Preparation method of bis (3-ethyl-5-methyl-4-maleimidophenyl) methane

Abstract

The invention relates to a preparation method of bis (3-ethyl-5-methyl-4-maleimido phenyl) methane, which comprises the following steps: dianhydride and diamine in an organic solvent are subjected to dehydration cyclization while obtaining bismaleamic acid under the action of a dehydration catalyst to obtain the bis (3-ethyl-5-methyl-4-maleimido phenyl) methane. A large number of tests show that p-toluene sulfonic acid is used as a catalyst, a mixed solution of toluene and N, N '-dimethylformamide (DMF) is used as a solvent, homogeneous reaction can be carried out with the solvent dosage not exceeding 10 times of equivalent weight, local overheating is effectively avoided, the reaction is stable, the reaction temperature is low, polymers are reduced, the product purity is high, and the yield is high; the bismaleamic acid generated by adopting a one-step synthesis process is immediately dehydrated and converted into the product bis (3-ethyl-5-methyl-4-maleimidophenyl) methane, there is no opportunity to generate inter-dehydration, the obtained residues are fewer than those obtained by adopting a two-step method, the synthesis time is shorter, the production cost is reduced, and the method is suitable for industrial mass production.

Description

Technical Field

[0001] The invention belongs to the technical field of chemical synthesis, and specifically relates to a preparation method of bis(3-ethyl-5-methyl-4-maleimidophenyl)methane. Background Art

[0002] Bis(3-ethyl-5-methyl-4-maleimidophenyl)methane is an important bismaleimide. Bis(3-ethyl-5-methyl-4-maleimidophenyl)methane (BMI-70) is a novel derivative produced by introducing methyl and ethyl groups into the two benzene rings of the BDM molecule. The melting point of its pure product is 163-166°C, and its appearance is white to light yellow.

[0003] There are three main methods for the synthesis of BMI, namely acetic anhydride dehydration method, thermal dehydration closed-loop method and azeotropic distillation dehydration method. The most widely used methods are the acetone method and the toluene method. The acetone method is a type of acetic anhydride dehydration method. It uses water precipitation to obtain the product with a high yield, but the quality is very poor, characterized by high acid value, low melting point, wide melting range, product agglomeration, dark color, and the reaction solvent is not easy to recover, resulting in large pollution; the toluene method uses distillation dehydration reaction, thermal closed-loop dehydration under the action of an acidic catalyst, and at the same time uses the azeotrope formed by water and solvent to evaporate water out of the reactor, thereby accelerating the thermal closed-loop reaction. The production efficiency is high and the reaction solvent can be recovered, but it is easy to produce brown viscous resin-like by-products.

[0004] Through the search of public documents, the following two public documents on the preparation and synthesis of bis(3-ethyl-5-methyl-4-maleimidophenyl)methane were found:

[0005] The Chinese patent with the authorization announcement number: CN112279798B discloses a method for preparing bis(3-ethyl-5-methyl-4-maleimidophenyl)methane. However, the method adopts a two-step process. It is firstly reacted by 4,4'-methylenebis(2-methyl-6-ethylaniline) and maleic anhydride in an organic solvent to obtain bismaleamic acid, and then dehydrated and cyclized in the presence of an acidic catalyst to obtain bis(3-ethyl-5-methyl-4-maleimidophenyl)methane. Since in the two-step synthesis process, the first step reacts very quickly, the intermediate product in the system is always excessive, and the second step of dehydration is always accompanied by intermolecular dehydration to form insoluble and infusible linear oligomers.

[0006] The article published by Qiu Li et al. (Qiu Li, Deng Jialun, Liu Xiaocheng, et al. Synthesis and structural characterization of bis(3-ethyl-5-methyl-4-maleimidophenyl)methane [J]. Chemistry and Bioengineering, 2020, 37(12): 36-39+68.) discloses a method for preparing bis(3-ethyl-5-methyl-4-maleimidophenyl)methane. BMI-70 was synthesized using maleic anhydride, MMEA, p-toluenesulfonic acid, toluene, etc. as raw materials. However, the method adopts a two-step synthesis method, which results in a large number of residuals, and the residuals are mainly oligomers formed by dehydration between BMA molecules. In addition, the synthesis time is long, which increases the production cost. Summary of the invention

[0007] The object of the present invention is to overcome the deficiencies of the prior art and provide a method for preparing bis(3-ethyl-5-methyl-4-maleimidophenyl)methane. The method adopts a one-step synthesis process, and the generated bismaleamic acid is immediately dehydrated and converted into the product bis(3-ethyl-5-methyl-4-maleimidophenyl)methane without the opportunity of fractional dehydration. The obtained residue is less than that of the two-step method, and the synthesis time is shorter, thereby reducing the production cost.

[0008] The present invention solves the technical problem by the following technical solutions:

[0009] A method for preparing bis(3-ethyl-5-methyl-4-maleimidophenyl)methane, characterized in that: dianhydride and diamine in an organic solvent are subjected to a dehydration catalyst to obtain bismaleamic acid and bis(3-ethyl-5-methyl-4-maleimidophenyl)methane at the same time of dehydration cyclization.

[0010] The steps of the method are:

[0011] S1, preparing a dianhydride solution: dissolving the dianhydride and the dehydration catalyst in the organic solvent and adding the organic solvent into a three-necked flask;

[0012] S2, preparing a diamine solution: dissolving the diamine in the organic solvent and slowly dropping the solution into the three-necked flask;

[0013] S3, after the addition is completed, the temperature is raised and refluxed for 3 hours, and water is separated by an oil-water separator during the reflux process;

[0014] S4. After the reaction is completed, the solution obtained in S3 is cooled to 60°C to 85°C, sodium carbonate solution is added, and the pH is adjusted to neutral;

[0015] S5, filtering the solution obtained in S4, separating the oil phase, washing with water; separating the oil phase, rotary drying to obtain a crude product;

[0016] S6. The crude product obtained in S5 is fully stirred and dissolved in toluene, and filtered. The filtrate is passed into a precipitation kettle with cooling water for crystallization, filtered, dried, crushed, and sieved to obtain white to light yellow bis(3-ethyl-5-methyl-4-maleimidophenyl)methane.

[0017] Moreover, the dianhydride is maleic anhydride, the dehydration catalyst is p-toluenesulfonic acid, the molar ratio of maleic anhydride to p-toluenesulfonic acid is 1:0.08-0.1; the organic solvent is a mixed solution of toluene and N,N'-dimethylformamide (DMF), and the volume ratio of toluene to N,N'-dimethylformamide (DMF) is 1:0.1-1:0.2; the amount of the S1 organic solvent does not exceed 10 times the equivalent of maleic anhydride.

[0018] Moreover, the diamine is 4,4'-methylenebis(2-methyl-6-ethylaniline), the rate of slow dripping of S2 is 0.5 ml / min, and the reaction temperature does not exceed 45°C; the amount of the S2 organic solvent does not exceed 10 times the equivalent of 4,4'-methylenebis(2-methyl-6-ethylaniline); the molar ratio of the 4,4'-methylenebis(2-methyl-6-ethylaniline) to maleic anhydride is 1:1.5 to 1:3.

[0019] Moreover, the S3 heating reflux temperature is 85°C to 110°C.

[0020] The positive effects that the present invention can produce are:

[0021] 1. After a large number of experiments, the present invention has found that using p-toluenesulfonic acid as a decatalyst and a mixed solution of toluene and N,N'-dimethylformamide (DMF) as a solvent can achieve a homogeneous reaction with a solvent dosage of no more than 10 times the equivalent, effectively avoiding local overheating, achieving a stable reaction, a low reaction temperature, a reduced polymer, a high product purity, and a high yield.

[0022] 2. This reaction adopts a one-step preparation method. The one-step preparation method is to react 4,4'-methylenebis(2-methyl-6-ethylaniline) with maleic anhydride in an organic solvent under the action of a dehydration catalyst of p-toluenesulfonic acid to obtain bismaleamic acid and at the same time dehydrate and cyclize to obtain bis(3-ethyl-5-methyl-4-maleimidophenyl)methane, thereby effectively reducing the side reactions caused by the excess of the intermediate product bismaleamic acid.

[0023] As the reaction proceeds, the concentration of the intermediate product in the system gradually increases, and the added 4,4'-methylenebis(2-methyl-6-ethylaniline) may undergo addition reaction and dehydration condensation to form peptide bonds. If the intermediate product in the system is excessive, it will also be accompanied by intermolecular dehydration during the dehydration process to form insoluble and infusible linear oligomers.

[0024] 3. The feed liquid of the present invention can be recycled as a solvent, and the reaction solvent obtained by rotary evaporation does not need to be post-processed and can be directly recycled, thereby reducing pollutant emissions, being environmentally friendly and low-cost.

[0025] 4. The relatively simple post-processing of the present invention obtains a higher reaction yield and product purity, thereby greatly reducing the production cost and being suitable for large-scale industrial production. BRIEF DESCRIPTION OF THE DRAWINGS

[0026] Figure 1 a) is the NMR spectrum of BMI-70 synthesized in Example 1 of the present invention, Figure 1 b) is the NMR spectrum of BMI-70 synthesized in comparative example;

[0027] Figure 2 This is a peak area calculation diagram of the BMI-70 nuclear magnetic spectrum of the present invention;

[0028] Figure 3 a) is the infrared spectrum of Inventive Example 1 BMI-70, Figure 3 b) is the infrared spectrum of electronic grade BMI-70. DETAILED DESCRIPTION

[0029] The present invention is further described in detail below through specific examples. The following examples are only illustrative and not restrictive, and the protection scope of the present invention cannot be limited thereto.

[0030] The present invention will be further described below in conjunction with the embodiments.

[0031] A method for preparing bis(3-ethyl-5-methyl-4-maleimidophenyl)methane, the innovation of which is that dianhydride and diamine in an organic solvent are subjected to a dehydration catalyst to obtain bismaleamic acid and bis(3-ethyl-5-methyl-4-maleimidophenyl)methane at the same time of dehydration and cyclization. The structural formula of the bis(3-ethyl-5-methyl-4-maleimidophenyl)methane is as follows:

[0032]

[0033] The steps of the method are:

[0034] S1, preparing a dianhydride solution: dissolving the dianhydride and the dehydration catalyst in the organic solvent and adding the organic solvent into a three-necked flask;

[0035] S2, preparing a diamine solution: dissolving the diamine in the organic solvent and slowly dropping the solution into the three-necked flask;

[0036] S3, after the addition is completed, the temperature is raised and refluxed for 3 hours, and water is separated by an oil-water separator during the reflux process;

[0037] S4. After the reaction is completed, the solution obtained in S3 is cooled to 60°C to 85°C, sodium carbonate solution is added, and the pH is adjusted to neutral;

[0038] S5, filtering the solution obtained in S4, separating the oil phase, washing with water; separating the oil phase, rotary drying to obtain a crude product;

[0039] S6. The crude product obtained in S5 is fully stirred and dissolved in toluene, and filtered. The filtrate is passed into a precipitation kettle with cooling water for crystallization, filtered, dried, crushed, and sieved to obtain white to light yellow bis(3-ethyl-5-methyl-4-maleimidophenyl)methane.

[0040] The dianhydride is maleic anhydride, the dehydration catalyst is p-toluenesulfonic acid, the diamine is 4,4'-methylenebis(2-methyl-6-ethylaniline), 4,4'-methylenebis(2-methyl-6-ethylaniline) and maleic anhydride are reacted in an organic solvent, with a mixed solution of toluene and N,N'-dimethylformamide (DMF) as the solvent, and p-toluenesulfonic acid as the dehydration catalyst, while obtaining bismaleamic acid, dehydration cyclization is performed to obtain bis(3-ethyl-5-methyl-4-maleimidophenyl)methane, and the synthesis route is as follows:

[0041]

[0042] Example 1

[0043] Add 29g of maleic anhydride (MA), 56.5g of 4,4'-methylenebis(2-methyl-6-ethylaniline) (MMEA), 7g of p-toluenesulfonic acid as catalyst, 184g of toluene, and 19g of N,N'-dimethylformamide (DMF) to the reactor, and stir and dissolve evenly at room temperature. Mix 56.5g of 4,4'-methylenebis(2-methyl-6-ethylaniline) (MMEA), 7g of p-toluenesulfonic acid as catalyst, and 184g of toluene evenly, and slowly add dropwise at a rate of 0.5ml / min, and the temperature of the reaction system does not exceed 75°C. After the addition is completed, stir for 2h, then heat and reflux (reflux begins at about 90°C), separate water and react until almost no water is separated. Cool to room temperature, adjust the pH to neutral, filter and separate the oil phase, wash with water (150ml×3), and dry by rotary evaporation to obtain a crude product.

[0044] Recrystallize with 15 times the amount of the crude product of methanol, filter while hot; cool the filtrate with water, stir slowly, cool in a refrigerator, and filter with suction to obtain bis(3-ethyl-5-methyl-4-maleimidophenyl)methane.

[0045] Example 2

[0046] Add 46g of maleic anhydride (MA), 56.5g of 4,4'-methylenebis(2-methyl-6-ethylaniline) (MMEA), 7g of p-toluenesulfonic acid as catalyst, 184g of toluene, and 19g of N,N'-dimethylformamide (DMF) to the reactor, and stir and dissolve evenly at room temperature. Mix 56.5g of 4,4'-methylenebis(2-methyl-6-ethylaniline) (MMEA), 7g of p-toluenesulfonic acid as catalyst, and 184g of toluene evenly, and slowly add dropwise at a rate of 0.5ml / min, and the temperature of the reaction system does not exceed 75°C. After the addition is completed, stir for 2h, then heat and reflux (reflux begins at about 90°C), separate water and react until almost no water is discharged. Cool to room temperature, adjust the pH to neutral, filter and separate the oil phase, wash with water (150ml×3), and dry by rotary evaporation to obtain a crude product.

[0047] Recrystallize with 15 times the amount of the crude product of methanol, filter while hot; cool the filtrate with water, stir slowly, cool in a refrigerator, and filter with suction to obtain bis(3-ethyl-5-methyl-4-maleimidophenyl)methane.

[0048] Comparative Example

[0049] Add 29g of maleic anhydride (MA), 184g of toluene, and 19g of N, N'-dimethylformamide (DMF) to the reactor, stir and dissolve evenly at room temperature; add 56.5g of 4,4'-methylenebis(2-methyl-6-ethylaniline) (MMEA), 184g of toluene, and 19g of N, N'-dimethylformamide (DMF), mix evenly, and slowly dropwise add, the slow dropwise addition rate is 0.5ml / min, and the temperature of the reaction system does not exceed 75℃. After the dropwise addition is completed, stir for 2h, and then add 7g of dehydration catalyst p-toluenesulfonic acid to the reaction liquid, heat and reflux (reflux begins at about 90℃), and separate water to react until almost no water is separated. Cool to room temperature, adjust the pH to neutral, filter and separate the oil phase, wash with water (150ml×3), and rotary evaporate to dry to obtain a crude product.

[0050] Recrystallize with 15 times the amount of the crude product of methanol, filter while hot; cool the filtrate with water, stir slowly, cool in a refrigerator, and filter with suction to obtain bis(3-ethyl-5-methyl-4-maleimidophenyl)methane.

[0051] The operation steps of Example 1 and Example 2 are the same, but the raw material ratios are different, which is intended to illustrate that the one-step method of the present invention can generate bis(3-ethyl-5-methyl-4-maleimidophenyl)methane within a certain range. Experiments have shown that Example 1 is the best ratio.

[0052] Taking Example 1 as an example, the bis(3-ethyl-5-methyl-4-maleimidophenyl)methane prepared in the comparative example was analyzed by nuclear magnetic resonance spectrum. Figure 1As shown, Figure 1 a) is the NMR spectrum of BMI-70 synthesized in Example 1 of the present invention, Figure 1 b) is the NMR spectrum of BMI-70 synthesized in comparative example.

[0053] from Figure 1 a) and b) show that the 1H NMR spectra of the products synthesized by the one-step method and the two-step method are similar, and the chemical shift, peak number and hydrogen atom number in the spectra are consistent. It can also be seen from the figure that, excluding the influence of the peak δ=3.3 of the solvent DMSO and the peak δ=2.5 of a small amount of water in the product, the peak of the obtained product is consistent with the standard 1H NMR peak of BMI-70. That is, the triplet at δ1.00-δ1.01 and the doublet at δ2.30-δ2.32 are the resonance signal peaks of methyl and methylene protons, respectively, indicating the presence of ethyl; the singlet at δ1.98 belongs to the resonance signal peak of the methyl proton of the substituent on the benzene ring, that is, there is a methyl substituent on the benzene ring; the singlet at δ3.92 is the methylene signal peak at the symmetrical structure of BMI-70; the singlets at δ7.09 and δ7.15 belong to the series of signal peaks of the benzene ring protons. It can be seen from the spectrum that although different synthesis methods are used, the inherent chemical structure of BMI-70 is not affected.

[0054] In addition, from Figure 1 It can be seen from a) and b) that the 1H NMR spectra of the products obtained by synthesizing BMI-70 by one-step method and two-step method, respectively, have fewer impurity peaks in a) than in b). There are 3 impurity peaks on the curve. By comparing the liquid phase analysis with the raw material diaminodiphenylmethane, maleic anhydride, intermediate amic acid and microporous filtration insoluble impurities, it is basically determined that: the a-type impurity is a mixture of the raw material maleic anhydride and the intermediate amic acid. The two substances cannot be completely separated in this analysis method, and the two peaks overlap; the b-type impurity is the raw material diaminodiphenylmethane; the c-type impurity is not a raw material or an intermediate, but should be a reaction by-product.

[0055] like Figure 2 This is a peak area calculation diagram of the nuclear magnetic spectrum of BMI-70 synthesized in Example 1 of the present invention. It can be seen from the figure that the 1H NMR of the product obtained by synthesizing BMI-70 using a one-step method. According to the peak height and peak area calculation ratio, the ratio of the corresponding peaks from right to left is 3:3:2:1:1:1:2, where the position of 2.5 is DMSO and 3.3 is water peak that is not integrated.

[0056] like Figure 3 This is the infrared spectrum of Example 1 of the present invention and electronic grade BMI-70, infrared analysis was performed using the potassium bromide tablet method. -1 、1393cm -1 、689cm-1 It is the vibration absorption of the imide ring, 1149cm -1 It is CNC vibration absorption, 1646cm -1 It is the vibration absorption of carbon-carbon double bond, 800~1000cm -1 It is the bending vibration of benzene ring CH, and the spectrum is basically consistent with the standard spectrum.

[0057] DSC spectrum analysis

[0058] The test results of the synthesis performance of Example 1 (one-step reaction) of the present invention and the comparative example (two-step reaction) are shown in Table 1. The two-step method has a lower melting point (Tm), a higher thermal polymerization start temperature (Ti), a longer gel time (GT), and a larger temperature difference (Ti~Tm) from melting to the start of polymerization. These properties indicate that the relative reactivity of BMI-70 synthesized by the two-step method is relatively low. Compared with the two-step method, the one-step method synthesized product has a slightly higher Tm, a slightly lower Ti, shorter GT and Ti~Tm, and the activity of BMI-70 is also relatively high. The more by-products are produced during the reaction, the stronger their ability to inhibit the reaction activity, the worse the polymerization activity of BMI-70, and the corresponding increase in GT.

[0059] Table 1 DSC data of BMI-70 synthesized by different synthesis methods

[0060]

[0061] Determination of acid content

[0062] The determination of the acid value content of the product is an indirect determination of the purity and quality of the product.

[0063] Weigh 0.25g of the sample using an analytical balance and place it in a 100ml conical flask. Add 10ml of DMAC, and after the sample is dissolved, add 2d of 0.1% bromothymol blue indicator. Take a microburette and titrate with KOH / C2H5OH standard solution. When the color of the test solution changes from yellow to green and remains unchanged for 30s, it is the end point. Perform parallel and blank tests at the same time.

[0064] Acid value = 56.1 × N (V1-V2) / m

[0065] Where: N——millimolar concentration of KOH / C2H5OH standard solution, mmol / ml;

[0066] V1——volume of KOH ethanol standard solution consumed in titration, ml;

[0067] V2——the volume of KOH / C2H5OH standard solution consumed in blank titration, ml;

[0068] m——the mass of the pattern, g;

[0069] 56.1—Millimolar mass of KOH, mg / mmol.

[0070] The error of parallel experiments was 0.2%. The average value of two measurements was taken as the result, and two significant figures were taken.

[0071] Due to the complexity of the reaction system, the untimely removal of water will trigger a series of side reactions, and the by-products contain relatively more organic acids, resulting in a higher acid value and an increase in the content of by-products. Table 2 shows that the acid value of the one-step method is lower, and the acid value of the two-step method is relatively high, which shows that the purity of the product obtained by the one-step method is higher.

[0072] Table 2 Comparison of parameters of BMI-70 synthesized by different synthesis methods

[0073]

[0074] This reaction adopts a one-step preparation method. The one-step preparation method is that 4,4'-methylenebis(2-methyl-6-ethylaniline) and maleic anhydride in an organic solvent are subjected to a dehydration catalyst of p-toluenesulfonic acid to obtain bismaleamic acid and at the same time dehydrate and cyclize to obtain bis(3-ethyl-5-methyl-4-maleimidophenyl)methane, which effectively reduces the side reactions caused by the excess of the intermediate product bismaleamic acid.

[0075] As the reaction proceeds, the concentration of the intermediate product in the system gradually increases, and the added 4,4'-methylenebis(2-methyl-6-ethylaniline) may undergo addition reaction (reaction formula (1)) and dehydration condensation to form a peptide bond (reaction formula (2)). If the intermediate product in the system is excessive, it will also be accompanied by intermolecular dehydration during the dehydration process to form an insoluble, infusible linear oligomer (reaction formula (3)).

[0076]

[0077]

[0078] Although the embodiments and drawings of the present invention are disclosed for illustrative purposes, those skilled in the art will appreciate that various substitutions, changes and modifications are possible without departing from the spirit and scope of the present invention and the appended claims. Therefore, the scope of the present invention is not limited to the contents disclosed in the embodiments and drawings.

Claims

1. A method for preparing bis(3-ethyl-5-methyl-4-maleimidophenyl)methane, characterized in that: The dianhydride and diamine in an organic solvent are subjected to a dehydration catalyst to obtain bismaleamic acid and bis(3-ethyl-5-methyl-4-maleimidophenyl)methane at the same time of dehydration cyclization. The steps of the method are: S1, preparing a dianhydride solution: dissolving the dianhydride and the dehydration catalyst in the organic solvent and adding the organic solvent into a three-necked flask; S2, preparing a diamine solution: dissolving the diamine in the organic solvent and slowly dropping the solution into the three-necked flask; S3, after the addition is completed, the temperature is raised and refluxed for 3 hours, and water is separated by an oil-water separator during the reflux process; S4. After the reaction is completed, the solution obtained in S3 is cooled to 60°C to 85°C, sodium carbonate solution is added, and the pH is adjusted to neutral; S5, filtering the solution obtained in S4, separating the oil phase, and washing with water; The oil phase was separated and dried by rotary evaporation to obtain a crude product; S6. The crude product obtained in S5 is fully stirred and dissolved in toluene, and filtered. The filtrate is passed into a precipitation kettle with cooling water for crystallization, filtered, dried, crushed, and sieved to obtain white to light yellow bis(3-ethyl-5-methyl-4-maleimidophenyl)methane.

2. The method for preparing bis(3-ethyl-5-methyl-4-maleimidophenyl)methane according to claim 1, characterized in that: The dianhydride is maleic anhydride, the dehydration catalyst is p-toluenesulfonic acid, the molar ratio of maleic anhydride to p-toluenesulfonic acid is 1:0.08-0.1; the organic solvent is a mixed solution of toluene and N,N'-dimethylformamide (DMF), the volume ratio of toluene to N,N'-dimethylformamide (DMF) is 1:0.1-1:0.2; the amount of the S1 organic solvent does not exceed 10 times the equivalent of maleic anhydride.

3. The method for preparing bis(3-ethyl-5-methyl-4-maleimidophenyl)methane according to claim 2, characterized in that: The diamine is 4,4'-methylenebis(2-methyl-6-ethylaniline), the rate of slow dripping of S2 is 0.5 ml / min, and the reaction temperature does not exceed 45°C; the amount of the S2 organic solvent does not exceed 10 times the equivalent of 4,4'-methylenebis(2-methyl-6-ethylaniline); the molar ratio of 4,4'-methylenebis(2-methyl-6-ethylaniline) to maleic anhydride is 1:2.0 to 1:2.

4.

4. The method for preparing bis(3-ethyl-5-methyl-4-maleimidophenyl)methane according to claim 1, characterized in that: The S3 heating reflux temperature is 85°C to 110°C.

Images