3-[1-(4-Sulfamoylphen­yl)-5-p-tolyl-1H-pyrazol-3-yl]propanoic acid and 3-[5-(4-bromo­phen­yl)-1-(4-sulfamoyl­phen­yl)-1H-pyrazol-3-yl]­propanoic acid–dichloro­methane–diethyl ether–water (2/0.72/1/1)

The syntheses of 3-[1-(4-sulfamoylphenyl)-5-p-tolyl-1H-pyra­zol-3-yl]propanoic acid, C₁₉H₁₉N₃O₄S, (I), and 3-[5-(4-bromo­phen­yl)-1-(4-sulfamoyl­phen­yl)-1H-pyrazol-3-yl]­propanoic acid–dichloro­methane–diethyl ether–water (2/0.72/1/1), 2C₁₈H₁₆BrN₃O₄S·0.72CH₂Cl₂·C₄H₁₀O·H₂O, (II), are regio­specific. However, correct identification by spectroscopic techniques of the regioisomer formed is not trivial and single-crystal X-ray analysis provided the only means of unambiguous structure determination. Both structures make extensive use of hydrogen bonding and while compound (I) forms a straightforward unsolvated Z′ = 1 structure, compound (II) crystallizes as an unusual mixed solvate, with two crystallographically unique mol­ecules of the pyrazole derivative present in the asymmetric unit. The structure of (II) also features Br...Br inter­actions.

S1. Comment

Non-steroidal anti-inflammatory drugs are divided into three different categories, classical cyclooxygenase-1 (COX1) inhibitors, cyclooxygenase-2 (COX2) inhibitors and dual inhibitors (Charlier & Michaux, 2003). Pharmacologically, they possess analgesic, anti-inflammatory and antipyretic effects (Charlier & Michaux, 2003; Antoniou et al., 2007). COX1 inhibitors were replaced by COX2 inhibitors due to problems of severe gastrointestinal irritation and renal impairment experienced by COX1 patients (Copeland et al., 1995). In the USA, only the COX2 inhibitor celecoxib is approved for the treatement of various forms of arthritis and even then the Food and Drug Administration requires a warning label highlighting the potential of an increased risk of cardiovascular events (Antoniou et al., 2007). This prompted us to synthesize celecoxib analogues and to investigate their pharmacological properties. In the process of synthesizing these analogues, we found that a mixture of regioisomers was possible, identified as 1 and 2 in the scheme. Efforts to identify unambiguously the correct regioisomer by heteronuclear multiple-bond correlation (two-dimensional HMBC) and one-dimensional nuclear Overhauser effect (one-dimensional NOE) NMR spectroscopy were not successful, leaving single-crystal X-ray diffraction as the only possible means of unambiguous identification. We report here the structures of two related analogues, the title compounds, (I) and (II).

The asymmetric unit of (I) is shown in Fig. 1. The molecular dimensions are unexceptional and the compound is unambiguously regioisomer 1. A mean plane fitted through the central pyrazole ring has an r.m.s. deviation of 0.0036 Å, showing it to be essentially planar. The benzenesulfonamide ring is rotated by 28.73 (9)° from the pyrazole ring, while the tolyl ring is essentially planar (r.m.s. deviation of a plane fitted through all seven C atoms is 0.0137 Å) and is rotated by 70.26 (6)° from the pyrazole ring. The propanoic acid group has an extended structure but is not planar, with the C16—C17—C18—O4 torsion angle being -138.85 (16)°, and the r.m.s. deviation of a mean plane fitted through atoms C16, C17, C18 O3 and O4 is 0.2287 Å. This mean plane is rotated by 48.01(0.08)° from the pyrazole ring.

The crystal packing of (I) involves O—H···O, N—H···O, N—H···N and C—H···O hydrogen-bonding interactions. Fig. 2 shows the interactions involving O acceptor sites. There are two discrete motifs (Bernstein et al., 1995), an R²₂(10) interaction around an inversion centre formed by symmetry-related C—H···O interactions, and an R³₃(11) interaction formed by O—H···O, N—H···O and C—H···O interactions from three adjacent molecules. N—H···N interactions form a large discrete motif involving sites related by inversion symmetry. Hydrogen bonding is supported by C—H···π interactions and overall forms a three-dimensional hydrogen-bonded structure.

Compound (II) crystallizes, unusually, with three separate and chemically different solvent molecules of crystallization (dichloromethane, diethyl ether and water) present in the asymmetric unit, along with two molecules of the pyrazole derivative itself (Fig. 3). Thus, Z' = 1, since this represents the empirical chemical formula. In the following discussion, reference is made to the molecule containing atoms Br1–C18 (molecule A), with details for the molecule containing atoms Br51–C68 (molecule B) given in square brackets. Both molecules A and B are unambiguously regiosiomer 1.

The presence of three separate solvent molecules is rather unusual. Diethyl ether and dichloromethane were used for recrystallization and the identity of the remaining solvent molecule was established by analysis of difference Fourier maps, which clearly showed the water H atoms (they are also involved in hydrogen bonding, which is discussed below). The source of the water is probably due to using bench, rather than rigourously dried, solvents for recrystallization. The displacement ellipsoids for dichloromethane are rather large, especially when compared with the remainder of the structure and when considering that the data were measured at 115 K. In this case free refinement of the dichloromethane atom occupancies suggests that it is only ca 0.72 occupied, consistent with the observation that the crystals lost solvent when removed from the mother liquor. This model also yields lower refinement residuals than a fully ordered model. The presence of three different solvent molecules is not without precedent. The Cambridge Structural Database (CSD, Version 5.30 plus two updates; Allen, 2002) has 21 examples of reported structures containing diethyl ether, dichloromethane and water solvent molecules, all of them metal complexes.

The molecular dimensions of (II) are unexceptional. A mean plane fitted through the central pyrazole ring has an r.m.s. deviation of 0.0018 Å [0.0038 Å], showing it to be essentially planar. The benzenesulfonamide ring is rotated by 46.79 (10)° [48.72 (7)°] from the pyrazole ring, while the bromobenzene ring is essentially planar (r.m.s. deviation of a plane fitted through the one Br and all six C atoms is 0.0303 Å [0.0196 Å]) and is rotated by 44.85 (8)° [35.11 (9)°] from the pyrazole ring. The propanoic acid group has an extended planar structure (r.m.s. deviation of a mean plane fitted through atoms C16, C17, C18 O3 and O4 is 0.0581 Å [0.0403 Å]) and the group is rotated by 83.07 (10)° [24.85 (12)°] from the pyrazole ring. Fig. 4 shows an overlay of the two independent molecules, formed by fitting the two pyrazole rings, and from this the differences in the relative orientations of the benzyl rings and the propanoic acid groups can be clearly seen.

The crystal structure makes extensive use of hydrogen bonding, forming a thick two-dimensional hydrogen-bonded structure. Fig. 5 shows a c-axis projection of part of the structure, showing how two different hydrogen-bonding motifs, one R³₃(11) and one R³₃(13), allow the structure to propagate along the b axis. The role of water is crucial here since it acts as both donor (two O—H···O interactions) and acceptor (one N—H···O interaction), allowing both ring motifs to form. By contrast, the diethyl ether acts as a space-filling hydrogen-bond acceptor in a D(3) interaction with one sulfonamide donor site of molecule B. Further D(3) interactions, one N—H···O with sulfonamide as both donor and acceptor and a second N—H···O with sulfonamide as donor and an adjacent propanoic acid group as acceptor, allow the two-dimensional hydrogen-bonded sheet structure to grow.

The third direction is dominated by Br···Br interactions. The refined Br···Br distance is 3.5787 (9) Å. This is consistent with data derived from the CSD. A search for non-bonded Br···Br contacts between two Br atoms bonded to benzyl rings yielded 741 hits, with an average Br···Br distance of 3.576 Å. The Br···Br interactions, propagating along the [101] direction, link the hydrogen-bonded sheets together to form the overall crystal structure. Molecules of dichloromethane are also found in between the sheets, although there are no significant interactions between dichloromethane and adjacent molecules.

S2. Experimental

The title compounds were synthesized in a two-step procedure. 6-(4-Bromophenyl)-4,6-dioxohexanoic acid and 4,6-dioxo-6-p-tolylhexanoic acid were synthesized by a modified literature method (Murray et al., 1991), using NaHMDS in place of LiHMDS; further details are available in the archived CIF.

For the preparation of (I), a mixture of 4,6-dioxo-6-p-tolylhexanoic acid (1.639 g, 7 mmol), 4-sulfonamidophenylhydrazine hydrochloride (1.56 g, 7 mmol) and Et₃N (0.97 ml, 7 mmol) were combined in MeOH (8 ml) and stirred at room temperature for 6 h. The mixture was then concentrated in vacuo to a residue which was partitioned between Et₂O (40 ml) and 5% aqueous HCl (12.5 ml). The ether layer was separated, washed with 5% aqueous HCl (2 × 10 ml) and brine (10 ml), dried over Na₂SO₄, filtered, and concentrated to a residue. The crude residue was flash chromatographed on silica gel with a 6:2:1 eluant of hexane–EtOAc–AcOH, then recrystallized from methanol, yielding colourless crystals of (I). C₁₉H₁₉N₃O₄S, calculated mass 385.4 g mol^-1, observed mass (LQ-ESI MS) 386.1 g mol^-1.

For the preparation of (II), a mixture of 6-(4-bromophenyl)-4,6-dioxohexanoic acid (299 mg, 1 mmol), 4-sulfonamidophenylhydrazine hydrochloride (224 mg, 1 mmol) and Et₃N (0.1 ml, 1 mmol) were combined in MeOH (8 ml) and stirred at room temperature for 6 h. The mixture was then concentrated in vacuo to a residue which was partitioned between Et₂O (40 ml) and 5% aqueous HCl (12.5 ml). The ether layer was separated, washed with 5% aqueous HCl (2 × 10 ml) and brine (10 ml), dried over Na₂SO₄, filtered, and concentrated to a residue. The crude residue was flash chromatographed on silica gel with a 1:1 eluant of hexane and EtOAc, and recrystallized from diethyl ether and dichloromethane, yielding colourless crystals of (II). C₁₈H₁₆BrN₃O₄S, yield 0.47 g, calculated mass 450.31 g mol^-1, observed mass (LQ-ESI MS) 452.0 g mol^-1.

S3. Refinement

In (I), all atoms, including H atoms, were freely refined. In (II), O- and N-bound H atoms were refined with U_iso(H) = 1.2U_eq(O,N) but without distance restraints. Other H atoms were refined with U_iso(H) = 1.2U_eq(C) or 1.5U_eq(C_methyl), and with fixed C—H distances of 0.95 for aryl, 0.98 for methyl and 0.99 Å for methylene H atoms. The dichloromethane atom site occupancies were freely refined to 0.722.

Computing details

For both compounds, data collection: SMART (Bruker, 2007); cell refinement: SAINT (Bruker, 2007); data reduction: SAINT (Bruker, 2007); program(s) used to solve structure: SHELXTL (Sheldrick, 2008); program(s) used to refine structure: SHELXTL (Sheldrick, 2008); molecular graphics: ORTEP-3 for Windows (Farrugia, 1997) and Mercury (Version 2.2; Macrae et al., 2008); software used to prepare material for publication: SHELXTL (Sheldrick, 2008) and local programs.

Figures

	Fig. 1. The molecular structure of (I), with the atom-numbering scheme. Displacement ellipsoids are drawn at the 50% probability level and H atoms are shown as small spheres of arbitrary radii.
	Fig. 2. Hydrogen-bonding interactions (dotted lines) involving O acceptor sites in (I).
	Fig. 3. The asymmetric unit of (II), with the atom-numbering scheme. Displacement ellipsoids are drawn at the 50% probability level. C-bound H atoms have been omitted.
	Fig. 4. An overlay of molecules A (lighter shading) and B (black) in (II), formed by fitting the pyrazole rings, with an r.m.s. deviation of 0.00724(s.u.?) Å.
	Fig. 5. Part of the crystal structure of (II), projected along the c axis. The long a axis has been truncated. Molecules are coloured according to symmetry equivalence as in Fig. 4. Dashed lines indicate hydrogen bonds. Dichloromethane has been omitted. (In the electronic version of the journal, water is indicated in light purple and diethyl ether is shown in red. Blue dashed lines indicate hydrogen bonds in the direction of the b axis, while red dashed lines indicate further hydrogen bonding which propagates the structure in the c-axis direction.)

(I) 3-[1-(4-Sulfamoylphenyl)-5-p-tolyl-1H-pyrazol-3-yl]propanoic acid

Crystal data

C19H19N3O4S	Z = 2
Mr = 385.43	F(000) = 404
Triclinic, P1	Dx = 1.428 Mg m^−3
Hall symbol: -P 1	Mo Kα radiation, λ = 0.71073 Å
a = 5.8382 (14) Å	Cell parameters from 3944 reflections
b = 12.582 (3) Å	θ = 2.8–26.0°
c = 13.279 (3) Å	µ = 0.21 mm^−1
α = 106.928 (3)°	T = 115 K
β = 97.777 (3)°	Prism, colourless
γ = 101.077 (3)°	0.52 × 0.25 × 0.15 mm
V = 896.5 (4) Å^3

Data collection

Bruker SMART 1000 CCD area-detector diffractometer	3300 independent reflections
Radiation source: sealed tube	2824 reflections with I > 2σ(I)
Graphite monochromator	Rint = 0.025
thin–slice ω scans	θmax = 25.5°, θmin = 1.6°
Absorption correction: numerical (SADABS Version 2008/1; Sheldrick, 1996)	h = −7→7
Tmin = 0.898, Tmax = 0.989	k = −15→15
6690 measured reflections	l = −16→16

Refinement

Refinement on F^2	Primary atom site location: structure-invariant direct methods
Least-squares matrix: full	Secondary atom site location: difference Fourier map
R[F^2 > 2σ(F^2)] = 0.037	Hydrogen site location: difference Fourier map
wR(F^2) = 0.109	All H-atom parameters refined
S = 1.06	w = 1/[σ^2(Fo^2) + (0.0648P)^2 + 0.3322P] where P = (Fo^2 + 2Fc^2)/3
3300 reflections	(Δ/σ)max < 0.001
320 parameters	Δρmax = 0.43 e Å^−3
0 restraints	Δρmin = −0.41 e Å^−3

Special details

Experimental. 4,6-dioxo-6-p-tolylhexanoic acid

1.1 M of NaHMDS solution (56.8 ml, 62.5 mmol) and THF (100 ml) were added to a nitrogen-filled dry round-bottomed flask containing a stirrer and addition funnel maintained at 253 K. 4'-Methylacetophenone (8.386 g,) in THF (50 ml) was added to this solution slowly over 5 min and the solution was stirred at 253 K for 30 min. Succinic anhydride (2.5 g, 25 mmol) in THF (100 ml) was added to this solution. It was stirred for 1 h at 253 K, allowed to warm to room temperature and stirred overnight. At this time, 3 N aqueous HCl (50 ml) and Et₂O (250 ml) were added. The layers were separated, and the Et₂O/THF layer was extracted with 1 N NaOH (2 × 50 ml). The base extracts were combined and acidified to the cloudpoint (approximately pH 2) with 3 N aqueous HCl. The precipitate which formed was collected by filtration and dried under high vacuum. The residue was recrystallized from EtOAc. 4,6-Dioxo-6-p-tolylhexanoic acid, C₁₃H₁₄O₄, white solid (yield 1.93 g, 33%). Mass calculated: 234.25; mass observed: LCQ-ESI MS 235.0.

Geometry. All e.s.d.'s (except the e.s.d. in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell e.s.d.'s are taken into account individually in the estimation of e.s.d.'s in distances, angles and torsion angles; correlations between e.s.d.'s in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell e.s.d.'s is used for estimating e.s.d.'s involving l.s. planes.

Refinement. Refinement of F² against ALL reflections. The weighted R-factor wR and goodness of fit S are based on F², conventional R-factors R are based on F, with F set to zero for negative F². The threshold expression of F² > σ(F²) is used only for calculating R-factors(gt) etc. and is not relevant to the choice of reflections for refinement. R-factors based on F² are statistically about twice as large as those based on F, and R- factors based on ALL data will be even larger.

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

	x	y	z	Uiso*/Ueq
S1	−0.48826 (7)	0.25029 (4)	0.42341 (3)	0.01551 (15)
O1	−0.6249 (2)	0.15155 (11)	0.33376 (10)	0.0221 (3)
O2	−0.6121 (2)	0.32605 (11)	0.48363 (10)	0.0209 (3)
O3	0.8431 (2)	1.01701 (11)	0.38423 (11)	0.0269 (3)
O4	1.1563 (2)	0.94718 (12)	0.34640 (12)	0.0247 (3)
H4O	1.222 (5)	1.021 (3)	0.354 (2)	0.054 (8)*
N1	0.2549 (3)	0.63100 (12)	0.27877 (12)	0.0171 (3)
N2	0.1831 (3)	0.51422 (12)	0.23132 (12)	0.0164 (3)
N3	−0.3459 (3)	0.20193 (15)	0.50397 (13)	0.0191 (4)
H3A	−0.286 (4)	0.250 (2)	0.563 (2)	0.028 (6)*
H3B	−0.278 (4)	0.150 (2)	0.475 (2)	0.040 (7)*
C1	0.2966 (3)	0.47763 (16)	0.14826 (14)	0.0175 (4)
C2	0.4473 (3)	0.57394 (16)	0.14405 (15)	0.0195 (4)
H2	0.554 (4)	0.5750 (17)	0.0932 (17)	0.021 (5)*
C3	0.4159 (3)	0.66676 (15)	0.22625 (14)	0.0171 (4)
C4	0.0243 (3)	0.45057 (15)	0.27776 (13)	0.0156 (4)
C5	0.0334 (3)	0.33912 (16)	0.27229 (14)	0.0175 (4)
H5	0.149 (3)	0.3030 (16)	0.2403 (16)	0.013 (5)*
C6	−0.1226 (3)	0.27852 (16)	0.31774 (14)	0.0175 (4)
H6	−0.112 (3)	0.2031 (18)	0.3141 (16)	0.018 (5)*
C7	−0.2840 (3)	0.33043 (15)	0.36936 (14)	0.0154 (4)
C8	−0.2889 (3)	0.44215 (15)	0.37791 (14)	0.0180 (4)
H8	−0.402 (4)	0.4767 (17)	0.4124 (17)	0.019 (5)*
C9	−0.1349 (3)	0.50225 (16)	0.33127 (14)	0.0180 (4)
H9	−0.143 (3)	0.5755 (18)	0.3359 (16)	0.018 (5)*
C10	0.2531 (3)	0.35711 (15)	0.07841 (14)	0.0168 (4)
C11	0.4297 (3)	0.29761 (17)	0.08549 (15)	0.0214 (4)
H11	0.578 (4)	0.334 (2)	0.1343 (19)	0.032 (6)*
C12	0.3909 (4)	0.18445 (17)	0.02208 (15)	0.0225 (4)
H12	0.516 (4)	0.142 (2)	0.029 (2)	0.041 (7)*
C13	0.1770 (3)	0.12691 (16)	−0.05111 (14)	0.0203 (4)
C14	0.0036 (4)	0.18796 (17)	−0.06031 (15)	0.0227 (4)
H14	−0.143 (4)	0.151 (2)	−0.114 (2)	0.034 (6)*
C15	0.0396 (3)	0.30120 (17)	0.00393 (15)	0.0211 (4)
H15	−0.085 (4)	0.3428 (19)	−0.0031 (18)	0.027 (6)*
C16	0.5447 (3)	0.79016 (16)	0.25976 (16)	0.0187 (4)
H16A	0.452 (4)	0.8383 (19)	0.3009 (18)	0.028 (6)*
H16B	0.557 (4)	0.8101 (18)	0.1985 (18)	0.024 (6)*
C17	0.7966 (3)	0.81288 (16)	0.32558 (16)	0.0198 (4)
H17A	0.890 (4)	0.7658 (18)	0.2871 (17)	0.020 (5)*
H17B	0.792 (4)	0.7959 (18)	0.3901 (19)	0.026 (6)*
C18	0.9303 (3)	0.93609 (15)	0.35570 (14)	0.0177 (4)
C19	0.1375 (4)	0.00314 (17)	−0.11757 (17)	0.0266 (5)
H19A	0.155 (4)	−0.042 (2)	−0.071 (2)	0.035 (6)*
H19B	0.250 (4)	−0.008 (2)	−0.165 (2)	0.038 (7)*
H19C	−0.017 (5)	−0.027 (2)	−0.164 (2)	0.054 (8)*

Atomic displacement parameters (Ų)

	U^11	U^22	U^33	U^12	U^13	U^23
S1	0.0154 (2)	0.0149 (2)	0.0153 (2)	0.00330 (17)	0.00347 (17)	0.00365 (17)
O1	0.0210 (7)	0.0199 (7)	0.0194 (7)	−0.0009 (5)	0.0010 (5)	0.0025 (5)
O2	0.0218 (7)	0.0202 (7)	0.0233 (7)	0.0080 (5)	0.0086 (6)	0.0075 (6)
O3	0.0286 (8)	0.0184 (7)	0.0346 (8)	0.0097 (6)	0.0118 (6)	0.0052 (6)
O4	0.0177 (7)	0.0168 (7)	0.0365 (8)	0.0029 (5)	0.0059 (6)	0.0049 (6)
N1	0.0188 (8)	0.0136 (7)	0.0164 (8)	0.0026 (6)	0.0016 (6)	0.0028 (6)
N2	0.0171 (8)	0.0154 (7)	0.0143 (7)	0.0024 (6)	0.0027 (6)	0.0026 (6)
N3	0.0241 (9)	0.0180 (8)	0.0150 (8)	0.0079 (7)	0.0045 (7)	0.0031 (7)
C1	0.0168 (9)	0.0224 (10)	0.0122 (8)	0.0060 (7)	0.0021 (7)	0.0038 (7)
C2	0.0207 (10)	0.0215 (9)	0.0151 (9)	0.0042 (7)	0.0050 (8)	0.0040 (7)
C3	0.0170 (9)	0.0191 (9)	0.0155 (9)	0.0053 (7)	0.0014 (7)	0.0064 (7)
C4	0.0133 (9)	0.0187 (9)	0.0113 (8)	0.0007 (7)	−0.0007 (7)	0.0032 (7)
C5	0.0173 (9)	0.0198 (9)	0.0154 (9)	0.0072 (7)	0.0035 (7)	0.0040 (7)
C6	0.0195 (9)	0.0157 (9)	0.0169 (9)	0.0056 (7)	0.0026 (7)	0.0044 (7)
C7	0.0142 (9)	0.0179 (9)	0.0122 (8)	0.0015 (7)	0.0014 (7)	0.0041 (7)
C8	0.0181 (10)	0.0199 (9)	0.0149 (9)	0.0067 (7)	0.0046 (7)	0.0019 (7)
C9	0.0210 (10)	0.0137 (9)	0.0177 (9)	0.0052 (7)	0.0027 (7)	0.0027 (7)
C10	0.0183 (9)	0.0192 (9)	0.0117 (9)	0.0030 (7)	0.0048 (7)	0.0033 (7)
C11	0.0188 (10)	0.0258 (10)	0.0159 (9)	0.0041 (8)	0.0020 (8)	0.0029 (8)
C12	0.0248 (11)	0.0238 (10)	0.0197 (10)	0.0108 (8)	0.0052 (8)	0.0049 (8)
C13	0.0276 (10)	0.0192 (9)	0.0137 (9)	0.0033 (8)	0.0071 (8)	0.0050 (7)
C14	0.0206 (10)	0.0242 (10)	0.0173 (9)	0.0008 (8)	0.0004 (8)	0.0024 (8)
C15	0.0209 (10)	0.0234 (10)	0.0186 (9)	0.0071 (8)	0.0027 (8)	0.0058 (8)
C16	0.0201 (10)	0.0184 (9)	0.0195 (10)	0.0046 (7)	0.0062 (8)	0.0078 (8)
C17	0.0184 (10)	0.0189 (10)	0.0226 (10)	0.0054 (8)	0.0050 (8)	0.0069 (8)
C18	0.0194 (9)	0.0195 (9)	0.0139 (9)	0.0054 (7)	0.0029 (7)	0.0047 (7)
C19	0.0353 (13)	0.0208 (10)	0.0206 (10)	0.0052 (9)	0.0046 (9)	0.0038 (8)

Geometric parameters (Å, º)

S1—O1	1.4485 (13)	C7—C8	1.383 (3)
S1—O2	1.4313 (13)	C8—H8	0.95 (2)
S1—N3	1.5931 (17)	C8—C9	1.388 (3)
S1—C7	1.7735 (18)	C9—H9	0.92 (2)
O3—C18	1.211 (2)	C10—C11	1.394 (3)
O4—H4O	0.90 (3)	C10—C15	1.397 (3)
O4—C18	1.326 (2)	C11—H11	0.95 (2)
N1—N2	1.373 (2)	C11—C12	1.383 (3)
N1—C3	1.330 (2)	C12—H12	0.99 (3)
N2—C1	1.374 (2)	C12—C13	1.394 (3)
N2—C4	1.428 (2)	C13—C14	1.396 (3)
N3—H3A	0.82 (3)	C13—C19	1.505 (3)
N3—H3B	0.85 (3)	C14—H14	0.97 (2)
C1—C2	1.374 (3)	C14—C15	1.389 (3)
C1—C10	1.481 (2)	C15—H15	0.98 (2)
C2—H2	0.98 (2)	C16—H16A	0.98 (2)
C2—C3	1.408 (2)	C16—H16B	0.93 (2)
C3—C16	1.494 (3)	C16—C17	1.534 (3)
C4—C5	1.394 (3)	C17—H17A	0.97 (2)
C4—C9	1.390 (3)	C17—H17B	0.94 (2)
C5—H5	0.96 (2)	C17—C18	1.504 (3)
C5—C6	1.387 (3)	C19—H19A	0.96 (3)
C6—H6	0.95 (2)	C19—H19B	0.98 (3)
C6—C7	1.391 (3)	C19—H19C	0.96 (3)
O1—S1—O2	118.72 (8)	C8—C9—H9	118.3 (13)
O1—S1—N3	106.37 (9)	C1—C10—C11	119.66 (16)
O1—S1—C7	105.96 (8)	C1—C10—C15	121.67 (17)
O2—S1—N3	107.94 (9)	C11—C10—C15	118.66 (17)
O2—S1—C7	108.10 (8)	C10—C11—H11	120.2 (14)
N3—S1—C7	109.54 (9)	C10—C11—C12	120.48 (18)
H4O—O4—C18	109.3 (18)	H11—C11—C12	119.3 (14)
N2—N1—C3	105.55 (14)	C11—C12—H12	120.0 (15)
N1—N2—C1	111.17 (14)	C11—C12—C13	121.46 (18)
N1—N2—C4	118.11 (14)	H12—C12—C13	118.6 (15)
C1—N2—C4	130.52 (15)	C12—C13—C14	117.82 (17)
S1—N3—H3A	113.0 (16)	C12—C13—C19	120.40 (18)
S1—N3—H3B	116.1 (17)	C14—C13—C19	121.78 (18)
H3A—N3—H3B	121 (2)	C13—C14—H14	119.1 (14)
N2—C1—C2	106.25 (16)	C13—C14—C15	121.17 (18)
N2—C1—C10	124.67 (16)	H14—C14—C15	119.7 (14)
C2—C1—C10	129.06 (17)	C10—C15—C14	120.36 (18)
C1—C2—H2	125.3 (12)	C10—C15—H15	119.4 (13)
C1—C2—C3	106.23 (17)	C14—C15—H15	120.2 (13)
H2—C2—C3	128.5 (12)	C3—C16—H16A	110.0 (13)
N1—C3—C2	110.79 (16)	C3—C16—H16B	108.4 (13)
N1—C3—C16	120.90 (16)	C3—C16—C17	111.73 (15)
C2—C3—C16	128.24 (17)	H16A—C16—H16B	107.5 (18)
N2—C4—C5	120.44 (16)	H16A—C16—C17	110.5 (13)
N2—C4—C9	119.17 (16)	H16B—C16—C17	108.6 (13)
C5—C4—C9	120.37 (16)	C16—C17—H17A	112.0 (12)
C4—C5—H5	122.3 (12)	C16—C17—H17B	111.4 (14)
C4—C5—C6	119.62 (17)	C16—C17—C18	111.88 (15)
H5—C5—C6	118.0 (12)	H17A—C17—H17B	106.2 (18)
C5—C6—H6	118.3 (12)	H17A—C17—C18	107.9 (12)
C5—C6—C7	119.45 (17)	H17B—C17—C18	107.2 (13)
H6—C6—C7	122.2 (12)	O3—C18—O4	123.06 (17)
S1—C7—C6	118.87 (14)	O3—C18—C17	124.42 (17)
S1—C7—C8	119.94 (14)	O4—C18—C17	112.52 (15)
C6—C7—C8	121.18 (16)	C13—C19—H19A	110.1 (14)
C7—C8—H8	120.7 (12)	C13—C19—H19B	111.8 (14)
C7—C8—C9	119.33 (17)	C13—C19—H19C	112.4 (16)
H8—C8—C9	119.9 (12)	H19A—C19—H19B	108 (2)
C4—C9—C8	120.00 (17)	H19A—C19—H19C	109 (2)
C4—C9—H9	121.7 (13)	H19B—C19—H19C	105 (2)
C3—N1—N2—C1	−0.96 (19)	N3—S1—C7—C8	−125.47 (15)
C3—N1—N2—C4	174.50 (15)	S1—C7—C8—C9	−177.27 (13)
N1—N2—C1—C2	0.9 (2)	C6—C7—C8—C9	2.0 (3)
N1—N2—C1—C10	−177.90 (16)	C7—C8—C9—C4	−0.8 (3)
C4—N2—C1—C2	−173.84 (17)	N2—C4—C9—C8	−179.32 (15)
C4—N2—C1—C10	7.4 (3)	C5—C4—C9—C8	−1.2 (3)
N2—C1—C2—C3	−0.5 (2)	N2—C1—C10—C11	−110.9 (2)
C10—C1—C2—C3	178.26 (18)	N2—C1—C10—C15	69.9 (2)
N2—N1—C3—C2	0.6 (2)	C2—C1—C10—C11	70.6 (3)
N2—N1—C3—C16	−176.73 (15)	C2—C1—C10—C15	−108.6 (2)
C1—C2—C3—N1	−0.1 (2)	C1—C10—C11—C12	179.00 (17)
C1—C2—C3—C16	177.01 (18)	C15—C10—C11—C12	−1.8 (3)
N1—N2—C4—C5	−148.48 (16)	C10—C11—C12—C13	0.6 (3)
N1—N2—C4—C9	29.7 (2)	C11—C12—C13—C14	1.4 (3)
C1—N2—C4—C5	25.9 (3)	C11—C12—C13—C19	−178.80 (18)
C1—N2—C4—C9	−155.91 (18)	C12—C13—C14—C15	−2.2 (3)
N2—C4—C5—C6	−179.90 (15)	C19—C13—C14—C15	177.99 (18)
C9—C4—C5—C6	2.0 (3)	C13—C14—C15—C10	1.0 (3)
C4—C5—C6—C7	−0.8 (3)	C1—C10—C15—C14	−179.82 (17)
C5—C6—C7—S1	178.08 (13)	C11—C10—C15—C14	1.0 (3)
C5—C6—C7—C8	−1.2 (3)	N1—C3—C16—C17	100.8 (2)
O1—S1—C7—C6	−59.09 (16)	C2—C3—C16—C17	−76.0 (2)
O1—S1—C7—C8	120.17 (15)	C3—C16—C17—C18	177.72 (16)
O2—S1—C7—C6	172.65 (13)	C16—C17—C18—O3	40.4 (3)
O2—S1—C7—C8	−8.09 (17)	C16—C17—C18—O4	−138.85 (16)
N3—S1—C7—C6	55.27 (16)

Hydrogen-bond geometry (Å, º)

D—H···A	D—H	H···A	D···A	D—H···A
O4—H4O···O1^i	0.90 (3)	1.83 (3)	2.705 (2)	164 (3)
N3—H3A···N1^ii	0.82 (3)	2.16 (3)	2.941 (2)	160 (2)
N3—H3B···O3^iii	0.85 (3)	2.07 (3)	2.910 (2)	170 (2)
C8—H8···O2^iv	0.95 (2)	2.44 (2)	3.167 (2)	132.6 (16)
C16—H16A···O4^v	0.98 (2)	2.44 (2)	3.387 (2)	162.1 (18)

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

(II) Bis{3-[5-(4-bromophenyl)-1-(4-sulfamoylphenyl)-1H-pyrazol-3-yl]propanoic acid} dichloromethane 0.72-solvate diethyl ether solvate monohydrate

Crystal data

2C18H16BrN3O4S·0.72CH2Cl2·C4H10O·H2O	F(000) = 4307
Mr = 1054.11	Dx = 1.508 Mg m^−3 Dm = 0 Mg m^−3 Dm measured by not measured
Monoclinic, C2/c	Mo Kα radiation, λ = 0.71073 Å
Hall symbol: -C 2yc	Cell parameters from 8341 reflections
a = 49.255 (15) Å	θ = 2.2–25.5°
b = 11.702 (3) Å	µ = 1.98 mm^−1
c = 16.181 (5) Å	T = 115 K
β = 95.567 (4)°	Plate, colourless
V = 9283 (5) Å^3	0.51 × 0.31 × 0.05 mm
Z = 8

Data collection

Bruker SMART 1000 CCD area-detector diffractometer	8605 independent reflections
Radiation source: sealed tube	6781 reflections with I > 2σ(I)
Graphite monochromator	Rint = 0.033
thin–slice ω scans	θmax = 25.5°, θmin = 1.8°
Absorption correction: numerical (SADABS, Version 2008/1; Sheldrick, 1996)	h = −51→59
Tmin = 0.432, Tmax = 0.908	k = −10→14
23405 measured reflections	l = −19→19

Refinement

Refinement on F^2	Primary atom site location: structure-invariant direct methods
Least-squares matrix: full	Secondary atom site location: difference Fourier map
R[F^2 > 2σ(F^2)] = 0.037	Hydrogen site location: difference Fourier map
wR(F^2) = 0.105	H atoms treated by a mixture of independent and constrained refinement
S = 1.02	w = 1/[σ^2(Fo^2) + (0.0604P)^2 + 10.1055P] where P = (Fo^2 + 2Fc^2)/3
8605 reflections	(Δ/σ)max = 0.002
595 parameters	Δρmax = 0.84 e Å^−3
2 restraints	Δρmin = −0.43 e Å^−3

Special details

Experimental. 6-(4-bromophenyl)-4, 6-dioxohexanoic acid

1.1 M of NaHMDS solution (56.8 ml, 62.5 mmol) and THF (100 ml) were added to a nitrogen-filled dry round-bottomed flask containing a stirrer and addition funnel, and maintained at 253 K. 4'-Bromoacetophenone (12.44 g, 62.5 mmol) in THF (50 ml) was added to this solution slowly over 5 min and the solution was stirred at 253 K for 30 min. Succinic anhydride (2.5 g, 25 mmol) in THF (100 ml) was added to this solution. It was stirred for 1 h at 253 K, allowed to warm to room temperature and stirred overnight. At this time, 3 N aqueous HCl 50 ml and Et₂O 250 ml was added. The layers were separated, and the Et₂O/THF layer was extracted with 1 N NaOH (2 × 50 ml). The base extracts were combined and acidified to the cloudpoint (approximately pH 2) with 3 N aqueous HCl. The precipitate which formed was collected by filtration and dried under high vacuum. The residue was recrystallized from EtOAc. 6-(4-bromophenyl)-4,6-dioxohexanoic acid, C₁₂H₁₁BrO₄, white solid (yield 3.63 g, 48.5%). Mass calculated: 299.12; mass observed: LCQ-ESI MS 298.8.

Geometry. All e.s.d.'s (except the e.s.d. in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell e.s.d.'s are taken into account individually in the estimation of e.s.d.'s in distances, angles and torsion angles; correlations between e.s.d.'s in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell e.s.d.'s is used for estimating e.s.d.'s involving l.s. planes.

Refinement. Refinement of F² against ALL reflections. The weighted R-factor wR and goodness of fit S are based on F², conventional R-factors R are based on F, with F set to zero for negative F². The threshold expression of F² > σ(F²) is used only for calculating R-factors(gt) etc. and is not relevant to the choice of reflections for refinement. R-factors based on F² are statistically about twice as large as those based on F, and R- factors based on ALL data will be even larger.

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

	x	y	z	Uiso*/Ueq	Occ. (<1)
Br1	0.053486 (6)	0.58331 (3)	0.22339 (2)	0.03752 (11)
S1	0.171923 (13)	1.14155 (6)	0.29404 (4)	0.01934 (15)
O1	0.15423 (4)	1.19084 (17)	0.34983 (12)	0.0281 (5)
O2	0.16411 (4)	1.15060 (17)	0.20642 (12)	0.0257 (4)
O3	0.28741 (4)	0.31142 (16)	0.49517 (11)	0.0214 (4)
O4	0.29017 (4)	0.26197 (17)	0.36315 (11)	0.0229 (4)
H4O	0.3038 (4)	0.228 (2)	0.3827 (18)	0.028*
N1	0.21614 (4)	0.61947 (18)	0.40372 (13)	0.0166 (5)
N2	0.19044 (4)	0.64946 (18)	0.37132 (13)	0.0161 (5)
N3	0.20128 (5)	1.2017 (2)	0.31365 (16)	0.0244 (5)
H3A	0.2139 (7)	1.169 (3)	0.292 (2)	0.029*
H3B	0.2063 (6)	1.204 (3)	0.367 (2)	0.029*
C1	0.17324 (5)	0.5572 (2)	0.36694 (15)	0.0160 (5)
C2	0.18858 (5)	0.4656 (2)	0.39690 (16)	0.0180 (6)
H2	0.1825	0.3890	0.4017	0.022*
C3	0.21497 (5)	0.5077 (2)	0.41900 (15)	0.0166 (5)
C4	0.18517 (5)	0.7672 (2)	0.35227 (15)	0.0152 (5)
C5	0.17103 (5)	0.7975 (2)	0.27739 (15)	0.0180 (6)
H5	0.1644	0.7404	0.2389	0.022*
C6	0.16672 (5)	0.9125 (2)	0.25928 (16)	0.0192 (6)
H6	0.1572	0.9350	0.2080	0.023*
C7	0.17644 (5)	0.9940 (2)	0.31673 (15)	0.0162 (5)
C8	0.19055 (5)	0.9633 (2)	0.39217 (16)	0.0193 (6)
H8	0.1970	1.0204	0.4309	0.023*
C9	0.19502 (5)	0.8490 (2)	0.41004 (16)	0.0187 (6)
H9	0.2047	0.8265	0.4611	0.022*
C10	0.14423 (5)	0.5628 (2)	0.33579 (15)	0.0169 (5)
C11	0.13328 (6)	0.4779 (2)	0.28209 (16)	0.0219 (6)
H11	0.1445	0.4165	0.2676	0.026*
C12	0.10613 (6)	0.4818 (3)	0.24947 (17)	0.0256 (6)
H12	0.0988	0.4241	0.2125	0.031*
C13	0.09004 (5)	0.5712 (3)	0.27178 (16)	0.0227 (6)
C14	0.10003 (5)	0.6541 (2)	0.32799 (17)	0.0217 (6)
H14	0.0884	0.7132	0.3443	0.026*
C15	0.12708 (5)	0.6495 (2)	0.35991 (16)	0.0191 (6)
H15	0.1341	0.7057	0.3986	0.023*
C16	0.24003 (5)	0.4457 (2)	0.45524 (16)	0.0187 (6)
H16A	0.2346	0.3838	0.4920	0.022*
H16B	0.2519	0.4995	0.4895	0.022*
C17	0.25610 (5)	0.3946 (2)	0.38805 (16)	0.0191 (6)
H17A	0.2435	0.3494	0.3493	0.023*
H17B	0.2635	0.4575	0.3560	0.023*
C18	0.27922 (5)	0.3193 (2)	0.42215 (16)	0.0164 (5)
Br51	0.492625 (6)	1.03361 (3)	0.61729 (2)	0.04198 (12)
S51	0.399305 (14)	1.63701 (6)	0.43441 (4)	0.01941 (15)
O51	0.38078 (4)	1.70006 (16)	0.47994 (12)	0.0281 (5)
O52	0.42773 (4)	1.63621 (17)	0.46228 (12)	0.0285 (5)
O53	0.25523 (4)	0.86444 (18)	0.33345 (13)	0.0316 (5)
O54	0.26711 (4)	0.71210 (17)	0.41108 (12)	0.0248 (4)
H54O	0.2518 (3)	0.686 (3)	0.4019 (19)	0.030*
N51	0.33516 (4)	1.13208 (19)	0.40102 (13)	0.0169 (5)
N52	0.36116 (4)	1.15427 (18)	0.43420 (13)	0.0159 (5)
N53	0.39626 (5)	1.6870 (2)	0.34092 (14)	0.0217 (5)
H53A	0.3798 (7)	1.688 (3)	0.3222 (19)	0.026*
H53B	0.4078 (7)	1.662 (3)	0.315 (2)	0.026*
C51	0.37494 (5)	1.0551 (2)	0.45528 (15)	0.0169 (5)
C52	0.35705 (5)	0.9671 (2)	0.43323 (16)	0.0183 (6)
H52	0.3605	0.8875	0.4393	0.022*
C53	0.33273 (5)	1.0185 (2)	0.40016 (15)	0.0160 (5)
C54	0.37061 (5)	1.2695 (2)	0.43335 (15)	0.0153 (5)
C55	0.39497 (5)	1.2957 (2)	0.40020 (16)	0.0185 (6)
H55	0.4054	1.2371	0.3777	0.022*
C56	0.40379 (5)	1.4081 (2)	0.40053 (16)	0.0191 (6)
H56	0.4206	1.4271	0.3796	0.023*
C57	0.38785 (5)	1.4933 (2)	0.43187 (15)	0.0176 (6)
C58	0.36334 (5)	1.4673 (2)	0.46264 (16)	0.0189 (6)
H58	0.3525	1.5263	0.4827	0.023*
C59	0.35481 (5)	1.3545 (2)	0.46392 (15)	0.0173 (5)
H59	0.3382	1.3355	0.4857	0.021*
C60	0.40282 (5)	1.0513 (2)	0.49616 (16)	0.0184 (6)
C61	0.41998 (5)	0.9615 (2)	0.47758 (17)	0.0213 (6)
H61	0.4134	0.9044	0.4391	0.026*
C62	0.44630 (6)	0.9549 (3)	0.51439 (18)	0.0270 (7)
H62	0.4578	0.8932	0.5019	0.032*
C63	0.45587 (5)	1.0388 (3)	0.56956 (18)	0.0268 (7)
C64	0.43928 (6)	1.1266 (3)	0.59094 (18)	0.0290 (7)
H64	0.4460	1.1825	0.6302	0.035*
C65	0.41279 (6)	1.1325 (2)	0.55485 (17)	0.0233 (6)
H65	0.4012	1.1922	0.5700	0.028*
C66	0.30632 (5)	0.9671 (2)	0.36527 (17)	0.0200 (6)
H66A	0.3059	0.9649	0.3040	0.024*
H66B	0.2912	1.0172	0.3793	0.024*
C67	0.30137 (5)	0.8481 (2)	0.39636 (16)	0.0171 (5)
H67A	0.3136	0.7940	0.3710	0.020*
H67B	0.3059	0.8459	0.4573	0.020*
C68	0.27235 (5)	0.8103 (2)	0.37624 (15)	0.0174 (6)
O70	0.06540 (4)	1.0870 (2)	0.26448 (13)	0.0363 (5)
C73	0.10180 (7)	0.9800 (3)	0.3327 (2)	0.0388 (8)
H73A	0.1087	0.9627	0.2794	0.058*
H73B	0.1064	0.9172	0.3717	0.058*
H73C	0.1101	1.0508	0.3553	0.058*
C70	0.03701 (7)	1.1042 (4)	0.2460 (3)	0.0520 (10)
H70A	0.0283	1.1140	0.2982	0.062*
H70B	0.0288	1.0365	0.2166	0.062*
C72	0.07185 (7)	0.9939 (3)	0.3204 (2)	0.0425 (9)
H72A	0.0633	0.9227	0.2972	0.051*
H72B	0.0646	1.0094	0.3743	0.051*
C71	0.03203 (7)	1.2075 (3)	0.1930 (2)	0.0465 (9)
H71A	0.0408	1.2738	0.2214	0.070*
H71B	0.0124	1.2211	0.1829	0.070*
H71C	0.0397	1.1957	0.1400	0.070*
Cl1	−0.02610 (3)	0.88634 (17)	0.49011 (12)	0.0792 (7)	0.722 (3)
Cl2	0.00563 (4)	0.81360 (17)	0.35698 (10)	0.0813 (7)	0.722 (3)
C74	0.00165 (12)	0.8135 (6)	0.4615 (4)	0.0620 (16)	0.722 (3)
H74A	0.0004	0.7332	0.4800	0.074*	0.722 (3)
H74B	0.0183	0.8468	0.4916	0.074*	0.722 (3)
O7	0.24801 (5)	1.0920 (2)	0.26813 (14)	0.0340 (5)
H7A	0.2520 (7)	1.026 (3)	0.289 (2)	0.041*
H7B	0.2636 (8)	1.145 (3)	0.277 (2)	0.041*

Atomic displacement parameters (Ų)

	U^11	U^22	U^33	U^12	U^13	U^23
Br1	0.01759 (15)	0.0565 (2)	0.03656 (18)	−0.00299 (14)	−0.00699 (12)	0.00352 (15)
S1	0.0219 (3)	0.0143 (3)	0.0214 (3)	0.0000 (3)	0.0001 (3)	0.0046 (3)
O1	0.0330 (11)	0.0166 (11)	0.0357 (11)	0.0069 (9)	0.0083 (9)	0.0041 (9)
O2	0.0294 (11)	0.0218 (11)	0.0245 (10)	−0.0036 (9)	−0.0042 (8)	0.0076 (8)
O3	0.0211 (10)	0.0209 (11)	0.0212 (10)	0.0023 (8)	−0.0028 (8)	−0.0014 (8)
O4	0.0195 (10)	0.0265 (12)	0.0224 (10)	0.0107 (8)	0.0001 (8)	−0.0020 (8)
N1	0.0138 (10)	0.0160 (12)	0.0197 (11)	0.0014 (9)	−0.0001 (8)	−0.0011 (9)
N2	0.0139 (10)	0.0138 (12)	0.0203 (11)	−0.0009 (9)	0.0000 (8)	−0.0005 (9)
N3	0.0273 (13)	0.0195 (14)	0.0259 (13)	−0.0038 (10)	0.0007 (11)	−0.0004 (11)
C1	0.0164 (13)	0.0148 (14)	0.0171 (12)	−0.0004 (10)	0.0039 (10)	−0.0046 (10)
C2	0.0197 (13)	0.0138 (14)	0.0211 (13)	0.0001 (11)	0.0045 (10)	−0.0030 (11)
C3	0.0176 (13)	0.0142 (14)	0.0186 (12)	0.0011 (10)	0.0045 (10)	−0.0009 (10)
C4	0.0137 (12)	0.0126 (14)	0.0197 (13)	0.0014 (10)	0.0034 (10)	0.0013 (10)
C5	0.0213 (13)	0.0177 (15)	0.0151 (12)	−0.0030 (11)	0.0026 (10)	−0.0027 (11)
C6	0.0208 (13)	0.0212 (15)	0.0150 (12)	−0.0015 (11)	−0.0014 (10)	0.0023 (11)
C7	0.0162 (13)	0.0134 (14)	0.0193 (13)	−0.0009 (10)	0.0029 (10)	0.0040 (10)
C8	0.0207 (13)	0.0161 (15)	0.0204 (13)	−0.0034 (11)	−0.0015 (11)	−0.0005 (11)
C9	0.0193 (13)	0.0173 (15)	0.0186 (13)	0.0001 (11)	−0.0024 (10)	0.0024 (11)
C10	0.0176 (13)	0.0162 (14)	0.0169 (12)	−0.0023 (11)	0.0026 (10)	0.0007 (11)
C11	0.0238 (14)	0.0209 (15)	0.0215 (13)	−0.0011 (12)	0.0048 (11)	−0.0040 (12)
C12	0.0252 (15)	0.0282 (17)	0.0232 (14)	−0.0073 (13)	0.0007 (12)	−0.0051 (12)
C13	0.0136 (13)	0.0334 (18)	0.0203 (13)	−0.0057 (12)	−0.0018 (10)	0.0066 (12)
C14	0.0183 (13)	0.0212 (16)	0.0259 (14)	0.0011 (11)	0.0036 (11)	0.0034 (12)
C15	0.0184 (13)	0.0208 (15)	0.0186 (13)	−0.0014 (11)	0.0035 (10)	−0.0016 (11)
C16	0.0189 (13)	0.0157 (14)	0.0216 (13)	0.0022 (11)	0.0028 (11)	0.0021 (11)
C17	0.0174 (13)	0.0181 (15)	0.0217 (13)	0.0035 (11)	0.0015 (10)	0.0002 (11)
C18	0.0144 (12)	0.0117 (14)	0.0229 (14)	−0.0036 (10)	0.0014 (10)	−0.0001 (11)
Br51	0.01818 (16)	0.0604 (3)	0.0445 (2)	−0.00678 (14)	−0.01157 (13)	0.01223 (17)
S51	0.0265 (3)	0.0133 (3)	0.0180 (3)	−0.0033 (3)	0.0002 (3)	−0.0009 (3)
O51	0.0447 (12)	0.0140 (10)	0.0266 (10)	−0.0014 (9)	0.0089 (9)	−0.0037 (8)
O52	0.0301 (11)	0.0232 (11)	0.0301 (11)	−0.0073 (9)	−0.0079 (9)	0.0023 (9)
O53	0.0212 (10)	0.0305 (12)	0.0412 (12)	−0.0035 (9)	−0.0068 (9)	0.0151 (10)
O54	0.0176 (9)	0.0208 (11)	0.0343 (11)	−0.0077 (8)	−0.0059 (8)	0.0063 (9)
N51	0.0152 (11)	0.0164 (12)	0.0188 (10)	0.0017 (9)	0.0012 (8)	0.0021 (9)
N52	0.0139 (10)	0.0143 (12)	0.0192 (11)	0.0000 (9)	−0.0012 (8)	0.0008 (9)
N53	0.0228 (12)	0.0216 (13)	0.0207 (12)	0.0000 (11)	0.0015 (10)	0.0026 (10)
C51	0.0184 (13)	0.0152 (14)	0.0171 (12)	0.0030 (11)	0.0014 (10)	0.0026 (10)
C52	0.0174 (13)	0.0147 (14)	0.0228 (13)	−0.0014 (11)	0.0014 (10)	0.0039 (11)
C53	0.0175 (13)	0.0135 (14)	0.0171 (12)	−0.0017 (10)	0.0028 (10)	0.0027 (10)
C54	0.0179 (12)	0.0124 (13)	0.0146 (12)	−0.0008 (10)	−0.0032 (10)	0.0029 (10)
C55	0.0186 (13)	0.0159 (15)	0.0208 (13)	0.0021 (11)	0.0022 (10)	0.0004 (11)
C56	0.0196 (13)	0.0167 (15)	0.0217 (13)	−0.0008 (11)	0.0050 (11)	0.0014 (11)
C57	0.0225 (14)	0.0154 (14)	0.0140 (12)	−0.0021 (11)	−0.0025 (10)	0.0014 (10)
C58	0.0220 (14)	0.0162 (15)	0.0182 (13)	0.0037 (11)	0.0001 (10)	−0.0009 (11)
C59	0.0178 (13)	0.0187 (15)	0.0157 (12)	−0.0003 (11)	0.0023 (10)	0.0009 (11)
C60	0.0166 (13)	0.0172 (14)	0.0210 (13)	−0.0025 (11)	0.0004 (10)	0.0053 (11)
C61	0.0204 (14)	0.0174 (15)	0.0256 (14)	−0.0006 (11)	0.0005 (11)	0.0032 (11)
C62	0.0186 (14)	0.0281 (17)	0.0340 (16)	0.0035 (12)	0.0001 (12)	0.0074 (13)
C63	0.0137 (13)	0.0365 (18)	0.0283 (15)	−0.0053 (12)	−0.0070 (11)	0.0131 (13)
C64	0.0298 (16)	0.0270 (17)	0.0277 (15)	−0.0061 (13)	−0.0093 (12)	0.0034 (13)
C65	0.0262 (15)	0.0184 (15)	0.0243 (14)	−0.0011 (12)	−0.0036 (11)	0.0020 (12)
C66	0.0174 (13)	0.0193 (15)	0.0229 (13)	−0.0002 (11)	−0.0004 (11)	0.0037 (11)
C67	0.0160 (13)	0.0166 (14)	0.0185 (12)	0.0001 (11)	0.0011 (10)	−0.0015 (11)
C68	0.0180 (13)	0.0179 (15)	0.0159 (12)	−0.0031 (11)	0.0006 (10)	−0.0033 (11)
O70	0.0277 (11)	0.0464 (15)	0.0352 (12)	0.0004 (10)	0.0051 (9)	0.0110 (11)
C73	0.044 (2)	0.042 (2)	0.0291 (16)	−0.0014 (16)	−0.0039 (14)	0.0079 (15)
C70	0.0313 (18)	0.055 (3)	0.071 (3)	0.0071 (17)	0.0131 (18)	0.017 (2)
C72	0.042 (2)	0.040 (2)	0.047 (2)	−0.0008 (16)	0.0131 (16)	0.0127 (16)
C71	0.0365 (19)	0.061 (3)	0.0431 (19)	0.0124 (17)	0.0086 (16)	0.0072 (18)
Cl1	0.0474 (9)	0.0938 (14)	0.0966 (13)	0.0122 (8)	0.0075 (8)	−0.0056 (10)
Cl2	0.0996 (14)	0.0839 (14)	0.0610 (10)	−0.0189 (10)	0.0115 (9)	0.0005 (9)
C74	0.055 (4)	0.072 (4)	0.058 (3)	0.006 (3)	0.001 (3)	0.009 (3)
O7	0.0326 (12)	0.0317 (14)	0.0369 (12)	0.0045 (11)	−0.0013 (10)	0.0037 (10)

Geometric parameters (Å, º)

Br1—C13	1.898 (3)	N52—C51	1.371 (3)
S1—O1	1.435 (2)	N52—C54	1.427 (3)
S1—O2	1.436 (2)	N53—H53A	0.84 (3)
S1—N3	1.612 (3)	N53—H53B	0.79 (3)
S1—C7	1.775 (3)	C51—C52	1.380 (4)
O3—C18	1.214 (3)	C51—C60	1.466 (4)
O4—H4O	0.816 (10)	C52—H52	0.950
O4—C18	1.324 (3)	C52—C53	1.400 (4)
N1—N2	1.368 (3)	C53—C66	1.494 (4)
N1—C3	1.333 (3)	C54—C55	1.395 (4)
N2—C1	1.370 (3)	C54—C59	1.384 (4)
N2—C4	1.430 (3)	C55—H55	0.950
N3—H3A	0.84 (3)	C55—C56	1.386 (4)
N3—H3B	0.88 (3)	C56—H56	0.950
C1—C2	1.372 (4)	C56—C57	1.394 (4)
C1—C10	1.470 (4)	C57—C58	1.384 (4)
C2—H2	0.950	C58—H58	0.950
C2—C3	1.403 (4)	C58—C59	1.387 (4)
C3—C16	1.501 (4)	C59—H59	0.950
C4—C5	1.384 (4)	C60—C61	1.399 (4)
C4—C9	1.392 (4)	C60—C65	1.398 (4)
C5—H5	0.950	C61—H61	0.950
C5—C6	1.390 (4)	C61—C62	1.375 (4)
C6—H6	0.950	C62—H62	0.950
C6—C7	1.384 (4)	C62—C63	1.379 (4)
C7—C8	1.392 (4)	C63—C64	1.377 (4)
C8—H8	0.950	C64—H64	0.950
C8—C9	1.383 (4)	C64—C65	1.378 (4)
C9—H9	0.950	C65—H65	0.950
C10—C11	1.393 (4)	C66—H66A	0.990
C10—C15	1.400 (4)	C66—H66B	0.990
C11—H11	0.950	C66—C67	1.509 (4)
C11—C12	1.390 (4)	C67—H67A	0.990
C12—H12	0.950	C67—H67B	0.990
C12—C13	1.381 (4)	C67—C68	1.501 (3)
C13—C14	1.387 (4)	O70—C70	1.416 (4)
C14—H14	0.950	O70—C72	1.432 (4)
C14—C15	1.383 (4)	C73—H73A	0.980
C15—H15	0.950	C73—H73B	0.980
C16—H16A	0.990	C73—H73C	0.980
C16—H16B	0.990	C73—C72	1.478 (5)
C16—C17	1.527 (4)	C70—H70A	0.990
C17—H17A	0.990	C70—H70B	0.990
C17—H17B	0.990	C70—C71	1.489 (5)
C17—C18	1.502 (4)	C72—H72A	0.990
Br51—C63	1.899 (3)	C72—H72B	0.990
S51—O51	1.432 (2)	C71—H71A	0.980
S51—O52	1.429 (2)	C71—H71B	0.980
S51—N53	1.615 (2)	C71—H71C	0.980
S51—C57	1.773 (3)	Cl1—C74	1.712 (6)
O53—C68	1.216 (3)	Cl2—C74	1.722 (6)
O54—H54O	0.814 (10)	C74—H74A	0.990
O54—C68	1.317 (3)	C74—H74B	0.990
N51—N52	1.365 (3)	O7—H7A	0.86 (4)
N51—C53	1.334 (3)	O7—H7B	0.98 (4)
O1—S1—O2	118.06 (12)	C52—C51—C60	129.8 (2)
O1—S1—N3	106.76 (14)	C51—C52—H52	126.9
O1—S1—C7	109.42 (12)	C51—C52—C53	106.2 (2)
O2—S1—N3	108.15 (13)	H52—C52—C53	126.9
O2—S1—C7	106.98 (12)	N51—C53—C52	110.6 (2)
N3—S1—C7	106.99 (13)	N51—C53—C66	118.6 (2)
H4O—O4—C18	110 (2)	C52—C53—C66	130.8 (2)
N2—N1—C3	105.5 (2)	N52—C54—C55	120.3 (2)
N1—N2—C1	111.2 (2)	N52—C54—C59	118.7 (2)
N1—N2—C4	118.1 (2)	C55—C54—C59	121.0 (2)
C1—N2—C4	130.5 (2)	C54—C55—H55	120.4
S1—N3—H3A	114 (2)	C54—C55—C56	119.2 (2)
S1—N3—H3B	111 (2)	H55—C55—C56	120.4
H3A—N3—H3B	107 (3)	C55—C56—H56	120.2
N2—C1—C2	106.3 (2)	C55—C56—C57	119.5 (2)
N2—C1—C10	123.9 (2)	H56—C56—C57	120.2
C2—C1—C10	129.8 (2)	S51—C57—C56	119.8 (2)
C1—C2—H2	126.9	S51—C57—C58	119.1 (2)
C1—C2—C3	106.3 (2)	C56—C57—C58	121.1 (2)
H2—C2—C3	126.9	C57—C58—H58	120.3
N1—C3—C2	110.7 (2)	C57—C58—C59	119.4 (2)
N1—C3—C16	119.8 (2)	H58—C58—C59	120.3
C2—C3—C16	129.5 (2)	C54—C59—C58	119.8 (2)
N2—C4—C5	120.1 (2)	C54—C59—H59	120.1
N2—C4—C9	118.3 (2)	C58—C59—H59	120.1
C5—C4—C9	121.7 (2)	C51—C60—C61	119.0 (2)
C4—C5—H5	120.4	C51—C60—C65	122.5 (2)
C4—C5—C6	119.1 (2)	C61—C60—C65	118.4 (2)
H5—C5—C6	120.4	C60—C61—H61	119.6
C5—C6—H6	120.3	C60—C61—C62	120.8 (3)
C5—C6—C7	119.3 (2)	H61—C61—C62	119.6
H6—C6—C7	120.3	C61—C62—H62	120.4
S1—C7—C6	120.2 (2)	C61—C62—C63	119.3 (3)
S1—C7—C8	118.3 (2)	H62—C62—C63	120.4
C6—C7—C8	121.5 (2)	Br51—C63—C62	119.5 (2)
C7—C8—H8	120.4	Br51—C63—C64	119.2 (2)
C7—C8—C9	119.3 (2)	C62—C63—C64	121.3 (3)
H8—C8—C9	120.4	C63—C64—H64	120.3
C4—C9—C8	119.1 (2)	C63—C64—C65	119.4 (3)
C4—C9—H9	120.4	H64—C64—C65	120.3
C8—C9—H9	120.4	C60—C65—C64	120.6 (3)
C1—C10—C11	119.1 (2)	C60—C65—H65	119.7
C1—C10—C15	122.0 (2)	C64—C65—H65	119.7
C11—C10—C15	118.9 (2)	C53—C66—H66A	108.7
C10—C11—H11	119.6	C53—C66—H66B	108.7
C10—C11—C12	120.9 (3)	C53—C66—C67	114.1 (2)
H11—C11—C12	119.6	H66A—C66—H66B	107.6
C11—C12—H12	120.6	H66A—C66—C67	108.7
C11—C12—C13	118.8 (3)	H66B—C66—C67	108.7
H12—C12—C13	120.6	C66—C67—H67A	109.1
Br1—C13—C12	119.6 (2)	C66—C67—H67B	109.1
Br1—C13—C14	118.7 (2)	C66—C67—C68	112.4 (2)
C12—C13—C14	121.7 (2)	H67A—C67—H67B	107.9
C13—C14—H14	120.5	H67A—C67—C68	109.1
C13—C14—C15	119.1 (3)	H67B—C67—C68	109.1
H14—C14—C15	120.5	O53—C68—O54	123.0 (2)
C10—C15—C14	120.7 (2)	O53—C68—C67	124.3 (2)
C10—C15—H15	119.7	O54—C68—C67	112.7 (2)
C14—C15—H15	119.7	C70—O70—C72	113.3 (2)
C3—C16—H16A	109.2	H73A—C73—H73B	109.5
C3—C16—H16B	109.2	H73A—C73—H73C	109.5
C3—C16—C17	112.0 (2)	H73A—C73—C72	109.5
H16A—C16—H16B	107.9	H73B—C73—H73C	109.5
H16A—C16—C17	109.2	H73B—C73—C72	109.5
H16B—C16—C17	109.2	H73C—C73—C72	109.5
C16—C17—H17A	108.9	O70—C70—H70A	109.7
C16—C17—H17B	108.9	O70—C70—H70B	109.7
C16—C17—C18	113.3 (2)	O70—C70—C71	110.0 (3)
H17A—C17—H17B	107.7	H70A—C70—H70B	108.2
H17A—C17—C18	108.9	H70A—C70—C71	109.7
H17B—C17—C18	108.9	H70B—C70—C71	109.7
O3—C18—O4	122.9 (2)	O70—C72—C73	109.0 (3)
O3—C18—C17	124.8 (2)	O70—C72—H72A	109.9
O4—C18—C17	112.3 (2)	O70—C72—H72B	109.9
O51—S51—O52	119.66 (13)	C73—C72—H72A	109.9
O51—S51—N53	106.84 (13)	C73—C72—H72B	109.9
O51—S51—C57	106.46 (12)	H72A—C72—H72B	108.3
O52—S51—N53	107.28 (13)	C70—C71—H71A	109.5
O52—S51—C57	107.51 (12)	C70—C71—H71B	109.5
N53—S51—C57	108.74 (12)	C70—C71—H71C	109.5
H54O—O54—C68	117 (2)	H71A—C71—H71B	109.5
N52—N51—C53	105.9 (2)	H71A—C71—H71C	109.5
N51—N52—C51	111.1 (2)	H71B—C71—H71C	109.5
N51—N52—C54	118.1 (2)	Cl1—C74—Cl2	115.8 (3)
C51—N52—C54	130.4 (2)	Cl1—C74—H74A	108.3
S51—N53—H53A	110 (2)	Cl1—C74—H74B	108.3
S51—N53—H53B	110 (2)	Cl2—C74—H74A	108.3
H53A—N53—H53B	122 (3)	Cl2—C74—H74B	108.3
N52—C51—C52	106.2 (2)	H74A—C74—H74B	107.4
N52—C51—C60	123.9 (2)	H7A—O7—H7B	111 (3)
C3—N1—N2—C1	0.4 (3)	C53—N51—N52—C54	172.4 (2)
C3—N1—N2—C4	177.1 (2)	N51—N52—C51—C52	1.0 (3)
N1—N2—C1—C2	−0.5 (3)	N51—N52—C51—C60	−176.8 (2)
N1—N2—C1—C10	179.2 (2)	C54—N52—C51—C52	−171.3 (2)
C4—N2—C1—C2	−176.6 (2)	C54—N52—C51—C60	10.9 (4)
C4—N2—C1—C10	3.1 (4)	N52—C51—C52—C53	−0.7 (3)
N2—C1—C2—C3	0.3 (3)	C60—C51—C52—C53	176.9 (3)
C10—C1—C2—C3	−179.4 (2)	N52—N51—C53—C52	0.4 (3)
N2—N1—C3—C2	−0.2 (3)	N52—N51—C53—C66	−178.8 (2)
N2—N1—C3—C16	179.9 (2)	C51—C52—C53—N51	0.2 (3)
C1—C2—C3—N1	0.0 (3)	C51—C52—C53—C66	179.3 (3)
C1—C2—C3—C16	179.8 (2)	N51—N52—C54—C55	−127.4 (2)
N1—N2—C4—C5	134.3 (2)	N51—N52—C54—C59	50.9 (3)
N1—N2—C4—C9	−44.5 (3)	C51—N52—C54—C55	44.5 (4)
C1—N2—C4—C5	−49.7 (4)	C51—N52—C54—C59	−137.2 (3)
C1—N2—C4—C9	131.4 (3)	N52—C54—C55—C56	−179.6 (2)
N2—C4—C5—C6	−178.4 (2)	C59—C54—C55—C56	2.1 (4)
C9—C4—C5—C6	0.4 (4)	C54—C55—C56—C57	−1.7 (4)
C4—C5—C6—C7	−0.6 (4)	C55—C56—C57—S51	178.8 (2)
C5—C6—C7—S1	178.47 (19)	C55—C56—C57—C58	0.0 (4)
C5—C6—C7—C8	0.3 (4)	O51—S51—C57—C56	−172.0 (2)
O1—S1—C7—C6	114.7 (2)	O51—S51—C57—C58	6.8 (2)
O1—S1—C7—C8	−67.1 (2)	O52—S51—C57—C56	−42.6 (2)
O2—S1—C7—C6	−14.3 (2)	O52—S51—C57—C58	136.2 (2)
O2—S1—C7—C8	164.0 (2)	N53—S51—C57—C56	73.2 (2)
N3—S1—C7—C6	−130.0 (2)	N53—S51—C57—C58	−108.0 (2)
N3—S1—C7—C8	48.2 (2)	S51—C57—C58—C59	−177.40 (19)
S1—C7—C8—C9	−178.05 (19)	C56—C57—C58—C59	1.4 (4)
C6—C7—C8—C9	0.2 (4)	N52—C54—C59—C58	−179.0 (2)
C7—C8—C9—C4	−0.3 (4)	C55—C54—C59—C58	−0.7 (4)
N2—C4—C9—C8	178.9 (2)	C57—C58—C59—C54	−1.0 (4)
C5—C4—C9—C8	0.0 (4)	N52—C51—C60—C61	−146.7 (3)
N2—C1—C10—C11	136.1 (3)	N52—C51—C60—C65	35.0 (4)
N2—C1—C10—C15	−45.3 (4)	C52—C51—C60—C61	36.0 (4)
C2—C1—C10—C11	−44.3 (4)	C52—C51—C60—C65	−142.2 (3)
C2—C1—C10—C15	134.3 (3)	C51—C60—C61—C62	179.8 (2)
C1—C10—C11—C12	−178.2 (2)	C65—C60—C61—C62	−1.8 (4)
C15—C10—C11—C12	3.2 (4)	C60—C61—C62—C63	−0.7 (4)
C10—C11—C12—C13	−0.5 (4)	C61—C62—C63—Br51	−177.5 (2)
C11—C12—C13—Br1	176.5 (2)	C61—C62—C63—C64	2.6 (4)
C11—C12—C13—C14	−2.4 (4)	Br51—C63—C64—C65	178.3 (2)
Br1—C13—C14—C15	−176.4 (2)	C62—C63—C64—C65	−1.8 (4)
C12—C13—C14—C15	2.6 (4)	C63—C64—C65—C60	−0.9 (4)
C13—C14—C15—C10	0.2 (4)	C51—C60—C65—C64	−179.1 (3)
C1—C10—C15—C14	178.4 (2)	C61—C60—C65—C64	2.6 (4)
C11—C10—C15—C14	−3.1 (4)	N51—C53—C66—C67	−157.0 (2)
N1—C3—C16—C17	−92.2 (3)	C52—C53—C66—C67	24.0 (4)
C2—C3—C16—C17	87.9 (3)	C53—C66—C67—C68	166.6 (2)
C3—C16—C17—C18	−172.5 (2)	C66—C67—C68—O53	6.2 (4)
C16—C17—C18—O3	−10.5 (4)	C66—C67—C68—O54	−172.8 (2)
C16—C17—C18—O4	170.1 (2)	C72—O70—C70—C71	175.6 (3)
C53—N51—N52—C51	−0.9 (3)	C70—O70—C72—C73	177.5 (3)

Hydrogen-bond geometry (Å, º)

D—H···A	D—H	H···A	D···A	D—H···A
O7—H7A···O53	0.86 (4)	2.02 (4)	2.874 (3)	171 (3)
O7—H7B···O4^i	0.98 (4)	2.28 (4)	3.164 (3)	149 (3)
O4—H4O···N51^ii	0.82 (1)	1.91 (1)	2.708 (3)	165 (3)
O54—H54O···N1	0.81 (1)	1.92 (1)	2.726 (3)	169 (3)
N3—H3A···O7	0.84 (3)	1.97 (3)	2.796 (4)	166 (3)
N3—H3B···O3^iii	0.88 (3)	2.22 (3)	3.094 (3)	170 (3)
N53—H53A···O2^iv	0.84 (3)	2.21 (3)	3.028 (3)	165 (3)
N53—H53B···O70^iv	0.79 (3)	2.12 (3)	2.910 (3)	172 (3)
C8—H8···O3^iii	0.95	2.39	3.327 (3)	169
C9—H9···O54^iii	0.95	2.42	3.364 (3)	173
C15—H15···O51^v	0.95	2.43	3.187 (3)	137
C52—H52···O51^ii	0.95	2.47	3.395 (3)	164
C59—H59···O3^i	0.95	2.53	3.443 (3)	160
C5—H5···N51^vi	0.95	2.60	3.465 (3)	152
C17—H17B···O7^vi	0.99	2.57	3.415 (4)	143
C67—H67A···O2^vi	0.99	2.42	3.398 (3)	169
C71—H71C···O52^vi	0.98	2.51	3.451 (4)	160
C67—H67A···O2^vi	0.99	2.42	3.398 (3)	169
C71—H71C···O52^vi	0.98	2.51	3.451 (4)	160

Symmetry codes: (i) x, y+1, z; (ii) x, y−1, z; (iii) −x+1/2, −y+3/2, −z+1; (iv) −x+1/2, y+1/2, −z+1/2; (v) −x+1/2, −y+5/2, −z+1; (vi) −x+1/2, y−1/2, −z+1/2.