Method and device for continuously synthesizing cyclopropane compounds

Abstract

The invention discloses a method and a device for continuously synthesizing cyclopropane compounds. The method comprises the following steps of: continuously carrying out a synthesis reaction of a diazomethane precursor in a first reactor, flowing a reaction product of the first reactor into a separator for layering, overflowing an organic phase obtained by layering into a second reactor, continuously consuming the diazomethane precursor in the second reactor to prepare diazomethane, and carrying out an electron-rich mono-olefin cyclopropanation reaction in situ to obtain the cyclopropane compounds. The method can realize automatic control, reduce the transfer of high-risk materials, avoid the risk of pipeline transfer of a diazomethane solution, and effectively improve the production safety, also has simple equipment, can save equipment investment, and can safely and quantitatively realize simultaneous diazomethane generation and olefin cyclopropanation reaction.

Description

technical field [0001] The invention relates to the field of medicine and chemical industry, in particular to a method and device for continuous synthesis of cyclopropane compounds. Background technique [0002] Cyclopropane compounds can participate in the construction of various heterocyclic compound skeletons due to the tension of the three-membered ring and the unique double bond characteristics. Many natural products and active ingredients are cyclopropane compounds or derived from cyclopropane compounds. It has important application value in the field of medicine and chemical industry. Synthesis of cyclopropane compounds by cyclopropanation of alkenes is a common way. [0003] The Simmons-Smith reaction is a widely used reaction in the cyclopropanation reaction of olefins. Diethyl zinc or zinc-copper alkene, diiodomethane (or methylene bromide) produces carbene intermediates and reacts with olefins to generate cyclopropanes compound. This type of reaction is easy to...

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Problems solved by technology

Both of these studies rely on the controlled feeding of the diazomethane precursor to realize the simultaneous formation of diazomethane and the cyclopropanation of olefins in a two-phase system. If the feeding rate of the diazomethane precursor is too fast, the diazomethane unit The amount of production is large within a period of time, and the catalyst catalyzes the decomposition of diazomethane at an accelerated rate to generate by-products such as ethylene. If the feeding rate is too slow, it may cause the precipitation of the catalyst and affect the catalytic activity. These all increase the risk of operating the diazomethane precursor

[0006] In summary, the prior art mainly has the following disadvantages: 1) Although the continuous preparation of the diazomethane precursor and the continuous preparation and application of the diazomethane solution can be realized, the separation of the diazomethane precursor and the diazomethane can be greatly reduced And the risk of use, but the continuous reaction equipment chain is long and involves the pipeline transfer risk of diazomethane solution; 2) prepare diazomethane by continuous reaction, though permeable membrane separation of diazomethane can realize the separation of diazomethane and substrate In-situ reaction, but the manufacturing cost of the permeable membrane is high, the production capacity is small, and large-scale application cannot be realized in a short time; 3) The batch one-pot method realizes the simultaneous generation of diazomethane and olefin cyclopropanation, but increases Risks of handling diazomethane precursors

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