Benzimidazole carboxamides

Despite their close chemical relationship, the benzimidazole carboxamides 53 and... 

BIMU 1 is a benzimidazole-carboxamide derivative, a selective (S-HT -subtype) 5-hydroxytryptamine receptor AGONIST. It has antiemetic properties, and is used as a pharmacological tool. 

CASRN 148-79-8 molecular formula C10H7N3S FW 201.25 Photolytic. When thin films of thiabendazole on glass plates were exposed to sunlight for 128 d, benzimidazole-2-carboxamide and benzimidazole formed as photolysis products. Both compounds also formed when aqueous methanolic solutions of thiabendazole were subjected to UV light for 1 h (Zbozinek, 1984). 

Diaminoethane and 1,2-diaminobenzene do not furnish cyclic derivatives of tetramic acid. Independent of the reaction time and the molar ratio of the reactants, the corresponding 3-carboxamides 18 and 19 are the only products [88UP1 cf, 67JCS(C)693]. Heating 19 in a sublimation apparatus to 220-240°C gives benzimidazole 20 in 65% yield (88UP1). (See Fig. 10.)... 

Martin, N. Biinzli, J.-C. G. McKee, V. Piguet, C. Hopfgartner, G. Self-assembled dinuclear lanthanide helicates substantial luminescence enhancement upon replacing terminal benzimidazole groups by carboxamide binding units. Inorg. Chem. 1998, 37, 577-589. 

Apart from the chemistry of the 4-hydroxy derivative (see p. 126) relatively little investigation in this area has been conducted. Thiocoumarin-3-carbonyl compounds have proved to be effective precursors for the synthesis of the pharmaceutically useful 3-(2-benzimidazolyl) derivatives. Thus, on interaction of the 3-carboxamide with o-phenylenediamine or the 3-aldehyde with o-nitroanilines, the above benzimidazoles or their TV-oxides are formed. 

The most important applications of the in situ photochemical fluorodediazoniation start from heterocyclic amines for which the diazonium tetrafluoroborates are impossible to isolate. In this way, fluorinated imidazoles,123-253,254-257 261 benzimidazoles,262 pyrazoles,254-256,262 indazoles,158 thiazoles,259 and triazoles259-262 have been prepared (Table 4). Some of these are the precursors of biologically active compounds such as fluoro-substituted histidines or histamines,123,253-257,258 or 5-fluoro-l/ -D-ribofuranosylimidazole-4-carboxamide.261... 

Imidazole and thiazole rings have demonstrated instability under photolysis conditions. For example, the API thiabendazole undergoes cleavage of the thiazole ring to form benzimidazole-2-carboxamide and benzimidazole as well as cleavage of the imidazole ring to form thiazole-4-(7V-carbomethoxy)-carboxamide (Fig. 116) (106). 

OHDPAT, 8-hydroxy-2(di- -propylamino)tetralin ACPD, trans-1 -amino-cyclopenty 1 -1,3 -dicarboxylate AMP A, DL-cr-amino-3-hydroxy-5-methylisoxazole-4-propionate BIMU8, [endo-A-8-methyl-8-azabicyclo(3.2.1)oct-3-yl]-2,3-dihydro-3-isopropyl-2-oxo-177-benzimidazol-l-carboxamide hydrochloride CGP 35348, 3-aminopropyl(diethoxymethyl)phosphinic acid CNQX, 6-cyano-7-nitroquinoxaline-2,3-dione CP 99994, (+)-(2 , 3A)-3-(2-methoxybenzylamino)-2- ... 

Preparation of l-(2-chlorophenyl)-3-[2-(diethylamino)ethyl]-2-oxo-7-(trifluoro methyl) -2,3-dihydro-lH-benzimidazole-5-carboxamide... 

FIGURE 15.35 Benzimidazoles, indazolones, and indoles as carboxamides bioisosters. 

Conversion of 4,5,6-triaminopyrimidine into purines by heating at 160-240 C with an anhydride, a carboxamide or a nitrile gives yields which vary from 36 to 96% [2304]. Aroyl halides in DMF give moderate-to-good yields of 2-aryl-benzimidazoles, and some esters cyclize the triamine similarly [2506, 2979. ... 

The unsymmetrical tridentate NNO ligands L19, in which the central pyridine ring is decorated with one benzimidazole unit and one carboxamide group, have been s)mthesized by using either 2-carboxamido-... 

The evolution of the formation constants of the binuclear triple-stranded helicates [1 2(L11)3] (NNN-S-NNN donor sets) and [R2(L13 )3] " " (ONN-S-NNO donor sets) along the lanthanide series mimics the size-discriminating effects previously established with the mononuclear precursors (Figure 31). When NNN donor sites are used in Lll, the stability constants drops for the smaller R , a trend removed when the terminal benzimidazole rings are replaced with carboxamide units in (Table 8). The connection of electron-withdrawing halo-... 

Ketone syntheses. Acyl derivatives that favor the arrestment of Grignard reactions beyond the first round include A-acylpyrazoles, acyl hemiacetals, and acyl tributylphosphonium chlorides (generated in situ from RCOCl and Bu,P). The protocol involving Al-methoxy-Al-methyl carboxamides has been extended to the preparation of a-chloro ketones, a-keto amides, and a-diketones (the last two from the oxalyl diamides). Symmetrical diketones are obtained by the Grignard reaction of bis(benzimidazole) methiodides. Note that an analogous reaction of 1,3-disubstituted benzimidazolium salts furnishes aldehydes. ... 

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