New Synthesis of 3-Aminohydantoins via Condensation of Hydrazines with Isocyanates Derived from α-Amino Esters

Abstract

A new, simple, and efficient method for the synthesis of 3-aminohydantoins was reported in two steps, starting from the corresponding l -amino esters. Commercially available α-amino esters were converted into the corresponding isocyanate derivatives, which were then subjected to the condensation reaction with hydrazine hydrate and arylhydrazines, in the presence of DMAP and DIPEA. This method provides the corresponding 3-aminohydantoins in moderate and good yields under a simple and practical protocol.

Key words

3-aminohydantoins - α-amino esters - hydrazines - isocyanates - cyclization

Publication History

Received: 17 October 2023

Accepted after revision: 22 November 2023

Accepted Manuscript online:
24 November 2023

Article published online:
11 December 2023

• References and Notes

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• 22 Experimental Procedure and Characterization DataIsocyanate 2 (5 mmol), hydrazine hydrate (0.25 mL, 5 mmol), DIPEA (2.55 mL, 15 mmol), and DMAP (0.122 g, 1 mmol) were dissolved in anhydrous dimethyl sulfoxide (2 mL). The mixture was stirred for 0.5 h at 0 °C and then heated for 0.5 h at 100 °C in a pressure tube. The progress of the reaction was monitored by TLC. After cooling the reaction mixture to room temperature, the product was precipitated by adding diethyl ether (5 mL). The precipitate was then filtered and purified by flash chromatography using CH₂Cl₂/MeOH (90:10) as the eluent. 5-[2-(Methylthio)ethyl]-3-(phenylamino)imidazolidine-2,4-dione (4f)According to the general procedure, the product was isolated as white solid (0.966 g, 3.6 mmol, 73%); R_f = 0.44 (CH₂Cl₂/CH₃OH, 95:5); mp 164–166 °C. IR (KBr): 3359, 3108, 1778, 1732 cm^–1. ¹H NMR (500 MHz, DMSO-d ₆): δ = 8.52 (s, 1 H, Ph–NH), 8.34 (s, 1 H, NH–CO), 7.22–6.67 (m, 5 H, Ph), 4.37 (dd, J¹ = 6.8 Hz, J² = 5.0 Hz, 1 H, CH–CH₂), 2.62 (m, 2 H, S–CH₂), 2.07 (s, 3 H, CH₃–S), 1.90 (m, 2 H, CH₂–CH). ¹³C NMR (125 MHz, DMSO-d ₆): δ = 173.0, 155.6, 147.2, 129.3, 120.0, 112.5, 54.3, 31.6, 29.1, 15.0. HRMS: m/z calcd for C₁₂H₁₅N₃O₂S [M⁺]: 266.0959; found [M + H⁺]: 266.0958.
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