A preparation process of Grignard alcohol

Abstract

The present invention discloses a preparation process of Grignard alcohol, which uses magnesium and methyl chloride as reaction raw materials, tetrahydrofuran as a solvent, and iodine crystals as an initiator. The Grignard reaction is carried out under nitrogen to generate a Grignard reagent, and then the Grignard reagent reacts with p-chlorobenzophenone by an addition reaction to generate Grignard alcohol. The magnesium includes pre-treated magnesium powder and magnesium strips. By simultaneously using magnesium powder and magnesium strips with specific mass ratios and size ratios and pre-treating them, the present invention can ensure the stable progress of the reaction and improve the reaction yield; in addition, by carrying out the treatment of removing water and peroxides from tetrahydrofuran, while ensuring the process safety, the yield of the Grignard alcohol product can be further improved.

Description

Technical Field

[0001] The present invention belongs to the technical field of the chemical industry, and particularly relates to a preparation process of Grignard alcohol. Background Art

[0002] Grignard alcohol, chemically named p-chlorodiphenylethanol, is a light yellow liquid in appearance; generally, the content is required to exceed 90%; molecular formula: ClC6H4COC6H5. As a main chemical intermediate in the synthesis of the raw material of statastine hydrochloride, the quality of Grignard alcohol directly affects the synthesis quality of statastine hydrochloride and the yield of the finished product.

[0003] In the Grignard reaction, most of the magnesium used is a single magnesium (magnesium powder, magnesium strip or magnesium shavings). Because of the small particle size and large surface area of magnesium powder or magnesium shavings, once initiated in the Grignard reaction, it is very difficult to control. And the reaction rate of a single magnesium strip is relatively slow due to the small contact area.

[0004] The invention patent CN200710051865.0 discloses a preparation process of Grignard alcohol, which uses magnesium and monochloromethane as reaction raw materials, tetrahydrofuran as a solvent, and iodine crystal as an initiator. The Grignard reaction is carried out under a nitrogen atmosphere to generate a Grignard reagent, and then the Grignard reagent reacts with p-chlorobenzophenone by an addition reaction to generate Grignard alcohol. This patent solves the problems in the previous process that when using bromobenzene and magnesium for the Grignard reaction, the addition reaction between the two liquids is too violent, the reaction is not easy to control, and the cost is relatively high. Bromobenzene has adverse factors such as carcinogenicity, teratogenicity and mutagenicity. However, this patent has the following problems: the Grignard reaction process in this patent belongs to the reaction of gaseous monochloromethane passing into the solvent and reacting with magnesium. When the reaction rate is too fast or too slow, it will lead to difficult control of the input amount of gaseous monochloromethane. When the input rate and consumption rate of monochloromethane in the reaction kettle do not match, side reactions and raw material waste are likely to occur. And the Grignard reaction in this application is not initiated by external heating, but is naturally initiated by monochloromethane. Therefore, the speed of the reaction also directly affects the stability of the reaction temperature. Obviously, simply using magnesium powder in this patent is difficult to maintain the balance and stability of the Grignard reaction rate.

[0005] Therefore, it is necessary to reasonably control the size of magnesium to control the initiation rate and make it in a dynamic equilibrium state.

[0006] Other existing technologies also have the following problems: (1) Most existing methods for removing magnesium oxide film use acid leaching, which is not environmentally friendly and the residual acid solution is difficult to handle. (2) The existing dehydration treatment of tetrahydrofuran (relative density 0.89) generally uses common desiccants (such as potassium carbonate, sodium hydroxide) or molecular sieves for pre-drying, and then adds sodium or calcium hydride for reflux treatment. However, this operation uses flammable and explosive items (sodium and calcium hydride), which is extremely dangerous and needs to be improved. In addition, the existing technology uses safe anhydrous calcium chloride (density 2.1g / cm 3 ) replaces the flammable substance calcium hydride (density 1.7g / cm 3 ) When refluxed, anhydrous calcium chloride is deposited at the bottom and easily boils violently. (3) When sodium hydroxide is used to remove peroxides from existing tetrahydrofuran, if the peroxide content is high, sodium hydroxide is prone to produce violent reactions, which is not conducive to the removal of peroxides and also poses a safety hazard.

[0007] In summary, how to provide a preparation process for Grignard alcohol by reasonably controlling the size of magnesium and the pretreatment method, and safely removing water from tetrahydrofuran and removing peroxides is an urgent problem to be solved. Summary of the invention

[0008] The object of the present invention is to provide a preparation process of Grignard alcohol, which can ensure stable reaction and improve reaction yield by using magnesium powder and magnesium bars with specific mass ratio and size ratio at the same time and pretreating them; in addition, by removing water from tetrahydrofuran and removing peroxide, the Grignard alcohol product yield can be further improved while ensuring process safety.

[0009] The scheme of the present invention is achieved in this way:

[0010] A preparation process of Grignard alcohol, which uses magnesium and methyl chloride as reaction raw materials, tetrahydrofuran as solvent, and iodine crystal as initiator, performs Grignard reaction under nitrogen flow to generate Grignard reagent, and then generates Grignard alcohol by addition reaction of Grignard reagent and p-chlorobenzophenone, which specifically comprises the following steps:

[0011] (1) Add 0.9 kg of magnesium, 0.006 kg of iodine crystals, and 1500 mL of tetrahydrofuran into a reaction kettle under nitrogen flow, stir gently, and maintain the flow time for not less than 3 minutes, then turn off the nitrogen and stirring.

[0012] (2) Methyl chloride was introduced into the reaction kettle to initiate the reaction at room temperature. Heat was released in the kettle. When the temperature reached above 60°C and a large number of bubbles were observed, indicating that the reaction was successfully initiated, the methyl chloride was turned off, the stirring speed was increased, 5250 mL of tetrahydrofuran was added, and the reaction was cooled to 50°C-60°C. Methyl chloride was continued to be introduced for reaction.

[0013] (3) When there is almost no magnesium left in the reaction flask and the reaction temperature drops significantly, the Grignard reaction ends. Stop passing chloromethane and pass nitrogen for protection. Continue stirring for 10 minutes to obtain the Grignard reagent.

[0014] (4) Weigh 5.62 kg of 4-chlorobenzophenone and add it to another reaction kettle. Then add 4500 mL of tetrahydrofuran and stir for 10 minutes.

[0015] (5) Drop the Grignard reagent after the reaction into the mixed solution of 4-chlorobenzophenone, and control the dropping temperature below 60 °C.

[0016] (6) After the dropping is completed, wash the bottle wall once with 750 mL of tetrahydrofuran, and then drop the washed reagent into the reaction solution. Start heating to 50 °C and control the temperature at 50 °C - 55 °C for a constant-temperature reflux reaction for more than 2 hours. After the reaction is complete, cool down to below 25 °C for the next operation.

[0017] (7) During the above constant-temperature reaction process, slowly drop 2.7 kg (1500 ml) of concentrated sulfuric acid into a bucket filled with 10 kg of crushed ice and stir continuously.

[0018] (8) Drop the reaction solution in step (6) into the diluted sulfuric acid solution in step (7) and stir continuously for a hydrolysis reaction for 30 minutes. The temperature of the reaction solution shall not exceed 50 °C.

[0019] (9) Let it stand for cooling and stratification. Take the upper organic phase and wash the organic phase with a saturated sodium bicarbonate solution prepared with 4.5 kg of sodium bicarbonate. Then stratify and take the upper organic phase for vacuum distillation.

[0020] (10) Install the vacuum device, pour the upper organic phase after washing and stratification into a four-necked flask for vacuum distillation. Control the vacuum pressure at -0.08 MPa. Distill until there are no bubbles and no boiling phenomenon, and end the distillation to obtain a yellow-green Grignard alcohol liquid (4-chlorodiphenyl ethanol).

[0021] Among them, the magnesium includes pre-treated magnesium powder and magnesium strips with a mass ratio of 1:(0.2 - 0.5). The feeding rate of chloromethane in the Grignard reaction in step (2) is (0.2 - 0.3)*X mol / h, where X is the molar mass of magnesium.

[0022] The pre-treatment method of the magnesium powder and magnesium strips includes the following steps:

[0023] Put magnesium powder with a mesh size of 20 - 60 into a sealed pulverizer, and intermittently stir and pulverize it 2 - 4 times at a rotation speed of 3000 - 4000 r / min, with each stirring and pulverizing for 10 - 25 s and an intermittent time of 15 - 30 s. Then screen the pulverized magnesium powder; Take magnesium strips, polish them with sandpaper until the surface is shiny, and cut them into small magnesium strips; Place the screened magnesium powder and small magnesium strips into a sealed mixer, add anhydrous Lewis acid, and stir for 8 - 12 h under nitrogen flow and at 2000 - 3000 r / min. That's it.

[0024] Further, the particle size distribution of the screened magnesium powder is as follows: the mass proportion of particles with a particle size of 100 - 200 μm is 5 - 10%, the mass proportion of particles with a particle size of 50 - 99 μm is 26 - 45%, the mass proportion of particles with a particle size of 10 - 49 μm is 20 - 40%, and the rest are particles with a particle size < 10 μm.

[0025] The size distribution of the small magnesium strips is as follows: the mass proportion of those with a size of (6 mm - 12 mm) * (2 mm - 4 mm) is 8 - 14%, the mass proportion of those with a size of (3 mm - 5 mm) * (0.5 mm - 1 mm) is 14 - 28%, and the rest are (0.5 mm - 2 mm) * (0.2 mm - 0.4 mm).

[0026] Further, the anhydrous Lewis acid is lutetium trifluoromethanesulfonate, and its addition amount is 0.3 - 0.5% of the total mass of the magnesium powder and magnesium strips.

[0027] The tetrahydrofuran used in the present invention is treated for water removal as follows:

[0028] Add anhydrous calcium chloride to the tetrahydrofuran raw material, let it stand for 1 - 3 days for preliminary water removal, then take out the pre - dehydrated tetrahydrofuran, add supported calcium chloride and the indicator benzophenone, and carry out a reflux stirring reaction (300 - 500 r / min) under nitrogen protection. When the reaction solution turns blue, it meets the anhydrous requirement.

[0029] The preparation method of the supported calcium chloride includes the following steps:

[0030] S1. Pumice pretreatment: Immerse pumice (1 - 3 mm) in a sodium carbonate solution for 2 - 4 h, filter out the solution, wash it with deionized water until neutral, then place it in an organic acid solution, stir for 3 - 5 h, filter, wash it with deionized water until neutral, and dry it;

[0031] S2. Prepare a calcium chloride solution, then immerse the pretreated pumice in the calcium chloride solution for 4 - 6 h, filter out the solution, wash it with deionized water, and then place it in a muffle furnace at 300 - 320 °C and dry it until the mass no longer decreases, thus obtaining the supported calcium chloride.

[0032] Further, the addition amounts of the anhydrous calcium chloride, supported calcium chloride, and the indicator benzophenone are respectively 5-10%, 3-5%, and 0.01-0.03% of the mass of the tetrahydrofuran raw material.

[0033] Further, in the step S1, the mass ratio of pumice to the sodium carbonate solution and the organic acid solution is 1:(12-25):(10-20), the mass concentration of the sodium carbonate solution is 15-25%, and the mass concentration of the organic acid solution is 8-20%;

[0034] In the step S2, the mass ratio of the pretreated pumice to the calcium chloride solution is 1:(15-25), and the mass concentration of the calcium chloride solution is 20-40%.

[0035] Further, the organic acid is furan-2,3,4,5-tetracarboxylic acid.

[0036] Before the water treatment of tetrahydrofuran, it is also necessary to conduct peroxide inspection and removal on the tetrahydrofuran.

[0037] The peroxide inspection method is as follows: Take 5 ml of the tetrahydrofuran reagent to be detected, mix it with an equal volume of a 2% KI solution by mass concentration, add 3-5 drops of a 5% dilute hydrochloric acid by mass concentration, and shake it together. If it can make the starch solution turn purple or blue, it proves the existence of peroxides.

[0038] Removal of peroxides: Add porous caustic soda to the tetrahydrofuran, stir for 2-5 h, and then filter off the porous caustic soda.

[0039] The preparation method of the porous caustic soda is as follows:

[0040] Mix the caustic soda and the additive evenly, then dry-press (under a pressure of 20-30 tons) into a shape, place it at 320-350 °C for sintering for 1-3 h, then cool it to room temperature, then wash it with dichloromethane, and then dry it to obtain the porous caustic soda; the additive includes ammonium bicarbonate and a reactive silane compound with a mass ratio of 1:(0.5-1), and the boiling point of the reactive silane compound is higher than 320-350 °C.

[0041] Further, the addition amount of the porous caustic soda is 3-5% of the mass of the tetrahydrofuran, and the additive is 3-5% of the mass of the caustic soda.

[0042] Further, the reactive silane compound is allyltriphenylsilane.

[0043] The beneficial effects of the present invention are:

[0044] 1. In the present invention, magnesium powder and magnesium strips with specific mass ratios and size ratios are simultaneously used, which can ensure that the initiation of magnesium in the Grignard reaction matches the consumption of methyl chloride, maintaining a dynamic equilibrium state, stable system temperature, and a fast and stable reaction rate. The reaction is more gentle and safe, and the yield of the Grignard alcohol product is significantly improved.

[0045] 2. The magnesium powder and magnesium strips in the present invention are pretreated. Through intermittent pulverization of the magnesium powder and polishing of the magnesium strips, combined with subsequent high-speed mixing, the oxide film on the surface can be quickly removed, and magnesium powder and magnesium strips with specific sizes can be obtained simultaneously, improving the effect of the Grignard reaction and making the subsequent reaction more complete.

[0046] 3. When the magnesium powder and magnesium strips are pretreated in the present invention, anhydrous Lewis acid is also added, which can promote the reaction activity of the subsequent addition reaction of the Grignard reagent and p-chlorobenzophenone and improve the yield. In addition, the anhydrous Lewis acid in the present invention is further selected as anhydrous lutetium trifluoromethanesulfonate, which not only plays an antioxidant role during the pretreatment process, but also can ensure that on the basis of further removing the oxide film, the destruction of the specific sizes of the magnesium powder and magnesium strips is reduced, maintaining their stable size forms. And anhydrous lutetium trifluoromethanesulfonate has strong selectivity for the subsequent addition reaction, and can significantly reduce the residue of p-chlorobenzophenone in the product Grignard alcohol.

[0047] 4. When the present invention treats tetrahydrofuran to remove water, anhydrous calcium chloride is mainly used. This raw material is inexpensive, environmentally friendly, and not prone to safety hazards. In the water treatment process, the present invention first pre-removes water with anhydrous calcium chloride, and then uses anhydrous calcium chloride supported on pumice to remove water. The pumice has a relatively small specific gravity, and after loading calcium chloride, it can solve the problem that anhydrous calcium chloride deposited at the bottom is prone to violent boiling.

[0048] 5. When the present invention prepares the supported calcium chloride, the pumice is also treated with sodium carbonate and pretreated with organic acid to remove impurities on the surface or in the pores of the pumice that affect the adsorption capacity, which can improve the loading amount of calcium chloride.

[0049] The organic acid in the present invention is further selected as furan-2,3,4,5-tetracarboxylic acid. Since the pumice is softened by the alkali treatment of sodium carbonate, when the pumice is further immersed in the acid solution, furan-2,3,4,5-tetracarboxylic acid can also expand and expand the pores of the pumice, reducing the bulk density of the pumice; in addition, the alkali treatment of sodium carbonate on the pumice also increases the roughness of the pumice, making it easier for calcium chloride to be loaded in the pumice; together, the loading amount of calcium chloride is effectively increased.

[0050] 6. If there are peroxides in tetrahydrofuran, it is easy to oxidize the lutetium trifluoromethanesulfonate added together with magnesium, weakening its effect, and there is a safety hazard of explosion during reflux in the subsequent water treatment of tetrahydrofuran due to the presence of peroxides. Therefore, the present invention also needs to pre-remove the peroxides in tetrahydrofuran.

[0051] The present invention uses porous sodium hydroxide flakes. A large number of pores are introduced into the sodium hydroxide flakes, enabling them to slowly and effectively remove peroxides in tetrahydrofuran, avoiding violent reactions, and being safe and effective.

[0052] 7. When preparing the porous sodium hydroxide flakes in the present invention, an additive is mixed with the sodium hydroxide flakes and then sintered at a high temperature, so that a large number of pores are obtained in the sodium hydroxide flakes. The additive of the present invention contains ammonium bicarbonate, which decomposes into carbon dioxide and ammonia under heating conditions to form pores. In addition, the additive also contains a reactive silane compound, which plays a role in increasing viscosity and enhancing the binding between ammonium bicarbonate and the sodium hydroxide flakes, facilitating the creation of uniform pores. After sintering and cooling, the reactive silane compound is removed by solvent washing to avoid affecting the composition of the porous sodium hydroxide flakes.

[0053] The reactive silane compound of the present invention is further selected as allyltriphenylsilane, which can further expand the pores on the basis of the pore formation by ammonium bicarbonate. Moreover, during the thermal decomposition process of ammonium bicarbonate, allyltriphenylsilane can also protect the pores and reduce the influence of decomposition products on the composition of the sodium hydroxide flakes. Specific Embodiments

[0054] The present invention will be further described below in conjunction with embodiments. Obviously, the described embodiments are only a part of the embodiments of the present invention, rather than all the embodiments. All other embodiments obtained by those of ordinary skill in the art based on the embodiments of the present invention without making creative efforts fall within the scope of protection of the present invention.

[0055] Embodiment 1

[0056] This embodiment provides a preparation process for Grignard alcohol, which specifically includes the following steps:

[0057] (1) Under a nitrogen atmosphere, 0.9 kg of magnesium, 0.006 kg of iodine crystals, and 1500 mL of tetrahydrofuran are added to the reaction kettle, and gently stirred. The ventilation time is maintained for not less than 3 minutes, and then the nitrogen and stirring are turned off.

[0058] (2) Chloromethane is introduced into the reaction kettle, and the reaction is initiated at room temperature. Heat is released inside the kettle. When the temperature reaches above 60 °C and there are a large number of bubbles, it proves that the reaction is successfully initiated. The chloromethane is turned off, the stirring speed is increased, 5250 mL of tetrahydrofuran is added, and the temperature is cooled to 50 °C - 60 °C. Then, chloromethane is continuously introduced for reaction.

[0059] (3) When almost no magnesium remains in the reaction flask and the reaction temperature significantly decreases, the Grignard reaction ends. The introduction of chloromethane is stopped, nitrogen is introduced for protection, and stirring is continued for 10 minutes to obtain the Grignard reagent.

[0060] (4) Weigh 5.62 kg of 4-chlorobenzophenone and add it to another reaction kettle. Then add 4500 mL of tetrahydrofuran and stir for 10 minutes.

[0061] (5) Drop the Grignard reagent after the reaction into the mixed solution of 4-chlorobenzophenone, and control the dropping temperature below 60 °C.

[0062] (6) After the dropping is completed, wash the bottle wall once with 750 mL of tetrahydrofuran, and then drop the washed reagent into the reaction solution. Start heating to 50 °C, and control the temperature at 50 °C - 55 °C for a constant temperature reflux reaction for more than 2 hours. After the reaction is complete, cool down to below 25 °C for the next operation.

[0063] (7) During the above constant temperature reaction process, slowly drop 2.7 kg (1500 ml) of concentrated sulfuric acid into a bucket filled with 10 kg of crushed ice, and stir continuously.

[0064] (8) Drop the reaction solution in step (6) into the sulfuric acid solution diluted in step (7), and stir continuously for a hydrolysis reaction for 30 minutes. The temperature of the reaction solution shall not exceed 50 °C.

[0065] (9) Let it stand for cooling and stratification. Take the upper organic phase, and prepare a saturated sodium bicarbonate solution with 4.5 kg of sodium bicarbonate to wash the organic phase. Then stratify, and take the upper organic phase for vacuum distillation.

[0066] (10) Install the vacuum device, pour the upper organic phase after washing and stratification into a four-necked flask for vacuum distillation. Control the vacuum pressure at -0.08 MPa. Distill until there are no bubbles and no boiling phenomenon, and end the distillation to obtain a yellow-green Grignard alcohol liquid (4-chlorodiphenylmethanol).

[0067] The reaction route is as follows:

[0068]

[0069] Among them, the magnesium includes pre-treated magnesium powder and magnesium strips with a mass ratio of 1:0.2, and the feeding rate of methyl chloride in the Grignard reaction is 7.5 mol / h.

[0070] The pre-treatment method of magnesium powder and magnesium strips includes the following steps:

[0071] Take 20-mesh magnesium powder and place it in a sealed pulverizer. Stir and crush it intermittently at a speed of 3000 r / min for 4 times, with each stirring and crushing for 10 s and an intermittent time of 15 s. Screen the crushed magnesium powder; the particle size distribution of the screened magnesium powder is as follows: the mass ratio of particles with a particle size of 100 - 200 μm is 5%, the mass ratio of particles with a particle size of 50 - 99 μm is 45%, the mass ratio of particles with a particle size of 10 - 49 μm is 20%, and the rest are particles with a particle size < 10 μm.

[0072] After polishing the magnesium strip with sandpaper until its surface is shiny, cut it into small magnesium strips. The size distribution is as follows: the mass ratio of (6mm - 12mm) * (2mm - 4mm) is 8%, the mass ratio of (3mm - 5mm) * (0.5mm - 1mm) is 28%, and the rest is (0.5mm - 2mm) * (0.2mm - 0.4mm).

[0073] Place the sieved magnesium powder and small magnesium strips in a sealed mixer, add anhydrous Lewis acid (lutetium trifluoromethanesulfonate) accounting for 0.3% of the total mass of the magnesium powder and magnesium strips, and stir for 12 h under nitrogen gas and at 2000 r / min to complete the pretreatment of the magnesium powder and magnesium strips.

[0074] Example 2

[0075] On the basis of Example 1, this example provides a preparation process of Grignard alcohol. Tetrahydrofuran is used after the following water treatment:

[0076] Add anhydrous calcium chloride to the tetrahydrofuran raw material, place it for 1 day for preliminary water removal, then take out the pre - dehydrated tetrahydrofuran, add supported calcium chloride and the indicator benzophenone, and carry out reflux stirring (300 r / min) reaction under nitrogen protection. The reaction solution reaches the anhydrous requirement until it turns blue. The addition amounts of anhydrous calcium chloride, supported calcium chloride, and the indicator benzophenone are 5%, 5%, and 0.01% of the mass of the tetrahydrofuran raw material respectively.

[0077] The preparation method of the supported calcium chloride includes the following steps:

[0078] S1. Pumice pretreatment: Immerse pumice (1 - 3mm) in a sodium carbonate solution with a mass concentration of 15% for 2 - 4 h, filter out the solution, wash it with deionized water until neutral, then place it in an organic acid (furan - 2,3,4,5 - tetracarboxylic acid) solution with a mass concentration of 8%, stir for 3 h, filter, wash it with deionized water until neutral, and dry. The mass ratio of pumice to the sodium carbonate solution and the organic acid solution is 1:25:20;

[0079] S2. Prepare a calcium chloride solution with a mass concentration of 20%, then immerse the pretreated pumice in 25 times the amount of the calcium chloride solution for 4 h, filter out the solution, wash it with deionized water, and then place it in a muffle furnace at 300 °C and dry until the mass no longer decreases to obtain the supported calcium chloride.

[0080] The rest is the same as in Example 1.

[0081] Example 3

[0082] Based on Example 2, this example provides a preparation process of Grignard alcohol. Before the water treatment of tetrahydrofuran, peroxide inspection and removal of tetrahydrofuran are also required.

[0083] The peroxide inspection method is as follows: Take 5 ml of the tetrahydrofuran reagent to be detected and mix it with an equal volume of a 2% KI solution by mass concentration. Add 3 - 5 drops of 5% dilute hydrochloric acid by mass concentration and shake it together. If it can make the starch solution turn purple or blue, it proves the existence of peroxide.

[0084] Removal of peroxide: Add porous caustic soda to tetrahydrofuran, stir for 2 h, and then filter off the porous caustic soda. The addition amount of porous caustic soda is 3% of the mass of tetrahydrofuran.

[0085] The preparation method of porous caustic soda is as follows:

[0086] Mix caustic soda evenly with an additive accounting for 3% of the mass of caustic soda, then dry press (under a pressure of 20 tons) into a shape, sinter at 320 °C for 3 h, then cool to room temperature, wash with dichloromethane, and then dry to obtain porous caustic soda; the additive includes ammonium bicarbonate and a reactive silane compound (allyltriphenylsilane) with a mass ratio of 1:0.5.

[0087] The rest is the same as in Example 2.

[0088] Example 4

[0089] This example provides a preparation process of Grignard alcohol. For the specific steps, refer to Example 1.

[0090] Among them, magnesium includes pre-treated magnesium powder and magnesium strips with a mass ratio of 1:0.35, and the feeding rate of methyl chloride in the Grignard reaction is 9.375 mol / h.

[0091] The pre-treatment method of magnesium powder and magnesium strips includes the following steps:

[0092] Take 40 - mesh magnesium powder and place it in a sealed crusher. Stir and crush it intermittently at a speed of 3500 r / min for 3 times, with each stirring and crushing for 15 s and an intermittent time of 20 s. Screen the crushed magnesium powder; the particle size distribution of the screened magnesium powder is as follows: the mass proportion of particles with a particle size of 100 - 200 μm is 7%, the mass proportion of particles with a particle size of 50 - 99 μm is 35%, the mass proportion of particles with a particle size of 10 - 49 μm is 30%, and the rest are particles with a particle size < 10 μm.

[0093] Take magnesium strips, polish them with sandpaper until the surface is bright, and then cut them into small magnesium strips. Their size distribution is as follows: the mass proportion of (6 mm - 12 mm) * (2 mm - 4 mm) is 11%, the mass proportion of (3 mm - 5 mm) * (0.5 mm - 1 mm) is 21%, and the rest are (0.5 mm - 2 mm) * (0.2 mm - 0.4 mm).

[0094] Place the sieved magnesium powder and small magnesium strips in a sealed blender, add anhydrous Lewis acid (lutetium trifluoromethanesulfonate) accounting for 0.4% of the total mass of the magnesium powder and magnesium strips, and stir for 10 h under nitrogen gas flow and at 2500 r / min to complete the pretreatment of the magnesium powder and magnesium strips.

[0095] Tetrahydrofuran is used after the following treatments:

[0096] A. Peroxide test: Take 5 ml of the tetrahydrofuran reagent to be detected, mix it with an equal volume of a 2% (mass concentration) KI solution, add 3 - 5 drops of 5% (mass concentration) dilute hydrochloric acid, and shake well. If it can make the starch solution turn purple or blue, it proves the existence of peroxides.

[0097] B. Removal of peroxides: Add porous sodium hydroxide flakes to tetrahydrofuran, stir for 3.5 h, and then filter off the porous sodium hydroxide flakes. The addition amount of the porous sodium hydroxide flakes is 4% of the mass of tetrahydrofuran.

[0098] The preparation method of the porous sodium hydroxide flakes is as follows:

[0099] Mix sodium hydroxide flakes evenly with an additive accounting for 4% of the mass of the sodium hydroxide flakes, then dry - press (under a pressure of 25 tons) into a mold, sinter at 335 °C for 2 h, then cool to room temperature, wash with dichloromethane, and then dry to obtain the porous sodium hydroxide flakes; the additive includes ammonium bicarbonate and a reactive silane compound (allyltriphenylsilane) with a mass ratio of 1:0.75.

[0100] C. Dewatering treatment: Add anhydrous calcium chloride to the tetrahydrofuran raw material, place it for 2 days for preliminary dewatering, then take out the pre - dewatered tetrahydrofuran, add supported calcium chloride and the indicator benzophenone, and carry out a reflux stirring (400 r / min) reaction under nitrogen protection. The reaction solution reaches the anhydrous requirement when it turns blue. The addition amounts of anhydrous calcium chloride, supported calcium chloride, and the indicator benzophenone are 7.5%, 4%, and 0.02% of the mass of the tetrahydrofuran raw material, respectively.

[0101] The preparation method of the supported calcium chloride includes the following steps:

[0102] S1. Pumice pretreatment: Immerse pumice (1 - 3 mm) in a 20% (mass concentration) sodium carbonate solution for 3 h, filter off the solution, wash with deionized water until neutral, then place it in a 14% (mass concentration) organic acid (furan - 2,3,4,5 - tetracarboxylic acid) solution, stir for 4 h, filter, wash with deionized water until neutral, and dry; the mass ratio of pumice to the sodium carbonate solution and the organic acid solution is 1:18:15;

[0103] S2. Prepare a calcium chloride solution, then place the pretreated pumice stone in 20 times the amount of the calcium chloride solution (mass concentration is 30%) and soak for 5 h. Filter out the solution, wash it with deionized water, and then place it in a muffle furnace at 310 °C and dry until the mass no longer decreases, thus obtaining the supported calcium chloride.

[0104] The rest is the same as in Example 3.

[0105] Example 5

[0106] This example provides a preparation process of Grignard alcohol. For the specific steps, refer to Example 1.

[0107] Among them, the magnesium includes pretreated magnesium powder and magnesium strips with a mass ratio of 1:0.5, and the feeding rate of methyl chloride in the Grignard reaction is 11.25 mol / h.

[0108] The pretreatment method of the magnesium powder and magnesium strips includes the following steps:

[0109] Take 60-mesh magnesium powder and place it in a sealed crusher. Stir and crush it intermittently at a speed of 4000 r / min for 2 times, with each stirring and crushing for 25 s and the intermittent time being 30 s. Screen the crushed magnesium powder; the particle size distribution of the screened magnesium powder is: the mass proportion of particles with a particle size of 100 - 200 μm is 10%, the mass proportion of particles with a particle size of 50 - 99 μm is 26%, the mass proportion of particles with a particle size of 10 - 49 μm is 40%, and the rest are particles with a particle size < 10 μm.

[0110] Take magnesium strips, polish them with sandpaper until the surface is shiny, and then cut them into small magnesium strips. Their size distribution is: the mass proportion of (6 mm - 12 mm) * (2 mm - 4 mm) is 14%, the mass proportion of (3 mm - 5 mm) * (0.5 mm - 1 mm) is 14%, and the rest are (0.5 mm - 2 mm) * (0.2 mm - 0.4 mm).

[0111] Place the screened magnesium powder and small magnesium strips in a sealed mixer, add 0.5% of anhydrous Lewis acid (lutetium trifluoromethanesulfonate) based on the total mass of the magnesium powder and magnesium strips, and stir for 8 h under the conditions of nitrogen passing and 3000 r / min, thus completing the pretreatment of the magnesium powder and magnesium strips.

[0112] Tetrahydrofuran is used after the following treatment:

[0113] A. Peroxide inspection: Take 5 ml of the tetrahydrofuran reagent to be detected, mix it with an equal volume of 2% KI solution by mass concentration, add 3 - 5 drops of 5% dilute hydrochloric acid by mass concentration and shake it together. If it can make the starch solution turn purple or blue, it proves the existence of peroxides.

[0114] B. Removal of peroxides: Add porous sodium hydroxide to tetrahydrofuran, stir for 5 h, and then filter out the porous sodium hydroxide. The addition amount of the porous sodium hydroxide is 5% of the mass of tetrahydrofuran.

[0115] The preparation method of porous sodium hydroxide flakes is as follows:

[0116] Mix sodium hydroxide flakes evenly with an additive accounting for 5% of the mass of sodium hydroxide flakes, then dry-press (under a pressure of 30 tons) into shape, sinter at 350 °C for 1 h, then cool to room temperature, then wash with dichloromethane, and then dry to obtain porous sodium hydroxide flakes; the additive includes ammonium bicarbonate and a reactive silane compound (allyltriphenylsilane) with a mass ratio of 1:1.

[0117] C. Water treatment: Add anhydrous calcium chloride to the tetrahydrofuran raw material, place it for 3 days for preliminary water removal, then take out the pre-dehydrated tetrahydrofuran, add supported calcium chloride and the indicator benzophenone, and carry out a reflux stirring (500 r / min) reaction under nitrogen protection. The reaction solution reaches the anhydrous requirement until it turns blue. The addition amounts of anhydrous calcium chloride, supported calcium chloride, and the indicator benzophenone are 10%, 3%, and 0.03% of the mass of the tetrahydrofuran raw material respectively.

[0118] The preparation method of supported calcium chloride includes the following steps:

[0119] S1. Pumice pretreatment: Immerse pumice (1 - 3 mm) in a sodium carbonate solution with a mass concentration of 25% for 4 h, filter out the solution, wash with deionized water until neutral, then place it in an organic acid (furan-2,3,4,5-tetracarboxylic acid) solution with a mass concentration of 20%, stir for 5 h, filter, wash with deionized water until neutral, and dry; the mass ratio of pumice to the sodium carbonate solution and the organic acid solution is 1:12:10;

[0120] S2. Prepare a calcium chloride solution with a mass concentration of 40%, then immerse the pretreated pumice in 15 times the amount of the calcium chloride solution for 6 h, filter out the solution, wash with deionized water, and then dry in a muffle furnace at 320 °C until the mass no longer decreases to obtain the supported calcium chloride.

[0121] The rest is the same as in Example 3.

[0122] Comparative Example 1

[0123] The difference between this comparative example and Example 1 is that the magnesium powder and magnesium strips are not pretreated.

[0124] Comparative Example 2

[0125] The difference between this comparative example and Example 1 is that all the magnesium is pretreated magnesium powder.

[0126] Comparative Example 3

[0127] The difference between this comparative example and Example 1 is that all the magnesium is pretreated magnesium strips.

[0128] Comparative Example 4

[0129] The difference between this comparative example and Example 1 is that the magnesium powder is not sieved during the pretreatment of the magnesium powder and magnesium strips.

[0130] Comparative Example 5

[0131] The difference between this comparative example and Example 1 is that the magnesium strips are not cut into pieces and classified during the pretreatment of the magnesium powder and magnesium strips.

[0132] Comparative Example 6

[0133] The difference between this comparative example and Example 1 is that during the pretreatment of the magnesium powder and magnesium strips, the particle size distribution of the sieved magnesium powder is such that the mass percentage of particles with a particle size of 50 - 99 μm is 45%, the mass percentage of particles with a particle size of 10 - 49 μm is 20%, and the rest have a particle size < 10 μm.

[0134] Comparative Example 7

[0135] The difference between this comparative example and Example 1 is that during the pretreatment of the magnesium powder and magnesium strips, the particle size distribution of the sieved magnesium powder is such that the mass percentage of particles with a particle size of 100 - 200 μm is 5%, the mass percentage of particles with a particle size of 10 - 49 μm is 20%, and the rest have a particle size < 10 μm.

[0136] Comparative Example 8

[0137] The difference between this comparative example and Example 1 is that during the pretreatment of the magnesium powder and magnesium strips, the particle size distribution of the sieved magnesium powder is such that the mass percentage of particles with a particle size of 100 - 200 μm is 5%, the mass percentage of particles with a particle size of 50 - 99 μm is 45%, and the rest have a particle size < 10 μm.

[0138] Comparative Example 9

[0139] The difference between this comparative example and Example 1 is that during the pretreatment of the magnesium powder and magnesium strips, the particle size distribution of the sieved magnesium powder is such that the mass percentage of particles with a particle size of 100 - 200 μm is 5%, the mass percentage of particles with a particle size of 50 - 99 μm is 45%, and the rest have a particle size of 10 - 49 μm.

[0140] Comparative Example 10

[0141] The difference between this comparative example and Example 1 is that during the pretreatment of the magnesium powder and magnesium strips, the size distribution of the small magnesium strips is: the mass percentage of (3 mm - 5 mm) * (0.5 mm - 1 mm) is 28%, and the rest are (0.5 mm - 2 mm) * (0.2 mm - 0.4 mm).

[0142] Comparative Example 11

[0143] The difference between this comparative example and Example 1 is that during the pretreatment of magnesium powder and magnesium strips, the size distribution of the small magnesium strips is as follows: the mass ratio of (6 mm - 12 mm) * (2 mm - 4 mm) is 8%, and the rest is (0.5 mm - 2 mm) * (0.2 mm - 0.4 mm).

[0144] Comparative Example 12

[0145] The difference between this comparative example and Example 1 is that during the pretreatment of magnesium powder and magnesium strips, the size distribution of the small magnesium strips is as follows: the mass ratio of (6 mm - 12 mm) * (2 mm - 4 mm) is 8%, and the rest is (3 mm - 5 mm) * (0.5 mm - 1 mm).

[0146] Comparative Example 13

[0147] The difference between this comparative example and Example 1 is that during the pretreatment of magnesium powder and magnesium strips, no anhydrous Lewis acid is added.

[0148] Comparative Example 14

[0149] The difference between this comparative example and Example 1 is that during the pretreatment of magnesium powder and magnesium strips, the anhydrous Lewis acid is changed to aluminum chloride.

[0150] Comparative Example 15

[0151] The difference between this comparative example and Example 2 is that during the treatment of tetrahydrofuran with water removal, the supported calcium chloride is replaced with ordinary calcium chloride.

[0152] Comparative Example 16

[0153] The difference between this comparative example and Example 2 is that the pumice in the supported calcium chloride is replaced with 13X molecular sieve.

[0154] Comparative Example 17

[0155] The difference between this comparative example and Example 2 is that the preparation method of the supported calcium chloride does not include step S1.

[0156] Comparative Example 18

[0157] The difference between this comparative example and Example 2 is that in step S1 of the preparation method of the supported calcium chloride, the pumice is not immersed in the sodium carbonate solution.

[0158] Comparative Example 19

[0159] The difference between this comparative example and Example 2 is that in step S1 of the preparation method of the supported calcium chloride, the pumice is not immersed in the organic acid solution.

[0160] Comparative Example 20

[0161] The difference between this comparative example and Example 2 lies in that in step S1 of the preparation method of the supported calcium chloride, the organic acid solution is an oxalic acid solution.

[0162] Comparative Example 21

[0163] The difference between this comparative example and Example 3 is that when removing peroxides from tetrahydrofuran, the porous flake caustic soda is changed to ordinary flake caustic soda.

[0164] Comparative Example 22

[0165] The difference between this comparative example and Example 3 is that the additive in the preparation of the porous flake caustic soda does not contain a reactive silane compound.

[0166] Comparative Example 23

[0167] The difference between this comparative example and Example 3 is that the reactive silane compound in the preparation of the porous flake caustic soda is octadecylsilane.

[0168] I. Reaction Yield of Preparing Grignard Alcohol in the Present Invention

[0169] Prepare Grignard alcohol according to the methods of Examples 1 - 5 and Comparative Examples 1 - 14 of the present invention, and calculate the total reaction yield. The results are shown in Table 1 below.

[0170] Table 1

[0171]

[0172]

[0173] As can be seen from Table 1, the yields of Grignard alcohol in Examples 1 - 5 of the present invention are extremely high, all reaching over 93%, especially the yields in Examples 3 - 5 are relatively better, reaching over 99.0%.

[0174] Compared with Example 1, in Comparative Examples 1 - 14, the type of magnesium and the pretreatment method are changed, and as a result, the yields are all reduced, indicating that using the magnesium powder and magnesium strip with the specific mass ratio and size ratio of the present invention, as well as the pretreatment method, can significantly improve the yield of the Grignard alcohol product.

[0175] II. Dehydration Effect of Tetrahydrofuran in the Present Invention

[0176] Carry out dehydration treatment on tetrahydrofuran according to the methods of Example 2 and Comparative Examples 15 - 20 of the present invention. The results are shown in Table 2 below.

[0177] Table 2

[0178]

[0179]

[0180] As can be seen from Table 2, compared with the comparative examples, in Example 2 of the present invention, the supported calcium chloride has a better water removal effect on tetrahydrofuran, reducing the water content of tetrahydrofuran to 30 ppm. Moreover, the loading amount of the supported calcium chloride reaches 258 mg / g, the reaction is mild, there is no bumping, and the process is safe.

[0181] Compared with Example 2, in Comparative Examples 15-20, the raw material for water removal of tetrahydrofuran and the preparation method of the supported calcium chloride were changed, resulting in a decrease in the loading amount of the supported calcium chloride and a significant decrease in the water removal effect. There were also varying degrees of bumping.

[0182] III. Peroxide Removal Effect of Tetrahydrofuran of the Present Invention

[0183] The peroxide removal treatment of tetrahydrofuran was carried out according to the methods of Example 3 of the present invention and Comparative Examples 21-23, and the results are shown in Table 3 below.

[0184] Table 3

[0185]

[0186]

[0187] As can be seen from Table 3, compared with the comparative examples, in Example 3 of the present invention, the porous sodium hydroxide has a better peroxide removal effect on tetrahydrofuran. After treatment, the peroxide content is as low as 0.001%, and the reaction is mild, the temperature rises steadily and remains unchanged after 30 min, and the reaction is relatively safe.

[0188] Compared with Example 3, in Comparative Examples 21-23, the type and preparation of the porous sodium hydroxide were changed, resulting in a decrease in the peroxide removal effect and varying degrees of severity in the reaction.

[0189] It should be noted that the above are only specific embodiments of the present invention and are not intended to limit the present invention. Any modifications, equivalent substitutions, improvements, etc. made within the spirit and principles of the present invention shall be included within the protection scope of the present invention.

Claims

1. A preparation process of Grignard alcohol, which uses magnesium and methyl chloride as reaction raw materials, tetrahydrofuran as a solvent, and iodine crystals as an initiator, and conducts a Grignard reaction under a nitrogen atmosphere to generate a Grignard reagent, and then generates Grignard alcohol through an addition reaction of the Grignard reagent and p-chlorobenzophenone, characterized in that: The magnesium includes pre-treated magnesium powder and magnesium strips with a mass ratio of 1:(0.2 - 0.5), and the feeding rate of methyl chloride in the Grignard reaction is (0.2 - 0.3) X mol / h, where X is the molar mass of magnesium. The pretreatment method of the magnesium powder and magnesium strip comprises the following steps: Put magnesium powder with a mesh size of 20-60 into a sealed crusher, intermittently stir and crush it at a rotation speed of 3000-4000 r / min for 2-4 times, stir and crush for 10-25 s each time, with an intermittent time of 15-30 s, and screen the crushed magnesium powder; Take magnesium strips, polish them with sandpaper until the surface is bright, and cut them into small magnesium strips; Put the screened magnesium powder and small magnesium strips into a sealed mixer, add anhydrous Lewis acid, and stir for 8-12 h under the conditions of nitrogen passing and 2000-3000 r / min; The anhydrous Lewis acid is lutetium trifluoromethanesulfonate, and its addition amount is 0.3-0.5% of the total mass of the magnesium powder and magnesium strip.

2. The preparation process of the Grignard alcohol according to claim 1, characterized in that: The particle size distribution of the screened magnesium powder is as follows: the mass ratio of particles with a particle size of 100-200 µm is 5-10%, the mass ratio of particles with a particle size of 50-99 µm is 26-45%, the mass ratio of particles with a particle size of 10-49 µm is 20-40%, and the rest are particles with a particle size <10 µm; The size distribution of the small magnesium strips is: (6 mm - 12 mm) (2 mm - 4 mm) accounts for 8 - 14% by mass, (3 mm - 5 mm) (0.5 mm - 1 mm) accounts for 14 - 28% by mass, and the rest is (0.5 mm - 2 mm) (0.2 mm - 0.4 mm).

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