Polymorphism in two biologically active dihydropyrimidinium hydrochloride derivatives: quantitative inputs towards the energetics associated with crystal packing

A new polymorph belonging to the tetrahydropyrimidinium class of compounds, namely 6-(4-chlorophenyl)-5-(methoxycarbonyl)-4-methyl-2-(3-(trifluoromethylthio)phenylamino)-3,6-dihydropyrimidin-1-ium chloride, and a hydrate of 2-(3-bromophenylamino)-6-(4-chlorophenyl)-5-(methoxycarbonyl)-4-methyl-3,6-dihydropyrimidin-1-ium chloride, have been isolated and characterized using single-crystal X-ray diffraction (XRD). A detailed comprehensive analysis of the crystal packing in terms of the associated intermolecular interactions and a quantification of their interaction energies have been performed for both forms of the two different organic salts (A and B) using X-ray crystallography and computational methods such as density functional theory (DFT) quantum mechanical calculations, PIXEL lattice-energy calculations (with decomposition of total lattice energy into the Coulombic, polarization, dispersion and repulsion contribution), the calculation of the Madelung constant (the EUGEN method), Hirshfeld and two-dimensional fingerprint plots. The presence of ionic [N—H]⁺...Cl⁻ and [C—H]⁺...Cl⁻ hydrogen bonds mainly stabilizes the crystal packing in both forms A and B, while in the case of B·H₂O [N—H]⁺...O_water and O_water—H...Cl⁻ hydrogen bonds along with [N—H]⁺...Cl⁻ and [C—H]⁺...Cl⁻ provide stability to the crystal packing. The lattice-energy calculations from both PIXEL and EUGEN methods revealed that in the case of A, form (I) (monoclinic) is more stable whereas for B it is the anhydrous form that is more stable. The analysis of the `Madelung mode' of crystal packing of two forms of A and B and its hydrates suggest that differences exist in the position of the charged ions/atoms in the organic solid state. The R/E (distance–energy) plots for all the crystal structures show that the molecular pairs in their crystal packing are connected with either highly stabilizing (due to the presence of organic R⁺ and Cl⁻) or highly destabilizing Coulombic contacts. The difference in crystal packing and associated intermolecular interactions between polymorphs (in the case of A) or the hydrates (in the case of B) have been clearly elucidated by the analysis of Hirshfeld surfaces and two-dimensional fingerprint plots. The relative contributions of the various interactions to the Hirshfeld surface for the cationic (dihydropyrimidinium) part and anionic (chloride ion) part for the two forms of A and B and its hydrate were observed to be different.

S1. Experimental

S1.1. Refinement

Crystal data, data collection and structure refinement details are summarized in Table 1.

S2. Results and discussion

Computing details

For both compounds, program(s) used to solve structure: SHELXS97 (Sheldrick, 1990); program(s) used to refine structure: SHELXL97 (Sheldrick, 1997).

Figures

(A)

Crystal data

C20H18ClF3N3O2S·Cl	Z = 2
Mr = 492.33	F(000) = 504
Triclinic, P1	Dx = 1.503 Mg m^−3
Hall symbol: -P 1	Mo Kα radiation, λ = 0.71073 Å
a = 7.7005 (6) Å	Cell parameters from 10753 reflections
b = 11.2405 (10) Å	θ = 2.0–28.5°
c = 13.7322 (12) Å	µ = 0.44 mm^−1
α = 111.249 (2)°	T = 100 K
β = 90.907 (2)°	Block, colourless
γ = 99.769 (2)°	0.17 × 0.09 × 0.04 mm
V = 1087.88 (16) Å^3

Data collection

Bruker KAPPA APEX II DUO diffractometer	3549 reflections with I > 2σ(I)
Radiation source: fine-focus sealed tube	Rint = 0.037
Graphite monochromator	θmax = 28.5°, θmin = 1.6°
Absorption correction: multi-scan SADABS	h = −9→10
Tmin = 0.929, Tmax = 0.983	k = −15→14
10760 measured reflections	l = −8→18
5436 independent reflections

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)] = 0.045	Hydrogen site location: inferred from neighbouring sites
wR(F^2) = 0.107	H atoms treated by a mixture of independent and constrained refinement
S = 1.01	w = 1/[σ^2(Fo^2) + (0.0463P)^2] where P = (Fo^2 + 2Fc^2)/3
5436 reflections	(Δ/σ)max < 0.001
294 parameters	Δρmax = 0.33 e Å^−3
0 restraints	Δρmin = −0.28 e Å^−3

Special details

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
Cl1	0.71093 (9)	−0.10790 (6)	0.58094 (5)	0.04017 (17)
Cl2	0.95862 (7)	−0.25306 (6)	−0.23737 (5)	0.03182 (15)
S1	0.90866 (9)	0.70416 (6)	0.28724 (5)	0.03918 (17)
F1	1.1525 (2)	0.68503 (18)	0.16265 (15)	0.0664 (5)
F2	1.1856 (2)	0.59124 (18)	0.27123 (16)	0.0683 (5)
F3	0.9900 (2)	0.50025 (16)	0.14173 (13)	0.0586 (5)
O1	0.6913 (2)	−0.22798 (15)	0.04957 (13)	0.0381 (4)
O2	0.4222 (2)	−0.29213 (18)	−0.03447 (15)	0.0526 (5)
N1	0.6339 (2)	0.13983 (18)	0.21102 (15)	0.0227 (4)
N2	0.3328 (2)	0.08126 (18)	0.17491 (15)	0.0241 (4)
N3	0.4562 (2)	0.29616 (18)	0.26597 (15)	0.0266 (4)
C1	0.7349 (4)	−0.3513 (2)	−0.0135 (2)	0.0466 (7)
H1A	0.6505	−0.4204	−0.0064	0.070*
H1B	0.8512	−0.3556	0.0097	0.070*
H1C	0.7322	−0.3598	−0.0856	0.070*
C2	0.5269 (3)	−0.2111 (2)	0.03164 (17)	0.0286 (5)
C3	0.4997 (3)	−0.0830 (2)	0.10345 (16)	0.0239 (5)
C4	0.3444 (3)	−0.0428 (2)	0.10522 (16)	0.0240 (5)
C5	0.1744 (3)	−0.1141 (2)	0.04042 (18)	0.0315 (5)
H5A	0.1858	−0.2015	−0.0008	0.047*
H5B	0.1474	−0.0708	−0.0051	0.047*
H5C	0.0810	−0.1156	0.0857	0.047*
C6	0.6500 (3)	0.0032 (2)	0.18417 (16)	0.0227 (5)
H6	0.7613	−0.0087	0.1515	0.027*
C7	0.6600 (3)	−0.0275 (2)	0.28398 (17)	0.0234 (5)
C8	0.5486 (3)	−0.1308 (2)	0.29594 (18)	0.0288 (5)
H8	0.4633	−0.1838	0.2422	0.035*
C9	0.5626 (3)	−0.1563 (2)	0.38743 (19)	0.0322 (5)
H9	0.4878	−0.2261	0.3950	0.039*
C10	0.6887 (3)	−0.0767 (2)	0.46638 (17)	0.0282 (5)
C11	0.8002 (3)	0.0274 (2)	0.45679 (18)	0.0320 (5)
H11	0.8836	0.0814	0.5114	0.038*
C12	0.7868 (3)	0.0508 (2)	0.36512 (17)	0.0288 (5)
H12	0.8636	0.1198	0.3576	0.035*
C13	0.4782 (3)	0.1746 (2)	0.21888 (16)	0.0225 (5)
C14	0.5967 (3)	0.4010 (2)	0.32548 (17)	0.0245 (5)
C15	0.6749 (3)	0.4871 (2)	0.28188 (17)	0.0266 (5)
H15	0.6390	0.4774	0.2140	0.032*
C16	0.8089 (3)	0.5893 (2)	0.34136 (19)	0.0283 (5)
C17	0.8616 (3)	0.6043 (2)	0.44282 (19)	0.0339 (6)
H17	0.9502	0.6733	0.4822	0.041*
C18	0.7822 (3)	0.5164 (2)	0.48560 (18)	0.0344 (6)
H18	0.8180	0.5261	0.5535	0.041*
C19	0.6492 (3)	0.4140 (2)	0.42696 (18)	0.0318 (5)
H19	0.5956	0.3545	0.4551	0.038*
C20	1.0644 (3)	0.6148 (3)	0.2136 (2)	0.0447 (7)
H1	0.727 (3)	0.195 (2)	0.2307 (18)	0.033 (7)*
H2	0.237 (4)	0.109 (2)	0.180 (2)	0.044 (8)*
H3	0.355 (3)	0.309 (2)	0.2650 (19)	0.039 (8)*

Atomic displacement parameters (Ų)

	U^11	U^22	U^33	U^12	U^13	U^23
Cl1	0.0472 (4)	0.0505 (4)	0.0318 (3)	0.0162 (3)	0.0084 (3)	0.0225 (3)
Cl2	0.0176 (3)	0.0345 (3)	0.0424 (3)	0.0027 (2)	0.0000 (2)	0.0142 (3)
S1	0.0402 (4)	0.0221 (3)	0.0512 (4)	0.0000 (3)	0.0034 (3)	0.0114 (3)
F1	0.0453 (10)	0.0759 (13)	0.0945 (14)	0.0033 (9)	0.0232 (10)	0.0538 (11)
F2	0.0374 (9)	0.0848 (14)	0.1007 (15)	0.0139 (9)	0.0032 (9)	0.0545 (12)
F3	0.0572 (11)	0.0440 (10)	0.0645 (11)	0.0100 (8)	0.0230 (9)	0.0073 (9)
O1	0.0307 (9)	0.0327 (10)	0.0411 (10)	0.0112 (8)	0.0002 (8)	0.0001 (8)
O2	0.0444 (11)	0.0420 (11)	0.0474 (11)	0.0108 (9)	−0.0154 (9)	−0.0120 (9)
N1	0.0146 (9)	0.0195 (10)	0.0317 (10)	−0.0012 (8)	−0.0016 (8)	0.0087 (8)
N2	0.0151 (9)	0.0259 (10)	0.0299 (10)	0.0015 (8)	−0.0006 (8)	0.0099 (8)
N3	0.0158 (9)	0.0234 (10)	0.0388 (11)	0.0021 (8)	−0.0001 (8)	0.0101 (9)
C1	0.0467 (16)	0.0343 (15)	0.0491 (16)	0.0166 (13)	0.0009 (13)	0.0003 (13)
C2	0.0305 (12)	0.0311 (13)	0.0227 (11)	0.0060 (10)	0.0010 (10)	0.0082 (10)
C3	0.0252 (11)	0.0239 (12)	0.0207 (10)	0.0005 (9)	−0.0016 (9)	0.0079 (9)
C4	0.0238 (11)	0.0244 (12)	0.0230 (11)	0.0004 (9)	−0.0009 (9)	0.0099 (9)
C5	0.0266 (12)	0.0320 (13)	0.0312 (12)	−0.0001 (10)	−0.0075 (10)	0.0091 (10)
C6	0.0178 (10)	0.0233 (11)	0.0257 (11)	0.0026 (9)	0.0006 (9)	0.0080 (9)
C7	0.0203 (10)	0.0226 (11)	0.0274 (11)	0.0055 (9)	0.0018 (9)	0.0088 (9)
C8	0.0250 (12)	0.0282 (13)	0.0305 (12)	0.0002 (10)	−0.0031 (10)	0.0102 (10)
C9	0.0299 (12)	0.0304 (13)	0.0397 (13)	0.0040 (10)	0.0074 (11)	0.0175 (11)
C10	0.0309 (12)	0.0326 (13)	0.0258 (11)	0.0132 (11)	0.0047 (10)	0.0131 (10)
C11	0.0346 (13)	0.0292 (13)	0.0285 (12)	0.0040 (11)	−0.0060 (10)	0.0077 (10)
C12	0.0272 (12)	0.0238 (12)	0.0324 (12)	−0.0032 (10)	−0.0057 (10)	0.0107 (10)
C13	0.0196 (10)	0.0240 (12)	0.0248 (11)	0.0005 (9)	−0.0008 (9)	0.0118 (9)
C14	0.0176 (10)	0.0209 (11)	0.0306 (12)	0.0048 (9)	0.0009 (9)	0.0040 (9)
C15	0.0259 (12)	0.0241 (12)	0.0267 (11)	0.0062 (10)	−0.0013 (9)	0.0052 (9)
C16	0.0245 (11)	0.0200 (12)	0.0367 (13)	0.0026 (9)	0.0019 (10)	0.0070 (10)
C17	0.0269 (12)	0.0248 (13)	0.0375 (14)	0.0033 (10)	−0.0048 (11)	−0.0021 (11)
C18	0.0302 (13)	0.0415 (15)	0.0274 (12)	0.0071 (11)	−0.0015 (10)	0.0078 (11)
C19	0.0269 (12)	0.0348 (14)	0.0346 (13)	0.0059 (10)	0.0049 (10)	0.0137 (11)
C20	0.0293 (14)	0.0458 (17)	0.0664 (19)	0.0013 (12)	0.0061 (13)	0.0318 (16)

Geometric parameters (Å, º)

Cl1—C10	1.743 (2)	C5—H5A	0.9600
S1—C20	1.784 (3)	C5—H5B	0.9600
S1—C16	1.785 (2)	C5—H5C	0.9600
F1—C20	1.344 (3)	C6—C7	1.533 (3)
F2—C20	1.335 (3)	C6—H6	0.9800
F3—C20	1.330 (3)	C7—C8	1.384 (3)
O1—C2	1.343 (3)	C7—C12	1.390 (3)
O1—C1	1.442 (3)	C8—C9	1.393 (3)
O2—C2	1.196 (3)	C8—H8	0.9300
N1—C13	1.317 (3)	C9—C10	1.374 (3)
N1—C6	1.472 (3)	C9—H9	0.9300
N1—H1	0.83 (2)	C10—C11	1.378 (3)
N2—C13	1.357 (3)	C11—C12	1.382 (3)
N2—C4	1.395 (3)	C11—H11	0.9300
N2—H2	0.84 (3)	C12—H12	0.9300
N3—C13	1.325 (3)	C14—C15	1.376 (3)
N3—C14	1.438 (3)	C14—C19	1.393 (3)
N3—H3	0.82 (3)	C15—C16	1.394 (3)
C1—H1A	0.9600	C15—H15	0.9300
C1—H1B	0.9600	C16—C17	1.387 (3)
C1—H1C	0.9600	C17—C18	1.386 (3)
C2—C3	1.473 (3)	C17—H17	0.9300
C3—C4	1.346 (3)	C18—C19	1.387 (3)
C3—C6	1.519 (3)	C18—H18	0.9300
C4—C5	1.496 (3)	C19—H19	0.9300
C20—S1—C16	98.55 (11)	C7—C8—H8	119.6
C2—O1—C1	116.46 (18)	C9—C8—H8	119.6
C13—N1—C6	121.19 (18)	C10—C9—C8	118.9 (2)
C13—N1—H1	121.3 (16)	C10—C9—H9	120.5
C6—N1—H1	116.7 (16)	C8—C9—H9	120.5
C13—N2—C4	122.11 (19)	C9—C10—C11	121.4 (2)
C13—N2—H2	114.7 (18)	C9—C10—Cl1	119.79 (18)
C4—N2—H2	121.4 (18)	C11—C10—Cl1	118.84 (17)
C13—N3—C14	123.34 (18)	C10—C11—C12	119.3 (2)
C13—N3—H3	116.8 (18)	C10—C11—H11	120.4
C14—N3—H3	119.6 (18)	C12—C11—H11	120.4
O1—C1—H1A	109.5	C11—C12—C7	120.8 (2)
O1—C1—H1B	109.5	C11—C12—H12	119.6
H1A—C1—H1B	109.5	C7—C12—H12	119.6
O1—C1—H1C	109.5	N1—C13—N3	123.54 (19)
H1A—C1—H1C	109.5	N1—C13—N2	118.3 (2)
H1B—C1—H1C	109.5	N3—C13—N2	118.19 (19)
O2—C2—O1	122.4 (2)	C15—C14—C19	121.4 (2)
O2—C2—C3	127.2 (2)	C15—C14—N3	119.57 (19)
O1—C2—C3	110.42 (18)	C19—C14—N3	119.1 (2)
C4—C3—C2	122.93 (19)	C14—C15—C16	118.7 (2)
C4—C3—C6	118.69 (19)	C14—C15—H15	120.6
C2—C3—C6	118.23 (18)	C16—C15—H15	120.6
C3—C4—N2	118.63 (19)	C17—C16—C15	120.6 (2)
C3—C4—C5	128.6 (2)	C17—C16—S1	119.95 (18)
N2—C4—C5	112.78 (19)	C15—C16—S1	119.42 (18)
C4—C5—H5A	109.5	C18—C17—C16	120.0 (2)
C4—C5—H5B	109.5	C18—C17—H17	120.0
H5A—C5—H5B	109.5	C16—C17—H17	120.0
C4—C5—H5C	109.5	C17—C18—C19	119.9 (2)
H5A—C5—H5C	109.5	C17—C18—H18	120.1
H5B—C5—H5C	109.5	C19—C18—H18	120.1
N1—C6—C3	108.80 (16)	C18—C19—C14	119.4 (2)
N1—C6—C7	110.11 (17)	C18—C19—H19	120.3
C3—C6—C7	114.37 (17)	C14—C19—H19	120.3
N1—C6—H6	107.8	F3—C20—F2	106.4 (2)
C3—C6—H6	107.8	F3—C20—F1	107.3 (2)
C7—C6—H6	107.8	F2—C20—F1	106.7 (2)
C8—C7—C12	118.82 (19)	F3—C20—S1	113.51 (18)
C8—C7—C6	122.47 (18)	F2—C20—S1	114.5 (2)
C12—C7—C6	118.71 (19)	F1—C20—S1	108.03 (19)
C7—C8—C9	120.9 (2)
C1—O1—C2—O2	−1.7 (3)	Cl1—C10—C11—C12	178.23 (17)
C1—O1—C2—C3	178.4 (2)	C10—C11—C12—C7	1.5 (3)
O2—C2—C3—C4	2.6 (4)	C8—C7—C12—C11	−0.9 (3)
O1—C2—C3—C4	−177.4 (2)	C6—C7—C12—C11	179.6 (2)
O2—C2—C3—C6	178.0 (2)	C6—N1—C13—N3	163.4 (2)
O1—C2—C3—C6	−2.0 (3)	C6—N1—C13—N2	−17.7 (3)
C2—C3—C4—N2	−178.94 (19)	C14—N3—C13—N1	−8.4 (3)
C6—C3—C4—N2	5.6 (3)	C14—N3—C13—N2	172.72 (19)
C2—C3—C4—C5	0.8 (4)	C4—N2—C13—N1	−13.0 (3)
C6—C3—C4—C5	−174.6 (2)	C4—N2—C13—N3	165.96 (19)
C13—N2—C4—C3	18.7 (3)	C13—N3—C14—C15	102.6 (2)
C13—N2—C4—C5	−161.09 (19)	C13—N3—C14—C19	−78.2 (3)
C13—N1—C6—C3	37.9 (3)	C19—C14—C15—C16	−0.2 (3)
C13—N1—C6—C7	−88.2 (2)	N3—C14—C15—C16	178.98 (19)
C4—C3—C6—N1	−30.9 (3)	C14—C15—C16—C17	−0.4 (3)
C2—C3—C6—N1	153.48 (19)	C14—C15—C16—S1	−178.64 (16)
C4—C3—C6—C7	92.7 (2)	C20—S1—C16—C17	98.8 (2)
C2—C3—C6—C7	−83.0 (2)	C20—S1—C16—C15	−83.0 (2)
N1—C6—C7—C8	127.0 (2)	C15—C16—C17—C18	0.7 (3)
C3—C6—C7—C8	4.2 (3)	S1—C16—C17—C18	178.92 (18)
N1—C6—C7—C12	−53.5 (2)	C16—C17—C18—C19	−0.4 (4)
C3—C6—C7—C12	−176.36 (19)	C17—C18—C19—C14	−0.2 (3)
C12—C7—C8—C9	0.0 (3)	C15—C14—C19—C18	0.5 (3)
C6—C7—C8—C9	179.5 (2)	N3—C14—C19—C18	−178.7 (2)
C7—C8—C9—C10	0.3 (3)	C16—S1—C20—F3	59.4 (2)
C8—C9—C10—C11	0.3 (3)	C16—S1—C20—F2	−63.1 (2)
C8—C9—C10—Cl1	−179.12 (17)	C16—S1—C20—F1	178.19 (18)
C9—C10—C11—C12	−1.1 (3)

(B)

Crystal data

C19H18BrClN3O2·Cl·H2O	F(000) = 992
Mr = 489.19	Dx = 1.524 Mg m^−3
Monoclinic, P21/c	Mo Kα radiation, λ = 0.71073 Å
Hall symbol: -P 2ybc	Cell parameters from 18016 reflections
a = 14.8702 (11) Å	θ = 2.3–28.3°
b = 8.0910 (5) Å	µ = 2.20 mm^−1
c = 17.7304 (13) Å	T = 100 K
β = 92.203 (2)°	Block, colourless
V = 2131.7 (3) Å^3	0.21 × 0.07 × 0.05 mm
Z = 4

Data collection

Bruker KAPPA APEX II DUO diffractometer	3720 reflections with I > 2σ(I)
Radiation source: fine-focus sealed tube	Rint = 0.045
Graphite monochromator	θmax = 28.3°, θmin = 2.3°
Absorption correction: multi-scan SADABS	h = −19→19
Tmin = 0.655, Tmax = 0.898	k = −10→7
18022 measured reflections	l = −23→23
5301 independent reflections

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)] = 0.036	Hydrogen site location: inferred from neighbouring sites
wR(F^2) = 0.083	H atoms treated by a mixture of independent and constrained refinement
S = 1.01	w = 1/[σ^2(Fo^2) + (0.0316P)^2 + 0.4954P] where P = (Fo^2 + 2Fc^2)/3
5301 reflections	(Δ/σ)max = 0.001
275 parameters	Δρmax = 0.52 e Å^−3
1 restraint	Δρmin = −0.54 e Å^−3

Special details

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
Br1	0.773951 (16)	0.63297 (3)	0.147297 (16)	0.04251 (9)
Cl1	0.06227 (5)	0.19129 (10)	−0.00064 (5)	0.0590 (2)
Cl2	0.40260 (5)	0.88638 (9)	0.09162 (4)	0.0564 (2)
O1	0.09635 (11)	0.8498 (2)	0.22248 (10)	0.0427 (4)
O2	0.07413 (11)	0.7885 (2)	0.34379 (11)	0.0480 (5)
O3	0.39984 (16)	0.3636 (2)	0.45714 (12)	0.0473 (5)
H3A	0.399 (2)	0.420 (4)	0.4933 (19)	0.064 (11)*
H3B	0.462 (3)	0.357 (4)	0.444 (2)	0.085 (12)*
N1	0.34522 (12)	0.6485 (2)	0.21693 (11)	0.0289 (4)
H1	0.3761 (16)	0.678 (3)	0.1830 (14)	0.032 (7)*
N2	0.33261 (13)	0.5433 (2)	0.33589 (11)	0.0298 (4)
H2	0.3577 (17)	0.487 (3)	0.3710 (15)	0.043 (8)*
N3	0.46614 (13)	0.5114 (2)	0.27450 (11)	0.0325 (4)
H3	0.4917 (16)	0.489 (3)	0.3157 (11)	0.048 (8)*
C1	0.01085 (18)	0.9361 (4)	0.22017 (19)	0.0601 (8)
H1A	−0.0368	0.8588	0.2281	0.090*
H1B	0.0014	0.9880	0.1718	0.090*
H1C	0.0113	1.0188	0.2590	0.090*
C2	0.12018 (15)	0.7798 (3)	0.28921 (15)	0.0340 (5)
C3	0.20736 (14)	0.6928 (3)	0.28405 (13)	0.0288 (5)
C4	0.24858 (15)	0.6200 (3)	0.34420 (13)	0.0293 (5)
C5	0.21731 (17)	0.6084 (3)	0.42329 (14)	0.0416 (6)
H5A	0.1580	0.6547	0.4255	0.062*
H5B	0.2579	0.6685	0.4566	0.062*
H5C	0.2160	0.4946	0.4385	0.062*
C6	0.24859 (14)	0.6864 (3)	0.20716 (13)	0.0284 (5)
H6	0.2426	0.7962	0.1842	0.034*
C7	0.20316 (14)	0.5618 (3)	0.15361 (13)	0.0291 (5)
C8	0.20346 (16)	0.3944 (3)	0.17155 (15)	0.0375 (6)
H8	0.2322	0.3586	0.2161	0.045*
C9	0.16120 (17)	0.2801 (3)	0.12362 (16)	0.0436 (6)
H9	0.1616	0.1683	0.1358	0.052*
C10	0.11888 (16)	0.3347 (3)	0.05803 (15)	0.0397 (6)
C11	0.11840 (16)	0.5000 (3)	0.03763 (14)	0.0405 (6)
H11	0.0907	0.5348	−0.0075	0.049*
C12	0.16061 (16)	0.6124 (3)	0.08669 (13)	0.0350 (5)
H12	0.1602	0.7241	0.0743	0.042*
C13	0.38142 (14)	0.5682 (3)	0.27474 (12)	0.0267 (5)
C14	0.51794 (15)	0.4971 (3)	0.20867 (13)	0.0286 (5)
C15	0.60471 (14)	0.5620 (3)	0.21006 (13)	0.0296 (5)
H15	0.6279	0.6167	0.2526	0.036*
C16	0.65579 (15)	0.5436 (3)	0.14707 (13)	0.0308 (5)
C17	0.62269 (17)	0.4628 (3)	0.08294 (14)	0.0387 (6)
H17	0.6575	0.4530	0.0407	0.046*
C18	0.53701 (18)	0.3972 (3)	0.08290 (14)	0.0403 (6)
H18	0.5144	0.3408	0.0406	0.048*
C19	0.48427 (16)	0.4141 (3)	0.14507 (14)	0.0351 (5)
H19	0.4265	0.3701	0.1443	0.042*

Atomic displacement parameters (Ų)

	U^11	U^22	U^33	U^12	U^13	U^23
Br1	0.03396 (13)	0.03986 (15)	0.05443 (18)	0.00419 (11)	0.01104 (11)	0.00159 (12)
Cl1	0.0429 (4)	0.0667 (5)	0.0672 (5)	−0.0056 (3)	0.0012 (3)	−0.0376 (4)
Cl2	0.0544 (4)	0.0838 (5)	0.0300 (3)	−0.0335 (4)	−0.0096 (3)	0.0209 (3)
O1	0.0329 (9)	0.0445 (10)	0.0506 (11)	0.0123 (8)	0.0002 (8)	−0.0004 (8)
O2	0.0362 (9)	0.0518 (11)	0.0571 (12)	0.0027 (8)	0.0166 (9)	0.0002 (9)
O3	0.0665 (14)	0.0398 (11)	0.0348 (11)	0.0051 (10)	−0.0069 (10)	−0.0046 (9)
N1	0.0236 (9)	0.0345 (11)	0.0287 (11)	−0.0040 (8)	0.0039 (8)	0.0074 (9)
N2	0.0306 (10)	0.0324 (11)	0.0261 (11)	−0.0024 (8)	0.0000 (8)	0.0042 (8)
N3	0.0290 (10)	0.0414 (12)	0.0267 (11)	0.0029 (8)	−0.0038 (9)	0.0031 (9)
C1	0.0412 (15)	0.0596 (18)	0.080 (2)	0.0218 (14)	0.0036 (15)	0.0065 (17)
C2	0.0280 (11)	0.0263 (12)	0.0479 (16)	−0.0070 (9)	0.0022 (11)	−0.0064 (11)
C3	0.0275 (11)	0.0248 (11)	0.0343 (13)	−0.0064 (9)	0.0037 (10)	−0.0023 (9)
C4	0.0293 (11)	0.0252 (11)	0.0336 (13)	−0.0068 (9)	0.0050 (10)	−0.0060 (10)
C5	0.0424 (14)	0.0482 (15)	0.0346 (14)	−0.0055 (12)	0.0083 (11)	−0.0037 (11)
C6	0.0233 (10)	0.0281 (11)	0.0335 (13)	−0.0007 (9)	0.0002 (9)	0.0047 (9)
C7	0.0234 (10)	0.0311 (11)	0.0331 (13)	−0.0013 (9)	0.0062 (9)	0.0004 (10)
C8	0.0369 (13)	0.0341 (13)	0.0411 (14)	−0.0041 (10)	−0.0037 (11)	0.0032 (11)
C9	0.0402 (14)	0.0333 (14)	0.0575 (18)	−0.0049 (11)	0.0026 (13)	−0.0052 (12)
C10	0.0277 (12)	0.0484 (16)	0.0433 (15)	−0.0036 (11)	0.0059 (11)	−0.0184 (12)
C11	0.0346 (13)	0.0529 (16)	0.0337 (14)	0.0045 (12)	−0.0015 (11)	−0.0076 (12)
C12	0.0355 (12)	0.0371 (13)	0.0324 (13)	0.0026 (10)	−0.0002 (10)	0.0035 (10)
C13	0.0274 (11)	0.0254 (11)	0.0272 (12)	−0.0046 (9)	−0.0011 (9)	0.0005 (9)
C14	0.0305 (11)	0.0284 (11)	0.0268 (12)	0.0059 (9)	−0.0003 (9)	0.0018 (9)
C15	0.0302 (11)	0.0284 (11)	0.0299 (12)	0.0058 (9)	−0.0039 (10)	−0.0034 (9)
C16	0.0311 (11)	0.0250 (11)	0.0361 (13)	0.0061 (9)	0.0006 (10)	0.0040 (10)
C17	0.0498 (15)	0.0348 (13)	0.0319 (14)	0.0131 (11)	0.0049 (12)	−0.0010 (10)
C18	0.0530 (16)	0.0352 (14)	0.0322 (14)	0.0058 (11)	−0.0067 (12)	−0.0080 (10)
C19	0.0351 (12)	0.0318 (12)	0.0379 (14)	−0.0017 (10)	−0.0063 (11)	−0.0024 (10)

Geometric parameters (Å, º)

Br1—C16	1.900 (2)	C5—H5B	0.9600
Cl1—C10	1.752 (2)	C5—H5C	0.9600
O1—C2	1.347 (3)	C6—C7	1.525 (3)
O1—C1	1.450 (3)	C6—H6	0.9800
O2—C2	1.209 (3)	C7—C12	1.385 (3)
O3—H3A	0.79 (3)	C7—C8	1.391 (3)
O3—H3B	0.96 (4)	C8—C9	1.390 (3)
N1—C13	1.312 (3)	C8—H8	0.9300
N1—C6	1.473 (3)	C9—C10	1.374 (4)
N1—H1	0.81 (2)	C9—H9	0.9300
N2—C13	1.343 (3)	C10—C11	1.386 (4)
N2—C4	1.408 (3)	C11—C12	1.391 (3)
N2—H2	0.85 (3)	C11—H11	0.9300
N3—C13	1.341 (3)	C12—H12	0.9300
N3—C14	1.428 (3)	C14—C19	1.389 (3)
N3—H3	0.831 (16)	C14—C15	1.392 (3)
C1—H1A	0.9600	C15—C16	1.383 (3)
C1—H1B	0.9600	C15—H15	0.9300
C1—H1C	0.9600	C16—C17	1.385 (3)
C2—C3	1.481 (3)	C17—C18	1.380 (4)
C3—C4	1.345 (3)	C17—H17	0.9300
C3—C6	1.517 (3)	C18—C19	1.384 (4)
C4—C5	1.497 (3)	C18—H18	0.9300
C5—H5A	0.9600	C19—H19	0.9300
C2—O1—C1	115.4 (2)	C12—C7—C6	121.0 (2)
H3A—O3—H3B	106 (3)	C8—C7—C6	120.3 (2)
C13—N1—C6	124.34 (19)	C9—C8—C7	120.7 (2)
C13—N1—H1	120.1 (17)	C9—C8—H8	119.7
C6—N1—H1	115.6 (17)	C7—C8—H8	119.7
C13—N2—C4	121.8 (2)	C10—C9—C8	119.1 (2)
C13—N2—H2	116.0 (18)	C10—C9—H9	120.5
C4—N2—H2	121.9 (18)	C8—C9—H9	120.5
C13—N3—C14	124.52 (19)	C9—C10—C11	121.9 (2)
C13—N3—H3	118.1 (19)	C9—C10—Cl1	118.9 (2)
C14—N3—H3	117.3 (19)	C11—C10—Cl1	119.1 (2)
O1—C1—H1A	109.5	C10—C11—C12	118.0 (2)
O1—C1—H1B	109.5	C10—C11—H11	121.0
H1A—C1—H1B	109.5	C12—C11—H11	121.0
O1—C1—H1C	109.5	C7—C12—C11	121.5 (2)
H1A—C1—H1C	109.5	C7—C12—H12	119.2
H1B—C1—H1C	109.5	C11—C12—H12	119.2
O2—C2—O1	122.7 (2)	N1—C13—N3	121.6 (2)
O2—C2—C3	127.0 (2)	N1—C13—N2	119.2 (2)
O1—C2—C3	110.3 (2)	N3—C13—N2	119.2 (2)
C4—C3—C2	122.2 (2)	C19—C14—C15	120.1 (2)
C4—C3—C6	120.7 (2)	C19—C14—N3	120.9 (2)
C2—C3—C6	117.2 (2)	C15—C14—N3	118.9 (2)
C3—C4—N2	119.3 (2)	C16—C15—C14	118.9 (2)
C3—C4—C5	128.4 (2)	C16—C15—H15	120.6
N2—C4—C5	112.3 (2)	C14—C15—H15	120.6
C4—C5—H5A	109.5	C15—C16—C17	121.6 (2)
C4—C5—H5B	109.5	C15—C16—Br1	119.61 (17)
H5A—C5—H5B	109.5	C17—C16—Br1	118.73 (18)
C4—C5—H5C	109.5	C18—C17—C16	118.7 (2)
H5A—C5—H5C	109.5	C18—C17—H17	120.6
H5B—C5—H5C	109.5	C16—C17—H17	120.6
N1—C6—C3	109.13 (18)	C17—C18—C19	120.8 (2)
N1—C6—C7	110.03 (17)	C17—C18—H18	119.6
C3—C6—C7	113.43 (17)	C19—C18—H18	119.6
N1—C6—H6	108.0	C18—C19—C14	119.8 (2)
C3—C6—H6	108.0	C18—C19—H19	120.1
C7—C6—H6	108.0	C14—C19—H19	120.1
C12—C7—C8	118.8 (2)
C1—O1—C2—O2	−0.4 (3)	C8—C9—C10—C11	1.1 (4)
C1—O1—C2—C3	178.8 (2)	C8—C9—C10—Cl1	−177.77 (19)
O2—C2—C3—C4	−4.5 (4)	C9—C10—C11—C12	−1.5 (4)
O1—C2—C3—C4	176.33 (19)	Cl1—C10—C11—C12	177.36 (18)
O2—C2—C3—C6	174.6 (2)	C8—C7—C12—C11	0.1 (3)
O1—C2—C3—C6	−4.5 (3)	C6—C7—C12—C11	−179.6 (2)
C2—C3—C4—N2	−178.26 (18)	C10—C11—C12—C7	0.9 (3)
C6—C3—C4—N2	2.6 (3)	C6—N1—C13—N3	167.8 (2)
C2—C3—C4—C5	1.2 (3)	C6—N1—C13—N2	−12.6 (3)
C6—C3—C4—C5	−177.8 (2)	C14—N3—C13—N1	−14.8 (3)
C13—N2—C4—C3	13.7 (3)	C14—N3—C13—N2	165.6 (2)
C13—N2—C4—C5	−165.9 (2)	C4—N2—C13—N1	−9.0 (3)
C13—N1—C6—C3	25.8 (3)	C4—N2—C13—N3	170.58 (19)
C13—N1—C6—C7	−99.3 (2)	C13—N3—C14—C19	−52.3 (3)
C4—C3—C6—N1	−20.0 (3)	C13—N3—C14—C15	130.3 (2)
C2—C3—C6—N1	160.91 (18)	C19—C14—C15—C16	0.6 (3)
C4—C3—C6—C7	103.1 (2)	N3—C14—C15—C16	178.05 (19)
C2—C3—C6—C7	−76.0 (2)	C14—C15—C16—C17	0.1 (3)
N1—C6—C7—C12	−119.6 (2)	C14—C15—C16—Br1	179.40 (15)
C3—C6—C7—C12	117.9 (2)	C15—C16—C17—C18	−1.0 (3)
N1—C6—C7—C8	60.8 (3)	Br1—C16—C17—C18	179.67 (17)
C3—C6—C7—C8	−61.8 (3)	C16—C17—C18—C19	1.2 (3)
C12—C7—C8—C9	−0.6 (3)	C17—C18—C19—C14	−0.5 (3)
C6—C7—C8—C9	179.1 (2)	C15—C14—C19—C18	−0.4 (3)
C7—C8—C9—C10	0.0 (4)	N3—C14—C19—C18	−177.8 (2)