Regioselective Synthesis of 4‐Nitro‐ or 4‐Chloro‐Tetrasubstituted Pyrazoles from Hydrazones and β‐Halo‐β‐nitrostyrenes

Abstract

We report an acid‐catalyzed cycloaddition reaction of hydrazones with β‐bromo‐ or β‐chloro‐β‐nitrostyrenes for the regioselective synthesis of 4‐nitro‐ or 4‐chloro‐tetrasubstituted pyrazoles. Arising from a common 4‐halo‐4‐nitropyrazolidine intermediate, the identity of the pyrazole product formed is dependent on the relative leaving group abilities of the halo and nitro substituents.

Acid‐Mediated Three Component Assembly of 4‐Fluoropyrazoles from α‐Fluoronitroalkenes, Hydrazines, and Aldehydes

“…In addition, single‐crystal X‐ray analysis was performed for pyrazole 3o (Figure ) . It should be also noted that in all cases only 4‐fluoroderivatives were isolated, while for similar annulation with chloro‐ and bromo‐nitroalkenes the formation of mixtures of 4‐halo and 4‐nitro‐pyrazoles was occasionally observed …”

“…From the mechanistic point of view, concerted and stepwise mechanisms of [3+2]‐cycloaddition are possible for this reaction , , . While stepwise mechanisms involving Michael addition/cyclization are known to be more favored for annulations of nitroalkenes in basic conditions involving strong nucleophilic reaction partners, mechanism of acid‐mediated annulations is a subject of discussions , . Comparatively to α‐unsubstituted nitroalkenes and even α‐alkylated nitroalkenes halonitroalkenes are considered to be weaker Michael acceptors.…”

Recent Developments in the Chemistry of gem‐Halonitro Compounds

“…A very recent work describes the regioselective synthesis of 4‐nitro‐ or 4‐chloro‐tetrasubstituted pyrazoles from hydrazones and 1‐halo‐1‐nitrostyrenes 66 . N ‐Alkylhydrazones, generated in situ, reacted with 1‐bromo‐1‐nitrostyrene ( 54q ) in either MeOH or CF 3 CH 2 OH in the presence of TFA (20 mol‐%) to give mainly 4‐nitropyrazoles 92 (Table 31).…”

DBU Promoted Polysubstituted Arene Formation via a Michael Addition/Cyclization/Elimination Cascade Reaction

“…Recently, the easily accessible α-brominated and chlorinated nitrostyrenes 1 and 2 [ 13 , 14 ] were emerged as powerful C 2 synthons in the synthesis of different ring systems ( Figure 1 a). In particular, with the utilization of different C 3 synthons, a series of polysubstituted heteroarenes were constructed through (3 + 2) cyclization process, including furans [ 15 , 16 , 17 , 18 ], pyrazoles [ 19 , 20 , 21 ], imidazoles [ 22 ], triazoles [ 23 , 24 , 25 ], and pyrroles [ 26 , 27 , 28 , 29 , 30 ]. The versatilities of nitrostyrenes 1-2 were based on the electron deficiency of the double bound and the high reactivity of the leaving group X (X= Cl, Br) [ 31 , 32 , 33 ].…”