Method for preparing aromatic nitrile based on aromatic aldehyde oxidation

Abstract

The invention provides a method for preparing aromatic nitrile based on aromatic aldehyde oxidation. The preparation method comprises the following steps: S1, adding organic high-valence iodide into a mixed solution containing aromatic aldehyde, ammonium salt, a surfactant and a solvent, and carrying out oxidation reaction to obtain a solution containing aromatic nitrile; s2, performing rotary evaporation on the solution containing the aromatic nitrile to obtain an aromatic nitrile crude product; and S3, dissolving the aromatic nitrile crude product in dichloromethane, and carrying out column chromatography separation to obtain the aromatic nitrile with the purity of more than or equal to 99.5%. According to the preparation method provided by the invention, the cheap aromatic aldehyde is adopted as the substrate to prepare the aromatic nitrile, the raw material cost is saved, the organic high-valence iodide is adopted to oxidize the substrate, the aromatic nitrile compound with high yield and high purity is prepared, and in addition, the preparation method is safe in reaction process, simple, mild in reaction condition and suitable for industrial production. Safety and efficiency are realized.

Description

Technical Field

[0001] The present invention relates to the technical field of organic compounds, and specifically relates to a method for preparing aromatic nitriles by oxidizing aromatic aldehydes. Background Art

[0002] Aromatic nitrile products have important applications in the field of drug synthesis. For example, o-nitrobenzonitrile can be used to prepare benzotriazole-substituted 2-phenylquinazoline, which can be used as an antitumor microtubule protein polymerization inhibitor; m-nitrobenzonitrile can be used to prepare a heterocyclic drug intermediate for treating tuberculosis; p-nitrobenzonitrile can be used to prepare an intermediate 3-(4-nitrophenyl)-1,2,4-oxadiazole for drugs against echinococcosis.

[0003] Currently, commercially available nitrobenzonitrile compounds have risks in their preparation raw materials and reaction processes, with uncontrollable safety, low yields and purities. Therefore, the price of high-purity nitrobenzonitrile compounds is relatively high, generally above 4,000 yuan / kg. Taking p-nitrobenzonitrile as an example, the main preparation methods include the following three:

[0004] 1) High-temperature one-pot method: p-Nitrobenzoic acid and toluenesulfonamide are mixed evenly and reacted at 225-230°C. The yield only reaches 72%, and this reaction is prone to side reactions at high temperatures, with an uncontrollable process and low product purity;

[0005] 2) 4-Nitrobenzyl alcohol conversion method: First, 2,2,6,6-tetramethylpiperidine-1-oxyl radical is used as an oxidant to oxidize it to an intermediate aldehyde in a DCM solvent, and then iodine and ammonia water are added to react to form p-nitrobenzonitrile, with a yield of 72%. And the reaction process is complex and the raw material price is high;

[0006] 3) p-Nitrostyrene conversion method: p-Nitrostyrene reacts with nitrite under the condition of CH3COOH containing MeCN to obtain p-nitrobenzonitrile with a yield of 84.5%. However, the reaction substrate p-nitrostyrene is expensive. Summary of the Invention

[0007] (1) Technical Problems to be Solved

[0008] Aiming at the deficiencies of the prior art, the present invention provides a method for preparing aromatic nitriles by oxidizing aromatic aldehydes, with low raw material costs, high yields, a green and environmentally friendly reaction process, safety and high efficiency, and solves the problems raised in the above background art.

[0009] (2) Technical Solutions

[0010] To achieve the above objectives, the present invention is achieved through the following technical solutions:

[0011] A method for preparing aromatic nitriles by oxidizing aromatic aldehydes, comprising the following steps:

[0012] S1. Add an organic hypervalent iodide to a mixed solution containing an aromatic aldehyde, an ammonium salt, a surfactant, and a solvent, and carry out an oxidation reaction to obtain a solution containing an aromatic nitrile;

[0013] S2. Rotavaporize the solution containing the aromatic nitrile to obtain a crude product of the aromatic nitrile;

[0014] S3. Dissolve the crude product of the aromatic nitrile in dichloromethane and carry out column chromatography separation to obtain an aromatic nitrile with a purity ≥99.5%.

[0015] Preferably, the organic hypervalent iodide is selected from at least one of iodobenzene diacetate, phenyliodine(III) oxide, bis(trifluoroacetoxy)iodobenzene, hydroxy(tosyloxy)iodobenzene, 2-iodoxybenzoic acid, Dess-Martin periodinane, or iodobenzene dichloride.

[0016] Preferably, the molar ratio of the organic hypervalent iodide to the aromatic aldehyde is 2-5:1.

[0017] Preferably, the aromatic aldehyde is selected from at least one of p-hydroxybenzaldehyde, p-cyanobenzaldehyde, phthalaldehyde, o-nitrobenzaldehyde, m-nitrobenzaldehyde, or p-nitrobenzaldehyde.

[0018] Preferably, the ammonium salt is selected from at least one of ammonium oxalate, ammonium persulfate, ammonium fluoride, ammonium dihydrogen phosphate, ammonium dichromate, ammonium carbonate, ammonium bicarbonate, or ammonium acetate.

[0019] Preferably, the molar ratio of the ammonium salt to the aromatic aldehyde is 5-30:1.

[0020] Preferably, the surfactant is selected from at least one of tetrabutylammonium bromide, sodium dodecyl sulfate, sodium dodecyl sulfonate, or Tween-80;

[0021] The molar ratio of the surfactant to the aromatic aldehyde is 0.001-0.005:1.

[0022] Preferably, before step S2, the solution containing the aromatic nitrile obtained in step S1 is extracted to obtain a reduction product of the organic hypervalent iodide, and after recovering the reduction product, the organic hypervalent iodide is synthesized again.

[0023] Preferably, the solvent is selected from water or dimethyl sulfoxide.

[0024] Preferably, the temperature of the oxidation reaction is 60-80°C, and the time of the oxidation reaction is 2-6 h.

[0025] (III) Beneficial effects

[0026] The present invention provides a method for preparing an aromatic nitrile based on the oxidation of an aromatic aldehyde. It has the following beneficial effects:

[0027] 1. The preparation method provided by this solution uses inexpensive aromatic aldehydes as substrates to prepare aromatic nitriles, saving raw material costs. Organic hypervalent iodides are used to oxidize the substrates, and aromatic nitrile compounds with high yields and high purities are prepared. In addition, the reaction process of the preparation method of the present invention is safe, the preparation method is simple, the reaction conditions are mild, and it is safe and efficient.

[0028] 2. The preparation method provided by the present invention allows the reduction products of the organic hypervalent iodides used to be recycled by pagination, which is environmentally friendly. Detailed Embodiments

[0029] To better illustrate and elaborate on the content of the present invention, the following will be described in detail with reference to specific examples.

[0030] Example 1

[0031] 30 mL of water, 1.51 g of p-nitrobenzaldehyde, 5.35 g of ammonium chloride, and 0.003 g of tetrabutylammonium bromide were successively added to a 100 mL four-necked flask. After stirring for 10 min, the mixture was homogenized. Then, 6.44 g of iodobenzene diacetate was added to the four-necked flask, and heating was started to 60 °C. After reacting for 4 h, heating was turned off and stirring was continued. The aqueous phase was separated and concentrated by rotary evaporation to obtain a crude product of aromatic nitrile. Then, it was dissolved in DCM and analyzed by column chromatography to obtain 1.25 g of pure p-nitrobenzonitrile, with a yield of 84.5% and a purity of 99.5%.

[0032] Example 2

[0033] 300 mL of water, 30.22 g of o-nitrobenzaldehyde, 462.6 g of ammonium acetate, and 0.13 g of tetrabutylammonium bromide were successively added to a 500 mL four-necked flask. After stirring for 15 min, the mixture was homogenized. Then, 132.0 g of iodobenzene oxide was added to the four-necked flask, and heating was started to 80 °C. After reacting for 5 h, heating was turned off and stirring was continued. The aqueous phase was separated and concentrated by rotary evaporation to obtain a crude product of aromatic nitrile. Then, it was dissolved in DCM and analyzed by column chromatography to obtain 26.84 g of pure o-nitrobenzonitrile, with a yield of 90.6% and a purity of 99.8%.

[0034] Example 3

[0035] 50 mL of dimethyl sulfoxide, 6.71 g of phthalaldehyde, 96.1 g of ammonium carbonate and 0.016 g of tetrabutylammonium bromide were successively added to a 100 mL four-necked flask. After stirring for 10 min, the mixture was homogenized. Then, 28.0 g of 2-iodoxybenzoic acid was added to the four-necked flask. The heating was started to 70 °C, and after reacting for 4 h, the heating was turned off and stirring was continued. The aqueous phase was separated and concentrated by rotary evaporation to obtain the crude product of aromatic nitrile. Then, it was dissolved in DCM and analyzed by column chromatography to obtain 5.7 g of pure phthalonitrile with a yield of 89.1% and a purity of 99.7%.

[0036] Example 4

[0037] 1000 mL of water, 61.1 g of p-hydroxybenzaldehyde, 1156.5 g of ammonium acetate and 0.16 g of tetrabutylammonium bromide were successively added to a 2000 mL four-necked flask. After stirring for 20 min, the mixture was homogenized. Then, 430.0 g of bis(trifluoroacetoxy)iodine was added to the four-necked flask. The heating was started to 65 °C, and after reacting for 6 h, the heating was turned off and stirring was continued. The aqueous phase was separated and concentrated by rotary evaporation to obtain the crude product of aromatic nitrile. Then, it was dissolved in DCM and analyzed by column chromatography to obtain 57.2 g of pure o-nitrobenzonitrile with a yield of 95.9% and a purity of 99.5%.

[0038] Although the embodiments of the present invention have been shown and described, it will be understood by those of ordinary skill in the art that various changes, modifications, substitutions and variations can be made in these embodiments without departing from the principles and spirit of the present invention. The scope of the present invention is defined by the appended claims and their equivalents.

Claims

1. A method for preparing aromatic nitriles by oxidizing aromatic aldehydes, characterized in that: It includes the following steps: S1. Add an organic hypervalent iodide to a mixed solution containing an aromatic aldehyde, an ammonium salt, a surfactant and a solvent, and carry out an oxidation reaction to obtain a solution containing an aromatic nitrile; S2. Carry out rotary evaporation on the solution containing the aromatic nitrile to obtain a crude product of the aromatic nitrile; S3. Dissolve the crude product of the aromatic nitrile in dichloromethane and carry out column chromatography separation to obtain an aromatic nitrile with a purity ≥ 99.5%.

2. A method for preparing aromatic nitriles by oxidizing aromatic aldehydes according to claim 1, characterized in that: The organic hypervalent iodide is selected from at least one of iodobenzene diacetate, iodobenzene oxide, bis(trifluoroacetoxy)iodine, hydroxy(toluenesulfonyloxy)iodobenzene, 2-iodoxybenzoic acid, Dess-Martin periodinane or iodobenzene oxide; 3. A method for preparing aromatic nitriles by oxidizing aromatic aldehydes according to claim 1, characterized in that: The molar ratio of the organic hypervalent iodide to the aromatic aldehyde is 2-5:

1.

4. A method for preparing aromatic nitriles based on the oxidation of aromatic aldehydes according to claim 1, characterized in that: The aromatic aldehyde is selected from at least one of p-hydroxybenzaldehyde, p-cyanobenzaldehyde, o-phthalaldehyde, o-nitrobenzaldehyde, m-nitrobenzaldehyde or p-nitrobenzaldehyde; 5. A method for preparing aromatic nitriles by oxidizing aromatic aldehydes according to claim 1, characterized in that: The ammonium salt is selected from at least one of ammonium oxalate, ammonium persulfate, ammonium fluoride, ammonium dihydrogen phosphate, ammonium dichromate, ammonium carbonate, ammonium bicarbonate or ammonium acetate; 6. The method for preparing aromatic nitriles based on the oxidation of aromatic aldehydes according to claim 1, wherein: The molar ratio of the ammonium salt to the aromatic aldehyde is 5-30:

1.

7. A method for preparing aromatic nitriles by oxidizing aromatic aldehydes according to claim 1, characterized in that: The surfactant is selected from at least one of tetrabutylammonium bromide, sodium dodecyl sulfate, sodium dodecyl sulfonate or Tween-80; The molar ratio of the surfactant to the aromatic aldehyde is 0.001-0.005:

1.

8. A method for preparing aromatic nitriles by oxidizing aromatic aldehydes according to claim 1, characterized in that: Before carrying out step S2, the solution containing the aromatic nitrile obtained in step S1 is extracted to obtain a reduction product of the organic hypervalent iodide, and the reduction product is recovered and then the organic hypervalent iodide is synthesized.

9. A method for preparing aromatic nitriles by oxidizing aromatic aldehydes according to claim 1, characterized in that: The solvent is selected from water or dimethyl sulfoxide.

10. A method for preparing aromatic nitriles by oxidizing aromatic aldehydes according to claim 1, characterized in that: The temperature of the oxidation reaction is 60-80 °C, and the time of the oxidation reaction is 2-6 h.