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A synthesis of dispiro derivatives from 5-methylidene-2-chalcogenimidazolones and azomethine ylides generated from isatins and N-substituted α-amino acids has been developed.
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... It may be noted that the 1 H, 13 C (and 19 F NMR in cases where the compounds contained fluorine) spectra of all ortho-phenyl-N(3)-substituted spiro-imidazolones (for example, compounds 35, 46, and 51, see Supplementary Information, Figures S23, S63, and S87 and similar) demonstrate two sets of signals. This can be explained by the hindered rotation around the single bond C(Ar)-N(imidazolone) of the imidazolone fragment and, consequently, the existence of each ortho-phenyl-substituted spirocompounds as two atropisomers (axially chiral heterocyclic analogs of biaryl derivatives similar to those described for others ortho-substituted 2-thiohydantoins) [25][26][27]. The NMR spectra of these compounds at ambient temperatures do not indicate the presence Different results of the reaction of diene 25 with hydantoin 1 and thiohydantoins 2, 3, 5, 6, 8-10 in the presence of ZnI 2 may be due to the fact that ZnI 2 as a soft Lewis acid is predominantly coordinated to the sulfur atom of 2-thioimidazolone, and varying the chalcogen (O or S) strongly affects the efficiency of binding the dienophile to the Lewis acid. ...
... It may be noted that the 1 H, 13 C (and 19 F NMR in cases where the compounds contained fluorine) spectra of all ortho-phenyl-N(3)-substituted spiro-imidazolones (for example, compounds 35, 46, and 51, see Supplementary Information, Figures S23, S63, and S87 and similar) demonstrate two sets of signals. This can be explained by the hindered rotation around the single bond C(Ar)-N(imidazolone) of the imidazolone fragment and, consequently, the existence of each ortho-phenyl-substituted spiro-compounds as two atropisomers (axially chiral heterocyclic analogs of biaryl derivatives similar to those described for others ortho-substituted 2-thiohydantoins) [25][26][27]. The NMR spectra of these compounds at ambient temperatures do not indicate the presence of intramolecular dynamic processes, apparently due to the high barrier to internal rotation. ...
Novel hydantion and thiohydantoin-based spiro-compounds were prepared via theDiels–Alder reactions between 5-methylidene-hydantoins or 5-methylidene-2-thiohydantoins and 1,3-dienes (cyclopentadiene, cyclohexadiene, 2,3-dimethylbutadiene, isoprene). It was shown that the cycloaddition reactions proceed regioselectively and stereoselectively with the formation of exo-isomers in the reactions with cyclic dienes andthe less sterically hindered products in the reactions with isoprene. Reactions of methylideneimidazolones with cyclopentadiene proceed viaco-heating the reactants; reactions with cyclohexadiene, 2,3-dimethylbutadiene, and isoprene require catalysis by Lewis acids. It was demonstrated that ZnI2 is an effective catalyst in the Diels–Alder reactions of methylidenethiohydantoins with non-activated dienes. The possibility of alkylation and acylation of the obtained spiro-hydantoinsat the N(1)nitrogen atoms with PhCH2Cl or Boc2O and the alkylation of the spiro-thiohydantoinsat the S atoms with MeI or PhCH2Cl in high yields have been demonstrated. The preparativetransformation of spiro-thiohydantoins into corresponding spiro-hydantoinsin mild conditions by treating with 35% aqueous H2O2 or nitrile oxide has been carried out. The obtained compounds show moderate cytotoxicity in the MTT test on MCF7, A549, HEK293T, and VA13 cell lines. Some of the tested compounds demonstrated some antibacterial effect against Escherichia coli (E. coli) BW25113 DTC-pDualrep2 but were almost inactive against E. coli BW25113 LPTD-pDualrep2.
Cycloaddition of N‐benzylazomethine methylide with various arylidene‐azolones is able to synthesize promising series of substituted spirocyclic structures that are highly attractive for design of biologically active compounds. Systematic study of the scope and stereochemical outcome of proposed [3+2]‐cycloaddition are performed. Reaction in almost all cases produce single isomers of spirocyclic products in excellent yields, which stereochemistry is probably thermodynamically determined. image
The established strategy unveils a metal and mediator‐free electrochemical [3+2] cycloaddition approach among α‐amino carbonyls and tosylmethyl isocyanide (TosMIC) fabricating substituted imidazole scaffolds. Implementation of electro‐redox conditions on this cycloaddition approach eliminates the essential requirement of transition metal catalysts and chemical oxidants. A wide variety of different functionalities are well tolerated under this reaction condition, contributing to the substrate scope and applicability. Several control experiments and cyclic voltammetry studies suggest an electro‐oxidation triggered successive C−C and C−N bond formations followed by rapid aromatization for constructing the five‐membered core structure.
Nitrogen-containing heterocyclic compounds are some of the most significant that are produced artificially or naturally. These heterocyclic rings are virtually always present in biological systems, from the smallest eukaryotes to...
