4,6-Dimeth­oxy­pyrimidin-2-amine–2-(1H-indol-3-yl)acetic acid (1/1)

Samuel Ebenezer; Packianathan Thomas Muthiah

doi:10.1107/S1600536810037724

. 2010 Sep 25;66(Pt 10):o2634–o2635. doi: 10.1107/S1600536810037724

4,6-Dimethoxypyrimidin-2-amine–2-(1H-indol-3-yl)acetic acid (1/1)

Samuel Ebenezer ^a, Packianathan Thomas Muthiah ^a,^*

PMCID: PMC2983259 PMID: 21587607

Abstract

In the title co-crystal C₆H₉N₃O₂·C₁₀H₉NO₂, the 4,6-dimethoxypyrimidin-2-amine molecule interacts with the carboxyl group of the 2-(1H-indol-3-yl)acetic acid molecule through N—H⋯O and O—H⋯N hydrogen bonds, forming a cyclic hydrogen-bonded R ₂ ²(8) motif, which is further linked by an N—H⋯N hydrogen bond, forming a supramolecular chain along the c axis. Neighboring chains are interlinked via C—H⋯O hydrogen bonds, forming a supramolecular ladder

Related literature

For background to crystal engineering, 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 ▶). 2-Aminopyrimidine forms a wide variety of 1:1 adducts with mono and dicarboxylic acids (Etter & Adsmond, 1990 ▶) rather than individual self-assembly compounds (Scheinbeim & Schempp, 1976 ▶). The Inline graphic (8) motif is frequently observed when a carboxylic acid interacts with a 2-amino heterocyclic ring system, see: Lynch & Jones (2004 ▶). It is also one of the most commonly occuring motifs, see: Allen et al. (1998 ▶). For the biological activity of aminopyrimidine derivatives and 2-(1H-indol-3-yl)acetic acid, see: Hunt et al. (1980 ▶); Arteca (1996 ▶). For related structures, see: Karle et al. (1964 ▶); Low et al. (2002 ▶). For related co-crystals of aminopyrimidines, see: Thanigaimani et al. (2006 ▶, 2007 ▶, 2008 ▶). For stacking interactions, see: Hunter (1994 ▶). For hydrogen-bond motifs, see:, see: Bernstein et al. (1995 ▶); Etter (1990 ▶).

Experimental

Crystal data

C₁₀H₉NO₂·C₆H₉N₃O₂
M _r = 330.34
Triclinic,
a = 7.4555 (1) Å
b = 10.7197 (2) Å
c = 11.2537 (2) Å
α = 62.981 (1)°
β = 85.863 (1)°
γ = 85.584 (1)°
V = 798.16 (2) Å³
Z = 2
Mo Kα radiation
μ = 0.10 mm⁻¹
T = 293 K
0.30 × 0.25 × 0.22 mm

Data collection

Bruker SMART APEXII CCD area-detector diffractometer
Absorption correction: multi-scan (SADABS; Bruker, 2008 ▶) T _min = 0.970, T _max = 0.978
19719 measured reflections
5363 independent reflections
3979 reflections with I > 2σ(I)
R _int = 0.028

Refinement

R[F ² > 2σ(F ²)] = 0.046
wR(F ²) = 0.137
S = 1.06
5363 reflections
220 parameters
H-atom parameters constrained
Δρ_max = 0.23 e Å⁻³
Δρ_min = −0.22 e Å⁻³

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 ▶); software used to prepare material for publication: PLATON.

Supplementary Material

Crystal structure: contains datablocks global, I. DOI: 10.1107/S1600536810037724/bv2155sup1.cif

e-66-o2634-sup1.cif^{(22.3KB, cif)}

Structure factors: contains datablocks I. DOI: 10.1107/S1600536810037724/bv2155Isup2.hkl

e-66-o2634-Isup2.hkl^{(257.3KB, hkl)}

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

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

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
N2—H2A⋯O4	0.86	2.04	2.8927 (14)	171
O3—H3⋯N1	0.82	1.88	2.6979 (12)	172
N4—H4⋯N3ⁱ	0.86	2.45	3.2184 (17)	149
C10—H10A⋯O4ⁱⁱ	0.97	2.59	3.5491 (18)	172

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

Acknowledgments

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

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). The prime importance of aminopyrimidine-carboxylate interactions is due to their involvement in protein-nuleic acid recognition and protein-drug binding (Hunt et al., 1980; Baker & Santi, 1965). Aminopyrimidines readily pair up with carboxylic acids to form adducts rather than individual self-assembly compounds which is evident from the fact that 2-aminopyrimidine forms a wide variety of 1:1 adducts with mono and dicarboxylic acids (Etter & Adsmond, 1990) rather than individual self-assembly compounds (Scheinbeim & Schempp, 1976). 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). Auxin is a plant growth hormone which induces cell elongation in stems. 2-(1H-indol-3-yl)acetic acid is the first isolated auxin (Arteca, 1996). The crystal structures of 4,6-dimethoxypyrimidin-2-amine (Low et al., 2002) and 2-(1H-indol-3-yl)acetic acid (Karle et al.,1964) have already been reported. Several cocrystals of 4,6-dimethoxypyrimidin-2-amine with various carboxylic acids such as 4,6-dimethoxypyrimidin-2-amine 4-aminobenzoic acid (1/1) (Thanigaimani et al., 2006), 4,6-dimethoxypyrimidin-2-amine phthalic acid (1/1) (Thanigaimani et al., 2007) and 4,6-dimethoxypyrimidin-2-amine anthranilic acid (1/1) (Thanigaimani et al., 2008) have been recently reported from our group. In the present study, the various hydrogen-bonding patterns in the 4,6-dimethoxypyrimidin-2-amine (1H-indol-3-yl)acetic acid (1/1) cocrystal, (I), are thoroughly investigated.

The asymmetric unit (Fig. 1) contains a molecule of 4,6-dimethoxypyrimidin-2-amine and a molecule of 2-(1H-indol-3-yl)acetic acid, which are linked by N—H···O and O—H···N hydrogen bonds (Table. 1), forming an eight-membered ring with graph-set notation R₂²(8) (Etter, 1990; Bernstein et al., 1995). This motif is further linked by an N—H···N hydrogen bond, involving the N3 atom of 4,6-dimethoxypyrimidin-2-amine and N4 atom of the 2-(1H-indol-3-yl)acetic acid molecule, to form a supramolecular chain along the c axis. This supramolecular chain is further interlinked with a neighboring chain through a couple of C—H···O hydrogen bonds. These C—H···O hydrogen bonds form another R₂²(8) motif. Further N—H···O, N—H···N and C—H···O hydrogen bonds combine together to form a large ring motif, with graph-set notation R₆⁴(22). This ring motif extends to give a one dimensional supramolecular ladder as shown in Fig. 2. π-π stacking interaction is observed between two aminopyrimidine rings. They have an interplanar distance, centroid-to-centroid distance and a slip angle (the angle between the centroid vector and the normal to the plane) of 3.4413 (4) Å, 3.4937 (6) Å and 9.93° respectively. These are typical aromatic stacking values (Hunter, 1994).

Experimental

A hot ethanolic solution (20 ml) of 4,6-dimethoxypyrimidin-2-amine (38 mg, Aldrich) and 2-(1H-indol-3-yl)acetic acid (44 mg, Loba Chemie) was warmed for half an hour over a water bath. The mixture was cooled slowly and kept at room temperature; afer a few days, colourless plate-like crystals were obtained.