A chemo- and regiocontrolled approach to bipyrazoles and pyridonesviathe reaction of ethyl 5-acyl-4-pyrone-2-carboxylates with hydrazines

Abstract

Chemo- and regiocontrolled syntheses of pyrazoles and pyridones are presented on the basis of 4-pyrones. A novel approach towards highly functionalized 3,4'-bipyrazoles has been developed by using reactions of ethyl 5-acylcomanoates with hydrazines. The acid-promoted double cyclocondensation allows switching of the structure of the pyrazole rings easily through changing both the nature of hydrazine and the reaction conditions. The transformation of 4-pyrones with phenylhydrazine in EtOH at -20 °C leads to hydroxypyridones as monoaddition products which can be used as precursors for the preparation of pyridone and pyrazole derivatives. A novel rearrangement of 2-hydroxypyridone to pyrazolyl-1,3-diketones in DMSO was found. The structure and regiochemistry of bipyrazoles were confirmed by X-ray analysis and 2D NMR experiments.

2,6-Dicyano-4-pyrone as a Novel and Multifarious Building Block for the Synthesis of 2,6-Bis(hetaryl)-4-pyrones and 2,6-Bis(hetaryl)-4-pyridinols

“…When the reaction mixture was maintained at −20 °C for 30 days, the yield of product 5b was achieved to 55%. The structure of pyrazole 5b 23 The desired amidrazone 6 was isolated in only trace amounts (2%) as a byproduct, and all our attempts to improve the yield of the target product were unsuccessful. When the reaction of dicyanopyrone 4 with phenylhydrazine was carried out in benzene, the direction of the attack strongly changed, and it proceeded at the C-4 atom to obtain phenylhydrazone 7 (59%).…”

Synthetic Routes to Bioactive Bipyrazole Derivatives

“…Reaction of 4‐pyrones 132 with hydrazine hydrochloride or with methyl hydrazine acetate in refluxing EtOH, afforded the bipyrazoles 133 in 57–90 % yields (Scheme 30). [81] …”

“…Reaction of 4-pyrones 132 with hydrazine hydrochloride or with methyl hydrazine acetate in refluxing EtOH, afforded the bipyrazoles 133 in 57-90 % yields (Scheme 30). [81] Heating equimolar quantities of 3-chloro-3-(4,9-dimethoxy-5-oxo-5H-furo[3,2-g]chromen-6-yl)prop-2-enal 134 and hydrazine hydrate or phenyl hydrazine in ethanol at reflux temperature led to the formation of the 3,4'-bipyrazole derivatives 137. The reaction proceeded via condensation of hydrazine with the formyl function then concurrent cyclization with HCl elimination gave the intermediate 135, which upon further attack of hydrazine gave the bipyrazole 137 via γpyrone ring opening followed by recyclization with elimination of water molecule through the intermediate 136 (Scheme 31).…”

2-Aryl-6-Polyfluoroalkyl-4-Pyrones as Promising RF-Building-Blocks: Synthesis and Application for Construction of Fluorinated Azaheterocycles

“…Mainly, pyrones are of interest as useful and versatile building-blocks for the synthesis of valuable molecules [ 6 , 7 , 8 , 9 ], including pharmaceuticals [ 10 ] and pyranic fluorophores [ 11 ]. Pyrones as polyelectrophilic substrates and cyclic enone are able to react regioselectively with nucleophiles to undergo ring-opening transformations affording azaheterocycles [ 12 , 13 , 14 , 15 , 16 ]. The formation of the product is usually very sensitive to the reaction conditions (acidity, solvent polarity, temperature) that allows divergent syntheses on the basis of 4-pyrones [ 15 , 16 ].…”

“…Pyrones as polyelectrophilic substrates and cyclic enone are able to react regioselectively with nucleophiles to undergo ring-opening transformations affording azaheterocycles [ 12 , 13 , 14 , 15 , 16 ]. The formation of the product is usually very sensitive to the reaction conditions (acidity, solvent polarity, temperature) that allows divergent syntheses on the basis of 4-pyrones [ 15 , 16 ].…”