Domino synthesis of 1,3,5-trisubstituted hydantoins: a DFT study

The mechanism of the reaction between carbodiimides and activated α,β-unsaturated carboxylic acids yielding fully substituted hydantoins and variable amounts of N-acyl urea by-products was studied using density functional theory calculations. Two alternative pathways featuring N-acyl ureas and imino-oxazolidinones as intermediates for the formation of the hydantoin product were taken into account. The results obtained using two different computational models indicate that the overall barriers are similar for the two pathways considered. In all cases, inclusion of a second molecule of carboxylic acid was required to mediate tautomerizations and rearrangement steps. The calculations successfully reproduce the experimentally observed regioselectivity with respect to both N-acyl urea and hydantoin products.     

Nickel-catalyzed synthesis of acrylamides from alpha-olefins and isocyanates

[reaction: see text] The nickel(0)-catalyzed coupling of alpha-olefins and isocyanates proceeds in the presence of the N-heterocyclic carbene ligand IPr to provide alpha,beta-unsaturated amides. Carbon-carbon bond formation occurs preferentially at the 2-position of the olefin. The N-tert-butyl amide products can be converted to the corresponding primary amides under acidic conditions.     

Heterocycles from heterocycles. - III[1]. 1,3,5-trisubstituted hexahydro-1,3,5-triazines-2-ones from 1,3,5-trisubstituted hexahydro-1,3,5-triazines and organic isocyanates

1,3,5-Triscubstituted hexahydro-1,3,5-trazin-2-ones 3 are easily obtained by the reaction of 1,3,5-trisub-stituted hexahydro-1,3,5-triazines 1 with organic isocyanates 2 . The reaction is believed to occur by the sequential addition to 2 of two molecules of the monomeric N-methyleneamines in thermal equilibrium with 1. Substituent scrambling at the operating temperature (120°) was negligible. The crystal structure of 1,3,5-triphenylhexahydro-1,3,5-triazin-2-one (3a) has been determined by X-ray diffraction methods.     

Efficient solid-phase synthesis of 1,3,5-trisubstituted 1,3,5-triazine-2,4,6-triones

The solid-phase synthesis of 1,3-disubstituted and 1,3,5-trisubstituted 1,3,5-triazine-2,4,6-triones from MBHA and Wang resin is described. Reaction of resin-bound amino acids with isocyanates yield resin-bound ureas, which further react with chlorocarbonyl isocyanate in toluene at 65 degrees C to selectively afford the resin-bound 1,3-disubstituted 1,3,5-triazine-2,4,6-triones. Selective alkylation at the N-5 position of the resin-bound 1,3-disubstituted 1,3,5-triazine-2,4,6-triones was accomplished by treatment with alkyl halides in the presence of 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU). The desired products were cleaved from their solid support and obtained in good yield and purity. The method can be employed in production of toltrazuril analogue libraries for identification of new anticoccidial agents.     

Nickel-catalyzed cycloaddition of alkynes and isocyanates

A mild and general route for preparing 2-pyridones from isocyanates and diynes is described. Ni imidazolyidene complexes were used to mediate cyclizations between both internal and terminal diynes with aryl and alkyl isocyanates. In addition, the efficacy of this protocol allows for the preparation of a fused seven-membered pyridone and for three component cyclizations.     

Synthesis and thermotropic properties of new discotic 1,3,5-trisubstituted s-triazinetriones obtained by cyclotrimerization of isocyanates

The synthesis of a number of s-triazine-2,4,6-triones (isocyanurates) by cyclotrimerization of 4-monoalkoxy-, 3,4-dialkoxy-, or 3,4,5-trialkoxyphenyl-, benzyl-, or styryl-isocyanates is reported. The thermal and phase behaviour of the novel compounds were investigated by optical polarized light microscopy and thermal analysis. No mesophase could be observed for any of the precursors except 4-decyloxybenzoic acid. Mesophases of the isocyanurates were observed only in the series containing 3,4-dialkoxyphenyl moieties. A vinylene group between the inner s-triazine ring and the outer phenylene rings gives low melting points and enantiotropic mesophases for C₈ and longer alkyl chains. The phenylisocyanurates may exhibit a monotropic mesophase and normally have the highest melting points of the three types, whereas a methylene spacer suppresses formation of a mesophase. According to the textures observed, the mesophases are hexagonal columnar. This will have to be confirmed by X-ray scattering techniques.     

Nickel-catalyzed intermolecular codimerization of acrylates and alkynes

The linear codimerization of acrylates and alkynes to produce 1,3-dienes is successfully demonstrated using a nickel catalyst in association with 2-aminopyridine as an additive.     

Design and synthesis of 1,3,5-trisubstituted 1,2,4-triazoles as CYP enzyme inhibitors

A series of 1,3,5-trisubstituted 1,2,4-triazoles was designed and synthesized as potential inhibitors of steroidogenic CYP enzymes. The 1,2,4-triazole is part of the core structure fixing the geometry of the substances. A pyridine moiety was introduced as heme-binder. The target compounds were synthesized in two to four steps using silver carbonate mediated ring closure and Suzuki cross coupling reaction as key synthetic transformations. Biological testing of the synthesized compounds for the inhibition of the most important steroidogenic CYPs revealed compounds 29a and 30 as moderate inhibitors of aldosterone synthase (CYP11B2).     

A new simple synthesis of 3,5-disubstituted 1-amino-1,3,5-triazine-2,4,6-triones from ethoxycarbonylhydrazones and isocyanates

The 3,5-disubstituted 1-amino-1,3,5-triazine-2,4,6-triones were synthesized in good yields from aromatic aldehyde or ketone ethoxycarbonylhydrazones by treatment with aryl or methyl isocyanates in boiling triethylamine followed by hydrolysis with hydrochloric acid solution.     

Synthesis of 1,3,5-trisubstituted 1,2,4-triazolio-4-nitroimides

A method for the synthesis of 1,3,5-trisubstituted 1,2,4-triazolio-4-nitroimides was developed. The method is based on the alkylation of the corresponding salts of 3,5-disubstituted 4-nitramino-1,2,4-triazoles.     

Diastereoselective synthesis of 1,3,5-trisubstituted 4-nitropyrrolidin-2-ones via a nitro-Mannich/lactamization cascade

A versatile one-pot nitro-Mannich/lactamization cascade for the direct synthesis of 1,3,5-trisubstituted 4-nitropyrrolidin-2-ones has been developed. The reaction is easy to perform and broad in scope, and high levels of diastereoselectivity can be achieved.     

Fluorous synthesis of hydantoins and thiohydantoins

[reaction: see text] A fluorous synthesis of hydantoins is introduced. The reaction of perfluoroalkyl (Rfh)-tagged amino esters with an isocyanate is followed by the cyclization of ureas and simultaneous cleavage of the fluorous tag to afford hydantoins. The product purification is performed by solid-phase extraction over FluoroFlash cartridges, and no fluorous solvent is involved in either the reaction or the separation processes. The same method applies to synthesis of thiohydantoins.     

Nickel-catalyzed coupling of isocyanates with 1,3-iodoesters and halobenzenes: a novel method for the synthesis of imide and amide derivatives

Substituted imide and amide derivatives were conveniently prepared from the reaction of isocyanates with o-iodobenzoates and haloarenes catalyzed by the NiBr2(dppe)/dppe/Zn system in moderate to good yields with excellent tolerance of functional groups.     

Efficient synthesis of 1,3,5-trisubstituted benzenes via three Pd-mediated carbon-sulfur, carbon-nitrogen and carbon-carbon bond formation reactions

An efficient synthesis of 1,3,5-trisubstituted benzenes via a sequential Pd-mediated carbon-sulfur, carbon-nitrogen, and carbon-carbon bond formation reactions is reported. Selective amidation and sulfonamidation reactions are accomplished via Pd-catalyzed reactions between aryl chlorides and an acetamide or a methanesulfonamide.     

TBPA+·mediated aromatization of 1,3,5-trisubstituted pyrazolines

1,3,5-Trisubstituted pyrazolines were oxidized to the corresponding pyrazoles in high yield with tris(4-bromophenyl)aminium (TBPA ·) hexachloroantimonate in chloroform at room temperature.     

Nickel-catalyzed synthesis of five-membered heterocycles

In recent decades, a large number of reports related to the synthesis of N-, O- and S-containing heterocycles have appeared owing to a wide variety of their biological activity. The investigation of methods for the chemical synthesis is a growing area of interest due to increasing environmental issues. The use of catalysts in organic reactions has gained extensive interest. Metal and nonmetal catalysts provided a new improved alternative to traditional methods in modern synthetic chemistry. The aim of present review is to focus on the applications of nickel for the synthesis of five-membered heterocylces.     

Nickel-catalyzed synthesis of phosphonium salts

The nickel-catalyzed synthesis of phosphonium salts from aryl halides and triphenylphosphine is reported.The formation of phosphonium salts occurs by the oxidative addition reaction of Ni[P(C₆H₅)₃]₃ on the aryl halides and reaction of the coordinated aryl groups with triphenylphosphine.The influence of substituents on the aromatic nucleus is studied.