Transcript Alcohols - City University of New York

Alcohols
Hydrogen Bonding
Three ethanol molecules.
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
Earlier Discussion of Acidity
RO-H

RO – (solvated) +
H + (solvated)
Alkoxide ion, base
Increasing Hinderance of Solvation
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)
Alcohols behave similarly
ROH + Na Na+ + OR- + ½ H2(g)
Also: ROH + NaH Na+ + OR- + ½ H2(g)
Alkoxide, strong base, strong
nucleophile (unless sterically
hindered)
-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…
Conversion to Alkyl Halide,
HX + ROH  RX + H2O
When a carbocation can be formed (Tertiary, Secondary alcohols)
beware of rearangement. SN1
H+
R3COH
XR3COH2
R3C + + H2O
R3CX
Expect both
configurations.
When a carbocation cannot be formed. Methanol, primary. SN2
H
RCH2OH
X-
+
RCH2OH2
RCH2X
But sometimes experiment does
not agree with our ideas…
X
HX
CH2OH
Observed reaction
CH2X
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….
H3C
H
CH2OH
+
X
H3
C
H3C
CH2OH2+
CH3
CH2.......OH2
H2O
Not a primary carbocation
X-
Other ways to convert: ROH  RX
We have used acid to convert OH into a good leaving group
H+
XR3C + + H2O
R3COH2
R3COH
R3CX
There are other ways to accomplish the conversion to the halide.
primary, secondary
Br -
PBr3
RCH2-O(H)PBr2
RCH2-OH
RCH2Br + HOPBr2
Leaving group.
primary, secondary, tertiary
Cl -
SOCl2
RCH2-OS(O)Cl
RCH2-OH
RCH2Cl + SO2
amine
Leaving group.
Next, a very useful alternative to halide…
An alternative to making the halide:
ROH  ROTs
CH3
CH3
Preparation from
alcohols.
ROH +
O
S
O
O
S
O
Cl
p-toluenesulfonyl
chloride
Tosyl chloride
TsCl
The configuration of
the R group is
unchanged.
O
R
Tosylate
group, -OTs,
good leaving
group,
including the
oxygen.
Example
CH3
CH3
TsCl
H
H
OTs
C3H7
CH3
OH
C3H7
CH3
C2H5
Preparation of tosylate.
Retention of configuration
C2H5
Substitution on a tosylate
The –OTs group is an excellent leaving group
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.
Primary alcohols
Problem: primary carbocations are not observed. Need a modified, non-carbocation
mechanism.
Recall these concepts:
1. 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.
2. 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???
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.
Principle of Microscopic Reversibility
Same mechanism in either
direction.
Pinacol Rearrangement: an example of
stabilization of a carbocation by an adjacent lone
pair.
Overall:
Mechanism
Reversible
protonation.
Elimination of
water to yield
tertiary
carbocation.
1,2
rearrangement
to yield
resonance
stabilized cation.
Deprotonation.
This is a
protonated
ketone!
Oxidation
Primary alcohol
RCH2OH
Na2Cr2O7
Na2Cr2O7
RCH=O
RCO2H
Na2Cr2O7 (orange)  Cr3+
(green) Actual reagent is
H2CrO4, chromic acid.
Secondary
Na2Cr2O7
R2CHOH
R2C=O
KMnO4 (basic) can also be
used. MnO2 is produced.
Tertiary
R3COH
NR
The failure of an attempted
oxidation (no color change) is
evidence for a tertiary alcohol.
Example…
OH
OH
Na2Cr2O7
acid
HO
CH2OH
O
CO2H
Oxidation using PCC
Primary alcohol
PCC
RCH2OH
RCH=O
Secondary
PCC
R2CHOH
R2C=O
Stops here, is not oxidized to
carboxylic acid
Periodic Acid Oxidation
OH
O
OH
HIO4
glycol
O
+
HIO3
two aldehydes
OH
O
O
HIO4
HO
O
+
aldehydes
carboxylic acid
O
O
O
HO
HIO4
O
+
OH
carboxylic acid
HIO3
carboxylic acid
OH
O
O
2 HIO4
+ 2 HIO3
HO
O
OH
OH
O
HIO3
Mechanistic Notes
Cyclic structure is formed during
the reaction.
Evidence of cyclic intermediate.
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