CHAPTER7

ALCOHOLS,THIOLS,PHENOLS,ETHERS
Severalnewfunctionalgroupsarepresentedinthischapter.Allofthe

functions are based on oxygen and sulfur in the sp hybridized state. The
functional groups contain two pairs of nonbonding electrons and are the
cornerstone of many organic processes. The structures for alcohols, phenols,
thiols,ethersandthioethersareshownbelow.
AlkylOHPhOH AlkylSH
alcoholphenol
thiol

RORRSR
etherthioether

7.1Alcohols
7.1aNomenclature
Prioritiesinnomenclature
Severalfunctionalgroupshavebeenencounteredaswehaveadvanced
throughthechapters.Whenanewfunctionalgroupispresented,itsnomenclature
isalwaysbasedontheparentnamewithanendingthatdesignatesthefunctional
group.Whenseveralfunctionalgroupsarepresentinamolecule,priorityrules
mustbeusedtodeterminewhichfunctionistheparentsystemthatdeterminesthe
numberingofthesystemandthesuffixusedinthefinalname.
Theprioritylistisasfollows:
carboxylicacids>aldehydes>ketones>alcohols>amines>alkene>
alkyne>alkyl,halogen,nitro
Thusacompoundthatcontainedhydroxy,alkeneandketonefunctions
wouldbenamedasaketonewiththeketonegettingthelowestnumberpossible,
andsubstituentsarenumberedaccordinglyandnamedinalphabeticalorder.
Belowthecompoundontheleftisnamedasanalcohol,buttheoneonthe
rightisnamedasaketoneeventhoughbothcompoundshavethesevencarbon
backbone.

124Ch7Alcohols,Thiols,Phenols,Ethers
OH

OH

Cl

Cl

O
7chloro3hepten2ol

1chloro6hydroxy4hepten3one

OHhaspriority

ketonehaspriority

AlcoholNomenclature
Hydroxycompoundsareencounteredfrequentlyinorganicchemistryand
theOHfunctionisofhighprioritywithonlyacids,aldehydesandketoneshaving
higherpriority.Thusmanycompoundshavethealcoholparentsystem.
TheIUPACsystemnamesthelongestchainhydrocarbonastheparent,
dropstheendingeandaddsanewendingofol.Thealcoholhasahigherpriority
innomenclaturethanalkenes,alkynes,alkylgroupsandhalogenandisgivena
numberlowerthananyofthosegroups.Oncetheparentcompoundisidentified
andthelocationofthealcoholfunctionisspecified,otherfunctionsarenamedin
alphabeticalorder.
TheIUPACandcommonnamesforseveralalcoholsaregivenbelow.
Structure
CH3OH

Common
methylalcohol

IUPAC
methanol

CH3CH2OH

ethylalcohol

ethanol

CH3CH2CH2OH

npropylalcohol

1propanol

CH3

CHCH3

isopropylalcohol

2propanol

CH3

tertbutylalcohol

2methyl2propanol

OH
CH3

COH
CH3

7.2Thiols125
CH3CH2CH2CH2OH

nbutylalcohol

1butanol

CH3

CHCH2CH3
OH

secbutylalcohol

2butanol

CH3

CHCH2OH

isobutylalcohol

3methyl1propanol

CH3

cyclohexylalcohol cyclohexanol

OH

benzylalcohol

CH2OH

phenylmethanol

Whenmorethanonehydroxylgroupispresent,theIUPACsystemuses
numberstodesignatethelocationofthehydroxylsalongwithaprefixdi,tri,to
denotethenumberofhydroxyls.Somesystemswithmorethanonehydroxylhave
commonnamesasshown.
OH
CH2 CH2
OH OH
1,2ethandiol

CH2 CHCH2
OHOH
1,2,3propantriol

ethyleneglycol

HOOH
1,2cyclohexandiol

glycerol

Aliphatic alcohols are classified as primary, secondary or tertiary,

according to the type of carbon atom attached to the alcohol function. If the
carbonattachedcarriesonealkylgroup,thealcoholisprimary.Withtwoalkyl
groupsattachedtothecarbonthealcoholissecondary,andthreealkylgroups
attachedthealcoholistertiary.
'

'

RCH2OH

RCHOH

R
RCOH

primary

secondary

tertiary

R''

7.1bPhysicalPropertiesofAlcohols
Manyofthephysicalpropertiesofalcoholsaredirectlyrelatedtothe
hydrogenbondingexhibitedbythehydroxylgroup.Inpurealcoholsystems,extra

126Ch7Alcohols,Thiols,Phenols,Ethers
energymustbeaddedinordertocausethesampletoboil,thushighboilingpoints
areobserved.Also,alcoholsformhydrogenbondswith
waterandasaresultareverysolubleinwaterunless
morethansixcarbonatomsarepresent.
H
R

OH OR

High boiling points of alcohols as a result of hydrogen bonding are

demonstratedintheexamplesgivenbelow.Thehydrocarbonofclosestmassis
shownbeloweachalcohol.Thedifferenceinboilingpointsisasmuchas153

becauseofthehydrogenbonding.
CH3OH

CH3CH3
0

CH3CH2CH2CH2OH
o

97

CH3CH2CH3
42

CH3CH2CH2OH
o

78

65

88

CH3CH2OH

118

CH3CH2CH2CH3
0.5

CH3CH2CH2CH2CH3
0

35

Hydrogenbondingisexceptionallyimportantinbiologicalfunction.Many
moleculesthatareactiveinbiologicalprocesseshavetheOHfunctionpresent.
When the molecule is in a living system it must interact with a protein. The
interactionmusthaveaspecificfitastotheshapeandstereochemistryoftheprotein
andthemolecule,andmuchoftheintermolecularattractioncomesfromhydrogen

bondingfromthehydroxylsofthemoleculetooxygenandnitrogensitespresent
in the protein as shown below for pyridoxine, vitamin B 6 interacting with a
proteinreceptor.
proteinreceptor
OH

Pyridoxine

HO
CH3

OH
N

VitaminB6
(grains,milk,eggs)

7.2Thiols
127

7.1cNaturallyOccurringAlcohols
TheROHfunctionistrulyabundantinnature.Allcarbohydrates,also
calledsugars,arecompoundsthatcontainthealcoholfunction.Afewcommon
compoundsarelistedbelow.Bothcitronellolandgeraniolarefoundinplantsand
trees and belong to a family of compounds called terpenes. They are usedas
blends in perfumes and spices. Citronellol is used in candles to help repel
mosquitoes.Mesoinisotol,acarbohydrate,isacompoundfoundinfoodsources
andisimportantinhealthymetabolism.Theaflavinefoundinblacktea,contains
bothaliphaticandaromatichydroxylfunctionsandetherfunctions.

HO

HO

Geraniol

Citronellol

OH
OH OH
OH
HO

HO

O
OH
OH
theaflavine
fromblacktea

HO

HO

OH
OH

OH

OH
Mesoinositolpossible
cellgrowthfactor

(fruits,vegetables,meats)
7.1dPreparationofAlcohols

128Ch7Alcohols,Thiols,Phenols,Ethers
Severalofthelowmolecularmassalcoholsarepreparedonanindustrial
scalethatproducesmillionsoftons.Thealcoholsare
usedthroughoutthechemicalandacademicworld,
commercially as solvents, as medicinal preparations, and in alcoholic drinks
(ethanol)
Methanol is produced in a special process that involves catalytic
hydrogenationofcarbonmonoxide.Methanolisextremelytoxicandcauses
blindnesswheningested.
ZnO/Cr2O4
CO

H2

hightempandpress

CH3OH

Bothethylalcoholandisopropylalcoholaresynthesizedbyacidcatalyzed
additionofwatertoethyleneandpropylenerespectively.
H3O
CH2=CH2

CH3CH2OH
H3O

CH2=CHCH3

CH3 CHCH3

OH
Ethanolisalsoproducedasasupplementforautofuelsbyfermentationofthe
carbohydratesfoundingrain.Theprocessgivesethanolthatcontains5%waterafter
distillation.Thewaterisremovedbyreactionwithlime,calciumoxide.

GrignardReactionswithCarbonylCompounds
Grignardreagentswereintroducedinthehalogenchapter.Theiruseisso
valuable and general in organic chemistry that their reactions will be shown
throughoutmanychapters.Theexampleshownbelowcouldbeexpandedinto
many variations just by changing the halide and the carbonyl compound.
Variationswithothertypesoforganometalliccompoundsarealsoavailable.
7.2Thiols129
CH3CH2Br+Mg

diethylether

CH3CH2MgBr
ethercomplex

1)CH3CH2MgBr

OH

CH2CH3

2)H3O
TherearemanyexamplesoftheuseofGrignardreactions.Theexample
abovecouldbeexpandedintomanyvariationsjustbychangingthehalideandthe
carbonylcompound.Variationswithothertypesoforganometalliccompoundare
alsoavailable.Thereactionisgiveninmoredetailinchapter8onaldehydesand
ketones.
HydrationofAlkenes
Thereactionsshowntoprepareethanolandisopropylalcoholindustrially
areexamplesofelectrophilicadditionofwatertoanalkene.Thepreparationof
higher molecular weight alcohols by hydration is not as important because
rearrangementsoccurandproductyieldsarereduced.
Oxymercurationdemercurationprovidesalcoholsfromalkenesundermild
conditionswithoutrearrangement.Mercuricacetatereactswiththealkenetoform
acyclicmercuriniumionwithapositivecharge.Waterattackstheintermediate
fromthecarbonwiththehighestpositivecharge,thetertiarycarbonhere,and
fromthebacksideofthemercuryatom.Waterandmercurywillbeantiinan
intermediate product which is not isolated, but it is reacted with sodium
borohydridetoconvertthecarbonmercurybondintoacarbonhydrogenbond.
Thefinalresultistheproductionofthealcoholatthemostsubstitutedcarbonof
thealkene,theMarkovnikovproduct.
Oxymercurationdemercuration

CH

Hg(OAc)2

H2O
H2 O

CH3
+

HgOAc

CH3
HgOAc

OAc

OH
CH

+
3

HgOAc
NaBH4
OH
CH3

130Ch7Alcohols,Thiols,Phenols,Ethers

Alkenesreactwithborane,BH3 ether,bysynadditionofhydrogenand
borontothealkene.Theboronatomaddstotheleastsubstitutedcarbonatom.
After three alkene units have added the intermediate is treated with basic
hydrogen peroxide to form the alcohol. The process is called hydroboration
oxidation.TheprocessprovidesthealcoholwithantiMarkovnikovselectivity.
Hydroborationoxidation

CH3

CH3

BH3

B
H3C
H2O2
OH

CH3

CH3
OH

ReactionsofHaloalkanes
Halogenatedalkanescanbeconvertedtoalcoholsbyreactionsdescribed
inchapter5on NucleophilicSubstitutionandElimination. Themainpointsof
reactions of alkyl halides are that the primary halides react by S N2 and E2
reactions,whilesecondaryandtertiarysubstratesreactprimarilybyS N1,E1and
E2reactions.Resultsareshownforreactionsofprimaryandtertiaryhalideswith
hydroxide,whichisbothagoodnucleophileandstrongbase.
SN 2

E2

CH3CH2Br+ OH
CH

CH3CH2OH +Br
CH3

CH3 CBr+OH
CH3

CH2=C

+ H2O Br
CH3

Reactionsofthesamesubstrateswithwater(orwaterinasolvent),whichis

7.2Thiols131

verynonnucleophilicandnonbasic,showonlySN1andE1processeswiththe
tertiaryhalide.
CH3CH2Br

H2O
CH3

CH3

CH3

NoReaction
CH3

H2O

CBr

CH3 COH

CH3

CH2=C

CH3

CH3

SN1

E1
H2O

Br

ReductionofAcids,Esters,AldehydesandKetones
Thecarbonylgroupofseveralfunctionalgroupsmaybeconvertedtothe
alcohol by reducing agents. The reduction of a carboxylic acid with lithium
aluminumhydrideandthereductionofaketonewithsodiumborohydrideare
shownbelow.Bothreactionsexemplifyverycommonandreliableprocedures.
Thesereactionsaregivenindetailinthealdehydeandketonechapter8.
1)LiAlH4
CH3CH2CH2COOH

CH CH CH CH OH
3

2)H3O
1)NaBH4

O
2)H3O
OxidationofAlkenestoVicinalDiols

Compoundswithhydroxylgroupsonadjacentcarbonsarecalledvicinal
diols.OxidationofalkeneswithcoldKMnO4orOsO4providesoccurswithsyn
additionandprovidescisvicinaldiols.Transvicinaldiolscanbepreparedbyring
openingofanoxirane,athreememberedringcontainingoxygen.

OH

132Ch7Alcohols,Thiols,Phenols,Ethers
OH
KMnO4

cis

cold

OH
OH

OH

trans
OH

7.1eReactionsofAlcohols
Acidicpropertiesofalcohols
The high electronegativity of the oxygen atom in alcohols causes the
oxygentotakeelectronsawayfromthehydrogenatom.TheOHbondispolarized

and is ableto giveupa proton,H .Thus alcohols areweakacids,butcan

becomestrongeracidsdependingonthetypesoforganicsubstituentspresent.

ROH
RO
H
Theionization constantfortheaboveequilibriumisgivenbyKa=

[RO ][H ]/[ROH]. AcidityisoftenexpressedaspKawhichisthenegative

logarithmoftheKa.Thus,pK a=logKa.ThepKaisshownbelowforseveral
alcohols. Electron donating groups weaken the acidity (higher pK a) while
electron attracting groups strengthen the acidity (lower pK a). Phenol, the last
entry,representsaveryacidicclassoforganiccompoundsandispresentedlater
inthischapter.
H2OCH3OH

pK

a15.7

16

CH3CH2OH
17

CF3CH2OH
12.4

OH
10

Theacidicpropertyofalcoholsisimportantasitpermitstheformationof
alcoholatesalts,calledalkoxides.Alkoxidesareusefulbothasstrongbasesandas
goodnucleophilesforSN2reactions.Alkalimetalsandotherverystrongbasescan

beusedtogeneratethealkoxides.
2CH3OH
CH3OH

2Na
NaH

2CH3O

Na

H2

CH3O

Na

H2

7.2Thiols133

ConversionofAlcoholstoAlkylHalides
ReactionwithHydrogenHalides
Aliphaticalcoholsreactwithhydrogenhalidestoproducealkylhalides.
ROH

HX

H2O

RX

X=Cl,Br,I
Themechanismofthereactiondependsonthestructureofthealcohol,but
thefirststepalwaysinvolvesprotonationofthealcoholtoformanoxoniumion.
ROH

ROH2
X
oxoniumion

HX

The OH2group isanexcellentleavinggroupasitformsaneutral

moleculeofwater.Therulesforsubstitutionandeliminationreactionsapplyherejustas
withalkylhalides.PrimaryalcoholsreactbytheS N2E2mechanismwhilesecondary
andtertiaryalcoholsfollowSN1E1carbocationpaths.
ThereactionofnbutylalcoholwithHBrgivesfirsttheoxoniumionwhich

thenisattackedfromthebacksideinaSN2mannertogive1bromobutane.

HBr

CH3CH2CH2OH

+
CH3CH2CH2OH2

CH3CH2CH2Br
+H2O

Br

Thereactionoftertbutylalcohol,atertiaryalcohol,withHBrgivesthe
oxoniumionfirstalso.Butinthiscase,waterislosttogivethetertbutylcation.

ThecationreactswithBr togivemostlythesubstitutionproductaccompanied
bysomealkeneeliminationproduct.
CH3
CH3

COH
CH3

CH 3+
HBr

CH3C

H2O

OH2

CH3C

CH3
CH

Br

CH3

CH3

CH3
CH2

CBr+
CH3

CH3C

CH3

SN1

E1

134Ch7Alcohols,Thiols,Phenols,Ethers
Thereactionsthatinvolvecarbocationsarethemorecomplicatedbecause
oncethecationisformedmanypossibilitiesexistfor
theirreaction:substitution,elimination,and
rearrangement.
Thereactionof3methyl2butanolwithHClgoesthroughtheoxonium
iontothecarbocation.Butthesecondarycationrearrangestothemorestable
tertiarycation.Theproductarisesfromattackofchlorideonthetertiarycation.
CH3 H

H
CH3
CH3

CH3

HCl

OH

CH3

CH3

H
CH3 H

H2O
CH3

C+

CH3

OH2

CH3 H
C

CH3

2 carbocation

CH3

3 carbocation

CH3 H

Cl

CH3 C
Cl

CH3

Bothalcoholsandhalidescanbeusedforgeneratingcarbocations,with
the resulting products depending on reaction conditions. The example below
illustratestheformationofastableallyliccarbocation.
CH3CH=CHCH2Cl
CH3CH=CHCH2OH

HCl

Cl
CH3CHCHCH2

CH3CH=CHCH2Cl

H2O

+
CH3CHCH=CH3

Cl

H2O

CH3CH=CHCH2OH
+
CH3CHCH=CH3

OH
ReactionwithPhosphorusandSulfurHalides
Manyreagentsareknowntoconvertalcoholstohalides.Phosphorus
7.2Thiols135
halidesandthionylchloridearecommonlyusedaswaspresentedinchapter6.
SOCl2
PBr3
Cl
OH
Br
TheMitsunobureactioncanemploythehalideasanucleophiletodisplace
thehydroxylfunctioninaSN2process.Thusthechiralityofthehalideproductis
invertedfromthatofthestartingalcohol.Inthisreactionthehydroxylgroup,whichis

normallyaverypoorleavinggroupasOH ,leaveseasilyasaphosphineoxide.Thus
alcoholsmaybedisplacedintheSN2reactionwithoutbeingconvertedto
anotherfunction(halide,sulfonate)first.

MitsunobuReaction
H

CH3

OH

H3CH2C

CH3
H

Ph3P, KI
EtO2C

Rconfiguration

CO2Et

CH2CH3

SConfiguration

N=N

Dehydration
Whensecondaryandtertiaryalcoholsaretreatedwithacid,acarbocationis
formed.Whenanucleophileispresent,suchashalideintheaboveexample,analkyl
halideisproducedintheSN1process.Butifanucleophileisabsent,thenthe
E1processisfollowedtogiveanalkene.AlcoholsareeasilydehydratedbytheE1

reaction with sulfuric acid. The sulfate formed is too poor to serve as a
nucleophile, thus only elimination is observed. But carbocations are the
intermediatesandthereactionscanbecomplicatedbecauseofrearrangements.
CH3

CHCH3

H2SO4

+OH2

OH
H2O

CH3CHCH3
H

CH

CHCH

CH3CH=CH2

Thedehydrationofthetwomethylcyclohexanolsbelowshowsthatthe
major alkene formed is the most substituted (Saytzeff) product. Also

rearrangementwilloccurtothemoresubstitutedcarbocation.Thusthedifferent
alcoholsgivethesameE1products.
136Ch7Alcohols,Thiols,Phenols,Ethers

CH3
OH

H2SO4

CH3

H2SO4

CH2

major
Saytzeff

minor

CH3

OH
Primary alcohols are not good starting materials for dehydration because
primarycarbocationsarenotgoodintermediates.Reactionofethanolwithsulfuric
acidgivesdiethylether,butdehydrationcanbeachievedwithanaluminacatalystat

hightemperature.
CH3CH2OH
CH3CH2OH
Oxidationofalcohols

H2SO4
150

CH3CH2OCH2CH3

Al2O3,300

CH2=CH2

Twoextremelyvaluablefunctionsinorganicchemistryarethealcoholand
carbonyl groups. The oxidation of alcohols and the reduction of carbonyl
compoundsrepresentsajunctureinwhicheachfunctioncanbepreparedfromthe
other.Anyalcoholthatcontainsandalphahydrogenatomcanbeoxidizedtoa
carbonylcompoundasshown.
HCOH

alcohol

1o

[O]
[H]

[O]
RCH2OH

20

R2CHOH

30

R3COH

C=O

[O]
[O]

carbonyl
[O]

RCH=O
aldehyde
R2C=O ketone
nooxidation

RC=O

OHacid

7.2Thiols137

Oxidation of alcohols is so important that hundreds of reagents and

procedures have bee developed to perform the oxidation. The reagents are in
classes of oxidants such as chromium (VI), silver (I), aluminum (III),
manganese(IV),manganese(VII),cerium(IV),iodine(V),anddimethylsulfoxide.
The wide variety of reagents have been developed in order to achieve mild
conditionsandselectivitythatavoidsoxidizingotherfunctions.Alsooxidationof
primaryalcoholstoaldehydesrequiresspecialreagentstoavoidoveroxidationto
theacid.Onlyafewcommonoxidationreagentswillbeusedhere.
Primaryalcoholsareeasilyoxidizedtocarboxylicacidswithpotassium
dichromateinsulfuricacid(Beckmannreagent).Theintermediatealdehydeis
oxidizedfurthertotheacid.Thereactioninvolvesformationofanintermediate
chromateesterwhichconvertstochromium(IV).
K2CrO4

CH3CH2CH2CH2OH

H2SO4

CH3CH2CH2COOH

Secondaryalcoholsareeasilyconvertedtoketones.Furtheroxidationof
the ketone occurs only under very harsh conditions. The mechanism of the
oxidationinvolvesformationofachromate(VI)esterofthealcoholfollowedby
lossofchromous(IV)acid.
Tertiaryalcoholsdonotpossessanalphahydrogenandcannotbeoxidized,
buttheconditionsofoxidationcansometimescauseE1eliminationreactions.

CH3

CH3
C=O

K2CrO4
HCOH
Mechanism

K CrO
2

4+

CH3

CH3

H2SO4

H2CrO4 +K2SO4

CH3
HCOH+

H2SO4

CH3
H2CrO4

CH3

HCOCrO3H+ H2O

CH3
CH3

CH3
C=O+

H2O+HCOCrO3H

+
H3O

CH 3Cr(VI)

CH3

+
HCrO3

Cr(IV)

138Ch7Alcohols,Thiols,Phenols,Ethers
A solution of CrO3, H2SO4 and acetone, known as Jones reagent, is
commonlyusedinmanyoxidationprocedures.
JonesOxidation
OH

O
CrO3
H2SO4
acetone

Oxidationswithdimethylsulfoxideinthepresenceofaceticanhydrideor
oxalylchloride(Swernoxidation)areespeciallyusefulforconversionofprimary
alcohols to aldehydes without further oxidation to the acid. Pyridinium
chlorochromatealsoservesforthisselectiveoxidation.
O
CH3SCH3
CH2OH

Ac2O
cold

CH=O

ClCrO3

H
Ingested alcohol is oxidized in the liver by an enzyme called alcohol
dehydrogenase. The first product of the oxidation is acetaldehyde which is
responsibleforthewellknown"hangover".Thealdehydeiseventuallyfurther
oxidizedtoacetateandthenontocarbondioxide.
enzyme
CH3CH2OH

7.2Thiols

[O]
CH3CH=O

[O]
CH3 C=O
O

CO2

7.2aNomenclature
Sulfurisonerowdownfromoxygenintheperiodictable.Compoundsthat
containsulfurinsteadofoxygenmightbeexpectedtobearsimilarcharacteristicsof

7.2Thiols139

theoxygencompound.But,thechemistryoftheSHfunctionismuchdifferent
fromtheOHfunction.TheSHgroupiscalledasulfhydrylfunction,butorganic
compoundscontainingtheSHarecalledthiolsintheIUPACsystem,orcalled
mercaptansinoldernomenclature.ThiolnamesintheIUPACsystemarederived
fromtheparentalkanebydroppingtheefollowedbyaddingthiol.Anumberis
usedtolocatethepositionofthethiol.Oldermercaptannamesareobtainedby
namingthealkylgroupfollowedbyasecondword,mercaptan.

SH

CH3SH
methanthiol

thiophenol

methylmercaptan

phenylmercaptan

CH2 CH2
SHSH

CH3CH=CHCH2SH
2buten1thiol

ethandithiol

7.2bPropertiesofThiols
Thiols,unlikealcohols,donotformhydrogenbonds andthereforeare
volatilelowboilingcompounds.Thiolshaveveryunpleasantodors.The2buten
1thiolaboveisoneofthecomponentsofskunkspray.Methanthiolispurposely
addedtobottledgasandnaturalgasinordertorevealleaks.Thiols(pKa=10)are
moreacidicthanalcohols(pKa=16),andtheirprotoncanberemovedbyreaction
withbase.
CH3SH

CH3SNa

NaOH

H 2O

7.2cPreparationandReactionsofThiols
ThiolsarereadilypreparedbytheSN2displacementofhalidesby

sulfhydrylion.Sulfhydrylanionisanextremelygoodnucleophile.
RX

+NaSH

RSH+NaX

X=Cl,Br,I
Thiolsareeasilyoxidizedtodisulfides,andthedisulfidesareeasily
reducedbacktothiols.
CH3CH2SH

I2
NaBH4

CH3CH2SSCH2CH3
disulfide

Theeasyoxidationreductionisimportantinproteinstructure.Keratinisa

140Ch7Alcohols,Thiols,Phenols,Ethers
proteinfoundinhair,anditcontainsthedisulfideunitknownascystine.Hair
treatmentsfirstreducethedisulfidebondandallowthehairtobemanaged.Then
thedisulfidebondsarereformedtokeepthehairinthedesiredshape.
O

O
CHCOH

HOCCHCH2SSCH2

NH2

cystine

reduction

oxidation 2HOCCHCH2SH
NH2

NH2

reduction
CH

CH2

oxidation

CH

SH
2

CH2
HS
Hairnobody

Hairwithbody

7.3Phenols
Phenolsareaclassofcompoundsthatcontainthehydroxylfunctionbonded
to an aromatic ring. Although phenols and alcohols contain the OH group, their
chemistryismuchdifferent.Phenolshaveastronglyacidichydrogen,theCObondis
verydifficulttobreak,andmanyreactionstakeplaceinthearomaticring.

OH

phenol

7.3aNomenclatureofphenols
Thenamesofphenolsarederivedfromoldercommonnames.Thenames
havebeenretainedintheIUPACsystem.Somecommonphenoliccompoundsare
shownbelow.
OH OH

OH

CH3

CH3
ocresolmcresol

pcresol

CH3

7.3Phenols141
OH

OH

OH

OH
OH
catechol

OH
hydroquinone

resorcinol
OH

OH

1naphthol

2naphthol

naphthol

naphthol

7.3bNaturallyOccurringPhenols
Manyphenolsareobtainedbythedistillationofcoal.Vanillin,foundin
vanillabeans,isusedasaflavoringforfood.Salicylicacidisusedtoprepare
aspirin.Resveratrol,foundingrapesandpeanuts,maybeananticanceragent.
Cyanidin,averyabundantcompoundbelongtotheflavoneclassofcompounds,is
responsible for the red coloring in roses. When cyanidin is made basic with
potassiumionsitformsabluecolorfoundinthebluecornflower.
OH
OH

OCH

OH

OH

O
Oglucose

CHO
vanillin

Oglucose
cyanidin
redcolorofroses

142Ch7Alcohols,Thiols,Phenols,Ethers
OH

OH

COO
H
OH

OH

W
resverat
rol
salicylic
acid
7.3c
Reactions
of
Phenols
Phenols

Br2/H2O

Br
Other
electrophilic
substitutionsoccur
readilyundermild
conditionsasseen

arestrongeracids
than alcohols.

belowfornitrationand
OH

acylation.

7.3Phenols143
OH

OH

OH

HNO3

NO2

SiO2
NO2
OH

OH
Ac2O
SnCl4
H3CO

ReductionandOxidation
Cyclohexanolisproducedfromphenolbyreductionwithanickelcatalyst.
Thearomaticringislostinthisprocedure.
OH OH
H2
Ni,heat
pressure
Hydroquinoneissmoothlyoxidizedtothehighlycoloredcompoundknown
asquinone.Quinoneisusedinphotographicprocesses.Thereactionisreversibleand
quinonemaybereconvertedtohydroquinone.Oxidationreductionofthistype

isimportantinbiologicaltransformations.
O

OH

K2CrO4/H
OH

NaBH4

VitaminK,anaturallyoccurringquinonethatplaysaroleinblood
clotting,containsthenaphthoquinonestructureshown.

144Ch7Alcohols,Thiols,Phenols,Ethers
O

CH3
O CH3

CH3

CH

CH3

Phytonadione
VitaminK
(greenvegetables)

Reactionwithfreeradicals
Freeradicalsreacteasilywithphenolstoabstractthehydrogenatomfrom
theOHgroup.Hydroquinoneisveryefficientinreactionswithradicalsthatitis
usedtoterminateorinhibitradicalreactions.Inhibitionofradicalsisimportant
whenfreeradicalsmaybepresentinareactionandcauseundesiredreactions.
Certainethersareknowntoundergofreeradicaloxidationswithoxygentogive
unstableperoxides.Whenthebottleofethercontainingtheperoxideisshaken,the
peroxideexplodes.Additionofaninhibitorsuchashydroquinonetotheether
prevents formation of radicals and peroxides, and the ether remains free of
explosivetendencies.
O2

light
O

HO

OH
+ O

O
Vitamin E contains a phenolic ring in which the OH reacts with free
radicalstoinhibittheirformation.ManypeopletakevitaminEsupplementsto
suppress radical formation in the body because some theories indicate that

biologicalfreeradicalscausecancer.

7.3Phenols145
CH3
OH
CH3
CH3

CH3

CH3

O
CH3

CH
CH3

CH3

R(freeradical)

CH3

CH3
CH3

Tocopherol
VitaminE
(eggs,meats,oils)

O CH
3

CH3

CH

CH3
+RH

7.4Ethers
Ethersarecompoundsthathavetwoorganicgroupsattachedtooxygen.
Thebondsbetweentheorganicgroupsandtheoxygenformanangleof110and
consequentlyareslightlypolar.Thenonbondingelectronsontheoxygenatom
cause ethers to act slightly basic. Ethers are wellknown for their anesthetic
propertiesbuttheypossessotherusefulchemicalpropertiesaswell.Structuresof
twoanestheticethersareshownbelow,butbetteranestheticsarenowinuse.
CH3CH2OCH2CH3 ClCFHCF2OCH2F2
ether

ethrane

diethylether
7.4aNomenclatureofEthers
Ethersarenamedbytreatingeachsideasasubstituentwithanalkylor
arylnamefollowedbythewordether.Theindividualnamesareseparate.

146Ch7

Alcohols,Thiols,Phenols,Ethers

CH3
CH3CH2OCCH3

CH3CH2OCH2CH3

diethylether

oxirane

CH3
methyltertbutylether
O
O
oxetane
oxolane
OCH3

CH3CH2CH2CH2OCH(CH3)2
nbutylisopropylether

O
oxane

methylphenylether
anisole

Complexethersarenamedbyprefixingthebasenameofahydrocarbon
systemwithanalkoxygroup.
CH3OCH2CH2OCH
1,2dimethoxyethane

CyclicethersarenamedbytheIUPACsystemdevelopedforheterocyclic
compounds.Heretheoxinthenamedenotesoxygen.
7.4bPhysicalPropertiesofEthers
Ethers have boiling points similar to the hydrocarbon obtained if the
oxygenisreplacedbyaCH2group.
CH3CH2OCH2CH3

CH3CH2CH2CH2OCH2CH2CH2CH3
o

bp142

bp35

CH3CH2CH2CH2CH3CH3CH2CH2CH2CH2CH2CH2CH2CH3
o

bp36

bp151

Thenonbondingelectronsonalkyletherscauseaslightlybasiccharacter.
Thusweakhydrogenbondsareformedwithwater,andetherslightlydissolvesin
water.Theetheroxygenisprotonatedinthepresenceofstrongacids.

7.4Summary147

HCl
C2H5OC2H5
H2SO4

C2H5 OC2H5
H

Cl

C2H5 OC2H5HSO

Grignardreagentsrequirethepresenceofanether,usuallydiethyletheror
tetrahydrofuran,becausetheetheroxygenformsacomplexwiththemagnesiumin

thereagent.
C2H5OC2H5
C2H5OC2H5

R X Mg

RMgX
C2H5OC2H5

A unique class of ethers containing several oxygen atoms in a cyclic

structureidcalledcrownethersbecausetheyadoptacrownshape.Thecrown
ethershownbelowiscalled18crown6becauseitcontains18atomsand6ofthe
atomsareoxygen.Thenonbondingelectronsoftheoxygenatomscomplexwith
alkali metal cations. Thus salts such as KF can dissolve in organic solutions
containingthecrownether.
O

O
18crown6

O
18crown6PotassiumComplex

18crown6
model

148Ch7Alcohols,Thiols,Phenols,Ethers
7.4cPreparationofEthers
Diethyl ether is prepared from ethanol and sulfuric acid. The reaction
involves the SN2 displacement by ethanol on another positively charged

molecule.The OH2isaverygoodleavinggroup.
H2SO4
C2H5OH

+C2H5OH
C2H5OH

C2H5OC2H5+H2O+

TheuseofanalkoxideintheSN2displacementofprimaryhalidesleadsto
etherproducts.TheprocessiscalledtheWilliamsonethersynthesis.The
alkoxideispreparedbyreactingsodiummetalwiththealcohol.

CH3OH

+ Na
+ CH3CH2Br

CH3O

CH3ONa

CH3O

CH3OCH2CH3+

+ Na
Br

UsuallytworoutesarepossibleintheWilliamsonethersynthesis.Therules
ofSN2reactionsmustbefollowedinthattertiaryalkylhalidescannotbeused.
Thusofthetwochoicespossibleforthepreparationoftertbutylmethyl

ether,theroutethatusesmethylbromideisacceptable,buttheuseoftertbutyl
bromidewillonlygiveE2elimination.MTBEisanenvironmentallysafeadditive
togasoline.
SN2

CH2
CH3 CO

E2

CH3
CH3Br

COCH3

CH3

CH3

CH3

CH3 CH2
CH3

CH3 CBr
CH3

CH3O

MTBE
CH3OH

C
CH3

7.4dReactionsofEthers
Oneofthemainfeaturesofethersisthattheyarerelativelyinert,andthus
serveasexcellentsolvents.Hydriodicacidcanbeusedtocleavetheetherbondas
shown.

7.4Summary149
HI

OCH3

OH+

7.4eFormationofHydroperoxides
A major danger in handling ether solvents is the possibility that some
hydroperoxidehasformedinthesolvent,anditcausesthesolventtoexplode
whenhandled.Thereactionoccursbetweenethersandoxygenandiscatalyzedby
light.Diethylether,diisopropyletherandtetrahydrofuranareespeciallyproneto
theformationofhydroperoxides.
OOH
O2
CH3CH2OCH2CH3
CH3CH2O CHCH
OOH

OOH

(CH3)2CHOC(CH3)2

Notallhydroperoxidesareundesired,andsomeareusedasinitiatorsin
freeradicalreactions.Specialcontroloftheirpreparationisnecessary..
7.4fOxiranes(Epoxides)
Ethers contained in a threemembered ring are called oxiranes by the
IUPACrules,butacommonnameforthesystemisepoxide.Theoxiranesystem
ishighlystrainedandthusshowshighreactivity.Thereactionscausetheringto
openandrelievetheinherentstrain.
Preparationofoxiranes
The simplest oxirane is also called ethylene oxide and is prepared by
oxidationofethylenewithoxygen.
O2/Ag2O
CH2=CH2

250

Peroxidereagents,suchmchloroperoxybenzoicacid,canbeusedtooxidize
alkenestooxiranes.Basicsolutionofordinaryhydrogenperoxide,H 2O2,canalso
beusedtoprepareoxiranesfromalkenes.

CH3I

150Ch7Alcohols,Thiols,Phenols,Ethers
HO
O

Cl

O
CH=CH2

Reactionsofepoxides
Bothacidsandbasescausetheringopeningofthehighlystrainedoxirane.
acidreaction

O
ClCH2CH2OH

Cl
basereaction
O
OCH2CH2OCH2CH3

CH3CH2O

H
HOCH2CH2OCH2CH3

Grignardreagents,andorganolithiumreagents,reactwithoxiranetogive,
afterprotonation,analcoholthatistwocarbonslongerthanthestartingGrignard
reagent.
2

CH3CH2MgBr

7.4g

2)H

CH3CH2CH2CH2OH

Thioethers(Sulfides)

Sulfuranalogsofethers,knownasthioethersorsulfidesaremuchless
knownthanthenormaloxygenether.Butseveralimportantcompoundsinthis
familydeservementioning.Mostofthecompoundshaveeitheracommonname

oranamederivedfromnamingthesubstituentsfollowedbythewordsulfide.
7.4Summary151
CH3SCH3

PhSPh

dimethylsufide

S
S
diphenylsulfide
thiolane
thiophene
tetrahydrothiophene

Thioetherssmelljustasterribleasthiols,perhapsworse.Inadditionsome
thioethersinplants,suchasgarlicandonion,contributetothetaste.Garlic,which
hasseveralhelpfulhealthrelatedpropertiesincludingloweringofbloodpressure,
hastwostructuresofsimilarstructure.Allicinisapotentantibacterialagentwhile
allylingivesthecharacteristicbadodorofgarlic.

Allylin

Allicin
Anantibacterialfoundingarlic

Odorofgarlic

ThioethersarepreparedbyaprocedurerelatedtotheWilliamsonether
synthesis.Sulfideanions,whichareexcellentnucleophiles,reactinSN2
displacementofhalidesinalkylhalides.
CH3S ICH2CH3

Br

CH3SCH2CH3

Br

Na2S

Biotin(VitaminH)containsacyclicsulfidering.Biotinisacoenzyme(that
meansitworksinconjunctionwithanenzyme)involvedinthetransferofCO 2in
biologicalreactions.

152Ch7Alcohols,Thiols,Phenols,Ethers

NH NH

OH
S
O
Biotin
VitaminH(egg
yolk,kidney)

A common reaction of thioethers is their oxidation to sulfoxides and

sulfones.Hydrogenperoxide,andotherperoxidereagents,canoxidethesulfur
atomonceortwicedependingontheamountofperoxideused.

CH3SCH3

H2O2

O
CH3SCH3

dimethylsulfoxide

H2O2

O
CH3SCH3
O
dimethylsulfone

Dimethylsulfoxide(DMSO)iswellknowninorganicchemistryforits
abilitytodissolvemanysubstancesincludingsomesalts.Inmedicine,dimethyl
sulfoxideisusedtotreatarthritisasitisadsorbedthroughtheskin.Thusrubbing
affected areas with dilute DMSO solutions gives relief. Some drugs may be
administeredbydissolvinginDMSOandabsorbingthroughtheskin.DMSOhas
afainttasteofoysters.

7.4Summary153

7.5Summary
AnaliphaticorganiccompoundcontaininganOHfunctionistermedan
alcohol.Alcoholsareslightlyacidicandarecapableofformingstronghydrogen
bondsgivingrisetoincreasedboilingpoints.Alcoholsareclassifiedasprimary,
secondaryandtertiary.
Alcoholsarepreparedbyregioandstereoselectivehydrationofalkenes
by oxymercurationdemercuration, hydroborationoxidation, and by direct
hydroxylation.Grignardreactionswithcarbonylcompoundsgivealcohols.
Nucleophilicsubstitutionofprimaryalkylhalideswithhydroxideionproduces
hydroxylic compounds. Reduction of carboxylic acids, aldehydes, esters,
aldehydes and ketones also yields alcohols. Mild oxidation of alkenes with
permanganateorperoxideproducesvicinaldiols.
Alcohols,asmildacids,reactwithalkalimetaltogivealkoxidethatare
usefulbasesandnucleophiles.Alcoholsreactwithhydrogenhalidestoproduce
alkylhalidesinreactionsthatinvolveS N2mechanismforprimaryalcohols,and
SN1andE1mechanismsforsecondaryandtertiaryalcohols.Alkylhalidesare
alsopreparedfromthionylchlorideandphosphorushalidereagents.Alcoholsare
dehydratedwithsulfuricacidinreactionprocessesthatinvolvecarbocations.
Alcoholsareoxidizedwithawidevarietyorreagentstogiveacid,aldehydesand
ketones.
Thiols arerelatedtoalcoholsbyhavingthe sulfhydrylfunction,SH, in
placeofthehydroxylfunction,OH.Butthiolsareverydifferentfromalcoholsin
their properties, most notably possessing foul odors. Conversion of thiols to
disulfidesisanimportantbiologicalprocessinproteinstructure.
Aromaticalcohols,knownasphenols,bearlittleresemblancetoaliphatic
alcohols. Phenols are solids, highly polar, highly acidic, and do not have
reactionsthatbreaktheCObond.Thearomaticringofphenolsisveryreactive
toelectrophilicaromaticsubstitution.Oxidationreductionprocessesthatinvolve
phenolsandquinonesareimportantbiologicaltransformations.
Ethersarerelativelyinert,lowboilingcompoundsusefulassolventsfor
organic reactions. The Williamson ether synthesis is often used in their
preparation.Cyclic,threememberedethers,knownas oxiranesorepoxides are
reactivespeciesusefulinseveralringopeningreactionswithnucleophiles.

154Ch7Alcohols,Thiols,Phenols,Ethers

7.6ProblemSet
7.1ProvideIUPACnamesforthestructuresad,andprovidestructuresforeh.
a)4methyl2pentanol
c)trans4tertbutylcyclohexanol
OH
e)

f)Cl
OH

H3C

Cl

g)

CH(CH3)2

HO

b)4,4,4trifluoro2butanol
d)trans1,2cyclohexandiol

CH3

CH3

CH3 OH

h)

CH3CH2 CCH2 CHCH2Br

CH3

7.2 Classifythealcoholsinproblem7.1asprimary,secondary,tertiary,allylic,
phenolic.
7.3 Showtheproductforthereactionsofafwithhydroxide.

a)

CH3CH2CH2OH

c)

b)CH3CH2CH2Br

e)

OHf)

Br

CH3
d)
CH3 CBr
CH3

CH3
CH3 COH
CH3

7.4GivetheproductsforthereactionsofeachsubstratebelowwithPhMgBr/

H3O ,metachloroperoxybenzoicacid(MCPBA),andHI.
O
OCH3CH3CH=CHCH3
CH3CH2CH2OH

OH

7.5 a)Reactionofmethanethiolwithiodinegivesanewcompound,C 2H6S2,that

isahamstersexattractant.Whatisthestructure?b)Allylin,sect7.4g,reacts
withNaBH4,togiveathiol.Whatisthethiol?

7.6ProblemSet155

7.6 Useanalkoxideandanalkylhalidetopreparetheethersbelow.
b)
a)
O

CH3

CH3

CH3

7.7 ProvidestructuresforthereactionproductsAHbelow.
O
1)CH3CH2MgBr
A PBr3

2)H3O
CH3 1)BH3

C H2SO4
D

2)H2O2,OH
CH3CH2CH2C=O

OH

1)NaBH4
2)HBr
H2SO4

K2CrO4
E

OtertBu

KMnO4
cold