Powder study of chloro­thia­zide N,N-dimethyl­formamide solvate

Fernandes, P.; Florence, A.J.; Shankland, K.; Shankland, N.; Johnston, A.

doi:10.1107/S1600536806015674

organic compounds

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ISSN: 2056-9890

Volume 62| Part 6| June 2006| Pages o2216-o2218

https://doi.org/10.1107/S1600536806015674

Powder study of chlorothiazide N,N-dimethylformamide solvate

Philippe Fernandes,^a Alastair J. Florence,^a ^* Kenneth Shankland,^b Norman Shankland ^a and Andrea Johnston ^a

^aSolid-State Research Group, Department of Pharmaceutical Sciences, University of Strathclyde, 27 Taylor Street, Glasgow G4 0NR, Scotland, and ^bISIS Facility, Rutherford Appleton Laboratory, Chilton, Didcot, Oxon OX11 0QX, England
^*Correspondence e-mail: alastair.florence@strath.ac.uk

(Received 3 April 2006; accepted 28 April 2006; online 10 May 2006)

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 R_wp of 0.050. Hydrogen bonds to N,N-dimethylformamide form the rungs of a ladder motif, which is further stabilized by a π⋯halogen dimer interaction. The benzene rings in adjacent ladders engage with each other in an offset face-to-face π–π interaction.

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 crystal structure of (I) (Fig. 1) was determined after recollecting powder diffraction data from a sample of (I) in a rotating capillary (Fig. 2). The intermolecular interactions in (I) combine to create the ladder motif shown in Fig. 3. The stiles of the ladder comprise infinite [1 $[\overline{1}]$ 0] chains of CT molecules linked by N1⋯N3 hydrogen bonds, with rungs formed by hydrogen bonds N1⋯O4A and N2⋯O4A to DMF (Table 1). This motif is further stabilized by a π⋯halogen dimer interaction (Rahman et al., 2004 ), wherein two CT molecules associate by means of one aromatic offset face-face interaction, supplemented by two aromatic π⋯halogen interactions, to create the centrosymmetric building block (Fig. 3), with the following geometric parameters (Cg2 is the centroid of ring R2; atoms C1/C5/C6/C4/C2/C7): Cg2⋯Cg2′ = 4.44 (2) Å, Cl1⋯Cg2′ = 3.84 (1) Å and C6—Cl1⋯Cg2′ = 79 (1)°; primed atoms are generated by the symmetry operation (2 − x, 2 − y, 1 − z). The benzene rings in adjacent ladders engage with each other in an offset face-to-face π–π interaction, with Cg2⋯Cg2ⁱ = 4.26 (2) Å [symmetry code: (i) 1 − x, 2 − y, 1 − z].

Figure 1
The molecular structure of (I)

. Displacement ellipsoids are shown at the 50% probability level.

Figure 2
Final observed (points), calculated (line) and difference [(y_obs − y_calc)/σ(y_obs)] profiles for the Rietveld refinement of (I)

Figure 3
The hydrophilic and hydrophobic interactions in (I)

. In the π⋯halogen dimer interaction, two Cl atoms are positioned over the π-systems of the R2 and R2′ rings. Atoms O4A and O4A′ are in the dimethylformamide molecules at (1 + x, y, z) and (2 − x, 1 − y, 1 − z), respectively.

Experimental

A polycrystalline sample of (I) was purchased from Sigma–Aldrich (CAS 58–94-6) and recrystallized from a dimethylformamide solution by slow evaporation over 48 h at 278 K.

Crystal data

C₇H₆ClN₃O₄S₂·C₃H₇NO
M_r = 368.83
Triclinic, $[P \overline 1]$
a = 7.9822 (4) Å
b = 8.8830 (5) Å
c = 11.1075 (6) Å
α = 86.689 (3)°
β = 75.078 (3)°
γ = 73.196 (3)°
V = 728.41 (7) Å³
Z = 2
D_x = 1.682 Mg m⁻³
Cu Kα₁ radiation
μ = 5.30 mm⁻¹
T = 100 K
Specimen shape: cylinder
10 × 0.7 × 0.7 mm
Specimen prepared at 0 kPa
Specimen prepared at 293 K
Particle morphology: needle, colourless

Data collection

Bruker D8 Advance diffractometer
Specimen mounting: 0.7 mm borosilicate capillary
Specimen mounted in transmission mode
Scan method: step
Absorption correction: none
2θ_min = 6, 2θ_max = 64°
Increment in 2θ = 0.014°

Refinement

Refinement on F²
R_p = 0.039
R_wp = 0.050
R_exp = 0.036
R_B = 3.2
S = 1.41
Wavelength of incident radiation: 1.54056 Å
Excluded region(s): none
Profile function: fundamental parameters with axial divergence correction
108 parameters
Only H-atom coordinates refined
Weighting scheme based on measured s.u.'s, 1/σ(y_o)²
(Δ/σ)_max = 0.049
Preferred orientation correction: none

Table 1
Hydrogen-bond geometry (Å, °)

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
N2—H4⋯O4Aⁱ	0.9 (2)	1.8 (2)	2.71 (3)	164
N1—H5⋯O4Aⁱⁱ	0.9 (3)	2.0 (2)	2.78 (3)	140
N1—H6⋯N3ⁱⁱⁱ	0.9 (2)	2.4 (2)	3.05 (3)	129
Symmetry codes: (i) -x+1, -y+2, -z+1; (ii) x+1, y, z; (iii) x+1, y-1, z.

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 2θ (Shankland et al., 1997 ; Hill & Madsen, 2002 $[Hill, R. J. & Madsen, I. C. (2002). Structure Determination from Powder Diffraction Data, edited by W. I. F. David, K. Shankland, L. B. McCusker & Ch. Baerlocher, pp. 114-116. Oxford University Press.]$ ). The diffraction pattern indexed to a triclinic cell [F(22) = 64.2, M(22) = 22.9; DICVOL91 (Boultif & Louer, 1991 )], and space group P $[\overline{1}]$ was assigned from volume considerations and a lack of systematic absences. The data set was background-subtracted and truncated to 51.35° 2θ for Pawley fitting (Pawley, 1981 ; χ²_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 (Latosińska, 2003 ) and with the single-crystal structure of CT. The best SA solution had a favourable χ²_SA/χ²_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° 2θ) 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.

Data collection: DIFFRAC plus XRD Commander (Kienle & Jacob, 2003 ); cell refinement: TOPAS (Coelho, 2003); data reduction: DASH (David et al., 2001); program(s) used to solve structure: DASH; program(s) used to refine structure: TOPAS; molecular graphics: PLATON (Version 011105; Spek, 2003 ); software used to prepare material for publication: enCIFer (Version 1.1; Allen et al., 2004 ).

Supporting information

Crystal structure: contains datablocks global, I. DOI: https://doi.org/10.1107/S1600536806015674/cv2034sup1.cif

Rietveld powder data: contains datablock I. DOI: https://doi.org/10.1107/S1600536806015674/cv2034Isup2.rtv

Computing details top

Data collection: DIFFRAC plus XRD Commander (Kienle & Jacob, 2003); cell refinement: TOPAS (Coelho, 2003); data reduction: DASH (David et al., 2001); program(s) used to solve structure: DASH; program(s) used to refine structure: TOPAS; molecular graphics: PLATON (Version 011105; Spek, 2003); software used to prepare material for publication: enCIFer (Version 1.1; Allen et al., 2004).

6-Chloro-4H-1,2,4-benzothiadiazine-7-sulfonamide 1,1-dioxide–N,N-dimethylformamide (1/1) top

Crystal data top

C₇H₆ClN₃O₄S₂·C₃H₇NO	Z = 2
M_r = 368.83	F(000) = 380
Triclinic, P1	D_x = 1.682 Mg m⁻³
Hall symbol: -P 1	Cu Kα₁ radiation, λ = 1.54056 Å
a = 7.9822 (4) Å	µ = 5.30 mm⁻¹
b = 8.8830 (5) Å	T = 100 K
c = 11.1075 (6) Å	Particle morphology: needle
α = 86.689 (3)°	colourless
β = 75.078 (3)°	cylinder, 10 × 0.7 mm
γ = 73.196 (3)°	Specimen preparation: Prepared at 293 K
V = 728.41 (7) Å³

Data collection top

Bruker D8 Advance diffractometer	Data collection mode: transmission
Radiation source: sealed X-ray tube, Bruker D8	Scan method: step
Primary focussing, Ge 111 monochromator	2θ_min = 6°, 2θ_max = 64°, 2θ_step = 0.014°
Specimen mounting: 0.7 mm borosilicate capillary

Refinement top

Least-squares matrix: selected elements only	108 parameters
R_p = 0.039	95 restraints
R_wp = 0.050	1 constraint
R_exp = 0.036	Only H-atom coordinates refined
R_Bragg = 3.2	Weighting scheme based on measured s.u.'s 1/σ(Y_o)²
4001 data points	(Δ/σ)_max = 0.049
Profile function: Fundamental parameters with axial divergence correction	Background function: Chebyshev polynomial

Special details top

Geometry. Bond distances, bond angles and H-bond geometries were calculated using PLATON (Spek, 2003)

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å²) top

	x	y	z	U_iso*/U_eq
C4A	0.843 (4)	0.803 (3)	−0.098 (3)	0.019*
H4A	0.96 (3)	0.76 (3)	−0.09 (3)	0.038*
H5A	0.83 (3)	0.77 (3)	−0.17 (2)	0.038*
H6A	0.82 (3)	0.92 (3)	−0.10 (2)	0.038*
C5A	0.713 (4)	0.600 (4)	0.022 (2)	0.019*
H7A	0.83 (3)	0.53 (3)	0.03 (2)	0.038*
H8A	0.68 (3)	0.57 (3)	−0.05 (2)	0.038*
H9A	0.62 (3)	0.59 (3)	0.10 (2)	0.038*
C6A	0.611 (4)	0.870 (3)	0.091 (3)	0.019*
H10A	0.61 (3)	0.98 (3)	0.08 (2)	0.038*
N4A	0.719 (3)	0.761 (3)	0.008 (2)	0.019*
O4A	0.500 (2)	0.8452 (18)	0.1848 (17)	0.019*
S1	0.5677 (9)	1.2894 (9)	0.3026 (7)	0.019*
S2	1.0585 (9)	0.7185 (9)	0.2401 (8)	0.019*
Cl1	0.9970 (9)	0.6972 (8)	0.5391 (7)	0.019*
C1	0.806 (4)	1.001 (4)	0.291 (2)	0.019*
N1	1.254 (3)	0.672 (3)	0.270 (2)	0.019*
C2	0.646 (3)	1.108 (4)	0.497 (3)	0.019*
C3	0.403 (4)	1.349 (4)	0.530 (3)	0.019*
N2	0.514 (3)	1.225 (3)	0.5732 (19)	0.019*
C4	0.744 (4)	0.977 (4)	0.549 (3)	0.019*
C5	0.905 (3)	0.871 (3)	0.343 (3)	0.019*
C6	0.874 (4)	0.858 (3)	0.472 (3)	0.019*
O1	0.690 (2)	1.3805 (17)	0.2528 (13)	0.019*
O2	1.0807 (19)	0.7839 (16)	0.1184 (15)	0.019*
C7	0.680 (4)	1.121 (3)	0.368 (3)	0.019*
O3	0.483 (2)	1.2453 (17)	0.2168 (14)	0.019*
O4	0.9905 (18)	0.5842 (17)	0.2625 (14)	0.019*
N3	0.411 (3)	1.389 (2)	0.4159 (19)	0.019*
H1	0.83 (3)	1.01 (3)	0.203 (18)	0.038*
H2	0.72 (3)	0.97 (3)	0.64 (2)	0.038*
H3	0.31 (3)	1.42 (3)	0.59 (2)	0.038*
H4	0.50 (3)	1.22 (3)	0.66 (2)	0.038*
H5	1.29 (3)	0.76 (3)	0.27 (2)	0.038*
H6	1.24 (3)	0.63 (3)	0.35 (2)	0.038*

Geometric parameters (Å, º) top

Cl1—C6	1.73 (3)	N4A—C4A	1.44 (4)
S1—O1	1.429 (18)	C1—C5	1.39 (4)
S1—O3	1.431 (18)	C1—C7	1.39 (4)
S1—N3	1.62 (2)	C2—C7	1.39 (5)
S1—C7	1.73 (3)	C2—C4	1.39 (5)
S2—O2	1.429 (18)	C4—C6	1.39 (4)
S2—O4	1.432 (17)	C5—C6	1.39 (5)
S2—N1	1.61 (3)	C1—H1	1.0 (2)
S2—C5	1.77 (3)	C3—H3	1.0 (2)
O4A—C6A	1.24 (4)	C4—H2	1.0 (2)
N2—C3	1.35 (4)	C4A—H4A	0.9 (3)
N2—C2	1.38 (4)	C4A—H5A	0.9 (2)
N3—C3	1.29 (4)	C4A—H6A	1.0 (3)
N1—H6	0.9 (2)	C5A—H7A	1.0 (3)
N1—H5	0.9 (3)	C5A—H8A	1.0 (2)
N2—H4	0.9 (2)	C5A—H9A	1.0 (2)
N4A—C6A	1.32 (4)	C6A—H10A	1.0 (3)
N4A—C5A	1.44 (4)

O1—S1—O3	116 (1)	N2—C2—C4	120 (3)
O1—S1—N3	108 (1)	C4—C2—C7	120 (3)
O1—S1—C7	109 (1)	N2—C3—N3	128 (3)
O3—S1—N3	108 (1)	C2—C4—C6	120 (3)
O3—S1—C7	109 (1)	S2—C5—C6	122 (2)
N3—S1—C7	106 (1)	S2—C5—C1	118 (2)
O2—S2—O4	119 (1)	C1—C5—C6	120 (3)
O2—S2—N1	107 (1)	Cl1—C6—C5	121 (2)
O2—S2—C5	106 (1)	C4—C6—C5	120 (3)
O4—S2—N1	108 (1)	Cl1—C6—C4	119 (2)
O4—S2—C5	107 (1)	C1—C7—C2	120 (3)
N1—S2—C5	110 (1)	S1—C7—C2	120 (2)
C2—N2—C3	124 (2)	S1—C7—C1	120 (2)
S1—N3—C3	121 (2)	O4A—C6A—N4A	124 (2)
C4A—N4A—C6A	120 (2)	S2—N1—H5	109 (14)
C5A—N4A—C6A	121 (2)	S2—N1—H6	107 (16)
C4A—N4A—C5A	120 (2)	C2—N2—H4	119 (15)
C5—C1—C7	120 (2)	C3—N2—H4	117 (15)
N2—C2—C7	120 (3)

Hydrogen-bond geometry (Å, º) top

D—H···A	D—H	H···A	D···A	D—H···A
N2—H4···O4Aⁱ	0.9 (2)	1.8 (2)	2.71 (3)	164
N1—H5···O4Aⁱⁱ	0.9 (3)	2.0 (2)	2.78 (3)	140
N1—H6···N3ⁱⁱⁱ	0.9 (2)	2.4 (2)	3.05 (3)	129

Symmetry codes: (i) −x+1, −y+2, −z+1; (ii) x+1, y, z; (iii) x+1, y−1, z.

Acknowledgements

The authors thank the Basic Technology Programme of the UK Research Councils for funding under the project `Control and Prediction of the Organic Solid State' (www.cposs.org.uk), the EPSRC for grants GR/N07462/01 and GR/S10162/01, and the CCLRC Centre for Molecular Structure and Dynamics for studentship funding for PF.

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