A method for preparing 6,7-dihydrocyclopenta[b]pyridin-5-one by catalytic oxidation

Abstract

The invention belongs to the technical field of fine chemicals, and specifically relates to a method for preparing 6,7-dihydrocyclopenta[b]pyridine-5-one by catalytic oxidation. 2,3-cyclopentapyridine is used as a raw material, tungsten trioxide is used as a catalyst in a solution in the presence of a base, and an oxidant is oxidized to obtain a product. The preparation method of the invention has high yield, mild reaction conditions, low catalyst price, simple operation, and is suitable for industrial production.

Description

Technical Field

[0001] The invention belongs to the technical field of fine chemicals, and specifically relates to a method for preparing 6,7-dihydrocyclopenta[b]pyridine-5-one by catalytic oxidation. Background Art

[0002] The preparation methods of 6,7-dihydrocyclopenta[b]pyridin-5-one mainly include the following:

[0003] Method 1: Gao Shuang et al. reported in patent CN201410664914.8 that the yield of oxidation reaction was 91% using manganese bis(trifluoromethanesulfonate) as catalyst and tert-butyl hydroperoxide as oxidant. This method has poor repeatability when the raw material input is more than 10g and is not suitable for industrial production.

[0004] Method 2: Laudadio, Gabriele et al. reported in Angewandte Chemie, International Edition (2018), 57(15), 4078-4082 that a microchannel oxidation reaction was carried out under light using homemade sodium tungstate / tetrabutylammonium bromide as a catalyst and oxygen as an oxidant, with a yield of 86%. This method has a high cost when the catalyst is homemade, and an expensive microchannel reactor is required for the reaction. It is only suitable for homemade samples in the laboratory, but not for commercial production.

[0005] Method 3, Fang Yuanfei et al. reported in patent CN201910617533.7 that ferric chloride was used as a catalyst, hydrogen peroxide was used as an oxidant, and the reaction temperature was 50°C for 24 hours, with a yield of 72%. This method uses hydrogen peroxide, which is too dangerous compared to tert-butyl hydroperoxide, and in the presence of trivalent iron, there is a risk of explosion if the material temperature is out of control during production.

[0006] Method 4: Bandyopadhyay, Anish et al. reported in India, IN201811004277 A2019-08-09 that potassium permanganate was used as an oxidant to carry out an oxidation reaction in tert-butyl alcohol and water as solvents, with a yield of 45%. This method uses potassium permanganate as an oxidant. In batch production, the material temperature in the kettle is difficult to control and is not suitable for industrial production. Small batch samples can be prepared in the laboratory. Summary of the invention

[0007] The object of the present invention is to solve the above problems and provide a method for preparing 6,7-dihydrocyclopenta[b]pyridin-5-one by catalytic oxidation.

[0008] To achieve the above purpose, the present invention adopts the following technical solution:

[0009] A method for preparing 6,7-dihydrocyclopenta[b]pyridin-5-one by catalytic oxidation, wherein the reaction formula is

[0010]

[0011] 2,3-cyclopentenopyridine is used as the raw material, and tungsten trioxide is used as the catalyst and the oxidant is used to oxidize the product in the presence of a base in a solution.

[0012] Take 2,3-cyclopentenopyridine as the raw material, add a base and a catalyst tungsten trioxide into the solution, raise the temperature to 50-90°C (preferably 60-80°C), add tert-butyl hydroperoxide dropwise, and carry out oxidation reaction at 50-90°C (preferably 60-80°C) for 3-15h (preferably 8-12h) to obtain the product 6,7-dihydrocyclopentano[b]pyridine-5-one.

[0013] The oxidation product is extracted with ethyl acetate, dehydrated, and the solvent is evaporated to obtain the product.

[0014] The solvent is water, wherein the amount of the solvent added is 2 to 15 times (preferably 6 to 10 times) the mass of the raw material 2,3-cyclopentapyridine.

[0015] The base is sodium hydroxide, potassium hydroxide, sodium carbonate, sodium bicarbonate, potassium carbonate or potassium bicarbonate (preferably sodium hydroxide or potassium hydroxide); wherein the molar amount of the added base is 0.5 to 15 times (preferably 1 to 3 times) the molar amount of the raw material 2,3-cyclopentenopyridine.

[0016] The molar amount of the catalyst tungsten trioxide is 0.01 to 0.3 times (preferably 0.02 to 0.08 times) the molar amount of the raw material 2,3-cyclopentenopyridine.

[0017] The oxidant is tert-butyl hydroperoxide, and the molar amount of the oxidant is 1 to 16 times (preferably 6 to 8 times) the molar amount of the raw material 2,3-cyclopentenopyridine.

[0018] Compared with the prior art, the present invention has the following advantages:

[0019] 1. The present invention adopts tert-butyl hydroperoxide as an oxidant, which is green and environmentally friendly. Compared with potassium permanganate or hydrogen peroxide, tert-butyl hydroperoxide as an oxidant is safer and easy to control during production.

[0020] 2. The catalyst tungsten trioxide used in the present invention is easily available and cheap.

[0021] 3. The present invention has low requirements on the process equipment used, is low in price, and is suitable for industrial production. DETAILED DESCRIPTION

[0022] The technical solutions in the embodiments of the present invention will be described clearly and completely below in conjunction with the embodiments of the present invention. The contents of the embodiments should not be construed as limiting the protection scope of the present invention.

[0023] Example 1

[0024] 1. Add 500ml of water to a three-necked flask, add 50.35g of sodium hydroxide under stirring in a water bath, and maintain the material temperature at 80°C after addition. Add 1.95g of tungsten trioxide and 50.0g of raw material 2,3-cyclopentene pyridine. Add 432.17g of tert-butyl hydroperoxide dropwise, maintain the material temperature at 80±5°C, and keep stirring for 8h after addition.

[0025] 2. After the reaction, extract with 150 ml of ethyl acetate twice, combine the ethyl acetate phases, add 50.0 g of anhydrous sodium sulfate, and stir at room temperature overnight. The next day, filter out the sodium sulfate, remove the solvent from the filtrate, and obtain 52.0 g of the product, with a yield of 93.1% and a purity of 99.6%.

[0026] Example 2

[0027] 1. Add 300ml of water to a three-necked flask, add 16.78g of sodium hydroxide under stirring in a water bath, and maintain the material temperature at 60°C after addition. Add 7.78g of tungsten trioxide and 50.0g of raw material 2,3-cyclopentene pyridine. Add 324.13g of tert-butyl hydroperoxide dropwise, maintain the material temperature at 60±5°C, and keep stirring for 12h after addition.

[0028] 2. After the reaction, extract with 150 ml of ethyl acetate twice, combine the ethyl acetate phases, add 50.0 g of anhydrous sodium sulfate, and stir at room temperature overnight. The next day, filter out the sodium sulfate, remove the solvent from the filtrate, and obtain 49.5 g of the product, with a yield of 88.6% and a purity of 99.1%.

[0029] Example 3

[0030] 1. Add 400ml of water to a three-necked flask, add 47.09g of potassium hydroxide under stirring in a water bath, and maintain the material temperature at 70°C after addition. Add 4.86g of tungsten trioxide and 50.0g of raw material 2,3-cyclopentene pyridine. Add 378.15g of tert-butyl hydroperoxide dropwise, maintain the material temperature at 70±5°C, and keep stirring for 10 hours after addition.

[0031] 2. After the reaction, extract with 150 ml of ethyl acetate twice, combine the ethyl acetate phases, add 50.0 g of anhydrous sodium sulfate, and stir at room temperature overnight. The next day, filter out the sodium sulfate, remove the solvent from the filtrate, and obtain 51.0 g of the product, with a yield of 91.3% and a purity of 99.5%.

[0032] Example 4

[0033] 1. Add 750 kg of water to a 2t reactor, start stirring, cool the jacket with cold water, slowly add 75.53 kg of sodium hydroxide, and after adding, pass hot water through the jacket to raise the material temperature to 80°C. Add 2.92 kg of tungsten trioxide and 75.0 kg of raw material 2,3-cyclopentene pyridine. Add 648.25 kg of tert-butyl hydroperoxide dropwise, maintain the material temperature at 80±5°C, and keep warm and stir for 8 hours after the addition is completed.

[0034] 2. Cool water is passed through the jacket of reactor 1 to reduce the material temperature to 25±5℃. Add 225L of ethyl acetate and stir for 15min. Let stand and separate the liquids. The lower aqueous phase is pumped into 2t reactor 2. The upper organic phase is pumped into 1t reactor 3.

[0035] Add 225L of ethyl acetate to the second reactor and stir for 15 minutes, let it stand, separate the liquids, and pump the lower aqueous phase into the waste liquid storage tank. Pump the upper organic phase into the third reactor.

[0036] Add 75 kg of anhydrous sodium sulfate to the reactor 3 and stir at 25±5℃ for 12 hours. Centrifuge to remove sodium sulfate, place the filtrate in a 1t solvent recovery kettle to remove the solvent, and raise the product temperature to 70-75℃. Open the bottom valve, barrel and package while hot to obtain 79.37 kg of product, with a yield of 94.7% and a purity of 99.7%.

Claims

1. A method for preparing 6,7-dihydrocyclopenta[b]pyridin-5-one by catalytic oxidation, characterized in that: The reaction formula is Take 2,3-cyclopenta[b]pyridine as the raw material, add alkali and catalyst tungsten trioxide into water, raise the temperature to 50-90°C, add tert-butyl hydroperoxide dropwise, and perform oxidation reaction at 50-90°C for 3-15h to obtain the product 6,7-dihydrocyclopenta[b]pyridine-5-one; The molar amount of the catalyst tungsten trioxide is 0.01 to 0.3 times the molar amount of the raw material 2,3-cyclopentenopyridine; The molar amount of the tert-butyl hydroperoxide is 1 to 16 times the molar amount of the raw material 2,3-cyclopentapyridine; The base is sodium hydroxide, potassium hydroxide, sodium carbonate, sodium bicarbonate, potassium carbonate or potassium bicarbonate; wherein the molar amount of the added base is 0.5 to 15 times the molar amount of the raw material 2,3-cyclopentenopyridine.

2. The method for preparing 6,7-dihydrocyclopenta[b]pyridin-5-one by catalytic oxidation according to claim 1, characterized in that: The oxidation product is extracted with ethyl acetate, dehydrated, and the solvent is evaporated to obtain the product.

3. The method for preparing 6,7-dihydrocyclopenta[b]pyridin-5-one by catalytic oxidation according to claim 1, characterized in that: The amount of water added is 2 to 15 times the mass of the raw material 2,3-cyclopentene pyridine.

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