Phenols Ar-OH Phenols are compounds with an –OH group attached to an aromatic carbon. Although they share the same functional group with alcohols, where the –OH group is attached to an aliphatic carbon, the chemistry of phenols is very different from that of alcohols.

Nomenclature Phenols are usually named as substituted phenols. The methylphenols are given the special name, cresols. Some other phenols are named as hydroxy compounds.

Physical Properties Phenols are polar and can form hydrogen bond Phenols are water insoluble Phenols are stronger acids than water and will dissolve in 5% NaOH Phenols are weaker acids than carbonic acid and do not dissolve in 5% NaHCO3 Acidity of Phenols. Phenols are more acidic than aliphatic alcohols ROH + H2O H3O+ + RO- ArOH + H2O H3O+ + ArO-

Phenol Acidity Phenols (pKa ~10) are much more acidic than alcohols (pKa ~ 16) due to resonance stabilization of the phenoxide ion Phenols react with NaOH solutions (but alcohols do not), forming soluble salts that are soluble in dilute aqueous A phenolic component can be separated from an organic solution by extraction into basic aqueous solution and is isolated after acid is added to the solution

Factors that influence acidity: Inductive effect: CH3CH2OH FCH2CH2OH F2CHCH2OH F3CCH2OH (F3C)3COH pKa ~ 16.0 14.4 13.3 12.4 5.4 Electron-withdrawing groups make an alcohol a stronger acid by stabilizing the conjugate base (alkoxide) A benzene ring is generally considered electron withdrawing and stabilizes the negative charge through inductive effects Resonance effect: the benzene ring stabilizes the phenoxide ion by resonance delocalization of the negative charge

Substituent Effects on the Acidity of Phenols Electron-donating substituents make a phenol less acidic by destabilizing the phenoxide ion (resonance effect) X= -H -CH3 -OCH3 -NH2 pKa ~ 10 10.3 10.2 10.5

The influence of a substituent on phenol acidity is also Electron-withdrawing substituents: make a phenol more acidic by stabilizing the phenoxide ion through delocalization of the negative charge and through inductive effects. X= -H -Cl -Br -NO2 pKa ~ 10 9.4 9.3 7.2 The influence of a substituent on phenol acidity is also dependent on its position relative to the -OH pKa X= para meta -NO2 7.2 8.4 -OCH3 10.2 9.6 -CH3 10.3 10.1

The effect of multiple substituents on phenol acidity is additive.

Intramolecular Hydrogen Bonding: is possible in some ortho-substituted phenols. This intramolecular hydrogen bonding reduces water solubility and increases volatility. Thus, o-nitrophenol is steam distillable while the isomeric p-nitrophenol is not.

Phenols, syntheses: From diazonium salts 2. Alkali Fusion of Sulfonates

From Hydrolysis of Aryl Halides (Dow Process) From the Oxidation of isopropenyl benzene (Cumene) When exposed to oxygen of the air , hydroperoxide forms

From aryl ketones Reactions: alcohols phenols HX NR PX3 NR dehydration NR as acids phenols are more acidic ester formation similar oxidation NR

Phenols, reactions: as acids ester formation ether formation EAS a) nitration f) nitrosation b) sulfonation g) coupling with diaz. salts c) halogenation h) Kolbe d) Friedel-Crafts alkylation i) Reimer-Tiemann e) Friedel-Crafts acylation

As acids: with active metals: with bases: CH4 < NH3 < HCCH < ROH < H2O < phenols < H2CO3 < RCOOH < HF

NaHCO3 is weak base while NaOH is a strong base CH4 < NH3 < HCCH < ROH < H2O < phenols < H2CO3 < RCOOH < HF NaHCO3 is weak base while NaOH is a strong base

water 5% NaOH 5% NaHCO3 insoluble soluble phenols carboxylic acids

We use the ionization of acids in water to measure acid strength (Ka): HBase + H2O H3O+ + Base- Ka = [H3O+ ][ Base ] / [ HBase] ROH Ka ~ 10-16 - 10-18 ArOH Ka ~ 10-10 Why are phenols more acidic than alcohols?

ROH + H2O H3O+ + RO- ArOH + H2O H3O+ + ArO- Resonance stabilization of the phenoxide ion, lowers the PE of the products of the ionization, decreases the ΔH, shifts the equil farther to the right, makes phenol more acidic than an alcohol

effect of substituent groups on acid strength? Electron withdrawing groups will decrease the negative charge in the phenoxide, lowering the PE, decreasing the ΔH, shifting the equil farther to the right, stronger acid. Electron donating groups will increase the negative charge in the phenoxide, increasing the PE, increasing the ΔH, shifting the equilibrium to the left, weaker acid.

Number the following acids in decreasing order of acid strength (let # 1 = most acidic, etc.) 3 5 1 4 2 1 2 3 4

Ester Formation (similar to alcohols)

Ether Formation (Williamson Synthesis) Ar-O-Na+ + R-X  Ar-O-R + NaX note: R-X must be 1o or CH3 Because phenols are more acidic than water, it is possible to generate the phenoxide in situ using NaOH.

Electrophilic Aromatic Substitution The –OH group is a powerful activating group in EAS and an ortho/para director. a) Nitration

b) Halogenation

c) Sulfonation At low temperature the reaction is non-reversible and the lower Eact ortho-product is formed (rate control). At high temperature the reaction is reversible and the more stable para-product is formed (kinetic control).

d) Friedel-Crafts alkylation.

e) Friedel-Crafts acylation

Fries rearrangement of phenolic esters. Acylation of Phenols. In the absence if AlCl3, phenols react with acid chlorides to afford phenyl esters.

f) Nitrosation

g) Coupling with Diazonium Salts (EAS with the weak electrophile diazonium)

h) Kolbe reaction (carbonation)

i) Reimer-Tiemann reaction

Spectroscopy of phenols: Infrared: O—H stretching, strong, broad 3200-3600 cm-1 C—O stretch, strong, broad ~1230 cm-1 (alcohols ~ 1050 – 1200) nmr: O—H 4-7 ppm (6-12 ppm if intramolecular hydrogen bonding)

o-cresol C--O O--H

o-cresol c b a

ethyl salicylate (intramolecular hydrogen bonding) d c b a