Transcript Chapter 17 Aromaticity

8-methyl-N-vanillyl-6-nonenamide (Capsaicin)
Chapter 17: Benzene and
Aromaticity
Buckminsterfullerene
TNT
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
Benzene
1st isolated by Michael Faraday in 1825
From “Benzoin,” corrupt form of the Arabic "luban jawi” for the “frankincense of Java”
Frankincense
Not “aromatic” in the technical
sense
triterpene
Cancer drug
anti-inflammatory
hepatotoxicity
Boswellia sacra
Aromatic-fragrant
myrth
Commiphora myrrha tree
Antiseptic, embalming agent, incense
Cinnamon
(2E)-3-phenylprop-2-enal
cinnamaldehyde
Diabetes
Antimicrobial
antioxidant
Capsaicin
8-methyl-N-vanillyl-6-nonenamide (Capsaicin)
16,000,000 Scovilles
psoriasis
relieve the pain of peripheral neuropathy
trigger apoptosis in human colon and lung cancer
Vanilla
Tincture (ethanol extract) of vanilla
aphrodisiac and a remedy for fevers
catecholamines (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
Skin Damage
• 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.
12
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
Polychlorinatedbiphenyls
PCB’s
Thermally stable, electrically
insulating heat transfer liquid
Casting wax for lost wax process for making metal things
dichlorodiphenyltrichloroethane
Malaria
mosquito
Mueller 1948 Nobel
Prize in Medicine
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):
fluoro
nitro
ethyl
F
NO2
CH2CH3
fluorobenzene
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
CH 3CH 2CH 2
CH2CH2CH3
CHCH2CH2CH2CH2CH3
=
CHCH 2CH 2CH 2CH 2CH 3
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.
CH2
the benzyl group
CH2Br
benzyl bromide
CH2CH
OH 2Br
benzyl alcohol
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 Benzenes
ortho- (abbreviated o- )
= 1,2-disubstituted
(two groups on adjacent carbons on the ring)
F
F
CH2CH3
Br
o-difluorobenzene
or
1,2-difluorobenzene
o-bromoethylbenzene
or
1-bromo-2-ethylbenzene
Disubstituted Benzenes
meta- (abbreviated m- )
= 1,3-disubstituted
(two groups having one unsubstituted carbon between
them)
Br
Br
m-dibromobenzene
or
1,3-dibromobenzene
Br
NO2
m-bromonitrobenzene
or
1-bromo-3-nitrobenzene
Disubstituted Benzenes
para- (abbreviated p- )
= 1,4-disubstituted
(two groups on opposite sides of the ring)
Br
Cl
Cl
p-dichlorobenzene
or
1,4-dichlorobenzene
Cl
p-bromochlorobenzene
or
1-bromo-4-chlorobenzene
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.
Br
4
1
OH
3
1 2 Cl
2
NH 2
p-bromoaniline
or
4-bromoaniline
o-chlorophenol
or
2-chlorophenol
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
o-xylene
m-xylene
CH3
CH3
p-xylene
OH
o-cresol
CH3
CH3
OH
m-cresol
OH
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.
CH2CH3
F 1
2
3
4
NO2
2-ethyl-1-fluoro-4-nitrobenzene
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
toluene
CH3
listed in alphabetical
1
Cl chloro
order.
bromo
Br 5
2
3
4
5-bromo-2-chlorotoluene
Polysubstituted Benzenes
Br
4
OH
1
3
2 CH2CH3
1
NO2
4-bromo-2-ethyl-1-nitrobenzene
Cl
2
Br 5
3
4
5-bromo-2-chlorophenol
Polysubstituted Benzenes
Br
2
3
O2N 4
Br
1
1 CH3
6
6 Cl
5
2-bromo-6-chloro-4-nitrotoluene
O2N 5 4
2 CH2CH3
3
Cl
1-bromo-3-chloro-2-ethyl-5-nitrobenzene
Naming Benzene as a Substituent
• 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.
38
Polycyclic Aromatic Hydrocarbons
(PAH)
anthracene
naphthalene
phenanthrene
pyrene
benzo [a] pyrene
Metabolic byproducts of benzo [a] pyrene react with
DNA to form adducts, leading to carcinogenesis (cancer).
Naphthalene Orbitals
 Three resonance forms and delocalized electrons
40
13C
NMR Absorptions of Dibromobenzenes
Figure 17.2
• 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.
41
Drugs that Contain a Benzene Ring
Figure 17.5
42
Heterocyclic Aromatics
Heterocyclic Aromatics
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
45
Protonation of Pyrroles and
Pyridines
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
47
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
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
50
32 kcal/mole
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
52
The Criteria for Aromaticity
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.
53
The Criteria for Aromaticity
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.
54
The Criteria for Aromaticity
3. A molecule must be completely conjugated.
• Aromatic compounds must have a p orbital on every atom.
55
The Criteria for Aromaticity
4. A molecule must satisfy Hückel’s rule, and contain a particular number of  electrons.
Hückel's rule:
• Benzene is aromatic and especially stable because it contains 6 
electrons.
• Cyclobutadiene is antiaromatic and especially unstable because it
contains 4  electrons.
56
• Hückel’s rule refers to the number of  electrons, not the number of
atoms in a particular ring.
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
58
Bonding and Antibonding Orbitals
• 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.
59
Formation of π and π* Molecular Orbitals
• Two atomic p orbitals combine to form two molecular orbitals.
• The bonding  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
60
 Molecular Orbitals for Benzene
• 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
61
Inscribed Polygon Method of Predicting
Aromaticity
62
Inscribed Polygon Method of Predicting
Aromaticity
• 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.
63
Inscribed Polygon Method of Predicting
Aromaticity
Figure 17.10
64
Buckminsterfullerene—Is it Aromatic?
• 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.
65
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
66
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
67
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
68
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
69
NMR and Aromaticity
• 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.
70
Larger Aromatic Rings
• 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.
71
Hückel’s Rule and Number of  Electrons
• [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.
72
Biochemically Relevant Aromatics
Amino Acids
Biologically Relevant Aromatics
Nicotinamide adeine dinucleotide, the biolgical hydrogenator
NADH
NAD+