One‐Pot Synthesis of 1,2,4,5‐Tetrasubstituted Imidazoles in Ionic Liquid

The four‐component condensation of benzil, aromatic aldehyde, primary amine, and ammonium acetate catalyzed by TFA in ionic liquid [Bpy]BF₄ at 80°C provided 1,2,4,5‐tetrasubstituted imidazoles in moderate to high yields.     

One‐Pot Synthesis of 2,4,5‐Triphenyl Imidazoles from 1,2‐Diols as Key Reagents

A simple one‐pot procedure for the preparation of 2,4,5‐triphenyl imidazole derivatives is presented. The procedure involves the lead tetraacetate oxidation of 1,2‐diols to give aldehydes in situ , which then undergo a three‐component reaction with benzil and ammonium acetate to yield the imidazole derivatives.     

Catalytic Enantioselective α‐Fluorination of 2‐Acyl Imidazoles via Iridium Complexes

The first highly enantioselective α‐fluorination of 2‐acyl imidazoles utilizing iridium catalysis has been accomplished. This transformation features mild conditions and a remarkably broad substrate scope, providing an efficient and highly enantioselective approach to obtain a wide range of fluorine‐containing 2‐acyl imidazoles which are found in a variety of bioactive compounds and prodrugs. A large scale synthesis has also been tested to demonstrate the potential utility of this fluorination method.     

Catalytic Asymmetric Michael Reaction of 5H‐Oxazol‐4‐Ones with α,β‐Unsaturated Acyl Imidazoles

The asymmetric Michael reaction between 5H‐oxazol‐4‐ones and α,β‐unsaturated acyl imidazoles is reported. A novel 2‐benzo[b]thiophenyl‐modified chiral ProPhenol species is synthesized and used as a ligand, leading to good enantioselectivities in this asymmetric conjugate addition reaction. Furthermore, the introduction of phenol additives as achiral co‐ligands is found to improve the reaction’s chemical yields, diastereoselectivities, and enantioselectivities.     

The One‐Pot Synthesis of 2,4,5‐Triaryl‐Imidazoles Using Heteropolyacids as Heterogeneous and Recyclable Catalysts

2,4,5‐triaryl imidazoles were obtained in high yields with excellent purity from the condensation of benzaldehydes, NH₄OAc and 1,2‐diketone in the presence of a catalytic amount of various heteropolyacids (HPAs).     

A Transition‐Metal‐Free Synthesis of Multisubstituted Imidazoles

A novel and simple t‐BuOLi/I₂‐mediated synthesis of 1,2,4‐trisubstituted imidazoles was developed without transition‐metal added. The transition‐metal‐free strategy tolerated a range of substrates and provided products in moderate to good yields with 100% regioselectivity.     

Light‐Induced Direct Arylation in the Solid Crystalline State as a Strategy Towards π‐Expanded Imidazoles

π‐Expanded imidazoles bearing the 2‐iodophenyl substituent at position 2 undergo direct photoinduced intramolecular arylation in the solid, crystalline state leading to large non‐planar heterocycles. An analogous reaction employing 2‐bromophenyl and 2‐chlorophenyl substituents is considerably slower. Such processes have never before been demonstrated to occur in crystals and have allowed the efficient synthesizes of structurally unique compounds containing either the phenanthro[9′,10′:4,5]imidazo[1,2‐f]phenanthridine moiety or structurally related skeletons. The reaction occurs in the thin crystalline layers irradiated with UV photons in an almost quantitative manner over 48–72 h. Several previously unknown architectures have been prepared using this methodology. Furthermore, the optical properties of these π‐expanded imidazoles can be altered with the addition of heteroatoms and/or electron‐donating groups.     

Rh/Lewis Acid Catalyzed Regio‐, Diastereo‐ and Enantioselective Addition of 2‐Acyl Imidazoles with Allenes

A highly regio‐, diastereo‐ and enantioselective addition of 2‐acyl imidazoles or 2‐acyl pyridines with allenes promoted by Rh/Lewis acid synergistically catalytic system is described. This atom economic approach leads to the formation of the branched allylic alkylated products including acyclic quaternary all‐carbon stereogenic centres in good yields with good to excellent diastereo‐ and enantioselectivities. Kinetic studies reveal that the rate‐determining step in this process is the oxidative addition of Rh(I) with C—H bond.     

Synthesis of Glucuronic,Mannuronic, and Galacturonic Acid‐Derived Imidazoles as Inhibitors of Bovine Liver β‐Glucuronidase

The gluco‐, manno‐, and galacto‐configured imidazopyridine‐5‐carboxylates 5 – 7 , respectively, were synthesized and evaluated as inhibitors of bovine liver β‐glucuronidase. The gluconolactam 15 was transformed into the gluco‐ and manno‐imidazoles 5 and 6 in nine steps and in an overall yield of 9 and 12%, respectively. Oxidation and esterification of the selectively protected gluco‐ and manno‐configured hydroxymethyl‐imidazopyridines 23 and 25 , respectively (both obtained from gluconolactam 15 ), provided the benzhydryl esters 24 and 26 , respectively. Hydrogenolysis afforded the gluco‐imidazopyridine‐carboxylic acid 5 and the manno‐isomer 6 . Similarly, the hydroxymethyl‐imidazopyridine 33 , obtained from galactonolactam 27 , was subjected to oxidation, esterification, and deprotection to afford the galacto‐configured imidazopyridine‐carboxylate 7 in ten steps from the galactonolactam 27 and in an overall yield of 13%. The gluco‐configured imidazole 5 is the strongest known inhibitor of β‐glucuronidases (K_i = 12 nM ), while the manno‐ and galacto‐configured imidazoles 6 and 7 are micromolar inhibitors of bovine β‐glucuronidase. The small difference between the inhibitory strength of the imidazopyridine‐carboxylic acid 5 and the tetrazolopyridine‐carboxylic acid 1 , and the difference between the configurational selectivity of 5 – 7 as compared to the unselectivity of the corresponding lactams 3 and 4 are discussed.     

Rhodium(III)/Amine Synergistically Catalyzed Enantioselective Alkylation of Aldehydes with α,β‐Unsaturated 2‐Acyl Imidazoles

A synergistic catalysis combination of chiral‐at‐metal rhodium complex and amine catalyst was developed for enantioselective alkylation of aldehydes with α,β‐unsaturated 2‐acyl imidazoles. The corresponding adducts were obtained in good yields with excellent enantioselectivities (up to 99% ee).     

pH‐Dependent Optical Properties of Synthetic Fluorescent Imidazoles

New pH‐sensitive probe design : A peek into the structure of fluorescent proteins led to the synthesis of fluorescent imidazoles. The prepared compounds demonstrated an array of remarkable pH‐dependent optical properties including at least two types of excited‐state charge transfers (see picture).

     

Transition‐Metal‐Free Synthesis of N‐(1‐Alkenyl)imidazoles by Potassium Phosphate‐Promoted Addition Reaction of Alkynes to Imidazoles

The addition reaction of alkynes to N‐heterocycles by simply heating in DMSO with potassium phosphate is reported. Good yields with high stereoselectivity could be achieved for a range of substrates. The scope is quite general for both amines and phenylacetylenes. In addition, internal alkynes and α‐bromostyrene were also examined in this reaction. This process is efficient and useful for the synthesis of (Z)‐N‐(1‐alkenyl)imidazoles and related Z products. Thus, the reaction is useful because of the importance of the imidazole scaffold.     

8‐Hydroxyquinoline Functionalized PEG‐1000 Bridged Dicationic Ionic Liquid as a Novel Ligand for Copper‐catalyzed N‐Arylation of Imidazoles

A novel 8‐hydroxyquinoline functionalized PEG‐1000 bridged dicationic ionic liquid ([HQ‐PEG₁₀₀₀‐DIL][BF₄]) was synthesized and characterized. It was applied as an efficiently recyclable ligand for copper‐catalyzed N‐arylation of nitrogen‐containing heterocycles with aryl halides. The catalytic system could be easily recovered and reused for at least five runs without obvious loss of catalytic activity.     

New Method for Synthesis of Multi‐substituted Imidazoles

Here, we reported two methods for the synthesis of multi‐substituted imidazoles, firstly via four‐component cyclocondensation reaction of benzil, aliphatic amines (allylamine or pentylamine), and aromatic aldehyde and ammonium acetate. Using an ionic liquid catalyst namely, diethyl ammonium hydrogen sulfate, and under solvent‐free conditions. Secondly, via the alkylation of synthesized NH imidazoles with alkyl halide (allyl bromide and pentyl bromide) gave 8a–c in high yield (average 90%), the products can be purified by a non‐chromatographic method, and these newly synthesized compounds have been characterized by spectral data: FTIR, IR, ¹H, ¹³C nuclear magnetic resonance, the elemental analysis, and the X‐ray structure.     

Copper(I) complex of 1,3‐DimethylBarbituric acid modified SBA‐15 and its catalytic role for the synthesis of 2,3‐Dihydroquinazolin‐4(1H)‐ones and Imidazoles

An efficient one‐pot method for synthesis of 2,3‐dihydroquinazolin‐4(1H)‐ones and tri/tetra substituted‐1H‐imidazoles has been accomplished in the presence of catalytic amounts of Cu(I)‐1,3‐dimethylbarbituric acid modified SBA‐15 as heterogeneous catalyst with good to excellent yields. The catalyst is reusable and can be applied several times without any decrease in product yield. The synthesized catalyst was characterized by scanning electron microscopy (SEM), X‐ray diffraction (XRD), energy dispersive X‐ray spectroscopy (EDS), thermal gravimetric analysis (TGA), N₂ adsorption/desorption isotherms (BET), Fourier transform infrared spectroscopy (FT‐IR) and atomic absorption spectroscopy (AAS).     

Synthesis of 1,2,4,5‐Tetrasubstituted Imidazoles Using Sulfuric Acid ([3‐(3‐Silicapropyl)sulfanyl]propyl]ester as a Recyclable Solid Acid

Sulfuric acid ([3‐(3‐silicapropyl)sulfanyl]propyl]ester (SASPSPE) is used as a recyclable catalyst for the synthesis of 1,2,4,5‐tetrasubstituted imidazoles. A range of various polysubstituted imidazoles was synthesized via four‐component condensation of benzil, aldehydes, amines, and ammonium acetate in the presence of SASPSPE under solvent‐free conditions at 140°C. The heterogeneous catalyst was recycled for five runs on the reaction of benzil, 4‐methylbenzaldehyde, benzyl amine, and ammonium acetate without losing its catalytic activity.     

Enantioselective Alkynylation of 2‐Trifluoroacetyl Imidazoles Catalyzed by Bis‐Cyclometalated Rhodium(III) Complexes Containing Pinene‐Derived Ligands

Chiral rhodium(III) complexes containing two cyclometalating 2‐phenyl‐5,6‐(S,S)‐pinenopyridine ligands and two additional acetonitriles are introduced as excellent catalysts for the highly enantioselective alkynylation of 2‐trifluoroacetyl imidazoles. Whereas the ligand‐based chirality permits the straightforward synthesis of the complexes in a diastereomerically and enantiomerically pure fashion, the metal‐centered chirality is responsible for the asymmetric induction over the course of the catalysis. For comparison, the analogous iridium congeners provide only low enantioselectivity, and previously reported benzoxazole‐ and benzothiazole‐based catalysts do not show any catalytic activity for this reaction under standard reaction conditions.     

从Baylis-Hillman溴化物方便的合成N-取代的咪唑和苯并三氮唑

在室温下, 通过Baylis-Hillman溴化物与咪唑或苯并三氮唑反应, 方便的合成了N-取代的咪唑和苯并三氮唑衍生物. 该方法的优点为操作简单, 反应条件温和, 产率高, 好的区域和立体选择性.