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Azetidinium salts are important motifs in organic synthesis but are difficult to obtain due to extremely long synthetic protocols. Herein, a rapid continuous-flow process for the on-demand synthesis of azetidinium salts is described. In particular, the nucleophilic addition of secondary amines and the subsequent intramolecular N-cyclization have be...
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Context 1
... investigate the reaction performance under flow conditions, we have decided to study the effect of temperature on the synthesis of 3, evaluating the reaction in water and EtOH as solvents, and keeping 60 min as the residence time ( Figure 2A). Preliminary tests conducted in water led in all cases to the clogging of the reactor, mainly because of the low solubility of epichlorohydrin in water. ...
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... avoid these issues, EtOH was chosen as a solvent. This has enabled us to obtain comparative data between the batch and flow process, showing the increased yields under flow conditions ( Figure 2B). The enhancement of the reaction rate is corroborated by the vis-à -vis comparison of batch and flow data in Table S1 and by the values of the activation energy determined by the Arrhenius analysis under kinetic conditions. ...
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... enhancement of the reaction rate is corroborated by the vis-à -vis comparison of batch and flow data in Table S1 and by the values of the activation energy determined by the Arrhenius analysis under kinetic conditions. In fact, the reaction under batch conditions requires an activation energy of 49 kJ mol −1 , while the same reaction under flow mode needs only 4 kJ mol −1 ( Figure 2C). ...
Citations
... The Vilé group recently published their continuous flow synthesis of azetidinium salts (37) via epichlorohydrin aminolysis, where an improvement in yield was observed by transferring the batch process to flow without further modifications. [38] Using diethylamine and epichlorohydrin as in the model reaction, the optimum conditions in batch involved the use of water as reaction solvent at 80°C. However, due to poor solubility of the substrates in water, this could not be transferred to flow. ...
... However, in batch this reaction requires cryogenic conditions (À 78°C) and long reaction times (> 3 h). To improve the efficiency of this reaction Kappe, Luisi and coworkers developed a continuous flow system for the synthesis and functionalisation of Li-ABB (38). [39] Initial batch experiments were carried out to identify the important reaction parameters and found s-BuLi to be the most effective base for accessing the desired product. ...
Small carbo‐ and heterocyclic ring systems have experienced a significant increase in importance in recent years due to their relevance in modern pharmaceuticals, as building blocks for designer materials or as synthetic intermediates. This necessitated the development of new synthetic methods for the preparation of these strained ring systems focusing on effectiveness and scalability. The high ring strain of these entities as well as the use of high‐energy reagents and intermediates has often challenged their synthesis. Continuous flow approaches have thus emerged as highly effective means to safely and reliably access these strained scaffolds. In this short review, key developments in this field are summarised showcasing the power of continuous flow approaches for accessing 3‐ and 4‐membered ring systems via thermal, photo‐ and electrochemical processes.
В обзоре обобщены современные литературные данные, опубликованные в период с 2010 по 2021 г. и частично в 2022 г., по химии эпоксидов — важного класса соединений, которые являются ценными "строительными блоками" при конструировании новых структур, лежащих в основе многих практически значимых веществ. Эпоксипроизводные давно привлекали внимание химиков-синтетиков, что подтверждает ряд именных реакций, связанных с их синтезом. В данном обзоре представлены методы получения эпоксисоединений — как усовершенствованные классические, так и новые, описаны химические реакции с участием эпоксидов, обсуждено практическое значение таких соединений на примере синтеза природных, лекарственных и полимерных структур, а также утилизации CO и CO<sub>2</sub>. Большое внимание уделено вопросам асимметрического синтеза, без которых невозможно создать общее представление о современных тенденциях в химии эпоксидов. Представлены самые неожиданные перегруппировки функционализированных эпоксидов, а также показана роль эпоксисоединений при получении различных карбо- и гетероциклических систем.
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We report an improved approach for the integration of flow synthesis and continuous chromatography, for applications in the end-to-end preparation of pharmaceutically-relevant small molecules. It involves the combination of sequential...
