Chapter 23 Aryl Halides

1
Chapter 23Aryl Halides
2
23.1Bonding in Aryl Halides
3
Aryl Halides

• Aryl halides are halides in which the halogen is
  attached directly to an aromatic ring.
• Carbon-halogen bonds in aryl halides are shorter
  and stronger than carbon-halogen bonds in alkyl
  halides.

4
Table 23.1 CH and CCl Bond Dissociation
Energies of Selected Compounds
Bond EnergykJ/mol (kcal/mol)
X H
X Cl
CH3CH2X
sp3
410 (98)
339 (81)
sp2
452 (108)
368 (88)
sp2
469 (112)
406 (97)
5
Aryl Halides

• Aryl halides are halides in which the halogen is
  attached directly to an aromatic ring.
• Carbon-halogen bonds in aryl halides are shorter
  and stronger than carbon-halogen bonds in alkyl
  halides.
• Because the carbon-halogen bond is stronger, aryl
  halides react more slowly than alkyl halides when
  carbon-halogen bond breaking is rate determining.

6
23.2Sources of Aryl Halides
7
Preparation of Aryl Halides

• Halogenation of arenes (Section 12.5)
• The Sandmeyer reaction (Section 22.17)
• The Schiemann reaction (Section 22.17)
• Reaction of aryl diazonium salts with iodide ion
  (Section 22.18)

8
23.3Physical Properties of Aryl Halides
9
Physical Properties of Aryl Halides

• resemble alkyl halides
• all are essentially insoluble in water
• less polar than alkyl halides

? 1.7 D
? 2.2 D
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23.4Reactions of Aryl HalidesA Review and a
Preview
11
Reactions of Aryl Halides

• Electrophilic Aromatic Substitution (Section
  12.14)
• Formation of aryl Grignard reagents (Section
  14.4)
• We have not yet seen any nucleophilic
  substitution reactions of aryl halides.
  Nucleophilic substitution on chlorobenzene occurs
  so slowly that forcing conditions are required.

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Example
(97)
13
Reasons for Low Reactivity

• SN1 not reasonable because
• 1) CCl bond is strong therefore, ionization
  to a carbocation is a high-energy process
• 2) aryl cations are less stable than alkyl
  cations

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Reasons for Low Reactivity

• SN2 not reasonable because ring blocks attack of
  nucleophile from side opposite bond to leaving
  group

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23.5Nucleophilic Substitution inNitro-Substitute
d Aryl Halides
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But...

• nitro-substituted aryl halides do
  undergonucleophilic aromatic substitution readily

CH3OH


NaOCH3
NaCl
85C
(92)
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Effect of nitro group is cumulative

• especially when nitro group is ortho and/orpara
  to leaving group

1.0
too fast to measure
18
Kinetics

• follows second-order rate law rate karyl
  halidenucleophile
• inference both the aryl halide and the
  nucleophile are involved in rate-determining
  step

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Effect of leaving group

• unusual order F gt Cl gt Br gt I

X
Relative Rate
F
312
Cl
1.0
Br
0.8
I
0.4
NaOCH3, CH3OH, 50C
20
General Conclusions About Mechanism

• bimolecular rate-determining step in
  whichnucleophile attacks aryl halide
• rate-determining step precedes carbon-halogenbond
  cleavage
• rate-determining transition state is stabilized
  byelectron-withdrawing groups (such as NO2)

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23.6The Addition-Elimination Mechanismof
Nucleophilic Aromatic Substitution
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Addition-Elimination Mechanism

• Two step mechanism
• Step 1) nucleophile attacks aryl halide and
  bonds to the carbon that bears the
  halogen (slow aromaticity of ring lost in
  this step)
• Step 2) intermediate formed in first step
  loses halide (fast aromaticity of ring
  restored in this step)

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Reaction
CH3OH


NaOCH3
NaF
85C
(93)
24
Mechanism
Step 1

• bimolecular
• consistent with second-order kinetics first
  order in aryl halide, first order in nucleophile

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Mechanism
Step 1
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Mechanism

• intermediate is negatively charged
• formed faster when ring bears electron-withdrawing
  groups such as NO2

H
H


H
H
NO2
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Stabilization of Rate-Determining Intermediateby
Nitro Group
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Stabilization of Rate-Determining Intermediateby
Nitro Group
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Mechanism
Step 2
H
H


H
H
NO2
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Mechanism
Step 2
H
H
fast
H
H
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Leaving Group Effects
F gt Cl gt Br gt I is unusual, but consistentwith
mechanism

• carbon-halogen bond breaking does not occuruntil
  after the rate-determining step
• electronegative F stabilizes negatively charged
  intermediate

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23.7Related Nucleophilic AromaticSubstitution
Reactions
33
Example Hexafluorobenzene
(72)

• Six fluorine substituents stabilize negatively
  charged intermediate formed in rate-determining
  step and increase rate of nucleophilic aromatic
  substitution.

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Example 2-Chloropyridine
NaOCH3
CH3OH
50C

• 2-Chloropyridine reacts 230,000,000 times faster
  than chlorobenzene under these conditions.

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Example 2-Chloropyridine

• Nitrogen is more electronegative than carbon,
  stabilizes the anionic intermediate, and
  increases the rate at which it is formed.

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Example 2-Chloropyridine


N
Cl

• Nitrogen is more electronegative than carbon,
  stabilizes the anionic intermediate, and
  increases the rate at which it is formed.

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23.8The Elimination-Addition Mechanismof
Nucleophilic Aromatic SubstitutionBenzyne
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Aryl Halides Undergo Substitution WhenTreated
With Very Strong Bases
KNH2, NH3
33C
(52)
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Regiochemistry

• new substituent becomes attached to eitherthe
  carbon that bore the leaving group orthe carbon
  adjacent to it

NaNH2,NH3

33C
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Regiochemistry

• new substituent becomes attached to eitherthe
  carbon that bore the leaving group orthe carbon
  adjacent to it

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Regiochemistry
NaNH2, NH3
33C


42
Same result using 14C label

(48)
(52)
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Mechanism
Step 1
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Mechanism
Step 1

• compound formed in this step is called benzyne

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Benzyne

• Benzyne has a strained triple bond.
• It cannot be isolated in this reaction, but is
  formed as a reactive intermediate.

46
Mechanism
Step 2
47
Mechanism
Step 2

• Angle strain is relieved. The two sp-hybridized
  ring carbons in benzyne become sp2 hybridized in
  the resulting anion.

48
Mechanism
Step 3


NH2

49
Mechanism
Step 3


NH2

50
Hydrolysis of Chlorobenzene

• 14C labeling indicates that the high-temperature
  reaction of chlorobenzene with NaOH goes via
  benzyne.

NaOH, H2O
395C

(54)
(43)
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23.9Diels-Alder Reactions of Benzyne
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Other Routes to Benzyne

• Benzyne can be prepared as a reactive
  intermediate by methods other than treatment of
  chlorobenzene with strong bases.
• Another method involves loss of fluoride ion from
  the Grignard reagent of 1-bromo-2-fluorobenzene.

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Other Routes to Benzyne
FMgBr

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Benzyne as a Dienophile

• Benzyne is a fairly reactive dienophile, and
  gives Diels-Alder adducts when generated in the
  presence of conjugated dienes.

55
Benzyne as a Dienophile
Br

F
(46)
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23.10m-Benzyne and p-Benzyne
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1,3- and 1,4-Dehydrobenzene

• Benzyne can exist as 1,3-Dehydrobenzene or
  m-Benzyne and 1,4-Dehydrobenzene or p-Benzyne.

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End of Chapter 23