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Synlett 2025; 36(07): 904-908
DOI: 10.1055/a-2456-9704
DOI: 10.1055/a-2456-9704
letter
Acid-Catalyzed Condensation of Primary/Secondary Amines with 2-Oxo-2-aryl-N-arylethanethioamides: A Highly Regioselective Synthesis of α-Oxoamidines
K.S.R. thanks CSIR and ISCA for providing Emeritus Scientist and Asutosh Mookerjee fellowships respectively. K.M. is grateful for a DBT Glue grant (no. BT/PR23078/MED/29/1253/2017, dated 22/03/2018) and a VGST Project Grant [No. Ksteps/VGST/GRD-681/KFIST(L1)/2018, dated 27-08-2018].
Abstract
In this letter, we present a synthesis of a-oxoamidines by the condensation of primary/secondary amines with N-aryl-α-oxothioamides catalyzed by benzoic acid in toluene at 80 °C. The required N-aryl-α-oxothioamide substrates were synthesized by the sodium hydride-induced condensation of aromatic amines with α-oxodithioesters. The amines reacted with high regioselectivity toward thiocarbonyl groups over carbonyl groups to afford α-oxoamidines. The present method overcomes the limitations of previously reported methods.
Supporting Information
- Supporting information for this article is available online at https://doi.org/10.1055/a-2456-9704.
- Supporting Information
Publication History
Received: 14 June 2024
Accepted after revision: 29 October 2024
Accepted Manuscript online:
30 October 2024
Article published online:
18 November 2024
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- 49 α-Oxoamidines 3; General Procedure BzOH (0.5 mmol) was added to a solution of the appropriate N-aryl-oxothioamide 1 (1 mmol) and secondary amine 2 (1 mmol) in toluene (2 mL), and the mixture was stirred at 80 °C for 2–3 h until the reaction was complete (TLC). 5% aq NaHCO3 (25 mL) was added, and the resulting mixture was extracted with EtOAc (2 × 25 mL). The combined organic layer was washed with brine (25 mL) and then concentrated under reduced pressure. The crude product was purified by column chromatography [silica gel, hexane–EtOAc (9:1)]. 2-(3,4-Dihydroisoquinolin-2(1H)-yl)-1-phenyl-2-(phenylimino)ethanone (3a) Yellow solid; yield: 289 mg (85%; E/Z = 65:35); mp 160–162 °C. IR (KBr/Nujol): 2926, 2857, 1662, 1419, 1269, 1165, 758, 730 cm–1. 1H NMR (400 MHz, CDCl3): δ = 2.93 (t, J = 8.0 Hz, 2 H, CH2), 3.16 (t, J = 8.0 Hz, 2 H, CH2), 3.87 (t, J = 8.0 Hz, 2 H, CH2), 4.45 (t, J = 8.0 Hz, 2 H, CH2), 4.73 (s, 2 H, CH2), 5.36 (s, 2 H, CH2), 7.03–7.54 (m, 20 H, Ar–H), 7.60–7.66 (m, 2 H, Ar–H), 7.98 (d, J = 4.0 Hz, 2 H, Ar–H), 8.03–8.06 (m, 4 H, Ar–H). 13C NMR (100 MHz, CDCl3): δ = 29.3, 29.7, 45.9, 49.3, 49.4, 52.6, 111.8, 115.1, 115.3, 115.9, 122.4, 122.5, 123.5, 126.0, 126.9, 127.0, 127.2, 127.3, 127.9, 128.4, 128.5, 128.6, 128.7, 128.9, 129.0, 129.3, 129.9, 130.0, 131.0, 131.2, 133.0, 133.4, 134.3, 134.4, 187.9, 188.0, 195.4, 195.7. HRMS (ESI): m/z [M + H]+ calcd for C23H20N2O: 341.1654; found: 341.1651.