Crystal Structure Theory and Applications, 2012, 1, 92-96 Published Online December 2012 (
Crystal and Molecular Structure of 2-Amino-3-Ethyl
Carboxamido-4-Metyl-5-Carboxy Ethyl Thiophene
Dhananjay Dey1, Venugopal Prakash2, Vasu3, Janardhanan Saravanan4, Deepak Chopra1*
1Department of Chemistry, Indian Institute of Science Education and Research, Bhopal, India
2Shirdi Sai Engineering College, Bangalore, India
3Vivekananda Degree College, Bangalore, India
4PES College of Pharmacy, Bangalore, India
Received October 18, 2012; revised November 15, 2012; accepted November 28, 2012
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 ge-
ometry 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) Å3, D = 1.352
g·cm–3, 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.
Keywords: Crystal; Molecular Conformation; Intermolecular Interactions; Spectroscopy; Diffraction
1. Introduction
Thiophene derivatives [1] are of importance in medicinal
chemistry and have recently been incorporated into new
pharmaceutical and chemical compounds tested as anti-
inflammatory agents [2]. This class of compounds ex-
hibit pharmacological activity [3-5]. These are also use-
ful in polymer chemistry because of their mechanical
strength, ease of fabrication, flexibility in design, stabil-
ity, resistance to corrosion and low cost [6]. In view of
the importance of this class of heterocycles from a bio-
logical and pharmaceutical perspective, we report in this
manuscript the synthesis of 2-Amino-3-ethyl carbox-
amido-4-methyl-5-carboxy ethyl thiophene. The com-
pound has been purified and characterized spectroscopi-
cally using FT-IR, 1H and 13C NMR techniques. The pu-
rity 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.
2. Experimental
2.1. Synth esis of 2- Am ino-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 pur-
poses. Melting point: 106˚C.
Scheme 1
*Corresponding author.
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D. DEY ET AL. 93
2.2. Spec tr oscopic Characterization (FTI R , 1H and
13C NMR) of the Synthesized Compound
FTIR (in cm–1: KBr): 3408, 3290, 1681, 1660. 1H NMR
(400 MHz, CDCl3): δ 6.43 (s, 2H), 4.24 (q, J = 7.13 Hz,
2H), 4.19 (q, J = 7.12 Hz, 2H), 2.63(s, 3H), 1.30 (t, J =
7.12 Hz, 3H), 1.26 (t, J = 7.12 Hz, 3H). 13C NMR (400
MHz, CDCl3): δ 166.13, 166.09, 162.88, 148.03, 108.53,
108.60, 60.41, 60.09, 16.12, 14.40, 14.34.
2.3. X-Ray Crystall ogra ph y
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 re-
fined by least-squares method on the basis of all ob-
served reflections using SHELXL-97 [7] present in
WinGx [8] (version 1.80). Empirical absorption correc-
tion 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 Mer-
cury (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 col-
lection and structure refinements are shown in Table 1.
3. Results and Discussion
This compound (Figure 1) crystallizes in the monoclinic
centro-symmetric space group P21/c with four asymmet-
ric units in one unit cell. The crystal structure of the com-
pound (C11H16N2O3S) contains one thiophene moiety.
One ethyl amide group is connected with C(3) atom and
one ethyl carboxyl group is attached with C(1) atom. The
core structure of the molecule is approximately planar.
The geometrical restrictions placed on the intermolecular
H-bonds are the sum of the van der Waals radii + 0.4 Å
and the directionality is greater than 110˚ [15]. Table 2
lists all the intra-molecular and intermolecular interac-
tions. The two intra-molecular C(11)-H(11A)...O(2) and
N(2)-H(2A)...O(1) hydrogen bonds stabilize the molecu-
lar conformation. Strong N(2)-H(2B)...O(2) hydrogen
bonds forms molecular chains along the crystallographic
b-axis utilising the screw axis as a symmetry element,
whereas weak C(10)-H(10A)...N(1) and C(6)-H(6B)...
O(3) intermolecular interactions pack the molecules along
the c-axis utilizing the glide plane. These interactions
have been recognized as key elements for supramo-
lecular association in the solid state [16-21]. The hydro-
gen bonding capacity of O(1) atom is more than the other
oxygen atom present in the title molecule. All intermo-
lecular interactions are shown in the packing diagram
(Figure 2).
Selected bond distances are shown in Table 3. In Ta-
ble 4 the experimental torsion angles have been reported.
Table 1. Crystallographic and refine ment data of T1.
Empirical formula C11 H16 N2 O3 S
Formula weight 256.32 g/mole
Crystal colour Pink
Temperature 298 K
Wavelength 0.71073 Å
Crystal system Monoclinic
Space group P21/c
Unit cell dimensions a = 8.1344(3) Å, b = 13.7392(4) Å,
c = 11.4704(4) Å, β = 100.769(2)˚
Volume 1259.36 (7) Å3
Z, Calculated density 4, 1.352 Mg·m–3
Absorption coefficient 0.256 mm–1
F(000) 544
Crystal size 0.2, 0.1, 0.1 mm
Theta range for data collection2.34˚ to 27.43˚
Limiting indices –10 h 10, –16 k 17, –14 k 14
collected/unique 10475/2853[R(int) = 0.0275]
Completeness to theta = 27.430.99%
Max. and min. transmission0.9749, 0.9506
Refinement method Full-matrix least-squares on F2
Goodness-of-fit on F2 1.076
Final R indices
[I > 2 sigma(I)] R1 = 0.0475, wR2 = 0.1449
R indices (all data) R1 = 0.0655, wR2 = 0.1554
Largest diff. peak and hole0.563 e·Å–3, and 0.637 e·Å–3
Figure 1. ORTEP of the synthesized molecule drawn with
50% ellipsoidal probability. The dotted lines indicates in-
tra-molecular N(2)-H(2A)...O(1) and C(11)-H(11A)...O(2)
hydrogen bonds. Bending arrows are showing the torsion
angles in the asymmetric unit.
Copyright © 2012 SciRes. CSTA
Table 2. Intra- and Intermolecular Interactions in the com-
D-H...A D-H
C(11)-H(11A)...O(2 ) 1.08 3.027(3)2.21 131 x, y, z
N(2)-H(2A)...O(1) 1.03 2.685(2)1.99 122 x, y, z
C(10)-H(10A)...N(1) 1.08 3.593(3)2.75 134 x + 1, –y +
1/2, z + 1/2
C(6)-H(6B)...O(3) 1.08 3.762(3)2.79 150 x – 1, –y +
1/2, z – 1/2
C(10)-H(10B)...O(1) 1.08 3.762(3)2.71 162 x + 1, y, z + 1
N(2)-H(2B)...O(2) 1.03 2.931(2)1.95 158 –x, y + 1/2,
–z + 1/2
Figure 2. Packing diagram and intermolecular H bonds.
Table 3. Selected bond distanc e s.
Bond Distance (Å)
C(3)-C(5) 1.46(3)
C(5) = O(1) 1.21(3)
C(5)-N(1) 1.34(3)
N(1)-C(6) 1.45(3)
C(1)-C(8) 1.45(3)
C(8) = O(2) 1.21(3)
C(8)-O(3) 1.34(3)
O(3)-C(9) 1.44(2)
Table 4. Selected torsion angles in degree (˚).
Torsion Angles (˚)
C(5)-N(1)-C(6)-C(7) 178.4(2), 159.6(1)a
C(6)-N(1)-C(5)-C(3) 179.0(2), 176.1(1)
C(4)-C(3)-C(5)-N(1) 179.8(2), 171.6(1)
C(2)-C(1)-C(8)-O(3), 177.3(2), 179.4(1)
C(9)-O(3)-C(8)-C(1) 180.0(2), 179.8(1)
C(8)-O(3)-C(9)-C(10) 176.3(2), 179.4(1)
(a: Italicised values obtained from theoretical B3LYP/6-31G**calculation).
It is of interest to note that the torsion C(2)-C(1)-C(8)-
O(3) and C(4)-C(3)-C(5)-N(1) are 177.2(2)˚ and 179.8(2)˚
indicating planarity with the thiophene ring assisted by
delocalisation between the carboxy and carboxamide
groups at C(1) and C(3) respectively. The theoretical
B3LYP/6-31G** calculations, after geometrical optimiza-
tion of the molecule, reveal torsion angles and these have
been compared with the experimental values. In most of
the cases the experimental torsion angles are compare-
able with the theoretical values. But for C(5)-N(1)-
C(6)-C(7), the difference in torsion angle is approxi-
mately 18˚ - 19˚, signifying the importance of crystal
forces in the packing of molecules. In Table 5 the search
information, retrieved from the Cambridge Structural
Database [22] on the presence of specific functional
groups on the thiophene moiety has been presented.
Search numbers 1 and 2 for the presence of carboxy ester
and carboxamide moiety only on the thiophene ring re-
vealed 1 hit only [Structures (A) and (B), Table 5].
Search numbers 3 and 4 revealed no hits. It is of interest
to compare the torsion angles C(2)-C(1)-C(8)-O(3) and
C(4)-C(3)-C(5)-N(1) in the present compounds with
those in (A) [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 cor-
respondence, thereby confirming the single phase be-
haviour of the compound (Figure 3 ).
4. Conclusion
The title compound is of biological importance and the
synthesis of related thiophene compounds is of signifi-
cance. This is reflected from the CSD wherein related
compounds having different functionalities are scarce
and hence new compounds can be synthesised, charac-
terized 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 ra-
mifications in the pharmaceutical industry.
Figure 3. Experimental and theoretical powder pattern for
the title compound.
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Table 5. CSD [17] search information.
Search number Moiety No. of hitsStructure Details
1 Space group = P21/n
Cell: a = 6.398 Å, b = 23.237 Å, c =
10.314 Å, β = 90.37˚ [23].
1 Space group = Pna21
Cell: a = 9.723(1) Å, b = 9.251(1) Å, c =
10.618(1) Å [24].
0 - -
0 - -
5. Acknowledgements
DC thanks IISER Bhopal for research facilities and DST-
Fast track scheme for research funding.
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