台灣大學開放式課程

有機化學乙
蔡蘊明 教授

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Chapter 21
Phenols, aryl halides and sulfur compounds

※ Structure and nomenclature of phenols

CH3

OH H3C OH
OH

phenol 4-methylphenol
(p-cresol) 2-methylphenol
(o-cresol)
OH
OH

1-naphthol 2-naphthol
(α-naphthol) (β-naphthol)

OH
HO OH
HO OH HO
hydroquinone
1,2-benzenediol resorcinol
(catechol)
※ Properties
Alcohol like, but more acidic

OH O− O O O

H+ +

resonance stabilized
H
O

etc.

Not as stabilized
due to charge separation
 O
OH OH
H3C OH

pKa = 9.89 pKa = 18 pKa = 4.74

OH OH Cl OH

Cl Cl
8.11 8.80 9.20
OH OH
NO2 O2N NO2
OH OH O2N OH

NO2 O2N NO2 NO2

7.17 8.28 7.15
3.96 0.38

picric acid
O no such O 苦味酸
N O
stabilization O
N O
O
 OH + NaOH O− Na+ + H2O

water insoluble water soluble

OH + NaHCO3 x

not basic enough

can be used to separate phenols from acids
※ Synthesis of phenol
 From diazonium salt
HONO H3O+
Ar NH2 Ar N2 Ar OH
∆

例
NH2 OH
o
1) NaNO2, H2SO4, 0-5 C
2) H3O+, ∆
NO2 NO2
※ Reactions of the oxygen

◎ O-alkylation or acylation
OH ONa OCH3
NaOH CH3OSO2OCH3

anisole

OH OEt + NaOSO2OCH3
1) NaOH
2) EtI

CH3 CH3

OH O O

R Cl O R
or
O O
R O R
 O

OH O CH3
COOH Ac2O COOH
+ CH3COOH

acetylsalicylic acid
(Aspirin)

cf.
OH

CH3
acetaminophen
(Tylenol) C COOH
H
HN CH3
ibuprofen (Advil)
O
◎ Reactions of the ring
 Electrophilic aromatic substitution
Phenols are electron rich
 highly reactive
OH OH
Br Br
H2O
+ 3 Br2 + 3 HBr

Lewis acid
not necessary Br
※ Quinones
OH O
−2 e−
+ 2 H+
−
+2 e
OH O
hydroquinone p-benzoquinone
Reduction potential: Eo = 0.699
 In photography
hν
AgBr AgBr*
sesitized
OH O

+ AgBr* + Ago
black
OH O
 Biological system
O
H3CO CH3 ubiquinones (n = 6-10)
(coenzyme Q) involved in
H3CO H electron-transport systems
O n

O
CH3
Vitamin K
H
O n

1,4-naphthoquinone This part is to promote fat solubility

structure (Eo = 0.47)
※ Antioxidant
CH3
H3C O
CH3
α-tocopherol
CH3
n (vitamin E)
HO
CH3 a natural antioxidant

OH
butylated hydroxytoluene
(BHT)
CH3
a food preservative

O
very unreactive
 resonance stabilization and steric effect
CH3
※ Nucleophilic aromatic substitution
Cl
H2O
+ NaOH NR
reflux

but Cl
o
ONa OH
NO2 130 C +
NO2 H NO2
+ NaHCO3(aq)
(OH−)

Cl OH
NO2 100 oC NO2
H+
+ NaHCO3(aq)

NO2 NO2

Cl OH
O2N NO2 O2N NO2
35 oC H+
+ NaHCO3(aq)

NO2 NO2
Reason: an addition followed by elimination mechanism
Cl Cl OH Cl OH Cl OH
−
OH

N N N N
O O O O O O O O

OH Cl OH Cl OH
−Cl−

NO2 NO2 N
O O

NO2 at 2, 4 and 6 position

 more effective A resonance stabilized
delocalized carbanion
 more NO2, more stabilization
(Meisenheimer complex)
NO2 at meta position:
Cl
H2O
+ NaOH NR
reflux
NO2
※ Thiols, Thioethers and disulfides

RSH thiols RSR’ thioethers

RS-SR’ disulfides
 Thiols
also called mercaptans

OH
Used as antidote for mercury poisoning
HS SH

CH3CH2SH PrSH SH
ethanethiol 1-propanethiol 3-methyl-1-butanethiol
(ethyl mercaptan) (in onion) (in skunks)

SH 2-propene-1-thiol
(in garlic)
※ Special feature of sulfur

 More polarizable than oxygen

RSH RS− + H+
pKa ~9-10
more stable than RO−
 RSH is more acidic than ROH

− −
 RS is a stronger nucleophile than RO

larger: less solvation

more polarizable: stabilizes transition state
 RSH oxidized easily
H2O2
2 RSH RSSR

 Stabilizes negative charge on adjacent atom

SCH3 + BuLi SCH2 + BuH

Li+
thioanisole

CH3Br CH3 base CH3

CH3SCH3 H3C S CH3 H3C S CH2

Br− a sulfur ylide

※ Preparation of thiols and sulfides
EtOH
R Br + KOH + H2S R SH + KBr + H2O
∆
(excess)

KOH
R SH + R' Br R S R'

R
S EtOH S 1) HO−, H2O
+ R Br R SH
+
H2N NH2 H2N NH2 2) H
+

−
O
HO
H2N NH2
R
S

H2N NH2
O
H

HO−
Chapter 23 Lipids

Compounds of biological origin

Insoluble in water
Soluble in organic solvent

Fats

Oils

Terpenoids and steroids

※ Terpenes and terpenoids

Structurally build up from C5 units: isoprene units

C
C C
C C
isoprene
(2-methyl-1,3-butadiene) an isoprene unit
 Terpenes: hydrocarbons
C10 monoterpenes
C15 sesquiterpenes
C20 diterpenes
C30 triterpenes

 Terpenoids: with extra oxygen functionalities

例

OH

limonene menthol

caryophyllene
(from cloves)
 Related biological chemistry
O OH O O OH O OPO32−
− − −
O SCoA O OH O OP2O63−

HMG-CoA

OP2O63−

+
isopentenyl pyrophosphate
H

OP2O63− OP2O63−
OP2O63−
H
B−

OP2O63− OP2O63− OP2O63−

geranyl diphosphate