Some fused 1,4-dihydropyridine derivatives have been synthesized in one-pot, multi-component condensation of dimedone, aldehyde, malononitrile and ammonium acetate using glycerol, an eco-friendly, readily available green solvent which costs virtually nothing. The targeted molecules are obtained in a yield, which is excellent, to say the least. The synthesized compounds were purified by simple recrystallisation.
In general, the hydride ion is a poor leaving group and occurs only in a few heterocyclic reactions. They include the , which yields pyridine derivatives at the 2-position. Here, is used as the nucleophile yielding 2-aminopyridine. The hydride ion released in this reaction combines with a proton of an available amino group, forming a hydrogen molecule.
Hantzsch pyridine synthesis - overview - ChemTube3D
In contrast to benzene, pyridine efficiently supports several nucleophilic substitutions. The reason for this is relatively lower electron density of the carbon atoms of the ring. These reactions include substitutions with elimination of a ion and elimination-additions with formation of an intermediate configuration, and usually proceed at the 2- or 4-position.
The Hantzsch dihydropyridine synthesis is found to benefit ..
Many reactions that are characteristic of benzene proceed with pyridine either at more complicated conditions or with low yield or both. Owing to the decreased electron density in the aromatic system, s are suppressed in pyridine and its derivatives in favor of of nucleophiles at the electron-rich nitrogen atom. The nucleophilic addition at the nitrogen atom leads to a further deactivation of the aromatic properties and hindering of the electrophilic substitution. On the other hand, free-radical and occur more readily in pyridine than in benzene.
Hantzsch pyridine synthesis - ResearchGate
Several pyridine derivatives play important roles in biological systems. While its biosynthesis is not fully understood, (vitamin B3) occurs in some , , and s. Mammals synthesize nicotinic acid through oxidation of the , where an intermediate product, , creates a pyridine derivative, . On the contrary, the bacteria and produce nicotinic acid by condensation of and .
The Hantzsch thiazole synthesis under acidic conditions: ..
The provides a fairly general method for generating substituted pyridines using pyridine itself as a reagent which does not become incorporated into the final product. The reaction of pyridine with α-bromos give the related salt, wherein the is highly acidic. This species undergoes a to α,β-unsaturated carbonyls in the presence of to undergo ring closure and formation of the targeted substituted pyridine as well as pyridinium bromide.
reactions such as the Hantzsch pyridine synthesis
Partially hydrogenated derivatives are obtained under milder conditions. For example, reduction with yields a mixture of 1,4-dihydropyridine, 1,2-dihydropyridine, and 2,5-dihydropyridine. Selective synthesis of 1,4-dihydropyridine is achieved in the presence of organometallic complexes of and , and (Δ3,4)-tetrahydropyridine is obtained by electrochemical reduction of pyridine.