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Experimental and Theoretical Study of Selectivity in Mechanochemical Cocrystallization of Nicotinamide with Anthranilic and Salicylic Acid

Cite this: Cryst. Growth Des. 2018, 18, 3, 1539–1547
Publication Date (Web):February 27, 2018
Copyright © 2018 American Chemical Society

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    Selectivity in mechanochemical cocrystal formation between nicotinamide and anthranilic acid or salicylic acid was studied using tandem in situ reaction monitoring by powder X-ray diffraction (PXRD) and Raman spectroscopy. Selectivity was probed by offering a competing cocrystal coformer to a previously prepared cocrystal or under competitive reaction conditions where all cocrystal coformers, in different stoichiometric ratios, were introduced together in the starting reaction mixture. Reaction paths were dependent on the starting mixture composition, and we find that the formation of intermediates and the final product can be predicted from solid-state ab initio calculations of relative energies of possible reaction mixtures. In some cases, quantitative assessment revealed different reaction profiles derived from PXRD and Raman monitoring, directly indicating, for the first time, different mechanochemical reactivity on the molecular and the bulk crystalline level of the reaction mixture.

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    The Supporting Information is available free of charge on the ACS Publications website at DOI: 10.1021/acs.cgd.7b01512.

    • PXRD and Raman spectra; Rietveld fit data; crystallographic ad refinement data (PDF)

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    CCDC 15817821581783 contain the supplementary crystallographic data for this paper. These data can be obtained free of charge via, or by emailing [email protected], or by contacting The Cambridge Crystallographic Data Centre, 12 Union Road, Cambridge CB2 1EZ, UK; fax: +44 1223 336033.

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