Benzimidazolone formation

DAIB-induced conversions of the anthranilamides 195 and salicylamides 196 to the benzimidazolones 197 and benzoxazolones 198, respectively, and similar rearrangements of two representative pyridinecarboxamides, are recent examples of direct heterocyclic ring-construction by the iodine(III)-Hofmann pathway (Scheme 57) (01S541). These reactions may be contrasted with BTIB-oxidations of the 2-aminonicotinamides 67 and amidopyridones 69 in aqueous DMF (Section II.A.2) which lead, without rearrangement, to N-N and N-O bond formation (97SC2217). 

PAR-1, results in the formation of platelet aggregation causing thrombotic disorders such as myocardial infarction, stroke, angina, and atherosclerosis. Benzimidazolone peptidomimetic derivatives effective as thrombin receptor antagonists have been prepared to address this disorder. 

The solid 5-acetamido-2-methoxyaniline and its A-(2-cyanoethyl) derivative were discussed earlier in the section on alkoxyanilines. Finally, we turn to 5-aminobenzimidazolone with its reported solid-phase enthalpy of formation of —418.0 0.7 kJmol-1 from Reference 74. This value may be contrasted to the —85.1 3.2 and —190.3 1.7 kJmol-1 reported for the solid benzimidazolone in References 74 and 116 neither value is compatible with the aforementioned value for the 5-amino derivative. 

The ring cleavage reactions and formation of pseudo bases have been described in detail in CHEC-I. Under more severe conditions the quaternary salt (83) can be converted directly into the benzimidazolone (85) and the reduced benzimidazole (86). Structures (85) and (86) are also disproportionation products of heating (84) in an inert atmosphere or in the absence of solvent (Scheme 33) <85CHE1398>. 

There are a number of examples also of the formation of 2-imidazolones and 2-benzimidazolones from reaction of 2-halogeno salts with dilute sodium hydroxide <81AG(E)612, 82CHE830>. With... 

Beneperidol has a pK of 7.90, and is a sufficiently weak base to be extracted by organic solvents from aqueous acid solution. It has been found in the present work that, due to the presence of the benzimidazolone ring system, beneperidol can also act as a weak acid when dissolved in strong alkali (pHll). Evidence of salt formation is seen in the bathochromic shift, from 279nm to 288nm, which occurs in the ultraviolet absorption spectrum of beneperidol when its aqueous solution is made alkaline."... 

The formation of PhNCO from PhNOa catalysed by this palladium catalyst supports this suggestion [37]. We observed that 2(lH)-benzimidazolone is actually formed when o-nitroaniline alone is carbonylated under the conditions of Table 9. On the other hand, one of the by-products usually obtained in small amounts is l,2-benzenediamine-N,N -bis(arylmethylene). Thus it can be also concluded that water, formed in Scheme 6 under CO pressure, reduces... 

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-... 

The fact that the formation of the benzimidazolone derivatives in the reactions of the self-condensation of 3-(a-azidophenylalkyl)quinoxalin-2(lf/)-ones 160 (Scheme 6.70) (Saifina 2009) and in the condensation of 3-(benzimidazo-2-yl) quinoxalin-2(17/)-one 37s with its predecessor-3-(benzimidazol-2-yl)methylene-quinoxalin-2(17/)-one 107 (Scheme 6.68) gives reason to propose a new hypothesis, that any of the spiro-derivatives of 1,2,3,4-tetrahydroquinoxalin-3-one without any mobile hydrogen atom in their spiro-forming component are on their way to the benzimidazolone derivative with the spiro-forming component at position 1 (Scheme 6.71). 

G with the aziridine ring system (b) the acid-catalyzed ring-opening in intermediates G and E with the formation of the final l-(pyrrol-2-yl)- 162 and 1-(pyrrol-3-yl)benzimidazolone 163 derivatives. 

The formation of the benzimidazolone derivatives in the one-pot reactions of 3-BQs 37, methylaryl(hetaryl)ketones and ammonium acetate (NHqOAc) in methanol at reflux conditions with good to excellent yields (Table 6.19 Scheme 6.72) confirm the previously proposed hypothesis (Scheme 6.71). 

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