Inter­molecular inter­action energies and molecular conformations in N-substituted 4-aryl-2-methyl­imidazoles with promising in vitro anti­fungal activity

A convenient one-pot synthesis of 4-aryl-2-methyl-N-phenacyl­imidazoles (4) through a microwave-assisted pseudo-tricomponent reaction of α-bromo­aceto­phenones (1) with acetamidine hydro­chloride (2) is reported. Ketones (4) were successfully used as substrates for the preparation of the respective N-(2-hy­droxy­ethyl)­imidazoles (5) with yields up to 87%. The synthesized compounds were characterized by NMR and high-resolution mass spectrometry analyses, and several structures were confirmed and studied by single-crystal X-ray diffraction. The analysis of the whole-of-molecule inter­actions shows that, despite the difference in the atom–atom contacts forming the crystals, dispersion energies make the largest contribution to the formation of the solids, giving an isotropic tendency in the topology of the energy framework diagrams for pairs of molecules. In addition, the in vitro anti­fungal activity of both families of compounds [ketones (4) and alcohols (5)] against Candida albicans and Cryptococcus neoformans was evaluated, where the 2,4-di­chloro­phenyl-substituted alcohol (5f), an isomer of the drug miconazole, showed the highest activity (IC₅₀ = 7.8 µg ml⁻¹ against C. neoformans).

Computing details

For all structures, data collection: CrysAlis PRO, Agilent Technologies, Version 1.171.37.35 (release 13-08-2014 CrysAlis171 .NET) (compiled Aug 13 2014,18:06:01); cell refinement: CrysAlis PRO, Agilent Technologies, Version 1.171.37.35 (release 13-08-2014 CrysAlis171 .NET) (compiled Aug 13 2014,18:06:01); data reduction: CrysAlis PRO, Agilent Technologies, Version 1.171.37.35 (release 13-08-2014 CrysAlis171 .NET) (compiled Aug 13 2014,18:06:01); program(s) used to solve structure: Superflip (Palatinus & Chapuis, 2007); program(s) used to refine structure: SHELXL2016/6 (Sheldrick, 2015a); molecular graphics: Mercury (Macrae et al., 2008); software used to prepare material for publication: SHELXL2014 (Sheldrick, 2015b).

(4b)

Crystal data

C18H14Cl2N2O	F(000) = 712
Mr = 345.21	Dx = 1.358 Mg m^−3
Monoclinic, P21/c	Mo Kα radiation, λ = 0.71073 Å
a = 11.351 (3) Å	Cell parameters from 1699 reflections
b = 16.259 (6) Å	θ = 3.1–22.3°
c = 9.589 (3) Å	µ = 0.39 mm^−1
β = 107.41 (3)°	T = 298 K
V = 1688.5 (10) Å^3	Parallelepiped, brown
Z = 4	0.13 × 0.09 × 0.08 mm

Data collection

'Agilent SuperNova Dual Source diffractometer with an Atlas detector'	3441 independent reflections
Radiation source: SuperNova (Mo) X-ray Source	1468 reflections with I > 2σ(I)
Detector resolution: 5.3072 pixels mm^-1	Rint = 0.113
ω scans	θmax = 26.4°, θmin = 3.1°
Absorption correction: multi-scan (CrysAlis PRO; Agilent, 2014)	h = −14→14
Tmin = 0.198, Tmax = 1.000	k = −20→20
17514 measured reflections	l = −11→11

Refinement

Refinement on F^2	Primary atom site location: iterative
Least-squares matrix: full	Secondary atom site location: difference Fourier map
R[F^2 > 2σ(F^2)] = 0.076	Hydrogen site location: inferred from neighbouring sites
wR(F^2) = 0.232	H-atom parameters constrained
S = 1.06	w = 1/[σ^2(Fo^2) + (0.0869P)^2] where P = (Fo^2 + 2Fc^2)/3
3441 reflections	(Δ/σ)max < 0.001
209 parameters	Δρmax = 0.21 e Å^−3
30 restraints	Δρmin = −0.30 e Å^−3

Special details

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

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

	x	y	z	Uiso*/Ueq
Cl1	0.19897 (11)	0.85133 (10)	0.06229 (14)	0.1040 (6)
C2	0.3192 (4)	0.8392 (3)	0.2237 (5)	0.0721 (8)
C3	0.3958 (4)	0.9048 (3)	0.2826 (4)	0.0726 (9)
H3	0.384342	0.955621	0.235828	0.087*
C4	0.4887 (3)	0.8940 (3)	0.4107 (4)	0.0666 (12)
H4	0.540647	0.937993	0.449029	0.080*
C5	0.5081 (3)	0.8199 (3)	0.4851 (4)	0.0574 (10)
C6	0.6069 (4)	0.8103 (3)	0.6244 (4)	0.0630 (11)
N7	0.6767 (3)	0.8763 (2)	0.6909 (4)	0.0701 (10)
C8	0.7553 (4)	0.8469 (3)	0.8115 (5)	0.0717 (13)
N9	0.7392 (3)	0.7652 (3)	0.8251 (4)	0.0695 (10)
C10	0.6450 (4)	0.7419 (3)	0.7042 (4)	0.0689 (12)
H10	0.613578	0.689119	0.681882	0.083*
C11	0.8175 (3)	0.7098 (3)	0.9323 (4)	0.0729 (13)
H11A	0.770413	0.661228	0.940792	0.088*
H11B	0.842956	0.736759	1.026800	0.088*
C12	0.9297 (4)	0.6842 (3)	0.8918 (5)	0.0704 (13)
O13	0.9438 (3)	0.7056 (3)	0.7760 (3)	0.1016 (12)
C14	1.0220 (3)	0.6312 (3)	0.9949 (4)	0.0603 (11)
C15	1.1332 (4)	0.6163 (3)	0.9693 (5)	0.0839 (14)
H15	1.146970	0.637053	0.885217	0.101*
C16	1.2236 (4)	0.5714 (3)	1.0656 (5)	0.0816 (9)
H16	1.297351	0.560858	1.045281	0.098*
C17	1.2063 (4)	0.5420 (3)	1.1909 (5)	0.0808 (9)
Cl18	1.32474 (13)	0.49072 (11)	1.31794 (17)	0.1244 (7)
C19	1.0959 (4)	0.5539 (3)	1.2181 (5)	0.0799 (9)
H19	1.082388	0.531637	1.301324	0.096*
C20	1.0046 (4)	0.5994 (3)	1.1210 (4)	0.0706 (12)
H20	0.930281	0.608654	1.140723	0.085*
C21	0.8507 (4)	0.8960 (3)	0.9219 (5)	0.0978 (17)
H21A	0.931385	0.875389	0.928194	0.147*
H21B	0.836901	0.891308	1.015611	0.147*
H21C	0.844953	0.952678	0.892689	0.147*
C22	0.4292 (4)	0.7546 (3)	0.4208 (5)	0.0749 (13)
H22	0.440647	0.703691	0.467142	0.090*
C23	0.3360 (4)	0.7635 (3)	0.2920 (5)	0.0737 (9)
H23	0.285194	0.719319	0.251446	0.088*

Atomic displacement parameters (Ų)

	U^11	U^22	U^33	U^12	U^13	U^23
Cl1	0.0818 (9)	0.1314 (14)	0.0828 (9)	0.0142 (8)	0.0002 (7)	0.0107 (8)
C2	0.0619 (15)	0.089 (2)	0.0624 (18)	0.0056 (14)	0.0145 (14)	0.0029 (13)
C3	0.0634 (16)	0.089 (2)	0.0632 (19)	0.0060 (15)	0.0151 (15)	0.0042 (14)
C4	0.066 (3)	0.063 (3)	0.074 (3)	−0.007 (2)	0.025 (2)	−0.003 (2)
C5	0.055 (2)	0.063 (3)	0.058 (2)	0.001 (2)	0.0225 (19)	−0.001 (2)
C6	0.057 (2)	0.082 (3)	0.056 (3)	−0.004 (2)	0.024 (2)	−0.008 (2)
N7	0.064 (2)	0.080 (3)	0.063 (2)	0.0040 (19)	0.0133 (19)	−0.0072 (19)
C8	0.060 (3)	0.090 (4)	0.066 (3)	0.002 (3)	0.021 (2)	−0.016 (3)
N9	0.064 (2)	0.088 (3)	0.057 (2)	0.000 (2)	0.0192 (18)	0.0033 (19)
C10	0.065 (2)	0.082 (4)	0.058 (3)	−0.002 (2)	0.017 (2)	0.007 (2)
C11	0.064 (3)	0.097 (4)	0.055 (3)	0.006 (2)	0.014 (2)	0.008 (2)
C12	0.065 (3)	0.094 (4)	0.056 (3)	−0.002 (2)	0.025 (2)	−0.005 (2)
O13	0.096 (2)	0.157 (4)	0.063 (2)	0.026 (2)	0.0405 (17)	0.028 (2)
C14	0.058 (2)	0.070 (3)	0.056 (2)	−0.004 (2)	0.022 (2)	−0.007 (2)
C15	0.077 (3)	0.097 (4)	0.090 (3)	0.001 (3)	0.042 (3)	0.017 (3)
C16	0.0806 (18)	0.084 (2)	0.086 (2)	0.0083 (17)	0.0339 (16)	0.0014 (17)
C17	0.0811 (17)	0.083 (2)	0.0835 (19)	0.0088 (17)	0.0322 (16)	0.0008 (16)
Cl18	0.1140 (11)	0.1207 (14)	0.1395 (14)	0.0560 (10)	0.0397 (10)	0.0339 (10)
C19	0.0817 (18)	0.082 (2)	0.081 (2)	0.0082 (17)	0.0325 (16)	0.0012 (16)
C20	0.063 (2)	0.092 (4)	0.061 (3)	0.007 (2)	0.025 (2)	0.001 (2)
C21	0.092 (3)	0.118 (5)	0.075 (3)	−0.002 (3)	0.012 (3)	−0.022 (3)
C22	0.077 (3)	0.076 (3)	0.071 (3)	−0.003 (2)	0.021 (2)	0.009 (2)
C23	0.0630 (16)	0.090 (2)	0.0636 (19)	0.0030 (15)	0.0124 (15)	0.0033 (14)

Geometric parameters (Å, º)

Cl1—C2	1.741 (4)	C12—O13	1.219 (5)
C2—C23	1.381 (6)	C12—C14	1.483 (6)
C2—C3	1.385 (6)	C14—C15	1.377 (5)
C3—C4	1.370 (5)	C14—C20	1.383 (5)
C3—H3	0.9300	C15—C16	1.369 (6)
C4—C5	1.384 (6)	C15—H15	0.9300
C4—H4	0.9300	C16—C17	1.361 (6)
C5—C22	1.406 (6)	C16—H16	0.9300
C5—C6	1.473 (5)	C17—C19	1.368 (6)
C6—C10	1.346 (6)	C17—Cl18	1.733 (5)
C6—N7	1.372 (5)	C19—C20	1.382 (5)
N7—C8	1.321 (5)	C19—H19	0.9300
C8—N9	1.353 (6)	C20—H20	0.9300
C8—C21	1.497 (6)	C21—H21A	0.9600
N9—C10	1.374 (5)	C21—H21B	0.9600
N9—C11	1.454 (5)	C21—H21C	0.9600
C10—H10	0.9300	C22—C23	1.373 (5)
C11—C12	1.497 (5)	C22—H22	0.9300
C11—H11A	0.9700	C23—H23	0.9300
C11—H11B	0.9700
C23—C2—C3	120.8 (4)	O13—C12—C11	120.7 (4)
C23—C2—Cl1	118.8 (4)	C14—C12—C11	118.4 (4)
C3—C2—Cl1	120.3 (4)	C15—C14—C20	117.9 (4)
C4—C3—C2	119.2 (4)	C15—C14—C12	119.1 (4)
C4—C3—H3	120.4	C20—C14—C12	122.9 (4)
C2—C3—H3	120.4	C16—C15—C14	121.1 (4)
C3—C4—C5	122.4 (4)	C16—C15—H15	119.4
C3—C4—H4	118.8	C14—C15—H15	119.4
C5—C4—H4	118.8	C17—C16—C15	120.4 (4)
C4—C5—C22	116.7 (4)	C17—C16—H16	119.8
C4—C5—C6	121.3 (4)	C15—C16—H16	119.8
C22—C5—C6	122.0 (4)	C16—C17—C19	120.0 (4)
C10—C6—N7	109.8 (4)	C16—C17—Cl18	120.2 (4)
C10—C6—C5	129.1 (4)	C19—C17—Cl18	119.8 (4)
N7—C6—C5	121.1 (4)	C17—C19—C20	119.5 (4)
C8—N7—C6	105.6 (4)	C17—C19—H19	120.2
N7—C8—N9	111.3 (4)	C20—C19—H19	120.2
N7—C8—C21	125.7 (5)	C19—C20—C14	120.9 (4)
N9—C8—C21	123.0 (4)	C19—C20—H20	119.5
C8—N9—C10	106.5 (3)	C14—C20—H20	119.5
C8—N9—C11	127.3 (4)	C8—C21—H21A	109.5
C10—N9—C11	125.6 (4)	C8—C21—H21B	109.5
C6—C10—N9	106.8 (4)	H21A—C21—H21B	109.5
C6—C10—H10	126.6	C8—C21—H21C	109.5
N9—C10—H10	126.6	H21A—C21—H21C	109.5
N9—C11—C12	112.1 (3)	H21B—C21—H21C	109.5
N9—C11—H11A	109.2	C23—C22—C5	122.2 (4)
C12—C11—H11A	109.2	C23—C22—H22	118.9
N9—C11—H11B	109.2	C5—C22—H22	118.9
C12—C11—H11B	109.2	C22—C23—C2	118.7 (4)
H11A—C11—H11B	107.9	C22—C23—H23	120.7
O13—C12—C14	120.9 (4)	C2—C23—H23	120.7
C23—C2—C3—C4	−0.4 (7)	C10—N9—C11—C12	89.5 (5)
Cl1—C2—C3—C4	179.1 (3)	N9—C11—C12—O13	−4.3 (6)
C2—C3—C4—C5	−0.9 (6)	N9—C11—C12—C14	176.7 (4)
C3—C4—C5—C22	1.6 (6)	O13—C12—C14—C15	9.7 (7)
C3—C4—C5—C6	−178.6 (3)	C11—C12—C14—C15	−171.3 (4)
C4—C5—C6—C10	−173.9 (4)	O13—C12—C14—C20	−173.9 (4)
C22—C5—C6—C10	5.9 (7)	C11—C12—C14—C20	5.1 (6)
C4—C5—C6—N7	5.2 (6)	C20—C14—C15—C16	0.0 (7)
C22—C5—C6—N7	−175.0 (4)	C12—C14—C15—C16	176.5 (4)
C10—C6—N7—C8	−0.8 (5)	C14—C15—C16—C17	−1.5 (8)
C5—C6—N7—C8	179.9 (3)	C15—C16—C17—C19	3.1 (8)
C6—N7—C8—N9	0.2 (5)	C15—C16—C17—Cl18	−175.9 (4)
C6—N7—C8—C21	−179.6 (4)	C16—C17—C19—C20	−3.1 (7)
N7—C8—N9—C10	0.5 (5)	Cl18—C17—C19—C20	175.9 (4)
C21—C8—N9—C10	−179.7 (4)	C17—C19—C20—C14	1.6 (7)
N7—C8—N9—C11	171.5 (4)	C15—C14—C20—C19	0.0 (7)
C21—C8—N9—C11	−8.8 (7)	C12—C14—C20—C19	−176.4 (4)
N7—C6—C10—N9	1.1 (5)	C4—C5—C22—C23	−1.1 (6)
C5—C6—C10—N9	−179.7 (4)	C6—C5—C22—C23	179.1 (4)
C8—N9—C10—C6	−1.0 (5)	C5—C22—C23—C2	−0.2 (6)
C11—N9—C10—C6	−172.2 (4)	C3—C2—C23—C22	0.9 (7)
C8—N9—C11—C12	−79.8 (5)	Cl1—C2—C23—C22	−178.6 (3)

Hydrogen-bond geometry (Å, º)

D—H···A	D—H	H···A	D···A	D—H···A
C4—H4···N7	0.93	2.57	2.903 (5)	101
C11—H11B···O13^i	0.97	2.50	3.462 (5)	170

Symmetry code: (i) x, −y+3/2, z+1/2.

(4d)

Crystal data

C18H14F2N2O	Dx = 1.354 Mg m^−3
Mr = 312.31	Mo Kα radiation, λ = 0.71073 Å
Orthorhombic, Pbca	Cell parameters from 2571 reflections
a = 11.984 (3) Å	θ = 3.5–21.1°
b = 9.537 (2) Å	µ = 0.10 mm^−1
c = 26.808 (7) Å	T = 298 K
V = 3064.1 (12) Å^3	Parallelepiped, brown
Z = 8	0.15 × 0.12 × 0.07 mm
F(000) = 1296

Data collection

'Agilent SuperNova Dual Source diffractometer with an Atlas detector'	3121 independent reflections
Radiation source: SuperNova (Mo) X-ray Source	1625 reflections with I > 2σ(I)
Detector resolution: 5.3072 pixels mm^-1	Rint = 0.119
ω scans	θmax = 26.4°, θmin = 3.1°
Absorption correction: multi-scan (CrysAlis PRO; Agilent, 2014)	h = −14→14
Tmin = 0.239, Tmax = 1.000	k = −11→11
30609 measured reflections	l = −33→33

Refinement

Refinement on F^2	Secondary atom site location: difference Fourier map
Least-squares matrix: full	Hydrogen site location: inferred from neighbouring sites
R[F^2 > 2σ(F^2)] = 0.062	H-atom parameters constrained
wR(F^2) = 0.183	w = 1/[σ^2(Fo^2) + (0.0739P)^2 + 0.5522P] where P = (Fo^2 + 2Fc^2)/3
S = 1.05	(Δ/σ)max < 0.001
3121 reflections	Δρmax = 0.21 e Å^−3
210 parameters	Δρmin = −0.17 e Å^−3
0 restraints	Extinction correction: SHELXL-2016/6 (Sheldrick 2016), Fc^*=kFc[1+0.001xFc^2λ^3/sin(2θ)]^-1/4
Primary atom site location: iterative	Extinction coefficient: 0.0024 (6)

Special details

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

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

	x	y	z	Uiso*/Ueq
F1	0.21766 (15)	0.05087 (17)	0.22087 (7)	0.0806 (6)
C2	0.3028 (2)	0.0971 (3)	0.25005 (11)	0.0564 (8)
C3	0.3440 (3)	0.2281 (3)	0.24106 (12)	0.0649 (9)
H3	0.315858	0.283226	0.215338	0.078*
C4	0.4286 (2)	0.2759 (3)	0.27141 (12)	0.0615 (8)
H4	0.458339	0.364677	0.266009	0.074*
C5	0.4701 (2)	0.1938 (3)	0.30992 (11)	0.0488 (7)
C6	0.4263 (2)	0.0617 (3)	0.31681 (11)	0.0570 (8)
H6	0.454493	0.004811	0.341992	0.068*
C7	0.3412 (2)	0.0126 (3)	0.28696 (12)	0.0629 (8)
H7	0.310943	−0.076023	0.291983	0.075*
C8	0.5600 (2)	0.2529 (3)	0.34171 (10)	0.0530 (7)
O9	0.59992 (18)	0.3672 (2)	0.33351 (8)	0.0777 (7)
C10	0.5996 (2)	0.1670 (3)	0.38575 (12)	0.0602 (8)
H10A	0.541077	0.163531	0.410718	0.072*
H10B	0.614506	0.071825	0.374894	0.072*
N11	0.69948 (19)	0.2254 (2)	0.40773 (9)	0.0539 (6)
C12	0.7081 (2)	0.3340 (3)	0.44012 (11)	0.0539 (7)
N13	0.81298 (18)	0.3691 (2)	0.44761 (9)	0.0547 (6)
C14	0.8742 (2)	0.2784 (3)	0.41801 (10)	0.0496 (7)
C15	0.8055 (2)	0.1905 (3)	0.39307 (11)	0.0543 (8)
H15	0.825915	0.120824	0.370600	0.065*
C16	0.9971 (2)	0.2855 (3)	0.41665 (10)	0.0500 (7)
C17	1.0536 (2)	0.3817 (3)	0.44604 (12)	0.0608 (8)
H17	1.012694	0.441542	0.466429	0.073*
C18	1.1684 (3)	0.3916 (3)	0.44605 (13)	0.0727 (9)
H18	1.205166	0.456857	0.465903	0.087*
C19	1.2250 (3)	0.3033 (4)	0.41622 (15)	0.0799 (10)
F20	1.33875 (17)	0.3109 (3)	0.41585 (10)	0.1248 (9)
C21	1.1749 (3)	0.2075 (4)	0.38626 (14)	0.0795 (10)
H21	1.217164	0.148852	0.365967	0.095*
C22	1.0602 (3)	0.1989 (3)	0.38653 (13)	0.0682 (9)
H22	1.024738	0.133809	0.366136	0.082*
C23	0.6096 (2)	0.4013 (4)	0.46405 (13)	0.0714 (9)
H23A	0.557712	0.430225	0.438782	0.107*
H23B	0.633510	0.481675	0.482787	0.107*
H23C	0.574134	0.335490	0.486002	0.107*

Atomic displacement parameters (Ų)

	U^11	U^22	U^33	U^12	U^13	U^23
F1	0.0738 (12)	0.0764 (12)	0.0916 (14)	−0.0072 (9)	−0.0347 (10)	−0.0005 (10)
C2	0.0488 (17)	0.0571 (18)	0.063 (2)	0.0012 (14)	−0.0108 (15)	−0.0059 (14)
C3	0.069 (2)	0.0581 (19)	0.068 (2)	0.0045 (16)	−0.0176 (17)	0.0079 (15)
C4	0.065 (2)	0.0511 (17)	0.068 (2)	−0.0024 (14)	−0.0069 (16)	0.0062 (14)
C5	0.0439 (16)	0.0483 (16)	0.0540 (18)	0.0016 (12)	0.0022 (13)	0.0007 (12)
C6	0.0537 (18)	0.0575 (18)	0.0597 (19)	0.0000 (14)	−0.0085 (14)	0.0097 (14)
C7	0.061 (2)	0.0579 (18)	0.070 (2)	−0.0083 (15)	−0.0087 (16)	0.0013 (16)
C8	0.0482 (17)	0.0531 (17)	0.0577 (19)	−0.0011 (14)	−0.0009 (14)	0.0047 (13)
O9	0.0844 (16)	0.0658 (14)	0.0830 (17)	−0.0252 (11)	−0.0232 (12)	0.0217 (11)
C10	0.0470 (18)	0.0646 (18)	0.069 (2)	−0.0107 (13)	−0.0100 (15)	0.0113 (15)
N11	0.0446 (15)	0.0570 (14)	0.0602 (16)	−0.0025 (11)	−0.0079 (12)	0.0077 (12)
C12	0.0455 (19)	0.0596 (17)	0.0565 (19)	0.0020 (13)	−0.0005 (14)	0.0069 (14)
N13	0.0452 (15)	0.0621 (15)	0.0568 (16)	0.0006 (11)	0.0001 (11)	−0.0039 (11)
C14	0.0450 (17)	0.0541 (16)	0.0498 (18)	0.0008 (13)	−0.0034 (13)	0.0045 (13)
C15	0.0509 (19)	0.0556 (17)	0.0564 (19)	0.0045 (13)	−0.0082 (14)	0.0003 (13)
C16	0.0483 (18)	0.0553 (16)	0.0465 (17)	0.0017 (13)	−0.0030 (13)	0.0053 (13)
C17	0.0513 (19)	0.0695 (19)	0.062 (2)	0.0031 (14)	−0.0041 (15)	−0.0090 (15)
C18	0.050 (2)	0.087 (2)	0.081 (2)	−0.0101 (17)	−0.0098 (17)	−0.0092 (18)
C19	0.0345 (19)	0.102 (3)	0.103 (3)	0.0001 (17)	0.0021 (18)	0.000 (2)
F20	0.0431 (13)	0.169 (2)	0.162 (2)	−0.0026 (13)	0.0057 (13)	−0.0263 (17)
C21	0.052 (2)	0.091 (2)	0.095 (3)	0.0064 (17)	0.0092 (19)	−0.016 (2)
C22	0.056 (2)	0.073 (2)	0.076 (2)	0.0007 (15)	0.0033 (17)	−0.0132 (16)
C23	0.0486 (19)	0.093 (2)	0.072 (2)	0.0007 (16)	0.0096 (16)	0.0039 (17)

Geometric parameters (Å, º)

F1—C2	1.359 (3)	C12—C23	1.488 (4)
C2—C7	1.356 (4)	N13—C14	1.385 (3)
C2—C3	1.365 (4)	C14—C15	1.352 (4)
C3—C4	1.378 (4)	C14—C16	1.474 (4)
C3—H3	0.9300	C15—H15	0.9300
C4—C5	1.388 (4)	C16—C22	1.380 (4)
C4—H4	0.9300	C16—C17	1.386 (4)
C5—C6	1.377 (4)	C17—C18	1.379 (4)
C5—C8	1.484 (4)	C17—H17	0.9300
C6—C7	1.378 (4)	C18—C19	1.345 (4)
C6—H6	0.9300	C18—H18	0.9300
C7—H7	0.9300	C19—C21	1.357 (5)
C8—O9	1.211 (3)	C19—F20	1.365 (4)
C8—C10	1.513 (4)	C21—C22	1.377 (4)
C10—N11	1.446 (3)	C21—H21	0.9300
C10—H10A	0.9700	C22—H22	0.9300
C10—H10B	0.9700	C23—H23A	0.9600
N11—C12	1.356 (4)	C23—H23B	0.9600
N11—C15	1.371 (3)	C23—H23C	0.9600
C12—N13	1.317 (3)
C7—C2—F1	118.8 (3)	N11—C12—C23	123.1 (3)
C7—C2—C3	123.4 (3)	C12—N13—C14	105.1 (2)
F1—C2—C3	117.8 (3)	C15—C14—N13	110.3 (2)
C2—C3—C4	117.7 (3)	C15—C14—C16	128.7 (3)
C2—C3—H3	121.2	N13—C14—C16	121.0 (2)
C4—C3—H3	121.2	C14—C15—N11	105.8 (2)
C3—C4—C5	121.1 (3)	C14—C15—H15	127.1
C3—C4—H4	119.4	N11—C15—H15	127.1
C5—C4—H4	119.4	C22—C16—C17	117.4 (3)
C6—C5—C4	118.6 (3)	C22—C16—C14	122.3 (3)
C6—C5—C8	123.1 (2)	C17—C16—C14	120.3 (3)
C4—C5—C8	118.3 (2)	C18—C17—C16	122.2 (3)
C5—C6—C7	121.0 (3)	C18—C17—H17	118.9
C5—C6—H6	119.5	C16—C17—H17	118.9
C7—C6—H6	119.5	C19—C18—C17	117.4 (3)
C2—C7—C6	118.2 (3)	C19—C18—H18	121.3
C2—C7—H7	120.9	C17—C18—H18	121.3
C6—C7—H7	120.9	C18—C19—C21	123.4 (3)
O9—C8—C5	121.6 (2)	C18—C19—F20	118.4 (3)
O9—C8—C10	120.3 (3)	C21—C19—F20	118.2 (3)
C5—C8—C10	118.1 (2)	C19—C21—C22	118.6 (3)
N11—C10—C8	111.7 (2)	C19—C21—H21	120.7
N11—C10—H10A	109.3	C22—C21—H21	120.7
C8—C10—H10A	109.3	C21—C22—C16	121.0 (3)
N11—C10—H10B	109.3	C21—C22—H22	119.5
C8—C10—H10B	109.3	C16—C22—H22	119.5
H10A—C10—H10B	107.9	C12—C23—H23A	109.5
C12—N11—C15	107.4 (2)	C12—C23—H23B	109.5
C12—N11—C10	128.2 (2)	H23A—C23—H23B	109.5
C15—N11—C10	123.8 (3)	C12—C23—H23C	109.5
N13—C12—N11	111.4 (2)	H23A—C23—H23C	109.5
N13—C12—C23	125.6 (3)	H23B—C23—H23C	109.5
C7—C2—C3—C4	−0.2 (5)	N11—C12—N13—C14	0.5 (3)
F1—C2—C3—C4	178.6 (3)	C23—C12—N13—C14	179.7 (3)
C2—C3—C4—C5	−0.3 (5)	C12—N13—C14—C15	0.2 (3)
C3—C4—C5—C6	1.1 (4)	C12—N13—C14—C16	−179.8 (2)
C3—C4—C5—C8	−179.0 (3)	N13—C14—C15—N11	−0.8 (3)
C4—C5—C6—C7	−1.4 (4)	C16—C14—C15—N11	179.2 (3)
C8—C5—C6—C7	178.6 (3)	C12—N11—C15—C14	1.0 (3)
F1—C2—C7—C6	−178.9 (3)	C10—N11—C15—C14	172.9 (2)
C3—C2—C7—C6	−0.1 (5)	C15—C14—C16—C22	1.8 (4)
C5—C6—C7—C2	1.0 (4)	N13—C14—C16—C22	−178.3 (3)
C6—C5—C8—O9	177.0 (3)	C15—C14—C16—C17	−178.5 (3)
C4—C5—C8—O9	−2.9 (4)	N13—C14—C16—C17	1.5 (4)
C6—C5—C8—C10	−4.1 (4)	C22—C16—C17—C18	−0.5 (4)
C4—C5—C8—C10	176.0 (3)	C14—C16—C17—C18	179.8 (3)
O9—C8—C10—N11	−11.3 (4)	C16—C17—C18—C19	−0.2 (5)
C5—C8—C10—N11	169.8 (2)	C17—C18—C19—C21	0.7 (6)
C8—C10—N11—C12	80.7 (4)	C17—C18—C19—F20	−179.7 (3)
C8—C10—N11—C15	−89.5 (3)	C18—C19—C21—C22	−0.6 (6)
C15—N11—C12—N13	−1.0 (3)	F20—C19—C21—C22	179.8 (3)
C10—N11—C12—N13	−172.4 (2)	C19—C21—C22—C16	−0.1 (5)
C15—N11—C12—C23	179.8 (3)	C17—C16—C22—C21	0.6 (5)
C10—N11—C12—C23	8.4 (4)	C14—C16—C22—C21	−179.7 (3)

Hydrogen-bond geometry (Å, º)

D—H···A	D—H	H···A	D···A	D—H···A
C17—H17···N13	0.93	2.54	2.886 (3)	101

(4f)

Crystal data

C18H12Cl4N2O	Z = 2
Mr = 414.10	F(000) = 420
Triclinic, P1	Dx = 1.561 Mg m^−3
a = 4.4932 (5) Å	Mo Kα radiation, λ = 0.71073 Å
b = 10.9707 (11) Å	Cell parameters from 5042 reflections
c = 18.786 (2) Å	θ = 3.2–27.5°
α = 76.483 (9)°	µ = 0.68 mm^−1
β = 83.305 (9)°	T = 298 K
γ = 78.976 (9)°	Parallelepiped, colorless
V = 881.25 (17) Å^3	0.31 × 0.25 × 0.19 mm

Data collection

'Agilent SuperNova Dual Source diffractometer with an Atlas detector'	3884 independent reflections
Radiation source: SuperNova (Mo) X-ray Source	2874 reflections with I > 2σ(I)
Detector resolution: 5.3072 pixels mm^-1	Rint = 0.054
ω scans	θmax = 27.1°, θmin = 3.3°
Absorption correction: multi-scan (CrysAlis PRO; Agilent, 2014)	h = −5→5
Tmin = 0.675, Tmax = 1.000	k = −13→14
18954 measured reflections	l = −24→24

Refinement

Refinement on F^2	Primary atom site location: iterative
Least-squares matrix: full	Secondary atom site location: difference Fourier map
R[F^2 > 2σ(F^2)] = 0.052	Hydrogen site location: inferred from neighbouring sites
wR(F^2) = 0.142	H-atom parameters constrained
S = 1.04	w = 1/[σ^2(Fo^2) + (0.053P)^2 + 0.7031P] where P = (Fo^2 + 2Fc^2)/3
3884 reflections	(Δ/σ)max < 0.001
227 parameters	Δρmax = 0.61 e Å^−3
6 restraints	Δρmin = −0.65 e Å^−3

Special details

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

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

	x	y	z	Uiso*/Ueq
Cl1	−0.60587 (19)	−0.31348 (7)	0.37758 (5)	0.0602 (2)
Cl2	−0.0645 (2)	0.04939 (8)	0.20013 (4)	0.0624 (3)
Cl3	0.6175 (3)	0.39234 (9)	0.10711 (6)	0.1046 (4)
Cl4	0.8534 (3)	0.85871 (10)	−0.01204 (6)	0.0968 (4)
O1	−0.0285 (5)	0.5488 (2)	0.25152 (13)	0.0606 (6)
N1	−0.0739 (5)	0.2074 (2)	0.40291 (12)	0.0402 (5)
N2	0.2349 (5)	0.30652 (19)	0.31861 (12)	0.0394 (5)
C1	−0.4340 (6)	−0.1802 (2)	0.36694 (15)	0.0411 (6)
C2	−0.3214 (6)	−0.1250 (2)	0.29794 (15)	0.0438 (6)
H2	−0.335948	−0.158534	0.257580	0.053*
C3	−0.1857 (6)	−0.0184 (2)	0.28983 (14)	0.0389 (6)
C4	−0.1553 (6)	0.0341 (2)	0.34828 (14)	0.0355 (5)
C5	−0.2713 (6)	−0.0272 (2)	0.41691 (15)	0.0412 (6)
H5	−0.252718	0.004215	0.457788	0.049*
C6	−0.4115 (6)	−0.1317 (2)	0.42686 (15)	0.0431 (6)
H6	−0.489484	−0.168677	0.473242	0.052*
C7	−0.0192 (5)	0.1477 (2)	0.34416 (14)	0.0353 (5)
C8	0.1700 (6)	0.2090 (2)	0.29173 (14)	0.0391 (6)
H8	0.241126	0.188879	0.246665	0.047*
C9	0.0811 (6)	0.3020 (2)	0.38563 (14)	0.0394 (6)
C10	0.0886 (8)	0.3946 (3)	0.43159 (17)	0.0555 (8)
H10A	0.295184	0.393243	0.440660	0.083*
H10B	−0.027677	0.371882	0.477451	0.083*
H10C	0.003074	0.478379	0.406345	0.083*
C11	0.4203 (6)	0.3991 (2)	0.27935 (16)	0.0443 (6)
H11A	0.576160	0.359217	0.247797	0.053*
H11B	0.521005	0.426278	0.314429	0.053*
C12	0.2364 (6)	0.5147 (2)	0.23312 (15)	0.0404 (6)
C13	0.3906 (6)	0.5950 (2)	0.16928 (14)	0.0390 (6)
C14	0.5715 (8)	0.5514 (3)	0.11298 (16)	0.0530 (7)
C15	0.7129 (8)	0.6315 (3)	0.05688 (17)	0.0612 (9)
H15	0.833692	0.599943	0.019326	0.073*
C16	0.6719 (8)	0.7583 (3)	0.05762 (17)	0.0579 (8)
C17	0.4909 (8)	0.8066 (3)	0.11200 (17)	0.0577 (8)
H17	0.463236	0.892815	0.111880	0.069*
C18	0.3510 (7)	0.7246 (3)	0.16680 (16)	0.0494 (7)
H18	0.225585	0.757111	0.203402	0.059*

Atomic displacement parameters (Ų)

	U^11	U^22	U^33	U^12	U^13	U^23
Cl1	0.0691 (5)	0.0433 (4)	0.0743 (6)	−0.0281 (4)	0.0098 (4)	−0.0176 (4)
Cl2	0.0947 (6)	0.0572 (5)	0.0370 (4)	−0.0296 (4)	0.0131 (4)	−0.0092 (3)
Cl3	0.1795 (11)	0.0503 (5)	0.0836 (7)	−0.0235 (6)	0.0292 (7)	−0.0296 (5)
Cl4	0.1166 (9)	0.0757 (7)	0.0745 (7)	−0.0256 (6)	0.0280 (6)	0.0207 (5)
O1	0.0402 (12)	0.0544 (13)	0.0751 (15)	−0.0077 (9)	−0.0010 (10)	0.0083 (11)
N1	0.0476 (13)	0.0358 (11)	0.0377 (12)	−0.0151 (10)	0.0013 (10)	−0.0049 (9)
N2	0.0378 (12)	0.0331 (11)	0.0443 (12)	−0.0123 (9)	0.0010 (9)	0.0005 (9)
C1	0.0401 (14)	0.0307 (12)	0.0527 (16)	−0.0088 (11)	−0.0004 (12)	−0.0084 (11)
C2	0.0490 (16)	0.0382 (14)	0.0456 (15)	−0.0079 (12)	0.0013 (12)	−0.0135 (12)
C3	0.0425 (14)	0.0332 (13)	0.0374 (13)	−0.0053 (11)	0.0036 (11)	−0.0047 (10)
C4	0.0357 (13)	0.0292 (12)	0.0384 (13)	−0.0040 (10)	−0.0004 (10)	−0.0034 (10)
C5	0.0491 (15)	0.0359 (13)	0.0392 (14)	−0.0139 (11)	0.0029 (11)	−0.0067 (11)
C6	0.0495 (16)	0.0354 (13)	0.0419 (15)	−0.0133 (12)	0.0049 (12)	−0.0022 (11)
C7	0.0348 (13)	0.0324 (12)	0.0373 (13)	−0.0076 (10)	−0.0013 (10)	−0.0035 (10)
C8	0.0400 (14)	0.0335 (13)	0.0407 (14)	−0.0064 (11)	0.0030 (11)	−0.0048 (11)
C9	0.0423 (14)	0.0336 (13)	0.0404 (14)	−0.0114 (11)	−0.0041 (11)	0.0003 (11)
C10	0.076 (2)	0.0478 (16)	0.0491 (17)	−0.0281 (15)	−0.0038 (15)	−0.0090 (13)
C11	0.0366 (14)	0.0380 (14)	0.0535 (16)	−0.0135 (11)	0.0018 (12)	0.0027 (12)
C12	0.0369 (14)	0.0374 (13)	0.0476 (15)	−0.0118 (11)	−0.0050 (11)	−0.0051 (11)
C13	0.0430 (14)	0.0368 (13)	0.0362 (13)	−0.0102 (11)	−0.0050 (11)	−0.0019 (11)
C14	0.073 (2)	0.0376 (14)	0.0471 (16)	−0.0109 (14)	0.0011 (14)	−0.0089 (12)
C15	0.074 (2)	0.0563 (19)	0.0449 (17)	−0.0052 (16)	0.0107 (15)	−0.0064 (14)
C16	0.067 (2)	0.0513 (17)	0.0453 (17)	−0.0133 (15)	0.0015 (15)	0.0083 (13)
C17	0.078 (2)	0.0339 (14)	0.0532 (18)	−0.0094 (14)	0.0031 (16)	0.0019 (13)
C18	0.0582 (18)	0.0393 (15)	0.0455 (16)	−0.0052 (13)	−0.0001 (13)	−0.0032 (12)

Geometric parameters (Å, º)

Cl1—C1	1.741 (3)	C7—C8	1.364 (3)
Cl2—C3	1.745 (3)	C8—H8	0.9300
Cl3—C14	1.745 (3)	C9—C10	1.486 (4)
Cl4—C16	1.735 (3)	C10—H10A	0.9600
O1—C12	1.213 (3)	C10—H10B	0.9600
N1—C9	1.316 (3)	C10—H10C	0.9600
N1—C7	1.386 (3)	C11—C12	1.515 (4)
N2—C9	1.359 (3)	C11—H11A	0.9700
N2—C8	1.375 (3)	C11—H11B	0.9700
N2—C11	1.449 (3)	C12—C13	1.497 (4)
C1—C6	1.374 (4)	C13—C14	1.377 (4)
C1—C2	1.379 (4)	C13—C18	1.389 (4)
C2—C3	1.390 (4)	C14—C15	1.382 (4)
C2—H2	0.9300	C15—C16	1.371 (5)
C3—C4	1.384 (4)	C15—H15	0.9300
C4—C5	1.399 (4)	C16—C17	1.371 (4)
C4—C7	1.472 (3)	C17—C18	1.377 (4)
C5—C6	1.376 (4)	C17—H17	0.9300
C5—H5	0.9300	C18—H18	0.9300
C6—H6	0.9300
C9—N1—C7	106.1 (2)	C9—C10—H10B	109.5
C9—N2—C8	107.1 (2)	H10A—C10—H10B	109.5
C9—N2—C11	127.8 (2)	C9—C10—H10C	109.5
C8—N2—C11	125.0 (2)	H10A—C10—H10C	109.5
C6—C1—C2	120.9 (2)	H10B—C10—H10C	109.5
C6—C1—Cl1	120.0 (2)	N2—C11—C12	112.6 (2)
C2—C1—Cl1	119.1 (2)	N2—C11—H11A	109.1
C1—C2—C3	118.7 (2)	C12—C11—H11A	109.1
C1—C2—H2	120.6	N2—C11—H11B	109.1
C3—C2—H2	120.6	C12—C11—H11B	109.1
C4—C3—C2	122.8 (2)	H11A—C11—H11B	107.8
C4—C3—Cl2	121.5 (2)	O1—C12—C13	119.7 (2)
C2—C3—Cl2	115.7 (2)	O1—C12—C11	120.2 (2)
C3—C4—C5	115.6 (2)	C13—C12—C11	119.8 (2)
C3—C4—C7	126.1 (2)	C14—C13—C18	116.9 (3)
C5—C4—C7	118.2 (2)	C14—C13—C12	125.7 (2)
C6—C5—C4	123.2 (2)	C18—C13—C12	117.4 (2)
C6—C5—H5	118.4	C13—C14—C15	122.1 (3)
C4—C5—H5	118.4	C13—C14—Cl3	121.0 (2)
C1—C6—C5	118.7 (2)	C15—C14—Cl3	116.8 (2)
C1—C6—H6	120.6	C16—C15—C14	118.8 (3)
C5—C6—H6	120.6	C16—C15—H15	120.6
C8—C7—N1	109.1 (2)	C14—C15—H15	120.6
C8—C7—C4	131.8 (2)	C17—C16—C15	121.3 (3)
N1—C7—C4	119.0 (2)	C17—C16—Cl4	119.8 (2)
C7—C8—N2	106.5 (2)	C15—C16—Cl4	118.9 (3)
C7—C8—H8	126.8	C16—C17—C18	118.6 (3)
N2—C8—H8	126.8	C16—C17—H17	120.7
N1—C9—N2	111.3 (2)	C18—C17—H17	120.7
N1—C9—C10	125.6 (2)	C17—C18—C13	122.3 (3)
N2—C9—C10	123.1 (2)	C17—C18—H18	118.9
C9—C10—H10A	109.5	C13—C18—H18	118.9
C6—C1—C2—C3	−0.4 (4)	C8—N2—C9—N1	0.5 (3)
Cl1—C1—C2—C3	179.7 (2)	C11—N2—C9—N1	177.4 (2)
C1—C2—C3—C4	0.8 (4)	C8—N2—C9—C10	−178.6 (3)
C1—C2—C3—Cl2	−177.3 (2)	C11—N2—C9—C10	−1.8 (4)
C2—C3—C4—C5	−0.1 (4)	C9—N2—C11—C12	−87.3 (3)
Cl2—C3—C4—C5	177.9 (2)	C8—N2—C11—C12	89.0 (3)
C2—C3—C4—C7	−179.0 (2)	N2—C11—C12—O1	29.3 (4)
Cl2—C3—C4—C7	−1.0 (4)	N2—C11—C12—C13	−157.4 (2)
C3—C4—C5—C6	−1.0 (4)	O1—C12—C13—C14	−133.7 (3)
C7—C4—C5—C6	178.0 (2)	C11—C12—C13—C14	52.9 (4)
C2—C1—C6—C5	−0.6 (4)	O1—C12—C13—C18	47.0 (4)
Cl1—C1—C6—C5	179.2 (2)	C11—C12—C13—C18	−126.4 (3)
C4—C5—C6—C1	1.4 (4)	C18—C13—C14—C15	1.1 (5)
C9—N1—C7—C8	−0.3 (3)	C12—C13—C14—C15	−178.2 (3)
C9—N1—C7—C4	178.0 (2)	C18—C13—C14—Cl3	−175.8 (2)
C3—C4—C7—C8	−18.7 (4)	C12—C13—C14—Cl3	4.9 (4)
C5—C4—C7—C8	162.5 (3)	C13—C14—C15—C16	0.2 (5)
C3—C4—C7—N1	163.6 (2)	Cl3—C14—C15—C16	177.2 (3)
C5—C4—C7—N1	−15.3 (3)	C14—C15—C16—C17	−1.0 (5)
N1—C7—C8—N2	0.6 (3)	C14—C15—C16—Cl4	179.1 (3)
C4—C7—C8—N2	−177.3 (2)	C15—C16—C17—C18	0.4 (5)
C9—N2—C8—C7	−0.7 (3)	Cl4—C16—C17—C18	−179.7 (3)
C11—N2—C8—C7	−177.6 (2)	C16—C17—C18—C13	0.9 (5)
C7—N1—C9—N2	−0.2 (3)	C14—C13—C18—C17	−1.7 (5)
C7—N1—C9—C10	179.0 (3)	C12—C13—C18—C17	177.7 (3)

Hydrogen-bond geometry (Å, º)

D—H···A	D—H	H···A	D···A	D—H···A
C5—H5···N1	0.93	2.47	2.825 (3)	103
C8—H8···Cl2	0.93	2.59	3.110 (3)	116
C11—H11A···Cl3	0.97	2.57	3.268 (3)	129