Scheme 4. Approach to complex thiazolylhydantoins. Pyrazolones

The group ofTietze described syntheses of variously substituted pyrazolones 18 starting from solid phase-bound (3-ketoesters. Single or iterative alkylation of the dianion of immobilized acetoacetate with allyl-, benzyl- or alkylhalides produced a set of y-substituted ketoesters 16 which could be transformed to the phenylhydrazones 17. Treatment of these intermediates in toluene at 100° C produced 1-phenylpyrazolone derivatives 18 in 40-75 % yield (Scheme 5) [12].

The same group reported an approach to trisubstituted pyrazolones beginning with a solution-phase acylation of Meldrum's acid 19 and resin-capturing of the intermediates 20 with the acid-insensitive resin 25. The products 21 were a-alkylated using tetrabutylammonium fluoride (TBAF) and primary alkyl halides under strict exclusion of moisture, as the yields dropped dramatically otherwise. Treatment of the products 22 with phenylhydrazines produced the corresponding hydrazones 23, which were cleaved from the solid phase by cycliza-tion using 2 % TFA in acetonitrile at room temperature (Scheme 6) to form pyrazolones 24


Resin-capturing: Acyl Meldrum's acid 20 (5 equiv.) was heated with the spacer modified polystyrene-resin 25 inTHF at reflux for 4 h to give the polymer-bound p-ketoester 21.

16 r2 17

18 R2

Scheme 5. Cyclative cleavage of pyrazolones from the solid phase.

21 R 22

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