A process for the catalytic preparation of 2-chloroethoxyethanol

Abstract

The application relates to the technical field of organic synthesis, and particularly discloses a method for preparing 2-chloroethyloxy ethanol through combined catalysis, which comprises the following steps: under the catalysis of a main catalyst and an auxiliary catalyst, 2-chloroethanol and ethylene oxide are subjected to an alkylation reaction; after the alkylation reaction is completed, the alkylation reaction liquid is heated and desoluted to obtain a concentrated liquid, and 2-chloroethanol is recovered; and the concentrated liquid is distilled to obtain the target product 2-chloroethyloxy ethanol. The main catalyst and the auxiliary catalyst are combined to catalyze, the addition amount of boron trifluoride diethyl ether is greatly reduced, the generation amount of three wastes is reduced, the catalytic reaction rate is controllable, the side reaction is less, and the product has high purity.

Description

TECHNICAL FIELD

[0001] The present application relates to the technical field of organic synthesis, in particular to a method for preparing 2-chloroethoxy ethanol by combined catalysis. BACKGROUND

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

[0003]

[0004] 2-chloroethoxy ethanol is a colorless transparent liquid with a boiling point of 183℃, a relative density of 1.18 and a flash point of 90℃. 2-chloroethoxy ethanol is an important pharmaceutical intermediate, which is mainly used for synthesizing quetiapine, a central nervous cough-relieving drug; cetirizine, an antiallergic drug; and hydroxyzine, an antihistamine drug. In addition, 2-chloroethoxy ethanol is also a commonly used solvent and intermediate in fine chemical industry, which can be used to synthesize a selective desulfurization and decarburization agent TBEE for natural gas, and plays a great role in the carbon neutralization process.

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

[0006] Chinese patent CN104003850A discloses the following technical solution: using excess 2-chloroethanol and ethylene oxide as raw materials, and using boron trifluoride ether as a catalyst to generate 2-chloroethoxy ethanol under certain conditions. In the above-mentioned solution, boron trifluoride ether as a catalyst will continuously catalyze the reaction system, which is easy to cause over-reaction and thus affect the purity of the product. In addition, a large amount of fluorine-containing waste liquid will be generated due to the large amount of boron trifluoride ether added in the above-mentioned reaction, 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: using diethylene glycol as a raw material, performing a reaction with metaboric anhydride in a solvent to obtain metaboric acid tri-(2-hydroxyethoxy-1-yl)-ethyl ester, treating the product with thionyl chloride to obtain metaboric acid tri-(2-chloroethoxy-1-yl)-ethyl ester, and hydrolyzing the product to obtain 2-(2-chloroethoxy) ethanol. The above-mentioned method uses a large number of materials, is complicated to operate, has many by-products and high pollution, and is not suitable for large-scale production. SUMMARY

[0008] The technical problem solved by the present application is to provide a method for preparing 2-chloroethoxy ethanol by combined catalysis, which greatly reduces the addition amount of boron trifluoride diethyl ether, reduces the generation amount of three wastes, and has controllable catalytic reaction rate, less side reaction, and high product purity.

[0009] To solve the above technical problems, the technical solution of the present application is:

[0010] A method for preparing 2-chloroethoxy ethanol by combined catalysis, comprising the following steps:

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

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

[0013] (3) The concentrated liquid is distilled to obtain the target product 2-chloroethoxy ethanol.

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

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

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

[0017] Preferably, in step (1), the addition amount of the main catalyst is 0.5-10‰ of the total mass of the reaction system, and further 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℃, and the total reaction time is 2-4h, and further preferably, the temperature is 40-50℃, and the reaction time is 2-3h.

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

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

[0022] Preferably, in step (2), the desolventizing condition is that the temperature is 70-80 DEG C, and the vacuum degree is -0.1 to -0.098 MPa.

[0023] Preferably, in step (3), the distillation condition is that the temperature is 105-130 DEG C, and the vacuum degree is ≤400 Pa.

[0024] Due to the adoption of the above technical solutions, the present application has the following beneficial effects:

[0025] The present application provides a method for preparing 2-chloroethoxyethanol by combined catalysis, which uses 2-chloroethanol and ethylene oxide as raw materials, adopts a catalyst system composed of a main catalyst and an auxiliary catalyst, and effectively controls the addition time and addition speed of the main catalyst and the auxiliary catalyst, so as to control the reaction rate in real time, reduce the reaction rate of the side reaction, reduce the impurity content, reduce the amount of three wastes, and greatly improve 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 DRAWINGS

[0026] In order to more clearly illustrate the technical solutions in the embodiments of the present application or the prior art, the following will briefly introduce the drawings needed to be used in the embodiments or the prior art description. Obviously, the drawings in the following description are only embodiments of the present application, and for those skilled in the art, other drawings can also be obtained without creative labor on the basis of the provided drawings.

[0027] Figure 1 The content of 2-chloroethoxyethanol in the alkylation reaction liquid of examples 1-2 and comparative examples 1-4 in the alkylation reaction process changes with the reaction time;

[0028] Figure 2 The content of impurity 1 in the alkylation reaction liquid of examples 1-2 and comparative examples 1-4 in the alkylation reaction process changes with the reaction time;

[0029] Figure 3 The content of impurity 2 in the alkylation reaction liquid of examples 1-2 and comparative examples 1-4 in the alkylation reaction process changes with the reaction time. DETAILED DESCRIPTION

[0030] In order to enable one skilled in the art to better understand the above-mentioned objects, features and advantages of the present application, the solutions of the present application will be further described below. It should be noted that the embodiments of the present application 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 in order to provide a thorough understanding of the present application, but the present application can be practiced in other ways different from those described herein; obviously, the embodiments in the specification are only some of the embodiments of the present application, not all the embodiments.

[0032] In order to solve the problems of multiple side reactions, high impurity content, complicated process and high pollution in the preparation of 2-chloroethoxy ethanol in the background art, the present application provides the following technical solutions:

[0033] A method for preparing 2-chloroethoxy ethanol 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 are subjected to an alkylation reaction;

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

[0036] (3) The concentrated liquid is distilled to obtain the target product 2-chloroethoxy ethanol.

[0037] The present application uses 2-chloroethanol and ethylene oxide as raw materials, and adopts a main catalyst and an auxiliary catalyst for catalysis, so that the reaction rate is controllable, the impurity content of the prepared product is low, the purity is high, the catalyst usage is less, the whole process is simple to operate, the three wastes are less generated, and energy saving and environmental protection are achieved.

[0038] Regarding step (1):

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

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

[0041] The present application uses boron trifluoride etherate as the main catalyst to ensure the smooth progress of the reaction; one or more of ion exchange resin, sodium bicarbonate, triethylamine, anhydrous calcium chloride and calcium hydroxide is mixed as the auxiliary catalyst, which 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 application, 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 in excess. Specifically, the 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 application, the amount of the main catalyst added is 0.5-10‰ of the total mass of the reaction system, and further preferably 1-4‰.

[0044] In some embodiments of the present application, 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 application effectively adjusts the amount of the main catalyst and the auxiliary catalyst. Specifically, the amount of the main catalyst added is preferably 2-3‰ of the total mass of the reaction system, but is not limited thereto; and the molar ratio of the main catalyst to the auxiliary catalyst is preferably 1:(1.5-2), but is not limited thereto.

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

[0047] In some embodiments of the present application, ethylene oxide is added within 1-1.5h during the alkylation reaction, and the auxiliary catalyst is added in the reaction system when 1 / 3-2 / 3 of ethylene oxide is added.

[0048] In some embodiments of the present application, 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; and the total addition time of the auxiliary catalyst is 40-60min.

[0049] Regarding step (2):

[0050] In some embodiments of the present application, the heating and desolubilization conditions in step (2) are as follows: the temperature is 70-80℃, and the vacuum degree is -0.1 to -0.098MPa. Specifically, the heating and desolubilization can be performed multiple times to fully recover the unreacted 2-chloroethanol.

[0051] Regarding step (3):

[0052] In some embodiments of the present application, the distillation conditions are as follows: the temperature is 105-130℃, and the vacuum degree is ≤400Pa.

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

[0054] In order to further understand the present application, the preferred embodiments of the present application are described below in conjunction with examples, but it should be understood that these descriptions are only for further illustrating the features and advantages of the present application, and are not limitations on the claims of the present application.

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

[0056] Example 1

[0057] A method for jointly catalytically preparing 2-chloroethoxyethanol, comprising the following steps:

[0058] S1: weigh 345 g (4.285 mol) of 2-chloroethanol, 0.9 g (0.006 mol) of boron trifluoride etherate, 15 g (0.341 mol) of ethylene oxide, and 0.9 g (0.012 mol) of calcium hydroxide, and add the above-mentioned 2-chloroethanol and boron trifluoride etherate into a 500 ml four-necked flask, stir at a speed of 500 revolutions per minute, and warm up to 40°C, slowly pass in ethylene oxide, when 10 g of ethylene oxide is passed in, add calcium hydroxide, and the calcium hydroxide is added in three equal portions with the same time interval, and the last addition is after the completion of the passage of ethylene oxide, and continue to stir and react for 1 h after the end of the process, in the above-mentioned process, the passage time of ethylene oxide is controlled to be 1.5 h, and the addition time of each batch of calcium hydroxide is 20 min; 367.9 g of alkylated reaction liquid is obtained after the reaction is completed; the alkylated reaction process is sampled multiple times to track the reaction conversion rate and impurity generation;

[0059] S2: pour the above-mentioned alkylated reaction liquid into a 500 ml single-necked flask, and rotary evaporate at 70°C under reduced pressure for 2 h, with a vacuum degree of -0.098 mPa, to obtain 57.1 g of a first concentrated liquid, and 312.8 g of 2-chloroethanol is recovered in the process;

[0060] S3: transfer the above-mentioned first concentrated liquid into a 100 ml single-necked flask, and rotary evaporate at 70°C under reduced pressure for 2 h, with a vacuum degree of -0.098 mPa, and rotary evaporate again for 2 h, to obtain 50.4 g of a second concentrated liquid, and 5.6 g of 2-chloroethanol is recovered in the process; combine the 2-chloroethanol in steps S2 and S3 and apply it to the alkylated reaction in step (1);

[0061] S4: The secondary concentrated liquid is distilled under reduced pressure at 105-110°C, vacuum degree 400 Pa, 8.3 g of the front fraction is collected, which is used in the next batch of heating desolventizing treatment; continue to heat to 111-115°C, vacuum degree 200 Pa, 34.4 g of the middle fraction is collected, which is a colorless transparent solution, namely the finished product 2-chloroethoxyethanol, gas phase purity 99.4%, yield 80.98%.

[0062] Example 2

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

[0064] S1: Take 345 g (4.285 mol, 317.6 g recovered in Example 2 + 27.4 g new) of 2-chloroethanol, 0.9 g (0.006 mol) of boron trifluoride etherate, 15 g (0.341 mol) of ethylene oxide, and 1.1 g (0.010 mol) of anhydrous calcium chloride, and add the above-mentioned 2-chloroethanol and boron trifluoride etherate into a 500 ml four-necked flask, stir at a speed of 500 rpm, and heat to 40°C, then slowly introduce ethylene oxide, when 10 g of ethylene oxide is introduced, add calcium hydroxide, and the calcium hydroxide is added in three equal portions with the same time interval, and the last addition is after the introduction of ethylene oxide is completed, and continue to heat and stir for 1 h after the end of the reaction, in the above process, the ethylene oxide introduction time is controlled to be 1.5 h, and the addition time of each batch of calcium hydroxide is 20 min; after the reaction is completed, 368.6 g of alkylated reaction liquid is obtained; the alkylated reaction process is sampled multiple times to track the reaction conversion rate and impurity generation;

[0065] S2: Mix the above-mentioned alkylated reaction liquid with 8.3 g of the front fraction in Example 1, and pour it into a 500 ml single-necked flask, and rotary evaporate under reduced pressure at 70°C for 2 h, vacuum degree -0.098 mPa, to obtain 54.3 g of the first concentrated liquid, and recover 312.8 g of 2-chloroethanol;

[0066] S3: Transfer the above-mentioned first concentrated liquid into a 100 ml single-necked flask, and rotary evaporate under reduced pressure at 70°C for 2 h, vacuum degree -0.098 MPa, to obtain 49.8 g of the secondary concentrated liquid, and recover 4.6 g of 2-chloroethanol; combine the 2-chloroethanol in steps S2 and S3 and use it in the alkylated reaction of step (1);

[0067] S4: Distill the above-mentioned secondary concentrated liquid under reduced pressure at 105-110°C, vacuum degree 400 Pa, first collect 7.8 g of the front fraction, then continue to heat to 111-115°C, vacuum degree 200 Pa, collect 33.7 g of the middle fraction, which is a colorless transparent solution, namely the finished product 2-chloroethoxyethanol, gas phase purity 99.3%, yield 79.34%.

[0068] Comparative Example 1

[0069] 2-chloroethoxyethanol was prepared by the following steps:

[0070] S1: 345 g (4.285 mol) of 2-chloroethanol, 0.9 g (0.006 mol) of boron trifluoride etherate, and 15 g (0.341 mol) of oxirane were weighed, and the 2-chloroethanol and boron trifluoride etherate were added to a 500 ml four-necked flask. The mixture was stirred at a speed of 500 rpm and heated to 40°C, and 15 g (0.341 mol) of oxirane was slowly introduced. The introduction of oxirane was completed in 1.5 h, and the mixture was continuously stirred at 40°C for 1 h to obtain 361.1 g of an alkylated reaction solution. The alkylated reaction process was sampled several times for gas phase tracking;

[0071] S2: The alkylated reaction solution was poured into a 500 ml single-necked flask, and rotary evaporation was performed at 70°C under reduced pressure for 2 h, with a vacuum degree of -0.098 MPa, to obtain 64.9 g of a first concentrated solution, and 293.7 g of 2-chloroethanol was recovered;

[0072] S3: The first concentrated solution was transferred into a 100 ml single-necked flask, and rotary evaporation was performed at 70°C under reduced pressure for 2 h, with a vacuum degree of -0.098 MPa, to obtain 45.9 g of a second concentrated solution, and 17.5 g of 2-chloroethanol was recovered. The recovered 2-chloroethanol from steps S2 and S3 was reused in the next batch of alkylated reaction;

[0073] S4: The second concentrated solution was subjected to reduced pressure distillation at 105-110°C, with a vacuum degree of 400 Pa. First, 9.2 g of a front fraction was collected, and then the temperature was increased to 111-115°C, and a vacuum degree of 200 Pa was maintained to collect 22.4 g of a middle fraction, 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] Comparative Example 2 was the same as Example 1, except that in step S1, calcium hydroxide was added at once after the introduction of oxirane was completed. 25.1 g of 2-chloroethoxyethanol was obtained, with a gas phase purity of 99.2% and a yield of 59.1%.

[0076] Comparative Example 3

[0077] Comparative Example 3 was the same as Example 1, except that in step S1, calcium hydroxide and oxirane were added simultaneously, and the last addition was made after the introduction of oxirane was completed. 26.9 g of 2-chloroethoxyethanol was obtained, with a gas phase purity of 99.5% and a yield of 62.6%.

[0078] Comparative Example 4

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

[0080] From Figures 1 to 3 It can be seen that in the alkylating reaction liquid, as the reaction time progresses, the contents of the target product 2-chloroethoxyethanol, impurity 1 and impurity 2 also increase, and after 2.5 h of reaction, the contents of 2-chloroethoxyethanol, impurity 1 and impurity 2 no longer increase substantially.

[0081] Compared with the comparative example, the present application uses boron trifluoride etherate as the main catalyst, and adds an appropriate amount of auxiliary catalyst to effectively regulate the reaction process, and adjusts the addition time of the auxiliary catalyst and other conditions, greatly improving the purity and yield of the target product with less catalyst usage.

[0082] The principles and implementations of the present application are described herein using specific examples. The above description of the examples is intended to help understand the method of the present application and its core idea, including the best mode, and also enable any person skilled in the art to practice the present application, including manufacturing and using any device or system, and implementing any combined method. It should be noted that for those skilled in the art, without departing from the principles of the present application, several improvements and modifications can be made to the present application, and these improvements and modifications also fall within the scope of protection of the claims of the present application. The scope of protection of the present application is defined by the claims, and can include other embodiments that can be conceived 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 within the scope of the claims.

Claims

1. A method for the combined catalytic preparation of 2-chloroethoxyethanol, characterized in that, Includes the following steps: (1) Under the catalysis of a main catalyst and an auxiliary catalyst, 2-chloroethanol and ethylene oxide undergo an alkylation reaction; the auxiliary catalyst is one or more of anhydrous calcium chloride and calcium hydroxide; the main catalyst is boron trifluoride diethyl ether; during the alkylation reaction, ethylene oxide is added completely within 1-2 hours, and when 1 / 3-2 / 3 of the ethylene oxide has been added, the auxiliary catalyst is added to the reaction system; the auxiliary catalyst is added in batches, with the last addition occurring after the ethylene oxide addition is completed, and the total addition time is 40-60 minutes. (2) After the alkylation reaction is completed, the alkylation reaction solution is heated to remove the solvent, and a concentrated solution is obtained and 2-chloroethanol is recovered; (3) Distill the concentrated solution to obtain the target product 2-chloroethoxyethanol.

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

1.

3. The method for preparing 2-chloroethoxyethanol by co-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.

4. The method for preparing 2-chloroethoxyethanol by co-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).

5. The method for preparing 2-chloroethoxyethanol by co-catalysis according to claim 1, characterized in that: In step (1), the alkylation reaction is carried out at a temperature of 40-60℃ and the total reaction time is 2-4h.

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

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