Synthesis and tautomerism of spiro-pyrazolines

Abstract

An experimental study on the synthesis, tautomerism and acid promoted structural changes of spiro-pyrazolines is described. The target was achieved through a [3+2]-dipolar cycloaddition of an alkene with nitrile imines generated in situ and was isolated in high yield. The synthesized cycloadduct displayed a tendency to exhibit an imine-enamine type of tautomerism as evidenced by X-ray crystal and NMR studies. Furthermore, addition of an acid resulted in the transformation of an imine tautomer to an enamine. The current report constitutes a first formal observation of this kind of tautomerism observed in spiro-indoline pyrazolines.

3-Pyrazolines (2,3-dihydro-1H-pyrazoles): synthesis, reactivity, and physical and biological properties

“…In the first paper (series a, R = H) the authors explained that the formation of pyrazole 219a (X-ray structure, refcode CORTEJ) from 2-pyrazoline 217a involves a non-isolated 3-pyrazoline 218a. 172 Our calculations agree with the data reported for the isolated compounds 217a and 219a, including a hydrogen bond between the N-H and the π-system of the pyrazole ring. 171 The second paper is more contentious and it concerns series b (R = OMe).…”

“…144 We devoted a paper 170 to the analysis of two publications by Hamme II et al and these are summarized in Scheme 56. 171,172 Scheme 56. Structures of the compounds studied by Hamme II.…”

The Tautomerism of Pyrazolines (Dihydropyrazoles)

“…The availability of standard theoretical calculations of absolute shieldings (σ, ppm) and the robustness of the empirical equations to transform them into chemical shifts (δ, ppm) has allowed to correct an structural error of the literature, 11 and confirm that Δ 3 -pyrazolines are stable only when both N atoms are substituted.…”

“…11 They reported the X-ray structure of 12b, but the CCDC deposition number 701051 actually corresponds to 13a although the Figure that appears in their paper is that of 12b. They described the properties of both tautomers that depend on the solvent: in benzene (12b, yellow solution) and in chloroform (14b, pink solution).…”

QM study on regioselectivity in the synthesis of pyrimido[4,5-b][1,4]benzothiazines: kinetic and thermodynamic point of view

“…Regioselectivity is the preference of one direction of chemical bond making or breaking of over all other possible directions [36]. As a matter of fact in heterocyclic chemistry, often the generation of a preferential tautomer leads to regioselectivity [37].…”