Download Chapter 10 Outline: Alcohols

C341/Spring 2010
Chapter 10
Chapter 10 Outline: Alcohols
Review Nomenclature, Structure & Physical Properties on your own
1. Acidity of Alcohols
2. Reactions of Alcohols
3. Reactions of Thiols
You should do all the problems in the textbook, but these are some suggested
homework problems: 10.15, 10.16, 10.18, 10.20, 10.21, 10.26 – 10.31, 10.35,
10.35 – 10.40, 10.42, 10.43, 10.45, 10-51 – 10.54.
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Chapter 10
Roadmap for chapter 10:
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C341/Spring 2010
Chapter 10
1. Acidity of Alcohols
Alcohols have pKas in the range of 16-18. Only methanol has an acidity less than
water (pKa 15.5 and will protonate water preferentially). In general, all alcohols
will be less polar and less acidic than water. What happens when water is in
solution with ethanol (pKa = 15.9)?
Reaction of an alcohol with strong base, like sodium hydride, or Group I
metals (Li, Na, K):
• CH3OH + NaH →
• 2 CH3OH + 2 Na →
CH3ONa
+
H2
+
H2
sodium methoxide
2 CH3ONa
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Chapter 10
2. Reactions of Alcohols – how to make a good leaving group?
All of these reactions you will learn in this chapters have one common theme –
converting the –OH group into a good, stable leaving group!!
What if we protonate the –OH group? Does that become a better leaving group?
A strong, non-halide containing acid like H3PO4 or H2SO4 or TsOH is used to
protonate an alcohol.
= TsOH
SO3H
p‐toluene sulfonic acid
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Chapter 10
a. ROH reaction with HCl, HBr & HI
(converting a ROH →RX)
1o ROH react through an SN2 mechanism:
2o/3o ROH react through an SN1 mechanism:
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b.
Chapter 10
Reaction with PX3, X = Cl, Br (converting a ROH →RBr)
Reaction Observations:
o This reaction can only be used with 1o and 2o ROH only
o Reaction always occurs with inversion of configuration.
o What substitution mechanism does this support?
Mechanism?
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c.
Chapter 10
Reaction with Thionyl Halide (SOX2, X = Cl, Br) (converting a ROH →RX)
Reaction Observations:
o This reaction can only be used with 1o and 2o ROH only
o Reaction always occurs with inversion of configuration.
o What substitution mechanism does this support?
Mechanism?
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Chapter 10
d. Formation of Tosylates to provide good leaving groups
What is important about this? Sulfonate anions are weak bases, making them
VERY GOOD leaving groups. Look at H2SO4 and consider its acidity:
Since alcohols make poor leaving groups, reacting them with sulfonyl chlorides
converts them into better leaving groups.
Most common sulfonyl chloride reagents:
O
O
H3C
S
Cl
H3C
S
Cl
O
O
TsCl
(Para-toluene sulfonyl chloride)
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MsCl
(mesyl chloride)
C341/Spring 2010
Chapter 10
How do these reactions work overall? It’s a two step reaction, (1) react the
desired alcohol with the tosyl chloride without inversion, and (2) react it with the
nucleophile leading to inversion of configuration:
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Chapter 10
e. Acid-catalyzed Dehydration of Alcohols to Alkenes (β-elimination reaction)
Compare to:
E1 mechanism is observed for 2o and 3o ROHs:
How do you think the mechanism differs for a 1o ROH?
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Chapter 10
Provide the mechanism for the following transformation:
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f.
Chapter 10
Dehydration of ROH using POCl3 & Pyridine (converting a ROH →alkene)
This mechanism is known to go through an E2 mechanism.
Mechanism?
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Chapter 10
g. Pinnacol Rearragenment
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h.
Chapter 10
Oxidation of Alcohols (no mechanism to know)
• Primary alcohols are oxidized to either aldehydes or carboxylic acids,
depending on the reagent employed:
• Secondary alcohols are oxidized to ketones.
• Tertiary alcohols cannot be oxidized – why?
Common oxidizing reagents are:
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o
Chapter 10
1 ROH give different products depending on the reagent used:
OH
PCC
K2Cr2O7
OH
H2SO4, H2O
2o ROH give same products regardless of the reagent used:
Provide the organic product for the following reactions. You do not need to
balance the byproducts of the reaction.
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Chapter 10
i. Reaction of glycols with periodic acid
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Chapter 10
3. Reactions of Thiols
L-Cysteine =
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Chapter 10
Alcohol Reactions. Provide correct organic product(s) and the mechanism for the
following reactions. If stereochemistry pertains, ensure it is clearly demonstrated.
If there is more than one product, then circle the major product.
OH
H3PO4, heat
Mechanism?
OH
POCl3
pyridine
Mechanism?
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Chapter 10
OH
PBr3
Mechanism?
OH
HBr
Mechanism?
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Chapter 10
OH
SOCl2
pyridine
Mechanism?
OH
1. TsCl, pyridine
O
2.
ONa
Mechanism?
OH
1. NaH
2. CH3CH2Br
Mechanism?
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Chapter 10
Provide viable steps to bring about the following transformation.
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Chapter 10
Provide viable steps to bring about the following transformation.
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Chapter 10
Provide viable steps to bring about the following transformation.
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