1,2,6-Thiadiazine 1,1-dioxides tautomerism

The single crystal X-ray structure of 3-methyl-4//-pyrido[2,3- ] l>2,4-thiadiazine 1,1,-dioxide 13 was compared to that of diazoxide 14 in order to determine the predominant tautomeric form and it was found that both these thiadiazine-dioxides exist in the AH tautomeric form in the solid state <1995AXG2064>. 

Other thiadiazine dioxides have been investigated (70CRV593). The 2//-tautomer (48) is favoured over the 4JT-tautomer (49) and structure (50) in which the tautomeric proton is on oxygen. The dihydro-1,2,6-thiadiazine dioxides are also thought to exist in the tautomeric equilibrium (51) i(52). 

The tautomerism of 4-amino-1 //-pyrazino[2,3-c]-1,2,6-thiadiazine 2,2-dioxides 213 has been investigated in the gas phase and in solution by different solvent simulations (Scheme 139) [98JCS(P2)1889]. 

Tautomeric equilibrium in amino-substituted 1,2,6-thiadiazine 1,1-dioxides fused with five- or six-membered nitrogen heterocycles has been extensively studied by Goya and colleagues. No amino group participation in tautomeric equilibria in these systems has been observed. 

The tautomerism of 4-aminopyrido[2,3- ]-l>2,6-thiadiazine-2,2-dioxide, an acid with a of 5.85, has been investigated by PSez et al. (Scheme 1). The 8/f-tautomer 10a is characterized by an ultraviolet (UV) maximum at 365 nm and the 1/f-tautomer 10b by a band at 320 nm, thus allowing the determination of the tautomeric equilibrium by UV spectroscopy. This conclusion that the aminopyridothiadiazinedioxide 10 exists as the 8f/-tautomer in aqueous and dimethyl sulfoxide (DMSO) solutions was based upon a comparison with the UV spectra of the 8-methyl derivative 11 (- max 365 nm) and the 1-methyl derivative 12 322 nm) <2004JST83>. 

The tautomerism of the pyrazino[2,3-f]-l,2,6-thiadiazine 2,2-dioxide ring present in compound 21 has been studied in solution <1998J(P2)1889>, particularly with reference to the acidity (p 1 ) of the H-N(l) (21, R = H) proton. Further advances in the study of the tautomeric forms of the systems that appear in this chapter have not appeared since CHEC-II(1996), and the detailed and interesting discussion contained therein remains pertinent <1996CHEC-II(7)785>. 

UV spectra at different pH of aminopyrido[2,3-f]-1,2,6-thiadiazine 2,2-dioxides(17,17 ) have been reported (86CS607). Comparison of UV spectra of the molecular neutral form to those of the 1- and 8-methyl derivatives reveals unambiguously the tautomeric relations. Substitution at N-1 is associated with a long-wavelength absorption at 320 nm, whereas N-8 substitution effects a red-shift to about 360 nm. 

The two possible forms of prototropic tautomerism, annular and ring-substituent, have been described in 1,2,6-thiadiazine 1,1-dioxide derivatives. Studies have been mainly carried out by H, C, N, and UV spectroscopy in DMSO and water and by X-ray analysis in the solid state. 

The Mitsunobu cyclizations of 3-(co-hydroxyalkyl)-l,2,4-thiadiazine 1,1-dioxides to the angular, rather than to the linear fused thiadiazine systems (see Section 6.14.7.5), are cited as chemical evidence in support of the earlier theoretical and spectroscopic data for the AH- rather than the 2H-tautomeric form of these heterocycles <91PS(59)529,91S159>. 

Comparison of the experimentally determined dipole (6.42 D) for tautomeric 5-methyl-1,2,6-thiadiazine 1,1-dioxide with the vectorially calculated values for individual tautomers (15) and (16) has been used to determine the equilibrium position of this tautomeric system <82JOC536> (Section... 

A detailed comparative study of the chemistry of 1,2,6-thiadiazine 1,1-dioxides and related pyrazoles has been carried out <82JOC536>. Useful comparisons can be made regarding tautomeric equilibria, C NMR chemical shifts, and the general reactivity of the 4-positions. As expected however, the lack of aromaticity of the 1,2,6-thiadiazine 1,1-dioxide system (Section 6.16.4.1) imparts substantial differences to their general chemistry. 

Ab initio calculations on the three tautomeric forms of 2//-1,2,6-thiadiazine 1,1-dioxide reveals that for the 2H- (17) and 4H- (20) tautomers the planar conformers are less stable than the nonplanar boat conformers by 2.7 and 1.2 kcal moU, respectively. For the 3,5-dimethyl- derivative there is reasonable agreement between the calculated bond angles and those obtained by x-ray crystallographic measurements <90JP0470>. In contrast, for the fully conjugated tautomer (18) theoretical calculations reveal that the planar form is the more stable and that aromatic character is to be... 

UV Spectroscopy has been instrumental in determining not only the tautomeric nature of 1,2,6-thiadiazine 1,1-dioxides and their oxo-derivatives, but also the site of alkylation and glycosylation of these systems and of 1,2,6-thiadiazine 1,1-dioxides fused to other heterocyclic rings, for example pyrazino[2,3-c][l,2,6]thiadiazine 2,2-dioxides. A detailed account of these studies is available <88AHC(44)8l>, as is a brief review on the UV spectra of 1,2,6-thiadiazine 1,1-dioxides <70CRV593>. 

The prototropic annular and substituent tautomerism of 1,2,6-thiadiazine 1,1-dioxides and their... 

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