CHAPTER 8

ALCOHOL- PHENOL

LECTURER: PHAN THỊ HOÀNG ANH 1

 A. ALCOHOL

Common name: Alkyl + alcohol

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NOMENCLATURE

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PREPARATION

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• Hydration of alkenes

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• Diols from alkenes

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• Alcohol from RX and Grignard reagents

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Reduction of carbonyl compounds
Reducing agents H2 (Pd, Pt, Ni..)
NaBH4/methanol
1. LiAlH4/diethyl ether, 2. H2O

NaBH4, LiAlH4 do not

reduce >C=C< 9
• NaBH4 and LiAlH4 function as a source of hydride (H-) and
the solvent functions as the source of a proton (H+)

LAN (LiAlH4) is much stronger reagent than NaBH4, reacts violently

with protic solvent → a protic source is added in a separated step.10
Reduction of acids, esters
Reducing agents : 1.LiBH4, diethyl ether, 2.H2O

H2 , NaBH4 cannot reduce acids and acid derivatives 11

REACTIONS OF ALCOHOLS
Nucleophile

weak acid

Electrophile

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Acidity of alcohols, phenols
RH < NH3 < HC≡CH < C2H5-OH < H2O < C6H5-OH
pKa 50 36 25 16 15.7 10

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2. Nucleophilic substitution of ROH
SN

HO- is a strong base (a poor leaving group) → cannot

undergo nucleophilic substitution unless OH is converted
to a group that is a weak base (better leaving group) 14
2.1. Reaction with HX

Poor leaving group

Better leaving group

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 Mechanism: 1o alcohol → SN2
2o and 3o alcohols → SN1 →
carbocation rearrangement ??

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2.2. Reaction with SOCl2 (thionyl chloride)
PBr3, PI3 (phosphorus trihalide)
pyridine

pyridine

SN2 mechanism → no carbocation rearrangement

tertiary alcohols give poor yields

pyridine

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Pl3, PBr3, SOCl2 convert –OH into a good leaving group

Good leaving
group

SN2

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SN2

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2.3. Conversion of alcohols to ethers

Effective only with 1o alcohol

Elimination to form alkene predominates with 2o and 3o
alcohols and higher temperature

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Step 1

Step 2

Step 3

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2.4. Dehydration of alcohols → alkenes

Acid catalyst, H2SO4, H3PO4 are the most commonly used

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 2o, 3o alcohols → E1 → carbocation rearrangement ??

carbocation rearrangement

Major product follow Zaitsev’s rule

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1o alcohol : E2, however, rearrange can occur
1-alkene forming in acidic solution can rearrange to form
internal 2-alkene

1-Alkenes
rearrange in
acidic solution

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3. ROH as a Nucleophile

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3.1. Fischer esterification of alcohols

Reactivity :
RCOCl > (RCO)2O > RCOOH (need acid catalysts)
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3.2. Converting alcohols to sulfonate esters:

→ Convert OH → OSO2R – an excellent leaving group

Poor leaving group Excellent leaving group 30

Some common sulfonyl chlorides

SN2

100 times better than a chloride

ion as a leaving group

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Pyridine is used both as the solvent and to prevent HCl from building up.

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4. Oxidation of alcohols
Common oxidation reagents:
KMnO4, H2CrO4, CrO3/H+, Na2CrO4/H+ … oxidize 1o alcohol
to an carboxylic acid

PCC (pyridinium chlorochromate)

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 PCC, PDC do not affect
double bonds

Tertiary alcohols have no hydrogen on their hydroxyl-bearing

carbon and do not undergo oxidation readily. 35
B. PHENOL

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 PREPARATION OF PHENOL
1. Oxidation of cumene (industrial method)

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2. Hydrolysis chlorobenzene:

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3. From benzenesulfonic acid:

4. Hydrolysis of diazonium

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 REACTIONS OF PHENOL
1. Acidity of phenol:
H2CO3 > phenol > H2O > ROH

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2. Preparation of aryl ether:

→ Williamson reaction

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3. Acylation of phenol:
3.1. O-acylation (esterification of OH phenol)

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3.2. C-acylation → Friedel-Crafts acylation
Without AlCl3 or Lewis acis →
O-acylation

In the presence of AlCl3

or Lewis acid
→ C-acylation
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4. Electrophilic substitution of phenol:
OH is a strong activating group → SE in phenols occurs far faster,
and under milder conditions, than in benzene.
Non-polar solvent →
4.1. Halogenation mono-substitution

Polar solvent →
multi-substitution

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4.2. Nitration, sulfonation of phenol

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4.3. Alkylation and acylation F-C:

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4.4. Kolbe-Schmitt reaction
Introduce COOH substituent to ortho-position of phenol

→ Aspirin synthesis

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5. Oxidation of phenol
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4
M.-pr.24.17
to
a)

b)

c)

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d)

e)

f)

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g)

h)

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