1

AlcoholAlcoholJully Tan

School of Engineering

EP101 / EG101 2

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

EP101 / EG101 3

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 4

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

EP101 / EG101 5

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 6

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

EP101 / EG101 7

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 8

Unsaturated 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

EP101 / EG101 9

Naming Phenols Phenol is an aromatic compound. Hydroxyl (-OH) group attach to a benzene ring. -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-methylphenolpara-cresol

EP101 / EG101 10

Solubility decreases as the size of the alkyl group increases.

Physical 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.

EP101 / EG101 11

2. 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 12

3. 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!!

EP101 / EG101 13

Molecular Structure and AcidityResonance 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 H2O CH3CH2O - H3O++An alcohol An alkoxide ion

+ pKa = 15.9

EP101 / EG101 14

Molecular Structure and AcidityElectron-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)

EP101 / EG101 15

Solvation & Steric Effect

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 17

Acidity 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 (pKa difference 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 18

• 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

EP101 / EG101 19

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 20

Synthesis of Alcohol

Reduction of carbonyl Catalytic hydrogenation if aldehyde & ketone Reduction of aldehyde & ketone by hidride

From Alkene Hydration of alkene Hydroboration-oxidation of alkene Hydroxylation of alkene

Addition of grignard to carbonyl

EP101 / EG101 21

.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 22

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.

EP101 / EG101 23

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

OH

anti-Markovnikov product

A2.

NaOH, H2OH2O2

BH2 HH

OH HHretention

EP101 / EG101 24

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.

EP101 / EG101 25

B. Reduction 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 26

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

EP101 / EG101 27

Sodium Borohydride 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 28

Comparison of Reducing Agents

LiAlH4 is stronger. LiAlH4 reduces more stable compounds

which are resistant to reduction.

EP101 / EG101 29

Reaction 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

HOHR C OH

OH

C. Addition of Grignard to Carbonyl

C

CH3

RO

R MgBr + C

CH3

R

OR MgBr

HOH

C

CH3

R

OHR

EP101 / EG101 30

Some Grignard ReagentsBr

+ Mgether MgBr

CH3CHCH2CH3

Clether

+ Mg CH3CHCH2CH3

MgCl

CH3C CH2

Br + Mgether CH3C CH2

MgBr

EP101 / EG101 31

C1-Synthesis of 1° AlcoholsGrignard + formaldehyde yields a primary alcohol with one additional carbon.

HOHCH3 CH

CH3

CH2 CH2 C

H

H

O H

C OH

HCCH3

H3C CH2 C MgBrH

HHCH3 CH

CH3

CH2 CH2 CH

HO MgBr

C2- 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 32

C3- Synthesis of 3º AlcoholsGrignard + 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

EP101 / EG101 33

Synthesis Phenol

EP101 / EG101 34

Sulfonation & Fused Alkylation

EP101 / EG101 35

Reaction of Alcohol

Oxidation of ROH Reduction of ROH Breaking of Carbon–OH bond

ROHRX ROHC=C

Breaking of O-H Formation of esther

EP101 / EG101 36

A. 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

EP101 / EG101 37

1o & 2o Alcohol 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 38

3o Alcohol 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? 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

EP101 / EG101 39

B. Reduction of Alcohol

alcoholCH3CHCH3

OHTsCl

CH3CHCH3

OTsLiAlH4

alkaneCH3CH2CH3

tosylate

EP101 / EG101 40

C. Breaking of Carbon-Hydroxyl Bond

EP101 / EG101 41

Reaction 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 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 42

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

EP101 / EG101 43

P bonds to -OH as Br- leaves Br- attacks backside HOPBr2 leaves

C2.3. Reaction with Phosphorus halogen, PX3

EP101 / EG101 44

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.

EP101 / EG101 45

D1. Esterification 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 46

aldehyde RCOOHketone

ROR

alkyne

alkene

RH

RX

ROH

Alcohols are central to organic syntheses

EP101 / EG101 47