Benzene is aromatic: a cyclic conjugated compound with 6 electrons Reactions of benzene lead to the retention of the aromatic core Electrophilic aromatic substitution replaces a proton on benzene with another electrophile Substitution Reactions of Benzene and Its Derivatives:Electrophilic Addition/Elimination Reactions.
Aromatic Substitutionsvia the Wheland Intermediates • All electrophile additions involve a cationic intermediate that was first proposed by G. W. Wheland of the University of Chicago and is often called the Wheland intermediate.
Bromination of Aromatic Rings • Benzene’s electrons participate as a Lewis base in reactions with Lewis acids • The product is formed by loss of a proton, which is replaced by bromine • FeBr3 is added as a catalyst to polarize the bromine reagent
Addition Intermediate in Bromination • The addition of bromine occurs in two steps • In the first step the electrons act as a nucleophile toward Br2 (in a complex with FeBr3) • This forms a cationic addition intermediate from benzene and a bromine cation • The intermediate is not aromatic and therefore high in energy
Formation of the Product from the Intermediate • The cationic addition intermediate transfers a proton to FeBr4- (from Br- and FeBr3) • This restores aromaticity (in contrast with addition in alkenes)
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)
Alkylation of Aromatic Rings:The Friedel–Crafts Reaction • Aromatic substitution of a R+ for H • Aluminum chloride promotes the formation of the carbocation • 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)
Acylation of Aromatic Rings • Reaction of an acid chloride (RCOCl) and an aromatic ring in the presence of AlCl3 introduces acyl group, COR
Reduction of Aryl Alkyl Ketones Allows Synthesis of Non-rearranged Alkyl Benzenes. • Aromatic ring activates neighboring carbonyl group toward reduction. • Ketone is converted into an alkylbenzene by catalytic hydrogenation over Pd catalyst, or Wolff-Kishner or Clemensen reductions.
Reduction of Aryl Alkyl Ketones Allows Synthesis of Non-rearranged Alkyl Benzenes.
Summary of reduction nucleophiles in 1,2-additions to aromatic C=O groups.
Substituent Effects in Aromatic Rings • Substituents can cause a compound to be (much) more or (much) less reactive than benzene and affect the orientation of the reaction. • There substituents are: ortho- and para-directing activators, ortho- and para-directing deactivators, and meta-directing deactivators.
Summary Table:Effect of Substituents in Aromatic Substitution
The Explanation of Substituent Effects • Activating groups donate electrons to the ring, stabilizing the Wheland intermediate (carbocation). • Deactivating groups withdraw electrons from the ring, destabilizing the Wheland intermediate.
Origins of Substituent Effects: Inductive Effects • The overall effect of a substituent is defined by the interplay of inductive effects and resonance effects. • Inductive effect - withdrawal or donation of electrons through s bonds. • Controlled by electronegativity and the polarity of bonds in functional groups, i.e. halogens, C=O, CN, and NO2withdraw electrons through s bond connected to ring. • Alkyl group inductive effect is to donate electrons.
Origins of Substituent Effects: Resonance Effects • 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. • C=O, CN, and NO2 substituents withdraw electrons from the aromatic ring by resonance, i.e. the electrons flow from the rings to the substituents.
Origins of Substituent Effects: Resonance Effects • 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. • Halogen, OH, alkoxyl (OR), and amino substituents donate electrons, i.e. the electrons flow from the substituents to the ring.
Meta-Directing Deactivators • Inductive and resonance effects reinforce each other. • Ortho and para intermediates destabilized by deactivation of the carbocation intermediate
Disubstituted Benzenes:Additivity of Effects • If the directing effects of the two groups are the same, the result is additive.
Disubstituted Benzenes:Opposition of Effects • If the directing effects of the two groups are different, the more powerful activating group decides the principal outcome. Usually the mixture of productsresults.
Diazonium Salts: The Sandmeyer Reaction • Primary arylamines react with HNO2, yielding stable arenediazonium salts. • The N2 group can be replaced by a nucleophile.
Reactions of Arenediazonium Salts Allow Formation of “Impossibly” Substituted Aromatic Rings. • Typical synthetid sequence consists of: • (1) nitration, (2) reduction, (3) diazotization, and (4) nucleophilic substitution
Preparation of Aryl Halides • Reaction of an arenediazonium salt with CuCl or CuBr gives aryl halides (Sandmeyer Reaction). • Aryl iodides form from reaction with NaI without a copper(I) salt.
Preparation of Aryl Nitriles and Carboxylic Acids • An arenediazonium salt and CuCN yield the nitrile, ArCN, which can be hydrolyzed to ArCOOH.
Reduction to a CH aromatic bond • By treatment of a diazonium salt with hypophosphorous acid, H3PO2