Cocrystal hydrogen bond patterns

We have been unsuccessful in preparing this 1 1 cocrystal of 2,5-diaminopyrimidine and 2-amino-5-nitropyrimidine from solution but we have prepared a 1 1 cocrystal of the two components by solid-state grinding and heating. Neither the crystal structure nor the hydrogen-bond pattern is known at this point, but the X-ray powder pattern of the cocrystal product is distinctly different from those of the starting materials. 

While the polymorphic forms of carbamazepine all exhibit an anticarboxamide hydrogen-bond dimer motif, the related compounds oxcarbazepine (10-oxo-10,l l-dihydro-5H-dibenzo[fr,/]azepine-5-carboxamide) and dihy-drocarbamazepine (10,ll-dihydro-5H-dibenzo[fc/]azepine-5-carboxamide) adopt hydrogen-bond chain motifs in their crystal structures [47]. The structures of several cocrystals of the structurally related compound cyten amide (5H-dibenzo[fl,d][7]annulene-5-carboxamide) have been reported, with the details of the hydrogen-bonding patterns being discussed [48-51]. 

An additional example for a cocrystal of N,N -bis(para-Br-phenyl)melamine 2-Vin and barbital 2-IX Zerkowski et al. (1997). There are clearly a number of potentially different hydrogen-bonding donor and acceptor sites on each molecule (in fact that was part of the rationale for studying these cocrystalline materials). The two polymorphic stmctures have identical tape hydrogen-bonding patterns, but the tertiary structure, as defined by the arrangement of the tapes within the crystal is quite different (Fig. 2.22). 

Examination of the crystal structures of solvates reveals hydrogen-bonding arrangements that can be applied to cocrystal formation. In many solvates, the solvent molecule is hydrogen-bonded to the API molecule, as shown for water or acetone in the CBZ structures in Figs. 6A and B. The solvent molecule is held by the exterior N-H... O hydrogen bond and occupies the space between two pairs of CBZ carboxamide homodimers. These solvates of CBZ confirm that the propensity of an API molecule to form solvates is related to molecular structures, hydrogen bond patterns. 

Hydrogen bonding is the most important directional Interaction responsible for supramolecular construction [17], Appendix 1 illustrates several typical hydrogen bond patterns which are present in two-component molecular crystals. Appendix 2 exemplifies a variety of reported cocrystals selected mainly fiom the recent papers [18], Not only strong hydrogen bonds (i.e, 0—H "0, 0—H- N,... 

Fig. 21. Hydrogen-bonded patterns formed in cocrystals of 36 with 37, 38 and 39...

Diphenylurea Crystallization. 1,3-hfsphenylurea (13) is the parent compound of a large family of derivatives, most of which do not cocrystallize with guest molecules (Etter et al. 1990). Even when put into solution with strong hydrogen bond acceptors, e.g., dimethyl sulfoxide (DMSO), triphenylphosphineoxide (TPPO) and tetrahydrofuran (THF), most diphenyl ureas crystallize with other molecules of the same kind in a connectivity pattern viewed as is shown below (14), instead of forming cocrystals (e.g., 15). 

An interesting example oftautomerism in sulfamethazine is a recently reported 2 1 cocrystal with theophylline [96]. In this three-component system, the sulfamethazine occurs in both tautomeric forms, stabilized by a rich pattern of hydrogen bonds with the theophylline molecules (Scheme 13.14). Amido tautomer forms R2 (7) hydrogen bond system, where the pyrimidine nitrogen... 

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