Method for preparing 2-chloroethoxyethanol through combined catalysis

Abstract

The invention relates to the technical field of organic synthesis, and particularly discloses a method for preparing 2-chloroethoxyethanol through combined catalysis, which comprises the following steps: under the catalysis of a main catalyst and an auxiliary catalyst, carrying out alkylation reaction on 2-chloroethanol and ethylene oxide, after the alkylation reaction is finished, heating and desolventizing an alkylation reaction solution to obtain a concentrated solution, and recovering 2-chloroethanol; and distilling the concentrated solution to obtain the target product 2-chloroethoxyethanol. The main catalyst and the auxiliary catalyst are adopted for combined catalysis, the adding amount of boron trifluoride diethyl etherate is greatly reduced, the output of three wastes is reduced, the catalytic reaction rate is controllable, side reactions are few, and the product purity is high.

Description

Technical Field

[0001] The invention relates to the technical field of organic synthesis, and in particular to a method for preparing 2-chloroethoxyethanol by combined catalysis. Background Art

[0002] 2-Chloroethoxyethanol, also known as 2-(2-chloroethoxy)ethanol, has a CAS number of 628-89-7 and the structural formula is as follows:

[0003]

[0004] 2-Chloroethoxyethanol is a colorless transparent liquid with a boiling point of 183°C, a relative density of 1.18 and a flash point of 90°C. 2-Chloroethoxyethanol is an important pharmaceutical intermediate, mainly used to synthesize psychotropic drugs such as quetiapine, central nervous system cough suppressant pentoxyverine citrate, antiallergic drugs such as cetirizine, and antihistamine drugs such as hydroxyzine. It is also a commonly used solvent and intermediate in fine chemicals, and can be used to synthesize TBEE, a selective desulfurization and decarbonization agent for natural gas, which plays a great role in the carbon neutralization process.

[0005] At present, there are two methods for preparing 2-chloroethoxyethanol: one is to prepare it by alkylation reaction of 2-chloroethanol and ethylene oxide; the other is to react diethylene glycol with metaboric anhydride, then treat it with thionyl chloride to obtain metaboric acid tri-(2-chloroethoxy-1-yl)-ethyl ester, and finally hydrolyze it to prepare it.

[0006] Chinese patent CN104003850A discloses the following technical scheme: using excess 2-chloroethanol and ethylene oxide as raw materials, boron trifluoride etherate as catalyst, and generating 2-chloroethoxyethanol under certain conditions. In the above scheme, boron trifluoride etherate as catalyst will continuously catalyze the reaction system, easily causing overreaction, thereby affecting product purity; and in addition, the amount of boron trifluoride etherate added in the above reaction is large, which will produce a large amount of fluorine-containing waste liquid, which will not only cause serious equipment corrosion, but also increase the cost of three waste treatment.

[0007] Chinese patent CN101665415A provides the following technical solution: diethylene glycol is used as a raw material, reacted with metaboric anhydride in a solvent to obtain metaboric acid tris-(2-hydroxyethoxy-1-yl)-ethyl ester, treated with thionyl chloride to obtain metaboric acid tris-(2-chloroethoxy-1-yl)-ethyl ester, and hydrolyzed to obtain 2-(2-chloroethoxy)ethanol. The above method uses a wide variety of materials, is cumbersome to operate, has many by-products, is highly polluting, and is not suitable for large-scale production. Summary of the invention

[0008] The technical problem to be solved by the present invention is: in view of the shortcomings of the prior art, a method for preparing 2-chloroethoxyethanol by combined catalysis is provided. The method adopts a main catalyst and an auxiliary catalyst for combined catalysis, which greatly reduces the amount of boron trifluoride etherate added and the amount of three wastes generated, and the catalytic reaction rate is controllable, the side reactions are small, and the purity of the product is high.

[0009] In order to solve the above technical problems, the technical solution of the present invention is:

[0010] A method for preparing 2-chloroethoxyethanol by combined catalysis comprises the following steps:

[0011] (1) Under the catalysis of a main catalyst and an auxiliary catalyst, 2-chloroethanol and ethylene oxide undergo an alkylation reaction;

[0012] (2) After the alkylation reaction is completed, the alkylation reaction solution is heated and desolventized to obtain a concentrated solution, and 2-chloroethanol is recovered;

[0013] (3) distilling the concentrated liquid to obtain the target product 2-chloroethoxyethanol.

[0014] Preferably, in step (1), the auxiliary catalyst is a mixture of one or more of ion exchange resin, sodium bicarbonate, triethylamine, anhydrous calcium chloride and calcium hydroxide. Further, the ion exchange resin is preferably a strongly acidic cation exchange resin.

[0015] Preferably, in step (1), the main catalyst is boron trifluoride etherate.

[0016] Preferably, in step (1), the molar ratio of 2-chloroethanol to ethylene oxide is (10-30):1, and more preferably (10-15):1.

[0017] Preferably, in step (1), the amount of the main catalyst added is 0.5-10‰ of the total mass of the materials in the reaction system, and more preferably 1-4‰.

[0018] Preferably, in step (1), the molar ratio of the main catalyst to the auxiliary catalyst is 1:(1-2).

[0019] Preferably, in step (1), the temperature of the alkylation reaction is 40-60°C, and the total reaction time is 2-4h. More preferably, the temperature is 40-50°C, and the reaction time is 2-3h.

[0020] Preferably, in step (1), the ethylene oxide is added completely within 1-2 hours during the alkylation reaction, more preferably within 1-1.5 hours; when 1 / 3-2 / 3 of the ethylene oxide is added, the auxiliary catalyst is added to the reaction system.

[0021] Preferably, the auxiliary catalyst is added in batches, with the last addition being after the addition of ethylene oxide is complete, and the total addition time of the auxiliary catalyst is 40-60 minutes.

[0022] Preferably, in step (2), the conditions for heating and desolvation are: temperature of 70-80° C. and vacuum degree of -0.1 to -0.098 MPa.

[0023] Preferably, in step (3), the distillation conditions are: temperature of 105-130° C. and vacuum degree ≤400 Pa.

[0024] Due to the adoption of the above technical solution, the beneficial effects of the present invention are:

[0025] The invention provides a method for preparing 2-chloroethoxyethanol by combined catalysis. The method uses 2-chloroethanol and ethylene oxide as raw materials, adopts a catalyst system consisting of a main catalyst and an auxiliary catalyst for catalysis, and effectively controls the adding timing and adding speed of the main catalyst and the auxiliary catalyst, thereby controlling the reaction rate in real time, reducing the reaction rate of side reactions, reducing side reactions, reducing impurity content, reducing the amount of three wastes generated, and greatly improving the purity of the product; the whole reaction is mild, the operation is simple, and the method is suitable for industrial production. BRIEF DESCRIPTION OF THE DRAWINGS

[0026] In order to more clearly illustrate the embodiments of the present invention or the technical solutions in the prior art, the drawings required for use in the embodiments or the description of the prior art will be briefly introduced below. Obviously, the drawings described below are only embodiments of the present invention. For ordinary technicians in this field, other drawings can be obtained based on the provided drawings without paying creative work.

[0027] Figure 1 The alkylation reaction is performed in the alkylation reaction solution of Example 1-2 and Comparative Example 1-4, and the content of 2-chloroethoxyethanol changes with the reaction time;

[0028] Figure 2 The following is a curve showing the change of the content of impurity 1 with the reaction time in the alkylation reaction liquid of Examples 1-2 and Comparative Examples 1-4 during the alkylation reaction;

[0029] Figure 3 The following is a curve showing the change of the content of impurity 2 with the reaction time in the alkylation reaction liquid of Examples 1-2 and Comparative Examples 1-4 during the alkylation reaction. DETAILED DESCRIPTION

[0030] In order to more clearly understand the above-mentioned objectives, features and advantages of the present invention, the scheme of the present invention will be further described below. It should be noted that the embodiments of the present invention and the features in the embodiments can be combined with each other without conflict.

[0031] In the following description, many specific details are set forth to facilitate a full understanding of the present invention, but the present invention may also be implemented in other ways different from those described herein; it is obvious that the embodiments in the specification are only part of the embodiments of the present invention, rather than all of the embodiments.

[0032] In order to solve the problems of many side reactions, high impurity content, complicated process and high pollution in the preparation of 2-chloroethoxyethanol pointed out in the background technology, the present invention provides the following technical solutions:

[0033] A method for preparing 2-chloroethoxyethanol by combined catalysis comprises the following steps:

[0034] (1) Under the catalysis of a main catalyst and an auxiliary catalyst, 2-chloroethanol and ethylene oxide undergo an alkylation reaction;

[0035] (2) After the alkylation reaction is completed, the alkylation reaction solution is heated and desolventized to obtain a concentrated solution, and 2-chloroethanol is recovered;

[0036] (3) distilling the concentrated liquid to obtain the target product 2-chloroethoxyethanol.

[0037] The invention uses 2-chloroethanol and ethylene oxide as raw materials, adopts a main catalyst and an auxiliary catalyst for catalysis, not only the reaction rate is controllable, the impurity content in the prepared product is small, the purity is high, and the catalyst is used in small amounts, the whole process is simple to operate, the three wastes are less, and energy conservation and environmental protection are achieved.

[0038] Regarding step (1):

[0039] In some embodiments of the present invention, the auxiliary catalyst is a mixture of one or more of ion exchange resin, sodium bicarbonate, triethylamine, anhydrous calcium chloride and calcium hydroxide. Preferably, the ion exchange resin is a strongly acidic cation exchange resin.

[0040] In some embodiments of the present invention, the main catalyst is boron trifluoride etherate.

[0041] The invention adopts boron trifluoride etherate as the main catalyst to ensure the smooth progress of the reaction process; one or more of ion exchange resin, sodium bicarbonate, triethylamine, anhydrous calcium chloride and calcium hydroxide are mixed as auxiliary catalysts, and the auxiliary catalyst can effectively control the reaction rate and the purity of the product by adjusting the reaction environment, improving the activity of the reactants and inhibiting the occurrence of side reactions.

[0042] In some embodiments of the present invention, the molar ratio of 2-chloroethanol to ethylene oxide is (10-30):1, and further, preferably (12-15):1. In order to ensure the smooth progress of the reaction, 2-chloroethanol needs to be excessive. The specific molar ratio of 2-chloroethanol to ethylene oxide is preferably (12-13):1, but is not limited thereto.

[0043] In some embodiments of the present invention, the amount of the main catalyst added is 0.5-10‰ of the total mass of the materials in the reaction system, and further, preferably 1-4‰.

[0044] In some embodiments of the present invention, the molar ratio of the main catalyst to the auxiliary catalyst is 1:(1-2).

[0045] In order to ensure the smooth progress of the alkylation reaction, the present invention effectively adjusts the dosage of the main catalyst and the auxiliary catalyst. Specifically, the addition amount of the main catalyst is preferably 2-3‰ of the total mass of the materials in the reaction system, but not limited thereto; the molar ratio of the main catalyst to the auxiliary catalyst is preferably 1: (1.5-2), but not limited thereto.

[0046] In some embodiments of the present invention, the alkylation reaction temperature is 40-60°C, and the reaction time is 2-4h. Specifically, the alkylation reaction temperature is preferably 40-50°C, but not limited thereto; the alkylation reaction time is preferably 2-3h, but not limited thereto.

[0047] In some embodiments of the present invention, during the alkylation reaction, the addition of ethylene oxide is completed within 1-1.5 hours, and when 1 / 3-2 / 3 of the ethylene oxide is added, an auxiliary catalyst is added to the reaction system.

[0048] In some embodiments of the present invention, the auxiliary catalyst is added in batches, and the last addition is after the addition of ethylene oxide is completed. Specifically, in order to facilitate operation and ensure the smooth progress of the reaction, the auxiliary catalyst is added in equal amounts in batches; the total addition time of the auxiliary catalyst is 40-60 minutes.

[0049] Regarding step (2):

[0050] In some embodiments of the present invention, in step (2), the conditions for heating and desolventizing are: temperature of 70-80° C. and vacuum degree of -0.1 to -0.098 MPa. Specifically, the heating and desolventizing can be performed multiple times so that the unreacted 2-chloroethanol can be fully recovered.

[0051] Regarding step (3):

[0052] In some embodiments of the present invention, the distillation conditions are: temperature of 105-130° C., vacuum degree ≤ 400 Pa;

[0053] In some embodiments of the present invention, the yield of the target product 2-chloroethoxyethanol = the weight of the obtained target product / (molecular weight of the target product*molar amount of ethylene oxide).

[0054] In order to further understand the present invention, preferred embodiments of the present invention are described below in conjunction with examples. However, it should be understood that these descriptions are only for further illustrating the features and advantages of the present invention, rather than limiting the claims of the present invention.

[0055] Product yield (%) = (actual product output / theoretical product output) × 100%.

[0056] Example 1

[0057] A method for preparing 2-chloroethoxyethanol by combined catalysis comprises the following steps:

[0058] S1: Weigh 345g (4.285mol) of 2-chloroethanol, 0.9g (0.006mol) of boron trifluoride etherate, 15g (0.341mol) of ethylene oxide, and 0.9g (0.012mol) of calcium hydroxide, add the above 2-chloroethanol and boron trifluoride etherate into a 500ml four-necked flask, stir and heat to 40°C at a speed of 500 rpm, slowly introduce ethylene oxide, and when 10g of ethylene oxide is introduced, add calcium hydroxide, and add equal amounts of calcium hydroxide in 3 times, with the same time interval between the 3 additions, and the last addition time is after the ethylene oxide is introduced. After the end, continue to stir and react for 1h. In the above process, the ethylene oxide introduction time is controlled to 1.5h, and the addition time of each batch of calcium hydroxide is 20min; the reaction is completed to obtain 367.9g of alkylation reaction liquid; the alkylation reaction process is repeatedly sampled for gas phase tracking to understand the reaction conversion rate and impurity generation;

[0059] S2: Pour the above alkylation reaction liquid into a 500 ml single-mouth bottle, and evaporate under reduced pressure at 70°C for 2 h, with a vacuum degree of -0.098 mPa, to obtain 57.1 g of primary concentrated liquid. In this process, 312.8 g of 2-chloroethanol was recovered;

[0060] S3: The primary concentrated solution was transferred into a 100 ml single-mouth bottle, and vacuum-evaporated at 70°C for 2 h, with a vacuum degree of -0.098 mPa, and vacuum-evaporated again for 2 h to obtain 50.4 g of secondary concentrated solution. 5.6 g of 2-chloroethanol was recovered in this process; the 2-chloroethanol in steps S2 and S3 was combined and applied to the alkylation reaction in step (1);

[0061] S4: The above secondary concentrated liquid is subjected to vacuum distillation at 105-110°C, with a vacuum degree of 400Pa, and 8.3g of the front fraction is collected and applied to the next batch of heating and desolventizing treatment; the temperature is then continued to be raised to 111-115°C, with a vacuum degree of 200Pa, and 34.4g of the middle section fraction is collected, which is a colorless and transparent solution, i.e., the finished product 2-chloroethoxyethanol, with a gas phase purity of 99.4% and a yield of 80.98%.

[0062] Example 2

[0063] A method for preparing 2-chloroethoxyethanol by combined catalysis comprises the following steps:

[0064] S1: Weigh 345g (4.285mol, 317.6g + 27.4g recovered in Example 2) of 2-chloroethanol, 0.9g (0.006mol) of boron trifluoride etherate, 15g (0.341mol) of ethylene oxide, and 1.1g (0.010mol) of anhydrous calcium chloride, add the above 2-chloroethanol and boron trifluoride etherate into a 500ml four-necked flask, stir at 500 rpm and heat to 40°C, slowly introduce ethylene oxide, and when ethylene oxide is added, add 100g (0.01mol) of ethylene oxide to the flask. When the amount of ethylene oxide introduced is 10 g, calcium hydroxide is added. The calcium hydroxide is added in equal amounts in 3 times. The time intervals between the 3 additions are the same. The last addition is after the ethylene oxide is introduced. After the end, the reaction is continued with heat preservation and stirring for 1 hour. During the above process, the ethylene oxide introduction time is controlled to be 1.5 hours, and the addition time of each batch of calcium hydroxide is 20 minutes. After the reaction is completed, 368.6 g of alkylation reaction liquid is obtained. During the alkylation reaction process, gas phase sampling is performed for multiple times to track the reaction conversion rate and impurity generation.

[0065] S2: The alkylation reaction liquid was mixed with 8.3 g of the fore fraction in Example 1 and poured into a 500 ml single-necked bottle. The mixture was subjected to vacuum rotary evaporation at 70° C. for 2 h with a vacuum degree of -0.098 mPa to obtain 54.3 g of a primary concentrate and recover 312.8 g of 2-chloroethanol.

[0066] S3: The primary concentrated solution was transferred into a 100 ml single-mouth bottle and subjected to reduced pressure rotary evaporation at 70°C for 2 h with a vacuum degree of -0.098 MPa to obtain 49.8 g of secondary concentrated solution and recover 4.6 g of 2-chloroethanol; the 2-chloroethanol in steps S2 and S3 was combined and applied to the alkylation reaction in step (1);

[0067] S4: The above secondary concentrated liquid was subjected to vacuum distillation at 105-110°C, vacuum degree 400Pa, 7.8g of the front fraction was collected first, and then the temperature was continued to be raised to 111-115°C, vacuum degree 200Pa, and 33.7g of the middle section fraction was collected, which was a colorless transparent solution, i.e. the finished product 2-chloroethoxyethanol, with a gas phase purity of 99.3% and a yield of 79.34%.

[0068] Comparative Example 1

[0069] The preparation method of 2-chloroethoxyethanol comprises the following steps:

[0070] S1: Weigh 345g (4.285mol) of 2-chloroethanol, 0.9g (0.006mol) of boron trifluoride etherate, and 15g (0.341mol) of ethylene oxide, add 2-chloroethanol and boron trifluoride etherate into a 500ml four-necked flask, stir at 500 rpm and heat to 40°C, slowly introduce 15g (0.341mol) of ethylene oxide, add ethylene oxide within 1.5h, continue to keep warm and stir for 1h after ventilation, and obtain 361.1g of alkylation reaction liquid. Sample the gas phase for multiple times during the alkylation reaction;

[0071] S2: Pour the above alkylation reaction liquid into a 500 ml single-necked bottle, and evaporate under reduced pressure at 70°C for 2 h with a vacuum degree of -0.098 MPa to obtain 64.9 g of primary concentrated liquid, and recover 293.7 g of 2-chloroethanol;

[0072] S3: The primary concentrated solution was transferred into a 100 ml single-mouth bottle, and vacuum evaporated at 70° C. for 2 h with a vacuum degree of -0.098 MPa to obtain 45.9 g of secondary concentrated solution, and 17.5 g of 2-chloroethanol was recovered. The 2-chloroethanol recovered in steps S2 and S3 was recovered and applied to the next batch of alkylation reactions;

[0073] S4: The above secondary concentrated liquid was subjected to vacuum distillation at 105-110°C, vacuum degree 400Pa, 9.2g of the front fraction was collected first, and then the temperature was continued to be raised to 111-115°C, vacuum degree 200Pa, and 22.4g of the middle section fraction was collected, which was a colorless transparent solution, i.e. the finished product 2-chloroethoxyethanol, with a gas phase purity of 99.3% and a yield of 52.8%.

[0074] Comparative Example 2

[0075] Compared with Example 1, the difference is that in step S1, calcium hydroxide is added all at once after the ethylene oxide is introduced, and other conditions are the same as those in Example 1; 25.1 g of 2-chloroethoxyethanol is obtained, the gas phase purity is 99.2%, and the yield is 59.1%.

[0076] Comparative Example 3

[0077] Compared with Example 1, the difference is that: in step S1, calcium hydroxide and ethylene oxide are added simultaneously, and the last addition time is after the ethylene oxide is completed, and other conditions are the same as in Example 1; 26.9 g of 2-chloroethoxyethanol is obtained, the gas phase purity is 99.5%, and the yield is 62.6%.

[0078] Comparative Example 4

[0079] Compared with Example 1, the difference is that in step S1, the end time of the introduction of calcium hydroxide and ethylene oxide is the same, and other conditions are the same as in Example 1; 26.2 g of 2-chloroethoxyethanol is obtained, the gas phase purity is 99.5%, and the yield is 61.7%.

[0080] from Figures 1 to 3 It can be seen that in the alkylation reaction liquid, as the reaction time proceeds, the contents of the target product 2-chloroethoxyethanol, impurity 1, and impurity 2 also increase accordingly. After 2.5 hours of reaction, the contents of 2-chloroethoxyethanol, impurity 1, and impurity 2 basically no longer increase.

[0081] Compared with the comparative example, the present invention adopts boron trifluoride etherate as the main catalyst, and adds a proper amount of auxiliary catalyst to effectively regulate the reaction process, and adjusts the conditions such as the time of adding the auxiliary catalyst, thereby greatly improving the purity and yield of the target product with a smaller amount of catalyst.

[0082] Specific examples are used herein to illustrate the principles and implementation methods of the present invention. The description of the above embodiments is only used to help understand the method of the present invention and its core ideas, including the best mode, and also enable any technician in the field to practice the present invention, including making and using any device or system, and implementing any combined method. It should be pointed out that for ordinary technicians in this technical field, without departing from the principle of the present invention, the present invention can also be improved and modified, and these improvements and modifications also fall within the scope of protection of the claims of the present invention. The scope of patent protection of the present invention is defined by the claims and may include other embodiments that can be thought of by those skilled in the art. If these other embodiments have structural elements similar to the literal expression of the claims, or if they include equivalent structural elements that are not substantially different from the literal expression of the claims, then these other embodiments should also be included in the scope of the claims.

Claims

1. A method for preparing 2-chloroethoxyethanol by combined catalysis, characterized in that: The following steps are involved: (1) Under the catalysis of a main catalyst and an auxiliary catalyst, 2-chloroethanol and ethylene oxide undergo an alkylation reaction; (2) After the alkylation reaction is completed, the alkylation reaction solution is heated and desolventized to obtain a concentrated solution, and 2-chloroethanol is recovered; (3) distilling the concentrated solution to obtain the target product 2-chloroethoxyethanol.

2. The method for preparing 2-chloroethoxyethanol by combined catalysis according to claim 1, characterized in that: In step (1), the auxiliary catalyst is a mixture of one or more of ion exchange resin, sodium bicarbonate, triethylamine, anhydrous calcium chloride and calcium hydroxide.

3. The method for preparing 2-chloroethoxyethanol by combined catalysis according to claim 1, characterized in that: In step (1), the main catalyst is boron trifluoride etherate.

4. The method for preparing 2-chloroethoxyethanol by combined catalysis according to claim 1, characterized in that: In step (1), the molar ratio of 2-chloroethanol to ethylene oxide is (10-30):

1.

5. The method for preparing 2-chloroethoxyethanol by combined catalysis according to claim 1, characterized in that: In step (1), the amount of the main catalyst added is 0.5-10‰ of the total mass of the materials in the reaction system.

6. The method for preparing 2-chloroethoxyethanol by combined catalysis according to claim 1, characterized in that: In step (1), the molar ratio of the main catalyst to the auxiliary catalyst is 1:(1-2).

7. The method for preparing 2-chloroethoxyethanol by combined catalysis according to claim 1, characterized in that: In step (1), the temperature of the alkylation reaction is 40-60° C., and the total reaction time is 2-4 h.

8. The method for preparing 2-chloroethoxyethanol by combined catalysis according to claim 1, characterized in that: In step (1), during the alkylation reaction, the addition of ethylene oxide is completed within 1-2 hours. When 1 / 3-2 / 3 of the ethylene oxide is added, an auxiliary catalyst is added to the reaction system.

9. The method for preparing 2-chloroethoxyethanol by combined catalysis according to claim 8, characterized in that: The auxiliary catalyst is added in batches, with the last addition being after the addition of ethylene oxide is completed, and the total addition time is 40-60 minutes.

10. The method for preparing 2-chloroethoxyethanol by combined catalysis according to claim 1, characterized in that: In step (2), the conditions for heating and desolvation are: temperature of 70-80°C and vacuum degree of -0.1 to -0.098 MPa; and / or in step (3), the conditions for distillation are: temperature of 105-130°C and vacuum degree ≤400 Pa.

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