Imidazole Fragment Research Articles

One-Pot Enantioselective Michael-Aldol Approach to Imidazole Derivatives

Reported is the highly diastereo- and enantioselective one-pot Michael-aldol reaction of α,β-unsaturated aldehydes 1 with imidazoles 2 to give fused heterocycles 3. The reaction is proposed to proceed first via an intermolecular Michael addition, followed by an intramolecular ­aldol reaction. Both steps are mediated by the same organocatalyst. Aromatic α,β-unsaturated aldehydes participate efficiently in the reaction, regardless of electronic character and substitution pattern. Aliphatic aldehydes gave inferior results (65-67% yield). High yields of products were also obtained irrespective of substitution on the imidazole fragment. Excellent diastereo- and enantioselectivities were observed in all cases, and the absolute configuration of one example was proved by X-ray crystallographic analysis. A mechanism is proposed without evidence.

Reaction of 5-(2-furyl)-1-methyl-1H- and 1-methyl-5-(2-thienyl)-1H-imidazoles with electrophilic reagents

5-(2-Furyl)-1-methyl-1H- and 1-methyl-5-(2-thienyl)-1H-imidazoles were synthesized. The electronwithdrawing effect of the 5- and 2-imidazole substituents on the furan ring was studied by 1H NMR spectroscopy and quantum-chemical calculations. Some electrophilic substitution reactions were investigated (nitration, bromination, sulfonation, hydroxymethylation, formylation, and acylation). In some cases, depending on the reaction conditions, both the furan and thiophene ring and the imidazole fragment undergo electrophilic attack.

Diaqua[5,5′-dicarboxy-2,2′-(ethane-1,2-diyl)bis(1H-imidazole-4-carboxylato)]cobalt(II)

In the title complex, [Co(C12H8N4O8)(H2O)2], the CoII atom is coordinated by two N and two O atoms of the tetra­dentate 5,5′-dicarb­oxy-2,2′-(ethane-1,2-di­yl)bis­(1H-imidazole-4-carboxy­l­ate) anion. The slightly distorted octa­hedral coordination environment is completed by the O atoms of two water mol­ecules in axial positions. An intra­molecular O—H⋯O hydrogen bond between the carb­oxy and carboxyl­ate groups stabilizes the mol­ecular configuration. Adjacent mol­ecules are linked through O—H⋯O and N—H⋯O hydrogen bonds between the carb­oxy/carboxyl­ate groups, water mol­ecules and imidazole fragments into a three-dimensional network.

Uracyl derivatives functionalized with N-, S-, O-heterocycles

Reactions of 1,3-bis(bromopentyl)-5(6)-substituted uracyls with a series of five-membered heterocycles containing in the ring N, S, or O atoms and a mercapto group as a substituent at the carbon atom of the ring afforded uracyl derivatives of acyclic and macrocyclic structure with 2-thiobenzoxazole, 2-thio-5-methyl-1,3,4-thiadiazole, 2-thiobenzimidazole, and 2,5-dithio-1,3,4-thiadiazole fragments. N atoms of benzoxazole and imidazole fragments of compounds obtained undergo alkylation and quaternization with alkyl iodides and alkyl tosylates.

Comparative Study of Thermal Degradation of N-vinylimidazole/Phenoxy- and Methoxyethylmethacrylate Copolymers

Copolymerization reactions involving N-vinylimidazole and its derivatives have stimulated great interest due to the wide possibilities of the preparation of new materials, including the synthetic analogues of biopolymers with imidazole fragments. The role of the imidazole group in polymers is very important, especially due to the high thermal stability at elevated temperatures when it is copolymerized with methacrylates, which contain highly electronegative atoms like oxygen [10,11]. Accordingly, copolymers of N-vinylimidazole with phenoxy- and methoxyethylmethacrylate have been prepared and subjected to thermogravimetric analysis to discover their thermal stability. Copolymers are also characterized by FTIR and 1H-NMR spectroscopic methods. Results show that the thermal stability is greater for N-vinylimidazole-co-phenoxyethylmethacrylate than for those with N-vinylimidazole-methoxyethylmethacrylate.

New assembly of transition metal complexes based on [GeW9O34]10− building blocks: Syntheses, crystal structures and magnetic properties

Two new polyoxotungstates Na 3 H(C 3 H 5 N 2 ) 4 [{Cu(C 3 N 2 H 4 ) 2 } 2 Cu 4 (H 2 O) 2 (GeW 9 O 34 ) 2 ]·27H 2 O ( 1 ) and Na 10 H 10 [Mn 6 Ge 3 W 24 O 94 (H 2 O) 2 ]·37H 2 O ( 2 ) have been synthesized. Complex 1 is a Weakley-type species capped by two [Cu(C 3 N 2 H 4 ) 2 ] 2+ units on two opposite W 4 O 4 faces, which is the first case of the copper(II)–imidazole fragment coordinated with four bridging oxygen atoms from sandwich-type polyoxotungstogermanates. Complex 2 is a banana-shaped POM consisting of two tri-Mn substituted [Mn 3 GeW 9 O 34 ] 4− Keggin units and a hexavacant bridging cluster [GeW 6 O 26 ] 12− . Two new polyoxotungstates Na 3 H(C 3 H 5 N 2 ) 4 [{Cu(C 3 N 2 H 4 ) 2 } 2 Cu 4 (H 2 O) 2 (GeW 9 O 34 ) 2 ]·27H 2 O ( 1 ) and Na 10 H 8 [Mn 6 Ge 3 W 24 O 94 (H 2 O) 2 ]·37H 2 O ( 2 ) have been synthesized in aqueous solution. The polyoxoanion frameworks of the two compounds are built on the lacunary Keggin-type polyanion [GeW 9 O 34 ] 10− . The structure of compound 1 is a Weakley-type species capped by two [Cu(C 3 N 2 H 4 ) 2 ] 2+ units through four bridging oxygen atoms on two opposite W 4 O 4 faces. Compound 2 is a banana-shaped polyoxometalate consisting of two tri-Mn substituted [Mn 3 GeW 9 O 34 ] 4− Keggin units and a hexavacant bridging cluster [GeW 6 O 26 ] 12− . The magnetic investigations demonstrate the presence of both antiferromagnetic and ferromagnetic exchange interactions for 1 and weak antiferromagnetic interactions for 2 .

Bis[2-(benzimidazol-2-ylsulfanyl)acetato]bis(2,2′-bipyridine)cadmium(II)

In the structure of the title compound, [Cd(C9H7N2O2S)2(C10H8N2)2], the complex mol­ecules are located on a crystallographic twofold rotation axis and the CdII ion is octa­hedrally coordinated by two chelating 2,2′-bipyridine ligands and two O atoms from the carboxyl­ate groups of two 2-(benzimidazol-2-ylsulfan­yl)acetate ligands. The two carboxyl­ate ligands adopt a cis configuration with respect to each other. Within each of these ligands, the imidazole fragments are bent back in a loop towards the acetyl groups, forming intra­molecular N—H⋯O hydrogen bonds, which help to stablilize the mononuclear complex. Adjacent mol­ecules are further linked by weak C—H⋯O hydrogen bonds, resulting in a chain along the c axis.

The hydrogen bond in thermal strengthening of aramid systems containing polyamide-benzimidazole fragments

An IR-spectroscopic study was conducted in aramid systems containing benzamide and benzimidazole fragments which allowed evaluating the character and magnitude of the enthalpy of formation of intermolecular hydrogen bonds under the effect of high temperatures. Strengthening of the H bond in benzimidazole groups and weakening of the bond in benzamide (benzimidole) groups were demonstrated. The possible co-existence of imidole-quinoid groups with benzamide and imidazole fragments was established. Polarization studies of the oriented state demonstrated high anisotropy of absorption for most vibrations in the 400-4500 cm -1 region.

1-(1H-Benzimidazol-1-ylmethyl)-3-[2-(diisopropylamino)ethyl]-1H-benzimidazolium bromide 0.25-hydrate

The title N-heterocyclic carbene derivative, C23H30N5 +·Br−·0.25H2O, was synthesized using microwave heating and was characterized by 1H and 13C NMR spectroscopy and a single-crystal X-ray diffraction study. The structure of the title compound are stabilized by a network of intra- and inter­molecular C—H⋯Br hydrogen-bonding inter­actions. The crystal structure is further stabilized by π–π stacking inter­actions between benzene and imidazole fragment rings of parallel benzo[d]imidazole rings, with a separation of 3.486 (3) Å between the centroids of the benzene and imidazole rings. There is also an inter­molecular C—H⋯π inter­action in the crystal structure. The C—N bond lengths for the central benzimidazole ring are shorter than the average single C—N bond, thus showing varying degrees of double-bond character and indicating partial electron delocalization within the C—N—C—N—C fragment. The isopropyl group is disordered over two sites with occupancies of 0.792 (10) and 0.208 (10).

Imidazole–imidazole stacking in some inorganic complexes

Reaction of CuCl 2 · 2H 2O with the 1:1 condensate (L) of 2-(2-aminoethyl)pyridine and 1-methyl-2-imidazolecarboxaldehyde in methanol yields monomeric CuLCl 2.H 2O ( 1). Recrystallisation of 1 from aqueous methanol medium containing excess of PF 6 − affords the 1D coordination polymer [CuLCl] n (PF 6) n ( 2). A chloride bridge results in the coordination polymer. A face-to-face interaction is observed between the imidazole rings in 2. The interaction influences the structure and magnetic properties of 2 markedly. The complex 2 is ferromagnetic with a J value of 1.79 ± 0.01 cm −1. The imidazole fragments in 2 are coordinated to the metal. In mononuclear [ HgL 2 ″ ] (ClO 4) 2, where L′′ is the 1:2 condensate of ethylenediamine and 1-methyl-2-imidazolecarboxaldehyde, the imidazolyl moieties are not under the direct influence of the metal. Here the imidazole – imidazole interaction is angular and more distant.

Polyfused nitrogen heterocycles: XIX. Oxidative imidazo-fusion of 3-benzoylquinoxalin-2-ones with benzylamines in the synthesis of bis(imidazo[1,5-a]quinoxalin-1- and -5-yl) derivatives

Oxidative cyclocondensation of bis(3-benzoylquinoxalin-1-yl)alkanes and oxaalkanes with benzylamine and 3-benzoylquinoxalinones with m-xylylenediamine proceeded with the formation of bis-(imidazo[1,5-a]quinoxalinyl) derivatives where the hetaryl fragments were linked by a spacer both through the imidazole and quinoxaline fragments

Synthesis of 3,4-dihydro-2H-imidazo-[2,1-b][1,3,4]thiadiazines

Thiomethylene-active derivatives of N-imidazolylimines undergo intramolecular cyclization to give 3,4-dihydro-2H-imidazo[2,1-b][1,3,4]thiadiazines. This reaction is a new convenient method for the fusion of a dihydrothiadiazine ring to an imidazole fragment through formation of a C-C bond.

{(R)-1,1′-Bis(1-naphthylmethyl)-3,3′-[1,1′-binaphthyl-2,2′-diyldi(oxyethylene)]di-1H-imidazol-2-yl}mercury(II) bis(hexafluoridophosphate) acetonitrile 3.5-solvate

In the title compound, [Hg(C52H42N4O2)](PF6)2·3.5CH3CN, the linear coordination geometry of the Hg ion [C—Hg—C = 174.4 (2)°] is formed by two C atoms from the imidazole fragments [Hg—C = 2.072 (6) and 2.090 (6) A]. The crystal packing exhibits weak inter­molecular C—H⋯F and C—H⋯N hydrogen bonds.

1-Methylimidazol-2-yl-functionalized cyclopentadienyl titanium and zirconium complexes. Crystal structure of [η 5:η1-C5H4CPh2CH2-(1-MeC3H2N2)]TiCl3

The new side-chain functionalized cyclopentadienyl ligand LiC5H4CPh2CH2R (R is 1-methylimidazol-2-yl) as lithium salt 2, the trimethylsilyl derivative Me3SiC5H4CPh2CH2R (3), and the ligand in the CH form (4) were prepared starting from 6,6-diphenylfulvene and 1,2-dimethylimidazole lithiated at the 2-Me group (1) and then characterized. The half-sandwich complexes (η5:η 1-C5H4CPh2CH2R)TiCl3 (5) and (η5:η 1-C5H4CPh2CH2R)ZrCl3 (6) were synthesized. The molecular structure of complex 5 was established by X-ray diffraction. Complexes 5 and 6 exhibit dynamic behavior in solution associated with degenerate interconversion of the pseudo-six-membered metallacycle. For titanium complex 5 in a solvating solvent, a dynamic process due to intramolecular dissociation—coordination of the imidazole fragment was observed.

Synthesis of the first imidazolyl-triphosphines containing a Triphos unit

Since biphasic liquid–liquid continuous-flow catalytic processes often require the use of cationic phosphine ligands for the metal sequestration in the polar phase, we have prepared the first imidazolyl triphosphines, named Triphosim and Triphosmim. These ligands contain the Triphos unit [-P(CH 2CH 2PPh 2)] which is linked to the imidazole fragment and have been obtained in three steps from imidazole (or 2-methylimidazole), diethylvinylphosphonate and diphenylvinylphosphine with global yields of 42–48%. The Triphosim ligand adopts a tridentate P-coordination mode in a palladium dichloride complex and the reaction of the dangling imidazole function with alkyl halides leads to a new kind of imidazolium-phosphine complexes.

Explorations on the Total Synthesis of the Unusual Marine Alkaloid Chartelline A

In work directed toward a total synthesis of chartelline A (1a), a strategy was investigated to construct the 10-membered ring of this marine alkaloid via an intramolecular aldehyde/beta-lactam cyclocondensation to form the macrocyclic enamide functionality. Therefore, spiro-beta-lactam and imidazole fragments were first prepared. Tribromooxindole beta-lactam 24 was synthesized from commercially available 5-nitroisatin (18) in seven steps and 30% overall yield via a Staudinger ketene-imine [2 + 2]-cycloaddition strategy. The requisite 2-bromoimidazole subunit 40 bearing a terminal alkyne and a masked aldehyde was efficiently prepared from the readily available imidazole ester 25 in 10 steps. With both advanced intermediates available, the addition of the lithium acetylide generated from 2-bromoimidazole subunit 40 to the gamma-lactam carbonyl group of N-Boc-tribromooxindole 24 was investigated, affording the desired N-Boc-aminal 41. Hydrolysis of the acetonide moiety of 41, followed by oxidative cleavage of the resulting diol, gave the aldehyde 42. Unfortunately, treatment of aldehyde 42 with p-toluenesulfonic acid did not give the desired 10-membered macrocyclic (Z)-enamide 46, but rather the highly unsaturated seven-membered ring compound 44.

Gas-Phase Structure of Protonated Histidine and Histidine Methyl Ester: Combined Experimental Mass Spectrometry and Theoretical ab Initio Study

Gas-phase H/D exchange experiments with CD3OD and D2O and quantum chemical ab initio G3(MP2) calculations were carried out on protonated histidine and protonated histidine methyl ester in order to elucidate their bonding and structure. The H/D exchange experiments show that both ions have three equivalent fast hydrogens and one appreciably slower exchangeable hydrogen assigned to the protonated amino group participating in a strong intramolecular hydrogen bond (IHB) with the nearest N(sp2) nitrogen of the imidazole fragment and to the distal ring NH-group, respectively. It is taken for granted that the proton exchange in the IHB is much faster than the H/D exchange. Unlike in other protonated amino acids (glycine, proline, phenylalanine, tyrosine, and tryptophan) studied earlier, the exchange rate of the carboxyl group in protonated histidine is slower than that of the amino group. The most stable conformers and the enthalpies of neutral and protonated histidine and its methyl ester are calculated at the G3(MP2) level of theory. It is shown that strong intramolecular hydrogen bonding between the amino group and the imidazole ring nitrogen sites is responsible for the stability and specific properties of the protonated histidine. It is found that the proton fluctuates between the amino and imidazole groups in the protonated form across an almost vanishing barrier. Proton affinity (PA) of histidine calculated by the G3(MP2) method is 233.2 and 232.4 kcal mol(-1) for protonation at the imidazole ring and at the amino group nitrogens, respectively, which is about 3-5 kcal mol(-1) lower than the reported experimental value.

Coupling properties of imidazole dimer radical cation assisted by embedded water molecule: Toward understanding of interaction character of hydrogen-bonded histidine residue side-chains

Geometry optimizations are performed at the DFTB3LYP6-311+G* level. Four intriguing coupling modes, totally eight stable structures are found in the potential energy surfaces of the water-assisted coupling of imidazole dimer radical cation. In these isomers, the water molecules are embedded between two imidazole moieties, and the oxygen atom is tridentate or quadridentate, respectively. The distinct redshifts of the vibrational frequencies of the O-H...N and N-H...O type H bonds indicate the strong interaction of two imidazole rings of respective isomer. Inspection of the highest occupied molecular orbital predicts the alterations of the geometry structures on oxidation and reduction. The low barrier of the fragment rotation demonstrates that the isomerization processes by experiencing the distinct transition states are easy to fulfill, especially for those with O-H...N and C-H...O H bonds. Both the energy difference of the 0 degrees-cis and 180 degrees-trans orientation and the barriers of the fragment rotation are lowered by the water assisting. The range of the zero point vibrational energy correction indicates that the influence on the complexes with N-H...O and O-H...N H bonds (0.13-0.17 kcal/mol) is more significant than those with O-H...N and C-H...O H bonds (+/-0.03 kcal/mol). The dissociation energies of these isomers indicate that the charges transfer easily through water in the dissociation process and then are distributed mainly over the imidazole ring connecting with water molecule. The isomer with proton transfer between imidazole fragments is the most stable one.

A second polymorph of 4,5-diphenyl-1H-imidazole

The title compound, C15H12N2, (II)(499), contains two mol­ecules in the asymmetric unit and is a polymorphic form of a previously reported structure, (I)(495), of the same mol­ecule. The mol­ecules in both polymorphs exhibit nearly identical bond distances, but show significantly different phenyl/imidazole dihedral angles and pack differently in the crystalline state. In each polymorph, strong hydrogen-bonded polymer chains, involving the N atoms of the imidazole fragments in adjacent mol­ecules, are formed.

1,2-dimethyl-4-nitro-5-morpholinoimidazole and its hydrate: a case of a centrosymmetric-noncentrosymmetric ambiguity.

The compound studied is 1,2-dimethyl-4-nitro-5-morpholinoimidazole (1) in its anhydrous (1) and hydrated [(1).H(2)O] crystal forms. In spite of the strong electron-withdrawing effect of the nitro group, the unsubstituted N atom of the imidazole moiety retains its basic character and acts as an acceptor for intermolecular hydrogen bonds: either weak C-H....N bonds in (1) or strong O-H...N bonds, with the water molecules, in (1).H(2)O. The packing in (1) is determined by weak C-H.N and C-H.O hydrogen bonds, van der Waals interactions and the stacking of imidazole fragments. The crystal structure of (1).H(2)O is determined by strong O-H(water)...N3(imidazole) and O-H(water)...O(water) hydrogen bonds. This structure consists of a centrosymmetric 'matrix' of imidazole derivative molecules and locally noncentrosymmetric arrays of hydrogen-bonded water molecules. Each of these arrays is strictly homodromic, i.e. it runs only in one direction:.H-O....H-O....H-O.... or....O-H....O-H....O-H.... These homodromic domains are statistically distributed within the crystal.