CHAPTER 21PHENOLS 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 OHH3C

Phenol(苯酚）

4-Methylphenol(4-甲基苯酚）

Naphthols or phenanthrols: Compounds that have a hydroxyl group attached to a polycyclic benzenoid ring.

For example:

21.1A NOMENCLATURE OF PHENOLS

(1) In many compounds phenol is the base name. For example:

OH

OH

HO

1

2

2 1

3

34 455 6

6

7

7

88

9 10

1-Naphthol (1-ÝÁ·Ó£©

2-Naphthol (2-ÝÁ·Ó£©

9-Phenanthrol (9-·Æ·Ó£©

Cl OH

NO2

OH

Br

OH4-Chlerophenol(对-氯苯酚）

2-Nitrophenol(临-硝基苯酚）

3-Bromophenol(间-溴苯酚）

(3) The benzenediols also have common names.

(2) The methylphenols are commonly called cresols. For example:

CH3

OH

CH3

OH

H3C OH

2-Methylphenol(临-甲酚）

3-Methylphenol(间-甲酚）

4-Methylphenol(对-甲酚）

OH

OH

OH

OH

HO 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:

OHCH3

H

H

H

HO

OH

Y

CONH2

OH

OH

HN(CH3)2ZHO CH3

O OOH

Estradiol(´Æ¶þ´¼)

Y = Cl, Z = H; Aureomycin (½ðùËØ)Y = H, Z = OH; terramycin (ÍÁùËØ£©

CH2CHCO2-HO

CO2CH3

OH

CH2CH=CH2

OCH3

OH

CH3

OH

CH(CH3)2

NH3+

oil of wintergreen£¨ ¶¬ÇàÓÍ£©

Methyl salicylate(Ë®ÑîËá¼×õ¥£© Eugenol (×Ó¶¡ Ïã ·Û)

Thymo (÷êÏ㠲ݷÓ)thyme (÷êÏã ²ÝÊô)

Tyrosine(ÀÒ°±Ëá)oil of cloves (¶¡ Ïã ÓÍ£©

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-NH2HONO Ar-N2

+ H3O+

heat Ar-OH

Specific Examples:

21.4B INDUSTRIAL SYNTHESIS

1. Hydrolysis of Chlorobenzene

Cl

350¡æ (high pressure)

ONaNaOH HCl

OH

NH2

R

NH2

OH

R

OH

Br

CH3

Br

CH3

(1) NaNO2, H2SO4 0-5¡æ

(2) H3O+, heat

(1) NaNO2, H2SO4 0-5¡æ

(2) H3O+, heat

R = Br 3-Bromophenol 66%R = NO2 3-Nitrophenol 80%

2-Bromo-4-methylphenol 80-92%

2. Alkali Fusion of Sodium Benzenesulfonate

SO3Na

350¡æ (high pressure)

ONaNaOH HCl

OH

benzenesulfonate (±½»ÇËáÄÆ£©

Sodium

3. From Cumene Hydroperoxide

+ CH2=CHCH3 250¡æ

H3PO4pressure

Cumene(Òì±û»ù±½)

Friedel-Crafts alkylation:

Oxidization:

+ O295-135¡æ O O H Cumene hydroperoxide

(¹ý Ñõ»¯Òì±û»ù±½)

Corresponding Mechanism:

Friedel-Crafts alkylation:

H+H

- H+

Oxidization:

HR O2 O O

O O + O O H + C•

Hydrolytic rearrangement:

O O H H+, H2O

50-90¡æOH

O

+Acetone (±ûͪ £©

Hydrolytic rearrangement:

21.5A STRENGTH OF PHENOLS AS ACIDS

25.1 REACTIONS OF PHENOLS AS ACIDS

O O H H+O OH2

- H2O+

O+

phenyl anionmigrationto oxygen

OH2O OO

H

H

HOO

H

C

CH3

CH3

OH- H+

O +

Phenols are much stronger acids than alcohols. For example:

OH OH

Cyclohexanol(»· ¼º́ ¼£©pKa = 18

Phenol(±½·Ó£©pKa = 9.89

(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:

OH

OH

OH

OH

OH

The reason :

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 O-Na+ + H2O

Stronger acidpKa = 10(slightly soluble)

Stronger base

Weaker base (soluble)

Weaker acid pKa = 16

H2O

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:

OOH RCCl

O

baseCR

O

+ Cl

21.6A PHENOLS IN THE WILLIAMSON SYNTHESIS

Phenols can be convert to ethers through the williamson synthesis.

General reaction:

ArOHNaOH ArO-Na+ R-X

X = Cl, Br, I, OSO2R' or ,OSO2OR.

ArOH + NaX

Specific Examples:

OH

CH3

O-Na+

CH3

OCH2CH3

CH3

NaOH CH2CH3_I

+ NaI

OH O-Na+OCH3

+ NaOH H2O 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:

21.8 REACTION OF THE BENZENE RING OF PHENOLS

Bromination:OH

+ 3Br2H2O

OH

BrBr

Br

+ 3 HBr

2,4,6-Tribromophenol (2,4,6-Èýäå±½·Ó£©

H2OOCH3H3C + HBr OHH3C + CH3Br

p-Methylanisole(¶Ô-¼×»ù±½¼×ÃÑ)

4-Methylphenol(4-¼×»ù±½·Ó£©

HBr

no reaction

Methyl bromide (¼×»ùä廯Îï £©

Nitration:

OH OH OH

NO2

NO2

20% HNO3

25¡æ+

(30 - 40 %) (15 %)

Sulfonation:

OH

OH

OH

SO3H

SO3H

concdH2SO4

25¡æ

100¡æ

concd H2SO4, 100¡æ

Major product, rate control

Major product, equilibrium control

The ortho and para can be separated by steam distillation

Kolbe Reaction:

O

OH

COOH

OCCH3

COOH

CH3C_2O+ H+

O

+ CH3COH

O

Salicylic acid (Ë®ÑîËᣩ

Acetic anhydride (ÒÒËáôû£©

Axetylsalicylic acid (ÒÒõ£Ë®ÑîËᣩ

21.9 THE CLAISEN REARRANGEMENT

Claisen rearrangement: heating allyl phenyl ether to 200℃ effects an intramolecular reaction.

OCH2CH=CH2

200¡æ

OH

CH2CH=CH2

o-Allylphenol(¶ÔÏ©±û»ù±½·Ó£©

Allyl phenol ether (Ï©±û»ù·ÓÃÑ£©

14

14

Mechanism:

OCH2

CH

CH2

O

CH2

H

CH

H2C

tautomerization-H+, +H+

OH

CH2

CH

H2C

14 14 14

A Claisen rearrangement also takes place when allyl vinyl ethers are heated.

O heat O O

Allyl vinyl ether(Ï©±û»ùÏ©¶¡ »ùÃÑ£©

Aromatictransition state(·¼»· ¹ý ¶É̬£©

4-Pentenal

21.10 QUINONES

Hydroquinones produces ρ-Benzoquinone by mide oxidizing agents

OH

OH

O

O

-2e-

+2e-

Hydroquinone (¶Ô±½¶þ·Ó)

p-Benzoquinone (¶Ô-±½õ«)

+ 2H+

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 ADDITION – ELIMINATION: THE SNAr MECHANISM

Nucleophilic substitution can occur when strong electron-withdrawing groupsare ortho or para to the halogen atom.

Cl

NO2

OH

NO2

+ OH- aq. NaHCO3

130¡æ

H+

Cl

NO2

NO2

OH

NO2

NO2

+ OH- aq. NaHCO3

100¡æ

H+

Cl

NO2

NO2

O2N

OH

NO2

NO2

O2N

+ OH- aq. NaHCO3

35¡æ

H+

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

NO2

+ OH- additionslow

OHCl

NO2

elimination

fastOH-

+ Cl-

O-

NO2

OH

NO2

+ Cl-

HO Cl

NO O

HO Cl

NO O

HO Cl

NO O

HO Cl

NO O

The delocalized carbanion is stabilized by electron-withdrawing groups in the positions ortho and para to the halogen atom.

CF3

ClNaNH2

NH3

CF3

NH2

m-(Trifluoromethyl)aniline (¶Ô-Èý·ú ¼×»ù±½°±£©

21.11B NUCLEOPHILIC AROMATIC SUBSTITUTION THROUGH AN

ELIMINATION-ADDITION MECHANISM: BENZYNE

Chlorobenzene can be converted to phenol by heating it with aqueous sodiumhydroxide in a pressurized reactor .

Cl

350¡æ (high pressure)

ONaNaOH HCl

OH

Bromobenzene reacts with the very powerful base, in liquid ammonia

Br

+ K+ NH-33¡æ

NH3

NH

+ 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.

Br

K+NH2- NH2

-

NH3

NH2

NH2

(50%)

(50%)

1414

14

14

When the ortho derivative 1 is treated with sodium amide, the only organic product obtained is m-(trifluoromethyl)aniline.

CF3

ClNaNH2

NH3

CF3

NH2

m-(Trifluoromethyl)aniline (¶Ô-Èý·ú ¼×»ù±½°±£©

Mechanism:

CF3

NH

NH3

CF3

NH2

CF3

Cl

H

NaNH2

NH3(-HCl)

CF3

+ NH2

CF3

NH2

NH3

X

1 2

3

4

Less stablecarbanion

More stable cabanion

Carbanion 3 is more stable than 4 because the carbon atom bearing the negative charge is closer to the highly electronegative trifluoro-methyl group.