Pyrazole-4,5-diones, condensation with

The original azole approach to the synthesis of this system, as outlined in CHEC-I, has been continued. The pyrazole dione (124) condenses with a 2-substituted formamidine derivative and is cyclized with aqueous potassium carbonate <84JHC923,84JPR994) or heat <88JPR57> giving the derivatives (125) in poor yield (Equation (10)). An alternative approach is shown in Equation (11)... 

Biradar and Sasidhar (2011) reported a new series of novel indole analogs via Knoevenagel condensation and evaluated their in vitro antioxidant and cytotoxin activities using three tumor cell lines. 2,5-Disubstituted indole-3-carboxaldehydes undergo NH OAc catalyzed Knoevenagel condensation with barbiturates, thiazoli-dine-2,4-dione and 3-methyl-lH-pyrazol-5(4H)-one in solvent-free microwave-assisted reaction. 

The condensation products (1 1) of pentane-2,4-dione and 1,3-diphenyl-propane-1,3-dione with thiosemicarbazide, 4-methylthiosemicarbazide, and aminoguanidinium nitrate were formed (86KGS128 87ZOB584 90-KGS1260) as the cyclic isomers 78, which sometimes readily underwent dehydration to the corresponding pyrazoles. 

The Knorr pyrazole synthesis has bestowed a futile ground for medicinal chemists to practice their craft in drug discovery. The most conspicuous example is the synthesis of celecoxib (Celebrex), a selective COX-2 inhibitor prescribed as an analgesic. As shown below, the substrate dione was prepared by the Claisen condensation of 4-methylacetophenone with ethyl trifluoroacetate in the presence of NaOMe in methanol under reflux. Subsequent diarylpyrazole formation from the condensation of the dione and 4-sulfonamidophenyl-hydrazine hydrochloride then delivered celecoxib. ... 

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