Transcript CHAPTER 21 PHENOLS AND ARYL HALIDES

CHAPTER 21
PHENOLS AND ARYL HALIDES
NUCLEOPHILIC AROMATIC
SUBSTITUTION
21.1 STRUCTURE AND NOMENCLATURE OF PHENOLS
Phenol: Compounds that have a hydroxyl group directly attached to a benzene
ring
For example:
OH
H3C
OH
Phenol
4-Methylphenol
(苯酚）
(4-甲基苯酚）
Naphthols or phenanthrols: Compounds that have a hydroxyl group attached
to a polycyclic benzenoid ring.
For example:
HO
OH
8
1
7
2
6
3
5
1
8
OH
2
7
4
1-Naphthol
(1-ÝÁ·Ó£©
9 10
6
2-Naphthol
(2-ÝÁ
·Ó£©
5
4
3
9-Phenanthrol
(9-·Æ·Ó£©
21.1A NOMENCLATURE OF PHENOLS
(1) In many compounds phenol is the base name. For example:
Br
NO2
Cl
OH
OH
4-Chlerophenol
(对-氯苯酚）
2-Nitrophenol
(临-硝基苯酚）
OH
3-Bromophenol
(间-溴苯酚）
(2) The methylphenols are commonly called cresols. For example:
CH3
CH3
OH
H3C
OH
OH
2-Methylphenol
(临-甲酚）
4-Methylphenol
(对-甲酚）
3-Methylphenol
(间-甲酚）
(3) The benzenediols also have common names.
OH
OH
OH
HO
OH
OH
1,2-Benzenediol
(¶ù²è ·Ó,ÁÙ±½¶þ·Ó)
1,3-Benzenediol
(À×Ëö·Ó,¼ä±½¶þ·Ó£©
1,4-Benzenediol
(¶Ô±½¶þ·Ó)
21.2 NATURALLY OCCURRING PHENOLS
Phenols and related compounds occur widely in nature. For
example:
CH2CH=CH2
CO2CH3
CH3
OH
NH3+
CH2CHCO2-
HO
Tyrosine(ÀÒ°±Ëá)
OCH3
OH
OH
CH(CH3)2
Methyl salicylate
Eugenol (×Ó¶¡ Ïã ·Û)
(Ë®ÑîËá¼×õ¥£©
Thymo (÷êÏ㠲ݷÓ)
oil of wintergreen
oil of cloves (¶¡ Ïã ÓÍ£©thyme (÷êÏã ²ÝÊô)
£¨¶¬ÇàÓÍ£©
CH3 OH
OH
O
OH
H
H
O
CONH2
H
HO
Estradiol
(´Æ¶þ´¼)
OH
Y
HO
CH3 Z
H
OH
N(CH3)2
Y = Cl, Z = H; Aureomycin
(½ðùËØ)
Y = H, Z = OH; terramycin
(ÍÁùËØ£©
21.3 PHYSICAL PROPERTIES OF PHENOLS
(1) Having higher boiling points: phenols are able to form
strong intermolecular hydrogen bonds . For example: phenol
(bp,182℃) has a boiling point more than 70℃ higher than
toluene(bp,110.6℃),even though the two molecular have
almost the same molecular weight.
(2) Modest solubility in water: the ability to form strong hydrogen
bonds to molecules of water
21.4 SYNTHESIS OF PHENOLS
21.4A LABORATORY SYNTHESIS
General Reaction:
Ar-NH2
HONO
Ar-N2+
H3O+
heat
Ar-OH
Specific Examples:
NH2
OH
(1) NaNO2, H2SO4
0-5¡æ
(2) H3O+, heat
R
R = Br 3-Bromophenol 66%
R = NO2 3-Nitrophenol 80%
R
NH2
OH
Br
Br
(1) NaNO2, H2SO4
0-5¡æ
(2) H3O+, heat
CH3
2-Bromo-4-methylphenol 80-92%
CH3
21.4B INDUSTRIAL SYNTHESIS
1. Hydrolysis of Chlorobenzene
Cl
NaOH
350¡æ (high pressure)
ONa
OH
HCl
2. Alkali Fusion of Sodium Benzenesulfonate
SO3Na
ONa
NaOH
350¡æ (high pressure)
OH
HCl
Sodium
benzenesulfonate
(±½» ÇËáÄÆ
£©
3. From Cumene Hydroperoxide
Friedel-Crafts alkylation:
+ CH2=CHCH3
H3PO4
250¡æ pressure
Cumene
(Òì±û» ù±½)
Oxidization:
+ O2
95-135¡æ
O O H
Cumene hydroperoxide
(¹ý Ñõ» ¯Òì±û» ù±½)
Hydrolytic rearrangement:
O O H
O
H+, H2O
50-90¡æ
OH
Acetone
+
(±ûͪ £©
Corresponding Mechanism:
Friedel-Crafts alkylation:
H
H+
- H+
Oxidization:
H
R
O O
O2
+
O O
O O H
+
C•
Hydrolytic rearrangement:
O O H
H+
H2O
O
O+
O
O
H
CH3H
O
- H2O
H
phenyl anion
migration
to oxygen
H
+
O OH2
C
O
- H+
O
+
HO
CH3
25.1 REACTIONS OF PHENOLS AS ACIDS
21.5A STRENGTH OF PHENOLS AS ACIDS
Phenols are much stronger acids than alcohols. For example:
Cyclohexanol
OH
Phenol
(» ·¼º´¼£©
OH
pKa = 18
(±½·Ó£©
pKa = 9.89
The reason :
(1) The carbon atom that bears the hydroxyl group in phenol is
sp2-hybridized, whereas, in cyclohexane , it is sp3 –hybridized.
(2) Resonance structures for phenol:
H
O
H
O
H
H
O
O
H
O
21.5B DISTINGUISHING AND SEPARATING PHENOLS
FROM ALCOHOLS AND CARBOXYLIC ACIDS
Phenols dissolve in aqueous sodium hydroxide : Phenols are more
acidic than water.
OH + NaOH
Stronger acid
Stronger
pKa = 10
base
(slightly soluble)
H2O
O-Na+ + H2O
Weaker
base
(soluble)
Weaker acid
pKa = 16
Whereas most alcohols with six carbon atoms or more do not
dissolve in aqueous sodium hydroxide .
we can distinguish And separate phenols from most alcohols
by this way.
21.6 OTHER REACTION PF THE OH- GROUP OF PHENOL
Phenols react with carboxylic acid anhydrides and acid chlorides
to form esters. For example:
OH
O
RCCl
O
O CR
base
+ Cl
21.6A PHENOLS IN THE WILLIAMSON SYNTHESIS
Phenols can be convert to ethers through the williamson synthesis.
General reaction:
ArOH
NaOH
ArO-Na+
R-X
X = Cl, Br, I, OSO2R'
or ,OSO2OR.
ArOH + NaX
Specific Examples:
O-Na+
OH
CH2CH3_ I
NaOH
CH3
OCH2CH3
CH3
+ NaI
CH3
O-Na+
OH
+ NaOH H2O
OCH3
CH3OSO3OCH3
+ NaOSO2OCH3
21.7 CLEAVAGE OF ALKYL ARYL ETHERS
When alkyl aryl ethers react with strong acids such as HI and HBr,
the reaction produces an alkyl halide and a phenol. For example:
Specific Example:
H3C
OCH3 + HBr H2O
OH + CH3Br
H3C
4-Methylphenol
p-Methylanisole
(4-¼×» ù±½·Ó£©
(¶Ô-¼×» ù±½¼×ÃÑ)
Methyl bromide
(¼×» ùäå » ¯Îï £©
HBr
no reaction
21.8 REACTION OF THE BENZENE RING OF PHENOLS
Bromination:
OH
OH
Br
+ 3Br2
Br
H2O
+ 3 HBr
Br
2,4,6-Tribromophenol
(2,4,6-Èýäå ±½·Ó£©
Nitration:
OH
OH
OH
The ortho and para
can be separated by
steam distillation
NO2
20% HNO3
+
25¡æ
(30 - 40 %)
NO2
(15 %)
Sulfonation:
OH
SO3H
OH
25¡æ
Major product, rate control
concd
OH
H2SO4
concd H2SO4, 100¡ æ
100¡æ
Major product, equilibrium control
SO3H
Kolbe Reaction:
O
OH
OCCH3
COOH
+
Salicylic acid
(Ë®ÑîËᣩ
COOH
O
CH3C_ O
2
+
H
Acetic anhydride
O
+ CH3COH
Axetylsalicylic acid
(ÒÒõ£Ë®ÑîËᣩ
(ÒÒËáôû£©
21.9 THE CLAISEN REARRANGEMENT
Claisen rearrangement: heating allyl phenyl ether to 200℃ effects an
intramolecular reaction.
14
OCH2CH=CH2
OH
14
200¡æ
Allyl phenol ether
(Ï©±û» ù·ÓÃÑ£©
CH2CH=CH2
o-Allylphenol
(¶ÔÏ©±û» ù±½·Ó£©
Mechanism:
O
CH
O
H2C
H2C
CH2
14CH
14 CH
2
2
OH
CH
H
tautomerization
-H+, +H+
CH
14CH
2
A Claisen rearrangement also takes place when allyl vinyl ethers are heated.
O
heat
Allyl vinyl ether
(Ï©±û» ùÏ©¶¡ » ùÃÑ£©
O
Aromatic
transition state
(·¼» ·¹ý ¶É̬ £©
O
4-Pentenal
21.10 QUINONES
Hydroquinones produces ρ-Benzoquinone by mide oxidizing agents
OH
O
-2e+2e-
OH
Hydroquinone
(¶Ô±½¶þ·Ó)
+ 2H+
O
p-Benzoquinone
(¶Ô-±½õ«)
ρ-Benzoquinone is easily reduced by mild reducing agents to hydroquinones
21.11 ARYL HALIDES AND NUCLEOPHILIC AROMATIC
SUBSTITUTION
Aryl halides and vinylic halides are relatively unreactive toward
nucleophilic substitution under conditions that give facile nucleophilic
substitution with alkyl halides.
Reason:
(1) Phenyl cations are very unstable.
(2) Halogen bonds of aryl (and vinylic) halides are shorter and
stronger than those of alkyl, allylic, and benzylic halides because
of the hybridized state and the resonance.
But aryl halides can be remarkably reactive toward nucleophiles
if they bear certain substituents or when we allow them to react
under the proper conditions.
21.11A NUCLEOPHILIC AROMATIC SUBSTITUTION BY ADD
ELIMINATION: THE SNAr MECHANISM
Nucleophilic substitution can occur when strong electron-withdrawing groups
are ortho or para to the halogen atom.
Cl
OH
NO2
NO2
H+
aq. NaHCO3
+ OH130¡æ
OH
Cl
NO2
+ OH-
NO2
+
H
aq. NaHCO3
100¡æ
NO2
NO2
OH
Cl
O2N
NO2
+ OHNO2
aq. NaHCO3
+
O2N
NO2
H
35¡æ
NO2
The temperature
is related to the
number of ortho or
para nitro groups
But the meta-nitro group does not produce a similar activating effect.
Mechanism:
Cl
Cl
elimination
fast
addition
slow
-
+ OH
NO2
NO2
CF3
O-
OH
OH
+ Cl- OH
+ ClNO2
NO2
CF3
Cl
m-(Trifluoromethyl)aniline
NaNH2
NH3
(¶Ô-Èý·ú ¼×» ù±½°±£©
NH2
The delocalized carbanion is stabilized by electron-withdrawing groups in the
positions ortho and para to the halogen atom.
HO
O
N
Cl
HO
O
O
Cl
HO
O
O
N
N
Cl
HO
O
O
Cl
N
O
21.11B NUCLEOPHILIC AROMATIC SUBSTITUTION THROUGH AN
ELIMINATION-ADDITION MECHANISM: BENZYNE
Chlorobenzene can be converted to phenol by heating it with aqueous sodium
hydroxide in a pressurized reactor .
Cl
ONa
NaOH
350¡æ (high pressure)
OH
HCl
Bromobenzene reacts with the very powerful base, in liquid ammonia
Br
NH
+
K+ NH
-33¡æ
NH3
+ KBr
Aniline
(±½°· £©
C-14 bromobenzene is treated with amide ion in liquid ammonia, the aniline that
is produced between the 1 and 2 position.
14
Br
14
14
K+NH2-
NH2
(50%)
NH2NH3
14
(50%)
NH2
When the ortho derivative 1 is treated with sodium amide, the only organic
product obtained is m-(trifluoromethyl)aniline.
CF3
CF3
Cl
m-(Trifluoromethyl)aniline
NaNH2
NH3
(¶Ô-Èý·ú ¼×» ù±½°±£©
NH2
Mechanism:
CF3
CF3
Cl
H
1
NaNH2
X
NH3
NH3
(-HCl)
Less stable
carbanion
NH
CF3
CF3
4
CF3
2
NH2
NH3
+ NH2
NH2
3
More stable
cabanion
Carbanion 3 is more stable than 4 because the carbon atom bearing
the negative charge is closer to the highly electronegative trifluoromethyl group.