phenolsphenols. infrared spectrum of p-cresol 01.02.03.04.05.06.07.08.09.010.0 chemical shift ( ,...

PhenolsPhenolsPhenolsPhenols

Infrared Spectrum of Infrared Spectrum of pp-Cresol-CresolInfrared Spectrum of Infrared Spectrum of pp-Cresol-Cresol

01.02.03.04.05.06.07.08.09.010.0

Chemical shift (Chemical shift (, ppm), ppm)

Proton NMRProton NMRProton NMRProton NMR

CCHH33HHOO

HH HH

HHHH

OOCHCH33

129.5129.5

114.0114.0

159.7159.7

120.7120.7

Oxygen of hydroxyl group deshields carbonOxygen of hydroxyl group deshields carbonto which it is directly attached.to which it is directly attached.

The most shielded carbons of the ring are those thatThe most shielded carbons of the ring are those thatare ortho and para to the oxygen.are ortho and para to the oxygen.

1313C NMRC NMR1313C NMRC NMR

OOHH

129.8129.8

115.5115.5

155.1155.1

121.1121.1

128.5128.5

Prominent peak for molecular ion. Most intense Prominent peak for molecular ion. Most intense peak in phenol is for molecular ion.peak in phenol is for molecular ion.

m/z m/z 9494

Mass SpectrometryMass SpectrometryMass SpectrometryMass Spectrometry

OHOH••++

••••

The OH group of phenols allows hydrogen bondingThe OH group of phenols allows hydrogen bondingto other phenol molecules and to water.to other phenol molecules and to water.

Physical PropertiesPhysical PropertiesPhysical PropertiesPhysical Properties

HH OOOO

Hydrogen Bonding in PhenolsHydrogen Bonding in PhenolsHydrogen Bonding in PhenolsHydrogen Bonding in Phenols

Physical PropertiesPhysical PropertiesPhysical PropertiesPhysical Properties

CC66HH55CHCH33 CC66HH55OHOH CC66HH55FF

Molecular weightMolecular weight 9292 9494 9696

––9595 4343 ––4141Melting point (°C)Melting point (°C)

BoilingBoilingpoint (°C,1 atm)point (°C,1 atm)

111111 132132 8585

Solubility inSolubility inHH22O (g/100 mL,25°C)O (g/100 mL,25°C)

0.050.05 8.28.2 0.20.2

Acidity of PhenolsAcidity of Phenols

Their most characteristic propertyTheir most characteristic property

CompareCompareCompareCompare

OO HH••••••••

ppKKaa = 10 = 10++HH ++

OO••••••••

••••––

CHCH33CHCH22OO HH••••

••••

ppKKaa = 16 = 16++HH ++ CHCH33CHCH22OO

••••

••••

––••••

Delocalized negative charge in phenoxide ionDelocalized negative charge in phenoxide ionDelocalized negative charge in phenoxide ionDelocalized negative charge in phenoxide ion

•••• OO••••

HH

HH

HH

HH

HH

••••––

•••• OO••••

HH

HH

HH

HH

HH

––••••

Delocalized negative charge in phenoxide ionDelocalized negative charge in phenoxide ionDelocalized negative charge in phenoxide ionDelocalized negative charge in phenoxide ion

•••• OO••••

HH

HH

HH

HH

HH

––••••

•••• OO••••

HH

HH

HH

HH

HH––••••

Delocalized negative charge in phenoxide ionDelocalized negative charge in phenoxide ionDelocalized negative charge in phenoxide ionDelocalized negative charge in phenoxide ion

•••• OO••••

HH

HH

HH

HH

HH––••••

•••• OO••••

HH

HH

HH

HH

HH

––••••

Phenols are converted to phenoxide ionsPhenols are converted to phenoxide ionsin aqueous basein aqueous base

Phenols are converted to phenoxide ionsPhenols are converted to phenoxide ionsin aqueous basein aqueous base

OO HH••••••••

OO••••••••

••••––

++ HOHO–– ++ HH22OO

stronger acidstronger acid weaker acidweaker acid

Substituent EffectsSubstituent Effectson theon the

Acidity of PhenolsAcidity of Phenols

Substituent EffectsSubstituent Effectson theon the

Acidity of PhenolsAcidity of Phenols

QuestionQuestionQuestionQuestion

Which one of the following has the lowest pWhich one of the following has the lowest pKKaa??

A)A) B)B)

C)C) D)D)

Electron-releasing groups have little or no effectElectron-releasing groups have little or no effectElectron-releasing groups have little or no effectElectron-releasing groups have little or no effect

OOHH

CHCH33

OOHH OOHH

OCHOCH33

ppKKaa:: 1010 10.310.3 10.210.2

Electron-withdrawing groups increase acidityElectron-withdrawing groups increase acidityElectron-withdrawing groups increase acidityElectron-withdrawing groups increase acidity

OOHH

ClCl

OOHH OOHH

NONO22

ppKKaa:: 1010 9.49.4 7.27.2

Effect of electron-withdrawing groups is mostEffect of electron-withdrawing groups is mostpronounced at ortho and para positionspronounced at ortho and para positions

Effect of electron-withdrawing groups is mostEffect of electron-withdrawing groups is mostpronounced at ortho and para positionspronounced at ortho and para positions

OOHH

NONO22

OOHH

NONO22

OOHH

NONO22

ppKKaa:: 7.27.2 8.48.4 7.27.2

Effect of strong electron-withdrawing groupsEffect of strong electron-withdrawing groupsis cumulativeis cumulative

Effect of strong electron-withdrawing groupsEffect of strong electron-withdrawing groupsis cumulativeis cumulative

OOHH

NONO22

OOHH

NONO22

NONO22

OOHH

NONO22

NONO22

OO22NN

ppKKaa:: 7.27.2 4.04.0 0.40.4

Picric acidPicric acid

Resonance Resonance Resonance Resonance

•••• OO••••

NN

HH

HH

HH

HH

••••OO OO

••••

••••

•••••••••••• ––

++

••••

––

•••• OO••••

NN

HH

HH

HH

HH

••••

––

OO OO

••••

••••

•••••••••••• ––

++

QuestionQuestionQuestionQuestion

Which of the following compounds is more Which of the following compounds is more acidic?acidic?

A)A) oo-Cresol-Cresol

B)B) oo-Chlorophenol-Chlorophenol

C)C) oo-Methoxyphenol-Methoxyphenol

D)D) oo-nitrophenol-nitrophenol

E) m-nitrophenolE) m-nitrophenol

Preparation of Aryl EthersPreparation of Aryl EthersPreparation of Aryl EthersPreparation of Aryl Ethers

Typical Preparation is by Williamson SynthesisTypical Preparation is by Williamson SynthesisTypical Preparation is by Williamson SynthesisTypical Preparation is by Williamson Synthesis

OONaNa ++ RRXX

OORR NaNaXX++SSNN22

but the other combinationbut the other combination

XX ++ RROONaNa

fails because aryl halides are normally unreactivefails because aryl halides are normally unreactivetoward nucleophilic substitutiontoward nucleophilic substitution

acetone, heatacetone, heat

ExampleExampleExampleExample

OOHH ++

(86%)(86%)

HH22CC CHCHCHCH22BrBr

KK22COCO33

OOCHCH22CHCH CHCH22

Aryl Ethers from Aryl HalidesAryl Ethers from Aryl HalidesAryl Ethers from Aryl HalidesAryl Ethers from Aryl Halides

FF

NONO22

++ KKOOCHCH33

CHCH33OHOH

25°C25°C

OOCHCH33

NONO22

++ KKFF

(93%)(93%)

nucleophilic aromatic substitution is effective nucleophilic aromatic substitution is effective with nitro-substituted (ortho and/or para) aryl with nitro-substituted (ortho and/or para) aryl halides halides

Claisen RearrangementClaisen Rearrangement

of Allyl Aryl Ethersof Allyl Aryl Ethers

Claisen RearrangementClaisen Rearrangement

of Allyl Aryl Ethersof Allyl Aryl Ethers

Allyl Aryl Ethers Rearrange on HeatingAllyl Aryl Ethers Rearrange on HeatingAllyl Aryl Ethers Rearrange on HeatingAllyl Aryl Ethers Rearrange on Heating

OOCHCH22CHCH CHCH22

200°C200°C

OOHH

CHCH22CHCH CHCH22

(73%)(73%)

allyl group allyl group migrates to migrates to ortho positionortho position

rewrite as rewrite as

MechanismMechanismMechanismMechanism

OOCHCH22CHCH CHCH22

OO

OO

HH

keto-to-enolketo-to-enolisomerizationisomerization

OOHH

Claisen rearrangement is an example of a Claisen rearrangement is an example of a sigmatropic rearrangement. A sigmatropic rearrangement. A bond migrates bond migratesfrom one end of a conjugated from one end of a conjugated electron system electron systemto the other.to the other.

this this bond breaks bond breaks

this this bond forms bond forms

““conjugated conjugated electron system” electron system” is the allyl groupis the allyl group

Sigmatropic RearrangementSigmatropic RearrangementSigmatropic RearrangementSigmatropic Rearrangement

OO

OO

HH

QuestionQuestionQuestionQuestion

What will be the Claisen rearrangement What will be the Claisen rearrangement product of the carbon-14 labeled ether product of the carbon-14 labeled ether shown here? shown here?

A) A) B)B)

C)C) D)D)

Oxidation of Phenols:Oxidation of Phenols:QuinonesQuinones

Oxidation of Phenols:Oxidation of Phenols:QuinonesQuinones

The most common examples of phenol oxidationsThe most common examples of phenol oxidationsare the oxidations of 1,2- and 1,4-benzenediolsare the oxidations of 1,2- and 1,4-benzenediolsto give quinones. to give quinones.

(76-81%)(76-81%)

QuinonesQuinonesQuinonesQuinones

OOHH

OOHH

OO

OO

NaNa22CrCr22OO7,7, H H22SOSO44

HH22OO

The most common examples of phenol oxidationsThe most common examples of phenol oxidationsare the oxidations of 1,2- and 1,4-benzenediolsare the oxidations of 1,2- and 1,4-benzenediolsto give quinones. to give quinones.

(68%)(68%)

QuinonesQuinonesQuinonesQuinones

OO

OOAgAg22OO

diethyl etherdiethyl ether

OOHH

OOHH

CHCH33

CHCH33

AlizarinAlizarin(red pigment)(red pigment)

Some quinones are dyesSome quinones are dyesSome quinones are dyesSome quinones are dyes

OO

OO

OHOH

OHOH

maxmax

204 nm204 nm256 nm256 nm

maxmax

210 nm210 nm270 nm270 nm

maxmax

235 nm235 nm287 nm287 nm

Oxygen substitution on ring shifts Oxygen substitution on ring shifts maxmax to longer to longer

wavelength; effect is greater in phenoxide ion.wavelength; effect is greater in phenoxide ion.

UV-VISUV-VISUV-VISUV-VIS

OHOH

OO––

Vitamin KVitamin K

(blood-clotting factor)(blood-clotting factor)

Some quinones are important biomoleculesSome quinones are important biomoleculesSome quinones are important biomoleculesSome quinones are important biomolecules

OO

CHCH33

OO CHCH33 CHCH33 CHCH33 CHCH33

CHCH33

Some quinone precursors are important in foodsSome quinone precursors are important in foodsSome quinone precursors are important in foodsSome quinone precursors are important in foods

Antioxidants can protect against the cell-Antioxidants can protect against the cell-damaging effects of free radicals. Some dietary damaging effects of free radicals. Some dietary phenolics are oxidized to quinones as free phenolics are oxidized to quinones as free radical-antioxidant traps.radical-antioxidant traps.

Eg. Reservatrol / FlavonoidsEg. Reservatrol / Flavonoids