Basic Organic Chemistry Course code: CHEM 12162 (Pre-requisites : CHEM 11122) Chapter – 05 Chemistry of Alcohols

Dr. Dinesh R. Pandithavidana Office: B1 222/3 Phone: (+94)777-745-720 (Mobile) Email: [email protected]

Structure of Alcohols

• • • • • •

Hydroxyl (OH) functional group Oxygen is sp3 hybridized. Primary: carbon with –OH is bonded to one other carbon. Secondary: carbon with –OH is bonded to two other carbons. Tertiary: carbon with –OH is bonded to three other carbons. Aromatic (phenol): -OH is bonded to a benzene ring.

IUPAC Nomenclature • Find the longest carbon chain containing the carbon with the -OH group. • Drop the -e from the alkane name, add -ol. • Number the chain, starting from the end closest to the -OH group. • Number and name all substituents.

Name these: CH3 CH3

CH CH2OH

OH CH3

2-methyl-1-propanol

CH CH2CH3 2-butanol

CH3 CH3

OH

C OH CH3 Br

2-methyl-2-propanol

CH3

3-bromo-3-methylcyclohexanol

Naming Priority

• • • • • •

Acids Esters Aldehydes Ketones Alcohols Amines

• • • • •

Alkenes Alkynes Alkanes Ethers Halides

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

OH CH2CH2CH2COOH 4-hydroxybutanoic acid

Naming Diols • Two numbers are needed to locate the two -OH groups. • Use -diol as suffix instead of -ol. OH

HO

1,6-hexanediol CH2CH2 OH OH

CH2CH2CH3 OH OH

1,2-ethanediol ethylene glycol

1,2-propanediol propylene glycol

Naming 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-chlorophenol meta-chlorophenol

OH H3C

4-methylphenol para-cresol

Solubility in Water

• Unusually high boiling points due to hydrogen bonding between molecules. • Solubility decreases as the size of the alkyl group increases

Acidity of Alcohols • pKa range: 15.5-18.0 (water: 15.7) • Acidity decreases as alkyl group increases. • Halogens increase the acidity. • Phenol is 100 million times more acidic than cyclohexanol!

Table of Ka Values

CH3

OH

Formation of Alkoxide Ions React methanol and ethanol with sodium metal (redox reaction). CH3CH2OH +

Na

CH3CH2O

Na

1 + /2 H2

React less acidic alcohols with more reactive potassium. (CH3)3C OH +

K

(CH3)3CO

K

1 + /2 H2

Formation of Phenoxide Ion Phenol reacts with hydroxide ions to form phenoxide ions - no redox is necessary.

O

O H + pKa = 10

OH

+

HOH pKa = 15.7

Synthesis (Review) • Nucleophilic substitution of OH- on alkyl halide • Hydration of alkenes (Refer the Chapter of Alkenes)
water in acid solution (not very effective)
oxymercuration - demercuration
hydroboration - oxidation

Organometallic Reagents • Carbon is bonded to a metal (Mg or Li). • Carbon is nucleophilic (partially negative). • It will attack a partially positive carbon.
C - X
C = O • A new carbon-carbon bond forms.

Some Grignard Reagents Br +

Mg

ether

Cl CH3CHCH2CH3

CH3 C Br

+

Mg

CH2 +

Mg

ether

ether

MgBr

MgCl CH3CHCH2CH3

CH3 C

CH2

MgBr

Synthesis of 1° Alcohols Grignard + formaldehyde yields a primary alcohol with one additional carbon. CH3 H3C C CH2

C

H

H

CH3

H

H MgBr

C O H

CH3

CH2

C O H

CH3 CH3

CH CH2

H

CH CH2

H CH2

C O H H

HOH

MgBr

Synthesis of 2º Alcohols Grignard + aldehyde yields a secondary alcohol. CH3 H3C C CH2

C

H

H

CH3

H3C

H MgBr

C O

CH3

H

CH2

C O H

CH3 CH3

CH CH2

CH3

CH CH2

CH3 CH2

C O H H

HOH

MgBr

Synthesis of 3º Alcohols Grignard + ketone yields a tertiary alcohol.

CH3 H3C C CH2

C

H

H

CH3

H3C

H MgBr

C O

CH3

CH CH2

H3C

CH2

C O CH3

CH3 CH3

CH3

CH CH2

CH3 CH2

C O H CH3

HOH

MgBr

Grignard + Acid Chloride • Grignard attacks the carbonyl. • Chloride ion leaves. CH3

H3C R

MgBr

C O Cl

CH3 R C O Cl

R C O

MgBr

Cl CH3

MgBr

R C

+

MgBrCl

O

Reaction with one mole of Grignard reagent produces a ketone intermediate, which reacts with the second mole of Grignard reagent.

Grignard and Ester • Grignard attacks the carbonyl. • Alkoxide ion leaves ! H?... ! CH3

H3C R

MgBr

C O CH3O

CH3 R C O OCH3

R C O

MgBr

OCH3 CH3

MgBr

R C

+ O

MgBrOCH3

Ketone intermediate

Second step of reaction • Second mole of Grignard reacts with the ketone intermediate to form an alkoxide ion. • Alkoxide ion is protonated with dilute acid. CH3

CH3 R

MgBr

+

R C

R C O O

R

HOH CH3 R C OH R

MgBr

Grignard Reagent + Ethylene Oxide • Epoxides are unusually reactive ethers. • Product is a 1º alcohol with 2 additional carbons. O

O MgBr

+

CH2

CH2CH2

CH2

HOH O H CH2 CH2

MgBr

Limitations of Grignard • No water or other acidic protons like O-H, N-H, S-H, or -C—C-H. Grignard reagent is destroyed, becomes an alkane. • No other electrophilic multiple bonds, like C=N, C—N, S=O, or N=O.

Reduction of Carbonyl Compounds • Reduction of aldehyde yields 1º alcohol. • Reduction of ketone yields 2º alcohol. • Reagents:
Sodium borohydride, NaBH4
Lithium aluminum hydride, LiAlH4
Raney nickel

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. O C H

H

H C

H

O +

H

H3O

C

O H H

Lithium Aluminum Hydride • Stronger reducing agent than sodium borohydride, but dangerous to work with. • Converts esters and acids to 1º alcohols. O C

OCH3

H LAH

H3O+

C

O H H

Comparison of Reducing Agents

• LiAlH4 is stronger. • LiAlH4 reduces more stable compounds which are resistant to reduction.

Catalytic Hydrogenation • Add H2 with Raney nickel catalyst. • Also reduces any C=C bonds. OH

O

NaBH4

OH H2, Raney Ni

Types of Alcohol Reactions • Dehydration to alkene • Oxidation to aldehyde, ketone • Substitution to form alkyl halide • Reduction to alkane • Esterification • Tosylation • Williamson synthesis of ether

Oxidation States • Easy for inorganic salts
CrO42- reduced to Cr2O3
KMnO4 reduced to MnO2

• Oxidation: loss of H2, gain of O, O2, or X2 • Reduction: gain of H2 or H-, loss of O, O2, or X2

Oxidation of 2° Alcohols • • • •

2° alcohol becomes a ketone Reagent is Na2Cr2O7/H2SO4 Active reagent probably H2CrO4 Color change: orange to greenish-blue OH

CH3CHCH2CH3

Na2Cr2O7 / H2SO4

O CH3CCH2CH3

Oxidation of 1° Alcohols • 1° alcohol to aldehyde to carboxylic acid • Difficult to stop at aldehyde • Use pyridinium chlorochromate (PCC) to limit the oxidation. • PCC can also be used to oxidize 2° alcohols to ketones. OH CH3CH2CH2CH2

N H CrO 3Cl

O CH3CH2CH2CH

3° Alcohols Don’t Oxidize • Cannot lose 2 H’s • Basis for chromic acid test

Alcohol as a Nucleophile

H C

O

R X

• ROH is weak nucleophile • RO- is strong nucleophile • New O-C bond forms, O-H bond breaks. =>

Alcohol as an Electrophile • OH- is not a good leaving group unless it is protonated, but most nucleophiles are strong bases which would remove H+. • Convert to tosylate (good leaving group) to react with strong nucleophile (base)

H ∂+

C

O

C-Nuc bond forms, C-O bond breaks

Formation of Tosylate Ester H C

O

C

C

H O

O

Cl O

S

O

N

CH3

p-toluenesulfonyl chloride TsCl, “tosyl chloride”

O

S

O

CH3

O

S

O

CH3

ROTs, a tosylate ester

SN2 Reactions of Tosylates • • • • • •

With hydroxide produces alcohol With cyanide produces nitrile With halide ion produces alkyl halide With alkoxide ion produces ether With ammonia produces amine salt With LiAlH4 produces alkane

Reduction of Alcohols • Dehydrate with conc. H2SO4, then add H2 • Tosylate, then reduce with LiAlH4 OH CH3CHCH3

H2SO4

CH2

CHCH3

alcohol

alkene

OH

OTs

CH3CHCH3 alcohol

TsCl

CH3CHCH3 tosylate

H2 Pt

LiAlH4

CH3CH2CH3 alkane

CH3CH2CH3 alkane

Reaction with HBr • • • •

-OH of alcohol is protonated -OH2+ is good leaving group 3° and 2° alcohols react with Br- via SN1 1° alcohols react via SN2

R O H

H3O

+

H R O H

-

Br

R Br

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.

Reactions with Phosphorus Halides • Good yields with 1° and 2° alcohols • PCl3 for alkyl chloride (but SOCl2 better) • PBr3 for alkyl bromide • P and I2 for alkyl iodide (PI3 not stable)

Mechanism with PBr3

• P bonds to -OH as Br- leaves • Br- attacks backside (SN2) • HOPBr2 leaves

Reaction with Thionyl Chloride

• • • •

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

Dehydration Reactions • • • • • •

Conc. H2SO4 produces alkene Carbocation intermediate Saytzeff product Bimolecular dehydration produces ether Low temp, 140°C and below, favors ether High temp, 180°C and above, favors alkene

Dehydration Mechanisms H OH CH3CHCH3

H2SO4

OH CH3CHCH3

CH3CHCH3

alcohol H2O

CH3OH

H3O

CH2

CHCH3

+

CH3

OH2

CH3

O CH3 H

CH3OH

H2O

CH3OCH3

=>

Energy Diagram, E1

Unique Reactions of Diols: Pinacol Rearrangement • Pinacol: 2,3-dimethyl-2,3-butanediol • Dehydration with sulfuric acid CH3 CH3 CH3

C

C

CH3

OH

OH

H

CH3

CH3 CH3

+

CH3

C

C CH3

OH

OH

CH3

C OH

C

CH3 CH3

H

CH3 CH3

C OH

C

CH3 CH3

CH3 CH3

C

C CH3

OH

CH3

CH3 CH3

CH3 CH3

C

C

O

CH3

pinacolone

CH3

C

C CH3

OH

CH3

Unique Reactions of Diols: Periodic Cleavage of Glycols Same products formed as from ozonolysis of the corresponding alkene. CH3

H

CH3

C

C CH3

OH

OH

HIO4 CH3

H

C

O O3 (CH3)2S

OsO4 H2O2 H C H3C

C

CH3 CH3

CH3 +

O

C

CH3

Esterification • Fischer: alcohol + carboxylic acid • Tosylate esters • Sulfate esters • Nitrate esters • Phosphate esters

Fischer Esterification • Acid + Alcohol yields Ester + Water • Sulfuric acid is a catalyst. • Each step is reversible. O CH3

C OH

CH3 + H O CH2CH2CHCH3

+

H

O

CH3

CH3C OCH2CH2CHCH3 + HOH

Tosylate Esters • Alcohol + p-Toluenesulfonic acid, TsOH • Acid chloride is actually used, TsCl O CH3CH2

O H

+

HO

S

CH3

O O CH3CH2

O

S O

CH3 => + HOH

Sulfate Esters Alcohol + Sulfuric Acid O HO

S

O

+

OH

H

+ H O CH2CH3

O

S

OCH2CH3

O

O CH3CH2O H + HO

HO

S O

O

+

OCH2CH3

H

CH3CH2O

S O

OCH2CH3

Nitrate Esters O O

+

N OH

+

H O CH2CH3

H

O

N OCH2CH3

O

CH2

O H

CH2

O H

CH2

O H

glycerine

+

3 HO NO2

CH2

O NO 2

CH2

O NO 2

CH2

O NO 2

nitroglycerine

Phosphate Esters O HO

P OH

O OH

CH3OH

CH3O

P

OH

CH3OH

O CH3O

P OH

OH

CH3OH O CH3O

P

OCH3

OCH3

OCH3

Summary Table