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- Title
Crystal structures of the pyrazinamide- p-aminobenzoic acid (1/1) cocrystal and the transamidation reaction product 4-(pyrazine-2-carboxamido)benzoic acid in the molten state.
- Authors
Thorat, Shridhar H.; Sahu, Sanjay Kumar; Gonnade, Rajesh G.
- Abstract
The synthesis of pharmaceutical cocrystals is a strategy to enhance the performance of active pharmaceutical ingredients (APIs) without affecting their therapeutic efficiency. The 1:1 pharmaceutical cocrystal of the antituberculosis drug pyrazinamide (PZA) and the cocrystal former p-aminobenzoic acid ( p-ABA), C7H7NO2·C5H5N3O, (1), was synthesized successfully and characterized by relevant solid-state characterization methods. The cocrystal crystallizes in the monoclinic space group P21/ n containing one molecule of each component. Both molecules associate via intermolecular O-H...O and N-H...O hydrogen bonds [O...O = 2.6102 (15) Å and O-H...O = 168.3 (19)°; N...O = 2.9259 (18) Å and N-H...O = 167.7 (16)°] to generate a dimeric acid-amide synthon. Neighbouring dimers are linked centrosymmetrically through N-H...O interactions [N...O = 3.1201 (18) Å and N-H...O = 136.9 (14)°] to form a tetrameric assembly supplemented by C-H...N interactions [C...N = 3.5277 (19) Å and C-H...N = 147°]. Linking of these tetrameric assemblies through N-H...O [N...O = 3.3026 (19) Å and N-H...O = 143.1 (17)°], N-H...N [N...N = 3.221 (2) Å and N-H...N = 177.9 (17)°] and C-H...O [C...O = 3.5354 (18) Å and C-H...O = 152°] interactions creates the two-dimensional packing. Recrystallization of the cocrystals from the molten state revealed the formation of 4-(pyrazine-2-carboxamido)benzoic acid, C12H9N3O3, (2), through a transamidation reaction between PZA and p-ABA. Carboxamide (2) crystallizes in the triclinic space group P with one molecule in the asymmetric unit. Molecules of (2) form a centrosymmetric dimeric homosynthon through an acid-acid O-H...O hydrogen bond [O...O = 2.666 (3) Å and O-H...O = 178 (4)°]. Neighbouring assemblies are connected centrosymmetrically via a C-H...N interaction [C...N = 3.365 (3) Å and C-H...N = 142°] engaging the pyrazine groups to generate a linear chain. Adjacent chains are connected loosely via C-H...O interactions [C...O = 3.212 (3) Å and C-H...O = 149°] to generate a two-dimensional sheet structure. Closely associated two-dimensional sheets in both compounds are stacked via aromatic π-stacking interactions engaging the pyrazine and benzene rings to create a three-dimensional multi-stack structure.
- Subjects
CRYSTAL structure; PYRAZINAMIDE; TREATMENT effectiveness
- Publication
Acta Crystallographica Section C: Structural Chemistry, 2015, Vol 71, Issue 11, p1010
- ISSN
2053-2296
- Publication type
Article
- DOI
10.1107/S2053229615019828