Synthesis method of 2, 6-diethyl-4-methyl bromobenzene

Abstract

The invention relates to a synthetic method of 2, 6-diethyl-4-methyl bromobenzene, which specifically comprises the following steps: reacting 2, 6-diethyl-4-methylaniline hydrobromide with phosphorus pentoxide and alkyl nitrite in the presence of an organic solvent. According to the method disclosed by the invention, water in the system can be fully removed, the generation of hydrolysis side reaction is avoided, the content of phenol impurities is reduced, meanwhile, the bromination reaction balance can be shifted rightwards, the bromination reaction yield is improved, and the production cost is greatly reduced. In addition, an alkali washing impurity removal step in an existing post-treatment procedure is avoided, impurities can be fully removed through simplified operation, the discharge amount of three wastes is reduced, and industrial production is facilitated.

Description

Technical Field

[0001] This invention relates to the field of organic synthesis technology, specifically to a method for synthesizing 2,6-diethyl-4-methylbromobenzene. Background Technology

[0002] 2,6-Diethyl-4-methylbromobenzene is an important intermediate in the synthesis of the herbicide clodinafop-propargyl. Existing methods for its preparation all use 2,6-diethyl-4-methylaniline, hydrobromic acid, inorganic nitrites or nitrite esters as starting materials, followed by diazotization and bromination reactions. However, these reactions inevitably produce a series of impurities, such as 2,6-diethyl-4-methylphenol, as follows:

[0003]

[0004] 2,6-Diethyl-4-methylphenol is the main impurity, typically ranging from 3% to 10%, while other impurities total around 1%. The reaction system exhibits low atom utilization and difficulty in improving the reaction yield. Furthermore, the impurities and product have similar boiling points, making separation and purification challenging. The main impurity is caused by the hydrolysis of diazonium salts. The hydrolysis of diazonium salts is related to numerous factors, including reaction temperature, system pH, and brominating agent concentration. Therefore, it is necessary to reduce the formation of 2,6-diethyl-4-methylphenol to improve the purity of the target product and the reaction yield.

[0005] In the prior art, Chinese patent application CN116751106A uses a chemical method to react impurities in crude 2,6-diethyl-4-methylbromobenzene with sulfonyl chloride compounds to obtain sulfonate esters. The target product is then purified by vacuum distillation, yielding a high-purity product, but this does not improve the reaction yield, thus its economic efficiency needs improvement. Chinese patent application CN109134187A uses sodium nitrite as a reactant, adding additives, phase transfer catalysts, or moderately strong acids, and reacting in an aqueous acidic environment with pH < 7. This avoids the formation of ether impurities in the product; however, 3-5% phenol impurities still exist during the reaction, requiring removal by alkaline washing, which is not conducive to industrial production.

[0006] To solve the above technical problems, there is an urgent need for a method for synthesizing 2,6-diethyl-4-methylbromobenzene that can minimize the formation of 2,6-diethyl-4-methylphenol, improve atom utilization, product purity and reaction yield, reduce production costs, and be suitable for industrial production. Summary of the Invention

[0007] In view of this, the present invention provides a method for synthesizing 2,6-diethyl-4-methylbromobenzene, which can significantly reduce the generation of 2,6-diethyl-4-methylphenol, improve atom utilization, product purity and reaction yield, reduce production costs, and is suitable for industrial production.

[0008] This invention provides a method for synthesizing 2,6-diethyl-4-methylbromobenzene, specifically comprising the following steps:

[0009] 2,6-Diethyl-4-methylaniline hydrobromide was reacted with phosphorus pentoxide and alkyl nitrite in the presence of an organic solvent.

[0010] The alkyl nitrite is selected from one of n-amyl nitrite, isoamyl nitrite, n-butyl nitrite, and tert-butyl nitrite.

[0011] The organic solvent is selected from one or more of toluene, xylene, chlorobenzene, dichlorobenzene, dibromomethane, dichloroethane, and methylcyclohexyl. It is preferably o-dichlorobenzene.

[0012] In this process, the molar ratio of 2,6-diethyl-4-methylaniline hydrobromide to phosphorus pentoxide is 1:0.2 to 0.7, preferably 1:0.2 to 0.4.

[0013] In this embodiment, the molar ratio of 2,6-diethyl-4-methylaniline hydrobromide to alkyl nitrite is 1:1.0 to 1.5, preferably 1:1.0 to 1.2.

[0014] The reaction temperature is 35-60℃, preferably 45-55℃.

[0015] Further, the specific reaction steps include: controlling the system temperature at 35-60℃, adding phosphorus pentoxide to 2,6-diethyl-4-methylaniline hydrobromide, then adding isoamyl nitrite dropwise, and after the addition is complete, maintaining the temperature to react, to obtain 2,6-diethyl-4-methylbromobenzene.

[0016] Furthermore, the reaction also includes a post-treatment step: after the reaction is completed, the mixture is allowed to stand and separate into layers. The high-concentration wastewater in the lower layer and the phosphoric acid generated from the reaction of phosphorus pentoxide and water are separated and combined for wastewater treatment. The upper reaction solution is adjusted to pH 7-8, washed with water, and the organic phase is separated. The organic phase is evaporated to remove the solvent to obtain crude 2,6-diethyl-4-methylbromobenzene, which is then purified by distillation to obtain a high-purity product.

[0017] The reactant 2,6-diethyl-4-methylaniline hydrobromide can be prepared by conventional methods, referring to CN102603444A. 2,6-diethyl-4-methylaniline and o-dichlorobenzene are added to a sodium bromide solution, and 48% hydrobromic acid is added dropwise under controlled temperature. After the addition is complete, the temperature is controlled, and the mixture is refluxed under reduced pressure to separate the water.

[0018] The impurity 2,6-diethyl-4-methylphenol in this invention is an oily substance, which cannot be purified and separated by conventional methods such as recrystallization and pulping. Furthermore, 2,6-diethyl-4-methylphenol has a boiling point of 230°C, which is close to the boiling point of 2,6-diethyl-4-methylbromobenzene (259°C), making it difficult to remove by vacuum distillation. Existing methods typically use alkaline washing to remove phenol impurities, but these methods are cumbersome, generate large amounts of waste, and have high production costs.

[0019] The applicant discovered through research that the formation of the impurity 2,6-diethyl-4-methylphenol is caused by the hydrolysis of diazonium salts. Controlling the moisture content in the system to be as low as possible helps reduce phenol formation. Patent application CN102603444A can remove most of the moisture introduced by the acidic aqueous solution through azeotropic distillation, but it cannot completely remove it. This invention, by adding phosphorus pentoxide during the reaction process, can effectively control the moisture in the system, avoiding the formation of hydrolysis side reactions and reducing the phenol impurity content, as follows: P2O5 + 3H2O → 2H3PO4. Simultaneously, it can shift the bromination reaction equilibrium to the right, increasing the bromination yield and thus significantly reducing production costs. As a supplement, adding acetic anhydride during the reaction process can also achieve the same purpose.

[0020] Compared with the prior art, the present invention has the following beneficial technical effects:

[0021] 1. This invention, by adding phosphorus pentoxide during the reaction process, can effectively control the moisture in the system, avoiding the formation of hydrolysis side reactions. The phenol impurity content in the system is reduced from 5% to 0.5%, and the bromination reaction equilibrium is shifted to the right, increasing the bromination reaction yield from 84% to 89%. After comprehensive calculation, the production cost per batch can be reduced by 10-20%.

[0022] 2. The byproduct phosphoric acid generated by adding phosphorus pentoxide in this invention can be removed simply by adding alkali, avoiding the multiple alkali washing and impurity removal steps in the existing post-processing. By simplifying the operation, impurities can be fully removed, reducing the amount of waste emissions, which is beneficial to industrial production. Attached Figure Description

[0024] Figure 1 Product Analysis Chart of Embodiment 4 of the Invention

[0025] Figure 2 Comparative Example 1: Product Analysis Chart of this Invention Detailed Implementation

[0026] Example 1

[0027] Conditions: 1 eq of 2,6-diethyl-4-methylaniline, 0.1 eq of phosphorus pentoxide, 1.05 eq of n-amyl nitrite, system temperature at 45-50℃, and dropping time at 3.5-4h.

[0028] Specific implementation: 1000 kg of 2,6-diethyl-4-methylaniline (1 eq) and 3500 kg of o-dichlorobenzene were added to a reaction vessel, along with 30 kg of 30% sodium bromide solution. 1040 kg of 48% hydrobromic acid was added dropwise under controlled temperature. After the addition was complete, the mixture was refluxed under reduced pressure to separate the water. After reflux and water separation, 2,6-diethyl-4-methylaniline hydrobromide was obtained. The system temperature was controlled at 45-50℃. 87.0 kg of phosphorus pentoxide (0.1 eq) was added to the system, followed by dropwise addition of 753.4 kg of n-amyl nitrite (1.05 eq) over a time of 3.5-4 h. After the addition was complete, the reaction was maintained at this temperature for 0.5 h. The product purity was 90.8%, and the 2,6-diethyl-4-methylphenol content was 3.2%.

[0029] After the reaction was completed, the mixture was allowed to stand and separate into layers. The lower layer of highly concentrated bromine water was combined with the upper layer of refluxed aqueous phase and sent to wastewater treatment. The phosphoric acid produced by the reaction of phosphorus pentoxide and water was also separated into layers and sent to wastewater treatment. The pH of the upper reaction solution was adjusted to 7-8, washed with water, and the organic phase was separated. The solvent was removed from the organic phase to obtain a crude product, which was then purified by distillation to obtain 1242.8 kg of 2,6-diethyl-4-methylbromobenzene, with a reaction yield of 85.4%.

[0030] Example 2

[0031] Conditions: 1 eq of 2,6-diethyl-4-methylaniline, 0.2 eq of phosphorus pentoxide, 1.05 eq of n-pentyl nitrite, system temperature at 45-50℃, and dropping time at 3.5-4h.

[0032] Specific implementation: 1000 kg of 2,6-diethyl-4-methylaniline (1 eq) and 3500 kg of o-dichlorobenzene were added to the reaction vessel, along with 30 kg of 30% sodium bromide solution. 1040 kg of 48% hydrobromic acid was added dropwise under controlled temperature. After the addition was complete, the mixture was refluxed under reduced pressure to separate the water. After reflux and water separation, 2,6-diethyl-4-methylaniline hydrobromide was obtained. The system temperature was controlled at 45-50℃. 173.8 kg of phosphorus pentoxide (0.2 eq) was added to the system, followed by 753.4 kg of n-amyl nitrite (1.05 eq), with the addition time controlled at 3.5-4 h. After the addition was complete, the reaction was maintained at this temperature for 0.5 h. The product purity was 91.7%, and the 2,6-diethyl-4-methylphenol content was 0.9%.

[0033] After the reaction was completed, the mixture was allowed to stand and separate into layers. The lower layer of highly concentrated bromine water was combined with the upper layer of refluxed aqueous phase and sent to wastewater treatment. The phosphoric acid produced by the reaction of phosphorus pentoxide and water was also separated into layers and sent to wastewater treatment. The pH of the upper reaction solution was adjusted to 7-8, washed with water, and the organic phase was separated. The solvent was removed from the organic phase to obtain a crude product, which was then purified by distillation to obtain 1237.1 kg of 2,6-diethyl-4-methylbromobenzene, with a reaction yield of 86.7%.

[0034] Example 3

[0035] Conditions: 1 eq of 2,6-diethyl-4-methylaniline, 0.3 eq of phosphorus pentoxide, 1.05 eq of n-pentyl nitrite, system temperature at 45-50℃, and dropping time at 3.5-4h.

[0036] Specific implementation: 1000 kg of 2,6-diethyl-4-methylaniline (1 eq) and 3500 kg of o-dichlorobenzene were added to the reaction vessel, along with 30 kg of 30% sodium bromide solution. 1040 kg of 48% hydrobromic acid was added dropwise under controlled temperature. After the addition was complete, the mixture was refluxed under reduced pressure to separate the water. After reflux and water separation, 2,6-diethyl-4-methylaniline hydrobromide was obtained. The system temperature was controlled at 45-50℃. 260.8 kg of phosphorus pentoxide (0.3 eq) was added to the system, followed by 753.4 kg of n-amyl nitrite (1.05 eq), with the addition time controlled at 3.5-4 h. After the addition was complete, the reaction was maintained at this temperature for 0.5 h. The product purity was 92.0%, and the 2,6-diethyl-4-methylphenol content was 0.6%.

[0037] After the reaction was completed, the mixture was allowed to stand and separate into layers. The lower layer of highly concentrated bromine water was combined with the upper layer of refluxed aqueous phase and sent to wastewater treatment. The phosphoric acid produced by the reaction of phosphorus pentoxide and water was also separated into layers and sent to wastewater treatment. The pH of the upper reaction solution was adjusted to 7-8, washed with water, and the organic phase was separated. The solvent was removed from the organic phase to obtain a crude product, which was then purified by distillation to obtain 1250.0 kg of 2,6-diethyl-4-methylbromobenzene, with a reaction yield of 88.5%.

[0038] Example 4

[0039] Conditions: 1 eq of 2,6-diethyl-4-methylaniline, 0.4 eq of phosphorus pentoxide, 1.05 eq of n-pentyl nitrite, system temperature at 45-50℃, and dropping time at 3.5-4h.

[0040] Specific implementation: 1000 kg of 2,6-diethyl-4-methylaniline (1 eq) and 3500 kg of o-dichlorobenzene were added to the reaction vessel, along with 30 kg of 30% sodium bromide solution. 1040 kg of 48% hydrobromic acid was added dropwise under controlled temperature. After the addition was complete, the mixture was refluxed under reduced pressure to separate the water. After reflux and water separation, 2,6-diethyl-4-methylaniline hydrobromide was obtained. The system temperature was controlled at 45-50℃. 347.7 kg of phosphorus pentoxide (0.4 eq) was added to the system, followed by 753.4 kg of n-amyl nitrite (1.05 eq), with the addition time controlled at 3.5-4 h. After the addition was complete, the reaction was maintained at this temperature for 0.5 h. The product purity was 92.1%, and the 2,6-diethyl-4-methylphenol content was 0.5%.

[0041] After the reaction was completed, the mixture was allowed to stand and separate into layers. The lower layer of highly concentrated bromine water was combined with the upper layer of refluxed aqueous phase and sent to wastewater treatment. The phosphoric acid produced by the reaction of phosphorus pentoxide and water was also separated into layers and sent to wastewater treatment. The pH of the upper reaction solution was adjusted to 7-8, washed with water, and the organic phase was separated. The solvent was removed from the organic phase to obtain a crude product, which was then purified by distillation to obtain 1290.0 kg of 2,6-diethyl-4-methylbromobenzene, with a reaction yield of 91.8%.

[0042] Example 5

[0043] Conditions: 1 eq of 2,6-diethyl-4-methylaniline, 0.5 eq of phosphorus pentoxide, 1.05 eq of n-amyl nitrite, system temperature at 45-50℃, and dropping time at 3.5-4h.

[0044] Specific implementation: 1000 kg of 2,6-diethyl-4-methylaniline (1 eq) and 3500 kg of o-dichlorobenzene were added to the reaction vessel, along with 30 kg of 30% sodium bromide solution. 1040 kg of 48% hydrobromic acid was added dropwise under controlled temperature. After the addition was complete, the mixture was refluxed under reduced pressure to separate the water. After reflux and water separation, 2,6-diethyl-4-methylaniline hydrobromide was obtained. The system temperature was controlled at 45-50℃. 434.7 kg of phosphorus pentoxide (0.5 eq) was added to the system, followed by 753.4 kg of n-amyl nitrite (1.05 eq), with the addition time controlled at 3.5-4 h. After the addition was complete, the reaction was maintained at this temperature for 0.5 h. The product purity was 91.0%, and the 2,6-diethyl-4-methylphenol content was 1.1%.

[0045] After the reaction was completed, the mixture was allowed to stand and separate into layers. The lower layer of highly concentrated bromine water was combined with the upper layer of refluxed aqueous phase and sent to wastewater treatment. The phosphoric acid produced by the reaction of phosphorus pentoxide and water was also separated into layers and sent to wastewater treatment. The pH of the upper reaction solution was adjusted to 7-8, washed with water, and the organic phase was separated. The solvent was removed from the organic phase to obtain a crude product, which was then purified by distillation to obtain 1262.6 kg of 2,6-diethyl-4-methylbromobenzene, with a reaction yield of 89.3%.

[0046] Example 6

[0047] Conditions: 1 eq of 2,6-diethyl-4-methylaniline, 0.6 eq of phosphorus pentoxide, 1.05 eq of n-amyl nitrite, system temperature at 45-50℃, and dropping time at 3.5-4h.

[0048] Specific implementation: 1000 kg of 2,6-diethyl-4-methylaniline (1 eq) and 3500 kg of o-dichlorobenzene were added to the reaction vessel, along with 30 kg of 30% sodium bromide solution. 1040 kg of 48% hydrobromic acid was added dropwise under controlled temperature. After the addition was complete, the mixture was refluxed under reduced pressure to separate the water. After reflux and water separation, 2,6-diethyl-4-methylaniline hydrobromide was obtained. The system temperature was controlled at 45-50℃. 521.7 kg of phosphorus pentoxide (0.6 eq) was added to the system, followed by 753.4 kg of n-amyl nitrite (1.05 eq), with the addition time controlled at 3.5-4 h. After the addition was complete, the reaction was maintained at this temperature for 0.5 h. The product purity was 89.8%, and the 2,6-diethyl-4-methylphenol content was 2.3%.

[0049] After the reaction was completed, the mixture was allowed to stand and separate into layers. The lower layer of highly concentrated bromine water was combined with the upper layer of refluxed aqueous phase and sent to wastewater treatment. The phosphoric acid produced by the reaction of phosphorus pentoxide and water was separated into layers and combined with the refluxed aqueous phase and sent to wastewater treatment. The pH of the upper reaction solution was adjusted to 7-8, washed with water, and the organic phase was separated. The solvent was removed from the organic phase to obtain a crude product, which was then purified by distillation to obtain 1248.0 kg of 2,6-diethyl-4-methylbromobenzene, with a reaction yield of 86.3%.

[0050] Example 7

[0051] Conditions: 1 eq of 2,6-diethyl-4-methylaniline, 0.7 eq of phosphorus pentoxide, 1.05 eq of n-pentyl nitrite, system temperature at 45-50℃, and dropping time at 3.5-4h.

[0052] Specific implementation: 1000 kg of 2,6-diethyl-4-methylaniline (1 eq) and 3500 kg of o-dichlorobenzene were added to the reaction vessel, along with 30 kg of 30% sodium bromide solution. 1040 kg of 48% hydrobromic acid was added dropwise under controlled temperature. After the addition was complete, the mixture was refluxed under reduced pressure to separate the water. After reflux and water separation, 2,6-diethyl-4-methylaniline hydrobromide was obtained. The system temperature was controlled at 45-50℃. 575 kg of phosphorus pentoxide (0.7 eq) was added to the system, followed by 753.4 kg of n-amyl nitrite (1.05 eq), with the addition time controlled at 3.5-4 h. After the addition was complete, the reaction was maintained at this temperature for 0.5 h. The product purity was 87.2%, and the 2,6-diethyl-4-methylphenol content was 4.7%.

[0053] After the reaction was completed, the mixture was allowed to stand and separate into layers. The lower layer of highly concentrated bromine water was combined with the upper layer of refluxed aqueous phase and sent to wastewater treatment. The phosphoric acid produced by the reaction of phosphorus pentoxide and water was also separated into layers and sent to wastewater treatment. The pH of the upper reaction solution was adjusted to 7-8, washed with water, and the organic phase was separated. The solvent was removed from the organic phase to obtain a crude product, which was then purified by distillation to obtain 1248.0 kg of 2,6-diethyl-4-methylbromobenzene, with a reaction yield of 84.5%.

[0054] Example 8

[0055] Conditions: 1 eq of 2,6-diethyl-4-methylaniline, 0.4 eq of phosphorus pentoxide, 1 eq of n-pentyl nitrite, system temperature at 45-50℃, and dropping time at 3.5-4h.

[0056] Specific implementation: 1000 kg of 2,6-diethyl-4-methylaniline (1 eq) and 3500 kg of o-dichlorobenzene were added to the reaction vessel, along with 30 kg of 30% sodium bromide solution. 1040 kg of 48% hydrobromic acid was added dropwise under controlled temperature. After the addition was complete, the mixture was refluxed under reduced pressure to separate the water. After reflux and water separation, 2,6-diethyl-4-methylaniline hydrobromide was obtained. The system temperature was controlled at 45-50℃. 347.7 kg of phosphorus pentoxide (0.4 eq) was added to the system, followed by 717.5 kg of n-pentyl nitrite (1 eq), with the addition time controlled at 3.5-4 h. After the addition was complete, the reaction was maintained at this temperature for 0.5 h. The product purity was 91.7%, and the 2,6-diethyl-4-methylphenol content was 0.6%.

[0057] After the reaction was completed, the mixture was allowed to stand and separate into layers. The lower layer of highly concentrated bromine water was combined with the upper layer of refluxed aqueous phase and sent to wastewater treatment. The phosphoric acid produced by the reaction of phosphorus pentoxide and water was also separated into layers and sent to wastewater treatment. The pH of the upper reaction solution was adjusted to 7-8, washed with water, and the organic phase was separated. The solvent was removed from the organic phase to obtain a crude product, which was then purified by distillation to obtain 1213.6 kg of 2,6-diethyl-4-methylbromobenzene, with a reaction yield of 86.1%.

[0058] Example 9

[0059] Conditions: 1 eq of 2,6-diethyl-4-methylaniline, 0.4 eq of phosphorus pentoxide, 1.1 eq of n-amyl nitrite, system temperature at 45-50℃, and dropping time at 3.5-4h.

[0060] Specific implementation: 1000 kg of 2,6-diethyl-4-methylaniline (1 eq) and 3500 kg of o-dichlorobenzene were added to the reaction vessel, along with 30 kg of 30% sodium bromide solution. 1040 kg of 48% hydrobromic acid was added dropwise under controlled temperature. After the addition was complete, the mixture was refluxed under reduced pressure to separate the water. After reflux and water separation, 2,6-diethyl-4-methylaniline hydrobromide was obtained. The system temperature was controlled at 45-50℃. 347.7 kg of phosphorus pentoxide (0.4 eq) was added to the system, followed by 789.3 kg of n-pentyl nitrite (1.1 eq), with the addition time controlled at 3.5-4 h. After the addition was complete, the reaction was maintained at this temperature for 0.5 h. The product purity was 90.4%, and the 2,6-diethyl-4-methylphenol content was 0.9%.

[0061] After the reaction was completed, the mixture was allowed to stand and separate into layers. The lower layer of highly concentrated bromine water was combined with the upper layer of refluxed aqueous phase and sent to wastewater treatment. The phosphoric acid produced by the reaction of phosphorus pentoxide and water was separated into layers and combined with the refluxed aqueous phase and sent to wastewater treatment. The pH of the upper reaction solution was adjusted to 7-8, washed with water, and the organic phase was separated. The solvent was removed from the organic phase to obtain a crude product, which was then purified by distillation to obtain 1252.7 kg of 2,6-diethyl-4-methylbromobenzene, with a reaction yield of 88.6%.

[0062] Example 10

[0063] Conditions: 1 eq of 2,6-diethyl-4-methylaniline, 0.4 eq of phosphorus pentoxide, 1.2 eq of n-pentyl nitrite, system temperature at 45-50℃, and dropping time at 3.5-4h.

[0064] Specific implementation: 1000 kg of 2,6-diethyl-4-methylaniline (1 eq) and 3500 kg of o-dichlorobenzene were added to a reaction vessel, along with 30 kg of 30% sodium bromide solution. 1040 kg of 48% hydrobromic acid was added dropwise under controlled temperature. After the addition was complete, the mixture was refluxed under reduced pressure to separate the water. After reflux and water separation, 2,6-diethyl-4-methylaniline hydrobromide was obtained. The system temperature was controlled at 45-50℃. 347.7 kg of phosphorus pentoxide (0.4 eq) was added to the system, followed by 861.0 kg of n-amyl nitrite (1.2 eq), with the addition time controlled at 3.5-4 h. After the addition was complete, the reaction was maintained at this temperature for 0.5 h. The product purity was 89.5%, and the 2,6-diethyl-4-methylphenol content was 2.4%.

[0065] After the reaction was completed, the mixture was allowed to stand and separate into layers. The lower layer of highly concentrated bromine water was combined with the upper layer of refluxed aqueous phase and sent to wastewater treatment. The phosphoric acid produced by the reaction of phosphorus pentoxide and water was also separated into layers and sent to wastewater treatment. The pH of the upper reaction solution was adjusted to 7-8, washed with water, and the organic phase was separated. The solvent was removed from the organic phase to obtain a crude product, which was then purified by distillation to obtain 1260 kg of 2,6-diethyl-4-methylbromobenzene, with a reaction yield of 87.4%.

[0066] Example 11

[0067] Conditions: 1 eq of 2,6-diethyl-4-methylaniline, 0.4 eq of phosphorus pentoxide, 1.3 eq of n-amyl nitrite, system temperature at 45-50℃, and dropping time at 3.5-4h.

[0068] Specific implementation: 1000 kg of 2,6-diethyl-4-methylaniline (1 eq) and 3500 kg of o-dichlorobenzene were added to the reaction vessel, along with 30 kg of 30% sodium bromide solution. 1040 kg of 48% hydrobromic acid was added dropwise under controlled temperature. After the addition was complete, the mixture was refluxed under reduced pressure to separate the water. After reflux and water separation, 2,6-diethyl-4-methylaniline hydrobromide was obtained. The system temperature was controlled at 45-50℃. 347.7 kg of phosphorus pentoxide (0.4 eq) was added to the system, followed by 932.8 kg of n-pentyl nitrite (1.3 eq), with the addition time controlled at 3.5-4 h. After the addition was complete, the reaction was maintained at this temperature for 0.5 h. The product purity was 88.5%, and the 2,6-diethyl-4-methylphenol content was 3.4%.

[0069] After the reaction was completed, the mixture was allowed to stand and separate into layers. The lower layer of highly concentrated bromine water was combined with the upper layer of refluxed aqueous phase and sent to wastewater treatment. The phosphoric acid produced by the reaction of phosphorus pentoxide and water was also separated into layers and sent to wastewater treatment. The pH of the upper reaction solution was adjusted to 7-8, washed with water, and the organic phase was separated. The solvent was removed from the organic phase to obtain a crude product, which was then purified by distillation to obtain 1258.7 kg of 2,6-diethyl-4-methylbromobenzene, with a reaction yield of 86.4%.

[0070] Example 12

[0071] Conditions: 1 eq of 2,6-diethyl-4-methylaniline, 0.4 eq of phosphorus pentoxide, 1.4 eq of n-amyl nitrite, system temperature at 45-50℃, and dropping time at 3.5-4h.

[0072] Specific implementation: 1000 kg of 2,6-diethyl-4-methylaniline (1 eq) and 3500 kg of o-dichlorobenzene were added to the reaction vessel, along with 30 kg of 30% sodium bromide solution. 1040 kg of 48% hydrobromic acid was added dropwise under controlled temperature. After the addition was complete, the mixture was refluxed under reduced pressure to separate the water. After reflux and water separation, 2,6-diethyl-4-methylaniline hydrobromide was obtained. The system temperature was controlled at 45-50℃. 347.7 kg of phosphorus pentoxide (0.4 eq) was added to the system, followed by 1004.5 kg of n-amyl nitrite (1.4 eq), with the addition time controlled at 3.5-4 h. After the addition was complete, the reaction was maintained at this temperature for 0.5 h. The product purity was 87.0%, and the 2,6-diethyl-4-methylphenol content was 4.8%.

[0073] After the reaction was completed, the mixture was allowed to stand and separate into layers. The lower layer of highly concentrated bromine water was combined with the upper layer of refluxed aqueous phase and sent to wastewater treatment. The phosphoric acid produced by the reaction of phosphorus pentoxide and water was also separated into layers and sent to wastewater treatment. The pH of the upper reaction solution was adjusted to 7-8, washed with water, and the organic phase was separated. The solvent was removed from the organic phase to obtain a crude product, which was then purified by distillation to obtain 1252.1 kg of 2,6-diethyl-4-methylbromobenzene, with a reaction yield of 84.6%.

[0074] Example 13

[0075] Conditions: 1 eq of 2,6-diethyl-4-methylaniline, 0.4 eq of phosphorus pentoxide, 1.05 eq of n-amyl nitrite, system temperature at 35-40℃, and dropping time at 3.5-4h.

[0076] Specific implementation: 1000 kg of 2,6-diethyl-4-methylaniline (1 eq) and 3500 kg of o-dichlorobenzene were added to the reaction vessel, along with 30 kg of 30% sodium bromide solution. 1040 kg of 48% hydrobromic acid was added dropwise under controlled temperature. After the addition was complete, the mixture was refluxed under reduced pressure to separate the water. After reflux and water separation, 2,6-diethyl-4-methylaniline hydrobromide was obtained. The system temperature was controlled at 35-40℃. 347.7 kg of phosphorus pentoxide (0.4 eq) was added to the system, followed by 753.4 kg of n-amyl nitrite (1.05 eq), with the addition time controlled at 3.5-4 h. After the addition was complete, the reaction was maintained at this temperature for 0.5 h. The product purity was 88.1%, and the 2,6-diethyl-4-methylphenol content was 4.3%.

[0077] After the reaction was completed, the mixture was allowed to stand and separate into layers. The lower layer of highly concentrated bromine water was combined with the upper layer of refluxed aqueous phase and sent to wastewater treatment. The phosphoric acid produced by the reaction of phosphorus pentoxide and water was also separated into layers and sent to wastewater treatment. The pH of the upper reaction solution was adjusted to 7-8, washed with water, and the organic phase was separated. The solvent was removed from the organic phase to obtain a crude product, which was then purified by distillation to obtain 1217.1 kg of 2,6-diethyl-4-methylbromobenzene, with a reaction yield of 83.2%.

[0078] Example 14

[0079] Conditions: 1 eq of 2,6-diethyl-4-methylaniline, 0.4 eq of phosphorus pentoxide, 1.05 eq of n-pentyl nitrite, system temperature at 40-45℃, and dropping time at 3.5-4h.

[0080] Specific implementation: 1000 kg of 2,6-diethyl-4-methylaniline (1 eq) and 3500 kg of o-dichlorobenzene were added to the reaction vessel, along with 30 kg of 30% sodium bromide solution. 1040 kg of 48% hydrobromic acid was added dropwise under controlled temperature. After the addition was complete, the mixture was refluxed under reduced pressure to separate the water. After reflux and water separation, 2,6-diethyl-4-methylaniline hydrobromide was obtained. The system temperature was controlled at 40-45℃. 347.7 kg of phosphorus pentoxide (0.4 eq) was added to the system, followed by 753.4 kg of n-amyl nitrite (1.05 eq), with the addition time controlled at 3.5-4 h. After the addition was complete, the reaction was maintained at this temperature for 0.5 h. The product purity was 89.1%, and the 2,6-diethyl-4-methylphenol content was 2.3%.

[0081] After the reaction was completed, the mixture was allowed to stand and separate into layers. The lower layer of highly concentrated bromine water was combined with the upper layer of refluxed aqueous phase and sent to wastewater treatment. The phosphoric acid produced by the reaction of phosphorus pentoxide and water was also separated into layers and sent to wastewater treatment. The pH of the upper reaction solution was adjusted to 7-8, washed with water, and the organic phase was separated. The solvent was removed from the organic phase to obtain a crude product, which was then purified by distillation to obtain 1235.1 kg of 2,6-diethyl-4-methylbromobenzene, with a reaction yield of 86.2%.

[0082] Example 15

[0083] Conditions: 1 eq of 2,6-diethyl-4-methylaniline, 0.4 eq of phosphorus pentoxide, 1.05 eq of n-amyl nitrite, system temperature at 50-55℃, and dropping time at 3.5-4h.

[0084] Specific implementation: 1000 kg of 2,6-diethyl-4-methylaniline (1 eq) and 3500 kg of o-dichlorobenzene were added to a reaction vessel, along with 30 kg of 30% sodium bromide solution. 1040 kg of 48% hydrobromic acid was added dropwise under controlled temperature. After the addition was complete, the mixture was refluxed under reduced pressure to separate the water. After reflux and water separation, 2,6-diethyl-4-methylaniline hydrobromide was obtained. The system temperature was controlled at 50-55℃. 347.7 kg of phosphorus pentoxide (0.4 eq) was added to the system, followed by 753.4 kg of n-amyl nitrite (1.05 eq), with the addition time controlled at 3.5-4 h. After the addition was complete, the reaction was maintained at this temperature for 0.5 h. The product purity was 91.2%, and the 2,6-diethyl-4-methylphenol content was 1.7%.

[0085] After the reaction was completed, the mixture was allowed to stand and separate into layers. The lower layer of highly concentrated bromine water was combined with the upper layer of refluxed aqueous phase and sent to wastewater treatment. The phosphoric acid produced by the reaction of phosphorus pentoxide and water was also separated into layers and sent to wastewater treatment. The pH of the upper reaction solution was adjusted to 7-8, washed with water, and the organic phase was separated. The solvent was removed from the organic phase to obtain a crude product, which was then purified by distillation to obtain 1262.4 kg of 2,6-diethyl-4-methylbromobenzene, with a reaction yield of 88.2%.

[0086] Example 16

[0087] Conditions: 1 eq of 2,6-diethyl-4-methylaniline, 0.4 eq of phosphorus pentoxide, 1.05 eq of n-pentyl nitrite, system temperature at 55-60℃, and dropping time at 3.5-4h.

[0088] Specific implementation: 1000 kg of 2,6-diethyl-4-methylaniline (1 eq) and 3500 kg of o-dichlorobenzene were added to the reaction vessel, along with 30 kg of 30% sodium bromide solution. 1040 kg of 48% hydrobromic acid was added dropwise under controlled temperature. After the addition was complete, the mixture was refluxed under reduced pressure to separate the water. After reflux and water separation, 2,6-diethyl-4-methylaniline hydrobromide was obtained. The system temperature was controlled at 55-60℃. 347.7 kg of phosphorus pentoxide (0.4 eq) was added to the system, followed by 753.4 kg of n-amyl nitrite (1.05 eq), with the addition time controlled at 3.5-4 h. After the addition was complete, the reaction was maintained at this temperature for 0.5 h. The product purity was 89.3%, and the 2,6-diethyl-4-methylphenol content was 2.7%.

[0089] After the reaction was completed, the mixture was allowed to stand and separate into layers. The lower layer of highly concentrated bromine water was combined with the upper layer of refluxed aqueous phase and sent to wastewater treatment. The phosphoric acid produced by the reaction of phosphorus pentoxide and water was also separated into layers and sent to wastewater treatment. The pH of the upper reaction solution was adjusted to 7-8, washed with water, and the organic phase was separated. The solvent was removed from the organic phase to obtain a crude product, which was then purified by distillation to obtain 1265.2 kg of 2,6-diethyl-4-methylbromobenzene, with a reaction yield of 87.3%.

[0090] Example 17

[0091] Conditions: 1 eq of 2,6-diethyl-4-methylaniline, 0.4 eq of phosphorus pentoxide, 1.05 eq of n-amyl nitrite, system temperature at 60-65℃, and dropping time at 3.5-4h.

[0092] Specific implementation: 1000 kg of 2,6-diethyl-4-methylaniline (1 eq) and 3500 kg of o-dichlorobenzene were added to the reaction vessel, along with 30 kg of 30% sodium bromide solution. 1040 kg of 48% hydrobromic acid was added dropwise under controlled temperature. After the addition was complete, the mixture was refluxed under reduced pressure to separate the water. After reflux and water separation, 2,6-diethyl-4-methylaniline hydrobromide was obtained. The system temperature was controlled at 60-65℃. 347.7 kg of phosphorus pentoxide (0.4 eq) was added to the system, followed by 753.4 kg of n-amyl nitrite (1.05 eq), with the addition time controlled at 3.5-4 h. After the addition was complete, the reaction was maintained at this temperature for 0.5 h. The product purity was 88.4%, and the 2,6-diethyl-4-methylphenol content was 4.0%.

[0093] After the reaction was completed, the mixture was allowed to stand and separate into layers. The lower layer of highly concentrated bromine water was combined with the upper layer of refluxed aqueous phase and sent to wastewater treatment. The phosphoric acid produced by the reaction of phosphorus pentoxide and water was also separated into layers and sent to wastewater treatment. The pH of the upper reaction solution was adjusted to 7-8, washed with water, and the organic phase was separated. The solvent was removed from the organic phase to obtain a crude product, which was then purified by distillation to obtain 1261.5 kg of 2,6-diethyl-4-methylbromobenzene, with a reaction yield of 85.6%.

[0094] Example 18

[0095] Conditions: 1 eq of 2,6-diethyl-4-methylaniline, 1.05 eq of n-pentyl nitrite, system temperature of 35-60℃, dropping time of 3.5-4h, batch feeding.

[0096] Specific implementation: Add 1000 kg of 2,6-diethyl-4-methylaniline (1 eq), 3500 kg of o-dichlorobenzene, and 30 kg of 30% sodium bromide solution to the reaction vessel, and add 1040 kg of solution dropwise under controlled temperature. The reaction was carried out with 48% hydrobromic acid. After the addition was complete, the temperature was controlled, and the mixture was refluxed under reduced pressure to separate the water. After the water separation was completed, 2,6-diethyl-4-methylaniline hydrobromide was obtained. The system temperature was controlled at 50-55℃, and 250 kg of n-pentyl nitrite (0.35 eq) was added dropwise. Then, 110 kg of phosphorus pentoxide (0.13 eq) was added to the system, and the mixture was stirred for 0.5 hours. The addition of 250 kg of n-pentyl nitrite (0.35 eq) and 110 kg of phosphorus pentoxide (0.13 eq) was repeated for 0.5 hours. The product purity was 88.7%, and the 2,6-diethyl-4-methylphenol content was 3.6%.

[0097] After the reaction was completed, the mixture was allowed to stand and separate into layers. The lower layer of highly concentrated bromine water was combined with the upper layer of refluxed aqueous phase and sent to wastewater treatment. The phosphoric acid produced by the reaction of phosphorus pentoxide and water was also separated into layers and sent to wastewater treatment. The pH of the upper reaction solution was adjusted to 7-8, washed with water, and the organic phase was separated. The solvent was removed from the organic phase to obtain a crude product, which was then purified by distillation to obtain 1257.5 kg of 2,6-diethyl-4-methylbromobenzene, with a reaction yield of 86.5%.

[0098] Comparative Example 1

[0099] Conditions: 1 eq of 2,6-diethyl-4-methylaniline, 1.05 eq of n-pentyl nitrite, system temperature at 35-60℃, dropping time at 3.5-4 h, and no phosphorus pentoxide added.

[0100] 1000 kg of 2,6-diethyl-4-methylaniline (1 eq) and 3500 kg of o-dichlorobenzene were added to a reaction vessel, followed by 30 kg of 30% sodium bromide solution. 1040 kg of 48% hydrobromic acid was then added dropwise under controlled temperature. After the addition was complete, the mixture was refluxed under reduced pressure to separate the water. After water separation, 2,6-diethyl-4-methylaniline hydrobromide was obtained. The system temperature was controlled at 35-60℃, and then 753.4 kg of n-pentyl nitrite (1.05 eq) was added dropwise over 3.5-4 hours. After the addition was complete, the reaction was maintained at this temperature for 0.5 hours. The product purity was 87.7%, and the 2,6-diethyl-4-methylphenol content was 5.5%.

[0101] After the reaction was completed, the mixture was allowed to stand and separate into layers. The lower layer of highly concentrated bromine water was combined with the upper layer of refluxed aqueous phase and sent to wastewater treatment. The pH of the upper reaction solution was adjusted to 7-8, washed with water, and the organic phase was separated. The organic phase was evaporated to remove the solvent, yielding a crude product. After distillation, 1248.8 kg of 2,6-diethyl-4-methylbromobenzene was obtained, with a reaction yield of 84.2%.

[0102] Comparative Example 2

[0103] Conditions: 1 eq of 2,6-diethyl-4-methylaniline, 0.4 eq of phosphorus pentoxide, 1.05 eq of n-pentyl nitrite, system temperature at 45-50℃, dropping time at 3.5-4 h, and phosphorus pentoxide added after the dropping is completed.

[0104] Specific implementation: 1000 kg of 2,6-diethyl-4-methylaniline (1 eq) and 3500 kg of o-dichlorobenzene were added to a reaction vessel, along with 30 kg of 30% sodium bromide solution. 1040 kg of 48% hydrobromic acid was added dropwise under controlled temperature. After the addition was complete, the mixture was refluxed under reduced pressure to separate the water. After reflux and water separation, 2,6-diethyl-4-methylaniline hydrobromide was obtained. The system temperature was controlled at 50-55℃, and 753.4 kg of n-pentyl nitrite (1.05 eq) was added dropwise. The reaction was maintained at this temperature for 0.5 h. Then, 330 kg of phosphorus pentoxide (0.4 eq) was added to the system, and the mixture was stirred for 2 hours. The product purity was 85.1%, and the 2,6-diethyl-4-methylphenol content was 6.1%.

[0105] After the reaction was completed, the mixture was allowed to stand and separate into layers. The lower layer of highly concentrated bromine water was combined with the upper layer of refluxed aqueous phase and sent to wastewater treatment. The phosphoric acid produced by the reaction of phosphorus pentoxide and water was also separated into layers and sent to wastewater treatment. The pH of the upper reaction solution was adjusted to 7-8, washed with water, and the organic phase was separated. The solvent was removed from the organic phase to obtain a crude product, which was then purified by distillation to obtain 1210.4 kg of 2,6-diethyl-4-methylbromobenzene, with a reaction yield of 81.0%.

[0106] The above description is only a preferred embodiment of the present invention and is not intended to limit the present invention. Any modifications, equivalent substitutions, improvements, etc., made within the spirit and principles of the present invention should be included within the scope of protection of the present invention.

Claims

1. A method for synthesizing 2,6-diethyl-4-methylbromobenzene, characterized in that, Specifically, the following steps are included: 2,6-Diethyl-4-methylaniline hydrobromide was reacted with phosphorus pentoxide and alkyl nitrite in the presence of an organic solvent.

2. The synthesis method according to claim 1, characterized in that, The alkyl nitrite is selected from one of n-amyl nitrite, isoamyl nitrite, n-butyl nitrite, and tert-butyl nitrite.

3. The synthesis method according to claim 1, characterized in that, The organic solvent is selected from one or more of toluene, xylene, chlorobenzene, dichlorobenzene, dibromomethane, dichloroethane, and methylcyclohexyl.

4. The synthesis method according to claim 1, characterized in that, The ratio of 2,6-diethyl-4-methylaniline hydrobromide to phosphorus pentoxide, calculated by molar amount, is 1:0.2 to 0.7, preferably 1:0.2 to 0.

4.

5. The synthesis method according to claim 1, characterized in that, The ratio of 2,6-diethyl-4-methylaniline hydrobromide to alkyl nitrite, calculated by molar amount, is 1:1.0 to 1.5, preferably 1:1.0 to 1.

2.

6. The synthesis method according to claims 1-5, characterized in that, The reaction temperature of the method is 35-60℃.

7. The synthesis method according to claims 1-5, characterized in that, The specific steps of the method include: controlling the system temperature at 35-60℃, adding phosphorus pentoxide to 2,6-diethyl-4-methylaniline hydrobromide, then adding isoamyl nitrite dropwise, and after the addition is complete, maintaining the temperature for reaction to obtain 2,6-diethyl-4-methylbromobenzene.

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