ABSTRACT The assembly mechanism of the target 4‐benzylpyrazole and side 1‐benzylpyrazole from phenylacetylene and phenylaldazine in NaOBu t /DMSO superbasic media, as well as other possible side reactions, has been studied using a quantum chemical B2PLYP‐D2/6‐311+G**//B3LYP/6‐31+G* approach. It was found that the key reaction stages determining the selectivity of pyrazole formation are competing isomerizations of the N ‐propargylhydrazone anion: (i) conformational, (ii) propyne‐allene, and (iii) hydrazone‐diazene. Isomerizations (i) and (ii) with close barriers lead to the formation of 4‐benzylpyrazole, both in the presence of the free − OBu t anion and the NaOBu t ·4DMSO complex. The formation of the by‐product 1‐benzylpyrazole occurs via isomerization (iii), which, in the presence of only the − OBu t anion, has a significantly higher barrier than isomerizations (i) and (ii). However, in the presence of the NaOBu t ·4DMSO complex, the difference in activation barriers is reduced and better corresponds to the ratio of 4‐ and 1‐benzylpyrazoles observed in the experiment. It was shown that the system also undergoes side reactions, which occur with activation barriers similar to or lower than the rate‐determining barrier for the formation of 4‐benzylpyrazole. This explains the moderate yields of the target 4‐benzylpyrazole, as well as the need for dropwise introduction of phenylaldazine.
Orel et al. (Sun,) studied this question.