CN115710169B

CN115710169B - Preparation method of squaric acid

Info

Publication number: CN115710169B
Application number: CN202211444773.XA
Authority: CN
Inventors: 宋也
Original assignee: Beijing Chengyu Specialty Chemical Co ltd
Current assignee: Beijing Chengyu Specialty Chemical Co ltd
Priority date: 2022-11-18
Filing date: 2022-11-18
Publication date: 2024-05-28
Anticipated expiration: 2042-11-18
Also published as: CN115710169A

Abstract

The invention belongs to the field of chemical industry, and particularly relates to a preparation method of squaric acid, which comprises the following steps: under the action of alkali, performing cycloaddition reaction on polyethylene glycol divinyl ether and dichloroacetyl chloride to obtain chlorocyclobutanone connected with glycol ether chain; the chloro-cyclobutanone obtained above is subjected to bromination reaction to obtain bromo-substituted cyclobutanone reaction mixed solution; directly heating the obtained reaction mixture, and obtaining a crude product of a target product through hydrolysis reaction; purifying the crude product of the target product, and recrystallizing to obtain the target product. The synthesis method has the advantages of readily available raw materials, good reaction selectivity, high purity, good yield, mild reaction conditions, simplicity, high efficiency, strong reaction stability and suitability for large-scale production.

Description

Preparation method of squaric acid

Technical Field

The invention belongs to the field of chemical industry, and particularly relates to a preparation method of squaric acid.

Background

Squaric acid (3, 4-dihydroxy-3-cyclobutene-1, 2-dione, 1) is an important intermediate for synthesizing medicines, pesticides, photosensitive materials, dyes and the like.

The name was given to the four-membered ring structure and the strongly acidic nature, and was originally synthesized by Cohen et al in 1959 (Cohen, M.; lacher, R.; park, D.J. am. Chem. Soc.; 1959,8l: 3480). Because of the unique chemical structure and active chemical nature of squaraines, chemistry of squaraines has been intensively and widely studied by various countries.

As a typical molecule in a carbon-oxygen type aromatic system, squaraine is very chemically reactive and can react with many compounds in various ways, known as universal intermediates. Simple derivatives thereof, such as squarates, squaramides and squaryl chlorides, also show good chemical activity (Maahs, g.; hegenberg, p.angelw.chem. Internal. Edit.,1966, 5:888).

The squaraine compound formed by condensing squaraine with an electricity-rich aromatic ring such as aromatic amine, phenols, nitrogen-containing heterocyclic compound and the like is a novel near-infrared dye with excellent performance, has high molar extinction coefficient in a near-infrared region, is strongly absorbed in the near-infrared region, has obvious effect in sensitizing singlet oxygen, can be used as a triplet photosensitizer, has good application prospect in the field of photodynamic therapy, and can solve the problem that the existing cyanine dye has low singlet oxygen quantum yield when being used for photodynamic therapy. In addition, because many cyanine dyes have strong fluorescence emission in the near infrared region, the cyanine dyes can be used as good near infrared fluorescent probes for analyzing bioactive substances, thereby being applied to the front fields of life sciences such as near infrared fluorescent immunoassay, DNA sequence determination and the like (Yasemin,G.I.;Ingin,U.A.Tetrahedron Lett.,1997,38:7417;Ayyappanpillai,A.;Easnavan,A.Org.Lett.,2001,7:3135;CN110128844A).

The organic electrode material containing squaraine can be used as a positive electrode active material and a negative electrode active material, can obtain excellent electrochemical performances when being respectively used as a positive electrode active material, a negative electrode active material and a full-organic battery, and is beneficial to realizing large-scale application (CN 114409894A).

The specific capacity of the lithium squarate is up to 440 milliamp hours per gram, and the specific capacity of the lithium squarate is twice that of the traditional positive electrode material. The decomposition voltage of the lithium squarate is between 4.1 and 4.8V, and the lithium squarate is suitable for being used as a sacrificial lithium salt to compensate irreversible capacity loss of lithium ions (CN 113443973A, NC 110683944A).

As the existing method for synthesizing squaric acid, cohcen and its partners, as early as 1959, starting from chlorotrifluoroethylene, generate hexafluoro-dichloro cyclobutane through polymerization, then reduce with zinc powder to obtain perfluoro-cyclobutene, then generate corresponding intermediate under the action of ethanol and alkali, and then obtain squaric acid through acidic hydrolysis (Cohen,M.;Lacher,R.;Park,D.J.Am.Chem.Soc.,1959,8l：3480;Park,D.;Cohen,M.;Lacher,R.J.Am.Chem.Soc.,1962,84：2919;Cohen,S.;Cohen,S.G.J.Am.Chem.Soc.,1966.88:1553).

This is the earliest synthetic route in the preparation of squaraines, which has been gradually replaced by chlorinated olefins (DE 2618567;DE 334431) due to serious destruction of the ozone layer in the atmosphere by fluorine-containing olefins and environmental pollution due to low degradation rate, but dimerization of chlorinated olefins is difficult to control and conversion rate is low.

In 1963, maahhs proposed a perchloro-l, 3-butadiene intramolecular cycloaddition method, which was subjected to alcoholysis and reduction to give tetrachlorocyclobutanone, which was finally hydrolyzed to give a mixture comprising squaric acid with an isolated yield of 35% (Maahs, G.Angew.Chem.,1963,75:985;Maahs,G.Justus Liebigs Ann.Chem.,1965,686: 55).

In 1966, maahs et al modified the above process by substituting morpholine as a nucleophile to give 1, l, 3-trichloro-2, 4-tri-morpholin-1, 3-butadiene, and then cyclizing hydrolysis and concentrated hydrochloric acid treatment to give squaric acid in a total yield of about 40% (Maahs, g.; hegenberg.P.Angew.Chem.,1966,78:927;DE l56829l). The improvement of the method is further researched by the scholars in China, so that the yield is improved to about 60 percent (Li Xiangcai, shosen, yuan Deji, etc., chemical reagents, 1992, 14:115).

The starting materials of the above processes, perchloro-l, 3-butadiene, are relatively expensive and have not yet been stably commercially available. In addition, the intramolecular cycloaddition reaction stage involved in the synthesis process requires higher reaction temperature, so that the decomposition of intermediates is aggravated, side reactions are more, the selectivity is poor, a lot of disadvantages are brought in the later product purification process, and the mass production is limited.

In 1979, bacillus proposed the preparation of squaric acid by cycloaddition with substituted acid chloride compounds starting from ethylene tetraalkyl ether under triethylamine catalysis, followed by hydrolysis (Bacillus, D.; fishev, H.P. Helv.Chim. Acta.,1978,6l: 1784).

The synthetic route is simpler, the total yield is about 40%, but the initial raw materials are not supplied with industrial products, and the synthesis is needed, so that the industrial application value of the route is reduced.

In 1979 Pericas, a synthetic process for the preparation of squaric acid by cyclization of di-tert-butoxyacetylene was proposed. Di-tert-butoxyacetylene is cyclized, then NBS treated and converted to di-tert-butyl squarate under the action of palladium chloride catalyst, and finally hydrolyzed in trifluoroacetic acid to give squaric acid (Bou, A.; pericas, M.A.; serratosa.F.tetrahedron Lett.; 1982, 23:361).

The practical application of this synthetic route is limited because of the difficulty in preparing di-t-butoxyacetylene in large quantities.

In the process of preparing squaric acid by cycloaddition reaction, readily available vinyl ether is used as a raw material to obtain cyclobutanone, and then the cyclobutanone is subjected to bromination and hydrolysis to synthesize squaric acid, which is a valuable preparation method (Brady,W.T.;Waters,Q.H.J.Org.Chem.,1967,32:3703;Brady,W.T.Tetrahedron Lett.,1982,23:361;WO 97/37961).

However, the used small molecular vinyl ether has poor stability and is easy to polymerize, so that side reactions are more in cycloaddition reaction stage, and the selectivity is poor, so that the separation and purification processes of the later products bring about a plurality of disadvantages, and the industrialization value is reduced.

In addition, electrochemical methods (Silvestri,G.;Salvator,G.Gazz.Chim.Ital.,1972,102:18;Silvestri,G.;Salvator,G.Electrochim.Acta.,1978,23:413), using carbon monoxide as a raw material and a new approach for preparing squaric acid by a biological fermentation method have been developed in the study of the synthesis method of squaric acid (JP 0116 590 (1989)). The electrosynthesis method has the disadvantages that the product is difficult to purify and separate, the reaction stability is poor, and the product is difficult to repeat; the biological fermentation method needs long time and has low production efficiency.

From the above process routes for synthesizing squaric acid, various organic chemical methods provide main process routes for synthesizing squaric acid, and electrochemical and biochemical synthesis methods show potential value, but no ideal method for realizing large-scale synthesis of squaric acid exists at present.

Disclosure of Invention

Aiming at the problems existing in the existing method for synthesizing squaraine, the invention provides the method for preparing squaraine, which has the advantages of high yield, simplicity, high efficiency, good reaction selectivity, mild reaction condition and suitability for large-scale production.

In order to solve the technical problems, the invention is realized as follows:

a process for preparing squaric acid uses polyethylene glycol divinyl ether and dichloroacetyl chloride as initial raw materials, and includes cycloaddition reaction, bromination and hydrolysis reaction.

The preparation method of the squaric acid comprises the following steps:

(1) Under the action of alkali, performing cycloaddition reaction on polyethylene glycol divinyl ether and dichloroacetyl chloride to obtain chlorocyclobutanone connected with glycol ether chain;

(2) The chloro-cyclobutanone obtained above is subjected to bromination reaction to obtain bromo-substituted cyclobutanone reaction mixed solution;

(3) Directly heating the reaction mixture obtained in the step (2), and obtaining a crude product of a target product through hydrolysis reaction;

(4) Purifying the crude product of the target product obtained in the step (3), and recrystallizing to obtain the target product.

Further, the polyethylene glycol divinyl ether of the present invention has the following structure:

Further, in the step (1), the molar ratio of the polyethylene glycol divinyl ether, the dichloroacetyl chloride and the alkali is sequentially 1: 2-3: 2 to 3.

Further, the polyethylene glycol divinyl ether is diethylene glycol divinyl ether or triethylene glycol divinyl ether; the alkali is one of triethylamine, tri-n-propylamine or diisopropylethylamine; the solvent is one of dichloromethane, dichloroethane or chloroform; the reaction temperature is controlled at-10 to 50 ℃; the reaction time is 1-24 h.

Further, in the step (2), the mol ratio of the chlorinated cyclobutanone to the brominating reagent in the bromination reaction is 1:4-6.

Further, the brominating reagent is bromine; the reaction solvent is water, and the reaction temperature is controlled between 0 and 120 ℃; the reaction time is 1-24 h.

Further, in the step (3), the reaction mixture for preparing the bromine-substituted cyclobutanone is directly heated, and the reaction temperature is controlled at 50-100 ℃; the reaction time is 1-24 h.

Further, in the step (4), the solvent for recrystallization is deionized water.

The reaction principle of the invention is as follows:

The synthesis method has the advantages of readily available raw materials, good reaction selectivity, high purity, good yield, mild reaction conditions, simplicity, high efficiency, strong reaction stability and suitability for large-scale production.

Drawings

The invention is further described below with reference to the drawings and the detailed description. The scope of the present invention is not limited to the following description.

FIG. 1 shows the results of liquid chromatography detection of squaraine prepared in example 1.

FIG. 2 shows the results of liquid chromatography detection of squaraine prepared in example 2.

Detailed Description

The invention will be further described with reference to specific examples, but the invention is not limited to these examples.

Example 1

1) Diethylene glycol divinyl ether (79.1 g, 0.5 mol), dichloroacetyl chloride (161.1 g, 1.1 mol) and methylene chloride (500 ml) were added to a 2L three-port reaction flask, cooled to-5 ℃ with ice water, and tri-n-propylamine (157.6 g, 1.1 mol) was added dropwise, and the addition rate was controlled so that the temperature of the reaction solution did not exceed 10 ℃ and the dropping was completed for about 2 hours. The reaction was brought to room temperature and allowed to react for 8h, water (200 ml) was added, the organic layer was separated, washed with water (2×100 ml), dried, and concentrated to give the chlorocyclobutanone product (175 g, 92% yield). The purity was 97.3% by liquid chromatography.

2) In a 2L three-port reaction flask, the chloro-cyclobutanone (175 g, 0.45 mol) and water (400 ml) obtained in the above steps were added, and bromine (320 g, 2.0 mol) was slowly added dropwise under vigorous stirring, keeping the temperature at 0-10℃for about 2 hours; the reaction is carried out for 2 hours at room temperature; then the temperature was raised to 80℃and the reaction was carried out for 10 hours. Cooled to room temperature, left to stand for 10 hours, and filtered to give crude product of squaric acid (97 g, yield 95%). The purity was found to be 96.8% by liquid chromatography.

3) And recrystallizing the product prepared in the above process by deionized water to obtain white crystalline powder with a melting point of more than 300 ℃.

The purity of the liquid chromatography detection is 99.3 percent. ( Detection conditions: chromatograph: LC-10ATVp; chromatographic column: 250x4.6mm SS EXSII.ODS5 μm; column temperature: 25 ℃; detection wavelength: 254nm; a detector: SPD-10/AVp; mobile phase: CH ₃CN/H₂ o=7:3; flow rate: 0.5ml/min )

Example 2

1) To a 2L three-port reaction flask, triethylene glycol divinyl ether (101.2 g, 0.5 mol), dichloroacetyl chloride (176.9 g, 1.2 mol) and dichloroethane (500 ml) were added, cooled to-10℃with ice water, and triethylamine (131.6 g, 1.3 mol) was added dropwise, and the addition rate was controlled so that the temperature of the reaction solution did not exceed 10℃and the dropwise addition was completed for about 2 hours. The reaction was brought to room temperature for 10h, water (300 ml) was added, the organic layer was separated, washed with water (2×100 ml), dried, and concentrated to give the chlorocyclobutanone product (199.5 g, 94% yield). The purity was 98.1% by liquid chromatography.

2) In a 2L three-port reaction flask, the above steps of chloro cyclobutanone (199.5 g, 0.46 mol) and water (500 ml) were added, and bromine (352 g, 2.2 mol) was slowly added dropwise under vigorous stirring, keeping the temperature at 0-10℃for about 2 hours; the reaction is carried out for 3 hours at room temperature; then the temperature was raised to 90℃and the reaction was carried out for 7 hours. Cooled to room temperature, left to stand for 10 hours, and filtered to give crude product of squaric acid (105 g, yield 96%). The purity was found to be 96.2% by liquid chromatography.

3) And recrystallizing the product prepared in the above process by deionized water to obtain white crystalline powder with a melting point of more than 300 ℃ and a purity of 99.8% detected by liquid chromatography.

Example 3

1) To a 2L three-port reaction flask, triethylene glycol divinyl ether (101.2 g, 0.5 mol), dichloroacetyl chloride (191.6 g, 1.3 mol) and chloroform (400 ml) were added, cooled to-5℃with ice water, diisopropylethylamine (193.9 g, 1.5 mol) was added dropwise, and the temperature of the reaction mixture was controlled to not exceed 10℃by controlling the addition rate, and the dropping was completed for about 2 hours. The reaction was brought to room temperature and was reacted for 12h, water (300 ml) was added, the organic layer was separated, washed with water (2×100 ml), dried, and concentrated to give the chlorocyclobutanone product (203.7 g, yield 96%). The purity was 97.5% by liquid chromatography.

2) In a 2L three-port reaction flask, the above-obtained chlorocyclobutanone (203.7 g, 0.47 mol) and water (500 ml) were added, and bromine (368 g, 2.3 mol) was slowly added dropwise with vigorous stirring, keeping the temperature at 0-10℃for about 2 hours; the reaction is carried out for 3 hours at room temperature; then the temperature was raised to 80℃and the reaction was carried out for 8 hours. Cooled to room temperature, left to stand for 10 hours, and filtered to give crude product of squaric acid (100 g, yield 94%). The purity was 97.1% by liquid chromatography.

3) And recrystallizing the product prepared in the above process by deionized water to obtain white crystalline powder with a melting point of more than 300 ℃ and a purity of 99.5% detected by liquid chromatography.

Example 4

1) Diethylene glycol divinyl ether (237.3 g, 1.5 mol), dichloroacetyl chloride (515.9 g, 3.5 mol) and methylene chloride (1500 ml) were added to a 5L three-port reaction flask, cooled to-5℃with ice water, and triethylamine (404.8 g, 4.0 mol) was added dropwise thereto, and the addition rate was controlled so that the temperature of the reaction solution did not exceed 10℃and the dropwise addition was completed for about 3 hours. The reaction was brought to room temperature and was reacted for 10h, water (1000 ml) was added, the organic layer was separated, washed with water (2×500 ml), dried, and concentrated to give the chlorocyclobutanone product (535 g, yield 94%). The purity was found to be 96.5% by liquid chromatography.

2) In a 5L three-port reaction flask, the chloro-cyclobutanone (500 g, 1.26 mol) and water (1000 ml) obtained in the above steps were added, and bromine (880 g, 5.5 mol) was slowly added dropwise under vigorous stirring, keeping the temperature between 0 and 10℃for about 3 hours; the reaction is carried out for 2 hours at room temperature; then the temperature was raised to 90℃and the reaction was carried out for 5 hours. Cooled to room temperature, left to stand for 10 hours, and filtered to give crude product of squaric acid (275 g, yield 96%). The purity was 95.7% by liquid chromatography.

Example 5

1) To a 5L three-port reaction flask, triethylene glycol divinyl ether (404.6 g, 2.0 mol), dichloroacetyl chloride (479.0 g, 4.6 mol) and dichloroethane (1500 ml) were added, cooled to-5℃with ice water, and tri-n-propylamine (716.5 g, 5.0 mol) was added dropwise, and the addition rate was controlled so that the temperature of the reaction solution did not exceed 10℃and the dropwise was completed for about 4 hours. The reaction was brought to room temperature and was reacted for 12h, water (800 ml) was added, the organic layer was separated, washed with water (2×500 ml), dried, and concentrated to give the chlorocyclobutanone product (780 g, yield 92%). The purity was 98.2% by liquid chromatography.

2) In a 5L three-port reaction flask, the above steps of chloro cyclobutanone (600 g, 1.38 mol) and water (200 ml) were added, and bromine (1040 g, 6.5 mol) was slowly added dropwise under vigorous stirring, keeping the temperature at 0-10℃for about 5 hours; the reaction is carried out for 5 hours at room temperature; then the temperature was raised to 95℃and the reaction was carried out for 4 hours. Cooled to room temperature, left to stand for 10 hours, and filtered to give crude product of squaric acid (283 g, yield 90%). The purity was found to be 96.4% by liquid chromatography.

3) And recrystallizing the product prepared in the above process by deionized water to obtain white crystalline powder with a melting point of more than 300 ℃ and a purity of 99.4% detected by liquid chromatography.

Referring to FIG. 1, FIG. 1 shows the results of liquid chromatography detection of squaraine prepared in example 1.

Peak number	Component name	Retention time	Peak shape	Half width of peak	Area of	Height of (1)	Concentration of
										min		min	μVs	μV	％
1		3.859	BB	0.118	5218	749	0.1415
								2		4.407	BB	0.301	3661648	151642	99.3028
3		22.905	BB	0.348	20489	886	0.5557
								4	Totals to				3687355	153277	100.0000

Referring to FIG. 2, FIG. 2 shows the results of liquid chromatography detection of the squaric acid prepared in example 2.

Peak number	Component name	Retention time	Peak shape	Half width of peak	Area of	Height of (1)	Concentration of
									min		min	μVs	μV	％
1		3.866	BB	0.187	2230	209	0.0167
								2	4.402	BB	0.248	13302337	728312	99.8621
3		12.215	BB	0.214	1792	129	0.0135
								4	22.853	BB	0.343	14345	635	0.1077
5	Totals to				13320704	729285	100.0000

Although embodiments of the present invention have been shown and described, it will be understood by those skilled in the art that various changes, modifications, substitutions and alterations can be made therein without departing from the principles and spirit of the invention, the scope of which is defined in the appended claims and their equivalents.

Claims

1. The preparation method of the squaric acid is characterized by comprising the following steps of:

(1) 79.1 g, 0.5 mol of diethylene glycol divinyl ether, 161.1 g,1.1 mol of dichloroacetyl chloride and 500ml of dichloromethane are added into a 2L three-port reaction bottle, the temperature is reduced to-5 ℃ under the cooling of ice water, 157.6 g and 1.1 mol of tri-n-propylamine are added dropwise, and the adding speed is controlled so that the temperature of a reaction solution is not more than 10 ℃ and the dripping is finished for 2 hours; converting to room temperature, reacting for 8 hours, adding 200 ml of water, separating out an organic layer, washing 2x100 ml of water, drying and concentrating to obtain 175 g of chlorocyclobutanone product with the yield of 92%; the purity of the product is 97.3 percent through liquid chromatography detection;

(2) 175 g, 0.45 mol of chlorocyclobutanone and 400 ml of water obtained in the steps are added into a 2L three-port reaction bottle, 320 g of bromine and 2.0 mol of bromine are slowly added dropwise under intense stirring, and the temperature is kept between 0 and 10 ℃ for 2 hours; the reaction is carried out for 2 hours at room temperature; then heating to 80 ℃, reacting for 10 hours, cooling to room temperature, standing for 10 hours, and filtering to obtain 97 g of crude product squaric acid with the yield of 95%; the purity is 96.8% by liquid chromatography detection;

(3) And recrystallizing the product prepared in the above process by deionized water to obtain white crystalline powder with a melting point of more than 300 ℃.

2. The preparation method of the squaric acid is characterized by comprising the following steps of:

(1) 101.2 g, 0.5 mol of triethylene glycol divinyl ether, 191.6 g, 1.3 mol of dichloroacetyl chloride and 400 ml of chloroform are added into a 2L three-port reaction bottle, cooled to-5 ℃ under ice water cooling, 193.9 g and 1.5 mol of diisopropylethylamine are dropwise added, the temperature of the reaction solution is controlled to be not more than 10 ℃ by controlling the adding speed, the reaction is completed after 2 hours, the reaction is carried out at room temperature for 12 hours, 300 ml of water is added, an organic layer is separated, 2x100 ml of water is washed, and 203.7 g of chlorocyclobutanone product is obtained by drying and concentration, and the yield is 96%; the purity of the product is 97.5 percent through liquid chromatography detection;

(2) 203.7 g, 0.47 mol of chlorocyclobutanone and 500 ml of water obtained in the steps are added into a 2L three-port reaction bottle, 368 g and 2.3 mol of bromine are slowly added dropwise under intense stirring, and the temperature is kept between 0 and 10 ℃ for 2 hours; the reaction is carried out for 3 hours at room temperature; then heating to 80 ℃ and reacting for 8 hours; cooling to room temperature, standing for 10 hours, and filtering to obtain 100 g of crude product squaric acid with the yield of 94%; the purity of the product is 97.1 percent through liquid chromatography detection;

(3) And recrystallizing the product prepared in the above process by deionized water to obtain white crystalline powder with a melting point of more than 300 ℃ and a purity of 99.5% detected by liquid chromatography.

3. The preparation method of the squaric acid is characterized by comprising the following steps of:

(1) 237.3 g, 1.5 mol of diethylene glycol divinyl ether, 515.9 g, 3.5 mol of dichloroacetyl chloride and 1500 ml of dichloromethane are added into a 5L three-port reaction bottle, cooled to-5 ℃ under ice water cooling, 404.8 g and 4.0 mol of triethylamine are added dropwise, the adding speed is controlled, the temperature of the reaction solution is not more than 10 ℃ after 3 hours, the reaction is carried out for 10 hours, 1000 ml of water is added, an organic layer is separated, 2x500 ml of water is washed, dried and concentrated, 535 g of chlorocyclobutanone product is obtained, and the yield is 94%; the purity is 96.5% by liquid chromatography detection;

(2) 500 g, 1.26 mol of chlorocyclobutanone and 1000 ml of water obtained in the steps are added into a 5L three-port reaction bottle, 880 g of bromine and 5.5 mol of bromine are slowly added dropwise under intense stirring, and the temperature is kept between 0 and 10 ℃ for 3 hours; the reaction is carried out for 2 hours at room temperature; then heating to 90 ℃ and reacting for 5 hours; cooling to room temperature, standing for 10 hours, and filtering to obtain 275 g of crude product squaric acid with the yield of 96%; the purity is 95.7% through liquid chromatography detection;

4. The preparation method of the squaric acid is characterized by comprising the following steps of:

(1) Adding 404.6 g, 2.0 mol of triethylene glycol divinyl ether, 479.0 g, 4.6 mol of dichloroacetyl chloride and 1500 ml of dichloroethane into a 5L three-port reaction bottle, cooling to-5 ℃ under ice water cooling, dropwise adding 716.5 g and 5.0 mol of tri-n-propylamine, controlling the adding speed to ensure that the temperature of a reaction solution is not more than 10 ℃ after 4 hours, converting the reaction solution into room temperature, reacting for 12 hours, adding 800 ml of water, separating an organic layer, washing 2x500 ml with water, drying and concentrating to obtain 780 g of chlorinated cyclobutanone product, wherein the yield is 92%; the purity is 98.2% by liquid chromatography detection;

(2) 600 g, 1.38 mol of chlorocyclobutanone and 200ml of water obtained in the steps are added into a 5L three-port reaction bottle, 1040 g and 6.5 mol of bromine are slowly added dropwise under intense stirring, and the temperature is kept between 0 and 10 ℃ for 5 hours; the reaction is carried out for 5 hours at room temperature; then heating to 95 ℃, reacting for 4 hours, cooling to room temperature, standing for 10 hours, and filtering to obtain 283 g of crude product squaric acid with the yield of 90%; the purity is 96.4% by liquid chromatography detection;

(3) And recrystallizing the product prepared in the above process by deionized water to obtain white crystalline powder with a melting point of more than 300 ℃ and a purity of 99.4% detected by liquid chromatography.