2-Amino-4,6-dimeth­oxy­pyrimidin-1-ium p-toluene­sulfonate

Sundaramoorthy Gomathi; Packianathan Thomas Muthiah

doi:10.1107/S160053681103755X

. 2011 Sep 17;67(Pt 10):o2679–o2680. doi: 10.1107/S160053681103755X

2-Amino-4,6-dimethoxypyrimidin-1-ium p-toluenesulfonate

Sundaramoorthy Gomathi ^a, Packianathan Thomas Muthiah ^a,^*

PMCID: PMC3201388 PMID: 22064770

Abstract

In the title salt, C₆H₁₀N₃O₂ ⁺·C₇H₇O₃S⁻, the 2-amino-4,6-dimethoxypyrimidinium cation interacts with the sulfonate group of the p-toluenesulfonate anion via a pair of N—H⋯O hydrogen bonds, forming a cyclic hydrogen-bonded R ₂ ²(8) motif, which in the crystal is linked by further intemolecular N—H⋯O hydrogen bonds, forming supramolecular chains along the c axis. Furthermore, neighboring chains are interlinked via weak C—H⋯O hydrogen bonds and C—H⋯π interactions, forming layers.

Related literature

For background to crystal engineering and supramolecular chemistry, see: Desiraju (1989 ▶). For the role of aminopyrimidine–carboxylate interactions in protein-nuleic acid recognition and protein-drug binding, see: Hunt et al. (1980 ▶); Baker & Santi (1965 ▶). For the role of sulfate–protein interactions, see: Pflugrath & Quiocho (1985 ▶); Jacobson & Quiocho (1988 ▶). For information on carboxylic acid interactions with a 2-amino heterocyclic ring system, see: Etter & Adsmond (1990 ▶); Lynch & Jones (2004 ▶); Allen et al. (1998 ▶). For a survey of hydrogen-bonding patterns involving sulfonate salts, see: Haynes et al. (2004 ▶). For hydrogen-bonding patterns involving sulfonate groups in biological systems and metal complexes, see: Russell et al. (1994 ▶); Cai et al. (2001 ▶). For hydrogen-bond motifs, see: Bernstein et al. (1995 ▶); Etter (1990 ▶). For related structures, see: Low et al. (2002 ▶); Arora & Sundaralingam (1971 ▶); Balasubramani et al. (2007 ▶); Hemamalini et al. (2005 ▶); Thanigaimani et al. (2007 ▶, 2008 ▶); Ebenezer & Muthiah (2010 ▶).

Experimental

Crystal data

C₆H₁₀N₃O₂ ⁺·C₇H₇O₃S⁻
M _r = 327.37
Orthorhombic,
a = 15.2116 (2) Å
b = 12.1422 (2) Å
c = 8.3497 (1) Å
V = 1542.21 (4) Å³
Z = 4
Mo Kα radiation
μ = 0.24 mm⁻¹
T = 296 K
0.20 × 0.18 × 0.15 mm

Data collection

Bruker SMART APEXII CCD area-detector diffractometer
Absorption correction: multi-scan (SADABS; Bruker, 2008 ▶) T _min = 0.954, T _max = 0.965
35029 measured reflections
5264 independent reflections
4257 reflections with I > 2σ(I)
R _int = 0.032

Refinement

R[F ² > 2σ(F ²)] = 0.035
wR(F ²) = 0.098
S = 1.04
5264 reflections
202 parameters
1 restraint
H-atom parameters constrained
Δρ_max = 0.21 e Å⁻³
Δρ_min = −0.23 e Å⁻³
Absolute structure: Flack (1983 ▶) 2449, Friedel pairs
Flack parameter: −0.01 (6)

Data collection: APEX2 (Bruker, 2008 ▶); cell refinement: SAINT (Bruker, 2008 ▶); data reduction: SAINT; program(s) used to solve structure: SHELXS97 (Sheldrick, 2008 ▶); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008 ▶); molecular graphics: PLATON (Spek, 2009 ▶) and POV-RAY (Cason, 2004) ▶; software used to prepare material for publication: PLATON.

Supplementary Material

Crystal structure: contains datablock(s) global, I. DOI: 10.1107/S160053681103755X/lh5333sup1.cif

e-67-o2679-sup1.cif^{(28.3KB, cif)}

Structure factors: contains datablock(s) I. DOI: 10.1107/S160053681103755X/lh5333Isup2.hkl

e-67-o2679-Isup2.hkl^{(252.6KB, hkl)}

Supplementary material file. DOI: 10.1107/S160053681103755X/lh5333Isup3.cml

Additional supplementary materials: crystallographic information; 3D view; checkCIF report

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

Cg is the centroid of the C9–C14 ring.

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
N1—H1⋯O4	0.86	1.90	2.7441 (16)	169
N2—H2A⋯O3ⁱ	0.86	2.20	3.0233 (19)	161
N2—H2B⋯O3	0.86	2.12	2.9398 (18)	159
C8—H8B⋯O5ⁱⁱ	0.96	2.37	3.248 (2)	152
C7—H7A⋯Cgⁱⁱⁱ	0.96	2.96	3.7815 (18)	145

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Symmetry codes: (i) Inline graphic ; (ii) ; (iii) .

Acknowledgments

The authors thank the DST-India (FIST programme) for the use ofthe diffractometer at the School of Chemistry, Bharathidasan University. Tiruchirappalli, Tamilnadu, India

supplementary crystallographic information

Comment

A study of non-covalent interactions, such as hydrogen bonding, plays a key role in molecular recognition and crystal engineering (Desiraju, 1989). Pyrimidines and aminopyrimidine derivatives are biologically important compounds and they manifest themselves in nature as components of nucleic acids. Some aminopyrimidine derivatives are used as antifolate drugs (Hunt et al., 1980; Baker & Santi, 1965). Their interactions with carboxylic acids are of utmost importance since they are involved in protein-nucleic acid recognition and drug-protein recognition processes, where the pyrimidine moiety of a drug forms hydrogen bonding with the carboxyl group of the protein. Aminopyrimidines readily pair up with carboxylic acids to form a wide variety of 1:1 adducts with mono and dicarboxylic acids (Etter & Adsmond, 1990). The R₂²(8) motif is a robust synthon which is frequently observed when a carboxylic acid interacts with a 2-amino heterocyclic ring system (Lynch & Jones, 2004). This motif is also recognized to be one of the top 5 motifs among the 24 commonly occurring motifs in crystal structures (Allen et al., 1998). 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). Hydrogen bonding patterns involving sulfonate groups in biological systems and metal complexes are of current interest (Russell et al., 1994; Cai et al., 2001). Such interactions can be used for designing supramolecular architectures.

The crystal structures of 2-amino-4, 6-dimethoxy pyrimidine (Low et al., 2002) and p-toluene sulfonic acid monohydrate (Arora & Sundaralingam, 1971) have already been reported. Investigations of a fairly large number of crystal structure of 2-amino-4,6-dimethoxy/dimethyl pyrimidine salts and co crystals involving carboxylates (Thanigaimani et al., 2007; Thanigaimani et al., 2008; Ebenezer & Muthiah, 2010) and a few sulfonates (Balasubramani et al., 2007; Hemamalini et al., 2005) have already been reported from our laboratory. They reveal the formation of certain robust motifs and a variety of supramolecular architectures. A survey by Haynes et al. (2004) on the sulfonate salts, revealed various hydrogen bonding patterns and their preferences with specific functional groups. As part of our investigation to gain more insight into hydrogen bonding interactions involving aminopyrimidine and sulfonates, the crystal structure of title compound is presented herein.

The asymmetric unit of the title compound (I) (Fig. 1) contains one 2-amino-4,6-dimethoxypyrimidinium cation and one p-toluenesulfonate anion. The 2- amino-4,6-dimethoxy pyrimidinium cation is protonated at N1. Protonation of the pyrimidine base on the N1 site is reflected by an increase in bond angle. The C2—N3—C4 angle of the unprotonated atom N3 is 116.52 (12)° while for protonated atom N1, the C2—N1—C6 angle is 120.64 (11)°. The sulfonate group of the p-toluenesulfonate anion interacts with 2-amino-4,6-dimethoxypyrimidinium cation via a pair of N—H···O hydrogen bonds, forming a hydrogen bonded ring motif with graph-set notation R₂²(8) (Etter, 1990; Bernstein et al., 1995). The sulfonate group mimics the carboxylate anion's mode of association, which is more commonly seen when binding with 2-aminopyrimidines. The R₂²(8) motif links O3 and O4 atoms of sulfonate anion with the protonated atom N1 and the 2- amino group of the pyrimidinium cation.

This motif is further interlinked by an N—H···O hydrogen bond, involving 2- amino group of the 2-amino-4,6-dimethoxy pyrimidinium cation and O3ⁱ (symmetry code: i - x,-y,-1/2 + z)) atom of p-toluenesulfonate anion to form a supramolecular chain along the c axis (Fig. 2). The neighboring supramolecular chain is further interlinked via C—H···O hydrogen bond involving a methoxy group (C8) of cation and O5ⁱⁱ (symmetry code: 1/2 - x, y, -1/2 + z) atom of sulfonate anion. Thus intermolecular hydrogen bonds generate a 2-D supramolecular network. The crystal structure is further stabilized by C—H··· π interaction. The C—H···π interaction is observed between the methoxy group (C7—H7A) of pyrimidinium cation with phenyl ring of p-toluenesulfonate anion (C—H···π = 3.7815 (18) Å, 145°). The identification of such supramolecular patterns will help us design and construct preferred hydrogen bonding patterns on drug like molecules.

Experimental

A hot ethanolic solution (20 ml) of 2-amino-4,6-dimethoxypyrimidine (38 mg, Aldrich) and p-toluene sulfonic acid (47 mg, Loba Chemie) was warmed for half an hour over a water bath. The mixture was cooled slowly and kept at room temperature; after a few days, colorless prismatic crystals were obtained.