Preparation method of 2-methyl-1, 4-naphthoquinone

Abstract

The invention discloses a preparation method of 2-methyl-1, 4-naphthoquinone, which comprises the following steps: carrying out oxidative dehydrogenation reaction on 2-methyl-1, 4-tetrahydronaphthoquinone in an organic solvent under the condition of microwave radiation in the presence of a catalyst and an oxidizing agent to generate the 2-methyl-1, 4-naphthoquinone, the catalyst comprises a copper-based catalyst, and the oxidant comprises oxygen; the method provided by the invention has the advantages of low catalyst dosage, simple catalyst, green and environment-friendly oxidant, reusable solvent and the like, and is beneficial to industrial large-scale production.

Description

Technical Field

[0001] The present invention relates to the technical field of fine chemicals, and particularly relates to a preparation method of 2-methyl-1,4-naphthoquinone. Background Art

[0002] Vitamin K3, also known as menadione, namely 2-methyl-1,4-naphthoquinone, is an organic compound with a yellow crystalline powder appearance. Vitamin K belongs to a coagulant in clinical practice and can be used to treat hemorrhagic diseases caused by vitamin K deficiency. In addition, it plays an important role in the metabolism of high-energy compounds and oxidative phosphorylation, as well as in the metabolism of other fat-soluble vitamins, and has the function of reducing blood pressure. At present, 2-methyl-1,4-naphthoquinone is mainly prepared by the oxidative dehydrogenation of 2-methyl-1,4-tetrahydronaphthoquinone. Specifically, under the catalytic system of copper bromide / manganese bromide, dimethyl sulfoxide (DMSO) is used as a solvent and an oxidant to oxidize 2-methyl-1,4-tetrahydronaphthoquinone. However, this process uses dimethyl sulfoxide as a solvent and an oxidant, and the post-treatment is relatively complex. Moreover, the dosage of the copper bromide / manganese bromide catalyst is large (1 part of 2-methyl-1,4-tetrahydronaphthoquinone, 0.2 - 0.4 parts of copper bromide, 0.2 - 0.4 parts of manganese bromide), it is easy to remain, the production cost is high, and it is not conducive to industrial production. Summary of the Invention

[0003] The purpose of the present invention is to overcome one or more deficiencies of the prior art and provide an improved preparation method of 2-methyl-1,4-naphthoquinone.

[0004] Furthermore, the preparation method of 2-methyl-1,4-naphthoquinone of the present invention can have the advantages of low catalyst dosage, simple catalyst, green and environmentally friendly oxidant, and recyclable solvent.

[0005] To achieve the above purpose, the technical solution adopted by the present invention is:

[0006] A preparation method of 2-methyl-1,4-naphthoquinone, the preparation method comprising: subjecting 2-methyl-1,4-tetrahydronaphthoquinone to an oxidative dehydrogenation reaction in the presence of a catalyst and an oxidant to generate 2-methyl-1,4-naphthoquinone;

[0007] Particularly:

[0008] Controlling that the oxidative dehydrogenation reaction is also carried out in an organic solvent under microwave radiation conditions;

[0009] The catalyst comprises a copper-based catalyst, and the oxidant comprises oxygen.

[0010] According to some preferred aspects of the present invention, the copper-based catalyst is a copper salt.

[0011] In some embodiments of the present invention, the copper salt is a combination of one or more selected from copper bromide, copper chloride, copper acetate, copper sulfate, and copper nitrate.

[0012] According to the present invention, in the reaction system of the present invention, the amount of the catalyst used is small; further, the molar ratio of the copper-based catalyst to 2-methyl-1,4-tetrahydronaphthoquinone is 0.001 - 0.0045:1, further 0.002 - 0.0045:1.

[0013] In some embodiments of the present invention, the molar ratio of the copper-based catalyst to 2-methyl-1,4-tetrahydronaphthoquinone is 0.002:1, 0.003:1, 0.004:1, 0.0045:1, etc.

[0014] In some embodiments of the present invention, the catalyst is solely the copper-based catalyst. In the present invention, compared with the existing composite catalyst, only the copper-based catalyst can be used, greatly simplifying the catalyst formulation, reducing the usage quantity and weight of materials such as the catalyst, and being beneficial to large-scale industrial production.

[0015] In some embodiments of the present invention, an oxygen-containing gas mixture or pure oxygen gas with a purity greater than or equal to 99% is introduced into the reaction system to provide the oxidant. In the reaction system of the present invention, green and environmentally friendly oxygen can be used as the oxidant, avoiding the use of difficult-to-treat, complex-to-prepare, and toxic substances for oxidative dehydrogenation in the existing reaction system.

[0016] In some embodiments of the present invention, the molar input amount of the oxygen is more than 1.1 times the molar amount of 2-methyl-1,4-tetrahydronaphthoquinone, further 1.2 - 2 times.

[0017] According to some preferred aspects of the present invention, the microwave power under the microwave radiation conditions is 50 - 180W, further 90 - 150W, and still further 100 - 110W.

[0018] According to some preferred aspects of the present invention, the radiation time under the microwave radiation conditions is 1 - 25 min, further 5 - 15 min, and still further 8 - 10 min.

[0019] In some embodiments of the present invention, the organic solvent is a combination of one or more selected from toluene, acetonitrile, ethyl acetate, and dichloroethane.

[0020] In some embodiments of the present invention, the mass ratio of the organic solvent to 2-methyl-1,4-tetrahydronaphthoquinone in the feed is 1-6:1. According to some specific aspects of the present invention, the mass ratio of the organic solvent to 2-methyl-1,4-tetrahydronaphthoquinone in the feed is 1:1, 1.5:1, 2:1, 2.5:1, 3:1, 3.5:1, 4:1, 4.5:1, 5:1, 5.5:1, 6:1, etc.

[0021] In some embodiments of the present invention, the embodiments for preparing 2-methyl-1,4-naphthoquinone include: adding 2-methyl-1,4-tetrahydronaphthoquinone, an organic solvent, and a catalyst into a reaction vessel, sealing it, replacing the gas with nitrogen multiple times, then introducing oxygen into the reaction vessel, and then performing microwave radiation and reaction to generate 2-methyl-1,4-naphthoquinone.

[0022] Further, after the reaction is completed, the organic solvent is recovered by distillation and reused in the next batch of reactions, and the residue in the kettle is crystallized to obtain 2-methyl-1,4-naphthoquinone.

[0023] Further, the reaction vessel can be a microwave reaction kettle.

[0024] Due to the application of the above technical solutions, the present invention has the following advantages compared with the prior art:

[0025] Based on the defects of complex post-treatment of oxidants, complex catalysts with large dosages and easy residues when preparing 2-methyl-1,4-naphthoquinone by oxidative dehydrogenation of 2-methyl-1,4-tetrahydronaphthoquinone in the prior art, the inventors of the present invention unexpectedly found in a large number of experimental studies that when using microwave radiation-assisted oxidative dehydrogenation reaction and using a copper-based catalyst as the catalyst, not only the reaction rate is extremely fast and the reaction can be completed in a short time, but also the dosage of the catalyst can be very small (only less than 1% of the molar amount of 2-methyl-1,4-tetrahydronaphthoquinone in the feed, even less than 0.5%), and at the same time the solvent can be recycled. In particular, green and environmentally friendly oxygen can be used as the oxidant without using some difficult-to-treat or dangerous peroxyacids and dimethyl sulfoxide as oxidants, which is beneficial to safe and green environmental protection production. BRIEF DESCRIPTION OF THE DRAWINGS

[0026] Figure 1 It is the gas chromatogram of 2-methyl-1,4-naphthoquinone prepared in Example 1 of the present invention (solvent at 4.3 min, internal standard naphthalene at 10.7 min, 2-methyl-1,4-naphthoquinone at 15.8 min). DETAILED DESCRIPTION OF THE EMBODIMENTS

[0027] The above solution will be further described below in conjunction with specific embodiments; it should be understood that these embodiments are used to illustrate the basic principles, main features and advantages of the present invention, and the present invention is not limited by the scope of the following embodiments; the implementation conditions adopted in the embodiments can be further adjusted according to specific requirements, and the implementation conditions not specified are usually the conditions in conventional experiments.

[0028] Unless otherwise specified in the following embodiments, all raw materials are obtained from commercial purchases or prepared by conventional methods in the art.

[0029] Example 1

[0030] This example provides a preparation method of 2-methyl-1,4-naphthoquinone, and the preparation method includes:

[0031] Weigh 100 g of 2-methyl-1,4-tetrahydronaphthoquinone, 0.3 g of copper chloride (0.4 mol%, that is, the molar percentage of the molar amount of copper chloride as the catalyst in the molar amount of the charged 2-methyl-1,4-tetrahydronaphthoquinone, the same below) and 400 g of toluene into a 1 L feeding bottle, and shake well. Slowly introduce 27 g (0.85 mol, 1.5 eq) of oxygen into the microwave high-pressure reactor, turn on the stirrer of the microwave reactor, set the microwave power to 100 W, and the radiation time to 9 min. After the reaction is completed, distill out the remaining organic solvent for reuse to obtain a toluene solution of 2-methyl-1,4-naphthoquinone. Quantitative analysis by GC shows a conversion rate of 99.7%, a selectivity of 95.29%, and a yield of 95.0%. See the Figure 1 gas chromatogram shown (testing conditions: inlet: 250 °C; chromatographic column type: HP-5 40 °C - 300 °C: 30 m * 320 μm * 0.25 μm; column oven: maintain at 60 °C for 1 min, increase to 200 °C at 10 °C / min, maintain for 1 min, increase to 280 °C at 20 °C / min, maintain for 2 min; detector: 250 °C, air flow rate 400 mL / min, hydrogen gas flow rate 30 mL / min, nitrogen gas flow rate 25 mL / min; injection volume 0.5 μL).

[0032] Example 2

[0033] This example provides a preparation method of 2-methyl-1,4-naphthoquinone. Compared with Example 1, the difference is that the catalyst is replaced with copper bromide with the same added amount, and the rest is the same as in Example 1. The specific results are shown in Table 1.

[0034] Example 3

[0035] This example provides a preparation method of 2-methyl-1,4-naphthoquinone. Compared with Example 1, the difference is that the catalyst is replaced with copper acetate with the same added amount, and the rest is the same as in Example 1. The specific results are shown in Table 1.

[0036] Example 4

[0037] This example provides a method for preparing 2-methyl-1,4-naphthoquinone. Compared with Example 1, the difference is that the catalyst is replaced with copper nitrate with the same addition amount, and the rest is the same as Example 1. The specific results are shown in Table 1.

[0038] Example 5

[0039] This example provides a method for preparing 2-methyl-1,4-naphthoquinone. Compared with Example 1, the difference is that the dosage of copper chloride is 0.2 mol%, and the rest is the same as Example 1. The specific results are shown in Table 1.

[0040] Example 6

[0041] This example provides a method for preparing 2-methyl-1,4-naphthoquinone. Compared with Example 1, the difference is that the dosage of copper chloride is 0.25 mol%, and the rest is the same as Example 1. The specific results are shown in Table 1.

[0042] Example 7

[0043] This example provides a method for preparing 2-methyl-1,4-naphthoquinone. Compared with Example 1, the difference is that the dosage of copper chloride is 0.35 mol%, and the rest is the same as Example 1. The specific results are shown in Table 1.

[0044] Example 8

[0045] This example provides a method for preparing 2-methyl-1,4-naphthoquinone. Compared with Example 1, the difference is that the dosage of copper chloride is 0.45 mol%, and the rest is the same as Example 1. The specific results are shown in Table 1.

[0046] Example 9

[0047] This example provides a method for preparing 2-methyl-1,4-naphthoquinone. Compared with Example 1, the difference is that the solvent used is acetonitrile, and the rest is the same as Example 1. The specific results are shown in Table 1.

[0048] Example 10

[0049] This example provides a method for preparing 2-methyl-1,4-naphthoquinone. Compared with Example 1, the difference is that the organic solvent used is ethyl acetate, and the rest is the same as Example 1. The specific results are shown in Table 1.

[0050] Example 11

[0051] This example provides a method for preparing 2-methyl-1,4-naphthoquinone. Compared with Example 1, the difference is that the organic solvent used is dichloromethane, and the rest is the same as Example 1. The specific results are shown in Table 1.

[0052] Example 12

[0053] This example provides a method for preparing 2-methyl-1,4-naphthoquinone. Compared with Example 1, the difference lies in that the microwave power used is 150 W, and the rest is the same as in Example 1. The specific results are shown in Table 1.

[0054] Example 13

[0055] This example provides a method for preparing 2-methyl-1,4-naphthoquinone. Compared with Example 1, the difference lies in that the microwave power used is 90 W, and the rest is the same as in Example 1. The specific results are shown in Table 1.

[0056] Example 14

[0057] This example provides a method for preparing 2-methyl-1,4-naphthoquinone. Compared with Example 1, the difference lies in that the microwave power used is 110 W, and the rest is the same as in Example 1. The specific results are shown in Table 1.

[0058] Example 15

[0059] This example provides a method for preparing 2-methyl-1,4-naphthoquinone. Compared with Example 1, the difference lies in that the radiation time is 5 min, and the rest is the same as in Example 1. The specific results are shown in Table 1.

[0060] Example 16

[0061] This example provides a method for preparing 2-methyl-1,4-naphthoquinone. Compared with Example 1, the difference lies in that the radiation time is 8 min, and the rest is the same as in Example 1. The specific results are shown in Table 1.

[0062] Example 17

[0063] This example provides a method for preparing 2-methyl-1,4-naphthoquinone. Compared with Example 1, the difference lies in that the radiation time is 10 min, and the rest is the same as in Example 1. The specific results are shown in Table 1.

[0064] Example 18

[0065] This example provides a method for preparing 2-methyl-1,4-naphthoquinone. Compared with Example 1, the difference lies in that the radiation time is 15 min, and the rest is the same as in Example 1. The specific results are shown in Table 1.

[0066] Table 1

[0067]

[0068]

[0069] Comparative Example 1

[0070] This example provides a method for preparing 2-methyl-1,4-naphthoquinone. Compared with Example 1, the difference is that no catalyst is added during the reaction process, and the rest is the same as in Example 1. After reacting for 9 minutes, the conversion rate is only 8.7%, the selectivity is 41.30%, and the yield is 3.59%. When the reaction time is extended by 1 hour, the reaction conversion rate basically does not change.

[0071] Comparative Example 2

[0072] This example provides a method for preparing 2-methyl-1,4-naphthoquinone. Compared with Example 1, the difference is that a microwave reactor is not used, and at the same time, the temperature is controlled at room temperature of 25°C, and the rest is the same as in Example 1. After reacting for 9 minutes, the reaction basically does not occur, and no relevant products are detected. When the reaction time is extended to 2 hours, the reaction still basically does not occur, and no relevant products are detected.

[0073] Comparative Example 3

[0074] This example provides a method for preparing 2-methyl-1,4-naphthoquinone. Compared with Example 1, the difference is that a microwave reactor is not used, and at the same time, the temperature is controlled at 80°C, and the rest is the same as in Example 1. After reacting for 9 minutes, the reaction conversion rate is only 2%. When the reaction time is extended to 2 hours later, the conversion rate is 31.12%, the selectivity is 77.46%, and the yield is 24.10%.

[0075] Comparative Example 4

[0076] This example provides a method for preparing 2-methyl-1,4-naphthoquinone. Compared with Example 1, the difference is that a microwave reactor is not used, and at the same time, the temperature is controlled at 100°C, and the rest is the same as in Example 1. After reacting for 9 minutes, the reaction conversion rate is only 5%. When the reaction time is extended to 2 hours later, the conversion rate is 56.31%, the selectivity is 74.69%, and the yield is 42.06%.

[0077] Comparative Example 5

[0078] This example provides a method for preparing 2-methyl-1,4-naphthoquinone. Compared with Example 1, the difference is that the catalyst is replaced with cobalt acetate with the same addition amount (i.e., 0.4 mol%), and the rest is the same as in Example 1. After reacting for 9 minutes, the conversion rate is only 43.6%, the selectivity is 80.96%, and the yield is 35.3%.

[0079] Comparative Example 6

[0080] This example provides a method for preparing 2-methyl-1,4-naphthoquinone. Compared with Example 1, the difference lies in that the catalyst is replaced with nickel chloride with the same addition amount (i.e., 0.4 mol%), and the rest is the same as in Example 1. After reacting for 9 minutes, the conversion rate is only 52.4%, the selectivity is 76.72%, and the yield is 40.2%.

[0081] The above examples are only for illustrating the technical concept and features of the present invention, and the purpose is to enable those skilled in the art to understand the content of the present invention and implement it accordingly. It should not be used to limit the protection scope of the present invention. Any equivalent changes or modifications made according to the spirit and essence of the present invention should be covered within the protection scope of the present invention.

[0082] In the ranges disclosed herein, the endpoints and any values are not limited to the exact ranges or values, and these ranges or values should be understood to include values close to these ranges or values. For numerical ranges, the endpoint values of each range, between the endpoint values of each range and individual point values, and between individual point values can be combined with each other to obtain one or more new numerical ranges, and these numerical ranges should be regarded as specifically disclosed herein.

Claims

1. A method for preparing 2-methyl-1,4-naphthoquinone, the preparation method comprising: The oxidative dehydrogenation reaction of 2-methyl-1,4-tetrahydronaphthoquinone is carried out in the presence of a catalyst and an oxidant to produce 2-methyl-1,4-naphthoquinone; It is characterized in that: It is controlled that the oxidative dehydrogenation reaction is also carried out in an organic solvent under microwave radiation conditions; The catalyst comprises a copper-based catalyst, and the oxidant comprises oxygen.

2. The preparation method of 2-methyl-1,4-naphthoquinone according to claim 1, characterized in that: The copper-based catalyst is a copper salt.

3. The preparation method of 2-methyl-1,4-naphthoquinone according to claim 2, characterized in that: The copper salt is a combination of one or more selected from copper bromide, copper chloride, copper acetate, copper sulfate and copper nitrate.

4. The preparation method of 2-methyl-1,4-naphthoquinone according to claim 1, characterized in that: The molar feeding ratio of the copper-based catalyst to the 2-methyl-1,4-tetrahydronaphthoquinone is 0.001-0.005∶1, further 0.002-0.0045∶1.

5. The preparation method of 2-methyl-1,4-naphthoquinone according to claim 1, characterized in that: The oxidant is provided by introducing an oxygen-containing gas mixture or pure oxygen gas with a purity of greater than or equal to 99% into the reaction system.

6. The preparation method of 2-methyl-1,4-naphthoquinone according to claim 1, characterized in that: The molar input amount of the oxygen is more than 1.1 times the molar amount of the 2-methyl-1,4-tetrahydronaphthoquinone, further 1.2-2 times.

7. The preparation method of 2-methyl-1,4-naphthoquinone according to claim 1, wherein: The microwave power under the microwave radiation conditions is 50-180W, further 90-150W, and still further 100-110W.

8. The preparation method of 2-methyl-1,4-naphthoquinone according to claim 1 or 7, characterized in that: The radiation time under the microwave radiation conditions is 1-25min, further 5-15min, and still further 8-10min.

9. The preparation method of 2-methyl-1,4-naphthoquinone according to claim 1, characterized in that: The organic solvent is a combination of one or more selected from toluene, acetonitrile, ethyl acetate and dichloroethane; and / or, the feeding mass ratio of the organic solvent to the 2-methyl-1,4-tetrahydronaphthoquinone is 1-6∶1.

10. The preparation method of 2-methyl-1,4-naphthoquinone according to claim 1, characterized in that: The implementation method for preparing the 2-methyl-1,4-naphthoquinone includes: adding 2-methyl-1,4-tetrahydronaphthoquinone, an organic solvent and a catalyst into a reaction vessel, sealing, replacing with nitrogen for multiple times, then introducing oxygen into the reaction vessel, and then carrying out microwave radiation and reaction to produce the 2-methyl-1,4-naphthoquinone.

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