Synthesis, and Molecular Structure Investigations of a New s-Triazine Derivatives Incorporating Pyrazole/Piperidine/Aniline Moieties

Abstract

In this work, we synthesized two new s-triazine incorporates pyrazole/piperidine/aniline moieties. Molecular structure investigations in the light of X-ray crystallography combined with Hirshfeld and DFT calculations were presented. Intermolecular interactions controlling the molecular packing of 4-(3,5-dimethyl-1H-pyrazol-1-yl)-N-phenyl-6-(piperidin-1-yl)-1,3,5-triazin-2-amine; 5a and N-(4-bromophenyl)-4-(3,5-dimethyl-1H-pyrazol-1-yl)-6-(piperidin-1-yl)-1,3,5-triazin-2-amine; 5b were analyzed using Hirshfeld calculations. The most dominant interactions are the H...H, N...H and H...C contacts in both compounds. The N...H and H...C interactions in 5a and the N...H, Br...H and H...H interactions in 5b are the most important. In addition, DFT calculations were used to compute the molecular structures of 5a and 5b; then, their electronic properties, as well as the 1H- and 13C-NMR spectra, were predicted. Both compounds are polar where 5a (1.018 Debye) has lower dipole moment than 5b (4.249 Debye). The NMR chemical shifts were calculated and very good correlations between the calculated and experimental data were obtained (R2 = 0.938–0.997).

Synthesis and Antiproliferative Activity of a New Series of Mono- and Bis(dimethylpyrazolyl)-s-triazine Derivatives Targeting EGFR/PI3K/AKT/mTOR Signaling Cascades

“…The initial derivatization step of cyanuric chloride 1 in this synthetic route was carried out via nucleophilic aromatic substitution of the chlorine atom by aromatic nitrogen-containing nucleophiles, such as aniline and p -substituted aniline, in the presence of an alkaline medium of sodium hydrogen carbonate as the hydrogen chloride receptor, following the previously reported method ( Supporting Information (SI) ). 38 The regioselectivity of this reaction was thermally optimized by performing the reaction at 0 °C to ensure the replacement of only one chlorine atom, leaving the two other chlorine units in the triazine moiety, which afforded the dichloro-monosubstituted- s -triazine derivatives 2a – d .…”

“…The second synthetic step involved a further displacing of one of the chlorine atoms in monosubstituted triazine derivatives 2a – d by aliphatic nitrogen-containing nucleophiles such as piperidine, pyrrolidine, and morpholine. The same synthetic methodology as the previous step ( SI ) 38 was applied, but the reaction time was increased to 12 h to overcome the deactivation behavior of the amino electron-donating group, which was inserted in the first step toward nucleophilic aromatic substitution. This approach afforded 2-chloro-4,6-disubstituted s -triazine derivatives 3a – l in good yield and purity, as indicated from the spectral data ( SI ).…”

“…This approach afforded 2-chloro-4,6-disubstituted s -triazine derivatives 3a – l in good yield and purity, as indicated from the spectral data (SI). The monochloro 3a – l and dichloro 2a – d derivatives were then treated with hydrazine hydrate (80%) in EtOH overnight under reflux to afford the hydrazine derivatives, which, without further purification, reacted directly with acetylacetone in the presence of triethylamine and DMF as solvent following the method reported by our group and others ,, to render the target products 4a – l and 5a – d , respectively (Scheme ) (Material and methods, SI). The chemical structures for all of the new synthesized compounds were assigned based on different spectroscopic tools including NMR, MS, IR, and CHN analysis.…”

“…General Procedure for the Synthesis of Mono-and Bispyrazolyl-s-triazine Derivatives. Mono-pyrazolyl-s-triazine derivatives 4a−l and bis-pyrazolyl-s-triazine 5a−d were prepared from the reaction of the hydrazine-s-triazine derivatives with acetylacetone in the presence of triethylamine as a base following the methods reported by our group and others 28,35,37,38 to give the desired products in good yield and purity (Material and Methods, SI).…”

Bis(dimethylpyrazolyl)-aniline- s -triazine derivatives as efficient corrosion inhibitors for C-steel and computational studies

“…To explore further the application of the s-triazine-based molecules as corrosion inhibitors, three compounds having different electronic effects with either electron donating or withdrawing effects were selected, resynthesized and characterized by the El-Faham group [45]. The target compounds were prepared according to scheme 1 [45,66]. The structures of the three derivatives PTA-1-PTA-3 were confirmed by NMR and agreed with the reported data [45] (electronic supplementary material, synthetic method).…”