Benzimidazolones, synthesis

Cyclization can also be performed via nucleophilic attack of nitrogen nucleophiles as shown for the release of cyclic urea derivatives. Dressman et al. examined a methodology to cleave hydantoins 222 via treatment of carbamate linkers with an intramolecular amide functionahty and base [188]. In the case of resin-bound substrate 221 (Scheme 33), the resulting heterocycle is a five-membered ring system but other heterocycles containing a urea-type unit can also be synthesized as published by diverse other groups (c.f. benzimidazolone-synthesis of li et al. [199]). 

Benzil, 3 594 14 594 Benzilonium bromide, 4 359t Benzimidazoles, microwave-assisted synthesis of, 16 574-575 Benzimidazolethiols, 25 197 Benzimidazolone dioxazine, 19 446 Benzimidazolone pigments, 19 432 433 Benzimidazolone Violet, pigment for plastics, 7 367t Benzine, 3 597... 

The product from the formal replacement of the benzimidazolone function in itasetron (57-6, Chapter 10) by a quinolone has been reported to display much the same serotonin antagonists activity of the former. In the absence of a specific reference to the synthesis, the starting quinolone is speculatively formed by reaction of cyclo-hexylaniline (50-1) with EMME to produce the enamide (50-2) from displacement... 

The same authors have also reported on the solid-phase synthesis of benzimidazolones 7 from resin-bound 4-fluoro-3-nitrobenzoic acid lb, amines, disuccinimidocarbonate (DSC), and alkyl halides (Scheme 14).10... 

Vernin et a/.154 have recently described the synthesis of 1-alkyl- and l,3-dialkyl-2-benzimidazolones from benzimidazolones, using PTC. 

Xu XJ, Zong YX (2007) Microwave-assisted traceless synthesis of benzimidazolones. Tetrahedron Lett 48 129-132... 

Related to the above synthesis is the process which converts the o-diaminc into the diisocyanate (41) (Y = O) in the presence of excess phosgene (Scheme 2.1.18). When (41) (Y = O) reacts with water, methanol or aniline, the product is a benzimidazolone [81, 106]. The corresponding... 

Recently, benzyloxycarbonyl-based linkers have been described for the synthesis of carbolines of type 13 [23], substituted benzimidazolones 14 [24], and quinoxa-lines 15 [25] (Fig. 3). 

There are general reviews on heterocyclic syntheses by cycloaddition reactions of isocyanates and on the use of heterocyclic cations in preparative organic chemistry. More specific topics are 5-hydroxymethylfuran-2-carb-aldehyde, isobenzofurans and related ort/io-quinonoid systems, the conversion of 2//-cyclohepta[Zj] furan-2-one (1) into derivatives of azulene, the synthesis of indoles from o-alkylphenyl isocyanides, and abnormal Fischer indolization reactions of o-methoxyphenylhydrazones. Two reviews on isoindoles have appeared and a lecture on highly conducting charge-transfer complexes that are based on heterocyclic selenium and tellurium donors has been reprinted.Recent advances in the chemistry of imidazole and in the use of nitro-imidazoles as radiosensitizers have been summarized. There have been reviews on benzimidazole A -oxides and on dihydrobenzimidazoles, benzimidazolones, benzimidazolethiones, and related compounds. Other topics are synthetic applications of 1,3-dithiolium and 1,3-oxathiolium salts and of isoxazoles, the chemistry of benzisoxazoles, 2-amino-oxazoles, 5-oxazolones (2), furoxans, benzofuroxans, and related systems, the synthesis of five-membered meso-ionic compounds, and tetrazoles. ... 

Schaus JM. Thompson DC. Bloomquist WE, et al. Synthesis and structure-activity relationships of potent and orally active 5-HT4 receptor antagonists indazole and benzimidazolone derivatives. J Med Chem 1998 41 1943-1955. 

The synthesis of substituted benzimidazolone analogues (Xi H) was started from appropriate 2-chloronitrobenzenes (VII) as outlined in Scheme 3. The reaction of VII with aminoalkanols in an inert solvent afforded N-hydroxy-alkyl-2-nitroanilines (VIII). Catalytic hydrogenation of the nitro group resulted in o-phenylene-diamines (IX) which reacted with urea to give the N-hydroxyalkyl-benzimidazol-2-ones (X). After treatment of Xwith thionylchlo-ride, the desired chloroalkylbenzimidazol-2-ones (I) could be isolated. 

The synthesis of N-alkyl and N-aryl derivatives started from N - substituted o-phenylenediamines which reacted with urea to the benzimidazolones and were then alkylated with 1-bromo-3-chloropropane as described in Scheme 2. 

Ellis KK, Wilke B, Zhang Y, Diver ST (2000) A new method for the synthesis of imidazolidinone- and benzimidazolone-containing [2.2]cyclophanes. Org Lett 2(24) 3785-3788... 

Preparation of the benzimidazolone-dioxazine pigments usually involves a multi-step synthesis followed by finishing. A typical reaction scheme depicting the synthesis of the unsubstituted derivative, but which can be generalized for all other substituents, is shown in Figure 20-15. 

Figure 20-15 Typical synthesis of benzimidazolone-dioxazine pigments.

Hence, according to crystal engineering the ideal molecule would be the mixed methyl-ethyl compound 4c (R = CHj, R = QHs). However, this unsymmetical compound is difRcult to synthesize in pure form performing the synthesis with a 1 1 mixture of 1-methyl- and 1-ethyl-benzimidazolones results in a mixture of dimethyl (4b), methyl-ethyl (4c), and diethyl (4d) compounds in a ratio of 4b 4c 4d = 1 2 1. This ternary mixture forms a solid solution (mixed crystal). Upon syntheses the solid solution emerges as a dull crude material, which is isostructural to the 6-phase of 4b a subsequent finish in N-methyl-pyrroUdone or isobutanol causes a phase transition to the desired p-phase [21]. For organic compounds, such phase transitions from one ternary solid solutions to another without separation into the individual compounds have rarely been reported. 

Returning to the synthesis of 2,3-few(benzimidazol-2-yl)quinoxalines 100a-g (Scheme 6.41 Table 6.5) it should be noted that in one case, i.e., in the case of the synthesis of 2,3-fcw(benzimidazol-2-yl)-6-nitroquinoxaline lOOe, the less-reactive l,2-diamino-4-nitrobenzene 5h was used as a reagent. In this case a derivative of pyrrolo[l,2-a]quinoxaline containing one benzimidazolone (in position 1) and two benzimidazole (at positions 2 and 3) fragments in the newly formed pyrrole ring from the reaction mixture were isolated in trace amounts as an unexpected product. The formation of compound 159 could be due to the condensation of 3-(benzimidazo-2-yl) quinoxalin-2(lf/)-one 37s with its predecessor-3-(benzimidazol-2-yl)methylene-... 

Synthesis of 1-Pyrrolylbenzimidazolones via the New Rearrangements. .. Table 6.19 Synthesis of l-(pyrrolyl)benzimidazolones... 

Scheme 6.72 Synthesis of eompounds with one and two l-(pyrrol-2-yl)benzimidazolone structural blocks...

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