Method for synthesizing halogenated alkane by high-selectivity halogenated saturated carbon-hydrogen bonds

Abstract

The invention discloses a synthesis method for highly selectively chlorinating or brominating a saturated carbon-hydrogen bond in alkane into corresponding chlorinated or brominated alkane under an electrochemical condition, and relates to the technical field of medicine synthesis. The synthesis method comprises the following steps: in an electrochemical reaction tank, dissolving alkane, a catalyst, an electrolyte and a halogen source in a solvent, connecting an electrode, and electrifying and reacting at room temperature, thereby selectively halogenating saturated carbon-hydrogen bonds in the alkane into corresponding halogenated alkane. The method can be widely applied to large-scale synthesis of various medicines.

Description

technical field [0001] The invention relates to the technical field of drug synthesis, in particular to a synthesis method for highly selective halogenation of saturated carbon-hydrogen bonds into halogenated alkanes under electrochemical conditions. Background technique [0002] saturated C(sp 3 )-H bonds widely exist in organic molecules and drug molecules, and saturated C(sp 3 )-H bond functionalization is of great significance to the green and efficient synthesis of drugs, the structural modification of inert sites of drug molecules and the discovery of active drug molecules. First of all, a large number of Chinese herbal medicine components and active natural drug molecules contain chlorine or bromine atoms, such as vancomycin, chlorothioester, losartan, diazepam, ambroxol, etc. In addition, halides are widely used in drug synthesis and transformation. Therefore, the direct introduction of halogen atoms by highly selective activation of saturated carbon-hydrogen bond...

AI Technical Summary

Problems solved by technology

Disadvantages: This method needs to use highly toxic chlorine or bromine as a halogen source, which has low safety, high requirements for operation and equipment, and serious environmental pollution; in addition, the reaction site selectivity is poor, and monohalogenated and polyhalogenated compounds are often obtained. mixture

Disadvantages: This method only examines six types of substrates, and the substrate applicability and functional group tolerance are poor; using hexafluoroisopropanol as a reaction solvent does not meet the requirements of green chemical development; excessive hypervalent iodine (BIN 3 ) reagents involved, while BIN 3 Expensive, dangerous and prone to explosion, therefore, this method is difficult to achieve industrial production

Disadvantages: the reaction temperature of this method is high (65°C); although N-chloroamide is used as the chlorine source, although it is easy to prepare, the operation is cumbersome; although this method is applied with high selectivity in the total synthesis of (+)-Chlorolissoclimide It is mainly used in the chlorination reaction of sclareolactone, but the selectivity of this method is poor in the chlorination reaction of other small molecules, and a mixture of primary carbon and secondary carbon chlorination products is often obtained.

Disadvantages: This method is suitable for a small amount of active secondary carbon, tertiary carbon and benzylic C (sp 3 Chlorination of small molecular compounds with )-H bonds, poor substrate applicability and functional group tolerance; tert-butoxyl groups will be generated in the reaction system, which will affect the selectivity of the reaction; for some complex natural products such as mint Alcohol, menthone, citronellol, etc., often to obtain a mixture; this reaction requires the use of silver catalysts, which is not economical and environmentally friendly

Disadvantage: This method still needs to use excessive hypervalent iodine (BIN 3 ) reagent, which is expensive, dangerous and explosive; in addition, this method also requires an excessive amount of (phen) CuCl 2 The complex is used as a chlorine source, and the cost is high; therefore, this method is also not suitable for industrial production

[0018] In summary, the existing methods for the selective halogenation of saturated C-H bonds have obvious deficiencies, and none of them can realize industrial scale-up production, so improvement is urgently needed

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