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Synlett 2014; 25(08): 1124-1126
DOI: 10.1055/s-0033-1341049
letter
© Georg Thieme Verlag Stuttgart · New York

β-Lactam-Synthon-Interceded Facile Synthesis of Functionally Decorated Thiohydantoins

Vishu Mehra
a   Department of Chemistry, Guru Nanak Dev University, Amritsar 143005, India   Fax: +91(183)225881920   Email: vipan_org@yahoo.com
,
Parvesh Singh
b   School of Chemistry, University of Kwazulu Natal, Durban 4000, South Africa
,
Neha Manhas
b   School of Chemistry, University of Kwazulu Natal, Durban 4000, South Africa
,
Vipan Kumar*
a   Department of Chemistry, Guru Nanak Dev University, Amritsar 143005, India   Fax: +91(183)225881920   Email: vipan_org@yahoo.com
› Author Affiliations
Further Information

Publication History

Received: 31 January 2014

Accepted after revision: 02 March 2014

Publication Date:
27 March 2014 (online)

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Abstract

Base-promoted facile synthesis of thiohydantoins has been described via intramolecular amidolysis of C-3 functionalized 2-azetidinones. This approach provides a convenient and rapid access to diversely functionalized thiohydantoins compared to conventional protocols.

Key words

β-lactam synthon - thiohydantoin - intramolecular amidolysis
 

  • References and Notes

  • 2 Elokdah H, Sulkowski TS, Abou-Gharbia M, Butera JA, Chai SY, McFarlane GR, McKean M, Babiak JL, Adelman SJ, Quinet EM. J. Med. Chem. 2004; 47: 681
    CrossrefSearch in Google Scholar
  • 3 Zhang Y, Li D, Houtman JC, Witiak DT, Seltzer J, Bertics PJ, Lauhon CT. Bioorg. Med. Chem. Lett. 1999; 9: 2823
    CrossrefSearch in Google Scholar
  • 4 Takahashi A, Matsuoka H, Ozawa Y, Uda Y. J. Agric. Food Chem. 1998; 46: 5037
    CrossrefSearch in Google Scholar
  • 5 Theodoridis G. US Patent 4902338, 1990 ; Chem. Abstr. 1990, 113, 24243
  • 7 Al-Obaid AM, El-Subbagh HI, Khodair AI, Elmazar MM. Anticancer Drugs 1996; 7: 873
    CrossrefSearch in Google Scholar
  • 8 El-Barbary AA, Khodair AI, Pedersen EB, Nielsen C. J. Med. Chem. 1994; 37: 73
    CrossrefSearch in Google Scholar
  • 9 Chérouvrier JR, Carreaux F, Bazureau JP. Molecules 2004; 9: 867
    CrossrefSearch in Google Scholar
  • 10 Khodair AI, El-Subbagh HI, El-Emam AA. Bull. Chim. Farm. 1997; 136: 561
    Search in Google Scholar
  • 11 Archer S, Unser MJ. J. Am. Chem. Soc. 1956; 78: 6182
    CrossrefSearch in Google Scholar
    • 12a Lacroix G, Bascou JP, Perez J, Gadras A. US Patent 6018052, 2000
    • 12b Lacroix G, Bascou JP, Perez J, Gadras A. US Patent 5650519, 1997
    • 12c Marton J, Enisz J, Hosztafi S, Timar T. J. Agric. Food Chem. 1993; 41: 148
      CrossrefSearch in Google Scholar
  • 13 Curran AC. W. US Patent 3984430, 1976
  • 14 Kumar R, Chauhan PM. S. Tetrahedron Lett. 2008; 49: 5475
    CrossrefSearch in Google Scholar
  • 15 Ohberg L, Westman J. Synlett 2001; 1893
    Thieme Connect
  • 16 Sim MM, Ganesan A. J. Org. Chem. 1997; 62: 3230
    CrossrefSearch in Google Scholar
  • 17 Park KH, Kurth MJ. J. Org. Chem. 1999; 64: 9297
    CrossrefSearch in Google Scholar
  • 18 Kidwai M, Venkataramanan R, Dave B. Green Chem. 2001; 3: 278
    CrossrefSearch in Google Scholar
  • 22 Alcaide B, Almendros P, Alonso JM. J. Org. Chem. 2004; 69: 993
    CrossrefSearch in Google Scholar
  • 24 Mehra V, Kumar V. Tetrahedron Lett. 2013; 54: 6041
    CrossrefSearch in Google Scholar
  • 26 Typical Procedure for the Preparation of Thiourea 2: To a stirred solution of 2-isothiocyanateazetidin-2-one 1 (1 mmol) was added a solution of the amine (1 mmol) in anhyd acetone (20 mL). The reaction mixture was allowed to stir at r.t. for 15–20 min and the reaction progress was monitored by TLC. The solvent was removed in vacuo resulting in a solid that was recrystallized from Et2O to yield the desired product 2. 1-(2-Oxo-4-styryl-1-p-tolylazetidin-3-yl)-3-phenylthiourea (2a): white solid; mp 156–157 °C. 1H NMR (300 MHz, CDCl3): δ = 2.35 (s, 3 H, Me), 4.64 (dd, J = 4.8, 6.4 Hz, 1 H, H2), 4.92 (dd, J = 4.8, 7.2 Hz, 1 H, H1), 6.08 (dd, J = 6.4, 15.6 Hz, 1 H, H3), 6.61 (d, J = 15.6 Hz, 1 H, H4), 6.80–7.02 (m, 5 H, ArH), 7.06 (d, J = 8.1 Hz, 2 H, ArH), 7.12 (d, J = 8.1 Hz, 2 H, ArH), 7.16–7.32 (m, 5 H, ArH), 7.82 (d, J = 7.2 Hz, 1 H, NH, D2O exch.). 13C NMR (75 MHz, CDCl3): δ = 20.6, 59.0, 63.4, 120.0, 123.3, 124.8, 125.5, 126.2, 127.3, 127.8, 128.1, 128.8, 129.6, 133.1, 134.9, 137.4, 139.4, 170.5, 178.1. MS: m/z = 414 [M+]. Anal. Calcd for C25H23N3OS: C, 72.61; H, 5.61; N, 10.16. Found: C, 72.51; H, 5.57; N, 10.22.
  • 27 Typical Procedure for the Sodium Methoxide Mediated Synthesis of 3-Aryl/Alkyl-5-(3-phenylallylidene)-2-thioxoimidazolidin-4-ones 4: To a stirred solution of thiourea 2 (1 mmol) in anhyd MeOH was added a solution of sodium methoxide (1 mmol) in anhyd MeOH. The reaction mixture was allowed to stir at r.t. for 50–60 min and the progress of the reaction was monitored by TLC. On completion, the precipitated crude product was filtered and recrystallized from EtOAc–hexane (60:40) to yield 3-aryl/alkyl-5-(3-phenylallylidene)-2-thioxoimidazolidin-4-one 4 as yellow crystals. 3-Phenyl-5-(3-phenylallylidene)-2-thioxoimidazolidin-4-one (4a): yellow solid; mp >220 °C. 1H NMR (300 MHz, CDCl3): δ = 6.54 (d, J = 11.7 Hz, 1 H, H1), 7.00 (dd, J = 11.7, 15.0 Hz, 1 H, H2), 7.18 (d, J = 15.0 Hz, 1 H, H3), 7.32–7.80 (m, 10 H, ArH), 12.63 (s, 1 H, NH, D2O exch.). 13C NMR (75 MHz, CDCl3): δ = 112.5, 113.9, 114.2, 120.8, 125.6, 125.9, 127.2, 127.4, 128.9, 129.0, 134.8, 138.6, 161.3, 175.0. HRMS (ESI): m/z [M + H]+ calcd for C18H14N2OS: 307.0827; found: 307.0838. Anal. Calcd for C18H14N2OS: C, 70.56; H, 4.61; N, 9.14. Found: C, 70.50; H, 4.56; N, 9.19