A method for synthesizing squaric acid

Abstract

This invention relates to a method for synthesizing squaric acid, the method comprising the following steps: (1) reacting alkyl vinyl ether, trichloroacetyl chloride, and zinc to obtain 2,2-dichloro-3-alkoxycyclobutanone; (2) subjecting 2,2-dichloro-3-alkoxycyclobutanone to chlorination with chlorine to obtain 2,2,4,4-tetrachloro-3-alkoxycyclobutanone; (3) subjecting 2,2,4,4-tetrachloro-3-alkoxycyclobutanone to elimination reaction with a base to obtain 2,4,4-trichloro-3-alkoxycyclobuten-1-one; and (4) subjecting 2,4,4-trichloro-3-alkoxycyclobuten-1-one to hydrolysis to obtain the squaric acid. The synthesis method provided by this invention avoids the use of the prohibited raw material perchloro-1,3-butadiene and has lower energy consumption, meeting the needs of green and clean production.

Description

TECHNICAL FIELD

[0001] The present application relates to the technical field of organic synthesis, and particularly relates to a synthesis method of squaric acid. BACKGROUND

[0002] Squaric acid (3,4-dihydroxy-3-cyclobutene-1,2-dione) is an important intermediate for the synthesis of medicines, pesticides, photosensitive materials and dyes. Organic electrode materials containing squaric acid can be used as positive active materials or negative active materials. When used as positive and negative electrode active materials, respectively, and in all-organic batteries, excellent electrochemical performance can be obtained, which is conducive to large-scale application.

[0003] There are several synthesis routes for squaric acid at present. CN120518450A and CN119735493A disclose a method in which perchloro-1,3-butadiene is used as a raw material to react with morpholine, then cyclization and rearrangement are carried out in a buffer solution, and finally hydrolysis is carried out under acidic conditions. This route needs to use the limited raw material perchloro-1,3-butadiene, which has been prohibited from being used as a raw material in industrial production.

[0004] CN115710169A discloses a method for synthesizing a cyclobutanone intermediate product using polyethylene glycol divinyl ether and dichloroacetyl chloride, and then directly hydrolyzing the intermediate product to obtain squaric acid. However, the hydrolysis product is a mixture of hydrogen chloride and hydrogen bromide aqueous solution, which cannot be separated and is not conducive to environmental protection.

[0005] CN1269778A discloses a method for synthesizing squaric acid by reacting a vinyl ether with a haloacetyl halide, halogenating, removing hydrogen halide, and hydrolyzing. However, in the first step of the method, N-methylmorpholine is added dropwise into a mixed solution of alkyl vinyl ether and chloroacetyl chloride. However, N-methylmorpholine and chloroacetyl chloride can also generate N-methyl-N-chloroacetyl morpholine, which reduces the yield and concentration of the target product 2-chloro-3-alkyl cyclobutanone. In addition, chlorides are generated after the reaction of alkyl vinyl ether and chloroacetyl chloride. The reaction is promoted in the forward direction by the reaction of N-methylmorpholine and hydrogen chloride. However, the reaction product is a solid, which needs to be washed with water, layered, and the organic layer is dehydrated, etc. The post-processing steps are complex.

[0006] Therefore, it is a technical problem to be solved in the field to provide a squaric acid preparation method that avoids using the banned raw material perchloro-1,3-butadiene and meets the needs of clean production. SUMMARY

[0007] To solve the above technical problems, the present application provides a synthesis method of squaric acid. The synthesis method provided by the present application can avoid using the banned raw material perchloro-1,3-butadiene, has low energy consumption, and can meet the needs of green and clean production.

[0008] To achieve this objective, the present invention adopts the following technical solution:

[0009] This invention provides a method for synthesizing squaric acid, the method comprising the following steps:

[0010] (1) Alkyl vinyl ether, trichloroacetyl chloride and zinc are reacted to give 2,2-dichloro-3-alkoxycyclobutanone;

[0011] (2) The 2,2-dichloro-3-alkoxycyclobutanone from step (1) undergoes a chlorination reaction with chlorine to obtain 2,2,4,4-tetrachloro-3-alkoxycyclobutanone;

[0012] (3) The 2,2,4,4-tetrachloro-3-alkoxycyclobutanone from step (2) undergoes an elimination reaction with a base to obtain 2,4,4-trichloro-3-alkoxycyclobuten-1-one;

[0013] (4) The 2,4,4-trichloro-3-alkoxycyclobuten-1-one from step (3) is hydrolyzed to obtain the squaric acid.

[0014] The reaction formula of this invention is as follows:

[0015] ;

[0016] Where R represents a straight-chain or branched alkyl group.

[0017] This invention prepares dichlorovinyl ketone by reacting trichloroacetyl chloride with zinc powder, and then produces 2,2-dichloro-3-alkoxycyclobutanone intermediate by reacting alkyl vinyl ether with dichlorovinyl ketone. This reaction can be prepared in a one-pot process, and then squaric acid is synthesized through chlorination, elimination and hydrolysis steps. This technical route avoids the use of raw materials that have been banned, and the reaction conforms to the 2+2 enone cyclization reaction mechanism.

[0018] Preferably, the alkyl vinyl ether in step (1) includes C1-C10 (e.g., C1, C2, C4, C6, C8, C10, etc.) straight-chain or branched alkyl vinyl ethers.

[0019] Preferably, the alkyl vinyl ether has been pre-dehydrated to a moisture content of ≤100ppm.

[0020] Preferably, the molar ratio of the alkyl vinyl ether to trichloroacetyl chloride in step (1) is 1:(1.05~1.3) (for example, it can be 1:1.05, 1:1, 1:2, 1:3, etc.), and the molar ratio of the alkyl vinyl ether to zinc is 1:(0.8~1) (for example, it can be 1:0.8, 1:0.85, 1:0.9, 1:0.95, 1:1, etc.).

[0021] Preferably, the temperature of the reaction in step (1) is -5~30℃ (for example, it can be -5℃, 0℃, 5℃, 10℃, 20℃, 30℃, etc.), the reaction time is 8~14h (for example, it can be 8h, 10h, 12h, 14h, etc.), and the reaction is carried out under ultraviolet light irradiation.

[0022] In this invention, irradiation with ultraviolet light can promote the forward reaction, accelerate the cyclization reaction, and improve the yield and purity of the reaction.

[0023] Preferably, the alkyl vinyl ether in step (1) includes any one or a combination of at least two of ethyl vinyl ether, n-propyl vinyl ether, isopropyl vinyl ether, n-butyl vinyl ether or isobutyl vinyl ether.

[0024] Preferably, the reaction in step (1) is carried out in the presence of a solvent. The reaction specifically includes: mixing alkyl vinyl ether and solvent, then cooling, adding a solution of trichloroacetyl chloride and solvent under controlled temperature, and adding zinc, and then continuing the reaction. After purification, 2,2-dichloro-3-alkoxycyclobutanone is obtained.

[0025] Preferably, the solvents are all methyl tert-butyl ethers.

[0026] Preferably, all solvents are pre-dehydrated, with a moisture content ≤100ppm.

[0027] Preferably, the cooling temperature is -5~5℃ (for example, it can be -5℃, -2℃, 0℃, 2℃, 5℃, etc.).

[0028] Preferably, the temperature for temperature control is 0~10℃ (e.g., 0℃, 2℃, 5℃, 8℃, 10℃, etc.), and the time for temperature control is 8~12h (e.g., 8h, 9h, 10h, 11h, 12h, etc.).

[0029] Preferably, the temperature for the continued reaction is 10~30℃ (e.g., 10℃, 15℃, 20℃, 25℃, 30℃, etc.), and the duration of the continued reaction is 0.5~2h (e.g., 0.5h, 1h, 1.5h, 2h, etc.).

[0030] Preferably, the purification includes: filtering the reaction system and distilling the resulting liquid under reduced pressure to obtain 2,2-dichloro-3-alkoxycyclobutanone.

[0031] Preferably, the vacuum distillation includes first removing the solvent by distillation at 50~70℃ (e.g., 50℃, 55℃, 60℃, 65℃, 70℃, etc.) and a vacuum degree of -0.01~-0.09MPa (e.g., -0.01MPa, -0.04MPa, -0.06MPa, -0.08MPa, -0.09MPa, etc.), and then distilling at 70~85℃ (e.g., 70℃, 75℃, 80℃, 85℃, etc.) and a vacuum degree of 0~5mbar (e.g., 0.1mbar, 0.5mbar, 1mbar, 2mbar, 3mbar, 5mbar, etc.) to obtain 2,2-dichloro-3-alkoxycyclobutanone.

[0032] Preferably, the molar ratio of 2,2-dichloro-3-alkoxycyclobutanone and chlorine in step (2) is 1:(2.1~3) (for example, it can be 1:2.1, 1:2.25, 1:2.5, 1:2.75, 1:3, etc.).

[0033] Preferably, the temperature of the chlorination reaction in step (2) is 0~10℃ (for example, it can be 0℃, 2℃, 5℃, 8℃, 10℃, etc.), and the time of the chlorination reaction is 8~16h (for example, it can be 8h, 10h, 12h, 14h, 16h, etc.).

[0034] Preferably, the chlorination reaction in step (2) is carried out in the presence of a base. The chlorination reaction specifically includes: passing chlorine gas into 2,2-dichloro-3-alkoxycyclobutanone, adding a base at the same time, and reacting to obtain 2,2,4,4-tetrachloro-3-alkoxycyclobutanone.

[0035] Preferably, the base comprises any one or a combination of at least two of triethylamine, pyridine, or N-methylmorpholine.

[0036] Preferably, the molar ratio of chlorine to alkali is 1:(1~1.1) (for example, it can be 1:1, 1:1.02, 1:1.05, 1:1.08, 1:1, etc.).

[0037] Preferably, the alkali in step (3) includes any one or a combination of at least two of sodium ethoxide, potassium ethoxide, or sodium tert-butoxide.

[0038] Preferably, the molar ratio of 2,2,4,4-tetrachloro-3-alkoxycyclobutanone to the base is 1:1 to 1.25 (e.g., it can be 1:1, 1:1.05, 1:1.1, 1:1.15, 1:1.2, 1:1.25, etc.).

[0039] Preferably, the alkali in step (3) is added in the form of an alkali solution, the concentration of which is 5wt% to 20wt% (for example, it can be 5wt%, 8wt%, 10wt%, 15wt%, 20wt%, etc.).

[0040] Preferably, the solvent in the alkaline solution includes ethanol.

[0041] Preferably, the temperature of the elimination reaction in step (3) is 30~50℃ (e.g., 30℃, 35℃, 40℃, 45℃, 50℃, etc.), and the time of the elimination reaction is 6~12h (e.g., 6h, 8h, 10h, 12h, etc.).

[0042] Preferably, step (3) further includes a post-treatment step of filtering the reaction system and evaporating the solvent after the elimination reaction.

[0043] Preferably, the hydrolysis reaction in step (4) is carried out in the presence of an acid solution, the acid including sulfuric acid and / or hydrochloric acid, and the concentration of the acid solution is 10wt% to 30wt% (e.g., 10wt%, 15wt%, 20wt%, 25wt%, 30wt%, etc.).

[0044] Preferably, the temperature of the hydrolysis reaction in step (4) is 90~115℃ (for example, it can be 90℃, 100℃, 110℃, 115℃, etc.), and the time of the hydrolysis reaction is 8~24h (for example, it can be 8h, 16h, 20h, 24h, etc.).

[0045] Preferably, the reaction in step (4) further includes post-processing steps such as cooling and filtration.

[0046] Compared with the prior art, the present invention has at least the following beneficial effects:

[0047] 1. This invention uses alkyl vinyl ether, a raw material not restricted by regulations, to react with dichloroethylene ketone, which is produced by the reaction of trichloroacetyl chloride and zinc powder, to generate cyclobutanone intermediate, thereby generating squaric acid. This overcomes the problem of raw material limitations in the current perchloro-1,3-butadiene route. All raw materials used in this invention are industrial grade and can be used for large-scale industrial production.

[0048] 2. This invention uses 2+2 enone cyclization to synthesize cyclobutanone intermediates. Compared with the traditional reaction using perchloro-1,3-butadiene and morpholine, it does not require heating, saving the energy required for heating and achieving clean production. Attached Figure Description

[0049] Figure 1 This is the HPLC chromatogram of the squaric acid obtained in Example 1. Detailed Implementation

[0050] To facilitate understanding of the present invention, the following embodiments are provided. Those skilled in the art should understand that these embodiments are merely illustrative and should not be construed as limiting the scope of the invention.

[0051] The activated zinc powder used in the following examples was purchased from Merck Reagent Zinc Powder.

[0052] Example 1

[0053] This embodiment provides a method for preparing squaric acid, including the following steps:

[0054] 1. Preparation: In a dry reaction flask, add 72.1 g (1 mol) of ethyl vinyl ether and 500 mL of methyl tert-butyl ether, stir under nitrogen protection and cool to 0°C;

[0055] 2. Dropping and Addition: While maintaining vigorous stirring, slowly add a solution of trichloroacetyl chloride in methyl tert-butyl ether (199.5 g, 1.1 mol of trichloroacetyl chloride dissolved in 100 mL of methyl tert-butyl ether) dropwise to the reaction flask from step 1 through a dropping funnel; simultaneously, carefully add 52.3 g (0.8 mol) of activated zinc powder in multiple batches to the reaction flask under nitrogen purging, controlling the reaction time to 12 hours, maintaining the reaction temperature at 10℃, and irradiating the reaction with 254 nm ultraviolet light;

[0056] 3. Reaction: After the addition is complete, remove the ice bath and allow the reaction temperature to rise to 25°C to continue for 1 hour;

[0057] 4. Purification: Filter, remove the solvent methyl tert-butyl ether by rotary evaporation under vacuum of -0.05 MPa at 60℃, and distill the crude product under vacuum of 2 mbar at 80℃ to obtain 135.2 g of pure 2,2-dichloro-3-ethoxycyclobutanone (purity 95%, yield 70.2%).

[0058] 5. Halogenation: 135.2 g (95% purity, 0.70 mol) of the prepared 2,2-dichloro-3-ethoxycyclobutanone was passed through 42 L (1.88 mol) of chlorine gas at 5 °C for 8 hours. At the same time, 189.75 g (1.88 mol) of triethylamine was added dropwise to remove the hydrogen chloride generated in the reaction. After the reaction was completed, the triethylamine hydrochloride was filtered out to obtain 150.0 g of 2,2,4,4-tetrachloro-3-ethoxycyclobutanone.

[0059] 6. Elimination reaction: 150.0 g of 2,2,4,4-tetrachloro-3-ethoxycyclobutanone (93% purity, 0.55 mol) was added to 408.3 g of 10 wt% sodium ethoxide solution (0.68 mol sodium ethoxide) to carry out the elimination reaction. After the reaction was completed, the mixture was filtered and the solvent ethanol was evaporated to obtain 131.4 g of 2,4,4-trichloro-3-ethoxycyclobuten-1-one.

[0060] 7. Hydrolysis reaction: 131.4g of 2,4,4-trichloro-3-ethoxycyclobuten-1-one (90% purity, 0.55mol) was added to 300g of 30wt% sulfuric acid, and the mixture was heated under reflux at 110℃ for 12 hours. During the reaction, squaric acid crystals continuously precipitated out. After the hydrolysis reaction was completed, the mixture was allowed to stand and cool to 25℃, and after filtration, 55.8g of squaric acid product was obtained (98.0% purity, 47.9% yield).

[0061] The HPLC detection chromatogram of squaric acid is shown below. Figure 1 As shown, the detection methods include:

[0062] Chromatographic column: C18 reverse-phase column (10cm);

[0063] Flow rate: 0.7 mL / min;

[0064] Injection volume: 10 μL;

[0065] Column oven: 25℃;

[0066] Detector: Ultraviolet detector;

[0067] Wavelength: 210nm;

[0068] Mobile phases: Phase A is water, and Phase B is acetonitrile;

[0069] The elution procedure is shown in Table 1 below:

[0070] Table 1

[0071]

[0072] The NMR data for squaric acid are as follows:

[0073] ¹H NMR (DMSO-d6): δ 13.7 ppm.

[0074] Carbon NMR (¹³C-NMR DMSO-d6): δ 189.9 ppm.

[0075] Example 2

[0076] This embodiment provides a method for preparing squaric acid, including the following steps:

[0077] 1. Preparation: In a dry reaction flask, add 101.2 g (1 mol) of isobutyl vinyl ether and 500 mL of methyl tert-butyl ether, stir under nitrogen protection and cool to 0 °C;

[0078] 2. Dropping and Addition: While maintaining vigorous stirring, slowly add a solution of trichloroacetyl chloride in methyl tert-butyl ether (199.5 g, 1.1 mol of trichloroacetyl chloride dissolved in 100 mL of methyl tert-butyl ether) dropwise to the reaction flask from step 1 through a dropping funnel; simultaneously, carefully add 52.3 g (0.8 mol) of activated zinc powder in multiple batches to the reaction flask under nitrogen purging; control the reaction time for 12 hours, maintain the reaction temperature at 10℃, and irradiate the reaction with 254 nm ultraviolet light;

[0079] 3. Reaction: After the addition is complete, remove the ice bath and allow the reaction temperature to rise to 25°C to continue for 2 hours;

[0080] 4. Purification: Filter, remove the solvent methyl tert-butyl ether by rotary evaporation under reduced pressure of -0.05 MPa at 60℃; the crude product is then distilled under reduced pressure of 3 mbar at 80℃ to obtain 162.3 g of pure 2,2-dichloro-3-isobutoxycyclobutanone (purity 98.0%, yield 75.4%).

[0081] 5. Halogenation: 162.3 g of the prepared 2,2-dichloro-3-isobutoxycyclobutanone (purity 98.0%, 0.75 mol) was passed through 43.7 L (1.95 mol) of chlorine gas at 5 °C for 8 hours. At the same time, 197.3 g (1.95 mol) of triethylamine was added dropwise to remove the hydrogen chloride generated in the reaction. After the reaction was completed, the triethylamine hydrochloride was filtered out to obtain 167.1 g of 2,2,4,4-tetrachloro-3-isobutoxycyclobutanone.

[0082] 6. Elimination reaction: 167.1 g of 2,2,4,4-tetrachloro-3-isobutoxycyclobutanone (purity 97.2%, 0.59 mol) was added to 428.7 g of 10 wt% sodium ethoxide solution (0.63 mol sodium ethoxide) to carry out the elimination reaction. After the reaction was completed, the mixture was filtered and the solvent ethanol was evaporated to obtain 142.7 g of 2,4,4-trichloro-3-isobutoxycyclobuten-1-one.

[0083] 7. Hydrolysis reaction: 137.1g of 2,4,4-trichloro-3-isobutoxycyclobuten-1-one (purity 99.5%, 0.58mol) was added to 300g of 30wt% sulfuric acid, and the mixture was heated under reflux at 110℃ for 12 hours. During the reaction, squaric acid crystals continuously precipitated out. After the hydrolysis reaction was completed, the mixture was allowed to stand and cool to 25℃, and after filtration, 65.4g of squaric acid product was obtained (purity 98.5%, yield 56.5%).

[0084] Example 3

[0085] This embodiment provides a method for preparing squaric acid, including the following steps:

[0086] 1. Preparation: In a dry reaction flask, add 101.2 g (1 mol) of isobutyl vinyl ether and 500 mL of methyl tert-butyl ether, stir under nitrogen protection and cool to 0 °C;

[0087] 2. Dropping and Addition: While maintaining vigorous stirring, slowly add a solution of trichloroacetyl chloride in methyl tert-butyl ether (199.5 g, 1.1 mol of trichloroacetyl chloride dissolved in 100 mL of methyl tert-butyl ether) dropwise through a dropping funnel; simultaneously, carefully add 52.3 g (0.8 mol) of activated zinc powder in multiple batches to the reaction flask under nitrogen purging; control the reaction time for 12 hours, maintain the reaction temperature at 3℃, and irradiate the reaction with 254 nm ultraviolet light;

[0088] 3. Reaction: After the addition is complete, remove the ice bath and allow the reaction temperature to rise to 25°C to continue for 1 hour;

[0089] 4. Purification: Filter, remove the solvent methyl tert-butyl ether by rotary evaporation under reduced pressure of -0.05 MPa at 60℃; pass the crude product through a vacuum of 0.2 MPa at 80℃ to obtain 190.1 g of pure 2,2-dichloro-3-isobutoxycyclobutanone (purity 99.2%, yield 89.4%).

[0090] 5. Halogenation: 190.1 g of the prepared 2,2-dichloro-3-isobutoxycyclobutanone (purity 99.2%, 0.89 mol) was passed through 45.7 L (1.95 mol) of chlorine gas at 5 °C for 8 hours. At the same time, 202.3 g (2 mol) of triethylamine was added dropwise to remove the hydrogen chloride generated in the reaction. After the reaction was completed, the triethylamine hydrochloride was filtered out to obtain 220.6 g of 2,2,4,4-tetrachloro-3-isobutoxycyclobutanone.

[0091] 6. Elimination reaction: 220.6 g of 2,2,4,4-tetrachloro-3-isobutoxycyclobutanone (purity 99.0%, 0.8 mol) was added to 520 g of 10 wt% sodium ethoxide solution (sodium ethoxide 0.8 mol) to carry out the elimination reaction. After the reaction was completed, the mixture was filtered and the solvent ethanol was evaporated to obtain 186.5 g of 2,4,4-trichloro-3-isobutoxycyclobuten-1-one.

[0092] 7. Hydrolysis reaction: 186.5g of 2,4,4-trichloro-3-isobutoxycyclobuten-1-one (purity 99.3%, 0.78mol) was added to 300g of 30wt% sulfuric acid, and the mixture was heated under reflux at 110℃ for 12 hours. During the reaction, squaric acid crystals continuously precipitated out. After the hydrolysis reaction was completed, the mixture was allowed to stand and cool to 25℃, and after filtration, 87.9g of squaric acid product was obtained (purity 99.1%, yield 76.4%).

[0093] Example 4

[0094] This embodiment provides a method for preparing squaric acid, which differs from Example 3 only in that ultraviolet light irradiation is not used in step 2. The specific steps are as follows:

[0095] 1. Preparation: In a dry reaction flask, add 101.2 g (1 mol) of isobutyl vinyl ether and 500 mL of methyl tert-butyl ether, stir under nitrogen protection and cool to 0 °C;

[0096] 2. Dropping and Addition: While maintaining vigorous stirring, slowly add a solution of trichloroacetyl chloride in methyl tert-butyl ether (199.5 g, 1.1 mol of trichloroacetyl chloride dissolved in 100 mL of methyl tert-butyl ether) dropwise through a dropping funnel; simultaneously, carefully add 52.3 g (0.8 mol) of activated zinc powder in multiple batches to the reaction flask under nitrogen purging; control the reaction time for 12 hours and the reaction temperature at 5℃; do not use 254 nm ultraviolet light irradiation during the reaction.

[0097] 3. Reaction: After the addition is complete, remove the ice bath and allow the reaction temperature to rise to 25°C to continue for 1 hour;

[0098] 4. Purification: Filter, remove the solvent methyl tert-butyl ether by rotary evaporation under reduced pressure of -0.05 MPa at 60℃; pass the crude product through a vacuum of 0.2 MPa at 80℃ to obtain 128.7 g of pure 2,2-dichloro-3-isobutoxycyclobutanone (purity 80.5%, yield 49.1%).

[0099] 5. Halogenation: 128.7 g of the prepared 2,2-dichloro-3-isobutoxycyclobutanone (purity 80.5%, 0.49 mol) was passed through 27.4 L (1.22 mol) of chlorine gas at 5 °C for 8 hours. At the same time, 131.5 g (1.3 mol) of triethylamine was added dropwise to remove the hydrogen chloride generated in the reaction. After the reaction was completed, the triethylamine hydrochloride was filtered out to obtain 140.5 g of 2,2,4,4-tetrachloro-3-isobutoxycyclobutanone.

[0100] 6. Elimination reaction: 140.5 g of 2,2,4,4-tetrachloro-3-isobutoxycyclobutanone (purity 85.5%, 0.44 mol) was added to 306.2 g of 10 wt% sodium ethoxide solution (0.45 mol sodium ethoxide) to carry out the elimination reaction. After the reaction was completed, the mixture was filtered and the solvent ethanol was evaporated to obtain 98.8 g of 2,4,4-trichloro-3-isobutoxycyclobuten-1-one.

[0101] 7. Hydrolysis reaction: 98.8g of 2,4,4-trichloro-3-isobutoxycyclobuten-1-one (purity 96.2%, 0.4mol) was added to 300g of 30wt% sulfuric acid and heated to reflux at 110℃ for 12 hours. During the reaction, squaric acid crystals continuously precipitated out. After the hydrolysis reaction was completed, the mixture was allowed to stand and cool to 25℃. After filtration, 39.5g of squaric acid product was obtained (purity 96.1%, yield 33.3%).

[0102] Example 5

[0103] This embodiment provides a method for preparing squaric acid, including the following steps:

[0104] 1. Preparation: In a dry reaction flask, add 86.1 g (1 mol) of n-propyl vinyl ether and 500 mL of methyl tert-butyl ether, stir under nitrogen protection and cool to 0°C;

[0105] 2. Dropping and Addition: While maintaining vigorous stirring, slowly add a solution of trichloroacetyl chloride in methyl tert-butyl ether (199.5 g, 1.1 mol of trichloroacetyl chloride dissolved in 100 mL of methyl tert-butyl ether) dropwise through a dropping funnel; simultaneously, carefully add 52.3 g (0.8 mol) of activated zinc powder in multiple batches to the reaction flask under nitrogen purging; control the reaction time for 8 hours, maintain the reaction temperature at 5℃, and irradiate the reaction with 254 nm ultraviolet light;

[0106] 3. Reaction: After the addition is complete, remove the ice bath and allow the reaction temperature to rise to 25°C to continue for 1 hour;

[0107] 4. Purification: Filter, remove the solvent methyl tert-butyl ether by rotary evaporation under reduced pressure of -0.05 MPa at 60℃; pass the crude product through a vacuum of 0.2 MPa at 80℃ to obtain 165.9 g of pure 2,2-dichloro-3-n-propoxycyclobutanone (purity 99.3%, yield 83.6%).

[0108] 5. Halogenation: 165.9 g of the prepared 2,2-dichloro-3-n-propoxycyclobutanone (purity 99.3%, 0.84 mol) was passed through 47.0 L (2.1 mol) of chlorine gas at 5 °C for 8 hours. At the same time, 212.5 g (2.1 mol) of triethylamine was added dropwise to remove the hydrogen chloride generated in the reaction. After the reaction was completed, the triethylamine hydrochloride was filtered out to obtain 203.9 g of 2,2,4,4-tetrachloro-3-n-propoxycyclobutanone.

[0109] 6. Elimination reaction: 203.9 g of 2,2,4,4-tetrachloro-3-n-propoxycyclobutanone (purity 99.1%, 0.76 mol) was added to 520 g of 10 wt% sodium ethoxide solution (0.8 mol sodium ethoxide) to carry out the elimination reaction. After the reaction was completed, the mixture was filtered and the solvent ethanol was evaporated to obtain 166.9 g of 2,4,4-trichloro-3-n-propoxycyclobuten-1-one.

[0110] 7. Hydrolysis reaction: 166.9g of 2,4,4-trichloro-3-n-propoxycyclobuten-1-one (purity 99.0%, 0.72mol) was added to 300g of 30wt% sulfuric acid, and the mixture was heated under reflux at 110℃ for 12 hours. During the reaction, squaric acid crystals continuously precipitated out. After the hydrolysis reaction was completed, the mixture was allowed to stand and cool to 25℃, and after filtration, 81.6g of squaric acid product was obtained (purity 98.3%, yield 70.4%).

[0111] Example 6

[0112] This embodiment provides a method for preparing squaric acid, including the following steps:

[0113] 1. Preparation: In a dry reaction flask, add 86.1 g (1 mol) of isopropyl vinyl ether and 500 mL of methyl tert-butyl ether, stir under nitrogen protection and cool to 0 °C;

[0114] 2. Dropping and Addition: While maintaining vigorous stirring, slowly add a solution of trichloroacetyl chloride in methyl tert-butyl ether (199.5 g, 1.1 mol of trichloroacetyl chloride dissolved in 100 mL of methyl tert-butyl ether) dropwise through a dropping funnel; simultaneously, carefully add 52.3 g (0.8 mol) of activated zinc powder in multiple batches to the reaction flask under nitrogen purging; control the reaction time for 8 hours, maintain the reaction temperature at 5℃, and irradiate the reaction with 254 nm ultraviolet light;

[0115] 3. Reaction: After the addition is complete, remove the ice bath and allow the reaction temperature to rise to 25°C to continue for 1 hour;

[0116] 4. Purification: Filter, remove the solvent methyl tert-butyl ether by rotary evaporation under reduced pressure of -0.05 MPa at 60℃; pass the crude product through a vacuum of 0.2 mbar at 80℃ to obtain 165.6 g of pure 2,2-dichloro-3-isopropoxycyclobutanone (purity 99.0%, yield 83.2%).

[0117] 5. Halogenation: 165.6 g of the prepared 2,2-dichloro-3-isopropoxycyclobutanone (purity 99.2%, 0.83 mol) was passed through 40.0 L (1.76 mol) of chlorine gas at 5 °C for 8 hours. At the same time, 182.2 g (1.8 mol) of triethylamine was added dropwise to remove the hydrogen chloride generated in the reaction. After the reaction was completed, the triethylamine hydrochloride was filtered out to obtain 201.8 g of 2,2,4,4-tetrachloro-3-isopropoxycyclobutanone.

[0118] 6. Elimination reaction: 201.8 g of 2,2,4,4-tetrachloro-3-isopropoxycyclobutanone (purity 98.8%, 0.75 mol) was added to 530 g of 10 wt% sodium ethoxide solution (sodium ethoxide 0.78 mol) to carry out the elimination reaction. After the reaction was completed, the mixture was filtered and the solvent ethanol was evaporated to obtain 172.9 g of 2,4,4-trichloro-3-isopropoxycyclobuten-1-one.

[0119] 7. Hydrolysis reaction: 172.9g of 2,4,4-trichloro-3-isopropoxycyclobuten-1-one (purity 98.2%, 0.74mol) was added to 300g of 30wt% sulfuric acid and heated to reflux at 110℃ for 12 hours. During the reaction, squaric acid crystals continuously precipitated out. After the hydrolysis reaction was completed, the mixture was allowed to stand and cool to 25℃. After filtration, 83.9g of squaric acid product was obtained (purity 98.5%, yield 72.5%).

[0120] Table 2 summarizes the yield and purity data of 2,2-dichloro-3-alkoxycyclobutanone intermediate and squaric acid in the preparation method of squaric acid provided in the above embodiments.

[0121] Table 2

[0122]

[0123] The test results show that the route provided by Examples 1-6 of this invention, which prepares 2,2-dichloro-3-alkoxycyclobutanone intermediates through the reaction of alkyl vinyl ethers, trichloroacetyl chloride and zinc, and then prepares squaric acid through chlorination, elimination and hydrolysis, not only avoids the limitation of using the raw material perchloro-1,3-butadiene, but also has high yield and purity.

[0124] A comparison of Examples 3 and 4 shows that ultraviolet light irradiation can promote the cyclization of 2+2 enones, which is beneficial to improving the yield and purity of the reaction.

[0125] A comparison of Examples 3 and 1-2 shows that the synthesis temperature in the first step should be controlled at around 5°C for the best yield. Using isobutyl vinyl ether as the starting material resulted in the highest yield and purity under the same conditions.

[0126] The applicant declares that the above description is only a specific embodiment of the present invention, but the protection scope of the present invention is not limited thereto. Those skilled in the art should understand that any changes or substitutions that can be easily conceived by those skilled in the art within the technical scope disclosed in the present invention fall within the protection and disclosure scope of the present invention.

Claims

1. A method for synthesizing squaric acid, characterized in that, The synthesis method includes the following steps: (1) Alkyl vinyl ether, trichloroacetyl chloride and zinc are reacted to give 2,2-dichloro-3-alkoxycyclobutanone, the reaction being carried out under ultraviolet light irradiation; (2) The 2,2-dichloro-3-alkoxycyclobutanone from step (1) undergoes a chlorination reaction with chlorine to obtain 2,2,4,4-tetrachloro-3-alkoxycyclobutanone; (3) The 2,2,4,4-tetrachloro-3-alkoxycyclobutanone from step (2) undergoes an elimination reaction with a base to obtain 2,4,4-trichloro-3-alkoxycyclobuten-1-one; (4) The 2,4,4-trichloro-3-alkoxycyclobuten-1-one from step (3) is hydrolyzed to obtain the squaric acid.

2. The synthesis method according to claim 1, characterized in that, The alkyl vinyl ether in step (1) includes C1-C10 straight-chain or branched alkyl vinyl ethers; In step (1), the molar ratio of the alkyl vinyl ether to trichloroacetyl chloride is 1:(1.05~1.3), and the molar ratio of the alkyl vinyl ether to zinc is 1:(0.8~1). The reaction temperature in step (1) is -5~30℃, and the reaction time is 8~14h.

3. The synthesis method according to claim 2, characterized in that, The alkyl vinyl ether in step (1) includes any one or a combination of at least two of ethyl vinyl ether, n-propyl vinyl ether, isopropyl vinyl ether, n-butyl vinyl ether or isobutyl vinyl ether.

4. The synthesis method according to claim 1, characterized in that, The reaction in step (1) is carried out in the presence of a solvent. The reaction specifically includes: mixing alkyl vinyl ether and solvent, then cooling, adding a solution of trichloroacetyl chloride and solvent under controlled temperature, and adding zinc, and then continuing the reaction. After purification, 2,2-dichloro-3-alkoxycyclobutanone is obtained.

5. The synthesis method according to claim 4, characterized in that, All solvents are methyl tert-butyl ethers; The cooling temperature is -5~5℃; the temperature control temperature is 0~10℃, and the temperature control time is 8~12h; the temperature for continued reaction is 10~30℃, and the continued reaction time is 0.5~2h.

6. The synthesis method according to claim 4, characterized in that, The purification process includes: filtering the reaction system and distilling the resulting liquid under reduced pressure to obtain 2,2-dichloro-3-alkoxycyclobutanone; The vacuum distillation involves first removing the solvent by distillation at 50-70°C and a vacuum of -0.01 to -0.09 MPa, and then distilling at 70-85°C and a vacuum of 0-5 mbar to obtain 2,2-dichloro-3-alkoxycyclobutanone.

7. The synthesis method according to claim 1, characterized in that, The molar ratio of 2,2-dichloro-3-alkoxycyclobutanone and chlorine in step (2) is 1:(2.1~3). The chlorination reaction in step (2) is carried out at a temperature of 0~10℃ and for a time of 8~16h.

8. The synthesis method according to claim 1, characterized in that, The chlorination reaction in step (2) is carried out in the presence of a base. The chlorination reaction specifically includes: passing chlorine gas into 2,2-dichloro-3-alkoxycyclobutanone, adding a base at the same time, and reacting to obtain 2,2,4,4-tetrachloro-3-alkoxycyclobutanone. The alkali includes any one or a combination of at least two of triethylamine, pyridine, or N-methylmorpholine, and the molar ratio of chlorine to alkali is 1:(1~1.1).

9. The synthesis method according to claim 1, characterized in that, The base in step (3) includes any one or a combination of at least two of sodium ethoxide, potassium ethoxide or sodium tert-butoxide, and the molar ratio of 2,2,4,4-tetrachloro-3-alkoxycyclobutanone to the base is 1:(1~1.25). In step (3), the alkali is added in the form of an alkaline solution with a concentration of 5 wt% to 20 wt%. The solvent in the alkaline solution includes ethanol; The elimination reaction in step (3) is carried out at a temperature of 30-50°C for 6-12 hours. Step (3) after the elimination reaction also includes post-treatment steps such as filtering the reaction system and evaporating the solvent.

10. The synthesis method according to claim 1, characterized in that, The hydrolysis reaction in step (4) is carried out in the presence of an acid solution, wherein the acid includes sulfuric acid and / or hydrochloric acid, and the concentration of the acid solution is 10wt%~30wt%. The hydrolysis reaction in step (4) is carried out at a temperature of 90~115℃ and for a time of 8~24h.

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