Crystal structure and Hirshfeld surface analysis of ethyl (3E)-5-(4-fluoro­phen­yl)3-{[(4-meth­oxy­phen­yl)formamido]­imino}-7-methyl-2H,3H,5H-[1,3]thia­zolo[3,2-a]pyrimidine-6-carboxyl­ate 0.25-hydrate

The di­hydro­pyrimidine ring in the title mol­ecule is distinctly non-planar. In the crystal, zigzag chains parallel to [010] are formed by N—H⋯N hydrogen bonds and are connected into layers parallel to (100) by O—H⋯O, O—H⋯F, C—H⋯O, C—H⋯F and C—H⋯N hydrogen bonds. Further C—H⋯O hydrogen bonds connect the layers.

Abstract

In the title compound, C₂₄H₂₃FN₄O₄S·0.25H₂O, the di­hydro­pyrimidine ring is distinctly non-planar, with the flap C atom deviating by 0.297 (2) Å from the least-squares plane. In the crystal, zigzag chains are formed by N—H⋯N hydrogen bonds parallel to [010] and are connected into layers parallel to (100) by O—H⋯O, O—H⋯F, C—H⋯O, C—H⋯F and C—H⋯N hydrogen bonds. Additional C—H⋯O hydrogen bonds connect the layers into a three-dimensional network. A Hirshfeld surface analysis indicates that the most significant contributions to the crystal packing are from H⋯H (42.6%), O⋯H/H⋯O (16.8%) and C⋯H/H⋯C (15.5%) contacts.

1. Chemical context

Inter­est in the anti­cancer activities of di­hydro­pyrimidines (DHPMs) has been increasing since 1999, when monastrol was discovered (Mayer et al., 1999 ▸; Leizerman et al., 2004 ▸). In addition, 1,3,4-oxa­diazole has been reported to exhibit a significant anti­cancer activity (Yadagiri et al., 2015 ▸; Valente et al., 2014 ▸; El-Din et al., 2015 ▸). Since the combination of two or more pharmacophoric structural moieties can possibly augment the bioactivity, it was of inter­est to hybridize the DHPM moiety with 1,3,4-oxa­diazole, hoping to discover potent anti­cancer agents.

In this context, a target compound was designed through the condensation of 6-methyl-4-aryl-1,2,3,4-tetra­hydro­pyrim­idine-2(1H)-thione derivatives and 2-(chloro­meth­yl)-5-aryl-1,3,4-oxa­diazole derivatives (Ragab et al., 2017 ▸). Unexpectedly, an intra­molecular cyclization and ring opening of 1,3,4-oxa­diazole occurred. The resulting product was chosen as an example of this series for further structural elucidation through X-ray crystallography. Herein we report the crystal structure and Hirshfeld analysis of the title compound, C₂₄H₂₃FN₄O₄S·0.25H₂O.

2. Structural commentary

In the title compound (Fig. 1 ▸), the di­hydro­pyrimidine portion (N1/C3/C2/C1/N2/C4) of the central ring is planar to within 0.0286 (9) Å (r.m.s. deviation of the fitted atoms = 0.0211 Å), with the flap C1 atom being 0.297 (2) Å out of this plane towards the bonded 4-fluoro­phenyl group. A puckering analysis (Cremer & Pople, 1975 ▸) of this ring yielded the parameters Q = 0.2074 (15) Å, θ = 112.1 (4)° and φ = 3.5 (4)°. The dihedral angle between the C5–C10 phenyl ring and the least-squares plane of the di­hydro­pyrimidine plane is 88.76 (5)°. The C4/N2/C15/C16/S1 ring is planar to within 0.0191 (8) Å (r.m.s. deviation of the fitted atoms = 0.0140 Å) and is inclined to the N1/C3/C2/C1/N2/C4 plane by 3.99 (9)°. The dihedral angle between the C4/N2/C15/C16/S1 ring and the C18–C23 phenyl ring is 9.28 (8)°.

Figure 1.

The title mol­ecule with the labelling scheme and displacement ellipsoids drawn at the 30% probability level.

3. Supra­molecular features

In the crystal, mol­ecules are connected into zigzag chains running parallel to [010] by N4—H4⋯N1 hydrogen bonds (Table 1 ▸). The chains are connected into (100) layers by O5—H5B⋯O3 and O5—H5A⋯F1 hydrogen bonds involving the water mol­ecule, as well as by C13—H13B⋯F1, C16—H16A⋯N1 and all of the C—H⋯O hydrogen bonds listed in Table 1 ▸, except for the C24—H24C⋯O1 hydrogen bond (Figs. 2 ▸, 3 ▸ and 4 ▸) that serves to link the layers into a three-dimensional network.

Table 1. Hydrogen-bond geometry (Å, °).

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
N4—H4⋯N1i	0.885 (19)	2.164 (19)	2.9888 (17)	154.8 (16)
C1—H1⋯O5ii	0.987 (17)	2.345 (18)	3.307 (5)	164.7 (13)
C7—H7⋯O4iii	0.97 (2)	2.41 (2)	3.285 (2)	148.7 (17)
C13—H13B⋯F1ii	0.98 (3)	2.49 (3)	3.386 (2)	153.0 (19)
C16—H16A⋯N1i	0.98 (2)	2.58 (2)	3.4019 (19)	142.4 (15)
C16—H16B⋯O5iv	0.98 (2)	2.37 (2)	3.282 (5)	154.6 (16)
C24—H24A⋯O1v	0.99 (2)	2.53 (2)	3.450 (3)	154.6 (18)
C24—H24C⋯O1vi	0.95 (2)	2.57 (2)	3.504 (2)	167.8 (17)
O5—H5A⋯F1	0.87	1.76	2.479 (5)	138
O5—H5B⋯O3vii	0.87	2.00	2.863 (5)	174

Symmetry codes: (i) ; (ii) ; (iii) ; (iv) ; (v) ; (vi) ; (vii) .

Figure 2.

View of the mol­ecular packing along [100]. O—H⋯O, O—H⋯F, C—H⋯ O, C—H⋯N and C—H⋯F hydrogen bonds are shown as dashed lines.

Figure 3.

View of the mol­ecular packing along [010]. Hydrogen bonds are depicted as in Fig. 2 ▸.

Figure 4.

View of the mol­ecular packing along [001]. Hydrogen bonds are depicted as in Fig. 2 ▸.

4. Hirshfeld surface analysis

A Hirshfeld surface analysis was performed, and two-dimensional fingerprint plots were constructed using Crystal Explorer17.5 to qu­antify the inter­molecular inter­actions in the title mol­ecule (Turner et al., 2017 ▸). Fig. 5 ▸ depicts the Hirshfeld surface plotted over d _norm in the range −0.7253 to +1.4745 arbitrary units, with red patches indicating putative hydrogen bonding in the crystal structure.

Figure 5.

(a) Front and (b) back sides of the three-dimensional Hirshfeld surface of the title compound mapped over d _norm, with a fixed colour scale of −0.7253 (red) to +1.4745 (blue) a.u.

The intensity of the red patches is more pronounced for N4—H4⋯N1, C1—H1⋯O5, C16—H16B⋯O5, C24—H24A⋯O1, C24—H24C⋯O1 and O5—H5B⋯O3, thus revealing the strongest inter­actions when compared to other red spots on the Hirshfeld surface. Table 2 ▸ gives numerical data for close inter­molecular contacts. The two-dimensional fingerprint plots (Fig. 6 ▸) shows that the largest contributions are from H⋯H (42.6%; Fig. 6 ▸ b), O⋯H/H⋯O (16.8%; Fig. 6 ▸ c) and C⋯H/H⋯C (15.5%; Fig. 6 ▸ d) inter­actions. Other inter­actions contributing less to the crystal packing are from F⋯H/H⋯F (6.7%), N⋯H/H⋯N (4.5%), S⋯H/H⋯S (3.4%), S⋯C/C⋯S (3.4%), C⋯C (2.8%), S⋯N/N⋯S (1.4%),N⋯C/C⋯N (1.4%), O⋯C/C⋯O (0.7%), N⋯N (0.5%), O⋯N/N⋯O (0.2%) and S⋯O/O⋯S (0.1%) inter­actions.

Table 2. Summary of short inter­atomic contacts (Å) in the title compound.

Asterisks relate to atoms of the underoccupied water mol­ecule.

Contact	Distance	Symmetry operation
N1⋯H4	2.165	1 − x, −  + y,  − z
F1⋯H13B	2.49	x,  − y, −  + z
F1⋯*H5A	1.76	x, y, z
F1⋯H14C	2.66	x, 1 + y, z
H14A⋯H24C	2.56	1 + x, −1 + y, z
H12C⋯O1	2.66	2 − x, 1 − y, 1 − z
H16B⋯O3	2.49	1 − x, 1 − y, 1 − z
O3⋯*H5B	2.00	x,  − y,  + z
H7⋯O4	2.41	1 − x, 2 − y, 1 − z
H16B⋯*H5B	2.05	1 − x, −  + y,  − z
H13A⋯H24B	2.41	1 + x,  − y,  + z
H14C⋯*O5	2.87	x, −1 + y, z

Figure 6.

Two-dimensional fingerprint plots for the title compound, showing (a) all inter­actions, and delineated into (b) H⋯H, (c) O⋯H/H⋯O and (d) C⋯H/H⋯C inter­actions. The d _i and d _e values are the closest inter­nal and external distances (in Å) from given points on the Hirshfeld surface.

5. Database survey

A search of the Cambridge Structural Database (CSD, Version 5.42, update of September 2021; Groom et al., 2016 ▸) for compounds most closely related to the 2,3-di­hydro-5H-[1,3]thia­zolo[3,2-a]pyrimidine unit of the title compound gave the following hits: refcodes ZOWXAM (I) (Krishnamurthy et al., 2014 ▸); PONVOF (II) (Krishnamurthy & Begum, 2014 ▸); AFIZUM (III) (Fathima et al., 2013 ▸); YAYHAJ (IV) (Nagarajaiah et al., 2012 ▸); KUSQUL (V) (Jotani et al., 2010a ▸); PUJRIW (VI) (Jotani et al., 2010b ▸); DIWSIM (VII) (Jotani & Baldaniya, 2008 ▸); TICHAP (VIII) (Jotani & Baldaniya, 2007 ▸); AWUPAK (IX) (Fun et al., 2011 ▸); XETKOX (X) (Sridhar et al., 2006 ▸) and XETKOX01 (XI) (Sridhar et al., 2006 ▸).

In the crystal of (I), pairs of weak C—H⋯O hydrogen bonds link mol­ecules related by twofold rotation axes, forming (10) rings, which in turn are linked by weak C—H⋯N inter­actions to form chains parallel to [010]. In addition, weak C—H⋯π(arene) inter­actions link the chains into layers parallel to (001), and π–π inter­actions connect these layers into a three-dimensional network.

In (II), weak C—H⋯F and C— H⋯O hydrogen bonds connect mol­ecules, forming zigzag chains parallel to [010]. In addition, π–π stacking inter­actions connect these chains into ladders via inversion-related 4-fluoro­phenyl groups.

In (III), pairs of weak C—H⋯O hydrogen bonds lead to the formation of inversion dimers. A weak C—H⋯π inter­action and π–π stacking inter­actions are observed.

In (IV), O—H⋯N and C— H⋯S inter­actions result in (001) layers. The supra­molecular assembly is stabilized by π–π stacking inter­actions between the 2-bromo­benzyl­idene and thia­zolo­pyrimidine rings. In addition, C—H⋯π inter­actions are also observed.

In (V), co-operative C—H⋯O and C—H⋯π inter­actions lead to supra­molecular chains parallel [100]. These chains are connected via π–π inter­actions.

The crystal packing of (VI) is influenced by weak inter­molecular C—H⋯π inter­actions and π–π stacking between the thia­zole and phenyl rings, which stack the mol­ecules parallel to [001].

In (VII), in addition to inter­molecular C— H⋯O hydrogen bonding, short intra­molecular C—H⋯S contacts and π–π stacking inter­actions contribute to the crystal packing.

In (VIII), short inter­molecular C—H⋯O, C—H⋯π and π–π stacking inter­actions contribute to the stability of the crystal packing.

In (IX), mol­ecules are linked into a three-dimensional network by inter­molecular C— H⋯O and C—H⋯F hydrogen bonds. The crystal structure is further stabilized by a C—H⋯π inter­action.

Compounds (X) and (XI) crystallize in two polymorphic forms having the same space-group type, viz. P1, with Z′ = 2 and Z′ = 1. In both polymorphs, the mol­ecules are linked by N—H⋯O and C—H⋯O hydrogen bonds.

6. Synthesis and crystallization

A mixture of ethyl 4-(4-fluoro­phen­yl)-6-methyl-2-thioxo-1,2,3,4-tetra­hydro­pyrimidine-5-carboxyl­ate (2 mmol), 2-(chlor­o­meth­yl)-5-(4-meth­oxy­phen­yl)-1,3,4-oxa­diazole (2 mmol), potassium iodide (2 mmol) and triethyl amine (2.5 mmol), was refluxed for 4 h in absolute ethanol (20 ml). The reaction mixture was poured onto crushed ice (40 g) and acidified with acetic acid (2 ml). The deposited precipitate was filtered off, washed with cold water, dried and recrystallized from a methanol/DMF mixture.

Yield: 95%; melting point: 493–495 K; IR (KBr) ν_max/cm⁻¹ 3390, 3178, 1693, 1654. ¹H NMR (400 MHz, DMSO-d ₆) δ 10.60 (s, 1H, NH), 7.81 (d, J = 8.7 Hz, 2H, Ar—H), 7.44 (t, J = 7.7 Hz, 2H, Ar—H), 7.15 (t, J = 7.7 Hz, 2H, Ar—H), 7.03 (d, J = 8.7 Hz, 2H, Ar—H), 6.13 (s, 1H, C4—H), 4.45 (d, J = 17.4 Hz, 1H, S—CH₂), 4.35 (d, J = 17.3 Hz, 1H, S—CH₂), 4.03 (q, J = 7.1 Hz, 2H, CH₂—CH₃), 3.82 (s, 3H, OCH₃), 2.34 (s, 3H, C6-CH₃), 1.11 (t, J = 7.1 Hz, 3H, CH₂—CH₃). ¹³C NMR (125 MHz, DMSO-d ₆) δ 165.59, 163.23, 163.20, 162.65, 153.92, 153.58, 130.57, 130.50, 130.03, 125.90, 115.64, 115.47, 114.05, 105.95, 60.28, 55.87, 54.89, 28.56, 23.06, 14.45. Analysis calculated for C₂₄H₂₃FN₄O₄S (482.53): C 59.74, H 4.80, N 11.61. Found: C 60.02, H 4.89, N 11.87.

7. Refinement

Crystal data, data collection and structure refinement details are summarized in Table 3 ▸. The H atoms were found in difference-Fourier maps; all C and N-bound H atoms were refined freely. The water mol­ecule was found to be occupationally disordered and was refined with a fixed site occupation factor of 1/4. The H atoms of the water mol­ecules were located in a difference-Fourier map, their bond lengths set to an ideal value of 0.87 Å, and were refined with U _iso(H) = 1.5 U _eq(O) using a riding model.

Table 3. Experimental details.

Crystal data
Chemical formula	C24H23FN4O4S·0.25H2O
M r	487.03
Crystal system, space group	Monoclinic, P21/c
Temperature (K)	150
a, b, c (Å)	14.4316 (3), 10.8518 (2), 15.5940 (3)
β (°)	109.941 (1)
V (Å3)	2295.74 (8)
Z	4
Radiation type	Cu Kα
μ (mm−1)	1.68
Crystal size (mm)	0.15 × 0.14 × 0.11
Data collection
Diffractometer	Bruker D8 VENTURE PHOTON 100 CMOS
Absorption correction	Multi-scan (SADABS; Krause et al., 2015 ▸)
T min, T max	0.75, 0.84
No. of measured, independent and observed [I > 2σ(I)] reflections	17597, 4576, 4142
R int	0.029
(sin θ/λ)max (Å−1)	0.625
Refinement
R[F 2 > 2σ(F 2)], wR(F 2), S	0.035, 0.088, 1.04
No. of reflections	4576
No. of parameters	409
H-atom treatment	H atoms treated by a mixture of independent and constrained refinement
Δρmax, Δρmin (e Å−3)	0.34, −0.56

Computer programs: APEX3 and SAINT (Bruker, 2016 ▸), SHELXT (Sheldrick, 2015a ▸), SHELXL (Sheldrick, 2015b ▸), DIAMOND (Brandenburg & Putz, 2012 ▸) and publCIF (Westrip, 2010 ▸).

Supplementary Material

CCDC reference: 2177565

Additional supporting information: crystallographic information; 3D view; checkCIF report

supplementary crystallographic information

Crystal data

C24H23FN4O4S·0.25H2O	F(000) = 1018
Mr = 487.03	Dx = 1.409 Mg m−3
Monoclinic, P21/c	Cu Kα radiation, λ = 1.54178 Å
a = 14.4316 (3) Å	Cell parameters from 9970 reflections
b = 10.8518 (2) Å	θ = 3.3–74.4°
c = 15.5940 (3) Å	µ = 1.68 mm−1
β = 109.941 (1)°	T = 150 K
V = 2295.74 (8) Å3	Block, colourless
Z = 4	0.15 × 0.14 × 0.11 mm

Data collection

Bruker D8 VENTURE PHOTON 100 CMOS diffractometer	4576 independent reflections
Radiation source: INCOATEC IµS micro–focus source	4142 reflections with I > 2σ(I)
Mirror monochromator	Rint = 0.029
Detector resolution: 10.4167 pixels mm-1	θmax = 74.4°, θmin = 3.3°
ω scans	h = −17→18
Absorption correction: multi-scan (SADABS; Krause et al., 2015)	k = −13→12
Tmin = 0.75, Tmax = 0.84	l = −19→18
17597 measured reflections

Refinement

Refinement on F2	Secondary atom site location: difference Fourier map
Least-squares matrix: full	Hydrogen site location: difference Fourier map
R[F2 > 2σ(F2)] = 0.035	H atoms treated by a mixture of independent and constrained refinement
wR(F2) = 0.088	w = 1/[σ2(Fo2) + (0.0389P)2 + 1.1637P] where P = (Fo2 + 2Fc2)/3
S = 1.04	(Δ/σ)max < 0.001
4576 reflections	Δρmax = 0.34 e Å−3
409 parameters	Δρmin = −0.56 e Å−3
0 restraints	Extinction correction: SHELXL-2018/1 (Sheldrick, 2015b), Fc*=kFc[1+0.001xFc2λ3/sin(2θ)]-1/4
Primary atom site location: structure-invariant direct methods	Extinction coefficient: 0.00229 (19)

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.

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 > 2sigma(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. Refinement of the site occupancy factor for the lattice water (O5) converged at ca. 0.25. This was fixed at this value for the remainder of the refinement, the attached hydrogen atoms were located in a difference map and included as riding contributions in idealized positions.

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

	x	y	z	Uiso*/Ueq	Occ. (<1)
S1	0.45709 (2)	0.29846 (3)	0.22568 (2)	0.02637 (11)
F1	0.81951 (11)	0.85095 (10)	0.24433 (11)	0.0709 (4)
O1	0.93592 (8)	0.24379 (11)	0.47803 (8)	0.0365 (3)
O2	0.88439 (7)	0.41670 (10)	0.52684 (7)	0.0294 (2)
O3	0.55706 (8)	0.71812 (10)	0.54550 (7)	0.0307 (2)
O4	0.17420 (9)	1.04606 (11)	0.46165 (8)	0.0390 (3)
N1	0.64445 (8)	0.22708 (11)	0.27415 (8)	0.0220 (2)
N2	0.60560 (8)	0.39869 (10)	0.34918 (8)	0.0200 (2)
N3	0.54560 (8)	0.55654 (10)	0.41266 (8)	0.0206 (2)
N4	0.46512 (8)	0.62737 (11)	0.41154 (8)	0.0209 (2)
H4	0.4182 (14)	0.6419 (17)	0.3587 (13)	0.032 (5)*
C1	0.70873 (9)	0.43284 (13)	0.40035 (10)	0.0213 (3)
H1	0.7122 (12)	0.4512 (15)	0.4634 (11)	0.022 (4)*
C2	0.77324 (10)	0.32264 (13)	0.39918 (10)	0.0224 (3)
C3	0.74171 (10)	0.23233 (13)	0.33574 (10)	0.0224 (3)
C4	0.58287 (10)	0.30597 (12)	0.28731 (9)	0.0207 (3)
C5	0.73684 (9)	0.54708 (13)	0.35807 (10)	0.0233 (3)
C6	0.76870 (10)	0.65331 (14)	0.40974 (11)	0.0291 (3)
H6	0.7696 (14)	0.6545 (17)	0.4744 (13)	0.035 (5)*
C7	0.79756 (12)	0.75620 (15)	0.37183 (14)	0.0365 (4)
H7	0.8223 (15)	0.829 (2)	0.4092 (14)	0.048 (6)*
C8	0.79149 (13)	0.75033 (15)	0.28209 (14)	0.0410 (4)
C9	0.75793 (15)	0.64862 (16)	0.22793 (14)	0.0420 (4)
H9	0.7526 (16)	0.651 (2)	0.1629 (15)	0.050 (6)*
C10	0.73134 (12)	0.54590 (14)	0.26730 (11)	0.0314 (3)
H10	0.7067 (14)	0.4745 (19)	0.2304 (13)	0.038 (5)*
C11	0.87186 (10)	0.32007 (13)	0.46924 (10)	0.0253 (3)
C12	0.97996 (11)	0.42561 (17)	0.59855 (11)	0.0331 (3)
H12A	0.9878 (15)	0.353 (2)	0.6404 (14)	0.045 (5)*
H12B	1.0316 (14)	0.4216 (17)	0.5703 (12)	0.034 (5)*
H12C	0.9642 (16)	0.618 (2)	0.6014 (15)	0.052 (6)*
C13	0.98133 (13)	0.5454 (2)	0.64668 (13)	0.0412 (4)
H13A	1.0491 (17)	0.557 (2)	0.6929 (15)	0.055 (6)*
H13B	0.9329 (18)	0.545 (2)	0.6776 (16)	0.060 (7)*
C14	0.80354 (11)	0.12659 (15)	0.32406 (12)	0.0287 (3)
H14A	0.8649 (17)	0.155 (2)	0.3186 (15)	0.052 (6)*
H14B	0.8240 (16)	0.074 (2)	0.3764 (16)	0.054 (6)*
H14C	0.7663 (16)	0.079 (2)	0.2696 (15)	0.046 (5)*
C15	0.52713 (9)	0.47098 (12)	0.35314 (9)	0.0202 (3)
C16	0.43099 (10)	0.43208 (14)	0.28344 (10)	0.0260 (3)
H16A	0.4032 (14)	0.4974 (19)	0.2389 (13)	0.040 (5)*
H16B	0.3839 (15)	0.4099 (18)	0.3141 (14)	0.043 (5)*
C17	0.48023 (10)	0.71162 (13)	0.48039 (9)	0.0223 (3)
C18	0.39469 (10)	0.79431 (13)	0.47152 (9)	0.0230 (3)
C19	0.41359 (12)	0.90278 (14)	0.52329 (10)	0.0289 (3)
H19	0.4793 (15)	0.9188 (17)	0.5629 (13)	0.036 (5)*
C20	0.33869 (12)	0.98472 (15)	0.51747 (11)	0.0331 (3)
H20	0.3508 (16)	1.062 (2)	0.5510 (15)	0.053 (6)*
C21	0.24267 (11)	0.95909 (15)	0.46124 (10)	0.0294 (3)
C22	0.22193 (11)	0.85134 (15)	0.40997 (10)	0.0287 (3)
H22	0.1533 (15)	0.8314 (18)	0.3709 (13)	0.037 (5)*
C23	0.29829 (11)	0.76979 (14)	0.41584 (10)	0.0260 (3)
H23	0.2829 (13)	0.6946 (17)	0.3814 (12)	0.031 (5)*
C24	0.07367 (14)	1.0253 (2)	0.40748 (14)	0.0456 (5)
H24A	0.0502 (16)	0.946 (2)	0.4247 (15)	0.054 (6)*
H24B	0.0650 (16)	1.025 (2)	0.3411 (16)	0.053 (6)*
H24C	0.0390 (16)	1.093 (2)	0.4203 (14)	0.048 (6)*
O5	0.7191 (3)	0.9508 (5)	0.0994 (3)	0.0378 (10)	0.25
H5A	0.766259	0.901704	0.130626	0.057*	0.25
H5B	0.667996	0.902764	0.079072	0.057*	0.25

Atomic displacement parameters (Ų)

	U11	U22	U33	U12	U13	U23
S1	0.01757 (17)	0.0260 (2)	0.0312 (2)	0.00125 (12)	0.00266 (13)	−0.00720 (13)
F1	0.1061 (11)	0.0263 (6)	0.1191 (11)	−0.0171 (6)	0.0888 (10)	−0.0055 (6)
O1	0.0214 (5)	0.0345 (6)	0.0476 (7)	0.0093 (4)	0.0038 (5)	−0.0055 (5)
O2	0.0177 (5)	0.0313 (6)	0.0326 (6)	0.0026 (4)	0.0002 (4)	−0.0057 (4)
O3	0.0271 (5)	0.0336 (6)	0.0274 (5)	0.0038 (4)	0.0040 (4)	−0.0039 (4)
O4	0.0370 (6)	0.0405 (7)	0.0400 (6)	0.0175 (5)	0.0137 (5)	−0.0051 (5)
N1	0.0198 (5)	0.0194 (6)	0.0257 (6)	0.0010 (4)	0.0064 (5)	−0.0013 (4)
N2	0.0151 (5)	0.0186 (6)	0.0246 (6)	0.0011 (4)	0.0046 (4)	−0.0013 (4)
N3	0.0174 (5)	0.0202 (6)	0.0246 (6)	0.0028 (4)	0.0078 (4)	0.0011 (4)
N4	0.0179 (5)	0.0216 (6)	0.0231 (6)	0.0044 (4)	0.0069 (5)	0.0005 (4)
C1	0.0151 (6)	0.0211 (7)	0.0256 (7)	0.0001 (5)	0.0042 (5)	−0.0028 (5)
C2	0.0169 (6)	0.0208 (7)	0.0284 (7)	0.0019 (5)	0.0062 (5)	0.0005 (5)
C3	0.0190 (6)	0.0205 (7)	0.0276 (7)	0.0016 (5)	0.0079 (5)	0.0023 (5)
C4	0.0206 (6)	0.0181 (7)	0.0230 (7)	−0.0001 (5)	0.0067 (5)	0.0005 (5)
C5	0.0146 (6)	0.0199 (7)	0.0348 (8)	0.0012 (5)	0.0077 (5)	−0.0021 (5)
C6	0.0207 (7)	0.0237 (8)	0.0399 (9)	0.0007 (5)	0.0066 (6)	−0.0057 (6)
C7	0.0270 (8)	0.0204 (8)	0.0640 (11)	−0.0040 (6)	0.0179 (8)	−0.0093 (7)
C8	0.0439 (9)	0.0204 (8)	0.0744 (13)	−0.0032 (7)	0.0406 (9)	0.0001 (8)
C9	0.0582 (11)	0.0270 (9)	0.0568 (11)	−0.0018 (7)	0.0402 (10)	−0.0014 (7)
C10	0.0373 (8)	0.0227 (8)	0.0403 (9)	−0.0035 (6)	0.0212 (7)	−0.0051 (6)
C11	0.0191 (6)	0.0238 (7)	0.0312 (7)	0.0015 (5)	0.0064 (6)	−0.0005 (6)
C12	0.0177 (7)	0.0431 (10)	0.0315 (8)	0.0004 (6)	−0.0005 (6)	−0.0031 (7)
C13	0.0284 (8)	0.0560 (12)	0.0348 (9)	−0.0025 (8)	0.0053 (7)	−0.0140 (8)
C14	0.0239 (7)	0.0252 (8)	0.0356 (8)	0.0050 (6)	0.0083 (6)	−0.0037 (6)
C15	0.0171 (6)	0.0186 (7)	0.0246 (7)	0.0011 (5)	0.0068 (5)	0.0028 (5)
C16	0.0187 (6)	0.0254 (8)	0.0303 (8)	0.0020 (5)	0.0038 (6)	−0.0048 (6)
C17	0.0226 (7)	0.0217 (7)	0.0234 (7)	0.0007 (5)	0.0090 (5)	0.0015 (5)
C18	0.0246 (7)	0.0235 (7)	0.0234 (7)	0.0023 (5)	0.0113 (6)	0.0002 (5)
C19	0.0287 (8)	0.0288 (8)	0.0292 (8)	0.0003 (6)	0.0098 (6)	−0.0039 (6)
C20	0.0378 (9)	0.0286 (8)	0.0336 (8)	0.0043 (6)	0.0134 (7)	−0.0072 (6)
C21	0.0322 (8)	0.0313 (8)	0.0286 (8)	0.0110 (6)	0.0155 (6)	0.0018 (6)
C22	0.0254 (7)	0.0341 (8)	0.0283 (7)	0.0042 (6)	0.0114 (6)	−0.0016 (6)
C23	0.0256 (7)	0.0274 (8)	0.0273 (7)	0.0014 (6)	0.0121 (6)	−0.0035 (6)
C24	0.0357 (9)	0.0540 (12)	0.0455 (11)	0.0212 (9)	0.0119 (8)	−0.0026 (9)
O5	0.027 (2)	0.042 (3)	0.039 (3)	−0.0069 (19)	0.0036 (19)	0.006 (2)

Geometric parameters (Å, º)

S1—C4	1.7422 (14)	C9—C10	1.388 (2)
S1—C16	1.8130 (15)	C9—H9	0.99 (2)
F1—C8	1.3657 (19)	C10—H10	0.96 (2)
O1—C11	1.2133 (18)	C12—C13	1.498 (2)
O2—C11	1.3522 (18)	C12—H12A	1.00 (2)
O2—C12	1.4526 (17)	C12—H12B	0.988 (19)
O3—C17	1.2236 (17)	C13—H12C	1.03 (2)
O4—C21	1.3680 (18)	C13—H13A	1.00 (2)
O4—C24	1.426 (2)	C13—H13B	0.98 (3)
N1—C4	1.2996 (18)	C14—H14A	0.97 (2)
N1—C3	1.4058 (17)	C14—H14B	0.96 (2)
N2—C4	1.3546 (17)	C14—H14C	0.98 (2)
N2—C15	1.3963 (17)	C15—C16	1.5020 (19)
N2—C1	1.4762 (16)	C16—H16A	0.98 (2)
N3—C15	1.2750 (18)	C16—H16B	0.98 (2)
N3—N4	1.3880 (15)	C17—C18	1.4939 (19)
N4—C17	1.3698 (18)	C18—C23	1.391 (2)
N4—H4	0.885 (19)	C18—C19	1.401 (2)
C1—C2	1.5194 (18)	C19—C20	1.379 (2)
C1—C5	1.5226 (19)	C19—H19	0.96 (2)
C1—H1	0.987 (17)	C20—C21	1.392 (2)
C2—C3	1.356 (2)	C20—H20	0.97 (2)
C2—C11	1.4694 (19)	C21—C22	1.390 (2)
C3—C14	1.5024 (19)	C22—C23	1.392 (2)
C5—C10	1.391 (2)	C22—H22	0.99 (2)
C5—C6	1.392 (2)	C23—H23	0.960 (19)
C6—C7	1.392 (2)	C24—H24A	0.99 (2)
C6—H6	1.004 (19)	C24—H24B	1.00 (2)
C7—C8	1.373 (3)	C24—H24C	0.95 (2)
C7—H7	0.97 (2)	O5—H5A	0.8700
C8—C9	1.374 (3)	O5—H5B	0.8701
C4—S1—C16	92.44 (6)	C13—C12—H12B	112.3 (11)
C11—O2—C12	116.09 (11)	H12A—C12—H12B	108.7 (16)
C21—O4—C24	118.60 (14)	C12—C13—H12C	111.3 (12)
C4—N1—C3	116.27 (12)	C12—C13—H13A	107.9 (13)
C4—N2—C15	116.48 (11)	H12C—C13—H13A	110.2 (18)
C4—N2—C1	121.74 (11)	C12—C13—H13B	110.9 (14)
C15—N2—C1	121.23 (11)	H12C—C13—H13B	107.1 (18)
C15—N3—N4	115.33 (11)	H13A—C13—H13B	109.4 (19)
C17—N4—N3	116.80 (11)	C3—C14—H14A	111.4 (13)
C17—N4—H4	118.6 (12)	C3—C14—H14B	112.1 (14)
N3—N4—H4	118.8 (12)	H14A—C14—H14B	103.9 (18)
N2—C1—C2	107.75 (11)	C3—C14—H14C	109.4 (12)
N2—C1—C5	109.80 (11)	H14A—C14—H14C	109.8 (18)
C2—C1—C5	112.38 (11)	H14B—C14—H14C	110.1 (18)
N2—C1—H1	106.8 (9)	N3—C15—N2	118.03 (12)
C2—C1—H1	110.3 (9)	N3—C15—C16	130.06 (12)
C5—C1—H1	109.6 (10)	N2—C15—C16	111.90 (11)
C3—C2—C11	121.84 (12)	C15—C16—S1	106.69 (9)
C3—C2—C1	121.53 (12)	C15—C16—H16A	111.4 (12)
C11—C2—C1	116.62 (12)	S1—C16—H16A	109.4 (11)
C2—C3—N1	122.42 (12)	C15—C16—H16B	109.7 (12)
C2—C3—C14	125.10 (13)	S1—C16—H16B	109.9 (12)
N1—C3—C14	112.47 (12)	H16A—C16—H16B	109.8 (16)
N1—C4—N2	126.10 (12)	O3—C17—N4	123.09 (13)
N1—C4—S1	121.47 (10)	O3—C17—C18	121.90 (13)
N2—C4—S1	112.41 (10)	N4—C17—C18	115.00 (12)
C10—C5—C6	119.33 (14)	C23—C18—C19	118.49 (13)
C10—C5—C1	120.14 (13)	C23—C18—C17	124.17 (13)
C6—C5—C1	120.53 (13)	C19—C18—C17	117.34 (13)
C5—C6—C7	120.41 (16)	C20—C19—C18	120.67 (15)
C5—C6—H6	118.7 (11)	C20—C19—H19	120.6 (11)
C7—C6—H6	120.9 (11)	C18—C19—H19	118.8 (11)
C8—C7—C6	118.11 (15)	C19—C20—C21	120.16 (15)
C8—C7—H7	122.1 (12)	C19—C20—H20	121.9 (13)
C6—C7—H7	119.8 (12)	C21—C20—H20	117.9 (13)
F1—C8—C7	118.48 (16)	O4—C21—C22	124.66 (14)
F1—C8—C9	118.13 (17)	O4—C21—C20	115.13 (14)
C7—C8—C9	123.39 (16)	C22—C21—C20	120.20 (14)
C8—C9—C10	117.76 (17)	C21—C22—C23	119.12 (14)
C8—C9—H9	119.7 (13)	C21—C22—H22	120.7 (11)
C10—C9—H9	122.5 (13)	C23—C22—H22	120.2 (11)
C9—C10—C5	120.96 (15)	C18—C23—C22	121.34 (14)
C9—C10—H10	119.1 (12)	C18—C23—H23	120.2 (11)
C5—C10—H10	119.9 (12)	C22—C23—H23	118.4 (11)
O1—C11—O2	122.00 (13)	O4—C24—H24A	110.4 (13)
O1—C11—C2	127.18 (14)	O4—C24—H24B	110.9 (13)
O2—C11—C2	110.81 (11)	H24A—C24—H24B	110.1 (18)
O2—C12—C13	106.88 (13)	O4—C24—H24C	104.9 (13)
O2—C12—H12A	108.3 (12)	H24A—C24—H24C	111.1 (18)
C13—C12—H12A	112.1 (12)	H24B—C24—H24C	109.4 (18)
O2—C12—H12B	108.5 (11)	H5A—O5—H5B	104.0
C15—N3—N4—C17	173.45 (12)	C1—C5—C10—C9	−179.13 (15)
C4—N2—C1—C2	−21.62 (17)	C12—O2—C11—O1	1.5 (2)
C15—N2—C1—C2	167.22 (11)	C12—O2—C11—C2	−179.00 (12)
C4—N2—C1—C5	101.08 (14)	C3—C2—C11—O1	2.3 (2)
C15—N2—C1—C5	−70.08 (15)	C1—C2—C11—O1	−176.78 (15)
N2—C1—C2—C3	20.41 (18)	C3—C2—C11—O2	−177.21 (13)
C5—C1—C2—C3	−100.69 (15)	C1—C2—C11—O2	3.75 (18)
N2—C1—C2—C11	−160.54 (12)	C11—O2—C12—C13	173.66 (14)
C5—C1—C2—C11	78.36 (15)	N4—N3—C15—N2	178.26 (11)
C11—C2—C3—N1	173.50 (13)	N4—N3—C15—C16	−2.1 (2)
C1—C2—C3—N1	−7.5 (2)	C4—N2—C15—N3	177.79 (12)
C11—C2—C3—C14	−5.0 (2)	C1—N2—C15—N3	−10.60 (19)
C1—C2—C3—C14	174.03 (14)	C4—N2—C15—C16	−1.93 (17)
C4—N1—C3—C2	−7.2 (2)	C1—N2—C15—C16	169.67 (12)
C4—N1—C3—C14	171.48 (13)	N3—C15—C16—S1	−176.70 (12)
C3—N1—C4—N2	6.2 (2)	N2—C15—C16—S1	2.98 (14)
C3—N1—C4—S1	−171.99 (10)	C4—S1—C16—C15	−2.61 (11)
C15—N2—C4—N1	−178.53 (13)	N3—N4—C17—O3	−7.08 (19)
C1—N2—C4—N1	9.9 (2)	N3—N4—C17—C18	174.20 (11)
C15—N2—C4—S1	−0.18 (15)	O3—C17—C18—C23	−160.50 (14)
C1—N2—C4—S1	−171.74 (10)	N4—C17—C18—C23	18.2 (2)
C16—S1—C4—N1	−179.84 (12)	O3—C17—C18—C19	19.1 (2)
C16—S1—C4—N2	1.73 (11)	N4—C17—C18—C19	−162.14 (13)
N2—C1—C5—C10	−58.95 (16)	C23—C18—C19—C20	−1.5 (2)
C2—C1—C5—C10	60.97 (17)	C17—C18—C19—C20	178.83 (14)
N2—C1—C5—C6	121.37 (13)	C18—C19—C20—C21	1.3 (2)
C2—C1—C5—C6	−118.72 (14)	C24—O4—C21—C22	1.3 (2)
C10—C5—C6—C7	−1.9 (2)	C24—O4—C21—C20	−178.54 (16)
C1—C5—C6—C7	177.79 (13)	C19—C20—C21—O4	179.23 (14)
C5—C6—C7—C8	1.4 (2)	C19—C20—C21—C22	−0.6 (2)
C6—C7—C8—F1	179.90 (15)	O4—C21—C22—C23	−179.73 (14)
C6—C7—C8—C9	0.4 (3)	C20—C21—C22—C23	0.1 (2)
F1—C8—C9—C10	178.81 (16)	C19—C18—C23—C22	1.0 (2)
C7—C8—C9—C10	−1.7 (3)	C17—C18—C23—C22	−179.37 (13)
C8—C9—C10—C5	1.2 (3)	C21—C22—C23—C18	−0.3 (2)
C6—C5—C10—C9	0.6 (2)

Hydrogen-bond geometry (Å, º)

D—H···A	D—H	H···A	D···A	D—H···A
N4—H4···N1i	0.885 (19)	2.164 (19)	2.9888 (17)	154.8 (16)
C1—H1···O5ii	0.987 (17)	2.345 (18)	3.307 (5)	164.7 (13)
C7—H7···O4iii	0.97 (2)	2.41 (2)	3.285 (2)	148.7 (17)
C13—H13B···F1ii	0.98 (3)	2.49 (3)	3.386 (2)	153.0 (19)
C16—H16A···N1i	0.98 (2)	2.58 (2)	3.4019 (19)	142.4 (15)
C16—H16B···O5iv	0.98 (2)	2.37 (2)	3.282 (5)	154.6 (16)
C24—H24A···O1v	0.99 (2)	2.53 (2)	3.450 (3)	154.6 (18)
C24—H24C···O1vi	0.95 (2)	2.57 (2)	3.504 (2)	167.8 (17)
O5—H5A···F1	0.87	1.76	2.479 (5)	138
O5—H5B···O3vii	0.87	2.00	2.863 (5)	174

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

Funding Statement

The support of NSF-MRI grant No. 1228232 for the purchase of the diffractometer and Tulane University for support of the Tulane Crystallography Laboratory are gratefully acknowledged.