Chapter 17: Benzene and Aromaticity TNT 8-methyl-N-vanillyl-6-nonenamide (Capsaicin) Buckminsterfullerene.

Chapter 17: Benzene and Aromaticity

TNT

8-methyl-N-vanillyl-6-nonenamide (Capsaicin)

Buckminsterfullerene

Key points & objectives:

• Aromatic molecules are cyclic, conjugated, flat, and unusually stable

• 4n + 2 electrons (n = 0, 1, 2, ….• Hydrocarbon aromatics: benzene, naphthalene,

anthracene, toluene, xylylene• Heterocyclics: pyridine, pyrimidine, imidazole, pyrrole,

thiophene, furan, indole….• Molecular orbitals using Frost diagrams (inscribed

circles)• Ring current deshields NMR signals – downfield

Benzene1st isolated by Michael Faraday in 1825

From “Benzoin,” corrupt form of the Arabic "luban jawi” for the “frankincense of Java”

Frankincense

Boswellia sacra

triterpene

Cancer drug

anti-inflammatory

hepatotoxicity

Not “aromatic” in the technical sense

Aromatic-fragrant

myrth

Commiphora myrrha tree

Antiseptic, embalming agent, incense

Cinnamon

DiabetesAntimicrobialantioxidant

(2E)-3-phenylprop-2-enal

cinnamaldehyde

8-methyl-N-vanillyl-6-nonenamide (Capsaicin)

Capsaicin

16,000,000 Scovilles

psoriasis relieve the pain of peripheral neuropathytrigger apoptosis in human colon and lung cancer

Vanilla

Tincture (ethanol extract) of vanilla

aphrodisiac and a remedy for feverscatecholamines (including adrenaline)addictive

Aromatic molecules

• Flat• Conjugated• (4n +2) pi electrons• Unusually stable• Ring current (deshielding protons)

Anesthetics & analgesics

Advil, and Motrin

Sunscreens

Only complete UVA block

12

• Very high energy radiation (UVC) is currently blocked by the ozone layer (ozone hole issue)

• High energy radiation (UVB) does the most immediate damage (sunburns)

• But lower energy radiation (UVA) can penetrate deeper into the skin, leading to long term damage

Source: N.A. Shaath. The Chemistry of Sunscreens. In: Lowe NJ, Shaath NA, Pathak MA, editors. Sunscreens, development, evaluation, and regulatory aspects. New York: Marcel Dekker; 1997. p. 263-283.

Skin Damage

Sources and Names of Aromatic Hydrocarbons

From high temperature distillation of coal tar Heating petroleum at high temperature and pressure over

a catalyst

Aromatics are less reactive than Alkenes

Aromatics Nomeclature

Aromatics Nomeclature

Agent orange

PolychlorinatedbiphenylsPCB’s

Thermally stable, electrically insulating heat transfer liquid

Casting wax for lost wax process for making metal things

Mueller 1948 Nobel Prize in Medicine

dichlorodiphenyltrichloroethane

Malaria mosquito

Thermodynamic stability of benzene: Heats of Hydrogenation

Monosubstituted Benzenes• Most monosubstituted aromatics are named using

-benzene as the parent name preceded by the substituent name (as a prefix; all one word):

F NO2 CH2CH3

fluorobenzene

fluoro nitro ethyl

nitrobenzene ethylbenzene

Alkyl-substituted Benzenes• Alkyl substituted benzenes are named according to the

length of the carbon chain of the alkyl group.• With six carbons or fewer in the alkyl chain, they are named

as ‘alkylbenzene.’• e.g., propylbenzene:

CH2CH2CH3

Alkyl-substituted Benzenes• With more than six carbons in the alkyl chain, they are

named as a ‘phenylalkane,’ where the benzene ring is named as a substituent (phenyl) on the alkane chain• e.g., 4-phenylnonane

CHCH 2CH2CH2CH2CH3

CH3CH2CH2

CHCH2CH2CH2CH2CH3

CH2CH2CH3

CH3CH2CH2CHCH2CH2CH2CH2CH3=

4-phenylnonane

The Benzyl Group• The benzyl group is a common name for a methyl

substituted benzene (toluene) having substitution for one of the hydrogens on the methyl group.

CH2Br

the benzyl group benzyl bromide benzyl alcohol

CH2BrCH2 CH2OH

Common Names of Subs. Benzenes• There are a number of nonsystematic (common)

names commonly used for certain monosubstituted benzenes (see next slide)

• These ten common names should be memorized.• These common names are used as base names when

naming more their more highly substituted derivatives. Examples of these will be given later.

Mono-substituted Benzene Nomenclature: Common Names

Disubstituted Benzenes• Disubstituted benzenes can be named in one of two ways.

Each method describes the relative positions of the two groups on the benzene ring.• Systematic numbering of the aromatic ring.• Using the prefixes ortho-, meta-, or para-.

• When numbering the ring carbons, carbon # 1 is always a substituted carbon.

• The substituents are listed alphabetically.

Disubstituted Benzenesortho- (abbreviated o- ) = 1,2-disubstituted

(two groups on adjacent carbons on the ring)

o-difluorobenzene or1,2-difluorobenzene

F

F

F

F

o-bromoethylbenzene or1-bromo-2-ethylbenzene

CH2CH3

Br

Disubstituted Benzenesmeta- (abbreviated m- ) = 1,3-disubstituted

(two groups having one unsubstituted carbon between them)

m-dibromobenzene or1,3-dibromobenzene

BrBr

m-bromonitrobenzene or1-bromo-3-nitrobenzene

NO2Br

Disubstituted Benzenespara- (abbreviated p- ) = 1,4-disubstituted

(two groups on opposite sides of the ring)

p-dichlorobenzene or1,4-dichlorobenzene

Cl

Cl

p-bromochlorobenzene or1-bromo-4-chlorobenzene

Br

Cl

NH2

Br OH

Cl

Disubstituted Benzenes• When one of the substituents changes the base name,

either o-, m-, and p- or numbers may be used to indicate the position of the other substituent.

• Carbon # 1 is always the carbon bearing the substituent that changes the base name.

p-bromoaniline or4-bromoaniline

o-chlorophenol or2-chlorophenol

12

34 1 2

Common Names of Disubs. Benzenes• There are a few nonsystematic (common) names for

disubstituted benzenes that you should be familiar with:

CH3

CH3

CH3

CH3

CH3

CH3o-xylene m-xylene p-xylene

CH3

OH

CH3

OH

CH3

OHo-cresol m-cresol p-cresol

Disubstituted Benzenes Relative positions on a benzene ring

ortho- (o) on adjacent carbons (1,2) meta- (m) separated by one carbon (1,3) para- (p) separated by two carbons (1,4)

Describes reaction patterns (“occurs at the para position”)

Polysubstituted Benzenes• Polysubstituted benzenes must be named by numbering the

position of each substituent on the ring (with more than two substituents, o-, m-, and p-can NOT be used.)

• The numbering is carried out to give the substituents the lowest possible numbers. Carbon #1 always has a substituent.

• List the substituents alphabetically with their appropriate #s.

2-ethyl-1-fluoro-4-nitrobenzene

CH2CH3

NO2

F 1 234

Polysubstituted Aromatics having a Common base name

• Common names of the monosubstituted benzenes are used as parent names for polysubstituted aromatics when one of the substituents changes the base name.

• For such rings with common names, the carbon bearing the substituent responsible for the common name is always carbon #1.

• The substitutents are listed in alphabetical order.

5-bromo-2-chlorotoluene

CH3

Cl

Br

1

2

34

5

toluene

chloro

bromo

Polysubstituted Benzenes

Br

CH2CH3

NO2

OH

Cl

Br12

34

5

12

34

4-bromo-2-ethyl-1-nitrobenzene 5-bromo-2-chlorophenol

Polysubstituted Benzenes

CH3

Cl

Br

O2N

CH2CH3

Cl

Br

O2N

13

45

6

6

54

3

221

2-bromo-6-chloro-4-nitrotoluene 1-bromo-3-chloro-2-ethyl-5-nitrobenzene

38

• A benzene substituent is called a phenyl group, and it can be abbreviated in a structure as “Ph-”.

• Therefore, benzene can be represented as PhH, and phenol would be PhOH.

Naming Benzene as a Substituent

Polycyclic Aromatic Hydrocarbons (PAH)

anthracenephenanthrene

naphthalene

pyrene benzo [a] pyrene

Metabolic byproducts of benzo [a] pyrene react with

DNA to form adducts, leading to carcinogenesis (cancer).

40

Naphthalene Orbitals

Three resonance forms and delocalized electrons

41

Figure 17.2

13C NMR Absorptions of Dibromobenzenes

• The number of signals (lines) in the 13C NMR spectrum of a disubstituted benzene with two identical groups indicates whether they are ortho, meta, or para to each other.

42

Figure 17.5

Drugs that Contain a Benzene Ring

Heterocyclic Aromatics

Heterocyclic Aromatics

45

Pyridine A six-membered heterocycle with a nitrogen atom in its ring electron structure resembles benzene (6 electrons) The nitrogen lone pair electrons are not part of the aromatic system

(perpendicular orbital) Pyridine is a relatively weak base compared to normal amines but

protonation does not affect aromaticity

Protonation of Pyrroles and Pyridines

47

Pyrrole A five-membered heterocycle with one nitrogen electron system similar to that of cyclopentadienyl anion Four sp2-hybridized carbons with 4 p orbitals perpendicular to the ring

and 4 p electrons Nitrogen atom is sp2-hybridized, and lone pair of electrons occupies a p

orbital (6 electrons) Since lone pair electrons are in the aromatic ring, protonation destroys

aromaticity, making pyrrole a very weak base

Structure and Stability of Benzene: Molecular Orbital Theory

Benzene reacts slowly with Br2 to give bromobenzene (where Br replaces H)

This is substitution rather than the rapid addition reaction common to compounds with C=C, suggesting that in benzene there is a higher barrier

50

Heats of Hydrogenation as Indicators of Stability The addition of H2 to C=C normally gives off about 118 kJ/mol – 3 double

bonds would give off 356kJ/mol Two conjugated double bonds in cyclohexadiene add 2 H2 to give off 230

kJ/mol Benzene has 3 unsaturation sites but gives off only 206 kJ/mol on reacting

with 3 H2 molecules Therefore it has about 150 kJ more “stability” than an isolated set of three

double bonds

32 kcal/mole

52

Benzene’s Unusual Structure All its C-C bonds are the same length: 139 pm — between

single (154 pm) and double (134 pm) bonds Electron density in all six C-C bonds is identical Structure is planar, hexagonal C–C–C bond angles 120° Each C is sp2 and has a p orbital perpendicular to the

plane of the six-membered ring

53

Four structural criteria must be satisfied for a compound to be aromatic:1. A molecule must be cyclic. • To be aromatic, each p orbital must overlap with p orbitals on adjacent atoms.

The Criteria for Aromaticity

54

2. A molecule must be planar.• All adjacent p orbitals must be aligned so that the electron density can

be delocalized.

• Since cyclooctatetraene is nonplanar and not aromatic, it undergoes addition reactions just like those of other alkenes.

The Criteria for Aromaticity

55

3. A molecule must be completely conjugated.

• Aromatic compounds must have a p orbital on every atom.

The Criteria for Aromaticity

56

4. A molecule must satisfy Hückel’s rule, and contain a particular number of electrons.

• Benzene is aromatic and especially stable because it contains 6 electrons.

• Cyclobutadiene is antiaromatic and especially unstable because it contains 4 electrons.

Hückel's rule:

The Criteria for Aromaticity

• Hückel’s rule refers to the number of electrons, not the number of atoms in a particular ring.

58

Why 4n +2?

When electrons fill the various molecular orbitals, it takes two electrons (one pair) to fill the lowest-lying orbital and four electrons (two pairs) to fill each of n succeeding energy levels

This is a total of 4n + 2

59

• The combination of two p orbitals can be constructive—that is, with like phases interacting—or destructive, that is, with opposite phases interacting.

• When two p orbitals of similar phase overlap side-by-side, a bonding molecular orbital results.

• When two p orbitals of opposite phase overlap side-by-side, a * antibonding orbital results.

Bonding and Antibonding Orbitals

60

• Two atomic p orbitals combine to form two molecular orbitals.• The bonding p MO is lower in energy than the two p orbitals.• The * antibonding MO is higher in energy because a destabilizing node

results, which pushes nuclei apart when orbitals of opposite phase combine.

Figure 17.8

Formation of π and π* Molecular Orbitals

61

• Since each of the six carbon atoms in benzene has a p orbital, six atomic p orbitals combine to form six MOs.

Figure 17.9

Molecular Orbitals for Benzene

62

Inscribed Polygon Method of Predicting Aromaticity

63

• This method works for all monocyclic completely conjugated systems regardless of ring size.

• The total number of MOs always equals the number of vertices of the polygon.

• The inscribed polygon method is consistent with Hückel's 4n + 2 rule—there is always one lowest energy bonding MO that can hold two electrons and the other bonding MOs come in degenerate pairs that can hold a total of four electrons.

Inscribed Polygon Method of Predicting Aromaticity

64

Figure 17.10

Inscribed Polygon Method of Predicting Aromaticity

65

• Buckminsterfullerene (C60) is a third elemental form of carbon. • Buckminsterfullerene is completely conjugated, but it is not aromatic since it

is not planar (CAREFULL!!!)• It undergoes addition reactions with electrophiles in much the same way as

ordinary alkenes.

Buckminsterfullerene—Is it Aromatic?

66

Compounds With 4n Electrons Are Not Aromatic (May be Antiaromatic)

Planar, cyclic molecules with 4 n electrons are much less stable than expected (antiaromatic)

They will distort out of plane and behave like ordinary alkenes 4- and 8-electron compounds are not delocalized (single and double

bonds) Cyclobutadiene is so unstable that it dimerizes by a self-Diels-Alder

reaction at low temperature Cyclooctatetraene has four double bonds, reacting with Br2, KMnO4, and

HCl as if it were four alkenes

67

Aromatic Ions

The 4n + 2 rule applies to ions as well as neutral species Both the cyclopentadienyl anion and the cycloheptatrienyl

cation are aromatic The key feature of both is that they contain 6 electrons in a

ring of continuous p orbitals

68

Aromaticity of the Cyclopentadienyl Anion

1,3-Cyclopentadiene contains conjugated double bonds joined by a CH2 that blocks delocalization

Removal of H+ at the CH2 produces a cyclic 6-electron system, which is stable

Removal of H- or H• generates nonaromatic 4 and 5 electron systems

Relatively acidic (pKa = 16) because the anion is stable

69

Cycloheptatriene

Cycloheptatriene has 3 conjugated double bonds joined by a CH2

Removal of “H-” leaves the cation The cation has 6 electrons and is aromatic

70

• 1H NMR spectroscopy readily indicates whether a compound is aromatic. • The protons on sp2 hybridized carbons in aromatic hydrocarbons are

highly deshielded and absorb at 6.5–8 ppm, whereas hydrocarbons that are not aromatic absorb at 4.5–6 ppm.

NMR and Aromaticity

71

• Completely conjugated rings larger than benzene are also aromatic if they are planar and have 4n + 2 electrons.

• Hydrocarbons containing a single ring with alternating double and single bonds are called annulenes.

• To name an annulene, indicate the number of atoms in the ring in brackets and add the word annulene.

Larger Aromatic Rings

72

• [10]-Annulene has 10 electrons, which satisfies Hückel's rule, but a planar molecule would place the two H atoms inside the ring too close to each other.

• Thus, the ring puckers to relieve this strain.• Since [10]-annulene is not planar, the 10 electrons cannot delocalize

over the entire ring and it is not aromatic.

Hückel’s Rule and Number of Electrons

Biochemically Relevant Aromatics

NH2

O

OH

phenylalanine

NH2HO

O

OH

tyrosine

NH2

HN

OOH

tryptophan

HN

indole

HN

NN

N

purine

N

N

pyrimidine

Amino Acids

Biologically Relevant Aromatics

NN

O

NH2

R

H H

HR

NH2

O

Aromatic

NADH NAD+

Nicotinamide adeine dinucleotide, the biolgical hydrogenator