Reaction of 1,3,4‐oxadiazolones with free L‐α‐amino acids: A facile synthesis of novel 3,5‐disubstituted hydantoins

Abstract

A series of novel 3,5‐disubstituted hydantoins 3a‐1 were easily synthesized in one‐step from the reaction of 2‐phenyl‐1,3,4‐oxadiazolin‐5‐ones 1a‐h with various free L‐α‐amino acids 2a‐e in m‐cresol at 150°. An alternative route leading to the formation of 3‐benzamido‐5‐isopropylhydantoin 3c was also developed to make clear the reaction mechanism.

Palladium-Catalyzed Oxidative O–H/N–H Carbonylation of Hydrazides: Access to Substituted 1,3,4-Oxadiazole-2(3H)-ones

“…Melting points were measured with a melting point instrument and were uncorrected. 1 H and 13 C NMR spectra were recorded using a 400 MHz NMR spectrometer. The chemical shifts are referenced to signals at 7.24 and 77.0 ppm, respectively, and chloroform is solvent with TMS as the internal standard.…”

“…The residue was purified by column chromatography on silica gel to afford the corresponding products 4 with petroleum ether/ethyl acetate as the eluent. 13 C NMR (101 MHz,DMSO) δ 161.6,154.5,153.8,127.0,116.3,114.7,55.4; HRMS (ESI) m/z: calcd for C 9 H 8 N 2 NaO 3 [M + Na] + , 215.0427; found, 215.0429.…”

“…2−135.8. IR (KBr): 3270, 2964, 1783, 1619, 1346 H NMR (400 MHz, DMSO) δ 7.72 (d, J = 7.8 Hz, 2H), 7.56 (d, J = 7.8 Hz, 2H), 1.30 (s, 9H); 13 C NMR (101 MHz, DMSO) δ 154. 5, 154.3, 153.9, 126.0, 125.1, 121.2, 34.7, 30.8 4 Hz,2H), 7.51 (t, J = 7.0 Hz, 2H), 7.43 (t, J = 7.0 Hz, 1H); 13 C NMR (101 MHz, DMSO) δ 154.…”

Solid-Phase Synthesis of Acyclic and Cyclic Amino Acid Derived Urea Peptidomimetics Using Phoxime Resin

“…Key to this strategy is access to the amino acid derived carbamate resin 3 which can be further utilized to synthesize two other families of urea peptidomimetics, namely 3-aminohydantoins 7 and 1,2,4-triazine-3,6-diones 8 . Although similar functionality density and pharmacological behavior as hydantoins 25-29 can be expected for 7 and 8 , only a few investigations on the preparation of these compounds have been reported in the literature. − 1,2,4-Triazine-3,6-diones 8 and their ring isomer 3-aminohydantoins 7 are a relatively underinvestigated class of nitrogen heterocycles which can be viewed as constrained cyclic dipeptidomimetics. − There was also some dispute over the synthesis of 8 in the literature. , This article describes the methodology to prepare these three classes of compounds in a way suitable for combinatorial library generation.

1 Synthesis of α-Ureidoacetamides 5 Phoxime Resin 2

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A new synthesis of 3-arylideneamino- and 3-alkylideneamino-substituted hydantoins

“…Described syntheses of 3-aminohydantoin derivatives from acyclic precursors generally involve formation of one or two C-N bonds (e.g., N3-C4 [8,[12][13][14][15], C2-N3 [16][17][18], both N1-C2 and N3-C4 [19][20][21][22][23], both N1-C5 and N3-C4 bonds [24]). These compounds are also prepared using recyclizations of certain heterocyclic compounds [25][26][27][28][29][30][31][32][33]. It should be noted that there are only a few reports on the synthesis of N-alkylidene-and N-arylidene-3-aminohydantoins.…”