Synthesis and chemistry of benzo-1,2,4-thiadiazines

• Main Author: Clark, E. R.
• Published: University of Cambridge 2008
• Subjects: 547.6
• Online Access: http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.597719

Forty-five 3-aryl benzo-1,2,4-thiadiazine derivatives have been prepared and twenty-two derivatives characterised by X-ray diffraction. Their solid-state molecular structures reveal low energy pathways for deformation through (i) rotation of the aryl group; (ii) folding of the heterocycle about the transannular S^….N vector. This largely qualitative assessment has been supported by <i>ab initio</i> DFT (B3LYP/6-31G) calculations. Improvements to the published syntheses the related 3-aryl benzo-1,2,4-thiadiazine 1-chlorides have increased yields and selectivity. A new route to these salts has been developed utilising SOC1₂ as the source of S^IV which exhibits lower degrees of chlorination of the benzo-fused ring. A total of six benzo-substituted 3-aryl benzo-1,2,4-thiadiazine 1-chlorides have been prepared of which five were characterised by X-ray diffraction. Conformational polymorphism was identified in 1,6,7-trichloro-5-chloromethyl-8-methyl-3-phenyl-benzo-1,2,4-thiadiazine and the energy barrier to interconversion between polymorphs probed by <i>ab initio</i> DFT calculations. Electrochemical studies on the 1-chloride salts reveal a good correlation between the E_1/2 for their 1<i>e</i>^- reduction and their LUMO energies from <i>ab initio</i> DFT (B3LYP/6-31G) calculations. Solution state EPR studies have been performed on the radicals formed by oxidation of 3-aryl-benzo-1,2,4-thiadiazines <i>or</i> reduction of 3-aryl-benzo-1,2,4-thiadiazine 1-chlorides respectively. Correlation between the experimental heterocyclic spin density estimated from the McConnell relationship and the calculated spin density from semi-empirical (AM1, PM3, PM5) were found to be poor. 3-pyrid-2-yl benzo-1,2,4-thiadiazine (LH) has been shown to react with CuCl₂.2H₂O and anhydrous CoCl₂ to form the chelate complexes CuCl₂(LH), CuCl₂(LH)₂ and CoCl₂(LH)₂ which have been characterised by X-ray diffraction.