Activated Carbon-Promoted Oxidative Aromatization of Hantzsch 1,4-Dihydropyridines and 1,3,5-Trisubstituted Pyrazolines Using Molecular Oxygen

Abstract

In the presence of activated carbon, Hantzsch 1,4-dihydropyridines and 1,3,5-trisubstituted pyrazolines were aromatized with molecular oxygen to the corresponding pyridines and pyrazoles in excellent yields.

Key words

activated carbon - aromatization - oxidations - pyridines - pyrazolines - heterocycles

References

• 1a Gilchrist TL. Heterocyclic Chemistry   3rd ed.:  Addison-Wesley Longman, Ltd.; England: 1998. 
• 1b Lednicer D. Strategies for Organic Drugs, Synthesis and Design   Wiley; New York: 1998.  Chap. 8 and 9.
• 2 Böcker RH. Guengerich FP. J. Med. Chem.  1986,  29:  1596 
• 3 Meyers AI. Natale NR. Heterocycles  1982,  18:  13 
• 4 Loev B. Snader KM. J. Org. Chem.  1964,  30:  1914 
• 5 Pfister JR. Synthesis  1990,  689 
• 6 Maquestiau A. Eynde J.-JV. Tetrahedron Lett.  1991,  32:  3839 
• 7 Mashraqui SH. Karnik MA. Synthesis  1998,  713 
• 8 Varma RS. Kumar D. Tetrahedron Lett.  1999,  40:  21 
• 9a Sabitha G. Reddy GSKK. Reddy ChS. Fatima N. Yadav JS. Synthesis  2003,  1267 
• 9b See also, Pd/C or KMnO₄: Kamal A. Ahmad M. Mohd N. Hamid AM. Bull. Chem. Soc. Jpn.  1964,  37:  610 
• 9c RuCl₃/O₂: Mashraqui SH. Karnik MA. Tetrahedron Lett.  1998,  39:  4895 
• 9d hν/high pressure: Liu Z.-L. Jin M.-Z. Chem. Commun.  1998,  2451 
• 9e CrO₂: Ko K.-Y. Kim J.-Y. Tetrahedron Lett.  1999,  40:  3207 
• 9f NO: Cheng J.-P. Zhu X.-O. J. Org. Chem.  2000,  65:  8158 
• 9g Co-naphthenate/O₂: Chavan SP. Kharul RK. Kalkote UR. Shivakumar I. Synth. Commun.  2003,  33:  1333 
• 10a Kameyama T. Niwa H. Chem. Abstr.  1968,  69:  106704 
• 10b Batulin YuM. Chem. Abstr.  1969,  70:  2236 
• 10c Polevoi LG. Chem. Abstr.  1966,  65:  19147 
• 11 Gladstone WAF. Norman ROC. J. Chem. Soc., Chem. Commun.  1966,  1536 
• 12 Bhatnager I. George MV. Tetrahedron  1968,  24:  1293 
• 13 Auwers K. Heimke P. Liebigs Ann.  1927,  458:  186 
• 14a Strauss F. Muffat C. Heitz W. Ber. Dtsch. Chem. Ges.  1918,  51:  1457 
• 14b Smith LI. Howard KL. J. Am. Chem. Soc.  1943,  65:  159 
• 15 Dodwadmath RP. Wheeler TS. Proc. Ind. Acad. Sci.  1935,  2A:  438 
• 16 Singh SP. Kumar D. Prakash O. Kapoor RP. Synth. Commun.  1997,  27:  2683 
• 17 Nakamichi N. Kawashita Y. Hayashi M. Org. Lett.  2002,  4:  3955 
• 19a Recently, we reported that substituted 9,10-dihydroanthracenes were aromatized to anthracenes in xylene under oxygen in the presence of activated carbon: Nakamichi N. Kawabata H. Hayashi M. J. Org. Chem.  2003,  68:  8272 
• 19b We also reported that 2-arylbenzo-xazoles were directly synthesized from substituted 2-amino-phenols and aldehydes by using activated carbon in xylene under oxygen: Kawashita Y. Nakamichi N. Kawabata H. Hayashi M. Org. Lett.  2003,  5:  3713 

18

For example, the aromatization of pyrazoline 12 in MeCN and EtOH produced the corresponding pyrazole 18 only in low yield (1-33% yield). In the case of dihydropyridine, the use of MeCN and EtOH as a solvent was also ineffective.

20

We used a mixture of o-, m-, and p-xylene.

21

This conversion also proceeds efficiently in xylene instead of HOAc (for example, 81% yield for 7 h at 120 °C, for substrate 12).