Synthesis and Characterization of Some New Symmetrical Bis-Isatins Derived From p-Substituted Aromatic Amines

Authors: Faiq H. S.Hussain¹ & Hussein K A. Khudhur^2
1Research Center, Ishik University, Erbil, Iraq
²Lab Department, Rzgariy Teaching Hospital, Ministry of Health, Erbil, Iraq

Abstract:  A series of p-substituted isonitrosoacetanilide 2(a-g) were prepared via the condensation of p-substitutedaromatic amines (benzene-1,4-diamine,o-tolidine,4,4’-diaminodiphenylmethane, p bromoaniline p-nitroaniline, p-aminobenzoic acid and p-toluidine) with chloral hydrate and hydroxylamine hydrochloride in aqueous solution of sodium sulfate and absolute ethanol as a co-solvent under reflux conditions. The compounds 2(a-g) were cyclized in the presence of a strong acid to obtain 5-sudstituted isatin 3(a-f), which were condensed with aromatic diamines to some new bis-azomethine of isatin 4(a-h) in the presences of catalytic amounts of glacial acetic acid in EtOH. On the other hand some new bis Azomethine of isatin 5(a-d) were synthesized, from the reaction of di-isatins with aromatic monoamines (pyridin-2-amine and 5-chloropyridin-2-amine) in the presences of catalytic amounts of glacial acetic acid in DMSO. The new synthesized compounds were identified using spectroscopic techniques (IR, ¹H-NMR, ¹³C-NMR, DEPT-135, Elemental analysis and Mass Spectroscopy). Finally the prepared compounds have been screened for antimicrobial activity in vitro against two types of bacteria Staphylococcus-aureus (Gr+ve) and Escherichia-coli (Gr-ve) the results showed that most of the prepared compounds are sensitive against both types of tested bacteria.

Keywords: Bis-Isonitrosoacetanilide , 5-Substituted Isatin , Bis-Isatins, Bis-Azomethine

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doi: 10.23918/eajse.v4i1sip56

References

Alam, M., Zafar, M., & Naeem, M., (1989). An improved synthesis of isatin, Pak. J. Sci. Ind. Res, 32, 246.

Bal, T., Anand, B., Yogeeswari, P., & Sriram, D., (2005). Synthesis and evaluation of anti-HIV activity of isatin beta-thiosemicarbazone derivatives. Bioorg. Med. Chem. Lett., 15, 4451-4455.

Ballantine, J. A., Fenwick, R. G., & Alam, M. (1968). Fragmentations in the mass spectra of 2‐oxo‐3‐indolyl derivatives. Organic Mass Spectrometry, 1(3), 467-481.

Ballantine, J. A., Fenwick, R. G., & Popp, F. D. (1971). Rearrangement and cyclization reactions in the mass spectra of a series of isatin carbonyl derivatives of medicinal interest: 2‐Oxo‐3‐indolinylidene anils (n‐arylketimines), 2‐oxo‐3‐indolinylidene phenylhydrazones, 2‐oxo‐3, 3‐bis‐(o‐diaminoaryl) indolyl deriv‐atives and their 2, 3‐quinoxaline heterocyclic analogues. Organic Mass Spectrometry, 5(8), 1003-1014.

Bergman, J., Lindström, J., & Tilstam, U. (1985). The structure and properties of some indolic constituents in couroupita guianensis aubl. Tetrahedron, 41, 2879-2881.

Brana, M., & Gradillas, A. (2004). Synthesis, Biological Activity, and Quantitative Structure−Activity Relationship Study of Azanaphthalimide and Arylnaphthalimide Derivatives, J. Med. Chem., 47, 2236-2242.

Calvery, H. O., Noller, C. R., & Adams, R. (1925). Arsonophenyl-cinchoninic acid (arsonocinchophen) and derivatives. II. Journal of the American Chemical Society,47(12), 3058-3060.

Da Silva, J. F., Garden, S. J., & Pinto, A. C. (2001). The chemistry of isatins: a review from 1975 to 1999. Journal of the Brazilian Chemical Society, 12(3), 273-324.

Gassman, P., Cue, B., & Luh, T. (1977). Indole Ring Synthesis: From Natural Products to Drug Discovery. J. Org. Chem.42, 1344-1348.

Gottlieb, H., Kotlyar, V., & Nudelman, A. (1997). NMR Chemical Shifts of Common Laboratory Solvents as Trace Impurities, J.Org.Chem. 62, 7512-7515.

Guo, Y., & Chen, F. (1986).  TLC-UV-spectrophotometric and TLC-scanning determination of isatin in leaf of Isatis. Zhongcaoyao, 17, 8-11.

Ischia, M., Palumbo, A., & Prota, G. (1988). Adrenalin oxidation revisited. New products beyond the adrenochrome stage. Tetrahedron, 44, 6441-6446.

Kearney, T., Harris, P. A., Jackson, A., & Joule, J. A. (1992). Synthesis of isatin 3-oximes from 2-nitroacetanilides.Synthesis, 1992(08), 769-772.

Rodríguez-Argüelles, M. C., Cao, R., García-Deibe, A. M., Pelizzi, C., Sanmartín-Matalobos, J., & Zani, F. (2009). Antibacterial and antifungal activity of metal (II) complexes of acylhydrazones of 3-isatin and 3-(N-methyl) isatin. Polyhedron, 28(11), 2187-2195.

Sridhar, S., & Ramesh, A. (2001). Synthesis and pharmacological activities of hydrazones, Schiff and Mannich bases of isatin derivatives. Biol.Bull., 24(10), 1149-1152.

Srivastava, S. K., Srivastava, S., & Srivastava, S.D. (1999). Synthesis of new carbazolyl-thiadiazol-2-oxoazitines: Antimicrobial, anticonvulsant andante-flammatory agents. Indian J. Chem., 38(B), 183-187.

Thetaz, C., & Wentrup, C. (1976). 1H-Benzazirines. Intermediates in the ring contraction of iminocyclohexadienylidenes and arylnitrenes. Journal of the American Chemical Society, 98(5), 1258-1259.

Singh, W., & Dash, B. (1988). Synthesis of some new Schiff bases containing thiazole and oxazole nuclei and their fungicidal activity. Pesticides, 22,33.37.

Wei, L., Wang, Q., & Liu, X. (1982). Application of thin-layer chromatography in quality control of Chinese medicinal preparations. II. Qualitative analysis of some Chinese medicinal preparations of Chansu. Yaowu Fenxi Zazhi, 2(5), 288-291.

Yoshikawa, M., Murakami, T., Kishi, A., & Kubo, M. (1998). Novel Indole S, O-Bisdemoside, Calanthoside, the Precursop Glycoside of Tryptanthrine, Indirubin, and Isatin. Chem. Pharm. Bull., 46, 886-888.