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Chemistry I (Organic)
Aromatic Chemistry
LECTURE 3 – Electrophilic Substitution (part 2)
Alan C. Spivey
[email protected]
Dec 2009
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Format and scope of presentation
•
Electrophilic aromatic substitution (SEAr) – part 2:
–
–
Friedel-Crafts alkylation and acylation, nitrosation (diazonium salt formation & diazo-coupling, Sandmeyer
reactions),
Directing effects (ortho-/para- ratios, ipso-substitution)
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Friedel-Crafts alkylation
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Typical conditions: alkyl halides in the presence of Lewis acid promotors
FeBr3
RBr
R...FeBr4
alkyl halide-Lewis acid complex = E
–
–
–
–
–
‘Plagued’ by rearrangements (Wagner-Meerwein 1,2-hydride shifts)
Substantially reversible and therefore can de-alkylate!
Products are activated relative to starting materials hence extensive poly-alkylation
Alkyl halide-Lewis acid complex is a weak electrophile and deactivated aromatics do not react
The Lewis acid is a catalytic promotor
H
H
R'...FeBr4
R'
R'
FeBr4
R
R
FeBr4
R
HBr + FeBr3
Order of Lewis acid effectiveness: AlCl3 > FeCl3 > BF3 > TiCl3 > ZnCl2 > SnCl4
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Friedel-Crafts acylation
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Typical conditions: acid chlorides or anhydrides (also sulfonyl chlorides) ± Lewis acid promotor :
O
R
O
Cl
AlCl3
AlCl4
+
acylium ion = E
R
–
–
–
Lewis acid not required for activated aromatics
stoichiometric LAs: AlCl3 > FeCl3 > BF3 > TiCl3 > ZnCl2 > SnCl4
• Generally can’t be recycled via aqueous extraction
catalytic Lewis acids: lanthanide(III) halides/triflates e.g. GaCl3, InCl3, Hf(OTf)4
O
H
H
R'CO
R
R'
O
AlCl4
R
Cl3Al
R
HCl
R'
N.B. NOT
catalytic in
Lewis acid
because it
complexes to
product ketone
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Formylation
•
Aryl aldehyde formation: formyl chloride (HCOCl) is not stable so ‘standard’ F-C acylation is not
possible. A number of classical approaches have been developed:
O
Olah-Kuhn formylation:
H
BF3
H
F
O
H
Gatterman formylation:
R
HCl-AlCl3
C O
C O
Rieche-Gross-Hoft formylation:
O
H
(activated aromatics only)
Cl
H
OMe
H
O
Cl
AlCl3
Cl
O
Vilsmeier-Haack formylation:
H
H
OMe
Cl
POCl3
NMe2
H
NMe2
R
Gatterman-Koch formylation:
Zn(CN)2
HCl
H
N H
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Nitrosation
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Typical conditions: sodium nitrite and hydrochloric acid
Na
O
O N
HCl
O
H
O N
H
Cl
HCl
nitrous
acid
sodium
nitrite
–
–
–
–
O
H
O N
O
N
+ H2O
nitrosonium ion = E
Nitrosonium ion is weak electrophile: only ring nitrosates activated aromatics (e.g. phenols)
N-Alkyl anilines give N-nitroso anilines (i.e. N-nitrosation not ring nitrosation)
N-Nitroso anilines can undergo Fischer-Hepp rearrangement on heating to ring nitrosated products
Anilines give diazonium salts via initial N-nitrosation
NMe2
NRR'
NO
NO
R', R'' = H
R', R'' = Me
O
N
ring nitrosated
dialkyl aniline
N2
R' = H, R'' = Me
NO
O
N
N
Me
N-nitroso aniline
dia
zon
iu
m
salt
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Diazotisation & Sandmeyer reactions
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Mechanism of formation:
NH2
R
O
NO
N
R
NH2
H
N
O
H
R
N
N
N
N
N
R
R
diazonium salt
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Nucleophilic ipso-substitution (Sandmeyer reactions):
+ H2O
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Diazotisation & diazo-coupling
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Nucleophilic attack can also occur at the terminal nitrogen of diazonium ions (cf. at the ipsocarbon in Sandmeyer reactions)
–
e.g. triazine synthesis using amines as nucleophiles:
R'
N
X
N2
R'
–
R'
H
N
N
N
R''
R''
R'
e.g. diazo-compound synthesis (dyes) using phenols as C-nucleophiles:
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Aromatics as ambident nucleophiles
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cf. Aryl diazonium ions as ambident electrophiles:
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Aromatics as ambident nucleophiles (‘directing effects’):
substituent (e.g. N-) as nucleophile
ipso-carbon
as nucleophile
NR2
ortho-carbon as nucleophile
What governs position of reactivity?
meta-carbon as nucleophile
para-carbon as nucleophile