Phenol and its derivatives

1. Phenols Ar-OH
Phenols are compounds with an –OH group attached to an aromatic
carbon. Although they share the same functional group with
alcohols, where the –OH group is attached to an aliphatic carbon,
the chemistry of phenols is very different from that of alcohols.
M.M. COLLEGE OF PHARMACY
MAHARISHI MARKANDESHWAR (DEEMED TO BE UNIVERSITY),
MULLANA, AMBALA (INDIA)- 133207
(Established under section 3 of UGC, act 1956)
(Accredited By NAAC with Grade ‘A++’)

2. Nomenclature.
Phenols are usually named as substituted phenols. The
methylphenols are given the special name, cresols. Some other
phenols are named as hydroxy compounds.
OH
phenol
OH
Br
m-bromophenol
CH3
OH
o-cresol
OH
COOH
salicylic acid
OH
OH
OH
OH
OH
OH
catechol resorcinol hydroquinone
COOH
OH
p-hydroxybenzoic acid

3. physical properties
phenols are polar and can hydrogen bond
phenols are water insoluble
phenols are stronger acids than water and
will dissolve in 5% NaOH
phenols are weaker acids than carbonic acid and
do not dissolve in 5% NaHCO3

4. Intramolecular hydrogen bonding is possible in some
ortho-substituted phenols. This intramolecular hydrogen
bonding reduces water solubility and increases volatility.
Thus, o-nitrophenol is steam distillable while the
isomeric p-nitrophenol is not.
N
O
H
O
O
o-nitrophenol
bp 100oC at 100 mm
0.2 g / 100 mL water
volatile with steam
OH
NO2
p-nitrophenol
bp decomposes
1.69 g / 100 mL water
non-volatile with steam

5. phenols, syntheses:
1. From diazonium salts
2. Alkali fusion of sulfonates
N2
H2O,H+
OH
SO3 Na NaOH,H2O
300o
ONa
H+ OH

6. Reactions:
alcohols phenols
1. HX NR
2. PX3 NR
3. dehydration NR
4. as acids phenols are more acidic
5. ester formation similar
6. oxidation NR
M.M. COLLEGE OF PHARMACY
MAHARISHI MARKANDESHWAR (DEEMED TO BE UNIVERSITY),
MULLANA, AMBALA (INDIA)- 133207
(Established under section 3 of UGC, act 1956)
(Accredited By NAAC with Grade ‘A++’)

7. Phenols, reactions:
1. as acids
2. ester formation
3. ether formation
4. EAS
a) nitration f) nitrosation
b) sulfonation g) coupling with diaz. salts
c) halogenation h) Kolbe
d) Friedel-Crafts alkylation i) Reimer-Tiemann
e) Friedel-Crafts acylation

8. as acids:
with active metals:
with bases:
CH4 < NH3 < HCCH < ROH < H2O < phenols < H2CO3 < RCOOH < HF
OH
Na
ONa
sodium phenoxide
+ H2(g)
OH
+ NaOH
ONa
+ H2O
SA SB WB WA

9. CH4 < NH3 < HCCH < ROH < H2O < phenols < H2CO3 < RCOOH < HF
OH
+ NaOH
ONa
+ H2O
SA SB WB WA
water insoluble water soluble
OH
+ NaHCO3 NR phenol < H2CO3

10. insoluble soluble insoluble
insoluble soluble soluble
water 5% NaOH 5% NaHCO3
phenols
carboxylic
acids
CH4 < NH3 < HCCH < ROH < H2O < phenols < H2CO3 < RCOOH < HF

11. We use the ionization of acids in water to measure acid
strength (Ka):
HBase + H2O H3O+ + Base-
Ka = [H3O+ ][ Base ] / [ HBase]
ROH Ka ~ 10-16 - 10-18
ArOH Ka ~ 10-10
Why are phenols more acidic than alcohols?

12. ROH + H2O H3O+ + RO-
ArOH + H2O H3O+ + ArO-
OH OH O O O O O
Resonance stabilization of the phenoxide
ion, lowers the PE of the products of the
ionization, decreases the ΔH, shifts the equil
farther to the right, makes phenol more
acidic than an alcohol

13. effect of substituent groups on acid strength?
OH
G + H2O
O
G + H3O
Electron withdrawing groups will decrease the negative
charge in the phenoxide, lowering the PE, decreasing theΔH,
shifting the equil farther to the right, stronger acid.
Electron donating groups will increase the negative charge
in the phenoxide, increasing the PE, increasing the ΔH,
shifting the equilibrium to the left, weaker acid.

14. Number the following acids in decreasing order of acid
strength (let # 1 = most acidic, etc.)
OH OH OH OH OH
NO2 CH3 Br
3 5 1 4 2

15. SO3H COOH OH CH2OH
1 2 3 4
M.M. COLLEGE OF PHARMACY
MAHARISHI MARKANDESHWAR (DEEMED TO BE UNIVERSITY),
MULLANA, AMBALA (INDIA)- 133207
(Established under section 3 of UGC, act 1956)
(Accredited By NAAC with Grade ‘A++’)

16. 2. ester formation (similar to alcohols)
OH
CH3
+ CH3CH2C
O
OH
H+
CH3CH2C
O
O
H3C
+ H2O
OH
COOH
salicyclic acid
+ (CH3CO)2O
O
COOH
C
H3C
O
aspirin

17. O
COOH
C
H3C
O
aspirin
analgesic
anti-inflamatory
antipyrretic
anticoagulant
Reye's syndrome
not to be used by children
with high fevers!
OH
NH
C
H3C
O
acetaminophen
aspirin substitute
Tylenol
Kidney damage!

18. 3. ether formation (Williamson Synthesis)
Ar-O-Na+ + R-X  Ar-O-R + NaX
note: R-X must be 1o or CH3
Because phenols are more acidic than water, it is possible
to generate the phenoxide in situ using NaOH.
OH
CH3
+ CH3CH2Br, NaOH
OCH2CH3
CH3

19. 4. Electrophilic Aromatic Substitution
The –OH group is a powerful activating group in EAS
and an ortho/para director.
a) nitration
OH OH
NO2
NO2
O2N
polynitration!
OH
dilute HNO3
OH OH
NO2
NO2
+
HNO3

20. OH
Br2 (aq.)
OH
Br
Br
Br no catalyst required
use polar solvent
polyhalogenation!
OH
Br2, CCl4
OH OH
Br
Br
+
non-polar solvent
b) halogenation

21. c) sulfonation
OH
H2SO4, 15-20oC
OH
SO3H
H2SO4, 100o
C
OH
SO3H
At low temperature the reaction is non-reversible and the lower Eact ortho-
product is formed (rate control).
At high temperature the reaction is reversible and the more stable para-
product is formed (kinetic control).

22. d) Friedel-Crafts alkylation.
OH
+ H3C C CH3
CH3
Cl
AlCl3
OH
C CH3
CH3
H3C
M.M. COLLEGE OF PHARMACY
MAHARISHI MARKANDESHWAR (DEEMED TO BE UNIVERSITY),
MULLANA, AMBALA (INDIA)- 133207
(Established under section 3 of UGC, act 1956)
(Accredited By NAAC with Grade ‘A++’)

23. e) Friedel-Crafts acylation
OH
CH3CH2CH2C
O
Cl
+
AlCl3
OH
O
Do not confuse FC acylation with esterification:
OH
CH3CH2CH2C
O
Cl
+ O
O

24. OH
O
OH
CH3CH2CH2C
O
Cl
+ O
O
AlCl3
Fries rearrangement of phenolic esters.
M.M. COLLEGE OF PHARMACY
MAHARISHI MARKANDESHWAR (DEEMED TO BE UNIVERSITY),
MULLANA, AMBALA (INDIA)- 133207
(Established under section 3 of UGC, act 1956)
(Accredited By NAAC with Grade ‘A++’)

25. f) nitrosation
OH
HONO
OH
NO
EAS with very weak electrophile NO+
OH
CH3 NaNO2, HCl
OH
CH3
NO
p-nitrosophenol

26. g) coupling with diazonium salts
(EAS with the weak electrophile diazonium)
OH
CH3
+
N2 Cl
benzenediazonium
chloride
CH3
OH
N
N
an azo dye

27. h) Kolbe reaction (carbonation)
ONa
+ CO2
125oC, 4-7 atm.
OH
COONa
sodium salicylate
H+
OH
COOH
salicylic acid
EAS by the weakly
electrophilic CO2
O C O


28. i) Reimer-Tiemann reaction
OH
CHCl3, aq. NaOH
70oC
H+
OH
CHO
salicylaldehyde
The salicylaldehyde can be easily oxidized to salicylic acid

29. Reimer-Tiemann reaction (detail)
Chloroform (1) is deprotonated by a strong base (normally hydroxide) to form the
chloroform carbanion (2) which will quickly alpha-eliminate to give dichlorocarbene (3);
this is the principal reactive species. The hydroxide will also deprotonate the phenol (4) to
give a negatively charged phenoxide (5). The negative charge is delocalised into the
aromatic ring, making it far more nucleophilic. Nucleophilic attack on the dichlorocarbene
gives an intermediate dichloromethyl substituted phenol (7). After basic hydrolysis, the
desired product (9) is formed.