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1、24.6Sources of Phenols,Phenol is an important industrial chemical. Major use is in phenolic resins for adhesives and plastics. Annual U.S. production is about 4 billion pounds per year.,1. NaOH heat,2. H+,1. NaOH heat,2. H+,1. O2,2. H2O H2SO4,IndustrialPreparationsof Phenol,(81-86%),Laboratory Synth
2、esis of Phenols,from arylamines via diazonium ions,24.7Naturally Occurring Phenols,Many phenols occur naturally,CH(CH3)2,OH,CH3,Thymol(major constituent of oil of thyme),Example: Thymol,Cl,OH,Cl,2,5-Dichlorophenol(from defensive secretion ofa species of grasshopper),Example: 2,5-Dichlorophenol,24.8R
3、eactions of Phenols:Electrophilic Aromatic Substitution,Hydroxyl group strongly activates the ringtoward electrophilic aromatic substitution,Halogenation Nitration Nitrosation Sulfonation Friedel-Crafts Alkylation Friedel-Crafts Acylation,Electrophilic Aromatic Substitution in Phenols,Halogenation,m
4、onohalogenation in nonpolar solvent(1,2-dichloroethane),+,Br2,(93%),Halogenation,multiple halogenation in polar solvent(water),+,3Br2,H2O,25C,(95%),Halogenation Nitration Nitrosation Sulfonation Friedel-Crafts Alkylation Friedel-Crafts Acylation,Electrophilic Aromatic Substitution in Phenols,Nitrati
5、on,(73-77%),OH group controls regiochemistry,Halogenation Nitration Nitrosation Sulfonation Friedel-Crafts Alkylation Friedel-Crafts Acylation,Electrophilic Aromatic Substitution in Phenols,Nitrosation,OH,NO,(99%),only strongly activated rings undergo nitrosation when treated with nitrous acid,Halog
6、enation Nitration Nitrosation Sulfonation Friedel-Crafts Alkylation Friedel-Crafts Acylation,Electrophilic Aromatic Substitution in Phenols,SO3H,(69%),H2SO4,100C,Sulfonation,OH group controls regiochemistry,Halogenation Nitration Nitrosation Sulfonation Friedel-Crafts Alkylation Friedel-Crafts Acyla
7、tion,Electrophilic Aromatic Substitution in Phenols,Friedel-Crafts Alkylation,(63%),(CH3)3COH reacts with H3PO4 to give (CH3)3C+,Halogenation Nitration Nitrosation Sulfonation Friedel-Crafts Alkylation Friedel-Crafts Acylation,Electrophilic Aromatic Substitution in Phenols,24.9Acylation of Phenols,A
8、cylation can take place either on the ringby electrophilic aromatic substitution or onoxygen by nucleophilic acyl substitution,Friedel-Crafts Acylation,AlCl3,(74%),+,ortho isomer,(16%),under Friedel-Crafts conditions, acylation of the ring occurs(C-acylation),O-Acylation,(95%),in the absence of AlCl
9、3, acylation of the hydroxyl group occurs (O-acylation),O- versus C-Acylation,AlCl3,formed faster,more stable,O-Acylation is kinetically controlled process; C-acylation is thermodynamically controlled AlCl3 catalyzes the conversion of the aryl ester to the aryl alkyl ketones; this is called the Frie
10、s rearrangement,24.10Carboxylation of Phenols,Aspirin and the Kolbe-Schmitt Reaction,how is salicylic acid prepared?,Aspirin is prepared from salicylic acid,H2SO4,called the Kolbe-Schmitt reaction acidification converts the sodium salt shownabove to salicylic acid,Preparation of Salicylic Acid,CO2,1
11、25C, 100 atm,acid-base considerations provide an explanation:stronger base on left; weaker base on right,What Drives the Reaction?,+,CO2,stronger base: pKa of conjugate acid = 10,weaker base: pKa of conjugate acid = 3,how does carbon-carbon bond form? recall electron delocalization in phenoxide ion
12、negative charge shared by oxygen and by thering carbons that are ortho and para to oxygen,Preparation of Salicylic Acid,CO2,125C, 100 atm,O,C,Mechanism of ortho Carboxylation,O,H,O,C,Mechanism of ortho Carboxylation,O,O,H,O,H,Why ortho?Why not para?,weaker base: pKa of conjugate acid = 3,Why ortho?Why not para?,stronger base: pKa of conjugate acid = 4.5,Hydrogen bonding between carboxylate and hydroxylgroup stabilizes salicylate ion. Salicylate is less basic than para isomer and predominates under conditionsof thermodynamic control.,Intramolecular Hydrogen Bondingin Salicylate Ion,
