Crystal structure and Hirshfeld surface analysis of (E)-6-(4-hy-droxy-3-meth-oxy-styr-yl)-4,5-di-hydro-pyridazin-3(2H)-one.

In the title com-pound, C13H14N2O3, the dihydropyridazine ring (r.m.s. deviation = 0.166 Å) has a screw-boat conformation. The dihedral angle between its mean plane and the benzene ring is 0.77 (12)°. In the crystal, inter-molecular O-H⋯O hydrogen bonds generate C(5) chains and N-H⋯O hydrogen bonds produce R 2 2(8) motifs. These types of inter-actions lead to the formation of layers parallel to (12). The three-dimensional network is achieved by C-H⋯O inter-actions, including R 2 4(8) motifs. Inter-molecular inter-actions were additionally investigated using Hirshfeld surface analysis and two-dimensional fingerprint plots. The most significant contributions to the crystal packing are by H⋯H (43.3%), H⋯C/C⋯H (19.3%), H⋯O/H⋯O (22.6%), C⋯N/N⋯C (3.0%) and H⋯N/N⋯H (5.8%) contacts. C-H⋯π inter-actions and aromatic π-π stacking inter-actions are not observed. © Daoui et al. 2019.

Chemical context

For decades the chemistry of pyridazinones has been an inter­esting field. This nitro­gen heterocycle became a scaffold of choice for the development of potential drug candidates (Akhtar et al., 2016 ▸; Dubey & Bhosle, 2015 ▸) because pyridazinone and its substituted derivatives are important pharmacophores possessing many different biological applications (Asif, 2014 ▸). Such com­pounds are used as anti-HIV (Livermore et al., 1993 ▸), anti­microbial (Sönmez et al., 2006 ▸), anti­convulsant (Partap et al., 2018 ▸), anti­hypertensive (Siddiqui et al., 2011 ▸), anti­depressant (Boukharsa et al., 2016 ▸), analgesic (Gökçe et al., 2009 ▸), anti-inflammatory (Barberot et al., 2018 ▸), anti­histaminic (Tao et al. 2012 ▸), cardiotonic (Wang et al., 2008 ▸) and herbicidal agents (Asif, 2013 ▸) or as glucan synthase inhibitors (Zhou et al., 2011 ▸).

In continuation of our studies related to mol­ecular structures and Hirshfeld surface analysis of new heterocyclic derivatives (Daoui et al., 2019a ▸,b ▸; El Kalai et al., 2019 ▸; Karrouchi et al., 2015 ▸), we report herein on the synthesis, mol­ecular and crystal structures of (E)-6-(4-hy­droxy-3-meth­oxy­styr­yl)-4,5-di­hydro­pyridazin-3(2H)-one, as well as an analysis of the Hirshfeld surfaces.

Structural commentary

In the title mol­ecule (Fig. 1 ▸), the configuration relative to the double bond at C5 and C6 is E. The dihydropyridazine ring has a screw-boat conformation, with an r.m.s. deviation of 0.166 Å for the ring atoms, with the maximum deviation from the ring being 0.178 (3) Å for the C3 atom; the C2 atom lies −0.177 (3) Å out of the plane in the opposite direction relative to the C3 atom. The dihedral angle between the dihydropyridazine ring mean plane and the benzene ring (C7–C12) is 0.77 (12)°, indicating an almost planar conformation of the molecule favouring delocalization over the C4—C5=C6—C7 bridge.

Figure 1

The mol­ecular structure of the title com­pound. Displacement ellipsoids are drawn at the 50% probability level.

Supra­molecular features

In the crystal, mol­ecules are stacked in rows parallel to [100]. Notably, no significant C—H⋯π or π–π inter­actions are observed. O2—H2⋯O1i hydrogen bonds between the phenolic OH group and the carbonyl O atom of a neighbouring mol­ecule generate C(5) chains extending parallel to [101]. Likewise, N1—H1⋯O1ii hydrogen bonds between the N—H function of the di­hydro­pyridazine ring and the carbonyl O atom generate centrosymmetric dimers with an (8) motif. The two types of hydrogen bonding result in the formation of layers parallel to (12). A three-dimensional supra­molecular network is eventually formed through inter­molecular C13—H13A⋯O2iii and C13—H13C⋯O2iv hydrogen bonds with (8) motifs (Fig. 2 ▸ and Table 1 ▸).

Figure 2

The crystal packing of the title com­pound, with N—H⋯O, O—H⋯O and C—H⋯O inter­actions shown as blue, green and black dashed lines, respectively.

Table 1

Hydrogen-bond geometry (Å, °)

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
O2—H2⋯O1i	0.82	1.86	2.671 (2)	168
N1—H1⋯O1ii	0.86	2.02	2.875 (3)	170
C13—H13A⋯O2iii	0.96	2.51	3.465 (3)	172
C13—H13C⋯O2iv	0.96	2.57	3.489 (4)	159

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

Database survey

A search of the Cambridge Structural Database (CSD, Version 5.40, update November 2018; Groom et al., 2016 ▸) revealed two structures containing a similar pyridazinone moiety as in the title structure but with different substituents, viz. 6-phenyl-4,5-di­hydro­pyridazin-3(2H)-one (CSD refcode TADQUL; Abourichaa et al., 2003 ▸) and (R)-(−)-6-(4-amino­phen­yl)-5-methyl-4,5-di­hydro­pyridazin-3(2H)-one (ADIGOK; Zhang et al., 2006 ▸). In the structure of TADQUL, the di­hydro­pyridazine ring adopts a half-chair conformation, with atoms C1, N2, N3 and C4 in a common plane, with C5 0.222 (2) Å and C6 0.262 (2) Å on opposite sides of this plane. The plane is almost coplanar with the 4-aminophenyl ring, the dihedral angle between the two planes being 1.73 (9) Å. In the crystal, hydrogen-bonded centrosymmetric dimers are observed. The O1=C1 bond length is 1.2316 (14) Å. The N3—C4, N2—N3 and N2—C1 bond lengths are 1.3464 (15), 1.3877 (14) and 1.2830 (15) Å, respectively. In the structure of ADIGOK, the asymmetric unit consists of two mol­ecules of the same enanti­omer, and the crystal packing is stabilized by inter­molecular N—H⋯O hydrogen bonds.

Hirshfeld surface analysis

Hirshfeld surface analysis was used to qu­antify the inter­molecular inter­actions of the title com­pound, using CrystalExplorer17.5 (Turner et al., 2017 ▸). The Hirshfeld surface analysis was planned using a standard (high) surface resolution with the three-dimensional d norm surfaces plotted over a fixed colour scale of −0.7021 (red) to 2.2382 a.u. (blue). The surfaces mapped over relevant inter­molecular contacts are illustrated in Fig. 3 ▸. The Hirshfeld surface representations with the function d norm plotted onto the surface are shown for the H⋯H, H⋯C/C⋯H, H⋯O/O⋯H, C⋯N/N⋯C and H⋯N/N⋯H inter­actions in Figs. 4 ▸(a)–(e), respectively. The overall two-dimensional fingerprint plot and those delineated into H⋯H, H⋯C/C⋯H, H⋯O/O⋯H, C⋯N/N⋯C and H⋯N/N⋯H contacts are illustrated in Figs. 5 ▸(a)–(f), respectively. The largest inter­action is that of H⋯H, contributing 43.3% to the overall crystal packing. H⋯C/C⋯H contacts add a 19.3% contribution to the Hirshfeld surface, with the tips at d e + d i ∼ 2.72 Å. H⋯O/O⋯H contacts make a 22.6% contribution to the Hirshfeld surface and are represented by a pair of sharp spikes in the region d e + d i ∼ 2.70 Å in the fingerprint plot. H⋯O/O⋯H inter­actions arise from inter­molecular O—H⋯O hydrogen bonding and C—H⋯O contacts. The contributions of the other contacts to the Hirshfeld surface are negligible, i.e. C⋯N/N⋯C of 3.0% and H⋯N/N⋯H of 5.8%.

Figure 3

(a) d norm mapped on the Hirshfeld surface for visualizing the inter­molecular inter­actions, (b) d e mapped on the surface, (c) shape-index map of the title com­pound and (d) curvedness map of the title com­pound using a range from −4 to 4 Å.

Figure 4

The Hirshfeld surface representations with the function d norm plotted onto the surface for (a) H⋯H, (b) H⋯C/ C⋯H, (c) H⋯O/O⋯H, (d) C⋯N/N⋯C and (e) H⋯N/N⋯H inter­actions.

Figure 5

The full two-dimensional fingerprint plots for the title com­pound, showing (a) all inter­actions, and delineated into (b) H⋯H, (c) H⋯C/ C⋯H, (d) H⋯O/O⋯H, (e) C⋯N/N⋯C and (f) H⋯N/N⋯H inter­actions.

Synthesis and crystallization

To a solution of 6-(4-hy­droxy-3-meth­oxy­phen­yl)-4-oxohex-5-enoic acid (0.25 g, 1 mmol) in 20 ml of ethanol, an equimolar amount of hydrazine hydrate was added. The mixture was maintained under reflux until thin-layer chromatography (TLC) indicated the end of the reaction. After cooling, the precipitate which formed was filtered off, washed with ethanol and recrystallized from ethanol. Slow evaporation at room temperature led to the formation of single crystals of the title com­pound.

Refinement

Crystal data, data collection and structure refinement details are summarized in Table 2 ▸. H atoms on C atoms were placed in idealized positions and refined as riding, with C—H = 0.93–0.97 Å and U iso(H) = 1.5U eq(C) for methyl H atoms and 1.2U eq(C) otherwise. The NH and OH hydrogens were located in a difference Fourier map and were constrained with N—H = 0.86 Å and U iso(H) = 1.2U eq(N), and O—H = 0.86 Å and U iso(H) = 1.5U eq(O), using a riding model.

Table 2

Experimental details

Crystal data
Chemical formula	C13H14N2O3
M r	246.26
Crystal system, space group	Triclinic, P
Temperature (K)	293
a, b, c (Å)	6.0828 (9), 9.4246 (13), 11.1724 (16)
α, β, γ (°)	75.838 (11), 83.099 (12), 84.059 (11)
V (Å3)	614.70 (16)
Z	2
Radiation type	Mo Kα
μ (mm−1)	0.10
Crystal size (mm)	0.72 × 0.39 × 0.16
Data collection
Diffractometer	Stoe IPDS 2
Absorption correction	Integration (X-RED32; Stoe & Cie, 2002 ▸)
T min, T max	0.944, 0.989
No. of measured, independent and observed [I > 2σ(I)] reflections	6563, 2426, 1506
R int	0.054
(sin θ/λ)max (Å−1)	0.617
Refinement
R[F 2 > 2σ(F 2)], wR(F 2), S	0.056, 0.147, 1.00
No. of reflections	2426
No. of parameters	165
H-atom treatment	H-atom parameters constrained
Δρmax, Δρmin (e Å−3)	0.17, −0.17

Computer programs: X-AREA (Stoe & Cie, 2002 ▸), X-RED (Stoe & Cie, 2002 ▸), SHELXT2017 (Sheldrick, 2015a ▸), Mercury (Macrae et al., 2008 ▸), PLATON (Spek, 2009 ▸), WinGX (Farrugia, 2012 ▸), SHELXL2018 (Sheldrick, 2015b ▸) and publCIF (Westrip, 2010 ▸).

Crystal structure: contains datablock(s) I, global. DOI: 10.1107/S2056989019014130/wm5521sup1.cif

Structure factors: contains datablock(s) I. DOI: 10.1107/S2056989019014130/wm5521Isup3.hkl

CCDC references: 1959568, 1959568

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

C13H14N2O3	Z = 2
Mr = 246.26	F(000) = 260
Triclinic, P1	Dx = 1.330 Mg m−3
a = 6.0828 (9) Å	Mo Kα radiation, λ = 0.71073 Å
b = 9.4246 (13) Å	Cell parameters from 13077 reflections
c = 11.1724 (16) Å	θ = 2.2–30.7°
α = 75.838 (11)°	µ = 0.10 mm−1
β = 83.099 (12)°	T = 293 K
γ = 84.059 (11)°	Prism, yellow
V = 614.70 (16) Å3	0.72 × 0.39 × 0.16 mm

Stoe IPDS 2 diffractometer	1506 reflections with I > 2σ(I)
Detector resolution: 6.67 pixels mm-1	Rint = 0.054
rotation method scans	θmax = 26.0°, θmin = 2.2°
Absorption correction: integration (X-RED32; Stoe & Cie, 2002)	h = −7→7
Tmin = 0.944, Tmax = 0.989	k = −11→11
6563 measured reflections	l = −13→13
2426 independent reflections

Refinement on F2	0 restraints
Least-squares matrix: full	Hydrogen site location: inferred from neighbouring sites
R[F2 > 2σ(F2)] = 0.056	H-atom parameters constrained
wR(F2) = 0.147	w = 1/[σ2(Fo2) + (0.0747P)2] where P = (Fo2 + 2Fc2)/3
S = 1.00	(Δ/σ)max < 0.001
2426 reflections	Δρmax = 0.17 e Å−3
165 parameters	Δρmin = −0.17 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	0.7518 (3)	0.88682 (19)	0.99156 (15)	0.0601 (5)
O3	0.4960 (3)	0.58008 (19)	0.11563 (16)	0.0614 (5)
O2	0.1290 (3)	0.7317 (2)	0.05778 (16)	0.0636 (5)
H2	0.016474	0.786724	0.044599	0.095*
N1	0.4947 (3)	0.9323 (2)	0.85757 (17)	0.0525 (5)
H1	0.429651	0.995567	0.896673	0.063*
N2	0.3918 (3)	0.9139 (2)	0.75870 (17)	0.0519 (5)
C9	0.3982 (4)	0.6576 (2)	0.1986 (2)	0.0497 (6)
C5	0.3927 (4)	0.8291 (3)	0.5807 (2)	0.0506 (6)
H5	0.252921	0.878478	0.572201	0.061*
C1	0.6829 (4)	0.8631 (3)	0.8987 (2)	0.0492 (6)
C4	0.5043 (4)	0.8412 (2)	0.6851 (2)	0.0472 (6)
C8	0.4803 (4)	0.6645 (3)	0.3066 (2)	0.0521 (6)
H8	0.616062	0.614251	0.326018	0.062*
C11	0.0780 (4)	0.8118 (3)	0.2494 (2)	0.0538 (6)
H11	−0.059111	0.860442	0.230853	0.065*
C7	0.3664 (4)	0.7445 (2)	0.3875 (2)	0.0496 (6)
C10	0.1954 (4)	0.7364 (2)	0.1681 (2)	0.0487 (6)
C6	0.4707 (4)	0.7544 (3)	0.4962 (2)	0.0549 (6)
H6	0.607897	0.702171	0.507391	0.066*
C12	0.1607 (4)	0.8164 (3)	0.3580 (2)	0.0552 (6)
H12	0.078822	0.867751	0.411814	0.066*
C13	0.7007 (4)	0.4965 (3)	0.1419 (3)	0.0614 (7)
H13A	0.745228	0.441469	0.079994	0.092*
H13B	0.682204	0.430200	0.222071	0.092*
H13C	0.812721	0.561367	0.141331	0.092*
C2	0.7972 (5)	0.7565 (3)	0.8299 (3)	0.0694 (8)
H2A	0.761992	0.658432	0.875007	0.083*
H2B	0.956271	0.761159	0.827335	0.083*
C3	0.7375 (4)	0.7807 (3)	0.7002 (2)	0.0673 (8)
H3A	0.836608	0.847839	0.645178	0.081*
H3B	0.760060	0.688125	0.675416	0.081*

	U11	U22	U33	U12	U13	U23
O1	0.0632 (11)	0.0804 (12)	0.0479 (10)	0.0136 (8)	−0.0292 (8)	−0.0331 (8)
O3	0.0642 (11)	0.0739 (11)	0.0579 (10)	0.0218 (8)	−0.0273 (9)	−0.0392 (9)
O2	0.0633 (12)	0.0859 (13)	0.0537 (10)	0.0146 (9)	−0.0326 (9)	−0.0349 (9)
N1	0.0536 (12)	0.0686 (13)	0.0448 (11)	0.0094 (9)	−0.0204 (9)	−0.0299 (10)
N2	0.0510 (12)	0.0670 (13)	0.0450 (11)	0.0068 (9)	−0.0213 (9)	−0.0237 (10)
C9	0.0569 (14)	0.0515 (13)	0.0479 (13)	0.0029 (11)	−0.0190 (11)	−0.0217 (11)
C5	0.0550 (14)	0.0602 (14)	0.0422 (12)	0.0029 (11)	−0.0196 (11)	−0.0185 (11)
C1	0.0539 (14)	0.0552 (14)	0.0427 (12)	0.0056 (11)	−0.0182 (11)	−0.0172 (11)
C4	0.0524 (14)	0.0522 (13)	0.0416 (12)	0.0007 (10)	−0.0152 (11)	−0.0168 (10)
C8	0.0533 (14)	0.0584 (14)	0.0511 (14)	0.0074 (11)	−0.0248 (12)	−0.0207 (11)
C11	0.0495 (13)	0.0675 (15)	0.0506 (14)	0.0090 (11)	−0.0211 (11)	−0.0237 (12)
C7	0.0579 (14)	0.0565 (14)	0.0412 (12)	0.0011 (11)	−0.0181 (11)	−0.0204 (11)
C10	0.0540 (14)	0.0560 (14)	0.0432 (13)	−0.0004 (11)	−0.0192 (11)	−0.0202 (11)
C6	0.0601 (15)	0.0640 (15)	0.0467 (13)	0.0033 (12)	−0.0229 (12)	−0.0197 (12)
C12	0.0558 (15)	0.0681 (15)	0.0490 (14)	0.0056 (12)	−0.0149 (12)	−0.0274 (12)
C13	0.0656 (16)	0.0634 (15)	0.0600 (16)	0.0144 (12)	−0.0203 (13)	−0.0248 (13)
C2	0.0734 (18)	0.0867 (19)	0.0599 (16)	0.0316 (14)	−0.0365 (14)	−0.0406 (14)
C3	0.0576 (16)	0.098 (2)	0.0593 (16)	0.0136 (14)	−0.0231 (13)	−0.0423 (15)

O1—C1	1.241 (3)	C8—H8	0.9300
O3—C9	1.362 (3)	C11—C10	1.377 (3)
O3—C13	1.424 (3)	C11—C12	1.379 (3)
O2—C10	1.355 (2)	C11—H11	0.9300
O2—H2	0.8200	C7—C12	1.396 (3)
N1—C1	1.331 (3)	C7—C6	1.462 (3)
N1—N2	1.387 (2)	C6—H6	0.9300
N1—H1	0.8600	C12—H12	0.9300
N2—C4	1.288 (3)	C13—H13A	0.9600
C9—C8	1.378 (3)	C13—H13B	0.9600
C9—C10	1.406 (3)	C13—H13C	0.9600
C5—C6	1.327 (3)	C2—C3	1.493 (3)
C5—C4	1.451 (3)	C2—H2A	0.9700
C5—H5	0.9300	C2—H2B	0.9700
C1—C2	1.480 (3)	C3—H3A	0.9700
C4—C3	1.486 (3)	C3—H3B	0.9700
C8—C7	1.394 (3)
C9—O3—C13	117.98 (17)	O2—C10—C11	124.3 (2)
C10—O2—H2	109.5	O2—C10—C9	116.1 (2)
C1—N1—N2	127.3 (2)	C11—C10—C9	119.54 (19)
C1—N1—H1	116.4	C5—C6—C7	127.7 (2)
N2—N1—H1	116.4	C5—C6—H6	116.1
C4—N2—N1	117.42 (18)	C7—C6—H6	116.1
O3—C9—C8	126.0 (2)	C11—C12—C7	120.5 (2)
O3—C9—C10	115.23 (18)	C11—C12—H12	119.8
C8—C9—C10	118.8 (2)	C7—C12—H12	119.8
C6—C5—C4	126.4 (2)	O3—C13—H13A	109.5
C6—C5—H5	116.8	O3—C13—H13B	109.5
C4—C5—H5	116.8	H13A—C13—H13B	109.5
O1—C1—N1	120.4 (2)	O3—C13—H13C	109.5
O1—C1—C2	123.3 (2)	H13A—C13—H13C	109.5
N1—C1—C2	116.36 (19)	H13B—C13—H13C	109.5
N2—C4—C5	115.5 (2)	C1—C2—C3	114.4 (2)
N2—C4—C3	122.97 (19)	C1—C2—H2A	108.7
C5—C4—C3	121.5 (2)	C3—C2—H2A	108.7
C9—C8—C7	122.0 (2)	C1—C2—H2B	108.7
C9—C8—H8	119.0	C3—C2—H2B	108.7
C7—C8—H8	119.0	H2A—C2—H2B	107.6
C10—C11—C12	121.0 (2)	C4—C3—C2	113.3 (2)
C10—C11—H11	119.5	C4—C3—H3A	108.9
C12—C11—H11	119.5	C2—C3—H3A	108.9
C8—C7—C12	118.02 (19)	C4—C3—H3B	108.9
C8—C7—C6	118.9 (2)	C2—C3—H3B	108.9
C12—C7—C6	123.1 (2)	H3A—C3—H3B	107.7
C1—N1—N2—C4	−12.5 (4)	O3—C9—C10—O2	−3.3 (3)
C13—O3—C9—C8	0.8 (3)	C8—C9—C10—O2	176.6 (2)
C13—O3—C9—C10	−179.3 (2)	O3—C9—C10—C11	176.6 (2)
N2—N1—C1—O1	−177.3 (2)	C8—C9—C10—C11	−3.5 (4)
N2—N1—C1—C2	1.2 (4)	C4—C5—C6—C7	−177.5 (2)
N1—N2—C4—C5	−177.97 (19)	C8—C7—C6—C5	177.4 (3)
N1—N2—C4—C3	−1.5 (3)	C12—C7—C6—C5	0.0 (4)
C6—C5—C4—N2	−176.7 (3)	C10—C11—C12—C7	0.2 (4)
C6—C5—C4—C3	6.8 (4)	C8—C7—C12—C11	−2.2 (4)
O3—C9—C8—C7	−178.7 (2)	C6—C7—C12—C11	175.2 (2)
C10—C9—C8—C7	1.4 (4)	O1—C1—C2—C3	−159.6 (3)
C9—C8—C7—C12	1.4 (4)	N1—C1—C2—C3	21.9 (4)
C9—C8—C7—C6	−176.1 (2)	N2—C4—C3—C2	23.8 (4)
C12—C11—C10—O2	−177.4 (2)	C5—C4—C3—C2	−160.0 (2)
C12—C11—C10—C9	2.7 (4)	C1—C2—C3—C4	−32.7 (4)

D—H···A	D—H	H···A	D···A	D—H···A
O2—H2···O1i	0.82	1.86	2.671 (2)	168
N1—H1···O1ii	0.86	2.02	2.875 (3)	170
C13—H13A···O2iii	0.96	2.51	3.465 (3)	172
C13—H13C···O2iv	0.96	2.57	3.489 (4)	159