Aromatic Lect1

8/2/2019 Aromatic Lect1

1/80

Benzene has the empirical formula CH. Its molecular formula hasbeen shown to be C6H6, which implies four degrees ofunsaturation in the molecule.

Several incorrect structures of benzene have been proposed in thepast:

Of these, only Claus benzene has not been synthesized. All of theother structures represent unstable substances which isomerize tobenzene in very exothermic reactions.

The correct molecular structure of benzene is:


2/80


3/80

Naming the Benzenes

Benzene and its derivatives were originally called aromaticcompounds because of their strong aromas.

Benzene is considered the parent aromatic molecule.

The structure of benzene is written as a pair of resonancestructures or as a regular hexagon containing an inscribed circle:


4/80

Monosubstituted benzenes are often named by adding a prefix tothe word benzene:


5/80

Disubstituted benzenes are named using the prefixes:

1,2- (ortho-, or o-)

1,3- (meta-, or m-)1,4- (para-, or p-)

The substituents are then listed in alphabetical order:


6/80

For tri- and more highly substituted benzenes, the ring carbonsare numbered to give the substituents the lowest set of numbers,as in cyclohexane nomenclature:


7/80

The following benzene derivatives will be used often in thiscourse:


8/80

The naming of three substituted benzene systems do not followIUPAC nomenclature in the Chemical Abstracts indexingpreferences: phenol, benzaldehyde and benzoic acid.

Ring substituted compounds of these substances are named bynumbering the ring positions or using the prefixes o-, p- and m-.

The carbon carrying the substituent giving the compound its basename is given the number 1.


9/80

Several other common names have been accepted by IUPAC,including:


10/80

A substituted benzene is called an arene.

An arene, when used as a substituent, is called an aryl group(Ar).

The parent aryl substituent is phenyl, C6H5-. The group C6H5CH2-is called phenylmethyl (benzyl).


11/80

Structure and Resonance Energy ofBenzene: a First Look at Aromaticity

At room temperature, benzene is inert to acids, H2, Br2 and

KMnO4, reagents that usually add to conjugated alkenes.The cyclic 6-electron arrangement of double bonds imparts aspecial stability in the form of a large resonance energy.


12/80

The benzene ring contains six equally overlapping porbitals.

Experimentally, benzene can be shown to be a completely

symmetrical hexagon; there are no alternating single (long) anddouble (short) bonds.

The electronic structure of the benzene ring consists of 6 sp2carbon atoms, with each p-orbital overlapping the p-orbitals of itsnearest neighbors.


13/80

Benzene is especially stable: heats ofhydrogenation.

It is useful to compare the heats of hydrogenation of benzene,

1,3-cyclohexadiene and cyclohexene. In each case, cyclohexaneis the final product.

The heat of hydrogenation of benzene can be experimentallymeasured using special catalysts and is measured to be 29.6 kcalmol-1 less than the calculated heat for the hypothetical molecule,

1,3,5-cyclohexatriene.


14/80

Benzene is much more stable than a molecule containingalternating double and single bonds.

The difference in stability is called the resonance energy of

benzene, about 30 kcal mol-1

.


15/80

Molecular Orbitals of Benzene

Cyclic overlap modifies the energy of benzenesmolecular orbitals.

The molecular orbitals of benzene can be compared to those of1,3,5-hexatriene:


16/80

The cyclic system is stabilized relative to the acyclic one. Two ofthe orbitals have been lowered in energy in benzene (1 and 3)

while one has been raised (2). The drop in energy of1 and 3more than offsets the rise in energy of2.


17/80

Some reactions have aromatic transitionsstates.

The transition states in the Diels-Alder reaction, the addition ofosmium tetroxide to alkenes and the first step in ozonolysis allexhibit a cyclic overlap of six electrons in orbitals or orbitalshaving character:

These concerted aromatic transition states have lower energiesthan the alternative sequential bond-breaking and bond-makingmechanism.


18/80

Spectral Characteristics of the Benzene Ring

The UV-visible spectrum of benzene reveals itselectronic structure.

The energy gap between bonding and antibonding orbitals isgreater in benzene than for acyclic trienes.

The UV spectra of benzene shows absorbances at smallerwavelengths (higher energy) than does the spectra of 1,3,5-

hexatriene:


19/80

The electronic spectra of aromatic compounds varies with theintroduction of substituents (useful in designing dye molecules).

Simple substituted benzenes absorb between 250 and 290 nm.

4-Aminobenzoic acid (PABA) has a max of 289 nm and a highextinction coefficient of 18,600. It is used in sunscreen lotions tofilter out harmful UV light in this wavelength region.


20/80

The infrared spectrum reveals substitution patternsin benzene derivatives.

The IR spectra of benzene and its derivatives have characteristic bands in

three regions:3030 cm-1 phenyl-hydrogen stretching

1500-2000 cm-1 aromatic ring C-C stretching

650-1000 cm-1 C-H out-of-plane bending


21/80

The specific substitution pattern determines the precise location of theC-H out-of-plane bending absorptions. For the dimethylbenzenes:

1,2-dimethylbenzene (o-) 738 cm-1

1,4-dimethylbenzene (p-) 793 cm-1

1,3-dimethylbenzene (m-) 690 and 765 cm-1


22/80

The mass spectrum of benzene indicates stability.

The mass spectrum of benzene shows little fragmentation due toits unusual stability. The (M+1)+. peak shows the correct peak

height (6.8%) for the relative abundance of13C in a six-carbonmolecule.


23/80

The NMR spectra of benzene derivatives show theeffects of an electronic ring current.

The cyclic delocalization of the electrons in the aromatic ring gives

rise to unusual deshielding:Aromatic ring hydrogens: 6.5-8.5 ppm

Alkenyl hydrogens: 4.6-5.7 ppm

Benzene hydrogens: 7.27 ppm (single peak)

This aromatic deshielding is due to ring currents produced bythe electrons moving in the external magnet field, H0.


24/80

The magnetic field from the ring current opposes H0 inside theloop but opposes it outside the loop where the hydrogens arelocated, resulting in deshielding.

The effect is strongest closest to the ring and diminishes rapidlywith distance.

Benzylic nuclei are deshielded only about 0.4-0.8 ppm more thantheir allylic counterparts.

Hydrogens farther away from system have chemical shifts

similar to those in the alkanes.


25/80

Substituted benzenes may have more complicated NMR patterns.

The presence of a substituent renders the ortho, meta and parahydrogens non-equivalent and subject to mutual coupling.

(Benzene: 7.27 ppm)


26/80

4-(N,N-dimethylamino)benzaldehyde shows a large chemical shiftdifference between the two sets of ring hydrogens and a nearfirst-order pattern of two doublets. The 9 Hz coupling constant istypical of splitting between ortho protons.


27/80

All three types of coupling can be seen in the first order spectrumof 1-methoxy-2,4-dinitrobenzene (2,4-dinitroanisole).

Ortho hydrogen (to methoxy)

Doublet, =7.23 ppm, 9 Hz couplingHydrogen flanked by nitro groups

Doublet, =8.76 ppm, 3 Hz coupling

Remaining ring hydrogen

Doublet of doublets,

=8.45 ppm,

Para coupling betweenC3 and C6 is too small tobe resolved.


28/80

The 13C NMR spectra of benzene derivatives is not greatly affectedby ring current shifts, since the induced ring current flows directlyabove and below the ring carbons.

Benzene carbons exhibit chemical shifts similar to those inalkanes (120-135 ppm when unsubstituted). Benzene exhibits asingle line at =128.7 ppm.

P l li A i H d b


29/80

Polycyclic Aromatic Hydrocarbons

Molecules containing several fused benzene rings are calledpolycyclic benzenoid or polycyclic aromatic hydrocarbons

(PAHs).Common names are used for these systems, since there is nosimple naming system for them.

The series of linearly fused benzene rings is called the acenes.

Angular fusion(annulation) results in phenanthrene.

Quaternary carbons are numbered using the preceding carbon inthe sequence followed by a letter indicating its distance to the

preceding carbon.


30/80

Naphthalene is aromatic: a look at spectra.

Naphthalene is a colorless crystalline material with a melting pointof 80o C.

The UV spectrum of

naphthalene indicates anextended, conjugatedsystem with peaks atwavelengths as long as320 nm.


31/80

The electrons in naphthalene are more delocalized than inbenzene and several resonance structures can be drawn:

The overlap of the 10 p orbitals results in a fairly even distributionof electron density.


32/80

X-ray crystallographic measurements have determined the exactbond distances and angles in naphthalene.

The C-C bond distances deviate slightly from those in benzene, 1.39 ,C-C single bonds, 1.54 and C=C double bonds, 1.33 .


33/80

The 1H NMR spectrum of naphthalene shows two symmetricmultiples at = 7.49 and 786 ppm.

Coupling constants in the naphthalene nucleus are similar tothose in substituted benzenes:

Jortho = 7.5 Hz

Jmeta = 1.4 Hz

Jpara = 0.7 Hz

These peak positions arecharacteristic of ring-current deshielded

aromatic hydrogens.


34/80

The 13C NMR spectrum shows three lines with chemical shifts inthe range of other benzene derivatives:


35/80

Most fused benzenoid hydrocarbons are aromatic.

Linear and angular fusion of a third benzene ring ontonaphthalene result in anthracene and phenanthrene.

Anthracene is about 6 kcal mol-1 less stable than phenanthrenedue to differences in resonance stabilization.

Other C clic Pol enes Hckels R le


36/80

Other Cyclic Polyenes: Hckels Rule

Cyclic conjugated polyenes can be aromatic as long as theycontain 4n+2 electrons (n=0,1,2,).

Cyclic polyenes containing 4n electrons may be destabilized byconjugation, or are antiaromtic.

These observations are known as Hckels rule.

Nonplanar cyclic systems in which p-orbital overlap is disrupted

sufficiently to impart alkenelike properties are classified asnonaromatic.


37/80

1,3-Cyclobutadiene, the smallest cyclic polyene, isantiaromatic.

1,3-Cyclobutadiene is a 4n system and is antiaromatic.

It is air-sensitive and extremely reactive (compared to 1,3-butadiene or cyclobutene).

It is destabilized through overlap by more than 35 kcal mol-1.

Its structure is rectangular and it exists as two isomers,equilibrating through a symmetrical transition state, rather thanresonance forms.


38/80

Free 1,3-cyclobutadiene can be prepared and observed only atvery low temperatures.

Cyclobutadiene can act as either a diene or a dienophile in its

rapid Diels-Alder reactions:

Substituted cyclobutadienes are less reactive and have been usedto study the spectroscopic features of the 4 electron cyclicsystem.

In 1,2,3-tris(1,1-dimethylethyl)cyclobutadiene, the ring hydrogenresonates at = 5.38 ppm, much higher than expected for anaromatic system.


39/80

1,3,5,7-Cyclooctatetraene is non-planar and non-aromatic.

1,3,5,7-cyclooctatetraene is a 4n system and is antiaromatic.

It can be made by a nickel-catalyzed cyclotetramerization ofethyne.

It is a yellow liquid (b.p. 152oC), is stable while cold, butpolymerizes when heated.

It is oxidized by air, catalytically hydrogenated to cyclooctane,

and subject to electrophilic additions and to cycloadditions.


40/80

The 1H NMR spectrum shows a sharp singlet at = 5.68 ppm,typical of an alkene.

The molecular structure of cyclooctatetraene is non-planar and

tub shaped. The double bonds are nearly orthogonal and are notconjugated.


41/80

Only cyclic conjugated polyenes containing 4n+2 electrons are aromatic.

An alternative naming system for completely conjugated

monocyclic hydrocarbons, (CH)n, is [N]annulene, in which N isthe ring size.

The system 1,3,5,7,9,11,13,15,17-cyclooctadecanonaene, or[18]annulene, contains 18 electrons and is aromatic (4n+2,n=4).

[18]annulene is fairly planar with little alternation of single anddouble bonds. It is relatively stable and undergoes electrophilicaromatic substitution.

It can be described by a set of 2 resonance forms.


42/80

Hckels rule (2n+2) in cyclical conjugated polyenes can beexplained by the following:

The p orbitals mix to give an equal number of molecular

orbitals.All levels are composed of degenerate pairs of orbitals exceptfor the lowest bonding and highest antibonding orbitals.

A closed shell system (aromatic) is possible only if all of thebonding orbitals are fully occupied, 4n+2 electrons.

In the case of 4n electrons there will always be a pair of singly

occupied orbitals, an unfavorable electronic arrangement.

Hckels Rule and Charged Molecules


43/80

Hckel s Rule and Charged Molecules

The cyclopentadienyl anion and thecycloheptatrienyl cation are aromatic.

1,3-Cyclopentadiene is unusually acidic because the anionresulting from deprotonation contains a delocalized, aromaticsystem of six electrons:

The cyclopentadienyl cation (four electrons) can only be

produced at low temperatures and is highly reactive.

If 1 3 5 l h t t i i t t d ith b i t bl lt i


44/80

If 1,3,5-cycloheptatriene is treated with bromine, a stable salt isformed containing the cycloheptatrienyl cation, an aromatic, 6 electron system.

The cycloheptatrienyl cation is remarkably unreactive for a

carbocation, as expected for an aromatic system.The cycloheptatrienyl anion, on the other hand, is antiaromatic (8 electrons) and has a much lower acidity (pKa = 39) thancyclopentadiene (pKa ~ 16).


45/80

Non-aromatic cyclic polyenes can form aromaticdianions and dications.

Cyclic 4n systems can be converted into their aromatic

counterparts by two-electron oxidations and reductions.Cyclooctatetraene is reduced by alkali metals to a planar,aromatic dianion:

The dianion exhibits an aromatic ring current in 1H NMR.


46/80

[16]Annulene can be either reduced to its dianion or oxidized toits dication; both products are aromatic. On formation of thedication, the configuration of the molecule changes.

Synthesis of Benzene Derivatives: Electrophilic


47/80

Synthesis of Benzene Derivatives: ElectrophilicAromatic Substitution

Benzene undergoes substitution reactions with

electrophiles.Electrophiles attack benzene by substituting for a hydrogenatom, not addition to the ring.

Under the conditions of this type of reaction, ordinary non-aromaticconjugated polyenes would polymerize rapidly.

Electrophilic aromatic substitution in benzene


48/80

Electrophilic aromatic substitution in benzeneproceeds by addition of the electrophile followed byproton loss.

Electrophylic aromatic substitution is a two-step process. Thecationic intermediate is resonance-stabilized:

The initial attack of the electrophile is endothermic because thesp3 carbon generated interrupts the cyclic conjugation. Thetransition state is not aromatic.

The loss of the proton regenerates the sp2 carbon atom andaromaticity is restored. This process is more favored than the

nucleophilic trapping by the anion accompanying E+.

The overall reaction is exothermic because the bonds formed are


49/80

The overall reaction is exothermic because the bonds formed arestronger than the bonds broken.

Halogenation of Benzene: the Need for a


50/80

Halogenation of Benzene: the Need for aCatalyst

Benzene in normally unreactive to halogens because they are not

electronegative enough to disrupt its aromaticity.Halogens can be activated by Lewis acid catalysts, however, suchas ferric halides (FeX3) or aluminum halides (AlX3), to becomemuch more powerful electrophiles.

This activated bromine complex can attack the benzene molecule


51/80

This activated bromine complex can attack the benzene molecule,allowing the other bromine atom to depart with the good leavinggroup FeBr4-

The FeBr4- next abstracts a proton from the cyclohexadienylcation intermediate, and in the process regenerates the originalFeBr3 catalyst.

Bond energy calculations show that the electrophilic bromination


52/80

Bond energy calculations show that the electrophilic brominationof benzene is exothermic:

Phenyl-H +112 kcal mol-1

Br-Br +46 kcal mol-1

Phenyl-Br -81 kcal mol-1

H-Br -87.5 kcal mol-1---------------------------------------------------------

Reaction -10.5 kcal mol-1

Fluorination of benzene is very exothermic (explosive).

Chlorination and bromination require an activating catalyst.

Iodination is endothermic and does not occur.

Nitration and Sulfonation of Benzene


53/80

Nitration and Sulfonation of Benzene

Benzene is subject to electrophilic attack by thenitronium ion.

Benzene can be attacked byconcentrated nitric acid in thepresence of concentratedsulfuric acid.

Th f th lf i id i t t th


54/80

The purpose of the sulfuric acid is to generate the moreelectrophilic nitronium ion:

The nitronium ion subsequently attacks the benzene molecule:

A ti it ti i th b t t i t d it


55/80

Aromatic nitration is the best way to introduce nitrogen-containing substituents into the benzene ring.

The aromatic nitro group serves as a directing group in further

substitutions and as a masked amino function.

S lf ti i ibl


56/80

Sulfonation is reversible.

Fuming sulfuric acid (8% SO3 in concentrated H2SO4) reacts withbenzene to form benzenesulfonic acid.

Because the reaction of SO3 with water is so exothermic the


57/80

Because the reaction of SO3 with water is so exothermic, thesulfonation of benzene can be reversed by heatingbenzenesulfonic acid in dilute aqueous acid.

Because sulfonation is reversible, it can be used as a blockinggroup to control further aromatic substitution and then laterremoved.

B lf i id h i t t


58/80

Benzenesulfonic acids have important uses.

Long chain-branched alkylbenzenes can be sulfonated to thecorresponding sulfonic acids.

After conversion to their sodium salts, these compounds can beused as synthetic detergents.

Sulfonate detergents have now been replaced by morebiologically friendly, biodegradable detergents.

Sulfonation is often used to impart water solubility to organiccompounds, as in the manufacture of certain dyes.

Sulfonyl chlorides can be prepared by reaction of the sodium salt


59/80

Sulfonyl chlorides can be prepared by reaction of the sodium saltof the acid with PCl5 or SOCl2.

Sulfonyl chlorides are frequently used in synthesis, for example toconvert the hydroxy group of an alcohol into a good leavinggroup.

Sulfonamides are derived from the reaction of a sulfonyl chloride


60/80

Sulfonamides are derived from the reaction of a sulfonyl chloridewith an amine. An important class of sulfonamides are the sulfadrugs:

Friedel-Crafts Alkylation


61/80

y

Carbon-carbon bonds to benzene can be created using asufficiently electrophilic carbon based electrophile.

To create the necessary electrophilic carbon atom, a Lewis acidsuch as AlCl3 is employed.

A haloalkane reacts with benzene in the presence of an aluminumhalide to form an alkylbenzene and a hydrogen halide.

Reactivity of the haloalkane increases in the order:


62/80

Reactivity of the haloalkane increases in the order:

RI < RBr < RCl < RF (increasing bond polarity)

Typical Lewis acids are:

BF3, SbCl5, FeCl3, AlCl and AlBr3

The mechanism of the Friedel-Crafts alkylation with primary


63/80

The mechanism of the Friedel-Crafts alkylation with primaryhaloalkanes involves coordination of the Lewis acid to the halogenatom:

With secondary and tertiary haloalkanes, free carbocations areusually formed, which attack the benzene ring in the same way asthe cation NO2+.

A i b f d t th b l b f


64/80

A new ring can be fused onto the benzene nucleus by means ofan intramolecular Friedel-Crafts alkylation:

Any starting material that functions as a precursor to a


65/80

Any starting material that functions as a precursor to acarbocation can be used in a Friedel-Crafts alkylation:

Limitations of Friedel-Crafts Alkylations


66/80

y

Polyalkylation and carbocation rearrangement may cause theyield of desired products to diminish and lead to mixtures that

may be difficult to separate:

Polyalkylation occurs because the alkylbenzene first formed iselectron-rich and activates the ring towards further substitution.

This is in contrast to bromination, nitration and sulfonation, asthey deactivate the ring towards further substitution (electronwithdrawing substituents).

Skeletal rearrangement of the carbocation is the second


67/80

gunwanted side-reaction in aromatic alkylation.

The desired 1-propylbenzene is not obtained when benzene isalkyated using 1-bromopropane:

In the presence of the Lewis acid, the starting haloalkanerearranges to the secondary carbocation by a hydride shift:

Because of polysubstitution and rearrangement reactions, Friedel-


68/80

p y g ,Crafts alkylations are rarely used in synthesis.

Friedel-Crafts Alkanoylation (Acylation)


69/80

An alternate route to C-C bond formation to the aromatic nucleusthat doesnt have the problems encountered with alkylations isthe Friedel-Crafts alkanoylation, or acylation.

These reactions proceed through an acylium cation intermediate(RCO+).

Friedel-Crafts alkanoylation employs alkanoyl


70/80

ede a s a a oy a o e p oys a a oychlorides.

Benzene reacts with alkanoyl halides in the presence of aluminum

halide to give 1-phenylalkanones (phenyl ketones).

Alkanoyl halides react with Lewis acids to produce


71/80

Alkanoyl halides react with Lewis acids to produceacylium ions.

The key reactive intermediate in a Friedel-Crafts alkanoylation is

the acylium cation.The acylium cation can be formed from either an alkanoyl halideor a carboxylic anhydride:

The acylium cation is stabilized by resonance and is not prone to


72/80

The acylium cation is stabilized by resonance and is not prone torearrangement.

Most of the positive charge resides on the carbon atom (blue).

Acylium ions undergo electrophilic aromatic


73/80

Acylium ions undergo electrophilic aromaticsubstitution.

An acylium ion is capable of attacking benzene by the usual

aromatic substitution mechanism:

The alkanoyl substituent is electron withdrawing which

deactivates the ring and protects it from further substitution.

Also protecting the ring from further substitution is the formation


74/80

p g gof a strong complex between the newly formed carbonyl oxygenand the aluminum chloride:

Due to this complex formation, at least one full equivalent of AlCl3is required for the acylation reaction to go to completion.

An aqueous work-up is required to liberate the final ketone from


75/80

q p qthe aluminum chloride complex:

The ketone product of the Friedel-Crafts Alkanoylation can be


76/80

p yconverted into an alcohol by hydride reduction.

The resulting hydroxyl can be converted into a good leaving groupthat can be further reduced by hydride leading to thecorresponding hydrocarbon.

Important Concepts


77/80

1. Benzene Nomenclature Prefixes or suffixes are added to the word benzene

Disubstituted systems are labeled as 1,2-, 1,3- or1,4- (ortho, meta, para)

Certain substituted benzenes have common nameswhich are used as the base for naming further

substitutions. When used as a substituent, the benzene ring C6H5-

is referred to asphenyl. The C6H5CH2- substituentis referred to as phenylmethyl or benzyl.

2. Benzene Is A Delocalized System

Not acyclohexatriene by a system of six delocalized electrons.

The resonance energy or aromaticity is about 30kcal/mol

Important Concepts


78/80

3. Benzene Displays Unusual UV, IR, and NMRSpectral DataIn NMR spectra, the ring hydrogensare deshielded by an induced ring current

Substitution patterns are revealed by examination ofthe o, m and p coupling constants

4. Polycyclic Benzenoid Hydrocarbons

Linearly or angularly fused benzene rings(naphthalene, anthracene, phenanthrene, etc.)

5. Electrons Delocalized over All of theRingsElectronic spectra reveal extended

conjugation. Proton NMR reveals deshielding ring-current effects. There is little bond alternation.

Important Concepts


79/80

6. Hckels 4n+2 Rule Benzene is the smallestaromatic cyclic polyene member of this class

Most 4n systems are relatively reactive anti- ornon-aromatic species

Hckels Rule extends to charged aromatic systemssuch as the cyclopentadienyl anion,

cycloheptatrienyl cation and the cyclooctatetraenedianion

7. Electrophilic Aromatic Substitution The most important reaction of benzene

Rate determining step is addition by the electrophile Exothermic substitution preferred over endothermicaddition

Leads to halo- and nitrobenzenes, benzenesulfonicacids, alkylated and alkanoylated derivatives

Important Concepts


80/80

8. Sulfonationof benzene is reversible by heatingwith dilute aqueous acid

9. Benzenesulfonic AcidsPrecursors ofbenzenesulfonyl chlorides. These chlorides:

React with alcohols to form sulfonic esterscontaining useful leaving groups

React with amines to give sulfonamides (some ofwhich are medically important)

10. Friedel-Crafts AlkylationsActivate thearomatic ring to further electrophilic substitution which

leads to product mixtures

Aromatic Lect1

Documents

Transcript of Aromatic Lect1