1

Chapter 7

Alcohols, phenols, and Thiols

2

Structure of Alcohols

Hydroxyl (-OH) functional groupOxygen is sp3 hybridized.

3

Nomenclature of AlcoholsCompounds in which a hydrogen is replaced by an OH group.We distinguish three types:

C OHRR

R

• Tertiary alcohols

CH OHR

R• Secondary alcohols

CH2 OHR• Primary alcohols

4

Nomenclature of AlcoholsCommon names are the name of alkyl group followed by the word “alcohol”

OH

cyclohexylalcohol

OH isopropyl alcohol

5

Nomenclature of Alcohols

CH3CH2CH2CH2CHCH2OHCH2CH2CH3

123456

1 2 3

CNotice that numbering starts at alcohol group

2-propyl-1-hexanol

CH3CH2CH2CH2CHCH2OHCH2CH2CH3

CC

6

More Examples

HO

H3C

Br

CH31

2 3

45

3-bromo-2-pentanol

OH1

234

56

2,3-dimethyl-1-cyclohexanol

2,3-dimethyl-cyclohexanol

OHH3C

CH3

65

43

21

3-ethyl-5-methyl-1-cyclohexanol

3-ethyl-5-methyl-cyclohexanol

OH

H3C4

32

1

4-methyl-cyclopent-2-en-1-ol

4-methyl-cyclopent-2-enol

7

Naming PriorityAcidsEstersAldehydesKetonesAlcoholsAmines

AlkenesAlkynesAlkanesEthersHalides

8

Hydroxy SubstituentWhen -OH is part of a higher priority class of compound, it is named as hydroxy.Example:

4-hydroxybutanoic acid

O

OHHO

9

Nomenclature of PhenolsOH 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.OH is named as hydroxy.

OH

Cl

3-chlorophenolmeta-chlorophenol

OH

CHO4-hydroxybenzaldehyde

10

Hydrogen Bonding in Alcohols and Phenols

CH3C

Clchloroethane

HH

MW 65bp 12.3

11

Hydrogen Bonding in Alcohols and PhenolsUnusually high boiling points due to hydrogen bonding between molecules.A positively polarized ⎯OH hydrogen atom from one molecule is attracted to a lone pair of electrons on a negatively polarized oxygen atom of another moleculeThis produces a force that holds the two molecules togetherThese intermolecular attractions are present in solution but not in the gas phase, thus elevating the boiling point of the solution

O

R

H HO

H

R

O

R

O

R

H HO

H

R

O

R

12

Small alcohols are miscible in water, but solubility decreases as the size of the alkyl group increases.

13

Acidity and Basicity ReviewedBrønsted–Lowry

Acid donates a proton Base accepts a proton

• Strong reacts to give weak• The weaker the base, the stronger is its conjugate acid• Stable bases are weak bases

14

An Acid/Base Equilibrium

Ka: The acid dissociation constant

H2O + HA H3O+ + A-

[H3O+][A-]Ka = [H2O][HA]

pKa = -log Ka

The stronger the acid, the smaller is its pKa

15

The Most Common Organic Acids Are Carboxylic Acids

16

Lewis acid: accepting pair of electrons (AlCl3, BH3 and Mn+,like Zn2+, Mg2+, Na+, R3C+………)

Lewis base: donating pair of electrons ( H-, -OR, -NH2, R3C-, X-

H2O, NR3,

Lewis Acids and Bases

17

The Acidity of Alcohols and PhenolsAlchols and Phenols are Weak Brønsted AcidsCan transfer a proton to water to a very small extentProduces H3O+ and an alkoxide ion, RO−, or a phenoxideion, ArO−

18

pKa Values for Typical OH Compounds

19

Relative Acidities of AlcoholsSimple alcohols are about as acidic as water.Alkyl groups make an alcohol a weaker acid.Electron-withdrawing groups make an alcohol a stronger acid by stabilizing the conjugate base (alkoxide)

Inductive Effects

20

Generating Alkoxides from AlcoholsAlcohols are weak acids – requires a strong base to form an alkoxide such as NaH, or metal (K, Na) Alkoxides are bases used as reagents in organic chemistry

21

Phenol Acidity

Phenols (pKa ~10) are much more acidic than alcohols (pKa~ 16) due to resonance stabilization of the phenoxide ion

Phenols react with NaOH solutions (but alcohols do not), forming soluble salts that are soluble in dilute aqueous

22

Substituted Phenols

Can be more or less acidic than phenol itselfAn electron-withdrawing substituent makes a phenol more acidic by delocalizing the negative chargePhenols with an electron-donating substituent are less acidic because these substituents concentrate the charge

23

Nitro-PhenolsPhenols with nitro groups at the ortho and para positions are much stronger acidsThe pKa of 2,4,6-trinitrophenol is 0.6, a very strong acid

24

The Basicity of Alcohols and Phenols

Alcohols are weak Brønsted basesProtonated by strong acids to yield oxoniumions, ROH2

+

25

Dehydration of Alcohols to AlkeneDehydration (elimination) of water is commonly obtained using sulfuric acid (H2SO4) as a catalyst.

H3C

CH3

OH H2SO4

ΔH3CHC CHCH3 + H2O

The acid is mandatory to convert the poor leaving group OH– into a good leaving group H2O.

26

DehydrationFirst step is protonation of the hydroxyl group.

H3C

CH3

OH H2SO4

Δ

H3C

CH3

OH

H

H3C

CH3

OH

H - H2O H3C

CH3

Loss of water leads to a carbocation.

27

DehydrationSecond, a base removes a proton β to the carbocation center.

H3C

CH3H Hα

β

OSO3H

H3CHC CHCH3

+H2SO4

Notice that this reaction is an E1 reaction.•Rate-determining step is the formation of the carbocation.

28

DehydrationIn case we have a choice between several β-hydrogens, the most stable alkene usually predominates

CH3CHCH2CH3

CH3

OH

CHH3C

H3C

CH3

+ CH2H3C

H2C

CH3

H3PO4

Δ

84 % 16 %

29

DehydrationAs a result of the E1 mechanism, the ease of dehydration follows the order:

OHR

RR

OHR

HR

OHH

RH

> >

RR

R

RH

R

H

RH

> >

That directly reflects the stability of the intermediate carbocations.

30

DehydrationPrimary alcohols undergo dehydration by an E2 pathway.First, however, we generate the good leaving group.

OHH+

OH

H

H3C OH

H

HOSO3H

H3CCH

CH2

The subsequent steps, removal of water and deprotonation, take place simultaneously.

31

The Reaction of Alcohols with Hydrogen Halides

HOHI

ΔI + H2O

cyclohexanol iodocyclohexane

OHHCl

ΔCl + H2O

1-propanol 1-chloropropane

32

Primary, secondary, and tertiary alcohols all undergonucleophilic substitution reactions with HI, HBr, and HCl

33

Secondary and tertiary alcohols undergo SN1 reactions with hydrogen halides

34

Primary alcohols undergo SN2 reactions with hydrogen halides

ZnCl2 can be used to catalyze certain SN2 reactions

35

Other Ways to Prepare Alkyl Halides from AlcoholsUsing thionyl chloride (SOCl2) and Phosphorous halide (PX3)

3° alcohols are converted by HCl or HBr at low temperature SOCl2 and PBr3 are used mainly for 1° and 2° alcohols since their reactions with HX are slow.

36

A Comparison of Alcohols and Phenols

OH

HCl

OH

H

Cl-Cl

OH

HCl

OH

H

a phenyl cationvery unstablecan not formed

37

Oxidation of AlcoholsCan be accomplished by inorganic reagents, such as KMnO4, CrO3, and Na2Cr2O7 or by more selective, expensive reagents

38

Oxidation of Primary AlcoholsTo aldehyde: pyridinium chlorochromate (PCC, C5H6NCrO3Cl) in dichloromethaneOther reagents produce carboxylic acids

39

Oxidation of Secondary Alcohols

40

7.14 Reactions of PhenolsThe hydroxyl group is a strongly activating, making phenols substrates for electrophilichalogenation, nitration, sulfonation, and Friedel–Crafts reactionsReaction of a phenol with strong oxidizing agents yields a quinone

KMnO4Or

K2Cr2O7

41

7.17 Thiols, Sulfur Analogs of Alcohols and Phenols

Thiols (RSH), are sulfur analogs of alcohols• Named with the suffix –thiol• (stronger acid than alcohol due to the size of

sulfur S larger than O )• SH group is called “mercaptan”

42

Thiols: Formation and ReactionFrom alkyl halides by displacement with a sulfur nucleophile such as −SH • The alkylthiol product can undergo further reaction

with the alkyl halide to give a symmetrical sulfide, giving a poorer yield of the thiol

43

SulfidesThiolates (RS−) are formed by the reaction of a thiol with a baseThiolates react with primary or secondary alkyl halide to give sulfides (RSR’)Thiolates are excellent nucleophiles and react with many electrophiles

44

Oxidation of Thiols to DisulfidesReaction of an alkyl thiol (RSH) with bromine or iodine gives a disulfide (RSSR)The thiol is oxidized in the process and the halogen is reduced