Post on 03-Feb-2022
Ch. 21 - 2
1. Structure and Nomenclatureof Phenols
OH OHOH
Phenol 1-Naphthol(α-naphthol)
9-Phenanthrol
Ch. 21 - 3
1A. Nomenclature of Phenols
OH
4-Chlorophenol(p-chlorophenol)
2-Nitrophenol(o-nitrophenol)
3-Methylphenol(m-cresol)
Cl
NO2
OH OH
CH3
Ch. 21 - 4
The benzenediols also have common names
OH
1,2-Benzenediol(catechol)
1,3-Benzenediol(resorcinol)
1,4-Benzenediol(hydroquinone)
OH
OH
OH
OHOH
Ch. 21 - 5
2. Naturally Occurring Phenols
OH
OH
L-Tyrosine Methyl salicylate(oil of wintergreen)
Eugenol(oil of cloves)
HO
O−
O
NH3+H
CO2CH3
OCH3
EstradiolHO
H
H
H
CH3OH
Ch. 21 - 7
4. Synthesis of Phenols
NH2
R
N2
R
OH
RHONO H2O
Cu2O, Cu2+
4A. Laboratory Synthesis
NH2
1. NaNO2, HCl, 0-5oC
2. Cu2O, Cu2+, H2OCl CH3
OH
Cl CH3
e.g.
Ch. 21 - 8
4B. Industrial Syntheses Hydrolysis of chlorobenzene (Dow
Process)
Cl O Na
OH
2 NaOH
HCl
350oChigh pressure
+ NaCl + H2O
+ NaCl
Ch. 21 - 9
From cumene hydroperoxideH3PO4
O2
95-135oC
250oChigh pressure
+
+(Cumene)
OOH
(Cumenehydroperoxide)
50-90oC
H3O+OHO
Ch. 21 - 13
5. Reactions of Phenols as Acids
OH
OHH3C
OHCl
OH
OHO2N
OHO2N
pKa
9.89
10.17
9.20
pKa
7.15
3.96
0.38
O2N
NO2
NO2
NO2
Ch. 21 - 16
5B. Distinguishing and SeparatingPhenols from Alcohols andCarboxylic Acids
Question If you are given three unknown samples: one is
benzoic acid; one is phenol; and one is cyclohexyl alcohol; how would you distinguish them by simple chemical tests?● Recall: acidity of
OH
O OH
OH
> >
Ch. 21 - 17
O
R OH Na OH+
O
R O Na+ H2O
(soluble in water)
OH
+ NaOH
OH
+ NaOH
(immisciblewith H2O)
O Na
(soluble in water)
No Reaction
Ch. 21 - 18
O
OH
+ NaHCO3
O
O Na
+ CO2(g) + H2O
(gas evolved)
OH
+ NaHCO3 No Reaction
OH
+ NaHCO3 No Reaction
Ch. 21 - 20
6A. Phenols in the Williamson Synthesis
OH
R
OH 1. NaOH
2.
O
Br
e.g.
NaOH
O Na
R R X(X = halides,OTs, OMs)
OR
R
Ch. 21 - 21
7. Cleavage of Alkyl Aryl Ethers
O
R
R conc. HX
heat
OH
R
+ RX
Oconc. HCl
heat
OH
+ Cl
e.g.
Ch. 21 - 22
8. Reactions of the Benzene Ring of Phenols
OH
BrominationBr
+ 3 HBr
OH
Br
Br
3 Br2H2O
+ HBr
OH
Br
CS2, 5oC
Br2
(NO Lewis acid required for the brominations)
Ch. 21 - 26
ONa
O
C
O
● Mechanism
O
C
H
O
O
Na
tautomerization
OH
O
O
Na
Sodium salicylate
OH
O
OH
Salicylic acid
H3O+
Ch. 21 - 31
+ 2 e−, + 2 H+
- 2 e−, - 2 H+
O
O
Ubiquinones (n = 6-10)(coenzymes Q)
CH3H3CO
H3CO H
CH3n
OH
OH
Ubiquinol(hydroquinone form)
CH3H3CO
H3CO H
CH3n
Ch. 21 - 33
11. Aryl Halides and Nucleophilic Aromatic SubstitutionCl
+ NaOH NO substitutionH2O
heat
Cl + NaOH NO substitutionH2O
heat
XNu:
XNO reaction
Ch. 21 - 35
11A. Nucleophilic Aromatic Substitutionby Addition–Elimination:The SNAr Mechanism
NO2
Cl
+ OHH3O
+aq. NaHCO3
130oC
NO2
OH
Nucleophilic aromatic substitution can occur when strong electron-withdrawing groups are ortho or para to the halogen atom
Ch. 21 - 36
NO2
Cl
+ OHH3O
+aq. NaHCO3
130oC
NO2
OH
NO2 NO2
NO2
Cl
+ OH
H3O+
aq. NaHCO3
130oC
NO2
OH
NO2
NO2
O2N
O2N
Ch. 21 - 37
The mechanism that operates in these reactions is an addition–elimination mechanism involving the formation of a carbanion with delocalized electrons, called a Meisenheimer intermediate. The process is called nucleophilic aromatic substitution (SNAr)
Ch. 21 - 38
The SNAr mechanismCl
+ OH
NO2
addition
slow
NO2
Cl OH
eliminationfast
OH
NO2
+ClOH
O
NO2
+HOH
Ch. 21 - 40
11B. Nucleophilic Aromatic Substitution through an Elimination–Addition Mechanism: BenzyneCl
H3O+
350oC
OH
NaOH
ONa
Phenol
Br
-33oC
NH2
K :NH2+ KBr
Aniline
Ch. 21 - 41
The benzyne elimination–addition mechanism
Br
H
NH2
Br(-NH3) (-Br−)
Benzyne(or dehydrobenzene)
NH2NH2NH2
H
+NH2NH3
Ch. 21 - 44
NH2
NH2
NH2
CF3
CF3
CF3
NH3
less stablecarbanion
more stablecarbanion
NH2
CF3
+ NH2
>>
X
Ch. 21 - 45
Benzyne intermediates have been “trapped” through the use of Diels–Alder reactions
CO
O
NH3
Anthranilicacid
diazotizationC
O
O
NN
-CO2-N2
Benzyne(trapped in situ)
O
O
Ch. 21 - 47
12. Spectroscopic Analysis of Phenols and Aryl Halides
Infrared spectra (IR)
●
●
R
OH
O H stretching: 3400-3600 cm-1
R
OH
: characteristic absorptions of the benzene rings
and
R
X
Ch. 21 - 48
1H NMR spectra
OH
δ (ppm) of H
pure phenol:
in CCl4 (1%)
2.55
5.63
OH
O
OH
δ 0.5 – 1.0 ppm
intramolecularhydrogen bonding
Ch. 21 - 51
Mass spectra
● Mass spectra of phenols often display a prominent molecular ion peak, M
● Phenols that have a benzylic hydrogen produce an M – 1 peak that can be larger than the M peak