16 AROMATIC COMPOUNDS

• Predict the products of these reactions and use them.

• Predict the products of organometallic substitution and use them in synthesis.

• Predict the products of oxidation and reduction of the aromatic ring.

• For example, the aniline dye mauvine quickly replaced royal purple, but relatively few reactions that affect very expensive dye that was laboriously the bonds in the aromatic ring itself.
• Most of the reactions are unique to sea snails.

• Minor variations of aromatic substitution explain many reactions of benzene and its derivatives.
• We will look at how substituents on the ring affect the reactivity of the ring and the regiochemistry of the products.
• Other reactions of aromatic compounds include nucleophilic aromatic substitution, addition reactions, reactions of side chains, and special reactions of phenols.

• benzene has clouds of pi electrons above and below its sigma bond framework.
• Although benzene's pi electrons are in a stable aromatic system, they can be used to attack a strong electrophile to give a carbocation.

• The aromatic substitution product can be created by either a reversal of the first step or the loss of the protons on the carbon atom.

• A wide variety of reagents are used in this class of reactions.
• The most important method for synthesis of substituted aromatic compounds is electrophilic aromatic substitution, because it enables us to introduce functional groups directly onto the aromatic ring.

• The substitution product is given by the loss of a protons.

• The substitution product is given by deprotonation.

• We didn't consider the possibility of water acting as a nucleophile and attacking the carbocation in the step 2 of the iodination of benzene.

• There is a general mechanism for aromatic substitution.
• The formation of br+ is difficult because bromine is not sufficientlyphilic to react with benzene.
• A strong Lewis acid such as FeBr3 makes the reaction happen by forming a complex with another acid.

• Attack by benzene forms the sigma complexample Bromide ion from FeBr-4, which acts as a weak base to remove a proton from the sigma complex, giving the aromatic product and HBr, and regenerating the catalyst.

• The products are given by the loss of a protons.

• The transition state leading to the sigma complex occupies the highest energy point on the energy diagram.
• The step is endothermic because it forms a carbocation.
• The second step is exothermic because aromaticity is regained.
• The reaction is exothermic by 45 kJ>mol.

• Benzene is not as reactive as alkenes, which react rapidly with bromine at room temperature to give addition products.
• The reaction is exothermic by 121 kJ>mol.

• Under normal circumstances, the addition is not seen.
• The substitution requires a Lewis acid catalyst to make bromine stronger.

• Chlorination of benzene is similar to bromination, except that aluminum chloride is used as the Lewis acid catalyst.

• There is a mechanism for the aluminum chloride-catalyzed reaction of benzene with chlorine.

• Iodination of benzene requires an acidic oxidizer, such as carbon atoms ortho and nitric acid.
• An oxidant site of substitution is where Nitric acid is consumed in the reaction.

• Iodination probably involves a substitution of an aromatic with a cation.

• Benzene reacts with hot, concentrated nitric acid.
• A hot mixture of concentrated nitric acid with any oxidizable material could explode.
• A safer and more convenient procedure uses a mixture of acids.
• nitration can be done more quickly and at lower temperatures with the help of sphuric acid.

• Next, the mechanism is shown.
• The mechanism is similar to other dehydrations.
• The hydroxy group of nitric acid can leave as water and form a nitronium ion.
• The sigma complex is formed when the ion reacts with benzene.

• Similar to the dehydration of an alcohol, nitric acid has a hydroxy group that can become protonated and leave as water.

• The aromatic substitution by the ion gives it's name, nitrobenzene.

• There is a loss of a protons.

• Reduction followed by nitration is the best method for adding an aromatic ring.

• The accelerated rate is explained by resonance forms of the sigma complex.

• Strong acid catalysts are often used as nonpolar organic solvents.
• Arylsulfonic acids can be synthesised using sulfonation of benzene derivatives and sulfur trioxide.

• Benzene attacks sulfur trioxide, forming a sigma complexample loss of a protons on the carbon and oxygen gives benzenesulfonic acid.

• Sulfur trioxide is a powerful oxidizer.

• An aromatic ring is regenerated when a protons is lost.

• The sulfonate group may become acidic.

• alkylbenzene sulfonates are widely used as detergents.
• A alkylbenzenesulfonic acid is given by the shponation of an alkylbenzene.
• Section 25-4 covers detergents in more detail.

• The dipolar sigma complex shown in the sulfonation of benzene has its positive charge and negative charge delocalized over three carbon atoms.

• The aromatic ring is given by the first synthetic detergents of sulfur trioxide.
• SO3 is removed from had branched alkyl groups.
• The equilibrium is made up of hydrating it to sulfuric acid.

• The sigma complex can lose either of the two protons if benzene is attacked.
• We can show that the product has a deuterium atom in place of hydrogen by using a deuterium ion.
• Adding SO3 to some D2O will generate D2SO4.
• Benzene gives a deuterated product.

• The final products reflect the D/H ratio of the solution.
• A large amount of deuterium gives a product with all six of the benzene hydrogens.

• Until now, we have only considered benzene as a substitution for aromatics.
• If we want to make more complicated aromatic compounds, we need to consider the effects other substituents might have.

• Under the same conditions, toluene reacts 25 times faster than benzene.

• substitution at the ortho and para positions give a mixture of products.

• The product ratios show that the orientation of substitution is not random.
• There would be equal amounts of ortho and meta substitution and half as much para substitution.

• The prediction is based on the two ortho positions, two meta positions, and one para position available for substitution.

• The first step in forming the sigma complexample is matic substitution.
• The enhanced reaction rate and the preference for ortho and para substitution by Ultrasuss is considering the structures of the intermediate sigma complexes.

• There was no positive charge distributed over the carbon atoms.

• The sigma complexes for ortho and para attack are more stable than the sigma complex for nitration of benzene.

• The intermediate for substitution of benzene has the same positive charge spread as the sigma complex for meta substitution.
• The large rate enhancement seen with ortho and para substitution is not shown in the meta substitution of toluene.

• The rate-limiting transition state leads to the formation of the methyl group in toluene.
• When the positive charge is delocalized onto the tertiary carbon atom, the stabilizing effect is large.
• When substitution occurs at the meta position, the positive charge is not delocalized onto the tertiary carbon, and the methyl group has a smaller effect on the stability of the sigma complexample.

• The states leading to them are CH3.

• The other substituent that is activated by the benzene ring is the methyl group.
• In the next section, we look at groups that have the opposite effect.

• The results with toluene are general for any alkylbenzene.
• A transition state and intermediate with a positive charge shared by the tertiary carbon atom can be achieved with substitution ortho or para.
• The products of alkylbenzenes are mostly ortho and para-substituted.

• Another example of an aromatic substitution that is enhanced by stabilization is the reaction of ethylbenzene with bromine.
• With respect to the meta isomer, the rates of formation of the ortho- and para-substituted isomers are greatly enhanced.

• The sigma complex is lower in energy for substitution at the ortho and para positions than it is for substitution at the meta position.

• Styrene undergoes an aromatic substitution much faster than benzene, and the products are mostly ortho- and para-substituted.

• The results can be explained using resonance forms of the intermediates.

• The nitration of methoxybenzene is about 10,000 times faster than that of benzene and 400 times faster than toluene.
• Oxygen is a strongly negative group, yet it donates electron density to stabilizing the transition state and the sigma complexample.

• The EPM of anisole shows the aromatic ring to be electron-rich, consistent with the observation that anisole is only six each atom has eight strongly activated toward reactions.

• The second resonance form puts a positive charge on the oxygen atom, but it has more covalent bonds, and it provides each atom with an octet in its valence shell.
• The ortho and para positions are activated by the methoxy group of anisole.

• If the sigma complex is para to the site of substitution, the methoxy group can be effective in stabilizing it, but not if it is meta.

• Anisole quickly brominates in water without a catalyst, because a methoxy group is so strongly activated.
• In the presence of bromine, this reaction proceeds.

• A nitrogen atom with a nonbonding pair of electrons is a powerful group.
• Aniline undergoes a bromination in bromine water without a catalyst.

• The 2,4,6-tribromoaniline ring is more electron-rich than anisole.

• If an attack takes place ortho or para, nitrogen's nonbonding electrons provide resonance stabilization to the sigma complex.

• The complexes sigma related to bromination of aniline at the ortho, meta, and para positions are drawn.

• A sigma complexample can be provided by substituent with a lone pair of electrons on the atom bonding to the ring.
• All of these substituents are para-directing.

• The bromine color in both beakers is gone.

• nitration of nitrobenzene requires concentrated nitric and sulfuric acids.
• The meta isomer is the major product.

• The results should not be surprising.
• The carbon atoms ortho and para are affected by a substituent on a benzene ring.
• The ortho and para positions are primarily activated by an electron-donating substituent and an electron-drawing substituent.

• The products have meta substitution and the meta positions are the most reactive.

• The nitrogen atom has a positive charge no matter how we position the electrons.

• The positively charged nitrogen withdraws electron density from the aro aromatic ring.
• The aromatic ring is less electron-rich than benzene, so it is deactivated.

• The deactivating effect is strongest at ortho reactions.

• Each sigma complex has a positive charge spread over three carbon atoms.

• This close proximity of two positive charges is not stable.

• Positive charges are farther apart.

• NO2 is a meta-director.

• The reaction rates for NO2 are slower than for benzene.

• Most deactivating sub stituents are meta-directors.
• Deactivating substituents are groups with a positive charge on the atom of the aromatic ring.

• The only sigma complexes that don't put a positive charge on this ring shells are the safer high explosives and meta substitution complexes.
• It is sensitive to shock carbon.

• The ring has a positive charge on it.

• The reaction with benzene is quicker than the meta position.

• There are some common substituents listed in the summary table.
• The forms show how the atom bonds to the aromatic ring.

• Aniline reacts quickly with bromine to give 2,4,6-tribromoaniline.
• They are poor.

• Explain why nitration of aniline is so slow.

• Although nitration of aniline is slow, it goes quickly and gives mostly para substitution.
• There is a difference in reactivity.

• The general rules do not apply to the halobenzenes.
• There are groups that are deactivating and there are groups that are para-directors.

• There are two effects that oppose each other.

• The X bond has a carbon atom at the positive end of the dipole.
• The benzene ring has less electron-rich making it less reactive.

• The positive charge of the sigma complex is shared by the carbon atom and the halogen.
• Even though it is sigma-withdrawing, the resonance stabilization allows a halogen to be pi-donating.

• The sigma complex is not delocalized onto the carbon atom because of the reaction at the meta position.
• The meta intermediate is not stable by the ion structure.
• There is a preference for ortho and para substitution in the nitration of chlorobenzene.

• Remember which substituents are deactivating.
• Figure 17-4 shows the effect of the halogen atom graphically, with an energy para-directing, and deactivators diagram comparing energies of the transition states and intermediates for electrophilic are meta-directing, except for the attack on chlorobenzene and benzene.
• The reactions of halogens need higher energies.

• The intermediate for meta substitution is less stable than the other two.

• The reactivity of an aromatic ring is affected by two or more substituents.
• The result is easy to predict if the groups reinforce each other.
• The two methyl groups are both activated, so we can predict that all the xylenes are activated.
• In the case of a nitrobenzoic acid, both substituents are deactivating, so we think that the acid is going to be attacked.

• It is easy to predict the orientation of addition.
• There are two different positions for xylene, one ortho to one of the groups and the other para to the other.

• The two equivalent positions are wherephilic substitution occurs.
• There may be some substitution at the position between the two groups, but it is not as effective as the other two positions.
• The methyl group directs an electrolyte towards its ortho positions.

• The locations of the nitro group are its meta positions.

• When two or more substituents conflict, it's more difficult to predict where an electrophile will react.
• In many cases, the result is a mixture.
• mixtures of substitution products are given because xylene is activated at all the positions.

• When there is a conflict between two groups, the activated group usually directs the substitution.

• The deactivating groups are usually stronger than the active groups.

• It is helpful to separate substituents into three different classes.

• Powerful ortho, para-directors are used to stable the sigma complexes.

• The substituent in the stronger class is more dominant if there are two substituents.
• A mixture is likely if both are in the same class.
• The incoming substituent is directed by the stronger group.
• The methoxy group is a stronger group than the nitro group.
• substitution at the crowded position ortho to both the methoxy group and the nitro group is prevented by Steric effects.

• The aromatic ring has a nitrogen atom with a nonbonding pair of electrons bonding to it.
• The amide group is a stronger group than the chlorine atom, and substitution occurs mostly at the positions ortho to the amide.
• The amide is a particularly strong activated group, and the reaction gives some dibrominated product.

• The site of substitution for a biphenyl is determined by two factors: which phenyl ring is more activated (or less deactivated) and which position on that ring is most reactive.

• To show why a phenyl substituent should be para-directing, use resonance forms of a sigma complex.

• A new carbon-carbon bond can be formed by substitution onto aromatic rings.
• The first studies of reactions with aromatic compounds were done in 1877 by the French alkaloid chemist Charles Friedel and his American partner, James Crafts.
• alkylate benzene was found to give alkylbenzenes in the presence of Lewis acid catalysts.

• The gas is evolved.

• The butyl cation is acting as aphile.
• The catalyst is aluminum chloride.

• The catalyst is regenerated in the final step.

• A wide variety of primary, secondary, and tertiary alkyl halides are used in Friedel-Crafts alkylations.
• The carbocation is most likely caused by secondary and tertiary halides.

• Friedel-Crafts alkylation is an aromatic substitution in which an alkyl cation acts as the electrolyte.

• The alkylated product is regenerated by the loss of a protons.

• The free primary carbocation is too unstable with primary alkyl halides.
• A complex of aluminum chloride and alkyl halide is what the actual electrophile is.
• There is a weakened carbon-halogen bond and a positive charge on the carbon atom in this complex.

• Friedel-Crafts alkylations can be made using most of the ways we have seen.
• Two common methods are treatment of alkenes and alcohols.

• The Alkenes are given with air to give it's shape.
• The carbocation is not immediately attacked by floride ion.
• If benzene is present, a substitution occurs.
• The more stable carbocation, which alkylates the aromatic ring, is formed after the protonsation step.

• Alcohols are used in Friedel-Crafts alkylations.
• Lewis acids such as Boron trifluoride are used to treat alcohols.
• substitution may occur if benzene is present.

• Predict the products for each reaction by showing the generation of the electrophile.

• Friedel-Crafts alkylation has three major limitations that make it hard to use.

• Friedel-Crafts reactions only work with benzene, activated benzene derivatives, and halobenzenes.
• They fail with systems that are strongly deactivated.

• Friedel-Crafts reactions fail with deactivated systems.

• The correct product is given by nitration.
• The butyl group would fail.

• The Friedel-Crafts alkylation is susceptible to carbocation rearrangements.
• The Friedel-Crafts alkylation is not prone to rearrangement and can be used to synthesise butylbenzene, isopropylben Alkyl and ethylbenzene.
• Consider what happens.

• Friedel-Crafts alkylations are hard to avoid.
• This limitation can be very serious.
• We need to make ethyl to multiple alkylations.

• It is activated even faster than benzene when it is formed.
• There is a mixture of some diethylbenzenes, some triethylbenzenes, and a small amount of ethylbenzene.

• A large excess of benzene can be used to minimize the problem of overalkylation.
• The concentration of ethylbenzene is always low if 1 mole of ethyl chloride is used with 50 moles of benzene.
• The product is separated from excess benzene.
• The unreacted benzene can be recycled with a continuous distillation.

• In the laboratory, alkylate aromatic compounds are more expensive than benzene.
• A moreselective method is needed because we can't afford a large amount of starting material.
• The Friedel-Crafts acylation introduces just one group without the risk of polyalkylation or rearrangement.

• You may think that aluminum chloride is added as a catalyst.
• Predict the major products for the reactions that won't give a good yield.

• Acyl chlorides are made by reacting carboxylic acids with thionyl chloride.

• When we study acid derivatives in Chapter 21, we consider acyl chlorides.

• The acylium ion reacts with benzene to form acylbenzene.

• Friedel-Crafts acylation is an aromatic substitution with an acylium ion.

• A sigma complex is formed by anphilic attack and the loss of a protons.

• The free acylbenzene must be released from the product complex.

• A ketone is the product of acylation.
• The ketone's carbonyl group requires a full equivalent of Lewis acid in the acylation.
• The aluminum chloride complex is the initial product.
• The free acylbenzene comes from the addition of water.

• Para substitution usually occurs when the aromatic substrate has an ortho, para-directing group.

• One of the most attractive features of the Friedel-Crafts acylation is the de 888-282-0476 888-282-0476 888-282-0476 888-282-0476.
• A deactivating group is bonded to the aromatic ring of the acylbenzene.
• The acylation stops after one substitution because Friedel-Crafts reactions do not occur on strongly deactivated rings.

• The acylium ion is resonance-stabilized, so that no rearrangements occur, and the acylbenzene product is deactivated, so that no further reaction occurs.
• The acylation fails with aromatic rings.

• Only benzene, halobenzenes, and activated derivatives can be used with the alkylation.

• The alkylation may have some changes.

• The acylium is not prone to rearrangement.

• Polyalkylation is a problem.

• The acylbenzene does not react further after the acylation.

• A two-step sequence can make many alkylbenzenes that are impossible to make by direct alkylation.
• Friedel-Crafts alkylation cannot makepropylbenzene.
• There are two things that give isopropylbenzene, together with some diisopropylbenzene.

• The conditions used to reduce a nitro group to an amine are similar to those used for the Clemmensen reduction.
• In the following synthesis, aromatic substitution followed by reduction is used to make compounds with specific substitution patterns.

• Friedel- Crafts reactions use carboxylic acids and acid anhydride as acylating agents.
• When we study the reactions of carboxylic acids and their derivatives, we consider these acylating agents.

• Friedel-Crafts acylation cannot add a formyl group to benzene.
• Formyl chloride can't be bought or stored because it is unstable.

• A mixture of carbon monoxide and HCl together with a catalyst consisting of cuprous chloride and aluminum chloride can be used for mylation.
• The formyl cation could be generated through a small amount of formyl chloride.
• The formyl benzene is a result of the reaction with benzene.

• Friedel-Crafts acylations show how you can use Friedel-Crafts acylation, Clemmensen reduction, and/or free from Gatterman-Koch synthesis to prepare compounds.

• If there are strong electron-withdrawing groups ortho or para to the halide, nucleophiles can displace it.

• A strong nucleophile replaces a leaving group in aromatic substitution.
• Aryl halides can't achieve the correct geometry for back-side displacement.
• The back of the carbon bearing the halogen is blocked by the aromatic ring.

• The mechanism can't be involved.
• The reaction rate is proportional to the concentration of the nucleophile.
• The ratelimiting step must involve the nucleophile.

• Without a powerful electron-drawing group, nucleophilic aromatic substitution is difficult.

• In detail, aromatic substitutions have been studied.
• Depending on the reactants, either of two mechanisms may be involved.
• One mechanism is similar to the aromatic substitution mechanism, except that nucleophiles and carbanions are not involved.
• Benzyne is an interesting and unusual intermediate.

• Consider the reaction of 2,4-dinitrochlorobenzene with sodium hydroxide.
• A negatively charged sigma complex results when hydroxide attacks the chlorine.
• The negative charge is delocalized over the ring's ortho and para carbons.
• 2,4-dinitrophenol is deprotonated in this basic solution because of the loss of chloride from the sigma complex.

• The leaving group gives the product.

• The product is acidic and deprotonated by the base.

• After the reaction is complete, acid would be added to the phenoxide ion.

• The mechanism box shows the resonance forms that show how para to the halogen helps to stable the intermediate.
• Formation of the negatively charged sigma complex is unlikely without strong resonance-drawing groups in these positions.

• It is not very polarizable and is a poor leaving group.

• Strong electron-drawing substituents on the aromatic ring are required for the addition-elimination mechanism.

• The reaction takes place in liquid ammonia at -33 degrees.

• There is a mechanism different from the one we saw with the addition-elimination of halobenzenes.

• bromide ion can be expelled by the carbanion.
• The two carbon atoms bonding between them are given additional strength by the overlap of this orbital and filled one.
• The overlap of 2 orbitals is not very effective because they are directed away from each other.
• Triple bonds are usually linear, but this one is very strained.

• Amide ion is a strong nucleophilic, attacking at either end of the triple bond.
• The toluidine is given after the subsequent protonsation.

• The benzyne mechanism works when the halobenzene is not activated and forcing conditions are used with a strong base.
• There is a two-step elimination.
• The substituted product is given by a nucleusphilic attack.

• When a substitution with a powerful base and without strong electron-drawing groups takes place, the benzyne mechanism should be considered.

• There is a chance that the ring has no strong electron-drawing groups.
• It needs a powerful base or high temperatures.

• A carbanion is given by deprotonation adjacent to the leaving group.

• The leaving group is expelled by the carbanion.

• The product is given by reprotonation.

• Show the expected products of the following reactions.

• The benzyne mechanism is likely if stronger conditions are required.

• The triple bond of benzyne is very strong.
• Predict the product of the Diels-Alder reaction of benzyne.

• Many useful drugs, fabrics, and plastics require the synthesis of aromatic rings with alkyl, aryl, or vinyl groups attached in the presence of multiple types of functional groups.
• To avoid these limitations, organic chemists have developed a wide variety of methods that tolerate many other functional groups.

• Some of the most successfulcoupling reactions use transition metals that change valences easily, adding and eliminating substituents as they pass from one oxidation state to another.

• Aryl and vinyl halides are used to make substituted benzenes and alkenes.
• There are many new methods using other transition metals in the reagents and catalysts.

• Most of the reactions substitute organic groups for halogen atoms.
• First, we consider the use of organocuprates to couple with aromatic rings and alkenes, and then look at palladium-catalyzed reactions that form substituted aromatic rings.

• The reaction of two equivalents of an organolithium reagent with cuprous iodide creates the lithium dialkylcuprate reagents.
• A new carbon-carbon bond is formed when the dialkylcuprate is reacted with an alkyl, aryl, or vinyl halide.

• The mechanisms of organocuprate reactions are not well understood.
• Both vinyl and aryl halides can't undergo SN2 displacement.
• There is a wide variety of com pounds that can be made by organocuprate reactions.
• An aromatic ring can be found in either the aryl halide or dialkylcuprate reagent.
• Iodides, bromides, and chlorides can be used as the halides.

• The stereochemistry of the vinyl halide is preserved with an aryl cuprate.

• Acyl halide with organocuprate gives a ketone.

• The less substituted end of the alkene has a C bond.

• The alkene and the bromide are usually monosubstituted.
• The catalyst may be Pd(OAc)2 or PdCl2 or a variety of other compounds.
• A small amount of catalyst is needed.
• The HX released in the reaction is mitigated by adding a base such as triethylamine.
• Many reactions use triphenylphosphine to complex with the palladium, which helps strengthen it and enhances its reactivity.

• In drug synthesis, where the palladium catalysts can be recovered and recycled, the Heck reaction and its variant are used frequently.
• Water can be used as the solvent in some Heck reactions.
• The examples show the wide utility of the reaction.

• A nitrile with a vinyl halide.

• The Suzuki reaction is a substitution of an aryl or vinyl halide with an alkyl, alkenyl, or aryl boronic acid.

• A wide variety of required heavy metals and other toxic functional groups can be found in these types of couplings.

• B(OH) spent reagents.

• R'B(OR)2 by-products are less hazardous and easier to dispose of.

• The Suzukicoupling can use water as a solvent.
• Water based Suzuki reactions are attractive for both industrial processes and labs that want to minimize the purchase and disposal of toxic solvents.
• There are many combinations that can be coupled using Suzuki reactions.

• The stereochemistry of the reagents is preserved by a vinyl halide with an alkenylboronate ester.

• An aryl halide with arylboronic acid is used as a solvent.

• Water and palladium are used as a solvent and catalyst in the synthesis of the anti-Inflammatory drug flurbiprofen.

• alkyl-, vinyl-, and arylboronic acids can be used to make the boronate esters.
• The hydroboration of double and triple bonds is similar to that of alkenes and alkynes in Chapters 8 and 9.
• The less substituted end of a double or triple bond is usually added by the boron atom.
• The B and H add the same side of a triple bond to give a trans alkenylboronate ester.

• Adding a trialkyl borate allows the organolithium compound to form a carbon-boron bond and expel an alkoxide group.

• In the second step, the alkyl group from the negatively charged alkylboronate replaces the halogen on Pd.
• In the final step, the two alkyl groups on Pd couple together to release the Pd atom.
• The Pd atom can make more reactions happen.

• Adding oxidizer gives Pd a higher oxidation number.

• A lower oxidation number is given byeductive elimination from the Pd.

• If forcing conditions are used, aromatic compounds may be added.
• Some of the most important industrial reactions of aromatic compounds include these additions.

• When benzene is treated with an excess of chlorine under heat and pressure, six chlorine atoms add to form 1,2,3,4,5,6-hexachlorocyclohexane.

• Stereoisomers can be produced in different amounts.

• The process of hydrogenation of benzene to cyclohexane takes place at elevated temperatures and pressures.
• Disubstituted benzenes give a mixture of cis and trans isomers.

• The commercial method for producing cyclohexane and substituted cyclohexane derivatives is Catalytic Hydrogenation of benzene.
• The reduction can't be stopped at an intermediate stage because alkenes are reduced faster than benzene.

• In 1944, the Australian chemist A. J. Birch discovered that benzene derivatives can be reduced to nonconjugated cyclohexa-1,4-dienes by treating them with liquid ammonia and an alcohol.

• A solution of liquid ammonia contains solvated electrons that can add to benzene.
• A cyclohexadienyl radical is created by the basic radical anion and the alcohol in the solvent.
• The radical adds a solvated electron to form a cyclohexadienyl anion.
• The reduced product comes from the reduction of this anion.

• Adding a solvated electron and a protons to the aromatic ring is part of the Birch reduction.

• A radical is formed by the addition of an electron and a protons.

• The product is given by the addition of a second electron and a protons.

• The reduced carbon atoms go through intermediates.

• The carbanions are stable because of electron-withdrawing substituents.
• Reduction takes place on carbon atoms withdrawing substituents and not on carbon atoms withreleasing substituents.

• The aromatic ring can be deactivated by OCH3.
• A stronger reducing agent and a weaker source enhances the reduction.

• There are mechanisms for the Birch reductions of benzoic acid and anisole shown.

• Many reactions are unaffected by the presence of a nearby benzene ring, yet others depend on the aromatic ring to promote the reaction.
• The best way to reduce aliphatic ketones to alkanes is to reduce aryl ketones to alkylbenzenes.
• There are more side-chain reactions that show the effects of a ring.

• The product has a carboxylate salt.
• If any other functional groups are resistant to oxidation, this oxidation is useful for making benzoic acid derivatives.
• SO3H is usually able to survive this oxidation.

• Predict the major products of treating the compounds with hot, concentrated potassium permanganate.

• chloroethylbenzene reacts with chlorine in the presence of light.
• A dichlorinated product can be given further chlorination.

• The chlorine radical is too reactive to give completely benzylic substitution, so chlorination shows a preference for a substitution.
• Many isomers are produced.
• There is a lot of substitution at the b carbon in the chlorination of ethylbenzene.

• chlorination is more effective at killing chlorine radicals than bromination.
• The benzylic position is where bromide reacts.

• The reagent for benzylic bromination isbromosuccinimide.
• br2 can add to the double bond and bromosuccinimide is preferred for allylic bromination.
• Unless it has powerful substituents, this is not a problem with the relatively unreactive benzene ring.

• The bromination of ethylbenzene is shown.

• Predict the major products when the following compounds are irradiated by light.

• In Chapter 15 we saw that allylic halides are more reactive than alkyl halides.
• For reasons similar to those for allylic halides, benzylic halides are more reactive in these substitu tions.

• First-order substitution requires the ionization of the halide to give a carbocation.
• The resonance-stabilized carbocation is found in a benzylic halide.
• The stability of the 1-phenylethyl cation is similar to that of the 3deg alkyl cation.

• benzyl halides are more easy to react to than most alkyl halides.

• The stabilizing effects are added if a benzylic cation is bonding to more than one phenyl group.
• The triphenylmethyl cation is an extreme example.
• The positive charge is stable with three phenyl groups.
• For a long time, triphenylmethyl fluoroborate can be stored as a stable ionic solid.

• There is a mechanism for the reaction of benzyl bromide with alcohol.

• benzylic halides are 100 times more reactive than primary alkyl halides in displacement reactions.
• The reactivity of allylic halides is similar to that of this enhanced reactivity.

• The stabilizing conjugate lowers the transition state's energy.

• The conversion of aromatic methyl groups to functional groups is done efficiently by the SN2 reactions of benzyl halides.
• The functionalized product is given by substitution.

• The transition state for the displacement of a benzylic halide is stable with the pi electrons in the ring.

• Predict the product of addition of HBr to 1-phenylpropene based on what you know about the relative stabilities of alkyl cations and benzylic cations.

• There is a mechanism for this reaction.

• If you know the relative stabilities of alkyl radicals and benzylic radicals, you can predict the product of addition of HBr to 1-phenylpropene in the presence of a free-radical initiator.

• There is a mechanism for this reaction.

• Use the indicated starting materials to synthesise the following compounds.

• The chemistry of phenols is similar to that of aliphatic alcohols.
• Patients can take a small aspirin if phenols can be acylated to give esters, and phenoxide ion can serve as nucleophiles to reduce the danger of clotting in the Williamson ether synthesis.
• It is easy to form phenoxide ion in blood vessels because they are more acidic than water.

• This is a way for phenols to react.
• Bond breaks are not possible with phenols.
• phenols do not undergo acid-catalyzed elimination.

• There are reactions that are not possible with aliphatic alcohols.
• Some reactions are peculiar to phenols.

• There are apples, pears, and potatoes.
• In the presence of air, many phenols slowly autoxidize.

• The atmospheric oxygen is by O.

• Lemon juice and ascorbic acid add oxygen atoms to the ring, making it easy to oxidize.
• Silver bromide can be used to retard the growth of fruit.

• This reaction is the basis of black-and-white photographic film.
• A focused image shows a film containing small grains of silver bromide.
• The grains are activated when light strikes the brown film.
• There are dark areas where light struck the film.

• The bombardier beetle sprays a hot quinone solution from its abdomen.
• The solution is formed by the oxidation of hydroquinone.
• A balanced equation is needed for this oxidation.

• When threatened, the bombardier beetle Quinones occur in nature, where they serve as biological oxidation- mixes hydroquinone and H2O2 with reduction reagents.
• It seems that Peroxide oxidizes hydroquinone everywhere.
• Coenzyme Q to quinone is an oxidizer within the cells.
• The solution will boil after the following reaction.
• The reduced form of nicotinamide hot, irritating liquid sprays from the tip of adenine dinucleotide oxidizes to NAD+.

• The sigma complex formed by attack at the ortho or para position is stable because of the nonbonding electrons of the hydroxy group.
• The hydroxy group is para-directing.
• Some Friedel-Crafts reactions can be done with phenols.

• Because they are highly reactive, phenols are usually alkylated or acylated using relatively weak Friedel-Crafts catalysts.

• CH( CH ) 3 2 phenols are more reactive than CH( CH ) 3 2 phenols toward aromatic substitution.
• sigma neutral complexes with structures that look like quinones are created when phenoxide ion react with positively charged electrophiles.

• The phenoxide ion is so strongly activated that it undergoes an aromatic substitution with carbon dioxide.
• The carboxylation of phenoxide ion is an industrial synthesis of salicylic acid, which is converted to aspirin.

• A good Diels-Alder dienophile is 1,4-Benzoquinone.

• Synthetic tools have been important for over a century.
• Each new substitution affects where the next one will go.
• The earlier substituents direct later reactions toward the correct reaction sites must be planned in any multistep sequence.

• The product is determined by the order of substitution.

• Attach the o,p-director first to produce the ortho or para product.
• Attach the m-director first to produce the meta product.

• Friedel-Crafts do not work well on strongly deactivated rings.

• A strongly activated group wins when there is a conflict between substituents.

• Friedel-Crafts reactions add acyl and alkyl groups to aromatic compounds, but they have limitations.

• Straight-chain alkylbenzenes cannot be produced by simple Friedel-Crafts alkylation.

• The Friedel-Crafts acylation can be used to convert the acyl group to an alkyl group.
• If another group is to be added, it can be added to the acylbenzene to give meta orientation or it can be added to the alkylbenzene to give ortho,para orientation.

• A student tried the Friedel-Crafts alkylation of benzenesulfonic acid with bromoethane.
• An alternative synthesis can be proposed if not.

• In alkylation, substitution can happen more than once.

• A large excess of the starting aromatic compound is usually recycled through the process.

• Friedel-Crafts reactions do not work on strongly deactivated benzenes.

• The N: complexes with the AlCl3 catalyst become positively charged and become a deactivating group.

• The amine can be protected from strongly acidic reagents by converting it to an amide.
• The amide is compatible with Friedel-Crafts and many other reactions.
• The amide can be removed at the end of the synthesis.

• It works in Friedel-Crafts reactions.

• Other reactions may be useful.

• An aromatic ring can be attached to a carboxylic acid group by adding an alkyl group.
• At the alkylbenzene stage, ortho and para can be added, or they can be added meta after the oxidation.
• OH and NH2 substituents do not survive the oxidation.
• SO3H and NO2 survive the oxidation.

• This trisubstituted benzene starts from toluene.

• A blocking group is the SO3H group.

• The SO3H group can be used to block a position.
• When the para position is more reactive, this is a common procedure to make ortho isomers.
• The SO3H group can be used to block the para position, substitute the ortho position, and then remove the blocking group.

• Sulfuration can be reversed.

• If you start from toluene, you can propose synthetics for ortho-, meta-, and para-chlorobenzoic acid.

• This trisubstituted benzene can be synthesised starting from toluene.

• H2O reduction gives anilines.

• There is a mixture of cis and trans.

• The position of the benzylic is activated.

• A catalyst is a protic acid or a Lewis acid.

• There are no substitution of Aryl Halides for aryl halides in this section.
• Special conditions are required for 2 carbon, usually involving a metal.

• Chapter 17 has reactions shown in red.
• Reactions are shown in blue.

• A substituent makes the aromatic ring more reactive than benzene.

• Acyl group bonds to a chlorine atom.

• The position of the carbon atom of an alkyl group that is directly bonding to a benzene ring.

• The benzylic positions are circled.

• Benzyne is a benzene with two hydrogen atoms removed.
• It can be drawn with a strained triple bond.

• The products are usually cyclohexa-1,4-dienes.

• A substituent that makes the aromatic ring less reactive than benzene.

• The synthesis of benzaldehydes is done by treating a benzene derivative with CO and HCl.

• A positively charged ion has a positive charge on a halogen atom.

• The halogen atom has two bonds and a formal plus charge.

• The meta position is the least deactivated and most reactive of the ortho and para positions.

• A leaving group on an aromatic ring was replaced by a strong nucleophile.

• formula R2CuLi is a compound containing carbon- copper bonds.

• The ortho and para positions are activated by this substituent.

• quinones are relatively rare.

• Capable of donating electrons through resonance.
• It is possible to withdraw electron density through resonance.

• The sigma complex has a negative and positive charge in aromatic substitution.

• This can be done by heating with water or steam.

• A substitution that combines an aryl or vinyl halide with a alkyl, aryl, or vinyl boronic acid or boronate ester.

• Each skill is followed by problem numbers.

• Predict the position of aromatic substitution on molecule with substituents on one or more aromatic rings and use the influence of substituents to generate the correct isomers.

• Problems 17-58,68, 69, 70, mechanisms for both the addition-elimination type and the benzyne type are proposed.

• Predict the products of the organocuprate,Heck, and Suzuki reactions.

• Predict the products of the Birch reduction, hydrogenation, and chlorination of aromatic compounds.

• Predict the products of the reactions of phenols.

• Predict the major products when benzene reacts.

• Indane can be chlorinated at any of the alkyl positions.

• Take the possible monochlorinated products from this reaction.

• Draw the products that could be dichlorinated from this reaction.

• Show how you would synthesise the following compounds, starting with benzene or toluene.
• Para is the major product and separable from ortho.

• Predict the major products of bromination using the dark.

• A student added 3-phenylpropanoic acid to a molten salt consisting of a 1:1 mixture of Na and Al.
• After 5 minutes, he poured the molten mixture into the water.

• The yield of the product that was Evaporation was 98%.

• The compound reacts with a hot, concentrated solution of NaOH to give a mixture of two products.
• Give a mechanism to account for the formation of these products.

• Predict the structure of the product.

• At the 9-position of anthracene, aromatic substitution occurs.

• The alcohol and bromopent-1-ene are shown.

• Furan undergoes aromatic substitution more quickly than benzene.

• furan reacts with bromine to give 2-bromofuran.

• Take the resonance forms of each complex and compare them.

• There are three isomers of dihydroxybenzene.

• The isomers have melting points of 175, 199, and 168 degrees.
• The isomers were nitration to determine their structures.
• Two mononitro isomers are given by the isomer that melts at 175 degC.
• Three mononitro isomers are given by the isomer that is melted at 195 degC.
• Only one mononitro isomer isomer isomer when the isomer is melted at 168 degC.

• It is made from phenol and acetone.
• There is a mechanism for this reaction.

• sulfonation can be reversed, unlike most other aromatic substitution.

• When the temperature increases, explain the change in product ratios.

• Predict what will happen when the mixture is heated to 100 degrees.

• The SO3H group can be added to a benzene ring and removed later.

• 2,6-dibromotoluene can be made from toluene using sulfonation and desulfonation as intermediate steps.

• One of the bromine atoms is replaced when 1,2-dibromo-3,5-dinitrobenzene is treated with excess NaOH.

• The product you expect will be shown in the equation.
• There is a mechanism to account for the formation of your product.

• An interesting Diels-Alder adduct of formula C20H14 results is when anthracene is added to the reaction of chlorobenzene.
• The product has a singlet of area 2 around d 3 and a broad singlet of area 12 around d 7.
• Explain why one of the aromatic rings of anthracene reacted as a diene.

• In Chapter 14, we learned that Agent Orange contains 2,4,5-trichlorophenoxy) acetic acid.

• Write equations for the reactions when you draw the structures of the compounds.

• There is a way to show how 2,3,7,8-TCDD is formed in the synthesis of 2,4,5-T.

• After the first step and on completion of the synthesis, show how the contamination might be eliminated.

• The product of formula C6H3OBr 3 was created when phenol reacted with three equivalents of bromine.
• A yellow solid of formula C6H2OBr4 is created when this product is added to bromine water.
• The IR spectrum shows a strong absorption around 1680 cm-1.

• Show how you would synthesise the compound shown here.

• She repeated the reaction by using a small amount of furan as a solvent.
• She isolated a fair yield from this reaction.
• There is a mechanism for its formation.

• An interesting variation of the Birch reduction is involved in a common synthesis of methamphetamine.
• A solution of ephedrine in alcohol is added to liquid ammonia.
• The Birch reduction usually reduces the aromatic ring, but in this case it eliminates the hydroxy group of ephedrine to give meth.
• To explain the unusual course of the reaction, propose a mechanism similar to the Birch reduction.

• The Suzuki reaction would be used to synthesise the biaryl compound.
• You can use the two indicated compounds and any additional reagents you need.

• A bright yellow solution is created when triphenylmethanol is treated with concentrated sulfuric acid.
• As the yellow solution is mixed with water, its color disappears and a small amount of triphenylmethanol reappears.

• Explain the unusual behavior of the bright yellow species by suggesting a structure.

• The acid-base indicator of phenolphthalein is red in base and acid in base.
• The acid-catalyzed reaction of phthalic anhydride with 2 equivalents of phenol makes phenolphthalein.

• There is a mechanism for the synthesis of phenolphthalein.

• There is a red dianion in the base of phenolphthalein.

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