Sodium Hydride Mediated Cascade Reaction towards the Synthesis of 1,5-Disubstituted Uracil from Cyanamides Derived from Baylis-Hillman Adducts [1]

Abstract

The substituted cyanamides generated from Baylis-Hillman adducts afford 1,5-disubstituted uracils via a sodium hydride induced cascade reaction involving sequential intramolecular attack of the hydroxy group on the nitrile group, cyclization of the resulting ureide with the ester moiety, and rearrangement of the exocyclic double bond.

heterocycles - ring closure - 1,5-disubstituted uracil - cascade reaction - Baylis-Hillman reaction

References

<A NAME="RP11206SS-1">1</A>

CDRI communication number: 7125.

<A NAME="RP11206SS-2A">2a</A> Basavaiah D. Rao JR. Satyanarayana T. Chem. Rev.  2003,  811 

<A NAME="RP11206SS-2B">2b</A> Basavaiah D. Reddy RJ. Rao JS. Tetrahedron Lett.  2006,  47:  73 

<A NAME="RP11206SS-2C">2c</A> Coelho F. Veronese D. Pavam CH. de Paula VI. Buffon R. Tetrahedron  2006,  62:  4563 

<A NAME="RP11206SS-2D">2d</A> Chandrasekhar S. Basu D. Rambabu C. Tetrahedron Lett.  2006,  47:  3059 

<A NAME="RP11206SS-2E">2e</A> Kabalka GW. Venkataiah B. Chen C. Tetrahedron Lett.  2006,  47:  4187 

<A NAME="RP11206SS-2F">2f</A> Jean L. Marinetti A. Tetrahedron Lett.  2006,  47:  2141 

<A NAME="RP11206SS-2G">2g</A> Wasnaire P. Wiaux M. Touillaux R. Markó IE. Tetrahedron Lett.  2006,  47:  985 

<A NAME="RP11206SS-2H">2h</A> Mix S. Blechert S. Org. Lett.  2005,  47:  2015 

<A NAME="RP11206SS-2I">2i</A> Lee KY. Gowrisankar S. Lee YJ. Kim JN. Tetrahedron  2006,  62:  8798 

<A NAME="RP11206SS-2J">2j</A> Jayashankaran J. Durga R. Manian RS. Sivaguru M. Raghunathan R. Tetrahedron Lett.  2006,  47:  5535 

<A NAME="RP11206SS-2K">2k</A> Madapa S. Singh V. Batra S. Tetrahedron  2006,  62:  8740 

<A NAME="RP11206SS-2L">2l</A> Singh V. Batra S. Tetrahedron Lett.  2006,  47:  7043 

<A NAME="RP11206SS-2M">2m</A> Singh V. Kanojiya S. Batra S. Tetrahedron  2006,  62:  10100 

<A NAME="RP11206SS-3A">3a</A> Pathak R. Roy AK. Batra S. Synlett  2005,  848 

<A NAME="RP11206SS-3B">3b</A> Nag S. Pathak R. Kumar M. Shukla PK. Batra S. Bioorg. Med. Chem. Lett.  2006,  16:  3824 

<A NAME="RP11206SS-3C">3c</A> Singh V. Yadav GP. Maulik PR. Batra S. Tetrahedron  2006,  62:  8731 

<A NAME="RP11206SS-3D">3d</A> Pathak R. Nag S. Batra S. Synthesis  2006,  4205 

<A NAME="RP11206SS-3E">3e</A> Pathak R. Madapa S. Batra S. Tetrahedron  2007,  63:  451 

<A NAME="RP11206SS-4A">4a</A> Estaban-Gamboa A. Balzarini J. Esnouf R. De Clercq E. Camarasa M.-J. Perez-Perez M.-J. J. Med. Chem.  2000,  43:  971 

<A NAME="RP11206SS-4B">4b</A> Onishi T. Mukai C. Nakagawa R. Sekiyama T. Aoki M. Suzuki K. Nakazawa H. Ono N. Ohmura Y. Iwayama S. Okunishi M. Tsuji T. J. Med. Chem.  2000,  43:  278 

<A NAME="RP11206SS-4C">4c</A> Kumar R. Nath M. Tyrrell DLJ. J. Med. Chem.  2002,  45:  2032 

<A NAME="RP11206SS-4D">4d</A> Cole C. Reigan P. Gbaj A. Edwards PN. Douglas KT. Stratford IJ. Freeman S. Jaffar M. J. Med. Chem.  2003,  46:  207 

<A NAME="RP11206SS-4E">4e</A> Orr GF. Musso DL. Kelley JL. Joyner SS. Davis ST. Baccanari DP. J. Med. Chem.  1997,  40:  1179 

<A NAME="RP11206SS-4F">4f</A> Kim JC. Dong ES. Park J. Bae SD. Kim SH. Arch. Pharmacol. Res.  1994,  17:  480 

<A NAME="RP11206SS-4G">4g</A> Bibby MC. Double JA. McCormick JE. McElhinney RS. Radacic M. Pratesi G. Dumont P. Anticancer Drug Des.  1993,  8:  115 

<A NAME="RP11206SS-4H">4h</A> Imaizumi M. Kano F. Sakata S. Chem. Pharm. Bull.  1992,  40:  1808 

<A NAME="RP11206SS-5">5</A> Baker BR. Kelly JL. J. Med. Chem.  1970,  13:  461 

<A NAME="RP11206SS-6">6</A> Berillon L. Wagner R. Knochel P. J. Org. Chem.  1998,  63:  9117 ; intriguingly, refs. 6 and 7 describe different physical characteristics for the same compound (1,3,5-tribenzyluracil)

<A NAME="RP11206SS-7">7</A> Lee CG. Gowrisankar S. Kim JN. Bull. Korean Chem. Soc.  2005,  26:  481 

<A NAME="RP11206SS-8">8</A> Patra A. Batra S. Kundu B. Joshi BS. Roy R. Bhaduri AP. Synthesis  2001,  276 

<A NAME="RP11206SS-9">9</A> Batra S. Roy AK. Patra A. Bhaduri AP. Surin WS. Raghvan SAV. Sharma P. Kapoor K. Dikshit M. Bioorg. Med. Chem.  2004,  12:  2059 

<A NAME="RP11206SS-10">10</A>

Crystal data of compound 5c: C₁₉H₂₀N₂O₃, M = 324.37, monoclinic (solvent: CHCl₃), P2₁/n, a = 12.626 (2), b = 9.117 (1), c = 14.631 (1) Å, β = 90.81 (1)°, V = 1684.0(3) ų, Z = 4, D _c = 1.279 (2) g·cm^-3,
µ (Mo-K_α) = 0.09 mm^-1, F(000) = 688.0, colorless block, 0.225 × 0.20 × 0.175 mm, 4097 reflections measured (R _int = 0.0234), 2972 unique, wR ₂ = 0.1277, conventional R = 0.0497 on F ² values of 1573 reflections with I > 2σ(I), (Δ/σ) _max = 000), S = 0.962 for all data and 219 parameters. Unit cell determination and intensity data collection (2θ = 50°) were performed on a Bruker P4 diffractometer at 293 (2) K. Structure solutions by direct methods and refinements were by full-matrix least-squares methods on F ². Programs: XSCANS (Siemens Analytical X-ray Instrument Inc.: Madison, WI, USA, 1996) for data collection and data processing; SHELXTL-NT (Bruker AXS Inc.: Madison, Wisconsin, USA, 1997) for structure determination, refinements, and molecular graphics. Further details of the crystal structure investigation can be obtained from the Cambridge Crystallographic Data Centre, 12 Union Road, Cambridge, CB2 1EZ, UK (CCDC deposition no. 629774). (For queries related to the X-ray structure write to [e-mail]).

<A NAME="RP11206SS-11">11</A> B’Ouzide A. Org. Lett.  2002,  4:  1347