Chapter 10 Structure and Synthesis of Alcohols Jo Blackburn Richland College, Dallas, TX Dallas...

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

=>

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

=>

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+

=>

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

=>

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

=>

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

=>

Chapter 10 50

End of Chapter 10