c 2004 barry linkletter, upei substitution reactions of...
TRANSCRIPT
Chemistry 243 - Lecture 13 1
C 2004 Barry Linkletter, UPEI
Lecture 13
Chemistry of Aromatic Compounds
Chapter 5
Chemistry 243 - Lecture 13 2
C 2004 Barry Linkletter, UPEI
Substitution Reactions of Benzene and
Its Derivatives
� Benzene is aromatic: a cyclic conjugatedcompound with 6 ! electrons
� Reactions of benzene lead to the retention ofthe aromatic core
� Electrophilic aromatic substitution replaces aproton on benzene with another electrophile
Chemistry 243 - Lecture 13 3
C 2004 Barry Linkletter, UPEI
Bromination of Aromatic Rings
� Benzene�s ! electrons participate as a Lewis basein reactions with Lewis acids
� The product is formed by loss of a proton, whichis replaced by bromine
� FeBr3 is added as a catalyst to polarize thebromine reagent
Chemistry 243 - Lecture 13 4
C 2004 Barry Linkletter, UPEI
Addition Intermediate in Bromination
� The addition of bromine occurs in two steps
� In the first step the ! electrons act as anucleophile toward Br2 (in a complex with FeBr3)
� This forms a cationic addition intermediate frombenzene and a bromine cation
� The intermediate is not aromatic and thereforehigh in energy (see Figure 16.2)
Chemistry 243 - Lecture 13 5
C 2004 Barry Linkletter, UPEI
Formation of Product from
Intermediate
� The cationic additionintermediate transfersa proton to FeBr4
-
(from Br- and FeBr3)
� This restoresaromaticity (in contrastwith addition inalkenes)
Chemistry 243 - Lecture 13 6
C 2004 Barry Linkletter, UPEI
Other Aromatic Substitutions
� The reaction with bromine involves a mechanismthat is similar to many other reactions of benzenewith electrophiles
� The cationic intermediate was first proposed by G.W. Wheland of the University of Chicago and isoften called the Wheland intermediate
Chemistry 243 - Lecture 13 7
C 2004 Barry Linkletter, UPEI
Aromatic Chlorination and Iodination
� Chlorine and iodine (but not fluorine, which is too reactive)
can produce aromatic substitution with the addition of other
reagents to promote the reaction
� Chlorination requires FeCl3
� Iodine must be oxidized to form a more powerful I+ species
(with Cu+ or peroxide)
Chemistry 243 - Lecture 13 8
C 2004 Barry Linkletter, UPEI
Aromatic Nitration
� The combination of nitric acid and sulfuric acid producesNO2
+ (nitronium ion)
� The reaction with benzene produces nitrobenzene
Chemistry 243 - Lecture 13 9
C 2004 Barry Linkletter, UPEI
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
Chemistry 243 - Lecture 13 10
C 2004 Barry Linkletter, UPEI
Alkylation of Aromatic Rings: TheFriedel�Crafts Reaction
� Aromatic substitution ofa R+ for H
� Aluminum chloridepromotes the formationof the carbocation
� Wheland intermediateforms
Chemistry 243 - Lecture 13 11
C 2004 Barry Linkletter, UPEI
Limitations of the Friedel-Crafts
Alkylation
� Only alkyl halides can be used (F, Cl, I, Br)
� Aryl halides and vinylic halides do not react (theircarbocations are too hard to form)
� Will not work with rings containing an amino groupsubstituent or a strongly electron-withdrawing group
Chemistry 243 - Lecture 13 12
C 2004 Barry Linkletter, UPEI
Control Problems
� Multiple alkylations can occur because the first
alkylation is activating
Chemistry 243 - Lecture 13 13
C 2004 Barry Linkletter, UPEI
Carbocation Rearrangements During
Alkylation� Similar to those that occur during electrophilic additions to
alkenes
� Can involve H or alkyl shifts
Chemistry 243 - Lecture 13 14
C 2004 Barry Linkletter, UPEI
Acylation of Aromatic Rings
� Reaction of an acid chloride (RCOCl) and an aromatic ring inthe presence of AlCl3 introduces acyl group, !COR
� Benzene with acetyl chloride yields acetophenone
Chemistry 243 - Lecture 13 15
C 2004 Barry Linkletter, UPEI
Mechanism of Friedel-Crafts Acylation
� Similar to alkylation
� Reactive electrophile: resonance-stabilized acylcation
� An acyl cation does not rearrange
Chemistry 243 - Lecture 13 16
C 2004 Barry Linkletter, UPEI
Substituent Effects in Aromatic Rings
� Substituents can cause a compound to be (much) more or(much) less reactive than benzene
� Substituents affect the orientation of the reaction � thepositional relationship is controlled
� ortho- and para-directing activators, ortho- and para-directingdeactivators, and meta-directing deactivators
Chemistry 243 - Lecture 13 17
C 2004 Barry Linkletter, UPEI
Origins of Substituent Effects
� An interplay of inductive effects and resonanceeffects
� Inductive effect - withdrawal or donation of
electrons through a ! bond
� Resonance effect - withdrawal or donation of
electrons through a " bond due to the overlap of a
p orbital on the substituent with a p orbital on the
aromatic ring
Chemistry 243 - Lecture 13 18
C 2004 Barry Linkletter, UPEI
Inductive Effects
� Controlled by electronegativity and the polarity of
bonds in functional groups
� Halogens, C=O, CN, and NO2 withdraw electrons
through ! bond connected to ring
� Alkyl groups donate electrons
Chemistry 243 - Lecture 13 19
C 2004 Barry Linkletter, UPEI
Resonance Effects � Electron
Withdrawal
� C=O, CN, NO2 substituents withdraw electrons
from the aromatic ring by resonance
� ! electrons flow from the rings to the
substituents
Chemistry 243 - Lecture 13 20
C 2004 Barry Linkletter, UPEI
Resonance Effects � Electron Donation
� Halogen, OH, alkoxyl (OR), and amino substituentsdonate electrons
� ! electrons flow from the substituents to the ring
� Effect is greatest at ortho and para
Chemistry 243 - Lecture 13 21
C 2004 Barry Linkletter, UPEI
Contrasting Effects
� Halogen, OH, OR, withdraw electrons inductively
so that they deactivate the ring
� Resonance interactions are generally weaker,
affecting orientation
� The strongest effects dominate
Chemistry 243 - Lecture 13 22
C 2004 Barry Linkletter, UPEI
An Explanation of Substituent Effects
� Activating groupsdonate electrons tothe ring, stabilizingthe Whelandintermediate(carbocation)
� Deactivating groupswithdraw electronsfrom the ring,destabilizing theWhelandintermediate
Chemistry 243 - Lecture 13 23
C 2004 Barry Linkletter, UPEI
Ortho- and Para-Directing Activators:
Alkyl Groups
� Alkyl groups activate: direct further substitution topositions ortho and para to themselves
� Alkyl group is most effective in the ortho and para positions
Chemistry 243 - Lecture 13 24
C 2004 Barry Linkletter, UPEI
Ortho- and Para-Directing Activators:
OH and NH2
� Alkoxyl, and amino groups have a strong, electron-donating resonance effect
� Most pronounced at the ortho and para positions
Chemistry 243 - Lecture 13 25
C 2004 Barry Linkletter, UPEI
Ortho- and Para-Directing Deactivators:
Halogens
� Electron-withdrawing inductive effect outweighsweaker electron-donating resonance effect
� Resonance effect is only at the ortho and parapositions, stabilizing carbocation intermediate
Chemistry 243 - Lecture 13 26
C 2004 Barry Linkletter, UPEI
Meta-Directing Deactivators
� Inductive and resonance effects reinforce each other
� Ortho and para intermediates destabilized by deactivationfrom carbocation intermediate
� Resonance cannot produce stabilization
Chemistry 243 - Lecture 13 27
C 2004 Barry Linkletter, UPEI
Summary Table: Effect of Substituents inAromatic Substitution
Chemistry 243 - Lecture 13 28
C 2004 Barry Linkletter, UPEI
Trisubstituted Benzenes: Additivity of
Effects
� If the directing effects of the two groups are the
same, the result is additive
Chemistry 243 - Lecture 13 29
C 2004 Barry Linkletter, UPEI
Substituents with Opposite
Effects� If the directing effects of two groups oppose
each other, the more powerful activating group
decides the principal outcome
� Usually gives mixtures of products
Chemistry 243 - Lecture 13 30
C 2004 Barry Linkletter, UPEI
Meta-Disubstituted Compounds Are
Unreactive� The reaction site is too hindered
� To make aromatic rings with three adjacent substituents, itis best to start with an ortho-disubstituted compound
Chemistry 243 - Lecture 13 31
C 2004 Barry Linkletter, UPEI
Nucleophilic Aromatic Substitution
� Aryl halides withelectron-withdrawingsubstituents ortho andpara react withnucleophiles
� Form additionintermediate(Meisenheimer complex)that is stabilized byelectron-withdrawal
� Halide ion is lost to givearomatic ring
Chemistry 243 - Lecture 13 32
C 2004 Barry Linkletter, UPEI
Benzyne
� Phenol is prepared on an industrial scale by treatment ofchlorobenzene with dilute aqueous NaOH at 340°C underhigh pressure
� The reaction involves an elimination reaction that gives atriple bond
� The intermediate is called benzyne
Chemistry 243 - Lecture 13 33
C 2004 Barry Linkletter, UPEI
Evidence for Benzyne as an
Intermediate
� Bromobenzene with 14C only at C1 gives substitution productwith label scrambled between C1 and C2
� Reaction proceeds through a symmetrical intermediate inwhich C1 and C2 are equivalent� must be benzyne
Chemistry 243 - Lecture 13 34
C 2004 Barry Linkletter, UPEI
Structure of Benzyne
� Benzyne is a highly distorted alkyne
� The triple bond uses sp2-hybridized carbons, notthe usual sp
� The triple bond has one ! bond formed by p�poverlap and by weak sp2�sp2 overlap
Chemistry 243 - Lecture 13 35
C 2004 Barry Linkletter, UPEI
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, Ar!R "
Ar!CO2H
Chemistry 243 - Lecture 13 36
C 2004 Barry Linkletter, UPEI
Bromination of Alkylbenzene Side
Chains
� Reaction of an alkylbenzene with N-bromo-succinimide (NBS) and benzoyl peroxide (radicalinitiator) introduces Br into the side chain
Chemistry 243 - Lecture 13 37
C 2004 Barry Linkletter, UPEI
Mechanism of NBS (Radical) Reaction
� Abstraction of a benzylic hydrogen atom generates anintermediate 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
Chemistry 243 - Lecture 13 38
C 2004 Barry Linkletter, UPEI
Reduction of Aromatic Compounds
� Aromatic rings are inert to catalytic hydrogenation underconditions that reduce alkene double bonds
� Can selectively reduce an alkene double bond in the presenceof an aromatic ring
� Reduction of an aromatic ring requires more powerfulreducing conditions (high pressure or rhodium catalysts)
Chemistry 243 - Lecture 13 39
C 2004 Barry Linkletter, UPEI
Reduction of Aryl Alkyl Ketones
� Aromatic ring activates neighboring carbonylgroup toward reduction
� Ketone is converted into an alkylbenzene bycatalytic hydrogenation over Pd catalyst
Chemistry 243 - Lecture 13 40
C 2004 Barry Linkletter, UPEI
For Next Class
� Read Chapter 6
� Stereochemistry