Patterns of hydrogen bonding in mono- and di-substituted N-arylpyrazinecarboxamides

Abstract

The molecular and supramolecular structures of 18 N-arylpyrazinecarboxamides, Ar NHCO(C(4)H(3)N(2)), have been determined, including the stoichiometric monohydrate of N-(3-methoxyphenyl)pyrazinecarboxamide, and two polymorphs of N-(4-fluorophenyl)pyrazinecarboxamide having Z' values of 1 and 4, respectively. The aryl groups were selected to include the geometric isomers for a compact range of substituents, namely methyl, trifluoromethyl, fluoro, chloro, methoxy and nitro groups, which exhibit markedly varied electronic properties and markedly varied behaviour as hydrogen-bond donors and acceptors. However, not all isomers in each group could be structurally investigated. A small number of derivatives containing disubstituted aryl groups have also been included in this study. The crystal structures of the solvent-free carboxamides reported here exhibit a wide range of direction-specific intermolecular forces, including N-H...N, N-H...O, C-H...N and C-H...O hydrogen bonds, and pi...pi stacking interactions, while the structure of N-(3-methoxyphenyl)pyrazinecarboxamide monohydrate also contains O-H...N and O-H...O hydrogen bonds. The resulting supramolecular structures can be zero-, one- or two-dimensional, although no three-dimensional supramolecular aggregation has been observed. In the finite, zero-dimensional structures, pairs of molecules are linked by hydrogen bonds to form cyclic centrosymmetric dimers. The one-dimensional structures include chains formed by the pi-stacking of otherwise isolated molecules, simple chains generated by either C-H...O or C-H...N hydrogen bonds, and hydrogen-bonded chains of rings. The two-dimensional structures include examples of both pi-stacked hydrogen-bonded chains and hydrogen-bonded sheets.

Structures of arylaldehyde 7-chloroquinoline-4-hydrazones:supramolecular arrangements derived from N—H···N, C—H···X (X = N, O, or π) and π···π interactions

“…Such interests are exemplified by our reports on N-isonicotinoyl arylaldehyde hydrazones, 1 [1], N-arylpyrazinecarboxamides, 2 [2], (pyrazin-2-ylcarbonyl) hydrazones of substituted benzaldehydes, 3 [3--5], and 4-alkylamino-7-chloro-quinoline derivatives, 4 [6], see The quinoline nucleus is found in many synthetic and natural products having a wide range of pharmacological activities, such as anti-malarial [7], anti-viral [8], anti-cancer [9], anti-bacterial [10], anti-fungal [11], anti-obesity [12] and anti-inflammatory [13] activities. Of interest, the majority of drugs used against malaria, such as chloroquine [7], mefloquine [14], primaquine [15] and amodiaquine [15], possess a quinoline ring: such drugs have been the mainstay of malaria chemotherapy for much of the past 40 years.…”

(Pyrazinecarbonyl)hydrazone halobenzaldehydes: supramolecular arrays generated by face to face stacking of ribbons, formed from C–H–O interactions

“…This was well illustrated in the recent reports on the supramolecular structures of various N-isonicotinoyl arylaldehyde hydrazones [6], and N-arylpyrazi-necarboxamides [1]. We are also interested in the interplay between intra-and intermolecular forces and the interplay of hard and soft hydrogen bonds [8].…”

“…Following on from the study of N-arylpyrazinecarboxamides [1], and of pyrazine-2-carbohydrazide [13] we now wish to report on the crystal structures of acylhydrazones, derived from pyrazinoylhydrazine and monohalobenzaldehydes (7: N 2 C 4 H 3 CONHN¼CHC 6 …”

“…For example, syntheses of the series of N-arylpyrazinecarboxamides [1] was made with the knowledge that the parent compound pyrazinamide has well-known anti-mycobacterial activity and it is the one of the most important drugs used in tuberculosis treatment [9][10][11][12].…”

“…We have been very much interested in crystal structures of series of nitrogen containing compounds, including aromatic amido compounds (1-3) [1][2][3] and hydrazones derived from reactions of hydrazines with arenealdehydes, (4) [4], and arylketones (5) [5], acylhydrazones derived from are-nealdehydes and acylhydrazines (6) [6,7], see Fig. 1.…”