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Solid state Acid–Base Reactions of Arylamino Nicotinic Acids: X-ray Crystal Structures of Salts

S. Sudalai Kumar, M. Kannan


2-(Phenylamino)nicotinic acid (PNA), 2-(methyl(phenyl)amino)nicotinic acid (MPNA), 2-(p-tolylamino)nicotinic acid (TNA) and 2-(methyl(p-tolyl)amino)nicotinic acid (MTNA) are the ampholites which were synthesized by the coupling of respective aryl amines and 2-chloronicotinic acid in the presence of p-tolylsulfonic acid and pyridine. All these molecules were crystallized in different solvents to obtain intra and intermolecular proton transferred adducts in the solid state. TNA is an only compound which has under gone intra (zwitterion) and intermolecular proton transfer (salts) in the solid state from acid to pyridine N. The intermolecular proton transfer was also observed from carboxyl acid in PNA to base 2-aminopyridine and the abstraction of proton from 3,5-dinitrobenzoic acid to pyridine in PNA. MPNA has resulted only salt compound in the acid–base reaction with intermolecular proton transfer from 3-nitrobenzoic acid to pyridine N in MPNA. The crystallization of MTNA in different organic solvents and with different acidic and basic coformers gave only the guest free crystal structure even though the structure of MPNA is close to MTNA. The resulted ionic compounds in solid state acid–base reaction and the guest free structures were confirmed by single crystal X-ray diffractometer. The pKa rule was checked and validated in some salt structures.

Keywords: crystal structures, nicotinic acids, pKa, salts

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(a) Kumar S.S. 2015, DOI: 10.13140/RG.2.1.3839.2165; (b) Kumar S.S. 2015, DOI: 10.13140/RG.2.1.2051.7282.

(a) Nath N.K., Kumar S.S., Nangia A. Cryst Growth Des. 2011; 11: 4594; (b) Kumar S.S., Thakuria R., Nangia A. CrystEngComm. 2014; 16: 4722p.

Kumar S.S., Nangia A. Cryst Growth Des. 2014; 14: 1865p.

Cambridge Structural Database, ver. 5.31, ConQuest 1.13, November 2015 release,

(a) Long S., Parkin S., Siegler M.A., et al. Cryst Growth Des. 2008; 8: 4006p; (b) Long S., Li T. Cryst Growth Des. 2009; 9: 4993p; (c) Long S., Li T. Cryst Growth Des. 2010; 10; 2465p; (d) Long S., Parkin S., Siegler M., et al. Cryst Growth Des. 2008; 8: 3137p; (e) Long S., Siegler M.A., Mattei A., et al. Cryst Growth Des. 2011; 11; 414p.

(a) Williams P.A., Hughes C.E., Lim G.K., et al. Cryst Growth Des. 2012; 12: 3104p; (b) Orola L., Veidis M., Sarcevica I., et al. Int J Pharm. 2012; 432: 50p; (c) Trask A., Shan N., Motherwell W.D.S., et al. Chem Commun. 2005; 880p; (d) Takasuka M., Nakai H., Shiro M. J Chem Soc, Perkin Trans. 1982; 2: 1061p; (e) Mahapatra S., Venugopala K.N., Row T.N.G. Cryst Growth Des. 2010; 10: 1866p; (f) Fabbiani F.P.A., Dittrich B., Florence A.J., et al. CrystEngComm. 2009; 11: 1396p; (g) Hardy G.E., Kaska W.C., Chandra B.P., et al. J Am Chem Soc. 1981; 103: 1074p; (h) Ojala W.H., Etter M.C. J Am Chem Soc. 1992; 114: 10288p; (i) Carter P.W., Ward M.D. J Am Chem Soc. 1994; 116: 769p; (j) Brown C.J., Ehrenberg M. Acta Crystallogr, Sect C. 1985; C41: 441; (k) Takazawa H., Ohba S., Saito Y. Acta Crystallogr, Sect C. 1986; C42: 1880p; (l) Lu T.H.,

Chattopadhyay P., Liao F.L., et al. Anal Sci. 2001; 17: 905p; (m) Bag P., Reddy C.M. Cryst Growth Des. 2012; 12: 2740p; (n) Voogd J., Verzijl B.H.M., Duisenberg A.J.M. Acta Crystallogr, Sect B. 1980; 36: 2805p (o) Sv rd M., Nordstr m F.L., Jasnobulka T., et al. Cryst Growth Des. 2010; 10: 195p; (p) López-Mejías V., Kampf J.W., Matzger A.J. J Am Chem Soc. 2009; 131: 4554p; (q) Lee E.H., Byrn S.R., Carvajal M.T. Pharm Res. 2006; 23: 2375p.

(a) Sarma B., Nath N.K., Bhogala B.R., et al. Cryst Growth Des. 2009; 9: 1546p; (b) Kumar S.S. 2015; DOI: 10.13140/RG.2.1.1600.9128/1.

Cruz-Cabeza A.J. CrystEngComm. 2012; 14: 6362p.

SAINT-Plus, version 6.45, Bruker AXS Inc., Madison, WI; 2003.

Sheldrick G.M. SADABS, Program for Empirical Absorption Correction of Area Detector Data. University of Göttingen, Germany; 1997.

(a) SMART (Version 5.625) and SHELX-TL (Version 6.12), Bruker AXS Inc., Madison, WI; 2000; (b) Sheldrick G.M. SHELXS-97 and SHELXL-97, University of Göttingen, Germany; 1997.

Dolomanov O.V., Blake A.J., Champness N.R., et al. J Appl Cryst. 2003; 36: 1283p.


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