American Chemical Society, Crystal Growth and Design, 1(11), p. 210-220, 2010
DOI: 10.1021/cg101162a
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A combined experimental and computational study was undertaken to establish the solid-state forms of P-resorcylic acid (2,4-dihydroxybenzoic acid). The experimental search resulted in nine crystalline forms: two concomitantly crystallizing polymorphs, five novel solvates (with acetic acid, dimethyl sulfoxide, 1,4-dioxane, and two with N,N-dimethyl formamide), in addition to the known hemihydrate and a new monohydrate. Form 11 degrees, the thermodynamically stable polymorph at room temperature, was found to be the dominant crystallization product. A new, enantiotropically related polymorph (form I) was obtained by desolvation of certain solvates, sublimation experiments, and via a thermally induced solid solid transformation of form 11 degrees above 150 degrees C. To establish their structural features, interconversions, and relative stability, all solid-state forms were characterized with thermal, spectroscopic, X-ray crystallographic methods, and moisture-sorption analysis. The hemihydrate is very stable, while the five solvates and the monohydrate are rather unstable phases that occur as crystallization intermediates. Complementary computational work confirmed that the two experimentally observed beta-resorcylic acid forms 1 and H are the most probable polymorphs and supported the experimental evidence for form I being disordered in the p-OH proton position. These consistent outcomes suggest that the most practically important features of beta-resarcylic acid crystallization under ambient conditions have been established; however, it appears impractical to guarantee that no additional metastable solid-state form could be found.