Crystal and Molecular Structure of 2-Amino-3-Ethyl Carboxamido-4-Metyl-5-Carboxy Ethyl Thiophene

The crystal and molecular structure of 2-Amino-3-ethyl carboxamido-4-methyl-5-carboxy ethyl thiophene (C11H16N2O3S) has been investigated from single crystal X-ray diffraction data. The primary focus is to investigate the molecular geometry of this compound in the solid state along with the associated inter and intra-molecular hydrogen bonding and related weak interactions present in this molecule. This compound crystallizes in the monoclinic space group P21/c with cell parameters, a = 8.1344(3) Å, b = 13.7392(4) Å, c = 11.4704(4) Å, β = 100.769(2) ̊, V = 1259.36 (7) Å, D = 1.352 g·cm, Z = 4. The molecular geometry is stabilized by intra-molecular N-H...O=C and C-H...O interactions along with intramolecular C-H...N and C-H...O interactions which contribute towards the stability of the crystal packing.


Introduction
Thiophene derivatives [1] are of importance in medicinal chemistry and have recently been incorporated into new pharmaceutical and chemical compounds tested as antiinflammatory agents [2].This class of compounds exhibit pharmacological activity [3][4][5].These are also useful in polymer chemistry because of their mechanical strength, ease of fabrication, flexibility in design, stability, resistance to corrosion and low cost [6].In view of the importance of this class of heterocycles from a biological and pharmaceutical perspective, we report in this manuscript the synthesis of 2-Amino-3-ethyl carboxamido-4-methyl-5-carboxy ethyl thiophene.The compound has been purified and characterized spectroscopically using FT-IR, 1 H and 13 C NMR techniques.The purity of the phase has been established by powder X-Ray diffraction.Structural characterization of this compound has been achieved via single crystal X-ray diffraction study.Finally, an investigation of the CSD for related compounds containing the thiophene core has also been performed to compare the changes in geometry which accompany the introduction of a 3-ethyl carboxamide and 5-carboxy ester moiety on the thiophene ring.

Synthesis of 2-Amino-3-Ethyl Carboxamido-4-Methyl-5-Carboxy Ethyl Thiophene
A mixture of ethyl acetoacetate (5.2 g; 0.04 mol), ethyl cyanocetate (4.52 g; 0.04 mol) and sulphur powder (1.28 g; 0.04 mol) in ethanol (40 ml) were added in a round bottomed flask.To this, morpholine (4.0 ml) was added dropwise with stirring [Scheme 1].The mixture was stirred further for 1 h at 45˚C -50˚C, cooled overnight in ice and the solid product obtained was filtered, washed and recrystallised from ethanol.Pink coloured crystals were obtained and these were used for diffraction purposes.Melting point: 106˚C.

X-Ray Crystallography
Single-crystal X-ray diffraction data were collected on a three circle Bruker APEX-II diffractometer equipped with a CCD area detector using graphite monochromator and Mo-Kα radiation (λ = 0.70173 Å) in φ and ω scan modes.The crystal structure of this compound was refined by least-squares method on the basis of all observed reflections using SHELXL-97 [7] present in WinGx [8] (version 1.80).Empirical absorption correction was applied using SADABS [9].All hydrogen atoms are fixed in geometrical positions.Non-hydrogen atoms are refined with anisotropic displacement parameters.
The molecular connectivity was drawn using ORTEP [10] and the crystal packing diagram was drawn using Mercury (CCDC) program [11].Geometrical calculations were done using PARST [12] and PLATON [13].The geometrical optimization of the molecule was performed at the B3LYP/6-31G ** level of calculation using TUR-BOMOLE [14].The details of the crystal data, data collection and structure refinements are shown in Table 1.

Results and Discussion
This compound (Figure 1) crystallizes in the monoclinic centro-symmetric space group P2 1 /c with four asymmetric units in one unit cell.Selected bond distances are shown in Table 3.In Table 4 the experimental torsion angles have been reported.[23] and (B) [24] respectively.These values are 179.9˚and 170.2˚ respectively.The phase purity of the compound has been verified by powder X-ray diffraction.It is of interest to note that the experimental and simulated powder patterns (generated from crystallographic coordinates) have a one-to-one correspondence, thereby confirming the single phase behaviour of the compound (Figure 3).

Conclusion
The title compound is of biological importance and the synthesis of related thiophene compounds is of significance.This is reflected from the CSD wherein related compounds having different functionalities are scarce and hence new compounds can be synthesised, characterized and investigated for their crystal structures.It is of interest to investigate polymorphism in such solids and screen such compounds for their medicinal property.These are expected to have concomitant commercial ramifications in the pharmaceutical industry.

Figure 3 .
Figure 3. Experimental and theoretical powder pattern for the title compound.