Organic Chemistry II

1. Chapter 10
Structure and Synthesis
of Alcohols
Organic Chemistry

2. Chapter 10 2
Structure of Alcohols
• Hydroxyl (OH) functional group
• Oxygen is sp3
hybridized.
=>

3. 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.
=>

4. Chapter 10 4
Classify these:
CH3 CH
CH3
CH2OH CH3 C
CH3
CH3
OH
OH
CH3 CH
OH
CH2CH3 =>

5. 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. =>

6. Chapter 10 6
Name these:
CH3 CH
CH3
CH2OH
CH3 C
CH3
CH3
OH
CH3 CH
OH
CH2CH3
2-methyl-1-propanol
2-methyl-2-propanol
2-butanol
OH
Br CH3
3-bromo-3-methylcyclohexanol
=>

7. 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

8. Chapter 10 8
Naming Priority
• Acids
• Esters
• Aldehydes
• Ketones
• Alcohols
• Amines
• Alkenes
• Alkynes
• Alkanes
• Ethers
• Halides
=>

9. 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
=>

10. 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
=>

11. 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
=>

12. 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
=>

13. 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-methylphenol
para-cresol
=>

14. 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.
=>

15. Chapter 10 15
Boiling Points
=>

16. Chapter 10 16
Solubility in Water
Solubility decreases as the size
of the alkyl group increases.
=>

17. Chapter 10 17
Methanol
• “Wood alcohol”
• Industrial production from synthesis gas
• Common industrial solvent
• Fuel at Indianapolis 500
Fire can be extinguished with water
High octane rating
Low emissions
But, lower energy content
Invisible flame =>

18. 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
=>

19. Chapter 10 19
2-Propanol
• “Rubbing alcohol”
• Catalytic hydration of propene
=>
CH2 CH CH2 H2O
100-300 atm, 300°C
catalyst
+ CH3 CH
OH
CH3

20. 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!
=>

21. Chapter 10 21
Table of Ka Values
=>
CH3 OH

22. 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
=>

23. 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 = 10
pK a = 15.7
=>

24. Chapter 10 24
Synthesis (Review)
• Nucleophilic substitution of OH-
on alkyl
halide
• Hydration of alkenes
water in acid solution (not very effective)
oxymercuration - demercuration
hydroboration - oxidation
=>

25. Chapter 10 25
Glycols (Review)
• Syn hydroxylation of alkenes
osmium tetroxide, hydrogen peroxide
cold, dilute, basic potassium
permanganate
• Anti hydroxylation of alkenes
peroxyacids, hydrolysis
=>

26. 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 - X
C = O
• A new carbon-carbon bond forms.
=>

27. 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
primary
secondary
tertiary
vinyl
aryl =>

28. Chapter 10 28
Some Grignard
Reagents
Br
+ Mg
ether MgBr
CH3CHCH2CH3
Cl
ether
+ Mg CH3CHCH2CH3
MgCl
CH3C CH2
Br + Mg
ether
CH3C CH2
MgBr
=>

29. 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.
=>

30. 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.
R
C O R C O
HOH
R C OH
OH
=>

31. Chapter 10 31
Synthesis of 1° Alcohols
Grignard + formaldehyde yields a primary
alcohol with one additional carbon.
C O
H
H
C
CH3
H3C CH2 C MgBr
H
HH
CH3 CH
CH3
CH2 CH2 C
H
H
O MgBr
HOH
CH3 CH
CH3
CH2 CH2 C
H
H
O H
=>

32. 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 O
H
H3C
CH3 CH
CH3
CH2 CH2 C
CH3
H
O H
HOH
=>

33. 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 O
H3C
H3C
CH3 CH
CH3
CH2 CH2 C
CH3
CH3
O H
HOH
=>

34. Chapter 10 34
How would you
synthesize…
CH3CH2CHCH2CH2CH3
OH CH2OH
OH
CH3
C
OH
CH2CH3
CH3
=>

35. 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.
=>

36. Chapter 10 36
Grignard + Acid
Chloride (1)
C O
Cl
H3C
MgBrR MgBr C
CH3
Cl
OR
C
CH3
Cl
OR MgBr C
CH3
R
O
+ MgBrCl
Ketone intermediate =>
• Grignard attacks the carbonyl.
• Chloride ion leaves.

37. Chapter 10 37
Grignard and Ester (1)
• Grignard attacks the carbonyl.
• Alkoxide ion leaves! ? !
C O
CH3O
H3C
MgBrR MgBr C
CH3
OCH3
OR
C
CH3
OCH3
OR MgBr C
CH3
R
O
+ MgBrOCH3
Ketone intermediate =>

38. 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
R
O
R MgBr + C
CH3
R
OR MgBr
HOH
C
CH3
R
OHR
=>

39. Chapter 10 39
How would you
synthesize...
CH3CH2CCH3
OH
CH3
C
OH
CH3
Using an acid chloride or ester.
CH3CH2CHCH2CH3
OH
=>

40. Chapter 10 40
Grignard Reagent +
Ethylene Oxide
• Epoxides are unusually reactive ethers.
• Product is a 1º alcohol with 2 additional
carbons.
MgBr + CH2 CH2
O
CH2CH2
O MgBr
HOH
CH2CH2
O H
=>

41. 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.
=>

42. 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
=>

43. 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.
H
C
O
H
C
H
OH
C
H
OH H
H3O+
=>

44. Chapter 10 44
Lithium Aluminum
Hydride
• Stronger reducing agent than sodium
borohydride, but dangerous to work with.
• Converts esters and acids to 1º alcohols.
C
O
OCH3
C
OH H
H
H3O
+
LAH
=>

45. Chapter 10 45
Comparison of
Reducing Agents
• LiAlH4 is stronger.
• LiAlH4 reduces more
stable compounds
which are resistant
to reduction.
=>

46. Chapter 10 46
Catalytic Hydrogenation
• Add H2 with Raney nickel catalyst.
• Also reduces any C=C bonds.
O
H2, Raney Ni
OH
NaBH4
OH
=>

47. 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! =>

48. 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
=>

49. Chapter 10 49
Thiol Oxidation
• Easily oxidized to disulfides, an
important feature of protein structure.
R SH + RHS
Br2
Zn, HCl
R S S R + 2 HBr
• Vigorous oxidation with KMnO4,
HNO3, or NaOCl, produces sulfonic acids.
SH
HNO3
boil
S
O
O
OH
=>

50. Chapter 10 50
End of Chapter 10