摘要:
IntroductionPolymorphism – crystallization of a compound into different crystalline forms from different solvents – in fact, is the phenomenon that laid the foundation for the development of solidstate organic chemistry with the identification of different photochemical reactivities in different polymorphs oftranscinnamic acid crystals.1–3The pharmaceutical industry is one of the few areas to recognize the importance of the phenomenon as several drug molecules often crystallize in different polymorphs, with varying properties towards drug activity.4–6In this connection, the wellknown and unprecedented Ranitidine patent case is a representative example.7However, the phenomenon was often considered to be a nuisance in general chemistry as no definite means of either prediction or deliberate synthesis of the polymorhic forms were established, as exemplified by Dunitz and Bernstein recently in their article ‘Disappearing polymorphs’.8Also, it is believed that the success of obtaining a new polymorph of a specific compound is proportional to the number of manhours spent crystallizing the compounds (a test of patience!).9As a result, synthesis of new polymorphic forms becomes practically unattainable in a target synthesis both in terms of economics as well as timescales involved.However, in a recent statistical analysis10on known polymorphic structures, polymorphs of some compounds with multifunctional groups capable of interacting with each other have been found to be easily distinguishable from each other by the nature of intermolecular bonds, such as hydrogen bonds, formed by the constituent functional groups. For instance, 2,6dihydroxybenzoic acid forms two polymorphs with different types of hydrogen bonds formed by OH and COOH groups as shown inScheme 1. This suggests that deliberate synthesis of polymorphic structures is possible if the molecules possess a functional group capable of forming different types of intermolecular bonds. Indeed, it appears to be feasible, as noted from the analysis of the two polymorphic forms – triclinic and tetragonal – of thiodiglycolamide, obtained serendipitously in the process of cocrystallisation of the amide with 4,4′bipyridyl, and these results are discussed in this article.Schematic representation of different kinds of hydrogen bond patterns in different polymorphs of a hydroxybenzoic acid.
ISSN:1466-8033
DOI:10.1039/b100890k
出版商:RSC
年代:2001
数据来源: RSC