1,3,5-Trisubstituted and 5-Acyl-1,3-Disubstituted Hydantoin Derivatives via Novel Sequential Three-Component Reaction

Abstract

1,2-Diaza-1,3-dienes (DDs) react as Michael acceptors with primary amines to afford α-aminohydrazone derivatives that were in situ coupled with isocyanates. Intramolecular ring closure of the asymmetric urea derivatives so formed allows for a selectively substituted hydantoin ring to be obtained. The hydrazone side chain introduced by the conjugated heterodiene system at the 5-position of the heterocycle represents a valuable functionality for accessing novel 5-acyl derivatives difficult to obtain by other methods.

Unexpected Synthesis of 2,3,5,6‐Tetrahydro‐1H‐pyrrolo[3,4‐c]pyridine‐1,3,6‐triones by a Double Michael Addition/CS2 Extrusion/Double Cyclization Sequence

“…Further evidence of the proposed structure for compounds 6 was furnished by the hydrolytic cleavage of the hydrazone moiety in position 7 of the pyridine ring of compound 6e , chosen as an example, that was obtained under heterogeneous conditions with acetone/water (9:1) and Amberlyst 15H . Under these acidic conditions also the loss of the tert ‐butoxycarbonyl moiety occurred to give the corresponding 7‐acetyl‐5‐amino‐4‐methyl‐2‐phenyl‐1 H ‐pyrrolo[3,4‐ c ]pyridine‐1,3,6(2 H ,5 H )‐trione 7a in very good yield (83 %; Scheme ) …”

Acyclic and Cyclic Ureas (Update 2013)

“…Coupling of these products in situ with isocyanates leads to hydantoins (Scheme 98). [265] The advantage of this approach lies in the presence of the hydrazone moiety at the 5-position of the products from which a carbonyl group can easily be liberated by acidic hydrolysis. Scheme 98 Three-Component Hydantoin Synthesis from a 1,2-Diaza-1,3-diene, a Primary Amine, and an Isocyanate [265] 1,3,5,5-Tetrasubstituted hydantoins can be obtained by coupling two domino reactions.…”

“…[265] The advantage of this approach lies in the presence of the hydrazone moiety at the 5-position of the products from which a carbonyl group can easily be liberated by acidic hydrolysis. Scheme 98 Three-Component Hydantoin Synthesis from a 1,2-Diaza-1,3-diene, a Primary Amine, and an Isocyanate [265] 1,3,5,5-Tetrasubstituted hydantoins can be obtained by coupling two domino reactions. The first reaction involves the synthesis of but-2-ene-1,4-diones from 1,3-dicarbonyl compounds and methyl ketones or terminal arylalkenes in the presence of copper(II) oxide/iodine or 1-hydroxy-1,2-benziodoxol-3(1H)-one 1-oxide (2-iodylbenzoic acid; IBX)/copper(II) oxide/iodine, respectively.…”

Recent Advances in the Synthesis of Hydantoins: The State of the Art of a Valuable Scaffold

“…A method to obtain various 1,3-disubstituted, 5-azasubstituted hydantoins was developed by Attanasi et al starting from 1,2diaza-1,3-diene esters, primary amines, and isocyanates. 247,248 An aza-Michael addition occurred between the 1,2-diaza-1,3-diene Aranha Potter et al observed the formation of 1,3-dibenzyl-5ethoxy-hydantoin in the reaction between N-benzyl-2-ethoxycarbonyl-endo-or exo-azanorbornene and benzylisocyanate. 249 Instead of the expected Claisen rearrangement, a retro Diels− Alder reaction took place upon the addition of the isocyanate on the norbornene, leading to the formation of the hydantoin along with liberation of cyclopentadiene (Scheme 28).…”