Polymorphism of 2-(5-benzyl-6-oxo-3-phenyl-1,6-di-hydro-pyridazin-1-yl)acetic acid with two monoclinic modifications: crystal structures and Hirshfeld surface analyses.

Two polymorphs of the title compound, C19H16N2O3, were obtained from ethano-lic (polymorph I) and methano-lic solutions (polymorph II), respectively. Both polymorphs crystallize in the monoclinic system with four formula units per cell and a complete mol-ecule in the asymmetric unit. The main difference between the mol-ecules of (I) and (II) is the reversed position of the hy-droxy group of the carb-oxy-lic function. All other conformational features are found to be similar in the two mol-ecules. The different orientation of the OH group results in different hydrogen-bonding schemes in the crystal structures of (I) and (II). Whereas in (I) inter-molecular O-H⋯O hydrogen bonds with the pyridazinone carbonyl O atom as acceptor generate chains with a C(7) motif extending parallel to the b-axis direction, in the crystal of (II) pairs of inversion-related O-H⋯O hydrogen bonds with an R 2 2(8) ring motif between two carb-oxy-lic functions are found. The inter-molecular inter-actions in both crystal structures were analysed using Hirshfeld surface analysis and two-dimensional fingerprint plots. © Daoui et al. 2020.

Chemical context

Pyridazin-3(2H)-ones are an important family of heterocycles because of their great chemical reactivity (Chelfi et al., 2015 ▸; Zarrouk et al., 2010 ▸), with new products reported recently (Chakraborty et al., 2018 ▸; El Kalai et al., 2019a ▸). In addition, the importance of pyridazinones in medicinal chemistry has increased in recent years thanks to their pharmacological properties, including anti­cancer (Yarden & Caldes, 2013 ▸), anti-hypertensive (Siddiqui et al., 2011 ▸), anti­bacterial (Akhtar et al., 2016 ▸), anti-HIV (Livermore et al., 1993 ▸), anti-inflammatory (Singh et al., 2017 ▸), anti­depressant (Boukharsa et al., 2016 ▸), anti-convulsant (Partap et al., 2018 ▸) and cardiotonic (Costas et al., 2015 ▸) activities. Several pyridazinone-based products are already present in the pharmaceutical market such as Minaprine (Sotelo et al., 2003 ▸), Aza­nrinone (Mahmoodi et al., 2014 ▸), Indolidan (Abouzid et al., 2008 ▸) and Levosimendan (Archan & Toller, 2008 ▸).

In a continuation of our recent work on the synthesis and crystal structures of new pyridazin-3(2H)-one derivatives (El Kalai et al., 2019b ▸; Daoui et al., 2019a ▸,b ▸), we report here the synthesis, crystal structure and polymorphism of 2-(5-benzyl-6-oxo-3-phenyl­pyridazin-1(6H)-yl)acetic acid, which is going to be subjected to further pharmacological investigations.

Structural commentary

The title compound is dimorphic with two monoclinic polymorphs. The mol­ecular structure of polymorph (I) is shown in Fig. 1 ▸ and that of polymorph (II) in Fig. 2 ▸. The differences in the conformations of the two mol­ecules is shown in the structural overlap drawing (Fig. 3 ▸). The main difference between (I) and (II) pertains to the OH function of the carboxyl group, which is reversed in the two mol­ecules. All other conformational features are quite similar in the mol­ecules of the two polymorphs. In (I), the phenyl ring (C1–C6) and the pyridazine ring (N1/N2/C10–C7) are nearly co-planar, making a dihedral angle of 5.92 (2)° whereas the phenyl ring of the benzyl group (C14–C19) is perpendicular to the pyridazine ring, with a dihedral angle of 89.91 (1)° (Fig. 1 ▸). In (II), the corresponding values are 15.44 (2) and 89.13 (1)°, respectively. In the mol­ecule of (I), the carboxyl group has a C12—O2 bond length of 1.277 (2) Å between the C atom and the OH function, and the C12=O3 bond length of the carbonyl group is 1.187 (2) Å. The corresponding values in (II) are 1.3057 (16) and 1.2108 (18) Å. The differences in the bond lengths of the two carb­oxy­lic groups can be attributed to their different roles in inter­molecular hydrogen bonding (see below). In both mol­ecules, weak intra­molecular hydrogen bonds [C—H⋯N for (I) and C—H⋯O for (II); Figs. 1 ▸ and 2 ▸, Tables 1 ▸ and 2 ▸] stabilize the mol­ecular conformation.

Figure 1

The mol­ecular structure of (I) with displacement ellipsoids drawn at the 30% probability level.

Figure 2

The mol­ecular structure of (II) with displacement ellipsoids drawn at the 30% probability level.

Figure 3

Structural overlap of mol­ecules (I) and (II).

Table 1

Hydrogen-bond geometry (Å, °) for I

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
O2—H2⋯O1i	0.82	1.82	2.593 (2)	156
C1—H1⋯N1	0.93	2.47	2.780 (3)	100

Symmetry code: (i) .

Table 2

Hydrogen-bond geometry (Å, °) for II

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
C11—H11B⋯O1	0.97	2.39	2.7325 (19)	100
O2—H3⋯O3i	0.82	1.84	2.6599 (16)	177
C5—H5⋯O3ii	0.93	2.40	3.280 (2)	159
C11—H11A⋯O1iii	0.97	2.47	3.2814 (19)	141

Symmetry codes: (i) ; (ii) ; (iii) .

Supra­molecular features

In the crystal structure of (I), mol­ecules are linked by O2—H2⋯O1i hydrogen bonds between the carb­oxy­lic OH function and the pyridazinone carbonyl O1 atom of a neighbouring mol­ecule, generating C(7) chains extending parallel to the b-axis direction (Fig. 4 ▸, Table 1 ▸). A weak π–π stacking inter­action occurs between the pyridazinone rings of inversion-related mol­ecules [Cg1⋯Cg1(1 − x, 1 − y,1 − z)], with a centroid–to–centroid distance of 3.8437 (12) Å and a slippage of 1.690 (Cg1 is the centroid of the N1/N2/C10–C7 ring) (Fig. 4 ▸). As a result of the reversed orientation of the carb­oxy­lic hy­droxy function, in the crystal structure of (II) the hydrogen-bonding scheme is different. Here mol­ecules are linked by pairs of O3—H3⋯O2i hydrogen bonds between the carb­oxy­lic groups of neighbouring mol­ecules, forming inversion dimers with an (8) ring motif. The dimers are linked by weak C5—H5⋯O2ii and C11—H11A⋯O1iii hydrogen bonds, forming C(8) chains extending parallel to the b-axis direction (Table 2 ▸, Fig. 5 ▸). The crystal packing of (II) also features weak π–π inter­actions involving the centroids of the N1/N2/C7–C10 (Cg1) and C14–C19 (Cg3) rings, with Cg1⋯Cg3(x,  − y, − + z) = 4.3830 (12) Å.

Figure 4

The crystal packing of (I). The O—H⋯O hydrogen bonds are shown as blue dotteded lines, and π–π contacts are represented by green dotted lines. For clarity, only H atoms involved in hydrogen bonding (white sticks) were included.

Figure 5

The crystal packing of (II), with O—H⋯O and C—H⋯O inter­actions shown as blue and black dotted lines, respectively.

Database survey

A search of the Cambridge Structural Database (CSD, version 5.40, update August 2019; Groom et al., 2016 ▸) using 2-[6-oxopyridazin-1(6H)-yl]acetic acid as the main skeleton revealed the presence of three structures similar to the title compound, but with different substituents on the pyridazione ring, viz. ethyl 2-[6-oxo-3,4-diphenyl-1,6-di­hydro­pyridazin-1-yl]acetic acid acetate (CIPTOL; Aydın et al., 2007 ▸), ethyl 3-methyl-6-oxo-5-[3-(tri­fluoro­meth­yl)phen­yl]-1,6-di­hydro-1-pyridazine­acetate (QANVOR; Xu et al., 2005 ▸) and ethyl {4-[(5-chloro-1-benzo­furan-2-yl)meth­yl]-3-methyl-6-oxopyrida­zin-1(6H)-yl}acetate (XULSEE; Boukharsa et al., 2015 ▸). Like in (I) and (II), the packing within the crystal structures of these compounds is dominated by O—H⋯O hydrogen bonds and consolidated by C—H⋯O inter­actions. In CIPTOL, the pyridazinone ring and two phenyl rings are inclined to each other by 72.73 (11) and 49.97 (10)° compared to the corres­ponding dihedral angles of 5.92 (2), 89.91 (1) and 15.44 (2)°, 89.13 (1)° in (I) and (II), respectively. In QANVOR, the 3-(tri­fluoro­meth­yl)phenyl and pyridazinone rings are approximately coplanar with a dihedral angle of 4.84 (13)°. In XULSEE, the dihedral angle between the benzo­furan ring system [maximum deviation 0.014 (2) Å] and the pyridazinone ring is 73.33 (8)°.

Hirshfeld surface analysis

Hirshfeld surface analysis was applied to qu­antify the inter­molecular contacts in (I) and (II), using CrystalExplorer17.5 (Turner et al., 2017 ▸). A standard (high) surface resolution with the three-dimensional d norm surfaces plotted over a fixed colour scale of −0.7266 (red) to 1.4843 (blue) a.u. was used for (I) and of −0.7232 (red) to 1.3047 (blue) a.u. for (II). The bright-red spots on the Hirshfeld surface mapped over d norm show the presence of O—H⋯O inter­actions with neighbouring mol­ecules in (I) (Fig. 6 ▸ a) and (II) (Fig. 7 ▸ a), respectively. The presence of red and blue triangles on the shape-index map [Fig. 6 ▸ b (I) and 7b (II)] are indicative for the presence of π–π stacking inter­actions. The curvedness plots show flat surface patches characteristic of planar stacking (Fig. 6 ▸ c and 7c). The complete two-dimensional fingerprint plots are shown in Fig. 8 ▸ a and 9a for (I) and (II). The H⋯H, H⋯O, C⋯H, C⋯C, C⋯N, N⋯H and C⋯O inter­actions are illustrated in Fig. 8 ▸ b–h for (I), and H⋯H, C⋯H, H⋯O, N⋯H, C⋯C and C⋯O inter­actions are illustrated in Fig. 9 ▸ b–g for (II). In both crystal structures, H⋯H inter­actions make the largest contributions to the overall Hirshfeld surfaces [48.7% for (I) and 43.6% for (II)]. As expected from the inter­molecular O—H⋯O and C—H⋯O contacts detailed in Tables 1 ▸ and 2 ▸, H⋯O contacts also account for a high percentage contributions [21.5% (I) and 21.9% (II)] and are indicated by a pair of wings at d e + d i ∼1.7 Å [Fig. 8 ▸ c (I) and 9d (II)]. The C⋯H contacts,with percentage contributions of 19.2% in (I) and 22.5% in (II) appear in the fingerprint plots as two distinct spikes at d e + d i ∼2.9 Å in (I) and 3.0 Å in (II) (Fig. 8 ▸ d and 9c). The C⋯C contacts, which refer to π–π inter­actions, contribute 4.2% of the Hirshfeld surfaces for both (I) and (II) (Fig. 8 ▸ e and 9f). There are additional N⋯H (5.0%) and C⋯O (2.8%) contacts in (II), while in (I) (where N⋯H = 1.8% and C⋯O = 1.7%), C⋯N (2.9%) inter­actions are also observed.

Figure 6

(a) The Hirshfeld surface of (I) mapped over d norm, and plotted in the range −0.7266 (red) to 1.4843 (blue) a.u.; (b) the Hirshfeld surface mapped over shape-index; (c) the Hirshfeld surface mapped over curvedness.

Figure 7

(a) The Hirshfeld surface of (II) mapped over d norm, and plotted in the range −0.7232 (red) to 1.3047 (blue) a.u.; (b) the Hirshfeld surface mapped over shape-index, (c) the Hirshfeld surface mapped over curvedness.

Figure 8

Two-dimensional fingerprint plots for (I): (a) all inter­molecular inter­actions; (b) H⋯H contacts; (c) H⋯O contacts; (d) C⋯H contacts; (e) C⋯C contacts; (f) C⋯N contacts; (g) N⋯H contacts; (h) C⋯O contacts.

Figure 9

Two-dimensional fingerprint plots for (II): (a) all inter­molecular inter­actions; (b) H⋯H contacts; (c) C⋯H contacts; (d) H⋯O contacts; (e) N⋯H contacts; (f) C⋯C contacts; (g) C⋯O contacts.

Synthesis and crystallization

A suspension of ethyl 2-(5-benzyl-6-oxo-3-phenyl­pyridazin-1(6H)-yl)acetate (3.6 mmol), and 6 N NaOH (14.4 mmol) in ethanol (50 ml) was stirred at 353 K for 4 h. The mixture was then concentrated in vacuo, diluted with cold water, and acidified with 6 N HCl. The final product was filtered off by suction filtration and recrystallized from ethanol or methanol. Single crystals of (I) were obtained by slow evaporation of an ethano­lic solution at room temperature, and single crystals of (II) were obtained by slow evaporation of a methano­lic solution at room temperature.

Refinement

Crystal data, data collection and structure refinement details are summarized in Table 3 ▸. The atom labelling for mol­ecules of (I) and (II) is identical. In the refinement of (I), SIMU, DELU and ISOR commands were used for atoms C12 and O3. For both structures, hydrogen atoms of the carb­oxy­lic group were located in a difference-Fourier map and were refined with a fixed O—H distance of 0.82 Å and with U iso(H) = 1.5U eq(O). All other hydrogen atoms were placed in calculated positions, with C—H = 0.93–0.96 Å and allowed to ride on their parent atoms with U iso(H) = 1.5U eq(C-meth­yl) and 1.2U eq(C) for other H atoms.

Table 3

Experimental details

	I	II
Crystal data
Chemical formula	C19H16N2O3	C19H16N2O3
M r	320.34	320.34
Crystal system, space group	Monoclinic, P21/n	Monoclinic, P21/c
Temperature (K)	296	296
a, b, c (Å)	10.5500 (8), 9.3679 (6), 16.5606 (15)	10.5976 (6), 15.5500 (7), 10.3731 (7)
β (°)	93.886 (7)	109.120 (5)
V (Å3)	1632.9 (2)	1615.11 (17)
Z	4	4
Radiation type	Mo Kα	Mo Kα
μ (mm−1)	0.09	0.09
Crystal size (mm)	0.58 × 0.43 × 0.34	0.77 × 0.70 × 0.59
Data collection
Diffractometer	Stoe IPDS 2	STOE IPDS 2
Absorption correction	Integration (X-RED32; Stoe & Cie, 2002 ▸)	Integration (X-RED32; Stoe & Cie, 2002 ▸)
T min, T max	0.961, 0.981	0.950, 0.966
No. of measured, independent and observed [I > 2σ(I)] reflections	12987, 4603, 1989	12114, 4562, 2560
R int	0.039	0.037
(sin θ/λ)max (Å−1)	0.698	0.699
Refinement
R[F 2 > 2σ(F 2)], wR(F 2), S	0.053, 0.158, 0.89	0.049, 0.131, 0.98
No. of reflections	4603	4562
No. of parameters	217	218
No. of restraints	19	0
H-atom treatment	H-atom parameters constrained	H-atom parameters constrained
Δρmax, Δρmin (e Å−3)	0.35, −0.34	0.21, −0.21

Computer programs: X-AREA and X-RED32 (Stoe & Cie, 2002 ▸), SHELXT2017/1 (Sheldrick, 2015a ▸), SHELXL2018/3 (Sheldrick, 2015b ▸), Mercury (Macrae et al., 2020 ▸), WinGX (Farrugia, 2012 ▸), PLATON (Spek, 2020 ▸) and publCIF (Westrip, 2010 ▸).

Crystal structure: contains datablock(s) I, II. DOI: 10.1107/S2056989020002406/wm5541sup1.cif

Structure factors: contains datablock(s) I. DOI: 10.1107/S2056989020002406/wm5541Isup2.hkl

Structure factors: contains datablock(s) II. DOI: 10.1107/S2056989020002406/wm5541IIsup3.hkl

Click here for additional data file.

Supporting information file. DOI: 10.1107/S2056989020002406/wm5541Isup4.cml

CCDC references: 1985197, 1985196

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

C19H16N2O3	F(000) = 672
Mr = 320.34	Dx = 1.303 Mg m−3
Monoclinic, P21/n	Mo Kα radiation, λ = 0.71073 Å
a = 10.5500 (8) Å	Cell parameters from 9543 reflections
b = 9.3679 (6) Å	θ = 1.9–29.8°
c = 16.5606 (15) Å	µ = 0.09 mm−1
β = 93.886 (7)°	T = 296 K
V = 1632.9 (2) Å3	Prism, colorless
Z = 4	0.58 × 0.43 × 0.34 mm

Stoe IPDS 2 diffractometer	4603 independent reflections
Radiation source: sealed X-ray tube, 12 x 0.4 mm long-fine focus	1989 reflections with I > 2σ(I)
Plane graphite monochromator	Rint = 0.039
Detector resolution: 6.67 pixels mm-1	θmax = 29.7°, θmin = 2.4°
rotation method scans	h = −12→14
Absorption correction: integration (X-RED32; Stoe & Cie, 2002)	k = −13→12
Tmin = 0.961, Tmax = 0.981	l = −23→23
12987 measured reflections

Refinement on F2	19 restraints
Least-squares matrix: full	Hydrogen site location: inferred from neighbouring sites
R[F2 > 2σ(F2)] = 0.053	H-atom parameters constrained
wR(F2) = 0.158	w = 1/[σ2(Fo2) + (0.0772P)2] where P = (Fo2 + 2Fc2)/3
S = 0.89	(Δ/σ)max < 0.001
4603 reflections	Δρmax = 0.35 e Å−3
217 parameters	Δρmin = −0.34 e Å−3

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.

	x	y	z	Uiso*/Ueq
N2	0.63345 (14)	0.43785 (17)	0.40115 (9)	0.0550 (4)
N1	0.56137 (14)	0.34515 (16)	0.44077 (9)	0.0539 (4)
O1	0.66753 (13)	0.60906 (17)	0.31011 (10)	0.0811 (5)
O2	0.76216 (13)	0.27628 (19)	0.30333 (10)	0.0914 (6)
H2	0.804328	0.226747	0.274357	0.137*
C7	0.43814 (16)	0.35514 (19)	0.42800 (10)	0.0508 (4)
C6	0.36108 (18)	0.2513 (2)	0.47105 (11)	0.0536 (4)
C8	0.38202 (17)	0.4630 (2)	0.37706 (11)	0.0567 (5)
H8	0.294010	0.471278	0.371699	0.068*
C10	0.58990 (18)	0.5384 (2)	0.34591 (11)	0.0589 (5)
C12	0.83446 (19)	0.3288 (2)	0.36076 (12)	0.0612 (5)
C9	0.45351 (17)	0.5535 (2)	0.33636 (11)	0.0594 (5)
O3	0.94446 (16)	0.3027 (3)	0.37082 (12)	0.1213 (7)
C11	0.77005 (17)	0.4220 (2)	0.41864 (12)	0.0634 (5)
H11A	0.785002	0.382843	0.472680	0.076*
H11B	0.808847	0.515829	0.418553	0.076*
C14	0.26299 (19)	0.7017 (2)	0.29161 (12)	0.0638 (5)
C5	0.2306 (2)	0.2435 (2)	0.45719 (13)	0.0677 (6)
H5	0.189656	0.304979	0.419821	0.081*
C15	0.2264 (2)	0.7924 (3)	0.35035 (15)	0.0794 (7)
H15	0.288323	0.838285	0.383550	0.095*
C4	0.1600 (2)	0.1465 (3)	0.49763 (14)	0.0780 (6)
H4	0.072279	0.143929	0.487252	0.094*
C13	0.4010 (2)	0.6709 (3)	0.28207 (15)	0.0822 (7)
H13A	0.411644	0.644798	0.226260	0.099*
H13B	0.449726	0.757252	0.293614	0.099*
C17	0.0092 (2)	0.7521 (3)	0.31546 (16)	0.0888 (8)
H17	−0.075763	0.769037	0.323863	0.107*
C19	0.1676 (2)	0.6361 (3)	0.24455 (14)	0.0836 (7)
H19	0.188376	0.573613	0.203863	0.100*
C3	0.2156 (3)	0.0557 (3)	0.55173 (15)	0.0859 (7)
H3	0.167270	−0.008738	0.579307	0.103*
C1	0.4167 (2)	0.1565 (3)	0.52585 (16)	0.0904 (8)
H1	0.504386	0.157532	0.536391	0.109*
C16	0.1008 (2)	0.8173 (3)	0.36152 (17)	0.0958 (8)
H16	0.078911	0.880366	0.401664	0.115*
C18	0.0408 (2)	0.6619 (3)	0.25690 (16)	0.0901 (8)
H18	−0.022580	0.616712	0.224545	0.108*
C2	0.3444 (3)	0.0599 (3)	0.56547 (18)	0.1078 (10)
H2A	0.384238	−0.003519	0.602205	0.129*

	U11	U22	U33	U12	U13	U23
N2	0.0449 (8)	0.0597 (10)	0.0611 (9)	0.0062 (7)	0.0087 (7)	−0.0024 (8)
N1	0.0496 (9)	0.0560 (9)	0.0565 (8)	0.0062 (7)	0.0063 (7)	−0.0028 (7)
O1	0.0572 (9)	0.0901 (11)	0.0988 (11)	0.0021 (8)	0.0255 (8)	0.0262 (9)
O2	0.0511 (8)	0.1258 (14)	0.0963 (11)	0.0206 (9)	−0.0021 (8)	−0.0447 (10)
C7	0.0487 (10)	0.0515 (11)	0.0526 (9)	0.0073 (8)	0.0051 (8)	−0.0036 (8)
C6	0.0549 (11)	0.0523 (11)	0.0542 (10)	0.0049 (9)	0.0079 (8)	−0.0018 (8)
C8	0.0457 (10)	0.0611 (11)	0.0643 (11)	0.0097 (9)	0.0113 (8)	0.0068 (9)
C10	0.0512 (10)	0.0611 (12)	0.0662 (11)	0.0069 (10)	0.0176 (9)	0.0038 (10)
C12	0.0514 (7)	0.0670 (9)	0.0653 (8)	0.0051 (7)	0.0037 (7)	0.0008 (7)
C9	0.0503 (11)	0.0658 (12)	0.0638 (11)	0.0123 (9)	0.0163 (9)	0.0119 (9)
O3	0.0569 (8)	0.1817 (15)	0.1240 (12)	0.0325 (10)	−0.0028 (8)	−0.0424 (12)
C11	0.0459 (11)	0.0735 (14)	0.0701 (12)	0.0039 (9)	−0.0017 (9)	−0.0047 (10)
C14	0.0580 (12)	0.0676 (13)	0.0666 (12)	0.0121 (10)	0.0103 (10)	0.0237 (10)
C5	0.0596 (12)	0.0704 (14)	0.0739 (13)	0.0014 (10)	0.0100 (10)	0.0141 (10)
C15	0.0572 (13)	0.0833 (16)	0.0964 (16)	0.0031 (12)	−0.0039 (11)	−0.0097 (13)
C4	0.0619 (13)	0.0798 (15)	0.0939 (16)	−0.0060 (12)	0.0162 (11)	0.0109 (13)
C13	0.0623 (13)	0.0909 (17)	0.0962 (16)	0.0209 (12)	0.0249 (11)	0.0393 (14)
C17	0.0555 (13)	0.119 (2)	0.0923 (17)	0.0121 (14)	0.0047 (12)	−0.0046 (16)
C19	0.0876 (18)	0.0948 (18)	0.0684 (13)	0.0214 (14)	0.0051 (12)	−0.0045 (13)
C3	0.0887 (18)	0.0720 (15)	0.0992 (17)	−0.0067 (14)	0.0234 (14)	0.0203 (13)
C1	0.0660 (14)	0.0925 (18)	0.1114 (19)	0.0008 (13)	−0.0045 (13)	0.0438 (16)
C16	0.0666 (15)	0.118 (2)	0.1027 (18)	0.0164 (15)	0.0038 (13)	−0.0330 (17)
C18	0.0709 (16)	0.112 (2)	0.0846 (16)	−0.0008 (15)	−0.0154 (12)	−0.0093 (15)
C2	0.100 (2)	0.100 (2)	0.122 (2)	0.0027 (17)	−0.0042 (17)	0.0588 (18)

N2—N1	1.353 (2)	C14—C13	1.503 (3)
N2—C10	1.371 (2)	C5—C4	1.377 (3)
N2—C11	1.458 (2)	C5—H5	0.9300
N1—C7	1.306 (2)	C15—C16	1.371 (3)
O1—C10	1.235 (2)	C15—H15	0.9300
O2—C12	1.277 (2)	C4—C3	1.341 (3)
O2—H2	0.8200	C4—H4	0.9300
C7—C8	1.420 (2)	C13—H13A	0.9700
C7—C6	1.481 (3)	C13—H13B	0.9700
C6—C1	1.373 (3)	C17—C16	1.337 (3)
C6—C5	1.382 (3)	C17—C18	1.345 (4)
C8—C9	1.346 (3)	C17—H17	0.9300
C8—H8	0.9300	C19—C18	1.389 (3)
C10—C9	1.444 (3)	C19—H19	0.9300
C12—O3	1.187 (2)	C3—C2	1.363 (4)
C12—C11	1.494 (3)	C3—H3	0.9300
C9—C13	1.502 (3)	C1—C2	1.378 (4)
C11—H11A	0.9700	C1—H1	0.9300
C11—H11B	0.9700	C16—H16	0.9300
C14—C15	1.367 (3)	C18—H18	0.9300
C14—C19	1.375 (3)	C2—H2A	0.9300
N1—N2—C10	126.22 (15)	C6—C5—H5	119.3
N1—N2—C11	114.74 (15)	C14—C15—C16	121.6 (2)
C10—N2—C11	119.00 (16)	C14—C15—H15	119.2
C7—N1—N2	117.48 (15)	C16—C15—H15	119.2
C12—O2—H2	109.5	C3—C4—C5	121.1 (2)
N1—C7—C8	121.17 (17)	C3—C4—H4	119.4
N1—C7—C6	116.60 (16)	C5—C4—H4	119.4
C8—C7—C6	122.21 (16)	C9—C13—C14	113.43 (17)
C1—C6—C5	116.86 (19)	C9—C13—H13A	108.9
C1—C6—C7	121.27 (18)	C14—C13—H13A	108.9
C5—C6—C7	121.86 (17)	C9—C13—H13B	108.9
C9—C8—C7	121.38 (17)	C14—C13—H13B	108.9
C9—C8—H8	119.3	H13A—C13—H13B	107.7
C7—C8—H8	119.3	C16—C17—C18	119.6 (2)
O1—C10—N2	119.04 (17)	C16—C17—H17	120.2
O1—C10—C9	125.67 (19)	C18—C17—H17	120.2
N2—C10—C9	115.28 (16)	C14—C19—C18	120.9 (2)
O3—C12—O2	123.7 (2)	C14—C19—H19	119.5
O3—C12—C11	120.9 (2)	C18—C19—H19	119.5
O2—C12—C11	115.36 (17)	C4—C3—C2	118.6 (2)
C8—C9—C10	118.14 (18)	C4—C3—H3	120.7
C8—C9—C13	124.38 (17)	C2—C3—H3	120.7
C10—C9—C13	117.48 (17)	C6—C1—C2	121.0 (2)
N2—C11—C12	114.75 (16)	C6—C1—H1	119.5
N2—C11—H11A	108.6	C2—C1—H1	119.5
C12—C11—H11A	108.6	C17—C16—C15	120.9 (2)
N2—C11—H11B	108.6	C17—C16—H16	119.6
C12—C11—H11B	108.6	C15—C16—H16	119.6
H11A—C11—H11B	107.6	C17—C18—C19	120.3 (2)
C15—C14—C19	116.8 (2)	C17—C18—H18	119.9
C15—C14—C13	121.1 (2)	C19—C18—H18	119.9
C19—C14—C13	122.1 (2)	C3—C2—C1	121.1 (2)
C4—C5—C6	121.3 (2)	C3—C2—H2A	119.4
C4—C5—H5	119.3	C1—C2—H2A	119.4

D—H···A	D—H	H···A	D···A	D—H···A
O2—H2···O1i	0.82	1.82	2.593 (2)	156
C1—H1···N1	0.93	2.47	2.780 (3)	100

C19H16N2O3	F(000) = 672
Mr = 320.34	Dx = 1.317 Mg m−3
Monoclinic, P21/c	Mo Kα radiation, λ = 0.71073 Å
a = 10.5976 (6) Å	Cell parameters from 11065 reflections
b = 15.5500 (7) Å	θ = 2.0–30.2°
c = 10.3731 (7) Å	µ = 0.09 mm−1
β = 109.120 (5)°	T = 296 K
V = 1615.11 (17) Å3	Prism, colorless
Z = 4	0.77 × 0.70 × 0.59 mm

STOE IPDS 2 diffractometer	4562 independent reflections
Radiation source: sealed X-ray tube, 12 x 0.4 mm long-fine focus	2560 reflections with I > 2σ(I)
Plane graphite monochromator	Rint = 0.037
Detector resolution: 6.67 pixels mm-1	θmax = 29.8°, θmin = 2.0°
rotation method scans	h = −14→14
Absorption correction: integration (X-RED32; Stoe & Cie, 2002)	k = −21→21
Tmin = 0.950, Tmax = 0.966	l = −9→14
12114 measured reflections

Refinement on F2	0 restraints
Least-squares matrix: full	Hydrogen site location: inferred from neighbouring sites
R[F2 > 2σ(F2)] = 0.049	H-atom parameters constrained
wR(F2) = 0.131	w = 1/[σ2(Fo2) + (0.0658P)2] where P = (Fo2 + 2Fc2)/3
S = 0.98	(Δ/σ)max < 0.001
4562 reflections	Δρmax = 0.21 e Å−3
218 parameters	Δρmin = −0.21 e Å−3

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.

	x	y	z	Uiso*/Ueq
O1	0.72419 (10)	0.27629 (8)	0.59311 (12)	0.0685 (3)
O3	0.85719 (10)	0.46576 (8)	0.50173 (13)	0.0697 (3)
O2	0.97177 (11)	0.41088 (9)	0.37548 (13)	0.0746 (4)
H3	1.024031	0.449746	0.410547	0.112*
N1	0.56525 (10)	0.40450 (8)	0.30448 (12)	0.0469 (3)
N2	0.65255 (10)	0.35304 (8)	0.39742 (12)	0.0482 (3)
C7	0.45128 (12)	0.42124 (9)	0.32229 (14)	0.0448 (3)
C10	0.63572 (13)	0.31919 (10)	0.51338 (15)	0.0505 (3)
C8	0.41953 (13)	0.38747 (10)	0.43611 (15)	0.0518 (3)
H8	0.336938	0.399584	0.445235	0.062*
C6	0.35817 (13)	0.47589 (9)	0.21629 (14)	0.0467 (3)
C9	0.50740 (13)	0.33851 (10)	0.52997 (15)	0.0510 (3)
C12	0.87184 (13)	0.41235 (11)	0.42288 (15)	0.0540 (4)
C11	0.77702 (13)	0.33946 (10)	0.37033 (16)	0.0529 (4)
H11A	0.758711	0.333700	0.272786	0.064*
H11B	0.817891	0.286421	0.413433	0.064*
C14	0.34689 (14)	0.30038 (11)	0.65991 (16)	0.0559 (4)
C1	0.37838 (15)	0.48952 (12)	0.09292 (17)	0.0629 (4)
H1	0.450530	0.463405	0.076387	0.076*
C13	0.48712 (15)	0.29980 (13)	0.65443 (18)	0.0679 (5)
H13A	0.543928	0.330261	0.733863	0.082*
H13B	0.517681	0.240631	0.661889	0.082*
C2	0.29390 (17)	0.54093 (13)	−0.00593 (19)	0.0744 (5)
H2	0.309754	0.549564	−0.088011	0.089*
C5	0.25091 (17)	0.51563 (13)	0.23724 (19)	0.0733 (5)
H5	0.234983	0.508074	0.319510	0.088*
C3	0.18788 (19)	0.57899 (13)	0.0157 (2)	0.0814 (6)
H3A	0.129995	0.613227	−0.051425	0.098*
C19	0.3040 (2)	0.36098 (15)	0.7325 (2)	0.0846 (6)
H19	0.361300	0.405216	0.775869	0.102*
C15	0.25885 (18)	0.23814 (14)	0.5959 (2)	0.0837 (6)
H15	0.283752	0.197158	0.543528	0.100*
C17	0.09285 (19)	0.29337 (18)	0.6803 (3)	0.0941 (7)
H17	0.008047	0.290075	0.688145	0.113*
C4	0.1669 (2)	0.56655 (15)	0.1373 (2)	0.0960 (7)
H4	0.094447	0.592977	0.152843	0.115*
C18	0.1777 (2)	0.35732 (18)	0.7422 (3)	0.1008 (7)
H18	0.150476	0.399081	0.791625	0.121*
C16	0.1334 (2)	0.23488 (17)	0.6074 (3)	0.1056 (8)
H16	0.075399	0.191088	0.563708	0.127*

	U11	U22	U33	U12	U13	U23
O1	0.0598 (6)	0.0850 (8)	0.0606 (7)	0.0170 (6)	0.0196 (5)	0.0211 (6)
O3	0.0610 (6)	0.0868 (8)	0.0744 (8)	−0.0176 (6)	0.0402 (6)	−0.0276 (6)
O2	0.0615 (6)	0.1001 (10)	0.0777 (8)	−0.0164 (6)	0.0437 (6)	−0.0276 (7)
N1	0.0482 (5)	0.0524 (7)	0.0415 (6)	0.0005 (5)	0.0167 (5)	0.0007 (5)
N2	0.0435 (5)	0.0561 (7)	0.0464 (7)	0.0002 (5)	0.0166 (5)	−0.0001 (5)
C7	0.0457 (6)	0.0494 (8)	0.0417 (7)	−0.0021 (6)	0.0175 (5)	−0.0003 (6)
C10	0.0493 (7)	0.0556 (9)	0.0462 (8)	−0.0019 (6)	0.0152 (6)	0.0019 (7)
C8	0.0466 (6)	0.0643 (9)	0.0485 (8)	0.0003 (6)	0.0212 (6)	0.0065 (7)
C6	0.0499 (7)	0.0503 (8)	0.0442 (7)	0.0014 (6)	0.0212 (6)	0.0016 (6)
C9	0.0495 (7)	0.0586 (9)	0.0467 (8)	−0.0039 (6)	0.0180 (6)	0.0058 (7)
C12	0.0459 (7)	0.0737 (10)	0.0471 (8)	0.0002 (7)	0.0218 (6)	−0.0021 (7)
C11	0.0467 (7)	0.0654 (10)	0.0497 (8)	0.0037 (6)	0.0200 (6)	−0.0034 (7)
C14	0.0561 (7)	0.0661 (10)	0.0481 (8)	0.0005 (7)	0.0207 (6)	0.0174 (7)
C1	0.0595 (8)	0.0819 (12)	0.0563 (9)	0.0189 (8)	0.0310 (7)	0.0177 (8)
C13	0.0581 (8)	0.0897 (13)	0.0592 (10)	0.0047 (8)	0.0236 (7)	0.0264 (9)
C2	0.0784 (10)	0.0946 (13)	0.0575 (10)	0.0234 (10)	0.0323 (8)	0.0246 (9)
C5	0.0790 (10)	0.0930 (13)	0.0618 (10)	0.0284 (9)	0.0419 (9)	0.0175 (9)
C3	0.0832 (11)	0.0951 (15)	0.0701 (12)	0.0376 (10)	0.0307 (9)	0.0296 (10)
C19	0.0799 (11)	0.0973 (15)	0.0831 (14)	−0.0166 (10)	0.0355 (10)	−0.0194 (11)
C15	0.0728 (11)	0.0753 (13)	0.1021 (16)	−0.0058 (10)	0.0273 (10)	−0.0127 (11)
C17	0.0596 (10)	0.138 (2)	0.0901 (16)	−0.0055 (13)	0.0324 (10)	0.0234 (15)
C4	0.0908 (12)	0.1224 (18)	0.0917 (15)	0.0572 (13)	0.0528 (11)	0.0360 (13)
C18	0.0848 (13)	0.140 (2)	0.0911 (16)	0.0060 (14)	0.0478 (12)	−0.0147 (15)
C16	0.0719 (12)	0.0996 (17)	0.138 (2)	−0.0280 (12)	0.0244 (13)	−0.0066 (16)

O1—C10	1.2249 (17)	C14—C13	1.506 (2)
O3—C12	1.2108 (18)	C1—C2	1.375 (2)
O2—C12	1.3057 (16)	C1—H1	0.9300
O2—H3	0.8200	C13—H13A	0.9700
N1—C7	1.3064 (16)	C13—H13B	0.9700
N1—N2	1.3570 (16)	C2—C3	1.352 (2)
N2—C10	1.3771 (18)	C2—H2	0.9300
N2—C11	1.4513 (17)	C5—C4	1.375 (3)
C7—C8	1.4294 (19)	C5—H5	0.9300
C7—C6	1.4813 (19)	C3—C4	1.364 (3)
C10—C9	1.4568 (19)	C3—H3A	0.9300
C8—C9	1.342 (2)	C19—C18	1.376 (3)
C8—H8	0.9300	C19—H19	0.9300
C6—C5	1.372 (2)	C15—C16	1.374 (3)
C6—C1	1.381 (2)	C15—H15	0.9300
C9—C13	1.502 (2)	C17—C16	1.340 (4)
C12—C11	1.494 (2)	C17—C18	1.354 (3)
C11—H11A	0.9700	C17—H17	0.9300
C11—H11B	0.9700	C4—H4	0.9300
C14—C15	1.357 (2)	C18—H18	0.9300
C14—C19	1.373 (3)	C16—H16	0.9300
C12—O2—H3	109.5	C6—C1—H1	119.4
C7—N1—N2	117.63 (11)	C9—C13—C14	116.80 (13)
N1—N2—C10	126.35 (11)	C9—C13—H13A	108.1
N1—N2—C11	113.56 (11)	C14—C13—H13A	108.1
C10—N2—C11	119.97 (12)	C9—C13—H13B	108.1
N1—C7—C8	121.48 (12)	C14—C13—H13B	108.1
N1—C7—C6	115.55 (12)	H13A—C13—H13B	107.3
C8—C7—C6	122.96 (11)	C3—C2—C1	120.27 (16)
O1—C10—N2	120.56 (12)	C3—C2—H2	119.9
O1—C10—C9	124.76 (13)	C1—C2—H2	119.9
N2—C10—C9	114.67 (12)	C6—C5—C4	120.37 (16)
C9—C8—C7	120.84 (12)	C6—C5—H5	119.8
C9—C8—H8	119.6	C4—C5—H5	119.8
C7—C8—H8	119.6	C2—C3—C4	119.18 (17)
C5—C6—C1	117.74 (14)	C2—C3—H3A	120.4
C5—C6—C7	121.72 (13)	C4—C3—H3A	120.4
C1—C6—C7	120.53 (12)	C14—C19—C18	121.1 (2)
C8—C9—C10	118.94 (13)	C14—C19—H19	119.5
C8—C9—C13	126.17 (13)	C18—C19—H19	119.5
C10—C9—C13	114.88 (12)	C14—C15—C16	120.9 (2)
O2—C12—O3	124.45 (14)	C14—C15—H15	119.6
O3—C12—C11	123.16 (12)	C16—C15—H15	119.6
O2—C12—C11	112.38 (13)	C16—C17—C18	118.69 (19)
N2—C11—C12	111.36 (12)	C16—C17—H17	120.7
N2—C11—H11A	109.4	C18—C17—H17	120.7
C12—C11—H11A	109.4	C3—C4—C5	121.14 (16)
N2—C11—H11B	109.4	C3—C4—H4	119.4
C12—C11—H11B	109.4	C5—C4—H4	119.4
H11A—C11—H11B	108.0	C17—C18—C19	120.5 (2)
C15—C14—C19	117.36 (16)	C17—C18—H18	119.8
C15—C14—C13	120.40 (17)	C19—C18—H18	119.8
C19—C14—C13	122.19 (17)	C17—C16—C15	121.5 (2)
C2—C1—C6	121.30 (14)	C17—C16—H16	119.3
C2—C1—H1	119.4	C15—C16—H16	119.3

D—H···A	D—H	H···A	D···A	D—H···A
C11—H11B···O1	0.97	2.39	2.7325 (19)	100
O2—H3···O3i	0.82	1.84	2.6599 (16)	177
C5—H5···O3ii	0.93	2.40	3.280 (2)	159
C11—H11A···O1iii	0.97	2.47	3.2814 (19)	141