Pyrazole alkylation in basic media

A very important microwave-specific effect was evidenced in the absence of a base for the reaction of pyrazole with phenethyl bromide (reaction times MW = 8 min, A = 48 h, Eq. 41). When the same reaction was performed in the presence of KOH, the microwave effect disappeared (vide supra, Eq. 26). 

This effect could be predicted when considering the weak evolution of polarity between the GS and TS as the reactive species consist of loose ion pairs (involving a soft anion). 

Alkylations in dry media of the ambident 2-naphthoxide anion were performed under the action of focused microwave activation. Whereas the yields were identical to those obtained under the action of A for benzylation, they were significantly improved under microwave irradiation conditions for the more difficult n-octylation (a less reactive electrophilic reagent). No change in selectivity was observed, however, indicating the lack of influence of ionic polarization [94], 

The absence or weakness of the microwave effect was assumed to be related to loose ion pairs involving the soft naphthoxide anion in the GS and a small change in polarity in an early TS. When the TS occurred later along the reaction coordinates (e.g. for n-octylation requiring a higher temperature), more polarity is developed and, consequently, the microwave effect could appear (Eq. (42) and Tab. 3.17 limited here to the lithiated base). 

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