Highly selective synthesis of 4(5)-aryl-, 2,4(5)-diaryl-, and 4,5-diaryl-1H-imidazoles via Pd-catalyzed direct C-5 arylation of 1-benzyl-1H-imidazole (original) (raw)
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ChemInform, 2005
A variety of 1,5-diaryl-1H-imidazoles have been regioselectively synthesized by direct coupling of 1-aryl-1H-imidazoles with aryl iodides or bromides in DMF in the presence of CsF as the base and a catalyst precursor consisting of a mixture of Pd(OAc) 2 and AsPh 3 . The data obtained in this synthetic study support a reaction mechanism involving an electrophilic attack of an arylpalladium-(II) halide species onto the imidazole ring. Interestingly, some imidazole derivatives synthesized in this study have been found to exhibit significant cytotoxic activity against human tumor cell lines. (1) For a review on the palladium-catalyzed arylation of heteroarenes and other aromatic compounds, see: Miura, M.; Nomura, M. Top. Curr. Chem. 2002, 219, 211-241. (2) (a) Aoyagi, Y.; Inoue, A.; Koizumi, I.; Hashimoto, R.; Tokunaga, K.; Gohma, K.; Komatsu, J.; Sekine, K.; Miyafuji, A.; Kunoh, J.; Homma, R.; Akita, Y.; Ohta, A. Heterocycles 1992, 33, 257-272. (b) Ohta, A.; Akita, Y.; Ohkuwa, T.; Chiba, M.; Fukunaga, R.; Miyafuji, A.; Nakata, T.; Tani, N.; Aoyagi, N. Heterocycles 1990, 31, 1951-1958. (c) Glover, B.; Harvey, K. A.; Liu, B.; Sharp, M. J.; Tymoschenko, M. F. Org. Lett. 2003, 5, 301-304. (d) McClure, M. S.; Glover, B.; McSorley, E.; Millar, A.; Osterhaut, M. H.; Roschangar, F. Org. Lett. 2001, 3, 1677-1680. (3) (a) Lavenot, L.; Gozzi, C.; Ilg, K.; Orlova, I.; Penalva, V.; Lemaire, M. J. Organomet. Chem. 1998, 567, 49-55. (b) Gozzi, C.; Lavenot, L.; Ilg, K.; Penalva, V.; Lemaire, M. Tetrahedron Lett. 1997, 38, 8867-8870. (c) Sévignon, M.; Papillon, J.; Schultz, E.; Lemaire, M. Tetrahedron Lett. 1999, 40, 5873-5876. (d) Okazawa, T.; Satoh, T.; Miura, M.; Nomura, M. Okazawa, T.; Satoh, T.; Miura, M.; Nomura, M. Tetrahedron 2003, 59, 5685-5689. (c) Mori, A.; Sekiguchi, A.; Masui, K.; Shimada, T.; Horie, M.; Osakada, K.; Kawamoto, M.; Ikeda, T.
A Safe and Efficient Synthetic Route to a 2,5-Dimethyl-1-aryl-1 H -imidazole Intermediate
Organic Process Research & Development, 2011
An optimized route to an iodo-imidazole intermediate in the synthesis of 4-ethynyl-2,5-dimethyl-1aryl-1H-imidazoles (6) was devised. Important data for the optimization work was obtained by carrying out a DOE study to gain understanding of the parameters that affect the key intramolecular cyclization to build the imidazole ring. Additional information on the reaction mechanism of this step was obtained by carrying out a flow NMR experiment. In order to complete the proof of concept, the iodoimidazole intermediate was converted to two ethynyl imidazoles (6a, b) using metal-catalyzed reactions.
An expeditious green route toward 2-aryl-4-phenyl-1H-imidazoles
Organic and Medicinal Chemistry Letters, 2014
Background: Azaheterocycles are an important class of compounds because of their highly potent medicinal activities, and the imidazole subcategory is of special interest in regard to drug discovery research. Findings: An expeditious synthetic protocol of 2-aryl-4-phenyl-1H-imidazoles has been accomplished by reacting phenylglyoxal monohydrate, ammonium acetate, and aldehyde under sonication. Following this green approach a series of 2-aryl-4-phenyl-1H-imidazoles has been synthesized using diversely substituted aldehydes. Conclusions: A rapid and simple synthetic procedure to synthesize diversely substituted 2-aryl-4-phenyl-1H-imidazoles has been reported. Other salient features of this protocol include milder conditions, atom-economy, easy extraction, and minimum wastes. The present procedure may find application in the synthesis of biologically active molecules.
Tetrahedron Letters, 2007
Benzotriazole (BtH) is an efficient ligand for the Cu-catalyzed N-arylation of imidazoles with aryl and heteroaryl halides. A combination of CuI/BtH was found to be an efficient and inexpensive catalyst system to carry out the N-arylation of imidazoles affording the corresponding products in good to excellent yields.Benzotriazole is an efficient and inexpensive ligand for the N-arylation of imidazoles with aryl and heteroaryl halides using mild reaction conditions.
An Efficient Synthesis of 2,4,5-Trisubstituted and 1,2,4,5-Tetrasubstituted-1H-imidazoles
ChemInform, 2006
A simple, and environmentally benign synthesis of 2,4,5trisubstituted and 1,2,4,5-tetrasubstituted imidazoles has been successfully accomplished via multi-component cyclo-condensation of 1,2-dicarbonyl, aldehyde, and ammonium acetate and aniline respectively, using dihydroquinoline based novel orga-nocatalysts at refluxed temperature in ethanol. High yields (94 %), easy work-up and purification of products without column chromatography are the key advantages of the method.
ChemInform, 2010
Functionalized imidazole derivatives include compounds that are known to possess a broad range of significant biological properties or are important templates in medicinal chemistry. In the light of the importance of these heteroaromatic compounds a great deal of attention has been given to their synthesis and, in the past years, a number of methods has been described in the literature allowing for the construction of the heteroaromatic core of these substances by cyclization protocols. However, in recent years, much more attention has been focused on the design and development of efficient protocols that are based on the selective functionalization of the imidazole ring at the N-1, C-2, C-4 or C-5 position via transition metal-catalyzed reactions and enable the synthesis of imidazole derivatives, including bioactive and/or naturally occurring compounds, which cannot be accessed by other means. This critical review with 439 references covers developments in this hot area of research up to July 2009 and includes a description of synthetically important, regioselective transition metal-catalyzed Csp 2 -N, Csp-N, Csp 3 -N, Csp 2 -Csp 2 , and Csp-Csp 2 bond forming methods, their applications, and limitations. 6
PROSPECTS FOR THE CHEMISTRY OF IMIDAZOLE DERIVATIVES (Review)
Chemical Journal of Kazakhstan
The problem of creating new effective domestic pharmacological preparations, including the development of the methods for obtaining biologically active substances in compliance with the “green chemistry” principles, are among the priority areas for the development of chemical science. The choice of an initial molecule, which carries the potential of biological activity, is the guarantor of a successful experimental search. Imidazole derivatives occupy a unique place in the medicinal chemistry. An imidazole cycle is part of the natural compounds such as histamine, biotin, some alkaloids and nucleic acids, and is a structural fragment of medicinal preparations. The goalof the present review is to analyze the publications on the chemistry of imidazole derivatives with an emphasis on the methods of obtaining biologically active and other practically useful molecules with an obligatory imidazole cycle. The objects of the study:imidazole derivatives. The examples of the routes of synthesi...