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Synthesis of imidazoles and benzimidazoles

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Starting from 1,2-diketones and urotropine in the presence of ammonium acetate, a simple and efficient solventless microwave-assisted enabled the synthesis of 4,5-disubstituted imidazoles.
G. Bratulescu, Synthesis, 2009, 2319-2320.

A one-pot, four-component synthesis of 1,2,4-trisubstituted 1H-imidazoles was achieved in very good yields by heating a mixture of a 2-bromoacetophenone, an aldehyde, a primary amine, and ammonium acetate under solvent-free conditions.
M. Adib, S. Ansari, S. Feizi, J. A. Damavandi, P. Mirzaei, Synlett, 2009, 3263-3266.

A simple and efficient approach allows the preparation of biologically active 2,4(5)-diarylimidazoles by parallel synthesis. The formation of 2-aroyl-4(5)-arylimidazoles as side products strongly depends on the reaction conditions employed.
V. Zuliani, G. Cocconcelli, M. Fantini, C. Ghiron, M. Rivara, J. Org. Chem., 2007, 72, 4551-4553.

An improved and rapid one-pot synthesis of 2,4,5-triaryl imidazoles in a room temperature ionic liquid does not need any added catalyst. This one-pot methodology offers excellent isolated yields, simple work up procedures and efficient recovery and recycling of the ionic liquid.
S. A. Siddiqui, U. C. Narkhede, S. S. Palimkar, T. Daniel, R. J. Lahoti, K. V. Srinivasan, Tetrahedron, 2005, 61, 3539-3546.

The copper-catalyzed reaction between two different isocyanides produces imidazoles in good yields. The mechanism is discussed.
C. Kanazawa, S. Kamijo, Y. Yamamoto, J. Am. Chem. Soc., 2006, 128, 10662-10663.

A rhodium(II)-catalyzed reaction of stable and readily available 1-sulfonyl triazoles with nitriles gives the corresponding imidazoles in good to excellent yields via rhodium iminocarbenoids intermediates.
T. Horneff, S. Chuprakov, N. Chernyak, V. Gevorgyan, V. V. Fokin, J. Am. Chem. Soc., 2008, 130, 14972-14974.

Reactions of propargylamines with carbodiimides, in the presence of 5 mol% of the titanacarborane monoamide [σ:η¹:η⁵-(OCH₂)(Me₂NCH₂)C₂B₉H₉]Ti(NMe₂), afford a new class of substituted 2-aminoimidazoles via [3+2] annulation in good to excellent yields. A possible reaction mechanism is proposed.
Y. Wang, H. Shen, Z. Xie, Synlett, 2011, 969-973.

A highly efficient and convenient method for the synthesis of 1,2,4,5-tetrasubstituted imidazoles from readily accessible 2-azido acrylates and nitrones proceeded under mild conditions without the assistance of any metal, acid, or base.
B. Hu, Z. Wang, N. Ai, J. Zheng, X.-H. Liu, S. Shan, Z. Wang, Org. Lett., 2011, 13, 6362-6365.

A one-pot procedure for the conversion of aromatic and heteroaromatic 2-nitroamines into bicyclic 2H-benzimidazoles employs formic acid, iron powder, and NH₄Cl as additive to reduce the nitro group and effect the imidazole cyclization with high-yielding conversions generally within one to two hours. The compatibility with a wide range of functional groups demonstrates the general utility of this procedure.
E. J. Hanan, B. K. Chan, A. A. Estrada, D. G. Shore, J. P. Lyssikatos, Synlett, 2010, 2759-2764.

The reaction of ortho-substituted anilines with functionalized orthoesters yields benzoxazole, benzothiazole, and benzimidazole derivatives in an efficient and connective methodology. The versatility of this approach enables the development of new libraries of heterocycles containing multifunctional sites.
G. Bastug, C. Eviolitte, I. E. Markó, Org. Lett., 2012, 14, 3502-3505.

A convenient method for the synthesis of 2-substituted benzimidazoles and benzothizoles offers short reaction times, large-scale synthesis, easy and quick isolation of the products, excellent chemoselectivity, and excellent yields as main advantages.
K. Bahrami, M. M. Khodaei, F. Naali, J. Org. Chem., 2008, 73, 6835-6837.

A copper-catalyzed, one-pot, three-component reaction of 2-haloanilines, aldehydes, and NaN₃ enabled the synthesis of benzimidazoles in good yields using catalytic amounds of CuCl and TMEDA in DMSO at 120°C for 12 h. The reaction tolarated many functional groups such as ester, nitro, and chloro.
Y. Kim, M. R. Kumar, N. Park, Y. Heo, S. Lee, J. Org. Chem., 2011, 76, 9577-9583.

CuI/l-proline catalyzed coupling of aqueous ammonia with 2-iodoacetanilides and 2-iodophenylcarbamates affords aryl amination products at room temperature, which undergo in situ additive cyclization under acidic conditions or heating to give substituted 1H-benzimidazoles and 1,3-dihydrobenzimidazol-2-ones, respectively.
X. Diao, Y. Wang, Y. Jiang, D. Ma, J. Org. Chem., 2009, 74, 7974-7977.

An experimentally simple, general, efficient, and ligand-free synthesis of substituted benzimidazoles, 2-aminobenzimidazoles, 2-aminobenzothiazoles, and benzoxazoles via intramolecular cyclization of o-bromoaryl derivatives is catalyzed by copper(II) oxide nanoparticles in DMSO under air. The heterogeneous catalyst can be recovered and recycled without loss of activity.
P. Saha, T. Ramana, N. Purkait, M. A. Ali, R. Paul, T. Punniyamurthy, J. Org. Chem., 2009, 74, 8719-8725.

An efficient method for the transformation of N-benzyl bisarylhydrazones and bisaryloxime ethers to functionalized 2-aryl-N-benzylbenzimidazoles and 2-arylbenzoxazoles involves a copper(II)-mediated cascade C-H functionalization/C-N/C-O bond formation under neutral conditions. Substrates having either electron-donating or -withdrawing substituents undergo the cyclization at moderate temperature.
M. M. Guru, M. A. Ali, T. Punniyamurthy, J. Org. Chem., 2011, 76, 5295-5308.

A set of benzimidazoles, 3H-imidazo[4,5-b]pyridines, purines, xanthines and benzothiazoles was readily prepared from (hetero)aromatic ortho-diamines or ortho-aminothiophenol and aldehydes using chlorotrimethylsilane in DMF as a promoter and water-acceptor agent, followed by oxidation with air oxygen.
S. V. Ryabukhin, A. S. Plaskon, D. M. Volochnyuk, A. A. Tolmachev, Synthesis, 2006, 3715-3726.

A Pd-catalyzed amide coupling reaction enables a facile synthesis of imidazo[4,5-b]pyridines and -pyrazines. This reaction provides quick access to various substituted products. A model system relevant to the natural product pentosidine has been demonstrated, as well as the total synthesis of the mutagen 1-Me-5-PhIP.
A. J. Rosenberg, J. Zhao, D. A. Clark, Org. Lett., 2012, 14, 1761-1767.

A highly efficient and versatile method for the synthesis of a series of 2-substituted N-H, N-alkyl, and N-aryl benzimidazoles containing a wide range of functional groups was achieved in one step via the Na₂S₂O₄ reduction of o-nitroanilines in the presence of aldehydes.
D. Yang, D. Fokas, J. Li, L. Yu, C. M. Baldino, Synthesis, 2005, 47-56.

A simple and efficient procedure for the synthesis of substituted benzimidazoles through a one-pot condensation of o-phenylenediamines with aryl aldehydes in the presence of H₂O₂ and HCl in acetonitrile at room temperature features short reaction time, easy and quick isolation of the products, and excellent yields.
K. Bahrami, M. M. Khodaei, I. Kavianinia, Synthesis, 2007, 417-427.

Various 2-arylbenzimidazoles were synthesized from phenylenediamines and aldehydes via a one-step process using hypervalent iodine as oxidant. This method features mild conditions, short reaction times, high yields, and a simple procedure.
L-H. Du, Y.-G. Wang, Synthesis, 2007, 675-678.

Addition of oxone to a mixture of a 1,2-phenylenediamine and an aldehyde in wet DMF results in rapid formation of benzimidazoles under very mild conditions. Products are isolated in high purity in most cases by simple aqueous precipitation. The reaction is applicable to a wide range of substrates but does not allow the conversion of aldehydes that are sensitive to oxone under acidic reaction conditions.
P. L. Beaulieu, B. Haché, E. von Moos, Synthesis, 2003, 1683-1692.

A mild and efficient one-pot synthesis enables the preparation of 2-substituted benzimidazoles from 1,2-phenylenediamines and triacyloxyborane intermediates generated in situ from carboxylic acids and borane-THF. This protocol tolerates acid-labile functional groups.
W. Cui, R. B. Kargbo, Z. Sajjadi-Hashemi, F. Ahmed, J. F. Gauuan, Synlett, 2012, 247-250.

Efficient and general cascade reactions of o-aminoanilines or naphthalene-1,8-diamine with terminal alkynes and p-tolylsulfonyl azide allow a one-pot synthesis of functionalized benzimidazoles and 1H-pyrimidines in good yields.
J. She, Z. Jiang, Y. Wang, Synlett, 2009, 2023-2027.

A NaH-mediated reaction of carbonitriles and N-methyl-1,2-phenylenediamine allows the formation of N-methylbenzimidazole and tolerates acid-labile acetal protective groups. Products were further converted in Suzuki, Sonogashira, Heck and Buchwald-Hartwig reactions.
J. Sluiter, J. Christoffers, Synlett, 2009, 63-66.

A straightforward, efficient, and sustainable method for intramolecular N-arylation provides a library of benzimidazoles in high yields using Cu₂O as the catalyst, DMEDA as the ligand, and K₂CO₃ as the base. Remarkably, the reaction was exclusively carried out in water, rendering the methodology highly valuable from both environmental and economical points of view.
J. Peng, M. Ye, C. Zong, F. Hu, L. Feng, X. Wang, Y. Wang, C. Chen, J. Org. Chem., 2011, 76, 716-719.

Various N-aryl-1H-indazoles and benzimidazoles were synthesized from common arylamino oximes in good to excellent yields depending upon the base used in the reaction. Triethylamine promoted the formation of benzimidazoles, whereas 2-aminopyridine promoted the formation of N-arylindazoles.
B. C. Wray, J. P. Stambuli, Org. Lett., 2010, 12, 4576-4579.

An efficient Cu(I)-catalyzed cascade intermolecular addition/intramolecular C-N coupling process enables the synthesis of a wide variety of 2-heterobenzimidazoles from o-haloarylcarbodiimides and N- or O-nucleophiles.
X. Lv, W. Bao, J. Org. Chem., 2009, 74, 5618-5621.

2-Imidazolines were easily prepared in good yields from the reaction of aldehydes and ethylenediamine with iodine in the presence of potassium carbonate. The 2-imidazolines were smoothly oxidized to the corresponding imidazoles in good yields using (diacetoxyiodo)benzene at room temperature.
M. Ishihara, H. Togo, Synlett, 2006, 227-230.

A number of new reactions of IBX with heteroatom-containing substrates were discovered and their utility was demonstrated. IBX was used for the generation of imines from secondary amines in notably high yields, for the oxidative aromatization of nitrogen heterocycles and for the cleavage of dithianes.
K. C. Nicolaou, C. J. N. Mathison, T. Montagnon, Angew. Chem. Int. Ed., 2003, 42, 4077-4082.

A versatile and modular one-pot method allows the preparation of differently substituted symmetrical and unsymmetrical imidazolium salts from readily available formamidines and α-halo ketones. For many substitution patterns of the imidazolium salt products, this efficient strategy compares favorably with well-known processes in terms of yield, ease of synthesis, and robustness.
K. Hirano, S. Urban, C. Wang, F. Glorius, Org. Lett., 2009, 11, 1019-1022.

With a mixed Cu(I)-Cu(II) system in situ generated by partial reduction of CuSO₄ with glucose, an efficient and eco-friendly multicomponent cascade reaction of A³-coupling of heterocyclic amidine with aldehyde and alkyne, 5-exo-dig cycloisomerization, and prototropic shift has afforded therapeutically important versatile N-fused imidazoles.
S. K. Guchhait, A. L. Chandgude, G. Priyadarshani, J. Org. Chem., 2012, 77, 4438-4444.

A one-pot reaction of aldehydes, 2-aminopyridines, and terminal alkynes, in the presence of the copper(I) iodide-CuI-NaHSO₄•SiO₂ combination catalyst in refluxing toluene, generates the corresponding imidazo[1,2-a]pyridines in high to excellent yields.
S. Mishra, R. Ghosh, Synthesis, 2011, 3463-3470.

N-Phenacylpyridinium bromides, which were prepared in situ from the addition of pyridines to α-bromoketones, undergo nucleophilic addition of ammonium acetate under microwave irradiation and solvent-free conditions to afford the corresponding imidazo[1,2-a]pyridines in excellent yields.
M. Adib, A. Mohamadi, E. Sheikhi, S. Ansari, H. R. Bijanzadeh, Synlett, 2010, 1606-1608.

A simple and efficient protocol enables the synthesis of 3-arylimidazo[1,2-a]pyridines by a catalyst-free cascade process from 2-aminopyridine and 1-bromo-2-phenylacetylene or 1,1-dibromo-2-phenylethene in yields up to 86%.
Z. Wu, Y. Pan, X. Zhou, Synthesis, 2011, 2255-2260.

A copper-catalyzed one-pot procedure enables the synthesis of imidazo[1,2-a]pyridines with aminopyridines and nitroolefins using air as oxidant. This general reaction appears to be very suitable for the construction of various imidazo[1,2-a]pyridines.
R.-L. Yan, H. Yan, C. Ma, Z.-Y. Ren, X.-A. Gao, G.-S. Huang, Y.-M. Liang, J. Org. Chem., 2012, 77, 2024-2028.

In a regioselective and high-yielding Groebke-Blackburn-Bienaymé reaction, glyoxylic acid is used as formaldehyde equivalent leading to a regioselective, mild, convenient, and effective synthesis of 3-aminoalkyl imidazoazines.
A. Sharma, H.-y. Li, Synlett, 2011, 1407-1412.

An efficient microwave-assisted metal-free amino benzannulation of aryl(4-aryl-1-(prop-2-ynyl)-1H-imidazol-2-yl)methanone with dialkylamines affords various 2,8-diaryl-6-aminoimidazo[1,2-a]pyridines in good yield.
M. Nagaraj, M. Boominathan, S. Muthusubramanian, N. Bhuvanesh, Synlett, 2012, 1353-1357.

An efficient three-component coupling reaction of substituted picolinaldehydes, amines, and formaldehyde produces imidazo[1,5-a]pyridinium ions in high yields under mild conditions, allowing the incorporation of diverse functionality and chiral substituents. Higher order condensations are also described that provide access to multidentate NHC ligands useful for a variety of applications.
J. T. Hutt, Z. D. Aron, Org. Lett., 2011, 13, 5256-5259.

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An efficient copper(I) bromide catalyzed N-arylation of azoles with a variety of aromatic bromides and iodides under mild conditions displayed great functional group compatibility and excellent reactive selectivity.
H. Chen, D. Wang, X. Wang, W. Huang, Q. Cai, K. Ding, Synthesis, 2010, 1505-1511.

A copper-catalyzed N-arylation reaction of imidazole proceeds under very mild conditions in the absence of additional ligand. This protocol tolerates an array of thermally sensitive functional groups, but also achieves high chemoselectivity.
L. Zhu, G. Li, L. Luo, P. Guo, J. Lan, J. You, J. Org. Chem., 2009, 74, 2200-2202.

N-Arylation of azoles and amines with arylboronic acids was efficiently carried out with heterogeneous copper(I) oxide in methanol at room temperature under base-free conditions. Various arylboronic acids and amines were converted to the corresponding N-arylazoles and N-arylamines in very good yields, demonstrating the versatility of the reaction.
B. Sreedhar, G. T. Venkanna, K. B. S. Kumar, V. Balasubrahmanyam, Synthesis, 2008, 795-799.

A simple and efficient method enables the synthesis of N-alkynylheteroarenes from 1,1-dibromo-1-alkenes via a copper-catalyzed cross-coupling reaction. Good yields and functional-group tolerance were obtained with TMEDA as ligand using imidazole and benzimidazole substrates in dioxane.
M.-G. Wang, J. Wu, Z.-C. Shang, Synlett, 2012, 589-594.

A series of N,N′-asymmetrically substituted imidazolium iodides have been synthesized, starting from N-arylimidazoles and the less expensive, but less reactive, 1-chlorobutane or (3-chloropropyl)trimethoxysilane. The addition of potassium iodide and the use of 1,2-dimethoxyethane as a solvent allowed the synthesis of multigram quantities of these salts.
A. M. Oertel, V. Ritleng, M. J. Chetcuti, Synthesis, 2009, 1647-1650.

N-Methylimidazole is a promising catalyst for aza-Michael reactions. Various N-heterocycles were introduced to α,β-unsaturated carbonyl compounds employing N-methylimidazole in a highly efficient, rapid and high yielding synthesis of N-heterocyclic derivatives.
B. K. Liu, Q. Wu, X. Q. Qian, D. S. Lv, X. F. Lin, Synthesis, 2007, 2653-2659.

2-Lithioimidazole was prepared using lithium metal in the presence of a catalytic amount of isoprene in THF at room temperature. By reacting this organolithium compound with carbonyl electrophiles 2-(hydroxyalkyl)imidazoles and 2-(aminoalkyl)imidazoles were obtained in good yields.
R. Torregrosa, I. M. Pastor, M. Yus, Tetrahedron, 2005, 61, 11148-11155.