Extension of the Biginelli-Type Reaction: One-Pot Synthesis of Pyrimido-pyrimidines and Spirobi[pyrimidine]s Using Potassium Hydrogen Sulfate as a Catalyst

Abstract

The Biginelli-type compounds 4,5,8a-triarylhexahydropyrimido[4,5-d]pyrimidine-2,7(1H,3H)-diones and 6,6′-diaryl-4,4′-spirobi[hexahydropyrimidine]-2,2′-diones were synthesized by a one-pot three-component reaction with potassium hydrogen sulfate as the catalyst. This method has the advantages of higher yields, lower reaction times, broader substrate scope, and the use of simple substrate materials.

Key words

pyrimido[4,5-d]pyrimidine - spirobi[hexahydropyrimidine] - potassium hydrogen sulfate - multicomponent reactions - Michael additions

References

• 1 Biginelli P. Gazz. Chim. Ital.  1893,  23:  360 
• 2a Atwal KS. Swanson BN. Unger SE. Floyd DM. Moreland S. Hedberg A. O’Reilly BC. J. Med. Chem.  1991,  34:  806 
• 2b Rovnyak GC. Atwal KS. Hedberg A. Kimball SD. Moreland S. Gougoutas JZ. O’Reilly BC. Schwart J. Malley MF. J. Med. Chem.  1992,  35:  3254 
• 2c Grover GJ. Dzwonczyk S. Mcmullen DM. Normadinam CS. Slenph PG. Moreland SJ. J. Cardiovasc. Pharmacol.  1995,  26:  289 
• 3a Huang YJ. Yang FY. Zhu CJ. J. Am. Chem. Soc.  2005,  127:  16386 
• 3b Tu SJ. Fang F. Miao CB. Jiang H. Feng YJ. Shi DQ. Wang XS. Tetrahedron Lett.  2003,  44:  6153 
• 3c Tu SJ. Fang F. Zhu SL. Li TJ. Zhang XJ. Zhuang QY. Synlett  2004,  537 
• 3d Kappe CO. Falsone SF. Synlett  1998,  718 
• 3e Lu J. Bai Y. Wang Z. Yang B. Ma H. Tetrahedron Lett.  2000,  41:  9075 
• 3f Hu EH. Sidler DR. Dolling UH. J. Org. Chem.  1998,  63:  3454 
• 3g Ramalinga K. Vijayalaxmi P. Kaimal TNB. Synlett  2001,  863 
• 3h Kumar KA. Kasthuraiah M. Reddy CS. Reddy CD. Tetrahedron Lett.  2001,  42:  7873 
• 4 Zhu YL. Huang SL. Pan YJ. Eur. J. Org. Chem.  2005,  2354 
• 5a Sedova VF. Shkurko OP. Chem. Heterocycl. Compd. (Engl. Transl.)  2004,  40:  194 
• 5b Sedova VF. Baranova LV. Mamaev VP. Izv. Sib. Otd. Akad. Nauk SSSR, Ser. Khim, Nauk  1972,  6:  96 
• 5c Sedova VF. Mamaev VP. Khim. Geterotsikl. Soed.  1970,  5:  691 
• 6a Lunt E. Comprehensive Organic Chemistry   Vol. 4:  Barton D. Ollis WD. Pergamon; Oxford: 1974.  p.493 
• 6b Brown JD. Comprehensive Heterocyclic Chemistry   Vol. 3:  Katritzky AR. Rees CW. Pergamon; Oxford: 1984.  p.57 
• 6c Clercq ED. Beraaerts R. J. Biol. Chem.  1987,  262:  14905 
• 7 Coates WJ. inventors; EP  351,058.  ; Chem. Abstr. 1990, 113, 40711
• 8 Kitamura N, and Onishi A. inventors; EP  163,599.  ; Chem. Abstr. 1984, 104, 186439
• 9 inventors; Raddatz P., Bergmann R., Ger. Pat.  3601731.  ; Chem. Abstr. 1988, 109, 54786
• 10 Delia TJ. Baumann M. Bunker A. Heterocycles  1993,  35:  1397 
• 11a Hirota K. Kitade Y. Senda S. Halat MJ. Watanabe KA. Fox JJ. J. Org. Chem.  1981,  46:  846 
• 11b Su TL. Huang JT. Burchanal JH. Watanabe KA. Fox JJ. J. Med. Chem.  1986,  29:  709 
• 11c Prajapati D. Sandhu JS. Synthesis  1988,  342 
• 12 The single-crystal growth was carried out in EtOH-DMF at r.t. X-ray crystallographic analysis was performed with a Siemens SMART CCD and a Semens P4 diffractometer. Crystal data for 4p: C₂₈H₃₀Br₂N₅O_3.50, colorless, crystal dimension 0.33 × 0.21 × 0.14 mm, monoclinic, space group P2₁/n, a = 26.579 (3) Å, b = 6.8903 (13) Å, c = 31.343 (3) Å, α = γ = 90°, β = 92.660 (3)°, V = 5733.8 (13) ų, Mr = 652.39, Z = 8, Dc = 1.511 mg·m^-3, l(MoKα) = 0.71073 Å, µ = 2.868 mm^-1, F(000) = 2648, 2.62° < θ < 25.01°, R1 = 0.0620, wR2 = 0.1538. S = 1.034, Largest diff. Peak and hole: 0.816 and -0.551 e·Å^-3
• 13a Sedova VF. Mamaev VM. Khim. Geterotsikl. Soed.  1968,  5:  921 
• 13b Zigeuner G. Brunetti H. Ziegler H. Bayer M. Monatsh. Chem.  1970,  101:  1767 
• 13c Hatt HH. Aust. J. Chem.  1970,  23:  577 
• 13d Sedova VF. Baranova LV. Mamaev VP. Ser. Khim. Nauk  1972,  6:  96 
• 13e Sedova VF. Mamaev VP. Khim. Geterotsikl. Soed.  1970,  5:  691