Highly-substituted pyrazoles and pyridazines by MIRC reactions of hydrazone anions and nitrobutadienic fragments

Synthesis of poly-functionalized pyrazoles and pyridazines from nitrobutadienes: an interesting dichotomy of practical relevance

“…On the other hand, acidic quenching (excess TFA) after disappearance of substrate, effectively drives the reaction to completion favouring 13a the elimination of nitrous acid ( The observed configurational scrambling at the exocyclic double bond, only partial in the case of 15a, 10 but complete in the case of 16 (with the exception of 16da: Table 1, entry 7), may be rationalized considering that the intermediate open-chain nitronate A may delocalize the negative charge onto the adjacent double bond: a delocalization which is expected to be more important for sulfones 13 than for sulfides 12. It should also be considered that the closure of the pyrazolidine nucleus is probably a slow step, due to the low electrophilic character of the diazo group: thus the anion could be allowed to equilibrate according to the relevant stability of the two stereoisomers, and much more so for the sulfones which, thanks to effective charge delocalization, should experience a longer lifetime in the reaction conditions.…”

“…As outlined in the preliminary communication, 10 a reasonable mechanistic pathway to the pyrazole nucleus can be envisaged as depicted in Scheme 3, whereby a Michael-type addition of the hydrazone anion to the nitrovinyl moiety of 12 or 13 (step a) is followed by the intramolecular attack of the resulting nitronate A onto the diazo group (step b), 13 which exploits the driving force represented by intramolecularity.…”

“…2 In this field, over the last two decades our research group has provided a valuable contribution thanks to the versatility of building-blocks such as 4-11 (Scheme 1). Such polyfunctionalized units, most conveniently obtainable from the initial ring-opening of suitablysubstituted nitrothiophenes with secondary amines, [3][4][5] followed by modifications of the original functionalities so as to meet specific requirements, both structural and electronic (Scheme 1), exhibit a multi-faceted behaviour: 6 this obviously encompasses the well-known reactivity of e.g.…”

Synthesis and Biological Evaluation of S-Substituted Perhalo-2-nitrobuta-1,3-dienes as Novel Xanthine Oxidase, Tyrosinase, Elastase, and Neuraminidase Inhibitors

“…These synthesized compounds are important in pharmacology. S-, N-, N,S-substituted polyhalonitrobutadiene compounds obtained by the reactions of polyhalonitrobutadiene compounds with various nucleophilic reagents such as thiols, dithiols, and amines are given in the literature [1][2][3][4][5][6][7][8][9]. There are studies on antifungal, antibacterial, anticancer, and anti-HIV properties of these compounds [10][11][12][13][14][15][16].…”

Regioselective, One‐Pot, Three‐Component Synthesis of 1,3,4‐ and 1,3,5‐Triarylpyrazoles from 1‐ and 2‐Aryl‐1‐alkenyl Sulfones

“…[2] From this point of view, a formal [3+2] cycloaddition reaction between hydrazones and nitro alkenes is attractive because both of the substrates are readily available, and the routhe could lead to both 1,3,4-and 1,3,5-triarylpyrazoles regioselectively. [15][16][17][18][19][20][21][22][23][24][25] The Deng group has extensively studied the coupling between various hydrazones and nitroalkenes. Their optimized acidic conditions [10 equiv.…”