Benzimidazole dicarboxylic acid

Examples of cocrystals containing chains, ribbons, and other infinite ID motifs (Scheme 8) include bipyridine dihydroxybenzene, melamine cyanuric acid, bipyridine (fluorinated)dibromobenzene, 2-aminopyridine dicar-boxylic acids, triaminopyrimidine barbituric acid, 2-aminopyrimidine dicarboxylic acid, " 1,2,3-trihydroxy-benzeneihexamethylenetetramine, diols diamines, bis-benzimidazole dicarboxylic acids, and 2-amino-5-nitro-pyrimidine 2-amino-3-nitropyridine." ... 

Several routes have been reported for the synthesis of aromatic poly(azole)s such as poly(benzimidazole), poly(benzoaxazole), and poly(benzthiazole) melt polycondensation of dicarboxylic acid diphenyl esters with tetramines21 and high-temperature solution polycondensation of dicarboxylic acids or their derivatives with tetramine hydrochlorides in PPA.22 PPA acts as condensing agent and solvent. Ueda etal.23 developed a modified method for the synthesis ofpolyazoles with the use of PPM A. 

The reduced viscosity ofpoly(benzimidazole) from 15 and tetramine (24) is not high enough under the reaction conditions described above in PPMA. The reaction at 200°C for 24 h in PPMA affords only a low-molecular-weight polymer in a low yield owing to low solubility in PPMA and sublimination of dicarboxylic acid (15). However, an improved reduced viscosity of 0.59 dl/g is attained by a two-step method, first at 140°C for 24 h and then at 200°C for 24 h. 

The technical production of poly(benzimidazole) (PBI) is also carried out in two steps. In the first step an aromatic tetramine is condensed with the diphenyl ester of an aromatic dicarboxylic acid at 220-260 °C, yielding a poly(amino amid) with elimination of phenol. Ring closure with elimination of water occurs in the second step (solid-phase polycyclocondensation), conducted at 400 °C and yielding the polybenzimidazole (experimental procedure, see Table 2.3). 

Vigorous oxidation (e.g., with KMn04) usually degrades fused benzene rings in preference to many azole rings, especially under acidic conditions. Thus, benzimidazoles are oxidized by chromic acid or 30% hydrogen peroxide to imidazole-4,5-dicarboxylic acid, and 2,1,3-benzothiadiazole is oxidized by ozone or potassium permanganate to the dicarboxylic acid 553. 

That imidazoles and benzimidazoles have high stability has been known for many years. Resistance to acids, bases, heat and oxidation or reduction are common traits of these compounds, which display considerable aromatic character. Thus treatment of benzimidazole with permanganate leads to imidazole-4,5-dicarboxylic acid imidazoles, in general, are not easily oxidized or reduced (Sections 4.07.1.4.11, 4.07.1.5.6, 4.07.1.7.4). Thermal stability too is evidenced by the resistance of the imidazole nucleus to ring fission... 

Benzimidazole (but not 1-methylbenzimidazole) is oxidized by permanganate, dichromate or hydrogen peroxide to imidazole-4,5-dicarboxylic acid, while napth-[l,2-d]- and -[2,3-d]-imidazoles also form products in which the heterocyclic ring remains intact, hence demonstrating its stability to these conditions. With lead peroxide benzimidazole is subject to an unusual oxidation as it forms (101), also the reaction product of lead dioxide and 2,2 -bibenzimidazolyl. In dioxane, selenium dioxide oxidizes 2-methylbenzimidazole to o-hydroxyacetanilide (66RCR122). 

Electrophilic reagents preferentially attack benzimidazoles in the fused benzene ring, while nucleophiles react at C-2 which has enhanced nucleophilic activity because of the electron-withdrawal effect of the benzene moiety. The fused aryl ring appears to exhibit less aromatic stability than the heteroring as evidenced by the ready oxidation of benzimidazole to imidazole-4,5-dicarboxylic acid, and by its catalytic reduction over platinum... 

A seldom used route to imidazoles which may have the occasional application is that which oxidizes a benzimidazole to give the imidazole-4,5-dicarboxylic acid. Either chromic acid or 30% hydrogen peroxide is effective, but N-substituted benzimidazoles cannot be converted in the same way [27, 28]. 

To concentrated sulfuric acid (70 ml) and water (55 ml) at 90°C is added benzimidazole (5 g), followed by powdered potassium dichromate (37 g). After 10-15 min the reaction is quenched carefully with water. The product is filtered, and washed with water in about 70% yield, m.p. 290°C (dec.). Similar oxidation of 2-methylbenzimidazole gives 2-methylimidazole-4,5-dicarboxylic acid (52%). 

Usually decarboxylation is accomplished by heating the acids above their melting points, often in the presence of a copper-chromium catalyst. Imidazole-4,5-dicarboxylic acid can be monodecarboxylated by heating its monoanilide imidazole- and benzimidazole-2-carboxylic acids decarboxylate very readily indeed, so readily that the carboxyl function makes a useful blocking group in metallation procedures (see Scheme 7.2.1) [3-5]. A potentially useful method of preparation of imidazole-4-carboxylic acid derivatives heats the 4,5-dicarboxylic acid (2) with acetic anhydride to form (1), which is essentially an azolide and very prone to nucleophilic attack which cleaves the nitrogen-carbonyl bond (Scheme 8.3.1). With methanol the methyl ester (3) is formed with hydrazines the 4-hydrazides (4) result [6]. 

The condensation of a-ketoacids and o-phenylenediamines gives quinoxalin-2-ones,7 and mesoxalic acid and o-phenylenediamine undergo the expected condensation reaction to give quinoxalin-3-one-2-carboxylic acid (1). With sodium mesoxalate an anomalous reaction occurs, the initial products (1) and l,2-dihydrobenzimidazole-2,2-dicarboxylic acid (2) undergo an intermolecular hydrogen transfer reaction to yield l,2,3,4-tetrahydro-3-oxoquinoxaline-2-carboxylic acid (3) and benzimidazole-2-carboxylic acid (4).8... 

Poly(benzimidazoles) are produced from dicarboxylic acids and aromatic tetramines. Commercially, 3,3 -diaminobenzidine tetrahydrochloride and diphenyl isophthalate are preferentially used. The diphenyl ester is used because (a) the free acids decarboxylate under the high reaction temperatures of 250-400 C (b) the acyl chlorides react too fast, making ring closure difficult and (c) the amino groups are partially methylated if the methyl esters are used. The hydrochloride is used because it is more stable to oxidation than the free amine itself. The polycondensation is carried out in two stages. A prepolymer. A, is formed in the first stage with foaming and phenol elimination ... 

Poly(benzimidazoles) have high thermal stability, and there has been no lack of effort to increase the thermal stability even more through suitable choice of the initial monomers. If the dicarboxylic acids are replaced by tetracarboxylic acids or their anhydrides, and these are then converted with tetramines, then more or less perfect ladder polymers are formed. These ladder polymers all have a thermal stability about 100 K higher than PBI, and so can be used up to about 600° C. Poly(imidazopyrrolone) or pyrron, polypyrrolone, and poly(benzimidazobenzophenanthroline) or BBB may be specially mentioned in this respect. The synthesis of these difficultly soluble polymers must be mostly carried out in solvents such as polyphosphoric acid, zinc chloride, or eutectic mixtures of aluminum chloride and sodium chloride ... 

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