15.6Reactions of Alcohols:

A Review and a Preview

Table 15.2 Table 15.2 Review of Reactions of AlcoholsReview of Reactions of Alcohols

reaction with hydrogen halides reaction with hydrogen halides

reaction with thionyl chloridereaction with thionyl chloride

reaction with phosphorous tribromidereaction with phosphorous tribromide

acid-catalyzed dehydrationacid-catalyzed dehydration

conversion to conversion to pp-toluenesulfonate esters-toluenesulfonate esters

New Reactions of Alcohols in This ChapterNew Reactions of Alcohols in This Chapter

conversion to ethersconversion to ethers

esterificationesterification

esters of inorganic acidsesters of inorganic acids

oxidationoxidation

cleavage of vicinal diolscleavage of vicinal diols

15.7Conversion of Alcohols to Ethers

RCHRCH22OO

HH

CHCH22RR

OHOH

HH++

RCHRCH22OO CHCH22RR HH OHOH++

Conversion of Alcohols to EthersConversion of Alcohols to Ethers

acid-catalyzedacid-catalyzedreferred to as a "condensation"referred to as a "condensation"equilibrium; most favorable for primary alcoholsequilibrium; most favorable for primary alcohols

ExampleExample

2CH2CH33CHCH22CHCH22CHCH22OHOH

HH22SOSO44, 130°C, 130°C

CHCH33CHCH22CHCH22CHCH22OCHOCH22CHCH22CHCH22CHCH33

(60%)(60%)

Figure 15.2 Mechanism of Formation of Diethyl EtherFigure 15.2 Mechanism of Formation of Diethyl Ether

Step 1:Step 1:

CHCH33CHCH22OO•••• ••••

HH

HH OSOOSO22OHOH

CHCH33CHCH22OO ••••

HH

OSOOSO22OHOHHH

++ ––++

Figure 15.2 Mechanism of Formation of Diethyl EtherFigure 15.2 Mechanism of Formation of Diethyl Ether

Step 2:Step 2:

CHCH33CHCH22••••

HH

HH

++OO

CHCH33CHCH22OO•••• ••••

HH

++++

CHCH33CHCH22

CHCH33CHCH22OO ••••

HH

••••

HH

HH

OO••••

Figure 15.2 Mechanism of Formation of Diethyl EtherFigure 15.2 Mechanism of Formation of Diethyl Ether

Step 3:Step 3:

++++

CHCH33CHCH22

CHCH33CHCH22OO ••••

HHOSOOSO22OHOH

–– ••••••••••••

HH OSOOSO22OHOH••••••••

CHCH33CHCH22

CHCH33CHCH22OO ••••••••

reaction normally works wellreaction normally works wellonly for 5- and 6-memberedonly for 5- and 6-memberedringsrings

Intramolecular AnalogIntramolecular Analog

HOCHHOCH22CHCH22CHCH22CHCH22CHCH22OHOH

HH22SOSO44 130°130°

OO

(76%)(76%)

Intramolecular AnalogIntramolecular Analog

HOCHHOCH22CHCH22CHCH22CHCH22CHCH22OHOH

HH22SOSO44 130°130°

OO

(76%)(76%)

via:via:

OO

HH

++OO

HH

HH

••••

••••

••••

15.8Esterification

condensationcondensation

Fischer esterificationFischer esterification

acid catalyzedacid catalyzed

reversiblereversible

EsterificationEsterification

ROROHH HH22OO++HH++

++R'COHR'COH

OO

R'CR'COROR

OO

Example of Fischer EsterificationExample of Fischer Esterification

HH22OO++

CHCH33OHOH++COHCOH

OO

COCHCOCH33

OO

HH22SOSO44

0.1 mol0.1 mol 0.6 mol0.6 mol

70% yield based on benzoic acid70% yield based on benzoic acid

high yieldshigh yields

not reversible when carried outnot reversible when carried outin presence of pyridinein presence of pyridine

Reaction of Alcohols with Acyl ChloridesReaction of Alcohols with Acyl Chlorides

ROROHH HClHCl++ ++R'CClR'CCl

OO

R'CR'COROR

OO

pyridinepyridine

++ CClCClOO22NN

OOCHCH33CHCH22

CHCH33

OOHH

(63%)(63%)

NONO22

CHCH33CHCH22

CHCH33

OOCC

OO

ExampleExample

analogous to reaction with acyl chloridesanalogous to reaction with acyl chlorides

Reaction of Alcohols with Acid AnhydridesReaction of Alcohols with Acid Anhydrides

ROROHH ++ ++R'CR'COROR

OOOO

R'COCR'R'COCR'

OO

R'COHR'COH

OO

pyridinepyridine

(83%)(83%)

++CC66HH55CHCH22CHCH22OHOH

OO

FF33CCOCCFCCOCCF33

OO

CC66HH55CHCH22CHCH22OCCFOCCF33

OO

ExampleExample

15.9Esters of Inorganic Acids

Esters of Inorganic AcidsEsters of Inorganic Acids

ROH + HOEWGROH + HOEWG ROEWG + HROEWG + H22OO

EWG is an electron-withdrawing groupEWG is an electron-withdrawing group

HONOHONO22 (HO)(HO)22SOSO22 (HO)(HO)33PP OO++ ––

Esters of Inorganic AcidsEsters of Inorganic Acids

ROH + HOEWGROH + HOEWG ROEWG + HROEWG + H22OO

EWG is an electron-withdrawing groupEWG is an electron-withdrawing group

HONOHONO22 (HO)(HO)22SOSO22 (HO)(HO)33PP OO++ ––

CHCH33OH + HONOOH + HONO22 CHCH33ONOONO22 + H + H22OO

(66-80%)(66-80%)

15.10Oxidation of Alcohols

Primary alcoholsPrimary alcohols

Secondary alcoholsSecondary alcoholsfrom Hfrom H22OO

Oxidation of AlcoholsOxidation of Alcohols

RCHRCH22OHOH

OO

RCHRCH

OO

RCOHRCOH

OO

RCR'RCR'RCHR'RCHR'

OHOH

Aqueous solutionAqueous solution

Mn(VII) Mn(VII) Cr(VI)Cr(VI)

KMnOKMnO44 HH22CrOCrO44

HH22CrCr22OO77

Typical Oxidizing AgentsTypical Oxidizing Agents

Aqueous Cr(VI)Aqueous Cr(VI)

FCHFCH22CHCH22CHCH22CHCH22OHOH

KK22CrCr22OO77

HH22SOSO44

HH22OO

FCHFCH22CHCH22CHCH22COHCOH

(74%)(74%)

OO

Aqueous Cr(VI)Aqueous Cr(VI)

FCHFCH22CHCH22CHCH22CHCH22OHOH

KK22CrCr22OO77

HH22SOSO44

HH22OO

FCHFCH22CHCH22CHCH22COHCOH

(74%)(74%)

OO

NaNa22CrCr22OO77

HH22SOSO44

HH22OO

(85%)(85%)

HH

OHOH

OO

All are used in CHAll are used in CH22ClCl22

Pyridinium dichromate (PDC)Pyridinium dichromate (PDC)

(C(C55HH55NHNH++))2 2 CrCr22OO77

2–2–

Pyridinium chlorochromate (PCC)Pyridinium chlorochromate (PCC)

CC55HH55NHNH++ ClCrO ClCrO33––

Nonaqueous Sources of Cr(VI)Nonaqueous Sources of Cr(VI)

Example: Oxidation of Example: Oxidation of a primary alcohol with a primary alcohol with PCCPCC

CHCH33(CH(CH22))55CHCH22OHOHPCCPCC

CHCH22ClCl22

OO

CHCH33(CH(CH22))55CHCH

(78%)(78%)

ClCrOClCrO33––

NN

HH

++

PDCPDC CHCH22ClCl22

OO

(94%)(94%)

CHCH22OHOH(CH(CH33))33CC

CHCH(CH(CH33))33CC

Example: Oxidation of Example: Oxidation of a primary alcohol with a primary alcohol with PDCPDC

MechanismMechanism

involves formation involves formation and elimination of and elimination of a chromate estera chromate ester

CC

OOHH

HOHOCrOHCrOH

OO

OO

CC

OO

HH HHOO

OO

CrOHCrOH

MechanismMechanism

involves formation involves formation and elimination of and elimination of a chromate estera chromate ester

CC

OOHH

HOHOCrOHCrOH

OO

OO

CC

OO

HH HHOO

OO

CrOHCrOH

OO••••

••••

CC OO

15.11Biological Oxidation of Alcohols

alcohol alcohol dehydrogenasedehydrogenase

Enzyme-catalyzedEnzyme-catalyzed

CHCH33CCHH22OOHH ++ NADNAD++

++ ++ ++HHNADNAD HHCHCH33CCHH OO

nicotinamide adenine dinucleotide (oxidized form)nicotinamide adenine dinucleotide (oxidized form)

HOHO

HOHO

OOOO

NNNN

NHNH22

PPOO

PPOO

OO

HOHOOHOH

HH

CC

OO

NHNH22NN

OO OO OO OO

++

____

Figure 15.3 Structure of NADFigure 15.3 Structure of NAD++

Enzyme-catalyzedEnzyme-catalyzed

CHCH33CCHH22OOHH ++

NN

HH

CNHCNH22

OO

++

RR

++HH++

Enzyme-catalyzedEnzyme-catalyzed

NN

HH

CNHCNH22

OO

RR

CHCH33CCHH

OOHH

••••

15.1215.12Oxidative Cleavage of Vicinal DiolsOxidative Cleavage of Vicinal Diols

Cleavage of Vicinal Diols by Periodic AcidCleavage of Vicinal Diols by Periodic Acid

CCCC

HOHO OHOH

HIOHIO44 CC OO OO CC++

Cleavage of Vicinal Diols by Periodic AcidCleavage of Vicinal Diols by Periodic Acid

HIOHIO44

CHCH CCHCCH33

CHCH33

OHOHHOHO

CHCH33CCHCCH33

OO

CHCH

OO

++

(83%)(83%)

Cyclic Diols are CleavedCyclic Diols are Cleaved

HIOHIO44

OHOH

OHOH

OO

HCCHHCCH22CHCH22CHCH22CHCH

OO