1
Chamras
Chemistry 106 Lecture Notes
Examination 2 Materials
Chapter 16: Aromatic Compounds Benzene, the Most Commonly Known Aromatic Compound: The aromatic nature of benzene stabilizes it 36 kcal.mol–1.
Bond Order = 1.5Bond Length = 1.4 Å
OR
28.34 kcal.mol–1
56.63 kcal.mol–149.07 kcal.mol–1
OR
84.92 kcal.mol–1
ΔH
2
Aromatic Compounds: Definition: Organic compounds containing a continuous, cyclic array of π-electrons resulting in their overall stabilization. Examples: Benzene, cyclopropenyl cation. Geometric Property of Aromatic Systems: Planar Geometries.
MO’s of the π-system for Benzene
E
3
Circle Mneumonics Method To determine the relative energies of molecular orbitals for π-systems of the cyclic conjugated molecules: (As seen above for benzene) Example: Cyclobutadiene: Example: Cyclopropenium cation:
E
E
4
Example: Cyclopropenyl anion:
Huckel’s Rule 1. In a continuous cyclic array of π-electrons, the combination [4n+2] results in aromatic properties (overall stabilization), when {n= a whole number} 2. In a continuous cyclic array of π-electrons, the combination [4n] results in anti-aromatic properties (overall destabilization), when {n= a whole number} ***NOTE: In case the π-system is not continuous, the compound is classified as non-aromatic.
E
5
Practicing the Huckel’s Rule: Exercise: Label each structure shown below as A (aromatic), AA (anti-aromatic), or NA (non-aromatic).
N
O
6
Nomenclature of Benzene Derivatives …Remember the acronyms: Mono-substituted Benzene Derivatives:
phenyl fragment -> Ph(aryl fragment -> Ar) benzyl fragment
ø
OH
O
O OH
OMe NO2 NH2
Cl
Cl
7
Di-substitution Patterns in benzene Derivatives: Common: IUPAC: Nomenclature in Di-substituted Benzenes:
Br
Br
COOH
Cl
NO2
HO
8
Spectroscopic Remarks: IR: 1H–NMR: Decoupled 13C–NMR: Suggested Problems: 27, 28, 32, 36, 43a, 43b, 50.
!a) !Stretch!m! 3000+ cm–1
!!b) Stretch!mw! 1630 cm–1
CH
CH
HC
H
6.5–7.5 ppm A Variety of Splitting Patterns
C120–150 ppm
9
Chapter 17: Reactions of Aromatic Compounds
a) EAS: Electrophilic Aromatic Substitution b) NAS: Nucleophilic Aromatic Substitution c) Reactions of Phenols
____________________________________________________________________________
EAS: Electrophilic Aromatic Substitution General Equation: General Mechanism: A Sigma Complex
E+E
H
H
H
H
H
H
E+
Arenium Ion
Step 1
Step 2
10
Nitration of Benzene
Equation: Mechanism: 1. Generation of E+: E+ = NO2
+ (Role of HNO3 & H2SO4) 2. Addition of E+: 3. Elimination of H+:
HNO3, H2SO4
NO2
11
Energy Diagram for EAS Reactions
Halogenation of Benzene General Equation: Role of MX3: Example:
MX3, X2
X
FeBr3, Br2
Br
12
Mechanism:
Summary of Halogenation Details
Halogenation Type Commonly Applied Conditions
Chlorination AlCl3, Cl2
Bromination FeBr3, Br2
Iodination HNO3 (A strong oxidizing acid to oxidize I2 into I+), I2
13
Sulfonation of Benzene Equation: A Reversible Reaction Fuming Sulfuric Acid: 7% SO3 in H2SO4 Electrophile: SO3 Mechanism:
H2SO4, SO3 S
O
O
OH
14
Desulfonation Equation:
Deuteration of Benzene Equation: Mechanism:
Hexa-Deuterobenzene Synthesis
H+, HeatS
O
O
OH
D2SO4, D2OD
D2SO4, D2O(Large Excess)
D
DD
D
D D
15
EAS on Substituted Aromatic Compounds Effects of the Substituents on the Rates of EAS Reactions: 1. Activation 2. Deactivation Effects of the Substituents on the Orientations of EAS Reactions:
1. Ortho-Para Directing. 2. Meta Directing.
Mechanisms for Activation & Deactivation:
1. Induction (I) 2. Resonance (R)
Consider the Intermediate in an EAS Reaction: 1. To stabilize this intermediate, the + charge should be dispersed. If substituent Y helps spread the charge, then the intermediate is stabilized (Lowered in its energetic content) On the other hand, if the substituent intensifies the + charge, the intermediate will become less stable (higher in its energetic content).
E H
H
E H
H
Y
16
2. This stabilization / destabilization effect affects the energetics of the reaction as shown below. More specifically, it affects the activation energy for the first step (the RDS). Therefore: 1. Substituents that stabilize the CC+ intermediate end up activating the ring.
The EAS takes place with a faster rate.
2. Substituents that destabilize the CC+ intermediate end up deactivating the ring.
The EAS takes place with a slower rate.
Unsub
stitut
ed
Substi
tuted
With
Acti
vatin
g
Group
Substituted With
Deactivatin
g
Group
E
Reaction Progress
17
NH2
NH R
NR
R
OH
NH C
O
R
O R
O C
O
R
R
CH CH R
H
X (X = F, Cl, Br, I = halogen)
CH2 X
C
O
H
C
O
R
C
O
OH
C
O
O R
C
O
Cl
C N
S
O
O
OH
CF3
NO
O
Substitutent Effect on OrientationEffect on Rate
ortho, para-directing
meta-directing
Very strongly activating
Strongly activating
Activating
Strongly deactivating
Very strongly deactivating
ortho, para-directing
Classification of Substituents in Electrophilic Aromatic Substitution Reactions
(amino)
(alkylamino)
(dialkylamino)
(hydroxyl)
(acylamino)
(alkoxy)
(acyloxy)
(alkyl)
(aryl)
(alkenyl)
(halomethyl)
(formyl)
(acyl)
(carboxylic acid)
(ester)
(acyl chloride)
(cyano)
(sulfonic acid)
(trifluoromethyl)
(nitro)
(hydrogen, standard of comparison)
+R (+R prevails over –I)
+R (+R prevails over –I)
+R
–I controls rate+R controls orientation
–I, –R
–I, –R
–I
–I
Deactivating
+R
+I
Definitions:
+I = electron-donating via induction–I = electron-withdrawing via induction+R = electron-donating via resonance–R = electron-withdrawing via resonance
Deactivating
Activating
18
Mechanistic Examples of the Effects of the Substituents: a) b)
NH2
Br2, FeBr3
NO2
Br2, FeBr3
19
Orientation of E. A. Substitution for the Substituted Aromatic Compounds: Regioselectivity: 1. All the EDG’s result in ortho/para substitution. These are called ortho/para-directors. 2. All the EWG’s (with the exception of halogens and halomethyl) result in meta substitution. These are called meta-directors. ************************************************************************ Example: The effect of Amino group as a very strong EDG, ortho, para-director:
Para-Substitution
NH H
E
NH H
E
NH H
E
NH H
E
Possible Substitutions
Para MetaOrtho
NH H
E
20
Ortho-Substitution
Meta-Substitution
Example 2: The effect of Nitro group as a very strong EWG, meta-director:
NH H
E
NH H
E
NO O
E
Possible Substitutions
Para MetaOrtho
NO O
E
NO O
NO O
E
E
21
Para-Substitution
Ortho-Substitution
Meta-Substitution
NO O
E
NO O
E
NO O
E
22
Example 3: The effect of chloro group as an EWG, ortho, para-director:
Para-Substitution
Ortho-Substitution
Cl
E
Possible Substitutions
Para MetaOrtho
Cl
E
Cl Cl
E
E
Cl
E
Cl
E
23
Meta-Substitution
Orientation of Substitution in Rings with More Than One Substituent: 1. The simplest case: All available substitution sites are equivalent: Example: 2. If the available substituents reinforce each other: Example:
Cl
E
O
O O
NO2
Br2, FeBr3
24
3. More complicated cases: Example: Example: Example:
N
Cl
Br Br
CH3COOH
H
CH3
H3C
HNO3, H2SO4
CH3
HNO3, H2SO4
H3C
25
More EAS Reactions:
1. Friedel–Crafts Alkylation of Benzene: (1877) General Equation: Example:
Reaction Mechanism:
RX , AlX3
0oC
R
+Cl
AlCl3
26
Variations to the Original FC Alkylation: Generation of CC+ could be achieved differently. Examples:
2. Friedel–Crafts Acylation:
Acyl Group:
General Equation:
H+
H+
OH
R
O
X
AlX3 , CS2 , Heat
R
O
27
Example:
Mechanism: **************************************************************************** Problems with FC Alkylation:
1. Works with activated systems only. 2. Rearrangements of the CC+ will yield multiple products. 3. Multiple alkylations occur, since the product is more active.
Is there a better alternative? YES!: FC Acylation, followed by Reduction
R
O
Cl
AlCl3 , Heat
RO RO
+
28
Friedel–Crafts Acylation / Reduction of Benzene:
….as a more desirable alternative to F.C Alklyation.
Reaction Scheme: *Reduction Types Employed for Aryl Ketones:
a) Clemmensen: Zn (Hg), HCl Also employed for aldehydes.
b) Wolff–Kilshner: H2NNH2, KOH or NaOH, high-boiling alcohol (solvent), example: triethylene glycol, heat (175oC).
Also employed for aldehydes.
Important Points on the Regioselective Synthesis of Disubstituted Aromatic Compounds
Close attention must be paid to: 1. The directing effect, and 2. The activating/deactivating nature
…of the substituents.
Examples: a) Synthetic Target = Suggested Synthetic Pathway:
R
O
Reduction
CH2R
FC Acylation
Br
O
29
b) Synthetic Target = Suggested Synthetic Pathway: c) Synthetic Target = Suggested Synthetic Pathway:
O
Br
O
NO2
30
Nucleophilic Aromatic Substitution Example: Mechanism:
Cl
NO2NaOH
100oC
H+
OH
NO2
31
Birch Reduction Equation: Remember: Sodium-liquid ammonia reductions convert alkynes into trans-alkenes. With the methanol added, it is possible to reduce benzene into the non-conjugated 1,4-cyclohexadiene. Mechanism: Radical-Ionic
Na, NH3(l)
CH3OH
benzene 1,4-cyclohexadiene
Na
single e– transfer
Na
H
H
H
H
H
H
H
HH
H
H
H
OHH3C
H
H
H
H
H
H H
OH3C Na
+
single e– transfer
Na
H
H
H
H
H
H H
Na
OHH3C
H
H
H
H
H
H H
H
OH3C Na
+
32
Side-Chain Oxidation of Benzene Derivatives Example:
1. KMnO4(aq), 100oC
2. H+
OH
O
