PhenolsPhenols

Infrared Spectrum of p-Cresol

Chemical shift ( , ppm) Proton NMR CH3CH3CH3CH3 HOHOHOHOHHH H

OCH Oxygen of hydroxyl group deshields carbon to which it is directly attached. The most shielded carbons of the ring are those that are ortho and para to the oxygen. 13 C NMR OHOHOHOH

Prominent peak for molecular ion. Most intense peak in phenol is for molecular ion. m/z 94 Mass Spectrometry OH +

The OH group of phenols allows hydrogen bonding to other phenol molecules and to water. Physical Properties

HOO Hydrogen Bonding in Phenols

Physical Properties C 6 H 5 CH 3 C 6 H 5 OH C6H5FC6H5FC6H5FC6H5F Molecular weight –9543–41 Melting point (°C) Boiling point (°C,1 atm) Solubility in H 2 O (g/100 mL,25°C)

Acidity of Phenols Their most characteristic property

CompareCompare O H pK a = 10 +H + O – CH 3 CH 2 O H pK a = 16 +H + CH 3 CH 2 O –

Delocalized negative charge in phenoxide ion O H H H H H – OH H H H H –

Delocalized negative charge in phenoxide ion OH H H H H – OH H H H H –

Delocalized negative charge in phenoxide ion OH H H H H – OH H H H H –

Phenols are converted to phenoxide ions in aqueous base O H O –+ HO–+ H2OH2OH2OH2O stronger acid weaker acid

Substituent Effects on the Acidity of Phenols

QuestionQuestion Which one of the following has the lowest pK a ? A)B) C)D)

Electron-releasing groups have little or no effect OHOHOHOH CH 3 OHOHOHOH OHOHOHOH OCH 3 pKa:pKa:pKa:pKa:

Electron-withdrawing groups increase acidity OHOHOHOHCl OHOHOHOH OHOHOHOH NO 2 pKa:pKa:pKa:pKa:

Effect of electron-withdrawing groups is most pronounced at ortho and para positions OHOHOHOH NO 2 OHOHOHOH OHOHOHOH pKa:pKa:pKa:pKa:

Effect of strong electron-withdrawing groups is cumulative OHOHOHOH NO 2 OHOHOHOH OHOHOHOH O2NO2NO2NO2N pKa:pKa:pKa:pKa: Picric acid

ResonanceResonance ON H H H H O O – + – O N H H H H –O O – +

QuestionQuestion Which of the following compounds is more acidic? A)o-Cresol B)o-Chlorophenol C)o-Methoxyphenol D)o-nitrophenol E) m-nitrophenol E) m-nitrophenol

Preparation of Aryl Ethers

Typical Preparation is by Williamson Synthesis ONa + RXRXRXRX OROROROR NaX + SN2SN2SN2SN2 but the other combination X + RONa fails because aryl halides are normally unreactive toward nucleophilic substitution

acetone, heat ExampleExample OHOHOHOH + (86%) H2CH2CH2CH2C CHCH 2 Br K 2 CO 3 OCH 2 CH CH 2

Aryl Ethers from Aryl Halides F NO 2 + KOCH 3 CH 3 OH 25°C OCH 3 NO 2 + KFKFKFKF (93%) nucleophilic aromatic substitution is effective with nitro-substituted (ortho and/or para) aryl halides

Claisen Rearrangement of Allyl Aryl Ethers

Allyl Aryl Ethers Rearrange on Heating OCH 2 CH CH 2 200°C OHOHOHOH CH 2 CH CH 2 (73%) allyl group migrates to ortho position

rewrite as MechanismMechanism OCH 2 CH CH 2 O O H keto-to-enol isomerization OHOHOHOH

Claisen rearrangement is an example of a sigmatropic rearrangement. A  bond migrates from one end of a conjugated  electron system to the other. this  bond breaks this  bond forms “conjugated  electron system” is the allyl group Sigmatropic Rearrangement O O H

QuestionQuestion What will be the Claisen rearrangement product of the carbon-14 labeled ether shown here? A) B) C)D)

Oxidation of Phenols: Quinones

The most common examples of phenol oxidations are the oxidations of 1,2- and 1,4-benzenediols to give quinones. (76-81%) QuinonesQuinones OHOHOHOH OHOHOHOHOO Na 2 Cr 2 O 7, H 2 SO 4 H2OH2OH2OH2O

The most common examples of phenol oxidations are the oxidations of 1,2- and 1,4-benzenediols to give quinones. (68%) QuinonesQuinones O O Ag 2 O diethyl ether OHOHOHOH OHOHOHOH CH 3

Alizarin (red pigment) Some quinones are dyes OO OH OH

max 204 nm 256 nm max 204 nm 256 nm max 210 nm 270 nm max 210 nm 270 nm max 235 nm 287 nm max 235 nm 287 nm Oxygen substitution on ring shifts max to longer wavelength; effect is greater in phenoxide ion. UV-VISUV-VISOHO –

Vitamin K (blood-clotting factor) Some quinones are important biomolecules O CH 3 O

Some quinone precursors are important in foods Antioxidants can protect against the cell- damaging effects of free radicals. Some dietary phenolics are oxidized to quinones as free radical-antioxidant traps. Eg. Reservatrol / Flavonoids