Download PDF
Synlett 2002(6): 0947-0951
DOI: 10.1055/s-2002-31901
LETTER
© Georg Thieme Verlag Stuttgart · New York

Synthesis of 3,4-Diarylsubstituted Maleic Anhydride/Maleimide via Unusual Oxidative Cyclization of Phenacyl Ester/Amide [1]

Vijaya Raghavan Pattabiraman, Srinivas Padakanti, Venugopal Rao Veeramaneni, Manojit Pal*, Koteswar Rao Yeleswarapu
Discovery Chemistry, Dr. Reddy’s Research Foundation, Bollaram Road, Miyapur, Hyderabad 500050, India
Fax: +91(40)3045438/3045007; e-Mail: manojitpal@drreddys.com;
Further Information

Publication History

Received 28 March 2002
Publication Date:
07 February 2007 (online)

    Permissions and Reprints All articles of this category

Abstract

A simple and general method has been developed for the synthesis of 3,4-diarylsubstituted maleic anhydride and maleimide through tandem cyclization and oxidation reaction of phenacyl ester or amide. A wide variety of phenacyl esters or amides was treated with DBU under oxygen atmosphere to give the expected compounds in good to excellent yield. Mechanism of the reaction and application of the methodology have been discussed.

Key words

3,4-diarylsubstituted maleic anhydride/maleimide - oxidative cyclization - phenacyl ester/amide - oxygen

1

DRF Publication No. 185.

    References

  • 2 Gallagher TF. Seibel GL. Kassis S. Laydon JT. Blumenthal MJ. Lee JC. Lee D. Boehm JC. Fier-Thompson SM. Abt JW. Soreson ME. Smietana JM. Hall RF. Garigipati RS. Bender PE. Erhard KF. Korg AJ. Hofmann GA. Sheldrake PL. McDonnell PC. Kumar S. Young PR. Adams JL. Bioorg. Med. Chem.  1997,  5:  49 
    CrossrefGoogle Scholar
  • 3 Akahane A. Katayama H. Mitsunaga T. Kato T. Kinoshita T. Kita Y. Kusunoki T. Terai T. Yoshida K. Shiokawa Y. J. Med. Chem.  1999,  42:  779 
    CrossrefPubMedGoogle Scholar
  • 4 Sauerberg P. Olesen PH. Nielsen S. Treppendahl S. Sheardown MJ. Honore T. Mitch CH. Ward JS. Pike AJ. Bymaster FP. Sawyer BD. Shannon HE. J. Med. Chem.  1992,  35:  2274 
    CrossrefGoogle Scholar
  • 5 Penning TD. Talley JJ. Bertenshaw SR. Carter JS. Collins PW. Doctor S. Granto MJ. Lee LF. Malecha JW. Miyashiro JM. Rogers RS. Rogier DJ. Yu SS. Anderson GD. Burton EG. Cogburn JN. Gregory SA. Koboldt CM. Perkins WE. Seibert K. Veenhuizen AM. Zhang YY. Jackson PC. J. Med. Chem.  1997,  40:  1347 
    CrossrefPubMedGoogle Scholar
  • 6 Prasit P. Wang Z. Brideau C. Chan C.-C. Charleson S. Cromlish W. Either D. Evans JF. Ford-Hutchinson AW. Gauthier JY. Gordon R. Guay J. Gresser M. Kargman S. Kennedy B. Leblanc Y. Leger S. Mancini J. O Neil GP. Oullet M. Percival MD. Perrier H. Riendeau D. Rodger I. Tagari P. Therien M. Visco D. Patrick D. Bioorg. Med. Chem. Lett.  1999,  9:  1773 
    CrossrefGoogle Scholar
  • 7 Bosch J. Roca T. Catena J.-L. Llorens O. Perez J.-J. Lagunas C. Fernandez AG. Miquel I. Fernandez-Serrat A. Farrerons C. Bioorg. Med. Chem. Lett.  2000,  10:  1745 
    CrossrefGoogle Scholar
  • 8 Pal M, Rao YK, Rajagopalan R, Misra P, Kumar PM, and Rao CS. inventors; World Patent WO  01/90097.  ; Chem. Abstr. 2002, 136, 5893
  • 9 Yokoyama Y. inventors; Jpn. Kokai Tokkyo Koho JP 01050803 A2  27.  ; Chem. Abstr. 1989, 111, 227229r
  • 10a Fields EK. Behrend SJ. J. Org. Chem.  1990,  55:  5165 
    CrossrefGoogle Scholar
  • 10b Atkinson JG, and Wang Z. inventors; World Patent WO 9613483  A1.  ; Chem. Abstr. 1996, 125, 114294
    Crossref
  • 11a Kalgutkar AS. Crews BC. Marnett LJ. J. Med. Chem.  1996,  39:  1692 
    CrossrefGoogle Scholar
  • 11b Davis PD. Bit RA. Hurst SA. Tetrahedron Lett.  1990,  31:  2353 ; and references cited therein
    CrossrefGoogle Scholar
  • 12 Ichikawa Y, and Shiyoji M. inventors; Jpn. Kokai Tokkyo Koho JP 08231502 A2  10.  ; Chem Abstr. 1996, 125, 300818
  • 13 For an excellent review see: Collins I. J. Chem. Soc., Perkin Trans. 1  1999,  1377 
    CrossrefGoogle Scholar
  • 14a Rousset S. Thibonnet J. Abarbri M. Duchene A. Parrain J.-L. Synlett  2000,  260 
    CrossrefGoogle Scholar
  • 14b Bellina F. Biagetti M. Carpita A. Rossi R. Tetrahedron  2001,  57:  2857 
    CrossrefGoogle Scholar
  • 15a Kotora M. Negishi E.-i. Synthesis  1997,  121 ; and references cited therein
    CrossrefGoogle Scholar
  • 15b Kundu NG. Pal M. Nandi B. J. Chem. Soc., Perkin. Trans. 1  1998,  561 
    CrossrefGoogle Scholar
  • 16a Koelsch CF. Wawzonek S. J. Org. Chem.  1941,  6:  684 
    CrossrefGoogle Scholar
  • 16b Smith PAS. Friar JJ. Resemann W. Watson AC. J. Org. Chem.  1990,  55:  3351 
    CrossrefGoogle Scholar
  • 16c Florac C. Baudy-Floc’h M. Robert A. Tetrahedron  1990,  46:  445 
    CrossrefGoogle Scholar
  • 17 Beccalli EM. Gelmi ML. Marchesini A. Eur. J. Org. Chem.  1999,  6:  1421 
    Google Scholar
  • 18a Dikshit DK. Shing S. Sing MM. Kamboj VP. Ind. J. Chem.  1990,  29B:  950 
    Google Scholar
  • 18b Vijayaraghavan ST. Balasubramanian TR. Ind. J. Chem.  1986,  25B:  760 
    Google Scholar
  • 19 Habeeb AG. Praveen Rao PN. Knaus EE. J. Med. Chem.  2001,  44:  3039 
    CrossrefPubMedGoogle Scholar
  • 20 Formation of 18 could be accounted by the intermediacy of a tertiary hydroperoxide. For a similar mechanistic sequence see: Heaney H. Taha MO. Slawin AMZ. Tetrahedron Lett.  1997,  38:  3051 
    CrossrefGoogle Scholar
  • 22a

    A detailed study on the synthesis of compounds of biological interest and their biological activity is under investigation.
    Crossref
  • 22b Davis PD. Bit RA. Tetrahedron Lett.  1990,  31:  5201 
    CrossrefGoogle Scholar
1

DRF Publication No. 185.

21

A useful method for the synthesis of 3,4-diaryl-5-hydroxyfuranones has been developed by us and will be reported elsewhere.

23

Typical Procedure for the Synthesis of 3,4-Diaryl Substituted Maleic Anhydride: Preparation of 4: To a solution of 2-oxo-2-phenylethyl-2-phenylacetate (0.50 g, 1.968 mmol) in acetonitrile (8 mL) was added DBU (0.899 g, 5.905 mmol) slowly and dropwise at 25 °C in the presence of atmospheric oxygen. The mixture was stirred for 6 h. After completion of the reaction the mixture was poured into ice-cold 3 N HCl solution (20 mL) with stirring. The solid separated was filtered off, washed with water (2 × 10 mL) followed by petroleum ether (2 × 5 mL). Compound 4 was isolated in 77% yield as light yellow solid, mp 158-160 °C (lit [16] 159-160 °C).

24

Spectral data for 11: mp: 161.5-162 °C (1:9 EtOAc-hexane); IR max (KBr): 1833, 1766 cm-1; 1H NMR (200 MHz, CDCl3): δ = 7.31-7.54 (m, 5 H), 7.74 (d, J = 8.74 Hz, 2 H), 8.27 (d, J = 8.79 Hz, 2 H); Mass (CI method, I-butane): m/z (%) = 296(100) [MH+]; UV (MeOH): 268 nm. Elemental analysis found: C, 64.81; H, 3.11; N, 4.62. C16H9NO5 requires C, 65.09; H, 3.07; N, 4.74.

25

Spectral data for 12: mp: 121-122 °C (1:9 EtOAc-hexane); IR max (KBr): 1826, 1757 cm-1; 1H NMR (200 MHz, CDCl3): δ = 2.38 (s, 3 H), 7.18-7.26 (m, 3 H), 7.39-7.56 (m, 6 H); Mass (CI method, I-butane): m/z (%) = 265(100) [MH+]; UV (MeOH): 355 nm. Elemental analysis found: C, 77.55; H, 4.32. C17H12O3 requires C, 77.26; H, 4.58.