Pyrazole 2-oxide 1-methyl

IR spectra, 5, 201 Pyrazole, 1-methyl-anodic oxidation, 5, 247 hydrogen exchange acid-catalyzed, 5, 239 2-oxide... 

Pyrazole, 1 -(2-methylaminophenyl)-synthesis, 5, 283 Pyrazole, l-methyl-5-nitro-2-oxide... 

Surprisingly, there are very few examples of successful fV-oxidation of pyrazoles. Simple fV-alkylpyrazoles generally do not react with peracids (B-76MI40402,77JCS(P1)672). The only two positive results are the peracetic acid (hydrogen peroxide in acetic acid) transformation of 1-methylpyrazoIe into 1-methylpyrazole 2-oxide (268) in moderate yield and the peroxy-trifluoroacetic acid (90% hydrogen peroxide in trifluoroacetic acid) transformation of 5-amino-l-methylpyrazoIe into l-methyl-5-nitropyrazoIe 2-oxide (269). 

Bromine in chloroform and bromine in acetic acid are the reagents used most often to brominate pyrazole. When nitric acid is used as a solvent, both bromine and chlorine transform pyrazoles into pyrazolones (Scheme 24). Thus 3-methyl-l-(2,4-dinitrophe-nyOpyrazole is brominated at the 4-position (309). The product reacts with chlorine and nitric acid to give the pyrazolone (310). The same product results from the action of bromine and nitric acid on (311). The electrophilic attack of halogen at C-4 is followed by the nucleophilic attack of water at C-5 and subsequent oxidation by nitric acid. 

As regards toxicity, pyrazole itself induced hyperplasia of the thyroid, hepatomegaly, atrophy of the testis, anemia and bone marrow depression in rats and mice (72E1198). The 4-methyl derivative is well tolerated and may be more useful than pyrazole for pharmacological and metabolic studies of inhibition of ethanol metabolism. It has been shown (79MI40404) that administration of pyrazole or ethanol to rats had only moderate effects on the liver, but combined treatment resulted in severe hepatotoxic effects with liver necrosis. The fact that pyrazole strongly intensified the toxic effects of ethanol is due to inhibition of the enzymes involved in alcohol oxidation (Section 4.04.4.1.1). 

Diazoalkanes add to the carbon-carbon double bonds of 2,3-diphenylthiirene 1-oxide and 1,1-dioxide. The adducts lose SO or SO2 to give pyrazoles and related compounds (Scheme 103) (80CB1632). Mesoionic oxazolones (75CLH53), 4-methyl-5-phenyl-l,2-dithiolene-3-thione (80JOU395) and pyrylium betaines (72JOC3838) react similarly via intermediate adducts (Scheme 104). Enamines (Scheme 96) and ynamines add to the double bond of 2,3-diarylthiirene 1,1-dioxides to give acyclic and cyclic sulfones by a thermal. 

Tetraazafulvalenes bearing two pyrazole subunits could be prepared by an original way. Tlius, treatment of benzylidene acetophenone with iso-pentylnitrite leads to an A, A -dihydroxy-bipyrazolyl-A, A -oxide, which in turn can be oxidized to TAF of type 100 (72CC961, 79JOC3211). Another type of oxidative dimerization was observed by the reaction of the electron-rich l-methyl-2,4-bis(dimethylamino)imidazole with silver salts (83TL3563). A bis-cation was isolated in 30% yield in the presence of sodium tetrafluo-roborate an unsymmetrical structure 101 was predicted from its NMR data (Scheme 40). 

The 3,5-bis(trifluoromethyl)pyrazolate analog [Ir(cod)(/x-3,5-(CF3)2pz)]2 does not enter into oxidative addition with iodine, methyl iodide, or acetylenes. The mixture of pyrazolate and 3,5-bis(trifluoromethyl)pyrazolate gives [(rj -codllrf/x-pz)(/L-3,5-(CF3)2pz)Ir(rj -cod)], which reacts with bis(trifluoromethyl)acetylene in a peculiar manner [83JCS(CC)580], producing 145, where 3,5-bis(trifluoromethyl) pyrazolate is replaced by the ethylene bridge and the rj -coordination mode of one of the cod ligands is converted into the rj -allylic mode. 

However, addition of bromine is accompanied by bromination of 3,5-dimethyl-pyrazolate and pyrazolate ligands at position 4, which is blocked in 4-methyl-pyrazolate. The product of electrochemical oxidation of 175 (R -- R = Me, R = Br) is 177 (R = R = Me, R = Br, X = CIO4). Chlorination proceeds similarly to bromination. 

Aryl-substituted 6-methyl-4//-pyrazolo[3,4-c]-l,2,5-oxadiazoles 275 are easily obtained in 88-97% yields by the oxidation of 2-aryl-5-methyl-4-nitroso-2//-pyrazol-3-amines 274 with Pb(OAc)4 (Equation 52) <2000S72>. 

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