Method for synthesizing bis(N-methyl-N-hydroxyethylaminoethyl) ether and tubular reaction device used therein

Abstract

The present invention belongs to the field of chemical industry, specifically discloses a kind of tubular reaction device, the present invention also discloses a kind of method of synthesizing bis (N methyl bis (N hydroxyethyl aminoethyl) ether simultaneously, with bis (first aminoethyl) ether as raw material, utilize above-mentioned tubular reaction device, comprise the following steps:BMAEE and catalyst form mixed liquor one;Or by BMAEE, the middle distillate N, N '-dimethyl bis (N '-hydroxyethyl) bis (aminoethyl) ether obtained from reaction solution rectification and separation and catalyst form mixed liquor two;Mixed liquor one or mixed liquor two and EO carry out hydroxyethylation reaction, the obtained reaction solution carries out vacuum distillation, respectively obtains middle distillate N, N '-dimethyl bis (N '-hydroxyethyl) bis (aminoethyl) ether and product fraction BMHEAEE.The present invention preferably suppresses the by-product of product BMHEAEE and EO, improves product yield, and reaction system is isolated from the outside world, reduces reaction risk.

Description

Technical Field

[0001] The present invention belongs to the field of chemical industry, and particularly relates to a method for synthesizing an alcoholamine ether compound, namely a method for synthesizing bis(N-methyl-N-hydroxyethylaminoethyl) ether (BMHEAEE for short), and a tubular reaction device used therein. Background Art

[0002] BMHEAEE is a colorless or light yellow transparent liquid that is soluble in water. Its structural formula is shown in S-1.

[0003]

[0004] BMHEAEE has anticancer activity, so its synthesis method has attracted attention. However, there are few synthesis methods and the production process is not perfect. For example, the literature Chem Pharm Bull (Tokyo). 1958Apr; 6(2): 169-72. doi: 10.1248 / cpb.6.169. reported a method for synthesizing BMHEAEE: 2,2'-dibromodiethyl ether and N-methylethanolamine are used as raw materials. This method produces hydrogen bromide, which is then neutralized to produce halide-containing pollutants. Post-processing is difficult, the atom economy is poor, and the raw material 2,2'-dibromodiethyl ether is expensive. The reaction formula of this method is as follows S-2

[0005] Summary of the Invention

[0006] The technical problem to be solved by the present invention is to provide a method for synthesizing bis(N-methyl-N-hydroxyethylaminoethyl) ether (BMHEAEE for short) and a tubular reaction device used therefor.

[0007] In order to solve the above technical problems, the present invention provides a tubular reaction device: comprising a tubular reactor with a heating device, a liquid feed line connected to the inner cavity near the top of the tubular reactor, and a flow meter b provided on the liquid feed line;

[0008] The EO cylinder is connected to the inner cavity near the bottom of the tubular reactor through the EO feed pump, EO feed control valve and flow meter a;

[0009] The EO outlet at the top of the tubular reactor is connected to the inner cavity near the bottom of the tubular reactor through a pneumatic circulation pump;

[0010] A discharge flow pipe is provided at the bottom outlet of the tubular reactor, and a flow meter c and a stop valve are provided on the discharge flow pipe.

[0011] As an improvement to the tubular reactor of the present invention, a distributor is provided near the bottom of the inner cavity of the tubular reactor, and the EO provided by the EO cylinder and the EO discharged from the EO outlet at the top of the tubular reactor pass through the distributor and enter the middle inner cavity of the tubular reactor.

[0012] As a further improvement of the tubular reactor of the present invention: the heating device of the tubular reactor includes a thermostatic bath, a thermal oil circulation pump and a thermal oil jacket;

[0013] A thermal oil jacket is provided on the outer surface of the tubular reactor. The outlet of the thermal oil jacket is connected to the inlet of the thermal oil jacket through a constant temperature bath and a thermal oil circulation pump. The thermal oil jacket is responsible for supplying heat to the tubular reactor.

[0014] As a further improvement to the tubular reactor of the present invention, the EO outlet at the top of the tubular reactor is connected to the connecting pipe II through the connecting pipe I and the pneumatic circulation pump in sequence; a pressure relief valve is provided on the connecting pipe I;

[0015] The EO cylinder is connected to the connecting pipe II after passing through the EO feed pump, EO feed control valve and flow meter a in sequence;

[0016] The connecting pipe II is connected to the bottom of the distributor.

[0017] As a further improvement of the tubular reactor of the present invention: a liquid level gauge is provided on the tubular reactor, and the liquid level gauge is used to display the liquid level height in the inner cavity of the tubular reactor;

[0018] A U-shaped differential pressure gauge is also provided on the tubular reactor, and the function of the U-shaped differential pressure gauge is to measure the pressure inside the tubular reactor.

[0019] The present invention also provides a method for synthesizing bis(N-methyl-N-hydroxyethylaminoethyl) ether (BMHEAEE for short), using bis(methylaminoethyl) ether (BMAEE for short) as a raw material and utilizing the above-mentioned tubular reaction apparatus, comprising the following steps:

[0020] 1) Hydroxyethylation:

[0021] A mixed solution 1 is composed of BMAEE and a catalyst; or a mixed solution 2 is composed of BMAEE, an intermediate fraction N,N'-dimethyl-N'-hydroxyethyl bisaminoethyl ether obtained by fractionation of the reaction solution, and a catalyst;

[0022] Mixed liquid 1 or mixed liquid 2 continuously enters the inner cavity of the tubular reactor from the upper part, and EO (ethylene oxide, liquid) provided by the EO cylinder enters the inner cavity of the tubular reactor from the lower part;

[0023] The EO discharged from the top of the tubular reactor is continuously fed into the tubular reactor together with the EO provided by the EO cylinder under the action of the gas circulation pump; the temperature in the tubular reactor is maintained at a reaction temperature of 40 to 150° C. (preferably 60 to 120° C., more preferably 80 to 120° C.); the residence time of the mixed solution 1 or the mixed solution 2 in the tubular reactor (4) is 5 to 25 minutes (preferably 8 to 21 minutes, more preferably 10 to 21 minutes);

[0024] The resulting reaction liquid is discharged from the discharge port located at the bottom of the tubular reactor (4);

[0025] When using mixed solution 1: the material molar ratio is n(EO:BMAEE) = 0.7-1.3:1 (preferably 1-1.2:1); the weight ratio of catalyst:BMAEE = 0.5-5% (preferably 1-3%, more preferably 1.5-2.5%:1);

[0026] When mixed solution 2 is used: the material molar ratio is n(EO:NH) = 0.7-1.3:1 (preferably 1-1.2:1), where NH is the sum of the number of NH groups in the molecules of the raw material BMAEE and the intermediate distillate N,N'-dimethyl-N'-hydroxyethylbisaminoethyl ether; the weight ratio of catalyst: (BMAEE + N,N'-dimethyl-N'-hydroxyethylbisaminoethyl ether) = 0.5-5% (preferably 1-3%, more preferably 1.5-2.5%:1); n(BMAEE):n(N,N'-dimethyl-N'-hydroxyethylbisaminoethyl ether) = 1-8:1 (preferably 4-8:1, more preferably 5-8:1);

[0027] Note: NH, that is, the sum of 2 times the number of BMAEE molecules and 1 times the number of N,N'-dimethyl-N'-hydroxyethyl bisaminoethyl ether molecules; that is, the molar amount of EO: (2*molar amount of BMAEE + 1*molar amount of N,N'-dimethyl-N'-hydroxyethyl bisaminoethyl ether) = 0.7 to 1.3:1;

[0028] The composition of the reaction solution can be sampled at any time during the reaction process; when the content of the components of the reaction solution remains basically unchanged, it is considered stable and the reaction solution can be collected at this time;

[0029] 2) Distillation:

[0030] The reaction solution obtained in step 1) is subjected to vacuum distillation to obtain an intermediate fraction N,N'-dimethyl-N'-hydroxyethyl bisaminoethyl ether and a product fraction BMHEAEE, respectively. The intermediate fraction is recycled to step 1) as a reaction raw material.

[0031] As an improvement of the method for synthesizing bis(N-methyl-N-hydroxyethylaminoethyl) ether of the present invention:

[0032] The catalyst is any one of tetramethylammonium bromide solution, tetrabutylammonium bromide solution, tetramethylammonium chloride solution, triethylbenzylammonium chloride solution and trimethylhexadecylammonium chloride solution with a mass concentration of 30-50% (preferably 40%).

[0033] As a further improvement of the method for synthesizing bis(N-methyl-N-hydroxyethylaminoethyl) ether of the present invention:

[0034] BMAEE and catalyst are first mixed evenly to form a mixed liquid; then the mixed liquid enters the tubular reactor through the liquid feed line;

[0035] Alternatively, BMAEE, the intermediate fraction N,N'-dimethyl-N'-hydroxyethyl bisaminoethyl ether obtained by distillation separation of the reaction liquid, and the catalyst are first mixed uniformly to form a second mixed liquid; and then the mixed liquid is fed into the tubular reactor through a liquid feed line.

[0036] As a further improvement of the method for synthesizing bis(N-methyl-N-hydroxyethylaminoethyl) ether of the present invention: the catalyst is preferably a 40% tetramethylammonium bromide solution.

[0037] As a further improvement to the method for synthesizing bis(N-methyl-N-hydroxyethylaminoethyl) ether of the present invention: in the step 2), a fraction at 120-130°C / 7 mmHg is collected by vacuum distillation to obtain an intermediate fraction N,N'-dimethyl-N'-hydroxyethyl bisaminoethyl ether (used as a raw material for the next batch), and a fraction at 176-193°C / 7 mmHg is collected as the product BMEAEE.

[0038] In the present invention, the dimensions of the tubular reactor are, for example, 10 mm in inner diameter and 2 m in length, and the filler in the distributor is a stainless steel wire mesh.

[0039] Since mixed liquid 1 / mixed liquid 2 continuously enters the inner cavity of the tubular reactor, and EO provided by the EO cylinder also continuously enters the tubular reactor, the pressure in the tubular reactor is positive, and generally controlled to not exceed 0.5 MPa. Therefore, the pressure relief value of the pressure relief valve 15 can be set to 0.5 MPa to ensure the safety of the system.

[0040] The present invention first prepares bis(monomethylaminoethyl) ether (hereinafter referred to as BMAEE) by catalytic etherification of MMEA and concentrated sulfuric acid according to the existing technology (CN116283616A). Then, BMHEAEE is synthesized using ethylene oxide (hereinafter referred to as EO) as the main raw material according to the method set forth in the present invention.

[0041] The tubular reaction device of the present invention is as follows Figure 1Mixed liquid 1 (consisting of BMAEE and catalyst) or mixed liquid 2 (consisting of BMAEE, N,N'-dimethyl-N'-hydroxyethyl bisaminoethyl ether, an intermediate fraction obtained by fractionation of the reaction liquid, and catalyst) enters the reactor from the top, while EO enters the reactor from the bottom through a distributor. Gas from the upper reactor is discharged from the top, passed through a circulation pump, mixed with the newly introduced EO, and then re-enters the reactor. The reactor is heated in an oil bath to maintain a constant temperature. The reaction liquid discharge port is at the bottom of the reactor, and sampling can be performed at any time during the reaction to monitor the reaction liquid composition. The hydroxyethylation reaction equation is shown in S-3:

[0042]

[0043] It should be noted that: A small amount of by-product obtained from the reaction can also be separated in the subsequent distillation step.

[0044] The present invention first prepares bis(monomethylaminoethyl) ether (hereinafter referred to as BMAEE) by catalytic etherification of MMEA and concentrated sulfuric acid according to the existing technology (CN116283616A). Then, BMHEAEE is synthesized using ethylene oxide (hereinafter referred to as EO) as the main raw material according to the method set forth in the present invention.

[0045] The hydroxyethylation synthesis process uses a tubular reactor to continuously produce BMHEAEE, which effectively suppresses the by-products BMHEAEE and EO, improves product yield, isolates the reaction system from the outside world, and reduces reaction risks. Compared with intermittent reactors, the continuous production using a tubular reactor does not require an agitator, improves production safety, and is also conducive to increasing output. BRIEF DESCRIPTION OF THE DRAWINGS

[0046] The specific embodiments of the present invention are further described in detail below with reference to the accompanying drawings.

[0047] Figure 1 Schematic diagram of the tubular reaction apparatus. DETAILED DESCRIPTION

[0048] The present invention will be further described below with reference to specific examples, but the scope of protection of the present invention is not limited thereto. In the following examples, the content of the relevant components was detected by GC.

[0049] Device Example 1. A tubular reaction device, such as Figure 1As shown, it includes a U-shaped differential pressure gauge 1, a liquid feed pipeline 2, a flow meter b3, a tubular reactor 4 (inner diameter of 10 mm, length of 2 m), a constant temperature bath 5, a thermal oil circulation pump 6, a thermal oil jacket 7, a distributor 8 (filler is stainless steel wire mesh), an EO cylinder 9, a pneumatic circulation pump 10, an EO feed pump 11, a flow meter a12, a discharge logistics pipe 13, a flow meter c14, a pressure relief valve 15, a liquid level meter 16, and an EO feed control valve 17.

[0050] A thermal oil jacket 7 is provided on the outer surface of the tubular reactor 4 . The outlet of the thermal oil jacket 7 is connected to the inlet of the thermal oil jacket 7 through a constant temperature bath 5 and a thermal oil circulation pump 6 . The thermal oil jacket 7 is responsible for supplying heat to the tubular reactor 4 .

[0051] A liquid level gauge 16 is provided on the tubular reactor 4 , and the liquid level gauge 16 is used to display the liquid level height in the inner cavity of the tubular reactor 4 .

[0052] A flow meter b3 is provided on the liquid feed pipeline 2 , which is in communication with the inner cavity of the tubular reactor 4 ; the mixed liquid 1 or the mixed liquid 2 continuously enters the inner cavity of the tubular reactor 4 through the liquid feed pipeline 2 .

[0053] A distributor 8 is located near the bottom of tubular reactor 4. Filled with stainless steel mesh, distributor 8 ensures that EO enters the central portion of tubular reactor 4 evenly, allowing it to react fully with mixed liquid 1 or mixed liquid 2 flowing downward. At the temperature within tubular reactor 4, EO vaporizes.

[0054] The U-shaped differential pressure gauge 1 is connected to the inner cavity of the tubular reactor 4 , and the function of the U-shaped differential pressure gauge 1 is to measure the pressure inside the tubular reactor 4 .

[0055] The top EO outlet of the tubular reactor 4 is connected to the bottom of the distributor 8 through the connecting pipe I 18, the pneumatic circulation pump 10, and the connecting pipe II 19 in sequence. A pressure relief valve 15 is provided on the connecting pipe I 18.

[0056] The pressure in the tubular reactor 4 is positive pressure, which is generally controlled not to exceed 0.5 MPa. Therefore, the pressure relief value of the pressure relief valve 15 can be set to 0.5 MPa to ensure the safety of the system.

[0057] A discharge flow pipe 13 is provided at the bottom outlet of the tubular reactor 4 , and a flow meter c14 and a stop valve 20 are provided on the discharge flow pipe 13 .

[0058] The EO cylinder 9 is connected to the connecting pipe II 19 after passing through the EO feed pump 11, the EO feed control valve 17, and the flow meter a12 in sequence;

[0059] Therefore, the EO provided by the EO cylinder 9 and the EO discharged from the EO outlet at the top of the tubular reactor 4 pass through the distributor 8 and enter the middle inner cavity of the tubular reactor 4.

[0060] Its working process is:

[0061] 1. Open the stop valve 20 and use the discharge flow pipe 13 to fill the tubular reactor 4 with nitrogen to replace the air in the tubular reactor 4. The air is discharged from the pressure relief valve 15 to replace the tubular reactor 4. After the exhaust is completed, close the stop valve 20. This is a conventional technology.

[0062] The reaction temperature is maintained by a thermal oil jacket 7.

[0063] 2. The EO (ethylene oxide) in the EO cylinder 9 enters the tubular reactor 4 after passing through the EO feed pump 11, the EO feed control valve 17, and the flow meter a12; specifically, it enters the middle inner cavity of the tubular reactor 4 after passing through the distributor 8.

[0064] The function of flow meter a12 is to display the flow rate of EO provided by EO cylinder 9 and to control the EO flow rate by adjusting EO feed valve 17;

[0065] 3. Mixed liquid 1 (BMAEE and catalyst) or mixed liquid 2 (BMAEE, N,N'-dimethyl-N'-hydroxyethyl bisaminoethyl ether, an intermediate fraction obtained by fractionation of the reaction liquid, and catalyst) enters tubular reactor 4 via liquid feed line 2. When the liquid level in tubular reactor 4 reaches the set height (approximately 85%), stop valve 20 is opened. The discharge flow rate is controlled by adjusting stop valve 20 to maintain a stable liquid level in tubular reactor 4 at 80-90%. Flowmeter c14 displays the flow rate of the discharged reaction liquid.

[0066] The discharged reaction liquid is detected by GC, and the discharged reaction liquid is collected after the components are stabilized, and then distilled and separated.

[0067] 4. Since the EO in the reaction system is set to be in excess, during the reaction, the EO discharged from the top EO outlet of the tubular reactor 4 passes through the connecting pipe I 18, the pneumatic circulation pump 10, and the connecting pipe II 19 before entering the tubular reactor 4. Specifically, it passes through the distributor 8 and enters the middle inner cavity of the tubular reactor 4.

[0068] When the system pressure is higher than 0.5 MPa, the pressure relief valve 15 is opened to ensure the safety of the reaction system.

[0069] The preparation of BMAEE refers to Example 1 of patent CN116283616A:

[0070] MMEA is used as a raw material and sulfuric acid (concentrated sulfuric acid) is used as a catalyst for etherification reaction; the etherified liquid is neutralized, filtered (solid-liquid separation), and distilled to obtain the target product BMAEE, that is, after distillation separation, a 100-105°C / 760mmHg water fraction, a 60-70°C / 7mmHg MMEA fraction (137g, content 98.5%, recovered as raw material for etherification reaction), a 95-105°C / 760mmHg water fraction (137g, content 98.5%, recovered as raw material for etherification reaction) and a 100-105°C / 760mmHg water fraction are obtained in sequence.

[0071] / 7 mmHg BMAEE fraction (113.6 g, content 99.4%).

[0072] In the following examples, the tubular reactor 4 has an inner diameter of 10 mm and a length of 2 m. The BMAEE used is the above-mentioned BMAEE fraction; and the catalyst solutions are all prepared with deionized water.

[0073] Example 1: A method for synthesizing BMHEAEE, comprising the following steps:

[0074] 1) Hydroxyethylation:

[0075] a represents the EO flow rate provided by the EO cylinder 9;

[0076] The mixed liquid consists of BMAEE, the middle distillate N,N'-dimethyl-N'-hydroxyethyl bisaminoethyl ether, and a catalyst, where b represents the flow rate of the mixed liquid. In the mixed liquid, the ratio of n(BMAEE):n(N,N'-dimethyl-N'-hydroxyethyl bisaminoethyl ether) is 6:1. The catalyst is a 40% (mass %) tetramethylammonium bromide solution, and the amount of catalyst added is 2% by weight of (BMAEE + N,N'-dimethyl-N'-hydroxyethyl bisaminoethyl ether).

[0077] The middle distillate N,N'-dimethyl-N'-hydroxyethyl bisaminoethyl ether may be, for example, the middle distillate obtained in Example 1-1 below;

[0078] c represents the flow rate of the discharged reaction liquid.

[0079] The air in tubular reactor 4 was replaced with nitrogen. The reaction temperature of tubular reactor 4 was maintained at 80°C via thermal oil jacket 7. EO was then continuously pumped into tubular reactor 4 from EO cylinder 9. EO flow rate a was controlled at 31.5 g / h by adjusting EO feed valve 17. Simultaneously, a mixed solution consisting of BMAEE, intermediate distillate N,N'-dimethyl-N'-hydroxyethylbisaminoethyl ether, and catalyst was continuously introduced into tubular reactor 4 via liquid feed line 2 at a flow rate b of 49.4 g / h. The total feed material ratio n (EO:NH) was 1.1:1. When the liquid level in tubular reactor 4 reached approximately 85%, the reactor discharge valve (shutoff valve 20) was opened, and the discharge flow rate was controlled to maintain a stable liquid level within tubular reactor 4 at 80-90%. The discharged reaction liquid was subjected to GC analysis. After the composition stabilized (the composition of the reaction liquid remained essentially unchanged), 242.7 g of the discharged reaction liquid was collected over a 3-hour period and subjected to fractional distillation.

[0080] The residence time of the mixed liquid in the tubular reactor 4 is about 10.18 min; t=v / s, where t represents the residence time, v represents the volume of the tubular reactor 4, and S represents the volume flow rate of the total feed, ie, the total volume flow rate of the mixed liquid + EO.

[0081] 2) Distillation

[0082] The 242.7 g of the reaction liquid collected in step 1) was subjected to vacuum distillation at 7 mm / g to obtain an intermediate fraction of 1.58 g of N,N'-dimethyl-N'-hydroxyethyl bisaminoethyl ether at 120-130°C, and 219.92 g of BMHEAEE at 176-193°C; the obtained product has been verified to be correct.

[0083] Note: Due to the low content of by-products, they are no longer collected after vacuum distillation, the same applies below.

[0084] Example 1-1: When the reaction is initiated for the first time, the following changes are made relative to Example 1:

[0085] Step 1) comprises a mixed solution consisting of BMAEE and a catalyst, wherein the catalyst accounts for 2% by weight of the BMAEE; the flow rate b of the mixed solution is changed to 43.76 g / h, and the EO flow rate remains unchanged, i.e., a = 31.5 g / h. Therefore, the total feed material ratio n (EO:NH) = 1.1:1 remains unchanged, and the residence time of the reaction mixture in the tubular reactor 4 is 10.95 min; otherwise, the same as in Example 1.

[0086] Finally, 183.92 g of BMHEAEE was obtained with a purity of 99.5% and a yield of 85%. 18 g of the intermediate fraction N,N'-dimethyl-N'-hydroxyethyl bisaminoethyl ether was obtained with a purity of 98.5%.

[0087] In Examples 2 to 4 and Comparative Examples 1 to 2, only the reaction temperature in step 1) of Example 1 was changed, and the rest was the same as in Example 1. The results are shown in Table 1 below:

[0088] Table 1

[0089]

[0090]

[0091] Note: In Table 1:

[0092] Middle distillate: This represents the middle distillate N,N'-dimethyl-N'-hydroxyethyl bisaminoethyl ether separated from the discharged reaction liquid. The content is the purity.

[0093] Y = A / (B+C)*100%. Y represents the BMHEAEE yield, A represents the weight of the actual BMHEAEE obtained, B represents the weight of BMHEAEE generated from the added BMAEE, and C represents the weight of BMHEAEE generated from the added N,N'-dimethyl-N'-hydroxyethyl bisaminoethyl ether.

[0094] In Examples 5 to 7 and Comparative Examples 3 to 4, the molar ratio of EO to NH in step 1) of Example 1 was changed, the flow rate of the mixed solution remained unchanged at 49.4 g / h, and the EO flow rate a was changed accordingly, thereby changing n(EO:NH); the rest was the same as in Example 1. The results are shown in Table 2 below.

[0095] Table 2

[0096]

[0097] In Examples 8 to 10 and Comparative Examples 5 to 6, the catalyst content in step 1) of Example 1 was changed, and the rest was the same as in Example 1. The results are shown in Table 3 below:

[0098] Table 3

[0099]

[0100] In Examples 11 to 13 and Comparative Example 7, the feed flow rates in step 1) of Example 1 were changed (as shown in Table 4), the ratios of BMAEE, middle distillate N,N'-dimethyl-N'-hydroxyethylbisaminoethyl ether, and catalyst remained unchanged, and the n(EO:NH) ratio remained unchanged at 1.1:1; all other conditions were the same as in Example 1. The results are shown in Table 4:

[0101] Table 4

[0102]

[0103]

[0104] In Examples 14 to 19, the catalyst type in Example 1 was changed, and the rest was the same as in Example 1. The results are shown in Table 5 below:

[0105] Table 5

[0106]

[0107]

[0108] Example 20: In the mixed solution, the ratio of n(BMAEE):n(N,N'-dimethyl-N'-hydroxyethylbisaminoethyl ether) was changed from "6:1" to "5:1", while keeping n(EO:NH) = 1.1:1 unchanged. The residence time of the mixed solution in the tubular reactor 4 was about 10.06 min, and the rest was basically the same as in Example 1.

[0109] The yield of BMHEAEE product was 90.72%.

[0110] Example 21. In the mixed solution, the ratio of n(BMAEE):n(N,N'-dimethyl-N'-hydroxyethylbisaminoethyl ether) was changed from "6:1" to "7:1", while keeping n(EO:NH) = 1.1:1 unchanged. The residence time of the mixed solution in the tubular reactor 4 was about 10.28 min. The rest was basically the same as in Example 1.

[0111] The yield of BMHEAEE product was 93.47%.

[0112] Example 22: The ratio of n(BMAEE):n(N,N'-dimethyl-N'-hydroxyethylbisaminoethyl ether) in the mixed solution was changed from "6:1" to "4:1", while keeping n(EO:NH) = 1.1:1 unchanged. The residence time of the mixed solution in the tubular reactor 4 was about 9.89 min, and the rest was basically the same as in Example 1.

[0113] The yield of BMHEAEE product was 86.76%.

[0114] Example 23: The ratio of n(BMAEE):n(N,N'-dimethyl-N'-hydroxyethylbisaminoethyl ether) in the mixed solution was changed from "6:1" to "8:1", while keeping n(EO:NH) = 1.1:1 unchanged. The residence time of the mixed solution in the tubular reactor 4 was about 10.35 min, and the rest was basically the same as in Example 1.

[0115] The yield of BMHEAEE product was 92.65%.

[0116] Comparative Example 8: The tubular reactor in step (1) of Example 1 was changed to a batch reactor, specifically:

[0117] A mixture of 148.2 g (118.8 g BMAEE, 26.4 g intermediate fraction N,N'-dimethyl-N'-hydroxyethyl bisaminoethyl ether, and 3 g 40% tetramethylammonium bromide solution) was added to the reactor. The mixture had a ratio of n(BMAEE):n(N,N'-dimethyl-N'-hydroxyethyl bisaminoethyl ether) of 6:1. The catalyst in the mixture was a 40% (mass %) tetramethylammonium bromide solution, added in an amount equivalent to 2% of the weight of the BMAEE + N,N'-dimethyl-N'-hydroxyethyl bisaminoethyl ether) solution. The temperature was raised to 80°C and maintained stable. 94.5 g EO was slowly pumped into the reactor, resulting in a ratio of n(EO:NH4)=1. After the EO was pumped in, the reaction continued for two hours, with no changes in the composition. The yield of BMHEAEE was 84.5%.

[0118] Comparative Example 9: The catalyst used in step 1) of Example 1 was changed from 40% tetramethylammonium bromide solution to no catalyst. That is, the mixed solution consisted of BMAEE and the intermediate fraction N,N'-dimethyl-N'-hydroxyethylbisaminoethyl ether. The flow rate b of the mixed solution was slightly reduced accordingly (to about 48.4 g / h). The rest was basically the same as in Example 1.

[0119] The yield of BMHEAEE product was 64.3%.

[0120] Finally, it should be noted that the above examples are merely specific embodiments of the present invention. Obviously, the present invention is not limited to the above examples and is subject to numerous variations. All variations that can be directly derived or conceived by a person of ordinary skill in the art from the disclosure of the present invention are considered to be within the scope of protection of the present invention.

Claims

1. A method for synthesizing bis(N-methyl-N-hydroxyethylaminoethyl) ether, using bis(methylaminoethyl) ether as a raw material, characterized in that: A tubular reaction device is used, the tubular reaction device comprising a tubular reactor (4) with a heating device, a liquid feed line (2) being connected to an inner cavity near the top of the tubular reactor (4), and a flow meter b (3) being provided on the liquid feed line (2); The EO cylinder (9) is connected to the inner cavity near the bottom of the tubular reactor (4) through the EO feed pump (11), the EO feed control valve (17) and the flow meter a (12) in sequence; The EO outlet located at the top of the tubular reactor (4) is connected to the inner cavity near the bottom of the tubular reactor (4) through a pneumatic circulation pump (10); A discharge flow pipe (13) is provided at the bottom outlet of the tubular reactor (4), and a flow meter c (14) and a stop valve (20) are provided on the discharge flow pipe (13); The method for synthetic bis(N-methyl-N-hydroxyethylaminoethyl) ether comprises the following steps: 1) Hydroxyethylation: A mixed solution 1 is composed of bis(methylaminoethyl) ether and a catalyst; or a mixed solution 2 is composed of bis(methylaminoethyl) ether, an intermediate fraction N,N'-dimethyl-N'-hydroxyethyl bisaminoethyl ether obtained by fractionation of the reaction solution, and a catalyst; Mixed liquid 1 or mixed liquid 2 continuously enters the inner cavity of the tubular reactor (4) from the upper portion of the tubular reactor (4), and EO provided by the EO cylinder (9) enters the inner cavity of the tubular reactor (4) from the lower portion of the tubular reactor (4); The EO discharged from the top of the tubular reactor (4) is continuously fed into the tubular reactor (4) together with the EO provided by the EO cylinder (9) under the action of the gas circulation pump (10); the temperature in the tubular reactor (4) is maintained at a reaction temperature of 40 to 150°C; the residence time of the mixed solution 1 or the mixed solution 2 in the tubular reactor (4) is 5 to 25 minutes; The resulting reaction liquid is discharged from the discharge port located at the bottom of the tubular reactor (4); When using mixed solution 1: the material molar ratio is n(EO: bis(methylaminoethyl) ether) = 0.7~1.3:1; the weight ratio of catalyst: bis(methylaminoethyl) ether = 0.5~5%; When using mixed solution 2: the material molar ratio is n(EO:NH) = 0.7-1.3:1, where NH is the sum of the number of NH groups in the molecules of the raw material bis(methylaminoethyl) ether and the intermediate distillate N,N'-dimethyl-N'-hydroxyethyl bisaminoethyl ether; the weight ratio of catalyst: (bis(methylaminoethyl) ether + N,N'-dimethyl-N'-hydroxyethyl bisaminoethyl ether) = 0.5-5%; n(bis(methylaminoethyl) ether): n(N,N'-dimethyl-N'-hydroxyethyl bisaminoethyl ether) = 1-8:1; 2) Distillation: The reaction solution obtained in step 1) is subjected to vacuum distillation to obtain an intermediate fraction N,N'-dimethyl-N'-hydroxyethyl bisaminoethyl ether and a product fraction bis(N-methyl-N-hydroxyethylaminoethyl) ether, respectively. The intermediate fraction is recycled to step 1) as a reaction raw material.

2. The method for synthesizing bis(N-methyl-N-hydroxyethylaminoethyl) ether according to claim 1, wherein: The catalyst is any one of tetramethylammonium bromide solution, tetrabutylammonium bromide solution, tetramethylammonium chloride solution, triethylbenzylammonium chloride solution and trimethylhexadecylammonium chloride solution with a mass concentration of 30-50%.

3. The method for synthesizing bis(N-methyl-N-hydroxyethylaminoethyl) ether according to claim 2, wherein: Bis(methylaminoethyl)ether and the catalyst are first mixed evenly to form a mixed liquid 1; and then the mixed liquid enters the tubular reactor (4) through the liquid feed line (2); Alternatively, bis(methylaminoethyl) ether, the intermediate fraction N,N'-dimethyl-N'-hydroxyethyl bisaminoethyl ether obtained from the reaction solution by distillation, and the catalyst are first mixed uniformly to form a second mixed solution; and then the mixed solution is fed into the tubular reactor (4) through the liquid feed line (2).

4. The method for synthesizing bis(N-methyl-N-hydroxyethylaminoethyl) ether according to claim 2 or 3, wherein: The catalyst is a tetramethylammonium bromide solution with a mass concentration of 40%.

5. The method for synthesizing bis(N-methyl-N-hydroxyethylaminoethyl) ether according to claim 4, wherein: In the step 2), the fraction at 120-130°C / 7 mmHg is collected by vacuum distillation to obtain the intermediate fraction N,N'-dimethyl-N'-hydroxyethyl bisaminoethyl ether, and the fraction at 176-193°C / 7 mmHg is collected as the product BMEAEE.

6. The method for synthesizing bis(N-methyl-N-hydroxyethylaminoethyl) ether according to claim 5, wherein: A distributor (8) is provided near the bottom of the inner cavity of the tubular reactor (4), and EO provided by the EO cylinder (9) and EO discharged from the EO outlet located at the top of the tubular reactor (4) enter the middle inner cavity of the tubular reactor (4) through the distributor (8).

7. The method for synthesizing bis(N-methyl-N-hydroxyethylaminoethyl) ether according to claim 6, wherein: The heating device of the tubular reactor (4) includes a constant temperature bath (5), a thermal oil circulation pump (6) and a thermal oil jacket (7); A heat transfer oil jacket (7) is provided on the outer surface of the tubular reactor (4). The outlet of the heat transfer oil jacket (7) is connected to the inlet of the heat transfer oil jacket (7) through a constant temperature bath (5) and a heat transfer oil circulation pump (6) in sequence. The heat transfer oil jacket (7) is responsible for supplying heat to the tubular reactor (4).

8. The method for synthesizing bis(N-methyl-N-hydroxyethylaminoethyl) ether according to claim 7, wherein: The EO outlet located at the top of the tubular reactor (4) is connected to the connecting pipe II (19) through the connecting pipe I (18) and the pneumatic circulation pump (10) in sequence; a pressure relief valve (15) is provided on the connecting pipe I (18); The EO cylinder (9) is connected to the connecting pipe II (19) through the EO feed pump (11), the EO feed control valve (17) and the flow meter a (12) in sequence; The connecting pipe II (19) is connected to the bottom of the distributor (8).

9. The method for synthesizing bis(N-methyl-N-hydroxyethylaminoethyl) ether according to claim 8, wherein: A liquid level gauge (16) is provided on the tubular reactor (4), and a U-shaped differential pressure gauge (1) is also provided on the tubular reactor (4).

Images