The Retrosynthetic Analysis Approach to Designing Organic Syntheses-3
D. Oxidation of Alcohols to Ketones
1. Introduction:
In the previous section we learned how to use C-C disconnections, FGI’s of Grignard
reagents and FGI dehydrations to synthesize larger alkenes and alcohols from smaller
ketones or aldehydes and organic halides. This unit introduces methods for synthesizing
ketones from alcohols, another FGI, since these reactions change functional groups, but
do not alter the carbon structure of the reactant. The addition of this reaction to our
synthetic repertoire greatly increases our abilities to build larger molecules from a
number of smaller molecules.
2. Oxidation of 2˚ Alcohols to Ketones:
Chromium Trioxide (CrO3) in acidic aqueous solution (H2SO4) is a common reagent for
oxidation of alcohols. This metal oxide reagent is a relatively strong oxidizing reagent.
It smoothly converts 2˚ alcohols to ketones.
O
HO H
H2 SO4
+
CrO3
H OH
O
H2 SO4
+
CrO3
3. FGI-oxidation:
The following FGI Retrosynthetic step indicates that the ketone can be synthesized from
the corresponding alcohol by oxidation.
O
H OH
FGI
oxidation
Although this is a simple addition to our reagent list, this oxidation increases our abilities to
synthesize complex molecules from relatively simple ones. Consider the potential synthesis
of the complex molecule shown below. One Grignard C-C disconnection reveals that the
target molecule can be synthesized from phenyl magnesium chloride and 2,5-dimethyl-4heptanone.
Cl
Mg
C-C disconnection
O
Grignard
O
+
H
With only the Grignard C-C disconnection, we were able to disconnect the carbon structure
of an alcohol only once.
Retrosynthetic Analysis-3
2
However, we now see that the ketone precursor revealed by the above disconnection can
be synthesized from a 2˚ alcohol as indicated on page 80 and reproduced below:
O
H OH
FGI
oxidation
This FGI reveals a compound that can be further disconnected with a Grignard C-C to
reveal even simpler synthetic precursors.
H OH
O
C-C disconnection
Grignard
Mg
+
Br
H
If we recall that Grignard Reagents can be synthesized from alkyl halides, we can look at
the entire synthetic pathway as a set of disconnections and FGI's. The starting materials
are enclosed in rectangles.
Mg
Cl
O
C-C disconnection
O
+
Grignard
H
FGI-M
FGI
Oxidation
O
H OH
H
C-C disconnection
+
+ Mgo
Grignard
Mg
Cl
Br
FGI-M
Br
+ Mgo
Retrosynthetic Analysis-3
3
4. Out of Class Application:
For our next lab discussion period use retrosynthetic analysis to devise syntheses for the
following compounds from monosubstituted aromatic compounds and non-aromatic
compounds with four or fewer carbon atoms.
OH
O
Then write complete synthetic paths, including reagents and reaction conditions based on
your retrosynthetic analyses.
Be prepared to discuss both the retroanalysis and the synthesis.