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CN-122010677-A - Halogen exchange method for light-mediated bromoarene to chlorinated arene

CN122010677ACN 122010677 ACN122010677 ACN 122010677ACN-122010677-A

Abstract

The invention belongs to the technical field of organic synthesis and photocatalysis, and relates to a halogen exchange method from bromoarene to chloroarene by taking hydrochloric acid as a chlorine source in a light-mediated manner. The method takes hydrochloric acid (HCl) as a safe and cheap chlorine source, takes vanadyl acetylacetonate [ VO (acac) 2 ] as a catalyst and takes 2, 9-dimethyl-4, 7-diphenyl-1, 10-phenanthroline as a ligand under the irradiation of ultraviolet light, and realizes the efficient conversion of aryl bromide to aryl chloride in acetonitrile solvent. The reaction is carried out under the mild condition (0-30 ℃), and dangerous chlorinating agents such as chlorine, SOCl 2 and the like are not needed, so that the operation is simple, safe and environment-friendly. The method generates active chlorine species (Cl.or [ VO ] -Cl + ) through photoinduction metal-halogen bond activation, promotes C-Br bond cleavage and chlorine substitution reaction, and realizes high-selectivity Br-Cl conversion. The reaction has the advantages of wide substrate applicability, high selectivity, less side reaction, recyclable catalytic system and the like, and is particularly suitable for the later modification and green synthesis of fine chemicals and pharmaceutical intermediates. The invention provides a novel halogen exchange strategy which has high atom economy, is environment-friendly and can be popularized in large scale, and provides a novel technical path and industrial application prospect for the efficient chlorination of aryl halides.

Inventors

  • Dian Longyang
  • LIU KE
  • WU JING
  • MA ZHAOLUN
  • LI BINGJI
  • HU JIALE
  • SHAO YUXUAN

Assignees

  • 山东大学

Dates

Publication Date
20260512
Application Date
20251104

Claims (10)

  1. 1. A light-mediated halogen exchange method for bromoarene by taking hydrochloric acid as a chlorine source to chloroarene is characterized in that a metal catalyst, a bromoarene compound and a chlorine source are added into a solvent, the reaction is carried out under near visible light irradiation, and after the reaction is finished, a chloro substituent aromatic ring compound shown in the figure is obtained through treatment, wherein the reaction formula is as follows: Wherein R is one or more selected from chlorine (-Cl), fluorine (-F), hydrogen (-H), phenyl (-Ph), trifluoromethyl (-CF 3 ), methoxy (-OMe), tertiary butyl (-t-Bu), methyl (-Me) or aromatic ring replaced by other aromatic heterocycle such as thiophene, thiazole, benzothiophene, benzothiazole, etc.
  2. 2. The light-mediated halogen exchange method for bromoarene to chloroarene by taking hydrochloric acid as a chlorine source according to claim 1, wherein the molar ratio of the bromoaromatic ring compound to the metal catalyst, the ligand and the chlorine source is 1 (0.1-0.3): 10 and related proportions.
  3. 3. The light-mediated halogen exchange method for bromoarene to chloroarene using hydrochloric acid as chlorine source according to claim 1, wherein the metal catalyst includes, but is not limited to, transition metal catalysts such as vanadyl acetylacetonate, vanadium sulfate, ferric trichloride, cupric chloride, cerium chloride, nickel chloride, lanthanum chloride, etc.
  4. 4. A light-mediated halogen exchange process for bromoarenes to chloroarenes using hydrochloric acid as a chlorine source according to claim 1, wherein the reaction temperature includes, but is not limited to, 0-30 ℃, preferably 25 ℃, or heating.
  5. 5. A light mediated halogen exchange process for bromoarenes to chloroarenes using hydrochloric acid as a chlorine source according to claim 1, wherein the reaction system concentration comprises, but is not limited to, between 0.01 and 100 moles per liter, preferably 0.1 moles per liter.
  6. 6. A light-mediated halogen exchange process for bromoarenes to chloroarenes using hydrochloric acid as a chlorine source according to claim 1, wherein the reactive light source comprises, but is not limited to, between 365-765 nm, preferably 365-465 nm.
  7. 7. The method for exchanging halogen from bromoaromatic hydrocarbon to chloroaromatic hydrocarbon using hydrochloric acid as chlorine source according to claim 1, wherein the substituent R of the bromoaromatic ring compound a of the reaction substrate comprises, but is not limited to, one or more of chlorine (-Cl), fluorine (-F), hydrogen (-H), phenyl (-Ph), trifluoromethyl (-CF 3 ), methoxy (-OMe), tert-butyl (-t-Bu), methyl (-Me) or aromatic ring replaced by other aromatic heterocyclic ring such as thiophene, thiazole, benzothiophene and benzothiazole. One or more of chloro, fluoro, hydrogen, keto, trifluoromethyl, trifluoromethoxy, cyano, methyl or quinoline groups.
  8. 8. A light-mediated halogen exchange process for bromoarenes to chloroarenes using hydrochloric acid as a chlorine source according to claim 1, wherein the reaction solvent comprises one or more of acetonitrile, acetone, ethyl acetate, N-dimethylformamide, preferably acetonitrile.
  9. 9. The light-mediated halogen exchange method for bromoarene to chloroarene using hydrochloric acid as chlorine source according to claim 1, wherein the reaction time is 36-48 hours or other until the raw material is completely reacted.
  10. 10. The light-mediated halogen exchange method for bromoarene to chloroarene using hydrochloric acid as its chlorine source according to claim 1, wherein the waste chlorine source includes but is not limited to hydrochloric acid (HCl), chloroform (CHCl 3 ), N-chlorosuccinimide (NCS), magnesium chloride (MgCl 2 ), dichloroethane (DCE), and the like.

Description

Halogen exchange method for light-mediated bromoarene to chlorinated arene Technical Field The invention belongs to the technical field of organic synthesis and photocatalysis, and particularly relates to a method for realizing efficient conversion of aryl bromide to corresponding aryl chloride by utilizing hydrochloric acid as a chlorine source through photoinduction catalysis, which is particularly suitable for synthesis and modification of fine chemicals and pharmaceutical intermediates. Background Aryl halides (ARYL HALIDES) are important building blocks in organic synthesis, and are particularly widely used in metal-catalyzed cross-coupling, drug molecule modification and functional material synthesis. For certain molecular designs and post-modifications, it is often desirable to convert bromine substituents to chlorine to improve stability or adjust physicochemical properties. The traditional bromine-chlorine conversion method often depends on high-temperature halogen exchange, or uses halogen reagents (Cl 2、SOCl2 and the like) which are toxic or inconvenient to operate, or needs an expensive/complex catalytic system, and has the problems of poor selectivity, harsh conditions or potential safety hazards and the like. In recent years, photocatalysis, particularly photochemical strategies based on ligand-to-metal charge transfer (LMCT), have shown unique advantages in terms of halogen radical generation and mild halogen introduction. The light-induced metal-halogen bond can generate halogen free radical under room temperature condition, thereby realizing mild halogen exchange reaction. Based on the thought, the invention provides a high-selectivity conversion method of bromoarene to chloroarene by taking HCl as a chlorine source and combining light-induced LMCT or related photochemical paths through a metal catalytic system. Disclosure of Invention The invention aims to provide a Br- & gt Cl halogen exchange method which is simple and convenient to operate, safe and mild and has wide substrate applicability, hydrochloric acid is used as a chlorine source, the reaction is completed through photoinduction metal catalysis, the direct use of chlorine or other dangerous chlorination reagents is avoided, and meanwhile, high yield and high selectivity are realized. According to the invention, hydrochloric acid (HCl) is used as a chlorine source, and under the irradiation of ultraviolet or visible light, the efficient halogen exchange reaction from bromoarene to chloroarene is realized through the synergistic effect of low-cost metal catalysts such as vanadyl acetylacetonate (VO (acac) 2). The method generates active chlorine species (such as Cl or [ VO ] -Cl +) in situ by activating metal-halogen bond in a photoinduction catalytic system, thereby promoting the accurate occurrence of C-Br bond rupture and chlorine substitution in aryl bromide and completing the conversion of Br to Cl with high selectivity. Compared with the existing halogen exchange method, the invention has the following advantages: 1) The chlorine source is safe and economical, namely, cheap and easily available hydrochloric acid is used for replacing dangerous chlorinating agents such as chlorine, SO 2Cl2 and the like, the operation is safe, and the cost is low; 2) The reaction is carried out at room temperature and under illumination conditions without high temperature and high pressure, so that the use of a strong oxidant and a toxic solvent is avoided; 3) The high-efficiency selectivity is good, the conversion of the monosubstituted aryl bromide to the aryl chloride with high yield can be realized in the presence of various substituents, and the side reaction is less; 4) The catalyst system can be circulated, the catalyst utilization rate is high, the system is stable, and the activity can be kept in multiple circulation; 5) The environment-friendly method has the advantages of no need of extra halogen source or corrosive chlorinating agent, reduction of halogen waste liquid discharge and accordance with the concept of green chemistry and sustainable development. Therefore, the invention not only provides a simple, safe and efficient novel aryl bromide halogen exchange method, but also provides a novel thought and technical approach for green synthesis of halogen-containing aromatic hydrocarbon and post-modification of drug intermediates, and has wide industrial application prospect and environmental benefit. The technical scheme adopted by the invention is that the method for exchanging halogen from light-mediated bromoarene to chlorinated arene comprises the following steps: R is one or more selected from chlorine (-Cl), fluorine (-F), hydrogen (-H), phenyl (-Ph), trifluoromethyl (-CF 3), methoxy (-OMe), tert-butyl (-t-Bu), methyl (-Me) or aromatic ring replaced by other aromatic heterocyclic ring. The organic solvent is acetonitrile; the chlorine source is hydrochloric acid; The metal salt catalyst is selected from vanadyl acetylaceton