Pyrazoles 3. N-1 Protected 4-Substituted Pyrazoles — Synthesis and Nmr Investigation

I'C-Nmr Data (chemical shifts, substituent chemical shifts (SCSI, coupling constants) are reported for 26 1.4disubstituted pyrazoles, bearing a benzyl, benzoyl or(substituted] benzenesulfonyl protecting group at N-1.The pyrazole derivatives 8a-d were prepared from the corresponding NH-pyrazoles.In the synthesis of compounds 2-5 l-benzyl-4pyrazolecarbaldehyde served as the starting material.N-1 Protected pyrazoles are important synthetic intermediates in the construction of complex molecules containing the 1.2-diazole ring-system since the acidic NHmoiety strongly restricts the application of many types of standard synthetic methods.We here report on the preparation of novel 4-substituted pyrazoles bearing a benzyl or a substituted benzenesulfonyl group at N-1.Moreover, the results of a systematic I'C-nmr investigation of a large variety of 1.4disubstituted pyrazoles are reported. SynthesesThe formyl group in 1-benzyl-4-pyrazolecarbaldehyde (1).which is conveniently available from 1-benzylpyrazole according to a reported procedure,2 expectedly reacted smoothly with malonic acid and derivatives thereof thus providing access to the acrylic acid 26 and the condensation products 2a.b.c in reasonable yields.The styrylpyrazole derivative 2f as well as the ethyl acrylate 2e could be prepared from 1 by Wittig-Horner-type reactions.Whereas 2f under these conditions is obtained in 72% yield' it turned out to be advantageous to prepare 2e via esterification of 2d.1-Benzyl-4-pyrazolecarbonitrile ( 5 ) has been prepared by Jones from 1-benzyl-4-bromopyrazole.' A more convenient access to 5 is proposed in Scheme 1: refluxing of the oxime 3, obtained quantitatively from HETEROCYCLES, Vol 27, N o 10,