A method of synthesizing tetrabutyl glyoxal

Abstract

The application provides a method for synthesizing tetrabutyl phenolic aldehyde of formula (I), comprising the following steps: firstly, reacting para-tert-octyl phenol of formula (III) with formaldehyde under alkaline conditions to obtain 2,5-dihydroxymethyl para-tert-octyl phenol of formula (IV); then, reacting the 2,5-dihydroxymethyl para-tert-octyl phenol of formula (IV) with the para-tert-octyl phenol of formula (III) under acidic conditions to obtain phenolic aldehyde resin of formula (II); finally, reacting the phenolic aldehyde resin of formula (II) with ethylene oxide to obtain tetrabutyl phenolic aldehyde of formula (I).

Description

Invention Field

[0001] This invention belongs to the field of chemical synthesis, specifically relating to a method for synthesizing tetrabutylphenol aldehyde. Background Technology

[0002] Tetrabutylphenol is a high molecular weight polymer (as shown below) and belongs to the alkyl aromatic polyether alcohol type of nonionic liquid surfactant. The hydrophobic aromatic group increases the solubility of this molecule in oil, while the large number of hydrophilic ether alcohol groups increase the solubility of this molecule in water. Therefore, it is used as an emulsifier for water / oil and oil / water emulsions.

[0003]

[0004] In addition to being used as an emulsifier in the preparation of emulsions, creams and other formulations, tetrabutylphenol aldehyde is also widely used in the preparation of liquid formulations, such as nasal drops, eye drops, and oral solutions, as well as solid formulations, such as tablets and pills, due to its excellent solubilizing and dispersing properties. It can shorten the disintegration time of tablets and improve dissolution.

[0005] Tetrabutylphenol aldehyde, as an active ingredient in antitussive and expectorant preparations, reduces surface tension and liquefies mucus, making sputum easier to expel. It also functions as an emulsifier and penetration enhancer in formulations. Furthermore, it has been reported that tetrabutylphenol aldehyde is used in eyewashes (eye cleansers) with good cleaning and stain-removing effects. The concentration used as a pharmaceutical adjuvant should be determined based on the specific prescription, dosage form, and intended use; generally, the concentration is 0.1%–0.5%.

[0006] Currently, the main processes for synthesizing tetrabutylphenol aldehyde at home and abroad are as follows: 1) First, tert-octylphenol and ethylene oxide are reacted under high temperature and pressure in the presence of sodium hydroxide to generate polymeric phenol, and then tetrabutylphenol aldehyde is prepared by condensation of polymeric phenol with formaldehyde under acidic catalyst and heating conditions; 2) First, formaldehyde and p-tert-octylphenol are polymerized to obtain phenolic resin with qualified molecular weight, and then tetrabutylphenol aldehyde is synthesized by reacting qualified phenolic resin with ethylene oxide. Both of these routes tend to generate polymers with a degree of polymerization greater than 6 (pharmacopoeia standard m < 6) during phenolic polymerization, requiring high-temperature (above 160℃) vacuum distillation to retain the fraction at a specific temperature, which poses a great challenge to pilot-scale equipment and utilities.

[0007] Therefore, there is a demand in this field for tetrabutylphenolic resin with a degree of polymerization m<6, especially m=1, and its preparation method. Summary of the Invention

[0008] This invention addresses the shortcomings of the aforementioned synthesis methods by proposing a novel synthesis method and preparing tetrabutylphenol aldehyde with m=1. The method of this invention is simple to operate, yields a high-purity product, and is beneficial for industrial production.

[0009] Specifically, the present invention relates to the following technical solutions:

[0010] 1. Compound of formula (I):

[0011]

[0012] Where n = 6, 7, 8, 9, 10, 11 or 12; preferably, n = 8, 9 or 10; more preferably, n = 9.

[0013] 2. A method for preparing the compound of formula (I) according to technical solution 1,

[0014]

[0015] This includes the step of reacting compound (II) with ethylene oxide to obtain compound (I).

[0016] 3. The method of technical solution 2, wherein the molar ratio of compound of formula (II) to ethylene oxide is 1:19 to 1:37, preferably 1:25 to 1:32, more preferably 1:27 to 1:29, and more preferably 1:28.

[0017] 4. The method of technical solution 2 or 3, wherein the reaction of compound (II) with ethylene oxide is carried out in an aprotic solvent, preferably in an aprotic nonpolar solvent; preferably, the solvent is selected from alkanes, such as n-hexane, heptane, benzene, toluene, and especially toluene.

[0018] 5. The method of any one of technical solutions 2-4, wherein the reaction is carried out at a temperature above 60°C (e.g., 60-120°C), preferably at a temperature above 80°C (e.g., 80-100°C), and most preferably at a temperature of 100°C.

[0019] 6. The method of any one of technical solutions 2-5, wherein the reaction is carried out at a pressure of 0.2-0.8 MPa, preferably 0.3-0.8 MPa, and more preferably 0.3-0.5 MPa.

[0020] 7. The method of any one of technical solutions 2-6, wherein the reaction is carried out for at least 3 hours, preferably at least 5 hours.

[0021] 8. The method of any one of technical solutions 2-7, wherein the reaction is carried out in toluene at a temperature of 80-100°C and a pressure of 0.3-0.5 MPa for at least 5 hours, wherein the molar ratio of compound (II) to ethylene oxide is 1:28.

[0022] 9. Compound of formula (II):

[0023]

[0024] 10. A method for preparing a compound of formula (II),

[0025]

[0026] The process includes reacting compound (III) with compound (IV) under acidic conditions to obtain compound (II).

[0027] 11. The method of technical solution 10, wherein the molar ratio of compound (IV) to compound (III) is less than 1:2, preferably 1:2.1 to 1:3, more preferably 1:2.1 to 1:2.3, for example 1:2.1, 1:2.2 or 1:2.3.

[0028] 12. The method of technical solution 10 or 11, wherein the reaction is carried out in oxalic acid, acetic acid, sulfuric acid or hydrochloric acid, preferably in oxalic acid.

[0029] 13. The method of any one of technical solutions 10-12, wherein the reaction is carried out at a temperature above 80°C, preferably at 80-100°C, and most preferably at 100°C.

[0030] 14. The method of any one of technical solutions 10-13, wherein the reaction is carried out for at least 5 hours, preferably 5-8 hours, more preferably at least 6 hours, and most preferably 6 hours.

[0031] 15. The method of any one of technical solutions 10-14, wherein the reaction conditions are one of the following:

[0032] 1) Under acidic conditions (e.g., in oxalic acid, acetic acid, sulfuric acid or hydrochloric acid), the reaction is carried out at a temperature above 80°C for at least 5 hours, wherein the molar ratio of compound (IV) to compound (III) is less than 1:2;

[0033] 2) The reaction is carried out in glacial acetic acid at 100°C for at least 6 hours, wherein the molar ratio of compound (IV) to compound (III) is 1:2.2;

[0034] 3) The reaction is carried out in 2 mol / L sulfuric acid at 100 °C for at least 6 h, wherein the molar ratio of compound (IV) to compound (III) is 1:2.2;

[0035] 4) The reaction is carried out in 2 mol / L oxalic acid at 100 °C for at least 6 h, wherein the molar ratio of compound (IV) to compound (III) is 1:2.2.

[0036] 5) The reaction is carried out in 32% hydrochloric acid at 100°C for at least 6 hours, wherein the molar ratio of compound (IV) to compound (III) is 1:2.2.

[0037] 16. A method for preparing a compound of formula (IV),

[0038]

[0039] This includes the step of reacting compound (III) with formaldehyde under alkaline conditions to obtain compound (IV).

[0040] 17. The method of technical solution 16, wherein the molar ratio of the compound of formula (III) to formaldehyde is less than 1:2, preferably 1:2.1 to 1:5, more preferably 1:2.1 to 1:2.3, for example 1:2.1, 1:2.2 or 1:2.3.

[0041] 18. The method of technical solution 16 or 17, wherein the molar ratio of the compound of formula (III) to the base is less than 1:1, preferably 1:2 to 1:4, more preferably 1:2 to 1:3, and even more preferably 1:2.5.

[0042] 19. The method of any one of technical solutions 16-18, wherein the reaction is carried out in the presence of an inorganic base (preferably an alkali metal hydroxide, such as lithium hydroxide, sodium hydroxide or potassium hydroxide).

[0043] 20. The method of any one of technical solutions 16-19, wherein the reaction is carried out at a temperature above 60°C, preferably at 80-100°C.

[0044] 21. The method of any one of technical solutions 16-20, wherein the reaction is carried out for at least 2 hours, preferably at least 3 hours, and more preferably at least 4 hours.

[0045] 22. The method of any one of technical solutions 16-20, wherein the reaction conditions are one of the following:

[0046] 1) The reaction is carried out at a temperature above 60°C for at least 3 hours in the presence of an inorganic base (preferably an alkali metal hydroxide), wherein the molar ratio of the compound of formula (III) to formaldehyde is less than 1:2 and the molar ratio of the compound of formula (III) to the inorganic base is less than 1:1.

[0047] 2) The reaction is carried out at 80-100℃ for at least 3 hours in the presence of potassium hydroxide, wherein the molar ratio of compound (III) to formaldehyde is 1:2.2 and the molar ratio of compound (III) to potassium hydroxide is 1:2.5.

[0048] 3) The reaction is carried out at 80-100℃ for at least 3 hours in the presence of sodium hydroxide, wherein the molar ratio of compound (III) to formaldehyde is 1:2.2 and the molar ratio of compound (III) to sodium hydroxide is 1:2.5.

[0049] 23. A method for preparing a compound of formula (I),

[0050]

[0051] It includes the following steps:

[0052] 1) The compound of formula (III) reacts with formaldehyde in the presence of sodium hydroxide or potassium hydroxide at 80-100℃ for at least 3 hours; wherein the molar ratio of the compound of formula (III) to formaldehyde is 1:2.2, and the molar ratio of the compound of formula (III) to sodium hydroxide / potassium hydroxide is 1:2.5.

[0053] 2) React compound (III) and compound (IV) in 2 mol / L oxalic acid at 100 °C for at least 6 h; wherein the molar ratio of compound (IV) to compound (III) is 1:2.2;

[0054] 3) Compound (II) and ethylene oxide are reacted in toluene at 100°C and 0.3-0.5 MPa for at least 5 hours, wherein the molar ratio of compound (II) to ethylene oxide is 1:28.

[0055] The beneficial effects of this invention are:

[0056] The new method of this invention has the advantages of simple operation, mild reaction conditions, high purity of reaction products, and high yield, which is beneficial to industrial production. Detailed Implementation

[0057] definition

[0058] "Aprotic solvents," also known as non-proton-transferring solvents, are solvents without protons. These solvents exhibit extremely weak or no tendency for proton self-transfer reactions. Aprotic solvents can be classified as: non-protic nonpolar solvents, such as alkanes (e.g., hexane, heptane, benzene, toluene, diethyl ether, carbon tetrachloride); and non-protic polar solvents, such as amides, ketones, nitriles, dimethyl sulfoxide, pyridine, dichloromethane, N,N-dimethylformamide, acetone, etc.

[0059] "Acidic conditions" refer to a system with a pH less than 7, usually achieved by adding acid. Acids include organic and inorganic acids. Organic acids include carboxylic acids (R-COOH), sulfonic acids (R-SO3H), sulfinic acids (R-SOOH), and thiocarboxylic acids (R-SH), such as acetic acid, tartaric acid, oxalic acid, malic acid, citric acid, ascorbic acid, benzoic acid, and salicylic acid. Inorganic acids include hydrochloric acid, sulfuric acid, nitric acid, and phosphoric acid.

[0060] "Alkaline conditions" refer to a system with a pH greater than 7, usually achieved by adding a base. Bases include organic and inorganic bases. Organic bases include amine compounds and nitrogen-containing heterocyclic compounds, as well as broader organic bases such as alkali metal salts of alcohols (e.g., sodium methoxide, potassium ethoxide, potassium tert-butoxide), alkyl lithium compounds (e.g., butyllithium, phenyllithium), and amino lithium compounds (e.g., diisopropylaminolithium, hexamethyldisilaminolithium). Inorganic bases include lithium hydroxide, sodium hydroxide, potassium hydroxide, cesium hydroxide, barium hydroxide, calcium hydroxide, ammonium hydroxide, potassium carbonate, sodium carbonate, lithium carbonate, cesium carbonate, potassium bicarbonate, sodium bicarbonate, potassium bicarbonate, and cesium bicarbonate.

[0061] The technical solution of the present invention will be clearly and completely described below with reference to embodiments. Obviously, the described embodiments are merely illustrative of the present invention and not intended to limit the present invention. All other embodiments obtained by those skilled in the art based on the embodiments of the present invention without creative effort are within the scope of protection of the present invention.

[0062] The method for synthesizing tetrabutylphenol is shown below:

[0063]

[0064]

[0065] Where n = 6, 7, 8, 9, 10, 11 or 12; preferably, n = 8, 9 or 10; more preferably, n = 9.

[0066] Step 1: Compound (III) reacts with formaldehyde under alkaline conditions to obtain compound (IV);

[0067] Step 2: React compound (IV) with compound (III) under acidic conditions to obtain compound (II);

[0068] Step 3: React compound (II) with ethylene oxide to obtain compound (I).

[0069] Example

[0070] Example 1

[0071] Synthesis of 2,5-dihydroxymethyl-p-tert-octylphenol

[0072] 103.0 g of p-tert-octylphenol and 33 g of formaldehyde were added to a reaction flask, followed by 500 mL of water. 50.0 g of sodium hydroxide was added in portions. After the addition was complete, the temperature was raised to 100 °C, and the mixture was stirred for 3 h. After the reaction was complete, the reaction solution was extracted with dichloromethane to obtain the organic phase. The organic phase was washed once with distilled water and once with saturated brine, and then evaporated to dryness to obtain a yellow liquid, 117.6 g, yield 88.4%. ESI-MS [M+H] + =267.5.

[0073] Experiment 1: The effect of different bases on the preparation of compound (IV).

[0074] Table 1: Effects of different bases on the preparation of compound (IV)

[0075]

[0076]

[0077] Table 2: Effects of different bases on the preparation of compound (IV)

[0078] Example 1 Example 2 Example 3 Comparative Example 1 Mass of product (g) 117.6 88.2 111.3 No response Yield (%) 88.4 66.3 83.5 ESI-MS[M+H]+ 267.2 267.5 267.2

[0079] When the base used is too weak, the reaction cannot proceed normally. Therefore, alkali metal hydroxides can be used, preferably sodium hydroxide and potassium hydroxide.

[0080] Experiment 2: Effect of different reaction temperatures on the preparation of compound (IV).

[0081] Table 3: Effect of different reaction temperatures on the preparation of compound (IV)

[0082]

[0083] Table 4: Effect of different reaction temperatures on the preparation of compound (IV)

[0084] Example 1 Example 4 Example 5 Comparative Example 2 Mass of product (g) 117.6 109.5 112.1 43.4 Yield (%) 88.4 82.3 84.2 32.6 ESI-MS[M+H]+ 267.2 267.2 267.2 267.2

[0085] The above experimental results prove that the reaction requires a relatively high temperature to proceed. When the temperature is too low, the reaction cannot proceed completely in the same amount of time. Therefore, a temperature of 60℃ or higher is selected, preferably 80-100℃.

[0086] Experiment 3: Effect of formaldehyde feed ratio on the preparation of compound (IV).

[0087] Table 5: Effect of formaldehyde feed ratio on the preparation of compound (IV)

[0088]

[0089] Table 6: Effect of formaldehyde feed ratio on the preparation of compound (IV)

[0090] Example 6 Example 7 Example 1 Example 8 Mass of product (g) 86.7 111.0 117.6 118.1 Yield (%) 65.2 83.4 88.4 88.8 ESI-MS[M+H]+ 267.2 267.2 267.2 267.2

[0091] The above experimental results prove that the amount of formaldehyde required for this reaction needs to be slightly greater than twice the standard amount to ensure a stable yield. However, continuously increasing the amount of formaldehyde does not significantly improve the yield. Therefore, the selected amount of formaldehyde is >2 times, preferably 2.1-5 times, and more preferably 2.1-2.3 times.

[0092] Experiment 4: Effect of alkali feed ratio on the preparation of compound (IV).

[0093] Table 7: Effect of Alkali Feed Ratio on the Preparation of Compound (IV)

[0094]

[0095]

[0096] Table 8: Effect of Alkali Feed Ratio on the Preparation of Compound (IV)

[0097] Example 9 Example 1 Example 10 Example 11 Mass of product (g) 107.6 117.6 113.1 110.9 Yield (%) 80.9 88.4 85.0 83.4 ESI-MS[M+H]+ 267.2 267.2 267.2 267.2

[0098] The above experimental results show that the addition of different bases has little effect on the product yield. In order to ensure the completeness of the reaction, the molar ratio of compound (III) to base is determined to be less than 1:1, preferably 1:2 to 1:4, more preferably 1:2 to 1:3, and even more preferably 1:2.5.

[0099] Example 12

[0100] Synthesis of phenolic resins

[0101] 66.5 g of 2,5-dihydroxymethyl-p-tert-octylphenol and 113.3 g of p-tert-octylphenol were added to a reaction flask, along with 250 mL of purified water and 54 g of oxalic acid. After the addition was complete, the temperature was raised to 100 °C, and the mixture was stirred for 6 h. After the reaction was complete, the pH was adjusted to 7-8 with a 1 mol / L sodium hydroxide aqueous solution. The aqueous solution was extracted with dichloromethane to obtain the organic phase. The organic phase was washed once with distilled water and once with saturated brine, and then evaporated to dryness to obtain 127.7 g of a deep yellow liquid, with a yield of 79.6%. 1 H NMR(400MHz, CDCl3)δ7.77(s,2H),7.25(d,J=2.5Hz,3H),7.10-6.59(m,5H),3.89(d, J=12.5Hz,3H),1.67(d,J=5.4Hz,6H),1.31(d,J=5.6Hz,18H),0.68(d,J=5.9Hz,27H).

[0102] Experiment 5: Effect of Feed Ratio on the Preparation of Compound (II)

[0103] Table 9: Effect of Feed Ratio on the Preparation of Compound (II)

[0104]

[0105]

[0106] Table 10: Effect of Feed Ratio on the Preparation of Compound (II)

[0107] Example 13 Example 12 Example 14 Example 15 Mass of product (g) 117.4 127.7 123.2 126.6 Yield (%) 73.2 79.6 76.8 78.9

[0108] The above experimental results show that when the feed ratio is 1:2, there will be excess raw materials. The feed ratio required for this reaction needs to be slightly greater than 2 times the standard amount to ensure stable yield. However, continuously increasing the feed ratio does not significantly improve the yield. Therefore, a feed ratio of >2 times is preferable, preferably 2.1-3 times, and more preferably 2.1-2.3 times, such as 2.1, 2.2 or 2.3 times.

[0109] Experiment 6: Effects of different acids on the preparation of compound (II)

[0110] Table 11: Effects of different acids on the preparation of compound (II)

[0111]

[0112] Table 12: Effects of different acid ratios on the preparation of compound (II)

[0113] Example 12 Example 16 Example 17 Example 18 Mass of product (g) 127.7 117.1 100.2 98.7 Yield (%) 79.6 73.0 62.5 61.6

[0114] The above experiments demonstrate that the reaction proceeds smoothly under acidic conditions, with oxalic acid yielding the best results. Therefore, oxalic acid is the preferred choice.

[0115] Experiment 7: Effect of reaction time on the preparation of compound (II)

[0116] Table 13: Effect of reaction time on the preparation of compound (II)

[0117]

[0118] Table 14: Effect of reaction time on the preparation of compound (II)

[0119] Example 19 Example 12 Example 20 Comparative Example 21 Mass of product (g) 124.3 127.7 124.0 130.2 Yield (%) 77.5 79.6 77.3 81.2

[0120] The above experiments demonstrate that the reaction can proceed smoothly when the reaction time is not less than 5 hours. Extending the reaction time does not significantly change the yield. Therefore, to ensure the complete progress of the reaction, the reaction time is confirmed to be at least 5 hours, preferably 5-8 hours, preferably at least 6 hours, and more preferably 6 hours.

[0121] Example 22

[0122] Synthesis method of tetrabutylphenol aldehyde

[0123] 80.0 g of phenolic resin and 400.0 mL of toluene were added to a pressure-resistant reaction flask. The mixture was cooled to 0 °C, and 153.2 g of ethylene oxide was added. The flask was sealed and heated to 80-100 °C. At this point, the pressure in the reaction flask was approximately 0.3-0.5 MPa. The reaction was maintained at this temperature for 5 hours. After the reaction was complete, the mixture was cooled to 0 °C, and 400 mL of water and 1 mol / L sodium hydroxide aqueous solution were added to adjust the pH to 9. The mixture was separated to obtain the organic phase. The organic phase was washed once with water and once with saturated brine. The organic phase was collected, and the solvent was evaporated to dryness, yielding a yellow oily substance. 76.0 g of the pale yellow oily substance was collected by vacuum distillation, yielding a yield of 77.3% and a purity of 99.4%. 1 H NMR (400MHz, DMSO-d6) δ7.54-6.41(m,8H),4.54(t,J=5.4Hz,3H),4.28-3.78(m,4H),3.69(ddt,J=14 .5,9.3,4.1Hz,10H),3.76-3.40(m,98H),1.92-1.45(m,6H),1.36-1.04(m,18H),0.88-0.27(m,27H).

[0124] Experiment 8: Exploring the molar ratio of compound (II) to ethylene oxide

[0125] Table 15: Experimental Examples of Exploring the Molar Ratio of Compound (II) to Ethylene Oxide

[0126]

[0127] Table 16: Results of the exploration of the molar ratio of compound (II) to ethylene oxide

[0128]

[0129] The above experimental results demonstrate that the degree of polymerization of the compound can be controlled by the molar ratio of the compound of formula (II) to ethylene oxide. To obtain a product with a degree of polymerization of 9, the preferred feed ratio is 1:27 to 1:29, preferably 1:28.

[0130] Experiment Nine: Exploration of Reaction Temperature

[0131] Table 17: Experimental Examples of Reaction Temperature Exploration

[0132]

[0133] Table 18: Results of the reaction temperature exploration

[0134]

[0135]

[0136] The above experimental results show that the reactions can proceed normally. Therefore, it is confirmed that a temperature above 60°C (e.g., 60-120°C) is preferred, preferably above 80°C (e.g., 80-100°C), and more preferably 100°C.

[0137] Experiment 10: Exploration of Reaction Pressure

[0138] Table 19: Experimental Examples of Reaction Pressure Exploration

[0139]

[0140] Table 18: Results of the reaction pressure exploration

[0141] Comparative Example 3 Example 22 Example 30 Example 31 Mass of product (g) Incorrect product 76.0 77.8 76.7 Yield (%) 77.3 79.1 78.0

[0142] The above results prove that the reaction needs to be carried out under pressure. At normal pressure, only one ethylene oxide reacts, but polymerization cannot occur. The reaction must be under pressure. At the same time, the higher the pressure, the greater the risk of reaction. Through investigation, it was finally confirmed that the pressure can be 0.2-0.8 MPa, with 0.3-0.8 MPa being the best, and 0.3-0.5 MPa being the preferred.

[0143] Although the present invention has been disclosed above with reference to preferred embodiments, it is not intended to limit the present invention. Any person skilled in the art can make various modifications and alterations without departing from the spirit and scope of the present invention. Therefore, the scope of protection of the present invention should be determined by the claims.

Claims

1. A method for preparing a compound of formula (II), The reaction includes the step of reacting a compound of formula (III) with a compound of formula (IV) under acidic conditions to obtain a compound of formula (II), wherein the reaction is carried out in oxalic acid.

2. The method of claim 1, wherein the molar ratio of compound (IV) to compound (III) is less than 1:

2.

3. The method of claim 2, wherein the molar ratio of compound (IV) to compound (III) is from 1:2.1 to 1:

3.

4. The method of claim 2, wherein the molar ratio of compound (IV) to compound (III) is from 1:2.1 to 1:2.

3.

5. The method of claim 2, wherein the molar ratio of compound (IV) to compound (III) is 1:2.1, 1:2.2 or 1:2.

3.

6. The method of claim 1, wherein the reaction is carried out at a temperature above 80°C.

7. The method of claim 6, wherein the reaction is carried out at 80-100°C.

8. The method of claim 6, wherein the reaction is carried out at 100°C.

9. The method of claim 1, wherein the reaction is carried out for at least 5 hours.

10. The method of claim 9, wherein the reaction is carried out for 5-8 hours.

11. The method of claim 9, wherein the reaction is carried out for at least 6 hours.

12. The method of claim 9, wherein the reaction is carried out for 6 hours.

13. The method of claim 1, wherein the reaction conditions are as follows: In oxalic acid, the reaction is carried out at a temperature above 80°C for at least 5 hours, wherein the molar ratio of compound (IV) to compound (III) is less than 1:

2.

14. The method of claim 1, wherein the reaction conditions are as follows: The reaction is carried out in 2 mol / L oxalic acid at 100 °C for at least 6 h, wherein the molar ratio of compound (IV) to compound (III) is 1:2.

2.

15. A method for preparing a compound of formula (I), Where n = 6, 7, 8 or 9; It includes the following steps: 1) The compound of formula (III) reacts with formaldehyde in the presence of sodium hydroxide or potassium hydroxide at 80-100°C for at least 3 hours; The molar ratio of compound (III) to formaldehyde is 1:2.2, and the molar ratio of compound (III) to sodium hydroxide / potassium hydroxide is 1:2.

5. 2) React compound (III) and compound (IV) in 2 mol / L oxalic acid at 100 °C for at least 6 h; wherein the molar ratio of compound (IV) to compound (III) is 1:2.2; 3) Compound (II) and ethylene oxide are reacted in toluene at 100°C and 0.3-0.5 MPa for at least 5 hours, wherein the molar ratio of compound (II) to ethylene oxide is 1:28.

Images