Abstract
The cocrystallization landscape of benzamide and urea interacting with aliphatic and aromatic carboxylic acids was studied both experimentally and theoretically. Ten new cocrystals of benzamide were synthesized using an oriented samples approach via a fast dropped evaporation technique. Information about types of known bi-component cocrystals augmented with knowledge of simple binary eutectic mixtures was used for the analysis of virtual screening efficiency among 514 potential pairs involving aromatic carboxylic acids interacting with urea or benzamide. Quantification of intermolecular interaction was achieved by estimating the excess thermodynamic functions of binary liquid mixtures under supercooled conditions within a COSMO-RS framework. The smoothed histograms suggest that slightly more potential pairs of benzamide are characterized in the attractive region compared to urea. Finally, it is emphasized that prediction of cocrystals of urea is fairly direct, while it remains ambiguous for benzamide paired with carboxylic acids. The two known simple eutectics of urea are found within the first two quartiles defined by excess thermodynamic functions, and all known cocrystals are outside of this range belonging to the third or fourth quartile. On the contrary, such a simple separation of positive and negative cases of benzamide miscibility in the solid state is not observed. The difference in properties between urea and benzamide R2,2(8) heterosynthons is also documented by alterations of substituent effects. Intermolecular interactions of urea with para substituted benzoic acid analogues are stronger compared to those of benzamide. Also, the amount of charge transfer from amide to aromatic carboxylic acid and vice versa is more pronounced for urea. However, in both cases, the greater the electron withdrawing character of the substituent, the higher the binding energy, and the stronger the supermolecule polarization via the charge transfer mechanism.Electronic supplementary materialThe online version of this article (doi:10.1007/s00894-016-2964-6) contains supplementary material, which is available to authorized users.
Highlights
Cocrystals represent an interesting and practically important subgroup of multicomponent solids. They are homogenous crystalline systems containing stoichiometric amounts of one or more neutral molecular species, which are in the solid state under ambient temperature and pressure conditions [1]
It is worth mentioning that cocrystallization has been used widely in many fields, including the agrochemistry, electronics, textile and pharmaceutical industries
The cocrystallization of benzamide and urea with carboxylic acids can be represented by the model system of the RCOOH⋯H2NCOR’ R22(8) heterosynthon
Summary
Cocrystals represent an interesting and practically important subgroup of multicomponent solids By definition, they are homogenous crystalline systems containing stoichiometric amounts of one or more neutral molecular species, which are in the solid state under ambient temperature and pressure conditions [1]. They are homogenous crystalline systems containing stoichiometric amounts of one or more neutral molecular species, which are in the solid state under ambient temperature and pressure conditions [1] Species such as clathrates, solvates and salts are not usually classified as cocrystals. It is worth mentioning that cocrystallization has been used widely in many fields, including the agrochemistry, electronics, textile and pharmaceutical industries. The latter probably accounts for their the most valuable applications [2]. Supramolecular synthesis has been applied mainly to overcome the poor
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
