Accurate molecular structures of chlorothiazide and hydrochlorothiazide by joint refinement against powder neutron and X-ray diffraction data

The compounds chlorothiazide and hydrochlorothiazide (crystalline form II) have been studied in their fully hydrogenous forms by powder neutron diffraction on the GEM diffractometer. The results of joint Rietveld refinement of the structures against multi-bank neutron and single-bank X-ray powder data are reported and show that accurate and precise structural information can be obtained from polycrystalline molecular organic materials by this route.

Computing details

For both compounds, data collection: custom ISIS software; data reduction: custom ISIS software; program(s) used to solve structure: coordinates from single-crystal data; program(s) used to refine structure: Topas v3.1 (Coehlo, 2003).

Figures

(CTZ_GEM_neutron_130K) 6-chloro-4H-1,2,4-benzathiadiazine-7-sulfonamide-1,1-dioxide

Crystal data

C7H6ClN3O4S2	Z = 1
Mr = 295.72	Cell parameters included in refinement
Triclinic, P1	Dx = 1.877 Mg m^−3
Hall symbol: P1	Neutron radiation, λ = ? Å
a = 4.8499 (3) Å	µ = 0.12 mm^−1
b = 6.3694 (4) Å	T = 130 K
c = 8.9106 (6) Å	Particle morphology: Needle
α = 74.401 (1)°	Colourless
β = 83.865 (1)°	cylinder, 40 × 5 mm
γ = 80.524 (1)°	Specimen preparation: Prepared at 293 K
V = 260.93 (3) Å^3

Data collection

GEM, ISIS diffractometer	Scan method: Time of flight
Radiation source: Pulsed neutron source	Absorption correction: empirical (using intensity measurements) Mu = 0.122(2) cm^-1 parameter Mu refined from experimental data
Specimen mounting: 5mm vanadium cylinderical can	Tmin = ?, Tmax = ?
Data collection mode: transmission

Refinement

Least-squares matrix: selected elements only	149 parameters
Rp = 4.250	6 restraints
Rwp = 1.104	Only H-atom coordinates refined
Rexp = 0.414	Weighting scheme based on measured s.u.'s w = 1/σ(Yobs)^2
χ^2 = 6.885	(Δ/σ)max = 0.001
? data points	Background function: Chebyshev polynomial
Excluded region(s): excluded short and long TOF regions <1000.0/ms and >8000.0/ms excluded 9deg detector bank <1500.0/ms and >15000.0/ms excluded 18deg detector bank <1800.0/ms and >20000.0/ms excluded 35deg detector bank <2600.0/ms and >20200.0/ms excluded 64deg detector bank <3700.0/ms and >18000.0/ms excluded 90deg detector bank <5000.0/ms and >16600.0/ms excluded 153deg detector bank	Preferred orientation correction: none
Profile function: Full Voigt with double exponetial

Special details

Experimental. The neutron data were collected on 6 detector banks and refined simultanously:

The neutron data was refined in a simultanious refinement with X-ray lab powder data. The details of the Lab X-ray powder experiment are given in a seperate data block

Geometry. Bond distances, bond angles, torsion angles and H-bond geometries were calculated using PLATON (Spek, 2003; program version 280604)

Refinement. For 9deg detector bank: _refine_ls_goodness_of_fit_all 1.184 for 18deg detector bank: _refine_ls_goodness_of_fit_all 1.856 for 35deg detector bank: _refine_ls_goodness_of_fit_all 2.410 for 64deg detector bank: _refine_ls_goodness_of_fit_all 3.684 for 90deg detector bank: _refine_ls_goodness_of_fit_all 3.551 for 153deg detector bank: _refine_ls_goodness_of_fit_all 3.401

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Ų)

	x	y	z	Uiso*/Ueq
Cl1	−0.35395	0.36206	1.03940	0.013 (1)*
S1	0.5940 (5)	0.0210 (4)	0.5986 (3)	0.013 (1)*
S2	−0.0201 (5)	−0.1410 (4)	1.1524 (3)	0.013 (1)*
O1	0.8439 (6)	−0.0796 (5)	0.6790 (4)	0.013 (1)*
O2	0.4667 (6)	−0.1098 (4)	0.5258 (3)	0.013 (1)*
O3	0.1480 (6)	−0.3449 (5)	1.1439 (3)	0.013 (1)*
O4	−0.3208 (6)	−0.1350 (4)	1.1748 (3)	0.013 (1)*
N1	0.6614 (4)	0.2386 (3)	0.4653 (3)	0.013 (1)*
N2	0.2755 (4)	0.4769 (2)	0.5479 (3)	0.013 (1)*
N3	0.0764 (3)	−0.0590 (3)	1.2877 (3)	0.013 (1)*
C1	0.5019 (5)	0.4305 (3)	0.4490 (2)	0.013 (1)*
C2	0.1991 (6)	0.3302 (5)	0.6833 (4)	0.013 (1)*
C3	0.3477 (7)	0.1140 (5)	0.7312 (4)	0.013 (1)*
C4	0.2710 (5)	−0.0258 (3)	0.8744 (3)	0.013 (1)*
C5	0.0551 (6)	0.0426 (5)	0.9753 (4)	0.013 (1)*
C6	−0.0870 (6)	0.2599 (5)	0.9263 (4)	0.013 (1)*
C7	−0.0217 (6)	0.3993 (3)	0.7867 (4)	0.013 (1)*
H1	0.5506 (7)	0.5573 (4)	0.3475 (3)	0.027 (2)*
H2	0.1887 (7)	0.6340 (4)	0.5226 (6)	0.027 (2)*
H3A	−0.0494 (9)	0.0672 (4)	1.3225 (5)	0.027 (2)*
H3B	0.2826 (5)	−0.0597 (6)	1.2775 (5)	0.027 (2)*
H4	0.3846 (6)	−0.1853 (4)	0.9189 (5)	0.027 (2)*
H7	−0.1217 (7)	0.5672 (4)	0.7520 (6)	0.027 (2)*

Geometric parameters (Å, º)

Cl1—C6	1.7064	N2—H2	0.995 (3)
S1—O1	1.441 (4)	N3—H3B	0.994 (3)
S1—O2	1.429 (4)	N3—H3A	1.023 (4)
S1—N1	1.619 (3)	C2—C7	1.429 (4)
S1—C3	1.737 (4)	C2—C3	1.422 (5)
S2—O3	1.431 (4)	C3—C4	1.399 (4)
S2—O4	1.446 (4)	C4—C5	1.398 (4)
S2—N3	1.576 (3)	C5—C6	1.417 (5)
S2—C5	1.737 (4)	C6—C7	1.360 (5)
N1—C1	1.316 (3)	C1—H1	1.073 (3)
N2—C1	1.377 (3)	C4—H4	1.067 (4)
N2—C2	1.371 (4)	C7—H7	1.076 (4)
O1—S1—O2	117.8 (2)	N2—C2—C3	121.9 (3)
O1—S1—N1	109.0 (2)	N2—C2—C7	119.8 (3)
O1—S1—C3	107.8 (2)	C3—C2—C7	118.2 (3)
O2—S1—N1	107.4 (2)	C2—C3—C4	119.8 (3)
O2—S1—C3	108.4 (2)	S1—C3—C4	121.6 (2)
N1—S1—C3	105.89 (19)	S1—C3—C2	118.1 (3)
O3—S2—O4	118.2 (2)	C3—C4—C5	121.8 (2)
O3—S2—N3	109.4 (2)	S2—C5—C6	124.2 (3)
O3—S2—C5	104.8 (2)	C4—C5—C6	117.4 (3)
O4—S2—N3	107.4 (2)	S2—C5—C4	118.5 (2)
O4—S2—C5	108.1 (2)	C5—C6—C7	122.5 (3)
N3—S2—C5	108.6 (2)	Cl1—C6—C5	121.67
S1—N1—C1	122.7 (2)	Cl1—C6—C7	115.85
C1—N2—C2	123.55 (19)	C2—C7—C6	120.3 (3)
C1—N2—H2	114.3 (3)	N1—C1—H1	116.2 (3)
C2—N2—H2	121.5 (4)	N2—C1—H1	118.5 (2)
S2—N3—H3A	118.1 (3)	C3—C4—H4	122.6 (3)
S2—N3—H3B	110.6 (3)	C5—C4—H4	115.4 (3)
H3A—N3—H3B	118.8 (4)	C2—C7—H7	117.0 (4)
N1—C1—N2	125.28 (19)	C6—C7—H7	122.6 (4)
O1—S1—N1—C1	−130.7 (3)	C2—N2—C1—N1	4.6 (4)
O2—S1—N1—C1	100.6 (3)	C7—C2—C3—S1	174.2 (3)
C3—S1—N1—C1	−15.0 (3)	N2—C2—C3—C4	176.6 (3)
N1—S1—C3—C4	−170.4 (3)	C3—C2—C7—C6	−0.4 (4)
O2—S1—C3—C2	−97.8 (3)	C7—C2—C3—C4	1.6 (5)
N1—S1—C3—C2	17.2 (3)	N2—C2—C7—C6	−175.6 (3)
O1—S1—C3—C2	133.7 (3)	N2—C2—C3—S1	−10.8 (4)
O2—S1—C3—C4	74.7 (3)	S1—C3—C4—C5	−174.1 (3)
O1—S1—C3—C4	−53.8 (4)	C2—C3—C4—C5	−1.7 (5)
O4—S2—C5—C6	46.2 (4)	C3—C4—C5—C6	0.7 (4)
O3—S2—C5—C6	173.2 (3)	C3—C4—C5—S2	−178.7 (3)
N3—S2—C5—C6	−70.0 (3)	S2—C5—C6—Cl1	−0.63
O3—S2—C5—C4	−7.5 (3)	C4—C5—C6—C7	0.5 (5)
O4—S2—C5—C4	−134.4 (3)	C4—C5—C6—Cl1	−179.98
N3—S2—C5—C4	109.3 (3)	S2—C5—C6—C7	179.8 (3)
S1—N1—C1—N2	5.7 (4)	C5—C6—C7—C2	−0.6 (5)
C1—N2—C2—C7	173.8 (2)	Cl1—C6—C7—C2	179.84
C1—N2—C2—C3	−1.1 (4)

Hydrogen-bond geometry (Å, º)

D—H···A	D—H	H···A	D···A	D—H···A
N2—H2···O2^i	0.995 (3)	2.289 (4)	2.884 (3)	117.3 (3)
N2—H2···N3^ii	0.995 (3)	2.489 (5)	3.301 (3)	138.6 (4)
N3—H3A···N1^iii	1.023 (4)	2.154 (4)	3.134 (3)	159.9 (4)
N3—H3B···O2^iv	0.994 (3)	2.396 (5)	2.912 (3)	111.5 (3)
N3—H3B···O4^v	0.994 (3)	2.079 (4)	2.993 (3)	152.0 (4)
C1—H1···O4^vi	1.073 (3)	2.275 (4)	3.327 (3)	166.4 (2)
C4—H4···O3	1.067 (4)	2.273 (5)	2.779 (4)	107.0 (3)
C7—H7···O1^vii	1.076 (4)	2.151 (5)	3.173 (4)	157.9 (3)

Symmetry codes: (i) x, y+1, z; (ii) x, y+1, z−1; (iii) x−1, y, z+1; (iv) x, y, z+1; (v) x+1, y, z; (vi) x+1, y+1, z−1; (vii) x−1, y+1, z.

(HCT_GEM_neutron_295K) 6-chloro-3,4-dihydro-2H-1,2,4-benzothiadiazine-7-sulfonamide-1,1-dioxide

Crystal data

C7H8ClN3O4S2	Cell parameters included in refinement
Mr = 297.74	Dx = 1.801 Mg m^−3
Monoclinic, P21/c	Neutron radiation, λ = ? Å
Hall symbol: -P 2ybc	µ = 0.04 mm^−1
a = 9.4855 (3) Å	T = 295 K
b = 8.3325 (2) Å	Particle morphology: Needle
c = 15.1201 (4) Å	Colourless
β = 113.240 (3)°	cylinder, 40 × 5 mm
V = 1098.08 (6) Å^3	Specimen preparation: Prepared at 295 K
Z = 4

Data collection

GEM, ISIS diffractometer	Scan method: Time of flight
Radiation source: Pulsed neutron source	Absorption correction: empirical (using intensity measurements) Mu = 0.043(2) cm^-1 parameter Mu refined from experimental data
Specimen mounting: 5mm vanadium cylinderical can	Tmin = ?, Tmax = ?
Data collection mode: transmission

Refinement

Least-squares matrix: selected elements only	149 parameters
Rp = 1.660	24 restraints
Rwp = 0.722	Only H-atom coordinates refined
Rexp = 0.259	Weighting scheme based on measured s.u.'s w = 1/σ(Yobs)^2
χ^2 = 7.896	(Δ/σ)max = 0.001
? data points	Background function: Chebyshev polynomial
Excluded region(s): excluded short and long TOF regions <2000.0/ms and >8000.0/ms excluded 9deg detector bank <1900.0/ms and >15000.0/ms excluded 18deg detector bank <2800.0/ms and >20000.0/ms excluded 35deg detector bank <5000.0/ms and >20000.0/ms excluded 64deg detector bank <9000.0/ms and >18000.0/ms excluded 90deg detector bank <9000.0/ms and >16600.0/ms excluded 153deg detector bank	Preferred orientation correction: none
Profile function: Full Voigt with double exponetial

Special details

Experimental. The neutron data were collected on 6 detector banks and refined simultanously:

The neutron data was refined in a simultanious refinement with X-ray lab powder data. The details of the Lab X-ray powder experiment are given in a seperate data block

Geometry. Bond distances, bond angles, torsion angles and H-bond geometries were calculated using PLATON (Spek, 2003; program version 280604)

Refinement. For 9deg detector bank: _refine_ls_goodness_of_fit_all 1.141 for 18deg detector bank: _refine_ls_goodness_of_fit_all 2.085 for 35deg detector bank: _refine_ls_goodness_of_fit_all 2.627 for 64deg detector bank: _refine_ls_goodness_of_fit_all 4.380 for 90deg detector bank: _refine_ls_goodness_of_fit_all 3.125 for 153deg detector bank: _refine_ls_goodness_of_fit_all 4.381

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Ų)

	x	y	z	Uiso*/Ueq
Cl1	0.75038 (16)	0.3442 (3)	0.62501 (15)	0.019*
S1	0.03927 (16)	0.24694 (17)	0.44712 (9)	0.019*
S2	0.54301 (14)	0.50558 (17)	0.72842 (10)	0.019*
O1	−0.0122 (3)	0.2025 (5)	0.52140 (12)	0.019*
O2	−0.0291 (5)	0.3814 (2)	0.3869 (2)	0.019*
O3	0.41524 (18)	0.5393 (4)	0.75369 (18)	0.019*
O4	0.6265 (3)	0.6383 (3)	0.7136 (2)	0.019*
N1	0.01778 (18)	0.09117 (1)	0.37695 (10)	0.019*
N2	0.27510 (14)	0.0985 (2)	0.37870 (10)	0.019*
N3	0.65916 (15)	0.39576 (17)	0.81178 (11)	0.019*
C1	0.11034 (15)	0.10513 (17)	0.31977 (10)	0.019*
C2	0.33301 (15)	0.2004 (2)	0.45957 (11)	0.019*
C3	0.23925 (15)	0.2748 (3)	0.49878 (11)	0.019*
C4	0.30642 (14)	0.3675 (3)	0.58054 (11)	0.019*
C5	0.46443 (14)	0.3875 (3)	0.62381 (11)	0.019*
C6	0.55348 (15)	0.3192 (2)	0.57983 (11)	0.019*
C7	0.49119 (14)	0.2217 (3)	0.49984 (11)	0.019*
H1A	0.0766 (7)	0.2120 (2)	0.27492 (18)	0.023*
H1B	0.0847 (6)	0.0040 (2)	0.27023 (16)	0.023*
H2	0.3445 (2)	0.0615 (7)	0.34684 (14)	0.023*
H3A	0.76209 (18)	0.3974 (7)	0.8070 (3)	0.023*
H3B	0.6316 (8)	0.2808 (2)	0.8171 (4)	0.023*
H4	0.2314 (2)	0.4136 (8)	0.61311 (18)	0.023*
H5	0.0248 (5)	−0.0057 (2)	0.41790 (16)	0.023*
H7	0.5666 (2)	0.1785 (8)	0.46711 (14)	0.023*

Geometric parameters (Å, º)

Cl1—C6	1.730 (2)	N2—H2	1.005 (3)
S1—O1	1.439 (3)	N3—H3A	1.007 (3)
S1—O2	1.428 (3)	N3—H3B	1.005 (3)
S1—N1	1.6375 (16)	C2—C3	1.394 (2)
S1—C3	1.759 (2)	C2—C7	1.390 (2)
S2—O3	1.435 (3)	C3—C4	1.382 (3)
S2—O4	1.428 (3)	C4—C5	1.389 (2)
S2—N3	1.595 (2)	C5—C6	1.387 (2)
S2—C5	1.759 (2)	C6—C7	1.381 (2)
N1—C1	1.460 (2)	C1—H1A	1.088 (2)
N2—C1	1.463 (2)	C1—H1B	1.089 (2)
N2—C2	1.410 (2)	C4—H4	1.083 (4)
N1—H5	1.003 (2)	C7—H7	1.080 (3)
O1—S1—O2	119.4 (3)	N2—C2—C3	122.76 (15)
O1—S1—N1	107.94 (18)	C3—C2—C7	121.09 (16)
O1—S1—C3	109.03 (13)	C2—C3—C4	118.87 (14)
O2—S1—N1	107.44 (13)	S1—C3—C2	120.65 (15)
O2—S1—C3	108.6 (2)	S1—C3—C4	120.46 (14)
N1—S1—C3	103.24 (13)	C3—C4—C5	121.30 (16)
O3—S2—O4	118.0 (2)	S2—C5—C4	119.10 (14)
O3—S2—N3	107.13 (15)	S2—C5—C6	122.58 (13)
O3—S2—C5	104.25 (14)	C4—C5—C6	118.25 (16)
O4—S2—N3	108.38 (15)	Cl1—C6—C5	121.89 (14)
O4—S2—C5	110.88 (15)	Cl1—C6—C7	116.03 (14)
N3—S2—C5	107.77 (12)	C5—C6—C7	122.02 (15)
S1—N1—C1	111.74 (10)	C2—C7—C6	118.26 (15)
C1—N2—C2	117.55 (13)	N1—C1—H1A	109.7 (3)
S1—N1—H5	106.07 (17)	N1—C1—H1B	108.8 (3)
C1—N1—H5	121.4 (3)	N2—C1—H1A	113.0 (3)
C1—N2—H2	117.63 (18)	N2—C1—H1B	106.5 (3)
C2—N2—H2	119.7 (2)	H1A—C1—H1B	105.9 (2)
S2—N3—H3A	108.8 (3)	C3—C4—H4	116.8 (2)
S2—N3—H3B	119.3 (4)	C5—C4—H4	121.6 (2)
H3A—N3—H3B	108.0 (6)	C2—C7—H7	123.5 (2)
N1—C1—N2	112.57 (12)	C6—C7—H7	117.8 (2)
N2—C2—C7	116.14 (15)
O1—S1—N1—C1	−161.39 (16)	C1—N2—C2—C7	−164.54 (16)
O2—S1—N1—C1	68.6 (2)	C3—C2—C7—C6	−0.2 (3)
C3—S1—N1—C1	−46.03 (14)	N2—C2—C3—C4	177.35 (18)
O1—S1—C3—C2	129.9 (2)	C7—C2—C3—S1	179.97 (16)
O1—S1—C3—C4	−48.4 (3)	N2—C2—C3—S1	−0.9 (3)
O2—S1—C3—C2	−98.5 (2)	N2—C2—C7—C6	−179.34 (17)
O2—S1—C3—C4	83.2 (2)	C7—C2—C3—C4	−1.7 (3)
N1—S1—C3—C2	15.3 (2)	S1—C3—C4—C5	178.31 (18)
N1—S1—C3—C4	−162.96 (18)	C2—C3—C4—C5	0.0 (3)
O3—S2—C5—C4	8.0 (3)	C3—C4—C5—S2	−179.43 (18)
O3—S2—C5—C6	−175.2 (2)	C3—C4—C5—C6	3.6 (3)
O4—S2—C5—C4	−120.0 (2)	S2—C5—C6—C7	177.48 (17)
O4—S2—C5—C6	56.9 (2)	S2—C5—C6—Cl1	0.3 (3)
N3—S2—C5—C4	121.57 (19)	C4—C5—C6—Cl1	177.20 (18)
N3—S2—C5—C6	−61.5 (2)	C4—C5—C6—C7	−5.6 (3)
S1—N1—C1—N2	66.88 (15)	C5—C6—C7—C2	4.0 (3)
C2—N2—C1—N1	−50.24 (18)	Cl1—C6—C7—C2	−178.70 (17)
C1—N2—C2—C3	16.3 (2)

Hydrogen-bond geometry (Å, º)

D—H···A	D—H	H···A	D···A	D—H···A
N2—H2···O3^i	1.005 (3)	1.971 (4)	2.940 (3)	160.9 (3)
N3—H3A···Cl1	1.007 (3)	2.746 (5)	3.292 (3)	114.4 (3)
N3—H3A···N1^ii	1.007 (3)	2.233 (3)	3.148 (2)	150.4 (3)
N3—H3B···O3^iii	1.005 (3)	2.240 (4)	3.122 (4)	145.8 (5)
N3—H3B···O4^iii	1.005 (3)	2.593 (8)	3.357 (3)	132.8 (5)
N1—H5···O1^iv	1.003 (2)	1.906 (4)	2.901 (4)	171.1 (3)
C1—H1B···O2^v	1.089 (2)	2.445 (4)	3.455 (3)	153.6 (2)
C4—H4···O3	1.083 (4)	2.394 (4)	2.799 (3)	100.36 (19)
C4—H4···O2^vi	1.083 (4)	2.569 (6)	3.544 (4)	149.4 (4)

Symmetry codes: (i) x, −y+1/2, z−1/2; (ii) x+1, −y+1/2, z+1/2; (iii) −x+1, y−1/2, −z+3/2; (iv) −x, −y, −z+1; (v) −x, y−1/2, −z+1/2; (vi) −x, −y+1, −z+1.