Upload
bertram-ray
View
219
Download
0
Tags:
Embed Size (px)
Citation preview
CH 17: Alcohols and Phenols
Renee Y. Becker
CHM 2211
Valencia Community College
1
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
OH
an enol 2
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
3
Naming Alcohols
• General classifications of alcohols based on substitution on C to which OH is attached
4
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
5
6
Many Alcohols Have Common Names
• These are accepted by IUPAC
7
Example 1: Give the IUPAC names for these compounds
OH OH
OH
H3C CH3
OH
HO
2
13
4
8
Example 2: Draw the following structures
• 2-Ethyl-2-buten-1-ol
• 3-Cyclohexen-1-ol
• 1,4-Pentanediol
9
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
10
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
11
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
12
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+
13
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
14
15
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
16
Stronger acid
17
Inductive Effects
• Electron-withdrawing groups make an alcohol a stronger acid by stabilizing the conjugate base (alkoxide)
Stronger acid
18
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
19
Example 3:
2 2 K
1
2
3
4
5
OH
OH
OH
NaH
CH3MgBr
CH3Li
NaNH2CH3CH2OH
CH3OH
+
+
+
+
+
22 K
1
2
3
4
5
OH
OH
OH
NaH
CH3MgBr
CH3Li
NaNH2CH3CH2OH
CH3OH
+
+
+
+
+
20
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
21
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
22
Example 4:
p-Nitrobenzyl alcohol is more acidic than benzyl alcohol. Explain.
OH
O2N
OH
23
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
24
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
25
Review: Preparation of Alcohols by Regiospecific Hydration of Alkenes
• Hydroboration/oxidation: syn, non-Markovnikov hydration • Oxymercuration/reduction: Markovnikov hydration
26
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
27
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
28
Reduction of Aldehydes and Ketones
• Aldehydes gives primary alcohols
• Ketones gives secondary alcohols
29
Catalytic Hydrogenation:
RCH
O
aldehyde
+ H2Pt, Pd or Ni
RCH2OH
primary alcohol
RCR'O
ketone
+ H2Pt, Pd or Ni
RCHR'secondary alcohol
OH
30
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-”
31
32
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!!!
33
Reduction of Carboxylic Acids and Esters
• Carboxylic acids and esters are reduced to give primary alcohols
• LiAlH4 is used because NaBH4 is not effective
34
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
35
36
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
37
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.
38
Examples of Reactions of Grignard Reagents with Carbonyl Compounds
39
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
40
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
41
42
43
Synthesis of Diols
Catalytic hydrogenation:
HCCH2CHCH2CH
O O
CH3
3-Methylpentanedial
H2
Ni, 125oCCH2CH2CHCH2CH2
OH OH
CH3
3-Methyl-1,5-pentanediol
44
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
45
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
46
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!47
48
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)
Follows an E2 mechanism
N
pyridine
49
Mechanism 1: Dehydration of Alcohol (2 or 3 )
HCl
OH
P
O
ClClCl
O+H
POCl2
H
OPOCl2
N
N
Cl–
N
H
OPOCl2+
+
+
+
+H C l
OH
P
O
ClClCl
O+H
POCl2
H
OPOCl2
N
N
Cl–
N
H
OPOCl2+
+
+
+
+
50
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)
51
Mechanism 2:
52
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
53
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
54
55
56
Oxidation of Alcohols
• Can be accomplished by inorganic reagents, such as KMnO4, CrO3, and Na2Cr2O7 or by more selective, expensive
reagents
57
58
Oxidation of Primary Alcohols
• To aldehyde: pyridinium chlorochromate (PCC, C5H6NCrO3Cl) in dichloromethane
– Other reagents produce carboxylic acids
• Converts secondary alcohol to ketone
59
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.60
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
61
Oxidation of Secondary Alcohols
• Na2Cr2O7 in aqueous acetic acid is an inexpensive oxidizing agent:
CH3 OHNa2Cr2O7
acetic acidCH3 O
4-tert-Methylcyclohexanol 4-tert-Methylcyclohexanone
62
Example 5: Predict the major organic product
K2Cr2O7
acetic acidCl
OH
PCC
CH2Cl2OH
63
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
64
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
65
66
Protection-Deprotection
67
Preparation and Uses of Phenols
• Industrial process from readily available cumene
• Forms cumene hydroperoxide with oxygen at high temperature
68
Laboratory Preparation of Phenols
• From aromatic sulfonic acids by melting with NaOH at high temperature
• Limited to the preparation of alkyl-substituted phenols
69
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
70
71