Benzo benzimidazoles

Alkaline hydrolysis gives either 3//-l,5-benzodiazepine-2,4-diamine (5) or the benzo-triazepine 6 (see Section 4.2.4.4.2.). depending on the strength of the alkali. With hot water the benzimidazole 7 (see Houben-Weyl, Vol.E8c, p 1315) is produced.254... 

The reaction of 4-phenylbut-3-yn-2-one and TV-alkylated benzimidazoles 9 leads to benzo[b [l,4]diazocine derivatives 10 in very low yields.32... 

Benzimidazoles 248 - fluorous Ugi reactions 115 Benzo[fc]furans 247 Benzo[i)]thiophenes 248 Benzocondensed heterocycles 246,249, 252... 

The generation of other heteroq cles from Bfx and Fx has been the subject of exhaustive investigation. The most important transformation of Bfx to other heterocycles has been described by Haddadin and Issidorides, and is known as the Beirut reaction . This reaction involves a condensation between adequate substituted Bfx and alkene-type substructure synthons, particularly enamine and enolate nucleophiles. The Beirut reaction has been employed to prepare quinoxaline 1,4-dioxides [41], phenazine 5,10-dioxides (see Chap. Quinoxahne 1,4-dioxide and Phenazine 5,10-dioxide. Chemistry and Biology ), 1-hydroxybenzimidazole 3-oxides or benzimidazole 1,3-dioxides, when nitroalkanes have been used as enolate-producer reagent [42], and benzo[e] [ 1,2,4]triazine 1,4-dioxides when Bfx reacts with sodium cyan-amide [43-46] (Fig. 4). 

Amine complexes stabilized with phosphine ligands of the type [AuL(PR3)]+ have been obtained for L = bipy,2310 phen,2310,231 quinoline,23 1 acridine,2311 benzo[h]quinoline,2311 naphthyr-idine (388)2311 2,2 -biquinoline,2311 di-2-pyridyl-ketone,2311 di-2-pyridylamine,2311 2-(2-pyridyl)-benzimidazole, 2311 ferrocenylpyridine, 2-nitroaniline,2312 4-methoxyaniline,2312 NHPh2, 2 NHEt2,2312 NMe3,2312 quinuclidine,2313 NEt3,2314 2-aminothiazoline,2315 histidine,2316... 

Replacement of one or more of the C or N atoms of the indole nucleus by atoms of N, C, O or S will result in dialkyltryptamine analogs some of which are very likely to be psychedelic. Among the indole analogs are isoindole, indene, indazole, diazindoles, benzo-furan, benzothiophene and benzimidazole. The syntheses of several such compounds follows. 

Chiral hydroxy benzimidazole 267 was dialkylated with dibromomethane or benzaldehyde dimethyl acetal to form benzo[4,5]imidazo[l,2-f]oxazoles 268 and 269 (Equation 118) C1997TA1491, 1998TA2245>. After removal of the BOC group and formylation of the liberated amine, formylaminomethylthiazole cyclized in phosphoryl chloride to... 

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>. 

Oxidation of 1-aminobenzimidazoles with manganese dioxide or lead tetraacetate can give either 1,1 -azobenzimidazoles (735) or 3-substituted benzo-l,2,4-triazines (736). Electrochemical measurements have shown that the first step in this reaction is removal of an electron from a ir-orbital of benzimidazole rather than from the A-amino group. Because the cation radical which is formed must be stabilized by loss of a proton, for (736) to form the 2-substituent must contain an NH or OH group. This is unnecessary for the formation of the azo product (735) which may form via a nitrene intermediate. 

Developing their work on the use of microwave-assisted Niementowski reactions, the same group published the synthesis of novel triaza- and tetraaza-benzo a -indeno[l,2-c]anthracen-5ones by the condensation of anthranilic acid with 2-(2-aminophenyl)indole or benzimidazole (Scheme 3.49)78,79. 

Various heterocycle-fused thiadiazepines were synthesized by intramolecular cyclization of (o-aminoaryl)thio azaheterocycles. The un(substituted) benzimidazoles 109 (R2 = benzo) with thiourea-functionalized (Y = S ... 

The reaction of succinic acid anhydride 111 with 2-methyl-2,4-diphenyl-2,3-dihydroli/-benzo[Z ][l,4]diazepine 112 in toluene in the presence of potassium carbonate leads to 4-(2-methyl-2,4-diphenyl-2,5-dihydro-l/f-l,5-benzodiazepin-5-yl)-4-oxobutanoic acid 113 in 70% yield [110], while its treatment with 2,4-diphenyl-2,3-dihydro-l//-l,5-benzodiazepine 104 follows with chalcone elimination and yields 3-(benzimidazol-2-yl)propionic acid 114 [115] (Scheme 4.36). 

Furans and benzo[/>]furans are further building blocks for optical brighteners. They are used, for example, in combination with benzimidazoles and benzo[6]fur-ans as biphenyl end groups. 

The Beirut reaction has also been employed to prepare 1-hydroxybenz-imidazole 3-oxides or benzimidazole 1,3-dioxides, when nitroalkanes have been used as enolate-producer reagent [46,47], and benzo[e][l,2,4]triazine 1,4-dioxides when Bfx reacts with sodium cyanamide [48-50]. 

Halofuran and halothiophene derivatives undergo photochemical reactions with arylalkenes and arylalkynes and with benzo[6]furan513,514. With the arylalkenes and aryl-alkynes, heteroarylation takes place at the terminal alkene or alkyne carbon atom, while benzo[6]furan is substituted at position 2. The experimental results are interpreted in terms of solvent-separated or contact radical ion pairs. Iodothiophene and iodofuran derivatives can also be used to synthesize derivatives of benzimidazole by means of photochemical coupling515. The reaction of 5-iodothiophene-2-carboxaldehyde (157) with benzimidazole (158) giving the coupling product 159 is illustrated in equation 131. 

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