2,6-Di­amino-4-chloro­pyrimidine–succinic acid (2/1)

Chakkarapani, N.; Murugan, S.; Ibrahim, A.R.; Kavitha, S.J.; Hemamalini, M.; Rajakannan, V.

doi:10.1107/S2414314620012390

organic compounds

IUCrDATA

ISSN: 2414-3146

Volume 5| Part 9| September 2020| x201239

https://doi.org/10.1107/S2414314620012390

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2,6-Diamino-4-chloropyrimidine–succinic acid (2/1)

Nandhini Chakkarapani,^a Suganya Murugan,^b Abdul Razak Ibrahim,^c Savaridasan Jose Kavitha,^b Madhukar Hemamalini ^b and Venkatachalam Rajakannan ^a ^*

^aDepartment of Crystallography and Biophysics, University of Madras, Guindy Campus, Chennai-600 025, Tamil Nadu, India, ^bDepartment of Chemistry, Mother Teresa Women's University, Kodaikanal, Tamil Nadu, India, and ^cSchool of Physics, Universiti Sains Malaysia, 11800 USM, Penang, Malaysia
^*Correspondence e-mail: rajakannan@unom.ac.in

Edited by W. T. A. Harrison, University of Aberdeen, Scotland (Received 2 September 2020; accepted 8 September 2020; online 15 September 2020)

In the title 2:1 co-crystal, 2C₄H₅ClN₄·C₄H₆O₄ the complete succinic acid molecule is generated by a crystallographic centre of symmetry. In the crystal, pairwise O—H⋯N and N—H⋯O hydrogen bonds link the pyrimidine and succinic acid molecules, generating R₂²(8) loops. The pyrimidine molecules are linked by pairwise N—H⋯N hydrogen bonds, again generating R₂²(8) loops. Collectively, the hydrogen bonds link the components into corrugated (100) sheets. The Hirshfeld surface is presented.

Keywords: crystal structure; co-crystal; Hirshfeld surface analysis..

CCDC reference: 2003667

Structure description

Some aminopyrimidine derivatives are used as antifolate drugs (Hunt et al., 1980 ). The crystal structures of various aminopyrimidine derivatives (Schwalbe & Williams, 1982 ; Edison et al., 2014 ; Thanigaimani et al., 2012 ) have been reported. In the present study, the synthesis and structure of the title 2:1 co-crystal are described.

The complete succinic acid molecule is generated by a crystallographic centre of symmetry (Fig. 1), with key torsion angles O1—C5—C6—C6ⁱ = −2.5 (3)° and O2—C5—C6—C6ⁱ = 178.28 (18)° [symmetry code: (i) 2 − x, 3 − y, 1 − z].

Figure 1
The molecular structure of the title compound showing 50% displacement ellipsoids and hydrogen bonds indicated by dashed lines. Symmetry code: (i) 2 − x, 3 − y, 1 − z.

In the crystal, pairwise O2—H2⋯N2 and N4—H4A··O1 hydrogen bonds (for symmetry codes, see Table 1) link the pyrimidine and succinic acid molecules, generating R₂²(8) loops. The mean planes of the succinic acid and linked pyrimidine molecules are close to parallel [dihedral angle = 8.67 (6)°]. The pyrimidine molecules are linked by pairwise N3—H3A⋯N1ⁱ hydrogen bonds, again generating R₂²(8) loops. An N4—H4B⋯O1ⁱⁱ hydrogen bond also links the pyrimidine and succinic acid species. Collectively, the hydrogen bonds link the components into corrugated (100) sheets (Fig. 2).

Table 1
Hydrogen-bond geometry (Å, °)

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
O2—H2⋯N2	0.82	1.81	2.622 (2)	169
N3—H3A⋯N1ⁱ	0.86	2.19	3.048 (2)	173
N4—H4A⋯O1	0.86	1.94	2.794 (2)	169
N4—H4B⋯O1ⁱⁱ	0.86	2.04	2.8510 (19)	156
Symmetry codes: (i) -x+1, -y+1, -z+1; (ii) $[-x+2, y-{\script{1\over 2}}, -z+{\script{3\over 2}}]$ .

Figure 2
Partial packing diagram of the title compound showing hydrogen bonds as dashed lines.

The Hirshfeld surface (Turner et al., 2017 ) of the pyrimidine–succinic acid grouping is shown in Fig. 3, where red spots represent short intermolecular contacts associated with the various hydrogen bonds. The most significant contact percentages arising from two-dimensional fingerprint plots are: H⋯H = 32.5%, O⋯H/H⋯O = 19.7%, N⋯H/H⋯N = 13.6%, Cl⋯H/H⋯Cl = 7.9%, H⋯C/C⋯H = 5.5% and O⋯C/C⋯O = 4.8%. Other contact types contribute a negligible amount.

Figure 3
The Hirshfeld surface mapped over d_norm for the title compound.

Synthesis and crystallization

A 10 ml methanolic solution (hot) of 2,6-diamino-4-chloropyrimidine (32 mg) and a 10 ml aqueous solution (hot) of succinic acid (29 mg) were mixed and heated for 10 min and then cooled to room temperature. Colourless blocks grew over the course of a few days as the solvents evaporated.

Refinement

Crystal data, data collection and structure refinement details are summarized in Table 2.

Table 2
Experimental details

Crystal data
Chemical formula	2C₄H₅ClN₄·C₄H₆O₄
M_r	407.23
Crystal system, space group	Monoclinic, P2₁/c
Temperature (K)	296
a, b, c (Å)	13.2096 (14), 4.9765 (5), 13.5673 (14)
β (°)	98.603 (2)
V (Å³)	881.85 (16)
Z	2
Radiation type	Mo Kα
μ (mm⁻¹)	0.41
Crystal size (mm)	0.72 × 0.34 × 0.13

Data collection
Diffractometer	Bruker SMART APEXII CCD
Absorption correction	Multi-scan (SADABS; Krause et al., 2015 )
T_min, T_max	0.631, 0.746
No. of measured, independent and observed [I > 2σ(I)] reflections	15031, 2599, 2102
R_int	0.032
(sin θ/λ)_max (Å⁻¹)	0.707

Refinement
R[F² > 2σ(F²)], wR(F²), S	0.043, 0.128, 1.04
No. of reflections	2599
No. of parameters	118
H-atom treatment	H-atom parameters constrained
Δρ_max, Δρ_min (e Å⁻³)	0.33, −0.44
Computer programs: APEX2, SAINT and XPREP (Bruker, 2009 ), SHELXT (Sheldrick, 2015a ), SHELXL2018/3 (Sheldrick, 2015b ) and PLATON (Spek, 2020 ).

Structural data

CCDC reference: 2003667

Crystal structure: contains datablocks global, I. DOI: https://doi.org/10.1107/S2414314620012390/hb4365sup1.cif

Structure factors: contains datablock I. DOI: https://doi.org/10.1107/S2414314620012390/hb4365Isup2.hkl

Supporting information file. DOI: https://doi.org/10.1107/S2414314620012390/hb4365Isup3.cml

checkCIF report

Computing details top

Data collection: APEX2 (Bruker, 2009); cell refinement: APEX2 and SAINT (Bruker, 2009); data reduction: SAINT and XPREP (Bruker, 2009); program(s) used to solve structure: SHELXT (Sheldrick, 2015a); program(s) used to refine structure: SHELXL2018/3 (Sheldrick, 2015b); molecular graphics: PLATON (Spek, 2020); software used to prepare material for publication: PLATON (Spek, 2020).

2,6-Diamino-4-chloropyrimidine–succinic acid (2/1) top

Crystal data top

2C₄H₅ClN₄·C₄H₆O₄	F(000) = 420
M_r = 407.23	D_x = 1.534 Mg m⁻³
Monoclinic, P2₁/c	Mo Kα radiation, λ = 0.71073 Å
a = 13.2096 (14) Å	Cell parameters from 3778 reflections
b = 4.9765 (5) Å	θ = 2.6–29.9°
c = 13.5673 (14) Å	µ = 0.41 mm⁻¹
β = 98.603 (2)°	T = 296 K
V = 881.85 (16) Å³	Plate, colourless
Z = 2	0.72 × 0.34 × 0.13 mm

Data collection top

Bruker SMART APEXII CCD diffractometer	2102 reflections with I > 2σ(I)
Radiation source: fine-focus sealed tube	R_int = 0.032
ω and φ scan	θ_max = 30.2°, θ_min = 1.6°
Absorption correction: multi-scan (SADABS; Krause et al., 2015)	h = −18→18
T_min = 0.631, T_max = 0.746	k = −7→7
15031 measured reflections	l = −18→19
2599 independent reflections

Refinement top

Refinement on F²	Primary atom site location: structure-invariant direct methods
Least-squares matrix: full	Secondary atom site location: difference Fourier map
R[F² > 2σ(F²)] = 0.043	Hydrogen site location: inferred from neighbouring sites
wR(F²) = 0.128	H-atom parameters constrained
S = 1.04	w = 1/[σ²(F_o²) + (0.0642P)² + 0.3195P] where P = (F_o² + 2F_c²)/3
2599 reflections	(Δ/σ)_max = 0.001
118 parameters	Δρ_max = 0.33 e Å⁻³
0 restraints	Δρ_min = −0.44 e Å⁻³

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.

Refinement. The hydrogen atoms were positioned geometrically (C—H = 0.93–0.97 Å, N—H = 0.86) Å, O—H =0.82 Å) and were refined using a riding model with U_iso(H) = 1.2 U_eq(carrier).

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å²) top

	x	y	z	U_iso*/U_eq
Cl1	0.58724 (4)	0.10526 (9)	0.74117 (4)	0.06071 (19)
N2	0.74496 (9)	0.7549 (3)	0.60431 (9)	0.0345 (3)
O2	0.81782 (9)	1.1416 (3)	0.50401 (9)	0.0504 (3)
H2	0.803150	1.017333	0.538975	0.076*
O1	0.96386 (9)	1.1222 (3)	0.60813 (9)	0.0523 (3)
N1	0.60385 (10)	0.4544 (3)	0.60332 (10)	0.0400 (3)
C5	0.90949 (11)	1.2237 (3)	0.53630 (11)	0.0367 (3)
C2	0.74276 (13)	0.4470 (3)	0.73964 (12)	0.0420 (4)
H2A	0.771513	0.374017	0.800544	0.050*
C4	0.65260 (11)	0.6548 (3)	0.56340 (11)	0.0358 (3)
C6	0.94673 (11)	1.4522 (3)	0.47896 (12)	0.0391 (3)
H6A	0.899454	1.601474	0.478469	0.047*
H6B	0.946393	1.395885	0.410457	0.047*
N4	0.88038 (11)	0.7585 (3)	0.73071 (11)	0.0514 (4)
H4A	0.906878	0.884453	0.699449	0.062*
H4B	0.912066	0.700416	0.786646	0.062*
C1	0.65147 (12)	0.3614 (3)	0.68959 (12)	0.0392 (3)
C3	0.79074 (11)	0.6540 (3)	0.69271 (11)	0.0364 (3)
N3	0.60778 (11)	0.7630 (3)	0.47853 (11)	0.0532 (4)
H3A	0.549166	0.704581	0.450636	0.064*
H3B	0.637362	0.891492	0.451444	0.064*

Atomic displacement parameters (Å²) top

	U¹¹	U²²	U³³	U¹²	U¹³	U²³
Cl1	0.0568 (3)	0.0454 (3)	0.0867 (4)	0.00090 (19)	0.0328 (3)	0.0224 (2)
N2	0.0290 (6)	0.0381 (6)	0.0350 (6)	−0.0071 (5)	0.0006 (4)	0.0029 (5)
O2	0.0348 (6)	0.0595 (8)	0.0529 (7)	−0.0178 (5)	−0.0068 (5)	0.0173 (6)
O1	0.0417 (6)	0.0602 (8)	0.0495 (7)	−0.0200 (6)	−0.0111 (5)	0.0144 (6)
N1	0.0340 (6)	0.0392 (7)	0.0473 (7)	−0.0080 (5)	0.0078 (5)	0.0021 (5)
C5	0.0322 (7)	0.0381 (7)	0.0390 (7)	−0.0070 (6)	0.0028 (5)	−0.0001 (6)
C2	0.0424 (8)	0.0426 (8)	0.0415 (8)	0.0049 (6)	0.0077 (6)	0.0102 (6)
C4	0.0304 (6)	0.0397 (7)	0.0366 (7)	−0.0074 (6)	0.0028 (5)	−0.0005 (6)
C6	0.0324 (7)	0.0383 (8)	0.0456 (8)	−0.0076 (6)	0.0026 (6)	0.0048 (6)
N4	0.0412 (7)	0.0614 (10)	0.0462 (8)	−0.0086 (7)	−0.0113 (6)	0.0121 (7)
C1	0.0379 (7)	0.0333 (7)	0.0495 (8)	0.0011 (6)	0.0170 (6)	0.0052 (6)
C3	0.0336 (7)	0.0379 (7)	0.0372 (7)	0.0017 (6)	0.0030 (5)	0.0007 (6)
N3	0.0432 (7)	0.0651 (10)	0.0460 (8)	−0.0230 (7)	−0.0102 (6)	0.0136 (7)

Geometric parameters (Å, º) top

Cl1—C1	1.7356 (16)	C2—H2A	0.9300
N2—C3	1.3561 (18)	C4—N3	1.327 (2)
N2—C4	1.3572 (18)	C6—C6ⁱ	1.514 (3)
O2—C5	1.2911 (17)	C6—H6A	0.9700
O2—H2	0.8200	C6—H6B	0.9700
O1—C5	1.2294 (19)	N4—C3	1.325 (2)
N1—C1	1.327 (2)	N4—H4A	0.8600
N1—C4	1.3443 (19)	N4—H4B	0.8600
C5—C6	1.501 (2)	N3—H3A	0.8600
C2—C1	1.361 (2)	N3—H3B	0.8600
C2—C3	1.410 (2)

C3—N2—C4	118.71 (13)	C5—C6—H6B	108.8
C5—O2—H2	109.5	C6ⁱ—C6—H6B	108.8
C1—N1—C4	114.95 (13)	H6A—C6—H6B	107.7
O1—C5—O2	123.08 (14)	C3—N4—H4A	120.0
O1—C5—C6	121.62 (13)	C3—N4—H4B	120.0
O2—C5—C6	115.30 (13)	H4A—N4—H4B	120.0
C1—C2—C3	115.32 (14)	N1—C1—C2	126.81 (14)
C1—C2—H2A	122.3	N1—C1—Cl1	114.59 (12)
C3—C2—H2A	122.3	C2—C1—Cl1	118.61 (13)
N3—C4—N1	118.16 (13)	N4—C3—N2	116.94 (14)
N3—C4—N2	117.58 (14)	N4—C3—C2	123.14 (14)
N1—C4—N2	124.26 (14)	N2—C3—C2	119.91 (14)
C5—C6—C6ⁱ	113.62 (16)	C4—N3—H3A	120.0
C5—C6—H6A	108.8	C4—N3—H3B	120.0
C6ⁱ—C6—H6A	108.8	H3A—N3—H3B	120.0

C1—N1—C4—N3	−178.01 (15)	C4—N1—C1—Cl1	179.33 (11)
C1—N1—C4—N2	1.9 (2)	C3—C2—C1—N1	−0.8 (3)
C3—N2—C4—N3	177.81 (15)	C3—C2—C1—Cl1	179.50 (12)
C3—N2—C4—N1	−2.1 (2)	C4—N2—C3—N4	−179.40 (14)
O1—C5—C6—C6ⁱ	−2.5 (3)	C4—N2—C3—C2	0.7 (2)
O2—C5—C6—C6ⁱ	178.28 (18)	C1—C2—C3—N4	−179.27 (16)
C4—N1—C1—C2	−0.4 (2)	C1—C2—C3—N2	0.6 (2)

Symmetry code: (i) −x+2, −y+3, −z+1.

Hydrogen-bond geometry (Å, º) top

D—H···A	D—H	H···A	D···A	D—H···A
O2—H2···N2	0.82	1.81	2.622 (2)	169
N3—H3A···N1ⁱⁱ	0.86	2.19	3.048 (2)	173
N4—H4A···O1	0.86	1.94	2.794 (2)	169
N4—H4B···O1ⁱⁱⁱ	0.86	2.04	2.8510 (19)	156

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

Funding information

MH thanks the University Grants Commission (UGC) for a start-up research fellowship [No. F. 30–350/2017(BSR)].

References

Bruker (2009). APEX2, SAINT and XPREP. Bruker AXS Inc., Madison, Wisconsin, USA. Google Scholar
Edison, B., Balasubramani, K., Thanigaimani, K., Khalib, N. C., Arshad, S. & Razak, I. A. (2014). Acta Cryst. E70, o857–o858. CSD CrossRef IUCr Journals Google Scholar
Hunt, W. E., Schwalbe, C. H., Bird, K. & Mallinson, P. D. (1980). J. Biochem. 187, 533–536. CSD CrossRef CAS Web of Science Google Scholar
Krause, L., Herbst-Irmer, R., Sheldrick, G. M. & Stalke, D. (2015). J. Appl. Cryst. 48, 3–10. Web of Science CSD CrossRef ICSD CAS IUCr Journals Google Scholar
Schwalbe, C. H. & Williams, G. J. B. (1982). Acta Cryst. B38, 1840–1843. CSD CrossRef CAS Web of Science IUCr Journals Google Scholar
Sheldrick, G. M. (2015a). Acta Cryst. A71, 3–8. Web of Science CrossRef IUCr Journals Google Scholar
Sheldrick, G. M. (2015b). Acta Cryst. C71, 3–8. Web of Science CrossRef IUCr Journals Google Scholar
Spek, A. L. (2020). Acta Cryst. E76, 1–11. Web of Science CrossRef IUCr Journals Google Scholar
Thanigaimani, K., Khalib, N. C., Arshad, S. & Razak, I. A. (2012). Acta Cryst. E68, o3442–o3443. CSD CrossRef IUCr Journals Google Scholar
Turner, M. J., Mackinnon, J. J., Wolff, S. K., Grimwood, D. J., Spackman, P. R., Jayatilaka, D. & Spackman, M. A. (2017). CrystalExplorer. University of Western Australia. Google Scholar

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