Parallel Solid-Phase Synthesis of disubstituted 3-(1H-benzo[d]imidazol-2-yl)imidazolidine-2,4-diones and 3-(1H-benzo[d]imidazol-2-yl)-2-thioxoimidazolidin-4-ones

A multistep approach to construct novel 3-(1H-benzo[d]imidazol-2-yl)imidazolidine-2,4-diones and 3-(1H-benzo[d]imidazol-2-yl)-2-thioxoimidazolidin-4-ones from commercially available amino acids, amines, and carboxylic acids is described. Coupling of Fmoc-amino acid to resin-bound aminobenzimidazole provided following Fmoc elimination free amine. Treatment of the free amine with 1,1′-carbonyldiimidazole or 1,1′-thiocarbonyldiimidazole furnished the corresponding hydantoins and thiohydantoins via intramolecular cyclization. The desired aminobenzimidazole tethered hydantoins or thiohydantoins were isolated in good yields.     

Different synthetic routes to 4-(1H-benzo[d]imidazol-2-yl)aniline

The benzimidazole nucleus is an important pharmacophore in drug discovery, being a good bioisostere of naturally occurring nucleotides. This heterocycle may represent a type of privileged substructure which can interact with proteins and enzymes; it has, hence, been extensively utilized as a drug scaffold in medicinal chemistry. The connection between wide ranging biological activity and compounds containing the benzimidazole nucleus is known, and well documented in the literature. Benzimidazole derivatives have a multitude of interesting pharmacological activity, including antiviral, antitumor, antihypertensive, proton pump inhibitory, anthelmintic, antimicrobial, and anti-inflammatory activity. Accordingly, a brief survey is given below covering the synthesis of 2-phenybenzimidazole derivatives and their biological importance.     

Synthesis,Crystal Structure and Luminescent Property of Cadmium Complex Based on 2-（2-（1Hbenzo[d]imidazol-2-yl）benzyl）-1H-benzo[d]-imidazole

The complex [Cd(bbb)Cl2]·DMF·H2O, where bbb is 2-(2-(1H-benzo[d]imidazol-2-yl)benzyl)-1H-benzo[d]imidazole, was synthesized and characterized by X-ray single-crystal structure analyses. For the complex: C24H25Cl2CdN5O2, Mr = 598.77, crystal system, triclinic, space group P1, a = 9.9878(12), b = 10.0008(12), c = 13.2217(15) , α = 80.674(2), β = 72.158(2), γ = 86.776(2)°, V = 1240.5(3) 3, Z = 2, Dc = 1.598 g/cm3, λ = 0.71073, μ(MoKα) = 1.127 mm–1, F(000) = 600, S = 1.04, R = 0.0905 and wR = 0.3088 for 4805 observed reflections with I 2σ(I). It is a neutral complex. The distorted tetrahedral geometry of cadmium ion is coordinated by two nitrogen atoms of ligand and two chloride ions. The complex emits blue green luminescence with emission peaks at 480 nm in DMF solution.     

Synthesis,Crystal Structure and Luminescent Property of a Dinuclear Cadmium Complex Based on 2-(2-(1H-Benzo[d]imidazol-2-yl)-phenyl)-1-phenyl-1H-benzo[d]imidazole

A dinuclear cadmium complex [Cd_2(bppb)Cl_4×2DMF](1), where bppb is 2-(2-(1 Hbenzo[d]imidazol-2-yl)phenyl)-1-phenyl-~1 H-benzo[d]imidazole, was synthesized and characterized by X-ray single-crystal structure analyses. For 1: C_(58) H_(50) Cd_2 Cl_4 N_(10) O_2, M_r = 1285.68, monoclinic system, space group P2_1/n, a = 16.136(3), b = 10.612(2), c = 16.270(3) ?, β = 96.209(2)°, V = 2769.7(9) ?~3, Z = 2, D_c = 1.542 g/cm~3, λ = 0.71073 ?, μ(Mo Kα) = 1.013 mm~(–1), F(000) = 1296, S = 1.055, R = 0.0393 and wR = 0.1185 for 4876 observed reflections with I 2σ(I). One 9 mium ion which is five-coordinated by three chloride ions and two nitrogen atoms from bppb. Two cadmium ions are bridged by two chloride ions. The Cd_2(bppb)_2 Cl_2(μ-Cl_2) decomposes at 350 ℃ which is much lower by 70 ℃ than [Cd_2(bpbb)_2 Cl_2(μ-Cl_2)](420 ℃). The complex emits blue luminescence in both DMF solution and solid powder. Phenyl ring substituting NH hydrogen atom of benzimidazole group in ligand can not obviously change the UV-vis and luminescence spectra peaks location of the benzimidazole cadmium complex.     

A fluorescent probe for both pH and Zn2+ based on 2-(1-phenyl-1H-benzo[d]imidazol-2-yl)phenol

A sensitive fluorescent probe 2-(1-phenyl-1H-benzo[d]imidazol-2-yl)phenol (HBIZ) for pH and Zn2+ has been developed. Great changes have taken place in the UV-vis absorption and fluorescence spectra for HBIZ upon increasing pH of its aqueous solution, acting as a pH-induced emission "off-on-off" switch with large enhancement factors of ～290 and ～75 over the pH range of 1.00-5.40 and 5.20-10.40. A over 100-fold fluorescence enhancement was also observed after complexation of HBIZ to Zn2+ in N,N-dimethylformamide.     

Synthesis,Spectroscopic and Computational Analysis of 2-[(2-Sulfanyl-1H-benzo[d]imidazol-5-yl)iminomethyl]phenyl Naphthalene-2-sulfonate

Russian Journal of Organic Chemistry - 2-[(2-Sulfanyl-1H-benzo[d]imidazol-5-yl)iminomethyl]phenyl naphthalene-2-sulfonate was obtained as a result of the reactions of...     

Facile,catalyst-free,microwave-assisted access toward the synthesis of 2-aryl/alkyl-3-(1H-benzo[d]imidazol-2-yl)-2, 3-dihydroquinazolin-4(1H)-ones

An efficient, catalyst-free, microwave-assisted approach has been developed for the synthesis of 2-aryl/alkyl-3-(1H-benzo[d]imidazol-2-yl)-2,3-dihydroquinazolin-4(1H)-one derivatives by condensing 2-aminobenzamides with various aliphatic, aromatic, and heterocyclic aldehydes. This catalyst-free approach exhibited good functional group compatibility and produced the desired products in good to excellent yields in just 10–20?min. This approach can be seen as a better alternative of the metal-catalyzed protocols used for the synthesis of this class of compounds. The formation of desired compound has also been confirmed by X-ray analysis.     

In silico guided designing of 4-(1H-benzo[d]imidazol-2-yl)phenol-based mutual-prodrugs of NSAIDs: synthesis and biological evaluation

ABSTRACT

The free COOH group of conventional NSAIDs is a structural feature for non-selective cyclooxygenase (COX) inhibition and the molecular cause of their gastrointestinal (GI) toxicity. In this context, an in house database of synthesizable ester prodrugs of some well-known NSAIDs was developed by combining their -COOH group with -OH of a newly identified antioxidant 4-(1H-benzo[d]imidazol-2-yl)phenol (BZ). The antioxidant potential of BZ was unveiled through in silico PASS prediction and in vitro/in vivo evaluation. The in house database of NSAIDs-BZ prodrugs was first subjected to screening with our previously reported pharmacophore models of hCES1 (AAHRR.430) and hCES2 (AHHR.21) for determining hydrolytic susceptibility. Biotransformation behaviour of screened prodrugs was then assessed by using QM/MM and sterimol parameterization, followed by ADMET calculations to predict the drug likeness. On the basis of in silico results, five prodrugs were duly synthesized and the best three were subject to the in vivo evaluation for their anti-inflammatory, analgesic, antioxidant activities, and ulcerogenic index. Among these prodrugs, BN₂ and BN₅ displayed better anti-inflammatory and analgesics potential in comparison to their parent drugs. All the prodrugs were found to be gastro sparing in the rat model and significantly improved the levels of oxidative stress biomarkers in both blood plasma as well as gastric homogenate.     

N-(4-芳基-噻唑-2-基)--(1H-苯并三唑-1-基)苯乙酮腙类衍生物的合成

以苯并三唑为原料与-溴代芳基乙酮缩合得-(1H-苯并三唑-1-基)芳基乙酮, 再与硫代氨基脲缩合得到新的缩氨基硫脲. 然后分别与5种ω-溴代芳基乙酮环化得到一系列新的含苯并三唑和噻唑环的苯乙酮腙类Schiff碱. 其结构经IR, ¹H NMR, ¹³C NMR和MS及元素分析确证.     

Palladium-catalyzed annulation of 2-(aryldiazenyl) aniline with dimethyl sulfoxide to access N-aryl-1H-benzo[d]imidazol-1-amine

A palladium-catalyzed annulation of 2-(aryldiazenyl) aniline and dimethyl sulfoxide was developed to access N-aryl-1H-benzo[d]imidazol-1-amine in moderate to good yields. Activated by 1,4-diazabicyclo[2.2.2]octane bis(sulfur dioxide) adduct (DABSO), DMSO served as a “CH” fragment during this procedure. It represents a facile pathway leading to benzimidazoles.     

Anion and pH-regulated assembly of three Cd(II) coordination polymers based on 3,5-di(1H-benzo[d]imidazol-1-yl)benzoate

Three coordination polymers, {[CdI(DBBA)]?0.5H₂O}_n (1, DBBA = 3,5-di(1Hbenzo[d]imidazol-1-yl)benzoate), [Cd(DBBA)(CH₃COO)]_n (2) and [Cd(DBBA)₂]_n (3), were obtained through reactions between Cd(II) salts and 3,5-di(1H-benzo[d]imidazol-1-yl)benzoic acid under different pH conditions. Compounds 1 and 2 are 3-D frameworks with rtl topology based on different binuclear Cd(II) secondary building units. Compound 3 was formed at lower pH and showed a 1-D chain assembled with M₂L₂ ring units. Moreover, phase purities, thermal behaviors, and photoluminescent properties have also been investigated.     

(S)-2-(吡咯烷基-2)-1-苯并咪唑的合成及其对Aldol反应的催化作用

L-脯氨酸与邻苯二胺反应合成了(S)-2-(吡咯烷基-2)-1-苯并咪唑(1),其结构经1HNMR和MS表征。1与X(酸或联萘酚)复配制得复合催化体系(1-X)。以丙酮和N-甲基靛红的Aldol反应为模板考察了1-X的催化活性。研究结果显示,除1-OTf的催化活性较低以外,其余1-X均具有较高的催化活性,最高产率高于99%。Aldol反应产物具有一定的手性过量,结合过渡态结构分析了手性过量的原因。     

Synthesis,Crystal Structure and Luminescent Property of a Dinuclear Cadmium Complex Based on 1,2,3,4-Tetra(1H-benzo[d]imidazol-2-yl)butane

A complex [Cd2(tbb)Cl4]·4DMF·3H2O, where tbb is 1,2,3,4-tetra(1H-benzo[d]imidazol-2-yl)butane, was synthesized and characterized by X-ray single-crystal structure analyses. For this complex: C44H49Cd2Cl4N12O7, Mr = 1224.55, monoclinic system, space group C2/c, a =29.563(3), b = 14.2580(17), c = 26.355(3) A, β = 97.036(2)°, V = 11025(2) A3, Z = 8, Dc = 1.475g/cm3, λ = 0.71073 A, μ(Mo Kα) = 1.021 mm–1, F(000) = 4936, S = 1.047, R = 0.0680 and wR =0.1832 for 11812 observed reflections with I 2σ(I). It is a neutral dinuclear complex. One1,2,3,4-tetra(1H-benzo[d]imidazol-2-yl)butane coordinates to two cadmium ions. Each cadmium ion is coordinated by two nitrogen atoms of tbb and two chloride ions. The complex emits blue luminescence in DMF solution as well as in solid powder state.     

Transition-metal-free insertion of benzyl bromides into 2-(1H-benzo[d]imidazol-1-yl)benzaldehyde: One-pot switchable syntheses of benzo[4,5]imidazo[1,2-a]quinolin-5(7H)-ones and 3-arylquinolin-4-ones mediated by base

A transition-metal-free insertion of benzyl group between aldehyde and imidazole of 2-(1H-benzo[d]imidazol-1-yl)benzaldehyde was achieved for the first time. Two diverse sets of quinolin-4-one derivatives: benzo[4,5]imidazo[1,2-a]quinolin-5(7H)-ones (2) and 3-arylquinolin-4-ones (3) were synthesized based on identical starting materials 2-(1H-benzo[d]imidazol-1-yl)benzaldehydes (1) and benzyl bromides. In the preparations, two key intermediates I and II were involved and might be synthesized in situ through the reaction of an intra-Breslow intermediate with benzyl bromide via an enol attack in the presence of base or a NHC-based enamine attack in the absence of base, respectively, in which the intra-Breslow intermediate might function as a nucleophilic reagent by following two novel different pathways.     

Synthesis,Crystal Structure and Luminescent Property of a Dinuclear Cadmium Complex Based on 1,2-Bis(1-phenyl-1H-benzo[d]imidazol-2-yl)benzene

A dinuclear cadmium complex [Cd_2(bpbb)_2Cl_2(μ-Cl_2)], where bpbb is 1,2-bis(1-phenyl-1H-benzo[d]imidazol-2-yl)benzene, was synthesized and characterized by X-ray singlecrystal structure analyses. Crystal data: C_(64)H_(44)Cd_2Cl_4N_8, M_r = 1291.67, triclinic system, space group P1, a = 10.076(3), b = 12.730(4), c = 13.176(4) ?, α = 99.087(3), β = 109.859(3), γ = 112.551(3)°, V = 1384.8(7) ?~3, Z = 1, D_c = 1.549 g/cm~3, λ = 0.71073 ?, μ(Mo Kα) = 1.010 mm~(–1), F(000) = 648, S = 1.062, R = 0.0425 and wR = 0.1130 for 9688 observed reflections with I 2s(I). One 1,2-bis(1-phenyl-1H-benzo[d]imidazol-2-yl)benzene coordinates to one cadmium ion. The cadmium is five-coordinated by three chloride ions and two nitrogen atoms from bpbb. Each cadmium ion is bridged by two chloride ions. The decomposition temperature is up to 420 ℃. The complex emits blue luminescence in DMF solution and in solid powder state.     

达比加群酯中间体3-【【【2-{[(4-氰基苯基)氨基]甲基}-1-甲基-1H-苯并咪唑-5-基】羰基】(吡啶-2-基)氨基】丙酸乙酯的合成

以对氨基苯腈为起始原料,经胺化反应制得N-(4-氰基苯基)甘氨酸(4);4与N-[3-氨基-4-(甲基氨基)苯甲酰基]-N-2-吡啶-β-丙氨酸乙酯(5)经酰胺化后经闭环反应,合成了达比加群酯的关键中间体——3-【【【2-{[(4-氰基苯基)氨基]甲基}-1-甲基-1H-苯并咪唑-5-基】羰基】(吡啶-2-基)氨基】丙酸乙酯,总收率79.6%,其结构经~1H NMR和ESI-MS确证。     

Pd(II)-Catalyzed Benzimidazole-Assisted Annulation of 3-(1H-Benzo[d]imidazol-2-yl)-2H-chromen-2-one: Access to Imidazo[1,2-a]chromeno[3,4-c]pyridine

Palladium-catalyzed [4+2] oxidative annulation of coumarin-benzimidazoles with olefins for the synthesis of polycyclic aromatic hydrocarbons have been achieved. This synthetic protocol gives access to a wide range of structurally distinct imidazo[1,2-a]chromeno[3,4-c]pyridines in moderate to good yield with wide functional group tolerance. Further, photophysical properties of annulated scaffolds have been examined, which discloses their interesting solvatochromic emission behaviors.