On the deprotonation of chlorothiazide.

Abstract

Three alkali metal salt forms of the diuretic chlorothiazide (systematic name: 6-chloro-1,1-dioxo-2H-1,2,4-benzothiazine-7-sulfonamide, HCTZ) are described. When crystallized from aqueous solution, the Na and K salts, namely, poly[[μ-aqua-aqua(μ₃-6-chloro-1,1-dioxo-7-sulfamoyl-2H-1,2,4-benzothiadiazin-2-ido)sodium] hemihydrate], {[Na(C₇H₅ClN₃O₄S₂)(H₂O)₂]·0.5H₂O}_n, and poly[[diaqua(μ₅-6-chloro-1,1-dioxo-7-sulfamoyl-2H-1,2,4-benzothiadiazin-2-ido)potassium] hemihydrate], {[K(C₇H₅ClN₃O₄S₂)(H₂O)₂]·0.5H₂O}_n, are both found to have stoichiometry MCTZ·2.5H₂O, with CTZ deprotonated at a heterocyclic ring N atom. Both the stoichiometry and the deprotonation site are different to those described in previously published versions of these structures. The Cs salt form is found to be the monohydrate CsCTZ·H₂O, namely, poly[[aqua(μ₅-6-chloro-1,1-dioxo-7-sulfamoyl-2H-1,2,4-benzothiadiazin-2-ido)caesium], [Cs(C₇H₅ClN₃O₄S₂)(H₂O)]_n. As with the Na and K cognates, this structure is also deprotonated at the heterocyclic ring. NaCTZ is found to be a two-dimensional coordination polymer with bridges between Na centres formed by H₂O and SO₂ groups, and by links through the length of the coordinated CTZ anions. Water ligands in KCTZ and CsCTZ are terminal, rather than bridging between metal centres, but both compounds form structures where M-Cl interactions link two-dimensional motifs formed via M-O bonds (and in CsCTZ, M-N bonds) into three-dimensional coordination polymers.