Theoretical Study of Reactivity Based on the Hard-Soft/Acid-base (HSAB) in Isatoic Anhydride and Some Derivatives


  • Fernando R. Ramos-Morales Universidad Veracruzana
  • Sergio Durand-Niconoff Universidad Veracruzana
  • José Correa-Basurto Instituto Politécnico Nacional
  • Francisco J. Meléndez-Bustamante BUAP
  • J. Samuel Cruz-Sánchez Universidad Veracruzana



isatoic anhydride (ISA), molecular reactivity, Fukui functions, nucleophilic attack, electrophilic attack


In order to utilize the great chemical potential of isatoic anhidryde (ISA) as a precursor of several derived products, it was most important to determine its molecular reactivity. To this end, we have carried out theoretical calculations on ISA and some of its derivatives by using density functional theory (DFT), MP2, HF levels of theory with a correlated augmented basis set aug-cc-pvDZ. The B3LYP/aug-cc-pvDZ level yielded theoretical results that correlated very well with the experimental work. We used this method to get the global and local descriptors with Koopman’s approximation, taking into account two main ISA structural components: the aromatic and heterocyclic systems. The Fukui functions were calculated on the formalism of the quantum theory of atoms in molecules (QTAIM) which is a method for condensation. These theoretical calculations allow to study the electron-withdrawing or donating substituent of the aromatic ring. The results showed that, globally, the most reactive compound is ISA with the OCH3 substituent. Locally, it is confirmed that C2 is the molecular region most susceptible to suffer a nucleophilic attack against ISA.


Download data is not yet available.

Author Biographies

Fernando R. Ramos-Morales, Universidad Veracruzana

Unidad de Servicios de Apoyo en Resolución Analítica

Sergio Durand-Niconoff, Universidad Veracruzana

Instituto de Ciencias Básicas

José Correa-Basurto, Instituto Politécnico Nacional

Departamento de Farmacología y SEPI, Escuela Superior de Medicina

Francisco J. Meléndez-Bustamante, BUAP

Departamento de Fisicoquímica, Facultad de Ciencias Químicas

J. Samuel Cruz-Sánchez, Universidad Veracruzana

Instituto de Ciencias Básicas,


1. Erdmann, Ber. 1899, 32, 2159-2172.
2. Clark, R. H.; Wagner, E. C. J. Org. Chem. 1944, 9, 55-67.
3. Ger. pat. 500, 916, Frdl. 1930, 17, 500.
4. Sherwin Williams, Technical Bulletin No. 152. Available from Sherwin Williams Co.
5. Coppola, G. M. Synthesis 1980, 7, 505-536.
6. Shvekhgeimer, M. G. A. Chem. Heterocycl. Compd. 2001, 37, 385-443.
7. Weissleder. R.; Kelly, K.; Sun, E.; Shtatland, T.; Josephson, L. Nature Biotechnology 2005, 23, 1418-1423.
8. Kozminykh, E. N.; Goncharov, V. I.; Aitken, R. A.; Kozminykh, V. O.; Lomidze, K. Sh. Chem. Heterocycl. Comp. 2006, 42, 1107-1108.
9. Matos, M. A. R.; Miranda, M. S.; Morais, V. M. F.; Liebman, J. F. Org. Biomol. Chem. 2004, 2, 1647-1650.
10. Matos, M. A. R.; Miranda, M. S.; Morais, V. M. F.; Liebman, J. F. Org. Biomol. Chem. 2003, 1, 2566-2571.
11. Parr, R. G.; Yang, W. Density Functional Theory of Atoms and Molecules, Oxford University Press, New York, 1989.
12. Parr, R. G.; Yang, W. J. Am. Chem. Soc. 1984, 106, 4049-4050.
13. Yang, W.; Parr, R.G. Proc. Natl. Acad. Sci. USA, 1985, 82, 6723-6726.
14. Ghosh, S. K.; Berowitz, M. J. Chem. Phys. 1985, 83, 2976-2983.
15. Roy, R. K.; Krishnamurty, S.; Geerlings, P.; Pal, S. J. Phys. Chem. 1998, 102, 3746-3755.
16. Berkowitz, M.; Parr, R. G. J. Phys. Chem. 1988, 88, 2554-2557.
17. Pearson, R. G. J. Am. Chem. Soc. 1963, 83, 3533-3539.
18. Pearson, R. G. Chemical Hardness: Aplications from Molecules to Solid, Wiley-VCH Verlag GMBH, Weinheim, 1997.
19. Pearson, R. G. Science, 1966, 151, 172-177.
20. Sen, K. D.; Mingos, D. M. P. Chemical Hardness, Structure and Bonding, Ed., Springer-Verlag, Berlin, 1993.
21. Lee, C.; Yang, W.; Parr, R. G. J. Mol. Struct. (THEOCHEM), 1988, 163, 305-313.
22. Pearson, R. G. Coord. Chem. Rev. 1990, 100, 403-425.
23. Pearson, R. G.; Dowden, H. R., Hard and Soft Acids and Bases, Ed. Stroudsburg, PA, 1973.
24. Chattaraj, P. K. J. Phys. Chem. A. 2001, 105, 511-513.
25. Pearson, R. G. J. Chem. Educ. 1987, 64, 561-567.
26. Parr, R. G.; Chattaraj, P. K. J. Am. Chem. Soc. 1991, 113, 1854-1855.
27. Chattaraj, P. K.; Liu, G. H.; Parr, R. G. Chem. Phys. Lett. 1995, 237, 171-176.
28. Fukui, K. Science, 1982, 217, 747-784.
29. Fukui, K.; Yonezawa, T.; Shingu, H. J. Chem. Phys. 1952, 20, 722-725.
30. Fukui, K.; Yonezawa, T.; Nagata, C.; Shingu, H. J. Chem. Phys. 1954, 22,1433-1442.
31. Yang, W.; Mortier, W. J. J. Am. Chem. Soc. 1986, 108, 5708-5711.
32. Klopman, G. Chemical Reactivity and Reaction Paths, Wiley, New York, 1974.
33. Klopman, G. J. Am. Chem. Soc. 1968, 90, 223-234.
34. Hansch, C.; Leo, A.; Taft, R. W. Chem. Rev. 1991, 91, 165-195.
35. Hohenberg, P.; Kohn, W. Phys. Rev. 1964, 136 B, 864-871.
36. Parr, R. G.; Donelly, R. A.; Levy, M.; Place, W. E. J. Chem. Phys. 1978, 72, 3669- 3673.
37. Parr, R. G.; Pearson, R. G. J. Am. Chem. Soc. 1983, 105, 7512-7516.
38. Vela, A.; Gázquez, J. L. J. Am. Chem. Soc. 1990, 112, 1490-1492.
39. Kashino, S.; Nakashima, S.; Haisa, M. Acta, Cryst. 1978, B34, 2191-2195.
40. Roothan, C. C. J. Rev. Mod. Phys. 1951, 23, 69-89.
41. Head-Gordon, M.; Pople, J. A.; Frisch, M. J. J. Chem. Phys. Lett. 1988, 153, 503-506.
42. Becke, A. D. J. Chem. Phys. 1993, 98, 5648-5652.
43. Vosko, S. H.; Wilk, L.; Nusair, M. Can. J. Phys. 1980, 58, 1200- 1211.
44. Burke, K.; Perdew, J. P.; Wang, Y. Electronic Density Functional Theory: Recent Progress and New directions, ed. by J. F. Dobson, M. Gvignale, M. P. Das, Plenium, 1998.
45. Perdew, J. P.; Burke, K.; Ernzerhof, M. Phys. Rev. Lett. 1996, 77, 3865-3868.
46. Dunning, T. H. J. Chem. Phys. 1989, 90, 1007-1023.
47. Gaussian 03, Revision A.1, M. J. Frisch, G. W. Trucks, H. B. Schlegel, G. E. Scuseria, M. A. Robb, J. R. Cheeseman, J. A. Montgomery, Jr., T. Vreven, K. N. Kudin, J. C. Burant, J. M. Millam, S. S. Iyengar, J. Tomasi, V. Barone, B. Mennucci, M. Cossi, G. Scalmani, N. Rega, G. A. Petersson, H. Nakatsuji, M. Hada, M. Ehara, K. Toyota, R. Fukuda, J. Hasegawa, M. Ishida, T. Nakajima, Y. Honda, O. Kitao, H. Nakai, M. Klene, X. Li, J. E. Knox, H. P. Hratchian, J. B. Cross, C. Adamo, J. Jaramillo, R. Gomperts, R. E. Stratmann, O. Yazyev, A. J. Austin, R. Cammi, C. Pomelli, J. W. Ochterski, P. Y. Ayala, K. Morokuma, G. A. Voth, P. Salvador, J. J1. Erdmann, Ber. 1899, 32, 2159-2172.
48. Bader, R. F. W. Atoms in Molecules. A Quantum Theory, Claredon, Oxford (1990).
49. MORPHY 98, a program written by P. L. A. Popelier with a contribution from R. G. A. Bone, UMIST, Manchester, England (1998).
50. Melin, J.; Ayers, P.W.; Ortiz, J. V. J. Phys. Chem. A. 2007, 111, 10017, and included references there.
51. Roy, R. K. Bunshi Kozo Sogo Toronkai Koen Yoshishu, 1999, 34






Regular Articles