Functionalized imidazole

Novel cationic methyl and neutral methyl, chloro Pd11 complexes have been synthesized with various functionalized imidazole ligands. For the first time, structurally characterized examples of this type of Pd complex could be obtained. The chelate ligand is shown to adopt a boat conformation. Inversion of the chelate ring was established by NMR spectroscopy. Depending on electronic and steric features of the ligand, the complexes can act as catalysts in the CO/ethylene as well as the Fleck reaction.186... 

The crystal structure of the C-functionalized imidazole derivative of 1,5,9-triazcyclododecane (75) shows a five-coordinate zinc with four /V-donors from ligand and chloride in a distorted trigonal bipyramidal arrangement. The Zn—N imidazole bonds are the shortest at 2.025(3) A.678 Deprotonation of the imidazole group resulted in a bridging imidazolate to form dinuclear zinc complexes. The pATa of 10.3 varies from the pATa of bound water with similar ligands (as low as 7.3) and the complex is not catalytic for the hydrolysis of esters. 

Acetylated Meldrum s acid 172 and a-aminoesters 173 have been used as the building blocks to prepare the substituted imidazoles 174, which are then cyclized to give optically active dihydro products 175 <20030L3907> (Scheme 7). A modified four-component LJgi reaction has been used to prepare dihydro products 177 from the intermediate functionalized imidazole 176, isonitriles, and amines (Equation 24) <2005EJ04670>. 

All synthetic approaches to imidazo[2,l-f][l,2,4]triazines published during recent years utilize the ring closure of the six-membered triazine ring by conversion of a properly functionalized imidazole compound. 

Bazureau s group reported extensive work with TSILs for synthesis of various 4-thiazolidinones, 1,4-dihydropyridines, 3,4-dihydropyrimidin-2(lH)-ones and polyhydroquinones. They functionalized imidazole compounds with esters, which were then reacted with reagents to afford the target compound. They report that microwave dielectric heating is a useful aid to rapidly produce the desired product in high yields. 

By reacting N-functionalized imidazole-4,5-dicarboxylates 77 with guanidine-HCl and NaOMe/MeOH, Hosmane et al. prepared a series of ring-expanded nucleoside analogues 79 ( fat nucleobase analogues) (Equation 12), which... 

A number of specific functionalized imidazoles have been prepared by introduction of the substituents in the activated N-oxides followed by removal of the At-oxygen atom (2009JA3291) (Scheme 91). 

The same scheme was used by Canty et al.269 to synthesize a series of all nitrogen functionality, imidazole/pyrazole, imidazole/pyridine, and pyrazole/pyridine ligands (29-32). 

The highly functionalized imidazole 3 can be polymerized by active phosphite ester methods [4] to afford the A-B polyamide. The monomer is dissolved in a mixed solvent system of N-methylp3n rolidinone and pyridine containing dissolved lithium chloride. Upon addition of triphenyl phosphite, the reaction immediately takes on a yellow color. During the course of the polymerization, the color increases in intensity until the pol5rmerization mixture appears black. The products are isolated as fine yellow powders by precipitation in methanol followed by a methanol wash. 

The synthesis of saprisartan, reported by Judd and co-workers, used a Suzuki reaction as a key step to couple a benzofuran-based boronic acid with methyl 2-bromobenzoate in 30% yield. The resulting compound was then brominated and the methyl ester was hydrolyzed to produce the corresponding acid in 92% yield. Conversion of the acid to the Boc protected amine occurred with 18% yield. A second bromination, followed by substitution with a highly functionalized imidazole, gave the desired intermediate in 60% over two steps. Three additional steps were required to generate saprisartan in 1% overall yield. 

Similarly, several medicines or potential medicines have been made that contain imidazole. Structurally, the molecules can be vastly different and can affect very imique disease states. For example, metronidazole is an antibiotic effective against anaerobic bacteria, and it also acts as an anti-parasitic agent. It is a relatively simple functionalized imidazole. Cipralisant is a potent H3 receptor antagonist H3 antagonists are believed to have potential therapy to aid in sleep, cognition, food intake, and memory. ... 

From a disconnection perspective, the use of a-amido ketones is appealing for many functionalized imidazoles. However, it sometimes suffers from many steps and poor overall yields. Much development work has gone into the preparation of the amido-ketone. For example, the Merck group has published the preparation of substrates for cyclization using a Stetter-like multicomponent coupling reaction (MCR). ... 

A more direct route involves the treatment of a-amino-cyano-amide with a protected formamidimide. The reaction is reported to take place at ambient temperature and provide good yields of the 1,4,5-tri-substituted and more appropriately functionalized imidazole, which is subsequently transformed into temozolomide. ... 

Majhi, P.K., Sauerbrey, S., Schnakenburg, G., Arduengo, A.J., 111 and Streubel, R., S)mthesis of backbone P-functionalized imidazol-2-ylidene complexes En route to novel functional ionic liquids, Inorg. Chem. 51 (19), 10408-10416 (2012). 

Li et al. [83] also prepared blends fi om sPEEK and a variety of functionalized imidazoles. They evaluated the effect of the pKa of the added heterocycles on the unhumidified proton conductivities of the blend membranes over a temperature range from 40 to 150 °C. These membranes showed non-monotonous conductivities with respect to temperature and a clear correlation of the peak temperature conductivity with the pKa values of the heterocycles. The authors suggested a theoretical model based on the reaction equilibria between sPEEK sulfonic acid groups and the basicity of the added heterocycles in order to better tmderstand the mechanistic origins of the observed temperature-conductivity profiles. 

The additional stability gained because of the formation of a bidentate chelate ligand has been used to achieve imidazole to NHC tautomerization for a N-phosphane-functionalized imidazole in the presence of iridium and ruthenium " metal fragments (structure 22 in Fig. 15). An analogous activation occurred when 2-pyridylbenzimidazole is refluxed in THF with... 

Mendoza-Espinosa D, Donnadieu B, Bertrand G (2010) Synthesis of 4- tmd 4,5-functionalized imidazol-2-ylidenes from a single 4,5-unsubstituted imidazol-2-ylidene. J Am Chem Soc 132 7264-7265... 

Imidazole moiety, being a part of the side chain in histidine plays a major role in biological activity of many peptides and proteins. Several functionalized imidazole derivatives exhibit pharmacological property and play... 

Tagaki, W., Ogino, K., Fujita, T., Yosbida, T., Nishi, K. Inaba, Y. Hydrolytic metalloenzyme models catalysis in the hydrolysis of p-nitrophenyl 2-pyridine-carboxylate by copper and zinc ion complexes of anionic surfactants having functional imidazole and hydroxyl moieties. Bull. Chem. Soc. Jpn. 1993, 66(1), 140-147. 

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