A hydrogen bond and strong electron withdrawing group lead to the formation of surprisingly stable, cyclic hemiaminals

Abstract Hemiaminals are rarely stable, and usually arise during imine formation in the absence of acid using polar, aprotic solvents. Here, stable, cyclic hemiaminals from acidic or neutral ethanolic solutions are obtained. Using four 1,3-diketones (a–d) and four aromatic hydrazine derivatives (1–4), a hydrogen bond and strong electron withdrawing group (trifluoromethyl) are judged to be the two critical contributors to stability. Using resistance to dehydration as a surrogate for stability, these hemiaminals appear to be the most stable reported surviving in ambient, neat glacial acetic acid for long periods of time and requiring reflux for conversion to the corresponding pyrazole.