Video Experimental Relacionado

Updated: Jul 6, 2025

Preparation of Stable Bicyclic Aziridinium Ions and Their Ring-Opening for the Synthesis of Azaheterocycles

Preparation of Stable Bicyclic Aziridinium Ions and Their Ring-Opening for the Synthesis of Azaheterocycles

Published on: August 22, 2018

Estrategia general para la síntesis de N-{\displaystyle N-{{\displaystyle N}-{\displaystyle N}-{\displaystyle

Jake D Selingo¹, Jacob W Greenwood¹, Mary Katherine Andrews¹

¹Department of Chemistry, Colorado State University, Fort Collins, Colorado 80523, United States.

Journal of the American Chemical Society

|December 28, 2023

Resumen

Este estudio introduce un nuevo método de apertura y cierre de anillos de piridina para sintetizar N- (hetero) arilpiperidinas, compuestos farmacéuticos cruciales. La estrategia eficiente utiliza intermediarios de iminación de Zincke y experimentación de alto rendimiento para la generación de bibliotecas.

Área de la Ciencia:

Química orgánica
Química medicinal

Sus antecedentes:

Los andamios de piperidina son frecuentes en los productos farmacéuticos.
La síntesis eficiente de diversos derivados de la piperidina es esencial para el descubrimiento de fármacos.

Objetivo del estudio:

Desarrollar una estrategia general para la síntesis de las N- (hetero) arilpiperidinas.
Establecer un método que utilice la apertura y el cierre de anillos de piridina a través de intermediarios de imina de Zincke.

Principales métodos:

Formación de sales de piridinio a partir de piridinas sustituidas y de anilinas (hetero) arílicas.
Reacciones de hidrogenación y adición nucleofílica para obtener derivados de piperidina.
Aplicación de la experimentación de alto rendimiento (HTE) para la optimización.

Principales resultados:

Síntesis exitosa de diversos derivados de la N- (hetero) arilpiperidina.
Desarrollo de un proceso de una sola olla utilizando anilinas como nucleófilos.
Demostración de viabilidad para la generación de bibliotecas de piperidina.

Conclusiones:

La estrategia presentada ofrece un enfoque versátil para las N- ((hetero) arylpiperidines.
Este método facilita el acoplamiento convergente de fragmentos moleculares complejos.
El enfoque es adecuado para crear diversas bibliotecas de piperidina para aplicaciones farmacéuticas.

Más Videos Relacionados

Efficient Construction of Drug-like Bispirocyclic Scaffolds Via Organocatalytic Cycloadditions of α-Imino γ-Lactones and Alkylidene Pyrazolones

Efficient Construction of Drug-like Bispirocyclic Scaffolds Via Organocatalytic Cycloadditions of α-Imino γ-Lactones and Alkylidene Pyrazolones

Published on: February 7, 2019

Preparation of Enantiopure Non-Activated Aziridines and Synthesis of Biemamide B, D, and epiallo-Isomuscarine

Preparation of Enantiopure Non-Activated Aziridines and Synthesis of Biemamide B, D, and epiallo-Isomuscarine

Published on: June 13, 2022

Videos de Conceptos Relacionados

Preparation of 1° Amines: Azide Synthesis

Preparation of 1° Amines: Azide Synthesis

Direct alkylation of ammonia produces polyalkylated amines, along with a quaternary ammonium salt. To exclusively prepare primary amines, the azide synthesis method can be used.
Azide ions act as good nucleophiles and react with unhindered alkyl halides to form alkyl azides. Alkyl azides do not participate in further nucleophilic substitution reactions, thereby eliminating the chances of polyalkylated products. Alkyl azides are reduced by hydride-based reducing agents, like lithium aluminum...

Preparation of 1° Amines: Gabriel Synthesis

Preparation of 1° Amines: Gabriel Synthesis

Direct alkylation is not a suitable method for synthesizing amines because it produces polyalkylated products. Gabriel synthesis is the most preferred method to exclusively make primary amines. The method uses phthalimide, which contains a protected form of nitrogen that participates in alkylation only once to predominantly give primary amines.
Strong bases like NaOH or KOH deprotonate the phthalimide to form the corresponding anion, which acts as a nucleophile. Further, the anion attacks an...

Aldehydes and Ketones with Amines: Imine Formation Mechanism

Aldehydes and Ketones with Amines: Imine Formation Mechanism

Imine formation involves the addition of carbonyl compounds to a primary amine. It begins with the generation of carbinolamine through a series of steps involving an initial nucleophilic attack and then several proton transfer reactions. The second part includes the elimination of water, as a leaving group, to give the imine.
Imines are formed under mildly acidic conditions. A pH of 4.5 is ideal for the reaction.
If the pH is low or the solution is too acidic, the reaction slows down in the...

Diazonium Group Substitution with Halogens and Cyanide: Sandmeyer and Schiemann Reactions

Diazonium Group Substitution with Halogens and Cyanide: Sandmeyer and Schiemann Reactions

Arenediazonium substitution reactions occur when the diazonium group is substituted by various functional groups such as halides, hydroxyl, nitrile, etc. For instance, arenediazonium salts react with copper(I) salts of chloride, bromide, or cyanide to form corresponding aryl chlorides, bromides, and nitriles. These reactions are named Sandmeyer reactions. Although the mechanism of this reaction is complicated, as illustrated in Figure 1, they are believed to progress via an aryl copper...

Nucleophilic Aromatic Substitution of Aryldiazonium Salts: Aromatic SN1

Nucleophilic Aromatic Substitution of Aryldiazonium Salts: Aromatic S_N1

Treating arylamines with nitrous acid gives aryldiazonium salts that are effective substrates in nucleophilic aromatic substitution reactions. The diazonio group in these salts can be easily displaced by different nucleophiles, yielding a wide variety of substituted benzenes. The leaving group departs as nitrogen gas, and this easy elimination is the driving force for the substitution reaction.
In the Sandmeyer reaction, for example, the diazonio group is replaced by a chloro, bromo,...

Preparation of 1° Amines: Hofmann and Curtius Rearrangement Overview

Preparation of 1° Amines: Hofmann and Curtius Rearrangement Overview

In the presence of an aqueous base and a halogen, primary amides can lose the carbonyl (as carbon dioxide) and undergo rearrangement to form primary amines. This reaction, called the Hofmann rearrangement, can produce primary amines (aryl and alkyl) in high yields without contamination by secondary and tertiary amines.