Synthesis of Novel Functionalised Symmetric Bi-2(1H)-pyrazinones

Abstract

A simple and convenient synthesis for functionalised bi-2(1H)-pyrazinones 9, 11a-h starting from 3,5-dichloro-2(1H)-pyrazinones 7, 10a-h is described. The pyrazinone is homo-coupled by means of a Suzuki-type reaction of an in situ generated boronate. The reactions were carried out under conventional heating as well as under microwave irradiation and dramatic improvements in the rates and yields have been observed under the latter conditions.

Key words

bis-heterocycle - pyrazinone - Suzuki chemistry - bis(pinacolato)diboron

References

• 2a Sleiman H. Baxter P. Lehn JM. Rissanen K. J. Chem. Soc., Chem. Commun.  1995,  715 
• 2b Ziessel R. Youinou MT. Angew. Chem., Int. Ed. Engl.  1993,  32:  877 
• 2c Harding MM. Koert U. Lehn JM. Marquisrigault A. Piguet C. Siegel J. Helv. Chim. Acta  1991,  74:  594 
• 2d Hasenknopf B. Lehn JM. Kneisel BO. Baum G. Fenske D. Angew. Chem., Int. Ed. Engl.  1996,  35:  1838 
• 2e Baxter PNW. Lehn JM. Fischer J. Youinou MT. Angew. Chem., Int. Ed. Engl.  1994,  33:  2284 
• 2f Baxter PNW. Hanan GS. Lehn JM. Chem. Commun.  1996,  2019 
• 3a Lehn JM. Regnouf De Vains JB. Helv. Chim. Acta  1992,  75:  1221 
• 3b Papet AL. Marsura A. Synthesis  1993,  478 
• 3c Papet AL. Marsura A. Ghermani NE. Lecomte C. Friant P. Rivail JL. New J. Chem.  1993,  17:  181 
• 3d Bodar-Houillon F. Humbert T. Marsura A. Devains JBR. Dusausoy O. Bouhmaida N. Ghermani NE. Dusausoy Y. Inorg. Chem.  1995,  34:  5205 
• 4 Bodar-Houillon F. Marsura A. New J. Chem.  1996,  20:  1041 
• 5 The product most closely resembling these structures is [2,2′-biquinoxaline]-3,3′(4H,4′H)-dione reported in: Hünig S. Pütter H. Chem. Ber.  1977,  110:  2532 
• 6 Vekemans J. Pollers-Wieërs C. Hoornaert G. J. Heterocycl. Chem.  1983,  20:  919 
• 7a Azzam R. De Borggraeve W. Compernolle F. Hoornaert GJ. Tetrahedron Lett.  2004,  45:  1885 
• 7b Kaval N. Bisztray K. Dehaen W. Kappe CO. Van der Eycken E. Mol. Diversity  2003,  7:  125 
• 9 Comparable methodology for the synthesis of symmetrical biaryls was reported in: Nising CF. Schmid UK. Nieger M. Bräse S. J. Org. Chem.  2004,  69:  6830 
• 10a Van der Eycken E. Appukkuttan P. De Borggraeve W. Dehaen W. Dallinger D. Kappe CO. J. Org. Chem.  2002,  67:  7904 
• 10b Kaval N. Van der Eycken J. Caroen J. Dehaen W. Strohmeier GA. Kappe CO. Van der Eycken E. J. Comb. Chem.  2003,  5:  560 

1

Currently on a leave of absence from Helwan University, Cairo, Egypt.

8

We tried to suppress the homodimerisation by slowly adding a solution of pyrazinone 10b (1 mmol in 10 mL of dioxane) via an infusion pump (over a time period of 3 h) to a stirred suspension of [B(Pin)]₂ (1 mmol), K₂CO₃ (1 mmol) and tetrakis (3 mol%) in 10 mL of dioxane at 80 °C. However, even using slow addition, the formation of the bipyrazinones could not be prevented.

11

EM-Discover, CEM Corporation P.O. Box 200 Matthews, NC 28106.

12

Also in the microwave experiments, formation of minor amounts of protodeboronation product (<10%) could not be avoided.