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)


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.

 
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  • 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