Fast and Efficient Continuous Flow Method for the Synthesis of Ynones and Pyrazoles

Abstract

In this study, we developed a convenient and efficient two‐step method for the synthesis of ynones in a flow reactor, through the generation of lithium acetylide and its subsequent reactions with acid chlorides. Using this approach, we obtained the ynones in moderate to good yields at room temperature. Moreover, we transformed the ynones into pyrazole derivatives through coupling with hydrazines. This transition metal‐free process, mild reaction conditions, and broad functional group tolerance are all attractive features in comparison with conventional bench‐top methods.

In Situ Generation of Alkynylzinc and Its Subsequent Negishi Reaction in a Flow Reactor

“…We began our preliminary investigation by choosing phenylacetylene 1a and iodobenzene 2a as the model substrate for Negishi cross‐coupling reaction. The active lithium phenylacetylide was generated according to our previous reported literature using 1a with n ‐butyllithium at mixer M1 at 20 °C with the residence time (t R1 ). Subsequent reaction of the lithium phenylacetylide with ZnBr 2 at M2 provided the corresponding alkynylzinc in reactor R2 with the residence time (t R2 ) at 20 °C.…”

“…Nevertheless, applying these methods for the preparation of organozinc by a lithium base still demands a low temperature conditions nor further transformation in a batch reactor and excessive amount of starting materials. By considering the above facts and our continuing interest in lithium acetylide chemistry Herein, we designed an alternative approach for the synthesis of internal alkynes and enynes via Negishi cross‐coupling between an in situ generated alkynylzinc reagents and aryl or vinyl iodides in a simple and robust flow system using commercial catalyst and ligand that can enable the gram scale synthesis.…”

Efficient Synthesis of Symmetrical and Unsymmetrical Disulfides Using a Continuous Flow Method

“…A continuous flow chemistry system has many attractive features that can produce more efficient synthesis over a batch system, [12] offering the benefits of high degrees of control [13] over process parameters including temperature, pressure, minimizing the volume of reaction, and enhancing the mixing of sample and reagent. [14,15] Residence time is a key factor for controlling the yield and selectivity in a microreactor, [16][17][18] as in the context of producing very unstable and highly reactive intermediates, flow microreactors make an excellent replacement [19][20][21][22] to conventional batch reaction methods.…”

Continuous‐Flow Synthesis of β‐Ketoesters and Successive Reactions in One‐Flow using Heterogeneous Catalysis

“…Over the past decade, continuous‐flow technologies have attracted considerable attention in both academia and industries for sustainable chemical production. The approach has many advantages over conventional batch methods such as high productivity, improved catalytic efficiency, environmental compatibility, ease of scale‐up, and enhancement of process safety for industrial production [1–5] . An ultimate form of continuous‐flow organic synthesis is a sequential transformation from starting materials to final products through multi‐step flow reactions [6,7] .…”