Crystal structure, hydrogen bonding and Hirshfeld surface analysis of 2-amino-4-meth­oxy-6-methyl­pyrimidinium 4-chloro­benzoate

In the crystal structure of the title compound, C₆H₁₀N₃O⁺·C₇H₄Cl_O2⁻, the pyrimidine N atom of the cation is hydrogen-bonded to the 4-chloro­benzoate anion through a pair of N—H⋯O_carbox­yl hydrogen bonds, forming an (8) ring motif which is linked through centrosymmetric (8) ring motifs, forming a pseudo­tetra­meric DDAA array.

Abstract

In the crystal structure of the title salt, C₆H₁₀N₃O⁺·C₇H₄ClO₂ ⁻, the dihedral angle between the pyrimidine ring of the 2-amino-4-meth­oxy-6-methyl­pyrimidine cation and the the benzene ring of the 2-chloro­benzoate anion is 2.2 (1)°. In the anion, the benzene ring forms a dihedral angle of 8.5 (2)° with the carboxyl group. The pyrimidine N atom of the cation is protonated and the meth­oxy substituent is essentially coplanar with the parent ring. The protonated N atom and the N atom of the 2-amino group are hydrogen bonded to the 4-chloro­benzoate anion through a pair of N—H⋯O_carbox­yl hydrogen bonds, forming an R ² ₂(8) ring motif linked through a centrosymmetric R ² ₄(8) ring motif, resulting in a pseudo­tetra­meric DDAA array. These units are linked through inter­molecular meth­oxy C—H⋯Cl hydrogen bonds into ribbon-like chains extending along the c-axis direction. The crystal structure also features π–π stacking inter­actions between the rings in the cation and anion [minimum ring centroid separation = 3.7707 (12) Å].

Chemical context  

Pyrimidine and amino­pyrimidine derivatives are biologically important compounds and they occur in nature as components of nucleic acids such as cytosine, uracil and thymine. Pyrimidine derivatives are also important mol­ecules in biology and have many applications in the areas of pesticides and pharmaceutical agents (Condon et al., 1993 ▸). For example, imazosulfuron, ethirmol and mepanipyrim have been commercialized as agrochemicals (Maeno et al., 1990 ▸). Pyrimidine derivatives have also been developed as anti­viral agents, such as AZT, which is the most widely used anti-AIDS drug (Gilchrist, 1997 ▸). In order to study the hydrogen-bonding inter­actions, the title compound, the 2-amino-4-meth­oxy-6-methyl­pyrimidinium salt of 4-chloro­benzoate, C₆H₁₀N₃O⁺·C₇H₄ClO₂ ⁻, was synthesized and its structure, hydrogen-bonding and Hirshfeld surface analysis are reported herein.

Structural commentary  

The asymmetric unit of the title compound contains a 2-amino-4-meth­oxy-6-methyl­pyrimidinium cation and a 4-chloro­benzoate anion (Fig. 1 ▸), which are essentially coplanar, with a dihedral angle between the ring systems of the two species of 2.2 (1)°. In the cation, one of the pyrimidine nitro­gen atoms (N1) is protonated and this is reflected in an increase in bond angle at N1 [C11—N1—C13 = 120.53 (17)°], when compared with that at the unprotonated atom (N3) [C9—N3—C13 = 116.32 (18)°] and the corresponding angle of 116.01 (18)° in neutral 2-amino-4-meth­oxy-6-methyl­pyrimidine (Glidewell et al., 2003 ▸). The meth­oxy substituent group at C9 of the cation is essentially coplanar with the ring, the N3—C9—O3—C8 torsion angle being −2.9 (3)°. The bond lengths and angles are normal for the carboxyl­ate group of a 4-chloro­benzoate anion, and the benzene ring forms a dihedral angle of 8.5 (2)° with the carboxyl group.

Figure 1.

The asymmetric unit of the the title compound with atom labels, showing non-hydrogen atoms as 30% probability displacement ellipsoids. Inter-species hydrogen bonds are shown as dashed lines.

Supra­molecular features  

In the crystal, the protonated nitro­gen atom (N1) and the amino nitro­gen atom (N2) of the cation inter­act with the carboxyl oxygen atoms O2 and O1, respectively, of the anion through N—H⋯O hydrogen bonds (Table 1 ▸), forming an eight-membered (8) ring motif. This is extended into a DDAA array (where D represents a hydrogen-bond donor and A represents a hydrogen-bond acceptor) by N2—H1N⋯O1ⁱ hydrogen bonds in a centrosymmetric (8) association [symmetry code: (i) −x + 1, −y + 2, −z + 1], the corresponding graph-set notations for the hetero­tetra­mer being (8), (8), (8). The hetero­tetra­meric units are linked through meth­oxy C8—H8A⋯Clⁱⁱ hydrogen bonds, forming one-dimensional ribbon-like structures (Fig. 2 ▸) [symmetry code: (ii) x + 2, −y + , z + ]. Only very weak methyl C12—H⋯O2 inter­actions [C⋯O = 3.442 (3) Å; H⋯O2 = 2.76 Å] exist between ribbons. The crystal structure also features π–π stacking inter­actions between the aromatic pyrimidine ring of the cation (Fig. 3 ▸) and the benzene ring of the anion, with minimum centroid–centroid and perpendicular inter­planar distances of 3.7780 (12) and 3.7075 (8) Å, respectively, and a slip angle of 19.44° (Hunter et al., 1994 ▸).

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

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
N1—H1N1⋯O2	1.04 (3)	1.60 (3)	2.636 (3)	176 (2)
N2—H1N⋯O1i	0.86	2.12	2.846 (2)	142
N2—H2N⋯O1	0.86	1.97	2.824 (3)	169
C8—H8A⋯Cl1ii	0.96	2.82	3.770 (3)	171

Symmetry codes: (i) ; (ii) .

Figure 2.

Hydrogen bonding in the structure of the title compound showing the (8) and centrosymmetric (8) ring motifs and C—H⋯Cl extensions. Dashed lines indicate the hydrogen bonds.

Figure 3.

The overall view of the packing and stacking inter­actions in the title compound.

Hirshfeld surface analysis  

Three-dimensional (3D) d _norm surface analyis is a useful tool for analysing and visualizing the inter­molecular inter­actions. d _norm takes negative or positive values depending on whether the inter­molecular contact is shorter or longer, respectively, than the van der Waals radii (Spackman & Jayatilaka, 2009 ▸; McKinnon et al., 2007 ▸). The 3D d _norm surface of the title compound was shown in Fig. 4 ▸. The red points represent closer contacts and negative d _norm values on the surface corres­ponding to the N—H⋯O interactions, while C—H⋯O inter­actions are light red in colour. Two-dimensional fingerprint plots from the Hirshfeld surface analysis are shown in Fig. 5 ▸, revealing the inter­molecular contacts and their percentage distributions on the Hirshfeld surface. H⋯H inter­actions (44.8%) are present as a major contributor while O⋯H/H⋯O (14.6%), H⋯Cl/Cl⋯H (13.3%), C⋯H/H⋯C (7.5%), C⋯C (6.6%), N⋯H/H⋯N (3.4%), C⋯N/N⋯C (3.3%), Cl⋯N/N⋯Cl (1.8%), C⋯Cl/Cl⋯C (1.0%) and Cl⋯O/O⋯Cl (0.7%) contacts also make significant contributions to the Hirshfeld surface. Two ‘wingtips’ in the fingerprint plot are related to H⋯O and O⋯H inter­actions and are shown in Fig. 5 ▸.

Figure 4.

The three-dimensional d _norm surface of the title compound.

Figure 5.

Two-dimensional fingerprint plots with the relative contributions to the Hirshfeld surface.

Database survey  

A search of the Cambridge Structural Database (Version 5.37, update February 2017; Groom et al., 2016 ▸) for 2-amino-4-meth­oxy-6-methyl­pyrimidine yielded only seven structures of proton-transfer salts with carb­oxy­lic acids: VAQSOW [with 3-(N,N-di­methyl­amino)­benzoic acid]; VAQSUC [with methyl­ene hydrogen succinic acid (a monohydrate)]; VAQSEM (with 3-nitro­benzoic acid); VAQSIQ (with benzoic acid); VAQRUB (with 2-fluoro­benzoic acid) and VAQSAI (with 3-chloro­benzoic acid) (all from Aakeröy et al., 2003 ▸) and NUQTOJ (with picric acid; Jasinski et al., 2010 ▸).

Synthesis and crystallization  

The title compound was synthesized by the reaction of a 1:1 stoichiometric mixture of 2-amino-4-meth­oxy-6-methyl­pyrimidine [0.139 mg (Aldrich)] and 4-chloro­benzoic acid [0.156 mg (Merck)] in 20 ml of a hot methano­lic solution. After warming for a few minutes over a water bath, the solution was cooled and kept at room temperature. Within a few days, colourless block-shaped crystals suitable for the X-ray analysis were obtained (yield: 65%).

refinement  

Crystal data, data collection and structure refinement details are summarized in Table 2 ▸. N-bound pyrimidinium H atoms were located in a difference-Fourier map and refined freely [N—H = 1.03 (3) Å]. The remaining H atoms were positioned geometrically and refined using a riding model with (N—H = 0.86 Å and C—H = 0.93 or 0.96 Å) and U _iso(H) = 1.2 U _eq(C,N) or 1.5U _eq(methyl C). A rotating-group model was used for the methyl groups.

Table 2. Experimental details.

Crystal data
Chemical formula	C6H10N3O+·C7H4ClO2 −
M r	295.72
Crystal system, space group	Monoclinic, P21/c
Temperature (K)	296
a, b, c (Å)	10.1148 (8), 11.2236 (8), 14.579 (1)
β (°)	120.940 (5)
V (Å3)	1419.57 (19)
Z	4
Radiation type	Mo Kα
μ (mm−1)	0.28
Crystal size (mm)	0.35 × 0.30 × 0.20
Data collection
Diffractometer	Bruker Kappa APEXII CCD
Absorption correction	Multi-scan (SADABS; Bruker, 2004 ▸)
T min, T max	0.909, 0.946
No. of measured, independent and observed [I > 2σ(I)] reflections	10962, 3423, 2125
R int	0.024
(sin θ/λ)max (Å−1)	0.669
Refinement
R[F 2 > 2σ(F 2)], wR(F 2), S	0.047, 0.152, 0.99
No. of reflections	3423
No. of parameters	188
H-atom treatment	H atoms treated by a mixture of independent and constrained refinement
Δρmax, Δρmin (e Å−3)	0.26, −0.35

Computer programs: APEX2, SAINT and XPREP (Bruker, 2004 ▸), SIR92 (Altomare et al., 1999 ▸), SHELXL2017 (Sheldrick, 2015 ▸), ORTEP-3 (Farrugia, 2012 ▸) and Mercury (Macrae et al., 2008 ▸).

Supplementary Material

CCDC reference: 1835970

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

supplementary crystallographic information

Crystal data

C6H10N3O+·C7H4ClO2−	F(000) = 616
Mr = 295.72	Dx = 1.384 Mg m−3
Monoclinic, P21/c	Mo Kα radiation, λ = 0.71073 Å
a = 10.1148 (8) Å	Cell parameters from 3319 reflections
b = 11.2236 (8) Å	θ = 4.7–53.1°
c = 14.579 (1) Å	µ = 0.28 mm−1
β = 120.940 (5)°	T = 296 K
V = 1419.57 (19) Å3	Block, colorless
Z = 4	0.35 × 0.30 × 0.20 mm

Data collection

Bruker Kappa APEXII CCD diffractometer	2125 reflections with I > 2σ(I)
Radiation source: fine-focus sealed tube	Rint = 0.024
ω and φ scan	θmax = 28.4°, θmin = 2.7°
Absorption correction: multi-scan (SADABS; Bruker, 2004)	h = −13→12
Tmin = 0.909, Tmax = 0.946	k = −14→14
10962 measured reflections	l = −15→18
3423 independent reflections

Refinement

Refinement on F2	Secondary atom site location: difference Fourier map
Least-squares matrix: full	Hydrogen site location: mixed
R[F2 > 2σ(F2)] = 0.047	H atoms treated by a mixture of independent and constrained refinement
wR(F2) = 0.152	w = 1/[σ2(Fo2) + (0.0728P)2 + 0.324P] where P = (Fo2 + 2Fc2)/3
S = 0.99	(Δ/σ)max = 0.003
3423 reflections	Δρmax = 0.26 e Å−3
188 parameters	Δρmin = −0.34 e Å−3
0 restraints	Extinction correction: SHELXL2017 (Sheldrick, 2015), Fc*=kFc[1+0.001xFc2λ3/sin(2θ)]-1/4
Primary atom site location: structure-invariant direct methods	Extinction coefficient: 0.020 (3)

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.

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

	x	y	z	Uiso*/Ueq
O3	1.08061 (18)	0.73298 (18)	0.57812 (14)	0.0840 (5)
N1	0.62562 (18)	0.71035 (13)	0.45066 (13)	0.0513 (4)
N2	0.61625 (18)	0.91121 (14)	0.47011 (15)	0.0649 (5)
H1N	0.659761	0.979882	0.489408	0.078*
H2N	0.518251	0.904882	0.442578	0.078*
N3	0.85256 (18)	0.82711 (15)	0.52563 (13)	0.0555 (4)
C8	1.1555 (3)	0.8473 (3)	0.6048 (2)	0.0926 (9)
H8A	1.258389	0.838988	0.618161	0.139*
H8B	1.159254	0.877851	0.667577	0.139*
H8C	1.098704	0.901435	0.546305	0.139*
C9	0.9288 (2)	0.7287 (2)	0.53678 (16)	0.0616 (6)
C10	0.8601 (3)	0.6168 (2)	0.50699 (19)	0.0703 (6)
H10	0.919348	0.548952	0.518504	0.084*
C11	0.7049 (3)	0.60891 (17)	0.46085 (17)	0.0595 (5)
C12	0.6128 (3)	0.49752 (19)	0.4188 (2)	0.0872 (8)
H12A	0.531726	0.509732	0.346014	0.131*
H12B	0.568913	0.477063	0.461457	0.131*
H12C	0.678410	0.433995	0.421663	0.131*
C13	0.6995 (2)	0.81598 (16)	0.48261 (15)	0.0489 (4)
Cl1	−0.42873 (6)	0.70123 (7)	0.18780 (6)	0.0859 (3)
O1	0.30336 (15)	0.87707 (12)	0.40502 (13)	0.0710 (5)
O2	0.32766 (15)	0.68727 (12)	0.37489 (12)	0.0648 (4)
C1	0.2501 (2)	0.77506 (16)	0.37387 (15)	0.0506 (5)
C2	0.0808 (2)	0.75559 (16)	0.33048 (14)	0.0455 (4)
C3	0.0178 (2)	0.64290 (17)	0.30515 (16)	0.0532 (5)
H3	0.081505	0.577740	0.317181	0.064*
C4	−0.1384 (2)	0.62496 (19)	0.26221 (16)	0.0591 (5)
H4	−0.179743	0.548535	0.245653	0.071*
C5	−0.2314 (2)	0.72173 (19)	0.24443 (16)	0.0552 (5)
C6	−0.1725 (2)	0.83473 (19)	0.26959 (17)	0.0615 (5)
H6	−0.237007	0.899426	0.257249	0.074*
C7	−0.0160 (2)	0.85154 (17)	0.31355 (16)	0.0559 (5)
H7	0.025012	0.927932	0.332014	0.067*
H1N1	0.508 (3)	0.700 (2)	0.418 (2)	0.089 (8)*

Atomic displacement parameters (Ų)

	U11	U22	U33	U12	U13	U23
O3	0.0495 (9)	0.1165 (14)	0.0927 (12)	0.0275 (9)	0.0414 (9)	0.0152 (11)
N1	0.0479 (9)	0.0476 (9)	0.0551 (9)	0.0080 (7)	0.0242 (8)	−0.0032 (7)
N2	0.0389 (8)	0.0483 (9)	0.0946 (13)	0.0010 (7)	0.0251 (8)	−0.0125 (8)
N3	0.0411 (9)	0.0722 (11)	0.0533 (10)	0.0081 (7)	0.0243 (7)	−0.0019 (8)
C8	0.0457 (13)	0.140 (3)	0.0899 (19)	0.0033 (14)	0.0337 (13)	0.0031 (17)
C9	0.0507 (12)	0.0858 (15)	0.0564 (13)	0.0194 (10)	0.0333 (10)	0.0100 (11)
C10	0.0728 (15)	0.0697 (14)	0.0839 (16)	0.0340 (12)	0.0514 (13)	0.0182 (12)
C11	0.0738 (14)	0.0508 (11)	0.0653 (13)	0.0173 (9)	0.0439 (11)	0.0081 (9)
C12	0.112 (2)	0.0478 (12)	0.121 (2)	0.0116 (12)	0.0732 (18)	0.0017 (13)
C13	0.0406 (9)	0.0533 (10)	0.0497 (11)	0.0050 (8)	0.0210 (8)	−0.0029 (8)
Cl1	0.0454 (3)	0.1120 (6)	0.0929 (5)	−0.0142 (3)	0.0302 (3)	−0.0069 (4)
O1	0.0424 (7)	0.0458 (8)	0.1021 (12)	−0.0028 (6)	0.0210 (7)	−0.0149 (7)
O2	0.0454 (8)	0.0481 (7)	0.0872 (11)	0.0023 (6)	0.0242 (7)	−0.0098 (7)
C1	0.0404 (9)	0.0449 (10)	0.0527 (11)	0.0003 (7)	0.0141 (8)	−0.0010 (8)
C2	0.0406 (9)	0.0447 (9)	0.0424 (10)	0.0005 (7)	0.0149 (8)	0.0012 (7)
C3	0.0495 (11)	0.0465 (10)	0.0573 (11)	−0.0031 (8)	0.0230 (9)	−0.0053 (8)
C4	0.0549 (12)	0.0578 (12)	0.0623 (13)	−0.0144 (9)	0.0285 (10)	−0.0095 (10)
C5	0.0416 (10)	0.0722 (13)	0.0468 (11)	−0.0074 (9)	0.0191 (8)	−0.0020 (9)
C6	0.0429 (10)	0.0607 (12)	0.0702 (14)	0.0087 (9)	0.0215 (10)	0.0076 (10)
C7	0.0442 (10)	0.0459 (10)	0.0643 (12)	0.0007 (8)	0.0184 (9)	0.0034 (9)

Geometric parameters (Å, º)

O3—C9	1.331 (2)	C12—H12A	0.9600
O3—C8	1.438 (4)	C12—H12B	0.9600
N1—C13	1.350 (2)	C12—H12C	0.9600
N1—C11	1.356 (2)	Cl1—C5	1.7385 (19)
N1—H1N1	1.03 (3)	O1—C1	1.247 (2)
N2—C13	1.314 (2)	O2—C1	1.255 (2)
N2—H1N	0.8600	C1—C2	1.506 (2)
N2—H2N	0.8600	C2—C3	1.379 (3)
N3—C9	1.308 (3)	C2—C7	1.389 (3)
N3—C13	1.344 (2)	C3—C4	1.383 (3)
C8—H8A	0.9600	C3—H3	0.9300
C8—H8B	0.9600	C4—C5	1.372 (3)
C8—H8C	0.9600	C4—H4	0.9300
C9—C10	1.392 (3)	C5—C6	1.369 (3)
C10—C11	1.356 (3)	C6—C7	1.381 (3)
C10—H10	0.9300	C6—H6	0.9300
C11—C12	1.490 (3)	C7—H7	0.9300
C9—O3—C8	118.61 (18)	H12A—C12—H12C	109.5
C13—N1—C11	120.53 (17)	H12B—C12—H12C	109.5
C13—N1—H1N1	124.1 (13)	N2—C13—N3	119.43 (17)
C11—N1—H1N1	115.4 (13)	N2—C13—N1	117.68 (16)
C13—N2—H1N	120.0	N3—C13—N1	122.89 (16)
C13—N2—H2N	120.0	O1—C1—O2	124.51 (17)
H1N—N2—H2N	120.0	O1—C1—C2	118.10 (16)
C9—N3—C13	116.32 (18)	O2—C1—C2	117.39 (16)
O3—C8—H8A	109.5	C3—C2—C7	118.48 (17)
O3—C8—H8B	109.5	C3—C2—C1	121.00 (16)
H8A—C8—H8B	109.5	C7—C2—C1	120.51 (16)
O3—C8—H8C	109.5	C2—C3—C4	121.22 (18)
H8A—C8—H8C	109.5	C2—C3—H3	119.4
H8B—C8—H8C	109.5	C4—C3—H3	119.4
N3—C9—O3	119.7 (2)	C5—C4—C3	118.90 (18)
N3—C9—C10	123.68 (19)	C5—C4—H4	120.5
O3—C9—C10	116.64 (19)	C3—C4—H4	120.5
C11—C10—C9	118.62 (18)	C6—C5—C4	121.40 (18)
C11—C10—H10	120.7	C6—C5—Cl1	119.04 (16)
C9—C10—H10	120.7	C4—C5—Cl1	119.55 (16)
C10—C11—N1	117.9 (2)	C5—C6—C7	119.23 (18)
C10—C11—C12	125.36 (19)	C5—C6—H6	120.4
N1—C11—C12	116.74 (19)	C7—C6—H6	120.4
C11—C12—H12A	109.5	C6—C7—C2	120.74 (18)
C11—C12—H12B	109.5	C6—C7—H7	119.6
H12A—C12—H12B	109.5	C2—C7—H7	119.6
C11—C12—H12C	109.5
O1—C1—C2—C3	−173.20 (19)	C4—C5—C6—C7	0.2 (3)
O1—C1—C2—C7	7.8 (3)	C5—C6—C7—C2	1.2 (3)
O2—C1—C2—C3	7.7 (3)	C13—N1—C11—C10	2.1 (3)
O2—C1—C2—C7	−171.35 (18)	C13—N1—C11—C12	−177.2 (2)
C1—C2—C3—C4	−177.99 (18)	C11—N1—C13—N2	179.63 (19)
C7—C2—C3—C4	1.0 (3)	C11—N1—C13—N3	−0.1 (3)
C1—C2—C7—C6	177.29 (19)	C13—N3—C9—O3	179.53 (18)
C3—C2—C7—C6	−1.8 (3)	C13—N3—C9—C10	−0.1 (3)
C2—C3—C4—C5	0.3 (3)	C9—N3—C13—N1	−0.9 (3)
C8—O3—C9—C10	176.7 (2)	C9—N3—C13—N2	179.37 (19)
C8—O3—C9—N3	−2.9 (3)	O3—C9—C10—C11	−177.6 (2)
C3—C4—C5—C6	−0.9 (3)	N3—C9—C10—C11	2.0 (4)
C3—C4—C5—Cl1	178.62 (16)	C9—C10—C11—N1	−2.9 (3)
Cl1—C5—C6—C7	−179.32 (16)	C9—C10—C11—C12	176.3 (2)

Hydrogen-bond geometry (Å, º)

D—H···A	D—H	H···A	D···A	D—H···A
N1—H1N1···O2	1.04 (3)	1.60 (3)	2.636 (3)	176 (2)
N2—H1N···O1i	0.86	2.12	2.846 (2)	142
N2—H2N···O1	0.86	1.97	2.824 (3)	169
C8—H8A···Cl1ii	0.96	2.82	3.770 (3)	171

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

Funding Statement

This work was funded by Department of Science and Technology, Ministry of Science and Technology, Science and Engineering Research Board grant SB/FT/CS-058/2013 to P. Sivajeyanthi and K. Balasubramani.