Pyrazoline ring closure

The condensation of pyrazole-based chalcone 55 with hydrazine (in the presence of acetic acid) and with phen-ylhydrazine in PEG 400 resulted in the pyrazoline ring closure (Scheme 32) [56]. Some of the reaction products demonstrated anti-inflammatory and analgesic activities. The type and potency of the observed effects were mainly dependent on the substituents (Ar) with no significant difference between two types of compounds 56 and 57. 

The important synthesis of pyrazoles and pyrazolines from aldazines and ketazines belongs to this subsection. Formic acid has often been used to carry out the cyclization (66AHQ6)347) and N-formyl-A -pyrazolines are obtained. The proposed mechanism (70BSF4119) involves the electrocyclic ring closure of the intermediate (587) to the pyrazoline (588 R = H) which subsequently partially isomerizes to the more stable trans isomer (589 R = H) (Section 4.04.2.2.2(vi)). Both isomers are formylated in the final step (R = CHO). 

Scheme 7 shows formation of a new fused ring described by Mohan and Kataria <1998IJB819>. These authors reported that treatment of the benzylidene compound 19 with hydrazine hydrate in acetic acid in the presence of sodium acetate gave the tricyclic fused pyrazoline derivative 20 in acceptable yield (61%). The two hydrogen atoms at the site of the ring closure were found to be as. 

Many examples of ring closures by oxidation of hydrazone derivatives have been reported. Anodic oxidation of chalcone72 phenylhydrazone (17) performed in CH3CN—LiCI04 at platinum, using controlled potential electrolysis, gave 1,3,5-triphenylpyrazole (15-40% yield) (18), 1,3,5-triphenyl-A2-pyrazoline (19), l,3,5-triphenyl-A2-pyrazolinium perchlorate, 4,4-bis[3,5-diphenyl-A2-pyrazolinyl-(l)]-biphenyl (20), the diperchlorate of 20, and 4,4 -bis-[3,5-diphenylpyrazolyl-(l)]-biphenyl (21) [Eq. (30)]. 

The stable products of the reaction are the cyclopropanes and isomeric olefins. The decomposition of cis- and tra j-3,5-dimethyl-1-pyrazolines are of special interest in that they exhibit a stereochemical reversal in the dimethyl cyclopropane product. The cw-pyrazoline forms predominantly trans, and the franj-pyrazoline predominantly cw-dimethyl cyclopropane. This is a consequence of the orbital symmetry of the intermediate trimethylene species which requires a conrotatory motion as the preferred mode of ring closure, and as such lends experimental support to the validity of Hoffman s mo calculations. 

Irradiation of the homochiral pyrazoline (51) leads to the elimination of nitrogen and the stereospecific formation of the cyclopropane (52) (Jimenez et al). The reaction proceeds by way of triplet diradical intermediates but evidently, closure to give the cyclopropane ring is faster than C-C bond rotation. The multiplicity of the diradical from the low-temperature photolysis of dihydropyr-rolo[3,4-d(]pyridazines such as (53) is reported to be wavelength dependent and even at 77K, the singlet and triplet states do not equilibrate to a measurable extent (Bush et ai). The results reported by Motschiedler et al. from the triplet sensitised irradiation of 1,2-diaryldiazoethanes in methanol solution go some way to establishing that 1,2-H and 1,2-C shifts in a spin-equilibrated carbene compete... 

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