阅读说明：本技术 一种1-四氢萘酮的制备方法 (Preparation method of 1-tetralone ) 是由 张世界 南云 余志勤 于 2020-11-13 设计创作，主要内容包括：本发明提供一种1-四氢萘酮的制备方法,包括：雷尼镍催化下,反应温度为170～250℃,反应压力为3.0～5.0Mpa,1-萘酚与氢气发生加氢反应,得含有1-四氢萘酮的混合物。本发明的制备方法,采用廉价的1-萘酚与氢气进行加氢反应,通过控制加氢反应温度,有效减少了加氢反应的主要产物种类,降低了目标产物的分离难度。之后根据加氢反应后混合物中各物质的性质,依次采用多次碱洗和水洗,最后精馏的方式分离出纯度较高的目标产物1-四氢萘酮。本发明的制备方法,工艺简单,操作方便,加氢反应转化率高,反应过程无废水产生,原料和加工成本低。(The invention provides a preparation method of 1-tetralone, which comprises the following steps: under the catalysis of Raney nickel, the reaction temperature is 170-250 ℃, the reaction pressure is 3.0-5.0 Mpa, and the 1-naphthol and the hydrogen undergo hydrogenation reaction to obtain a mixture containing 1-tetralone. The preparation method of the invention adopts cheap 1-naphthol and hydrogen to carry out hydrogenation reaction, and effectively reduces the main product types of the hydrogenation reaction and the separation difficulty of the target product by controlling the hydrogenation reaction temperature. Then, according to the properties of all substances in the mixture after the hydrogenation reaction, sequentially adopting multiple times of alkali washing and water washing, and finally separating out the target product 1-tetralone with higher purity in a rectification mode. The preparation method has the advantages of simple process, convenient operation, high hydrogenation conversion rate, no wastewater generation in the reaction process and low raw material and processing cost.)

1. A method for preparing 1-tetralone, which is characterized by comprising the following steps:

under the catalysis of Raney nickel, the reaction temperature is 170-250 ℃, the reaction pressure is 3.0-5.0 Mpa, 1-naphthol and hydrogen are subjected to hydrogenation reaction to obtain a mixture containing 1-tetralone, and the 1-tetralone is obtained through post-treatment.

2. The process for producing 1-tetralone according to claim 1, wherein the hydrogenation reaction is carried out in a solvent-free state.

3. The method according to claim 1, wherein the hydrogenation is carried out in an organic solvent.

4. The method according to claim 3, wherein the organic solvent is one or a mixture of toluene and xylene.

5. The method according to claim 3, wherein the mass-to-volume ratio of the 1-naphthol to the organic solvent is (0.25 to 1) g/ml.

6. The method according to claim 1, wherein the hydrogenation reaction time is 7 to 20 hours.

7. The method for producing 1-tetralone according to claim 1, wherein the mass ratio of raney nickel to 1-naphthol is (0.01 to 0.05): 1.

8. the method for preparing 1-tetralone according to claim 7, wherein the mass ratio of raney nickel to 1-naphthol is (0.01-0.03): 1.

9. the method according to claim 1, wherein the hydrogenation reaction temperature is 200 to 250 ℃.

10. The process for producing 1-tetralone according to claim 1, wherein the post-treatment is carried out by the following steps:

and (3) carrying out alkali washing on the mixture containing the 1-tetralone, and then rectifying to obtain the 1-tetralone.

Technical Field

The invention belongs to the technical field of medicines, and particularly relates to a preparation method of 1-tetralone.

Background

The 1-tetralone is mainly used for synthesizing 18-methylnorethindrone (contraceptive) and rodenticide intermediates, and is also an important intermediate for synthesizing benazepril. In addition, it can be used as a solvent and a softener for plastics. The prior tetralone production methods mainly comprise four methods:

1. tetrahydronaphthalene oxidation process

The method adopts a chromium acetate and 2-methyl-5-ethylpyridine composite catalyst, and is prepared by adding oxygen for oxidation, and has the main problems of low single-pass conversion rate and easy generation of impurities such as 2-tetralone and the like.

2. Obtained by condensation of gamma-butyrolactone with benzene

The method has the main problem of producing a large amount of aluminum trichloride wastewater by treating aluminum trichloride.

3. Cyclization of gamma-phenylbutyric acid is carried out at 90 deg.C under action of phosphoric acid/phosphoric anhydride, polyphosphoric acid, hydrofluoric acid or concentrated sulfuric acid to obtain 1-tetralone.

The preparation method mainly has the advantages that the raw material gamma-phenylbutyric acid is expensive, the cost is high, and a large amount of waste water is generated.

4. The product is obtained by dehydrochlorination and cyclization in the presence of anhydrous aluminum trichloride or anhydrous stannic chloride by using a gamma-phenylbutyryl chloride cyclization method.

The preparation method mainly has the advantages that the raw material gamma-phenylbutyryl chloride is expensive and high in cost, and a large amount of aluminum trichloride wastewater or stannic chloride wastewater is generated.

Meanwhile, in the case of preparing 5,6,7, 8-tetrahydro-1-naphthol (2) by reducing 1-naphthol (1) with an aluminum-nickel alloy, the results different from the literature were obtained in the case of the document (Zhang Jinglei et al: re-study of the reaction of reducing 1-naphthol with an aluminum-nickel alloy, organic chemistry, 2008, volume 28, phase 4, 723 to 726) that a large amount of 3, 4-dihydro-2H-naphthalen-1-one (3) and 1,2,3, 4-tetrahydro-1-naphthol (4) were unexpectedly obtained in addition to a small amount of 2:

the yield of the 1-tetralone (namely 3, 4-dihydro-2H-naphthalene-1-ketone (3)) is 37-48%, the obtained compounds 2-4 need to be separated by column chromatography, on one hand, the yield is not ideal, and industrial mass production cannot be realized by adopting column chromatography. In addition, the boiling points of the compound 3 and the compound 4 in the product are relatively close, and the target product (3) cannot be completely separated by a simple distillation method.

In conclusion, the preparation method of 1-tetralone in the prior art has the problems of low conversion rate and purity, high raw material cost, large amount of waste water, high treatment difficulty, high cost and the like.

Disclosure of Invention

In order to solve the problems in the prior art, the invention provides a preparation method of 1-tetralone, which has the advantages of high conversion rate and purity, low raw material cost, no generation of a large amount of waste water in the preparation process and low production cost.

According to the method disclosed by the document, 1-tetralone and 1,2,3, 4-tetrahydro-1-naphthol are synthesized in the synthesis process of preparing 5,6,7, 8-tetrahydro-1-naphthol by using 1-naphthol in a Raney nickel catalyst, and the method for preparing 1-tetralone is obtained under multiple experiments.

A method for preparing 1-tetralone, comprising:

under the catalysis of Raney nickel, the reaction temperature is 170-250 ℃, the reaction pressure is 3.0-5.0 Mpa, 1-naphthol and hydrogen are subjected to hydrogenation reaction to obtain a mixture containing 1-tetralone, and the 1-tetralone is obtained through post-treatment.

In general, in the hydrogenation reaction of 1-naphthol, the main products of the reaction are (1)5, 6,7, 8-tetrahydronaphthalene-1-phenol, (2) 1-tetralone and (3)1, 2,3, 4-tetrahydronaphthalene-1-phenol, and the specific reaction process is as follows:

under various conditions, these several products coexist only in different proportions. In further experiments it was found that the product (2) is further converted into (3) and the product (3) is further converted into tetrahydronaphthalene (4), even under extreme conditions, the other ring on the naphthalene is further subjected to ring opening hydrogenation.

When the reaction temperature is lower than 150 ℃, the product (3) is dominant, the product (4) is less, when the reaction temperature is increased to 150-170 ℃, most of the product (3) is converted into the product (4), and when the reaction temperature is higher than 170 ℃, most of the product (3) is less and most of the product (4) exists.

Unreacted 1-naphthol may also exist in the mixture after the hydrogenation reaction, and because the boiling points of the 1-naphthol and the products (2), (3) and (4) are relatively close, the target product (2) cannot be completely separated by a simple rectification method.

The preparation method comprises the steps of controlling the hydrogenation reaction temperature to be 170-250 ℃, completely converting a product (3) into a product (4), performing alkali washing on the mixture by utilizing the characteristic that the product (1) and unreacted raw material 1-naphthol are dissolved in a certain amount of alkali, separating the raw material 1-naphthol and the product (1) from the mixture, and further rectifying to separate a pure target product (2), namely 1-tetralone, wherein the purity of the product is more than 98%.

In the step (1):

preferably, the hydrogenation reaction is carried out in a solvent-free state, and in this case, the 1-naphthol serves as both the reaction product and the solvent, thereby further reducing the difficulty in recovering the subsequent solvent.

The hydrogenation reaction can also be carried out in an organic solvent, and the organic solvent is preferably one or a mixture of toluene and xylene; further preferred is toluene. The mass volume ratio of the 1-naphthol to the organic solvent is (0.25-1) g/ml; more preferably (0.25-0.5) g/ml; still more preferably 0.25 g/ml.

Preferably, the hydrogenation reaction temperature is 200-250 ℃, so that the product (3) is converted into the product (4) as completely as possible.

Preferably, the hydrogenation reaction is carried out in the pressure kettle, and nitrogen is introduced for replacement for 2-5 times before hydrogen is introduced, so that air in the pressure kettle is removed, and the efficiency of the hydrogenation reaction is improved.

Preferably, the hydrogenation reaction time is 7-20 hours.

Preferably, the mass ratio of the Raney nickel to the 1-naphthol is (0.01-0.05): 1; more preferably (0.01 to 0.03): 1.

particularly preferably, the operation process of the step (1) is as follows:

dissolving 1-naphthol in a solvent, adding the solution into a pressure kettle, adding a catalyst, and introducing nitrogen for replacement for 2-5 times; and then introducing hydrogen to the pressure of 3.0-4.0 MPa, heating to 170-250 ℃, controlling the pressure to be 3-5 MPa, and carrying out hydrogenation reaction for 7-20 hours to obtain a mixture containing 1-tetralone.

Preferably, the post-treatment is performed by the following steps:

and (3) carrying out alkali washing on the mixture containing the 1-tetralone, and then rectifying to obtain the 1-tetralone. In the post-treatment process, multiple alkali washing is needed, preferably 2-5 times.

Compared with the prior art, the invention has the beneficial effects that:

the preparation method of the invention adopts cheap 1-naphthol and hydrogen to carry out hydrogenation reaction, and effectively reduces the main product types of the hydrogenation reaction and the separation difficulty of the target product by controlling the hydrogenation reaction temperature. Then, according to the properties of all substances in the mixture after the hydrogenation reaction, sequentially adopting multiple times of alkali washing and finally separating out the target product 1-tetralone with higher purity in a rectification mode. The preparation method has the advantages of simple process, convenient operation, high hydrogenation conversion rate, no wastewater generation in the reaction process and low raw material and processing cost.

Drawings

FIG. 1 is a nuclear magnetic hydrogen spectrum of 1-tetralone prepared in example 1 of the present invention.

Detailed Description

Example 1:

dissolving 100 g of 1-naphthol in 400ml of toluene in a pressure kettle, adding 2.5 g of raney nickel catalyst, replacing 3 times with nitrogen, then filling hydrogen to 3.0MPa, starting to raise the temperature to 235-240 ℃, then carrying out hydrogenation reaction for 10 hours under the pressure of 4.0-4.3 MPa, then cooling to normal temperature, detecting the content of a crude product by GC, wherein the product is 9.883%, the product is 11.973%, the raw material is 5.228%, the product is 71.768%, then carrying out alkali washing for 4 times, and rectifying to obtain 67% (the yield calculated by the molar weight of 1-naphthol, and the like in other examples) of the product 1-tetralone with the purity of 98.5%, and the nuclear magnetic data are shown in figure 1.

Example 2:

adding 400 g of 1-naphthol and 11 g of Raney nickel catalyst into a pressure kettle, replacing with nitrogen for 3 times, then filling hydrogen to the pressure of 3.0MPa, starting to heat to 200-205 ℃, then carrying out hydrogenation reaction for 8 hours under the pressure of 3.0-4.0 MPa, then cooling to normal temperature, detecting the content of a crude product GC, carrying out alkali washing on a product (4) 8.349%, a product (1) 7.459%, a raw material 5.082% and a product (2) 78.089%, and then rectifying to obtain the product 1-tetralone with the yield of 72%, wherein the purity is 98.0%.

Example 3:

dissolving 100 g of 1-naphthol in 400ml of toluene in a pressure kettle, adding 1.0 g of raney nickel catalyst, replacing 3 times with nitrogen, then filling hydrogen to 3.0MPa, starting to heat to 235-240 ℃, then carrying out hydrogenation reaction for 20 hours under the pressure of 4.0-5.0 MPa, then cooling to normal temperature, detecting the content of a crude product GC, carrying out alkali washing for 4 times, rectifying to obtain a product 1-tetralone with the yield of 70%, wherein the purity is 98.3%, and the product (4) is 9.687%, the product (1) is 7.221%, the raw material is 6.719%, and the product (2) is 75.024%.

Comparative example:

dissolving 100 g of 1-naphthol in 400ml of toluene, adding 10 g of Raney nickel catalyst, replacing 3 times with nitrogen, filling hydrogen, carrying out hydrogenation reaction for 7 hours at 200 ℃ under the pressure of 3.0-3.5 MPa, then cooling to normal temperature, and detecting the content of a crude product by GC (gas chromatography), wherein the product (2) is not detected.

As can be seen from comparative example 1, when the amount of the catalyst added is too large, the target product 1-tetralone is further converted into other by-products, and the final target product cannot be obtained.

In summary, the following steps: adding 1-4 times of toluene or no solvent into 1-naphthol, adding 0.01-0.03 times of Raney nickel catalyst, reacting for 7-20 hours at 200-250 ℃ under the pressure of 3.0-5.0 MPa of hydrogen to generate 1-tetralone with the conversion rate of 70-80%, and rectifying to obtain the 1-tetralone with the yield of 65-73%.