Benzimidazol-2-ones benzimidazole 3-oxides

Lieby-Muller E, Simon C, Imhof K, Constantieux T, Rodriguez J (2006) A multicomponent domino reaction and in situ aerobic oxidation sequence for the first one-pot synthesis of polycyclic benzimidazoles from 1,3-dicarbonyl derivatives. Synlett 1671-1674... 

The second class of benzo-fused heterocycles accessible from benzofuroxans are benzimidazole oxides. In this case only one carbon from the co-reactant is incorporated in the product. With primary nitroalkanes 2-substituted l-hydroxybenzimidazole-3-oxides (46) are formed via displacement of nitrite, and / -sulfones behave similarly. The nitrile group of a-cyanoacetamides is likewise eliminated to alford 2-amide derivatives (46 R = CONRjX and the corresponding esters are formed in addition to the expected quinoxaline dioxides from acetoacetate esters. Under similar conditions secondary nitroalkyl compounds afford 2,2-disubstituted 2//-benzimidazole-1,3-dioxides (47). Benzimidazoles can also result from reaction of benzofuroxans with phosphorus ylides <86T3631>, nitrones (85H(23)1625>, and diazo compounds <75TL3577>. 

Crystalline benzimidazoles have been obtained from all aldonic acids so far tested with only one exception that is known to the writer. Lohmar and Link29 reported that the condensation of D-glucosaminic acid (= 2-amino-2-desoxy-D-gIuconic acid) with o-phenylenediamine under a variety of conditions failed to yield a crystalline product. The direct oxidative condensation of D-glucosamine hydrochloride with o-phenylenediamine in the presence of cupric acetate yielded only the known 2-(D-arofro-tetrahydroxybutyl)quinoxaline (III) and not the desired benzimidazole. 

The last-mentioned authors22 have described also the oxidation of D-xylo-benzimidazole (XVII) with sodium periodate in 35% ethanol solution. Three molar equivalents of oxidant produced two molar equivalents of formic acid and one of formaldehyde 60% of the latter was isolated as the dimedon derivative. The remainder of the original mole-(31) A. Bistrzycki and G. Przeworski, Ber., 46, 3483 (1912). 

Using a different metal salt, Cd(NOj)2, instead of CdClj oxidation reaction results in a slightly higher yield of the cadmium texaphyrin complex [60, 65]. However, upon purification, the product is obtained as a mixture of crystalline and non-crystalline solids. A single crystal X-ray diffraction study of the crystalline portion of the sample gave an unexpected result. The structure obtained (Fig. 20) revealed a six-coordinate pentagonal pyramidal cadmium (II) complex 156 (c.f. Scheme 20) where one of the two possible axial ligation sites is occupied by a benzimidazole [65]. The five donor atoms of the pentadentate texaphyrin macrocycle complete the coordination sphere about the cadmium with the cadmium... 

One important point regarding relative reactivities of Af-unsubstituted and Af-substituted 2-chloroimidazoles with powerful nucleophiles such as alkoxide is that in the former there is competition between proton abstraction from N-1 (which severely hampers any nucleophilic attack at C-2) and the nucleophilic substitution at the 2-position. Thus, chloride is not displaced from 2-chlorobenzimidazole by alkoxide ions, whereas 2-chloro-l-methyl-benzimidazole reacts readily. That steric effects can also be important is evidenced by the lack of reactivity of 2-chloro-l-methylbenzimidazole with t-butoxide, and similar resistance to nucleophilic attack of 2-chloro-l-isopropylbenzimidazole. Alkoxide readily displaces chloride from 2-chloro-1 -isopropenylbenzimidazole, and the N- substituent may be removed subsequently by oxidative cleavage (74CRV279). 

There are a number of methods which cyclize o-amino- or o-nitroarylamincs to benzimidazoles or benzimidazole A -oxides. These include cases where one of the amino groups is a secondary or a tertiary amine. 

Base-induced conversion of lV,iV-disubstituted-o-nitroanilines (59) into benzimidazole A/-oxides may occur provided that one of the carbon substituents can be removed subsequently (e.g. cyano or arylsulfonyl). The reaction products, however, may well differ from those obtained from the monosubstituted analogues, e.g. cyclization of lV-alkyl(or aryl)-iV-cyanomethyl-onitroanilincs gives not the 2-cyanobenzimidazole M-oxides, but the 2- hydroxy derivatives [148J. These processes do not seem to have great synthetic utility. 

Anodic oxidation of azomethine, hydrazone, oxime, formazane, and semicarbazone structures has been used to initiate the intramolecular cyclization [119] under formation of heterocycles like triazoles [126,127], oxadiazoles [128,129], triazolinones [129], benzoxa-zoles [130,131], benzimidazoles [130,131], pyrazoles [132], indazoles [133], furoxanes [134], and tetrazolium salts [135] (see Chapter 18). Some of these reactions can be performed advantageously by indirect electrolysis using tris(4-bromophenyl)amin or 2,3-dihydro-2,2-dimethylphenothiazine-6(l/7)-one as mediators [119,136]. Two examples are given in Eqs. (19) and (20). 

Similar ring contractions in which the nitrogen-nitrogen bond is cleaved are found in the reductive ring contractions of pyridazines to pyrroles [148, 149], phthalazines to isoindoles [150], 5,6-diphenyl-1,2,4-triazinones to imidazolones [151], benzo-l,2,4-triazines to benzimidazoles [71], benzo-l,2,3-triazinone to indazolone [la, 152], benzo-l,2,3-triazin-3-oxide to indazole [la], benzo-2,3-diazepines to isoquinolines [153], benzo-l-pyrano-[4,3-e ]-as-triazin-3-one to benzopyranoimidazolone [154], and 2-methyl-4,5-dihydropyridazin-3-ones to pyrrolin-2-ones [155]. 

Dinitro-r-anilines constitute a major group of pre-emergent herbicides. The photodecomposition of these herbicides has been simulated by studying the photolysis of one typical example, Trifluralin 47 (74MI1). The major product from the action of sunlight in aqueous alkaline media was the benzimidazole 48, and the by-products included the dihyroxybenzimidazo-line 49, the benzimidazole Y-oxide, and benzimidazoline derivatives of 48, all being derived by r-amino-effect chemistry (Scheme 17). 

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