阅读说明：本技术 一种壳聚糖负载铜催化合成磷酸混酯类化合物的方法 (Method for synthesizing phosphate mixed ester compound by chitosan loaded copper catalysis ) 是由 焦林郁 宁资慧 洪乾 张泽 孙鸣 李卓 马晓迅 于 2020-06-30 设计创作，主要内容包括：本发明涉及一种壳聚糖负载铜催化合成磷酸混酯类化合物的方法,将叠氮磷酸酯类化合物、壳聚糖负载铜催化剂、碱和脂肪醇依次加入反应溶剂中,在40～80℃下反应3～24h,过滤整个反应体系,用环己烷溶剂洗涤,回收壳聚糖负载铜催化剂,将滤液在减压状态下浓缩,残留物用柱层析色谱分离纯化得到目标产物。本发明所述方法简单易行,方便高效,可适用于不同类型的底物,成功制备出相应的目标化合物。所述负载型催化剂用量低,且可回收使用,重复使用五次之后,仍然保持较高的催化活性,反应结束后易于分离,无金属残留,是一种新型的催化合成方法,适合大规模生产。(The invention relates to a method for synthesizing a phosphate mixed ester compound by chitosan-supported copper catalysis, which comprises the steps of sequentially adding an azido phosphate ester compound, a chitosan-supported copper catalyst, alkali and fatty alcohol into a reaction solvent, reacting for 3-24 hours at 40-80 ℃, filtering the whole reaction system, washing with a cyclohexane solvent, recovering the chitosan-supported copper catalyst, concentrating the filtrate under a reduced pressure state, and separating and purifying residues by column chromatography to obtain a target product. The method is simple and easy to implement, convenient and efficient, and can be applied to different types of substrates to successfully prepare corresponding target compounds. The supported catalyst is low in dosage and can be recycled, the supported catalyst still maintains high catalytic activity after being repeatedly used for five times, and the supported catalyst is easy to separate after reaction and free of metal residue, is a novel catalytic synthesis method and is suitable for large-scale production.)

1. A method for synthesizing a phosphate mixed ester compound by chitosan-supported copper catalysis is characterized in that an azido phosphate compound, a chitosan-supported copper catalyst, alkali and fatty alcohol are added into a solvent to obtain a mixture, and then the mixture is reacted for 3-24 hours at 40-80 ℃ to obtain the phosphate mixed ester compound; wherein the mass ratio of the azido phosphate compounds to the chitosan supported copper catalyst is 1: (0.02-0.2).

2. The method for catalytically synthesizing phosphate mixed ester compounds by using chitosan-supported copper as claimed in claim 1, wherein the azido phosphate ester compound is diphenylphosphoryl azide, bis (2-ethyl-phenyl) phosphorazide, bis (2-isopropyl-phenyl) phosphorazide or bis (3-methoxy-phenyl) phosphorazide.

3. The method for catalytically synthesizing the phosphate mixed ester compound by using chitosan-supported copper as claimed in claim 1, wherein the chitosan-supported copper catalyst is chitosan-supported elemental copper powder, chitosan-supported cuprous chloride, chitosan-supported cuprous iodide, chitosan-supported cupric chloride, chitosan-supported copper fluoride, chitosan-supported cupric oxide, chitosan-supported cupric sulfate or chitosan-supported cupric acetate.

4. The method for catalytically synthesizing the phosphate mixed ester compound by using chitosan-loaded copper as claimed in claim 1, wherein the alkali is sodium hydroxide, sodium carbonate or sodium bicarbonate.

5. The method for catalytically synthesizing the phosphate mixed ester compound by using chitosan-supported copper as claimed in claim 1, wherein the aliphatic alcohol is methanol, n-propanol, n-pentanol, isopentanol, cyclohexanol, cyclohexylmethanol or acetonide.

6. The method for synthesizing the phosphate mixed ester compound under the catalysis of the chitosan-loaded copper as claimed in claim 1, wherein the solvent is cyclohexane or dichloromethane.

7. The method for catalytically synthesizing mixed phosphate ester compounds by using chitosan-loaded copper as claimed in claim 1, wherein the molar concentration of the azido phosphate ester compounds in the mixture is 0.2-0.5 mol/L.

8. The method for catalytically synthesizing the phosphate mixed ester compound by using chitosan-loaded copper as claimed in claim 1, wherein the mass ratio of the azido phosphate ester compound to the alkali is 1: (0.2 to 1).

9. The method for catalytically synthesizing the phosphate mixed ester compound by using chitosan-loaded copper as claimed in claim 1, wherein the mass ratio of the azido phosphate ester compound to the fatty alcohol is 1: (2-10).

Technical Field

The invention relates to the fields of heterogeneous catalysis and fine organic chemical industry, in particular to a method for synthesizing a phosphate mixed ester compound by catalyzing chitosan loaded copper.

Background

The phosphate ester compound is a product obtained by substituting a part or all of hydrogen atoms of hydroxyl groups in a phosphoric acid molecule with an alkyl group, an aryl group or the like. Substituent R in phosphate structure¹、R²、R³May be the same or different alkyl or aryl groups, or may be different combinations of alkyl and aryl groups. When the hydrogen atoms of the hydroxyl groups in the phosphoric acid molecules are replaced by at least two groups which are not completely identical, the phosphoric acid mixed ester is obtained.

Phosphate-mixed ester compounds are a very important organic framework, widely exist in natural products, show good properties in the aspects of surfactants (J.Li, et.al.journal of Colloid and Interface Science,2017,486,67), flame retardants (S.V.Levchik, et.al.Polymer International,2005,54,981) and biological medicines (D.Kim, et.al.chemistry of Materials,2010,22,247), and the like, are increasingly applied industrially, and research on synthetic methods of the phosphate-mixed ester compounds has very important social and economic meanings.

The phosphate compounds are generally synthesized by coupling compounds such as P (O) -H, P (O) -Cl and P (O) -OH with nucleophiles (alcohols, phenols, amines, etc.) (F.R. Athero, et. al. Journal of Chemical Society,1945,382; B.R. Sculimenene, Journal of the American Chemical Society,2001,123,10125; D.S. Panmand, et. al. tetrahedron Letters,2014,55, 5898; B.Xiong, et. al. ACS Catalysis,2015,5, 537; G.Keglevich, et. al. organic & biological Chemistry 2012,10, 2011). However, in these conversion processes, some of the required reagents have the disadvantages of high corrosivity, poor stability, difficulty in preparation, high price and the like. In addition, these reactions also have the limitations of additional additives, harsh reaction conditions, limited substrate applicability, low reactivity, and environmental pollution.

Recently, a homogeneous catalysis system is developed by Jolin depression and Zhang et al, and the catalytic synthesis of mixed phosphate is successfully realized by using diphenyl azide phosphate and fatty alcohol as reactants (Jolin depression, Zhang et al, a copper-catalyzed synthesis method of mixed phosphate ester compounds, CN201910595417.X, an invention patent, L. -Y.Jiano, Z.Zhang, et al.J.Catal.2019,379, 39). The method has limitations, and in a homogeneous reaction system, the copper catalyst cannot be recovered, so that heavy metal residues in the product are easily caused, and the large-scale application of the copper catalyst is limited to a certain extent. Therefore, the development of an economical, efficient, simple and green synthetic process of the phosphate mixed ester compound is of great significance.

Disclosure of Invention

In order to solve the problems in the prior art, the invention aims to provide a method for synthesizing phosphate mixed ester compounds by chitosan-loaded copper catalysis, which is simple, feasible, convenient and efficient. The catalyst has high catalytic activity, low consumption, easy recovery, reusability, no metal residue in the product, and the catalytic synthesis process is suitable for large-scale production.

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

a method for synthesizing a mixed phosphate compound by chitosan-supported copper catalysis comprises the steps of adding a nitrine phosphate compound, a chitosan-supported copper catalyst, alkali and fatty alcohol into a solvent to obtain a mixture, and then reacting the mixture at 40-80 ℃ for 3-24 hours to obtain the mixed phosphate compound; wherein the mass ratio of the azido phosphate compounds to the chitosan supported copper catalyst is 1: (0.02-0.2).

The invention is further improved in that the azido phosphate ester compound is diphenyl azidophosphate, bis (2-ethyl-phenyl) azidophosphate, bis (2-isopropyl-phenyl) azidophosphate or bis (3-methoxy-phenyl) azidophosphate.

The further improvement of the invention is that the chitosan loaded copper catalyst is chitosan loaded elemental copper powder, chitosan loaded cuprous chloride, chitosan loaded cuprous iodide, chitosan loaded cupric chloride, chitosan loaded copper fluoride, chitosan loaded cupric oxide, chitosan loaded cupric sulfate or chitosan loaded cupric acetate.

A further improvement of the invention is that the base is sodium hydroxide, sodium carbonate or sodium bicarbonate.

In a further development of the invention, the aliphatic alcohol is methanol, n-propanol, n-pentanol, isopentanol, cyclohexanol, cyclohexylmethanol or acetonide.

In a further development of the invention, the solvent is cyclohexane or dichloromethane.

The further improvement of the invention is that the molar concentration of the azido phosphate compounds in the mixture is 0.2-0.5 mol/L.

The invention has the further improvement that the mass ratio of the azido phosphate ester compound to the alkali is 1: (0.2 to 1).

The invention is further improved in that the mass ratio of the azido phosphate ester compound to the fatty alcohol is 1: (2-10).

Compared with the prior art, the invention has the following beneficial effects: the method takes chitosan loaded copper as a catalyst, azido phosphate as a reaction substrate and common fatty alcohol as a reaction reagent, and realizes nucleophilic substitution of the substrate under mild conditions to prepare the aryl/alkyl phosphate mixed ester compound containing different substituent groups. The reaction mechanism of the catalytic synthesis is as follows: the chitosan loaded copper catalyst provides a place for the contact of reactants and plays the role of Lewis acid, firstly, the catalyst is coordinated with an O atom in a P ═ O double bond in azido phosphate, so that the electron cloud density of a P ═ O group is shifted to the O atom, the electron cloud density of the P atom is reduced, and under the alkaline condition, alkoxy in fatty alcohol is used as a nucleophilic reagent and can attack the P atom to replace the azido group, so that the corresponding phosphate mixed ester compound is generated. The catalytic synthesis method is simple and easy to implement, convenient and efficient, rich in raw material source and low in cost, and is beneficial to application of the method in actual production; the method can realize higher conversion rate and higher separation yield of the target compound only by using lower catalyst dosage; the method has mild reaction conditions, is simple and easy to operate, and can be used for carrying out reaction at the temperature of 40-80 ℃; the method has wide applicability, can be suitable for various substrates of different types, and can efficiently prepare the corresponding phosphate mixed ester compound. The catalytic synthesis reaction system is a multi-phase system, and the chitosan loaded copper catalyst can be recovered by simple filtration after the reaction is finished; the chitosan supported cuprous chloride catalyst can be recycled and can be reused; a series of representations of the morphology, functional groups, composition, element valence states, content and the like of the chitosan-loaded cuprous chloride catalyst are carried out by means of X-ray diffraction (XRD), a Scanning Electron Microscope (SEM), a Fourier transform infrared spectroscopy (FT-IR), an X-ray photoelectron spectroscopy (XPS), inductively coupled plasma spectroscopy (ICP) and the like, and the catalyst is proved to have good stability in the reaction system.

Drawings

The following describes embodiments of the present invention in further detail with reference to the accompanying drawings.

FIG. 1 is an XPS spectrum of a chitosan-supported cuprous chloride (CS @ CuCl) catalyst in example 1 of the present invention, wherein (a) is the newly prepared CS @ CuCl catalyst; (b) is the CS @ CuCl catalyst recovered after the catalytic reaction.

FIG. 2 is an SEM image of the CS @ CuCl catalyst in example 1 of the present invention, wherein (a) is a freshly prepared CS @ CuCl catalyst; (b) is the CS @ CuCl catalyst recovered after the catalytic reaction.

FIG. 3 is an XRD pattern of the CS @ CuCl catalyst in example 1 of the present invention, wherein (a) is chitosan and (b) is the newly prepared CS @ CuCl catalyst; (c) is the CS @ CuCl catalyst recovered after the catalytic reaction.

FIG. 4 is an FT-IR spectrum of the CS @ CuCl catalyst in example 1 of this invention, wherein a is the freshly prepared CS @ CuCl catalyst; b is the CS @ CuCl catalyst recovered after the catalytic reaction.

Detailed Description

In order to further understand the present invention, the following examples are further illustrated, which are only used for explaining the present invention and are not to be construed as limiting the scope of the present invention.

The method takes nitrine diphenyl phosphate (DPPA) and derivatives thereof as reaction substrates, takes chitosan loaded copper as a catalyst, takes fatty alcohol as a nucleophilic reagent, and carries out nucleophilic substitution under the auxiliary action of alkali, thereby preparing the target compound of mixed phosphate. The specific process is as follows:

sequentially adding an azido phosphate compound, a chitosan supported copper catalyst, alkali and fatty alcohol into a solvent to obtain a mixture, reacting for 3-24 h at 40-80 ℃, filtering the whole reaction system, washing with a cyclohexane solvent, recovering the chitosan supported copper catalyst, concentrating the filtrate under a reduced pressure state, and separating and purifying the residue by column chromatography to obtain the target product.

Under the action of a chitosan supported copper (CS @ Cu) catalyst, DPPA or a derivative thereof and fatty alcohol are respectively adsorbed on the surface of the catalyst, a copper atom in the catalyst is used as an active center, and under the action of Lewis acid, the DPPA and the derivative thereof are firstly coordinated with an O atom in a P ═ O double bond to form a composite metal complex, so that the electron cloud density of the P ═ O group is shifted to the O atom, the electron cloud density of the P atom is reduced, and under an alkaline condition, an alkoxy group in the fatty alcohol is used as a nucleophilic reagent to attack the P atom from the back side, and a nucleophilic substitution reaction is carried out, so that a target product is generated. After the reaction is finished, the chitosan loaded copper catalyst can be recovered through simple filtration. The chemical reaction equation is as follows:

wherein the azido phosphate ester compound is azido diphenyl phosphate (DPPA), azido bis (2-ethyl-phenyl) phosphate, azido bis (2-isopropyl-phenyl) phosphate or azido bis (3-methoxy-phenyl) phosphate.

The aliphatic alcohol is methanol, n-propanol, n-pentanol, isoamyl alcohol, cyclohexanol, cyclohexylmethanol or acetonide.

The chitosan loaded copper catalyst (CS @ Cu) is chitosan loaded elementary copper powder (CS @ Cu powder), chitosan loaded cuprous chloride (CS @ CuCl), chitosan loaded cuprous iodide (CS @ CuI) and chitosan loaded cupric chloride (CS @ CuCl)₂) And chitosan loaded copper fluoride (CS @ CuF)₂) Shell polymerSugar-loaded copper oxide (CS @ CuO) and chitosan-loaded copper sulfate (CS @ CuSO)₄) Or chitosan loaded copper acetate (CS @ Cu (OAc))₂) Among them, chitosan-supported cuprous chloride (CS @ CuCl) is more preferable.

The solvent is cyclohexane or dichloromethane; the molar concentration of the azido phosphate compounds in the mixture is 0.2-0.5 mol/L.

The alkali is sodium hydroxide, sodium carbonate or sodium bicarbonate.

The mass ratio of the azido phosphate compounds to the fatty alcohol is 1: (2-10), wherein the mass ratio of the azido phosphate compounds to the chitosan loaded copper catalyst is 1: (0.02-0.2), wherein the mass ratio of the azido phosphate compounds to the alkali is 1: (0.2 to 1).

The invention has the following advantages: (1) the catalytic synthesis method is simple and easy to implement, convenient and efficient, rich in raw material sources and low in cost, such as diphenyl phosphorazide, chitosan, cuprous chloride, fatty alcohol and the like, and is favorable for application of the method in actual production; (2) the method can realize higher conversion rate and higher separation yield of the target compound only by using lower catalyst dosage; (3) the method has mild reaction conditions, takes fatty alcohol as a solvent, performs reaction at the temperature of 40-80 ℃, and is simple and easy to operate; (4) the method has wide applicability, can be suitable for various substrates of different types, and can efficiently prepare corresponding target compounds. (5) The catalytic synthesis reaction is a heterogeneous system, and the chitosan loaded copper catalyst can be recovered by simple filtration after the reaction is finished; (6) the chitosan supported cuprous chloride catalyst can be recycled and can be reused, for example, a compound methyl phosphate diphenyl ester is prepared by taking DPPA and methanol as raw materials, after the reaction is finished, the chitosan supported cuprous chloride catalyst (CS @ CuCl) is recovered by filtering and directly used for the next round of reaction, the reaction is recycled for five times, the conversion rates of azide phosphate reactants are respectively 96%, 92%, 85%, 82% and 77%, the separation yields of target compounds are respectively 90%, 87%, 82%, 80% and 71%, and the catalyst is proved to have better cyclic usability and still have good catalytic activity after five times; (7) a series of representations are carried out on the morphology, functional groups, composition, element valence states, content and the like of the chitosan-loaded cuprous chloride catalyst by means of X-ray diffraction (XRD), a Scanning Electron Microscope (SEM), a Fourier transform infrared spectroscopy (FT-IR), an X-ray photoelectron spectroscopy (XPS), inductively coupled plasma spectroscopy (ICP) and the like, and the catalyst is proved to have good stability in the reaction system;

the morphology and the types of functional groups of the catalyst are not obviously changed before and after the catalyst is used, and the catalyst comprises Cu²⁺And Cu⁺Two valence copper species with the ratio of ion number of Cu²⁺：Cu⁺0.16-0.18: 1; the mass fraction of the copper element in the catalyst is 8.24-9.46%.

The invention discloses chitosan loaded elementary copper powder (CS @ Cu powder), chitosan loaded cuprous chloride (CS @ CuCl), chitosan loaded cuprous iodide (CS @ CuI) and chitosan loaded copper chloride (CS @ CuCl)₂) And chitosan loaded copper fluoride (CS @ CuF)₂) Chitosan loaded copper oxide (CS @ CuO) and chitosan loaded copper sulfate (CS @ CuSO)₄) Chitosan-supported copper acetate (CS @ Cu (OAc))₂) Prepared according to the methods described in the literature (c.shen, et.al.green Chemistry,2014,16,3007).

The following are specific examples.