Preparation method of 1-methyl o-carborane
By using decanoborane and ethyl 2-butynylate to perform cyclization and hydrolysis reactions under catalyst and alkaline conditions, the product yield of 1-methylo-o-carboborane was successfully improved, and the problems of harsh reaction conditions and low product yield in traditional synthesis methods were solved.
Patent Information
- Application Number
- CN202510178263.X
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- Filing Date
- 2025-02-18
- Publication Date
- 2025-04-01
AI Technical Summary
The traditional 1-methyl ortho-carboronane synthesis method has problems such as harsh reaction conditions and low product yields.
Decylborane and ethyl 2-butynylate were used as raw materials, and the cyclization reaction was carried out under the action of a catalyst to form an intermediate containing ester groups and methyl groups, and hydrolyzed under basic conditions to obtain 1-methyl ortho-carboborane.
The reaction is carried out under normal temperature without special environment, the reaction conditions are simple, and the product yield exceeds 80%, which significantly improves the product yield.
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Figure CN119735607A_ABST
Abstract
Description
Technical Field
[0001] The invention relates to the technical field of synthesis of carborane derivatives, and in particular to a method for preparing 1-methyl o-carborane. Background Art
[0002] Carborane and its derivatives have been applied in many fields, such as biomedicine, photochemistry, supramolecular and coordination chemistry, and material chemistry, due to their unique three-dimensional structure, low toxicity, and good thermal and chemical stability. Among them, 1-methyl-o-carborane is widely used as an important chemical raw material and pharmaceutical intermediate. Since the methyl group in 1-methyl-o-carborane can effectively change the physicochemical properties and physiological activity of the compound, and can also be effectively converted into other functional groups through oxidation reactions, 1-methyl-o-carborane is also a template substrate for the development of many organic methodologies. Therefore, the synthesis of 1-methyl-o-carborane has received widespread attention from researchers.
[0003] like Figure 2 As shown, the traditional method for synthesizing 1-methyl-o-carborane is mainly: first, the hydrogen of o-carborane is extracted by n-butyl lithium, then it reacts with methylchlorosilane, and then another hydrogen atom of o-carborane is extracted by n-butyl lithium again, and a nucleophilic substitution reaction occurs with iodomethane, and finally trimethylsilane is released in a potassium carbonate system to obtain the target product.
[0004] However, the traditional method for synthesizing 1-methyl-o-carborane has many drawbacks. For example, the n-butyl lithium used in the synthesis process needs to be used under anhydrous and oxygen-free conditions, and the reaction conditions involved are relatively harsh. In addition, the yield of synthesized 1-methyl-o-carborane is only 30%, and the product yield is too low. Summary of the invention
[0005] The purpose of the present invention is to overcome the deficiencies of the prior art and provide a method for preparing 1-methyl-o-carborane, which solves the technical problems of harsh reaction conditions and low product yield in the existing 1-methyl-o-carborane synthesis method.
[0006] In order to achieve the above object, the present invention adopts the following technical solutions.
[0007] The present invention provides a method for preparing 1-methyl-o-carborane, comprising the following steps: Under the action of a catalyst, decaborane and ethyl 2-butynoate are used as raw materials, and a cyclization reaction is carried out in a solvent system to obtain an intermediate containing an ester group and a methyl group; the intermediate containing an ester group and a methyl group is hydrolyzed under alkaline conditions to obtain 1-methyl o-carborane.
[0008] Compared with the prior art, the preparation method provided by the present invention uses decaborane and 2-ethyl butynoate as raw materials, is carried out at room temperature, does not require a special reaction environment, has simple reaction conditions, and has fewer reaction steps. Subsequent experiments have shown that the product yield of the present invention exceeds 80%, and the product yield is high. Therefore, the preparation method provided by the present invention can solve the technical problems that the existing 1-methyl o-carborane synthesis method has harsh reaction conditions and low product yield.
[0009] Optionally, the catalyst is a silver-containing catalyst. Preferably, the silver-containing catalyst is silver nitrate.
[0010] Optionally, the molar ratio of decaborane, ethyl 2-butynoate and the silver-containing catalyst is 1:1-2:0.01-0.1.
[0011] In order to ensure that the decaborane reacts completely, the amount of ethyl 2-butynoate should be one or more times the amount of decaborane. When the amount of ethyl 2-butynoate is twice the amount of decaborane, the decaborane has basically reacted completely. Therefore, when the molar ratio of decaborane to ethyl 2-butynoate is less than 1:2, unreacted ethyl 2-butynoate will be produced, resulting in a waste of raw materials; when the molar ratio of decaborane to ethyl 2-butynoate is greater than 1:1, unreacted decaborane will be produced, thereby affecting the yield of 1-methyl-o-carborane.
[0012] Optionally, the alkaline condition is formed by a base in a solvent system, and the concentration of the base in the solvent system is 0.5 mol / L to 2 mol / L.
[0013] Optionally, the base is any one of sodium hydroxide, lithium hydroxide, potassium hydroxide and cesium hydroxide.
[0014] Optionally, it is characterized in that the molar ratio of decaborane to the base is 1:1-2.
[0015] Optionally, the solvent system for forming alkaline conditions includes water and an organic solvent, and the organic solvent is tetrahydrofuran or an alcohol compound.
[0016] Optionally, the volume ratio of the water to the organic solvent is 1:1.
[0017] Optionally, the solvent for the cyclization reaction is any one of toluene, xylene, and mesitylene.
[0018] The beneficial effect of the present invention is that, compared with the prior art, the preparation method provided by the present invention uses decaborane and 2-ethyl butynoate as raw materials, is carried out at normal temperature, does not require a special reaction environment, has simple reaction conditions, and has fewer reaction steps. Subsequent experiments have shown that the product yield of the present invention exceeds 80%, and the product yield is high. Therefore, the preparation method provided by the present invention can solve the technical problems that the existing 1-methyl o-carborane synthesis method has harsh reaction conditions and low product yield. BRIEF DESCRIPTION OF THE DRAWINGS
[0019] Figure 1 The present invention provides a synthetic route for 1-methyl o-carborane.
[0020] Figure 2 The present invention is a synthetic route diagram of 1-methyl-o-carborane in the prior art.
[0021] Figure 3 This is the hydrogen spectrum of 1-methyl-o-carborane prepared in Example 1 provided by the present invention.
[0022] Figure 4 This is the boron spectrum of 1-methyl-o-carborane prepared in Example 1 provided by the present invention. DETAILED DESCRIPTION
[0023] In order to solve the above technical problems, the present invention provides a method for preparing 1-methyl-o-carborane. The technical scheme and embodiments of the present invention are now described in detail in conjunction with the accompanying drawings.
[0024] The present invention provides a method for preparing 1-methyl-o-carborane, comprising the following steps: Decaborane and ethyl 2-butynoate are used as raw materials, and a cyclization reaction is carried out in a solvent system to obtain an intermediate containing an ester group and a methyl group; the intermediate containing an ester group and a methyl group is subjected to a hydrolysis reaction in an alkali metal hydroxide solution to obtain 1-methyl o-carborane; wherein the concentration of the alkali metal hydroxide solution is 0.5 mol / L to 2 mol / L.
[0025] Compared with the prior art, the preparation method provided by the present invention uses decaborane and 2-ethyl butynoate as raw materials, is carried out at room temperature, does not require a special reaction environment, has simple reaction conditions, and has fewer reaction steps. Subsequent experiments have shown that the product yield of the present invention exceeds 80%, and the product yield is high. Therefore, the preparation method provided by the present invention can solve the technical problems that the existing 1-methyl o-carborane synthesis method has harsh reaction conditions and low product yield.
[0026] The present invention is described in detail below through specific examples. The examples are exemplary and intended to be used to explain the present invention, but should not be understood as limiting the present invention.
[0027] Example 1 See also Figure 1 This embodiment provides a method for preparing 1-methyl-o-carborane, and the specific steps are as follows: In a reaction flask, 0.1 mol of decaborane, 0.1 mol of ethyl 2-butynoate, 0.001 mol of silver nitrate and 100 mL of toluene were added, and the mixture was stirred and reacted under reflux for 8 h.
[0028] Then, toluene was removed by rotary evaporation under reduced pressure, and 0.1 mol of sodium hydroxide, 50 mL of tetrahydrofuran and 50 mL of water were added to the above mixture, and the mixture was stirred at room temperature for 3 h.
[0029] After the reaction was completed, the mixture was neutralized with saturated ammonium chloride solution to neutrality, 100 mL of ethyl acetate was added, and extraction was performed three times. The organic phases were combined, dried over anhydrous sodium sulfate, and column chromatography was performed to obtain 13.2 g of the target product with a yield of 83%.
[0030] Spectral data of 1-methyl-o-carborane: 1 H NMR (400 MHz, CDCl3) δ 3.49 (s, 1H), 1.96 (s, 3H),. 11 B{ 1 H} NMR (128MHz, CDCl3) δ -1.65 (1B), -6.68 (1B), -9.12 (2B), -10.55 - -11.32 (4B), -12.71 (2B). 13 C NMR δ (100 MHz, CDCl3) δ 61.4, 25.9. Figure 3 The hydrogen spectrum of 1-methyl-o-carborane prepared in Example 1 provided by the present invention, Figure 4 The boron spectrum of 1-methyl-o-carborane prepared in Example 1 provided by the present invention. Figure 3 and Figure 4 The characteristic diffraction peaks and spectral data in the embodiment indicate that 1-methyl-o-carborane was successfully prepared in this embodiment.
[0031] Example 2 See also Figure 1 This embodiment provides a method for preparing 1-methyl-o-carborane, and the specific steps are as follows: In a reaction flask, 0.1 mol of decaborane, 0.15 mol of ethyl 2-butynoate, 0.001 mol of silver nitrate and 100 mL of toluene were added, and the mixture was stirred and reacted under reflux for 8 h.
[0032] Then, toluene was removed by rotary evaporation under reduced pressure, and 0.1 mol of sodium hydroxide, 50 mL of tetrahydrofuran and 50 mL of water were added to the above mixture, and the mixture was stirred at room temperature for 3 h.
[0033] After the reaction was completed, the mixture was neutralized with saturated ammonium chloride solution to neutrality, 100 mL of ethyl acetate was added, and extraction was performed three times. The organic phases were combined, dried over anhydrous sodium sulfate, and the target product was obtained by column chromatography with a yield of 86%.
[0034] Example 3 See also Figure 1 This embodiment provides a method for preparing 1-methyl-o-carborane, and the specific steps are as follows: In a reaction flask, 0.1 mol of decaborane, 0.2 mol of ethyl 2-butynoate, 0.001 mol of silver nitrate and 100 mL of toluene were added, and the reaction was stirred under reflux for 8 h.
[0035] Then, toluene was removed by rotary evaporation under reduced pressure, and 0.1 mol of sodium hydroxide, 50 mL of tetrahydrofuran and 50 mL of water were added to the above mixture, and the mixture was stirred at room temperature for 3 h.
[0036] After the reaction was completed, the mixture was neutralized with saturated ammonium chloride solution to neutrality, 100 mL of ethyl acetate was added, and extraction was performed three times. The organic phases were combined, dried over anhydrous sodium sulfate, and the target product was obtained by column chromatography with a yield of 86%.
[0037] Example 4 See also Figure 1 This embodiment provides a method for preparing 1-methyl-o-carborane, and the specific steps are as follows: In a reaction flask, 0.1 mol of decaborane, 0.1 mol of ethyl 2-butynoate, 0.002 mol of silver nitrate and 100 mL of toluene were added, and the reaction was stirred under reflux for 8 h.
[0038] Then, toluene was removed by rotary evaporation under reduced pressure, and 0.1 mol of sodium hydroxide, 50 mL of tetrahydrofuran and 50 mL of water were added to the above mixture, and the mixture was stirred at room temperature for 3 h.
[0039] After the reaction was completed, the mixture was neutralized with saturated ammonium chloride solution to neutrality, 100 mL of ethyl acetate was added, and extraction was performed three times. The organic phases were combined, dried over anhydrous sodium sulfate, and the target product was obtained by column chromatography with a yield of 83%.
[0040] Example 5 See also Figure 1 This embodiment provides a method for preparing 1-methyl-o-carborane, and the specific steps are as follows: In a reaction flask, 0.1 mol of decaborane, 0.1 mol of ethyl 2-butynoate, 0.005 mol of silver nitrate and 100 mL of toluene were added, and the mixture was stirred and reacted under reflux for 8 h.
[0041] Then, toluene was removed by rotary evaporation under reduced pressure, and 0.1 mol of sodium hydroxide, 50 mL of tetrahydrofuran and 50 mL of water were added to the above mixture, and the mixture was stirred at room temperature for 3 h.
[0042] After the reaction was completed, the mixture was neutralized with saturated ammonium chloride solution to neutrality, 100 mL of ethyl acetate was added, and extraction was performed three times. The organic phases were combined, dried over anhydrous sodium sulfate, and the target product was obtained by column chromatography with a yield of 83%.
[0043] Example 6 See also Figure 1 This embodiment provides a method for preparing 1-methyl-o-carborane, and the specific steps are as follows: In a reaction flask, 0.1 mol of decaborane, 0.1 mol of ethyl 2-butynoate, 0.01 mol of silver nitrate and 100 mL of toluene were added, and the mixture was stirred and reacted under reflux for 8 h.
[0044] Then, toluene was removed by rotary evaporation under reduced pressure, and 0.1 mol of sodium hydroxide, 50 mL of tetrahydrofuran and 50 mL of water were added to the above mixture, and the mixture was stirred at room temperature for 3 h.
[0045] After the reaction was completed, the mixture was neutralized with saturated ammonium chloride solution to neutrality, 100 mL of ethyl acetate was added, and extraction was performed three times. The organic phases were combined, dried over anhydrous sodium sulfate, and the target product was obtained by column chromatography with a yield of 84%.
[0046] Example 7 See also Figure 1 This embodiment provides a method for preparing 1-methyl-o-carborane, and the specific steps are as follows: In a reaction flask, 0.1 mol of decaborane, 0.1 mol of ethyl 2-butynoate, 0.001 mol of silver nitrate and 100 mL of toluene were added, and the mixture was stirred and reacted under reflux for 8 h.
[0047] Then, toluene was removed by rotary evaporation under reduced pressure, and 0.2 mol of sodium hydroxide, 50 mL of tetrahydrofuran and 50 mL of water were added to the above mixture, and the mixture was stirred at room temperature for 3 h.
[0048] After the reaction was completed, the mixture was neutralized with saturated ammonium chloride solution to neutrality, 100 mL of ethyl acetate was added, and extraction was performed three times. The organic phases were combined, dried over anhydrous sodium sulfate, and the target product was obtained by column chromatography with a yield of 83%.
[0049] Comparative Example 1 This comparative example provides a method for preparing 1-methyl-o-carborane, and the specific steps are as follows: In a reaction flask, 0.1 mol of decaborane, 0.1 mol of ethyl 2-butynoate, 0.001 mol of silver nitrate and 100 mL of toluene were added, and the mixture was stirred and reacted under reflux for 8 h.
[0050] Then, toluene was removed by rotary evaporation under reduced pressure, and 0.1 mol of sodium carbonate, 50 mL of tetrahydrofuran and 50 mL of water were added to the above mixture, and the mixture was stirred at room temperature for 3 h.
[0051] After the reaction was completed, the mixture was neutralized with saturated ammonium chloride solution to neutrality, 100 mL of ethyl acetate was added, and extraction was performed three times. The organic phases were combined, dried over anhydrous sodium sulfate, and the target product was obtained by column chromatography with a yield of 0%.
[0052] Comparative Example 2 This comparative example provides a method for preparing 1-methyl-o-carborane, and the specific steps are as follows: In a reaction flask, 0.1 mol of decaborane, 0.1 mol of ethyl 2-butynoate, 0.001 mol of silver nitrate and 100 mL of toluene were added, and the mixture was stirred and reacted under reflux for 8 h.
[0053] Then, toluene was removed by rotary evaporation under reduced pressure, and 0.1 mol of sodium bicarbonate, 50 mL of tetrahydrofuran and 50 mL of water were added to the above mixture, and the mixture was stirred at room temperature for 3 h.
[0054] After the reaction was completed, the mixture was neutralized with saturated ammonium chloride solution to neutrality, 100 mL of ethyl acetate was added, and extraction was performed three times. The organic phases were combined, dried over anhydrous sodium sulfate, and the target product was obtained by column chromatography with a yield of 0%.
[0055] Comparative Example 3 This embodiment provides a method for preparing 1-methyl-o-carborane, and the specific steps are as follows: In a reaction flask, 0.1 mol of decaborane, 0.1 mol of ethyl 2-butynoate, 0.001 mol of silver nitrate and 100 mL of toluene were added, and the mixture was stirred and reacted under reflux for 8 h.
[0056] Then, toluene was removed by rotary evaporation under reduced pressure, and 0.3 mol of sodium hydroxide, 50 mL of tetrahydrofuran and 50 mL of water were added to the above mixture, and the mixture was stirred at room temperature for 3 h.
[0057] After the reaction was completed, the mixture was neutralized with saturated ammonium chloride solution to neutrality, 100 mL of ethyl acetate was added, and extraction was performed three times. The organic phases were combined, dried over anhydrous sodium sulfate, and the target product was obtained by column chromatography with a yield of 70%.
[0058] Comparative Example 4 This embodiment provides a method for preparing 1-methyl-o-carborane, and the specific steps are as follows: In a reaction flask, 0.1 mol of decaborane, 0.1 mol of ethyl 2-butynoate, 0.001 mol of silver nitrate and 100 mL of toluene were added, and the mixture was stirred and reacted under reflux for 8 h.
[0059] Then, toluene was removed by rotary evaporation under reduced pressure, and 0.5 mol of sodium hydroxide, 50 mL of tetrahydrofuran and 50 mL of water were added to the above mixture, and the mixture was stirred at room temperature for 3 h.
[0060] After the reaction was completed, the mixture was neutralized with saturated ammonium chloride solution to neutrality, 100 mL of ethyl acetate was added, and extraction was performed three times. The organic phases were combined, dried over anhydrous sodium sulfate, and the target product was obtained by column chromatography with a yield of 45%.
[0061] Table 1 is the statistical results of product yields of Examples 1 to 7 and Comparative Examples 1 to 4 under different preparation parameters.
[0062] Table 1 Effect of different parameters on product yield In conjunction with Table 1, the synthesis process of 1-methyl-o-carborane was optimized and studied. It was found that sodium carbonate and sodium bicarbonate could not promote the hydrolysis of esters. After being replaced with sodium hydroxide, the embodiment of the present invention could separate the target product with a yield of 83%. Increasing the dosage of 2-butynoic acid ethyl ester can also increase the yield of the product 1-methyl-o-carborane, but the increase is not large. After adjusting the dosage of silver nitrate, it was found that the dosage of 0.001mol was the best yield, and increasing the dosage could not increase the yield. Changing the concentration of sodium hydroxide has a greater impact on the yield of the product 1-methyl-o-carborane. When the concentration of sodium hydroxide is increased to 5M, the yield of 1-methyl-o-carborane is reduced to 45%, because the overly strong alkalinity can promote the decomposition of carborane. In summary, we have optimized the optimal equivalent ratio.
[0063] In summary, the preparation method of the embodiment of the present invention uses decaborane and ethyl 2-butynoate as raw materials, is carried out at room temperature, does not require a special reaction environment, has simple reaction conditions, fewer reaction steps, and the product yield exceeds 80%, and the product yield is high. Therefore, it is explained that the preparation method provided by the embodiment of the present invention can solve the technical problems of harsh reaction conditions and low product yield in the existing 1-methyl-o-carborane synthesis method.
[0064] The above description is only a preferred embodiment of the present invention, and the above specific embodiment is not intended to limit the present invention. Various deformations and modifications may occur within the scope of the technical concept of the present invention, and any modification, modification or equivalent replacement made by a person of ordinary skill in the art based on the above description shall fall within the scope of protection of the present invention.
Claims
1. A method for preparing 1-methyl-o-carborane, characterized in that: The steps include: Under the action of a catalyst, decaborane and ethyl 2-butynoate are used as raw materials, and a cyclization reaction is carried out in a solvent system to obtain an intermediate containing an ester group and a methyl group. The intermediate containing an ester group and a methyl group undergoes a hydrolysis reaction under alkaline conditions to prepare 1-methyl-o-carborane.
2. The method for preparing 1-methyl-o-carborane according to claim 1, characterized in that: The catalyst is a silver-containing catalyst.
3. The method for preparing 1-methyl-o-carborane according to claim 2, characterized in that: The silver-containing catalyst is silver nitrate.
4. The method for preparing 1-methyl-o-carborane according to claim 2, characterized in that: The molar ratio of decaborane, ethyl 2-butynoate and the silver-containing catalyst is 1:1-2:0.01-0.
1.
5. The method for preparing 1-methyl-o-carborane according to claim 1, characterized in that: The alkaline condition is formed by a base in a solvent system, and the concentration of the base in the solvent system is 0.5 mol / L to 2 mol / L.
6. The method for preparing 1-methyl-o-carborane according to claim 5, characterized in that: The alkali is any one of sodium hydroxide, lithium hydroxide, potassium hydroxide and cesium hydroxide.
7. The method for preparing 1-methyl-o-carborane according to claim 5 or 6, characterized in that: The molar ratio of decaborane to the base is 1:1-2.
8. The method for preparing 1-methyl-o-carborane according to claim 5, characterized in that: The solvent system for forming alkaline conditions comprises water and an organic solvent, wherein the organic solvent is tetrahydrofuran or an alcohol compound.
9. The method for preparing 1-methyl-o-carborane according to claim 1, characterized in that: The solvent for the cyclization reaction is any one of toluene, xylene and mesitylene.