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Structure analysis of a phenylpyrazole carboxylic acid derivative crystallizing with three molecules in the asymmetric unit (Z′ = 3) using X-ray powder diffraction

  • S. Ghosh (a1), S. Pramanik (a2) (a3) and A. K. Mukherjee (a2)


Crystal structure analysis of a pyrazole carboxylic acid derivative, 5-(trifluoromethyl)-1-phenyl-1H-pyrazole-4-carboxylic acid (1) has been carried out from laboratory powder X-ray diffraction data. The crystal packing in the pyrazole carboxylic acid derivative exhibits an interplay of strong O–H…O, C–H…N and C–H…F hydrogen bonds to generate a three-dimensional molecular packing via the formation of R22(8) and R22(9) rings. Molecular electrostatic potential calculations indicated that carbonyl oxygen, pyrazole nitrogen and fluorine atoms to be the strongest acceptors. The relative contribution of different interactions to the Hirshfeld surface of pyrazole carboxylic acid and a few related structures retrieved from CSD indicates that H…H, N…H and O…H interactions can account for almost 70% of the Hirsfeld surface area in these compounds.


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Aakeröy, C. B., Wijethunga, T. K., and Desper, J. (2015). “Molecular electrostatic potential dependent selectivity of hydrogen bonding,” New J. Chem. 39, 822828.
Allen, F. H., and Taylor, R. (2004). “Research applications of the Cambridge Structural Database (CSD),” Chem Soc Rev. 33, 463475.
Altomare, A., Giacovazzo, C., Guagliardi, A., Moliterni, A. G. G., Rizzi, R., and Werner, P.-E. (2000). “New techniques for indexing: n-TREOR in EXPO,” J. Appl. Crystallogr. 33, 11801186.
Altomare, A., Cuocci, C., Giacovazzo, C., Moliterni, A., Rizzi, R., Corriero, N., and Falcicchio, A. (2013). “EXPO2013: a kit of tools for phasing crystal structures from powder data,” J. Appl. Crystallogr. 46, 12311235.
Anderson, K. M., and Steed, J. W. (2007). “Comment on “On the presence of multiple molecules in the crystal asymmetric unit (Z′ > 1) by Gautam R. Desiraju,” CrystEngComm. 9, 328330.
Anderson, K. M., Afarinkia, K., Yu, H.-W., Goeta, A. E., and Steed, J. W. (2006). “When Z′ = 2 is better than Z = 1 supramolecular centrosymmetric hydrogen-bonded dimers in chiral systems,” Cryst. Growth Des. 6, 21092113.
Anderson, K. M., Probert, M. R., Goeta, A. E., and Steed, J. W. (2011). “Size does matter—the contribution of molecular volume, shape and flexibility to the formation of co-crystals and structures with Z′ > 1,” CrystEngComm. 13, 8387.
Antila, J. C., Baskin, J. M., Barder, T. E., and Buchwald, S. L. (2004). “Copper−Diamine-Catalyzed N-arylation of pyrroles, pyrazoles, indazoles, imidazoles, and triazoles,” J. Org. Chem. 69, 55785587.
Arlin, J. B., Bhardwaj, R. M., Johnston, A., Miller, G. J., Bardin, J., MacDougall, F., Fernandes, P., Shankland, K., David, W. I. F., and Florence, A. J. (2014). “Structure and stability of two polymorphs of creatine and its monohydrate,” CrystEngComm. 16, 81978204.
Bader, R. F. W., Carroll, M. T., Cheeseman, J. R., and Chang, C. (1987). “Properties of atoms in molecules: atomic volumes,” J. Am. Chem. Soc. 109, 79687979.
Becke, A. D. (1988). “Density-functional exchange-energy approximation with correct asymptotic behaviour,” Phys. Rev. A. 38, 30983100.
Berger, R., Resnati, G., Metrangolo, P., Weber, E., and Hulliger, J. (2011). “Organic fluorine compounds: a great opportunity for enhanced materials properties,” Chem. Soc. Rev. 40, 34963508.
Bernstein, J. (2011). “Polymorphism−A perspective,” Cryst. Growth Des. 11, 632650.
Bernstein, J., Dunitz, J. D., and Gavezzotti, A. (2008). “Polymorphic perversity: crystal structures with many symmetry-independent molecules in the unit cell,” Cryst. Growth Des. 8, 20112018.
Brock, C. P. (2016). “High-Z′ structures of organic molecules: their diversity and organizing principles,” Acta Cryst. B72, 807821.
Caruso, F., Raimondi, M. V., Daidone, G., Pettinari, C., and Rossi, M. (2009). “5-Amino-1-phenyl-3-trifluoromethyl-1H-pyrazole-4-carboxylic acid,” Acta Crystallogr. Sect E. 65, o2173o2173.
Chatterjee, P., Dey, T., Pal, S., and Mukherjee, A. K. (2017). “Two mefenamic acid derivatives: structural study using powder X-ray diffraction, Hirshfeld surface and molecular electrostatic potential calculations,” Z. Kristallogr. 232, 385394.
Das, D., Banerjee, R., Mondal, R., Howard, J. A. K., Boese, R., and Desiraju, G. R. (2006). “Synthon evolution and unit cell evolution during crystallisation. A study of symmetry-independent molecules (Z′>1) in crystals of some hydroxy compounds,” Chem. Commun., 555557.
Das, U., Chattopadhyay, B., Hazra, D. K., Sureshbabu, V. V., and Mukherjee, A. K. (2016). “Two carbamate derivatives with Z′ = 2 and 3: an interplay of strong and weak hydrogen bonds,” J. Mol. Str. 1122, 290298.
David, W. I. F., and Shankland, K. (2008). “Structure determination from powder diffraction data,” Acta Crystallogr. A. 64, 5264.
Delley, B. (1990). “An all-electron numerical method for solving the local density functional for polyatomic molecules,” J. Chem. Phys. 92, 508517.
Desiraju, G. R. (2007). “On the presence of multiple molecules in the crystal asymmetric unit (Z′>1),” CrystEngComm. 9, 9192.
Favre-Nicolin, V., and Cerný, R. (2004). “A better FOX: using flexible modelling and maximum likelihood to improve direct-space ab initio structure determination from powder diffraction,” Z. Krist. - Cryst. Mat. 219, 847856.
Hao, X., Siegler, M. A., Parkin, S., and Brock, C. P. (2005a). “[M(H2O)2(15-crown-5)](NO3)2: A system rich in polymorphic and modulated phases,” Cryst.Growth Des. 5, 22252232.
Hao, X., Chen, J., Cammers, A., Parkin, S., and Brock, C. P. (2005b). “A helical structure with Z′ = 10,” Acta Cryst. B61, 218226.
Harris, K. D. M., and Cheung, E. Y. (2004). “How to determine structures when single crystals cannot be grown: opportunities for structure determination of molecular materials using powder diffraction data,” Chem. Soc. Rev. 33, 526.
Harris, K. D. M., Tremayne, M., and Kariuki, B. M. (2001). “Contemporary advances in the Use of powder X-Ray diffraction for structure determination,” Angew. Chem. Int. Ed. 40, 16261651.
Jelsch, C., Ejsmont, K., and Huder, L. (2014). “The enrichment ratio of atomic contacts in crystals, an indicator derived from the Hirshfeld surface analysis,” IUCr J. 1, 119128.
Johnstone, R. D. L., Ieva, M., Lennie, A. R., McNab, H., Pidcock, E., Warren, J. E., and Parsons, S. (2010). “Pressure as a tool in crystal engineering: inducing a phase transition in a high-Z′ structure,” CrystEngComm. 12, 25202523.
Larson, A. C., and Von Dreele, R. B. (2000). “General Structure Analysis System (GSAS), Los Alamos Laboratory Report, LAUR,” 86–784.
Lee, C., Yang, W., and Parr, R. G. (1988). “Development of the colle-salvetti correlation-energy formula into a functional of the electron density,” Phys. Rev. B. 37, 785789.
Lehmler, H.-J., Parlin, S., and Brock, C. P. (2004). “Packing conflicts in the Z′ = 5 structure of CF3(CF2)3(CH2)10COOH,” Acta Cryst. B60, 325332.
Lodochnikova, O. A., Startseav, V. A., Nikitana, L. E., Bodrov, A. V., Klimovitskii, A. E., Klimovitskii, E. N., and Litvinov, I. A. (2014). “When two symmetrically independent molecules must be different: “crystallization-induced diastereomerization” of chiral pinanyl sulfone,” CrystEngComm. 16, 43144321.
Martin, T., Fleissner, J., Milius, W., and Breu, J. (2016). “Behind crime scenes: the crystal structure of commercial luminol,” Cryst. Growth Des. 16, 30143018.
McKinnon, J. J., Jayatilaka, D., and Spackman, M. A. (2007). “Towards quantitative analysis of intermolecular interactions with Hirshfeld surfaces,” Chem. Commun., 38143816.
Nichol, G. S., and Clegg, W. (2006). “The importance of weak C − H···O bonds and π···π stacking interactions in the formation of organic 1,8-Bis(dimethylamino)naphthalene complexes with Z‘>1,” Cryst. Growth Des. 6, 451460.
Owczarzak, A. M., Samshuddin, S., Narayana, B., Yathirajan, H. S., and Kubicki, M. (2013). “Pseudosymmetry, polymorphism and weak interactions: 4,4′′-difluoro-5′-hydroxy-1,1′:3′,1′′-terphenyl-4′-carboxylic acid and its derivatives,” CrystEngComm. 15, 98939898.
Pagola, S., Stephens, P. W., Bohle, D. S., Kosar, A. D., and Madsen, S. K. (2000). “The structure of malaria pigment β-haematin,” Nature. 404, 307310.
Perdew, J. P., Burke, K., and Ernzerhof, M. (1996). “Generalized gradient approximation made simple,” Phys. Rev. Lett. 77, 38653868.
Platteau, C., Lefebvre, J., Hemon, S., Baehtz, C., Danede, F., and Prevost, D. (2005). “Structure determination of forms I and II of phenobarbital from X-ray powder diffraction,” Acta Cryst B. 61, 8088.
Politzer, P., and Murray, J. S. (2015). “Quantitative analyses of molecular surface electrostatic potentials in relation to hydrogen bonding and Co-crystallization,” Cryst. Growth Des. 15, 37673774.
Pramanik, S., Dey, T., and Mukherjee, A. K. (2019). “Five benzoic acid derivatives: crystallographic study using X-ray powder diffraction, electronic structure and molecular electrostatic potential calculation,” J. Mol. Str. 1175, 185207.
Rehman, M. Z., Elsegood, M. R. J., Akbar, N., and Saleem, R. S. Z. (2008). “5-Amino-1-phenyl-1H-pyrazole-4-carboxylic acid,” Acta Crystallogr. Sec E. 64, 1312.
Rietveld, H. (1967). “Line profiles of neutron powder-diffraction peaks for structure refinement,” Acta Crystallogr. 22, 151152.
Rohl, A. L., Moret, M., Kaminsky, W., Claborn, K., McKinnon, J. J., and Kahr, B. (2008). “Hirshfeld surfaces identify inadequacies in computations of intermolecular interactions in crystals: pentamorphic 1,8-dihydroxyanthraquinone,” Cryst. Growth Des. 8, 45174525.
Spackman, M. A., and McKinnon, J. J. (2002). “Fingerprinting intermolecular interactions in molecular crystals,” CrystEngComm. 4, 378392.
Steed, K. M., and Steed, J. W. (2015). “Packing problems: high Z' crystal structures and their relationship to co-crystals, inclusion compounds, and polymorphism,” Chem. Rev. 115, 28952933.
Stewart, J. J. P. (2007). “Optimization of parameters for semiempirical methods V: modification of NDDO approximations and application to 70 elements,” J. Mol. Model. 13, 11731213.
Thompson, P., Cox, D. E., and Hastings, J. B. (1987). “Rietveld refinement of Debye-Scherrer synchrotron X-ray data from Al2O3,” J. Appl. Crystallogr. 20, 7983.
Watts, A. E., Maruyoshi, K., Hughes, C. E., Brown, S. P., and Harris, K. D. M. (2016). “Combining the advantages of powder X-ray diffraction and NMR crystallography in structure determination of the pharmaceutical material cimetidine hydrochloride,” Cryst.Growth Des. 16, 17981804.
Wen, H.-L., Kang, J.-J., Dai, B., Deng, R.-H., and Hu. Chin, H.-W. (2015) “Syntheses, crystal structures and antibacterial activities of 5-chloro-3-m ethyl-1-phenyl-1H-pyrazole-4-carboxylic acid and its copper(II) compound,” J. Struct. Chem. 34, 33.
Werner, P. E., Eriksson, L., and Westdahl, M. (1985). “TREOR, a semi-ex-haustive trial-and-error powder indexing program for all symmetries,” J. Appl. Cryst. 18, 367370.
Wolff, S. K., Grimwood, D. J., McKinnon, J. J., Turner, M. J., Jayatilaka, D., and Spackman, M. A. (2012). Crystal Explorer 3.1 (University of Western Australia, Perth, Australia).


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