Gram-Scale Synthesis of 1,8-Naphthyridines in Water: The Friedlander Reaction Revisited was written by Choudhury, Shubhranshu Shekhar;Jena, Subhrakant;Sahoo, Dipak Kumar;Shekh, Shamasoddin;Kar, Rajiv K.;Dhakad, Ambuj;Gowd, Konkallu Hanumae;Biswal, Himansu S.. And the article was included in ACS Omega in 2021.Reference of 3612-18-8 This article mentions the following:
Here, gram-scale synthesis of 1,8-naphthyridines I [R1 = H, Me, Ph, etc.; R2 = H, CO2Me, Ph, etc.; R1R2 = (CH2)3, (CH2)4, (CH2)5, etc.] in water using an inexpensive and biocompatible ionic liquid (IL) as a catalyst was introduced. This was the first-ever report on the synthesis of naphthyridines I in water. This was a one-step reaction, and the product separation was relatively easy. The choline hydroxide (ChOH) was used as a metal-free, nontoxic and water-soluble catalyst. In comparison to other catalysts reported in the literature, ChOH had the advantage of forming an addnl. hydrogen bond with the reactants, which was the vital step for the reaction to happen in water. D. functional theory (DFT) and noncovalent interaction (NCI) plot index anal. provided the plausible reaction mechanism for the catalytic cycle and confirmed that hydrogen bonds with the IL catalyst were pivotal to facilitate the reaction. Mol. docking and mol. dynamics (MD) simulations were also performed to demonstrate the potentialities of the newly synthesized products as drugs. Through MD simulations, it was established that the tetrahydropyrido derivative of naphthyridine I [R1R2 = CH2CH2N(Et)CH2] bound to the active sites of the ts3 human serotonin transporter (hSERT) (PDB ID: 6AWO) without perturbing the secondary structure, suggesting that compound I [R1R2 = CH2CH2N(Et)CH2] could be a potential preclin. drug candidate for hSERT inhibition and depression treatment. In the experiment, the researchers used many compounds, for example, 1-Ethylpiperidin-4-one (cas: 3612-18-8Reference of 3612-18-8).
1-Ethylpiperidin-4-one (cas: 3612-18-8) belongs to piperidine derivatives. The piperidine moiety constitutes an important building block for the synthesis of a variety of bioactive natural products, alkaloids and other drugs. Fluorinated piperidines are also the subject of continued interest in medicinal chemistry, for example in the synthesis of selective dipeptidyl peptidase II (DPP II) inhibitors. Piperidine derivatives are also used in solid-phase peptide synthesis (SPPS) and many degradation reactions.Reference of 3612-18-8
Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem