Highly efficient dialkylphosphate-mediated syntheses of hydantoins and a bicyclohydantoin under solvent-free conditions

A set of two broadly applicable procedures for the N-arylation of hydantoins is reported. The first one relies on the use of stoichiometric copper(I) oxide under ligandand base-free conditions and enables a clean regioselective arylation at the N 3 nitrogen atom, while the second one is based on the use of catalytic copper(I) iodide and trans-N,N′-dimethylcyclohexane-1,2-diamine and promotes arylation at the N 1 nitrogen atom. Importantly, the combination of these two procedures affords a straightforward entry to diarylated hydantoins.

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“…Solvent system for flash column chromatography: petroleum ether/EtOAc: 60/40. This compound has been previously reported …”

Section: Methodsmentioning

confidence: 99%

Copper-Mediated N-Arylations of Hydantoins

Thilmany

Gérard

Vanoost³

et al. 2018

J. Org. Chem.

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“…Yields of the second step improve when performing the cyclization in the presence of dibutyl hydrogen phosphate under solvent-free conditions at 100 8 8C. [269] Scheme Transition-metal-catalyzed hydantoin syntheses include the reaction of acrylates with two molecules of an isocyanate catalyzed by bis(h 4 -cycloocta-1,5-diene)nickel(0) in the presence of the N-heterocyclic carbene ligand 1,3-bis(2,6-diisopropylphenyl)-4,5-dihydroimidazol-2-ylidene (SIPr) to give 1,3,5-trisubstituted hydantoins (Scheme 102). [270] This process involves two sequential steps: regioselective formation of an N-substituted alkyl (E)-4-amino-4-oxobut-2-enoate, and ring closure with incorporation of another molecule of isocyanate.…”

Section: Methods 8: Cycloadditionsmentioning

confidence: 99%

Acyclic and Cyclic Ureas (Update 2013)

Banert¹,

Dobbs²,

Hall³

et al. 2013

Knowledge Updates 2013/3

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“…In an attempt to overcome this weakness, we employed dibutyl phosphate (DBP) as a mild reagent to hydrolyze and cyclize the substrate in one step, giving quantitative yields of the desired products without affecting acid-sensitive moieties. 77 The reaction conditions and various substituted products are described in Scheme 4 and Table 1, respectively. The wide varieties of substituted hydantoins 54-71 were successfully prepared in one to two hours.…”

Section: Account Synlettmentioning

confidence: 99%

Designed Synthesis of Diversely Substituted Hydantoins and Hydantoin-Based Hybrid Molecules: A Personal Account

Kumar¹

2021

Synlett

Self Cite

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Hydantoin and its analogs such as thiohydantoin and iminohydantoin have received substantial attention both from a chemical and biological point of view. Several compounds of this class have shown useful pharmacological activities such as anticonvulsant, antitumor, antiarrhythmic, herbicidal, and others that lead in some cases to clinical applications. Because of broad-spectrum activities, intensive research efforts have been dedicated in industry and academia to the synthesis and structural modifications of hydantoin and its derivatives. Realizing the importance of hydantoin in organic and medicinal chemistry, we also initiated a research program to successfully design and develop the new routes/methods resulting in the formation of hydantoin, thiohydantoin, and iminohydantoin substituted at different positions particularly at the N-1 position without following protection-deprotection strategy. Given the fact that the combination of two or more pharmacophoric groups may lead to hybrid molecules which result in a mixed mechanism of action on the biological target. We, therefore, further extended the developed strategy for the synthesis of new types of hydantoin-based hybrid molecules by combining hydantoin with a triazole, isoxazoline, and phosphate scaffolds as another pharmacophoric group to exploit diverse biological functions.

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Highly efficient dialkylphosphate-mediated syntheses of hydantoins and a bicyclohydantoin under solvent-free conditions

Cited by 18 publications

References 63 publications

Copper-Mediated N-Arylations of Hydantoins

Copper-Mediated N-Arylations of Hydantoins

Acyclic and Cyclic Ureas (Update 2013)

Designed Synthesis of Diversely Substituted Hydantoins and Hydantoin-Based Hybrid Molecules: A Personal Account

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