1. CH 17: Alcohols and Phenols
Renee Y. Becker
CHM 2211
Valencia Community College

2. Alcohols contain an OH group connected to a saturated C (sp3)
Alcohols and Phenols
Alcohols contain an OH group connected to a saturated C (sp3)
They are important solvents and synthesis intermediates
Enols also contain an OH group connected to an unsaturated C (sp2)
Phenols contain an OH group connected to a carbon in a benzene ring

3. Ethanol, CH3CH2OH, called ethyl alcohol, is a solvent, fuel, beverage
Alcohols and Phenols
Methanol, CH3OH, called methyl alcohol, is a common solvent, a fuel additive, produced in large quantities
Ethanol, CH3CH2OH, called ethyl alcohol, is a solvent, fuel, beverage
Phenol, C6H5OH (“phenyl alcohol”) has diverse uses - it gives its name to the general class of compounds

4. Naming Alcohols
General classifications of alcohols based on substitution on C to which OH is attached

5. IUPAC Rules for Naming Alcohols
Select the longest carbon chain containing the hydroxyl group, and derive the parent name by replacing the -e ending of the corresponding alkane with -ol
Number the chain from the end nearer the hydroxyl group
Number substituents according to position on chain, listing the substituents in alphabetical order

7. Many Alcohols Have Common Names
These are accepted by IUPAC

8. Example 1: Give the IUPAC names for these compounds3 1 2 4

9. Example 2: Draw the following structures
2-Ethyl-2-buten-1-ol
3-Cyclohexen-1-ol
1,4-Pentanediol

10. Name substituents on aromatic ring by their position from OH
Naming Phenols
Use “phene” (the French name for benzene) as the parent hydrocarbon name, not benzene
Name substituents on aromatic ring by their position from OH

11. Properties of Alcohols and Phenols: Hydrogen Bonding
The structure around O of the alcohol or phenol is similar to that in water, sp3 hybridized
Alcohols and phenols have much higher boiling points than similar alkanes and alkyl halides

12. Alcohols Form Hydrogen Bonds
A positively polarized OH hydrogen atom from one molecule is attracted to a lone pair of electrons on a negatively polarized oxygen atom of another molecule
This produces a force that holds the two molecules together
These intermolecular attractions are present in solution but not in the gas phase, thus elevating the boiling point of the solution

13. Properties of Alcohols and Phenols: Acidity and Basicity
Weakly basic and weakly acidic
Alcohols are weak Brønsted bases
Protonated by strong acids to yield oxonium ions, ROH2+

14. Alchols and Phenols are Weak Brønsted Acids
Can transfer a proton to water to a very small extent
Produces H3O+ and an alkoxide ion, RO, or a phenoxide ion, ArO

16. Relative Acidities of Alcohols
Simple alcohols are about as acidic as water
Alkyl groups make an alcohol a weaker acid
The more easily the alkoxide ion is solvated by water the more its formation is energetically favored
Steric effects are important

17. Stronger acid

18. Inductive Effects
Electron-withdrawing groups make an alcohol a stronger acid by stabilizing the conjugate base (alkoxide)
Stronger acid

19. Generating Alkoxides from Alcohols
Alcohols are weak acids – requires a strong base to form an alkoxide such as NaH, sodium amide NaNH2, and Grignard reagents (RMgX)
Alkoxides are bases used as reagents in organic chemistry

20. Example 3

21. Phenol Acidity
Phenols (pKa ~10) are much more acidic than alcohols (pKa ~ 16) due to resonance stabilization of the phenoxide ion
Phenols react with NaOH solutions (but alcohols do not), forming soluble salts that are soluble in dilute aqueous
A phenolic component can be separated from an organic solution by extraction into basic aqueous solution and is isolated after acid is added to the solution

22. Can be more or less acidic than phenol itself
Substituted Phenols
Can be more or less acidic than phenol itself
An electron-withdrawing substituent makes a phenol more acidic by delocalizing the negative charge
Phenols with an electron-donating substituent are less acidic because these substituents concentrate the charge

23. p-Nitrobenzyl alcohol is more acidic than benzyl alcohol. Explain.
Example 4
p-Nitrobenzyl alcohol is more acidic than benzyl alcohol. Explain.

24. The pKa of 2,4,6-trinitrophenol is 0.6, a very strong acid
Nitro-Phenols
Phenols with nitro groups at the ortho and para positions are much stronger acids
The pKa of 2,4,6-trinitrophenol is 0.6, a very strong acid

25. Preparation of Alchols: an Overview
Alcohols are derived from many types of compounds
The alcohol hydroxyl can be converted to many other functional groups
This makes alcohols useful in synthesis

26. Review: Preparation of Alcohols by Regiospecific Hydration of Alkenes
Hydroboration/oxidation: syn, non-Markovnikov hydration
Oxymercuration/reduction: Markovnikov hydration

27. Preparation of 1,2-Diols
Review: Cis 1,2-diols from hydroxylation of an alkene with OsO4 followed by reduction with NaHSO3
In Chapter 18: Trans-1,2-diols from acid-catalyzed hydrolysis of epoxides

28. Alcohols from Reduction of Carbonyl Compounds
Reduction of a carbonyl compound in general gives an alcohol
Note that organic reduction reactions add the equivalent of H2 to a molecule

29. Reduction of Aldehydes and Ketones
Aldehydes gives primary alcohols
Ketones gives secondary alcohols

30. Catalytic Hydrogenation:

31. Reduction Reagent: Sodium Borohydride
NaBH4 is not sensitive to moisture and it does not reduce other common functional groups
Lithium aluminum hydride (LiAlH4) is more powerful, less specific, and very reactive with water
Both add the equivalent of “H-”

33. Mechanism of Reduction
The reagent adds the equivalent of hydride to the carbon of C=O and polarizes the group as well
Not a complete mechanism!!!

34. Reduction of Carboxylic Acids and Esters
Carboxylic acids and esters are reduced to give primary alcohols
LiAlH4 is used because NaBH4 is not effective

35. Alcohols from Reaction of Carbonyl Compounds with Grignard Reagents
Alkyl, aryl, and vinylic halides react with magnesium in ether or tetrahydrofuran to generate Grignard reagents, RMgX
Grignard reagents react with carbonyl compounds to yield alcohols

37. Mechanism of the Addition of a Grignard Reagent
Grignard reagents act as nucleophilic carbon anions (carbanions, : R) in adding to a carbonyl group
The intermediate alkoxide is then protonated to produce the alcohol

38. Examples of Reactions of Grignard Reagents with Carbonyl Compounds
Formaldehyde reacts with Grignard reagents to yield primary alcohols.
Aldehydes react with Grignard reagents to yield secondary alcohols.
Ketones yield tertiary alcohols.

39. Examples of Reactions of Grignard Reagents with Carbonyl Compounds

40. Reactions of Esters and Grignard Reagents
Yields tertiary alcohols in which two of the substituents carbon come from the Grignard reagent
Grignard reagents do not add to carboxylic acids – they undergo an acid-base reaction, generating the hydrocarbon of the Grignard reagent

41. Grignard Reagents and Other Functional Groups in the Same Molecule
Can't be prepared if there are reactive functional groups in the same molecule, including proton donors

44. Catalytic hydrogenation:
Synthesis of Diols
Catalytic hydrogenation:

45. Some Reactions of Alcohols
Two general classes of reaction
At the carbon of the C–O bond
At the proton of the O–H bond

46. Dehydration of Alcohols to Yield Alkenes
The general reaction: forming an alkene from an alcohol through loss of O-H and H (hence dehydration) of the neighboring C–H to give  bond
Specific reagents are needed

47. Acid-Catalyzed Dehydration
Tertiary alcohols are readily dehydrated with acid
Secondary alcohols require severe conditions (75% H2SO4, 100°C) - sensitive molecules don't survive
Primary alcohols require very harsh conditions – impractical
Reactivity is the result of the nature of the carbocation intermediate (See Figure 17-5)
Note that Zaitsev’s rule is followed!

49. An E2 via an intermediate ester of POCl2 (see Figure 17.6)
Dehydration with POCl3
Phosphorus oxychloride in the amine solvent pyridine can lead to dehydration of secondary and tertiary alcohols at low temperatures
An E2 via an intermediate ester of POCl2 (see Figure 17.6)
pyridine
Follows an E2 mechanism

50. Mechanism 1: Dehydration of Alcohol (2 or 3 )

51. Conversion of Alcohols into Alkyl Halides
3° alcohols are converted by HCl or HBr at low temperature (Figure 17.7)
1° and alcohols are resistant to acid – use SOCl2 or PBr3 by an SN2 mechanism (ether solvent)

52. Mechanism 2:

53. Conversion of Alcohols into Tosylates
Reaction with p-toluenesulfonyl chloride (tosyl chloride, p-TosCl) in pyridine yields alkyl tosylates, ROTos
Formation of the tosylate does not involve the C–O bond so configuration at a chirality center is maintained
Alkyl tosylates react like alkyl halides

54. Stereochemical Uses of Tosylates
The SN2 reaction of an alcohol via a tosylate, produces inversion at the chiral center
The SN2 reaction of an alcohol via an alkyl halide proceeds with two inversions, giving product with same arrangement as starting alcohol

57. Oxidation of Alcohols
Can be accomplished by inorganic reagents, such as KMnO4, CrO3, and Na2Cr2O7 or by more selective, expensive reagents

59. Oxidation of Primary Alcohols
To aldehyde: pyridinium chlorochromate (PCC, C5H6NCrO3Cl) in dichloromethane
Other reagents produce carboxylic acids
Converts secondary alcohol to ketone

60. Oxidation of Primary Alcohols
Jones’ Reagent: CrO3 in aqueous sulfuric acid.
Oxidizes primary alcohols to carboxylic acids:
All of the oxidations occur via an E2 mechanism.

61. Mechanism of Chromic Acid Oxidation
Alcohol forms a chromate ester followed by elimination with electron transfer to give ketone
The mechanism was determined by observing the effects of isotopes on rates

62. Oxidation of Secondary Alcohols
Na2Cr2O7 in aqueous acetic acid is an inexpensive oxidizing agent:

63. Example 5: Predict the major organic product

64. Protection of Alcohols
Hydroxyl groups can easily transfer their proton to a basic reagent
This can prevent desired reactions
Converting the hydroxyl to a (removable) functional group without an acidic proton protects the alcohol

65. Methods to Protect Alcohols
Reaction with chlorotrimethylsilane in the presence of base yields an unreactive trimethylsilyl (TMS) ether
The ether can be cleaved with acid or with fluoride ion to regenerate the alcohol

67. Protection-Deprotection

68. Preparation and Uses of Phenols
Industrial process from readily available cumene
Forms cumene hydroperoxide with oxygen at high temperature

69. Laboratory Preparation of Phenols
From aromatic sulfonic acids by melting with NaOH at high temperature
Limited to the preparation of alkyl-substituted phenols

70. Reaction of a phenol with strong oxidizing agents yields a quinone
Reactions of Phenols
The hydroxyl group is a strongly activating, making phenols substrates for electrophilic halogenation, nitration, sulfonation, and Friedel–Crafts reactions
Reaction of a phenol with strong oxidizing agents yields a quinone
Fremy's salt [(KSO3)2NO] works under mild conditions through a radical mechanism