Chapter17

AlcoholsandPhenols

AlcoholsandPhenols
AlcoholsandStu
1.Oxida9on
A.Alcoholtocarbonyl

2.Reduc9on
A.Carbonyltoalcohol

3.GrignardAddi9on
A.Addi9onofalkylgrouptocarbonyl

4.AlkylHalideSubs9tu9on
A.Subs9tu9onofalcoholbyhalide

5.Dehydra9onElimina9on
A.Elimina9onofalcoholtoformalkene

AlcoholsandPhenols
ReducingAgents
NaBH4
1.Doesnotinterferewithotherfunc9onal
groupsoutsideofketonesandaldehydes
LiAlH4
1.Doesnotreducedoublebonds(namely,alkenes)
outsideofaldehydes,ketones,carboxylicacidsand
esters.

AlcoholsandPhenols
Reduc9onofAldehydes
Step1
Reactants:
1.or
2.
Solvents:
1.
2.

Step2:
Reactants
1.

Products:
1.

AlcoholsandPhenols
Reduc9onofAldehydes
Step1
Reactants:
1.NaBH4orLiAlH4
2.Aldehyde
Solvents:
1.Ethanol(forNaBH4)
2.Ether(forLiAlH4)

Step2:
Reactants
1.H3O+

Products:
1.Primaryalcohol

AlcoholsandPhenols
Reduc9onofKetones
Step1
Reactants:
1.or
2.
Solvents:
1.
2.

Step2:
Reactants
1.

Products:
1.

AlcoholsandPhenols
Reduc9onofKetones
Step1
Reactants:
1.NaBH4orLiAlH4
2.Ketone
Solvents:
1.Ethanol(forNaBH4)
2.Ether(forLiAlH4)

Step2:
Reactants
1.H3O+

Products:
1.Secondaryalcohol

AlcoholsandPhenols
Reduc9onofEsters
Step1
Reactants:
1.or
2.
Solvents:
1.
2.

Step2:
Reactants
1.

Products:
1.

Note:
1.

AlcoholsandPhenols
Reduc9onofEsters
Step1
Reactants:
1.NaBH4orLiAlH4
2.Ester
Solvents:
1.Ethanol(forNaBH4)
2.Ether(forLiAlH4)

Step2:

Reactants
1.H3O+

Products:

1.Primaryalcohol

Note:
1.NaBH4reducesestersveryslowly

AlcoholsandPhenols
Reduc9onofCarboxylicacids
Step1
Reactants:
1.
2.
Solvents:
1.

Step2:
Reactants
1.

Products:
1.

Note:
1.

AlcoholsandPhenols
Reduc9onofCarboxylicacids
Step1
Reactants:
1.LiAlH4
2.Carboxylicacid
Solvents:
1.Ether(forLiAlH4)

Step2:

Reactants
1.H3O+

Products:

1.Primaryalcohol

Note:
1.NaBH4doesnotreducecarboxylicacidsatall

AlcoholsandPhenols
Grignardaddi9onto:Formaldehyde
Step1
Reactants:
1.
2.
Solvents:
1.

Step2:
Reactants
1.

Products:
1.

AlcoholsandPhenols
Grignardaddi9onto:Formaldehyde
Step1
Reactants:
1.Formaldehyde
2.RMgBr
Solvents:
1.Ether

Step2:
Reactants
1.H3O+

Products:
1.Primaryalcohol
2.Stereochemistry

AlcoholsandPhenols
Grignardaddi9onto:Aldehyde
Step1
Reactants:
1.
2.
Solvents:
1.

Step2:
Reactants
1.

Products:
1.
2.

AlcoholsandPhenols
Grignardaddi9onto:Aldehyde
Step1
Reactants:
1.Aldehyde
2.RMgBr
Solvents:
1.Ether

Step2:
Reactants
1.H3O+

Products:
1.Secondaryalcohol
2.Stereochemistry

AlcoholsandPhenols
Grignardaddi9onto:Ketone
Step1

Reactants:
1.
2.
Solvents:
1.

Step2:

Reactants
1.

Products:
1.

Note:

1.
2.
3.

AlcoholsandPhenols
Grignardaddi9onto:Ketone
Step1

Reactants:
1.Ketone
2.RMgBr
Solvents:
1.Ether

Step2:

Reactants
1.H3O+

Products:

1.Ter9aryalcohol

Note:

1.WhenthreeofthegroupsaXachedtothealcoholcarbonaredierentitMUST
comefromaketone
2.IftwoofthegroupsaXachedtothealcoholcarbonarethesame,itmaycome
fromeitheraketoneoranester.
3.Stereochemistry

AlcoholsandPhenols
Grignardaddi9onto:Ester
Step1
Reactants:
1.
2.
Solvents:
1.

Step2:
Reactants
1.

Products:
1.

Notes
1.
2.

AlcoholsandPhenols
Grignardaddi9onto:Ester
Step1

Reactants:
1.Ester
2.RMgBr
Solvents:
1.Ether

Step2:

Reactants
1.H3O+

Products:

1.Ter9aryalcohol

Notes

1.IftwoofthegroupsaXachedtothealcoholcarbonarethesame,itmay
comefromeitheraketoneoranester.
2.Stereochemistry

AlcoholsandPhenols
Grignardaddi9onto:Carboxylicacids
Step1
1.

AlcoholsandPhenols
Grignardaddi9onto:Carboxylicacids
Step1
1.Itdoesntoccurbecausetheacidiccarboxylhydrogenreactswiththe
basisGrignardreagenttoyieldahydrocarbonandthemagnesiumsalt
oftheacid.

AlcoholsandPhenols
AlcoholtoAnion
Reactants
1.
2.

Products
1.

AlcoholsandPhenols
AlcoholtoAnion
Reactants
1.primary,secondaryorter9aryalcohol
2.NaH

Products
1.Na+O

AlcoholsandPhenols
GrignardLimita9ons
1.Grignardreagentcantbepreparedfromanorganohalideifother
reac9vefunc9onalgroupsarepresentinthesamemolecule.The
Grignardreagentwillbeprotonatedbythesefunc9onalgroups:
A.
B.
C.
D.

2.TheGrignardreagentaddstothesegroups
A.
B.
C.
D.
E.
F.

AlcoholsandPhenols
GrignardLimita9ons
1.Grignardreagentcantbepreparedfromanorganohalideifother
reac9vefunc9onalgroupsarepresentinthesamemolecule.The
Grignardreagentwillbeprotonatedbythesefunc9onalgroups:
A.OH(hydroxyl)
B.NH
C.SH(Thiol)
D.CO2H(Carboxylicacid)

2.TheGrignardreagentaddstothesegroups
A.HC=O(aldehyde)
B.RC=O(ketone)
C.NR2C=O(Amide)
D.C#N(Nitrile)
E.NO2(Nitrogroup)
F.SO2R(Thioester)

AlcoholsandPhenols
AlkylHalidesfrom:TerHaryAlcohols
Reactants:
1.
2.

Solvent:
1.

Temperature:
1.

Products:
1.

Regiochemistry:
1.

Notes:
1.
2.

AlcoholsandPhenols
AlkylHalidesfrom:TerHaryAlcohols
Reactants:

1.Ter9aryalcohol
2.HX(gas)

Solvent:

1.Ether

Temperature:
1.0C

Products:

1.Ter9aryalkylhalide

Regiochemistry:
1.Markovnikov

Notes:

1.Reac9vityorder:3>2>1
2.ViaanSN1reac9on

AlcoholsandPhenols
AlkylHalidesfrom:Primary&SecondaryAlcohols(PartI)
Reactants:
1.
2.

Solvent:
1.
2.

Intermediates:
1.

Products:
1.

Regiochemistry:
1.

Notes:
1.

AlcoholsandPhenols
AlkylHalidesfrom:Primary&SecondaryAlcohols(PartI)
Reactants:

1.Primaryorsecondaryalcohol
2.SOCl2(Thionylchloride)

Solvent:

1.Pyridineor
2.Et3N

Intermediates:

1.Chlorosulte

Products:

1.Primaryorsecondaryalkylhalide

Regiochemistry:

1.Markovnikov

Notes:

1.ViaanSN2reac9on

AlcoholsandPhenols
AlkylHalidesfrom:Primary&SecondaryAlcohols(PartII)
Reactants:
1.
2.

Solvent:
1.
2.

Intermediates:
1.

Products:
1.

Regiochemistry:
1.

Notes:
1.

AlcoholsandPhenols
AlkylHalidesfrom:Primary&SecondaryAlcohols(PartII)
Reactants:

1.Primaryorsecondaryalcohol
2.PBr3(Phosphoroustribromide)

Solvent:

1.Ether

Intermediates:

1.Dibromophosphite

Temperature:
1.35C

Products:

1.Primaryorsecondaryalkylhalide

Regiochemistry:
1.Markovnikov

Notes:

1.ViaanSN2reac9on

AlcoholsandPhenols
AlkylHalidesfrom:Primary&Secondary
Alcohols(PartIII)
Reactants:
1.
2.
3.

Solvent:
1.

Products:
1.

Regiochemistry:
1.

AlcoholsandPhenols
AlkylHalidesfrom:Primary&Secondary
Alcohols(PartIII)
Reactants:

1.Primaryorsecondaryalcohol
2.HFor
3.(CH3CH2)2NSF3(Diethylaminosulfurtriuoride)

Solvent:

1.Pyridine

Products:

1.Primaryorsecondaryalkylhalide

Regiochemistry:
1.Markovnikov

AlcoholsandPhenols

ConversionofalcoholstoTosylates
Step1
Reactants
1.
2.
Solvent:
1.
Step2:
Reactants:
1.
2.
Product
1.
Notes
1.
2.

AlcoholsandPhenols

ConversionofalcoholstoTosylates
Step1
Reactants
1.(S)Alcohol
2.Tosylate
Solvent:
1.Pyridine
Step2:
Reactants:
1.(S)Tosylatecomplex
2.Alkoxide
Product
1.(R)Ether
Notes
1.Tosylateshaveoneinversionofstereochemistryoverall
2.Alkylhalideshavetwoinversionsofstereochemistry,zerooverall

AlcoholsandPhenols
Reac9onsofalcohols:Dehydra9on
Reactants:
1.
2.
3.

Solvent
1.

Products:
1.

Note:
1.
2.

AlcoholsandPhenols
Reac9onsofalcohols:Dehydra9on
Reactants:
1.Ter9aryalcohol
2.H3O+
3.H2SO4

Solvent
1.THF

Products:
1.Alkene

Note:
1.UsesanE1mechanism
2.Secondaryandprimaryalcoholsrequirehigherconcentra9onsof
acidandarethusveryharshenvironments

AlcoholsandPhenols
Reac9onsofalcohols:Dehydra9on
Reactants:
1.
2.

Solvent
1.

Intermediates:
1.

Products:
1.

Note:
1.
2.

AlcoholsandPhenols
Reac9onsofalcohols:Dehydra9on
Reactants:
1.Secondaryandter9aryalcohols
2.POCl3

Solvent

1.Pyridine

Intermediates:
1.Dichlorophosphate

Products:
1.Alkene

Note:
1.UsesanE2mechanism
2.An9periplanarrela9onshipisneededbetweentheAlcoholandthe
Hydrogenofthecarbonthatisformingthedoublebond(thisonlyapplies
torings).

AlcoholsandPhenols
Oxida9on:PrimaryAlcohol
Reactants:
1.
2.or
3.or
4.or
5.

Products:
1.

Note:
1.
2.

AlcoholsandPhenols
Oxida9on:PrimaryAlcohol
Reactants:
1.Primaryalcohol
2.KMnO4or
3.CrO3(inH3O+andacetone)or
4.Na2Cr2O7(InH2O,CH3CO2H,heat)or
5.C5H6NCrO3Cl(akaPCC)

Products:
1.Aldehyde,whichwillproceedtocarboxylicacid(unstoppable)

Note:
1.Ter9arydoesnotreactwiththethreeabovemen9onedoxidants
2.NeitherdoesBenzyne

AlcoholsandPhenols
Oxida9on:PrimaryAlcohols
Reactants:
1.
2.or
3.

Solvent
1.

Products:
1.

AlcoholsandPhenols
Oxida9on:PrimaryAlcohols
Reactants:
1.Primaryalcohol
2.DessMar9nperiodinaneor
3.PCC

Solvent
1.CH2Cl2

Products:
1.Aldehyde

AlcoholsandPhenols
Oxida9on:SecondaryAlcohol
Reactants:
1.
2.or
3.or
4.
5.

Products:
1.

Note:
1.

AlcoholsandPhenols
Oxida9on:SecondaryAlcohol
Reactants:
1.Secondaryalcohol
2.KMnO4or
3.CrO3(inH3O+andacetone)or
4.Na2Cr2O7(InH2O,CH3CO2,heat)
5.C5H6NCrO3Cl(akaPCC)

Products:
1.Ketone

Note:
1.Ter9arydoesnotreactwiththethreeabovemen9onedoxidants

AlcoholsandPhenols
Oxida9on:SecondaryAlcohols
Reactants:
1.
2.or
3.

Solvent
1.

Products:
1.

AlcoholsandPhenols
Oxida9on:SecondaryAlcohols
Reactants:
1.Secondaryalcohol
2.DessMar9nperiodinane
3.PCC

Solvent
1.CH2Cl2

Products:
1.Ketone

AlcoholsandPhenols
Oxida9on:CarboxylicacidstoEsters
Reactants:
1.
2.

Solvent
1.
2.

Products:
1.

AlcoholsandPhenols
Oxida9on:CarboxylicacidstoEsters
Reactants:
1.Benzoicacid
2.Methanol

Solvent
1.HCl
2.Heat

Products:
1.MethylBenzoate

AlcoholsandPhenols
Oxida9onofPhenols
Reactants:
1.
2.or
3.

Solvent
1.

Products:
1.

AlcoholsandPhenols
Oxida9onofPhenols
Reactants:
1.Phenol
2.Na2Cr2O7(InH2O,CH3CO2,heat)or
3.(KSO3)2NO(akaFremysSalt)

Solvent
1.H2O

Products:
1.Benzoquinone(1,4dicyclohexanone)

AlcoholsandPhenols
RedoxofBenzoquinone
Reactants:
1.
2.or
3.

Products:
1.

AlcoholsandPhenols
RedoxofBenzoquinone
Reactants:
1.Benzoquinone
2.SnCl2,H2Oor
3.NaBH4

Products:
1.Hydroquinone(pdihydroxybenzene)

AlcoholsandPhenols
Protec9onofAlcohols
Reactants:
1.
2.

Intermediate:
1.

Solvent
1.

Products:
1.

Note:

1.
2.
3.
1.
2.
3.

AlcoholsandPhenols
Protec9onofAlcohols
Reactants:

1.Alcohols
2.ClSi(CH3)3(chlorotrimethylsilane)

Intermediate

1.ROSiR3(trimethylsilylether)

Solvent

1.N(CH2CH3)3(Triethylamine)

Products:

1.NormallyaGrignardreagentreactedalcohol

Note:

1.TMSethersreactwithuorideionoraqueousacidtoregeneratetheini9alalcohol(no
heat;ifheatisusedyoucans9llregeneratetheini9alalcoholbutwillalsodehydratevia
elimina9onanyotheralcoholspresentinthereac9on)
2.Althoughter9ary,theyundergoSN2reac9onsbecauseSibondsaremuchlongerthan
Cbonds.
3.TMSethersdontreactwith:
1.Oxida9on
2.Reduc9on
3.Grignardreagents