Cationic Benzimidazoles

5-Di(l-methylbenzimidazol-2-yl)furan [ 4751-43-3] [81], which has the ability to form salts, was one of the first cationic benzimidazole brighteners. More recently, cationic benzimidazoles have been developed as brilliant, chlorine-fast, lightfast brighteners for polyacrylonitrile and cellulose acetate (Table 7.7). They are marketed in the form of cold- and heat-resistant concentrated aqueous solutions with long shelf lives. 

In the synthesis of 47, 4-methoxysalicylaldehyde is condensed with 2-chloro-methyl-l-methyl-5-methylsulfonylbenzimidazole, ring closure is effected, and the product is quatemized with dimethyl sulfate [83], To enhance water solubility, the methyl sulfate anion is converted to the acetate anion the benzimidazole ring is 

Compound 47 can also be synthesized from 6-methoxybenzo[h]furan-2-car-boxylic acid and 2-methylamino-5-methylsulfonylaniline by cyclocondensation [83], 

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The reactivity of these compounds is somewhat similar to that of the azolonium ions, particularly when the cationic species is involved. However, although the typical reaction is with nucleophiles, the intermediate (20) can lose the iV-oxide group to give the simple a-substituted azole (21). Benzimidazole 3-oxides are readily converted into 2-chloroben-... 

Imidazoles and benzimidazoles (155) react with acid chloride and alkali to give compounds of type (157), but these are reactions of the cation (156). 1,2,4-Triazoles and tetrazoles similarly undergo ring opening. 

The first compound of this class with inhibitory activity on the enzyme and on acid secretion was the 2-(pyridylmethyl)sulfinylbenzimidazole, timopra-zole, and the fust pump inhibitor used clinically was omeprazole, 2-[[3,5-dimethyl-4-methoxypyridin-2-yl] methylsulfinyl]-5-methoxy- lH-benzimidazole. Omeprazole is an acid-activated prodrug. Omeprazole and the other PPIs are accumulated in the acidic space of the parietal cell due to the pKa of the pyridine nitrogen and these are converted due to protonation of the benzimidazole nitrogen first to a thiol-reactive cationic sulfenic acid and then dehydrated to form the sulfenamide (Fig. 1). These thiophilic cations then bind to luminally... 

Protonation shifts, obtained from nmr spectra in deutero-chloroform and trifluoroacetic acid, for 1-methylimidazoles also suggest that the cations show amidinium type resonance, because the signal of the proton on C-2 shifts downfield much more than those of the protons on C-4 and C-5 (Barlin and Batterham, 1967). Amidinium type resonance in benzimidazoles activates the proton on C-2, which becomes susceptible to base-catalysed exchange (Elvidge et al., 1973). The effects of protonation on electron densities in the imidazole ring have been calculated by extended Hiickel theory (Adam et al., 1967). 

The rather high basic strength of 3,5-diazaindole [91] (p/sTa = 6T) is not due to the protonation of the imidazole ring (for benzimidazole p g = 5-53), but rather of the pyridine ring. Cation [92] is formed and this is stabilized by the same kind of resonance as... 

Rates of detritiation of [2- H]-benzimidazole (10) and the corresponding 1-methyl compound have been measured over a pH range at 85° and the bell-shaped pH-rate profile (Fig. 1) accounted for in terms of rate-determining attack by OH on the benzimidazole cation with the formation of an ylide intermediate. Because of the ionization of the N-H group at high pH, the development of negative charge a to the... 

Cationic FBAs are used to brighten polyacrylonitrile fibres. The brightening of acrylic fibres is carried by the exhaust method at an acid pH, usually in the presence of sodium chlorite or bisulfite bleach. Pyrazolines produce very high whites but are unstable to bleach and therefore the quaternary benzimidazoles are the preferred class, e.g. (3.65) and (3.66). 

Heat stabilizers can be selected from benzothiazoles, benzimidazoles hydrazine compounds, and cation exchange materials (73). Moreover, the addition of heat stabilizers results in an improvement of the impact resistance. 

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. 

Hiickel m.o. calculations fail badly with benzimidazole. Localisation energies for the free base and the cation indicated C(4) to be the most reactive position towards electrophilic attack,156157 and led to the false conclusion that substitution involved the free base, the orientation being controlled by charge57 densities. 

A frontier-orbital MO treatment of the regioselectivity of the nitration of ben-zotriazole, benzimidazole, their IV-methyl derivatives, and their protonated cations gives predictions in accord with experimental observations.19 The preferred nitration site of the 1//-tautomer of benzimidazole (10), for example, is predicted to be the 5(6)-position, as observed experimentally. 

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