阅读说明：本技术 一种3,3,3-三氟丙醇的制备方法 (Preparation method of 3,3, 3-trifluoropropanol ) 是由 王瑞英 段琦 魏刚 王永千 燕东 崔传博 于 2021-08-19 设计创作，主要内容包括：本申请公开了一种3,3,3-三氟丙醇的制备方法,属于有机合成领域,其包括以下步骤：(1)在引发剂的作用下,氯三氟乙烷和镁在极性溶剂中反应制备得到格氏试剂CF-(3)CH-(2)MgCl溶液；(2)格氏试剂CF-(3)CH-(2)MgCl溶液与甲醛在极性溶剂中反应得到CF-(3)CH-(2)CH-(2)OMgCl溶液；所述极性溶剂不包括水；(3)向CF-(3)CH-(2)CH-(2)OMgCl溶液中加入酸,水解制备得到3,3,3-三氟丙醇。该方法是以氯三氟乙烷为原料,制备3,3,3-三氟丙醇,制备原料便宜易得,成本低,且制备工艺安全,反应条件温和,该制备方法3,3,3-三氟丙醇的收率高、副产物少,且溶剂可回收利用。(The application discloses a preparation method of 3,3, 3-trifluoropropanol, belonging to the field of organic synthesis and comprising the following steps: (1) under the action of an initiator, chlorotrifluoroethane and magnesium react in a polar solvent to prepare a Grignard reagent CF 3 CH 2 A MgCl solution; (2) grignard reagent CF 3 CH 2 Reacting MgCl solution with formaldehyde in polar solvent to obtain CF 3 CH 2 CH 2 OMgCl solution; the polar solvent does not include water; (3) to CF 3 CH 2 CH 2 And adding acid into the OMgCl solution, and hydrolyzing to obtain the 3,3, 3-trifluoropropanol. The method takes chlorotrifluoroethane as a raw material to prepare the 3,3, 3-trifluoropropanol, the preparation raw material is cheap and easy to obtain, the cost is low, the preparation process is safe, the reaction condition is mild, the preparation method has high yield of the 3,3, 3-trifluoropropanol and few byproducts,and the solvent can be recycled.)

1. A preparation method of 3,3, 3-trifluoropropanol is characterized by comprising the following steps:

(1) under the action of an initiator, chlorotrifluoroethane and magnesium react in a polar solvent to prepare a Grignard reagent CF₃CH₂A MgCl solution;

(2) grignard reagent CF₃CH₂Reacting MgCl solution with formaldehyde in polar solvent to obtain CF₃CH₂CH₂OMgCl solution; the polar solvent does not include water;

(3) to CF₃CH₂CH₂And adding an acidic solution into the OMgCl solution, and hydrolyzing to obtain the 3,3, 3-trifluoropropanol.

2. The method according to claim 1, wherein the initiator is at least one or more of iodine, bromine, methyl iodide, ethyl bromide, ethylene dibromide, and ethyl orthosilicate.

3. The method according to claim 2, wherein the polar solvent is at least one or more selected from the group consisting of diethyl ether, tetrahydrofuran, methyltetrahydrofuran, toluene, N-methylmorpholine, N-dimethylaniline and pyridine.

4. The method according to claim 3, wherein the polar solvent comprises tetrahydrofuran, toluene and N-methylmorpholine in a volume ratio of (6-8): 1-2.

5. The production method according to claim 4, wherein the mass of the polar solvent in the step (1) is 3 to 20 times that of the chlorotrifluoroethane.

6. The method according to claim 5, wherein the mass of the polar solvent in the step (2) is 0.5 to 5 times that of the formaldehyde.

7. The method according to claim 6, wherein the acidic solution is at least one or more of hydrochloric acid, sulfuric acid, nitric acid, acetic acid, and formic acid.

8. The method of claim 7, comprising the steps of:

(1) adding magnesium, a polar solvent and an initiator into a reaction vessel under the protection of nitrogen, dropwise adding a mixed solution of chlorotrifluoroethane and the polar solvent into the reaction vessel, stirring and refluxing for 1-3h to prepare a Grignard reagent CF₃CH₂A MgCl solution;

(2) dropwise adding the mixed solution of formaldehyde and a polar solvent into the prepared Grignard reagent CF₃CH₂Stirring and refluxing the MgCl mixed solution for 1-2h to prepare the CF₃CH₂CH₂OMgCl solution;

(3) to the prepared CF₃CH₂CH₂And adding an acidic solution into the OMgCl solution, stirring for reacting for 1-2h, and hydrolyzing to obtain the 3,3, 3-trifluoropropanol.

9. The process according to claim 8, wherein the reaction temperature of the stirring reflux in the step (1) is 10 to 30 ℃ and the reaction pressure is 0 to 0.2 MPa.

10. The process according to claim 9, wherein the reaction temperature of the stirring reflux in the step (2) is 20 to 50 ℃ and the reaction pressure is 0 to 0.1 MPa.

Technical Field

The application relates to a preparation method of 3,3, 3-trifluoropropanol, belonging to the field of organic synthesis.

Background

Fluorine-containing alcohols are compounds formed by replacing a hydrogen atom on a carbon in an organic alcohol with a fluorine atom. Compared with organic alcohol, the molecular structure of the fluorine-containing alcohol compound shows unique physical and chemical properties and physiological activity due to the existence of C-F bonds. 3,3, 3-trifluoro propanol is one of the fluorine-containing alcohols, is an important trifluoromethyl building block, can be used as an intermediate for synthesizing medicines and pesticides, can also be used as a raw material or an intermediate for synthesizing high-performance materials, and has wide application prospect.

The literature Chemical Communications (Cambridge, United Kingdom), (4), 386-387; 2002, reports a method for synthesizing 3,3, 3-trifluoropropanol by reacting 3,3, 3-trifluoropropene with dichloroborane, but the conditions are very harsh, the reaction needs to be carried out at about-70 ℃, and the operation safety is low.

U.S. Pat. Nos. 5777184 and 6111139 disclose the synthesis of esters by reaction of 1-chloro-3, 3, 3-trifluoropropene with an alcohol followed by hydrolysis to 3,3, 3-trifluoropropanol. In the method, the 1-chloro-3, 3, 3-trifluoropropene is expensive, relatively unstable and easy to polymerize.

Chinese patent CN201110244835 discloses a method for preparing 3,3, 3-trifluoropropanol by using 3,3, 3-trifluoropropionaldehyde as a raw material and performing high-pressure hydrogenation reduction under the action of a Raney Ni catalyst. Although the method has high yield, the raw material is expensive, the operational safety of the hydrogenation process is low, and the overall industrial application prospect is poor.

Chinese patents CN201210286304 and CN201210286302 and CN201210286343 and CN201210286371 respectively report that 2-bromo-3, 3, 3-trifluoropropene is used as a raw material to firstly generate 3,3, 3-trifluoropropenyl methyl ether, and then the 3,3, 3-trifluoropropenyl methyl ether is subjected to high-pressure hydrogenation under the action of inorganic ester or organic ester and Raney Ni catalyst to prepare the 3,3, 3-trifluoropropanol. However, the method has the advantages of expensive and not easily available raw materials, low operational safety of the hydrogenation process and low total yield (50-60%) of the two-step reaction.

Chinese patent CN201510750757 discloses a method for preparing 3,3, 3-trifluoropropanol by using 3,3, 3-trifluoropropene as a starting material, firstly generating an intermediate product 2-bromo-3, 3, 3-trifluoropropanol, and then performing a pressurized reaction on the 2-bromo-3, 3, 3-trifluoropropanol under the action of a solvent, a catalyst and an acid-binding agent to obtain the 3,3, 3-trifluoropropanol, wherein the yield is 85.7%. The method has the advantages of expensive and easily-obtained raw materials and high reaction pressure, and a large amount of waste organic solvents and acid-binding agents are generated in the preparation process, so that the method is not environment-friendly.

Disclosure of Invention

In order to solve the problems, the method for preparing the 3,3, 3-trifluoropropanol is provided, the method takes chlorotrifluoroethane as a raw material to prepare the 3,3, 3-trifluoropropanol, the preparation raw material is cheap and easy to obtain, the cost is low, the preparation process is safe, the reaction condition is mild, the yield of the 3,3, 3-trifluoropropanol is high, the byproducts are few, and the solvent can be recycled.

According to one aspect of the present application, there is provided a method for preparing 3,3, 3-trifluoropropanol, comprising the steps of:

(1) under the action of an initiator, chlorotrifluoroethane and magnesium react in a polar solvent to prepare a Grignard reagent CF₃CH₂A MgCl solution;

(2) grignard reagent CF₃CH₂Reacting MgCl solution with formaldehyde in polar solvent to obtain CF₃CH₂CH₂OMgCl solution; the polar solvent does not include water;

(3) to CF₃CH₂CH₂And adding an acidic solution into the OMgCl solution, and hydrolyzing to obtain the 3,3, 3-trifluoropropanol.

Preferably, the molar ratio of the magnesium to the chlorotrifluoroethane is (1.05-1.2): 1.

Preferably, the magnesium is magnesium strip, magnesium chip or magnesium powder. Most preferably, the magnesium is magnesium powder.

Optionally, the initiator is at least one or more of iodine, bromine, methyl iodide, ethyl bromide, ethylene dibromide, ethyl orthosilicate.

Preferably, the initiator is iodine.

Optionally, the polar solvent is at least one or more of diethyl ether, tetrahydrofuran, methyltetrahydrofuran, toluene, N-methylmorpholine, N-dimethylaniline, pyridine.

Optionally, the polar solvent consists of tetrahydrofuran, toluene and N-methylmorpholine, and the volume ratio of the tetrahydrofuran, the toluene and the N-methylmorpholine is (6-8): 1-2.

Optionally, the mass of the polar solvent in step (1) is 3-20 times that of the chlorotrifluoroethane.

Preferably, the mass of the polar solvent in the step (1) is 5 to 10 times that of the chlorotrifluoroethane.

Optionally, the mass of the polar solvent in the step (2) is 0.5-5 times of the mass of the formaldehyde.

Preferably, the mass of the polar solvent in the step (2) is 1 to 2 times that of the formaldehyde.

Optionally, the acidic solution is at least one or more of hydrochloric acid, sulfuric acid, nitric acid, acetic acid, and formic acid.

Preferably, the acidic solution is hydrochloric acid.

Alternatively, the method for preparing 3,3, 3-trifluoropropanol comprises the steps of:

(1) adding magnesium, a polar solvent and an initiator into a reaction vessel under the protection of nitrogen, dropwise adding a mixed solution of chlorotrifluoroethane and the polar solvent into the reaction vessel, stirring and refluxing for 1-3h to prepare a Grignard reagent CF₃CH₂A MgCl solution;

(2) dropwise adding the mixed solution of formaldehyde and a polar solvent into the prepared Grignard reagent CF₃CH₂Stirring and refluxing the mixture in the M gCl mixed solution for 1 to 2 hours to prepare CF₃CH₂CH₂OMgCl solution;

(3) to the prepared CF₃CH₂CH₂And adding an acidic solution into the OMgCl solution, stirring for reacting for 1-2h, and hydrolyzing to obtain the 3,3, 3-trifluoropropanol.

Optionally, the reaction temperature of stirring reflux in the step (1) is 10-30 ℃, and the reaction pressure is 0-0.2 MPa.

Optionally, the reaction temperature of the stirring reflux in the step (2) is 20-50 ℃, and the reaction pressure is 0-0.1 MPa.

In the present application, the "reaction vessel" is a reaction vessel.

Benefits of the present application include, but are not limited to:

1. according to the preparation method of the 3,3, 3-trifluoropropanol, the chlorotrifluoroethane is used as the raw material to prepare the 3,3, 3-trifluoropropanol, the preparation raw material is cheap and easy to obtain, the cost is low, the preparation process is safe, the reaction conditions are mild, the yield of the 3,3, 3-trifluoropropanol is high, the byproducts are few, and the solvent can be recycled.

2. According to the preparation method of 3,3, 3-trifluoropropanol of the application, chlorotrifluoroethane and magnesium react in a polar solvent by using an initiator, a magnesium atom is directly connected with carbon on a chlorine atom to form a polar covalent bond, the carbon on the chlorine atom is a negative end, MgCl is a positive end, thereby generating a Grignard reagent CF which can provide an electron cloud and has Lewis base property₃CH₂The MgCl solution provides nucleophilic groups for subsequent hydrolysis to generate alcohol so as to attack carbonyl carbon atoms on methanol, thereby realizing a new route for synthesizing 3,3, 3-trifluoropropanol.

3. According to the preparation method of the 3,3, 3-trifluoropropanol, the Grignard reagent CF is added₃CH₂Reacting MgCl solution with formaldehyde, using formaldehyde to ensure that a primary alcohol structure in 3,3, 3-trifluoropropanol is generated, combining positive charge Mg ions with carbonyl oxygen of the formaldehyde, attacking the carbonyl carbon atom of the formaldehyde by the other part of the Grignard reagent to form a transition state, generating alkoxide by single electron transfer, hydrolyzing MgCl groups by acid catalysis to obtain compounds of primary alcohol and magnesium, further obtaining the 3,3, 3-trifluoropropanol, fully combining the carbonyl oxygen of the formaldehyde with the Grignard reagent by limiting the dosage ratio of the polar solvent to the formaldehyde, improving the conversion rate of the alkoxide, and further improving the yield of the 3,3, 3-trifluoropropanol.

4. According to the preparation method of the 3,3, 3-trifluoropropanol, tetrahydrofuran, toluene and N-methylmorpholine are selected to form a polar solvent, the volume ratio of the tetrahydrofuran, the toluene and the N-methylmorpholine is limited, the reaction initiation difficulty is avoided, the nucleophilic addition reaction of the step (1) and the step (2) is easier to initiate, and the Grignard reagent CF is used for preparing the compound₃CH₂The MgCl solution can fully react with formaldehyde, and the polar solvent combination is more economical and safer, and the production cost is low.

5. According to the present applicationThe preparation method of 3,3, 3-trifluoropropanol of the present invention controls the reaction temperature and stirring time of step (2) to facilitate the nucleophilic reaction between formaldehyde and Grignard reagent, and to allow the reaction to proceed fully, and the reaction product CF₃CH₂CH₂OMgCl is not easy to decompose, and the yield of the 3,3, 3-trifluoropropanol prepared finally is high.

Detailed Description

The present application will be described in detail with reference to examples, but the present application is not limited to these examples.

Unless otherwise specified, the starting materials and catalysts in the examples of this application were purchased commercially, with the hydrochloric acid concentration being analytically pure and the seal agitator being model CJ, new chemicals machinery, wehai.

Example 1

The method specifically comprises the following steps:

(1) drying a reaction kettle provided with a sealed stirrer, a cooling pipe, a constant-pressure dropping funnel and a reflux condenser, adding 1.1mol of magnesium powder, 500ml of polar solvent (the volume ratio of the polar solvent is tetrahydrofuran: toluene: N-methylmorpholine: 6:2:2) and 0.5mol of iodine into the reaction kettle under the protection of nitrogen, dropwise adding a mixed solution of 1mol of chlorotrifluoroethane and 500ml of polar solvent (the volume ratio of the polar solvent is tetrahydrofuran: toluene: N-methylmorpholine: 6:2:2) into the reaction kettle, stirring and refluxing for 2 hours at 10 ℃ and 0.1MPa to prepare the Grignard reagent CF for reaction for 2 hours₃CH₂A MgCl solution;

(2) dropwise adding 1mol of mixed solution of formaldehyde and polar solvent into the Grignard reagent CF prepared in the step (1) by using a constant-pressure dropping funnel₃CH₂Dripping into MgCl mixed solution at a speed of 5ml/min, stirring and refluxing for 2h at 20 ℃ and 0.05MPa, wherein the stirring speed is 100r/min, and preparing to obtain CF₃CH₂CH₂OMgCl solution;

(3) to the CF prepared in step (2)₃CH₂CH₂Adding 2mol of hydrochloric acid into the OMgCl solution, stirring for reaction for 1.5h, and hydrolyzing to obtain 3,3, 3-trifluoropropanol;

(4) after the hydrolysis reaction is finished, rectifying the product to obtain 3,3, 3-trifluoropropanol, and weighing to calculate the yield.

Example 2

The method specifically comprises the following steps:

(1) drying a reaction kettle provided with a sealed stirrer, a cooling pipe, a constant-pressure dropping funnel and a reflux condenser, adding 1.05mol of magnesium powder, 500ml of polar solvent (the volume ratio of the polar solvent is tetrahydrofuran: toluene: N-methylmorpholine: 6:2:2) and 0.5mol of iodine into the reaction kettle under the protection of nitrogen, dropwise adding a mixed solution of 1mol of chlorotrifluoroethane and 500ml of polar solvent (the volume ratio of the polar solvent is tetrahydrofuran: toluene: N-methylmorpholine: 6:2:2) into the reaction kettle, stirring and refluxing for 2 hours at 20 ℃ and 0.05MPa to prepare the Grignard reagent CF₃CH₂A MgCl solution;

(2) dropwise adding 1mol of mixed solution of formaldehyde and polar solvent into the Grignard reagent CF prepared in the step (1) by using a constant-pressure dropping funnel₃CH₂Dripping into MgCl mixed solution at a speed of 5ml/min, stirring and refluxing for 2h at 30 ℃ and 0.05MPa, wherein the stirring speed is 100r/min, and preparing to obtain CF₃CH₂CH₂OMgCl solution;

(3) to the CF prepared in step (2)₃CH₂CH₂Adding 2.2mol of hydrochloric acid into the OMgCl solution, stirring for reaction for 1 hour, and hydrolyzing to obtain 3,3, 3-trifluoropropanol;

(4) after the hydrolysis reaction is finished, rectifying the product to obtain 3,3, 3-trifluoropropanol, and weighing to calculate the yield.

Example 3

The method specifically comprises the following steps:

(1) drying a reaction kettle provided with a sealed stirrer, a cooling pipe, a constant-pressure dropping funnel and a reflux condenser, adding 1.2mol of magnesium powder, 500ml of polar solvent (the volume ratio of the polar solvent is tetrahydrofuran: toluene: N-methylmorpholine: 6:2:2) and 0.5mol of iodine into the reaction kettle under the protection of nitrogen, dropwise adding a mixed solution of 1mol of chlorotrifluoroethane and 500ml of polar solvent (the volume ratio of the polar solvent is tetrahydrofuran: toluene: N-methylmorpholine: 6:2:2) into the reaction kettle, stirring and refluxing for 3 hours at 30 ℃ and 0.2MPa to prepare the Grignard reagent CF for reaction for 3 hours₃CH₂A MgCl solution;

(2) dropwise adding 1mol of mixed solution of formaldehyde and polar solvent into the Grignard reagent CF prepared in the step (1) by using a constant-pressure dropping funnel₃CH₂Dripping into MgCl mixed solution at a speed of 5ml/min, stirring and refluxing at 40 ℃ and 0.1MPa for 2h, wherein the stirring speed is 100r/min, and preparing to obtain CF₃CH₂CH₂OMgCl solution;

(3) to the CF prepared in step (2)₃CH₂CH₂Adding 2mol of hydrochloric acid into the OMgCl solution, stirring for reaction for 2 hours, and hydrolyzing to obtain 3,3, 3-trifluoropropanol;

(4) after the hydrolysis reaction is finished, rectifying the product to obtain 3,3, 3-trifluoropropanol, and weighing to calculate the yield.

Example 4

The method specifically comprises the following steps:

(1) drying a reaction kettle provided with a sealed stirrer, a cooling pipe, a constant-pressure dropping funnel and a reflux condenser, adding 1.1mol of magnesium powder, 500ml of polar solvent (the volume ratio of the polar solvent is tetrahydrofuran: toluene: N-methylmorpholine ═ 7:1.5:1.5) and 0.5mol of methyl iodide into the reaction kettle under the protection of nitrogen, dropwise adding a mixed solution of 1mol of chlorotrifluoroethane and 500ml of polar solvent (the volume ratio of the polar solvent is tetrahydrofuran: toluene: N-methylmorpholine ═ 7:1.5:1.5) into the reaction kettle, stirring and refluxing for 2 hours at 10 ℃ and 0.1MPa to prepare the Grignard reagent CF, wherein the Grignard reagent CF is prepared₃CH₂A MgCl solution;

(2) dropwise adding 1mol of mixed solution of formaldehyde and polar solvent into the Grignard reagent CF prepared in the step (1) by using a constant-pressure dropping funnel₃CH₂Dripping into MgCl mixed solution at a speed of 5ml/min, stirring and refluxing at 40 ℃ and 0MPa for 2h, wherein the stirring speed is 100r/min, and preparing to obtain CF₃CH₂CH₂OMgCl solution;

(3) to the CF prepared in step (2)₃CH₂CH₂Adding 2mol of hydrochloric acid into the OMgCl solution, stirring for reaction for 1.5h, and hydrolyzing to obtain 3,3, 3-trifluoropropanol;

(4) after the hydrolysis reaction is finished, rectifying the product to obtain 3,3, 3-trifluoropropanol, and weighing to calculate the yield.

Example 5

The method specifically comprises the following steps:

(1) drying a reaction kettle provided with a sealed stirrer, a cooling pipe, a constant-pressure dropping funnel and a reflux condenser, adding 1.1mol of magnesium powder, 500ml of polar solvent (the volume ratio of the polar solvent is tetrahydrofuran: toluene: N-methylmorpholine ═ 7:1.5:1.5) and 0.5mol of iodine into the reaction kettle under the protection of nitrogen, dropwise adding a mixed solution of 1mol of chlorotrifluoroethane and 500ml of polar solvent (the volume ratio of the polar solvent is tetrahydrofuran: toluene: N-methylmorpholine ═ 7:1.5:1.5) into the reaction kettle, stirring and refluxing for 2 hours at 20 ℃ and 0.1MPa to prepare the Grignard reagent CF, wherein the Grignard reagent CF is obtained₃CH₂A MgCl solution;

(2) dropwise adding 1mol of mixed solution of formaldehyde and polar solvent into the Grignard reagent CF prepared in the step (1) by using a constant-pressure dropping funnel₃CH₂Dripping into MgCl mixed solution at a speed of 5ml/min, stirring and refluxing for 2h at 20 ℃ and 0.05MPa, wherein the stirring speed is 100r/min, and preparing to obtain CF₃CH₂CH₂OMgCl solution;

(3) to the CF prepared in step (2)₃CH₂CH₂Adding 2mol of hydrochloric acid into the OMgCl solution, stirring for reaction for 1.5h, and hydrolyzing to obtain 3,3, 3-trifluoropropanol;

(4) after the hydrolysis reaction is finished, rectifying the product to obtain 3,3, 3-trifluoropropanol, and weighing to calculate the yield.

Example 6

The method specifically comprises the following steps:

(1) drying a reaction kettle provided with a sealed stirrer, a cooling pipe, a constant-pressure dropping funnel and a reflux condenser, adding 1.1mol of magnesium powder, 500ml of polar solvent (the volume ratio of the polar solvent is tetrahydrofuran: toluene: N-methylmorpholine ═ 7:1.5:1.5) and 0.5mol of bromine into the reaction kettle under the protection of nitrogen, dropwise adding a mixed solution of 1mol of chlorotrifluoroethane and 500ml of polar solvent (the volume ratio of the polar solvent is tetrahydrofuran: toluene: N-methylmorpholine ═ 7:1.5:1.5) into the reaction kettle, stirring and refluxing for 2 hours at 30 ℃ and 0.1MPa to prepare the Grignard reagent CF₃CH₂A MgCl solution;

(2) dropwise adding 1mol of mixed solution of formaldehyde and polar solvent into the Grignard reagent CF prepared in the step (1) by using a constant-pressure dropping funnel₃CH₂Dripping into MgCl mixed solution at a speed of 5ml/min, stirring and refluxing at 30 ℃ and 0.1MPa for 2h, wherein the stirring speed is 100r/min, and preparing to obtain CF₃CH₂CH₂OMgCl solution;

(3) to the CF prepared in step (2)₃CH₂CH₂Adding 2mol of hydrochloric acid into the OMgCl solution, stirring for reaction for 1.5h, and hydrolyzing to obtain 3,3, 3-trifluoropropanol;

(4) after the hydrolysis reaction is finished, rectifying the product to obtain 3,3, 3-trifluoropropanol, and weighing to calculate the yield.

Example 7

The method specifically comprises the following steps:

(1) drying a reaction kettle provided with a sealed stirrer, a cooling pipe, a constant-pressure dropping funnel and a reflux condenser, adding 1.1mol of magnesium powder, 500ml of polar solvent (the volume ratio of the polar solvent is tetrahydrofuran: toluene: N-methylmorpholine: 8:1:1) and 0.5mol of iodine into the reaction kettle under the protection of nitrogen, dropwise adding a mixed solution of 1mol of chlorotrifluoroethane and 500ml of polar solvent (the volume ratio of the polar solvent is tetrahydrofuran: toluene: N-methylmorpholine: 8:1:1) into the reaction kettle, stirring and refluxing for 2 hours at 10 ℃ and 0.1MPa to prepare the Grignard reagent CF for reaction for 2 hours₃CH₂A MgCl solution;

(2) dropwise adding 1mol of mixed solution of formaldehyde and polar solvent into the Grignard reagent CF prepared in the step (1) by using a constant-pressure dropping funnel₃CH₂Dripping into MgCl mixed solution at a speed of 5ml/min, stirring and refluxing for 2h at 30 ℃ and 0.05MPa, wherein the stirring speed is 100r/min, and preparing to obtain CF₃CH₂CH₂OMgCl solution;

(3) to the CF prepared in step (2)₃CH₂CH₂Adding 2mol of hydrochloric acid into the OMgCl solution, stirring for reaction for 1.5h, and hydrolyzing to obtain 3,3, 3-trifluoropropanol;

(4) after the hydrolysis reaction is finished, rectifying the product to obtain 3,3, 3-trifluoropropanol, and weighing to calculate the yield.

Example 8

The method specifically comprises the following steps:

(1) drying a reaction kettle provided with a sealed stirrer, a cooling pipe, a constant-pressure dropping funnel and a reflux condenser, adding 1.1mol of magnesium powder, 500ml of polar solvent (the volume ratio of the polar solvent is tetrahydrofuran: toluene: N-methylmorpholine: 8:1:1) and 0.5mol of bromoethane into the reaction kettle under the protection of nitrogen, dropwise adding a mixed solution of 1mol of chlorotrifluoroethane and 500ml of polar solvent (the volume ratio of the polar solvent is tetrahydrofuran: toluene: N-methylmorpholine: 8:1:1) into the reaction kettle, stirring and refluxing for 2 hours at 20 ℃ and 0.1MPa to prepare the Grignard reagent CF₃CH₂A MgCl solution;

(2) dropwise adding 1mol of mixed solution of formaldehyde and polar solvent into the Grignard reagent CF prepared in the step (1) by using a constant-pressure dropping funnel₃CH₂Dripping into MgCl mixed solution at a speed of 5ml/min, stirring and refluxing for 2h at 40 ℃ and 0.05MPa, wherein the stirring speed is 100r/min, and preparing to obtain CF₃CH₂CH₂OMgCl solution;

(3) to the CF prepared in step (2)₃CH₂CH₂Adding 2mol of hydrochloric acid into the OMgCl solution, stirring for reaction for 1.5h, and hydrolyzing to obtain 3,3, 3-trifluoropropanol;

(4) after the hydrolysis reaction is finished, rectifying the product to obtain 3,3, 3-trifluoropropanol, and weighing to calculate the yield.

Example 9

The method specifically comprises the following steps:

(1) drying a reaction kettle provided with a sealed stirrer, a cooling pipe, a constant-pressure dropping funnel and a reflux condenser, adding 1.1mol of magnesium powder, 500ml of polar solvent (the volume ratio of the polar solvent is tetrahydrofuran: toluene: N-methylmorpholine: 8:1:1) and 0.5mol of ethyl orthosilicate into the reaction kettle under the protection of nitrogen, dropwise adding a mixed solution of 1mol of chlorotrifluoroethane and 500ml of polar solvent (the volume ratio of the polar solvent is tetrahydrofuran: toluene: N-methylmorpholine: 8:1:1) into the reaction kettle, stirring and refluxing for 2 hours at 30 ℃ and 0.1MPa, and preparing the GerberReagent CF₃CH₂A MgCl solution;

(2) dropwise adding 1mol of mixed solution of formaldehyde and polar solvent into the Grignard reagent CF prepared in the step (1) by using a constant-pressure dropping funnel₃CH₂Dripping into MgCl mixed solution at a speed of 5ml/min, stirring and refluxing at 20 ℃ and 0.1MPa for 2h, wherein the stirring speed is 100r/min, and preparing to obtain CF₃CH₂CH₂OMgCl solution;

(3) to the CF prepared in step (2)₃CH₂CH₂Adding 2mol of hydrochloric acid into the OMgCl solution, stirring for reaction for 1.5h, and hydrolyzing to obtain 3,3, 3-trifluoropropanol;

(4) after the hydrolysis reaction is finished, rectifying the product to obtain 3,3, 3-trifluoropropanol, and weighing to calculate the yield.

Comparative example 1

Comparative example 1 the 1,1, 1-trifluorotrichloroethane was used in the step (1), and the conditions for the other steps and the amounts of the respective substances were the same as those in example 1.

Comparative example 2

Comparative example 2 the conditions of the metallic zinc used in the step (1), other steps, the amounts of the respective substances, and the like were the same as those in example 1.

Comparative example 3

Comparative example 3 the conditions for n-butyraldehyde used in step (2), other steps and the amounts of substances were the same as those in example 1.

Comparative example 4

Comparative example 4 the initiator used in step (1) was azobisisobutyronitrile, and the conditions for the other steps and the amounts of the substances were the same as those in example 1.

Comparative example 5

In comparative example 5, the composition of the polar solvent was tetrahydrofuran and N, N-dimethylformamide in a volume ratio of 8:2, and the other steps and the amounts of the substances were the same as those in example 1.

Comparative example 6

In comparative example 6, the volume ratio of the polar solvent is tetrahydrofuran: toluene: n-methylmorpholine: 3:1:3, and the other steps and the amounts of the substances were the same as in example 1.

Comparative example 7

In the step (2) of the comparative example 7, the reaction was carried out for 3.5 hours under reflux with stirring at 90 ℃ under the same conditions as those in the example 1 for the other steps and the amounts of the respective substances.

Comparative example 8

In comparative example 8, the reaction temperature in step (1) was 80 ℃ and the conditions of the other steps and the amounts of the respective substances were the same as those in example 1.

Example 103, 3, 3-Trifluoropropanol yield calculation

The final products of examples 1 to 9 and comparative examples 1 to 8 were weighed to calculate the yield, and the results are shown in Table 1.

TABLE 1 Experimental characterization results of examples and comparative examples

The results show that the yields of 3,3, 3-trifluoropropanol in examples 1-9 using the preparation method defined in the present application are all above 85%, wherein the yields in examples 7-9 are all above 90%, and a high yield of 3,3, 3-trifluoropropanol and a mild reaction condition of the synthetic route are achieved.

1,1, 1-trifluorotrichloroethane used in step (1) of comparative example 1, which caused difficulty in initiating the reaction, 2-dichloro-3, 3, 3-trifluoropropanol was finally produced by hydrolysis, and the yield of 3,3, 3-trifluoropropanol was finally 0.

The metal zinc used in the step (1) in the comparative example 2 is not a grignard reagent prepared in the step (1), and the initiation reaction is difficult, and the subsequent steps cannot realize nucleophilic addition reaction of formaldehyde and cannot hydrolyze to generate 3,3, 3-trifluoropropanol, and finally the yield of the 3,3, 3-trifluoropropanol is 0.

Comparative example 3 the nucleophilic addition reaction of n-butyraldehyde used in step (2) finally yielded a product having a secondary alcohol structure, which was not 3,3, 3-trifluoropropanol, and the yield of 3,3, 3-trifluoropropanol was 0 finally.

In comparative example 4, azobisisobutyronitrile was used as the initiator in step (1), the reaction in step (1) was difficult to initiate, and CF was formed₃CH₂MgCl was less, and the final yield of 3,3, 3-trifluoropropanol was 34.8%, which was very low.

In comparative example 5, the composition of the polar solvent was tetrahydrofuran and N, N-dimethylformamide in a volume ratio of 8:2, and the selection of the polar solvent affected the initiation of the reaction and the formation of the product, resulting in a yield of 46.6% of 3,3, 3-trifluoropropanol, which was low.

In comparative example 6, the volume ratio of the polar solvent is tetrahydrofuran: toluene: the ratio of N-methylmorpholine to tetrahydrofuran to N-methylmorpholine was low, the nucleophilic reaction was not sufficient, and the final yield of 3,3, 3-trifluoropropanol was 51.7%, which was low.

In the step (2) of the comparative example 7, the reaction was performed for 3.5 hours under stirring and refluxing at 90 ℃ for a long period of time at a high temperature to form CF₃CH₂CH₂The OMgCl partially decomposed and the final 3,3, 3-trifluoropropanol yield was 54.2%, which was low.

Comparative example 8 in step (1) the reaction temperature was 80 ℃ and the temperature was higher, the Grignard reagent CF was prepared₃CH₂The MgCl solution was unstable with a final yield of 61.1% and not high.

In conclusion, according to the preparation method of 3,3, 3-trifluoropropanol, the chlorotrifluoroethane is used as the raw material, the Grignard reagent is used for nucleophilic reaction and hydrolysis reaction, and various reaction substances and conditions are limited to prepare the 3,3, 3-trifluoropropanol, so that the process is safe, the reaction conditions are mild, the yield of the 3,3, 3-trifluoropropanol is high, the byproducts are few, the solvent can be recycled, the preparation raw material is cheap and easy to obtain, and the cost is low.

The above are merely examples of the present application, and the scope of the present application is not limited by these specific examples, but is defined by the claims of the present application. Various modifications and changes may occur to those skilled in the art. Any modification, equivalent replacement, improvement, etc. made within the technical idea and principle of the present application should be included in the protection scope of the present application.