1.3.4- Thiadiazoles 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. ... 

Hydroxy-l,2,4-thiadiazoles can exist in 3-tautomeric forms (Scheme 1). Chemical evidence suggests that the OH form 4 predominates however, UV data suggest that the lactam form 5 is the major tautomer in ethanol <1996CHEC-II(4)307>. 

Methyl-4-phenyl-l,2,5-thiadiazole 1,1-dioxide 21 suffers proton abstraction in basic nonaqueous media to give a resonance stabilized anion 43, neutralization of which using anhydrous TFA gives the orange tautomer 4-methylene-3-phenyl-l,2,5-thiadiazoline 1,1-dioxide 44 (Scheme 3) <2001JP0217>. The tautomeric equilibrium is practically displaced toward 21 in acetonitrile and toward 44 in DMF. 

Interestingly, the tautomeric isomer 44 was predicted to be a strong to moderate sensitizer with a probability of 90%, which was greater than that obtained for thiadiazole 21 (70%) <2003CRT1226, 2004JCI688>. 

The numbering of the 1,3,4-thiadiazole ring is given below. The present chapter is intended to update the previous work on the aromatic 1,3,4-thiadiazole 1, the nonaromatic A2-thiadiazolines 2, A3-thiadiazolines 3, the thiadiazoli-dines 4, the tautomeric forms 5 and 6, and the mesoionic systems 7. Reference is made to earlier chapters of CHEC(1984) and CHEC-II(1996) where appropriate. 

Tautomerism was reviewed quite extensively in CHEC(1984) <1984CHEC(6)545> and CHEC-II(1996) <1996CHEC-II(4)379>. The tautomeric ability of the 2-mercapto-5-methyl-l,3,4-thiadiazole 9 was studied by its reaction with the electrophilic Cl3 FnCSCl <2003JP01>. 2-Mercapto-5-methyl-l,3,4-thiadiazole 9 was considered to exist mainly as the thione tautomer however, electrophilic substitution occurred on the thiol (Scheme 1). 

Experimentally determined pA, values have been compared with Hammett substituent constants (Figure 1) and an excellent correlation was found. This result provided a further support - in accord with some nuclear magnetic resonance (NMR) measurements - for existence of one particular tautomeric form (Figure 1, structure a) among the three possible ones (Figure 1, a, b, c). 

Figure 1 Tautomeric possibilities of some [1,2,4]triazolo[3,4-b][1,3,4]thiadiazoles.

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... 

For 2-methyl-5-phenyl-s-triazolo[3,4-61-1,3,4-thiadiazole (350) and 4-methyl-s-triazolo[3,4-6]benzothiazole (182, R = Me), dipole moments were found to be 4.96 and 5.98, respectively.435 For compounds containing only nitrogen as a heteroatom, dipole moment measurements have been used to study annular tautomerism (Section IV,A,1) using Eq. (36).356... 

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