CHAPTER 21 PHENOLS AND ARYL HALIDES NUCLEOPHIILIC AROMATIC SUBSTITUTION 21.1 STRUCTURE AND NOMENCLATURE OF PHENOLS Phenol: Compounds that have a hydroxyl group directly attached to a benzene rins For example OH H3C一 OH 4-Methylphenol (苯酚) (4-甲基苯酚)
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 H3 C OH 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 OH HO 1-Naphthol 2-Naphthol 9-Phenanthrol (1-萘酚)(2-萘酚) (9-菲酚) 21.1A NOMENCLATURE OF PHENOLS (1In many compounds phenol is the base name. For example 4-Chlerophenol 2-Nitrophenol 3-Bromophenol (对-氯苯酚) (临-硝基苯酚) (间-溴苯酚)
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 5 4 5 4 3 6 6 7 7 8 8 9 10 1-Naphthol (1-萘酚） 2-Naphthol (2-萘酚） 9-Phenanthrol (9-菲酚） Cl OH NO2 OH Br OH 4-Chlerophenol (对-氯苯酚） 2-Nitrophenol (临-硝基苯酚） 3-Bromophenol (间-溴苯酚）
(2)The methylphenols are commonly called cresols. For example CH CH OH H2C OH OH 2-Methylphenol 3-Methylphenol 4-Methylphenol (临-甲酚) 间-甲酚) (对-甲酚) ()The benzenediols also have common names OH OH OH HO OH OH 1.2-Benzenediol 1.3-Benzenediol 1. 4-Benzenediol (儿茶酚临苯二酚)(雷琐酚,间苯二酚)(对苯二酚)
(3) The benzenediols also have common names. (2) The methylphenols are commonly called cresols. For example: CH3 OH CH3 OH H3 C 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 (儿茶酚,临苯二酚) 1,3-Benzenediol (雷琐酚,间苯二酚） 1,4-Benzenediol (对苯二酚)
21.2 NATURALLY OCCURRING PHENOLS Phenols and related compounds occur widely in nature For example CH,CH=CH CH CO,CH OH NH OCI OH HO CH2CHCO2 Methyl salicylate CH( CH3)2 (水杨酸甲酯) Tyrosine(酪氨酸) oil of wintergreen Eugenol(子丁香粉) Thyme(麝香草酚) (冬青油) oil of cloves(丁香油) thyme(麝香草属) oH O OH O OH CONH2 Y=Cl, Z=H; Aureomycin (金霉素) OH Y=H, Z=OH; terramycin Estradiol HO CH3 Z H N(CH3h (土霉素) (雌二醇)
21.2 NATURALLY OCCURRING PHENOLS Phenols and related compounds occur widely in nature. For example: OH CH3 H H H HO OH Y CONH2 OH OH H N(CH3 ) Z 2 HO CH3 O OH O Estradiol (雌二醇) Y = Cl, Z = H; Aureomycin (金霉素) Y = H, Z = OH; terramycin (土霉素） CH2 CHCO2 HO - CO2CH3 OH CH2 CH=CH2 OCH3 OH CH3 OH CH(CH3)2 NH3 + oil of wintergreen （冬青油） Methyl salicylate (水杨酸甲酯） Eugenol (子丁香粉) Thymo (麝香草酚) thyme (麝香草属) Tyrosine(酪氨酸) oil of cloves (丁香油）
213 PHYSICAL PROPERTIES OF PHENOLS (1) Having higher boiling points: phenols are able to form strong intermolecular hydrogen bonds. For example: phenol (bp, 182C)has a boiling point more than 70'C higher than toluene(bp, 110.6 C),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 214A LABORATORY SYNTHESIS General reaction HONO hao+ Ar-NH, Ar-N2 heat Ar-OH
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 + H3 O + heat Ar-OH
Specific Examples NH OH (1)NaNO, H2SOL R=Br 3-Bromophenol 66% (2)H3O, heat R=NO,3-Nitrophenol 80% R NH2 Br (1) NaNO2, H2So 0-5℃ (2)H3O, heat 2-Bromo-4-methylphenol 80-92% CH3 CH 214B INDUSTRIAL SYNTHESIS Hydrolysis of chlorobenzene Cl ONa Naoh 350℃( high pressure
Specific Examples: 21.4B INDUSTRIAL SYNTHESIS 1. Hydrolysis of Chlorobenzene Cl 350℃ (high pressure) ONa NaOH HCl OH NH2 R NH2 OH R OH Br CH3 Br CH3 (1) NaNO2 , H2SO4 0-5℃ (2) H3O + , heat (1) NaNO2 , H2 SO4 0-5℃ (2) H3O + , heat R = Br 3-Bromophenol 66% R = NO2 3-Nitrophenol 80% 2-Bromo-4-methylphenol 80-92%
2. Alkali Fusion of sodium benzenesul fonate SOrNa ONa Naoh HCI 350℃( high pressure) Sodiu benzenesulfonate (苯磺酸钠) 3. From Cumene hydroperoxide Friedel-Crafts alkylation HaPO Ch2-CHCa3 250C pressure Cumene (异丙基苯) Oxidization: 5-135℃ 0-0-H Cumene hydroperoxide (过氧化异丙基苯
2. Alkali Fusion of Sodium Benzenesulfonate SO3 Na 350℃ (high pressure) ONa NaOH HCl OH benzenesulfonate (苯磺酸钠） Sodium 3. From Cumene Hydroperoxide + CH2 =CHCH3 250℃ H3 PO4 pressure Cumene (异丙基苯) Friedel-Crafts alkylation: Oxidization: + O2 95-135℃ O O H Cumene hydroperoxide (过氧化异丙基苯)
Hydrolytic rearrangement 0-0-H H, HO Acetone oH 50-90℃ (丙酮) Corresponding mechanism Friedel-Crafts alkylation: Oxidization O O-0·+ O-0-H
Corresponding Mechanism: Friedel-Crafts alkylation: H + H - H + Oxidization: H R O2 O O O O + O O H + C• Hydrolytic rearrangement: O O H H + , H2O 50-90℃ OH O + Acetone (丙酮）
Hydrolytic rearrangement: 0-0-H H O-OH phenyl anion migration H2O to oxygen CH3H H-0-C-O CH 25.1 REACTIONS OF PHENOLS AS ACIDS 215A STRENGTH OF PHENOLS ASACIDS
Hydrolytic rearrangement: 21.5A STRENGTH OF PHENOLS AS ACIDS 25.1 REACTIONS OF PHENOLS AS ACIDS O O H H + O OH2 + - H2 O O + phenyl anion migration to oxygen O H2 O O O H H O HO H C CH3 CH3 H O - H+ O +
Phenols are much stronger acids than alcohols. For example C ycionexano Phenol OH(环己醇) OH(苯酚) pKa=l8 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 H H H O O O
Phenols are much stronger acids than alcohols. For example: OH OH Cyclohexanol (环己醇） pKa = 18 Phenol (苯酚） 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: O H O H O H O H O H The reason :