Crystal and Molecular Structures of Two 2-aminothiophene Derivatives

The crystal and molecular structures of two 2-aminothiophene derivatives, potential allosteric enhancers at the human A 1 adenosine receptor, are reported.


Introduction
2-Aminothiophene derivatives have been used in a number of applications in pesticides, dyes and pharmaceuticals.The synthesis and properties of these compounds were reviewed in 1999 by Sabinis et al. [1] and more recently by Puterová et al. [2].In particular, substituted 2-aminothiophenes with alkyl or cycloalkyl substituents in positions 4 and 5 (see Scheme 1), and aroyl group in position 3 are active as allosteric enhancers at the human A 1 adenosine receptor [3][4][5].According to these results, the 2-amino and 3-keto groups are necessary for the biological action, and the substituents at position 4 can further increase the activity.Scheme 1.A general structural formula of 2-amino-thiophene with the numbering scheme.

Results and Discussion
Although solid-state findings do not always translate into non-crystalline environments, the supposition that the presence of such a bond is important for the biological activity [8] seems to be obvious.
In both molecules the second hydrogen atom from the NH 2 group is involved in a relatively short and linear intermolecular hydrogen bond with the O10 atom.These bonds connect molecules in infinite chains along x in 1 (Figure 3) and along y in 2 (Figure 4).In 2, the chains are connected by a number of weak but directional C-H•••Cl interactions (Figure 5); in contrast 1 is a rare example of a structure without any short intermolecular contacts other than well-defined, "classical" hydrogen bonds.In the case of 2, the structures from the room temperature and 100 K data can be compared, and it turns out that the unit cell b parameter (i.e., along the hydrogen-bonded chain) does almost not change with temperature and the shrinking of the unit cell volume is almost exclusively caused by the shortening of the c unit cell parameter, the direction without any significant intermolecular interactions.

Experimental Section
The title compounds were obtained as a gift samples from R. L. Fine Chem., Bengaluru, India.Melting points: 373 K for 1, 368 K for 2.
The crystals appropriate for X-ray data collection were grown from 2-butanone solutions by slow evaporation.X-ray diffraction data for 1 and 2 were collected at room temperature using the ω-scan technique on an Agilent Technologies four-circle diffractometer equipped with Eos CCD-detector [13] using graphite-monochromatized MoK α radiation (λ = 0.71073 Å), and additionally for 2-due to the relatively low quality of room-temperature data-at 130(1) K on an Agilent SuperNova four-circle diffractometer equipped with Atlas CCD-detector [13] using mirror-monochromatized CuK α radiation from high-flux micro-focus source (λ = 1.54178Å).The data were corrected for Lorentz-polarization effects as well as for absorption [13].Accurate unit-cell parameters were determined by a least-squares fit of 1187 (1), 1335 (2, rt) and 3736 (2, 130 K) reflections of highest intensity, chosen from the whole experiment.The calculations were mainly performed with the WinGX program system [14].The structures were solved with SIR92 [15] and refined with the full-matrix least-squares procedure on F 2 by SHELXL97 [9].Scattering factors incorporated in SHELXL97 were used.The function w The final values of A and B are listed in Table 1.All non-hydrogen atoms were refined anisotropically, all hydrogen atoms in 2 (130 K) and amino hydrogens in 1 were found in difference Fourier maps and isotropically refined; other hydrogen atoms in 1 were placed in calculated positions and were refined as 'riding' on their parent atoms; the U iso 's of hydrogen atoms were set as 1.2 times the U eq value of the appropriate carrier atom.Relevant crystal data are listed in Table 3, together with refinement details.

Figures 1
Figures 1 and 2 show perspective views of molecules 1 and 2, respectively.

Figure 1 .
Figure 1.Ellipsoid representation of molecule 1 together with the atom labeling scheme[9].The ellipsoids are drawn at 50% probability level, hydrogen atoms are depicted as spheres with arbitrary radii.The intramolecular hydrogen bond is drawn as a dashed line.

Figure 2 .
Figure 2. Ellipsoid representation of molecule 2 together with the atom labeling scheme [9].The ellipsoids are drawn at 50% probability level, hydrogen atoms are depicted as spheres with arbitrary radii.The intramolecular hydrogen bond is drawn as a dashed line.

Figure 5 .
Figure 5.The crystal packing of 2 as seen along direction [12].N-H•••O hydrogen bonds and C-H•••Cl contacts are shown as dashed lines.

Table 3 .
Crystal data and refinement details.