Hirshfeld surface analysis of two bendroflumethia­zide solvates

Bendroflumethiazide, or 3-benzyl-6-(trifluoro­meth­yl)-3,4-dihydro-2H-1,2,4-benzothia­diazine-7-sulfonamide 1,1-dioxide, is reported to crystallize as 1:1 solvates with acetone, C₁₅H₁₄F₃N₃O₄S₂·C₃H₆O, and N,N-dimethyl­formamide, C₁₅H₁₄F₃N₃O₄S₂·C₃H₇NO. A detailed investigation of the crystal packing and inter­molecular inter­actions is presented by means of Hirshfeld surface analysis. This analysis confirms the atomic positions of methyl H atoms of the solvent mol­ecules that were inferred from the X-ray data and provides a useful tool for structure validation.

S1. Comment

Bendroflumethiazide (BFMZ) is a thiazide diuretic drug used in the treatment of hypertension. The work presented here forms part of a wider investigation that couples parallel crystallization searches (Florence et al., 2006) with crystal structure prediction methodology to investigate the basic science underlying the solid-state diversity in thiazide diuretics, including chlorothiazide (Fernandes et al., 2006, 2007) and hydrochlorothiazide (Johnston et al., 2007).

Novel solvates, (I) and (II) (Figs. 1 and 2), were obtained by crystallization from acetone and N,N-dimethylformamide (DMF) solutions, respectively. Bond lengths and angles in the BFMZ moiety are not significantly different in the two crystal structures, but the molecular conformations are, reflecting the conformational freedom associated with the heterocyclic ring and benzyl group, as demonstrated in a structure overlay (Fig. 3) and in the comparison of the selected, widest varying, torsion angles (Table 1).

The hydrogen bonding in both structures is best described as three-dimensional and, unsurprisingly, the hydrogen-bonding patterns are quite distinct, with different hydrogen-bonding capabilities satisfied in the two structures (Table 2). Acceptors outnumber donors in both structures and it is therefore not surprising that atoms O1 (in both structures) and O4 (in the DMF solvate only) are unused. When longer and weaker hydrogen bonds are taken into consideration, both structures acquire one extra contact, giving rise to bifurcated hydrogen bonds (see Table 2 and Steiner, 2000). A number of weaker C—H···π and C—H···O interactions are also present in the two structures.

When comparing the same molecule in different crystal environments, Hirshfeld surfaces and fingerprint plots (McKinnon et al., 1998, 2004; Spackman & McKinnon, 2002) have been shown to be a powerful tool for elucidating and comparing intermolecular interactions, complementing other tools currently available for the visualization of crystal structures and for their systematic description and analysis, e.g. graph-set analysis (Etter et al., 1990) and topological analysis (Blatov, 2006).

The number of Hirshfeld surfaces that are unique in a given crystal structure depends on the number of independent molecules in the asymmetric unit, implying that for the title compounds there are two resulting surfaces for each structure, viz. one for the solute and one for the solvent. Surfaces for BFMZ are shown in Figs. 4 and 5 (for the DMF solvate, a fully ordered BFMZ model was used); fingerprint plots for BFMZ and the solvents are shown in Fig. 6. d_e and d_i are defined as the distance from the surface to the nearest atom external and internal to the surface, respectively. A range of 0.8 (red in the online version of the journal) and 2.6 Å (blue online) for mapping d_e on the surfaces was employed here. The surfaces are shown as transparent to allow visualization of the BFMZ moiety, in similar orientation for both structures, around which they were calculated. It is clear that the information present in Table 2 is summarized effectively in these plots, with the large circular depressions (deep red in the online version of the journal [AUTHOR: note that we are unable to print diagrams in colour; colour will be shown in the online version only]) visible on the back and front views of the surfaces indicative of hydrogen-bonding contacts. The weak intramolecular hydrogen bonds listed in Table 2 are, of course, not visible on the Hirshfeld surfaces, whereas weak hydrogen bonds where BFMZ is the acceptor are. The feature labelled 1 on the DMF fingerprint is indicative of a long C—H···O interaction [H···A = 2.65 Å, D···A = 3.590 (4) Å and D—H··· A = 170°], where DMF is the donor. The small extent of area and light colour of this feature on the surface in Fig. 5 indicates that this contact is weaker and longer than other hydrogen bonds. The interaction is not clearly visible in the fingerprint of BFMZ as it overlaps with other interactions. The contact is clearly identifiable when the fingerprint is `decomposed' into an H···O interactions-only fingerprint (McKinnon & Spackman, 2007).

These fingerprint plots are quite asymmetric; this is because interactions occur between two chemical and crystallographically distinct molecules. Complementary regions are visible in the fingerprint plots where one molecule acts as a donor, where d_e > d_i, and the other as an acceptor, where d_e < d_i. Some complementary features are illustrated in Fig. 6, e.g. hydrogen bonding (labelled 2 - note that the spike in BFMZ is visibly thicker as more than one hydrogen bond is donated by BFMZ) and C—H···π interactions (labelled 3) between BFMZ and acetone, which are not present between BFMZ and DMF; C—H···π interactions within the BFMZ molecules are labelled 4.

The different conformations adopted by the BFMZ moiety can be partly understood in terms of favourable interactions formed with the two different solvents. The C—H···π interaction between BFMZ and acetone is visible on Fig. 4(a) as a deep large depression above the benzyl ring in the acetone solvate and is marked 3. The geometry of this interaction involves an H···Cg (Cg is the ring centroid) distance of 2.94 Å and a C—H···Cg bond angle of 72°. This interaction is not found between DMF and BFMZ in the DMF solvate, where a methyl H atom forms a close contact with a benzyl H atom instead, marked 5 in Fig. 5(a). This contributes to the observed `tighter' conformation adopted by BFMZ in the DMF solvate.

The pattern of the flat blue/green region marked 6 in Fig. 4(b) is characteristic of an offset π–π ring stacking. This is also labelled in Fig. 6(a), at a longer d_e = d_i ≈ 2.2 Å distance than the van der Waals separation typical of C atoms (i.e. near d_e = d_i ≈ 1.8 Å), owing to the presence of the trifluoro group, which for steric reasons prevents the C atoms from coming in closer proximity.

During the final stages of crystal structure refinement of the DMF solvate, our attention was drawn to the quasi-staggered 50° torsion (see Fig. 7) of the methyl groups belonging to DMF. This contrasts with the fully eclipsed conformation found in the low-temperature structure of DMF (Borrmann et al., 2000) and DFT calculations on free DMF (Stålhandske et al., 1997), which have shown that the fully staggered conformation is a transition state 9.6 kJ mol⁻¹ less stable than the eclipsed state. Furthermore, the majority of DMF molecules in the Cambridge Structural Database (CSD; Version 5.28; Allen, 2002) (subset: organic only, not disordered, not polymeric, not ionic, R-factor < 5%) lie in an eclipsed or nearly eclipsed conformation, i.e. 95 out of 117 entries with τ < 18°, 22 out of 117 entries with 18 < τ < 60°.

Nevertheless, confidence in this observed conformation is high, the H-atom locations coming directly from Fourier maps. Placing the H atoms in calculated positions to give an eclipsed conformation generated very short H···H contacts, as shown in Fig. 8 (labelled 8). With DMF in the observed staggered conformation, the shortest H···H contacts are found at d_e + d_i = 2.24 Å, whilst for the eclipsed conformation, d_e + d_i has the rather improbable value of 1.90 Å [Crystal Explorer (Wolff et al., 2005) normalizes distances to H atoms to neutron values].¹ Furthermore, Fig. 8 also shows a more extended area of points at high values of d_e and d_i where points are scarce, indicating more extended void regions. This evidence overall suggests a more efficient packing adopted when the DMF is in the staggered conformation. With the ability to interrogate fingerprint plots and Hirshfeld surfaces interactively, the unusually short contact is readily discernible as a C—H(DMF)···H1—N(BFMZ) contact.

¹Footnote: Unusually short contacts are rare but not unknown. For example, a very short but real contact of d_e = d_i = 1.02 Å is observed in the crystal structure of pyrene-II (Dunitz & Gavezzotti, 1999) and one at d_e + d_i = 2.05 Å has been recently identified in the Hirshfeld surface analysis of the OP polymorph of CSD refcode ROY (McKinnon & Spackman, 2007). To the best of our knowledge, the shortest intermolecular H···H contact in an organic crystal structure is that of the unstable polymorph of 1,2,3,5-tetra-O-acetyl-β-D-ribofuranose, with an H···H distance of 1.949 (7) Å (Bombicz et al., 2003).

The relatively contact-free space for the same H atom in the staggered DMF molecule could be interpreted either as a loss in number of contact points or as a relief from a close contact that arises at unfavourably short distances. A loss in number of contacts is offset by the gains to be realised with the formation of another favourable contact at 2.652 Å, namely a C18—H181···O4 interaction (labelled 1 in Fig. 5b). This favourable, multi-point contact from CH in DMF towards the formation of strong and weak hydrogen bonds between the solvent and solute molecules has been cited as a contributing factor to why DMF tends to appear frequently as a solvate (Nangia & Desiraju, 1999).

In a rapid structure validation excercize, we calculated fingerprint plots for the DMF molecules located in the CSD search and have found no striking anomalies in the fingerprint plots that might be due to incorrect conformation of the two methyl groups. Only one H···H contact below 2.0 Å (1.91 Å) involving methyl H atoms in DMF was found (refcode PEWZOG; Bertha et al., 1993), and for this structure, the staggered conformation gave an even closer contact of 0.78 Å. These results and the number of entries with torsion angles not equal to 0° indicate correct treatment of methyl H atoms during structural refinement of good-quality data, e.g. by determining the best torsion angle of an idealized CH₃ group, whilst retaining tetrahedral geometry.

Finally, this example underlines the utility of Hirshfeld surfaces and, in particular, fingerprint plot analysis for the `visual screening' and rapid detection of unusual crystal structure features (Fabbiani et al., 2007) through a `whole of structure' view of intermolecular interactions (McKinnon et al., 2004).

Related literature

For related literature, see: Bertha et al. (1993); Blatov (2006); Blessing (1995); Bombicz et al. (2003); Borrmann et al. (2000); Dunitz & Gavezzotti (1999); Etter et al. (1990); Fabbiani et al. (2007); Farrugia (1999); Fernandes et al. (2006, 2007); Florence et al. (2006); Johnston et al. (2007); McKinnon & Spackman (2007); McKinnon et al. (1998, 2004); Nangia & Desiraju (1999); Oxford Diffraction (2006); Spackman & McKinnon (2002); Stålhandske et al. (1997); Steiner (2000).

S2. Experimental

BFMZ was obtained from Medex and used as received. Single crystals of the title compounds were obtained by slow evaporation at room temperature from a saturated solution in the respective solvents.

S3. Refinement

All non-H atoms were modelled with anisotropic displacement parameters, with the exception of the minor component of the disordered site in the DMF solvate, for which one common isotropic displacement parameter was refined. H atoms were located in a difference Fourier map. The program CRYSTALS (Betteridge et al., 2003) allowed initial refinement of H-atoms positions using the X-ray data and soft restraints on bond lengths and angles to regularize their geometry. U_iso(H) were assigned in the range 1.2–1.5 times U_eq of the parent atom. H atoms were subsequently allowed to ride on their parent atoms, with the exception of those attached to N, whose positions were freely refined.

In the structure of the DMF solvate, unusually high peaks were observed in the final difference Fourier maps in the proximity of the terminal benzene ring, clearly indicating disorder of this group over a further site. Given the distorted geometry of the secondary orientation, the ring was refined as a rigid group subsequent to geometry regularization. Distance and bond angle restraints were used to ensure a reasonable orientation of this group with respect to the main ordered moiety, and to mimic rotation of the group about the C1—C7 axis. The occupancies of the two components refined to 0.934 (3) and 0.066 (3). Inclusion of the disorder model contributed to a significant improvement of the R factor as well as of the difference Fourier maps. A common isotropic displacement parameter was refined for the C atoms belonging to the secondary component and the disordered H atoms were placed in calculated positions.

Computing details

For both compounds, data collection: CrysAlis CCD (Oxford Diffraction, 2006); cell refinement: CrysAlis CCD [or RED?] (Oxford Diffraction, 2006); data reduction: CrysAlis CCD [or RED?] (Oxford Diffraction, 2006). Program(s) used to solve structure: SHELXS97 (Sheldrick, 1990) for (I); SIR92 (Altomare et al., 1993) for (II). For both compounds, program(s) used to refine structure: CRYSTALS (Betteridge et al., 2003); molecular graphics: ORTEP-3 (Farrugia, 1997) CRYSTAL EXPLORER (Wolff et al., 2005) and Mercury (Macrae et al., 2006); software used to prepare material for publication: PLATON (Spek, 2003) and publCIF (Westrip, 2007).

Figures

	Fig. 1. BFMZ acetone solvate, with displacement ellipsoids drawn at the 50% probability level. H atoms are shown as spheres of arbitrary radius.
	Fig. 2. BFMZ DMF solvate, with displacement ellipsoids drawn at the 50% probability level. H atoms are shown as spheres of arbitrary radius. The minor disordered site is shown in dashed lines.
	Fig. 3. A structural overlay of the BFMZ moieties in the DMF (red in the online version of the journal) and acetone (blue online) solvates, illustrating the different conformations adopted in the two crystal structures. Atoms overlayed: C9–C14, S1, C15; r.m.s. of overlay fit: 0.0515 Å.
	Fig. 4. Front (a) and back (b) view of the Hirshfeld surface for BFMZ in the acetone solvate structure (Hirshfeld surface mapped with de). The labels are referred to in the main text.
	Fig. 5. Front (a) and back (b) view of the Hirshfeld surface for BFMZ in the DMF solvate structure (Hirshfeld surface mapped with de). The labels are referred to in the main text.
	Fig. 6. Fingerprint plots for BFMZ and solvent molecules in the acetone (a, b) and DMF (c, d) solvates. The labels are referred to in the main text.
	Fig. 7. A molecular scheme of DMF: fully eclipsed methyl H atoms are defined at τ (1–2–3–4) = 0°, fully staggered at τ = 60°.
	Fig. 8. Fingerprint plots for BFMZ (a) and the solvent molecule (b) in the DMF solvate with DMF methyl H atoms calculated in an eclipsed conformation. The labels are referred to in the main text.

(I) 3-benzyl-6-(trifluoromethyl)-3,4-dihydro-2H-1,2,4-benzothiadiazine-7-sulfonamide 1,1-dioxide acetone solvate

Crystal data

C15H14F3N3O4S2·C3H6O	Z = 2
Mr = 479.50	F(000) = 496
Triclinic, P1	Dx = 1.527 Mg m^−3
Hall symbol: -P 1	Mo Kα radiation, λ = 0.71073 Å
a = 8.192 (2) Å	Cell parameters from 7054 reflections
b = 9.525 (2) Å	θ = 2–28°
c = 14.101 (2) Å	µ = 0.32 mm^−1
α = 99.538 (17)°	T = 150 K
β = 100.171 (17)°	Block, colourless
γ = 100.42 (2)°	0.25 × 0.16 × 0.07 mm
V = 1042.8 (4) Å^3

Data collection

Oxford Diffraction Gemini diffractometer	4702 independent reflections
Radiation source: Enhance (Mo) X-ray Source	3973 reflections with I > 2.0σ(I)
Graphite monochromator	Rint = 0.019
ϕ and ω scans	θmax = 28.5°, θmin = 2.4°
Absorption correction: multi-scan (CrysAlis RED; Oxford Diffraction, 2006)	h = −10→10
Tmin = 0.97, Tmax = 0.98	k = −12→12
12169 measured reflections	l = 0→18

Refinement

Refinement on F^2	Primary atom site location: structure-invariant direct methods
Least-squares matrix: full	Hydrogen site location: geom+difmap
R[F^2 > 2σ(F^2)] = 0.033	H atoms treated by a mixture of independent and constrained refinement
wR(F^2) = 0.079	Method = Modified Sheldrick w = 1/[σ^2(F^2) + ( 0.03P)^2 + 0.77P] , where P = (max(Fo^2,0) + 2Fc^2)/3
S = 1.01	(Δ/σ)max = 0.001
4702 reflections	Δρmax = 0.36 e Å^−3
292 parameters	Δρmin = −0.45 e Å^−3
0 restraints

Special details

Refinement. The following are the results of the online checkcif procedure available at https://checkcif.iucr.org/:

912_ALERT_3_B # Missing FCF Reflections Above STH/L=0.6 ······ 555 910_ALERT_3_C # Missing FCF Reflections Below TH(Min) ······.. 2 911_ALERT_3_C # Missing FCF Refl. Between TH(Min) & STH/L=0.6 1

The data collection strategy was devised so as to collect a complete and redundant dataset to 0.8 A ng. Resolution and completeness are given below.

================================================================================ Resolution & Completeness Statistics (Cumulative) ================================================================================ Theta sin(th)/Lambda Complete Expected Measured Missing ——————————————————————————– 20.82 0.500 0.999 2193 2191 2 23.01 0.550 0.999 2901 2899 2 25.24 0.600 0.999 3773 3770 3 ———————————————————— ACTA Min. Res. —- 27.51 0.650 0.953 4829 4601 228 28.47 0.671 0.894 5261 4703 558

244_ALERT_4_C Low 'Solvent' U_eq as Compared to Neighbors for C16

C16 is the central atom of the acetone moiety and it is therefore not unusual that it displays a smaller thermal parameter than its neighbouring, terminal atoms.

153_ALERT_1_C The su's on the Cell Axes are Equal (x 100000) 200 A ng. 431_ALERT_2_C Short Inter HL.·A Contact F1.. O5.. 2.87 A ng. 431_ALERT_2_C Short Inter HL.·A Contact F2.. O1.. 2.86 A ng. 793_ALERT_1_G Check the Absolute Configuration of C8 = ··· R

Noted, verified, no action taken. The compound is a racemate.

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

	x	y	z	Uiso*/Ueq
N1	0.3263 (2)	0.76756 (17)	0.73417 (12)	0.0247
N2	0.95117 (17)	0.77540 (16)	0.47155 (10)	0.0211
N3	0.76916 (16)	0.78877 (15)	0.31953 (10)	0.0170
F1	0.66511 (13)	0.67927 (12)	0.81547 (7)	0.0289
F2	0.69403 (14)	0.47667 (11)	0.73184 (8)	0.0336
F3	0.90881 (13)	0.65568 (14)	0.78673 (8)	0.0370
C1	1.0537 (2)	0.76878 (18)	0.21814 (12)	0.0209
C2	0.9714 (2)	0.6663 (2)	0.13295 (13)	0.0264
C3	0.9782 (3)	0.6984 (2)	0.04061 (14)	0.0337
C4	1.0657 (3)	0.8331 (2)	0.03274 (14)	0.0338
C5	1.1469 (2)	0.9360 (2)	0.11706 (14)	0.0322
C6	1.1414 (2)	0.90397 (19)	0.20922 (13)	0.0258
C7	1.0495 (2)	0.73265 (19)	0.31820 (12)	0.0217
C8	0.94491 (19)	0.81809 (18)	0.37591 (11)	0.0185
C9	0.82194 (19)	0.76150 (17)	0.51927 (11)	0.0171
C10	0.66463 (19)	0.79661 (16)	0.48492 (11)	0.0164
C11	0.52640 (19)	0.75988 (16)	0.52747 (11)	0.0174
C12	0.54168 (19)	0.69839 (16)	0.61016 (11)	0.0171
C13	0.70442 (19)	0.67802 (17)	0.65248 (11)	0.0178
C14	0.83878 (19)	0.70741 (18)	0.60731 (11)	0.0196
C15	0.7414 (2)	0.62168 (19)	0.74650 (12)	0.0237
C16	0.4866 (3)	0.7573 (3)	1.02453 (15)	0.0423
C17	0.6126 (3)	0.8889 (3)	1.0856 (2)	0.0581
C18	0.4279 (3)	0.6409 (3)	1.07781 (17)	0.0458
O1	0.47471 (14)	0.82450 (13)	0.32268 (9)	0.0246
O2	0.72315 (15)	1.02208 (12)	0.40378 (9)	0.0244
O3	0.21627 (14)	0.63242 (13)	0.56525 (9)	0.0240
O4	0.35993 (15)	0.51759 (12)	0.69143 (9)	0.0265
O5	0.4321 (3)	0.7450 (3)	0.93756 (12)	0.0762
S1	0.34931 (5)	0.64359 (4)	0.64943 (3)	0.0179
S2	0.64516 (5)	0.86881 (4)	0.37846 (3)	0.0170
H11	0.9111	0.5739	0.1384	0.0313*
H12	0.9246	0.6289	−0.0154	0.0402*
H13	1.0718	0.8544	−0.0302	0.0437*
H14	1.2072	1.0270	0.1131	0.0411*
H15	1.1984	0.9750	0.2658	0.0317*
H71	0.9994	0.6293	0.3099	0.0281*
H72	1.1634	0.7543	0.3578	0.0280*
H81	0.9897	0.9211	0.3844	0.0211*
H100	0.318 (3)	0.848 (2)	0.7154 (15)	0.0331*
H101	0.373 (3)	0.766 (2)	0.7901 (17)	0.0338*
H102	1.035 (3)	0.749 (2)	0.4952 (15)	0.0275*
H103	0.725 (2)	0.699 (2)	0.3019 (14)	0.0243*
H111	0.4202	0.7771	0.4981	0.0208*
H141	0.9452	0.6905	0.6328	0.0244*
H171	0.5721	0.9252	1.1428	0.0959*
H172	0.6304	0.9647	1.0499	0.0952*
H173	0.7186	0.8649	1.1066	0.0955*
H181	0.5262	0.6123	1.1122	0.0669*
H182	0.3684	0.6809	1.1264	0.0680*
H183	0.3554	0.5571	1.0330	0.0676*

Atomic displacement parameters (Ų)

	U^11	U^22	U^33	U^12	U^13	U^23
N1	0.0323 (8)	0.0258 (8)	0.0230 (8)	0.0133 (6)	0.0121 (6)	0.0099 (6)
N2	0.0138 (6)	0.0336 (8)	0.0180 (7)	0.0085 (6)	0.0016 (5)	0.0094 (6)
N3	0.0158 (6)	0.0171 (6)	0.0178 (7)	0.0034 (5)	0.0026 (5)	0.0043 (5)
F1	0.0313 (5)	0.0413 (6)	0.0189 (5)	0.0133 (5)	0.0097 (4)	0.0088 (4)
F2	0.0417 (6)	0.0302 (6)	0.0389 (6)	0.0176 (5)	0.0131 (5)	0.0195 (5)
F3	0.0223 (5)	0.0681 (8)	0.0255 (5)	0.0136 (5)	0.0016 (4)	0.0227 (5)
C1	0.0179 (7)	0.0279 (9)	0.0215 (8)	0.0114 (6)	0.0064 (6)	0.0086 (7)
C2	0.0263 (8)	0.0268 (9)	0.0260 (9)	0.0051 (7)	0.0055 (7)	0.0061 (7)
C3	0.0405 (11)	0.0376 (11)	0.0212 (9)	0.0090 (9)	0.0031 (8)	0.0041 (8)
C4	0.0408 (11)	0.0436 (11)	0.0245 (9)	0.0160 (9)	0.0111 (8)	0.0164 (8)
C5	0.0341 (10)	0.0308 (10)	0.0367 (11)	0.0073 (8)	0.0119 (8)	0.0160 (8)
C6	0.0260 (8)	0.0269 (9)	0.0256 (9)	0.0070 (7)	0.0061 (7)	0.0068 (7)
C7	0.0198 (8)	0.0277 (9)	0.0217 (8)	0.0097 (7)	0.0068 (6)	0.0091 (7)
C8	0.0147 (7)	0.0221 (8)	0.0191 (8)	0.0034 (6)	0.0036 (6)	0.0062 (6)
C9	0.0162 (7)	0.0175 (7)	0.0167 (7)	0.0035 (6)	0.0024 (6)	0.0017 (6)
C10	0.0175 (7)	0.0159 (7)	0.0160 (7)	0.0046 (6)	0.0021 (6)	0.0043 (6)
C11	0.0168 (7)	0.0182 (7)	0.0181 (8)	0.0060 (6)	0.0032 (6)	0.0045 (6)
C12	0.0157 (7)	0.0179 (7)	0.0187 (8)	0.0052 (6)	0.0050 (6)	0.0040 (6)
C13	0.0188 (7)	0.0182 (8)	0.0165 (8)	0.0057 (6)	0.0023 (6)	0.0034 (6)
C14	0.0151 (7)	0.0255 (8)	0.0184 (8)	0.0077 (6)	0.0005 (6)	0.0047 (6)
C15	0.0200 (8)	0.0334 (9)	0.0221 (8)	0.0110 (7)	0.0059 (7)	0.0109 (7)
C16	0.0457 (12)	0.0700 (15)	0.0294 (11)	0.0383 (11)	0.0190 (9)	0.0210 (10)
C17	0.0499 (14)	0.0584 (16)	0.0798 (19)	0.0156 (12)	0.0180 (13)	0.0440 (14)
C18	0.0509 (13)	0.0456 (13)	0.0379 (12)	0.0079 (10)	0.0081 (10)	0.0039 (10)
O1	0.0165 (5)	0.0350 (7)	0.0244 (6)	0.0082 (5)	0.0023 (5)	0.0117 (5)
O2	0.0259 (6)	0.0180 (6)	0.0327 (7)	0.0076 (5)	0.0089 (5)	0.0085 (5)
O3	0.0166 (5)	0.0286 (6)	0.0264 (6)	0.0043 (5)	0.0029 (5)	0.0075 (5)
O4	0.0253 (6)	0.0201 (6)	0.0375 (7)	0.0049 (5)	0.0085 (5)	0.0138 (5)
O5	0.1035 (16)	0.1280 (18)	0.0265 (8)	0.0780 (14)	0.0243 (9)	0.0293 (10)
S1	0.01655 (18)	0.01722 (19)	0.0220 (2)	0.00451 (14)	0.00565 (15)	0.00709 (15)
S2	0.01565 (18)	0.01844 (19)	0.01913 (19)	0.00609 (14)	0.00362 (15)	0.00785 (15)

Geometric parameters (Å, º)

N1—S1	1.5971 (16)	C7—H72	0.966
N1—H100	0.86 (2)	C8—H81	0.963
N1—H101	0.82 (2)	C9—C10	1.413 (2)
N2—C8	1.467 (2)	C9—C14	1.415 (2)
N2—C9	1.350 (2)	C10—C11	1.390 (2)
N2—H102	0.81 (2)	C10—S2	1.7463 (16)
N3—C8	1.4696 (19)	C11—C12	1.386 (2)
N3—S2	1.6347 (14)	C11—H111	0.950
N3—H103	0.84 (2)	C12—C13	1.422 (2)
F1—C15	1.3414 (19)	C12—S1	1.7801 (16)
F2—C15	1.336 (2)	C13—C14	1.375 (2)
F3—C15	1.3459 (19)	C13—C15	1.513 (2)
C1—C2	1.392 (2)	C14—H141	0.935
C1—C6	1.393 (2)	C16—C17	1.496 (4)
C1—C7	1.511 (2)	C16—C18	1.495 (3)
C2—C3	1.394 (3)	C16—O5	1.207 (3)
C2—H11	0.951	C17—H171	0.961
C3—C4	1.384 (3)	C17—H172	0.951
C3—H12	0.924	C17—H173	0.947
C4—C5	1.384 (3)	C18—H181	0.971
C4—H13	0.950	C18—H182	0.976
C5—C6	1.390 (3)	C18—H183	0.958
C5—H14	0.932	O1—S2	1.4267 (12)
C6—H15	0.943	O2—S2	1.4409 (13)
C7—C8	1.529 (2)	O3—S1	1.4379 (12)
C7—H71	0.975	O4—S1	1.4332 (12)
S1—N1—H100	113.6 (14)	C10—C11—C12	121.17 (14)
S1—N1—H101	115.7 (15)	C10—C11—H111	118.4
H100—N1—H101	122 (2)	C12—C11—H111	120.5
C8—N2—C9	125.56 (13)	C11—C12—C13	118.16 (14)
C8—N2—H102	117.5 (14)	C11—C12—S1	115.60 (11)
C9—N2—H102	116.6 (14)	C13—C12—S1	126.16 (12)
C8—N3—S2	113.13 (11)	C12—C13—C14	120.42 (14)
C8—N3—H103	112.7 (13)	C12—C13—C15	123.59 (14)
S2—N3—H103	108.6 (13)	C14—C13—C15	115.98 (14)
C2—C1—C6	118.75 (15)	C9—C14—C13	121.79 (14)
C2—C1—C7	120.37 (15)	C9—C14—H141	116.9
C6—C1—C7	120.88 (15)	C13—C14—H141	121.3
C1—C2—C3	120.41 (17)	C13—C15—F3	111.22 (13)
C1—C2—H11	119.2	C13—C15—F1	112.46 (13)
C3—C2—H11	120.3	F3—C15—F1	106.21 (14)
C2—C3—C4	120.28 (18)	C13—C15—F2	112.53 (14)
C2—C3—H12	119.6	F3—C15—F2	106.19 (13)
C4—C3—H12	120.1	F1—C15—F2	107.83 (13)
C3—C4—C5	119.68 (17)	C17—C16—C18	116.09 (18)
C3—C4—H13	120.2	C17—C16—O5	122.8 (2)
C5—C4—H13	120.1	C18—C16—O5	121.1 (2)
C4—C5—C6	120.18 (17)	C16—C17—H171	109.7
C4—C5—H14	120.8	C16—C17—H172	111.7
C6—C5—H14	119.0	H171—C17—H172	108.3
C1—C6—C5	120.70 (17)	C16—C17—H173	110.5
C1—C6—H15	120.3	H171—C17—H173	108.5
C5—C6—H15	119.0	H172—C17—H173	108.1
C1—C7—C8	113.57 (13)	C16—C18—H181	109.1
C1—C7—H71	109.1	C16—C18—H182	108.5
C8—C7—H71	107.5	H181—C18—H182	108.4
C1—C7—H72	110.0	C16—C18—H183	111.1
C8—C7—H72	107.1	H181—C18—H183	109.1
H71—C7—H72	109.5	H182—C18—H183	110.6
C7—C8—N3	109.75 (13)	C12—S1—N1	110.76 (8)
C7—C8—N2	108.78 (13)	C12—S1—O3	105.08 (7)
N3—C8—N2	111.13 (12)	N1—S1—O3	106.84 (8)
C7—C8—H81	109.8	C12—S1—O4	108.30 (7)
N3—C8—H81	106.7	N1—S1—O4	106.82 (8)
N2—C8—H81	110.7	O3—S1—O4	118.99 (8)
N2—C9—C10	123.12 (14)	C10—S2—N3	101.39 (7)
N2—C9—C14	120.26 (14)	C10—S2—O2	109.27 (8)
C10—C9—C14	116.61 (14)	N3—S2—O2	106.40 (7)
C9—C10—C11	121.20 (14)	C10—S2—O1	110.37 (7)
C9—C10—S2	116.89 (12)	N3—S2—O1	109.53 (7)
C11—C10—S2	121.52 (12)	O2—S2—O1	118.45 (7)

(II) 3-benzyl-6-(trifluoromethyl)-3,4-dihydro-2H-1,2,4-benzothiadiazine-7-sulfonamide 1,1-dioxide N,N-dimethylformamide solvate

Crystal data

C15H14F3N3O4S2·C3H7NO	F(000) = 1024
Mr = 494.51	Dx = 1.541 Mg m^−3
Monoclinic, P21/n	Mo Kα radiation, λ = 0.71073 Å
Hall symbol: -P 2yn	Cell parameters from 11940 reflections
a = 8.2527 (3) Å	θ = 3–29°
b = 17.8431 (7) Å	µ = 0.32 mm^−1
c = 14.9012 (5) Å	T = 150 K
β = 103.752 (4)°	Lath, colourless
V = 2131.35 (14) Å^3	0.19 × 0.09 × 0.07 mm
Z = 4

Data collection

Oxford Diffraction Gemini diffractometer	3954 reflections with I > 2.0σ(I)
Graphite monochromator	Rint = 0.034
ϕ & ω scans	θmax = 27.1°, θmin = 2.6°
Absorption correction: multi-scan (CrysAlis RED; Oxford Diffraction, 2006)	h = −10→10
Tmin = 0.88, Tmax = 0.98	k = 0→22
28698 measured reflections	l = 0→19
4615 independent reflections

Refinement

Refinement on F^2	Primary atom site location: structure-invariant direct methods
Least-squares matrix: full	Hydrogen site location: geom+difmap
R[F^2 > 2σ(F^2)] = 0.040	H atoms treated by a mixture of independent and constrained refinement
wR(F^2) = 0.091	Method = Modified Sheldrick w = 1/[σ^2(F^2) + ( 0.03P)^2 + 2.31P] , where P = (max(Fo^2,0) + 2Fc^2)/3
S = 1.01	(Δ/σ)max = 0.000401
4615 reflections	Δρmax = 0.42 e Å^−3
309 parameters	Δρmin = −0.46 e Å^−3
2 restraints

Special details

Refinement. Representative peak heights are as follows. For the methyl H-atoms attached to C(17): 0.71, 0.49, 0.53 e-Å-3. For the methyl H-atoms attached to C(18): 0.56, 0.56, 0.50 e-Å-3. For a ?good? H-atom, e.g. attached to C16: 0.69 e-Å-3, attached to C14: 0.9 e-Å-3. The average background noise level, defined as a root-mean-square electron density from a difference Fourier map is 0.09 e-Å-3.

The following are the results of the online checkcif procedure available at https://checkcif.iucr.org/:

911_ALERT_3_B # Missing FCF Refl. Between TH(Min) & STH/L=0.6 28 910_ALERT_3_C # Missing FCF Reflections Below TH(Min) ······.. 2 912_ALERT_3_C # Missing FCF Reflections Above STH/L=0.6 ······ 27

The data collection strategy was devised so as to collect a complete and redundant dataset to 0.8 A ng. a theta cut off of 27 ° was applied during data merging. Resolution and completeness are given below. ================================================================================ Resolution & Completeness Statistics (Cumulative) ================================================================================ Theta sin(th)/Lambda Complete Expected Measured Missing ——————————————————————————– 20.82 0.500 0.995 2236 2225 11 23.01 0.550 0.993 2977 2955 22 25.24 0.600 0.992 3852 3822 30 ———————————————————— ACTA Min. Res. —- 27.06 0.640 0.988 4672 4615 57

223_ALERT_4_C Large Solvent/Anion H U_eq(max)/U_eq(min) ··· 3.09 Ratio 244_ALERT_4_C Low 'Solvent' U_eq as Compared to Neighbors for N4

N4 is the central atom of the DMF moiety and it is therefore not unusual that it displays a smaller thermal parameter. H U_eq parameter were estimated in the range 1.2–1.5 times U_eq of the parent atom, as appropirate. The larger U_eq associated with methyl H atoms are not usual for such a chemical group.

301_ALERT_3_C Main Residue Disorder ························. 18.00 Perc. 432_ALERT_2_C Short Inter X···Y Contact C18.. C111.. 3.19 A ng. 720_ALERT_4_C Number of Unusual/Non-Standard Label(s) ······.. 5

Notes, no action taken. These alerts originate from the modelled disorder for the benzyl group, see main article text for disorder details.

793_ALERT_1_G Check the Absolute Configuration of C8 = ··· R 860_ALERT_3_G Note: Number of Least-Squares Restraints ······. 2

Noted, no action taken. The compound is a racemate.

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

	x	y	z	Uiso*/Ueq	Occ. (<1)
N1	0.8916 (2)	0.32480 (10)	0.25502 (13)	0.0255
N2	0.1032 (2)	0.38736 (10)	0.02868 (11)	0.0242
N3	0.1668 (2)	0.40018 (10)	−0.11929 (11)	0.0200
N4	0.7046 (3)	0.15461 (11)	0.06308 (12)	0.0358
C1	−0.1885 (3)	0.37684 (14)	−0.20985 (15)	0.0232	0.934 (3)
C2	−0.1851 (3)	0.42896 (13)	−0.27782 (16)	0.0315	0.934 (3)
C3	−0.2434 (4)	0.41047 (16)	−0.37029 (17)	0.0393	0.934 (3)
C4	−0.3040 (4)	0.34005 (18)	−0.39540 (17)	0.0395	0.934 (3)
C5	−0.3088 (4)	0.28796 (14)	−0.32758 (18)	0.0389	0.934 (3)
C6	−0.2513 (3)	0.30654 (13)	−0.23534 (16)	0.0315	0.934 (3)
C7	−0.1246 (3)	0.39558 (13)	−0.10922 (14)	0.0276
C8	0.0517 (2)	0.36745 (11)	−0.06902 (13)	0.0210
C9	0.2655 (2)	0.38998 (11)	0.07647 (13)	0.0203
C10	0.3996 (2)	0.38637 (10)	0.03365 (12)	0.0189
C11	0.5623 (2)	0.39405 (10)	0.08362 (13)	0.0198
C12	0.6013 (2)	0.40109 (10)	0.17860 (12)	0.0188
C13	0.4689 (2)	0.40096 (11)	0.22391 (12)	0.0211
C14	0.3067 (2)	0.39740 (11)	0.17367 (13)	0.0228
C15	0.4975 (3)	0.40130 (13)	0.32803 (14)	0.0295
C16	0.7466 (3)	0.21657 (12)	0.02685 (14)	0.0300
C17	0.6124 (4)	0.09506 (17)	0.00652 (18)	0.0543
C18	0.7432 (5)	0.14464 (18)	0.16254 (17)	0.0774
C110	−0.252 (4)	0.3306 (19)	−0.3980 (8)	0.045 (6)*	0.066 (3)
C111	−0.118 (3)	0.2934 (15)	−0.3355 (14)	0.045 (6)*	0.066 (3)
C112	−0.077 (3)	0.3104 (16)	−0.2411 (12)	0.045 (6)*	0.066 (3)
C113	−0.170 (3)	0.3645 (18)	−0.2092 (10)	0.045 (6)*	0.066 (3)
C114	−0.305 (3)	0.4017 (15)	−0.2717 (15)	0.045 (6)*	0.066 (3)
C115	−0.346 (3)	0.3847 (17)	−0.3661 (13)	0.045 (6)*	0.066 (3)
O1	0.46115 (18)	0.41872 (9)	−0.12572 (9)	0.0297
O2	0.35917 (19)	0.29232 (8)	−0.10118 (10)	0.0300
O3	0.89250 (17)	0.43569 (7)	0.16039 (9)	0.0223
O4	0.84095 (18)	0.44894 (8)	0.31570 (9)	0.0267
O5	0.8208 (2)	0.27041 (8)	0.06954 (10)	0.0337
S1	0.81675 (6)	0.40767 (3)	0.23184 (3)	0.0191
S2	0.35806 (6)	0.37157 (3)	−0.08570 (3)	0.0204
F1	0.61227 (17)	0.34999 (8)	0.36688 (8)	0.0377
F2	0.54579 (17)	0.46703 (8)	0.36671 (8)	0.0396
F3	0.35754 (17)	0.38298 (10)	0.35441 (8)	0.0450
H71	−0.1249	0.4498	−0.1037	0.0320*
H72	−0.1979	0.3743	−0.0733	0.0321*
H81	0.0545	0.3124	−0.0755	0.0245*
H100	0.882 (3)	0.3007 (14)	0.2081 (17)	0.0316*
H101	0.862 (3)	0.3037 (13)	0.3031 (17)	0.0312*
H102	0.033 (3)	0.3845 (13)	0.0585 (16)	0.0298*
H103	0.161 (3)	0.4474 (14)	−0.1236 (15)	0.0268*
H111	0.6484	0.3932	0.0523	0.0240*
H141	0.2230	0.3990	0.2062	0.0273*
H161	0.7155	0.2183	−0.0388	0.0364*
H11	−0.1456	0.4777	−0.2616	0.0386*	0.934 (3)
H12	−0.2407	0.4463	−0.4153	0.0483*	0.934 (3)
H13	−0.3406	0.3272	−0.4572	0.0460*	0.934 (3)
H14	−0.3532	0.2386	−0.3432	0.0456*	0.934 (3)
H15	−0.2560	0.2704	−0.1907	0.0387*	0.934 (3)
H171	0.6678	0.0472	0.0246	0.0842*
H172	0.6083	0.1066	−0.0580	0.0829*
H173	0.4980	0.0951	0.0152	0.0842*
H181	0.7202	0.0944	0.1764	0.1119*
H182	0.8572	0.1577	0.1866	0.1119*
H183	0.6719	0.1787	0.1862	0.1125*
H1131	−0.3671	0.4315	−0.2499	0.0528*	0.066 (3)
H1132	−0.4434	0.4083	−0.4133	0.0528*	0.066 (3)
H1133	−0.2861	0.3186	−0.4771	0.0530*	0.066 (3)
H1134	−0.0552	0.2530	−0.3783	0.0528*	0.066 (3)
H1135	0.0212	0.2762	−0.2150	0.0528*	0.066 (3)

Atomic displacement parameters (Ų)

	U^11	U^22	U^33	U^12	U^13	U^23
N1	0.0269 (10)	0.0240 (9)	0.0253 (9)	0.0036 (7)	0.0058 (8)	0.0040 (7)
N2	0.0155 (9)	0.0409 (10)	0.0167 (8)	−0.0004 (7)	0.0049 (7)	0.0006 (7)
N3	0.0193 (9)	0.0229 (8)	0.0175 (8)	0.0021 (6)	0.0036 (7)	0.0015 (6)
N4	0.0489 (13)	0.0375 (11)	0.0196 (9)	−0.0121 (9)	0.0054 (9)	−0.0038 (8)
C1	0.0156 (11)	0.0301 (12)	0.0224 (11)	−0.0001 (8)	0.0013 (9)	0.0027 (9)
C2	0.0327 (13)	0.0273 (11)	0.0320 (12)	−0.0036 (10)	0.0028 (10)	0.0020 (9)
C3	0.0434 (16)	0.0473 (15)	0.0265 (12)	−0.0020 (12)	0.0072 (11)	0.0121 (11)
C4	0.0383 (17)	0.0540 (18)	0.0222 (12)	0.0000 (14)	−0.0007 (11)	−0.0031 (11)
C5	0.0436 (16)	0.0340 (13)	0.0342 (13)	−0.0062 (11)	−0.0003 (12)	−0.0076 (11)
C6	0.0346 (14)	0.0307 (12)	0.0264 (12)	−0.0039 (10)	0.0017 (10)	0.0046 (9)
C7	0.0199 (11)	0.0389 (12)	0.0227 (10)	0.0014 (9)	0.0020 (8)	−0.0013 (9)
C8	0.0184 (10)	0.0266 (10)	0.0174 (9)	−0.0020 (7)	0.0032 (8)	0.0003 (7)
C9	0.0184 (10)	0.0232 (9)	0.0194 (9)	0.0007 (7)	0.0045 (8)	0.0013 (7)
C10	0.0190 (10)	0.0221 (9)	0.0153 (8)	0.0013 (7)	0.0037 (8)	−0.0003 (7)
C11	0.0189 (10)	0.0223 (9)	0.0189 (9)	0.0024 (7)	0.0059 (8)	0.0005 (7)
C12	0.0149 (9)	0.0231 (9)	0.0179 (9)	−0.0001 (7)	0.0032 (7)	0.0005 (7)
C13	0.0211 (10)	0.0265 (10)	0.0156 (9)	−0.0001 (8)	0.0044 (8)	−0.0004 (7)
C14	0.0187 (10)	0.0329 (11)	0.0179 (9)	0.0018 (8)	0.0066 (8)	0.0000 (8)
C15	0.0209 (11)	0.0500 (14)	0.0180 (10)	0.0014 (9)	0.0052 (9)	0.0007 (9)
C16	0.0335 (12)	0.0344 (12)	0.0227 (10)	0.0062 (9)	0.0080 (9)	0.0017 (9)
C17	0.0630 (19)	0.0634 (18)	0.0372 (14)	−0.0297 (15)	0.0134 (14)	−0.0196 (13)
C18	0.148 (4)	0.0555 (18)	0.0219 (12)	−0.051 (2)	0.0074 (17)	0.0024 (12)
O1	0.0229 (8)	0.0472 (9)	0.0203 (7)	−0.0019 (6)	0.0080 (6)	0.0035 (6)
O2	0.0327 (9)	0.0292 (8)	0.0254 (7)	0.0084 (6)	0.0020 (6)	−0.0084 (6)
O3	0.0186 (7)	0.0254 (7)	0.0230 (7)	−0.0017 (5)	0.0053 (6)	0.0030 (5)
O4	0.0234 (8)	0.0333 (8)	0.0218 (7)	−0.0022 (6)	0.0019 (6)	−0.0055 (6)
O5	0.0451 (10)	0.0264 (8)	0.0302 (8)	0.0010 (7)	0.0098 (7)	0.0018 (6)
S1	0.0167 (2)	0.0217 (2)	0.0180 (2)	−0.00035 (17)	0.00262 (18)	0.00055 (17)
S2	0.0189 (2)	0.0274 (2)	0.0148 (2)	0.00264 (18)	0.00409 (18)	−0.00176 (18)
F1	0.0357 (8)	0.0552 (9)	0.0206 (6)	0.0063 (6)	0.0037 (6)	0.0109 (6)
F2	0.0366 (8)	0.0556 (9)	0.0255 (6)	0.0026 (6)	0.0052 (6)	−0.0157 (6)
F3	0.0297 (8)	0.0884 (11)	0.0200 (6)	−0.0067 (7)	0.0119 (6)	0.0027 (6)

Geometric parameters (Å, º)

N1—S1	1.6081 (18)	C10—S2	1.7493 (18)
N1—H100	0.81 (3)	C11—C12	1.380 (2)
N1—H101	0.89 (3)	C11—H111	0.938
N2—C8	1.460 (2)	C12—C13	1.414 (3)
N2—C9	1.360 (3)	C12—S1	1.7706 (19)
N2—H102	0.81 (2)	C13—C14	1.371 (3)
N3—C8	1.464 (2)	C13—C15	1.513 (3)
N3—S2	1.6209 (17)	C14—H141	0.934
N3—H103	0.84 (2)	C15—F1	1.345 (3)
N4—C16	1.313 (3)	C15—F2	1.326 (3)
N4—C17	1.454 (3)	C15—F3	1.346 (2)
N4—C18	1.451 (3)	C16—O5	1.232 (3)
C1—C2	1.380 (3)	C16—H161	0.951
C1—C6	1.376 (3)	C17—H171	0.976
C1—C7	1.504 (3)	C17—H172	0.976
C2—C3	1.387 (3)	C17—H173	0.983
C2—H11	0.941	C18—H181	0.949
C3—C4	1.371 (4)	C18—H182	0.952
C3—H12	0.931	C18—H183	0.969
C4—C5	1.380 (4)	C110—C111	1.4303 (1)
C4—H13	0.927	C110—C115	1.388
C5—C6	1.383 (3)	C110—H1133	1.164
C5—H14	0.962	C111—C112	1.3994 (1)
C6—H15	0.935	C111—H1134	1.163
C7—C8	1.521 (3)	C112—C113	1.388
C7—H71	0.971	C112—H1135	1.015
C7—H72	0.976	C113—C114	1.4303 (1)
C7—C8	1.521 (3)	C114—C115	1.3994 (1)
C7—C113	1.550 (9)	C114—H1131	0.855
C7—H71	0.971	C115—H1132	1.026
C7—H72	0.976	O1—S2	1.4243 (15)
C8—H81	0.988	O2—S2	1.4331 (15)
C9—C10	1.404 (3)	O3—S1	1.4460 (13)
C9—C14	1.413 (3)	O4—S1	1.4230 (14)
C10—C11	1.379 (3)
S1—N1—H100	110.4 (18)	C13—C12—S1	126.42 (14)
S1—N1—H101	113.3 (15)	C12—C13—C14	120.27 (17)
H100—N1—H101	119 (2)	C12—C13—C15	122.67 (18)
C8—N2—C9	123.20 (16)	C14—C13—C15	117.01 (17)
C8—N2—H102	117.0 (17)	C9—C14—C13	121.99 (17)
C9—N2—H102	117.2 (17)	C9—C14—H141	120.5
C8—N3—S2	114.77 (13)	C13—C14—H141	117.5
C8—N3—H103	114.1 (16)	C13—C15—F1	111.15 (17)
S2—N3—H103	111.5 (16)	C13—C15—F2	114.00 (18)
C16—N4—C17	122.0 (2)	F1—C15—F2	107.86 (17)
C16—N4—C18	120.5 (2)	C13—C15—F3	111.30 (17)
C17—N4—C18	117.4 (2)	F1—C15—F3	105.93 (18)
C2—C1—C6	118.9 (2)	F2—C15—F3	106.15 (17)
C2—C1—C7	121.2 (2)	N4—C16—O5	126.3 (2)
C6—C1—C7	119.9 (2)	N4—C16—H161	114.7
C1—C2—C3	120.4 (2)	O5—C16—H161	119.0
C1—C2—H11	120.1	N4—C17—H171	109.5
C3—C2—H11	119.5	N4—C17—H172	108.0
C2—C3—C4	120.5 (2)	H171—C17—H172	111.1
C2—C3—H12	119.3	N4—C17—H173	108.0
C4—C3—H12	120.2	H171—C17—H173	111.5
C3—C4—C5	119.3 (2)	H172—C17—H173	108.7
C3—C4—H13	120.6	N4—C18—H181	109.4
C5—C4—H13	120.1	N4—C18—H182	108.2
C4—C5—C6	120.2 (2)	H181—C18—H182	112.3
C4—C5—H14	121.0	N4—C18—H183	106.9
C6—C5—H14	118.8	H181—C18—H183	110.0
C5—C6—C1	120.7 (2)	H182—C18—H183	109.9
C5—C6—H15	118.7	C111—C110—C115	120.476 (3)
C1—C6—H15	120.6	C111—C110—H1133	122.3
C1—C7—C8	113.27 (17)	C115—C110—H1133	117.2
C1—C7—H71	107.4	C110—C111—C112	121.268 (3)
C8—C7—H71	108.5	C110—C111—H1134	108.0
C1—C7—H72	110.2	C112—C111—H1134	130.7
C8—C7—H72	108.4	C111—C112—C113	118.255 (3)
H71—C7—H72	109.1	C111—C112—H1135	103.7
C8—C7—C113	104.6 (8)	C113—C112—H1135	138.1
C8—C7—H71	108.5	C7—C113—C112	123.4 (13)
C113—C7—H71	115.7	C7—C113—C114	115.7 (14)
C8—C7—H72	108.4	C112—C113—C114	120.476
C113—C7—H72	110.3	C113—C114—C115	121.269 (3)
H71—C7—H72	109.1	C113—C114—H1131	119.0
C7—C8—N3	110.06 (16)	C115—C114—H1131	119.4
C7—C8—N2	109.68 (16)	C114—C115—C110	118.256 (3)
N3—C8—N2	110.04 (15)	C114—C115—H1132	124.3
C7—C8—H81	109.4	C110—C115—H1132	117.4
N3—C8—H81	108.3	C12—S1—N1	109.21 (9)
N2—C8—H81	109.4	C12—S1—O3	104.89 (8)
N2—C9—C10	123.02 (17)	N1—S1—O3	105.35 (9)
N2—C9—C14	120.47 (17)	C12—S1—O4	110.13 (9)
C10—C9—C14	116.51 (17)	N1—S1—O4	108.70 (9)
C9—C10—C11	121.45 (17)	O3—S1—O4	118.21 (9)
C9—C10—S2	118.93 (15)	C10—S2—N3	101.97 (9)
C11—C10—S2	119.61 (14)	C10—S2—O2	107.79 (9)
C10—C11—C12	121.48 (17)	N3—S2—O2	107.70 (9)
C10—C11—H111	119.0	C10—S2—O1	110.14 (9)
C12—C11—H111	119.5	N3—S2—O1	108.63 (9)
C11—C12—C13	118.12 (17)	O2—S2—O1	119.22 (9)
C11—C12—S1	115.45 (14)