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16 -- Part 2: AROMATIC COMPOUNDS
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.
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