Nitropyrazoles: XII. Transformations of the 4-Methyl Group in 1,4-Dimethyl-3,5-dinitropyrazole and Cyclization of the Transformation Products

Abstract

A preparative procedure for the synthesis of 1,4-dimethyl-3,5-dinitropyrazole by nitration of 1,4-dimethylpyrazole was developed. The reaction of 1,4-dimethyl-3,5-dinitropyrazole with dimethoxymethyl-(dimethyl)amine (N,N-dimethylformamide dimethyl acetal) gave (E)-N,N-dimethyl-2-(1-methyl-3,5-dinitropyrazol-4-yl)ethenylamine. Acid hydrolysis of the latter afforded (1-methyl-3,5-dinitropyrazol-4-yl)acetaldehyde, and the reaction with sodium nitrite in hydrochloric acid led to formation of 2-hydroxymino-2-(1-methyl-3,5-dinitropyrazol-4-yl)acetaldehyde. The corresponding O-methyloxime and phenylhydrazone reacted with K 2 CO 3 to give 6-methyl-4-nitropyrazolo[4,3-d]isoxazole-3-carbaldehyde O-methyloxime and 1-methyl-3-nitro-4-(2-phenyl-2H-1,2,3-triazol-4-yl)pyrazol-5-ol, respectively. Treatment of (1-methyl-3,5-dinitropyrazol-4-yl)-acetaldehyde with benzenediazonium chloride gave (1-methyl-3,5-dinitropyrazol-4-yl)acetaldehyde phenylhydrazone which underwent intramolecular cyclization with replacement of the 5-nitro group by the action of K 2 CO 3 in acetonitrile; in the reaction with K 2 CO 3 in ethanol, the 5-nitro group was replaced by ethoxy.* For communication XI, see [1].

A concise review on synthesis, reactions and biological importance of thienopyrazoles

“…Zaitsev et al 48,49 found a new method for preparing of thieno [2,3-c]pyrazole derivatives starting from dinitropyrazole derivative 35. The carbonitrile 37 was synthesized from dinitropyrazole 35 by two methods.…”

Synthesis and Crystal Structures of Alkali and Alkaline Earth Metal Complexes of 3,5‐Dinitropyrazolyl‐4‐carboxylate

“…Subsequently, fuming nitric acid (10 mL) was added to the mixture under vigorous stirring at 30–40 °C. The mixture was then heated to 95 °C and reacted for 8 h. Afterwards, the obtained solution was cooled and poured into 250 mL of ice water, along with a lot of red brown nitrogen dioxide coming out from the solution . The mixture was neutralized with sodium hydrogen carbonate, followed by the extraction with ethyl acetate (3 × 20 mL).…”

CYTOTOXIC EVALUATION OF ORIGINAL PYRAZOLO[3,4-d]THIAZOLES AND PYRAZOLO[3,4-c]PYRAZOLES

“…In the scope of combining the potential of the two molecules, we focused on the synthesis of original cytotoxic endowed structures, highlighting poorly described fused [5:5] ring systems: pyrazolo- [3,4-d]thiazoles and pyrazolo [3,4-c]pyrazoles [4]. The access to the aforementioned heterobicycles is described by various methods [5][6][7][8] possessing several downsides including long reaction times, complex starting materials, modest yields or long synthetic pathways. Moreover, few examples were studied from a therapeutic standpoint [9][10][11][12], some of which had limited [9,12], or no biological (antiviral, antitumoural) activity [11] (Figure 1).…”