One-pot covalent and supramolecular synthesis of pharmaceutical co-crystals using the API isoniazid: A potential supramolecular reagent

Andreas Lemmerer, Joel Bernstein, Volker Kahlenberg

Research output: Contribution to journalArticlepeer-review

79 Scopus citations

Abstract

The synthon approach has been applied to synthesizing pharmaceutical co-crystals using the anti-tuberculosis drug isonicotinic acid hydrazide (ISONIAZID). Isoniazid has the potential to be a supramolecular reagent and so far has been put to very limited use in making co-crystals. In this report, we co-crystallize isoniazid with the dicarboxylic acids malonic (1), succinic (2), glutaric (3), adipic (4) and pimelic acid (5), and the monocarboxylic acids 4-hydroxybenzoic acid (6) and 2,4-dihydroxybenzoic acid (7). By surveying the literature through the Cambridge Structural Database, we identified the possible homosynthons and heterosynthons that are likely to form in the co-crystallization of isonizaid with carboxylic acids. The dominant interaction is the COOH⋯N hydrogen bond, which is used in all seven co-crystals. In addition, we present an example in which both a covalent and supramolecular synthesis occurs without affecting the vital supramolecular co-crystal forming synthon, the carboxylic acid⋯pyridine pair functionality, by reacting isoniazid with 2-butanone and acetone while co-crystallizing it with 3-hydroxybenzoic acid (8 and 9) in a one-pot synthesis.

Original languageEnglish
Pages (from-to)2856-2864
Number of pages9
JournalCrystEngComm
Volume12
Issue number10
DOIs
StatePublished - 1 Oct 2010

ASJC Scopus subject areas

  • General Chemistry
  • General Materials Science
  • Condensed Matter Physics

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