chapter 18 reactions of aromatic molecules benzene is aromatic: a cyclic conjugated compound with 6 ...
TRANSCRIPT
Chapter 18 Reactions of Aromatic molecules
•Benzene is aromatic: a cyclic conjugated compound with 6 electrons
•Reactions of benzene lead to the retention of the aromatic core
Types of Reactions
• Electrophilic substitution
• Diazonium chemistry
• Nucleophilic substitution
• Misc. modification of substituents
Electrophilic Substitution versus addition
Arenium ion: Wheland intermediateAlso called sigma complex
Energy diagram comparison of electrophilic substitution versus electrophilic addition
Is this kinetic or thermodynamic control?
Electrophilic Bromination of Aromatic Rings
ortho-bromotoluenepara-bromotoluenetoluene
meta-bromonitrobenzene
Regiochemistry (ortho, para, meta) will depend on relative stability of resonance structures for carbocation intermediates
Mechanism for Electrophilic Bromination of Aromatic Rings
ortho carbocation ortho carbocation
para carbocation
Aromatic Nitration• The combination of nitric acid and sulfuric acid produces
NO2+ (nitronium ion)
• The reaction with benzene produces nitrobenzene
Gun solvent
ortho & para Regioselectivity explained
Kinetics are more favorable for ortho and para isomers with electron donating substitutent on benzene
Too corrosive for artillery shells
•High explosive: Shock wave•Secondary explosive: requires primer (primary explosive) to detonate•Nitroaromatics are harmful: aplastic anemia and liver toxicity
Reactions of nitroaromatics
• Nitro is deactivating (destabilizes the Wheland intermediate & slows reactions).
• Reactions are 100,000 slower than with benzene• Meta directing
More polynitrationmono-brominationReduction to anilines and azo
compoundsNucleophilic aromatic substitution
Meta selective: electron withdrawing groups
•electron withdrawing group inductively destabilizes adjacent carbocations in ortho and para cases. • No adjacent carbocation in meta regiochemistry resonance structures
Reduction of Nitroaromatics to Aryl amines
Amine group is electron donating: changes subsequent regiochemistry from meta to ortho-para
Aromatic Sulfonation• Substitution of H by SO3 (sulfonation)• Reaction with a mixture of sulfuric acid and SO3• Reactive species is sulfur trioxide or its conjugate acid• Reaction occurs via Wheland intermediate and is
reversible
Alkali Fusion of Aromatic Sulfonic Acids
• Sulfonic acids are useful as intermediates• Heating with NaOH at 300 ºC followed by neutralization
with acid replaces the SO3H group with an OH• Example is the synthesis of p-cresol
Alkylation of Aromatic Rings: The Friedel–Crafts Reaction
• Aromatic substitution of a R+ for H• Aluminum chloride promotes the formation of
the carbocation• Rearrangement of carbocation can occur
Limitations of the Friedel-Crafts Alkylation
• Only alkyl halides can be used (F, Cl, I, Br)• Aryl halides and vinylic halides do not react (their
carbocations are too hard to form)• Will not work with rings containing an amino group
substituent or a strongly electron-withdrawing group
Acylation of Aromatic Rings
• Reaction of an acid chloride (RCOCl) and an aromatic ring in the presence of AlCl3 introduces acyl group, COR – Benzene with acetyl chloride yields acetophenone
Ortho- and Para-Directing Deactivators: Halogens
• Electron-withdrawing inductive effect outweighs weaker electron-donating resonance effect
• Resonance effect is only at the ortho and para positions, stabilizing carbocation intermediate
With multiple substitutents there can be antagonistic or reinforcing effects
Antagonistic or Non-Cooperative
D = Electron Donating Group (ortho/para-directing)W = Electron Withdrawing Group (meta-directing)
Reinforcing or Cooperative
Multiple Substituents in antagonistic systems
The most strongly activating substituent will determine the position of the next substitution. May have mixtures.
OCH3
O2N
SO3
H2SO4
OCH3
O2N
SO3H
OCH3
O2N
SO3H
+
=>
Electrophilic substitution reaction used to make plastics
Bakelite, NovolacAcid or base catalyzed reactions
Acid catalyzed reaction of phenol with formaldehyde
Electrophilic substitution reaction used to make plastics
Acid catalyzed reaction of phenol with formaldehyde
Electrophilic substitution reaction used to make plastics
Base catalyzed reaction of phenol with formaldehyde
Nucleophilic Aromatic Substitution
• While protons attached to electron-rich aromatics can be displaced by electrophiles, halogens attached to electron-depleted aromatics can be displaced by nucleophies
• Nucleophilic aromatic substitution is similar to SN1/SN2 in its outcome, but follows completely different mechanisms
Substitution Nucleophilic Aromatic (SNAr), the Benzyne Mech, and reaction of diazonium salts
Addition-Elimination Reactions
• Typical for aryl halides with nitro groups in ortho or para position
• Addition to form intermediates (Meisenheimer complexes) by electron-withdrawal
• Halide ion is then lost by elimination
Nucleophilic substitution aromatic
Strong EWG ortho or para to leaving group (F, Cl, Br, I, OTf)
Strong nucleophile (HO-, RO-, Amide, thiolate, carbanions)
Elimination-Addition: Benzynes • The reaction involves an elimination reaction that gives a
triple bond, followed by rapid addition of water
• The intermediate is called benzyne
Evidence for Benzyne as an Intermediate
• Bromobenzene with 14C only at C1 gives substitution product with label scrambled between C1 and C2
• Reaction proceeds through a symmetrical intermediate in which C1 and C2 are equivalent— must be benzyne
Structure of Benzyne• Benzyne is a highly distorted alkyne• The triple bond uses sp2-hybridized carbons, not the usual
sp• The triple bond has one bond formed by p–p overlap and
by weak sp2–sp2 overlap
Another Nucleophilic Like reaction using Diazonium Salts (made from Anilines)
ArNH2 is easily made from reduction of nitrobenzenes. Permits preparation of molecules impossible to make otherwise
Three possible reaction mechanisms for Nucleophilic substitution reactions with Diazonium salts
Thermal ionization (like SN1)
Organometallic
Redox (radical intermediate)
e.g. Formation of phenol
e.g. Sandmeyer reaction
16.10 Oxidation of Aromatic Compounds
• Alkyl side chains can be oxidized to CO2H by strong reagents such as KMnO4 and Na2Cr2O7 if they have a C-H next to the ring
• Converts an alkylbenzene into a benzoic acid, ArR ArCO2H
Bromination of Alkylbenzene Side Chains
• Reaction of an alkylbenzene with N-bromo-succinimide (NBS) and benzoyl peroxide (radical initiator) introduces Br into the side chain
Mechanism of NBS (Radical) Reaction
• Abstraction of a benzylic hydrogen atom generates an intermediate benzylic radical
• Reacts with Br2 to yield product• Br· radical cycles back into reaction to carry chain• Br2 produced from reaction of HBr with NBS
16.11 Reduction of Aromatic Compounds
• Aromatic rings are inert to catalytic hydrogenation under conditions that reduce alkene double bonds
• Can selectively reduce an alkene double bond in the presence of an aromatic ring
• Reduction of an aromatic ring requires more powerful reducing conditions (high pressure or rhodium catalysts)
Summary of reactions not involving aromatic substitution
• Reduction of nitrobenzenes to anilines• Conversion of benzenesulfonic acids to phenols• Side chain oxidation of alkylbenzenes to benzoic
acids• Side chain halogenation of alkylbenzenes• Reduction of benzenes to cyclohexanes• Reduction of aryl ketones to alkyl benzenes