Method for catalyzing addition of alpha-alkyl tin ester compound into hydroxy ketone or alkoxy ketone compound by stannous benzoate compound
By using stannous benzoate compounds as catalysts to catalyze the addition reaction of α-alkyltinyl ester compounds and hydroxyketone or alkoxyketone compounds, the harsh reaction conditions and low stereoselectivity in the existing technology are solved. solve the problem and achieve efficient and highly stereoselective synthesis, which has industrial application value.
Patent Information
- Application Number
- CN202411390487.9
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- Filing Date
- 2024-10-08
- Publication Date
- 2025-01-24
AI Technical Summary
In the prior art, when catalyzing the addition of α-alkyl tinyl ester compounds to hydroxyketones or alkoxyketone compounds, the reaction conditions are harsh and the stereoselectivity is not high, making it difficult to achieve efficient and highly stereoselective synthesis.
Stannous benzoate compounds are used as catalysts to achieve high efficiency and high stereoselectivity of the addition reaction through the reaction with α-alkyltinyl ester compounds and hydroxyketone or alkoxyketone compounds.
Under the catalysis of stannous benzoate, the reaction can achieve a yield of more than 90%, and its stereoselectivity can reach 99%, and the product can be further derived into other ester compounds or pharmaceutically active intermediates, which has industrial application value.
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Figure CN119350163A_ABST
Abstract
Description
Technical Field
[0001] The invention relates to the technical field of organic catalytic reactions, and in particular to a stannous benzoate compound catalyzing the addition of an alpha-alkyltinyl ester compound to a hydroxy ketone or an alkoxy ketone compound. Background Art
[0002] In organic chemical reactions, the synthesis of CC bonds with unique stereo configurations is undoubtedly very important, especially organic compounds containing hydroxyl and ether bonds. For example, the corresponding chiral intermediates can be constructed to synthesize antibiotics related to the drug (-)-decarestrictine D (Tetrahedron Lett. 1998, 39, 4421–4424), to construct precursors of the anticancer drug paclitaxel with unique chiral structures (J. Am. Chem. Soc. 1971, 93, 2325–2327), and to synthesize the raw materials of the trisodium salt of zagrelic acid A (Tetrahedron 2013, 69, 6639–6647). A large number of literature reports that it is feasible to use organic metal complexes for carbonyl addition to give the product a certain advantageous configuration, but the reaction conditions are often harsh and the stereoselectivity is not high, and the practical value is not great. Therefore, it is extremely important to develop and find new catalysts to achieve high stereoselectivity.
[0003] Internationally, Reetz et al. have developed a series of aldol-type addition reactions of α-alkoxyaldehydes with enol silanes in the presence of Lewis acid catalysts at relatively low temperatures (-78°C) for 1 hour or more through complexation (Tetrahedron, 1984, 40, 4327; Tetrahedron, 1992, 48, 5731; Tetrahedron Lett., 1993, 34, 1119), achieving generally high stereoselectivity. Japanese scholar Akio Baba used lithium diisopropylamide to react with alkyl ester compounds and then reacted them with α-alkoxy ketones to achieve moderate stereoselectivity, but the entire reaction was carried out at -78°C. When he chose stannous chloride, he found that it could catalyze the addition of α-alkyltin ester compounds to hydroxy ketones or alkoxy ketones with high stereoselectivity (Chem. Commun., 2001, 157–158). However, the use of stannous chloride can easily cause corrosion of the reactor or pipeline, increasing equipment maintenance costs. Therefore, finding a suitable catalyst is of great industrial significance. Summary of the invention
[0004] In view of the shortcomings of the prior art, the present invention provides a stannous benzoate compound that catalyzes the addition of an α-alkyltinyl ester compound to a hydroxyketone or alkoxyketone compound.
[0005] The purpose of the present invention can be achieved by the following technical solutions:
[0006] The first aspect of the present invention relates to a method for synthesizing a compound, comprising the following steps:
[0007] α-Alkyl tin ester compounds react with hydroxy ketone or alkoxy ketone compounds under the catalysis of stannous benzoate, and the chemical formula is:
[0008]
[0009] Wherein, the R1 is: C1~C 20 A linear, branched or cyclic alkyl group or H; R2 to R4 are: C1 to C 20 Straight chain, branched chain or cyclic alkyl group, C6~C 18 aryl or its substituted derivatives.
[0010] Optionally, the reaction is performed in a protective gas atmosphere.
[0011] Optionally, the α-alkyltin ester compound and the hydroxyketone or alkoxyketone compound are dissolved in an organic solvent.
[0012] Optionally, the organic solvent is: anhydrous acetonitrile.
[0013] Optionally, the method further comprises extracting, concentrating, drying and recrystallizing the solution after the reaction.
[0014] Optionally, the stannous benzoate compound has the structural formula:
[0015]
[0016] Wherein, the R1 is: C1~C 20 A linear, branched or cyclic alkyl group or H; R2 to R4 are: C1 to C 20 Straight chain, branched chain or cyclic alkyl group, C6~C 18 aryl or its substituted derivatives.
[0017] The second aspect of the present invention relates to a compound, characterized in that it comprises the following raw materials:
[0018] Stannous benzoate, α-alkyltin ester compounds and hydroxyketones or alkoxyketone compounds;
[0019] The compound structural formula is:
[0020]
[0021] Wherein, the R1 is: C1~C 20A linear, branched or cyclic alkyl group or H; R2 to R4 are: C1 to C 20 Straight chain, branched chain or cyclic alkyl group, C6~C 18 aryl or its substituted derivatives.
[0022] Optionally, the raw material further includes an organic solvent.
[0023] Optionally, the organic solvent is: anhydrous acetonitrile.
[0024] The third aspect of the present invention relates to the use of stannous benzoate as a catalyst in the addition of α-alkyltinyl ester compounds to hydroxyketones or alkoxyketone compounds.
[0025] Beneficial effects of the present invention:
[0026] Stannous benzoate can obtain a yield of more than 90% in the reaction of adding hydroxy ketone or alkoxy ketone, and its stereoselectivity can reach 99%. The product obtained by the invention can be further derived into other ester compounds or pharmaceutical active intermediates, so it has practical significance in industry. DETAILED DESCRIPTION
[0027] The technical solutions in the embodiments of the present invention are described clearly and completely below. Obviously, the described embodiments are only part of the embodiments of the present invention, not all of them. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without creative work are within the scope of protection of the present invention.
[0028] The compounds in each example of this application have been reported in the literature. For detailed NMR data, please refer to the literature: DOI: 10.1039 / b008493j.
[0029] Example 1
[0030] This embodiment provides a method for preparing a compound, comprising the following steps:
[0031] Under N2 protection, stannous benzoate (2.89 g, 8 mmol) and compound 1 (2.26 g, 10 mmol) were dissolved in 25 mL of acetonitrile, stirred evenly, and then α-alkyl tin ester compound A (4.53 g, 12 mmol) was slowly added. After stirring at room temperature for 2 hours, the reaction solution was poured into 300 mL of ether and 150 mL of 15% by mass ammonium fluoride aqueous solution and stirred for 30 min or more, and then the precipitate was filtered. After the filtrate was repeatedly extracted with 900 mL of ether for 3 times, an appropriate amount of anhydrous MgSO4 was added to dry and filter, and the solvent was evaporated under reduced pressure on a rotary evaporator. The obtained product was recrystallized in a mixed solution of toluene and n-hexane (toluene: n-hexane = 9:1 (volume ratio)), and finally a pure product 2 (mass 2.86 g, yield 91%) was obtained, and the selectivity was greater than 99%. The reaction formula involved in the above preparation method is as follows:
[0032]
[0033] Example 2
[0034] This embodiment provides a method for preparing a compound, comprising the following steps:
[0035] Under N2 protection, stannous benzoate (2.89 g, 8 mmol) and compound 3 (2.40 g, 10 mmol) were dissolved in 25 mL of acetonitrile, stirred evenly, and then α-alkyl tin ester compound A (4.53 g, 12 mmol) was slowly added. After stirring at room temperature for 2 hours, the reaction solution was poured into 300 mL of ether and 150 mL of 15% by mass ammonium fluoride aqueous solution and stirred for 30 min or more, and then the precipitate was filtered. After the filtrate was repeatedly extracted with 900 mL of ether for 3 times, an appropriate amount of anhydrous MgSO4 was added to dry and filter, and the solvent was evaporated under reduced pressure on a rotary evaporator. The obtained product was recrystallized in a mixed solution of toluene and n-hexane (toluene: n-hexane = 10:1 (volume ratio)), and finally a pure product 4 (mass 3.10 g, yield 94%) was obtained, and the selectivity was greater than 99%. The reaction formula involved in the above preparation method is as follows:
[0036]
[0037] Example 3
[0038] This embodiment provides a method for preparing a compound, comprising the following steps:
[0039] Under N2 protection, stannous benzoate (2.89 g, 8 mmol) and compound 5 (2.54 g, 10 mmol) were dissolved in 25 mL of acetonitrile, stirred evenly, and then α-alkyltin ester compound A (4.53 g, 12 mmol) was slowly added. After stirring at room temperature for 2 hours, the reaction solution was poured into 300 mL of ether and 150 mL of 15% by mass ammonium fluoride aqueous solution and stirred for 30 min or more, and then the precipitate was filtered. After the filtrate was repeatedly extracted with 900 mL of ether for 3 times, an appropriate amount of anhydrous MgSO4 was added to dry and filter, and the solvent was evaporated under reduced pressure on a rotary evaporator. The obtained product was recrystallized in a mixed solution of toluene and n-hexane (toluene: n-hexane = 10:1 (volume ratio)), and finally a pure product 6 (mass 2.94 g, yield 86%) was obtained, and the selectivity was greater than 99%. The reaction formula involved in the above preparation method is as follows:
[0040]
[0041] Example 4
[0042] This embodiment provides a method for preparing a compound, comprising the following steps:
[0043] Under N2 protection, stannous benzoate (2.89 g, 8 mmol) and compound 7 (1.64 g, 10 mmol) were dissolved in 25 mL of acetonitrile, stirred evenly, and then α-alkyltin ester compound A (4.53 g, 12 mmol) was slowly added. After stirring at room temperature for 2 hours, the reaction solution was poured into 300 mL of ether and 150 mL of 15% by mass ammonium fluoride aqueous solution and stirred for 30 min or more, and then the precipitate was filtered. After the filtrate was repeatedly extracted with 900 mL of ether for 3 times, an appropriate amount of anhydrous MgSO4 was added to dry and filter, and the solvent was evaporated under reduced pressure on a rotary evaporator. The obtained product was recrystallized in a mixed solution of toluene and n-hexane (toluene: n-hexane = 8:3 (volume ratio)), and finally a pure product 8 (mass 0.66 g, yield 26%) was obtained, and the selectivity was greater than 93%. The reaction formula involved in the above preparation method is as follows:
[0044]
[0045] Example 5
[0046] This embodiment provides a method for preparing a compound, comprising the following steps:
[0047] Under N2 protection, stannous benzoate (2.89 g, 8 mmol) and compound 9 (1.28 g, 10 mmol) were dissolved in 25 mL of acetonitrile, stirred evenly, and then α-alkyltin ester compound A (4.53 g, 12 mmol) was slowly added. After stirring at room temperature for 2 hours, the reaction solution was poured into 300 mL of ether and 150 mL of 15% by mass ammonium fluoride aqueous solution and stirred for 30 min or more, and then the precipitate was filtered. After the filtrate was repeatedly extracted with 900 mL of ether for 3 times, an appropriate amount of anhydrous MgSO4 was added to dry and filter, and the solvent was evaporated under reduced pressure on a rotary evaporator. The obtained product was recrystallized in a mixed solution of toluene and n-hexane (toluene: n-hexane = 9:2 (volume ratio)), and finally a pure product 10 (mass 1.08 g, yield 50%) was obtained, and the selectivity was greater than 90%. The reaction formula involved in the above preparation method is as follows:
[0048]
[0049] Example 6
[0050] This embodiment provides a method for preparing a compound, comprising the following steps:
[0051] Under N2 protection, stannous benzoate (2.89 g, 8 mmol) and compound 11 (2.12 g, 10 mmol) were dissolved in 25 mL of acetonitrile, stirred evenly, and then α-alkyltin ester compound A (4.53 g, 12 mmol) was slowly added. After stirring at room temperature for 2 hours, the reaction solution was poured into 300 mL of ether and 150 mL of 15% by mass ammonium fluoride aqueous solution and stirred for 30 min or more, and then the precipitate was filtered. After the filtrate was repeatedly extracted with 900 mL of ether for 3 times, an appropriate amount of anhydrous MgSO4 was added to dry and filter, and the solvent was evaporated under reduced pressure on a rotary evaporator. The obtained product was recrystallized in a mixed solution of toluene and n-hexane (toluene: n-hexane = 9:1 (volume ratio)), and finally a pure product 12 (mass 2.61 g, yield 87%) was obtained, and the selectivity was greater than 99%. The reaction formula involved in the above preparation method is as follows:
[0052]
[0053] Example 7
[0054] This embodiment provides a method for preparing a compound, comprising the following steps:
[0055] Under N2 protection, stannous benzoate (1.08 g, 3 mmol) and compound 13 (0.15 g, 1 mmol) were dissolved in 15 mL of acetonitrile, stirred evenly, and then α-alkyltin ester compound A (1.36 g, 3.6 mmol) was slowly added. After stirring at room temperature for 1.5 hours, the reaction solution was poured into 150 mL of ether and 75 mL of 15% by mass ammonium fluoride aqueous solution and stirred for 30 minutes or more, and then the precipitate was filtered. After the filtrate was repeatedly extracted with 450 mL of ether for 3 times, an appropriate amount of anhydrous MgSO4 was added to dry and filter, and the solvent was evaporated under reduced pressure on a rotary evaporator. The obtained product was recrystallized in a mixed solution of toluene and n-hexane (toluene: n-hexane = 9:2 (volume ratio)), and finally a pure product 14 (mass 0.17 g, yield 72%) was obtained, and the selectivity was greater than 99%. The reaction formula involved in the above preparation method is as follows:
[0056]
[0057] In the description of this specification, the description with reference to the terms "one embodiment", "example", "specific example", etc. means that the specific features, structures, materials or characteristics described in conjunction with the embodiment or example are included in at least one embodiment or example of the present invention. In this specification, the schematic representation of the above terms does not necessarily refer to the same embodiment or example. Moreover, the specific features, structures, materials or characteristics described can be combined in any one or more embodiments or examples in a suitable manner.
[0058] The above shows and describes the basic principles, main features and advantages of the present invention. Those skilled in the art should understand that the present invention is not limited to the above embodiments, and the above embodiments and descriptions are only for explaining the principles of the present invention. Without departing from the spirit and scope of the present invention, the present invention may have various changes and improvements, and these changes and improvements all fall within the scope of the present invention to be protected.
Claims
1. A method for synthesizing a compound, characterized in that: The following steps are involved: α-Alkyl tin ester compounds react with hydroxy ketone or alkoxy ketone compounds under the catalysis of stannous benzoate. The chemical reaction formula is: Wherein, the R1 is: C1~C 20 A linear, branched or cyclic alkyl group or H; R2 to R4 are: C1 to C 20 Straight chain, branched chain or cyclic alkyl group, C6~C 18 aryl or its substituted derivatives.
2. The method for preparing the compound according to claim 1, characterized in that: The reaction was set up in a protective gas atmosphere.
3. The method for preparing the compound according to claim 1, characterized in that: The α-alkyltin ester compound and the hydroxyketone or alkoxyketone compound are dissolved in an organic solvent.
4. The method for preparing the compound according to claim 3, characterized in that: The organic solvent is anhydrous acetonitrile.
5. The method for preparing the compound according to claim 1, characterized in that: The method also includes extracting, concentrating, drying and recrystallizing the solution after the reaction.
6. The method for preparing the compound according to claim 1, characterized in that: The structural formula of the stannous benzoate compound is: R5 to R9 are each independently selected from hydrogen, alkyl, alkoxy, halogen, trifluoromethyl, cyano, nitro, amino, alkylamino, C6 to C 18 aryl or its substituted derivatives.
7. A compound, characterized in that Including the following ingredients: Stannous benzoate, α-alkyltin ester compounds and hydroxyketones or alkoxyketone compounds; The compound structural formula is: Wherein, the R1 is: C1~C 20 A linear, branched or cyclic alkyl group or H; R2 to R4 are: C1 to C 20 Straight chain, branched chain or cyclic alkyl group, C6~C 18 aryl or its substituted derivatives.
8. The compound according to claim 7, characterized in that The raw materials also include an organic solvent.
9. The compound according to claim 8, characterized in that The organic solvent is anhydrous acetonitrile.
10. Use of stannous benzoate as a catalyst in the addition of hydroxyketones or alkoxyketones to α-alkyltin ester compounds.