Alcohols

Hydrogen Bonding

Three ethanol molecules.

Hydrogen Bonding & boiling pointIncreases 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

Methanol Ethanol 2-Propanol 2-Methyl-2-propanol

Increasing Hinderance of Solvation

RO-H RO – (solvated) + H + (solvated)

Increasing Acidity of the alcohol

Recall: H2O + Na Na+ + OH- + ½ H2(g)

Alcohols behave similarly

ROH + Na Na+ + OR- + ½ H2(g)

Alkoxide, strong base, strong nucleophile (unless sterically

hindered)

Also: ROH + NaH Na+ + OR- + ½ H2(g)

Increasing Basicity of Alkoxide Anion, the conjugate base

Alkoxide ion, base

Alkoxides can be produced in several ways…

-OH as a Leaving Group

R-OH + H + R-OH2+

Protonation of the alcohol sets-up a good leaving group, water.

Poor leaving group, hydroxide ion.

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

Expect both configurations.

When a carbocation cannot be formed. Methanol, primary. SN2

RCH2OH RCH2OH2

X -H +

RCH2X

R3COH R3COH2 R3C + + H2O

X -H +

R3CX

But sometimes experiment does not agree with our ideas…

Observed reaction CH2OH

HX

CH2X

X

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

CH2OH

H + H3C

CH2OH2+

CH2.......OH2

H3C CH3

H2O

X-X

Not a primary carbocation

Other ways to convert: ROH RXWe have used acid to convert OH into a good leaving group

There are other ways to accomplish the conversion to the halide.

RCH2-OHPBr3

RCH2-O(H)PBr2

Br -

RCH2Br + HOPBr2

primary, secondary

RCH2-OHSOCl2

RCH2-OS(O)ClCl -

RCH2Cl + SO2

primary, secondary, tertiary

amine

R3COH R3COH2 R3C + + H2O

X -H +

R3CX

Leaving group.

Leaving group.Next, a very useful alternative to halide…

An alternative to making the halide: ROH ROTs

p-toluenesulfonyl chloride

Tosyl chloride

TsCl

ROH +S OO

Cl

S OO

O

CH3 CH3

R Tosylate group, -OTs, good leaving

group, including the

oxygen.

The configuration of the R group is unchanged.

Preparation from alcohols.

Example

CH3

H OH

C2H5

C3H7 CH3

TsCl

CH3

H OTs

C2H5

C3H7 CH3

Preparation of tosylate.

Retention of configuration

Substitution on a tosylate

The –OTs group is an excellent leaving group

Acid Catalyzed Dehydration of an Alcohol, discussed earlier as reverse of hydration

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.

Secondary and tertiary alcohols, carbocations

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:

MechanismReversible 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 RCH=O RCO2H

Na2Cr2O7

Na2Cr2O7

Na2Cr2O7 (orange) Cr3+ (green) Actual reagent is H2CrO4, chromic acid.

Secondary

R2CHOH R2C=O

Tertiary

R3COH NR

KMnO4 (basic) can also be used. MnO2 is produced.

The failure of an attempted oxidation (no color change) is evidence for a tertiary alcohol.

Na2Cr2O7

OH

CH2OH

HO

Na2Cr2O7

acid

OH

CO2H

O

Example…

Oxidation using PCC

Primary alcohol

RCH2OH RCH=OPCC

PCCSecondary

R2CHOH R2C=O

Stops here, is not oxidized to carboxylic acid

Periodic Acid Oxidation

OH

OH

glycol

HIO4

O

O

two aldehydes

+ HIO3

OH

O HIO4

O

O

aldehydes

HO

carboxylic acid

+ HIO3

O

O HIO4

O

OHO

carboxylic acidcarboxylic acid

OH + HIO3

OH

O 2 HIO4

OH

O

OH

OHO

O

+ 2 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)

Acidity

H2S pKa = 7.0

RSH pKa = 8.5

Oxidation