Hydro­gen-bonding patterns in 2-amino-4,6-di­methyl­pyrimidinium hydrogen sulfate

In the title compound, C₆H₁₀N₃⁺·HSO₄^-, the asymmetric unit consists of a hydrogen sulfate anion and a 2-amino-4,6-di­methyl­pyrimidinium cation. The hydrogen sulfate anions self-assemble through O-H...O hydrogen bonds, forming supramolecular chains along the b axis, while the organic cations form base pairs via N-H...N hydrogen bonds. The amino­pyrimidinium cations join to the sulfate anions via a pair of hydrogen bonds donated from the pyrimidinium protonation site and from the exo amine group cis to the protonated site.

S1. Comment

Pyrimidine and aminopyrimidine derivatives are biologically very important compounds as they occur in nature as components of nucleic acids. Some aminopyrimidine derivatives are used as antifolate drugs (Hunt et al., 1980; Baker & Santi, 1965). 2-Aminopyrimidine and its derivatives are of particular interest as adduct formers because of their ability to form stable hydrogen-bonded chains via their stereochemically associative amine group and the ring N atoms (Lynch et al., 2000). The crystal structures of aminopyrimidine derivatives (Schwalbe & Williams, 1982), aminopyrimidine carboxylates (Hu et al., 2002) and cocrystals (Chinnakali et al., 1999; Goswami et al., 2000; Etter, 1990) have been reported in the literature. The crystal structure of 2,4-diaminopyrimidinium sulfate has also been reported by one of us (Muthiah et al., 2001). Hydrogen-bonding patterns involving sulfate and sulfonate groups in biological systems and metal complexes are also of current interest (Onoda et al., 2001). Benzoic acid and sulfuric acid form a stable hydrogen-bonded complex that favours aerosol formation in the atmosphere (Zhang et al., 2004). In a sulfate-binding protein, the sulfate anion is bound mainly by seven hydrogen bonds, five of which are from the main-chain peptide NH groups (Pflugrath & Quiocho, 1985; Jacobson & Quiocho, 1988). The present study is aimed at understanding the hydrogen-bonding networks in the title compound, (I).

In (I), the asymmetric unit consists of a hydrogen sulfate anion and a 2-amino-4,6-dimethylpyrimidinium cation (ampyH) (Fig. 1). The protonation of the pyrimidine base on the N1 site is reflected in the change in bond angle. The C2—N3—C4 angle at the unprotonated atom N3 is 117.6 (1)°, while for the protonated atom N1 the C2—N1—C6 angle is 122.3 (1)°. The geometry of the ampyH cation agrees with that of other ampyH cations reported in the literature (Panneerselvam et al., 2004). The S—O distances lie between 1.447 (1) and 1.560 (1) Å, while the O—S—O angle ranges between 104.0 (1) and 113.3 (1)° (Table 1), indicating a distorted tetrahedral environment around the S atom. The S—O bond lengths and O—S—O bond angles of the sulfate group are consistent with the fact that the H atom is attached only to atom O1. Atoms O2 and O4 interact with the protonated pyrimidine moiety through a pair of nearly parallel N—H···O hydrogen bonds (Table 2), which are reminiscent of the carboxylate–amine interaction seen in ASP-27 of dihydrofolate reductase and the 2,4-diamino-5-(3,4,5-trimethoxybenzyl)pyrimidine cation (Kuyper, 1990). Thus in compound (I), the pair of sulfate O atoms mimics the role of the carboxylate group in its hydrogen-bonded interaction with the aminopyrimidinium motif. This type of interaction has also been observed in the crystal structure of 2-amino-5-nitro-4,6-dipiperidino-pyrimidinium hydrogensulfate monohydrate (Quesada et al., 2003). This pattern is also remarkably similar to that observed in the adeninium/sulfate systems (Langer & Huml, 1978) and in cytidinium salts with composite XY_n anions capable of accepting hydrogen bonds through their Y atoms, e.g. NO₃⁻, HSO₄⁻, SO₄²⁻, H₂PO₄⁻ and SiF₆²⁻ (Gilski & Jaskólski, 1998).

The ampyH cations are paired centrosymmetrically through N2—H2A···N3ⁱⁱ and N3···H2Aⁱⁱ—N2ⁱⁱ hydrogen bonds (for symmetry code see Table 2). This configuration can be described by the graph-set notation R²₂(8) (Etter, 1990; Berstein et al., 1995). This type of base pairing has also been reported in trimethoprim salicylate methanol solvate (Panneerselvam et al., 2002), trimethoprim sulfate trihydrate (Muthiah et al., 2001), trimethoprimhydrogen maleate (Prabakaran et al., 2001) and trimethoprim perchlorate (Muthiah et al., 2002). The hydrogen sulfate ions self-assemble through O1—H1'···O3ⁱ hydrogen bonds, leading to a supramolecular chain along the b axis (Fig. 2). There is also a C—H···O hydrogen bond involving atoms C5 of the pyrimidine moiety and O1 of the hydrogen sulfate ion.

S2. Experimental

To a hot methanol solution of 2-amino-4,6-dimethylpyrimidine (62 mg, Aldrich) were added a few drops of sulfuric acid. The solution was warmed over a water bath for a few minutes. The resulting solution was allowed to cool slowly to room temperature. Crystals of (I) appeared from the mother liquor after a few days.

S3. Refinement

The positions of H atoms were determined from difference Fourier maps and refined freely along with their isotropic displacement parameters. The C—H, N—H and O—H bond lengths are 0.86 (2)–0.96 (2), 0.85 (2)–0.87 (2) and 0.82 (2) Å, respectively

Computing details

Data collection: CrysAlis CCD (Oxford Diffraction, 2004); cell refinement: CrysAlis RED (Oxford Diffraction, 2004); data reduction: CrysAlis RED; program(s) used to solve structure: SHELXS97 (Sheldrick, 1997); program(s) used to refine structure: SHELXL97 (Sheldrick, 1997); molecular graphics: PLATON (Spek, 2003) and ORTEPII (Johnson, 1976); software used to prepare material for publication: SHELXL97.

Figures

	Fig. 1. An ORTEPII (Johnson, 1976) diagram of the asymmetric unit of (I), showing 50% probability displacement ellipsoids.
	Fig. 2. The crystal structure of (I). Broken lines denote hydrogen bonds.

2-amino-4,6-dimethylpyrimidinium hydrogen sulfate

Crystal data

C6H10N3^+·HSO4^−	F(000) = 464
Mr = 221.24	Dx = 1.540 Mg m^−3
Monoclinic, P21/c	Mo Kα radiation, λ = 0.71073 Å
Hall symbol: -p 2ybc	Cell parameters from 4591 reflections
a = 7.025 (1) Å	θ = 3.4–25.7°
b = 6.724 (1) Å	µ = 0.33 mm^−1
c = 20.200 (4) Å	T = 293 K
β = 90.27 (3)°	Prism, colourless
V = 954.2 (3) Å^3	0.5 × 0.35 × 0.1 mm
Z = 4

Data collection

Kuma KM-4 CCD κ-geometry diffractometer	1793 independent reflections
Radiation source: fine-focus sealed tube	1622 reflections with I > 2σ(I)
Graphite monochromator	Rint = 0.026
ω scans	θmax = 25.7°, θmin = 4.7°
Absorption correction: multi-scan (XEMP; Siemens, 1990)	h = −6→8
Tmin = 0.877, Tmax = 0.970	k = −8→8
7253 measured reflections	l = −24→19

Refinement

Refinement on F^2	Secondary atom site location: difference Fourier map
Least-squares matrix: full	Hydrogen site location: Fmap
R[F^2 > 2σ(F^2)] = 0.027	All H-atom parameters refined
wR(F^2) = 0.072	w = 1/[σ^2(Fo^2) + (0.0395P)^2 + 0.4073P] where P = (Fo^2 + 2Fc^2)/3
S = 1.07	(Δ/σ)max = 0.001
1793 reflections	Δρmax = 0.24 e Å^−3
172 parameters	Δρmin = −0.51 e Å^−3
0 restraints	Extinction correction: SHELXL97, Fc^*=kFc[1+0.001xFc^2λ^3/sin(2θ)]^-1/4
Primary atom site location: structure-invariant direct methods	Extinction coefficient: 0.015 (2)

Special details

Geometry. All e.s.d.'s (except the e.s.d. in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell e.s.d.'s are taken into account individually in the estimation of e.s.d.'s in distances, angles and torsion angles; correlations between e.s.d.'s in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell e.s.d.'s is used for estimating e.s.d.'s 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 > σ(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
S1	1.03273 (5)	−0.16124 (5)	0.322692 (17)	0.01472 (14)
O1	1.04674 (16)	−0.39155 (16)	0.33076 (6)	0.0201 (3)
H1'	0.997 (3)	−0.450 (4)	0.2993 (11)	0.044 (7)*
O2	1.14645 (15)	−0.08421 (17)	0.37682 (6)	0.0234 (3)
O3	1.11085 (15)	−0.11503 (16)	0.25764 (5)	0.0229 (3)
O4	0.83239 (14)	−0.10580 (16)	0.32732 (5)	0.0200 (3)
N1	0.72693 (17)	0.25743 (19)	0.37687 (6)	0.0146 (3)
H1	0.768 (3)	0.150 (3)	0.3594 (10)	0.035 (6)*
N2	0.98587 (19)	0.2540 (2)	0.44805 (7)	0.0209 (3)
H2A	1.053 (3)	0.317 (3)	0.4756 (10)	0.027 (5)*
H2B	1.030 (3)	0.148 (3)	0.4284 (10)	0.029 (5)*
N3	0.77406 (17)	0.51565 (18)	0.45432 (6)	0.0162 (3)
C2	0.8301 (2)	0.3429 (2)	0.42631 (7)	0.0146 (3)
C4	0.6153 (2)	0.5999 (2)	0.43112 (7)	0.0165 (3)
C5	0.5043 (2)	0.5153 (2)	0.38065 (7)	0.0183 (3)
H5	0.389 (3)	0.576 (3)	0.3647 (9)	0.024 (5)*
C6	0.5637 (2)	0.3403 (2)	0.35286 (7)	0.0154 (3)
C7	0.5602 (3)	0.7933 (2)	0.46201 (9)	0.0214 (4)
H7A	0.450 (3)	0.831 (3)	0.4480 (11)	0.043 (6)*
H7B	0.568 (3)	0.785 (3)	0.5085 (11)	0.032 (5)*
H7C	0.647 (3)	0.887 (4)	0.4525 (11)	0.048 (6)*
C8	0.4639 (2)	0.2311 (3)	0.29889 (9)	0.0217 (4)
H8A	0.361 (3)	0.303 (3)	0.2824 (10)	0.036 (6)*
H8B	0.544 (3)	0.205 (3)	0.2650 (12)	0.047 (6)*
H8C	0.424 (3)	0.105 (3)	0.3144 (11)	0.040 (6)*

Atomic displacement parameters (Ų)

	U^11	U^22	U^33	U^12	U^13	U^23
S1	0.0161 (2)	0.0125 (2)	0.0155 (2)	0.00195 (13)	0.00042 (14)	−0.00116 (14)
O1	0.0274 (6)	0.0135 (6)	0.0194 (6)	0.0026 (4)	−0.0018 (5)	−0.0004 (4)
O2	0.0223 (6)	0.0221 (6)	0.0256 (6)	0.0027 (4)	−0.0061 (5)	−0.0067 (5)
O3	0.0264 (6)	0.0214 (6)	0.0209 (6)	0.0054 (5)	0.0065 (5)	0.0041 (5)
O4	0.0166 (5)	0.0183 (6)	0.0250 (6)	0.0022 (4)	0.0007 (4)	−0.0045 (4)
N1	0.0161 (6)	0.0137 (6)	0.0139 (6)	0.0003 (5)	0.0017 (5)	−0.0019 (5)
N2	0.0224 (7)	0.0191 (7)	0.0210 (7)	0.0061 (6)	−0.0070 (6)	−0.0081 (6)
N3	0.0193 (6)	0.0148 (6)	0.0146 (6)	0.0019 (5)	0.0001 (5)	−0.0012 (5)
C2	0.0175 (7)	0.0141 (7)	0.0122 (7)	−0.0003 (6)	0.0014 (5)	−0.0004 (5)
C4	0.0191 (7)	0.0149 (7)	0.0156 (7)	0.0012 (6)	0.0039 (6)	0.0023 (6)
C5	0.0172 (7)	0.0184 (8)	0.0192 (8)	0.0030 (6)	−0.0009 (6)	0.0027 (6)
C6	0.0157 (7)	0.0174 (7)	0.0133 (7)	−0.0017 (6)	0.0020 (6)	0.0033 (6)
C7	0.0246 (8)	0.0178 (8)	0.0219 (9)	0.0060 (7)	0.0008 (7)	−0.0019 (7)
C8	0.0206 (8)	0.0232 (9)	0.0211 (9)	−0.0012 (7)	−0.0039 (7)	−0.0023 (7)

Geometric parameters (Å, º)

S1—O2	1.4470 (12)	N3—C2	1.3518 (19)
S1—O4	1.4594 (11)	C4—C5	1.402 (2)
S1—O3	1.4599 (12)	C4—C7	1.494 (2)
S1—O1	1.5602 (11)	C5—C6	1.369 (2)
O1—H1'	0.82 (2)	C5—H5	0.962 (18)
N1—C2	1.3587 (19)	C6—C8	1.487 (2)
N1—C6	1.3621 (19)	C7—H7A	0.86 (2)
N1—H1	0.86 (2)	C7—H7B	0.94 (2)
N2—C2	1.320 (2)	C7—H7C	0.90 (3)
N2—H2A	0.85 (2)	C8—H8A	0.93 (2)
N2—H2B	0.87 (2)	C8—H8B	0.90 (3)
N3—C4	1.3337 (19)	C8—H8C	0.95 (2)
O2—S1—O4	112.91 (7)	C5—C4—C7	120.86 (14)
O2—S1—O3	113.30 (7)	C6—C5—C4	118.52 (13)
O4—S1—O3	111.72 (7)	C6—C5—H5	119.1 (11)
O2—S1—O1	104.01 (7)	C4—C5—H5	122.3 (11)
O4—S1—O1	107.89 (6)	N1—C6—C5	117.59 (13)
O3—S1—O1	106.35 (6)	N1—C6—C8	116.88 (14)
S1—O1—H1'	111.7 (16)	C5—C6—C8	125.52 (14)
C2—N1—C6	122.27 (13)	C4—C7—H7A	110.7 (15)
C2—N1—H1	118.8 (14)	C4—C7—H7B	110.6 (12)
C6—N1—H1	118.9 (14)	H7A—C7—H7B	112.9 (19)
C2—N2—H2A	116.9 (13)	C4—C7—H7C	110.1 (15)
C2—N2—H2B	120.9 (13)	H7A—C7—H7C	110 (2)
H2A—N2—H2B	120.8 (19)	H7B—C7—H7C	102.7 (19)
C4—N3—C2	117.57 (13)	C6—C8—H8A	111.6 (13)
N2—C2—N3	119.51 (13)	C6—C8—H8B	111.2 (15)
N2—C2—N1	119.46 (13)	H8A—C8—H8B	108.3 (19)
N3—C2—N1	121.03 (13)	C6—C8—H8C	109.8 (13)
N3—C4—C5	122.99 (14)	H8A—C8—H8C	110.6 (18)
N3—C4—C7	116.16 (14)	H8B—C8—H8C	105.1 (18)
C4—N3—C2—N2	−179.63 (14)	N3—C4—C5—C6	−1.5 (2)
C4—N3—C2—N1	−0.8 (2)	C7—C4—C5—C6	178.36 (14)
C6—N1—C2—N2	179.15 (13)	C2—N1—C6—C5	−0.4 (2)
C6—N1—C2—N3	0.3 (2)	C2—N1—C6—C8	−179.72 (13)
C2—N3—C4—C5	1.4 (2)	C4—C5—C6—N1	0.9 (2)
C2—N3—C4—C7	−178.48 (13)	C4—C5—C6—C8	−179.78 (15)

Hydrogen-bond geometry (Å, º)

D—H···A	D—H	H···A	D···A	D—H···A
N1—H1···O4	0.86 (2)	1.90 (2)	2.743 (2)	172 (2)
N2—H2B···O2	0.87 (2)	2.05 (2)	2.921 (2)	175 (2)
O1—H1′···O3^i	0.82 (2)	1.76 (2)	2.579 (2)	169 (2)
N2—H2A···N3^ii	0.85 (2)	2.17 (2)	3.017 (2)	179 (2)
C5—H5···O1^iii	0.96 (2)	2.51 (2)	3.422 (2)	159 (1)

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