Pyrazole 3 -amino-4-nitro

In Amino-substituierten 1 H-Pyrazolen werden die Amino-Gruppen durch Trifluor-peressigsau-re (Dichlormethan 2 h Riickfl.) zur Nitro-Gruppe oxidiert so werden aus 3-Amino- und 5-Ami no-1 -phenyl-1 H-pyrazol 3-Nitro-l-phenyl- bzw. 5-Nitro-l-phenyl-lH-pyrazol erhalten. Lediglich 5-Amino-l-methyl-1 H-pyrazol gibt in 10%iger Ausbeute l-Methyl-5-nitro-lH-pyr-azol-2-oxid (Schmp. 109°)1369. 

Nitro groups are easily reduced, catalytically or chemically, to give amino compounds, e.g. 4-nitroisothiazoles give the corresponding 4-amino derivatives (72AHC(i4)i). In the pyrazole series, intermediate nitroso compounds can be isolated. Nitrosoimidazoles are also relatively stable. 

Pyrazoles were synthesized in the authors laboratory by Le Blanc et al. from the epoxy-ketone as already stated in Sect. 3.1.1a, Scheme 35 [80]. The synthetic strategy employed by Le Blanc et al. [80] was based upon that the strategy published by Bhat et al. [81] who also described the synthesis of pyrazoles but did not report cytotoxic evaluation on the synthesized compounds. Scheme 48 shows the synthesis of the most active compound (178). Dissolution of the epoxide (179) with a xylenes followed by treatment with p-toluenesulfonic acid and hydrazine hydrate produced the pure nitro-pyrazole 180 in good yield (60%). Catalytic hydrogenation with palladium on activated carbon allowed the amino-pyrazole (178) to be obtained in a pure form. This synthesis allowed relatively large numbers of compounds to be produced as the crude product was sufficiently pure. Yield, reaction time, and purification compared to reported approaches were improved [50, 61, and 81]. Cytotoxicity of these pyrazole analogs was disappointing. The planarity of these compounds may account for this, as CA-4, 7 is a twisted molecule. 

Hrf.N C(CH,).C(NOj G.N N.NH6c(NO.,).-C(CH3) NilH mw 295.23, N 42.72% yel crysts, mp 151-2°, dec violently with evolution of gas dissolves in dil NaOH giving an intense violet-red soln, which on acidification reppt the compd unchanged insol in aq alk carbonates was prepd by treating 3-methyl-4-nitro-5-amino -pyrazole in HC1 at 0° with NaN02 and Na acetate for several hours. This compd forms an orn-red Silver salt reacts with diazomethane to form the trimethyl deriv, a yel compd, mp 163-4° (dec) and with phenylisocyanate,... 

This reaction acquires special significance as a result of the fact that it is possible to introduce a nitro group at position 3(5) of the pyrazole ring. This is impossible during direct nitration. /V-Nitroimida/oles [323, 326] and 1,2,4-triazoles [318, 577] enter into such a rearrangement. In a similar way A-nitroaminothiazoles isomerize to 2-amino-5-nitrothiazoles [231] (Scheme 110). 

A mass spectrometric study of 3-amino- and 5-amino-l-methyl-4-nitropyrazole and 3-nitro-, 5-nitro-4-amino-l-methylpyrazoles has been performed [1286], The highest relative intensity of the [M-NO]+ peak is observed with 5-amino-l-methyl-4-nitropyrazole. The authors believe this to be related with the pyrazole ring 7t-excessive position 4 and the easy transmission of the electronic effect of the amino group through the (C-4)-(C-5) bond. The [M-NO]+ peak relative intensity is minimal for 4-amino-l-methyl-3-nitropyrazole. This indicates a lower stabilization of the [M-NO]+ ion by the N-l atom compared with that produced by the N-2 atom seemingly due to the electron-withdrawing properties of the pyrazole ring N-2 atom [1286],... 

Mass spectrometry has been used for the structural determination of isomeric I -methyl-3(5)-nitro-4-pyrazolcarbonitriles [302], l,5-dimethyl-3,4-dinitropyrazole [279], 4,4-dinitro-l,l-methylenedipyrazole [1291], 3-amino-5-bcnzylamino-4-nitro-yrazole [317], amino derivatives of 4-nitropyrazole [1292], antibacterial compounds 3-(3-mcthyl-4-nitro- lf/-pyrazole-5-yl)- and 3-(3-methyl-4-nitro-l-alkylpyrazole-5-yl)-5-methyl-4-nitroisoxazoles [500], some l-heteroaryl-4-nitropyrazoles [311]. 

The catalytic activity of Ag/Pd bimetallic nanoparticles immobilized on quartz surfaces was tested for 4-nitro-3-pyrazole carboxylic acid with help from surface plasmon resonance, scanning electron microscopy, and surface-enhanced Raman scattering (SERS) measurements [1417], The SERS spectra showed that the nitro group reduces to amino group. 

Amino-3-ethylamino-2-nitro-E15/3, 2775 (4-Cl-6-NR2-5-NOj — pyrimidin/Base) lH-Pyrazol 3(5)-Diethylamino-4-nitro- E8b, 598 (NOz - NH2) Pyrimidin... 

Propan l-(2-Methoxy-5-methyl-phenyl)-2-nitro-l-nitroso-(dimer) X/l, 74 Propansaure 2-Amino-3-(4-hydroxy-phenyl)- -(carboxy-methylamid) XV/2, 195, 617 3H-Pyrazol 3-Cyclopropyl-4,5-dimethoxycarbonyl-3-methyl-E14, 994 (R2C = N2 4- In) Pyrimidin 2,6-Dimethoxy-5-(2-methoxycarbonyl-ethenyl)-4-methyl- E9b/2, 224f. 

Pyrazol 5-Amino-1-(l-anilino-2-nitro-ethenyl)-4-cyan-3-methyl-thio- E1S/3, 2795 [02N-CH = C(NHR)-NH-NH2 +... 

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