Thiadiazoles, amino-, tautomerism

Pyrazblin-5-one, 3-alkyl-(l,2,4-thiadiazol-5-yl)-reactions, 6, 483 2-Pyrazolin-5-one, 3-amino-tautomerism, 5, 215 2-Pyrazolin-5-one, 4,4-diazido-rearrangement, 5, 720 2-Pyrazolin-5-one, 3-hydroxy-tautomerism, 5, 215 2-Pyrazolin-5-one, 3-methyl-1 -phenyl-reactions, 5, 252... 

Thiadiazole, 2-amino-5-mercapto-azo dyes from, 1, 330 radioprotective agent, 6, 576 tautomerism, 6, 557... 

Polarographic techniques have been used by Sturm and Hans to demonstrate that certain amino-thiadiazoles and -benzthiazoles exist in the amino form (cf. also references 62, 63). This method, which involves comparison of the polarographic rdeuction potentials of the potentially tautomeric substance with those of alkylated reference compounds, has not been applied often, but may well prove to be a means to obtain qualitative information quickly. There is a possibility that the method can be modified to yield quantitative data. ... 

Proton, C, and N NMR spectroscopy has been employed to demonstrate the existence of ring-chain tautomerism between protonated forms of thiosemicarbazones and protonated 2-aryl-5-amino-2,3-dihydro-1,3,4-thiadiazoles <92KGS1689>. The use of NMR in various solvents, indicates that the isoxazoline (28) contains between 24% and 34% of the thiadiazoline (29) <85KGS1001>. Tautomerism was also discussed in Sections 4.10.2 <90BCJ2991> and 4.10.3.3 <83HCA1755>. 

A comparison of the dissociation constants shows that 5-amino-3-dialkylamino-l,2,4-thiadiazoles are only slightly more basic than the 3-alkyl-5-amino analogs. The low basicity of these compounds suggests that they exist, like the 5-monoamino analogs (see Section III,D, 1), as enamineB rather than as the more basic tautomeric ketimines.81,87 The prevalence of the 3-enamine form in 3-amino-5-anilino-1,2,4-thiadiazoles is supported by ultraviolet absorption data.122... 

The tautomerism of DMTD (31a, 31b), as well as those of 5-amino-l,3,4-thiadiazole-2-thiol (AMTD) (32a, 32b) and 5-methyl-l,3,4-thiadiazole-2-thiol (MMTD) (33a, 33b), were investigated by means of FT-Raman and FT-IR spectroscopic techniques by Edwards and coworkers136. 

Thiadiazoles were first described in 1882 by Fischer and further developed by Busch and his coworkers. The advent of sulfur drugs and the later discovery of mesoionic compounds greatly accelerated the rate of progress in the field of thiadiazoles. Thiadiazoles carrying mercapto, hydroxy and amino substituents can exist in many tautomeric forms and this property is being intensively studied using modern instrumental methods. 

The 1,3,4-thiadiazole ring system, with three heteroatoms, does not exhibit tautomerism in its fully conjugated form. However, when certain substituents are present, tautomerism is possible. l,3,4-Thiadiazolin-2-ones (39 X = 0) and -2-thiones (39 X = S) exist in the oxo and thione forms, respectively, as shown by spectroscopic and LCAO-MO calculations. 2-Amino-l,3,4-thiadiazoles exist in the amino form in solution and in the solid state the Kt value is 10s as shown by basicity measurements. UV spectroscopy and LCAO-MO calculations show that the amino tautomer is also the main species when there is an alkoxy group in the 5-position (40 R1 = alkoxy, R2 = NH2), or if the exocyclic nitrogen atom is part of a hydrazone group (40 R2 = NHN=CR2). 

C. Prototropic Tautomerism of Amino-, Hydroxy-.Vfercapto-l,3,4-thiadiazoles. ... 

Alkoxy-5-amino-1,3,4-thiadiazoles (41) are not particularly stable to hydrolysis. They were hydrolyzed by hot hydrochloric acid, first to 2-amino-l,3,4-thiadiazolin-5(4)-one (108) (or the tautomeric imine) and then to thiosemicarbazide. On diazotization in hydrochloric acid 41 gave 2-chloro-l,3,4-thiadiazolin-5(4)-one (107), and by hot alkali it was cleaved to 1-alkoxythiocarbonylsemicarbazide (109). ... 

The unsubstituted 1,3,4-thiadiazole is sufficiently basic to give a stable hydrochloride and hydrobromide, but it is described as very weakly basic, though no pK value has been published. 2-Amino- and 2-anilino-l,3,4-thiadiazoles are also weak bases, whereas the tautomeric imines are somewhat stronger. pK values have been useful in tautomerism studies, and some pKg values, i.e., pK values of the conjugate acids, have been collected in Table II and will be discussed in the following section. 

Within the huge field of heterocyclic rearrangements [53], the Dimroth rearrangement gives 5-mercapto-l,2,3-triazoles from 5-amino-l,2,3-thiadiazoles and allows interconversion of 5-amino-l,2,3-triazoles into a mixture of isomers under basic condition [54]. Thus, this reaction, discovered in 1909, involves a linear intermediate that can cyclize into two isomeric compounds (Scheme 15) [55]. This ring-chain tautomerization is reversible, but the equilibrium can be pushed toward an end if one of the two isomers is stabilized. 

Physical Properties.—The spectral properties of a series of 3-amino-4-aryl-5-aryl(or alkyl)-imino-4,5-dihydro-l,2,4-thiadiazoles are in accord with the proposed structures. The n.m.r. spectra indicate the preferred existence of the dihydro- rather than the tautomeric tetrahydro-thiadiazole structure. Mass spectral fragmentation patterns were proposed for these, and for compound (70). ... 

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