solomons and fryhle

Organic chemistry I
Zdeněk Friedl
Chapter 11
Hydroxy derivatives
Solomons & Fryhle: Organic
Chemistry 8th Ed., Wiley 2004
Hydroxy derivatives
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structure of hydroxy compounds and physical properties
reaction scheme of alcohols
nucleophilic substitution reactions SN1 and SN2
intramolecular nucleophilic substitution SNi
acid catalyzed E1 and E2 dehydration of alcohols
oxidation of alcohols
reaction scheme of phenols
electrophilic substitution reaction SEAr on phenols
oxidation of phenols
reaction scheme of naphthols, Bucherer reaction
2
The electrostatic potential map of methanol
3
Hydrogen bonding between molecules of methanol
4
Physical properties of alcohols
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The reaction scheme of alcohols
SN(H+) and E reactions
δ+
R CH C
SN (2,1)
δ−
O
H
Hβ
E (2,1)
δ+
H+
-
B
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Alcohols as the O acids
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pKa
Definition of acidity constants pKa
H-A + H2O D
A- + H3O+
Keq = [A-] [H3O+] / [HA] [H2O]
Ka = Keq [H2O] = [A-] [H3O+] / [HA]
pKa = - log Ka = log [HA] / [A-] - log [H3O+]
pKa = log [HA] / [A-] + pH
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pKa
Derivation of pKa constant for H2O
H2O + H2O D
OH- + H3O+
Keq = [OH-] [H3O+] / [H2O]2
Ka = Keq [H2O] = [OH-] [H3O+] / [H2O]
Ka = 1.0 x 10-14 / 55.6 = 1.80 x 10-16
pKa = 15.74
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pKa
Relative strength of selected acids
and their conjugate bases
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SN2
A mechanism for the reaction of alcohols with Br1° alcohols and methanol
without acid catalysis the SN2 reaction NOT PROCEEDS
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SN2
A mechanism for the reaction
of alcohols with HNu
1° alcohols and methanol
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SN2
A mechanism for the reaction of alcohols with HX
HI > HBr > HCl
(HF unreactive)
reaction of HCl with methanol, 1° and 2° alcohols needs catalysis of Lewis acid
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SN2
An intermolecular SN reaction of 2° and 3° alcohols
a INVERSION of configuration
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SNi
An intramolecular SN reaction of 2° and 3° alcohols
a RETENTION of configuration
Cl
CH3CH2
H
S O
H C O
Cl
H3C
(R) - SO2
- HCl
benzene
CH3CH2
H C O
H3C
S O
Cl
CH3CH2
H C Cl
H3C
(R) -
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SN1
A mechanism for the reaction of alcohols with HX
3°, allyl and benzyl alcohols
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SN1
Stereochemistry of a reaction of alcohols with HX
chiral alcohols a RACEMIZATION of product
(R) or (S)-3-methyl-3-hexanol gives a racemic form of
(±)-3-brom-3-methylhexane
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SN2 vs. E2
Intermolecular dehydration of alcohols
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E2
Acid-catalyzed dehydration of 1° alcohols
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E1
Acid-catalyzed dehydration of 2° and 3° alcohols
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E1
The relative Gibbs energy of activation for the
formation of 1°, 2° and 3° carbocations
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E1/RN
Rearrangements in dehydration of 2° alcohols
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E1/RN
Rearrangements in dehydration of 2° alcohols
ZAITSEV’S rule
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Oxidation of 1° alcohols
NONSELECTIVE oxidation to aldehydes and carboxylic acids
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Oxidation of 1° alcohols
SELECTIVE oxidation to aldehydes
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Oxidation of 2° alcohols to ketones
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Oxidation of 3° alcohols
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Summary of synthetic reactions of alcohols
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The reaction scheme of phenols
X
SNAr
δ
δ+
H
−
O
δ+
B-
SEAr
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The electrostatic potential map of phenol
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pKa
Relative acidity of alcohols and phenols
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pKa
pKa constants of substituted phenols
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SNAr
Cleavage of alkyl aryl ethers
The SNAr reaction does not occur
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SEAr
Alkylation of phenols:
The Lewis acids as AlCl3 cannot be used
R OH + BF 3
R [HO-BF 3]
OH
OH
+ R [HO-BF 3]
R
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RE
Alkylation (allylation) of phenols
CLAISEN rearrangement
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RE
Acylation of phenols
FRIES rearrangement
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SEAr
Bromination of phenols
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SEAr
Nitration of phenols
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SEAr
Sulfonation of phenols
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SEAr
Formylation of phenols
REIMER-TIEMANN reaction
O
O
O
\
O
_
CCl2
|CCl2
H
OH
CHCl2
CH=O
H2O
H
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SEAr
Carboxylation of phenols
KOLBE reaction
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Oxidation of phenols
electron transfer in nature
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The defense reactions of bugs
The Bombardier beetle’s noxious spray
OH
O
+ H2O2
OH
enzyme
+ 2 H2O (100 °C)
O
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The reaction scheme of 2-naphthol
(NH3)
SN
δ−
O
OH
δ+
SEAr
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SN
Nucleophilic 1,4-addition/substitution
BUCHERER reaction
OH
O
OH
NH4HSO3
H
NH
- NH4HSO3
NH3
H
SO3 NH4
NH2
SO3 NH4
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Summary of phenol synthetic reactions
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