Azo‐hydrazone molecular switches: Synthesis and NMR conformational investigation

Abstract

A series of five intramolecularly hydrogen-bonded arylhydrazone (aryl = phenol, p-nitrophenol, anisole, quinoline) derived molecular switches have been synthesized and characterized by NMR and HRMS techniques. It was found that the compounds exist as different isomers in solution. An investigation of both conformational and/or configurational changes of the azo-hydrazone compounds was carried out by 1D 1 H-and 13 C-spectra, 2D NOESY, COSY, HSQC, and HMBC techniques. It was found that these stimuli-responsive molecular switches exist mainly in the E form by intramolecularly hydrogen bonded between NH and the pyridine nitrogen at equilibrium. Deprotonation of the neutral E form yields the E 0 deprotonated isomer. Prediction of 13 C-NMR chemical shifts was achieved by DFT quantum mechanical calculations. Anions have traditionally been difficult to calculate correctly, so calculations of the anion using different functionals, basis sets, and solvent effects are also included. Deuterium isotope effects on the 13 C-NMR chemical shifts were employed in the assignments and furthermore utilized as indicators of intramolecular hydrogen bonding. Studies in various organic solvents including CDCl 3 , CD 3 CN, and DMSO-d 6 were also performed aiming to monitor dynamic changes over several days. The effect of the hydrogen bonded solvents leads to Z forms.

The Synergy between Nuclear Magnetic Resonance and Density Functional Theory Calculations

“…Nuclear shieldings can be difficult to calculate in negatively charged species due to large self-interaction errors [ 55 ]. In the case of the azo compound ethyl 2-(2-(2-hydroxyphenyl)hydrazineylidine)-2-(pyridin-2-yl)acetate (see Figure 26 ), the best agreement between the experimental 13 C chemical shifts and calculated ones was obtained with B3LYP/6-311++G(2d,p) + PCM and adding a water molecule, as seen in Figure 26 [ 56 ].…”

Nuclear Magnetic Resonance

“…78,79 Miyamoto and Hada 80 analyzed 13 C NMR chemical shifts in substituted benzenes using natural perturbation orbitals and substitution effects. Hansen et al 81 reported on the synthesis and NMR conformational characterization of azo-hydrazone molecular switches supported by GIAO NMR calculations. Erdog ˘an and Serdarog ˘lu 82 synthesized and characterized a novel pyrene-sulfathiazole-based potential drug candidate, (E)-4-((pyren-1-ylmethylene)amino)-N-(thiazol-2-yl)benzenesulfonamide.…”