1. Chapter 5 Alcohols Thiols Ethers

2. Structure of Water and Methanol
Oxygen is sp3 hybridized and tetrahedral.
The H—O—H angle in water is 104.5°.
The C—O—H angle in methyl alcohol is 108.9°.
Chapter 10 2 2

3. Classification of Alcohols
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 3 3

4. Examples of ClassificationsH 3 2 O * C H 3 O 2 * C H 3 O *
Chapter 10 4 4

5. Examples of ClassificationsH 3 2 O * C H 3 O 2 *
Primary alcohol C H 3 O *
Chapter 10 5 5

6. Examples of ClassificationsH 3 2 O * C H 3 O 2 *
Primary alcohol
Secondary alcohol C H 3 O *
Chapter 10 6 6

7. Examples of ClassificationsH 3 2 O * C H 3 O 2 *
Primary alcohol
Secondary alcohol C H 3 O *
Tertiary alcohol
Chapter 10 7 7

8. 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 giving the —OH group the lowest number possible.
Number and name all substituents and write them in alphabetical order.
Chapter 10 8 8

9. Examples of NomenclatureH 3 2 O C H 3 O 2
2-methyl-1-propanol
2-methylpropan-1-ol
2-butanol
butan-2-ol C H 3 O
2-methyl-2-propanol
2-methylpropan-2-ol
Chapter 10 9 9

10. Alkenols (Enols)
Hydroxyl group takes precedence. Assign the carbon with the —OH the lowest number.
End the name in –ol, but also specify that there is a double bond by using the ending –ene before -ol C H 2 3 O
4-penten-2-ol
pent-4-ene-2-ol
Chapter 10 10 10

11. Naming Priority Highest ranking Acids Esters Aldehydes Ketones
Alcohols
Amines
Alkenes
Alkynes
Alkanes
Ethers
Halides
Lowest ranking
Chapter 10 11 11

12. Hydroxy Substituent
When —OH is part of a higher priority class of compound, it is named as hydroxy.
carboxylic acid C H 2 O
4-hydroxybutanoic acid
also known as g-hydroxybutyric acid (GHB)
Chapter 10 12 12

13. Common Names Alcohol can be named as alkyl alcohol.
Useful only for small alkyl groups. C H 3 2 O C H 3 O 2
isobutyl alcohol
sec-butyl alcohol
Chapter 10 13 13

14. Naming Diols Two numbers are needed to locate the two —OH groups.
Use -diol as suffix instead of -ol.
hexane-1,6- diol
Chapter 10 14 14

15. Glycols 1, 2-diols (vicinal diols) are called glycols.
Common names for glycols use the name of the alkene from which they were made.
ethane-1,2- diol
ethylene glycol
propane-1,2- diol
propylene glycol
Chapter 10 15 15

16. Phenol Nomenclature —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.
3-chlorophenol
(meta-chlorophenol)
4-methylphenol
(para-cresol)
Chapter 10 16 16

17. Solved Problem 1 Solution
Give the systematic (IUPAC) name for the following alcohol.
Solution
The longest chain contains six carbon atoms, but it does not contain the carbon bonded to the hydroxyl group. The longest chain containing the carbon bonded to the —OH group is the one outlined by the green box, containing five carbon atoms. This chain is numbered from right to left in order to give the hydroxyl-bearing carbon atom the lowest possible number.
Copyright © 2006 Pearson Prentice Hall, Inc.
The correct name for this compound is 3-(iodomethyl)-2-isopropylpentan-1-ol.
Chapter 10 17 17

18. Physical Properties
Alcohols have 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 18 18

19. Boiling Points of alcohols
Alcohols have higher boiling points than ethers and alkanes because alcohols can form hydrogen bonds.
The stronger interaction between alcohol molecules will require more energy to break them resulting in a higher boiling point.
Chapter 10 19 19

20. Solubility in Water
Small alcohols are miscible in water, but solubility decreases as the size of the alkyl group increases.
Chapter 10 20 20

21. Methanol “Wood alcohol” Industrial production from synthesis gas
Common industrial solvent
Toxic Dose: 100 mL methanol
Used as fuel at Indianapolis 500
Fire can be extinguished with water
High octane rating
Low emissions
Lower energy content
Invisible flame
Chapter 10 21 21

22. 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
Chapter 10 22 22

23. Acidity of Alcohols pKa range: 15.5–18.0 (water: 15.7)
Acidity decreases as the number of carbons increase.
Halogens and other electron withdrawing groups increase the acidity.
Phenol is 100 million times more acidic than cyclohexanol!
Chapter 10 23 23

24. Table of Ka Values
Chapter 10 24 24

25. Formation of Alkoxide Ions
Ethanol reacts with sodium metal to form sodium ethoxide (NaOCH2CH3), a strong base commonly used for elimination reactions.
More hindered alcohols like 2-propanol or tert-butanol react faster with potassium than with sodium.
Chapter 10 25 25

26. Formation of Phenoxide Ion
The aromatic alcohol phenol is more acidic than aliphatic alcohols due to the ability of aromatic rings to delocalize the negative charge of the oxygen within the carbons of the ring.
Chapter 10 26 26

27. Charge Delocalization on the Phenoxide Ion
The negative charge of the oxygen can be delocalized over four atoms of the phenoxide ion.
There are three other resonance structures that can localize the charge in three different carbons of the ring.
The true structure is a hybrid between the four resonance forms.
Chapter 10 27 27

28. Synthesis of Alcohols (Review)
Alcohols can be synthesized by nucleophilic substitution of alkyl halide.
Hydration of alkenes also produce alcohols:
Chapter 10 28 28

29. Synthesis of Vicinal Diols
Vicinal diols can be synthesized by two different methods:
Syn hydroxylation of alkenes
Cold, dilute, basic potassium permanganate
Chapter 10 29 29

30. 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
Chapter 10 30 30

31. Sodium Borohydride NaBH4 is a source of hydrides (H-)
Hydride 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.
Chapter 10 31 31

32. Lithium Aluminum Hydride
LiAlH4 is source of hydrides (H-)
Stronger reducing agent than sodium borohydride, but dangerous to work with.
Reduces ketones and aldehydes into the corresponding alcohol.
Converts esters and carboxylic acids to 1º alcohols.
Chapter 10 32 32

33. Reduction with LiAlH4
The LiAlH4 (or LAH) will add two hydrides to the ester to form the primary alkyl halide.
The mechanism is similar to the attack of Grignards on esters.
Chapter 10 33 33

34. Reducing Agents
NaBH4 can reduce aldehydes and ketones but not esters and carboxylic acids.
LiAlH4 is a stronger reducing agent and will reduce all carbonyls.
Chapter 10 34 34

35. Catalytic Hydrogenation
Raney nickel is a hydrogen rich nickel powder that is more reactive than Pd or Pt catalysts.
This reaction is not commonly used because it will also reduce double and triple bonds that may be present in the molecule.
Hydride reagents are more selective so they are used more frequently for carbonyl reductions.
Chapter 10 35 35

36. Thiols (Mercaptans) Sulfur analogues of alcohols are called thiols.
The —SH group is called a mercapto group.
Named by adding the suffix -thiol to the alkane name.
They are commonly made by a substitution.
Primary alkyl halides work better.
Chapter 10 36 36

37. Synthesis of Thiols
The thiolate will attack the carbon displacing the halide.
This is a substitution reaction
methyl halides will react faster than primary alkyl halides.
To prevent dialylation use a large excess of sodium hydrosulfide with the alkyl halide.
Chapter 10 37 37

38. Alcohol Reactions Dehydration to alkene Oxidation to aldehyde, ketone
Substitution to form alkyl halide
Reduction to alkane
Esterification
Williamson synthesis of ether
Chapter 11 38

39. Summary Table
Chapter 11 39

40. Oxidation States Easy for inorganic salts (reduced, organic oxidized)
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
Neither: gain or loss of H+, H2O, HX
Chapter 11 40

41. Oxidation States Easy for inorganic salts (reduced, organic oxidized)
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
Neither: gain or loss of H+, H2O, HX
Chapter 11

42. 1º, 2º, 3º Carbons
Chapter 11

43. Oxidation of 2° Alcohols
2° alcohol becomes a ketone
Reagent is Na2Cr2O7/H2SO4 = H2CrO4
Active reagent probably H2CrO4
Color change: orange to greenish-blue
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Chapter 11

44. 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.
Chapter 11

45. 3° Alcohols Don’t Oxidize
Cannot lose 2 H’s
Basis for chromic acid test
Chapter 11

46. Alcohol as a Nucleophile
ROH is weak nucleophile
RO- is strong nucleophile
New O-C bond forms, O-H bond breaks.
Chapter 11

47. 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).
 +
C-Nuc bond forms,
C-O bond breaks
Chapter 11

48. Reduction of Alcohols Dehydrate with conc. H2SO4, then add H2
Chapter 11

49. 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
Chapter 11

50. 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.
Chapter 11

51. Limitations of HX Reactions
Poor yields of 1° and 2° chlorides
May get alkene instead of alkyl halide
Chapter 11

52. Reactions with Phosphorus Halides
Good yields with 1° and 2° alcohols
PCl3 for alkyl chloride (but SOCl2 better)
PBr3 for alkyl bromide
Chapter 11

53. Dehydration Reactions
Conc. H2SO4 (or H3PO4) produces alkene
Carbocation intermediate
Zaitsev product
Bimolecular dehydration produces ether
Low temp, 140°C and below, favors ether
High temp, 180°C and above, favors alkene
Chapter 11

54. Ethers Ethers contain an sp3 hybridized oxygen atom
Hydrogen Oxide
Aka Water
Alcohol
Ether
Ethers contain an sp3 hybridized oxygen atom
Ethers do not hydrogen bond between each other, but will hydrogen bond with water and alcohols.
Ethers are polar and water soluble

55. Ether Nomenclature Common System
Give alkyl names to the carbon groups (alkyl groups) bonded to the oxygen, followed by ether.
Examples

56. Ether Nomenclature Common System
Give alkyl names to the carbon groups (alkyl groups) bonded to the oxygen, followed by ether.
Examples
Dimethyl ether

57. Ether Nomenclature Common System
Give alkyl names to the carbon groups (alkyl groups) bonded to the oxygen, followed by ether.
Examples
Dimethyl ether
Ethylmethyl ether

58. Ether Nomenclature Common System
Give alkyl names to the carbon groups (alkyl groups) bonded to the oxygen, followed by ether.
Examples
Dimethyl ether
Ethylmethyl ether
Isopropylmethyl ether

59. Ether Nomenclature Common System
Give alkyl names to the carbon groups (alkyl groups) bonded to the oxygen, followed by ether.
Examples
Dimethyl ether
Ethylmethyl ether
Isopropylmethyl ether
Sec-butylcyclopropyl ether

60. Ether Nomenclature IUPAC System
Name the longest chain of carbons in the normal fashion. The oxygen containing group is named by giving the carbon portion the Latin root followed by oxy.
Examples
Methoxymethane

61. Ether Nomenclature IUPAC System
Name the longest chain of carbons in the normal fashion. The oxygen containing group is named by giving the carbon portion the Latin root followed by oxy.
Examples
Methoxymethane
Methoxyethane

62. Ether Nomenclature IUPAC System
Name the longest chain of carbons in the normal fashion. The oxygen containing group is named by giving the carbon portion the Latin root followed by oxy.
Examples
Methoxymethane
Methoxyethane
2-Methoxypropane

63. Ether Nomenclature IUPAC System
Name the longest chain of carbons in the normal fashion. The oxygen containing group is named by giving the carbon portion the Latin root followed by oxy.
Examples
Methoxymethane
Methoxyethane
2-Methoxypropane
2-Cyclopropoxybutane

64. Ether Formation Primary alcohols can dehydrate to ethers
This reaction occurs at lower temperature than the competing dehydration to an alkene
This method generally does not work with secondary or tertiary alcohols because elimination competes strongly
The mechanism is an SN2 reaction:

65. Williamson Ether Synthesis
Good for unsymmetrical ethers

66. Dehydration Mechanisms
Chapter 11

67. Esterification Fischer: alcohol + carboxylic acid Nitrate esters
Phosphate esters
Chapter 11

68. Fischer Esterification
Acid + Alcohol yields Ester + Water
Sulfuric acid is a catalyst.
Each step is reversible.
Chapter 11

69. Sulfate Esters
Alcohol + Sulfuric Acid
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Chapter 11

70. Nitrate Esters
Chapter 11

71. Phosphate Esters
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Chapter 11

72. Phosphate Esters in DNA
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Chapter 11

73. End of Chapter 5
Chapter 11