阅读说明：本技术 双马来酰亚胺烷基类化合物的制备方法 (Preparation method of bismaleimide alkyl compound ) 是由 蒋兆芹 杨晨 顾耿峰 于 2020-07-20 设计创作，主要内容包括：本发明提供一种双马来酰亚胺烷基类化合物的制备方法,包括如下步骤：步骤S1,使顺丁二烯马来酸酐与二氨基烷基化合物在第一溶剂中经过开环反应,得到中间体；步骤S2,使所述中间体在有机碱的存在下在第二溶剂中发生关环反应,得到所述双马来酰亚胺烷基类化合物。根据本发明实施例的双马来酰亚胺烷基类化合物的制备方法,使用廉价的原料顺丁烯二酸酐和二氨基烷基化合物为原料,且整个操作既避免了长时间高温反应,降低了生产成本；此外,后期的纯化避免了过柱子的麻烦,操作便利的同时收率也大大提高,适合于工业化生产,具有良好的应用前景。(The invention provides a preparation method of bismaleimide alkyl compounds, which comprises the following steps: step S1, carrying out ring-opening reaction on maleic anhydride of butadiene and diamino alkyl compound in a first solvent to obtain an intermediate; and step S2, carrying out a ring closing reaction on the intermediate in a second solvent in the presence of an organic base to obtain the bismaleimide alkyl compound. According to the preparation method of the bismaleimide alkyl compound provided by the embodiment of the invention, cheap raw materials, namely maleic anhydride and diaminoalkyl compound, are used as raw materials, and the whole operation avoids long-time high-temperature reaction and reduces the production cost; in addition, the trouble of column passing is avoided in the purification in the later stage, the yield is greatly improved while the operation is convenient, and the method is suitable for industrial production and has good application prospect.)

1. A preparation method of bismaleimide alkyl compounds is characterized by comprising the following steps:

step S1, carrying out ring-opening reaction on maleic anhydride of butadiene and diamino alkyl compound in a first solvent to obtain an intermediate;

and step S2, carrying out a ring closing reaction on the intermediate in a second solvent in the presence of an organic base to obtain the bismaleimide alkyl compound.

2. The method for preparing bismaleimidoalkyl compound according to claim 1, wherein in the step S1, the diaminoalkyl compound is one or more selected from compounds represented by formula (1),

wherein n is any integer of 1-6.

3. The method for preparing bismaleimidoalkyl according to claim 1, wherein in the step S1, the molar ratio of the maleic anhydride to the diaminoalkyl is (1.5-3):1, and the reaction temperature is 0-30 ℃.

4. The method for preparing bismaleimidoalkyl compound according to claim 1, wherein in the step S1, the first solvent is one or more of acetic acid, DMF, ethyl acetate, and toluene.

5. The method for preparing bismaleimidoalkyl compound according to claim 1, wherein in the step S2, the organic base is one or more of triethylamine, diisopropylethylamine, and pyridine.

6. The method for preparing bismaleimidoalkyl compound according to claim 5, wherein in the step S2, the second solvent is one or more of dichloromethane, chloroform, and 1, 2-dichloroethane.

7. The method for preparing bismaleimidoalkyl group compound according to claim 6, wherein in the step S2, the second solvent comprises a haloalkylsilane and a Lewis acid,

the halogenated alkyl silane is one or more of chlorotrimethylsilane, bromotrimethylsilane and iodotrimethylsilane,

the Lewis acid is one or more of zinc chloride, aluminum chloride and ferric chloride.

8. The process for preparing bismaleimidoalkyl according to claim 7, wherein the intermediate: lewis acid: haloalkyl silane: the molar ratio of the alkali is 1 (1.5-3) to 3-6 to 2-4.

9. The method for preparing bismaleimidoalkyl compound according to claim 1, wherein in the step S2, the reaction temperature of the ring closing reaction is 0-80 ℃.

10. The method for preparing bismaleimidoalkyl compound according to claim 1, further comprising the steps of:

and step S3, after the reaction is finished, cooling the reaction liquid, pouring the cooled reaction liquid into ice water, fully stirring and layering, collecting the organic phase, cleaning and drying the organic phase, and finally recrystallizing the organic phase by using ethyl acetate/petroleum ether to purify the bismaleimide alkyl compound.

Technical Field

The invention relates to the technical field of organic synthesis, in particular to a preparation method of bismaleimide alkyl compounds.

Background

Bismaleimide alkyl compounds are building blocks for polymer synthesis, and are commonly used in the synthesis of high molecular weight, step-growth polymers and crosslinkers. In addition, polyimide resins heat-set-adducted with bismaleimide alkyl compounds are a major component of aircraft engines and aircrafts due to their high temperature resistance, warm strength and fatigue resistance. In addition, the maleimide terminal group on the prepolymer may be polymerized or crosslinked by various means, for example, thermal curing, polymerization by conjugate addition with diamines, bisphenols, dithiols, cycloaddition, and radical polymerization.

Presently, bismaleimide alkyl compounds are often used as cross-linking agents to reveal and characterize modifications at specific sites of protein structures or biomolecules, and this cross-linking with protein oligomerization helps to determine intra-and intermolecular distances. Meanwhile, the bismaleimide alkyl compound has certain water solubility, so that the crosslinking reaction is homogeneous, and the bismaleimide alkyl compound is already applied to synthesis of glycoprotein on the surface of T-cells, synthesis of bradykinin antagonist dimer and crosslinking of diene modified DNA.

At present, the synthesis technology of bismaleimide alkyl compounds mainly comprises the following three methods:

route one: the target product (J.Am.chem.Soc.1959, 81 (5)) is obtained by refluxing cis-butadiene maleic anhydride and a diaminoalkyl compound in acetic anhydride at high temperature. The reaction route is shown as the following formula (2):

the method has the disadvantages that the reaction needs high temperature and overlong reaction time, the post-treatment purification process needs column passing to obtain a pure product, the yield is not high, and the method is not suitable for industrial production.

And a second route: maleimide is used as a raw material, N-methoxy carbonyl maleimide is synthesized, and then the N-methoxy carbonyl maleimide and a diaminoalkyl compound react under the action of alkali to obtain a target product (J.Med.chem.1992, 35(9), 1563-1572). The reaction route is shown as the following formula (3):

although the method does not need column purification in the later stage and can be used for purification by recrystallization, the yield is not high, the price of maleimide is not cheap, and the yield in the first step is about 55 percent, so the synthesis cost is too high and the method is not suitable for industrial production.

And a third route: and (3) synthesizing an intermediate (a) by using D-A reaction and tetrahydropyran, reacting the intermediate (a) with a dihalogenated alkyl compound (b) to generate an intermediate (c), and finally deprotecting the intermediate (c) at high temperature to obtain a target compound (tetrahedron. letters.2013, 54(37), 5011-5013). The reaction route is shown in the following formula (4):

the synthetic route is carried out in three steps, high temperature is required, the purification of the final product needs to be carried out through a column, and the application range of the product is limited due to the residue caused by the use of DMF in the last step, particularly in the biological field, so that the synthetic route is not suitable for industrial production.

Disclosure of Invention

In view of the above, the present invention aims to provide a method for preparing bismaleimide alkyl compounds, which is low in production cost, simple in operation, environment-friendly, and suitable for industrial production.

The preparation method of the bismaleimide alkyl compound according to the embodiment of the invention comprises the following steps:

step S1, carrying out ring-opening reaction on maleic anhydride of butadiene and diamino alkyl compound in a first solvent to obtain an intermediate;

and step S2, carrying out a ring closing reaction on the intermediate in a second solvent in the presence of an organic base to obtain the bismaleimide alkyl compound.

According to some embodiments of the present invention, in the step S1, the diaminoalkyl compound is any one or more selected from the group consisting of compounds having a chemical structural formula shown in formula (1),

wherein n is any integer of 1-6.

According to some embodiments of the invention, in the step S1, the molar ratio of the maleic anhydride to the diamino alkyl compound is (1.5-3):1, and the reaction temperature is 0-30 ℃.

According to some embodiments of the invention, in the step S1, the first solvent is one or more of acetic acid, DMF, ethyl acetate, and toluene.

According to some embodiments of the invention, in the step S2, the organic base is one or more of triethylamine, diisopropylethylamine, and pyridine.

According to some embodiments of the invention, in the step S2, the second solvent is one or more of dichloromethane, chloroform, and 1, 2-dichloroethane.

According to some embodiments of the invention, in the step S2, the second solvent contains a haloalkylsilane and a lewis acid.

According to some embodiments of the invention, the haloalkylsilane is one or more of chlorotrimethylsilane, bromotrimethylsilane, iodotrimethylsilane and the lewis acid is one or more of zinc chloride, aluminum chloride and ferric chloride.

According to some embodiments of the invention, the intermediate: lewis acid: haloalkyl silane: the molar ratio of the alkali is 1 (1.5-3) to 3-6 to 2-4.

According to some embodiments of the invention, in the step S2, the reaction temperature of the ring closing reaction is 0 to 80 ℃.

According to some embodiments of the invention, the method of preparing further comprises:

and step S3, after the reaction is finished, cooling the reaction liquid, pouring the cooled reaction liquid into ice water, fully stirring and layering, collecting the organic phase, cleaning and drying the organic phase, and finally recrystallizing the organic phase by using ethyl acetate/petroleum ether to purify the bismaleimide alkyl compound.

The technical scheme of the invention at least has one of the following beneficial effects:

according to the preparation method of the bismaleimide alkyl compound provided by the embodiment of the invention, cheap raw materials, namely maleic anhydride and diaminoalkyl compound, are used as raw materials, and the whole operation avoids long-time high-temperature reaction and reduces the production cost;

in addition, the trouble of column passing is avoided in the purification in the later stage, the yield is greatly improved while the operation is convenient, and the method is suitable for industrial production and has good application prospect.

Detailed Description

In order to make the objects, technical solutions and advantages of the embodiments of the present invention clearer, the technical solutions of the present invention will be clearly and completely described below with reference to the embodiments of the present invention. It is to be understood that the embodiments described are only a few embodiments of the present invention, and not all embodiments. All other embodiments, which can be derived by a person skilled in the art from the described embodiments of the invention, are within the scope of the invention.

Hereinafter, the preparation method of bismaleimidoalkyl compounds according to embodiments of the present invention is described in detail.

The preparation method of the bismaleimide alkyl compound according to the embodiment of the invention comprises the following steps:

step S1, the cis-butadiene maleic anhydride and the diamino alkyl compound are subjected to a ring-opening reaction in the first solvent to obtain an intermediate.

Specifically, the reaction formula is represented by the following formula (5):

the diaminoalkyl compound can be any one or more selected from compounds with the chemical structural formula shown in a formula (1),

wherein n is any integer of 1-6.

In other words, the diaminoalkyl compound may be a compound having the above structural formula in which n ═ 1, a compound having the above structural formula in which n ═ 2, a mixture of a compound having n ═ 1 and a compound having n ═ 2, and so on, and n may be any integer from 1 to 6, and is not enumerated here.

The molar ratio of the maleic anhydride to the diaminoalkyl compound may be (1.5-3):1, and preferably, may be 2: 1. Further, the reaction can be carried out at a low temperature without high-temperature heating, for example, the reaction temperature may be 0 to 30 ℃.

The first solvent may be one or more of acetic acid, DMF, ethyl acetate and toluene.

And step S2, carrying out a ring closing reaction on the intermediate in a second solvent in the presence of an organic base to obtain the bismaleimide alkyl compound.

That is, after the intermediate is obtained through the step S1, a ring closing reaction of the intermediate in a second solvent is performed in the presence of an organic base, so as to obtain the bismaleimide alkyl compound.

Specifically, the reaction formula is represented by the following formula (6):

wherein, the organic base can be one or more of triethylamine, diisopropylethylamine and pyridine.

In addition, the second solvent may be, for example, one or more of dichloromethane, chloroform, 1, 2-dichloroethane.

Further, the second solvent may further contain a haloalkylsilane and a lewis acid. In other words, the ring closure reaction is allowed to occur in the presence of an organic base, a haloalkylsilane, and a lewis acid in a second solvent.

Specifically, the halogenated alkyl silane is one or more of chlorotrimethylsilane, bromotrimethylsilane and iodotrimethylsilane; the Lewis acid is one or more of zinc chloride, aluminum chloride and ferric chloride.

Further, the intermediate: lewis acid: haloalkyl silane: the molar ratio of the base may be 1 (1.5-3) to (3-6) to (2-4), preferably 1:1.8:4: 3.

In addition, the reaction temperature of the ring closure reaction may be 0 to 80 ℃. That is, high temperature heat treatment is not required.

And step S3, after the reaction is finished, cooling the reaction liquid, pouring the cooled reaction liquid into ice water, fully stirring and layering, collecting the organic phase, cleaning and drying the organic phase, and finally recrystallizing the organic phase by using ethyl acetate/petroleum ether to purify the bismaleimide alkyl compound.

That is, after the end of the ring closure reaction in step S2, the target product is separated and purified. Specifically, after the reaction is finished, the reaction solution is firstly cooled and poured into ice water, the mixture is fully stirred until the mixture is layered, an organic phase is collected, and the organic phase is washed by saturated saline solution and then is dried, filtered and concentrated to obtain a crude product. And finally, recrystallizing the crude product by using ethyl acetate/petroleum ether to obtain the purified bismaleimide alkyl compound.

Hereinafter, the method for producing bismaleimidoalkyl compounds according to the embodiment of the present invention will be described in detail by way of specific examples.

The starting materials used in the examples which follow are all commercially available, chemically pure or analytically pure.