Page 1153 - Advanced Organic Chemistry Part B - Reactions & Synthesis

12.4.2. Ozonolysis 1129

The reaction of alkenes with ozone is a general and selective method of SECTION 12.4
cleaving carbon-carbon double bonds. 194 Application of low-temperature spectro- Oxidative Cleavage of
scopic techniques has provided information about the rather unstable intermediates Carbon-Carbon Double
Bonds
in the ozonolysis process. These studies, along with isotopic-labeling results, have
provided an understanding of the reaction mechanism. 195 The two key intermediates
in ozonolysis are the 1,2,3-trioxolane, or initial ozonide, and the 1,2,4-trioxolane,
or ozonide. The first step of the reaction is a 1,3-dipolar cycloaddition to give the
1,2,3-trioxolane. This is followed by a fragmentation and recombination to give the
isomeric 1,2,4-trioxolane. Ozone is a very electrophilic 1,3-dipole because of the
accumulation of electronegative oxygen atoms in the ozone molecule. The cycload-
dition, fragmentation, and recombination are all predicted to be exothermic on the
basis of thermochemical considerations. 196

O –
R H + O + O R H
O O O O C O R
C C + O O – R C C H C + C O C H
H R R H R O
H R H

The products isolated after ozonolysis depend upon the conditions of workup.
Simple hydrolysis leads to the carbonyl compounds and hydrogen peroxide, and these
can react to give secondary oxidation products. It is usually preferable to include a
mild reducing agent that is capable of reducing peroxidic bonds. The current practice
is to use dimethyl sulfide, though numerous other reducing agents have been used,
including zinc, 197 trivalent phosphorus compounds, 198 and sodium sulfite. 199 If the
alcohols resulting from the reduction of the carbonyl cleavage products are desired,
the reaction mixture can be reduced with NaBH . 200 Carboxylic acids are formed in
4
good yields from aldehydes when the ozonolysis reaction mixture is worked up in the
presence of excess hydrogen peroxide. 201
Several procedures that intercept the intermediates have been developed. When
ozonolysis is done in alcoholic solvents, the carbonyl oxide fragmentation product
can be trapped as an -hydroperoxy ether. 202 Recombination to the ozonide is then
prevented, and the carbonyl compound formed in the fragmentation step can also be

194
P. S. Bailey, Ozonization in Organic Chemistry, Vol. 1, Academic Press, New York, 1978.
195
R. P. Lattimer, R. L. Kuckowski, and C. W. Gillies, J. Am. Chem. Soc., 96, 348 (1974); C. W. Gillies,
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J. Am. Chem. Soc., 97, 5287 (1975); P. S. Bailey and T. M. Ferrell, J. Am. Chem. Soc., 100, 899
(1978); I. C. Histasune, K. Shinoda, and J. Heicklen, J. Am. Chem. Soc., 101, 2524 (1979); J.-I. Choe,
M. Srinivasan, and R. L. Kuczkowski, J. Am. Chem. Soc., 105, 4703 (1983). R. L. Kuczkowski, in
1,3-Dipolar Cycloaddition Chemistry, A. Padwa, ed., Wiley-Interscience, New York, Vol. 2, Chap. 11,
1984; R. L. Kuczkowski, Chem. Soc. Rev., 21, 79 (1992); C. Geletneky and S. Barger, Eur. J. Chem.,
1625 (1998); K. Schank, Helv. Chim. Acta, 87, 2074 (2004).
196 P. S. Nangia and S. W. Benson, J. Am. Chem. Soc., 102, 3105 (1980).
197
S. M. Church, F. C. Whitmore, and R. V. McGrew, J. Am. Chem. Soc., 56, 176 (1934).
198 W. S. Knowles and Q. E. Thompson, J. Org. Chem., 25, 1031 (1960).
199
R. H. Callighan and M. H. Wilt, J. Org. Chem., 26, 4912 (1961).
200
F. L. Greenwood, J. Org. Chem., 20, 803 (1955).
201 A. L. Henne and P. Hill, J. Am. Chem. Soc., 65, 752 (1943).
202
W. P. Keaveney, M. G. Berger, and J. J. Pappas, J. Org. Chem., 32, 1537 (1967).