Alcohols

1
Alcohols
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Hydrogen Bonding
Three ethanol molecules.
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Hydrogen Bonding boiling point
Increases boiling point, higher temperature
needed to separate the molecules.
Hexane 69
deg. 1-pentanol
138 1,4-butanediol 230
Ethanol 78 deg Dimethyl
ether 24
4
Earlier Discussion of Acidity
RO-H ? RO (solvated) H
(solvated)
Alkoxide ion, base
Methanol Ethanol
2-Propanol 2-Methyl-2-propanol
Increasing Basicity of Alkoxide Anion, the
conjugate base
Increasing Acidity of the alcohol
Alkoxides can be produced in several ways
Recall H2O Na? Na OH- ½ H2(g)
Alkoxide, strong base, strong nucleophile (unless
sterically hindered)
Alcohols behave similarly
ROH Na? Na OR- ½ H2(g)
Also ROH NaH? Na OR- ½ H2(g)
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-OH as a Leaving Group
Poor leaving group, hydroxide ion.
R-OH H ? R-OH2
Protonation of the alcohol sets-up a good leaving
group, water.
Another way to turn the OH into a leaving group
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Conversion to Alkyl Halide,HX ROH ? RX H2O
When a carbocation can be formed (Tertiary,
Secondary alcohols) beware of rearangement. SN1
Expect both configurations.
When a carbocation cannot be formed. Methanol,
primary. SN2
7
But sometimes experiment does not agree with our
ideas
Observed reaction

• The problem
• Rearrangement of carbon skeleton which usually
  indicates carbocations.
• Reacting alcohol is primary do not expect
  carbocation.
• Time to adjust our thinking a bit.

Not a primary carbocation
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Other ways to convert ROH ? RX
We have used acid to convert OH into a good
leaving group
There are other ways to accomplish the conversion
to the halide.
Leaving group.
Leaving group.
Next, a very useful alternative to halide
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An alternative to making the halide ROH ? ROTs
Preparation from alcohols.
p-toluenesulfonyl chloride Tosyl chloride TsCl
Tosylate group, -OTs, good leaving group,
including the oxygen.
The configuration of the R group is unchanged.
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Example
Preparation of tosylate. Retention of
configuration
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Substitution on a tosylate
The OTs group is an excellent leaving group
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Acid Catalyzed Dehydration of an Alcohol,
discussed earlier as reverse of hydration
Secondary and tertiary alcohols, carbocations
Protonation, establishing of good leaving group.
Elimination of water to yield carbocation in rate
determining step. Expect tertiary faster than
secondary. Rearrangements can occur.
Elimination of H from carbocation to yield
alkene. Zaitsev Rule followed.
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Primary alcohols

• Problem primary carbocations are not observed.
  Need a modified, non-carbocation mechanism.
• Recall these concepts
• Nucleophilic substitution on tertiary halides
  invokes the carbocation but nucleophilic
  substitution on primary RX avoids the carbocation
  by requiring the nucleophile to become involved
  immediately.
• The E2 reaction requires the strong base to
  become involved immediately.

Note that secondary and tertiary protonated
alcohols eliminate the water to yield a
carbocation because the carbocation is relatively
stable. The carbocation then undergoes a second
step removal of the H. The primary
carbocation is too unstable for our liking so we
combine the departure of the water with the
removal of the H.
What would the mechanism be???
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Here is the mechanism for acid catalyzed
dehydration of Primary alcohols
1. protonation
2. The carbocation is avoided by removing the H
at the same time as H2O departs (like E2).
As before, rearrangements can be done while
avoiding the primary carbocation.
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Principle of Microscopic Reversibility
Same mechanism in either direction.
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Pinacol Rearrangement an example of
stabilization of a carbocation by an adjacent
lone pair.
Overall
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Mechanism
Reversible protonation.
Elimination of water to yield tertiary
carbocation.
This is a protonated ketone!
1,2 rearrangement to yield resonance stabilized
cation.
Deprotonation.
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Oxidation
Primary alcohol
Na2Cr2O7
Na2Cr2O7
RCH2OH RCHO
RCO2H
Na2Cr2O7 (orange) ? Cr3 (green) Actual reagent
is H2CrO4, chromic acid.
Secondary
Na2Cr2O7
KMnO4 (basic) can also be used. MnO2 is produced.
R2CHOH R2CO
Tertiary
The failure of an attempted oxidation (no color
change) is evidence for a tertiary alcohol.
R3COH NR
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Example
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Oxidation using PCC
Primary alcohol
Stops here, is not oxidized to carboxylic acid
PCC
RCH2OH RCHO
Secondary
PCC
R2CHOH R2CO
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Periodic Acid Oxidation
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Mechanistic Notes
Cyclic structure is formed during the reaction.
Evidence of cyclic intermediate.
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Sulfur Analogs, Thiols
Preparation
RI HS- ? RSH SN2 reaction. Best
for primary, ok secondary, not tertiary (E2
instead)
Oxidation
Acidity H2S pKa 7.0 RSH pKa 8.5