Method for removing oxime from aldoxime

Abstract

The invention discloses a method for removing oxime from aldoxime in the field of organic synthetic chemistry, which comprises the following steps of: mixing benzene seleninic acid, metal salt and silica gel to obtain a catalyst premix, adding reactant aldoxime, adding water to prepare a gelatinous substance, placing the gelatinous substance in a gas environment containing oxygen, absorbing the oxygen in the gas environment, and removing the oxime from the reactant. And carrying out oxidation deoximation reaction on the reactant aldoxime to generate aldehyde. The reaction conditions are mild, so that the product aldehyde cannot be further oxidized into carboxylic acid and cannot be dehydrated to generate nitrile in the process.

Description

Technical Field

[0001] The invention belongs to the field of organic synthetic chemistry, and in particular relates to selective deoximation of aldoxime. Background Art

[0002] Deoximation is an important reaction. Since oximes are usually stable crystals with a high melting point, the oximation-deoximation step can be used to identify and purify organic products. In addition, oximes can also be synthesized from non-carbonyl raw materials, and carbonyl-containing mixtures can be finally produced through deoximation. For example, the last step in the synthesis of carvone from limonene is deoximation. On the other hand, since selenium has excellent oxygen-carrying function and can catalyze various oxidation reactions, our research group has previously reported some selenium-catalyzed oxidative deoximation reactions. However, this reaction is mostly applied to ketone oxime deoximation, and hydrogen peroxide needs to be added as an oxidant. When selenium catalyzes the deoximation of aldoxime, dehydration byproducts and carboxylic acid byproducts are inevitably produced, resulting in a decrease in the selectivity of the reaction. It is a challenging technical problem to inhibit the dehydration reaction of aldoxime and overcome the further oxidation reaction of the product aldehyde while ensuring that the oxidative deoximation reaction can occur. Summary of the invention

[0003] The invention develops a method for deoximation of aldoxime, which can inhibit further oxidation reaction of product aldehyde and avoid occurrence of side reactions while ensuring that the oxidative deoximation reaction is continuously carried out.

[0004] The object of the present invention is achieved in this way: a method for deoximation of aldoxime, comprising mixing phenylselenous acid, a metal salt and silica gel to obtain a catalyst premix, adding aldoxime as a reactant, and then adding water to form a gel-like substance, wherein the gel-like substance is placed in a gas environment containing oxygen, absorbs oxygen in the gas environment, and causes the aldoxime as a reactant to undergo an oxidative deoximation reaction to generate an aldehyde.

[0005] Compared with the prior art, the beneficial effect of the present invention is that: in the present invention, phenylselenous acid and metal salt are used as catalysts to prepare a gel-like substance together with silica gel and aldoxime, and silica gel is used as a carrier for the reaction, which can prevent the rapid progress of the reaction and make the reaction conditions mild. In the process, the product aldehyde will not be further oxidized to carboxylic acid, nor will it be dehydrated to generate nitrile.

[0006] Furthermore, the ratio of the molar amount of the aldoxime to the mass of the catalyst premix is ​​1 to 4 mmol / g, preferably 2 mmol / g.

[0007] Furthermore, in the catalyst premix, the mass ratio of phenylselenous acid, metal salt and silica gel is: (0.1-0.4): (0.2-0.8): 1. Preferably, the mass ratio of phenylselenous acid to silica gel is: 0.25: 1. Under the above conditions, it can be ensured that there are enough selenium sites in the reaction system to promote the reaction. And the catalytic activity will not be too high, and the product aldehyde will not be further oxidized due to the excessive oxidation ability of the system.

[0008] The metal salt is one of ferric chloride, ferric sulfate, ferrous sulfate, ferric nitrate, cupric sulfate, cupric chloride, and cupric acetate. The preferred metal salt is ferric chloride; on the one hand, ferric chloride has a good catalytic oxidation effect as trivalent iron, and it can also coordinate with aldoxime oxygen, which is conducive to the shedding of oxime groups. In addition, the chloride ions in ferric chloride have strong penetrating power, which helps to improve material properties and promote the contact between reactants and oxygen. The mass ratio of ferric chloride to silica gel is preferably: 0.5:1. Below this amount, it will be inactivated due to insufficient iron catalytic centers. Excessive use will also produce carboxylic acid by-products due to excessive oxidation.

[0009] Furthermore, the mass of the water used is 2 to 4 times the mass of the silica gel, preferably 3 times. The amount of water used is the key to realizing the technology of the present invention. If the amount of water used is too little, the system is too dry and the reactants cannot be fully contacted. If the amount of water used is too much, the excess water will form a liquid layer above the silica gel system, isolating the air from entering, making it difficult for the reaction to occur.

[0010] The oxidative deoximation reaction is carried out at 40-80° C., preferably 60° C. If the temperature is too low, the reaction is difficult to occur, while if the temperature is too high, on the one hand, it will lead to an increase in side reactions, and on the other hand, it will cause the system water to evaporate and dry, thereby stopping the reaction. The gas containing oxygen can be air. DETAILED DESCRIPTION

[0011] Example 1

[0012] The technical solution of the present invention is further illustrated by the following experiments:

[0013] The purity of the drugs used in this experiment is shown in Table 1 below:

[0014]

[0015]

[0016] The specific experimental method is carried out as follows:

[0017] (1) Catalyst material premixing:

[0018] Take 20g of silica gel for chromatography and bake it in an oven at 100℃ for 2h. After taking it out of the oven, put it in an alkaline dryer and cool it to room temperature for use. Take 10g of ferric chloride and 5g of phenylselenous acid, grind them into powder, add 20g of dried silica gel and mix them. Add anhydrous methanol, stir in a water bath at 90℃ for 2h, evaporate the methanol with a rotary evaporator, dry it in an oven at 100 degrees for 2h, and then put it in a tubular furnace and roast it at 350℃ for 2h to obtain a silica gel-loaded selenium-iron catalyst premix.

[0019] (2) Aldoxime deoximation:

[0020] In a 10mL reaction bottle, add 1mmol benzaldehyde oxime, 0.5g silica gel supported selenium-iron catalyst premix and a small stirrer. Under magnetic stirring, add 1.5g of water to make the mixture gel-like. In the open air condition, heat to 60℃ and stir for 24h. After cooling to room temperature, add 5mL of ether, filter and drain the solvent, and separate the residue by column chromatography (eluent petroleum ether / ethyl acetate volume ratio 15:1) to obtain benzaldehyde with a yield of 85%.

[0021] Example 2

[0022] The other conditions were the same as those in Example 1, and phenylselenous acid in different proportions of the silica gel mass was used to catalyze the reaction. The results are shown in Table 2.

[0023] Table 2 Results of catalytic reactions of phenylselenous acid at different proportions of silica gel mass

[0024]

[0025]

[0026] As can be seen from the above table, when the phenylselenous acid catalyst accounts for 5-25% of the silica gel mass ratio, the yield of the oxide increases linearly, and at 20%, the yield reaches 66%. When the used phenylselenous acid catalyst accounts for 25% of the silica gel mass ratio, the yield of benzaldehyde oxime deoximation reaches a peak value, which can reach 85%. When the proportion of phenylselenous acid is greater than 25%, the yield will not increase, but will decrease due to excessive oxidation to produce benzaldehyde. Therefore, the best proportion of phenylselenous acid catalyst to silica gel mass ratio is 25%. Considering its yield, it is advisable to select phenylselenous acid consumption to be 10-40% of the silica gel consumption, that is, the mass dosage ratio of phenylselenous acid to silica gel is: (0.1-0.4):1.

[0027] Example 3

[0028] The other conditions were the same as those in Example 1, and different types of metal salt catalysts were used to catalyze the reaction. The results are shown in Table 3.

[0029] Table 3 Catalytic reaction results of different types of metal salt catalysts

[0030]

[0031]

[0032] As shown in the results in the table above, during the catalyst preparation process, we screened the types of metal salts, and ferric chloride was clearly the best metal catalyst. Compared with ferric chloride, ferric sulfate has poor catalytic activity, which may be due to the lack of a penetrating chloride ion-activated silica gel carrier. If divalent iron such as ferrous sulfate is used, the catalytic effect is poor and the reaction is incomplete. When ferric nitrate is used, the formation of over-oxidation product benzaldehyde is observed, which may be because nitrate ions also catalyze oxidation reactions in acidic systems. Studies have shown that copper salts have stronger catalytic activity. Therefore, the use of various copper salts will lead to over-oxidation of the product benzaldehyde into benzoic acid, resulting in a decrease in yield.

[0033] Example 4

[0034] The other conditions were the same as those in Example 1, and the ferric chloride catalyst was used in different proportions of the silica gel mass to catalyze the reaction. The results are shown in Table 4.

[0035] Table 4 Effect of different mass ratios of ferric chloride catalyst on catalytic reaction

[0036]

[0037]

[0038] As can be seen from the table above, when the iron trichloride accounts for more than 10% of the silica gel mass, there is obvious catalytic activity. When the ratio is 10-50%, the yield of the oxide increases linearly. At 40%, the yield reaches 78%. When the iron trichloride used accounts for 50% of the silica gel mass, the yield of benzaldehyde oxime deoximation reaches a peak value of 85%. When the ratio is greater than 50%, the yield will not increase significantly. Therefore, the optional ratio is 20-80%, and the optimal ratio is 50%.

[0039] Example 5

[0040] Other conditions were the same as those in Example 1. The reactions were carried out at different molar amounts of aldoxime and the mass ratio of the catalyst premix. The experimental results are shown in Table 5.

[0041] Table 5 Effect of different aldoxime molar dosage and catalyst premix mass ratio on the reaction

[0042]

[0043] From the above results, it can be seen that when the molar dosage of aldoxime and the mass ratio of silica gel are 2mmol / g, the yield of aldoxime deoximation is the highest. Increasing or decreasing the mass ratio will reduce the yield of aldehyde. If too little aldoxime is used, a large amount of over-oxidation product benzoic acid will appear; if too much aldoxime is used, the catalyst activity is insufficient, the reaction is incomplete, and the yield decreases.

[0044] Example 6

[0045] Other conditions were the same as in Example 1, and the reactions were carried out at different ratios of water mass to catalyst premix mass. The experimental results are shown in Table 6.

[0046] Table 6 Effect of different water quality and catalyst premix quality ratio on the reaction

[0047]

[0048] As can be seen from the above table, in the present invention, the mass of water used is 200-400% of the mass of silica gel, preferably 300%. The amount of water used is the key to realizing the technology of the present invention. If the amount of water used is too little, the system is too dry and the reactants cannot be fully contacted. If the amount of water used is too much, the excess water will form a liquid layer above the silica gel system, isolating the air from entering, making it difficult for the reaction to occur.

[0049] Example 7

[0050] Other conditions were the same as in Example 1, and the reactions were carried out at different temperatures. The experimental results are shown in Table 7.

[0051] Table 7 Effect of temperature on reaction

[0052]

[0053]

[0054] From the above results, in a thermal reaction, temperature plays a special role. At 20°C, the yield of the target product is only 14%. As the reaction temperature increases, the yield of the target product is greatly improved. When the reaction temperature is 60°C, the yield reaches the highest 85%. However, when the temperature continues to increase, the yield of the target product is greatly reduced. Therefore, the optimal reaction temperature is determined to be 60°C.

[0055] Example 8

[0056] Other conditions were the same as in Example 1, and different aldoxime substrates were used to expand the application range of the substrate. The experimental results are shown in Table 8.

[0057] Table 8 Substrate expansion

[0058] serial number Substrate Yield (%) 1 p-Tolualdehyde oxime 79 2 4-Nitrobenzaldehyde oxime 77 3 3-Fluorobenzaldehyde oxime 84 4 p-Bromobenzaldehyde oxime 78 5 p-Chlorobenzaldehyde oxime 84 6 p-Nitrobenzaldehyde oxime 53 7 1-Naphthaldehyde oxime 80 8 n-Heptaldoxime 72 9 p-Anisaldehyde oxime 51 10 4-tert-Butylbenzaldehyde oxime 69

[0059] The above results show that the reaction has a wide range of substrate applications. In addition to benzaldehyde oxime, other electron-deficient, electron-rich, and sterically hindered aromatic aldehyde oximes are applicable, as are aliphatic aldehyde oximes.

[0060] The present invention is not limited to the above-mentioned embodiments. On the basis of the technical solution disclosed in the present invention, technicians in this field can make some substitutions and deformations to some technical features therein according to the disclosed technical content without creative labor, and these substitutions and deformations are all within the protection scope of the present invention.

Claims

1. A method for deoximation of aldoxime, characterized in that: The catalyst premix is ​​obtained by mixing phenylselenous acid, metal salt and silica gel, and then adding reactant aldoxime and adding water to form a gel-like substance. The gel-like substance is placed in a gas environment containing oxygen, absorbs oxygen in the gas environment, and causes the reactant aldoxime to undergo an oxidative deoxime reaction to generate aldehyde.

2. The method for deoximation of aldoxime according to claim 1, wherein: The ratio of the molar amount of the aldoxime to the mass of the catalyst premix is ​​1-4 mmol / g.

3. The method for deoximation of aldoxime according to claim 1, wherein: In the catalyst premix, the mass ratio of phenylselenous acid, metal salt and silica gel is: (0.1-0.4): (0.2-0.8):

1.

4. The method for deoximation of aldoxime according to claim 3, wherein: The mass ratio of phenylselenous acid to silica gel is 0.25:

1.

5. The method for deoximation of aldoxime according to claim 3, characterized in that: The metal salt is one of ferric chloride, ferric sulfate, ferrous sulfate, ferric nitrate, cupric sulfate, cupric chloride and cupric acetate.

6. The method for deoximation of aldoxime according to claim 5, characterized in that: The metal salt is ferric chloride; the mass ratio of ferric chloride to silica gel is 0.5:

1.

7. The method for deoximation of aldoxime according to claim 1, characterized in that: The ratio of the molar amount of added aldoxime to the mass of the catalyst premix is ​​2 mmol / g.

8. The method for deoximation of aldoxime according to claim 1, wherein: The mass of water used is 2 to 4 times the mass of silica gel.

9. The method for deoximation of aldoxime according to claim 1, wherein: The oxidative deoximation reaction is carried out at 40-80°C, and the gas containing oxygen is air.

10. The method for deoximation of aldoxime according to claim 9, characterized in that: The oxidative deoximation reaction was carried out at 60°C.

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