Simple, Efficient, High Yield Syntheses of Substituted and Unsubstituted 5-Benzoylbarbituric Acids, and Their Corresponding Schiff Base Phenylhydrazones

Journal of Heterocyclic Chemistry

Volumn 41, Issue 2, 2004, Pages 233-246

  Jursic, Branko S ^a   Neumann, Donna M ^a   Bowdy, Katharine L ^a   Stevens, Edwin D ^a  

^a UNIVERSITY OF NEW ORLEANS   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

5 BENZOYLBARBITURIC ACID; AMINE; BARBITURIC ACID DERIVATIVE; CHLOROFORM; NITROPHENYLHYDRAZONE DERIVATIVE; PHENYLHYDRAZONE DERIVATIVE; SCHIFF BASE; UNCLASSIFIED DRUG;

ARTICLE; CRYSTALLIZATION; DRUG STRUCTURE; EQUILIBRIUM CONSTANT; NUCLEAR MAGNETIC RESONANCE SPECTROSCOPY; PH; PHASE TRANSITION; SOLUBILITY; STRUCTURE ANALYSIS; SYNTHESIS; TEMPERATURE DEPENDENCE;

EID: 2342504045     PISSN: 0022152X     EISSN: None     Source Type: Journal    
DOI: 10.1002/jhet.5570410214     Document Type: Article

References (30)

1. For instance see: [a] B. G. Katzung, "Basic & Clinical Pharmacology" eighth edition, McGrawHill, New York, 2001;
2. [b] J. Y. De Belin, M.-R. Romero-Martin, P. W. Fin, L. G. Sayers, N. M. Law, D. Billington, S. Ryley and S. Bhattacharya, "Barbituric Acid Analogs as Therapeutic Agents" International Patent WO 01/93841A2; Chem. Abstr., 31669, 136 (2001) and references therein.
3. [2a] I. Watanabe, T. Andoh, R. Furuya, T. Sasaki, Y. Kamiya and H. Itoh, Anesthesia & Analgesia (Baltimore) 88, 1406 (1999);
4. [b] J. M. J. Gonzales, Neurochem., 64, 2559 (1995);
5. [c] K. Hirota, M. Kudo, T. Kudo, M. Kitayama, T. Kushikata, D. G. Lambert and A. Matsuki, Neuroscience Lett., 291, 175 (2000);
6. [d] P. R. Andrews, G. P. Jones and D. B. Poulton, Eur. J. Pharmacol., 79, 61 (1982);
7. [e] G. B. Young, W. T. Blume, C. F. Bolton and K. G. Warren, Can. J. Neurological Sciences, 7, 291 (1980).
8. [3a] T. R. Bailey and D. C. Young, "Methods for treating or preventing viral infections and associated diseases using barbituric acid and thiobarbituric acid derivatives" International Patent WO 13708(2000); Chem. Abstr., 203127, 132 (200);
9. [b] R. I. Ashkinazi, "Salts of 5,5′-arylidenebis[barbituric acids] and 5,5′-arylidenebis[2-thiobarbituric acids] having antibacterial, antichlamydial, antiviral and immuno-modulating activity" International Patent WO 25699 (1999); Chem. Abstr., 5267, 131 (1999);
10. [c] L. R. Morgan, B. S. Jursic, C. L. Hooper, D. M. Neumann, K. Thangaraj and B. LeBlanc, Bioorg. Med. Chem. Lett., 12, 3407 (2002).
11. [4a] D. L. Lee and C. G. Carter, "Herbicidal Method and Composition Utilizing Certain 5-(2-Substituted Benzoyl)-Barbituric Acids" United States Patent 4,797,147 (1989); Chem. Abstr., 148889, 111 (1989);
12. [b] I. T. Kay, F. C. Peacock and W. S. Waring, "5-Acyl Barbituric Acid Derivatives" United State Patent 3,828,043 (1974); Chem. Abstr., 72545, 76 (1972);
13. [c] Y. Hirono, H. Ishikawa, I. Iwataki, M. Sawaki and O. Nomura, "Herbicidal Barbituric Acid Derivatives" German Patent DE 252478 (1975); Chem. Abstr., 121891, 84 (1975).
14. For instance see: [a] B. S. Jursic and D. M. Neumann, Tetrahedron Lett., 42, 4103 (2001);
15. [b] B. S. Jursic and D. M. Neumann, Tetrahedron Lett., 42, 8435 (2001);
16. [c] D. M. Neumann, B. S. Jursic and K. L. Martin, Tetrahedron Lett., 43, 1603 (2002);
17. [d] B. S. Jursic, F. Douelle, K. Bowdy and E. D. Stevens, Tetrahedron Lett., 43, 2002 (2002);
18. [e] B. S. Jursic and E. D. Stevens, Tetrahedron Lett., 43, 5681 (2002);
19. [f] B. S. Jursic, J. Heterocyclic Chem. in press;
20. [g] Jursic, B. S.; Stevens, E. D. in press.
21. For preparation of barbituric acid derivatives by simple condensation of malonic esters with substituted urea see: (a) Vogel "Text-Book of Preparative Organic Chemistry", Third Edition, John Wiley, New York, 1966
22. (a) Buzz, Recreational Drugs, Loompanics Unlimited, 1989.
23. For methods of transformation of methyl aryl ethers into phenole derivatives (deprotetion of phenol OH group) see: T. W. Greene and P. G. M. Wuts, Protective Groups in Organic Synthesis 3rd Ed., John Wiley & Sons, Inc., New York, 1999.
24. Reaction was carried under conditions described in General Procedure E.
25. L. R. Morgan, B. S. Jursic, C. L. Hooper, D. M. Neumann, K. Thangaraj and B. LeBlanc, Bioorg. Med. Chem. Lett., 12, 3407 (2002).
26. In X-ray study of these compounds it was determined that in about 5% there was a presence of a cocrystal between a new derivative of 2g as well as 2g by itself. The derivative was formed by elimination of methyl from the methoxy group and by substitution of a hydrazone hydrogen with 1-propyloxy group. It is our speculation that this product was formed by crystallization of 2g from propanol with traces of sulfuric acid. In this unique reaction alcohol is added to the NN double bond of the hydrazone moiety and in this way a very exciting new compound with NOR moiety was formed. This reaction mechanism and outcome requires further studies and results will be published elsewhere.
27. Patent application in preparation.
28. All calculations were carried out with MOPAC version 6.0. Quantum Chemistry Program Exchange (QCPE), Program Number 455.
29. M. J. S. Dewar, E. G. Zoebisch, E. F. Healy and J. J. P. Stevart, J. Am. Chem. Soc., 107, 3902 (1985);
30. M. J. S. Dewar and E. G. Zoebisch, J. Mol. Struct. (Theochem), 180, 1 (1988).