Benzimidazoles, uses

Lu, J., Yang, B. and Bai, Y., Microwave irradiation synthesis of 2-substituted benzimidazoles using PPA as a catalyst under solvent-free conditions, Synth. Commun., 2002, 32, 3703-3709. 

Brain, C.T. and Steer, J.T., An improved procedure for the synthesis of benzimidazoles, using palladium-catalysed aryl-animation reaction chemistry,. Org. Chem., 2003,68, 6814-6816. 

Scheme 20 Synthesis of benzimidazoles using soluble PEG matrix...

Examples come from Hahn et al. [491] who synthesised the pincer imidazolium salt from a,a -dibromolutidine and A-alkyl-benzimidazole using a standard protocol. Synthesis of the palladium(ll) complex was then achieved with palladium(ll) acetate in DMSO. The structure is similar to that of the palladium(II) pincer carbene complexes with nonannulated pincer ligands. Temperature dependant H-NMR spectroscopy... 

Jacob RG, Dutra LG, Radatz CS et al (2009) Synthesis of 1, 2-disubstitued benzimidazoles using Si02/ZnC12. Tetrahedron Lett 50 1495-1497... 

The efficient synthesis of a potent topoisomerase I poison terbenzimidazole was developed in the laboratory of P.J. Smith. The desired aryl-aryl bonds were created via iterative Suzuki-cross couplings. The arylboronic ester was derived from 1-benzyl-5-iodo-1/-/-benzimidazole using the Miyaura boration. 

This is a general method of preparing benzimidazoles. Using an equivalent of acetic acid (45 g.) in place of formic acid, 2-methylbenzimidazole, m.p. 172-174°, can be prepared in 68 per cent yield. 

The parent compound is so reactive towards thiols that up to four sulfur groups can be introduced. In isopropanol at — 10°C, however, the monosuhstituted compounds (109) (Nu = PhS) can be made in reasonable yield. Further nucleophilic substitution of 5-nitro and 5-phenylsulfonyl derivatives occurs at the 4- and 6-positions the 1,3-dihydro products are isolated <92JCS(PI)685>. Conditions have been devised for substitution of one or two chlorines in 5,6-dichloro-2Ff-benzimidazoles using amines, thiolate, or oxyanionic nucleophiles in ethanol <88S87i>. Indeed nucleophilic displacements of hydrogen are not uncommon (Scheme 57) <90HCA902>. 

Albendazole (ABZ) is one of a class of benzimidazoles used to control helminth infections in cattle. It is generally administered as a single oral dose of 10 mg/kg b.w. either by bolus or drench. The residue levels and plasma pharmacokinetic profiles resulting from a single dose of ABZ are well documented (7). Recent studies have made important progress into alternative methods of anthelmintic... 

To date, most of the reported copper-mediated iV-arylations applied toward benzimidazoles use a polar organic solvent (e.g., DMA, 1,4-dioxane, DMSO, or NMP.) Peng and co-workers have recently reported a modified intramolecular arylation of amidines to provide C2-alkyl and aryl benzimidazoles in moderate to high yield. Remarkably, these arylations, which use CuaO (5 mol%), dimethylethylenediamine (DMEDA, 10%), and K2CO3, are conducted in water, lending potential environmental and economic advantage to this method. 

The sedative property which is so highly expressed in diphenhydramine existed in a less measure in other antihistamines. In an endeavour to lessen it, to help those who need medication at times when they must be alert, chlor-phenamine (9.57) (chlorpheniramine, Chlortrimeton ) was introduced. In this type, the second polar atom (N or O) has been eliminated from the aliphatic chain. The pAa values (4.0 and 9.2) resemble those of earlier compounds. Another type with a decreased incidence of drowsiness has the two nitrogen atoms of ethylenediamine joined by two saturated carbon atoms to give a piperazine ring. Chlorcyclizine 9.56a) ( Histantin , Diparalene ) provides an example. The search for Hi antagonists that could not cross the blood-brain barrier, and hence would be non-sedative, has produced the sterically-hindered astemizole ( Hismanol ) which is l-(p-fluorobenzyl)-2-[l-(l-/ methoxyphen-ethyl)-4-piperidylamino]benzimidazole, used for hay fever (Laduron et al., 1982). 

The less-weU studied C-2 arylation of imidazoles and benzimidazoles using aryl chlorides was reported by Shao and coworkers (2014JOC5806). 

Paul, S. and B asu, B. 2012. Ffighly selective synthesis of libraries of 1,2-disubstituted benzimidazoles using silica gel soaked with ferric sulfate. Tetrahedron Lett. 53(32) 4130-4133. 

Wan JP, Gan S-F (2009) Water mediated chemoselective synthesis of 1,2-disubstituted benzimidazoles using o-phenylenediamine and the extended synthesis of quinoxalines. Green Chem 11 1633 1637... 

Scheme 3.42 The synthesis of substituted quinoxalinones and benzimidazoles using green method...

Jacob RG, Dutra LG, Radatz CS, Mendes SR, Perin G, Lenardao EJ (2009) Synthesis of 1,2-disubstitued benzimidazoles using SiOj/ZnCl. Tet Lett 50 1495-1497 Salehi P, Dabiri M, Zolfigol MA, Otokesh S, Baghbanzadeh M (2006) Selective synthesis of 2-aryl-1-arylmethyl-l //-1,3-benzimidazoles in water at ambient temperature. Tet Lett... 

Brain CT, Steer JT (2003) An improved procedure for benzimidazoles, using palladium... 

Synthesis of 1 -p-Tolyl-1 H-benzimidazole Using Cupric Acetate and p-Tolylboronic Acid p-Tolylboronic acid (0.09 g, 0.667 mmol, 2 equiv), benzimidazole (0.039 g, 0.333 mmol), anhydrous cupric acetate (0.091 g,... 

Scheme 3.1. Combinatorial synthesis of benzimidazoles using 30(10 -1- 10-l 10) building blocks to prepare 1000(10 x 10 x 10) products in a combinatorial fashion. Reagents (i)amine/NaBH(AcO)3 in DMF/AcOH (ii) o-fluoronitrobenzene, DMSO, rt, overnight (iii) SnCl2-2H20 in NMP, rt, overnight (iv) acid chloride/DlEA in DCM, rt, overnight (v) AcOH, 80°C, overnight.

MeCo(dmgH)2(l,5,6-Me3-benzimidazole)] using /-coupled heteronuclear... 

C.S. Radatz, R.B. Silva, G. Perm, E.J. Lenardao, R.G. Jacob, D. Alves, Catalyst-free synthesis of benzodiazepines and benzimidazoles using glycerol as recyclable solvent. Tetrahedron Lett. 52 (2011) 4132-4136. 

SC HEME 9 SPOS of benzimidazole using Wang resins. 

SCHEME 11 A solid-phase traceless synthesis of benzimidazoles using three combinatorial steps. 

SCHEME 2 7 Synthesis of benzimidazole using silica sulfuric add (SSA). 

SCHEME 47 On-water synthesis of 1,2-benzimidazole using trimethylsilyl chloride. 

Among the known classes of heteroaromatic carbenes, the benzimidazole derivatives have received the least attention thus far. They [89] present new results in terms of the synthesis and properties of stable heteroaromatic monocarbenes and biscarbenes of the benzimidazole series. One of the major aims in this area was the attachment of sterically bulky groups to the benzimidazole nucleus. The introduction of the 1-adamantyl substituent into the benzimidazole system was achieved by direct adamantylation of benzimidazole using 1-bromoadamantane in the presence of sodium acetate in acetic acid. However, in this case the reaction was incomplete and yields of only 33% of pure salt 134 were realized. In o-dichlorobenzene in the presence of potassium carbonate, a 54% yield of l-(l-adamantyl)benzimidazole (86) can be achieved and this compound can be further quatemized by treatment with 1 -bromoadamantane in o-dichlorobenzene to afford a high yield of salt 134 (90%).As is well known, in the... 

The synthesis of 2-arylindoles via noble Rh-catalyzed intramolecular imine C(sp )-H amination reaction of 2-azideostilbenes has been reported by Driver and coworkers [2]. After that, they expanded the C-H amination strategy to synthesize benzimidazoles using iron(II) bromide as the catalyst, which proceeded via the intramolecular amination between an azide and an imine C(sp )-H bond (Scheme 9.1). The results showed that the mode of reactivity of the aryl azide relied on the composition of the linker between the aryl azide and the pendant C-H bond [3]. 

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