5- Nitropyrazoles, reduction

The presence of N-N02 fragment in 1-nitropyrazole significantly facilitates the process of electrochemical reduction E m=-0.95, It" xn=-. 73 V (acetonitrile). The first wave corresponds to a one-electron irreversible transfer the second wave is approximately 3.5 times higher and shows sharp drop prior to background discharge (Scheme 3.36). Analysis of the dependence of 1-nitropyrazole reduction potentials on pH shows that the second wave corresponds to the reduction of the N02 anion (nitrite ion) formed [851],... 

The character of spin density distribution in an RA of l-ethyl-4-nitropyrazole differs from that in 1-methyl-isomer. 1-Nitropyrazole does not show an ESR signal in the conditions of both pulse radiolysis [849] and electrochemical reduction [851],... 

Dumanovic with colleagues carried out polarographic investigation of various derivatives 3-, 5-nitropyrazoles and 2-, 4-, 5-nitroimidazoles in aqueous buffer solutions (pH 1.8-9.3) and 0.1 M solution NaOH [903-912], On polarograms all the investigated nitroazoles have one or two waves of reduction both in acid and neutral medium. The first four-electron wave corresponds to reduction of nitro group to hydroxylamine one. The second two-electron wave corresponds to further reduction of hydroxylamine derivative to aminoazole (Scheme 3.34). 

In polymerization reactions by methyl methacrylate [915] a relationship between the reduction potentials of l-methyl-3-nitropyrazole, l-methyl-5-nitropyrazole, and l,2-dimethyl-5-nitropyrazole and their inhibited properties has been established. 

The electrochemical reduction of C- and IV-nitroazoles has been investigated in detail in an aprotic media [850-853], The reduction potentials of nitropyrazoles in acetonitrile are presented in Section 3.3 (Table 3.36). iV-substituted 3(5)-nitro- and -4-nitropyrazoles in acetonitrile are reduced in two one-electron stages [850, 851],... 

The polarogram of 1,4-dinitropyrazole is considerably more complex and has five waves (Table 3.36, Section 3.3). This compound is reduced more easily than all the investigated nitroazoles. The first wave corresponds to an irreversible one-electron transfer (Scheme 3.19). As with 1-nitropyrazole, at this stage an unstable anion radical is formed and then breaks up at bond N-N02. The N02 anion is reduced at potential -1.7 V. 4-Nitropyrazolyl radical further is dimerized with subsequent reduction [851],... 

Comparison of the reduction potentials of some nitroazoles including nitropyrazoles with their radiosensitizing properties has been carried out (Table 3.43) [919],... 

High-performance liquid chromatography (HPLC) has been used to analyze metronidazole [1435-1437], misonidazole [1309,1438], and other nitroimidazoles [1435, 1439] in body fluids or pharmaceutical dosage forms. HPLC analysis of effect of hypoxic-cell radiosensitizer misonidazole on the radiation-induced reduction of DNA bases (thymine, cytosine, and adenine) has been carried out [1440, 1441], HPLC was employed to characterize different nitroimidazoles [327, 366, 388,409, 450, 1442-1444], nitropyrazoles [246, 301], nitrothiazoles [366], l-aryl(hetaryl)-4-nitro-l,2,3-triazoles [601], nitrobenzimidazoles [707], nitrobenzofurazans [774, 1445-1449], nitrobenzotriazoles [1450],... 

The corresponding V-nitro derivatives behave similarly306-308 in acid solution the hydrazines are produced in a six-electron reaction, in alkaline medium the first two-electron reduction results in the formation of the A7-nitroso derivatives which at a more negative potential are further reduced. iV-Nitropyrazole behaves slightly differently as the reduction in acid solution also results in a cleavage of the N-N bond with formation of nitrous acid. 2-Nitraminopyri-dine309 in acid solution is reduced to the hydrazine. In alkaline solution the anion is reducible, in contradistinction to most nitramines derived from primary amines. The four-electron reduction yields 2-aminopyridine. Pyridine 1-nitroimide is reduced to pyridine.309... 

Electrochemical reduction and chemical reduction by cysteine or potassium ferrocyanide of iV-nitropyrazoles provided a new source of nitric oxide <1996MC11>. 

Reduction of 1-nitropyrazol in acid medium results in a cleavage of the N-N bond and formation of nitrous acid at pH > 4 a competitive reduction to the nitrosamine occurs [100a]. 

Electrochemical reduction of 1-nitropyrazole (18) results in the cleavage of the N—N bond with formation of pyrazole and nitrous acid <92MI 301-02). The electrochemical properties of Difenzoquat (l,2-dimethyl-3,5-diphenylpyrazolium cation) were examined <91JEC169) the reduction gives pyr-azolines and dimers. 

The ci e-substitution of 1,4-dinitropyrazoles affords 4-nitro-3(5)-substituted pyrazoles including the antibiotics formycin and pyrazofurin <91JCS(P1)1077>. Makosza <89LA545> has illustrated his vicarious nucleophilic substitution of hydrogen by examples of 4-nitropyrazole derivatives. The reduction of 1-nitropyrazole into 1-aminopyrazole was achieved by lithium aluminum hydride... 

Reduction of A7-nitropyrazole into A -aminopyrazole has been succesfully achieved by lithium aluminum hydride <92AQ724>. Reactions of l-nitro-3,5-dimethyl-4-halopyrazoles (195) with dbu and dbn affords derivatives (196) <94X865>. Reaction of 5-chloro-2-nitroindazole with amines affords 3-amino-5-chloroindazoles <85Phaio5>, while 2,5-dinitroindazole on treatment with A -methylpiperazine affords 3,5-dinitroindazole and 3-(7V-methylpiperazino)-5-nitroindazole <94PHA319>. 

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