Crystal and Molecular Structures of Two 2-Aminothiophene Derivatives

Abstract

Abstract:The crystal and molecular structures of two 2-aminothiophene derivatives, potential allosteric enhancers at the human A 1 adenosine receptor, are reported. (2-Amino-4,5,6,7-tetrahydro-1-benzothiophen-3-yl)(phenyl)methanone (1) crystallizes in the orthorhombic space group Pna2 1 (a = 9.2080(4) Å, b = 14.0485(7) Å, c = 10.3826(6) Å), and (2-amino-5-ethylthiophen-3-yl)(2-chlorophenyl)methanone (2) crystalizes in the monoclinic P2 1 /c space group with unit cell parameters a = 10.6092(8) Å, b = 10.8355(8) Å, c = 11.1346(9) Å, β = 98.643(6)Å. In both molecules the intramolecular N-H···O=C hydrogen bonds close six-membered planar rings and significantly influence the molecular conformation. Intermolecular N-H···O bonds connect the molecules in infinite chains along a in case of 1, and along b in 2; in each case the appropriate unit cell axis is approximately 10 Å long.

Four closely related N-(3-benzoyl-4,5,6,7-tetrahydrobenzo[b]thiophen-2-yl)benzamides: order versus disorder, and similar molecular conformations but different modes of supramolecular aggregation, with a new disordered refinement of 2-amino-3-benzoyl-4,5,6,7-tetrahydrobenzo[b]thiophene

“…The structure of parent amine (VI) (see Scheme 2), namely 2-amino-3-benzoyl-4,5,6,7-tetrahydrobenzo[b]thiophene, has been reported recently (Kubicki et al, 2012) and the anisotropic displacement parameters suggest that there is disorder in the fused six-membered ring which was not accounted for in the original refinement. Accordingly, we undertook a new refinement of this structure, using the original data set, and found that there is indeed disorder in this ring, exactly comparable to the disorder found in compounds (I)-(III), with the two conformations having occupancies of 0.887 (9) and 0.113 (9) ( Fig.…”

“…It is somewhat disappointing to note that structures with unmodelled disorder, such as compound (VI) (Kubicki et al, 2012), are still being published and thus incorporated into the Cambridge Structural Database (Groom et al, 2016). In this connection, we have recently noted (Rajam et al, 2017) an example of unmodelled conformational disorder involving a simple thiophene group (Rajam et al, 2015).…”

“…In (II)-(IV), the corresponding values were À10.734 for 430 reflections in the range 0.000 < F c /F c (max) < 0.003, À3.962 for 481 reflections in the range 0.000 < F c /F c (max) < 0.005 and À6.754 for 992 reflections in the range 0.000 < F c /F c (max) < 0.004, respectively. The disorder in compound (VI), which was refined using the original data set (Kubicki et al, 2012), was handled exactly as in compounds (I)-(III), giving refined occupancies for the two disorder components of 0.887 (9) and 0.113 (9). The correct orientation of the structure of compound (VI) with respect to the polar-axis direction was established using the Flack x parameter (Flack, 1983), calculated (Parsons et al, 2013) …”

“…The molecular structure of compound (VI), showing the atom-labelling scheme and the disorder in the fused six-membered ring; the structure was refined using the original data set (Kubicki et al, 2012). The major conformer is drawn with full lines, the minor conformer with broken lines and displacement ellipsoids at the 30% probability level.…”

“…With this in mind, we synthesized and characterized a series of four variously sub- N-(3-benzoyl-4,5,6,7-tetrahydrobenzo[b]thiophen-2-yl)-benzamides (Scheme 1), whose structures we report here, namely N- (3-benzoyl-4,5,6,7-tetrahydrobenzo[b]thiophen-2-yl)-3-fluorobenzamide, (I), N-(3-benzoyl-4,5,6,7-tetrahydrobenzo-[b]thiophen-2-yl)-4-chlorobenzamide, (II), N-(3-benzoyl-4,5,6,7-tetrahydrobenzo[b]thiophen-2-yl)-2,6-difluorobenzamide, (III),5,6,thiophen-2-yl)-2-methoxybenzamide, (IV), and we compare the structures of (I)-(IV) with those of the recently reported analogue N- (3-benzoyl-4,5,6,7-tetrahydrobenzo[b]thiophen-2-yl)benzamide, (V) (Scheme 2) , and the parent amine 2-amino-3-benzoyl-4, 5,6,7-tetrahydrobenzo[b]thiophene, (VI) (Kubicki et al, 2012).…”