Synthesis of tetrasubstituted pyrazoles containing pyridinyl substituents

Abstract

A synthesis of tetrasubstituted pyrazoles containing two, three or four pyridinyl substituents is described. Hence, the reaction of 1,3-dipyridinyl-1,3-propanediones with 2-hydrazinopyridine or phenylhydrazine, respectively, affords the corresponding 1,3,5-trisubstituted pyrazoles. Iodination at the 4-position of the pyrazole nucleus by treatment with I2/HIO3 gives the appropriate 4-iodopyrazoles which served as starting materials for different cross-coupling reactions. Finally, Negishi cross-coupling employing organozinc halides and Pd catalysts turned out to be the method of choice to obtain the desired tetrasubstituted pyrazoles. The formation of different unexpected reaction products is described. Detailed NMR spectroscopic investigations (1H, 13C, 15N) were undertaken with all products prepared. Moreover, the structure of a condensation product was confirmed by crystal structure analysis.

Domino C-H Sulfonylation and Pyrazole Annulation for Fully Substituted Pyrazole Synthesis in Water Using Hydrophilic Enaminones

“…For examples, the transition-metal-catalyzed cross-coupling reactions, − [3+2] or [4+1] annulation using hydrazones, − annulation of azodicarboxylates with dipoles, electrophilic cyclization of functionalized hydrazones, − and annulation of diazo compounds , have been reported as effective methods. Despite the availability of these enriched synthetic pathways, the reaction of a hydrazine with a 1,3-electrophilic substrate such as 1,3-dicarbonyl substrates, − Michael acceptors, − tertiary enamines, and related multicomponent variants , remain as the predominant options. The advantages of such methods cover not only the stable and easily available substrates but also the fast generation of high molecular diversity from the varied reaction partners of hydrazines.…”

Homocoupling Reactions of Azoles and Their Applications in Coordination Chemistry

“…A handful of papers [ 22 , 23 ] have used the tactical placement of heteroatoms for the coordination of metals in the activation of specific C–H bonds. Other papers [ 24 , 25 ] utilize the possibility of the oxidative addition of Pd into a carbon halogen bond to form di-azole Pd complexes, which can undergo reductive elimination to form desired intermolecular homocoupled products.…”

“…The homocoupling reaction between trisubstituted 4-iodo pyrazoles in the C4 position was investigated by Jansa et al ( Scheme 10 ) [ 25 ]. The pyrazoles contain two to three pyridinyl substituents, which are synthesized from the reaction of 1,3-dipyridinyl-1,3-propanediones with 2-hydrazinopyridine or phenylhydrazine, affording the corresponding 1,3,5-trisubstituted pyrazoles.…”

Introducing chirality in halogenated 3-arylsydnones and their corresponding 1-arylpyrazoles obtained by 1,3-dipolar cycloaddition

“…Mesoionic compounds [1][2][3][4][5] are versatile intermediates in the synthesis of bioactive pyrrole and pyrazole derivatives. [6][7][8][9][10][11] Sydnones 12,13 in particular, have been employed as 1,3-dipoles in obtaining N-arylpyrazoles by 1,3-dipolar cycloaddition reaction. [14][15][16][17][18][19][20][21][22][23][24][25][26][27][28] N-Arylpyrazole derivatives have been shown to possess antithrombotic, 29 anticancer, 30 parathyroid dysfunction, 31 anti-biolm, 32 and antipain 33 activity which makes them valuable targets for the pharmaceutical eld.…”