Chapter 10Structure and Synthesis

of Alcohols

Jo BlackburnRichland College, Dallas, TX

Dallas County Community College District2003,Prentice Hall

Organic Chemistry, 5th EditionL. G. Wade, Jr.

Chapter 10 2

Structure of Alcohols

• Hydroxyl (OH) functional group• Oxygen is sp3 hybridized.

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Chapter 10 3

Classification

• 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. =>

Chapter 10 4

Classify these:

CH3 CH

CH3

CH2OH CH3 C

CH3

CH3

OH

OH

CH3 CH

OH

CH2CH3 =>

Chapter 10 5

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. =>

Chapter 10 6

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 =>

Chapter 10 7

Unsaturated Alcohols

• Hydroxyl group takes precedence. Assign that carbon the lowest number.

• Use alkene or alkyne name.

4-penten-2-ol (old)

pent-4-ene-2-ol (1997 revision of IUPAC rules) =>

CH2 CHCH2CHCH3

OH

Chapter 10 8

Naming Priority

• Acids• Esters• Aldehydes• Ketones• Alcohols• Amines

• Alkenes• Alkynes• Alkanes• Ethers• Halides

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Chapter 10 9

Hydroxy Substituent

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

• Example:

CH2CH2CH2COOH

OH

4-hydroxybutanoic acid

also known as GHB

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Chapter 10 10

Common Names

• Alcohol can be named as alkyl alcohol.

• Useful only for small alkyl groups.

• Examples:

CH3 CH

CH3

CH2OH CH3 CH

OH

CH2CH3

isobutyl alcohol sec-butyl alcohol

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Chapter 10 11

Naming Diols

• Two numbers are needed to locate the two -OH groups.

• Use -diol as suffix instead of -ol.

HO OH

1,6-hexanediol

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Chapter 10 12

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

CH2CH2CH3

OH OH

1,2-ethanediol

ethylene glycol

1,2-propanediol

propylene glycol =>

Chapter 10 13

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-methylphenolpara-cresol =>

Chapter 10 14

Physical Properties

• Unusually high boiling points due to hydrogen bonding between molecules.

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

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Chapter 10 15

Boiling Points

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Chapter 10 16

Solubility in Water

Solubility decreases as the size of the alkyl group increases.

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Chapter 10 17

Methanol• “Wood alcohol”

• Industrial production from synthesis gas

• Common industrial solvent

• Fuel at Indianapolis 500Fire can be extinguished with waterHigh octane ratingLow emissionsBut, lower energy contentInvisible flame =>

Chapter 10 18

Ethanol

• Fermentation of sugar and starches in grains• 12-15% alcohol, then yeast cells die.• Distillation produces “hard” liquors• Azeotrope: 95% ethanol, constant boiling• Denatured alcohol used as solvent• Gasahol: 10% ethanol in gasoline• Toxic dose: 200 mL ethanol, 100 mL methanol

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Chapter 10 19

2-Propanol

• “Rubbing alcohol”

• Catalytic hydration of propene

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CH2 CH CH2 H2O100-300 atm, 300°C

catalyst+ CH3 CH

OH

CH3

Chapter 10 20

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!

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Chapter 10 21

Table of Ka Values

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CH3 OH

Chapter 10 22

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.

+ K (CH3)3CO K + 1/2 H2)3C OH(CH3

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Chapter 10 23

Formation of Phenoxide Ion

Phenol reacts with hydroxide ions to form phenoxide ions - no redox is necessary.

O H

+ OH

O

+ HOH

pK a = 10pK a = 15.7

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Chapter 10 24

Synthesis (Review)

• Nucleophilic substitution of OH- on alkyl halide

• Hydration of alkeneswater in acid solution (not very effective)oxymercuration - demercurationhydroboration - oxidation

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Chapter 10 25

Glycols (Review)

• Syn hydroxylation of alkenesosmium tetroxide, hydrogen peroxidecold, dilute, basic potassium

permanganate

• Anti hydroxylation of alkenesperoxyacids, hydrolysis

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Chapter 10 26

Organometallic Reagents

• Carbon is bonded to a metal (Mg or Li).

• Carbon is nucleophilic (partially negative).

• It will attack a partially positive carbon.C - XC = O

• A new carbon-carbon bond forms. =>

Chapter 10 27

Grignard Reagents

• Formula R-Mg-X (reacts like R:- +MgX)• Stabilized by anhydrous ether• Iodides most reactive• May be formed from any halide

primarysecondarytertiaryvinylaryl =>

Chapter 10 28

Some Grignard Reagents

Br

+ Mgether MgBr

CH3CHCH2CH3

Clether

+ Mg CH3CHCH2CH3

MgCl

CH3C CH2

Br + Mgether

CH3C CH2

MgBr =>

Chapter 10 29

Organolithium Reagents

• Formula R-Li (reacts like R:- +Li)• Can be produced from alkyl, vinyl, or aryl

halides, just like Grignard reagents.• Ether not necessary, wide variety of

solvents can be used.

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Chapter 10 30

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.

RC O R C O

HOHR C OH

OH=>

Chapter 10 31

Synthesis of 1° Alcohols

Grignard + formaldehyde yields a primary alcohol with one additional carbon.

C OH

HC

CH3

H3C CH2 C MgBr

H

HH

CH3 CH

CH3

CH2 CH2 C

H

H

O MgBr

HOHCH3 CH

CH3

CH2 CH2 C

H

H

O H

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Chapter 10 32

Synthesis of 2º Alcohols

Grignard + 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

=>

Chapter 10 33

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

=>

Chapter 10 34

How would you synthesize…

CH3CH2CHCH2CH2CH3

OH CH2OH

OH

CH3C

OH

CH2CH3

CH3 =>

Chapter 10 35

Grignard Reactions with Acid Chlorides

and Esters• Use two moles of Grignard reagent.

• The product is a tertiary alcohol with two identical alkyl groups.

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

Chapter 10 36

Grignard + Acid Chloride (1)

C OCl

H3C

MgBrR MgBr C

CH3

Cl

OR

C

CH3

Cl

OR MgBr C

CH3

RO

+ MgBrCl

Ketone intermediate =>

• Grignard attacks the carbonyl.• Chloride ion leaves.

Chapter 10 37

Grignard and Ester (1)

• Grignard attacks the carbonyl.

• Alkoxide ion leaves! ? !

C OCH3O

H3C

MgBrR MgBr C

CH3

OCH3

OR

C

CH3

OCH3

OR MgBr C

CH3

RO

+ MgBrOCH3

Ketone intermediate =>

Chapter 10 38

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.

C

CH3

RO

R MgBr + C

CH3

R

OR MgBr

HOH

C

CH3

R

OHR

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Chapter 10 39

How would you synthesize...

CH3CH2CCH3

OH

CH3

C

OH

CH3

Using an acid chloride or ester.

CH3CH2CHCH2CH3

OH

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Chapter 10 40

Grignard Reagent + Ethylene Oxide

• Epoxides are unusually reactive ethers.

• Product is a 1º alcohol with 2 additional carbons.

MgBr + CH2 CH2

OCH2CH2

O MgBr

HOH

CH2CH2

O H

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Chapter 10 41

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.

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Chapter 10 42

Reduction of Carbonyl

• Reduction of aldehyde yields 1º alcohol.• Reduction of ketone yields 2º alcohol.• Reagents:

Sodium borohydride, NaBH4

Lithium aluminum hydride, LiAlH4

Raney nickel

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Chapter 10 43

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+

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Chapter 10 44

Lithium Aluminum Hydride

• Stronger reducing agent than sodium borohydride, but dangerous to work with.

• Converts esters and acids to 1º alcohols.

CO

OCH3C

OH H

HH3O+

LAH =>

Chapter 10 45

Comparison of Reducing Agents

• LiAlH4 is stronger.

• LiAlH4 reduces more stable compounds which are resistant to reduction. =>

Chapter 10 46

Catalytic Hydrogenation

• Add H2 with Raney nickel catalyst.

• Also reduces any C=C bonds.

O

H2, Raney Ni

OH

NaBH4

OH

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Chapter 10 47

Thiols (Mercaptans)

• Sulfur analogues of alcohols, -SH.

• Named by adding -thiol to alkane name.

• The -SH group is called mercapto.

• Complex with heavy metals: Hg, As, Au.

• More acidic than alcohols, react with NaOH to form thiolate ion.

• Stinks! =>

Chapter 10 48

Thiol Synthesis

Use a large excess of sodium hydrosulfide with unhindered alkyl halide to prevent dialkylation to R-S-R.

H S_

R X R SH +_

X

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Chapter 10 49

Thiol Oxidation• Easily oxidized to disulfides, an

important feature of protein structure.

R SH + RHSBr2

Zn, HClR S S R + 2 HBr

• Vigorous oxidation with KMnO4, HNO3, or NaOCl, produces sulfonic acids.

SHHNO3

boilS

O

O

OH

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Chapter 10 50

End of Chapter 10