pharmaceutical organic chemistry

1. ozonolysis of Alkenes

2. ozonolysis is a reaction in which the products are more highly
oxidized. In this reaction the carbon–carbon double bond is
cleaved to produce carbonyl compounds.
1. Alkenes react rapidly with ozone (O3 ) even at –78 °C.
2. Ozone is produced in the laboratory by a device called an
ozonator, which forms ozone by passing oxygen gas through an
arc discharge.
3. As the ozone forms, oxygen gas containing a few percent ozone
is passed through an inert solvent, such as dichloromethane,
that contains the alkene.
4. After the reaction is complete, the solution is worked up under
reductive conditions such as zinc in acetic acid.

3. Mechanism of Ozonolysis
Ozonolysis occurs in several steps. First, an unstable intermediate,
called a molozonide, forms by a cyclic concerted addition of the
terminal oxygen atoms of ozone to the π bond of the alkene. This
step requires a total of three electron pair shifts, as shown below.

4. In subsequent steps, the molozonide rapidly rearranges when the
π bond of the alkene and an O-O eroxide bond break. The
fragments then recombine to give an ozonide. The individual
fragments are reoriented to illustrate the addition reaction in the
second step

5. 1. The molozonide has two weak peroxide bonds, but the
ozonide has only one. This difference accounts for the
direction of the reaction.
2. The rearrangement of the molozonide is exothermic.
3. However, ozonides are explosively unstable compounds.
4. For that reason, the reaction mixture is maintained at low
temperatures and immediately reduced or oxidized after the
reaction is complete.

6. REDUCTIVE WORKUP
The ozonolysis reaction mixture is treated with reducing agents
such as zinc metal and aqueous acetic acid or dimethyl sulfide.
When zinc is used, the by-product is zinc oxide. When dimethyl
sulfide is the reducing agent, dimethyl sulfoxide, (CH3)2 SO, is a
by-product. In each case, the reducing agent removes one of the
oxygen atoms of the ozonide. The other two oxygen atoms of the
ozonide are found as carbonyl oxygen atoms in the product as
aldehydes or ketones.

7. If the ozonolysis reaction mixture is treated with an oxidizing agent
such as hydrogen peroxide, carboxylic acids rather than aldehydes
are produced. For example, the ozonolysis of cyclooctene with an
oxidative workup yields octanedioic acid (suberic acid). This
compound is one of several dicarboxylic acids excreted in large
amounts by persons suffering from diabetes.
The choice of reducing or oxidizing workup depends on the goal
of the synthesis, which may be to prepare aldehydes (or ketones)
or carboxylic acids.