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

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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

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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

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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

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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

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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

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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

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Mechanistic Examples of the Effects of the Substituents: a) b)

NH2

Br2, FeBr3

NO2

Br2, FeBr3

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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

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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

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Para-Substitution

Ortho-Substitution

Meta-Substitution

NO O

E

NO O

E

NO O

E

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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

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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

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3. More complicated cases: Example: Example: Example:

N

Cl

Br Br

CH3COOH

H

CH3

H3C

HNO3, H2SO4

CH3

HNO3, H2SO4

H3C

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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

+

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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

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b) Synthetic Target = Suggested Synthetic Pathway: c) Synthetic Target = Suggested Synthetic Pathway:

O

Br

O

NO2

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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