Organic chemistry I

Zdenk Friedl

Chapter 11

Hydroxy derivatives

Solomons & Fryhle: Organic

Chemistry 8th Ed., Wiley 2004

Hydroxy derivatives

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

The electrostatic potential map of methanol

Hydrogen bonding between molecules of methanol

Physical properties of alcohols

The reaction scheme of alcohols

SN(H+) and E reactions

R CH C

SN (2,1)

H
E (2,1)

H+

Alcohols as the O acids

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

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

pKa

Relative strength of selected acids

and their conjugate bases

10

SN2

A mechanism for the reaction of alcohols with Br1 alcohols and methanol
without acid catalysis the SN2 reaction NOT PROCEEDS

11

SN2

A mechanism for the reaction

of alcohols with HNu
1 alcohols and methanol

12

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

13

SN2

An intermolecular SN reaction of 2 and 3 alcohols

a INVERSION of configuration

14

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) -

15

SN1

A mechanism for the reaction of alcohols with HX

3, allyl and benzyl alcohols

16

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

17

SN2 vs. E2

Intermolecular dehydration of alcohols

18

E2

Acid-catalyzed dehydration of 1 alcohols

19

E1

Acid-catalyzed dehydration of 2 and 3 alcohols

20

E1

The relative Gibbs energy of activation for the

formation of 1, 2 and 3 carbocations

21

E1/RN

Rearrangements in dehydration of 2 alcohols

22

E1/RN

Rearrangements in dehydration of 2 alcohols

ZAITSEVS rule

23

Oxidation of 1 alcohols
NONSELECTIVE oxidation to aldehydes and carboxylic acids

24

Oxidation of 1 alcohols
SELECTIVE oxidation to aldehydes

25

Oxidation of 2 alcohols to ketones

26

Oxidation of 3 alcohols

27

Summary of synthetic reactions of alcohols

28

The reaction scheme of phenols

X
SNAr

O
+

B-

SEAr

29

The electrostatic potential map of phenol

30

pKa

Relative acidity of alcohols and phenols

31

pKa

pKa constants of substituted phenols

32

SNAr

Cleavage of alkyl aryl ethers

The SNAr reaction does not occur

33

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

34

RE

Alkylation (allylation) of phenols

CLAISEN rearrangement

35

RE

Acylation of phenols
FRIES rearrangement

36

SEAr

Bromination of phenols

37

SEAr

Nitration of phenols

38

SEAr

Sulfonation of phenols

39

SEAr

Formylation of phenols
REIMER-TIEMANN reaction

O
\

_
CCl2

|CCl2

OH
CHCl2

CH=O
H2O
H

40

SEAr

Carboxylation of phenols
KOLBE reaction

41

Oxidation of phenols
electron transfer in nature

42

The defense reactions of bugs

The Bombardier beetles noxious spray
OH

O
+ H2O2

OH

enzyme

+ 2 H2O (100 C)
O

43

The reaction scheme of 2-naphthol

(NH3)

SN

OH
+

SEAr

44

SN

Nucleophilic 1,4-addition/substitution
BUCHERER reaction

OH

OH

NH4HSO3

H
NH
- NH4HSO3

NH3

SO3 NH4
NH2

SO3 NH4

45

Summary of phenol synthetic reactions

46