N-methylisopropylamine and synthesis method thereof

Abstract

The invention provides a synthesis method of N-methylisopropylamine, which belongs to the technical field of intermediate synthesis, and comprises the following steps: mixing acetone and a monomethylamine aqueous solution, reacting by using a microchannel reaction method to obtain a material, and rectifying the material to obtain N-methylisopropylamine. The invention provides a synthetic method of N-methylisopropylamine, which avoids the generation of dimethyl substituted N-methylisopropylamine and improves the yield of N-methylisopropylamine.

Description

Technical Field

[0001] The invention relates to the technical field of intermediate synthesis, and in particular to N-methylisopropylamine and a synthesis method thereof. Background Art

[0002] N-methylisopropylamine is an organic compound with the molecular formula C4H 11 N, also known as N-isopropylmethylaniline or N-isopropylmethylamine, is an important pharmaceutical intermediate and a commonly used reagent in industry. Patent No. CN102070461A currently discloses a method for synthesizing N-methylisopropylamine, which produces N-methylisopropylamine through two steps: Mannich reaction and decomposition reaction. The synthesis process of this invention is relatively complicated. The first step is the Mannich reaction, and the reaction conditions are harsh, and the effective content and yield are low. The second step is the decomposition reaction, and the reaction produces a large amount of hydrochloric acid wastewater. In addition, the use of zinc powder is expensive, and the waste acid contains a large amount of zinc chloride. The treatment of the three wastes is relatively complicated, and the equipment is highly corrosive. See the reaction formula Figure 1 Chinese type I.

[0003] Patent No. CN106866424A discloses an intermittent preparation method of N-methylisopropylamine. The patent adopts the method of putting acetone and Raney nickel into a stainless steel hydrogenation kettle, introducing monomethylamine gas to react under pressure, and then introducing hydrogen to react under pressure. After the reaction is completed, the reaction is filtered and the filtrate is distilled under normal pressure to obtain N-methylisopropylamine. According to its specification, the process uses 5%-20% of the mass of acetone as a catalyst. The amount used is too large. Both ventilations use a high-temperature and high-pressure reactor. The process has relative risks, and a large amount of methylamine gas residues after the reaction is passed through the methylamine gas is difficult to remove. Since the boiling points of the raw materials acetone and N-methylisopropylamine are very close, it brings difficulties to the subsequent separation and purification. Reaction formula see Figure 1 Chinese type II.

[0004] Another patented technology of BASF in Germany is to prepare N-methylisopropylamine by using zirconium dioxide, 0.1-5% palladium and 0.1-5% platinum as catalysts, using a certain ratio of acetone, monomethylamine and hydrogen, preheating through a tubular reactor equipped with Shangshu catalyst, reacting at high temperature and high pressure, and then distilling to obtain the product. This method has a large investment in equipment, the process uses high temperature and high pressure reaction, the process is relatively dangerous, and the total yield of the material is 87%. The reaction formula is shown in Figure 1 Chinese type III.

[0005] The fourth method for preparing N-methylisopropylamine is to use water as solvent, monomethylamine and acetone in the presence of copper chromite or potassium dihydrogen phosphate and potassium hydroxide as catalysts, and react under hydrogen conditions. Although the reaction conditions of the materials become milder, the total yield of the materials is only 60%, and a large amount of high-salt wastewater is produced. The reaction formula is shown in FIG. Figure 1 Chinese type IV.

[0006] The above four routes all belong to methylation reactions and have their own disadvantages, but they have a common disadvantage, which is the production of disubstituted N,N-dimethylisopropylamine and a small amount of polymers, which cannot simultaneously meet the conversion rate and selectivity of the raw materials. Since the by-product N,N-dimethylisopropylamine is extremely similar in nature to the product, its separation is very difficult. Therefore, a method for synthesizing N-methylisopropylamine selectively and avoiding dimethyl-substituted N-methylisopropylamine is currently needed. Summary of the invention

[0007] In view of this, the present invention provides a method for synthesizing N-methylisopropylamine, which avoids the production of dimethyl-substituted N-methylisopropylamine and improves the yield of N-methylisopropylamine.

[0008] To achieve the above object, the present invention provides a method for synthesizing N-methylisopropylamine, comprising the following steps: mixing acetone and a monomethylamine aqueous solution, reacting using a microchannel reaction method to obtain a material, and distilling the material to obtain N-methylisopropylamine.

[0009] Optionally, the mass ratio of the acetone to the monomethylamine aqueous solution is 330-350:480-500. Optionally, the molar ratio of acetone to monomethylamine aqueous solution is 5-6:6-6.5.

[0010] Optionally, the microchannel reaction method includes the following steps: inputting a mixed solution of acetone and monomethylamine aqueous solution into a microchannel reactor for reaction, wherein the microchannel reactor includes a catalyst.

[0011] Optionally, the catalyst is Raney nickel.

[0012] Optionally, the working conditions of the microchannel reactor are an injection volume of 2-3 mL / min, a hydrogen pressure of 3.0 MPa, a hydrogen flow rate of 0.4 L / min, and a temperature of 130°C.

[0013] Optionally, during the distillation, a fraction at 43° C. is taken.

[0014] In order to achieve the above object, the present invention also provides N-methylisopropylamine prepared by a method for synthesizing N-methylisopropylamine.

[0015] The above technical solution of the present invention includes at least the following beneficial effects: The synthetic method of N-methylisopropylamine provided by the invention is simple to operate, avoids the generation of dimethyl-substituted N-methylisopropylamine, and improves the yield of N-methylisopropylamine. BRIEF DESCRIPTION OF THE DRAWINGS

[0016] Figure 1 The chemical reaction formulas of four methods for synthesizing N-methylisopropylamine in the prior art are as follows; Figure 2 It is the chemical reaction formula for synthesizing N-methylisopropylamine in the embodiment of the present invention. DETAILED DESCRIPTION

[0017] To make the purpose, technical solution and advantages of the embodiments of the present invention clearer, the following will be combined with the appended drawings of the embodiments of the present invention. Figure 1~2 , the technical scheme of the embodiment of the present invention is clearly and completely described. Obviously, the described embodiment is a part of the embodiment of the present invention, not all of the embodiments. Based on the described embodiment of the present invention, all other embodiments obtained by ordinary technicians in this field belong to the scope of protection of the present invention.

[0018] Example 1 Take a 1000mL beaker, add 338g (5.8196mol) of acetone and 487.5g (6.2782mol) of 40% monomethylamine aqueous solution, and the two solutions release heat significantly after mixing, and the temperature can reach up to 58°C. Use a microchannel reactor to react, use Raney nickel as a catalyst, set the injection volume to 2mL / min, the hydrogen pressure to 3.0MPa, the hydrogen flow rate to 0.4L / min, and the reaction temperature to 130°C. After the reaction, distill the resulting material and collect the 43°C fraction, which is N-methylisopropylamine. The fraction was tested, and the test results showed that the mass of N-methylisopropylamine was 420.93g, the yield was 98.90%, the mass of acetone accounted for 0.5% of the fraction, and the mass of N-methylisopropylamine accounted for 98.37%.

[0019] Example 2 Take a 1000mL beaker, add 338g (5.8196mol) of acetone and 487.5g (6.2782mol) of 40% monomethylamine aqueous solution, and the two solutions release heat significantly after mixing, and the temperature can reach up to 58°C. Use a microchannel reactor to react, use Raney nickel as a catalyst, set the injection volume to 3mL / min, the hydrogen pressure to 3.0MPa, the hydrogen flow rate to 0.4L / min, and the reaction temperature to 130°C. After the reaction, distill the resulting material and collect the 43°C fraction, which is N-methylisopropylamine. The fraction was tested, and the test results showed that the mass of N-methylisopropylamine was 389.23g, the yield was 91.45%, the mass of acetone accounted for 1.3% of the fraction, and the mass of N-methylisopropylamine accounted for 96.35%.

[0020] Example 3 Take a 1000mL beaker, add 338g (5.8196mol) of acetone and 487.5g (6.2782mol) of 40% monomethylamine aqueous solution, and the two solutions release heat significantly after mixing, and the temperature can reach up to 58°C. Use a microchannel reactor to react, use zinc powder as a catalyst, set the injection volume to 2mL / min, the hydrogen pressure to 3.0MPa, the hydrogen flow rate to 0.4L / min, and the reaction temperature to 130°C. After the reaction, distill the resulting material and collect the 43°C fraction, which is N-methylisopropylamine. The fraction was tested, and the test results showed that the mass of N-methylisopropylamine was 398.22g, the yield was 93.56%, the mass of acetone accounted for 4.22% of the fraction, and the mass of N-methylisopropylamine accounted for 93.34%.

[0021] Example 4 Take a 1000mL beaker, add 338g (5.8196mol) of acetone and 487.5g (6.2782mol) of 40% monomethylamine aqueous solution, and the two solutions release heat significantly after mixing, and the temperature can reach up to 58°C. Use a microchannel reactor to react, use zinc powder as a catalyst, set the injection volume to 3mL / min, the hydrogen pressure to 3.0MPa, the hydrogen flow rate to 0.4L / min, and the reaction temperature to 130°C. After the reaction, distill the resulting material and collect the 43°C fraction, which is N-methylisopropylamine. The fraction was tested, and the test results showed that the mass of N-methylisopropylamine was 367.89g, the yield was 86.44%, the mass of acetone accounted for 7.64% of the fraction, and the mass of N-methylisopropylamine accounted for 89.45%.

[0022] Comparative Example 1 Take a 1000mL beaker, add 338g (5.8196mol) of acetone and 487.5g (6.2782mol) of 40% monomethylamine aqueous solution, and the two solutions release heat significantly after mixing, and the temperature can reach 58°C. Use a microchannel reactor to react, use chromium dioxide as a catalyst, set the injection volume to 2mL / min, the hydrogen pressure to 3.0MPa, the hydrogen flow rate to 0.4L / min, and the reaction temperature to 130°C. After the reaction, distill the resulting material and collect the 43°C fraction, which is N-methylisopropylamine. The fraction was tested, and the test results showed that the mass of N-methylisopropylamine was 320.44g, the yield was 75..29%, the mass of acetone accounted for 10.25% of the fraction, and the mass of N-methylisopropylamine accounted for 78.22%.

[0023] Comparative Example 2 Take a 1000mL beaker, add 338g (5.8196mol) of acetone and 487.5g (6.2782mol) of 40% monomethylamine aqueous solution, and the two solutions release heat significantly after mixing, and the temperature can reach up to 58°C. Use a microchannel reactor to react, use chromium dioxide as a catalyst, set the injection volume to 3mL / min, the hydrogen pressure to 3.0MPa, the hydrogen flow rate to 0.4L / min, and the reaction temperature to 130°C. After the reaction, distill the resulting material and collect the 43°C fraction, which is N-methylisopropylamine. The fraction was tested, and the test results showed that the mass of N-methylisopropylamine was 276.96g, the yield was 65.07%, the mass of acetone accounted for 13.56% of the fraction, and the mass of N-methylisopropylamine accounted for 75.21%.

[0024] Test example Based on the synthetic method of Example 1, the influence of sample size and temperature on the yield of N-methylisopropylamine was tested respectively, that is, the influence of the test temperature on the yield of N-methylisopropylamine was tested at a fixed sample size of 10 ml / min, and the reaction temperature was changed to 90°C, 100°C, 110°C, 120°C, and 130°C, and repeated twice to obtain Table 1. The influence of the test sample size on the yield of N-methylisopropylamine was tested at a fixed reaction temperature of 130°C, and the influence of the test sample size on the yield of N-methylisopropylamine was tested at 2 ml / min, 3 ml / min, 4 ml / min, 5 ml / min, 6 ml / min, 7 ml / min, and 8 ml / min to obtain Table 2.

[0025] Table 1 Effect of temperature on the yield of N-methylisopropylamine

[0026] As can be seen from Table 1, the synthesis method of the present application obtains the target product, i.e., N-methylisopropylamine, when the reaction temperature is in the range of 90°C to 130°C, starting from 110°C, and the yield of the target product is the highest when the reaction temperature is 130°C.

[0027] Table 2 Effect of injection volume on the yield of N-methylisopropylamine

[0028] It can be seen from Table 2 that when the injection volume is in the range of 2-8 ml / min, the proportion of acetone is large when the injection volume is large, while the proportion of the target product N-methylisopropylamine is small. When the injection volume is 2-3 ml / min, the yield of N-methylisopropylamine can reach more than 90%.

[0029] Based on the synthetic method of Example 3, the influence of sample size and temperature on the yield of N-methylisopropylamine was tested respectively, that is, with a fixed sample size of 10 ml / min, the reaction temperature was changed to 90°C, 100°C, 110°C, 120°C, and 130°C to test the influence of temperature on the yield of N-methylisopropylamine, repeated twice, and Table 3 was obtained. With a fixed reaction temperature of 130°C, the influence of sample size on the yield of N-methylisopropylamine was tested at 2 ml / min, 3 ml / min, 4 ml / min, 5 ml / min, 6 ml / min, 7 ml / min, and 8 ml / min to obtain Table 4.

[0030] Table 3 Effect of temperature on yield of N-methylisopropylamine

[0031] As can be seen from Table 3, within the range of 90°C to 130°C, the reaction temperature of the synthesis method provided by the present application starts to produce N-methylisopropylamine at 110°C, and the yield is highest at 130°C.

[0032] Table 4 Effect of injection volume on the yield of N-methylisopropylamine

[0033] It can be seen from Table 4 that when the injection volume is in the range of 2~8ml / min, the proportion of acetone is high when the injection volume is large, and the proportion of acetone decreases when the injection volume is small. When the injection volume is 2~3ml / min, the yield of N-methylisopropylamine can reach more than 85%.

[0034] Based on the synthesis method of Comparative Example 1, the effects of injection volume and temperature on the yield of N-methylisopropylamine were tested, that is, the injection volume was fixed at 10 ml / min, and the reaction temperature was changed to 90°C, 100°C, 110°C, 120°C, and 130°C to test the effect of temperature on the yield of N-methylisopropylamine, and repeated twice to obtain Table 5. The reaction temperature was fixed at 130°C, and the injection volume was changed to 2 ml / min, 3 ml / min, 4 ml / min, 5 ml / min, 6 ml / min, 7 ml / min, and 8 ml / min to test the effect of injection volume on the yield of N-methylisopropylamine, and Table 6 was obtained.

[0035] Table 5 Effect of temperature on the yield of N-methylisopropylamine

[0036] It can be seen from Table 5 that within the range of 90°C to 130°C, the reaction temperature of the synthesis method provided by the present application starts to produce N-methylisopropylamine at 120°C, and the yield is highest at 130°C.

[0037] Table 6 Effect of injection volume on the yield of N-methylisopropylamine

[0038] It can be seen from Table 6 that when the injection volume is in the range of 2~8ml / min, the proportion of acetone is large when the injection volume is large, and the proportion of the target product N-methylisopropylamine is small. When the injection volume is 2ml / min, the yield of N-methylisopropylamine can reach as high as 75.29% or more.

[0039] Combined with the test examples, it can be seen that the catalytic effect of Raney nickel is the best, followed by the catalytic effects of zinc powder and chromium dioxide. Combined with the influence of injection volume and temperature on the yield of N-methylisopropylamine, the reaction conditions adopted in the present invention are injection volume 2-3 mL / min, temperature 130° C., and Raney nickel or zinc powder is used as the catalyst.

[0040] The above are preferred embodiments of the present invention. It should be pointed out that, for ordinary technicians in this technical field, several improvements and modifications can be made without departing from the principles of the present invention. These improvements and modifications should also be regarded as within the scope of protection of the present invention.

Claims

1. A method for synthesizing N-methylisopropylamine, characterized in that: The following steps are involved: Acetone and a monomethylamine aqueous solution are mixed, and a material is obtained by reaction using a microchannel reaction method, and the material is distilled to obtain N-methylisopropylamine.

2. The method for synthesizing N-methylisopropylamine according to claim 1, characterized in that The mass ratio of the acetone to the monomethylamine aqueous solution is 330-350:480-500.

3. The synthetic method of N-methylisopropylamine according to claim 2, characterized in that, The molar ratio of the acetone to the monomethylamine aqueous solution is 5-6:6-6.

5.

4. The method for synthesizing N-methylisopropylamine according to claim 1, characterized in that: The microchannel reaction method comprises the following steps: a mixed solution of acetone and monomethylamine aqueous solution is input into a microchannel reactor for reaction, wherein the microchannel reactor comprises a catalyst.

5. The method for synthesizing N-methylisopropylamine according to claim 4, characterized in that: The catalyst is Raney nickel or zinc powder.

6. The method for synthesizing N-methylisopropylamine according to claim 4, characterized in that: The working conditions of the microchannel reactor are injection volume 2-3 mL / min, hydrogen pressure 3.0 MPa, hydrogen flow rate 0.4 L / min, and temperature 130°C.

7. The method for synthesizing N-methylisopropylamine according to claim 1, characterized in that: During the distillation, the fraction at 43° C. is taken.

8. N-methylisopropylamine obtained by the synthesis method of N-methylisopropylamine as claimed in any one of claims 1 to 7.

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