CN116332866A

CN116332866A - Preparation method of 2,2' -bis (2-oxazoline)

Info

Publication number: CN116332866A
Application number: CN202310219269.8A
Authority: CN
Inventors: 吴林波; 葛浩栋
Original assignee: Zhejiang University ZJU
Current assignee: Zhejiang University ZJU
Priority date: 2023-03-02
Filing date: 2023-03-02
Publication date: 2023-06-27

Abstract

The invention relates to the technical field of polymer auxiliary synthesis, and discloses a preparation method of 2,2 '-bis (2-oxazoline). The preparation method takes cheap and easily available dimethyl oxalate as a raw material, and carries out ester-amide exchange reaction with ethanolamine at a lower temperature in the absence of a solvent or in the presence of a single solvent, and N, N' -bis (2-hydroxyethyl) oxamide is obtained by filtration; the N, N '-di (2-hydroxyethyl) oxamide and thionyl chloride are subjected to chlorination reaction under the condition of gradually heating in the range of 50-90 ℃, and the N, N' -di (2-chloroethyl) oxamide is obtained by filtering; methanol or ethanol is used as a single solvent, N, N '-bis (2-chloroethyl) oxamide and inorganic base are subjected to ring-closure reaction in the presence of a water absorbent, and the 2,2' -bis (2-oxazoline) with high purity is obtained through filtration and crystallization. Secondary crystallization of the crystallization mother liquor can further improve the yield; the dissolution used in the reaction can be recycled. The method has the advantages of simple process, high efficiency, energy conservation, environmental protection, low synthesis cost and high product yield and purity.

Description

Preparation method of 2,2' -bis (2-oxazoline)

Technical Field

The invention relates to the technical field of polymer additive synthesis, in particular to a preparation method of 2,2' -bis (2-oxazoline).

Background

The oxazoline compound has certain reactivity as a five-membered heterocyclic compound containing nitrogen, oxygen and double bonds, so that the oxazoline compound has wide application in the fields of medicines, catalysis, materials and the like. In the field of materials, the bisoxazoline has the advantages of higher reactivity, no small molecular byproducts generated during the reaction, and the like, and can be used as a chain extender to react with carboxyl end groups of polymers such as polyester, polyamide and the like, so that molecular chains are increased, and the molecular weight of the polymers is obviously improved. Currently, commercial bisoxazolines mainly include three types of 2,2' -bis (2-oxazoline) (BOZ), 1, 4-phenyl bisoxazoline (1, 4-PBO) and 1, 3-phenyl bisoxazoline (1, 3-PBO), but scale production and application are not realized, and the bisoxazoline is only supplied as a chemical reagent. Among them, 2' -bis (2-oxazoline) has good practical application value as the only non-benzene ring-containing bisoxazoline chain extender which is currently marketed, but has extremely high price due to high synthesis cost and limited practical application.

The synthesis of oxazoline includes three-step method, two-step method and one-pot method. The three-step process generally employs the reaction of an amino alcohol with a carboxylic acid, ester, acid chloride, or the like to form hydroxyethyl amide; the hydroxyethyl amide reacts with a chlorinating agent to generate chloroethyl amide; and (3) ring closure is carried out on chloroethylamide under alkaline conditions to obtain oxazoline. There are two ways of two-step processes. One is to obtain chloroethylamide first and then oxazoline in a closed loop. For example, CN113773271a employs acid chloride and chloroethylamine salt to react to obtain chloroethylamide, and then ring closure under alkaline conditions to obtain oxazoline; CN111233852A is prepared by reacting dibasic acid, oxalyl chloride and amino alcohol to obtain hydroxyethyl amide, and then ring-closing under the action of triphenylphosphine, carbon tetrachloride and triethylamine to obtain the bisoxazoline.

Regarding the one-pot method, CN114436989A, CN1150174A, tetrahedron letters (Vol.38, 1997: 7019-7020), tetrahedron (Vol.63, 2007: 1474-1480) reported that the one-step method of directly synthesizing the bisoxazoline from the substrate such as the aromatic diacid, the aromatic diacid diester, the aromatic dialdehyde and the amino alcohol is catalyzed by using hypophosphorous acid, alkyl hypophosphorous acid, phenyl hypophosphorous acid, lanthanum chloride, molecular iodine and the like as catalysts; in CN104876970A, zinc chloride is used for catalyzing the direct synthesis of the bisoxazoline by the one-pot method of the aromatic dinitrile and the amino alcohol. The one-pot method is seemingly simple, but is only suitable for synthesizing the aromatic bisoxazoline, and is difficult to synthesize the non-aromatic bisoxazoline, and is not reported in the literature.

For chiral oxazoline compounds, tetrahedron Letters (Vol.39, 1998: 459-462), chemical communications (Vol.25, 2006: 2711-2713), organic letters (Vol.7, 2005: 1971-1974), journal of the American Chemical Society (Vol.126, 2004: 6230-6231), tetrahedron Letters (Vol.51, 2010: 5313-5315) reported that natural argil can be used as a catalyst to catalyze aromatic nitrile, zinc compounds as a catalyst to catalyze ester substrates, molybdenum oxide compounds as a catalyst to catalyze hydroxyethylamides, p-toluenesulfonic acid as a catalyst to catalyze hydroxyethylamides, boric acid as a catalyst to catalyze hydroxyethylamides, and the like, a one-step method for directly synthesizing chiral oxazoline compounds was reported. However, the same method is not effective when used for the synthesis of non-aromatic bisoxazolines.

Commercially available 1,3-PBO and 1,4-PBO are usually synthesized from dinitriles. However, ethanedinitrile is a gas at room temperature and is highly toxic and unsuitable as a raw material for the synthesis of BOZ. In the prior art, diethyl oxalate is used as a raw material, and BOZ is synthesized by a three-step method. For example Journal of Polymer Science Part B Polymer Physics, vol.45, 2007:1976-1982 report that compound A1 can be obtained by slowly dropping an ethanol solution containing ethanolamine into an ethanol solution containing diethyl oxalate. The reaction mixture was heated to reflux in a boiling water bath until a dry precipitate was obtained. Then a large amount of ethanol was added, and the mixture was heated to dissolve the whole, followed by cooling to room temperature. Finally, white crystals of compound A1 were obtained in 94.1% yield. A1, thionyl chloride and toluene were mixed with stirring and heated on an oil bath. A1 is not dissolved, and the reaction system is sticky. The reaction product was cooled, filtered, washed with ethanol-boiling water-ethanol in sequence, and then recrystallized from ethylene glycol monoethyl ether. After washing with ethanol several times, B1 was obtained in a yield of 68.9%. Add B1, 0.67mol/L ethanol solution of potassium hydroxide and benzene to a three-necked flask and stir. The reaction is carried out for approximately 5 hours at the temperature of 110 ℃, the supernatant is obtained after filtering potassium hydroxide, the solvent is distilled off from the filtrate, the obtained white solid is recrystallized in toluene, and finally the product C1 is obtained with the yield of 82 percent. The total yield of the three steps was 53.2%. In the method, in the first step, the material is additionally heated and reacts at high temperature, so that the energy consumption is increased, and only diethyl oxalate with good heat stability but more high cost can be used as a raw material; a large amount of organic solvent is needed, and the operation steps are complicated. The second step has low yield of only 68.9%. And a plurality of different organic solvents are used in the second and third steps of reaction and/or purification, the process is complex, the high boiling point solvent is difficult to be completely recovered, and the yield is low.

CN104447601a discloses a method for synthesizing 2,2' -bis (2-oxazoline), which takes diethyl oxalate and ethanolamine as raw materials, and the raw materials are subjected to reflux reaction for 10 hours at 100 ℃ in toluene, and then are washed by cold toluene and normal hexane and then dried to obtain an intermediate product; the intermediate product reacts with thionyl chloride, and the inorganic base is closed to obtain pale yellow solid with the yield of 83 percent. However, on the one hand, this process uses diethyl oxalate as a raw material, increasing costs. On the other hand, a long time and high temperature reaction is required in the first step, increasing the energy consumption cost. In addition, the reaction time of the second step is still too long and the reaction conditions of the third step are cumbersome and various organic solvents are used. Most importantly, the N, N '-bis (2-chloroethyl) oxamide and the 2,2' -bis (2-oxazoline) prepared by the method are light yellow, and the purity is not high.

In summary, the synthesis of 2,2' -bis (2-oxazoline) has the problems of high cost of synthetic raw materials, high energy consumption in the process, environmental protection, complex product purification process, requirement of using various organic solvents and the like. Therefore, the synthesis of 2,2' -bis (2-oxazoline) by using cheap and easily available raw materials and a method with higher efficiency, more environmental protection, lower cost and lower energy consumption is still a technical problem to be solved.

Disclosure of Invention

Aiming at the problems of high synthesis cost, low yield or low purity of 2,2 '-bis (2-oxazoline) in the prior art, the invention provides a preparation method which not only reduces the cost, but also is more environment-friendly and lower in energy consumption, and simultaneously can realize higher yield and purity under a simple treatment process, thereby having important significance for the market popularization and application of the 2,2' -bis (2-oxazoline).

In order to achieve the above purpose, the invention adopts the following technical scheme:

a method for preparing 2,2' -bis (2-oxazoline), comprising the steps of:

step 1, adding oxalic acid diester into ethanolamine, controlling the reaction temperature to be not higher than 80 ℃, reacting for 10-120min, filtering, washing and drying a product to obtain N, N' -bis (2-hydroxyethyl) oxamide;

step 2, dispersing N, N' -bis (2-hydroxyethyl) oxamide in an organic solvent, adding thionyl chloride, and controlling the temperature of a system to be not higher than 50 ℃; then continuing the reaction, when the flow rate of reaction tail gas is not higher than 0.1mL/min/gN, N '-bis (2-hydroxyethyl) oxamide, heating to 3-10 ℃ for continuing the reaction, repeating the process until the reaction temperature reaches 90 ℃, and filtering, washing and drying the product after the reaction is finished to obtain the N, N' -bis (2-chloroethyl) oxamide;

And 3, carrying out reflux reaction on the N, N '-bis (2-chloroethyl) oxamide and inorganic alkali in methanol or ethanol solution containing water absorbent for 0.5-3h, carrying out hot filtration, cooling and crystallizing filtrate until no crystal is generated, and drying a crystal product to obtain the 2,2' -bis (2-oxazoline).

In the method, in the step 1, ethanolamine and oxalic acid diester are used as raw materials, the reaction is carried out in a solvent-free state at the temperature lower than 80 ℃ for more than 10min, the reaction can be carried out in an ethanolamine methanol/ethanol solution, and the obtained product can be obtained by simple filtration, washing and drying, wherein the impurity is very few, the yield is more than 86 percent, and the highest yield is 98.1 percent; in the step 2, a gradual heating mode is adopted, so that the yield can be unexpectedly improved, the raw material reaction is more complete, and the yield is up to 96.4%; in the step 3, a low-toxicity and nontoxic methanol or ethanol solvent is adopted, and the product only needs to be cooled, crystallized and recrystallized again, so that the total yield can reach more than 85 percent. The whole reaction process has mild condition, short time and simple treatment steps, particularly the time of the step 1 is greatly shortened, the energy consumption is greatly reduced, toxic organic solvents such as toluene and the like are not needed, ideal solvents such as methanol and ethanol are adopted in the step 3, the ideal solvents can be used as solvents for the reaction and can be used as crystallization solvents for the post-treatment, and additional organic solvents such as toluene and 1, 4-dioxane are not needed to be introduced. The yield and purity of the final product are high, which is of great significance for the application of BOZ.

Preferably, the oxalic acid diester is dimethyl oxalate or diethyl oxalate; according to the method, not only can diethyl oxalate be used, but also dimethyl oxalate with the raw material price far lower than that of the diethyl oxalate can be used, so that the dimethyl oxalate is optimized, and the synthetic raw material cost of BOZ can be reduced to a great extent;

step 1 also comprises solvent ethanol or methanol; in the step 1 of the invention, ethanol or methanol can be used as a solvent to absorb heat generated by the reaction, so that the reaction temperature is prevented from rising too fast;

preferably, the step 1 also comprises solvent ethanol, and the dissolution rate of the product N, N' -bis (2-hydroxyethyl) oxamide in ethanol is low, which is more beneficial to improving the yield.

Preferably, when the reaction of the step 1 is solvent-free, the product is filtered after being diluted by methanol or ethanol because the product is solid; the product of the step 1 is washed by using methanol or ethanol as a solvent;

preferably, when the reaction in step 1 comprises a solvent, the product is directly filtered, washed and dried;

when the oxalic acid diester is diethyl oxalate, the reaction in the step 1 is solvent-free, the stability of the diethyl oxalate is better, and the yield of the solvent-free reaction can reach more than 95%.

Preferably, the reaction time of step 1 is 10 to 60min, more preferably 10 to 30min, still more preferably 10 to 20min, and the reaction time is greatly shortened compared with the prior art while ensuring the yield and purity.

In the step 1, the molar ratio of oxalic acid diester to ethanolamine is 1:2.2-2.6; too low a molar ratio is detrimental to the reaction, resulting in low yields, and too high a molar ratio is detrimental to the utilization of the starting materials.

Preferably, the reaction temperature is 15-80 ℃; preferably, the reaction temperature is 40 to 80 ℃. An increase in the reaction temperature can improve the yield to some extent, but an excessive temperature may cause decomposition of dimethyl oxalate. Too low a temperature may affect the progress of the reaction, resulting in a decrease in yield.

When the step 1 also comprises methanol or ethanol as a solvent, the mass of the methanol or the ethanol is 1 to 5 times of that of the ethanolamine; preferably, the mass of methanol or ethanol is 3 to 5 times that of ethanolamine.

The organic solvent in the step 2 comprises any one or more of toluene, 1, 4-dioxane, butyl acetate and xylene.

In the step 2, the molar ratio of the N, N' -bis (2-hydroxyethyl) oxamide to the thionyl chloride is 1:2.2 to 4.0, preferably the molar ratio of N, N' -bis (2-hydroxyethyl) oxamide to thionyl chloride is 1:2.6 to 3.4;

in the step 2, the mass of the organic solvent is 3 to 5 times of the mass of the N, N '-bis (2-hydroxyethyl) oxamide, preferably, the mass of the organic solvent is 3.5 to 4.5 times of the mass of the N, N' -bis (2-hydroxyethyl) oxamide.

In the step 2, when the flow rate of the tail gas is less than 0.1mL/min/gN, N' -bis (2-hydroxyethyl) oxamide, the reaction temperature is raised by 3-10 ℃, and the reaction is continued; after the reaction temperature is raised to 90 ℃, the temperature is not raised, and the reaction is ended when the flow of reaction tail gas is smaller than 0.1mL/min/gN, N' -bis (2-hydroxyethyl) oxamide at the temperature; preferably, inert gas is introduced into the system after the reaction is finished so as to exhaust residual tail gas in the device.

In the step 3, the inorganic alkali is sodium hydroxide or potassium hydroxide; the molar ratio of the N, N' -di (2-chloroethyl) oxamide to the inorganic base is 1:2 to 3, preferably, the molar ratio of N, N' -bis (2-chloroethyl) oxamide to inorganic base is 1:2.0 to 2.5; the water absorbing agent is allochroic silica gel or molecular sieve, and the dosage of the water absorbing agent is 1.5-2 times of the mass of the N, N' -di (2-chloroethyl) oxamide.

The mass of the methanol or the ethanol in the step 3 is 4 to 10 times of that of the N, N '-bis (2-chloroethyl) oxamide, preferably, the mass of the methanol or the ethanol is 5 to 7 times of that of the N, N' -bis (2-chloroethyl) oxamide; the water content in methanol or ethanol is controlled below 0.3 wt%.

In the step 3, the filtering while the reaction is hot means that the filtering is performed immediately after the reaction is finished, and the cooling process is not performed so as to remove inorganic salt impurities.

Preferably, the filtrate in step 3 is cooled, crystallized and filtered, and then the crystallization mother liquor is secondarily crystallized to further improve the yield.

In the invention, the step 3 adopts low-toxicity or nontoxic methanol or ethanol as a solvent, the reaction temperature is in reflux reaction for 0.5-3 hours at the boiling point of 60-80 ℃, and the product can be directly filtered and crystallized after the reaction is finished, so that the higher purity can be achieved without a washing process, the advantages of mild reaction conditions, short time, no harmful organic solvent, simple treatment process and the like can be achieved, and the yield and the purity of the product can be ensured.

Preferably, the product is washed by methanol or ethanol, so that the purity of the product is further improved.

The reaction formula of each step in the preparation process of the invention is as follows:

the yield of each step is high and the purity is high, wherein the yield of the N, N' -bis (2-hydroxyethyl) oxamide in the step 1 is not lower than 85 percent, and the purity is not lower than 99 percent; preferably, the yield is not less than 88%, further preferably the yield is not less than 90%;

in the step 2, the yield of the N, N' -bis (2-chloroethyl) oxamide is not lower than 95 percent, and the purity is not lower than 99 percent; preferably, the yield is not less than 96%;

the yield of 2,2' -bis (2-oxazoline) in step 3 is not less than 85%, the purity is not less than 98%, and the preferred yield is not less than 85.5%.

In addition, in the invention, the filtrate in the step 1 is recycled for the reaction medium in the step 1, the filtrate in the step 2 is decolorized and then is used for the reaction medium in the step 2, and the crystallization mother liquor in the step 3 is recycled for the reaction medium in the step 3. Because the impurities generated in the reaction of each step are less, or only a very small amount of unreacted raw materials can be recycled for each step as a reaction medium, the preparation cost is further reduced.

When secondary crystallization is used in step 3, the secondary crystallization mother liquor may also be recycled for use in step 3.

Compared with the prior art, the invention has the following beneficial effects:

(1) The step 1 of the invention reacts at a lower temperature (less than or equal to 80 ℃), thereby reducing energy consumption, improving raw material adaptability, using diethyl oxalate as a raw material, using dimethyl oxalate with poor thermal stability but lower price and easy availability as a raw material, inhibiting side reaction and improving yield;

(2) The reaction in the step 1 does not need to use a solvent or only uses low-toxicity or nontoxic methanol or ethanol solvents, so that toxic organic solvents are avoided; the product N, N' -bis (2-hydroxyethyl) oxamide can be purified by simple filtration and washing, and has the advantages of simple process, low production cost and high yield;

(3) In the step 2, the reaction is more effectively promoted by controlling the reaction temperature and the reaction rate, so that the residual raw materials are prevented from not participating in the reaction, and the yield and the purity of the N, N' -bis (chloroethyl) oxamide are obviously improved;

(4) In the method, only a single solvent methanol or ethanol is adopted in the steps 1 and 3, and in the step 3, the methanol or ethanol is used as a reaction medium and is also used as a recrystallization solvent, so that the use of an additional recrystallization solvent is avoided, the purification operation is simplified, the solubility of 2,2' -bis (2-oxazoline) in the methanol or ethanol is more temperature-dependent than that in other solvents, the crystallization of the 2,2' -bis (2-oxazoline) is facilitated, and the improvement of the separation yield and purity of the 2,2' -bis (2-oxazoline) is facilitated;

in conclusion, the method integrates the characteristics and advantages of simple operation, low production cost, low energy consumption and high yield and purity, and can greatly relieve the problem of limited application caused by high synthesis cost and high price of the BOZ in the prior art.

Drawings

FIG. 1 shows nuclear magnetic resonance hydrogen spectra of N, N ' -bis (2-hydroxyethyl) oxamide, N ' -bis (2-chloroethyl) oxamide and 2,2' -bis (2-oxazoline) obtained in steps 1 to 3, respectively, of example 1.

FIG. 2 shows nuclear magnetic resonance spectra of 2,2' -bis (2-oxazoline) obtained in example 1 in the first crystallization step and the second crystallization step of the mother liquor.

FIG. 3 shows nuclear magnetic resonance spectrum of N, N' -bis (2-hydroxyethyl) oxamide obtained in step 1 of example 5.

FIG. 4 shows nuclear magnetic resonance spectra of N, N' -bis (2-chloroethyl) oxamide obtained in step 2 of example 1 and comparative example 3.

Detailed Description

The present invention will be described in further detail with reference to the following examples in order to make the objects, technical solutions and advantages of the present invention more apparent. It should be understood that the specific embodiments described herein are for purposes of illustration only and are not intended to limit the scope of the invention. Modifications and equivalents will occur to those skilled in the art upon understanding the present teachings without departing from the spirit and scope of the present teachings.

The raw materials and equipment used in the invention are common raw materials and equipment in the field unless specified otherwise; the methods used in the present invention are conventional in the art unless otherwise specified. The raw materials used in the following embodiments are all commercially available.

Nuclear magnetic hydrogen spectrum @ ¹ H NMR): testing with Avance NEO nuclear magnetic resonance apparatus (500 MHz) of Bruker, germany, with deuterated water or deuterated dimethyl sulfoxide (DMSO-d) ₆ ). For convenience of description, raw materials and abbreviations thereof used in the following detailed description are summarized in table 1.

Table 1 names and abbreviations for Compounds appearing in the detailed description

Names of Compounds	Abbreviations (abbreviations)
		Oxalic acid diethyl ester	DEO
Oxalic acid dimethyl ester	DMO
		Ethanolamine	MEA
N, N' -bis (2-hydroxyethyl) oxamide	BHEOA
		N, N' -bis (2-chloroethyl) oxamide	BCEOA
2,2' -bis (2-oxazoline)	BOZ

Example 1

DEO is used as a raw material, the DEO/MEA molar ratio is 1:2.2, the reaction in the step 1 is solvent-free, and the water bath is not heated

Step 1, adding 134.4g of MEA (2.2 mol) into a reactor under the condition of water bath (the water bath is not heated) and stirring, adding 146.1g of DEO (1.0 mol, which is added in 5 minutes), controlling the reaction temperature below 70 ℃, controlling the reaction temperature to 40 ℃ for most of the time, and continuing to react for 10 minutes after the addition is finished; the reaction mixture was filtered, the filter cake was washed with 500mL of ethanol, filtered, and oven dried to give 170.0g of BHEOA as a white powdered solid in 96.5% yield, ¹ the H NMR result (FIG. 1) showed no obvious impurity, purity not less than 99%.

Step 2, adding 52.9g of BHEOA (0.3 mol) prepared in the step 1 and 150mL of toluene into a reactor, stirring to uniformly disperse the BHEOA in the toluene, adding 107.1g of thionyl chloride (0.9 mol) in batches at room temperature, controlling the temperature in an oil bath, and absorbing tail gas generated by the reactor by using a sodium hydroxide aqueous solution at the temperature of not more than 50 ℃; after the dripping is finished, the temperature of the oil bath is increased to 50 ℃, and according to the gas generation condition, the flow rate of the tail gas is increased The reaction temperature is raised by 5 ℃ when the concentration of the N, N '-bis (2-hydroxyethyl) oxamide is less than 0.1mL/min/gN, N' -bis (2-hydroxyethyl) oxamide, and the reaction is continued; repeating the above process, heating to 90 ℃ and then not heating, and stopping the reaction when the flow of the reaction tail gas is smaller than 0.1mL/min/gN, N' -bis (2-hydroxyethyl) oxamide at the temperature, and then introducing nitrogen to sufficiently remove the residual tail gas in the device; the product was filtered, the filter cake obtained was washed sequentially with 200mL deionized water and 200mL ethanol, and oven dried to give 61.6g white powdered solid BCEOA in 96.3% yield, ¹ the H NMR result (FIG. 1) showed no obvious impurity, purity not less than 99%.

Step 3, adding 60mL of ethanol, 14.4g of allochroic silica gel and 3.2g of sodium hydroxide (0.08 mol) into a reactor, stirring to completely dissolve the sodium hydroxide, fully removing water in the ethanol, adding 8.6g of BCEOA (0.04 mol) prepared in the step 2, and stirring and reacting for 1h at the reflux temperature of the ethanol to obtain a suspension containing BOZ and inorganic salt; filtering while the solution is hot, removing inorganic salt, concentrating the filtrate until a small amount of crystals are separated out, cooling for crystallization, filtering and washing after the crystals are no longer produced, drying in an oven to obtain 4.12g of BOZ with the yield of 73.6%, ¹ The H NMR result (FIG. 1) showed no obvious impurity, purity not less than 99%. Performing secondary crystallization on the crystallization mother liquor to obtain 0.683g of BOZ, ¹ h NMR results (FIG. 2) showed that in addition to BOZ, a small amount of BHEOA was contained and the product purity was 97.7%. The total yield of BOZ obtained by the two crystallization is 85.8%, and the total purity is not lower than 98%. The conditions and results are shown in Table 2.

Example 2

DMO is used as a raw material, the mol ratio of DMO to MEA is 1:2.2, the reaction in the step 1 is solvent-free, and the water bath is not heated

Step 1, under the conditions of water bath (the water bath is not heated) and stirring, 134.4g of MEA (2.2 mol) is added into a reactor, 118.1g of DMO (1.0 mol, which is added in 4 minutes) is added in batches, the reaction temperature is controlled below 70 ℃, the reaction temperature is 40 ℃ for most of the time, and the reaction is continued for 10 minutes after the addition is completed; the reaction mixture was filtered, the filter cake was washed with ethanol, filtered, and oven dried to give 160.8g of white powdered solid BHEOA in 91.3% yield, ¹ the H NMR result shows that no obvious impurity exists, and the purity is not lower than 99％。

Adding 52.9g of BHEOA (0.3 mol) prepared in the step 1 and 150mL of toluene solvent into a reactor, stirring to uniformly disperse the BHEOA, adding 107.1g of thionyl chloride (0.9 mol) at room temperature, controlling the feeding rate to be less than or equal to 20g/min, controlling the temperature to be not more than 50 ℃, absorbing the generated tail gas by using sodium hydroxide aqueous solution, raising the temperature of an oil bath to 50 ℃ after the dripping, and continuously reacting at a temperature raised by 5 ℃ when the flow rate of the tail gas is less than 0.1mL/min/gN, and the N' -bis (2-hydroxyethyl) oxamide according to the gas generation condition; repeating the above process, heating to 90 ℃ and then not heating, and stopping the reaction when the flow of the reaction tail gas is smaller than 0.1mL/min/gN, N' -bis (2-hydroxyethyl) oxamide at the temperature, and then introducing nitrogen to sufficiently remove the residual tail gas in the device; the product was filtered, the filter cake obtained was washed sequentially with 200mL deionized water and 200mL ethanol, and oven dried to give 61.4g white powdered solid BCEOA in 96.1% yield, ¹ H NMR results showed no obvious impurity, purity not less than 99%.

Step 3, adding 60mL of ethanol, 14.4g of allochroic silica gel and 3.2g of sodium hydroxide (0.08 mol) into a reactor, stirring to completely dissolve the sodium hydroxide, removing water in the ethanol, adding 8.6g of BCEOA (0.04 mol) prepared in the step 2, and stirring at the reflux temperature of the ethanol for reacting for 1h to obtain a suspension containing BOZ and inorganic salt; filtering while the solution is hot, removing inorganic salt, concentrating the filtrate until a small amount of crystals are separated out, cooling for crystallization, filtering and washing after the crystals are no longer produced, drying in an oven to obtain 4.11g of BOZ with the yield of 73.4%, ¹ h NMR results show that no obvious impurity exists, and the purity is not lower than 99%; the mother liquor was subjected to secondary crystallization to give 0.678g of BOZ, and the purity of the product was 97.6%. The total yield of BOZ obtained by the two crystallization is 85.5%, and the total purity is not lower than 98%. The conditions and results are shown in Table 2.

Example 3

DMO is used as a raw material, the mol ratio of DMO to MEA is 1:2.6, and the reaction solvent ethanol and the anhydrous bath are used for controlling the temperature in the step 1

Step 1, under the condition of room temperature and stirring, 158.8g of MEA (2.6 mol) and 400mL of ethanol are added into a reactor (the reactor is not placed in a water bath and is not heated), 118.1g of DMO (1.0 mol and is added in 4 minutes) are added in batches, the reaction temperature is controlled to be lower than 40 ℃, the reaction temperature is 30 ℃ for most of the time, and the stirring reaction is carried out for 20 minutes; the reaction mixture was filtered, the filter cake was washed with ethanol, filtered and oven dried to give 152.4g of white powdered solid BHEOA in 86.5% yield, not less than 99% purity, and 1H NMR results indicated no significant impurities, not less than 99% purity.

Step 2, adding 52.9g of BHEOA (0.3 mol) prepared in the step 1 and 150mL of toluene solvent into a reactor, stirring to uniformly disperse the BHEOA, adding 107.1g of thionyl chloride (0.9 mol) at room temperature, controlling the feeding rate to be less than or equal to 20g/min, controlling the temperature to be not more than 50 ℃, and absorbing the generated tail gas by using sodium hydroxide aqueous solution; after the dripping is finished, the temperature of the oil bath is increased to 50 ℃, and according to the gas generation condition, when the flow rate of tail gas is less than 0.1mL/min/gN, N' -bis (2-hydroxyethyl) oxamide, the reaction temperature is increased by 5 ℃, and the reaction is continued; repeating the above process, heating to 90 ℃ and then not heating, and stopping the reaction when the flow of the reaction tail gas is smaller than 0.1mL/min/gN, N' -bis (2-hydroxyethyl) oxamide at the temperature, and then introducing nitrogen to sufficiently remove the residual tail gas in the device; the product was filtered, the filter cake obtained was washed sequentially with 200mL deionized water and 200mL ethanol, and oven dried to give 61.6g white powdered solid BCEOA in 96.4% yield, ¹ h NMR results showed no obvious impurity, purity not less than 99%.

Step 3, adding 60mL of ethanol, 14.4g of allochroic silica gel and 3.2g of sodium hydroxide (0.08 mol) into a reactor, stirring to completely dissolve the sodium hydroxide, removing water in the ethanol, adding 8.6g of BCEOA (0.04 mol) prepared in the step 2, and stirring at the reflux temperature of the ethanol for reacting for 1h to obtain a suspension containing BOZ and inorganic salt; filtering while the solution is hot, removing inorganic salt, concentrating the filtrate until a small amount of crystals are precipitated, cooling for crystallization, filtering after crystals are no longer produced, drying in an oven to obtain 4.09g of BOZ with the yield of 73.0%, ¹ H NMR results show that no obvious impurity exists, and the purity is not lower than 99%; the mother liquor was subjected to secondary crystallization to give 0.711g of BOZ, and the purity of the product was 97.5%. The total yield of BOZ obtained by the two crystallization is 85.7%, and the total purity is not lower than 98%. Conditions and knotsThe results are shown in Table 2.

Example 4

DMO is used as a raw material, the mol ratio of DMO to MEA is 1:2.6, and ethanol is used as a reaction solvent in the step 1 at the temperature of 40 DEG C

Step 1, under the conditions of water bath and stirring at 40 ℃, 158.8g of MEA (2.6 mol) and 400mL of ethanol are added into a reactor, 118.1g of DMO (1.0 mol, which is added in 4 minutes) is added in batches, the reaction temperature is basically kept at about 40 ℃, and stirring is carried out for 20 minutes; the reaction mixture was filtered, the filter cake was washed with ethanol, filtered, and oven dried to give 172.8g of white powdered solid BHEOA in 98.1% yield, ¹ the H NMR result (FIG. 3) showed no obvious impurity, purity not less than 99%.

Adding 52.9g of BHEOA (0.3 mol) prepared in the step 1 and 150mL of toluene solvent into a reactor, stirring to uniformly disperse the BHEOA, adding 107.1g of thionyl chloride (0.9 mol) at room temperature, controlling the feeding rate to be less than or equal to 20g/min, controlling the temperature to be not more than 50 ℃, absorbing the generated tail gas by using sodium hydroxide aqueous solution, raising the temperature of an oil bath to 50 ℃ after the dripping, and continuously reacting at a temperature raised by 5 ℃ when the flow rate of the tail gas is less than 0.1mL/min/gN, and the N' -bis (2-hydroxyethyl) oxamide according to the gas generation condition; repeating the above process, heating to 90 ℃ and then not heating, and stopping the reaction when the flow of the reaction tail gas is smaller than 0.1mL/min/gN, N' -bis (2-hydroxyethyl) oxamide at the temperature, and then introducing nitrogen to sufficiently remove the residual tail gas in the device; the product was filtered, the filter cake obtained was washed sequentially with 200mL deionized water and 200mL ethanol, and oven dried to give 61.6g white powdered solid BCEOA in 96.3% yield, ¹ H NMR results showed no obvious impurity, purity not less than 99%.

Step 3, adding 60mL of ethanol, 14.4g of allochroic silica gel and 3.2g of sodium hydroxide (0.08 mol) into a reactor, stirring to completely dissolve the sodium hydroxide, removing water in the ethanol, adding 8.6g of BCEOA (0.04 mol) prepared in the step 2, and stirring at the reflux temperature of the ethanol for reacting for 1h to obtain a suspension containing BOZ and inorganic salt; filtering while the solution is hot, removing inorganic salt, concentrating the filtrate to precipitate a small amount of crystals, cooling for crystallization, filtering after crystals are no longer generated, and drying in an oven to obtainTo 4.13g of BOZ, the yield was 73.8%, ¹ h NMR results show that no obvious impurity exists, and the purity is not lower than 99%; the mother liquor was subjected to secondary crystallization to give 0.655g of BOZ with a purity of 97.5%. The total yield of BOZ obtained by the two crystallization is 85.5%, and the total purity is not lower than 98%. The conditions and results are shown in Table 2.

Example 5

DMO is used as a raw material, the mol ratio of DMO to MEA is 1:2.6, and ethanol is used as a reaction solvent in the step 1 at the temperature of 60 DEG C

Step 1, under the conditions of water bath and stirring at 60 ℃, 158.8g of MEA (2.6 mol) and 400mL of ethanol are added into a reactor, 118.1g of DMO (1.0 mol, which is added in 4 minutes) is added in batches, the reaction temperature is basically kept at about 60 ℃, and stirring is carried out for 20 minutes; the reaction mixture was filtered, the filter cake was washed with ethanol, filtered, and oven dried to give 160.3g of white powdered solid BHEOA in 91.0% yield, ¹ H NMR results showed no obvious impurity, purity not less than 99%.

Adding 52.9g of BHEOA (0.3 mol) prepared in the step 1 and 150mL of toluene solvent into a reactor, stirring to uniformly disperse the BHEOA, adding 107.1g of thionyl chloride (0.9 mol) at room temperature, controlling the feeding rate to be less than or equal to 20g/min, controlling the temperature to be not more than 50 ℃, absorbing the generated tail gas by using sodium hydroxide aqueous solution, raising the temperature of an oil bath to 50 ℃ after the dripping, and continuously reacting at a temperature raised by 5 ℃ when the flow rate of the tail gas is less than 0.1mL/min/gN, and the N' -bis (2-hydroxyethyl) oxamide according to the gas generation condition; repeating the above process, heating to 90 ℃ and then not heating, and stopping the reaction when the flow of the reaction tail gas is smaller than 0.1mL/min/gN, N' -bis (2-hydroxyethyl) oxamide at the temperature, and then introducing nitrogen to sufficiently remove the residual tail gas in the device; the product was filtered, the filter cake obtained was washed sequentially with 200mL deionized water and 200mL ethanol, and oven dried to give 61.3g white powdered solid BCEOA in 95.9% yield, ¹ h NMR results showed no obvious impurity, purity not less than 99%.

Step 3, 60mL of ethanol, 14.4g of allochroic silica gel and 3.2g of sodium hydroxide (0.08 mol) are added into a reactor, stirring is carried out to completely dissolve the sodium hydroxide, the water in the ethanol is removed, and then Adding 8.6g of BCEOA (0.04 mol) prepared in the step 2, and stirring and reacting for 1h at the reflux temperature of ethanol to obtain a suspension containing BOZ and inorganic salt; filtering while the solution is hot, removing inorganic salt, concentrating the filtrate until a small amount of crystals are precipitated, cooling for crystallization, filtering after crystals are no longer produced, drying in an oven to obtain 4.12g of BOZ with the yield of 73.5%, ¹ h NMR results show that the impurities are absent and the purity is not lower than 99%; the mother liquor was subjected to secondary crystallization to give 0.655g of BOZ with a purity of 97.6%. The total yield of BOZ obtained by the two crystallization is 85.2%, and the total purity is not lower than 98%. The conditions and results are shown in Table 2.

Example 6

DMO is used as a raw material, the mol ratio of DMO to MEA is 1:2.6, and the reaction solvent methanol is reacted in the step 1 at 40 DEG C

Step 1, under the conditions of water bath and stirring at 40 ℃, 158.8g of MEA (2.6 mol) and 400mL of methanol are added into a reactor, 118.1g of DMO (1.0 mol, which is added in 4 minutes) is added in batches, the reaction temperature is basically kept at about 40 ℃, the reaction is stirred for 20 minutes, the reaction mixture is filtered after the reaction is stopped, a filter cake is washed by 500mL of methanol, filtered and dried in an oven, 156.1g of white powdery solid BHEOA is obtained, the yield is 88.6%, ¹ h NMR results showed no obvious impurity, purity not less than 99%.

Adding 52.9g of BHEOA (0.3 mol) prepared in the step 1 and 150mL of toluene solvent into a reactor, stirring to uniformly disperse the BHEOA, adding 107.1g of thionyl chloride (0.9 mol) at room temperature, controlling the feeding rate to be less than or equal to 20g/min, controlling the temperature to be not more than 50 ℃, absorbing the generated tail gas by using sodium hydroxide aqueous solution, raising the temperature of an oil bath to 50 ℃ after the dripping, and continuously reacting at a temperature raised by 5 ℃ when the flow rate of the tail gas is less than 0.1mL/min/gN, and the N' -bis (2-hydroxyethyl) oxamide according to the gas generation condition; repeating the above process, heating to 90 ℃ and then not heating, and stopping the reaction when the flow of the reaction tail gas is smaller than 0.1mL/min/gN, N' -bis (2-hydroxyethyl) oxamide at the temperature, and then introducing nitrogen to sufficiently remove the residual tail gas in the device; the obtained filter cake is washed by 200mL of deionized water and 200mL of ethanol in turn, and is dried in an oven to obtain 61.2g of white powdery solid BCEOA with the yield of 95.8%, ¹ h NMR results showed no obvious impurity, purity not less than 99%.

Step 3, adding 60mL of ethanol, 14.4g of allochroic silica gel and 3.2g of sodium hydroxide (0.08 mol) into a reactor, stirring to completely dissolve the sodium hydroxide, removing water in the ethanol, adding 8.6g of BCEOA (0.04 mol) prepared in the step 2, and stirring at the reflux temperature of the ethanol for reacting for 1h to obtain a suspension containing BOZ and inorganic salt; filtering while the solution is hot, removing inorganic salt, concentrating the filtrate until a small amount of crystals are precipitated, cooling for crystallization, filtering after crystals are no longer produced, drying in an oven to obtain 4.12g of BOZ with the yield of 73.6%, ¹ H NMR results show that the impurities are absent and the purity is not lower than 99%; the mother liquor was subjected to secondary crystallization to give 0.683g of BOZ, and the purity of the product was 97.8%. The total yield of BOZ obtained by the two crystallization is 85.8%, and the total purity is not lower than 98%. The conditions and results are shown in Table 2.

Example 7

DMO is used as a raw material, the mol ratio of DMO to MEA is 1:2.2, and the reaction solvent ethanol in the step 1 is reflux temperature

Step 1, adding 134.4g of MEA (2.2 mol) and 400mL of ethanol into a reactor under the conditions of water bath and stirring at 80 ℃, adding 118.1g of DMO (1.0 mol, which is added in 4 minutes) in batches, keeping the reaction temperature at the reflux temperature of the solvent, stirring and reacting for 20min, filtering the reaction mixture after stopping the reaction, washing a filter cake by ethanol, filtering, drying by a baking oven to obtain 140.7g of white powdery solid BHEOA with the yield of 88.9%, ¹ h NMR results showed no obvious impurity, purity not less than 99%.

Step 2, adding 52.9g of BHEOA (0.3 mol) prepared in the step 1 and 150mL of toluene solvent into a reactor, stirring to uniformly disperse the BHEOA, adding 107.1g of thionyl chloride (0.9 mol) at room temperature, controlling the feeding rate to be less than or equal to 20g/min, controlling the temperature to be not more than 50 ℃, absorbing the generated tail gas by using sodium hydroxide aqueous solution, raising the temperature of an oil bath to 50 ℃ after the dripping, and continuously reacting at the temperature of 5 ℃ when the flow rate of the tail gas is less than 0.1mL/min/gN, and the N' -bis (2-hydroxyethyl) oxamide according to the gas generation condition; repeating the above steps, and after the reaction temperature is raised to 90 deg.C, not raising the temperature, and making the tail gas flow be reacted at this temperature When the amount is less than 0.1mL/min/gN, N' -bis (2-hydroxyethyl) oxamide, the reaction is regarded as ending, and then nitrogen is introduced to fully exhaust residual tail gas in the device, and the reaction is regarded as stopping; the product was filtered, the filter cake obtained was washed sequentially with 200mL deionized water and 200mL ethanol, and oven dried to give 61.4g white powdered solid BCEOA in 96.1% yield, ¹ h NMR results showed no obvious impurity, purity not less than 99%.

Step 3, adding 60mL of ethanol, 14.4g of allochroic silica gel and 3.2g of sodium hydroxide (0.08 mol) into a reactor, stirring to completely dissolve the sodium hydroxide, removing water in the ethanol, adding 8.6g of BCEOA (0.04 mol) prepared in the step 2, and stirring at the reflux temperature of the ethanol for reacting for 1h to obtain a suspension containing BOZ and inorganic salt; filtering while the solution is hot, removing inorganic salt, concentrating the filtrate until a small amount of crystals are precipitated, cooling for crystallization, filtering after crystals are no longer produced, drying in an oven to obtain 4.11g of BOZ with the yield of 73.4%, ¹ h NMR results show that the impurities are absent and the purity is not lower than 99%; the mother liquor was subjected to secondary crystallization to give 0.700g of BOZ, and the purity of the product was 97.6%. The total yield of BOZ obtained by the two crystallization is 85.9%, and the total purity is not lower than 98%. The conditions and results are shown in Table 2.

Comparative example 1

DMO is used as a raw material, the mol ratio of DMO to MEA is 1:2.0, and the reaction solvent ethanol and the anhydrous bath are used for controlling the temperature in the step 1

Step 1, under the condition of room temperature and stirring, 122.2g of MEA (2.0 mol) and 400mL of ethanol are added into a reactor (the reactor is not heated), 118.1g of DMO (1.0 mol, which is added in 4 minutes) are added in batches, the reaction temperature is controlled to be lower than 40 ℃, the reaction temperature is 30 ℃ for most of the time, and the reaction is continued for 20 minutes; after the reaction was stopped, the reaction mixture was filtered, and the cake was washed by dilution with 500mL of ethanol, filtered, and oven-dried to give 82.1g of BHEOA as a white powdery solid in 46.6% yield, ¹ h NMR results showed no obvious impurity, purity not less than 99%.

Step 2, adding 52.9g of BHEOA (0.3 mol) prepared in the step 1 and 150mL of toluene solvent into a reactor, stirring to uniformly disperse the BHEOA, adding 107.1g of thionyl chloride (0.9 mol) at room temperature, controlling the feeding rate to be less than or equal to 20g/min, and controlling the temperature to be not more than 50Absorbing the generated tail gas by using sodium hydroxide aqueous solution, raising the temperature of the oil bath to 50 ℃ after the dripping is finished, and raising the reaction temperature to 5 ℃ when the flow rate of the tail gas is less than 0.1mL/min/gN, N' -bis (2-hydroxyethyl) oxamide according to the gas generation condition, and continuing the reaction; repeating the above process, heating to 90 ℃ and then not heating, and stopping the reaction when the flow of the reaction tail gas is smaller than 0.1mL/min/gN, N' -bis (2-hydroxyethyl) oxamide at the temperature, and then introducing nitrogen to sufficiently remove the residual tail gas in the device; the product was filtered, the filter cake obtained was washed sequentially with 200mL deionized water and 200mL ethanol, and oven dried to give 61.3g white powdered solid BCEOA in 95.9% yield, ¹ H NMR results showed no obvious impurity, purity not less than 99%.

Step 3, adding 60mL of ethanol, 14.4g of allochroic silica gel and 3.2g of sodium hydroxide (0.08 mol) into a reactor, stirring to completely dissolve the sodium hydroxide, removing water in the ethanol, adding 8.6g of BCEOA (0.04 mol) prepared in the step 2, and stirring at the reflux temperature of the ethanol for reacting for 1h to obtain a suspension containing BOZ and inorganic salt; filtering while the solution is hot, removing inorganic salt, concentrating the filtrate until a small amount of crystals are precipitated, cooling for crystallization, filtering after crystals are no longer produced, drying in an oven to obtain 4.11g of BOZ with the yield of 73.4%, ¹ h NMR results show that the impurities are absent and the purity is not lower than 99%; the mother liquor was subjected to secondary crystallization to give 0.672g of BOZ, and the purity of the product was 97.8%. The total yield of BOZ obtained by the two crystallization is 85.4%, and the total purity is not lower than 98%. The conditions and results are shown in Table 2.

Comparative example 2

DMO is used as a raw material, the mol ratio of DMO to MEA is 1:2.2, and the reaction in the step 1 is solvent-free and water-free, and the temperature is controlled by using a bath

Step 1, under the condition of no water bath and stirring at room temperature, 134.4g of MEA (2.2 mol) is added into a reactor (the reactor is not heated), 118.1g of DMO (1.0 mol, which is added in 4 minutes) is added in batches, the temperature is kept above 100 ℃ for a long time, bumping occurs in the reactor, and part of reactants are directly sputtered to all parts of the reactor due to high temperature and react for 10 minutes continuously; the reaction mixture was filtered, the filter cake was washed with ethanol, filtered and oven dried to give 141.5g White powdery solid BHEOA, yield 80.3%, ¹ h NMR results showed no obvious impurity, purity not less than 99%.

Step 2, adding 52.9g of BHEOA (0.3 mol) prepared in the step 1 and 150mL of toluene solvent into a reactor, stirring to uniformly disperse the BHEOA, adding 107.1g of thionyl chloride (0.9 mol) at room temperature, controlling the feeding rate to be less than or equal to 20g/min, controlling the temperature to be not more than 50 ℃, absorbing the generated tail gas by using sodium hydroxide aqueous solution, raising the temperature of an oil bath to 50 ℃ after the dripping, and continuously reacting at a reaction temperature of 5 ℃ when the flow rate of the tail gas is less than 0.1mL/min/gN, and N' -bis (2-hydroxyethyl) oxamide according to the gas generation condition; repeating the above process, heating to 90 ℃ and then not heating, and stopping the reaction when the flow of the reaction tail gas is smaller than 0.1mL/min/gN, N' -bis (2-hydroxyethyl) oxamide at the temperature, and then introducing nitrogen to sufficiently remove the residual tail gas in the device; the product was filtered, the filter cake obtained was washed sequentially with 200mL deionized water and 200mL ethanol, and oven dried to give 61.4g white powdered solid BCEOA in 96.1% yield, ¹ h NMR results showed no obvious impurity, purity not less than 99%.

Comparative example 3

DEO is used as a raw material, the DEO/MEA molar ratio is 1:2.2, the reaction in the step 1 is solvent-free, the water bath is not heated by temperature control, and the chlorination reaction in the step 2 is directly heated to 90 DEG C

Step 1, placing the reactor in a water bath (the water bath is not heated), adding 134.4g of MEA (2.2 mol) into the reactor, adding 146.1g of DEO (1.0 mol, which is added in 5 minutes), controlling the reaction temperature below 70 ℃, controlling the reaction temperature to 40 ℃ for most of the time, and continuing to react for 10 minutes after the addition is finished; the reaction mixture was filtered, the filter cake was washed with 500mL of ethanol, filtered, and oven dried to give 168.8g of white powdered solid BHEOA in 96.4% yield, ¹ h NMR results showed no obvious impurity, purity not less than 99%.

Step 2, placing the reactor in an oil bath, adding 52.9g of BHEOA (0.3 mol) prepared in the step 1 and 150mL of toluene solvent into the reactor at room temperature, stirring to uniformly disperse the BHEOA, adding 107.1g of thionyl chloride (0.9 mol), controlling the feeding rate to be less than or equal to 20g/min, controlling the temperature to be not more than 50 ℃, absorbing the generated tail gas by using a sodium hydroxide aqueous solution, directly raising the temperature of the oil bath to 90 ℃ after the dripping is finished, regarding the reaction as the end when the flow rate of the reaction tail gas is less than 0.1mL/min/gN, N' -bis (2-hydroxyethyl) oxamide at the temperature, and completely discharging the residual tail gas in the device by introducing nitrogen as the reaction stop; the product was filtered, and the obtained filter cake was washed sequentially with 200mL deionized water and 200mL ethanol, and dried in an oven to obtain 52.6g white powdery solid BCEOA, with a yield of 82.3% and a purity of less than 99%, and the conditions and results are shown in table 1, and as shown in fig. 4, the nuclear magnetic resonance spectrum shows that there is a residue of the raw material in the reactant, and thus the purity was reduced, and the purity was not less than 99%.

Step 3, adding 60mL of ethanol, 14.4g of allochroic silica gel and 3.2g of sodium hydroxide (0.08 mol) into a reactor, stirring to completely dissolve the sodium hydroxide, removing water in the ethanol, adding 8.6g of BCEOA (0.04 mol), and stirring at the reflux temperature of the ethanol for reacting for 1h to obtain a suspension containing BOZ and inorganic salt; filtering while the solution is hot, removing inorganic salt, concentrating the filtrate until a small amount of crystals are precipitated, cooling for crystallization, filtering after crystals are not produced any more, and drying in an oven to obtain 4.11g of BOZ, wherein the yield is 73.3%, and the 1H NMR result shows that the solution is free of impurities and the purity is not lower than 99%; the mother liquor was subjected to secondary crystallization to give 0.689g of BOZ, and the purity of the product was 97.4%. The total yield of BOZ obtained by the two crystallization is 85.6%, and the total purity is not lower than 98%. The conditions and results are shown in Table 2.

Comparative example 4

DEO is used as a raw material, the DEO/MEA molar ratio is 1:2.2, the reaction in the step 1 is solvent-free, the water bath is temperature-controlled and is not heated, and the step 3 adopts toluene as a second solvent for crystallization

Step 1, placing the reactor in a water bath (the water bath is not heated), adding 134.4g of MEA (2.2 mol) into the reactor, adding 146.1g of DEO (1.0 mol, which is added in 5 minutes), controlling the reaction temperature below 70 ℃, controlling the reaction temperature to 40 ℃ for most of the time, and continuing to react for 10 minutes after the addition is finished; the reaction mixture was filtered, the filter cake was washed with 500mL of ethanol, filtered, and oven dried to give 169.3g of BHEOA as a white powdered solid in 96.1% yield, ¹ H NMR results showed no obvious impurity, purity not less than 99%.

Step 2, adding 52.9g of BHEOA (0.3 mol) prepared in the step 1 and 150mL of toluene solvent into a reactor, stirring to uniformly disperse the BHEOA, adding 107.1g of thionyl chloride (0.9 mol) at room temperature, controlling the feeding rate to be less than or equal to 20g/min, controlling the temperature to be not more than 50 ℃, absorbing the generated tail gas by using sodium hydroxide aqueous solution, raising the temperature of an oil bath to 50 ℃ after the dripping, and continuously reacting at a reaction temperature of 5 ℃ when the flow rate of the tail gas is less than 0.1mL/min/gN, and N' -bis (2-hydroxyethyl) oxamide according to the gas generation condition; repeating the above process, heating to 90 ℃ and then not heating, and stopping the reaction when the flow of the reaction tail gas is smaller than 0.1mL/min/gN, N' -bis (2-hydroxyethyl) oxamide at the temperature, and then introducing nitrogen to sufficiently remove the residual tail gas in the device; the product was filtered, the filter cake obtained was washed sequentially with 200mL deionized water and 200mL ethanol, and oven dried to give 61.4g white powdered solid BCEOA in 96.0% yield, ¹ h NMR results showed no obvious impurity, purity not less than 99%.

Step 3, adding 60mL of ethanol, 14.4g of allochroic silica gel and 3.2g of sodium hydroxide (0.08 mol) into a reactor, stirring to completely dissolve the sodium hydroxide, removing water in the ethanol, adding 8.6g of BCEOA (0.04 mol) prepared in the step 2, and stirring at the reflux temperature of the ethanol for reacting for 1h to obtain a suspension containing BOZ and inorganic salt; filtering while the solution is hot to remove inorganic salts; after the filtrate was evaporated to dryness, the remaining solid was recrystallized from toluene, and the obtained crystals were oven-dried to give 2.30g of BOZ in 41.1% yield and 97.3% purity. The conditions and results are shown in Table 2.

Comparative example 5

Taking DEO as a raw material, wherein the DEO/MEA molar ratio is 1:2.2, the reaction in the step 1 is solvent-free, the water bath is temperature-controlled and is not heated, and the step 3 adopts a second solvent 1, 4-dioxane for crystallization

Step 1, placing the reactor in a water bath (the water bath is not heated), adding 134.4g of MEA (2.2 mol) into the reactor, adding 146.1g of DEO (1.0 mol, which is added in 5 minutes), controlling the reaction temperature below 70 ℃, controlling the reaction temperature to 40 ℃ for most of the time, and continuing to react for 10 minutes after the addition is finished; the reaction mixture was filtered, the filter cake was washed with 500mL of ethanol, filtered, and oven dried to give 170.2g of BHEOA as a white powdered solid in 96.6% yield, ¹ h NMR results showed no obvious impurity, purity not less than 99%.

Adding 52.9g of BHEOA (0.3 mol) prepared in the step 1 and 150mL of toluene solvent into a reactor, stirring to uniformly disperse the BHEOA, adding 107.1g of thionyl chloride (0.9 mol) at room temperature, controlling the feeding rate to be less than or equal to 20g/min, controlling the temperature to be not more than 50 ℃, absorbing the generated tail gas by using sodium hydroxide aqueous solution, raising the temperature of an oil bath to 50 ℃ after the dripping, and continuously reacting at a temperature raised by 5 ℃ when the flow rate of the tail gas is less than 0.1mL/min/gN, and the N' -bis (2-hydroxyethyl) oxamide according to the gas generation condition; repeating the above process, heating to 90 ℃ and then not heating, and stopping the reaction when the flow of the reaction tail gas is smaller than 0.1mL/min/gN, N' -bis (2-hydroxyethyl) oxamide at the temperature, and then introducing nitrogen to sufficiently remove the residual tail gas in the device; the product was filtered, the filter cake obtained was washed sequentially with 200mL deionized water and 200mL ethanol, and oven dried to give 61.5g white powdered solid BCEOA in 96.2% yield, ¹ H NMR results showed no obvious impurity, purity not less than 99%.

Step 3, adding 60mL of ethanol, 14.4g of allochroic silica gel and 3.2g of sodium hydroxide (0.08 mol) into a reactor, stirring to completely dissolve the sodium hydroxide, removing water in the ethanol, adding 8.6g of BCEOA (0.04 mol) prepared in the step 2, and stirring at the reflux temperature of the ethanol for reacting for 1h to obtain a suspension containing BOZ and inorganic salt; filtering while the solution is hot to remove inorganic salts; after the filtrate was evaporated to dryness, the remaining solid was subjected to crystallization using 1, 4-dioxane, and the obtained crystals were oven-dried to give 3.70g boz with a yield of 66.1% and a purity of 97.3%. The conditions and results are shown in Table 2.

Comparative example 6

DMO is used as a raw material, the mol ratio of DMO to MEA is 1:2.2, and the reaction solvent ethanol and the anhydrous bath are used for controlling the temperature in the step 1

Step 1, under the condition of room temperature and stirring, 134.4g of MEA (2.2 mol) and 400mL of ethanol are added into a reactor (the reactor is not placed in a water bath and is not heated), 118.1g of DMO (1.0 mol and is added in 4 minutes) are added in batches, the reaction temperature is controlled to be lower than 40 ℃, the reaction temperature is 30 ℃ for most of the time, and the stirring reaction is carried out for 20 minutes; the reaction mixture was filtered, the filter cake was washed with ethanol, filtered, and oven dried to give 93.7g of white powdered solid BHEOA in 53.2% yield, ¹ H NMR results showed no obvious impurity, purity not less than 99%.

Step 2, adding 52.9g of BHEOA (0.3 mol) prepared in the step 1 and 150mL of toluene solvent into a reactor, stirring to uniformly disperse the BHEOA, adding 107.1g of thionyl chloride (0.9 mol) at room temperature, controlling the feeding rate to be less than or equal to 20g/min, controlling the temperature to be not more than 50 ℃, and absorbing the generated tail gas by using sodium hydroxide aqueous solution; after the dripping is finished, the temperature of the oil bath is increased to 50 ℃, and according to the gas generation condition, when the flow rate of tail gas is less than 0.1mL/min/gN, N' -bis (2-hydroxyethyl) oxamide, the reaction temperature is increased by 5 ℃, and the reaction is continued; repeating the above process, heating to 90 ℃ and then not heating, and stopping the reaction when the flow of the reaction tail gas is smaller than 0.1mL/min/gN, N' -bis (2-hydroxyethyl) oxamide at the temperature, and then introducing nitrogen to sufficiently remove the residual tail gas in the device; the product was filtered, the filter cake obtained was washed sequentially with 200mL deionized water and 200mL ethanol, and oven dried to give 61.4g white powdered solid BCEOA in 96.0% yield, ¹ h NMR results showed no obvious impurity, purity not less than 99%.

Step 3, 60mL of the mixture was added to the reactorEthanol, 14.4g of allochroic silica gel and 3.2g of sodium hydroxide (0.08 mol), stirring to completely dissolve the sodium hydroxide, removing water in the ethanol, adding 8.6g of BCEOA (0.04 mol) prepared in the step 2, and stirring at the reflux temperature of the ethanol for reacting for 1h to obtain a suspension containing BOZ and inorganic salt; filtering while the solution is hot, removing inorganic salt, concentrating the filtrate to precipitate a small amount of crystals, cooling for crystallization, filtering and washing when crystals are not generated any more, drying in an oven to obtain 4.12g of BOZ with the yield of 73.5%, ¹ H NMR results show that no obvious impurity exists, and the purity is not lower than 99%; the mother liquor was subjected to secondary crystallization to give 0.700g of BOZ, and the purity of the product was 97.6%. The total yield of BOZ obtained by the two crystallization is 86.0%, and the total purity is not lower than 98%. The conditions and results are shown in Table 2.

Table 2 summary of reaction conditions and yields for examples and comparative examples

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In Table 2, the starting materials refer to the difference in oxalic acid diester in which the ethanolamine remains the same; t (T) _{(1) Environment(s)} Refers to the ambient temperature of the reactor in the step 1, T _{(1) In practice} The actual temperature of the reaction system in the step 1 is referred to as water bath reflux, the water bath heating is referred to as water bath heating, the reaction system is controlled to be in a reflux state, and the actual temperature is about 78 ℃; s is S ₍₁₎ Refers to the solvent used in the step 1, and if the solvent is not added, the solvent is denoted by "/"; r is R ₍₁₎ Refers to the molar ratio of ethanolamine to oxalic acid diester in the step 1; yield rate ₍₁₎ Refer to the isolated yield of BHEOA in step 1;

T ₍₂₎ the reaction temperature in the step 2 is gradually increased from 50 ℃ to 90 ℃ and is represented by 50-90, and the reaction at 90 ℃ is directly represented by 90; yield rate ₍₂₎ Referring to the isolated yield of BCEOA in step 2; s is S ₍₃₎ The crystallization solvent used in the step 3 is ethanol as the solvent in the ring-closure reaction in the step 3; yield rate ₍₃₎₁ The separation yield obtained by primary crystallization in the step 3 is referred to as the product obtained by primary crystallization ¹ No obvious impurity is found in the characterization of H NMR; yield rate _{(3) Total (S)} Refers to the sum of the separation yield obtained by the primary crystallization in the step 3 and the separation yield obtained by the secondary crystallization of the crystallization mother liquor.

Analysis of results

Comparing example 1 with example 2, the starting material was replaced by dimethyl oxalate from diethyl oxalate at the same temperature and the same molar ratio of ethanolamine to diethyl oxalate, and the yield of BHEOA in example 2 step 1 was reduced from 96.5% to 91.3% because dimethyl oxalate was less stable than diethyl oxalate and decomposed in the reaction.

In comparative example 2 and comparative example 6, ethanol was added as a solvent in the same molar ratio of ethanolamine to oxalic acid diester, and the exothermic heat of the ethanol absorption reaction reduced the temperature of the reaction system to 30 ℃, which was unfavorable for the reaction, so that the BHEOA yield in step 1 of comparative example 6 was reduced from 91.3% to 53.2%.

Comparing comparative example 6 with example 3, the ethanolamine/oxalic acid diester molar ratio was increased from 2.2 to 2.6 at the same temperature and ethanol as the solvent, and the yield in step 1 was increased from 53.2% of comparative example 6 to 86.5% of example 3, indicating that the appropriate ethanolamine/oxalic acid diester molar ratio favors the reaction.

Comparing comparative example 6 with example 7, the reaction temperature was increased from room temperature to reflux temperature with ethanol as solvent and the same ethanolamine/oxalic acid diester molar ratio, and the yield in step 1 was increased from 53.2% of example 3 to 88.9% of example 7, indicating that the reaction temperature was increased to favor the progress of the reaction.

Comparing example 3, example 4 and example 5, increasing the reaction temperature from example 3 near room temperature to example 4 at 40 ℃ with ethanol as solvent and the same ethanolamine/dimethyl oxalate molar ratio, the BHEOA yield in step 1 reached 98.1%; the reaction temperature was further increased at 60℃in example 5 and the BHEOA yield was decreased by 91.0% compared to example 4. This shows that the temperature has a significant effect on the yield, the reaction is not favored by too low temperature, and the decomposition of dimethyl oxalate is caused by poor stability of dimethyl oxalate when the temperature is too high, 40-50 ℃ is a preferable temperature for the reaction, and 40 ℃ is the optimal reaction temperature.

In comparative example 2 and comparative example 2, the reactor of example 2 was placed in a water bath at the same molar ratio of ethanolamine/dimethyl oxalate, the water bath was not heated, the reaction temperature reached 100 ℃ for a short time, but quickly dropped below 70 ℃, while comparative example 2 was free of water bath, the outer wall of the reactor was directly contacted with air, the reaction temperature was maintained above 100 ℃ for a long time, dimethyl oxalate was easily decomposed by heating, and bumping occurred in the reactor, and part of the reactants was directly sputtered to the whole place of the reactor due to high temperature, not only the yield was reduced to 80.3%, but also the synthesis process had a certain safety hazard.

Comparing example 4 with example 6, using ethanol (example 4) as solvent compared to methanol (example 6) at the same temperature and the same molar ratio of ethanolamine to oxalic acid diester advantageously increases the yield of BHEOA, because BHEOA has a greater solubility in methanol than ethanol, and a portion of the product is dissolved in methanol, resulting in a reduced isolation yield. On the other hand, the methanol is used as the reaction solvent, so that the solvent is consistent with the byproducts (both methanol) and is convenient to recycle.

Comparison of comparative example 6 with comparative example 1, the ethanolamine/oxalic acid diester molar ratio was reduced from 2.2 to 2.0, and the BHEOA yield in step 1 was reduced from 53.2% (comparative example 6) to 46.6% (comparative example 1) at the same temperature with ethanol as a solvent, indicating that excessively low reduction of the ethanolamine/oxalic acid diester molar ratio was detrimental to the reaction.

In the step 2, the step 1 adopts the step-by-step heating reaction at 50 ℃ to 90 ℃ under the same other conditions, the yield of BCEOA is as high as 96.3%, the step 3 adopts the step-by-step heating reaction at 90 ℃ to directly heat the reaction, the reactant in the reactor is in a caking phenomenon, the reaction is not easy to carry out, the yield of BCEOA is reduced to 82.3%, the product contains unreacted raw material BHEOA, the nuclear magnetic spectrum is shown in figure 4, and the raw material impurity peak is obvious.

In the invention, in the step 3, ethanol or methanol serving as a single solvent is adopted for reaction and crystallization. For example, in step 3 of example 1, the reaction and crystallization were performed using a single solvent ethanol, and the BOZ yield obtained by the primary crystallization was 73.6% and the total BOZ yield was 85.8%; in step 3 of comparative examples 4 and 5, ethanol was also used as a reaction solvent under the same conditions, but toluene (comparative example 4) and 1, 4-dioxane (comparative example 5) were used for recrystallization after the end of the reaction, and the total BOZ crystallization yield was reduced from 85.8% to 41.1% and 66.1%, respectively, with a significant difference. The reason for this is that the solubility of BOZ in toluene and 1, 4-dioxane is less dependent on temperature, whereas the solubility in ethanol is more dependent on temperature, ethanol being more suitable as a crystallization solvent for BOZ. The use of a single solvent, ethanol or methanol, is advantageous for solvent recovery in addition to improving the BOZ yield.

CN104447601a also synthesized BOZ in a three-step process, but only diethyl oxalate was used as the starting material. CN104447601A in step (i) adopts toluene as solvent, the reaction temperature is 100 ℃, the reaction time is 10 hours, after the reaction is finished, toluene and n-hexane are used for washing, and the yield of BHEOA is 98%. In comparison, in the step 1 of the invention, the reaction temperature is lower, the time is shorter, and the method is more efficient and energy-saving. The reaction process does not use a solvent or only ethanol or methanol is used as a single solvent for reaction and separation, a second solvent is not needed, the separation process is simpler, the solvent is convenient to recycle, and the BHEOA yield is 98.1 percent and the purity is high.

Meanwhile, in CN104447601A, the BCEOA product obtained in the step (ii) is light yellow, and is obvious in impurity, and the BCEOA product obtained in the step 2 is white, no obvious impurity is found, and the purity is higher. In CN104447601A, tetrahydrofuran is used as a reaction solvent in the step (iii) except ethanol, the reaction temperature is 100 ℃, the reaction time is up to 5 hours, and dichloromethane is added for extraction, evaporation and drying to obtain BOZ which is light yellow; in the embodiment 4 of the invention, in the step 3, other organic solvents are not needed except ethanol, the reaction is carried out for 1h at 80 ℃, and the filtrate is directly cooled and crystallized in a general way, so that the high-purity product can be obtained, and the method is more efficient, environment-friendly and lower in energy consumption.

Claims

1. A method for preparing 2,2' -bis (2-oxazoline), comprising the steps of:

step 2, dispersing N, N' -bis (2-hydroxyethyl) oxamide in an organic solvent, adding thionyl chloride, and controlling the temperature of a system to be not higher than 50 ℃; then continuing the reaction, and when the flow rate of the reaction tail gas is not higher than 0.1mL/min/gN, N' -di (2-hydroxyethyl) oxamide, heating to 3-10 ℃ to continue the reaction; repeating the above process until the reaction temperature reaches 90 ℃; filtering, washing and drying the product after the reaction is finished to obtain N, N' -bis (2-chloroethyl) oxamide;

2. The method for producing 2,2' -bis (2-oxazoline) according to claim 1, wherein the oxalic acid diester is dimethyl oxalate or diethyl oxalate.

3. The method for preparing 2,2' -bis (2-oxazoline) according to claim 1, wherein the step 1 further comprises solvent ethanol or methanol.

4. The method for producing 2,2' -bis (2-oxazoline) according to claim 3, wherein the step 1 further comprises the step of using 1 to 5 times the mass of ethanolamine when methanol or ethanol is used as a solvent.

5. The process for the preparation of 2,2' -bis (2-oxazoline) according to claim 1, the reaction time of step 1 is 10-60min; and/or the reaction temperature is 15-80 ℃.

6. The method for producing 2,2' -bis (2-oxazoline) according to claim 1, wherein the molar ratio of oxalic acid diester to ethanolamine in step 1 is 1:2.2 to 2.6.

7. The method for preparing 2,2 '-bis (2-oxazoline) according to claim 1, wherein the molar ratio of N, N' -bis (2-hydroxyethyl) oxamide to thionyl chloride in step 2 is 1:2.2 to 4.0;

And/or the organic solvent comprises any one or more of toluene, 1, 4-dioxane, butyl acetate and xylene;

and/or the dosage of the organic solvent is 3-5 times of the mass of the N, N' -di (2-hydroxyethyl) oxamide.

8. The method for preparing 2,2' -bis (2-oxazoline) according to claim 1, wherein in the step 3, the inorganic base is sodium hydroxide or potassium hydroxide; the molar ratio of the N, N' -di (2-chloroethyl) oxamide to the inorganic base is 1:2 to 3;

and/or the water absorbing agent in the step 3 is allochroic silica gel or molecular sieve, and the dosage of the water absorbing agent is 1.5-2 times of the mass of the N, N' -di (2-chloroethyl) oxamide;

and/or the dosage of the methanol or the ethanol in the step 3 is 4 to 10 times of the mass of the N, N' -bis (2-chloroethyl) oxamide; the water content in methanol or ethanol is controlled below 0.3 wt%.

9. The method for producing 2,2 '-bis (2-oxazoline) according to claim 1, wherein the yield of N, N' -bis (2-hydroxyethyl) oxamide in step 1 is not less than 85% and the purity is not less than 99%;

and/or, in the step 2, the yield of the N, N' -bis (2-chloroethyl) oxamide is not lower than 95%, and the purity is not lower than 99%;

And/or, the yield of 2,2' -bis (2-oxazoline) in the step 3 is not lower than 85%, and the purity is not lower than 98%.

10. The process for producing 2,2' -bis (2-oxazoline) according to claim 1, wherein the filtrate in step 1 is recovered for the reaction medium in step 1, the filtrate in step 2 is decolorized and then used for the reaction medium in step 2, and the crystallization mother liquor in step 3 is recovered for the reaction medium in step 3.