Generation of the Electrophile :O: H-O-S-O-H :O: = = :O: H-O-S-O-H :O: = = :O: H-O-S-O: :O: = = - :O: H-O-S-O-H H:O: : = = :O: H-O-S-O-H H:O: : = =. O. H 3 O S=O O = = Sulfur trioxide 20
(2) Electrophilic Attack O. H. O slow S=O O: O :O: = S= : : - etc. (3) Deprotonation and Re-aromatization : H O S = O: :O: = : - :O: - :O-S-O-H :O: = = Hydrogen sulfate fast Arenium ion :O: - S O:. H 2 SO 4.. O. = = Benzenesulfonate ion (4) Acid-Base Equilibrium :O: - :O: S O: fast H 3 O S O-H.. O.... O. = = = = H 2 O Synthetic Applications Benzenesulfonic acid pk a = 0.699 21
Friedel-Crafts Alkylation Friedel-Crafts Alkylation Discovered in 1877 by French chemist Charles Friedel and his American collaborator James Crafts, this alkylation reaction (one introducing an alkyl group) and the related acylation reaction (one introducing an acyl group) are among the most useful synthetic reactions. Alkylation of an Arene R-X AlCl 3 R HX Alkyl halide Alkylbenzene This reaction requires a Lewis acid catalyst, typically aluminum chloride, AlCl 3. Many variations of the Friedel-Crafts alkylation reaction have been developed. All proceed by similar mechanisms. 22
A Mechanism for the Alkylation Reaction The Lewis acid catalysts generally required in Friedel-Crafts reactions promote formation of strong electrophiles. (1) Generation of the Electrophile R-Cl: Lewis base AlCl 3 Lewis acid R-Cl-AlCl 3 - Complex With 1 o halides, the complex itself, acting as an R transfer agent, reacts with the arene. With 2 o and 3 o alkyl halides, dissociation to carbocation intermediates seems to occur, and the resulting R species react with the arene. R-Cl-AlCl 3 - R AlCl - 4 23
(2) Electrophilic Attack or R-Cl-AlCl 3 - H R etc. AlCl 4 - R AlCl 4 - Arenium ion (3) Deprotonation and Re-aromatization H R :Cl: :Cl - Al :Cl : Lewis base Cl: R Alkylbenzene HCl AlCl 3 Regenerated catalyst Note : Tertiary carbocations are usually effective in Friedel-Crafts alkylation 24
Friedel-Crafts Acylation Friedel-Crafts Acylation O Acylation is the introduction of an acyl group, R-C-, into a structure. Two important acyl groups are: O O C CH 3 C- Acetyl = Benzoyl = = The Friedel-Crafts acylation reaction attaches an acyl group to an arene. A Lewis acid catalyst is required to generate the electrophile from an acyl halide reactant. O O C-R =AlCl3 RCCl Acid (or acyl) chloride = A phenyl ketone HCl 25
A Mechanism for Friedel-Crafts Acylation (1) Generation of the Electrophile :O: R-C-Cl: = Acid chloride (Lewis base) AlCl 3 Lewis acid :O: R-C-Cl = - AlCl 3 R-C=O R-C O: AlCl 4 - Acylium ion Acylium ions are generally thought to be the electrophilic intermediates in Friedel-Crafts acylation reactions. As shown, these ions have two contributing resonance structures. 26
(2) Electrophilic Attack R-C=O slow step H C R :O: = etc. Arenium ion (3) Deprotonation and Re-aromatization H O C R - C-R :Cl-AlCl 3 HCl AlCl 3 :O: = = Aryl ketone 27
Limitations of the Friedel-Crafts Reactions (1) Rearrangements during Alkylations Whenever carbocation intermediates are formed, they are subject to rearrangements that produce more stable species. Example: During the Friedel-Crafts reaction of benzene with butyl bromide a 1,2-hydride shift, possibly concurrent with dissociation, produces some of the more stable sec-butyl carbocation. A mixture of products results. Br AlCl 3 - Br AlCl 3 - BrAlCl - Complex 3 H Butylbenzene (32-36%) sec-butylbenzene (64-68%) 28
Substituent Effects on Benzene Ring 29
Inductive effect Inductive effects stem from the electronegativity of the atoms in the substituent and the polarizability of the substituent group. Atoms more electronegative than carbon including N, O, and X pull electron density away from carbon and thus exhibit an electron-withdrawing inductive effect. Polarizable alkyl groups donate electron density, and thus exhibit an electron-donating inductive effect. 30
Resonance effect Resonance effects are only observed with substituents containing lone pairs or π bonds. Withdraw electron density O O O O O O O O N N N N Donate electron density NH 2 NH 2 NH 2 NH 2 31
Electrophilic Aromatic Substitution of Substituted Benzenes A substituent affects two aspects of electrophilic aromatic substitution: The rate of reaction: A substituted benzene reacts faster or slower than benzene itself. The orientation: The new group is located either ortho, meta, or para to the existing substituent. The identity of the first substituent determines the position of the second substituent. 32
Toluene Toluene reacts faster than benzene in all substitution reactions. Thus, its electron-donating CH 3 group activates the benzene ring to electrophilic attack. Although three products are possible compounds with the new group ortho or para to the CH 3 group predominate. The CH 3 group is therefore called an ortho, para director. CH 3 called activating group which causes the rate of electrophilic aromatic substitition to be higher than benzene. 33
Nitrobenzene Nitrobenzene reacts more slowly than benzene in all substitution reactions. Thus, its electron withdrawing NO 2 group deactivates the benzene ring to electrophilic attack. Although three products are possible, the compound with the new group meta to the NO 2 group predominates. The NO 2 group is called a meta director. NO 2 call deactivating group causes the rate of electrophilic aromatic substitition to be lower than benzene 34
Three Types of Substituents 1. Ortho, para directors and activators Substituents that activate a benzene ring and direct substitution ortho and para. 2. Ortho, para deactivators Substituents that deactivate a benzene ring and direct substitution ortho and para. 35
Three Types of Substituents 3. Meta directors - Substituents that direct substitution meta. - All meta directors deactivate the ring. 36
The CH 3 Group An ortho, para Director The CH 3 group directs electrophilic attack ortho and para to itself because an 37 electron-donating inductive effect stabilizes the carbocation intermediate.
The NH 2 Group An ortho, para Director The NH 2 group directs electrophilic attack ortho and para to itself because 38 the carbocation intermediate has additional resonance stabilization.
The NO 2 Group A meta Director With the NO 2 group (and all meta directors), meta attack occurs because attack at the ortho or para position gives a destabilized carbocation intermediate.. 39
Quiz 40
Halogenation of Activated Benzenes Benzene rings activated by strong electron donating groups OH and NH 2 undergo polyhalogenation when treated with X 2 and FeX 3. For example, aniline (C 6 H 5 NH 2 ) and phenol (C 6 H 5 OH) both give a tribromo derivative when treated with Br 2 and FeBr 3. Substitution occurs at all hydrogen atoms ortho and para to the NH 2 and OH groups. 41
What happens in electrophilic aromatic substitution when a disubstituted benzene ring is used as starting material? Rule 1: When the directing effects of two groups reinforce, the new substituent is located on the position directed by both groups. 42
Rule 2 : If the directing effects of two groups oppose each other, the more powerful activator "wins out." 43
Rule 3: No substitution occurs between two meta substituents because of crowding. 44
Quiz 45
Oxidation of Substituted Benzenes Arenes containing at least one benzylic C-H bond are oxidized with KMnO 4 to benzoic acid, a carboxylic acid with the carboxy group (COOH) bonded directly to the benzene ring. With some alkyl benzenes, this also results in the cleavage of carbon-carbon bonds, so the product has fewer carbon atoms than the starting material. 46
Substrates with more than one alkyl group are oxidized to dicarboxylic acids. Compounds without a benzylic C - H bond are inert to oxidation. 47
Reduction of Substituted Benzenes 48
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Example: The nitration and side-chain oxidation of toluene CH 3 Toluene (1) KMnO 4, HO -, heat HNO 3 H 2 SO 4 (2) H 3 O COOH HNO 3 H 2 SO 4 CH 3 CH 3 NO 2 COOH NO 2 m-nitrobenzoic acid All three possible positional isomers of nitrobenzoic acid may be synthesized by careful synthetic design. (1) KMnO 4, HO - heat (2) H 3 O COOH NO 2 ortho NO 2 (1) KMnO 4, HO - heat (2) H 3 O COOH NO 2 para 50
Reduction of Nitro Groups A nitro group (NO 2 ) is easily introduced on a benzene ring by nitration with strong acid. This process is useful because the nitro group is readily reduced to an amino group (NH 2 ) under a variety of conditions. The most common methods use H 2 and a catalyst, or a metal (such as Fe or Sn) and a strong acid like HCl. 51
Quiz 52
Quiz 15.01 Draw the three contributing resonance structures of the arenium ion intermediate produced in the addition of an electrophile, E, to benzene. H E E H E H E 53
Quiz 15.02 Draw the complex formed between bromine (Br 2 ) and FeBr 3 that is believed to be involved in the electrophilic bromination of benzene and other aromatics. Show the polarization of charge in the complex. :Br-Br: FeBr 3 :Br: - :Br-Br-Fe-Br: :Br: : : 54
Quiz 15.03a Draw the Lewis structure of the nitronium ion, NO 2, a strong electrophile. Solution NO 2 is a 16 valence electron system. The proper Lewis structure must conform to the Octet Rule and have formal charge(s) indicated, so the answer is: O=N=O 55
Quiz 15.03b Draw the resonance structures of the arenium ion intermediate formed from electrophilic attack of the nitronium ion on benzene. Note: Disregard resonance structures of the nitro group. - :O: - - :O: :O: O=N=O N=O N=O N=O H H H : : : 56
Quiz 15.05 Draw the contributing resonance structures of the acylium ion produced in the reaction below. : O: R-C-Cl = AlCl 3 R-C=O R-C O : 57
Quiz 15.07 Predict the major products (ortho/para or meta) from the nitration of the following substituted benzenes. CH 3 I II O CCH 3 = Cl HNO 3 H 2 SO 4 HNO 3 H 2 SO 4 ortho/para meta HNO 3 ortho/para H 2 SO 4 III What is the order of reactivity of the three substituted benzenes in the nitration reaction? I III II > > 58
Quiz 15.08 Draw the contributing resonance structures for the arenium ion intermediates formed from para and meta addition of Br to toluene. δ CH 3 δ δ H Br CH 3 H Br CH 3 H Br CH 3 H Br δ CH 3 δ δ Br H CH 3 Br H CH 3 Br H CH 3 Br H 59
Quiz 15.11 Draw the structure of the major monosubstitution product from each of these reactions. CH 3 Br HNO 3 H 2 SO 4 CH 3 Br NO 2 COOH CH 3 Br 2 Fe COOH CH 3 Br 60
Quiz 61
Quiz 62
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Quiz 64
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Phenol OH OH pka = 17 pka = 10 Phenols are stronger acids than alcohols H O O O O Resonance Stabilised Phenoxide anion 66
Synthesis of Phenols The only widely used laboratory synthesis of phenols is that from the corresponding anilines through a process called diazotization. This route from benzenoid compounds to phenols starts with the nitration reaction, followed by reduction of the nitro group ( NO 2 ) to an amino group ( NH 2 ), diazotization of the amine to a diazonium ion ( N 2 ), and finally displacement of the diazonium group by the hydroxyl group ( OH) upon heating in water: 67
Electrophilic Aromatic Substitution of Phenols very strong activator AlCl 3 / FeBr 3 68
O-Alkylation of Phenols (Williamson Ether Synthesis) Because phenols are acidic and can be converted easily into their phenoxide anions, it is very easy to form phenyl alkyl ethers via the Williamson ether synthesis of ethers usually brought about using methyl iodide for convenience. The methyl group can be readily removed by a typical ether cleavage. 69