Labelling rearrangement

Whereas diazotization of labelled anthranilic acid 130 at 84 °C (in the presence of excess unlabelled acid) gave biphenylene 131 without label rearrangement, pyrolysis of labelled phthalic anhydride 132 (again, with excess unlabelled anhydride, so that the presence of tetra-labelled biphenylene in the product is virtually nil) at 830 °C gave approximately a 1 1 mixture of 131 and 133. Similar labelling results were obtained in the pyrolysis of 134 cfll) at 650-830 °C. 

Photolytic deprotection of the ulosonic acid -nitrobenzyl glycoside (49) did not yield the expected enolpyranose but the rearranged 3-dehydroquinic acid (50) the stereospecific label rearrangement implies a chair transition state, and suggests the biosynthetic pathway by this route is not enzyme-catalysed. ... 

One way of proceeding is shown in the flow diagram of figure 2 for the ease of = 8, P = 3. The operation labeled PERMUTE rearranges the sequence of data. The /th member is placed into theyth position where] is calculated from i as follows... 

Nitraminothiazole. treated for 12 hr with 96% sulfuric acid, gives 2-amino-5-nitrothiazole (194). The mechanism of this rearrangement is not yet quite resolved even for nitraminobenzene derivatives (617). The series of kinetic determinations and appropriate labeling performed by Toth et al. provide, however, precious hints for this difficult problem (1578. 1579). 

The first mass spectrometric investigation of the thiazole ring was done by Clarke et al. (271). Shortly after, Cooks et al., in a study devoted to bicydic aromatic systems, demonstrated the influence of the benzo ring in benzothiazole (272). Since this time, many studies have been devoted to the influence of various types of substitution upon fragmentation schemes and rearrangements, in the case of alkylthiazoles by Buttery (273) arylthiazoles by Aune et al. (276), Rix et al. (277), Khnulnitskii et al. (278) functional derivatives by Salmona el al. (279) and Entenmann (280) and thiazoles isotopically labeled with deuterium and C by Bojesen et al. (113). More recently, Witzhum et al. have detected the presence of simple derivatives of thiazole in food aromas by mass spectrometry (281). 

Thermal Cope-type rearrangements between C-vinyl and nitrogen substituents bearing appropriately labeled unsaturation are also known, e.g. (147) -> (148) (67JA60S, 71JOC3076). 

Nucleophilic substitution in cyclohexyl systems is quite slow and is often accompanied by extensive elimination. The stereochemistry of substitution has been determined with the use of a deuterium-labeled substrate (entry 6). In the example shown, the substitution process occurs with complete inversion of configuration. By NMR amdysis, it can be determined that there is about 15% of rearrangement by hydride shift accon any-ing solvolysis in acetic acid. This increases to 35% in formic acid and 75% in trifiuoroacetic acid. The extent of rearrangement increases with decreasing solvent... 

The occurrence and extent of rearrangement of the 2-butyl cation have also been investigated by solvolysis studies using isotopic labeling. When 2-butyl tosylate is solvolyzed in acetic acid, C-2/C-3 rearrangement occurs only to the extent of 9% in the 2-butyl acetate which is isolated.Thus, under these conditions, most of the reaction proceeds by direct participation of the solvent. 

The reaction of phenyllithium and alfyl chloride labeled with C reveals that allylic rearrangement occurs. About three-fourths of the product results from bond formation at C-3 rather than C-1. This can be accounted for by a cyclic transition state. ... 

The rearrangement of the simplest possible case, 1,5-hexadiene, has been studied using deuterium labeling. The activation enthalpy is 33.5kcal/mol, and the entropy of activation is — 13.8eu. The substantially negative entropy reflects the formation of the cyclic transition state. 

Compound 1 undergoes rearrangement to 2 in SO2 at — 66°C. The deuterium label becomes imiformly scrambled among all the carbon atoms in 2. 

The di-7r-methane rearrangement has been studied in a sufficient number of cases to develop some of the patterns regarding substituent effects. When the central sf carbon is unsubstituted, the di-7i-methane mechanism becomes less favorable. The case of 1,1,5,5-tetraphenyl-l,4-pentadiene is illustrative. Although one of the products has the expected structure for a product of the di-7t-methane rearrangement, labeling with deuterium proves that an alternative mechanism operates ... 

They found that deuterium labeled 2-phenyl-5-methoxy-4-[(methoxy-d3)-carbonyl]oxazole (7) scrambled on heating to give a 1 1 equilibrium mixture of 7 and the corresponding rearranged ester 9 ... 

Deuterium-labeling and mass spectrometry prove that the mechanism of the thermal O to N rearrangement of 4-alkoxypyridines to N-alkyl-4-pyridones is intermolecular (88CS347). 

The reaction mechanism is supported by findings from experiments with 0-labeled benzophenone 6 after rearrangement, the labeled oxygen is found in the carbonyl group only ... 

This mechanism of a -elimination reaction is supported by experimental findings with " S- and C-labeled starting materials." The Chugaev reaction is analogous to the ester pyrolysis, but allows for milder reaction conditions—i.e. it occurs at lower temperatures. It is less prone to side reactions, e.g. the formation of rearranged products, and is therefore the preferred method. 

To illustrate the value of the mass spectra of the labeled compounds, the peaks at m/e 129 in Figures 7 and 8 will be considered first. These peaks could be from the loss of acetic acid (60 mass units) from m/e 189, or the loss of water (18 mass units) from m/e 189 followed by loss of ketene (42 mass units) structure 15, containing C-1-C-2-C-3 less a rearranged hydrogen atom from C2, is another possibility. The composition of this ion could be important for confirming the presence of a 3-hydroxyl group. 

Evidence for this mechanism comes from the observation that the rearrangement takes place with an inversion of the allyl group. That is, allyl phenyl ether containing a 14C label on the allyl ether carbon atom yields o-allylphenol in which the label is on the terminal vinylic carbon (green in Figure 18.1). It would be very difficult to explain this result by any mechanism other than a pericyclic one. We ll look at the reaction in more detail in Section 30.8. 

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