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Alcohol
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�
AlcoholAlcoholAlcoholAlcohol
Jully TanSchool of Engineering
EP101 / EG101 �
Alcohols
.
This family of organic compounds is characterized by the hydroxyl group: -OH. Note that when an R group (an alkyl group) replaces one H in the water molecule, an alcohol results
::
the alcoholfunctional group
C O-H
105o
water
HO
H
109o
an alcohol
RO
H
OH is the function group which is the center of the reactivity
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EP101 / EG101 �
Classification of Alcohols
.
Alcohols are classified as primary, secondary or tertiary according to the structure around the carbon to which the hydroxyl group is attached
ethyl alcohol
CH3CH2OH
a 1o alcohol
CCH3
H
HOH
isopropyl alcohol
(CH3)2CHOH
a 2o alcohol
CCH3
CH3
HOH
tertiary-butyl alcohol
(CH3)3COH
a 3o alcohol
CCH3
CH3OH
CH3
Aromatic (phenol): -OH is bonded to a benzene ring
OH
EP101 / EG101 �
Nomenclature of Alcohols
In the IUPAC naming system, there may be asmany as four components to the name:
Locant indicates the position of a substituent.Prefix names the substituent group.
Parent is the parent alkane.
Suffix names a key function.
Examples
CH3CH2CHCH3
OHCH3CHCH2CH2OH
CH3
2-butanol 3-methyl-1-butanol
locant parentsuffix
locant prefix locantsuffix
parent
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EP101 / EG101 �
IUPAC Rules for Naming Alcohols
(1) Select the longest continuous chain containing the hydroxyl group as the parent. Drop the "e" in the alkane name and add the suffix "ol."
.(2) Number the chain from the end that gives a lower number to the position of the hydroxyl group
CH3CH2CHCH2OHCH3
4 3 2 1
2-methyl-1-butanol
CH3CHCHCH3CH3
OH
3-methyl-2-butanol
EP101 / EG101 �
Common Names of Alcohols
Alkyl group names are approved by IUPAC for naming alcohols:"alkyl group + alcohol."
CH3CH2OH CH3CHCH3
OHCH3CCH2OH
CH3
CH3
ethyl alcohol isopropyl alcohol neopentyl alcohol
"Glycol" is a common name for compounds containing two hydroxyl groups. In the IUPAC system, they are diols.
HOCH2CH2OH CH3CHCH2OHOH
ethylene glycol
(1,2-ethanediol)
propylene glycol
(1,2-propanediol)
.
Note: The glycol name uses the common name of the alkene that yields the diol upon hydroxylation
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EP101 / EG101 �
Name these:Name these:Name these:Name these:
CH3 CH
CH3
CH2OH
CH3 C
CH3
CH3
OH
CH3 CH
OH
CH2CH32-methyl-1-propanol
2-methyl-2-propanol
2-butanol
OH
Br CH3
3-bromo-3-methylcyclohexanol
EP101 / EG101 �
Unsaturated AlcoholsUnsaturated AlcoholsUnsaturated AlcoholsUnsaturated Alcohols� Hydroxyl group takes precedence over double and triple bonds. � Assign carbon with –OH the lowest number.� Use alkene or alkyne name.
4-penten-2-olpent-4-ene-2-ol orCH2 CHCH2CHCH3
OH
HO OH 1,6-hexanediol
Glycols� 1, 2 diols (vicinal diols) are called glycols.� Common names for glycols use the name of the alkene from which they were made.
CH2CH2
OH OH
1,2-ethanediol
ethylene glycol
CH2CH2CH3
OH OH
1,2-propanediol
propylene glycol
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EP101 / EG101
Naming PhenolsNaming PhenolsNaming PhenolsNaming Phenols� -OH group is assumed to be on carbon 1.� For common names of disubstituted phenols, use ortho- for 1,2; meta- for 1,3; and para-
for 1,4.� Methyl phenols are cresols.
OH
Cl
3-chlorophenolmeta-chlorophenol
OH
H3C
4-methylphenol
para-cresol
EP101 / EG101 �
Solubility decreases as the size of the alkyl group increases.
Physical Properties of Alcohols: 1. SolubilityPhysical Properties of Alcohols: 1. SolubilityPhysical Properties of Alcohols: 1. SolubilityPhysical Properties of Alcohols: 1. Solubility
OH group is the hydrophilic part of alcohol (ROH) which form H bond with water molecules.
Therefore, ROH is soluble in water. BUT when C chain increased, the solubility in water decreased. (increase the hydrophobicity)
Increase branching increased the ROH solubility.
WHY??? Because the C atom (hydrophobic part) become more compact and smaller.
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EP101 / EG101 ��
2. Boiling Points2. Boiling Points2. Boiling Points2. Boiling Points
• ROH has bp higher than any HC of similar molecular mass.
•The large difference in bp is due to the intermolecular hydrogen bond in alcohol and phenol.
• Presence of –OH group causes polarization in the molecule to form intermolecular hydrogen bonds.
• van der waals < hydrogen bonds ; the energy/strength increase for H bonds. So more energy needed to break bonds.
• bp reduces by increased the branching of molecule due to smaller surface area and its reduce the dipole inter-reaction between molecules and less energy needed to break bonds.
•
EP101 / EG101 ��
3. Acidity of Alcohol & Phenol3. Acidity of Alcohol & Phenol3. Acidity of Alcohol & Phenol3. Acidity of Alcohol & Phenol
� ROH are weak acid� In aqueous, ROH donate proton to water to form alkoxide ion
� If given disassociation constant, Ka, the smaller the Ka the more acidic the ROH
� Delocalization of electron in the benzene ring makes phenoxide ion more acidic & stable in its form of as compared to alkoxide ion.
� Presence of e withdrawing grp phenol acidity.
R-OH + H2O � R-O- + H3O+
aaa KpKwherebyROH
ROOHK log
][]][[ 3 −==
−+ Smaller pKa= more acidic!!
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EP101 / EG101 ��
Molecular Structure and AcidityMolecular Structure and AcidityMolecular Structure and AcidityMolecular Structure and Acidity
C. Resonance delocalization of charge in A-
� the more stable the anion, the farther the position of equilibrium is shifted to the right
� ionization of the O-H bond of an alcohol gives an anion for which there is no resonance stabilization
CH3CH2O-H H2 O CH3CH2O - H3 O++
An alcohol An alkoxide ion
+ pKa = 15.9
EP101 / EG101 ��
Molecular Structure and AcidityMolecular Structure and AcidityMolecular Structure and AcidityMolecular Structure and Acidity
D. Electron-withdrawing inductive effect� the polarization of electron density of a covalent bond due to the
electronegativity of an adjacent covalent bond
� stabilization by the inductive effect falls off rapidly with increasing distance of the electronegative atom from the site of negative charge
C-CH2O-HH
HH
C-CH2O-HF
FF
EthanolpKa 15.9
2,2,2-TrifluoroethanolpKa 12.4
CF3 -CH2 -OH CF3 -CH2 -CH2 -OH CF3 -CH2 -CH2 -CH2 -OH2,2,2-Trifluoro-
ethanol(pKa 12.4)
3,3,3-Trifluoro-1-propanol(pKa 14.6)
4,4,4-Trifluoro-1-butanol
(pKa 15.4)
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EP101 / EG101 ��
� Simple alcohols are about as acidic as water.� Alkyl groups make an alcohol a weaker acid.� The more easily the alkoxide ion is solvated by water the more its formation is energetically
favored.� Steric effects are important.
EP101 / EG101 ��
The presence of halogens in the alcohol increases the acidity of the alcohol due to an inductive effect.The electronegative halogen atom polarizes the X-C bond producing a partial positive charge on the carbon atom. This charge is further transmitted through the C-O σ bond to the oxygen atom which is then better able to stabilize the negative charge on the alkoxide oxygen.Inductive effects increase with the number of electronegative groups and decreases with the distance from the oygen.
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EP101 / EG101 ��
Acidity of PhenolsAcidity of PhenolsAcidity of PhenolsAcidity of Phenols
• Phenols and alcohols both contain hydroxyl groups however they are classified as separate functional groups. Why?
Answer: Phenols have different properties than alcohols, most noteworthy is their acidity (pKadifference of 106)
OH O
+ H2O + H3O+ pKa = 9.95
H3C
H2C
OH + H2O H3C
H2C
O+ H3O+ pKa = 15.9
Solutions of alcohols in water are neutral, whereas a solution of 0.1 M phenol is slightly acidic (pH 5.4).
EP101 / EG101 ��
• Why are phenols more acidic?
Resonance. The charge is delocalized around the ring.
O O O O
This gives a qualitative explanation as to why phenols are more acidic than alcohols but for quantitative comparison, pKa’s must be determined experimentally.
• Ring substituents, especially halogens and nitro groups have marked effects on the acidity of phenol by a combination or resonance and inductive effects. Both m-cresol and p-cresol are weaker acids than phenol with pKa’s of 10.01 and 10.17 respectively.
OH OH
CH3CH3
m-cresolp-cresol
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EP101 / EG101 �
Influence of substituents on the acidity of phenol:Alkyl groups decrease the acidity of phenol where halogens increase the acidity of phenol through inductive effects.
O
CH3
Electron donating alkyl group destabilizesthis resonance structure
OH
XX = F, Cl, Br
X
OElectron withdrawing halogen groups stabilize the delocalized negative charge
Fluorine is most electronegative of the halogens, and therefore has the greatest influence on the acidity of halophenols. This trend follows electronegativity: Chlorine has less of an effect than fluorine and bromine an even smaller effect than chlorine.
OH
Cl
m-chlorophenol
pKa = 8.85
OH
CH3
p-cresol
pKa = 10.17
EP101 / EG101 �
Synthesis of AlcoholSynthesis of AlcoholSynthesis of AlcoholSynthesis of Alcohol
� Reduction of carbonyl� Catalytic hydrogenation if aldehyde & ketone� Reduction of aldehyde & ketone by hidride
� Nucleophilic substitution of alkyl halide
� From Alkene� Hydration of alkene� Hydroboration-oxidation of alkene� Hydroxylation of alkene
� Addition of grignard to carbonyl
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EP101 / EG101 ��
.Alkenes react with water in the presence of acids to give alcohols directly. Addition does not occur in the absence of acids
H3C
H3C H
H
+ H2OH+ OH
Acid-Catalyzed Direct Hydration of AlkenesA1.
A. Synthesis From Alkene
EP101 / EG101 ��
Mechanism of Direct Hydration of Alkenes
Step 1: electrophilic addition
++ slow
H OH
H + + H2O
Step 2: nucleophilic addition
+ + :
: fastOH
H+
tert-butyloxonium ion
OH2
+ :
: fast+OH
HOH2
Step 3: deprotonation
+OH+
H OH
H
Note: Hydronium ion is reformed, so the reaction is catalyzed by acid.
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EP101 / EG101 ��
Alcohols through Oxidation of Alkylboranes
Reaction of an alkylborane with hydrogen peroxide (H2O2) and base (NaOH) leads to replacement of the borane group with a hydroxyl group.
The sequence of hydroboration-oxidation of an alkene yields an alcohol with anti-Markovnikov orientation.
an alkene
O H
anti-M arkovnikov product
A2.
NaOH, H2OH2O2
BH2 HH
OH HHretention
EP101 / EG101 ��
Oxidations of Alkenes--Syn Hydroxylation
The stereospecific formation of 1,2-diols (or glycols) from alkenes may be carried out in two ways:
KMnO4, HO-
cold H2O HO OH
(i) OsO4, pyridine
(ii) Na2SO3/H2O or NaHSO3/H2O HO OH
A3.
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EP101 / EG101 ��
B. B. B. B. Reduction of CarbonylReduction of CarbonylReduction of CarbonylReduction of Carbonyl
� Reduction of aldehyde yields 1º alcohol.� Reduction of ketone yields 2º alcohol.� 2 Methods of reduction of carbonyl
� Catalytic hydrogenation of aldehyde & ketone, and � Reduction of aldehyde & ketone by hydride.
EP101 / EG101 ��
B1. Catalytic Hydrogenation
� Add H2 with Raney nickel catalyst.� Also reduces any C= bonds.� Hydrogenation of Ketone yields 20 alcohol� Hydrogenation of Aldehyde yields 10 alcohol
H2, NiCO
COH
H
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EP101 / EG101 ��
Sodium Sodium Sodium Sodium BorohydrideBorohydrideBorohydrideBorohydride� Hydride ion, H-, attacks the carbonyl carbon, forming an alkoxide ion.� Then the alkoxide ion is protonated by dilute acid.� Only reacts with carbonyl of aldehyde or ketone, not with carbonyls of esters or carboxylic acids.
HC
O
HC
H
OHC
H
OH HH3O+
B2. Reduction of aldehyde & ketone by hydride.
EP101 / EG101 ��
Comparison of Comparison of Comparison of Comparison of Reducing AgentsReducing AgentsReducing AgentsReducing Agents
� LiAlH4 is stronger.� LiAlH4 reduces more stable compounds
which are resistant to reduction.
15
EP101 / EG101 �
.A nucleophile has an unshared pair of electrons available for bonding to a positive center
Nucleophiles may be negatively charged:
HO , CH3O , I , NH2- - - -:
:
::
::
::::: :
or neutral:H2O , H3N, CH3OH
::
: ::
Nucleophiles attackelectropositive center.
Halide ionis the leavinggroup.
C Xδ+
δ−The polarity of the carbon-halogen bond determines the reactivity pattern:
C. Nucleophilic Substitution of Alkyl Halide
EP101 / EG101 �
Reaction of t-Butyl Chloride with Hydroxide:
:
The reaction of t-butyl chloride with sodium hydroxide in a mixture of water and acetone (to help dissolve the RCl) shows the following rate expression
+ HO-acetone
+ Cl-CH3-C-ClCH3
CH3
H2OCH3-C-OH
CH3
CH3
.The reaction rate depends on the concentration of t-butyl chloride, but shows no dependence on the concentration of hydroxide ion
A r e a c tio n r a te th a t d e p e n d s o n th e c o n c e n tr a tio n o f o n ly o n e r e a c ta n t ( to th e fir s t p o w e r ) is c a lle d fir s t-o r d e r o r u n im o le c u la r .
16
EP101 / EG101 ��
A Proposed Mechanism with a Carbocation Intermediate
:bond heterolysis
:nucleophilic addition
(2) + + :
:
nucleophile
fast +:
t-butyloxonium ion
CH3-CCH3
CH3
O-HH
CH3-CCH3
CH3
O-HH
:proton exchange
(3)+:
+ :
:
base
fast+CH3-C
CH3
CH3
O-HH
O-HH
CH3-CCH3
CH3
O-H H3O+
(1) slow step + +
t-butyl carbocationa high energy intermediate
CH3-C-ClCH3
CH3
CH3-CCH3
CH3
Cl-
EP101 / EG101 ��
Examples
(1) -+
nucleophile substrate
HOC Cl
H3CH
H
product leaving group
C OH
H3CH
H
+ Cl
(2) +
nucleophile substrate
C Cl
H3CH
H
HO
H
ethyloxonium ion leaving group
C O
H3CH
H
+ Cl
H
H
product
C OH
H3CH
H
+ H3O
H2O
17
EP101 / EG101 ��
Reaction with CarbonylReaction with CarbonylReaction with CarbonylReaction with Carbonyl
� R- attacks the partially positive carbon in the carbonyl.� The intermediate is an alkoxide ion.� Addition of water or dilute acid protonates the alkoxide to produce an alcohol.
R C O R C O
HO HR C O H
OH
D. Addition of Grignard to Carbonyl
C
C H3
RO
R MgB r + C
C H3
R
OR MgB r
HOH
C
C H3
R
OHR
EP101 / EG101 ��
Some Grignard ReagentsSome Grignard ReagentsSome Grignard ReagentsSome Grignard Reagents
Br
+ Mgether MgBr
CH3CHCH2CH3
Clether
+ Mg CH3CHCH2CH3
MgCl
C H 3C C H2
B r + M gether
C H3 C C H 2
M gB r
18
EP101 / EG101 ��
D1-Synthesis of 1° Alcohols
Grignard + formaldehyde yields a primary alcohol with one additional carbon.
HOHC H3 C H
C H3
C H2 C H2 C
H
H
O H
C OH
HCCH3
H3C CH2 C MgBrH
HHCH3 CH
CH3
CH2 CH2 CH
HO MgBr
D2- Synthesis of 2º AlcoholsGrignard + aldehyde yields a secondary alcohol.
MgBrCH3 CH
CH3
CH2 CH2 C
CH3
H
OC
CH3
H3C CH2 C MgBr
H
HH
C OH
H3C
CH3 CH
CH3
CH2 CH2 C
CH3
H
O HHOH
EP101 / EG101 ��
D3- Synthesis of 3º Alcohols
Grignard + ketone yields a tertiary alcohol.
MgBrCH3 CH
CH3
CH2 CH2 C
CH3
CH3
OC
CH3
H3C CH2 C MgBr
H
HH
C OH3C
H3C
CH3 CH
CH3
CH2 CH2 C
CH3
CH3
O HHOH
19
EP101 / EG101 ��
Synthesis PhenolSynthesis PhenolSynthesis PhenolSynthesis Phenol
EP101 / EG101 ��
SulfonationSulfonationSulfonationSulfonation & Fused Alkylation& Fused Alkylation& Fused Alkylation& Fused Alkylation
20
EP101 / EG101 �
Reaction of AlcoholReaction of AlcoholReaction of AlcoholReaction of Alcohol
� Oxidation of ROH� Reduction of ROH� Breaking of Carbon–OH bond
� ROH�RX� ROH�C=C� ROH� ROR
� Breaking of O-H� Formation of esther
EP101 / EG101 �
A. Oxidation of AlcoholA. Oxidation of AlcoholA. Oxidation of AlcoholA. Oxidation of Alcohol
-ROH is main source of C=O (carbonyl)C=O (carbonyl)-Oxidation of primary and secondary alcohol will give aldehyde and ketone respectively.
+ Cr3+ (green)
Cu or
CrO3/pyridine(C5H5N)
Chromic acid
H2CrO4
21
EP101 / EG101 ��
1111oooo & 2& 2& 2& 2oooo Alcohol OxidationsAlcohol OxidationsAlcohol OxidationsAlcohol Oxidations� Primary alcohols � aldehydes
� PCC/CH2Cl2 (pyridinium chlorochromate, C5H5NH+ClCrO3-)
� CrVI in one form or another (H2CrO4 or K2Cr2O7)� MnVII (KMnO4/NaOH/H2O/heat)
� Color of reagents can be useful.� CrVI is yellow; CrIII is blue
Cu or
CrO3/pyridine(C5H5N)
Chromic acid
H2CrO4
EP101 / EG101 ��
3333oooo Alcohol OxidationsAlcohol OxidationsAlcohol OxidationsAlcohol Oxidations
� Tertiary alcohols cannot be oxidized under normal conditions.
� Heat them too much in the presence of strong oxidizers; start cleaving C-C bonds.
Why?Why?Why?Why?
� When an alcohol is oxidized, a hydrogen is removed from the carbon. If that hydrogen is not present, no oxidation can occur.
H
OHO
[O]
OH
NRX
22
EP101 / EG101 ��
B. Reduction of AlcoholB. Reduction of AlcoholB. Reduction of AlcoholB. Reduction of Alcohol
alcohol
CH3CHCH3
OHTsCl
CH3CHCH3
OTsLiAlH4
alkaneCH3CH2CH3
tosylate
EP101 / EG101 ��
C. Breaking of CarbonC. Breaking of CarbonC. Breaking of CarbonC. Breaking of Carbon----Hydroxyl CarbonHydroxyl CarbonHydroxyl CarbonHydroxyl Carbon
23
EP101 / EG101 ��
Reaction with HClReaction with HClReaction with HClReaction with HCl� Chloride is a weaker nucleophile than bromide.� Add ZnCl2, which bonds strongly with
-OH, to promote the reaction.� The chloride product is insoluble.� Lucas test: ZnCl2 in conc. HCl
� 1° alcohols react slowly or not at all.� 2° alcohols react in 1-5 minutes.� 3° alcohols react in less than 1 minute.
Limitations of HX ReactionsLimitations of HX ReactionsLimitations of HX ReactionsLimitations of HX Reactions� HI does not react� Poor yields of 1° and 2° chlorides� May get alkene instead of alkyl halide� Carbocation intermediate may rearrange.
EP101 / EG101 ��
C2.2. Reaction with tionyl chloride, SOCl2
� Produces alkyl chloride, SO2, HCl� S bonds to -OH, Cl- leaves� Cl- abstracts H+ from OH� C-O bond breaks as Cl- transferred to C
24
EP101 / EG101 ��
� P bonds to -OH as Br- leaves
� Br- attacks backside � HOPBr2 leaves
C2.3. Reaction with Phosphorus halogen, PX3
EP101 / EG101 ��
Dehydration of AlcoholsAlkenes are also generally prepared by the dehydration of alcohols in the presence of a strong acid.
heatH+
C
H
C
OH
+ H2O
C3.
25
EP101 / EG101 �
D1. D1. D1. D1. EsterificationEsterificationEsterificationEsterification
� Fischer: alcohol + carboxylic acid� Tosylate esters� Sulfate esters� Nitrate esters� Phosphate esters� Acid + Alcohol yields Ester + Water� Sulfuric acid is a catalyst.� Each step is reversible.
CH3 C OH
O
+ CH2CH2CHCH3
CH3
OHH+
CH3C
O
OCH2CH2CHCH3
CH3
+ HOH
EP101 / EG101 �
aldehyde RCOOHketone
ROR
alkyne
alkene
RH
RX
ROH
Alcohols are central to organic syntheses
