Powder study of chlorothiazide N,N-dimethyl- formamide solvate

# 2006 International Union of Crystallography All rights reserved The crystal structure of the title compound [systematic name: 6-chloro-4H-1,2,4-benzothiadiazine-7-sulfonamide 1,1-dioxide–N,N-dimethylformamide (1/1)], C7H6ClN3O4S2 C3H7NO, was solved by simulated annealing from laboratory X-ray powder diffraction data collected at 100 K. Subsequent Rietveld refinement, using data collected to 1.5 Å resolution, yielded an Rwp of 0.050. Hydrogen bonds to N,N-dimethylformamide form the rungs of a ladder motif, which is further stabilized by a halogen dimer interaction. The benzene rings in adjacent ladders engage with each other in an offset face-to-face – interaction.

The crystal structure of the title compound [systematic name: 6-chloro-4H-1,2,4-benzothiadiazine-7-sulfonamide 1,1-dioxide-N,N-dimethylformamide (1/1)], C 7 H 6 ClN 3 O 4 S 2 Á-C 3 H 7 NO, was solved by simulated annealing from laboratory X-ray powder diffraction data collected at 100 K. Subsequent Rietveld refinement, using data collected to 1.5 Å resolution, yielded an R wp of 0.050. Hydrogen bonds to N,N-dimethylformamide form the rungs of a ladder motif, which is further stabilized by a Á Á Áhalogen dimer interaction. The benzene rings in adjacent ladders engage with each other in an offset face-to-faceinteraction.

Comment
The diuretic chlorothiazide (CT) promotes the excretion of water and electrolytes by the kidneys and was developed for the treatment of conditions such as oedema and congestive heart failure. The title compound, (I), was crystallized from N,N-dimethylformamide (DMF) during a preliminary solvent screen in preparation for an automated parallel crystallization study of CT. The sample was identified as a new form using multi-sample foil transmission X-ray powder diffraction analysis (Florence et al., 2003).
The sample was loaded into a 0.7 mm borosilicate glass capillary and rotated throughout the data collection to minimize preferred orientation effects. Data were collected using a variable count time (VCT) scheme in which the step time is increased with 2 (Shankland et al., 1997; Hill & Madsen, 2002). The diffraction pattern indexed to a organic papers The molecular structure of (I). Displacement ellipsoids are shown at the 50% probability level.

Figure 3
The hydrophilic and hydrophobic interactions in (I). In the Á Á Áhalogen dimer interaction, two Cl atoms are positioned over the -systems of the R2 and R2 0 rings. Atoms O4A and O4A 0 are in the dimethylformamide molecules at (1 + x, y, z) and (2 À x, 1 À y, 1 À z), respectively.  (Boultif & Louer, 1991)], and space group P1 was assigned from volume considerations and a lack of systematic absences. The data set was background-subtracted and truncated to 51.35 2 for Pawley fitting (Pawley, 1981; 2 Pawley = 1.33) and the structure was solved using the simulated annealing (SA) global optimization procedure, described previously (David et al., 1998), which is now implemented in the DASH computer program (David et al., 2001).
The SA structure solution used 273 reflections and involved the optimization of two fragments (including H atoms) totaling 14 degrees of freedom, with the internal degrees of freedom allowing rotations around the S2-C5 and N4A-C6A bonds. The sulfonamide conformation was fixed throughout the optimization, with antiperiplanar torsion angles assigned to H5-N1-S2-O4 and H6-N1-S2-O2, consistent with the conformation observed in the single-crystal structure of non-solvated CT (Johnston et al., 2006). The tautomeric H atom was placed on N2 (not N3), consistent with density functional calculations (Latosiń ska, 2003) and with the singlecrystal structure of CT. The best SA solution had a favourable 2 SA / 2 Pawley ratio of 2.3 and a chemically reasonable lattice packing arrangement, with no significant misfit to the diffraction data. The solved structure was then refined against the full data set (6-64 2) using a restrained Rietveld method (Rietveld, 1969), as implemented in TOPAS (Coelho, 2003), with R wp falling from 0.1369 to 0.0504 during the refinement. All atomic positions (including H atoms) were refined, subject to a series of restraints on bond lengths, bond angles and, where appropriate, planarity. The distance and angle restraints were based on the CT single-crystal structure. As reported elsewhere for famotidine (Shankland et al., 2002), rotating the CT sulfonamide group in increments of 120 about the S2-C5 bond (Fig. 1) results in three orientations that are similar in the sense that the X-ray scattering power of N1(H2) is on a par with that of atoms O2 and O4. In this case, the correctness of the orientation shown in Fig. 1 was confirmed by the superior R wp and intermolecular hydrogen-bonding pattern, compared with the two alternatives.