Imidazole catalytic reduction

Pyrazotes are very resistant to catalytic reduction, resisting hydrogenation over nickel at 150 °C and 100 atm (66AHC(6)347). Imidazoles are generally resistant to reduction. 

Sulfonamides (R2NSO2R ) are prepared from an amine and sulfonyl chloride in the presence of pyridine or aqueous base. The sulfonamide is one of the most stable nitrogen protective groups. Arylsulfonamides are stable to alkaline hydrolysis, and to catalytic reduction they are cleaved by Na/NH3, Na/butanol, sodium naphthalenide, or sodium anthracenide, and by refluxing in acid (48% HBr/cat. phenol). Sulfonamides of less basic amines such as pyrroles and indoles are much easier to cleave than are those of the more basic alkyl amines. In fact, sulfonamides of the less basic amines (pyrroles, indoles, and imidazoles) can be cleaved by basic hydrolysis, which is almost impossible for the alkyl amines. Because of the inherent differences between the aromatic — NH group and simple aliphatic amines, the protection of these compounds (pyrroles, indoles, and imidazoles) will be described in a separate section. One appealing proj>erty of sulfonamides is that the derivatives are more crystalline than amides or carbamates. 

H]GR 168320 was developed as a (stably labelled) tritiated H3 antagonist and evaluated for its in vitro use as a radioligand for the H3 receptor [29], As has been shown for thioperamide, the tritium labels at the 2 and 5 position of the imidazole moiety and at the 4 position of the piperidine moiety are sensitive to exchange with hydrogen from the storage solution. [3H]GR 168320 is labelled at the cyclohexane, by a catalytic reduction with 3H2, no details about the synthesis have been published (scheme 11). [3H]GR 168320 was isolated with a specific activity of 4.8 Ci/mmol. 

Imidazoles and benzimidazoles are generally quite resistant to such reduction reactions. Catalytic reduction of aryl- and furyl-substituted imidazoles affects only the aryl and furyl rings, but there has been an isolated report that 2-methyl-4,5-diphenylimidazole can be reduced over palladium to give the corresponding imidazolidine (70AHC(12)103). In the presence of palladium, platinum and rhodium catalysts in acid media, benzimidazoles were found to be reduced only in the fused benzene ring (73MI40700). 

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... 

Such substrates as a-(acylamino)enaminones (4) can be made by catalytic reduction of acylated 4-aminoisoxazoles (3) [16, 17J, or acetamidines made from 4-amino-5(4/f)-isoxazolones [18]. Although the starting materials require multistep syntheses, they are quite readily available in high yields, and their reduction and transformation into imidazoles are often quantitative (see Section 6.1.2(e)). 

Prolonged heating of an a-acylatninoazole with phosphorus oxychloride leads to the formation of a new imidazole ring. When the acylamino group is attached to one of the peri positions of a bicyciic molecule, the imidazole ring may be formed at the peri positions as in this example of a quinoxaline where catalytic reduction has also affected the pyrazine ring. 

Structural studies presented by Chibata and by Kamiya included similar total syntheses of eritadenine, each consisting of the condensation of 4-amino-6-chloro-5-nitropyridine with 4-amino-4-deoxy-2,3-C)-isopropyli-dene-D-erythromic acid, followed by catalytic reduction of the ni-tro group and imidazole ring closure by formic acid or its amide. This can be exemplified by Kamiya s procedure (400) shown in Scheme 83. Soon improved syntheses were reported from both laboratories by Kawazu et al. (401) and Kamiya et al. (402), each starting from adenine and methyl 2,3-0-isopropylidene-5-0-tosyl-)8-D-ribofuranoside or d-erythronolactone acetonide, respectively (Schemes 84 and 85). Kamiya... 

Figure 18.5 Plausible sequence of steps responsible for rapid and selective reduction of O2 to H2O by mixed-valence CcO. The square frames signify the catalytic site (Fig. 18.4c) imidazole ligation of Cub is omitted for clarity in some or aU intermediates, Cub may additionally be ligated by an exogenous ligand, such as H2O (in Cu ) or OH (in Cu ) such ligation is not established, and hence is omitted in all but compound Pm and the putative hydroperoxo intermediate. The dashed frames signify the noncatalytic redox cofactors. Typically used phenomenological names of the spectroscopically observed intermediates (compounds A, E, H, etc.) are also indicated.

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