Substituent Tautomerism

Although much work is still devoted to tautomerism of pyrazole derivatives, the methodology and the main conclusions remain unaltered. As an example of study of the tautomerism of pyr-azolinones using C NMR spectroscopy see 91JHC641 for the case of pyrazolone T. Katritzky 

The structure of indazolinone and some of its derivatives was determined by the combined used of crystallography, C CPMAS NMR, and N NMR 86JCS(P2)1677 . It was concluded that indazolinone exists as such (67a) in the solid state but only as a minor isomer (15%) in DMSO solution, where the 3-hydroxy-l//-indazole tautomer (67b) predominates (85%). The 3-hydroxy-2//-indazole tautomer (67c) has never been observed. The equilibrium between 2-hydroxy-3-methyl-indazole and 1/f-3-methylindazole-2-oxide has been studied in DMSO, methanol, and trifluoro-methanol by C and N NMR spectroscopy 87MRC721 . The position of the equilibrium was found to be dependent on the acidity of the solvent, the hydroxy form being predominant in weakly acidic media. 

The old problem of the autotropic tautomerism (both tautomers are identical) of rubazoic acid derivatives (68) and (69) has been studied by NMR in solution and in the solid state 93JCS(P2)1597 . 

Another example of the very rare case where two pyrazolinone tautomers are present in the same unit cell 84CHEC-1(5)167 has been described l/f-3-hydroxy-4-R-5-methylpyrazole OH tautomer)/ 

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Interesting results were also obtained on treatment of 2-amino-4,6,6-trimethyl-dihydropyrimidine 50 and 2,4,6,6-tetramethyldihydropyrimidine 51 with CD3OD in the absence of a base (91TL2057). It was shown that, under these conditions, the 4-methyl protons of 50, the 2,4-dimethyl protons of 51, and H(5) in 50 and 51 undergo H-D exchange. The suggested mechanism involves annular (1,4-dihydro 4,5-dihydro) as well as substituent tautomeric equilibria, as shown in Scheme 20 for H-D exchange in 50. 

A variety of 2H- (121, X = O) and 4H- (122, X = O) 1,3,5-oxadiazines has been studied and eharaeterized, whereas 2//-l,3,5-thiadiazines 121 (X = S), unlike the 4H isomers 122 (X = S), are uneommon. The most eommon type of tautomerie intereonversions for sueh systems is ring-ehain tautomerism. A few studies on substituent tautomerism have also been earried out however, no data on annular tautomerism have yet appeared in the literature. 

The reduction of aliphatic nitrocompounds in acid solution proceeds in two steps. First the nitrosocompound is formed. A low steady state concen ation of 2-methyl-2-nitrosopropane has been detected during the reduction of 2-methyl-2-nitropropane [13]. At the cathode potential necessary to attach the first electron to a nitro group, the nitroso intermediate undergoes further reduction to the hydroxyla-mine. When the nitrocompound has one a-hydrogen substituent, tautomerism of the nitroso intermediate to an oxime is in competition with further reduction. Both temperature and proton availability affect the rate of this isomerisation. Reduction of aliphatic nitrocompounds to the hydroxylamine is usually carried out in acid solution at 0-5° C to minimise oxime formation [14, 15], The hydroxylamine is stable towards further reduction in acid solution. Oximes in acid solution are reduced... 

The substituent tautomerism of six-membered ring heterocycles, including pyrimidines, quinazolines, and perimidines, has recently been reviewed in detail <2006AHC(91)1>. 

The last major section deals with tautomerism, including angular tautomerism where applicable and then substituent tautomerism. 

Although the compounds are not especially stable, the 2- and 3-aminothiophenes, in the absence of other substituents (see further), do not occur for significant amounts in the imine forms (78) and (80) (X = NH). Aminothiophenes are usually handled in the much more tractable form of salts in which the ammonium groups act as an electron withdrawing substituent. Tautomerization of aminothiophenes cannot occur, of course, with tertiary amino derivatives. 

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