Synthesis method of tert-butyl isocyanate

Abstract

The invention belongs to the technical field of organic synthesis, and particularly relates to a synthesis method of tert-butyl isocyanate. The synthesis method comprises the following steps: adding a composite catalyst, a cosolvent, cyanate and a stabilizer into a diester solvent, uniformly stirring, and heating to a reaction temperature; dropwise adding tert-butyl chloride at the reaction temperature, and after dropwise adding is completed, carrying out heat preservation reaction at the temperature; and after the reaction is finished, carrying out reduced pressure distillation and rectification to obtain the tert-butyl isocyanate. The bottleneck of the traditional process is broken through, the reaction period is effectively shortened, and the energy consumption is reduced; the product purity and the total yield are improved and are far superior to those in the prior art. In addition, the preparation process has the advantages of mild conditions, no need of special equipment, cheap and easily available raw materials, abandonment of highly toxic raw materials, no generation of a large amount of waste salt and toxic gas, safety and environmental protection.

Description

Technical Field

[0001] This invention belongs to the field of organic synthesis technology, specifically relating to a method for synthesizing tert-butyl isocyanate. Background Technology

[0002] The chemical structure of tert-butyl isocyanate is shown in formula (I). It is an important pharmaceutical and pesticide intermediate with wide application value in the field of fine chemicals, especially in pesticide production. The optimization and innovation of its preparation process has an important impact on the development of related industries.

[0003] Formula (I).

[0004] Currently, the existing methods for preparing tert-butyl isocyanate are mainly divided into two categories: one is to react tert-butylamine as a raw material with phosgene or phosgene-like substances, and the other is to react tert-butyl chloride as a raw material with sodium cyanate. However, both of these methods have many technical defects and are difficult to meet the actual needs of large-scale industrial production.

[0005] In the preparation route using tert-butylamine as a raw material, relevant patent literature reports various specific preparation processes, but all have significant shortcomings. For example, CN107935889 discloses a method for preparing tert-butyl isocyanate by reacting tert-butylamine with phosgene. This method uses highly toxic phosgene as a reactant, posing extremely high safety risks. Furthermore, the reaction must be carried out at a high temperature of 335–345°C, with stringent reaction conditions. This places extremely stringent requirements on the high-temperature resistance, corrosion resistance, and sealing of production equipment, significantly increasing production input and safety control difficulties, making it unsuitable for industrial-scale production. US2009176847 discloses a process for preparing tert-butyl isocyanate using tert-butylamine and triphosgene as raw materials. To reduce the pyrolysis temperature, triethylamine is added as an acid-binding agent in this process; however, the reaction yield is low, and a large amount of waste salt is generated during the reaction, leading to high production costs and contradicting the current industrial concepts of clean production and green environmental protection, thus limiting its industrial application prospects. In addition, CN108395383 discloses a process for preparing tert-butyl isocyanate by using tert-butylamine as a starting material, dropping it into a p-toluenesulfonamide solution that has been purged with phosgene, and then reacting it under reflux. This process requires the preparation of p-toluenesulfonamide isocyanate first, and then obtaining the target product through urea cleavage. However, it suffers from problems such as low raw material conversion rate and difficulty in completely carrying out the urea cleavage reaction, resulting in serious waste of raw materials and a significant increase in production costs.

[0006] In the preparation route using tert-butane chloride as a raw material and reacting with sodium cyanate, related patents also suffer from numerous technical bottlenecks. For example, CN106543036 discloses a preparation process using ethylene glycol ethyl ether acetate as a reaction solvent and zinc chloride as a catalyst, but it suffers from low reaction efficiency: the process of heating the reaction to 85°C is slow, the total reaction time is as long as 8–10 hours, and the yield of the target product is low, with the reported crude product yield being only 75%–82%, resulting in low production efficiency and high production costs. Furthermore, this process uses a large amount of sodium cyanate, and excess cyanate needs to be treated, further increasing the operational complexity in industrial production and hindering large-scale continuous production. CN119954686 also reports a similar route, which similarly fails to solve the core problems of long reaction cycles, low yields, and complex operations.

[0007] In summary, existing methods for preparing tert-butyl isocyanate generally suffer from problems such as harsh reaction conditions, excessive equipment requirements, low reaction yield, low production efficiency, high production costs, high safety risks, or poor environmental performance, making them difficult to adapt to the actual needs of large-scale industrial production.

[0008] Therefore, developing a new process for preparing tert-butyl isocyanate that is simple and feasible, has abundant and inexpensive raw material supply, mild reaction conditions, high yield and purity of the target product, and is environmentally friendly is of great significance for promoting the upgrading and development of related pharmaceutical and pesticide industries, reducing production energy consumption and costs, and improving production safety and environmental protection. It is a technical problem that urgently needs to be solved. Summary of the Invention

[0009] Based on the above technical background, the main objective of this invention is to provide a method for synthesizing tert-butyl isocyanate to overcome the shortcomings of the prior art.

[0010] To achieve the aforementioned objectives, the technical solution adopted by this invention includes: This invention provides a method for synthesizing tert-butyl isocyanate, the method comprising the following steps: Step 1: Add the composite catalyst, co-solvent, cyanate, and stabilizer to the diester solvent, stir until homogeneous, and heat to the reaction temperature; Step 2: Add tert-chlorobutane dropwise at the reaction temperature. After the addition is complete, maintain the temperature at the same level for the reaction. Step 3: After the reaction is complete, the crude product is distilled under reduced pressure to obtain tert-butyl isocyanate.

[0011] The steps described above are described in detail below.

[0012] In step 1, the diester solvent is selected from one or more of diethyl oxalate, dipropyl oxalate, dibutyl oxalate, ethylene glycol diacetate, ethylene glycol dipropionate, ethylene glycol diisobutyrate, propylene glycol diacetate, propylene glycol dipropionate, and propylene glycol diisobutyrate.

[0013] The diester solvents used are all polar aprotic solvents, which can form coordination compounds with the main catalyst, zinc chloride. With a small amount of co-solvent, zinc chloride can be completely dissolved in the solvent, which is beneficial for improving the catalytic activity of zinc ions. The biggest technical challenge of this reaction is the difficulty in removing chloride ions from tert-butane. This invention, through the addition of a composite catalyst, makes it easier to separate the chloride ions of tert-butane, forming tert-butyl cations. The resulting cyanate ions attack the tert-butyl cations to obtain tert-butyl isocyanate, greatly accelerating the reaction rate, shortening the reaction time, and improving production efficiency. Furthermore, lowering the reaction temperature can effectively reduce energy consumption.

[0014] Furthermore, the solvent used in this invention is low-cost, significantly reducing preparation costs. Using the solvent described in this invention reduces the amount of cyanate and catalyst required, achieving high yields and purity even with minimal use of cyanate and catalyst. This invention uses less cyanate and catalyst, resulting in less waste and aligning with the principles of clean production.

[0015] Preferably, the diester solvent is ethylene glycol diacetate.

[0016] The composite catalyst includes a main catalyst and a co-catalyst, wherein the main catalyst is zinc chloride and the co-catalyst is 4-dimethylaminopyridine.

[0017] The mass ratio of the main catalyst to the co-catalyst is 20.5:(0-4.1).

[0018] Preferably, the mass ratio of the main catalyst to the co-catalyst is 20.5:3.2.

[0019] The co-solvent is selected from one or more of N,N-dimethylformamide, sulfolane, tetrahydrofuran, and 1,4-dioxane.

[0020] Preferably, the co-solvent is sulfolane.

[0021] The cyanate is selected from one or more of sodium cyanate, potassium cyanate, and calcium cyanate.

[0022] Preferably, the cyanate is sodium cyanate.

[0023] The stabilizer is selected from one or both of magnesium chloride and magnesium sulfate.

[0024] Preferably, the stabilizer is magnesium chloride.

[0025] The stabilizers used in this invention are readily available and inexpensive. They can work synergistically with the composite catalyst, cosolvent, and cyanate to effectively prevent product decomposition and greatly improve reaction yield and product purity.

[0026] The mass ratio of the composite catalyst, co-solvent, cyanate, stabilizer and diester solvent is (20-31):(0-2.4):(73-80):(0-3):140.

[0027] Preferably, the mass ratio of the composite catalyst, co-solvent, cyanate, stabilizer and diester solvent is (23.4-30.5):2.1:(73.4-76.9):(2.1-2.7):140.

[0028] More preferably, the mass ratio of the composite catalyst, co-solvent, cyanate, stabilizer and diester solvent is 30.5:2.1:76.9:2.7:140.

[0029] In step 2, the molar ratio of cyanate to tert-butane chloride is (1.0-1.5):1.

[0030] Preferably, the molar ratio of the cyanate to tert-butane chloride is 1.05:1.

[0031] The reaction equation for this reaction is shown below: .

[0032] The reaction temperature is 30–75°C. After the addition is complete, the reaction is maintained at this temperature for 1–2.5 h.

[0033] Preferably, the reaction temperature is 45-50°C, and after the addition is complete, the reaction is maintained at this temperature for 2 hours.

[0034] In step 3, the transition fraction obtained by distillation can be reused in the next batch and distilled together with the crude product obtained by vacuum distillation.

[0035] The beneficial effects of this invention are as follows: (1) This invention creatively uses a composite catalytic system, which is combined with a diester solvent, a co-solvent, and a stabilizer to construct the reaction system. The combination of the composite catalyst and the diester solvent can effectively improve the reaction efficiency and reduce energy consumption; the synergistic effect of the composite catalyst and the stabilizer can suppress side reactions such as isobutylene formation, improve reaction selectivity, and increase product purity.

[0036] (2) In the composite catalyst of the present invention, the diester solvent can form a coordination compound with the main catalyst zinc chloride, thereby enhancing the catalytic activity. The co-catalyst 4-dimethylaminopyridine synergistically activates the substrate, which can significantly reduce the activation energy of the reaction, increase the reaction rate, and reduce energy consumption. Compared with the traditional single catalytic process, the present invention, by adding a composite catalyst, shortens the reaction cycle from 8-10h to 2-3h (reducing the reaction time by more than 60%), reduces the reaction temperature from 85℃ to 30-75℃, and significantly reduces energy consumption.

[0037] (3) The reaction conditions described in this invention are mild and do not require high-temperature and high-pressure equipment. Production can be carried out using conventional chemical equipment, which effectively reduces equipment investment and maintenance costs. At the same time, by strictly limiting the molar ratio of cyanate to tert-butane chloride, the complicated operation of using excess cyanate can be avoided, simplifying the preparation process.

[0038] (4) By precisely matching multiple systems of composite catalyst, cosolvent, cyanate, stabilizer and diester solvent, and strictly limiting the proportion of each substance, the present invention can achieve a product purity of 99.3% to 99.6% and a total yield of 93.2% to 96.0%. The transition fraction produced by distillation can be recycled and reused, further improving the resource utilization rate.

[0039] (5) The preparation method described in this invention eliminates highly toxic phosgene and phosgene-like raw materials, thereby eliminating safety hazards at the source and reducing the difficulty of control. The reaction process does not generate a large amount of toxic gases (such as isobutylene) or waste salts, the waste treatment is simple, the pollution load is low, and it meets the requirements of clean production.

[0040] (6) The preparation method described in this invention is simple to operate, the process is simple and controllable, the reaction conditions are mild, there are few impurities, the yield is high, the product and solvent are easy to separate, the product purity is high, which is conducive to continuous industrial production, and significantly reduces production costs and environmental protection costs, increases product added value, provides an efficient new route for the synthesis of tert-butyl isocyanate, which is of great significance to the upgrading of the pharmaceutical and pesticide industries and has broad application prospects. Detailed Implementation

[0041] The present invention will now be described in detail, and its features and advantages will become clearer and more apparent from these descriptions.

[0042] Example The present invention is further illustrated below with specific examples. These embodiments are merely illustrative and not intended to limit the scope of the invention. All raw materials used in the embodiments of the present invention are commercially available.

[0043] Example 1 140 g of ethylene glycol diacetate was added to a four-necked flask, and stirring was started. Then, 20.5 g (0.15 mol) of zinc chloride, 3.4 g of 4-dimethylaminopyridine, 2.1 g of sulfolane, 73.4 g (1.05 mol) of sodium cyanate, and 2.1 g of magnesium chloride were added. After the addition was complete, the temperature was raised to 45–50 °C. Maintaining the temperature at 45–50 °C, 93.4 g (1.0 mol) of tert-butane chloride was added dropwise. After the addition was complete, stirring was continued for 2 h. After the reaction was complete, the mixture was distilled under reduced pressure to obtain 128.3 g of crude product. Further distillation of the crude product yielded 90.2 g of tert-butyl isocyanate with a purity of 99.5% and a yield of 90.5%. A transition fraction of 13.2 g, after gas phase analysis, showed a tert-butyl isocyanate content of 38.3%. This transition fraction could be reused in the next batch of distillation. The overall yield was 95.6%.

[0044] Example 2 140 g of ethylene glycol diacetate was added to a four-necked flask, and stirring was started. Then, 20.5 g (0.15 mol) of zinc chloride, 2.9 g of 4-dimethylaminopyridine, 2.1 g of sulfolane, 73.4 g (1.05 mol) of sodium cyanate, and 2.1 g of magnesium chloride were added. After the addition was complete, the temperature was raised to 45–50 °C. The temperature was maintained at 45–50 °C, and 93.4 g (1.0 mol) of tert-butane chloride was added dropwise. After the addition was complete, the mixture was kept at this temperature and stirred for 2 h. After the reaction was complete, the mixture was distilled under reduced pressure to obtain 132.2 g of crude product. The crude product and the transition fraction obtained in Example 1 were combined and then distilled to obtain 95.0 g of tert-butyl isocyanate with a purity of 99.3% and a yield of 90.1% (excluding the reused crude product). The transition fraction, 15.8 g, showed a tert-butyl isocyanate content of 30.7% after gas phase analysis. This transition fraction can be reused in the next batch of distillation. The overall yield was 95.0%. Example 3 140 g of ethylene glycol diacetate was added to a four-necked flask, and stirring was started. Then, 20.5 g (0.15 mol) of zinc chloride, 2.9 g of 4-dimethylaminopyridine, 2.1 g of sulfolane, 76.9 g (1.1 mol) of sodium cyanate, and 2.1 g of magnesium chloride were added. After the addition was complete, the temperature was raised to 45–50 °C. Maintaining the temperature at 45–50 °C, 93.4 g (1.0 mol) of tert-butane chloride was added dropwise. After the addition was complete, stirring was continued for 2 hours. After the reaction was complete, the mixture was distilled under reduced pressure to obtain 126.6 g of crude product. The crude product and the transition fraction obtained in Example 2 were combined and then distilled to obtain 93.1 g of tert-butyl isocyanate with a purity of 99.3% and a yield of 88.4% (excluding the reused crude product). The transition fraction, 15.2 g, showed a tert-butyl isocyanate content of 31.3% after gas phase analysis. This transition fraction can be reused in the next batch of distillation. The overall yield was 93.2%. Example 4 140 g of ethylene glycol diacetate was added to a four-necked flask, and stirring was started. Then, 27.3 g (0.2 mol) of zinc chloride, 3.2 g of 4-dimethylaminopyridine, 2.1 g of sulfolane, 76.9 g (1.1 mol) of sodium cyanate, and 2.7 g of magnesium chloride were added. After the addition was complete, the temperature was raised to 50–55 °C. Maintaining the temperature at 50–55 °C, 93.4 g (1.0 mol) of tert-butane chloride was added dropwise. After the addition was complete, stirring was continued for 2 h. After the reaction was complete, the mixture was distilled under reduced pressure to obtain 138.0 g of crude product. The crude product and the transition fraction obtained in Example 1 were combined and then fractionally distilled to obtain 95.9 g of tert-butyl isocyanate with a purity of 99.6% and a yield of 91.6% (excluding the reused crude product). The transition fraction, 14.7 g, showed a tert-butyl isocyanate content of 29.7% after gas phase analysis. This transition fraction can be reused in the next batch of distillation. The overall yield was 96.0%. Example 5 The synthesis of tert-butyl isocyanate was carried out in a manner similar to that in Example 1, except that the co-catalyst 4-dimethylaminopyridine was not added. The crude product was distilled to obtain 58.5 g of tert-butyl isocyanate with a purity of 98.2% and a yield of 57.7%. A transition fraction of 13.6 g, after gas phase analysis, showed a tert-butyl isocyanate content of 37.2%. This transition fraction could be reused in subsequent batches of distillation. The overall yield was 62.8%.

[0045] Comparing Examples 1 and 5, it is evident that without the addition of a co-catalyst, the purity and yield of tert-butyl isocyanate decreased significantly. Furthermore, reusing the transition fraction also resulted in a significant decrease in the overall yield. These results indicate that the addition of a co-catalyst helps improve the purity of tert-butyl isocyanate and significantly increases its yield. Example 6 The synthesis of tert-butyl isocyanate was carried out in a manner similar to that in Example 1, except that the co-solvent sulfolane was not added. The crude product was distilled to obtain 69.2 g of tert-butyl isocyanate with a purity of 98.7% and a yield of 68.9%. A 12.5 g transition fraction, after gas phase analysis, showed a tert-butyl isocyanate content of 36.5%, which could be reused in subsequent batches. The overall yield was 73.5%.

[0046] Comparing Examples 1 and 6, it is evident that without the addition of a cosolvent, the purity of tert-butyl isocyanate decreases, with its yield decreasing from 90.5% to 68.9%. After using the transition fraction, the overall yield further decreases from 95.6% to 73.5%. These results indicate that the addition of a cosolvent helps improve the purity of tert-butyl isocyanate and has a significant impact on its yield; therefore, the addition of a cosolvent can significantly improve the yield of tert-butyl isocyanate.

[0047] Example 7 The synthesis of tert-butyl isocyanate was carried out in a manner similar to that in Example 1, except that the stabilizer magnesium chloride was not added. The crude product was distilled to obtain 75.7 g of tert-butyl isocyanate with a purity of 99.1% and a yield of 75.7%. A transition fraction of 14.1 g, after gas phase analysis, showed a tert-butyl isocyanate content of 35.8%. This transition fraction could be reused in subsequent batches of distillation. The overall yield was 80.8%.

[0048] Comparing Examples 1 and 7, it can be seen that without the addition of a stabilizer, the purity of tert-butyl isocyanate decreased from 99.5% to 99.1%, a relatively small decrease, indicating that the addition of the stabilizer has little impact on the purity of tert-butyl isocyanate. However, the yield of tert-butyl isocyanate decreased from 90.5% to 75.7%, and after using the transition fraction, the overall yield decreased from 95.6% to 80.8%, indicating that the stabilizer has a significant impact on the yield of tert-butyl isocyanate. Therefore, the addition of the aforementioned stabilizer can significantly improve the yield of tert-butyl isocyanate.

[0049] Comparative Example The experiment was conducted with reference to the embodiment in CN106543036, and the following examples are provided as comparative examples.

[0050] Comparative Example 1 160 mL of ethylene glycol ethyl ether acetate was added to a four-necked flask, and stirring was started. Then, 104.9 g (1.5 mol) of sodium cyanate, 93.4 g (1.0 mol) of tert-butane chloride, 15.0 g (0.11 mol) of zinc chloride, and 5.1 g (0.05 mol) of acetic anhydride were added sequentially. After the addition was complete, the temperature was raised to 85 °C. The mixture was kept at 85 °C and stirred for 3 h. After the reaction was complete, the mixture was distilled under reduced pressure to obtain 97.4 g of crude product. Gas chromatography analysis of the crude product showed that the content of tert-butyl isocyanate was 63.4%, with a yield of 62.3%. Comparative Example 2 To the crude product distillation solution of Comparative Example 1, 80 mL of ethylene glycol ethyl ether acetate was added, followed by 76.9 g (1.1 mol) sodium cyanate, 93.4 g (1.0 mol) tert-butane chloride, 6.8 g (0.05 mol) zinc chloride, and 3.1 g (0.03 mol) acetic anhydride. After the addition was complete, the temperature was raised to 85 °C. The mixture was kept at 85 °C and stirred for 3 h. After the reaction was complete, the mixture was distilled under reduced pressure to obtain 96.6 g of crude product. Gas chromatography analysis of the crude product showed that the content of tert-butyl isocyanate was 61.8%, with a yield of 60.2%.

[0051] Verification showed that the crude product yield of the example in CN106543036 was only 62%, and a large amount of isobutylene tail gas was generated. Tail gas treatment is difficult, and improper treatment could lead to high safety risks. Furthermore, the use of acetic anhydride produces tert-butyl acetate, which is difficult to separate from the product under simple distillation conditions, resulting in low product purity. The present invention has been described in detail above with reference to specific embodiments and exemplary examples; however, these descriptions should not be construed as limiting the present invention. Those skilled in the art will understand that various equivalent substitutions, modifications, or improvements can be made to the technical solutions and embodiments of the present invention without departing from the spirit and scope of the invention, and all such modifications and improvements fall within the scope of the present invention. The scope of protection of the present invention is defined by the appended claims.

Claims

1. A method for synthesizing tert-butyl isocyanate, characterized in that, The synthesis method includes the following steps: Step 1: Add the composite catalyst, co-solvent, cyanate, and stabilizer to the diester solvent, stir until homogeneous, and heat to the reaction temperature; Step 2: Add tert-chlorobutane dropwise at the reaction temperature. After the addition is complete, maintain the temperature at the same level for the reaction. Step 3: After the reaction is complete, the crude product is distilled under reduced pressure to obtain tert-butyl isocyanate.

2. The synthesis method according to claim 1, characterized in that, In step 1, The diester solvent is selected from one or more of diethyl oxalate, dipropyl oxalate, dibutyl oxalate, ethylene glycol diacetate, ethylene glycol dipropionate, ethylene glycol diisobutyrate, propylene glycol diacetate, and propylene glycol diisobutyrate.

3. The synthesis method according to claim 1, characterized in that, In step 1, The composite catalyst includes a main catalyst and a co-catalyst, wherein the main catalyst is zinc chloride and the co-catalyst is 4-dimethylaminopyridine; The mass ratio of the main catalyst to the co-catalyst is 20.5:(0-4.1).

4. The synthesis method according to claim 1, characterized in that, In step 1, The co-solvent is selected from one or more of N,N-dimethylformamide, sulfolane, tetrahydrofuran, and 1,4-dioxane.

5. The synthesis method according to claim 1, characterized in that, In step 1, The cyanate is selected from one or more of sodium cyanate, potassium cyanate, and calcium cyanate.

6. The synthesis method according to claim 1, characterized in that, In step 1, The stabilizer is selected from one or both of magnesium chloride and magnesium sulfate.

7. The synthesis method according to claim 1, characterized in that, In step 1, The mass ratio of the composite catalyst, co-solvent, cyanate, stabilizer and diester solvent is (20-31):(0-2.4):(73-80):(0-3):

140.

8. The synthesis method according to claim 1, characterized in that, In step 2, The molar ratio of the cyanate to tert-butane chloride is (1.0–1.5):

1.

9. The synthesis method according to claim 1, characterized in that, In step 2, The reaction temperature is 30–75°C. After the addition is complete, the reaction is maintained at this temperature for 1–2.5 h.