Method for debenzylating aromatic benzyl ether compound
By reacting with sodium thiosulfate at room temperature using iodine element and organic hydrosilane, the problem of high cost of metal catalysts and inapplicable to halogen-containing aryl benzyl ether compounds in the prior art is solved, and rapid , stable removal process and high product yield.
Patent Information
- Application Number
- CN202411227744.7
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- Filing Date
- 2024-09-03
- Publication Date
- 2024-12-13
AI Technical Summary
In the existing debenzyl aryl benzyl ether compound debenzyl, the metal catalyst is costly and is not suitable for halogen-containing compounds, and the reduction reaction is unstable, making it difficult to achieve a fast and stable removal process.
Iodine element and organic hydrosilane are used as reaction reagents, and react with sodium thiosulfate solution after stirring at room temperature to achieve debenzyl aryl benzyl ether compounds, avoiding the use of metal catalysts and are suitable for halogen-containing compounds.
The rapid and stable removal process without using metal catalysts is achieved. It is suitable for halogen-containing compounds, with simple operation and high product yield, and overcomes the problems of high cost and poor stability of metal catalysts in the prior art.
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Abstract
Description
Technical Field
[0001] The invention belongs to the field of organic synthetic chemistry, and particularly relates to a method for debenzylating an aromatic benzyl ether compound. Background Art
[0002] Benzyl is a commonly used protecting group, which is used to protect phenolic hydroxyl groups by generating aryl benzyl ethers.
[0003] (Org. Lett. 2019, 21, 6185; J. Am. Chem. Soc. 2010, 132, 15528; J. Am. Chem. Soc. 2005, 127, 12684; J. Am. Chem. Soc. 2006, 128, 7136).
[0004] The commonly used debenzylation methods for aryl benzyl ethers are reduction reactions such as H2 / Pd(OH)2 system (J.Am.Chem.Soc.2010,132,15528), H2 / Pd system (J.Am.Chem.Soc.2005,127,12684) and Et3SiH / Pd(OAc)2 system (Synthesis 1999,1999,1399). Since halogens (such as Br) can be reduced, reduction reactions are not suitable for the debenzylation of aryl benzyl ethers containing halogens. Moreover, when Pd metal is used for reduction, the cost is high and there is a problem of metal residue.
[0005] Therefore, a method for debenzylating aryl benzyl ether compounds which is simple to operate, has a fast removal rate and is more stable is needed in the art. Summary of the invention
[0006] Based on the above purpose, the purpose of the present application is to provide a new method for removing the benzyl protecting group of an aryl benzyl ether compound, using iodine and organohydrogen silane as reaction reagents, so that the entire reaction process can be carried out without using a metal catalyst, the operation is simple, the removal rate is fast, and it is also applicable to halogen-containing aryl benzyl ether compounds.
[0007] To this end, the technical solution of the present application discloses a method for debenzylating an aryl benzyl ether compound, comprising the following steps:
[0008] S1. mixing an aryl benzyl ether compound, an iodine element, an organohydrogen silane and a solvent to obtain a reaction mixture;
[0009] S2. The reaction mixture was stirred at room temperature for 30 min, quenched with sodium thiosulfate solution, and then the target compound was isolated.
[0010] Preferably, the organohydrogensilane is any one of triethylsilane, polymethylhydrogensiloxane, 1,1,3,3-tetramethyldisiloxane, triphenylsilane, diphenylsilane and dimethylchlorosilane.
[0011] Preferably, the solvent is any one of 1,2-dichloroethane, dichloromethane, ethyl acetate, acetonitrile, toluene and 1,4-dioxane.
[0012] Preferably, the concentration of the sodium thiosulfate solution is 0.5 mol / L.
[0013] Preferably, the molar ratio of the iodine element to the aryl methyl ether compound is 1.0 equiv, and the molar ratio of the organohydrogensilane to the aryl methyl ether compound is 1.0 equiv.
[0014] Preferably, the separation is obtained by extracting, drying and separating the stirred mixture by column chromatography.
[0015] Preferably, the extraction is performed using ethyl acetate, the extracted organic phase is dried using anhydrous sodium sulfate, the solvent is then removed, and the target compound is separated by column chromatography.
[0016] The beneficial effects of the present application are as follows: the present application uses iodine and organohydrogensilane as reaction reagents to remove aryl benzyl ether compounds, the entire reaction process does not require the use of a metal catalyst, and the reaction can be carried out only at room temperature; compared with the prior art, the present application overcomes the problem that the prior art is not suitable for debenzylation of halogen-containing aryl benzyl ether compounds when using a metal catalyst; at the same time, the operation is simple, the removal rate is fast, and the yield of the target product is high. DETAILED DESCRIPTION
[0017] The present invention is further described in detail below in conjunction with specific embodiments. This implementation case is implemented based on the technology of the present invention, and a detailed implementation method and specific operation process are now given to illustrate that the present invention is creative, but the protection scope of the present invention is not limited to the following embodiments.
[0018] Unless otherwise specified, the experimental methods used in the following examples are conventional methods.
[0019] Unless otherwise specified, the materials and reagents used in the following examples can be obtained from commercial sources.
[0020] The embodiment of the present application discloses a method for debenzylating an aryl benzyl ether compound, comprising the following steps:
[0021] S1. mixing an aryl benzyl ether compound, an iodine element, an organohydrogen silane and a solvent to obtain a reaction mixture;
[0022] S2. The reaction mixture was stirred at room temperature for 30 min, quenched with sodium thiosulfate solution, and then the target compound was isolated.
[0023] In this embodiment, the aryl benzyl ether compound comprises the structural formula as described in Ⅰ:
[0024]
[0025] Among them, R 1 The group represented by is one selected from 2-naphthyl, phenyl, 4-methylphenyl, 4-trifluoromethylphenyl, 4-fluorophenyl, 4-chlorophenyl, 4-bromophenyl, 4-iodophenyl, 3-bromophenyl, 2-bromophenyl, 2-methylphenyl, 4-methoxyphenyl, 4-methoxycarbonylphenyl, 4-ethoxycarbonylphenyl and 4-nitrophenyl.
[0026] After debenzylation using iodine and organohydrogensilane as reaction reagents, the reaction product is a phenol corresponding to the aryl benzyl ether compound, which has the structural formula shown in II:
[0027]
[0028] The above reaction formula is
[0029]
[0030] In some preferred embodiments, the organohydrogensilane is preferably any one of triethylsilane, polymethylhydrogensiloxane, 1,1,3,3-tetramethyldisiloxane, triphenylsilane, diphenylsilane and dimethylchlorosilane; the solvent is any one of 1,2-dichloroethane, dichloromethane, ethyl acetate, acetonitrile, toluene and 1,4-dioxane; the concentration of the sodium thiosulfate solution is 0.5 mol / L; the molar ratio of the iodine element to the aryl methyl ether compound is 1.0 equiv, and the molar ratio of the organohydrogensilane to the aryl methyl ether compound is 1.0 equiv.
[0031] It is understood that after the reaction is completed, the reaction product needs to be separated. In a preferred embodiment, the separation is to extract, dry and separate the stirred mixture by column chromatography. The extraction is to extract with ethyl acetate, and the extracted organic phase is dried with anhydrous sodium sulfate, and then the solvent is removed, and the target compound is separated by column chromatography.
[0032] The reaction process of the present application will be described in detail below through specific examples.
[0033] Example
[0034] Aryl benzyl ether compound (1.0mmol), solvent (2mL), organohydrogen silane (1.0mmol) and iodine (1.0mmol) were added to a 25mL round-bottom flask in sequence. The reaction mixture was stirred at room temperature for 30 minutes, quenched by adding 10mL of 0.5mol / L sodium thiosulfate solution, and then extracted once with 30mL of ethyl acetate. The organic phase was dried over sodium sulfate, and the solvent was removed by a rotary evaporator, and then the target product was separated by column chromatography.
[0035] The specific aryl benzyl ether compounds, solvents, and organohydrogen silanes are shown in Table 1; the reaction products, structural formulas, and yields are shown in Table 2.
[0036] Table 1
[0037]
[0038] Table 2
[0039]
[0040]
[0041]
[0042] Finally, it should be noted that the above implementation cases are only used to illustrate the technical solution of the present invention rather than to limit it. Although the present invention has been described in detail with reference to the preferred implementation cases, those skilled in the art should understand that the technical solution of the present invention can be modified or replaced by equivalents without departing from the purpose and scope of the technical solution of the present invention, which should be included in the scope of the claims of the present invention.
Claims
1. A method for debenzylating an aryl benzyl ether compound, It is characterized in that The steps include: S1. mixing an aryl benzyl ether compound, an iodine element, an organohydrogen silane and a solvent to obtain a reaction mixture; S2. The reaction mixture was stirred at room temperature for 30 min, quenched with sodium thiosulfate solution, and then the target compound was isolated.
2. The method according to claim 1, It is characterized in that The organohydrogensilane is any one of triethylsilane, polymethylhydrogensiloxane, 1,1,3,3-tetramethyldisiloxane, triphenylsilane, diphenylsilane and dimethylchlorosilane.
3. The method according to claim 1, It is characterized in that The solvent is any one of 1,2-dichloroethane, dichloromethane, ethyl acetate, acetonitrile, toluene and 1,4-dioxane.
4. The method according to claim 1, It is characterized in that The concentration of the sodium thiosulfate solution is 0.5 mol / L.
5. The method according to claim 1, It is characterized in that The molar ratio of the iodine element to the aryl methyl ether compound is 1.0 equiv, and the molar ratio of the organohydrogensilane to the aryl methyl ether compound is 1.0 equiv.
6. The method according to claim 1, It is characterized in that The separation is obtained by extracting, drying and separating the stirred mixture by column chromatography.
7. The method according to claim 6, It is characterized in that The extraction is performed by using ethyl acetate, and the extracted organic phase is dried using anhydrous sodium sulfate, and then the solvent is removed, and the target compound is separated by column chromatography.