04390nas a2200265   4500008004100000022001400041245017900055210006900234260007400303300001400377490000700391520332100398653003003719653004303749653001403792653002203806653002103828653002603849653002303875653002803898100002503926700002403951700002403975856012503999       2015                        eng d  a2053-229600aCrystal structures of the pyrazinamide-p-aminobenzoic acid (1/1) cocrystal and the transamidation reaction product 4-(pyrazine-2-carboxamido)-benzoic acid in the molten state0 aCrystal structures of the pyrazinamidepaminobenzoic acid 11 cocr  a2 ABBEY SQ, CHESTER, CH1 2HU, ENGLANDbINT UNION CRYSTALLOGRAPHYcNOV  a1010-U2760 v713 a<p>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 center dot center dot center dot O and NH center dot center dot center dot O hydrogen bonds [O center dot center dot center dot O = 2.6102 (15)angstrom and O-H center dot center dot center dot O = 168.3 (19)degrees; N center dot center dot center dot O = 2.9259 (18) angstrom and N-H center dot center dot center dot O = 167.7 (16)degrees] to generate a dimeric acidamide synthon. Neighbouring dimers are linked centrosymmetrically through N-H center dot center dot center dot O interactions [N center dot center dot center dot O = 3.1201 (18) angstrom and N-H center dot center dot center dot O = 136.9 (14)degrees] to form a tetrameric assembly supplemented by C-H center dot center dot center dot N interactions [C center dot center dot center dot N = 3.5277 (19) angstrom and C-H center dot center dot center dot N = 147 degrees]. Linking of these tetrameric assemblies through N-H center dot center dot center dot O [N center dot center dot center dot O = 3.3026 (19) angstrom and N-H center dot center dot center dot O = 143.1 (17)degrees], NH center dot center dot center dot N [N center dot center dot center dot N = 3.221 (2) angstrom and N-H center dot center dot center dot N = 177.9 (17)degrees] and C-H center dot center dot center dot O [C center dot center dot center dot O = 3.5354 (18) angstrom and C-H center dot center dot center dot O = 152 degrees] interactions creates the twodimensional 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 P1 with one molecule in the asymmetric unit. Molecules of (2) form a centrosymmetric dimeric homosynthon through an acid-acid O-H center dot center dot center dot O hydrogen bond [O center dot center dot center dot O = 2.666 (3) angstrom and O-H center dot center dot center dot O = 178 (4) degrees]. Neighbouring assemblies are connected centrosymmetrically via a C-H center dot center dot center dot N interaction [C center dot center dot center dot N = 3.365 (3) angstrom and C-H center dot center dot center dot N = 142 degrees] engaging the pyrazine groups to generate a linear chain. Adjacent chains are connected loosely via C-H center dot center dot center dot O interactions [C center dot center dot center dot O = 3.212 (3) angstrom and CH center dot center dot center dot O = 149 degrees] to generate a two-dimensional sheet structure. Closely associated two-dimensional sheets in both compounds are stacked via aromatic pi-stacking interactions engaging the pyrazine and benzene rings to create a threedimensional multi-stack structure.</p>10aacid-amide hetero-synthon10aactive pharmaceutical ingredient (API)10acocrystal10acrystal structure10ahydrogen bonding10amolten-state reaction10apowder diffraction10atransamidation reaction1 aThorat, Shridhar, H.1 aSahu, Sanjay, Kumar1 aGonnade, Rajesh, G.  uhttps://library.ncl.res.in/content/crystal-structures-pyrazinamide-p-aminobenzoic-acid-11-cocrystal-and-transamidation-1