Ozone is a toxic, corrosive and unstable gas, which can decompose
spontaneously to produce oxygen. This
decomposition may be explosive at elevated temperatures or in the presence
Ozone is produced by generating a high-voltage electrical discharge in air or oxygen. As a strong oxidant, it reacts with various oxidizable inorganic and organic materials. The reaction with unsaturated organic compounds gives unstable ozonides, which can decompose violently.
Benzyl ether protective groups are oxidatively removed by ozone under relatively mild conditions. Reaction products are benzoic ester, benzoic acid, and the corresponding alcohol. Subsequent deacylation with sodium methoxide affords a convenient debenzylation technique which has been applied to various O-benzyl protected carbohydrates.
P. Angibeaud, J. Defaye, A. Gadelle, J.-P. Utille, Synthesis, 1985, 1123-1125.
A mild one-pot ozonolysis-oxidation process enables the synthesis of carboxylic acids from alkenes. Conducting the ozonolysis in an aqueous organic solvent eliminates secondary ozonide formation and the intermediates generated are readily converted into a carboxylic acid by adding sodium chlorite. The desired acids are isolated in high purity and high yield by simple extraction after a reductive quench.
B. M. Cochran, Synlett, 2016, 27, 245-248.
Simple Diels-Alder-derived ketals could be selectively ozonolyzed to monoaldehydes. An overall procedure for the preparation of a key intermediate for porphyrin and heme synthesis is described.
D. F. Taber, K. Nakajima, J. Org. Chem., 2001, 70, 2515-2517.
The diastereoselectivity of the Griesbaum coozonolysis reaction with O-methyl 2-adamantanone oxime and 4-substituted cyclohexanones reveals that the major tetrasubstituted ozonide isomers possess cis configurations, suggesting a preferred axial attack of the carbonyl oxide on the cyclohexanone dipolarophiles.
Y. Tang, Y. Dong, J. M. Karle, C. A. DiTusa, J. L. Vennerstrom, J. Org. Chem., 2004, 69, 6470-6473.
The high reactivity of ozone and its propensity to overoxidize organic molecules, including most solvents can largely be mitigated by adsorbing both substrate and ozone onto silica gel, providing a solvent-free oxidation method. A flow-based packed bed reactor approach provides exceptional control of temperature and time for oxidation of amines to nitroalkanes and the synthesis of pyridine N-oxides.
E. A. Skrotzki, J. K. Vandavasi, S. G. Newman, J. Org. Chem., 2021, 86, 14169-14176.
A highly enantioselective method for catalytic reductive coupling of alkynes and aldehydes afforded allylic alcohols with complete E/Z selectivity, generally >95:5 regioselectivity, and in up to 96% ee. In conjunction with ozonolysis, this process allows the enantioselective synthesis of α-hydroxy ketones.
K. M. Miller, W.-S. Huang, T. F. Jamison, J. Am. Chem. Soc., 2003, 125, 3442-3443.
N-Tosyl-3-halo-3-butenylamines underwent efficient Ullmann-type coupling to afford 2-alkylideneazetidines, which could be readily converted to the corresponding β-lactams by oxidation with O3.
H. Lu, C. Li, Org. Lett., 2006, 8, 5365-5367.
The synthesis of α,β-unsaturated lactones from β-acetoxy aldehydes is achieved by reaction with the lithium enolate of methyl acetate. The reaction is relatively insensitive to structural changes in the aldehyde substrates. The process was extended to the synthesis of five-ring lactones from α-acetoxy aldehydes.
G. E. Keck, X.-Y. Li, C. E. Knutson, Org. Lett., 1999, 1, 411-413.