Crystal structure and Hirshfeld surface analysis of 3,6-bis­(pyrimidin-2-yl)-1,4-di­hydro-1,2,4,5-tetra­zine dihydrate

Khotchasanthong, K.; Jittirattanakun, S.; Chainok, K.

doi:10.1107/S2056989020002765

research communications

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Volume 76| Part 4| April 2020| Pages 473-476

https://doi.org/10.1107/S2056989020002765

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Crystal structure and Hirshfeld surface analysis of 3,6-bis(pyrimidin-2-yl)-1,4-dihydro-1,2,4,5-tetrazine dihydrate

Kenika Khotchasanthong,^a Siripak Jittirattanakun ^a and Kittipong Chainok ^b ^*

^aMultifunctional Crystalline Materials and Applications, Division of Chemistry, Faculty of Science and Technology, Thammasat University, Khlong Luang, Pathum Thani, 12121, Thailand, and ^bMultifunctional Crystalline Materials and Applications, Materials and Textile Technology, Faculty of Science and Technology, Thammasat University, Khlong Luang, Pathum Thani, 12121, Thailand
^*Correspondence e-mail: kc@tu.ac.th

Edited by W. T. A. Harrison, University of Aberdeen, Scotland (Received 17 February 2020; accepted 27 February 2020; online 3 March 2020)

In the title compound, C₁₀H₈N₈·2H₂O or H₂bmtz·2H₂O [bmtz = 3,6-bis(2′-pyrimidyl)-1,2,4,5-tetrazine], the asymmetric unit consists of one-half molecule of H₂bmtz and one water molecule, the whole H₂bmtz molecule being generated by a crystallographic twofold rotation axis passing through the middle point of the 1,4-dihydro-1,2,4,5-tetrazine moiety. In the crystal, N—H⋯O, N—H⋯N, O—H⋯O hydrogen bonds and aromatic π–π stacking interactions link the components into a three-dimensional supramolecular network. Hirshfeld surface analysis was used to further investigate the intermolecular interactions in the crystal structure.

Keywords: crystal structure; hydrogen bonds; Hirshfeld surface; pyrimidine.

CCDC reference: 1986751

1. Chemical context

The chemistry of nitrogen-containing heterocyclic compounds has attracted the attention of the scientific community for over a century. Many compounds of this class are bioactive (Jubeen et al., 2018 ) and show promising pharmacological properties (Alcaide et al., 2016 ; Varano et al., 2016 ). Among these, numerous pyrimidine derivatives have been studied extensively in the context of synthetic organic chemistry and coordination chemistry (Kaim, 2002 ). For instance, the tetrazine-based ligand 3,6-bis(2′-pyrimidyl)-1,2,4,5-tetrazine (bmtz) has been used as a polydentate ligand for the formation of silver(I) coordination polymers (Chainok et al., 2012 ) and for the self-assembly of the highly stable Fe^II pentagonal metallacycles (Giles et al., 2011 ). Herein, the crystal and molecular structures of the dihydrotetrazine-based compound 3,6-bis(pyrimidin-2-yl)-1,4-dihydro-1,2,4,5-tetrazine dihydrate, C₁₀H₈N₈·2H₂O or H₂bmtz·2H₂O (I), is described along with an analysis of its Hirshfeld surface.

2. Structural commentary

The molecular structure of (I) is shown in Fig. 1. The asymmetric unit consists of one-half molecule of H₂bmtz and one water molecule, in which the whole molecule of the H₂bmtz is generated by a crystallographic twofold rotation axis passing through the middle point of the 1,4-dihydro-1,2,4,5-tetrazine moiety. The H₂bmtz molecule is therefore not planar (r.m.s. deviation from planarity = 0.598 Å) with a C4—C5—N3—N4ⁱ torsion angle of 178.46 (14)° [symmetry code: (i) −x, y, $[{3\over 2}]$ − z]. The pyrimidine rings are twisted with respect to each other, making a dihedral angle of 43.67 (9)°. The 1,4-dihydro-1,2,4,5-tetrazine moiety adopts a twist-boat conformation with a C5—N3—N4ⁱ—C5ⁱ torsion angle of −41.17 (17)°. The N3—N4ⁱ and C5—N4 bond lengths of 1.423 (2) and 1.395 (2) Å, confirm their single-bond character, while the C3—N5 bond length of 1.278 (2) Å, is consistent with a double bond (compare QORNAM, Glöckle et al., 2001 ; ZASTAQ, Chainok et al., 2012). The C—C and C—N bond lengths in the pyrimidine ring are characteristic for a delocalized double bond and a typical single bond (QORNAM, Glöckle et al., 2001).

Figure 1
Molecular structure of (I) with displacement ellipsoids drawn at the 50% probability level. Unlabelled atoms are generated by the symmetry operation −x, y, 3/2 − z.

3. Supramolecular features

In the crystal, the H₂bmtz molecules are stacked along [010] into columns through π–π interactions between the pyrimidine rings [centroid-to-centroid distance = 3.726 (2) Å]. At the same time, the water molecules are connected by O—H⋯O hydrogen bonds (Table 1), resulting in the formation of a zigzag chain. These motifs are then connected together through N—H⋯O hydrogen bonds involving the tetrazine nitrogen atoms and the water molecules to form a sheet structure propagating in the ab plane, as shown in Fig. 2. The sheets are further linked into an overall three-dimensional supramolecular network through N—H⋯N hydrogen bonds with an R₂²(10) ring motif, Fig. 3, which involve the dihydro nitrogen atoms and the pyrimidine nitrogen atoms. A weak C—H⋯O interaction is also noted (Table 1).

Table 1
Hydrogen-bond geometry (Å, °)

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
O1—H1A⋯O1ⁱ	0.88 (1)	1.81 (1)	2.642 (4)	156 (2)
O1—H1B⋯N1	0.86 (1)	2.15 (4)	2.863 (3)	140 (5)
N4—H4⋯N2ⁱⁱ	0.85 (1)	2.57 (1)	3.221 (1)	133 (2)
C2—H2⋯O1ⁱⁱⁱ	0.93	2.43	3.278 (3)	151
Symmetry codes: (i) $[-x+{\script{1\over 2}}, y+{\script{1\over 2}}, -z+{\script{3\over 2}}]$ ; (ii) -x, -y+1, -z+2; (iii) $[x, -y, z+{\script{1\over 2}}]$ .

Figure 2
Partial packing diagram of (I), showing the O—H⋯O and O—H⋯N hydrogen bonds (dashed lines) and π–π stacking interactions propagating in the ab plane.

Figure 3
Partial packing diagram of (I) viewed along the b axis, showing the N—H⋯N hydrogen bonds (dashed lines).

4. Hirshfeld surface analysis

To further quantify the nature of the intermolecular interactions present in the crystal structure, Hirshfeld surfaces (McKinnon et al., 2007 ) and their associated two-dimensional fingerprint plots (Spackman & McKinnon, 2002 ) were generated using CrystalExplorer17 (Turner et al., 2017 ). The shorter and longer contacts are indicated as red and blue spots, respectively, on the Hirshfeld surfaces, and contacts with distances approximately equal to the sum of the van der Waals radii are represented as white spots. The contribution of interatomic contacts to the d_norm surface of the title compound is shown in Fig. 4. Analysis of the two-dimensional fingerprint plots, Fig. 4, reveals that H⋯H (36.8%) contacts are the major contributors toward the Hirshfeld surface, whereas H⋯N/N⋯H (26.1%) contacts (i.e. N—H⋯N) make a less significant contribution. The contribution of the H⋯O/O⋯H (9.0%) contacts (i.e. C—H⋯O and O—H⋯O) and other contacts such as C⋯C (7.1%) (i.e. π–π stacking), H⋯C/C⋯H (6.1%) and N⋯N (4.7%) make a small contribution to the entire Hirshfeld surface.

Figure 4
Two-dimensional fingerprint plots of the title compound (I), showing (a) all interactions, and those delineated into (b) H⋯H, (c) H⋯N/N⋯H, (d) C⋯N/N⋯C, (e) H⋯O/O⋯H, (f) C⋯C, (g) H⋯C/C⋯H, and (h) N⋯N contacts [d_e and d_i represent the distances from a point on the Hirshfeld surface to the nearest atoms outside (external) and inside (internal) the surface, respectively].

5. Database survey

A search of the Cambridge Crystallographic Database (CSD version 5.41, November 2019 update; Groom et al., 2016 ) using ConQuest gave 4261 hits, reflecting the large number of pyrimidine-containing heterocyclic compounds that have been characterized. However, searches for compounds related to H₂bmtz yielded just two hits for μ₂-1,4-dihydro-3,6-bis[(2′-pyrimidyl)-1,2,4,5-tetrazine]bis[bis(triphenylphosphine)copper(I)] bis(tetrafluoridoborate) dichloromethane solvate (QORNAM, Glöckle et al., 2001) and catena-[[μ₂-3,6-di(pyrimidin-2-yl)-1,4-dihydro-1,2,4,5-tetrazine][μ₂-(dicyanoethenylidene)amido][(dicyanoethenylidene)amido]acetonitriledisilver(I)] (ZASTAQ, Chainok et al., 2012).

6. Synthesis and crystallization

All commercially available chemicals and solvents were of reagent grade and were used as received without further purification. H₂bmtz was synthesized according to a literature method (Kaim & Fees, 1995 ). Single crystals for X-ray structure analysis were obtained by recrystallization from mixed solvents of CH₂Cl₂/H₂O (1:1, v/v).

7. Refinement

Crystal data, data collection and structure refinement details are summarized in Table 2. All H atoms were located in difference-Fourier maps: the carbon-bound H atoms were relocated to idealized positions and refined as riding atoms with C—H = 0.93 Å and U_iso(H) = 1.2U_eq(C). The 1,4-dihydro-1,2,4,5-tetrazine and water H atoms were located in difference-Fourier maps and were constrained to N—H = 0.86 ± 0.01 Å with U_iso(H) = 1.2U_eq(N) and O—H = 0.84 ± 0.01 Å with U_iso(H) = 1.5U_eq(O), respectively.

Table 2
Experimental details

Crystal data
Chemical formula	C₁₀H₈N₈·2H₂O
M_r	276.28
Crystal system, space group	Monoclinic, C2/c
Temperature (K)	296
a, b, c (Å)	23.4730 (12), 3.7262 (2), 13.9102 (7)
β (°)	95.687 (2)
V (Å³)	1210.67 (11)
Z	4
Radiation type	Mo Kα
μ (mm⁻¹)	0.11
Crystal size (mm)	0.32 × 0.2 × 0.2

Data collection
Diffractometer	Bruker D8 QUEST CMOS PHOTON II
Absorption correction	Multi-scan (SADABS; Bruker, 2016 )
T_min, T_max	0.714, 0.746
No. of measured, independent and observed [I > 2σ(I)] reflections	11339, 1487, 1145
R_int	0.030
(sin θ/λ)_max (Å⁻¹)	0.667

Refinement
R[F² > 2σ(F²)], wR(F²), S	0.053, 0.174, 1.05
No. of reflections	1487
No. of parameters	103
No. of restraints	4
H-atom treatment	H atoms treated by a mixture of independent and constrained refinement
Δρ_max, Δρ_min (e Å⁻³)	0.26, −0.39
Computer programs: APEX3 and SAINT (Bruker, 2016), SHELXT (Sheldrick, 2015a ), SHELXL2018 (Sheldrick, 2015b ) and OLEX2 (Dolomanov et al., 2009 ).

Supporting information

CCDC reference: 1986751

Crystal structure: contains datablocks I, global. DOI: https://doi.org/10.1107/S2056989020002765/hb7895sup1.cif

Structure factors: contains datablock I. DOI: https://doi.org/10.1107/S2056989020002765/hb7895Isup2.hkl

Supporting information file. DOI: https://doi.org/10.1107/S2056989020002765/hb7895Isup3.cdx

Supporting information file. DOI: https://doi.org/10.1107/S2056989020002765/hb7895Isup4.cml

checkCIF report

Computing details top

Data collection: APEX3 (Bruker, 2016); cell refinement: SAINT (Bruker, 2016); data reduction: SAINT (Bruker, 2016); program(s) used to solve structure: SHELXT (Sheldrick, 2015a); program(s) used to refine structure: SHELXL2018 (Sheldrick, 2015b); molecular graphics: OLEX2 (Dolomanov et al., 2009); software used to prepare material for publication: OLEX2 (Dolomanov et al., 2009).

3,6-Bis(pyrimidin-2-yl)-1,4-dihydro-1,2,4,5-tetrazine dihydrate top

Crystal data top

C₁₀H₈N₈·2H₂O	F(000) = 576
M_r = 276.28	D_x = 1.516 Mg m⁻³
Monoclinic, C2/c	Mo Kα radiation, λ = 0.71073 Å
a = 23.4730 (12) Å	Cell parameters from 4681 reflections
b = 3.7262 (2) Å	θ = 3.3–28.1°
c = 13.9102 (7) Å	µ = 0.11 mm⁻¹
β = 95.687 (2)°	T = 296 K
V = 1210.67 (11) Å³	Block, orange
Z = 4	0.32 × 0.2 × 0.2 mm

Data collection top

Bruker D8 QUEST CMOS PHOTON II diffractometer	1487 independent reflections
Radiation source: sealed x-ray tube	1145 reflections with I > 2σ(I)
Graphite monochromator	R_int = 0.030
Detector resolution: 7.39 pixels mm^-1	θ_max = 28.3°, θ_min = 2.9°
φ and ω scans	h = −30→29
Absorption correction: multi-scan (SADABS; Bruker, 2016)	k = −4→4
T_min = 0.714, T_max = 0.746	l = −18→18
11339 measured reflections

Refinement top

Refinement on F²	Primary atom site location: dual
Least-squares matrix: full	Hydrogen site location: mixed
R[F² > 2σ(F²)] = 0.053	H atoms treated by a mixture of independent and constrained refinement
wR(F²) = 0.174	w = 1/[σ²(F_o²) + (0.1061P)² + 0.7279P] where P = (F_o² + 2F_c²)/3
S = 1.05	(Δ/σ)_max < 0.001
1487 reflections	Δρ_max = 0.26 e Å⁻³
103 parameters	Δρ_min = −0.39 e Å⁻³
4 restraints

Special details top

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 (Å²) top

	x	y	z	U_iso*/U_eq
O1	0.21290 (11)	0.4286 (11)	0.71824 (16)	0.1166 (10)
H1A	0.2318 (9)	0.594 (5)	0.7537 (16)	0.060 (8)*
H1B	0.1796 (10)	0.400 (13)	0.738 (3)	0.19 (2)*
N1	0.14093 (6)	0.2128 (5)	0.86243 (11)	0.0426 (4)
N2	0.07173 (6)	0.2495 (4)	0.97609 (10)	0.0386 (4)
N3	0.05508 (6)	0.4046 (4)	0.72282 (9)	0.0372 (4)
N4	−0.00726 (6)	0.5326 (4)	0.83844 (9)	0.0381 (4)
H4	−0.0111 (9)	0.481 (6)	0.8970 (8)	0.052 (6)*
C1	0.17826 (8)	0.0798 (6)	0.93187 (14)	0.0488 (5)
H1	0.215005	0.024291	0.916985	0.059*
C2	0.16473 (8)	0.0213 (5)	1.02458 (14)	0.0468 (5)
H2	0.190969	−0.077223	1.071768	0.056*
C3	0.11048 (8)	0.1160 (5)	1.04382 (13)	0.0441 (5)
H3	0.100261	0.086189	1.106236	0.053*
C4	0.08877 (6)	0.2840 (4)	0.88786 (11)	0.0327 (4)
C5	0.04524 (7)	0.4139 (4)	0.81150 (11)	0.0323 (4)

Atomic displacement parameters (Å²) top

	U¹¹	U²²	U³³	U¹²	U¹³	U²³
O1	0.0846 (16)	0.196 (3)	0.0734 (14)	−0.0089 (18)	0.0266 (13)	−0.0020 (18)
N1	0.0327 (8)	0.0553 (9)	0.0399 (8)	0.0017 (6)	0.0047 (6)	−0.0006 (7)
N2	0.0387 (8)	0.0453 (8)	0.0319 (7)	0.0027 (6)	0.0038 (6)	0.0021 (6)
N3	0.0305 (7)	0.0496 (9)	0.0316 (7)	−0.0050 (6)	0.0040 (5)	−0.0019 (6)
N4	0.0353 (7)	0.0527 (9)	0.0263 (7)	0.0066 (6)	0.0039 (5)	−0.0024 (6)
C1	0.0348 (9)	0.0596 (12)	0.0516 (11)	0.0081 (8)	0.0020 (8)	−0.0018 (9)
C2	0.0453 (10)	0.0468 (10)	0.0460 (10)	0.0080 (8)	−0.0072 (8)	0.0021 (8)
C3	0.0503 (11)	0.0476 (10)	0.0342 (8)	0.0041 (8)	0.0034 (7)	0.0033 (7)
C4	0.0316 (8)	0.0331 (8)	0.0334 (8)	−0.0012 (6)	0.0029 (6)	−0.0029 (6)
C5	0.0313 (8)	0.0347 (8)	0.0312 (8)	−0.0022 (6)	0.0054 (6)	−0.0014 (6)

Geometric parameters (Å, º) top

O1—H1A	0.882 (10)	N4—H4	0.851 (9)
O1—H1B	0.860 (10)	N4—C5	1.395 (2)
N1—C1	1.334 (2)	C1—H1	0.9300
N1—C4	1.334 (2)	C1—C2	1.376 (3)
N2—C3	1.339 (2)	C2—H2	0.9300
N2—C4	1.334 (2)	C2—C3	1.373 (3)
N3—N4ⁱ	1.423 (2)	C3—H3	0.9300
N3—C5	1.278 (2)	C4—C5	1.480 (2)

H1A—O1—H1B	109 (2)	C3—C2—C1	116.54 (16)
C1—N1—C4	115.86 (15)	C3—C2—H2	121.7
C4—N2—C3	116.00 (15)	N2—C3—C2	122.46 (16)
C5—N3—N4ⁱ	111.21 (13)	N2—C3—H3	118.8
N3ⁱ—N4—H4	110.2 (15)	C2—C3—H3	118.8
C5—N4—N3ⁱ	113.47 (13)	N1—C4—C5	117.46 (14)
C5—N4—H4	111.5 (15)	N2—C4—N1	126.25 (15)
N1—C1—H1	118.6	N2—C4—C5	116.30 (14)
N1—C1—C2	122.79 (17)	N3—C5—N4	121.13 (14)
C2—C1—H1	118.6	N3—C5—C4	120.39 (14)
C1—C2—H2	121.7	N4—C5—C4	118.44 (13)

N1—C1—C2—C3	−1.6 (3)	N4ⁱ—N3—C5—C4	178.46 (14)
N1—C4—C5—N3	10.4 (3)	C1—N1—C4—N2	3.1 (3)
N1—C4—C5—N4	−172.09 (16)	C1—N1—C4—C5	−176.87 (15)
N2—C4—C5—N3	−169.62 (15)	C1—C2—C3—N2	1.8 (3)
N2—C4—C5—N4	7.9 (2)	C3—N2—C4—N1	−3.0 (3)
N3ⁱ—N4—C5—N3	41.7 (2)	C3—N2—C4—C5	176.97 (15)
N3ⁱ—N4—C5—C4	−135.76 (15)	C4—N1—C1—C2	−0.6 (3)
N4ⁱ—N3—C5—N4	1.0 (2)	C4—N2—C3—C2	0.4 (3)

Symmetry code: (i) −x, y, −z+3/2.

Hydrogen-bond geometry (Å, º) top

D—H···A	D—H	H···A	D···A	D—H···A
O1—H1A···O1ⁱⁱ	0.88 (1)	1.81 (1)	2.642 (4)	156 (2)
O1—H1B···N1	0.86 (1)	2.15 (4)	2.863 (3)	140 (5)
N4—H4···N2ⁱⁱⁱ	0.85 (1)	2.57 (1)	3.221 (1)	133 (2)
C2—H2···O1^iv	0.93	2.43	3.278 (3)	151

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

Acknowledgements

The authors thank the Faculty of Science and Technology, Thammasat University, for funds to purchase the X-ray diffractometer.

Funding information

Funding for this research was provided by: Faculty of Science and Technology, Thammasat University (contract No. SciGR8/2563 to Kittipong Chainok).

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