Ozonolysis, structure determination

Ozonolysis is sometimes used as a tool m structure determination By identifying the carboxylic acids produced we can deduce the structure of the alkyne As with many... 

Ozonolysis of alkenes (end of Section 6.4) and cleavage of glycols (Section 14.11) afford carbonyl compounds. These reactions, once used for structure determinations, have been superseded by spectral methods. 

A historically important use of the ozonolysis reaction was in the area of structure determination. In the days before the advent of spectroscopic techniques (Chapters 13-15), the structure of an unknown organic compound was determined by submitting it to a host of reactions. Often, a complex molecule was broken into several fragments to simplify the structural problem. After the individual fragments were identified, the original molecule could be mentally reconstructed from them. Alkenes were often cleaved to aldehydes and ketones by reaction with ozone. 

Use clues provided by the products of reactions, such as ozonolysis, to determine the structure of an unknown alkene. 

Chemical examination of Sarcophyton glaucum collected at Ishigaki island, Okinawa Prefecture, resulted in the isolation of seven cembranoid diterpenes, namely sarcophytol A (3), sarcophytol A acetate (4), sarcophytol B (5), sarcophy-tonin A (6), and minor constituents sarcophytol C (7), D (8), and E (9). These compounds were found to be susceptible to autooxidation while being purified. The structural determination of these compounds was made mainly based on proton and carbon nuclear magnetic resonance (NMR) spectral evidence and degradative studies by ozonolysis. X-ray crystallographic analysis for the two crystalline compounds, sarcophytol B (5) and D (8), has been reported. The total lipid extracts of S. glaucum comprise about 40% sarcophytol A (3), 5% each of sarcophytol A acetate (4) and sarcophytonin A (6), about 1% sarcophytol B (5), and minor amounts of sarcophytol C (7), D (8), and E (9). 

Ozonolysis as used below is the oxidation process involving addition of ozone to an alkene to form an ozonide intermediate which eventually leads to the final product. Beyond the initial reaction of ozone to form ozonides and other subsequent intermediates, it is important to recall that the reaction can be carried out under reductive and oxidative conditions. In a general sense, early use of ozonolysis in the oxidation of dienes and polyenes was as an aid for structural determination wherein partial oxidation was avoided. In further work both oxidative and reductive conditions have been applied . The use of such methods will be reviewed elsewhere in this book. Based on this analytical use it was often assumed that partial ozonolysis could only be carried out in conjugated dienes such as 1,3-cyclohexadiene, where the formation of the first ozonide inhibited reaction at the second double bond. Indeed, much of the more recent work in the ozonolysis of dienes has been on conjugated dienes such as 2,3-di-r-butyl-l,3-butadiene, 2,3-diphenyl-l,3-butadiene, cyclopentadiene and others. Polyethylene could be used as a support to allow ozonolysis for substrates that ordinarily failed, such as 2,3,4,5-tetramethyl-2,4-hexadiene, and allowed in addition isolation of the ozonide. Oxidation of nonconjugated substrates, such as 1,4-cyclohexadiene and 1,5,9-cyclododecatriene, gave only low yields of unsaturated dicarboxylic acids. In a recent specific example... 

The reported 114) formation of acetic acid on ozonolysis of conkurchine was confirmed by later reinvestigation 79). Obviously, ozonolysis is unsuitable for structure determination of pyrrolines. This is in accord with Witkop s conclusion 133) that ozonolysis cannot be applied for structure determinations in imine-enamine systems. 

The previous discussion clearly shows that total synthesis provides a viable approach to the avermectin disaccharide for use in the synthesis of avermectins. An alternative source of the disaccharide unit is chemical degradation of a natural avermectin. It is worth noting that the chemical degradation approach to the avermectin disaccharide unit could in principle use any natural avermectin or mixture of avermectins as a starting material. The ready availability of several natural avermectins from fermentation makes this approach particularly advantageous when a large amount of material is needed in a short period of time. The first example of this route to an avermectin disaccharide was reported by Albers-Schonberg et al. in 1981 [5]. As part of the structure determination of the avermectins they subjected avermectin A2a 123 to ozonolysis followed by... 

In Chapter 8 we also saw how this procedure has utility in structure determination. The following examples illustrate the synthesis of aldehydes by ozonolysis of alkenes. 

Thomas, M.C., Mitchell, T.W. and Blanksby, S.J. (2006) Ozonolysis of phosphohpid double bonds during electrospray ionization A new tool for structure determination. J. Am. Chem. Soc. 128, 58-59. 

Moore, B. P., and W. V. Brown Gas-liquid chromatographic identification of ozonolysis fragments as a basis for micro-scale structure determination. J. Chromatogr. 60, 157—166(1971). 

The structure determination of fasciculatin (96) and variabilin (97) isolated subsequently 37, 84) followed the same pattern as that used for ircinin-1 and ircinin-2. The stereochemistry of the double bond in fasciculatin (96) was derived from the coupling constants of the two ole-finic protons, and the S,S chirality at C-13 and C-18 followed from the production, on ozonolysis, of (2 S, 6 S)-2,6-dimethylpimelic acid. 

The structures of these two CaHie alkenes were determined by ozonolysis as described in Section 6.19. 

Until the second half of the twentieth century, the structure of a substance—a newly discovered natural product, for example—was determined using information obtained from chemical reactions. This information included the identification of functional groups by chemical tests, along with the results of experiments in which the substance was broken down into smaller, more readily identifiable fragments. Typical of this approach is the demonstration of the presence of a double bond in an alkene by catalytic hydrogenation and subsequent determination of its location by ozonolysis. After-considering all the available chemical evidence, the chemist proposed a candidate structure (or structures) consistent with the observations. Proof of structure was provided either by converting the substance to some already known compound or by an independent synthesis. 

The structure and carbon chain distribution of sodium vinylidenesulfonate (VOS) has been investigated by Hashimoto et al. [119] using NMR, IR, and chromatographic techniques. The double-bond distribution of VOS was determined using ozonolysis-reduction-GLC. The position of the sulfonic acid groups... 

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