Substituent effects on the crystallization mechanisms of 7-chloro-4-substituted-quinolines

Abstract

The crystallization mechanisms of a series of fourteen 7-chloro-4-substituted-quinolines (substituents: (1) OCH₃, (2) OCH₂CH₃, (3) OCH₂CHCH₂, (4) O(CH₂)₂OH, (5) O(CH₂)₃OH, (6) NH(CH₂)₂CH₃, (7) NH(CH₂)₃CH₃, (8) NH(CH₂)₂OH, (9) NHCH(CH₂CH₃)CH₂OH, (10) NH(CH₂)₂Cl, (11) NHNCH(C₆H₅), (12) NHNCH(2-FC₆H₄), (13) NHNCH(3-FC₆H₄), and (14) NHNCH(4-FC₆H₄)) were proposed based on a retrocrystallization approach using the supramolecular cluster as demarcation. Crystallization mechanism stage parameters – N_CG% and NG/NC – were determined. The 4-substituents present in quinolines caused six different mechanisms, starting from the monomers in solution to dimers, 1D nuclei, and 2D nuclei (6, 11, 12); 2D nucleus formation (5); 1D nuclei to 2D nuclei (7, 9); concomitant dimers and 1D nuclei to a 3D crystal (8); 1D nuclei directly to a 3D crystal lattice (1–4, 10, 14), and dimers to 2D nuclei and then to a 3D crystal (13). Analysis of G_AI showed atom⋯atom intermolecular interactions in the proposed first nuclei for compounds 4 and 5. The nucleation process inferred in the solid state was partially confirmed during the formation of the proto-crystal in solution due to the changes of the hydrogen chemical shift in variable-concentration ¹H-NMR experiments. Results revealed that the size of the alkyl chain and the presence of different functional groups in the 4-substituents influenced the crystallization process.