Imidazoles acidity

Moreover, polymer film electrolytes have been prepared by polymerization of the imidazole-acid mixtures. The copolymer was synthesized by imidazole... 

Imidazole acid halides are very reactive and are easily converted into other acid derivatives <82JHC56l, 84JOC1951>. They cannot, however, be used as precursors of acetyl functions in reaction with lithium dimethylcopper <92JHCl02i>. 

Thekinetics of nitration in sulphuric acid of both pyrazole and imidazole have been studied. Data have already been quoted (tables 8.1, 8.3) to support the view that the nitration of both of these compounds at C(4)... 

These compounds are easily prepared from the appropriate 2-aminothiazole and acyl chloride (see Section III.2.D) or by general heterocydization methods. Acyl chlorides may be replaced by the corresponding anhydrides (471). Acids themselves may be used as acylating agents provided that the imidazole-triphenyl phosphine mixture is used as a catalyst (472). The Curtius degradation of 247 yields 2-acetamido-4-phenylthiazole (248) (Scheme 149) (473). 

An imidazole ring is a structural unit m the ammo acid histidine (Section 27 1) and is involved m a large number of biological processes as a base and as a nucleophile... 

Given that the p/Ca of imidazolium ion is 7 is a 1 M aqueous solution of imidazolium chloride acidic basic or neutraP What about a 1 M solu tion of imidazole A solution containing equal molar quantities of imidazole and imidazolium chloride ... 

When the proportion of acid to amine groups is reversed-namely, l 2--a process rather similar to reaction (5.II) yields a polymer which ultimately contains the five-membered imidazole ring. This reaction is also carried out in the stages listed below and illustrated by reaction (5.JJ) ... 

Several biologically and pharmacologically active compounds have been prepared from the condensation of the acid chloride of 1-naphthoxyacetic acid with carbazole, iadole, or pyrrole ia 2A[ NaOH solution ia ethanol (63). Also, naphthyloxy derivatives of imidazole, benzimidazole, and benzotriazoles have been synthesized and screened for their antimicrobial, analgesic, and antiinflammatory activities. 2-Naphthyloxy derivatives are comparatively more active than 1-naphthyloxy derivatives (64). 

Ketoconazole. For treatment of systemic mycoses with amphotericin B or miconazole, the patient must be admitted to a hospital. This is not always possible, particularly in areas where systemic mycoses occur frequently, nor is it always desirable, because of the expense. For these reasons, it was desirable to find an antimycotic that combined safety and broad-spectmm activity with oral adraiinistration. Ketoconazole (10), which is orally active, met most of these requirements. This inhibitor of the ergosterol biosynthesis is an A/-substituted imidazole, that differs from its precursors by the presence of a dioxolane ring (6,7). Ketoconazole is rapidly absorbed in the digestive system after oral adrninistration. Sufficient gastric acid is required to dissolve the compound and for absorption. Therefore, medication that affects gastric acidity (for example, cimetidine and antacids) should not be combined with ketoconazole. 

Alloxan forms an oxime (1007) which is the same compound, violuric acid, as that formed by nitrosation of barbituric acid likewise, a hydrazone and semicarbazone. Reduction of alloxan gives first alloxantin, usually formulated as (1008), and then dialuric acid (1004 R = OH) the steps are reversible on oxidation. Vigorous oxidation with nitric acid and alkaline hydrolysis both give imidazole derivatives (parabanic acid and alloxanic acid, respectively) and thence aliphatic products. Alloxan and o-phenylenediamine give the benzopteridine, alloxazine (1009) (61MI21300). 

Values for the tt-electron densities in imidazole and two related ions are given in Figure 1, The TT-electron densities in the conjugate acid of imidazole are greater at the 2-position... 

Figure 1 The tt-electron densities in imidazole, its conjugate acid and base, and pyrazole...

Table 36 summarizes the known annular tautomerism data for azoles. The tautomeric preferences of substituted pyrazoles and imidazoles can be rationalized in terms of the differential substituent effect on the acidity of the two NFI groups in the conjugate acid, e.g. in (138 EWS = electron-withdrawing substituent) the 2-NFI is more acidic than 1-NFI and hence for the neutral form the 3-substituted pyrazole is the more stable. 

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