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CN-121021448-B - Preparation method of 2-alkyl-3-iodochromone compound

CN121021448BCN 121021448 BCN121021448 BCN 121021448BCN-121021448-B

Abstract

The invention discloses a preparation method of a 2-alkyl-3-iodochromone compound, belonging to the field of organic synthesis. The preparation method comprises the steps of taking an o-hydroxyphenylpropynylone compound and an iodination reagent as starting materials, and carrying out a serial cyclization reaction in the presence of halosilane and a solvent to obtain the 2-alkyl-3-iodochromone compound. The preparation method has the advantages of wide substrate application range, mild reaction, good atomic economy, simple and convenient post-treatment of the product and high yield, can be used for synthesizing compounds with different molecular structures, and is favorable for industrial production and application of the compounds.

Inventors

  • ZHOU ANXI
  • ZHU HAITAO
  • BIAN HONGPING
  • NIE FENGBIN
  • MAO LIULIANG
  • ZHU XIANHONG
  • ZHAN FULING

Assignees

  • 江西金丰药业有限公司
  • 上饶师范学院

Dates

Publication Date
20260508
Application Date
20250826

Claims (6)

  1. 1. The preparation method of the 2-alkyl-3-iodochromone compound is characterized by comprising the following steps: Taking a compound shown in a formula (I) and an iodination reagent as starting materials, taking halosilane as a catalyst, and performing serial cyclization reaction in the presence of a solvent, and performing aftertreatment to obtain a 2-alkyl-3-iodochromone compound shown in a formula (II); The structure of the formula (I) is as follows: 、 、 、 、 、 、 、 、 Or (b) ; The structure of formula (II) is: 、 、 、 、 、 、 、 、 Or (b) ; The iodination reagent adopts N-iodination succinimide, and the solvent is anhydrous methanol; The post-treatment comprises the steps of adding water into a reaction product for quenching, extracting with ethyl acetate for at least two times, merging organic phases, washing with water and saturated NaHCO 3 solution respectively, drying with anhydrous Na 2 SO 4 , performing reduced pressure rotary evaporation, and separating and purifying residues by column chromatography to obtain the 2-alkyl-3-iodochromone compound.
  2. 2. The method for preparing a 2-alkyl-3-iodochromone compound according to claim 1, wherein the catalyst is trimethylchlorosilane.
  3. 3. The method for preparing a 2-alkyl-3-iodochromone compound according to claim 1, wherein the compound shown in the formula (I) is iodinated agent=1:1-2.5 according to the molar ratio.
  4. 4. The method for preparing a 2-alkyl-3-iodochromone compound according to claim 2, wherein the compound shown in the formula (I) comprises a catalyst=1:1-2.5 according to a molar ratio.
  5. 5. The method for preparing a 2-alkyl-3-iodochromone compound according to claim 1, wherein the reaction temperature is 0-80 ℃.
  6. 6. The method for preparing a 2-alkyl-3-iodochromone compound according to claim 5, wherein the reaction time is 1-6 h.

Description

Preparation method of 2-alkyl-3-iodochromone compound Technical Field The invention belongs to the field of organic synthesis, and particularly relates to a preparation method of a 2-alkyl-3-iodochromone compound. Background Chromones are an important class of oxygen-containing heterocyclic structural units that are widely found in many natural products and drug molecules with important biological activities. In recent years, more and more studies have found that chromone derivatives have immunosuppressive activity. For molecules containing a chromone backbone, a close correlation between the different substituents and biological activity is shown, with the 2, 3-position being more pronounced in each substitution position of the chromone. Among various chromone compounds, the 2-substituent-3-iodo-chromone compound is an important class, and besides having biological activity and larger application value, the compound can also realize the functionalization of the No. 3 position through the coupling reaction of a carbon-iodine bond so as to obtain the chromone compound with more abundant structure, so that the compound has wider application value. Therefore, the 2-alkyl 3-iodized chromone compound is also an important intermediate in organic synthesis. At present, the preparation of the 2-alkyl-3-iodochromone compound is mainly realized through the iodination of the 2-alkyl chromone compound. In 1993, li Yulin et al achieved the iodination of flavonoids by the action of I 2/ceric ammonium nitrate at 55-60 ℃ (Synthesis 1993, 565). The method is only limited to iodination of flavone derivatives, has low overall product yield (mostly between 20 and 30 percent), even does not react, and simultaneously needs to add a large amount of oxidant ceric ammonium nitrate for reaction, needs to add a reducing agent for post-treatment, has large heat release quantity and is not beneficial to industrial production and application. In 2020, wang Lin research team also reported the iodination of flavonoids (tetrahedron lett. 2020,61, 151511), which was required to be carried out under the co-action of the oxidizing agent Oxone with KI. In 2007, wang Shaomeng group reported that the iodination of 8-isobutyl-5, 6, 7-trimethoxy-2-methylchromone was achieved by the action of silver I 2/trifluoroacetate at 0 ℃ (j. Med. Chem.2007,50,3163). The method only reports the synthesis of 3-iodine 8-isobutyl-5, 6, 7-trimethoxy-2-methyl chromone, other compounds are not reported, and meanwhile, the used reagent has expensive silver trifluoroacetate. In 2020, kenneth K. Laali et al used the NIS/BMIM-ILs reaction system to iodize 2-methyl-7-iodochromone at 100 ℃ (tetrahedron Lett. 2020,61, 152179). The method has higher reaction temperature, requires ionic liquid and synthesizes only 2-methyl-3, 7-diiodochromone. Based on this, in order to improve the synthesis efficiency and reduce the cost of 2-alkyl-3-iodo-chromone compounds, development of a novel green, economical and efficient preparation method is needed to be suitable for industrial production and promote practical application thereof. Disclosure of Invention The invention provides a preparation method of a 2-alkyl-3-iodochromone compound, which develops a novel green, economic and efficient preparation method, has a wide substrate application range, can be used for synthesizing compounds with different molecular structures, has mild reaction conditions, low-price and easily obtained reagents, good atomic economy, simple and convenient product post-treatment and high yield, and is suitable for industrial production and promotion of practical application. In order to solve the technical problems, the invention provides the following technical scheme that the preparation method of the 2-alkyl-3-iodochromone compound is characterized by comprising the following steps of: the method comprises the steps of taking a compound shown in a formula (I) and an iodination reagent as starting materials, taking halosilane as a catalyst, and carrying out a serial cyclization reaction in the presence of an anhydrous organic solvent to obtain the 2-alkyl-3-iodochromone compound shown in a formula (II). The structures of the above formula (I) and formula (II) are as follows: Wherein R 1 is selected from one of hydrocarbon groups; R 2 is selected from one of hydrogen, halogen, acyl, cyano, nitro, amino, hydroxyl, sulfonyl, sulfonic acid group, ester group, alkoxy, halogenated alkyl and hydrocarbon group. Further, the iodination reagent adopts N-iodinated succinimide. Further, the catalyst adopts trimethylchlorosilane. Further, the catalyst is diluted by adopting an anhydrous organic solvent, wherein the organic solvent is tetrahydrofuran or an alcohol solvent. Further, according to the molar ratio, the iodination reagent is 1:1-2.5. Further, according to the molar ratio, the compound shown in the formula I is trimethylchlorosilane=1:1-2.5. Further, the reaction temperature is 0-80 ℃. Further, the reaction