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.
=>
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
=>
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
=>
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
=>
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.
=>
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
=>
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!
=>
Chapter 10 21
Table of Ka Values
=>
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
=>
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
=>
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
=>
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
=>
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