Download Chapter 11

Alcohols
Have seen many reactions to synthesize alcohols:
In this chapter we will study reactions of the alcohols
Oxidation
Need to understand the nomenclature of organic reduction/oxidation
In general chemistry learn that reduction is gain of electrons and oxidation is loss of electrons
Definition works well with transition metals, but it is hard to distinguish RED/OX reactions in organic reactions by this definition
For organic compounds want to compare oxidation level of different compounds
It is very important that one recognizes whether two compounds are of the same oxidation
level or whether one is “oxidized” relative to the other
Anytime two compounds can be converted with only water, basic water (NaOH)
or acidic water (H+) then the two compounds are at the same oxidation level
For example:
All compounds are at the same oxidation level
oxidized form reduced form
Using LAH, however, creates two compounds at different oxidation levels
Comparison of Oxidation States
We can use a bookkeeping technique to assign oxidation states
In this technique assume every bond is ionic and the electrons are closer
to the more electronegative atom
This is obviously just for convenience – does not correspond to actual system with covalent bonds (where electrons are shared between two atoms)
Consider bonds to carbon:
C H
C H
C Cl
C Cl
C O
C O
Used only for bookkeeping - C-H bond is not ionic
Comparison of Oxidation States
With this bookkeeping technique, oxidation states can be compared
Oxidation state
compound
CnHx
-4 alkane
CH4
-2 0
+2
+4
alkene
C2H4
alkyne
C2H2
CHnClx
alkyl halide
CH3Cl
dihalide
CH2Cl2
trihalide
CHCl3
CHnOx
alcohol
CH3OH
aldehyde
CH2O
acids
carbon dioxide
HCO2H
CO2
CHnNx
amine
CH3NH2
imine
CH2NH
Oxidation
Reduction
nitrile
HCN
tetrahalide
CCl4
diimide
C(NH)2
Oxidation States Relative to Reactions
Oxidation state
CH3CH3
H2C=CH2
C2H2
CH3CH2Cl
CH3CHCl2
HCl
CH3CCl3
CCl4
CH3CO2H
CO2
CH3CN
C(NH)2
LAH
CH3CH2OH
CH3CHO
CH3CH2NH2
CH3CHNH
Interconversions between same oxidation state can occur with water or acidic/basic conditions
Interconversions between different oxidation states need an oxidizing (if going to the right) or reducing agent (if going to the left)
Choosing Reagents for an Organic Reaction
The proper choice of reagents therefore involves deciding whether a reaction changes oxidation states
If a reaction is more oxidized, then an oxidizing agent is required
If a reaction is more reduced, then a reducing agent is required
HO H
C
H3C
CH3
-3
0
-3
Need
oxidizing agent
O
C
H3C +2
CH3
-3
-3
Assign oxidation state to each carbon
The middle carbon changes from 0 to +2 oxidation state,
Therefore the carbon has been oxidized
Oxidation of Alcohols
Typical procedure to oxidize an alcohol is to use a chromium (VI) reagent
e.g. CrO3, H2Cr2O7, H2CrO4
B
OH
O
HO Cr OH
O
H
O
O Cr OH
O
O
Cr(IV)
The alcohol reacts with Cr(VI) to form a chromate ester
The chromate ester then reacts with base (usually water) to oxidize the alcohol
[and reduce the chromium reagent]
With 1˚ alcohols the initially formed aldehyde reacts further
The aldehyde equilibrates to the geminal diol form, called acetal
(which is further promoted in acidic conditions)
This acetal can behave like an alcohol to oxidize in a second step
1˚ alcohols therefore give almost exclusively carboxylic acids
(especially in acidic conditions)
One way to avoid this overoxidation is to use a Cr(VI) reagent in nonacidic conditions
The pyridine acts as a base and therefore there is less acetal formation and hence oxidation of 1˚ alcohols stop at the aldehyde stage
Other Oxidants
Cr(VI) is not the only oxidant for alcohols
Swern Oxidation
-another method to synthesize aldehydes from 1˚ alcohols
Advantages: mild method, easy to separate and purify products,
1˚ alcohol stops at aldehyde
In addition to oxidation, can also react alcohols as either nucleophiles or electrophiles
To make alcohols more nucleophilic, need to abstract the acidic hydrogen
(remember pKa’s!)
With this method, can make nucleophilic oxygen that can react through any SN2 type reaction already studied
Esterification
To form esters the alcohol can react as a nucleophile without forming the alkoxides
- generally need to activate the carbonyl first (through protonation) to make it more electrophilic
Esters can also be formed with alcohols by reacting alcohol with more reactive carbonyl groups
The better leaving group (chloride) allow the alcohol to react at the carbonyl without first protonating
Formation of Inorganic Esters
- Same type of mechanisms already observed
Tosylates are typically formed by reacting alcohols and tosyl chlorides
Using common abbreviations:
Other Common Ester Types
Follow same mechanism as seen earlier for ester formation
(alcohol reacts at carbonyl site {N=O or P=O in these examples} followed by loss of water)
Alcohols Reacting as Electrophiles
In these reactions the alcohol is the leaving group
(the C-O bond is broken during the reaction)
NUC
H
H
H
OH
H
NUC
H
H
OH
Usually the hydroxide, or alkoxide, is a BAD leaving group,
therefore we need to convert the alcohol into a GOOD leaving group
One Method is Tosylate Formation
The tosylate, which was seen earlier, is commonly used as a way to make the alcoholic
oxygen a good leaving group
NUC
H
H
H
OTs
H
NUC
H
H
OTs
Another method we have already observed is protonation
to form water as the leaving group
OH
H+
OH2
X
X
With either an SN1 or SN2 reaction the alcohol would need to be protonated first in order to make a better leaving group
For alcohol reactions what type of reaction that will occur (SN1 or SN2)
depends upon the order of the attached carbon
3˚ alcohols
2˚ alcohols
1˚ alcohols
must be SN1 (cannot undergo SN2)
mainly SN1
SN2 (1˚ carbocations are high in energy)
Lucas Reagent
Chloride reacts slower than bromide
(less nucleophilic)
Therefore often need to add an additional Lewis acid to convert an alcohol to alkyl chloride
(even with 2˚ and 3˚ alcohols that proceed through SN1)
-with Lucas reagent need to add ZnCl2 to increase reaction rate
While it is relatively easy to react alcohols with hydrobromic or hydrochloric acid, to generate alkyl bromides or alkyl chlorides, both HF and HI are difficult to react in this manner
Need different routes to these compounds
Alkyl iodides can be prepared with phosphorous halides
An example with PCl3:
SN2 reaction – works well for 1˚ and 2˚ alcohols, not a choice for 3˚ alcohols
Method of choice for Iodides
PI3 can be used
Often in practice PI3 is generated in situ from P/I2
Another method for conversion of alcohols to alkyl halides is thionyl chloride
Due to rapidity of the last step, these is retention of stereochemistry
In practice almost any alcohol can be converted into an alkyl halide
Type of alcohol and desired halide often determine which method is best
Best reagents for interconversions:
Type of alcohol
chloride
bromide
iodide
primary
SOCl2
PBr3
P/I2
secondary
SOCl2
PBr3
P/I2
tertiary
HCl
HBr
HI
Stereochemistry, and possibility of rearrangements, depends on mechanism for each reaction
Diol Reactions
Some reactions are unique to vicinal diols (glycols)
Pinacol rearrangement:
Periodic Cleavage of Glycols
HIO4 will react with glycols
Very important reaction to determine sugar structures
H OH
H OH
H O
HO
HO
H
H
OH
H
OCH3
HIO4
H O
O
H
O
H
methyl-!-D-glucopyranoside
Only vicinal diols react
OH
OCH3
O
H