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Mimics of a R 2 2 (8) Hydrogen‐Bond Dimer Motif: Synthesis and Influence on the Crystallisation of Sulfathiazole and Sulfapyridine
Author(s) -
Lawrence Simon E.,
McAuliffe Marie T.,
Moynihan Humphrey A.
Publication year - 2010
Publication title -
european journal of organic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.825
H-Index - 155
eISSN - 1099-0690
pISSN - 1434-193X
DOI - 10.1002/ejoc.200901042
Subject(s) - chemistry , sulfathiazole , sulfapyridine , dimer , hydrogen bond , crystallization , monoclinic crystal system , crystallography , sulfamerazine , piperazine , stereochemistry , crystal structure , organic chemistry , molecule , sulfadiazine , biochemistry , antibiotics
The bis[4‐(hydroxyamino)phenylsulfonyl]piperazine 5 , diketopiperazine 10 and benzene 14 were synthesised as mimics of an R 2 2 (8) motif, which occurs in one crystal polymorph of sulfathiazole and in several polymorphs of sulfapyridine. When present in crystallisations of sulfathiazole and sulfapyridine, these mimics were found to have little or no effect under crystallisation conditions that favour the formation of polymorphs not containing R 2 2 (8) motifs. However, the mimics were found to completely or partially inhibit the formation of form I sulfathiazole, which contains the R 2 2 (8) dimer, in crystallisations of sulfathiazole from 1‐propanol. In crystallisations of sulfapyridine, the mimics were found to promote the formation of form III, which does not contain the R 2 2 (8) motif. These compounds therefore appear to act as “tailor‐made” additives, displaying polymorph‐selective crystal nucleation inhibition based on interaction with hydrogen‐bond network motifs.