Copper(II) complexes derived from substituted 2,2′-bis-(4-isopropyl-4-methyl-4,5-dihydro-1H-imidazol-5-one) ligands: Synthesis,structure and catalytic activity

New chiral N,N-bidentate 2,2′-bis-(4-isopropyl-4-methyl-4,5-dihydro-1H-imidazol-5-one) ligands have been prepared and characterised by their ¹H and ¹³C NMR spectra and/or optical rotation. The ligands prepared were then tested for their ability to form complexes with copper(II) salts. It was found that the most stable complex is formed from the 2,2′-bis-(4-isopropyl-1,4-dimethyl-4,5-dihydro-1H-imidazol-5-one) ligand and copper(II) chloride. The structure of this complex was determined by means of quantum-chemical computations at the B3LYP or UB3LYP/6-31G(d,p) level. According to the computations, the geometry of the copper atom most resembles a tetrahedral arrangement, which was also confirmed by means of X-ray structural analysis. It was found that the structure of this copper(II) complex does not allow the copper atom to coordinate to additional ligands; therefore, it is catalytically inactive in the asymmetric Henry reaction.     

New chiral ligands and iron(III) complexes based on 2,6-bis(1-benzyl-4-isopropyl-4-methyl-4,5-dihydro-1H-imidazol-5-on-2-yl)pyridines

New ligands and their complexes with iron(III) chloride have been suggested and prepared: (R,S)-, (R,R)- and (S,S)-2,6-bis(1-benzyl-4-isopropyl-4-methyl-4,5-dihydro-1H-imidazol-5-on-2-yl) pyridines. Both the ligands and their complexes were characterised by ¹H and ¹³C NMR spectroscopy, optical rotation and X-ray diffraction.     

Unusual result of the reaction of 4-(1-methyl-1H-imidazol-2-yl)methylene-substituted 2-alkylthioimidazol-5(4H)-one with copper(ii) chloride

A reaction of potassium ({(4Z)-4-[(1-methyl-1H-imidazol-2-yl)methylene]-5-oxo-1-phenyl-4,5-dihydro-1H-imidazol-2-yl}thio)acetate with copper(II) chloride in methanol leads to bis(5-anilino-7-methoxycarbonyl-1-methyl-1H-imidazo[1,2-c]pyrimidin-4-ium) tetrachloro-cuprate(II), whose structure was confirmed by the X-ray diffraction studies.     

Synthesis of 7-iodo(arylsulfanyl)methyl-7,8-dihydro-[1,3]thiazolo[2,3-i]purinium pentaiodide (perchlorates) and their transformation into 4-amino-5-(1,3-thiazol-2-yl)imidazole derivatives

Intramolecular electrophilic cyclization of 6-allylsulfanylpurine by the action of iodine and arenesulfenyl chlorides gave 7-iodomethyl-7,8-dihydro[1,3]thiazolo[2,3-i]purin-6-ium pentaiodide and 7-arylsulfanylmethyl-7,8-dihydro[1,3]thiazolo[2,3-i]purin-6-ium perchlorates, respectively. 7-Iodomethyl-7,8-dihydro-[1,3]thiazolo[2,3-i]purin-6-ium iodide reacted with sodium and potassium alkoxides to produce alkyl N-[5-(4-methyl-1,3-thiazol-2-yl)-1H-imidazol-4-yl]formimidates, and its reaction with secondary cyclic amines afforded 5-(4-methyl-1,3-thiazol-2-yl)-N-[morpholin-4-yl(or piperidin-1-yl)methylidene]-1H-imidazol-4-amines. Successive treatment of 7-arylsulfanylmethyl-7,8-dihydro[1,3]thiazolo[2,3-i]purin-6-ium perchlorates with sodium acetate and morpholine led to the formation of 5-(4-arylsulfanylmethyl-4,5-dihydro-1,3-thiazol-2-yl)-N-(morpholin-4-ylmethylidene)-1H-imidazol-4-amines.     

Structure and catalytic activity of organopalladium(II) complexes based on 4,5-dihydro-1H-imidazol-5-one derivatives

The paper describes preparation of a chiral bidentate ligand - 2-(2-bromophenyl)-4,5-dihydro-1H-imidazol-5-one, and a tridentate ligand - 2-bromo-1,3-bis(4,5-dihydro-1H-imidazol-5-on-2-yl)benzene, whose oxidative addition reaction with Pd(0) giving neutral organopalladium(II) complexes has been studied. The structure of these complexes was studied by means of NMR spectroscopy and X-ray diffraction. After transformation of the neutral organopalladium(II) complexes into the corresponding ionic species the latter were studied as enantioselctive catalysts for asymmetric Friedel-Crafts alkylation and Michael addition.     

Synthesis,Structure and Cytotoxicity Testing of Novel 7-(4,5-Dihydro-1H-imidazol-2-yl)-2-aryl-6,7-dihydro-2H-imidazo[2,1-c][1,2,4]triazol-3(5H)-Imine Derivatives

The appropriate 1-arylhydrazinecarbonitriles 1a–c are subjected to the reaction with 2-chloro-4,5-dihydro-1H-imidazole (2), yielding 7-(4,5-dihydro-1H-imidazol-2-yl)-2-aryl-6,7-dihydro-2H-imidazo[2,1-c][1,2,4]triazol-3(5H)-imines 3a–c, which are subsequently converted into the corresponding amides 4a–e, 8a–c, sulfonamides 5a–n, 9, ureas 6a–I, and thioureas 7a–d. The structures of the newly prepared derivatives 3a–c, 4a–e, 5a–n, 6a–i, 7a–d, 8a–c, and 9 are confirmed by IR, NMR spectroscopic data, as well as single-crystal X-ray analyses of 5e and 8c. The in vitro cytotoxic potency of these compounds is determined on a panel of human cancer cell lines, and the relationships between structure and antitumor activity are discussed. The most active 4-chloro-N-(2-(4-chlorophenyl)-7-(4,5-dihydro-1H-imidazol-2-yl)-6,7-dihydro-2H-imidazo[2,1-c][1,2,4]triazol-3(5H)-ylidene)benzamide (4e) and N-(7-(4,5-dihydro-1H-imidazol-2-yl)-2-(p-tolyl)-6,7-dihydro-2H-imidazo[2,1-c][1,2,4]triazol-3(5H)-ylidene)-[1,1′-biphenyl]-4-sulfonamide (5l) inhibits the growth of the cervical cancer SISO and bladder cancer RT-112 cell lines with IC₅₀ values in the range of 2.38–3.77 μM. Moreover, N-(7-(4,5-dihydro-1H-imidazol-2-yl)-2-phenyl-6,7-dihydro-2H-imidazo[2,1-c][1,2,4]triazol-3(5H)-ylidene)-4-phenoxybenzenesulfonamide (5m) has the best selectivity towards the SISO cell line and induces apoptosis in this cell line.     

The synthesis and characterisation of N-(1-carbamoyl-1,1-dialkyl-methyl)-(S)-prolinamides and related pyrrolidin-2-yl-4,5-dihydro-1H-imidazol-5-ones as potential enantioselective organocatalysts

The acylation of substituted 2-aminopropanamides with (2S)-Boc-proline, (2S)-Cbz-proline and (2S)-Bn-proline was used to prepare substituted 1-protected N-(1-carbamoyl-1,1-dialkyl-methyl)-(S)-prolinamides (74-89%), whose subsequent deprotection gave N-(1-carbamoyl-1,1-dialkyl-methyl)-(S)-prolinamides (94-95%). The enantiomerically pure N-(1-carbamoyl-1,1-dialkyl-methyl)-(S)-prolinamides obtained were tested as organocatalysts for the aldol reaction of cyclohexanone with 4-nitrobenzaldehyde, with yields ranging from 38% to 79% ee. The highest enantioselectivity (89% ee) was achieved by catalysis with N-(1-carbamoyl-cyclopentyl)-(S)-prolinamide (methanol, l0% HCl). By the action of sodium methoxide, Boc-N-(1-carbamoyl-cyclopentyl)-(S)-prolinamide was quantitatively cyclised to 2-(1-Boc-pyrrolidin-2-yl)-1,3-diazaspiro[4.4]non-1-en-4-one, which was accompanied by racemisation at the stereogenic centre of the proline skeleton. Alternatively, the substituted 4,4-dialkyl-2-pyrrolidin-2-yl-4,5-dihydro-1H-imidazol-5-ones were prepared by oxidation of 4,4-dialkyl-2-((2S)-1-Boc-pyrrolidin-2-yl)-4,5-dihydro-1H-imidazolidin-5-ones (54-69%). In an acid medium, 2-pyrrolidin-2-yl-1,3-diazaspiro[4.4]non-1-en-4-one and (4S)-4-isopropyl-4-methyl-2-pyrrolidin-2-yl-4,5-dihydro-1H-imidazol-5-one underwent racemisation. Conversely, the free base of (2S)-2-pyrrolidin-2-yl-1,3-diazaspiro[4.4]non-1-en-4-one very easily underwent oxidation to give the achiral 2-(4,5-dihydro-3H-pyrrol-2-yl)-1,3-diazaspiro[4.4]non-1-en-4-one.     

Synthesis of 2-thioxoimidazolines via reaction of 1-unsubstituted 3-aminoquinoline-2,4-diones with isothiocyanates

3-Alkyl/aryl-3-amino-1H,3H-quinoline-2,4-diones react with alkyl/aryl isothiocyanates to give 3a-alkyl/aryl-1,2,3,3a-tetrahydro-9b-hydroxy-2-thioxo-5H-imidazo[4,5-c]quinolin-4(9bH)-ones in high yields. These compounds rearrange in boiling acetic acid or concd hydrochloric acid to give novel 4-(2-aminophenyl)-1H-imidazole-2(3H)-thiones, 1,3-bis(2-(2,3-dihydro-2-thioxo-1H-imidazol-5-yl)phenyl)ureas and minor N-(2-(2,3-dihydro-2-thioxo-1H-imidazol-4-yl)phenyl)acetamides. In the presence of ethanol, the starting compounds rearrange in boiling acetic acid to give ethyl 2-(2,3-dihydro-2-thioxo-1H-imidazol-4-yl)phenylcarbamates. All compounds were characterized by their ¹H, ¹³C, IR and MS spectra and some of them also by ¹⁵N NMR data. The structures of two compounds were supported by single-crystal X-ray diffraction.     

Iron(II) complexes of 2,6-bis(5-alkyl-1,5-dimethyl-4,5-dihydro-1H-imidazol-4-on-2-yl)pyridine ligands. Synthesis, characterisation and solvolytic stability

New 2,6-bis(5-alkyl-1,5-dimethyl-4,5-dihydro-1H-imidazol-4-on-2-yl)pyridines have been prepared and characterized by ¹H-, ¹³C-NMR and elemental analysis. These ligands form complexes with FeCl₂, which were isolated and characterized by elemental analysis and MS. Both in the solid phase and in aqueous and methanolic solutions the complexes have two ligand molecules per one ferrous ion. By means of the kinetic stopped-flow method, the rate constants of acid catalyzed decomposition, which proceeds as a system of two consecutive reactions, were determined. It was found that increasing steric demands of 5-alkyl substituent in the 4,5-dihydro-1H-imidazol-4-one cycle significantly retards the acid catalyzed solvolysis. The methyl derivative is solvolyzed cca two orders faster than the corresponding t-Bu derivative.     

Molecular rearrangement of 1-substituted 9b-hydroxy-3,3a,5,9b-tetrahydro-1H-imidazo[4,5-c]quinoline-2,4-diones—an unexpected pathway to new indole and imidazolinone derivatives

1-Substituted 3a-alkyl/aryl-9b-hydroxy-3,3a,5,9b-tetrahydro-1H-imidazo[4,5-c]quinoline-2,4-diones and 3′-substituted 3-alkyl/aryl-3-ureido-1H,3H-quinoline-2,4-diones react in boiling acetic acid to give 2-alkyl/aryl-1H-indol-3-yl-ureas and/or 1,3-bis[2-(2-oxo-2,3-dihydro-1H-imidazol-4-yl)-phenyl]-ureas. By the action of hydrochloric acid, the first of them rearrange to give 4-(2-aminophenyl)-1,3-dihydroimidazol-2-ones. The structure of 1,3-bis[2-(2-oxo-2,3-dihydro-1H-imidazol-4-yl)-phenyl]-ureas was confirmed by their synthesis. All compounds were characteried by their ¹H NMR, ¹³C NMR, IR spectra, atmospheric pressure chemical ioniation mass spectra, and some of them also by ¹⁵N NMR spectroscopic data.     

Synthesis and biotests of 2-aryl-5-arylmethylidene-substituted 1,3-oxazol-5(4<Emphasis Type="Italic">H</Emphasis>)-ones and <Emphasis Type="Italic">N</Emphasis>-methyl-3,5-dihydro-4<Emphasis Type="Italic">H</Emphasis>-imidazol-4-ones as combretastatin A-4 analogs

A series of 2-aryl-5-arylmethylidene-1,3-oxazol-5(4H)-ones and 2-aryl-5-arylmethylidene-N-methyl-3,5-dihydro-4H-imidazol-4-ones was synthesized as structural analogs of combret- astatin A-4 (a compound possessing antitumor activity). (5Z)-5-[(4-Methoxyphenyl)methyl-idene]-3-methyl-2-(4-methylphenyl)-3,5-dihydro-4H-imidazol-4-one was found to exhibit the highest cytotoxicity against cells of human A549 lung carcinoma line (EC₅₀ = 6±0.8 μmol L^?1).     

Synthesis and Anticholinesterase Activity of [(4<Emphasis Type="Italic">Z</Emphasis>)-2-Aryl-4-(arylmethylidene)-5-oxo-4,5-dihydro-1<Emphasis Type="Italic">H</Emphasis>-imidazol-1-yl]alkanoic Acids

ω-[(4Z)-2-Aryl-4-arylmethylidene-5-oxo-4,5-dihydro-1H-imidazol-1-yl]alkanoic acids were synthesized by reaction of N-substituted α,β-dehydropeptides with chloro(trimethyl)silane or 1,1,1,3,3,3-hexamethyldisilazane. Both initial peptides and (4H)-imidazol-5-one derivatives based thereon were tested for anticholinesterase activity.     

Heterospin complexes based on dinuclear CuII triketonate and nitroxides

Heterospin complexes of bis(μ₂-1,1,2,2,8,8,9,9-octafluorononane-3,5,7-trionato)dicopper(II) ([Cu₂L₂]) with nitronyl nitroxides 2-(1-methyl-1H-pyrazol-4-yl)-4,4,5,5-tetramethyl-4,5-dihydro-1H-imidazole-1-oxyl 3-oxide (2) and 4,4,5,5-tetramethyl-2-(3-pyridinyl)-4,5-dihydro-1H-imidazole-1-oxyl 3-oxide (1) were synthesized and structurally characterized. Crystals of the complexes are formed by the discrete bis[1-methyl-4-(4,4,5,5-tetramethyl-3-oxide-1-oxyl-4,5-dihydro-1H-imidazol-2-yl)-1H-pyrazole]-bis (μ₂-1,1,2,2,8,8,9,9-octafluorononane-3,5,7-trionato)dicopper(II) etherate (3) and bis[3-(4,4,5,5-tetramethyl-3-oxide-1-oxyl-4,5-dihydro-1H-imidazol-2-yl)pyridine]-bis (μ₂-1,1,2,2,8,8,9,9-octafluorononane-3,5,7-trionato)dicopper(II) (4) molecules. Each Cu atom of the dinuclear chelate fragment coordinates one paramagnetic ligand through the N atom of the pyrazole or pyridine fragment, respectively. In complex 3, the paramagnetic ligands are located on one side of the plane of the chelate fragment, whereas the ligands in complex 4 are located above and below the plane of the chelate fragment. The magnetic properties of complexes 3 and 4 are determined by dominant antiferromagnetic exchange interactions between the unpaired electrons of the Cu^II atoms in the dinuclear Cu₂L₂ moiety. Dedicated to Academician O. M. Nefedov on the occasion of his 75th birthday. Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 11, pp. 1836–1840, November, 2006.     

Molecular structures of methyl 4-[(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)methyl]-1-methyl-1H-pyrazol-5-carboxylate and methyl 4-[(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)methyl]-1-methyl-1H-pyrazol-3-carboxylate

The structure of methyl 4-[(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)methyl]-1-methyl-1H-pyrazol-5-carboxylate is determined by X-ray crystallography and further used to elucidate the structure of methyl 4-[(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)methyl]-1-methyl-1H-pyrazol-3-carboxylate, using the data of homo- and heteronuclear 2D NMR correlation spectroscopy.     

A systematic study of ligand intermolecular interactions in crystals of copper(II) complexes of bidentate guanidino derivatives

The synthesis and X-ray structures of four neutral copper(II) complexes and one cationic complex incorporating bidentate alkyl N-(4-oxo-5,5-diphenyl-4,5-dihydro-1H-imidazol-2-yl)imidocarbamate ligands are reported. The neutral complexes, which possess potential doublet (DA) hydrogen bonding motifs, form supramolecular structures based on synthons involving hydrogen bonding or phenyl embraces. The formation of sheets within the crystal through combination of these synthons, and the occurrence of guest molecules trapped in cavities between the sheets, are described. The cationic complex forms an extended hydrogen-bonded structure that incorporates nitrate ions. The structures of the five complexes are compared with others reported previously for complexes of related ligands.     

Synthesis 5-(pyrazolin-3-ylmethylidene)-2-thiohydantoins and 2-alkylsulfanyl-5-(pyrazolin-3-ylmethylidene)-3,5-dihydro-4<Emphasis Type="Italic">H</Emphasis>-imidazol-4-ones

A reaction of 3-allyl- and 3-phenylthiohydantoins with 1,5-diphenyl- and 1-phenyl-substituted 3-formyl-2-pyrazolines was used to obtain a series of 5-(pyrazolin-3-ylmethylidene)-2-thioxotetrahydro-4H-imidazol-4-ones, the subsequent alkylation of which with methyl iodide or ethyl chloroacetate gave the corresponding 2-alkylthio-5-(pyrazolin-3-ylmethylidene)-3,5-dihydro-4H-imidazol-4-ones in the yields from 30 to 77%. The oxidation of (5Z)-3-phenyl-5-[(1,5-diphenylpyrazolin-3-yl)methylidene]-2-methylsulfanyl-4,5-dihydroimidazol-4-one with lead tetraacetate led to the corresponding pyrazole in 48% yield.     

Synthesis of novel isoxazolines and isoxazoles of N-substituted pyrazolo[3,4-d]pyrimidin-4(5H)-one derivatives through [3+2] cycloaddition

3,6-Dimethyl-1-phenyl-1H-pyrazolo[3,4-d]pyrimidin-4(5H)-one 3 was prepared by an intramolecular cyclization of N-(4-cyano-3-methyl-1-phenyl-1H-pyrazol-5-yl) acetamide 2 in ethanol in the presence of piperidine. N-allylation and N-propargyl alkylation of N-substituted pyrazolo[3,4-d] pyrimidin-4(5H)-one 3 yielded the corresponding dipolarophiles 4 and 5 which afford by condensation with arylnitrile oxides in toluene the expected new isoxazolines 6 and isoxazoles 7, respectively. On the other hand, the aminopyrazole 1 in refluxing with ethanol in the presence of sodium hydroxide afforded the corresponding carboxamide 8, which then, was converted to its ethyl 3-methyl-4-oxo-1-phenyl-4,5-dihydro-1H-pyrazolo[3,4-d] pyrimidine-6-carboxylate 9 with neat diethyl oxalate. The dipolarophile 10 on regiospecific 1,3-dipolar cycloaddition with arylnitrile oxides affords isoxazoles 11 and the unexpected deethoxycarbonylated isoxazoles 12. The target compounds were completely characterized by ¹H NMR, ¹³C NMR, IR and HRMS.     

Synthesis of 4-(2-hydroxy-1-methyl-5-oxo-1H-imidazol-4(5H)-ylidene)-5-oxo-1-aryl-4,5-dihydro-1H-pyrrole-3-carboxylates, a new triazafulvalene system

(2E,3Z)-2-(1-Methyl-2,5-dioxoimidazolidin-4-ylidene)-3-[(arylamino- or heteroarylamino)methylene]succinate 5 obtained by [2+2] cycloaddition of (5Z)-5-[(dimethylamino)methylene]-3-methylimidazolidine-2,4-dione (1) and dimethyl acetylenedicarboxylate (2) followed by substitution of the dimethylamino group with aromatic or heteroaromatic amines, afforded by heating in ethanol in the presence of potassium hydroxide, potassium salts 6. Acidification of 6 with hydrochloric acid afforded mixtures of (E)- and (Z)-isomers of methyl 4-(2-hydroxy-1-methyl-5-oxo-1H-imidazol-4(5H)-ylidene)-5-oxo-1-phenyl-4,5-dihydro-1H-pyrrole-3-carboxylates. On the other hand, alkylation of compounds 6 with methyl iodide or benzyl bromide produced the corresponding methyl (E)-4-(2-methoxy- or 2-benzyloxy-1-methyl-5-oxo-1H-imidazol-4(5H)-ylidene)-5-oxo-1-phenyl-4,5-dihydro-1H-pyrrole-3-carboxylates 9, derivatives of a new triazafulvalene system.     

Imidazolyl derivatives of the chroman ring 3

The synthesis of 2-methyl-3-(1-methyl-1H-imidazol-2-yl)-4H-1-benzopyran-4-ones 4 is described starting from 2-acetoxybenzoyl chlorides and 1,2-dimethylimidazole. Chromones 4 undergo alkaline ring opening to the corresponding 1-(2-hydroxyphenyl)-2-(1-methyl-1H-imidazol-2-yl)ethenols 5 which give ring closure to 2-substituted 3-(1-methyl-1H-imidazol-2-yl)-4H-1-benzopyran-4-ones or 2,3-dihydro-3-(1-methyl-1H-imidazol-2-yl)-4H-1-benzopyran-4-ones. The corresponding chromanols and chromenes can be easily obtained from chromones 4 .     

Development of an N-heterocyclic carbene ligand based on concept of chiral mimetic

Development of a new N-heterocyclic carbene ligand based on the concept of a chiral mimetic is described. In Pd-catalyzed enantioselective intramolecular α-arylation of N-(2-bromophenyl)-N-methyl-2-arylpropanamide, (4R,5R)-4,5-diphenyl-1,3-diadamantylmethyl-4,5-dihydro-3H-imidazol-1-ium tetrafluoroborate is shown to function as a good N-heterocyclic carbene precursor.