Synthesis method of squaric acid

Abstract

The invention relates to a method for synthesizing squaric acid, which comprises the following steps of: (1) reacting alkyl vinyl ether, trichloroacetyl chloride and zinc to obtain 2, 2-dichloro-3-alkoxy cyclobutanone; (2) carrying out a chlorination reaction on the 2, 2-dichloro-3-alkoxy cyclobutanone and chlorine gas to obtain 2, 2, 4, 4-tetrachloro-3-alkoxy cyclobutanone, and carrying out a chlorination reaction on the 2, 2-dichloro-3-alkoxy cyclobutanone and chlorine gas to obtain 2, 2, 4, 4-tetrachloro-3-alkoxy cyclobutanone; (3) the 2, 2, 4, 4-tetrachloro-3-alkoxy cyclobutanone and alkali are subjected to an elimination reaction, and 2, 4, 4-trichloro-3-alkoxy cyclobutene-1-one is obtained; and (4) carrying out a hydrolysis reaction on the 2, 4, 4-trichloro-3-alkoxy cyclobutene-1-ketone, so as to obtain the squaric acid. The synthesis method provided by the invention can avoid the use of a forbidden raw material perchloro-1, 3 butadiene, also has lower energy consumption, and can meet the requirements 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 the purpose, the present application adopts the following technical solutions:

[0009] The present application provides a synthesis method of squaric acid, comprising the following steps:

[0010] (1) reacting alkyl vinyl ether, trichloroacetyl chloride and zinc to obtain 2,2-dichloro-3-alkoxycyclobutanone;

[0011] (2) performing chlorination reaction on 2,2-dichloro-3-alkoxycyclobutanone in step (1) and chlorine to obtain 2,2,4,4-tetrachloro-3-alkoxycyclobutanone;

[0012] (3) performing elimination reaction on 2,2,4,4-tetrachloro-3-alkoxycyclobutanone in step (2) and a base to obtain 2,4,4-trichloro-3-alkoxycyclobuten-1-one;

[0013] (4) performing hydrolysis reaction on 2,4,4-trichloro-3-alkoxycyclobuten-1-one in step (3) to obtain the squaric acid.

[0014] The reaction formula of the present application is as follows:

[0015] ;

[0016] In the formula, R represents linear or branched alkyl.

[0017] The present application prepares dichloroacetone by reacting trichloroacetyl chloride and zinc powder, produces 2,2-dichloro-3-alkoxycyclobutanone intermediate by reacting alkyl vinyl ether and dichloroacetone, and synthesizes squaric acid through chlorination, elimination and hydrolysis steps, which avoids using the raw material prohibited to be used and conforms to the 2+2 ketone cyclization reaction mechanism.

[0018] Preferably, the alkyl vinyl ether in step (1) comprises C1-C10 (for example, C1, C2, C4, C6, C8, C10, etc.) linear or branched alkyl vinyl ether.

[0019] Preferably, the alkyl vinyl ether is subjected to dehydration treatment in advance, and the moisture is ≤100 ppm.

[0020] Preferably, the molar ratio of the alkyl vinyl ether to trichloroacetyl chloride in step (1) is 1: (1.05-1.3) (for example, 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, 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 time of the reaction 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 the present application, the reaction can be promoted to proceed in the forward direction by irradiating ultraviolet light, the cyclization reaction can be accelerated, and the yield and purity of the reaction can be improved.

[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, and specifically includes: mixing the alkyl vinyl ether and the solvent, then cooling, adding a solution of trichloroacetyl chloride and the solvent after mixing under temperature control, and then adding zinc, and then continuing the reaction, and after purification, obtaining 2,2-dichloro-3-alkoxycyclobutanone.

[0025] Preferably, the solvent is methyl tert-butyl ether.

[0026] Preferably, the solvent is subjected to a dehydration treatment in advance, and the water content is ≤100ppm.

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

[0028] Preferably, the temperature of the temperature control is 0-10℃ (for example, it can be 0℃, 2℃, 5℃, 8℃, 10℃, etc.), and the time of the temperature control is 8-12h (for example, it can be 8h, 9h, 10h, 11h, 12h, etc.).

[0029] Preferably, the temperature of the continued reaction is 10-30℃ (for example, it can be 10℃, 15℃, 20℃, 25℃, 30℃, etc.), and the time of the continued reaction is 0.5-2h (for example, it can be 0.5h, 1h, 1.5h, 2h, etc.).

[0030] Preferably, the purification includes: filtering the reaction system, and reducing pressure distillation of the obtained liquid to obtain 2,2-dichloro-3-alkoxycyclobutanone.

[0031] Preferably, the reduced pressure distillation comprises first distilling to remove the solvent at 50-70°C (for example, it can be 50°C, 55°C, 60°C, 65°C, 70°C, etc.), a vacuum degree of -0.01 to -0.09 MPa (for example, it can be -0.01 MPa, -0.04 MPa, -0.06 MPa, -0.08 MPa, -0.09 MPa, etc.), and then distilling at 70-85°C (for example, it can be 70°C, 75°C, 80°C, 85°C, etc.), a vacuum degree of 0-5 mbar (for example, it can be 0.1 mbar, 0.5 mbar, 1 mbar, 2 mbar, 3 mbar, 5 mbar, etc.), to obtain 2,2-dichloro-3-alkoxycyclobutanone.

[0032] Preferably, the molar ratio of 2,2-dichloro-3-alkoxycyclobutanone to 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°C (for example, it can be 0°C, 2°C, 5°C, 8°C, 10°C, etc.), and the time of the chlorination reaction is 8-16 h (for example, it can be 8 h, 10 h, 12 h, 14 h, 16 h, etc.).

[0034] Preferably, the chlorination reaction in step (2) is carried out in the presence of a base, and the chlorination reaction specifically comprises: introducing chlorine into 2,2-dichloro-3-alkoxycyclobutanone, while adding a base, and then 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 the base 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 base in step (3) comprises 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 1:1-1.25 (for example, it can be 1:1, 1:1.05, 1:1.1, 1:1.15, 1:1.2, 1:1.25, etc.).

[0039] Preferably, the base in step (3) is added in the form of a base solution, and the concentration of the base solution is 5wt%-20wt% (for example, it can be 5wt%, 8wt%, 10wt%, 15wt%, 20wt%, etc.).

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

[0041] Preferably, the temperature of the elimination reaction in step (3) is 30-50℃ (for example, it can be 30℃, 35℃, 40℃, 45℃, 50℃, etc.), and the time of the elimination reaction is 6-12h (for example, it can be 6h, 8h, 10h, 12h, etc.).

[0042] Preferably, after the elimination reaction in step (3), a post-processing step of filtering and evaporating the solvent is further included.

[0043] Preferably, the hydrolysis reaction in step (4) is carried out in the presence of an acid solution, and the acid includes sulfuric acid and / or hydrochloric acid, and the concentration of the acid solution is 10wt%-30wt% (for example, it can be 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 a post-processing step of cooling and filtering.

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

[0047] 1. The present application uses the intermediate cyclobutanone produced by the reaction of the raw material alkyl vinyl ether after the reaction of trichloroacetyl chloride and zinc powder with p-toluenesulfonic acid to generate squaric acid, which gets rid of the problem of raw material restriction in the current per-chloro-1,3-butadiene route, and the raw materials used in the present application are all industrial products, which can be used for actual industrial large-scale production.

[0048] 2. The present application uses 2+2 enone cyclization to synthesize the intermediate cyclobutanone, which does not need heating compared with the traditional reaction using per-chloro-1,3-butadiene and morpholine, saves the energy required for heating, and achieves clean production. BRIEF DESCRIPTION OF DRAWINGS

[0049] Figure 1 It is the HPLC chart of squaric acid obtained in Example 1. DETAILED DESCRIPTION

[0050] To facilitate the understanding of the present application, the present application is illustrated by the following examples. Those skilled in the art should understand that the examples are only to facilitate the understanding of the present application, and should not be regarded as specific limitations of the present application.

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

[0052] Example 1

[0053] The present example provides a method for preparing squaric acid, comprising the following steps:

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

[0055] 2. Dropwise addition and feeding: Keep stirring, slowly drop the methyl tert-butyl ether solution of trichloroacetyl chloride (199.5 g, 1.1 mol of trichloroacetyl chloride dissolved in 100 mL of methyl tert-butyl ether) into the reaction flask of step 1 through a dropping funnel; at the same time, carefully add activated zinc powder 52.3 g (0.8 mol) in multiple batches to the reaction flask under nitrogen replacement, control the dropwise addition for 12 hours of reaction time, control the reaction temperature at 10°C, and use 254 nm ultraviolet light irradiation during the reaction;

[0056] 3. Reaction: After the dropwise addition is completed, remove the ice bath and let the reaction continue to react at 25°C for 1 hour;

[0057] 4. Purification: Filter, remove the solvent methyl tert-butyl ether under vacuum at 60°C and a vacuum degree of -0.05 MPa, and obtain pure 2,2-dichloro-3-ethoxycyclobutanone 135.2 g (purity 95%, yield 70.2%) by vacuum distillation at 80°C and a vacuum degree of 2 mbar;

[0058] 5. Halogenation: Pass chlorine gas 42 L (1.88 mol) into the prepared 2,2-dichloro-3-ethoxycyclobutanone 135.2 g (purity 95%, 0.70 mol) at 5°C, which needs to be passed for 8 hours, and dropwise add triethylamine 189.75 g (1.88 mol) to remove the generated hydrogen chloride, and after the reaction is completed, filter out the triethylamine hydrochloride to obtain 2,2,4,4-tetrachloro-3-ethoxycyclobutanone 150.0 g;

[0059] 6. Elimination reaction: Add 10 wt% ethanolic sodium ethoxide solution 408.3 g (sodium ethoxide 0.68 mol) to 2,2,4,4-tetrachloro-3-ethoxycyclobutanone 150.0 g (purity 93%, 0.55 mol) to perform the elimination reaction, filter after the reaction is completed, and evaporate the solvent ethanol to obtain 2,4,4-trichloro-3-ethoxycyclobuten-1-one 131.4 g.

[0060] 7. Hydrolysis reaction: 2,4,4-trichloro-3-ethoxycyclobuten-1-one 131.4 g (purity 90%, 0.55 mol) was added to 300 g of 30 wt% sulfuric acid, and heated to reflux at 110°C for 12 hours. During the reaction, the acid continuously crystallized out. After the hydrolysis reaction was completed, the mixture was cooled to 25°C, and the product was obtained by filtration. The yield of the product was 55.8 g (purity 98.0%, yield 47.9%).

[0061] The HPLC detection spectrum of the acid is shown in Figure 1 The detection method comprises:

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

[0063] Flow rate: 0.7 mL / min;

[0064] Injection volume: 10 microliters;

[0065] Column oven: 25°C;

[0066] Detector: UV detector;

[0067] Wavelength: 210 nm;

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

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

[0070] Table 1

[0071]

[0072] The nuclear magnetic resonance data of the acid are as follows:

[0073] Hydrogen spectrum (¹H-NMR DMSO-d6): δ 13.7 ppm.

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

[0075] Example 2

[0076] The present example provides a method for preparing an acid, comprising the following steps:

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

[0078] 2. Dropwise addition and feeding: keep stirring, slowly dropwise add the methyl tert-butyl ether solution of trichloroacetyl chloride (199.5 g, 1.1 mol of trichloroacetyl chloride dissolved in 100 mL of methyl tert-butyl ether) to the reaction flask of step 1 through a dropping funnel; at the same time, carefully add activated zinc powder 52.3 g (0.8 mol) in batches to the reaction flask under nitrogen replacement; control the dropwise addition for 12 hours, and control the reaction temperature at 10°C, and irradiate the reaction with ultraviolet light at 254 nm;

[0079] 3. Reaction: after the dropwise addition is completed, remove the ice bath, and let the reaction continue to react at 25°C for 2 hours;

[0080] 4. Purification: filter, remove the solvent methyl tert-butyl ether under reduced pressure at 60°C and a vacuum degree of -0.05 MPa; the crude product is distilled under reduced pressure at 80°C and a vacuum degree of 3 mbar to obtain pure 2,2-dichloro-3-isobutoxy cyclobutanone 162.3 g (purity 98.0%, yield 75.4%);

[0081] 5. Halogenation: pass chlorine gas 43.7 L (1.95 mol) into the prepared 2,2-dichloro-3-isobutoxy cyclobutanone 162.3 g (purity 98.0%, 0.75 mol) at 5°C, which needs to be passed for 8 hours, and dropwise add triethylamine 197.3 g (1.95 mol) to remove the generated hydrogen chloride, and after the reaction is completed, filter out the triethylamine hydrochloride to obtain 2,2,4,4-tetrachloro-3-isobutoxy cyclobutanone 167.1 g;

[0082] 6. Elimination reaction: add 10 wt% ethanolic sodium ethoxide solution 428.7 g (sodium ethoxide 0.63 mol) to 2,2,4,4-tetrachloro-3-isobutoxy cyclobutanone 167.1 g (purity 97.2%, 0.59 mol) to perform the elimination reaction, filter after the reaction is completed, and evaporate the solvent ethanol to obtain 2,4,4-trichloro-3-isobutoxy cyclobuten-1-one 142.7 g;

[0083] 7. Hydrolysis reaction: add 30 wt% sulfuric acid 300 g to 2,4,4-trichloro-3-isobutoxy cyclobuten-1-one 137.1 g (purity 99.5%, 0.58 mol), heat to reflux at 110°C for 12 hours, and continuously crystallize the sulfuric acid during the reaction; after the hydrolysis reaction is completed, stand and cool to 25°C, and filter to obtain the finished product of sulfuric acid 65.4 g (purity 98.5%, yield 56.5%).

[0084] Example 3

[0085] The example provides a method for preparing sulfuric acid, which comprises the following steps:

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

[0087] 2. Dropwise addition and feeding: keep stirring, slowly dropwise add the methyl tert-butyl ether solution of trichloroacetyl chloride (199.5 g, 1.1 mol of trichloroacetyl chloride dissolved in 100 mL of methyl tert-butyl ether) through a dropping funnel; at the same time, carefully add activated zinc powder 52.3 g (0.8 mol) in multiple batches to the reaction flask under nitrogen replacement; control the dropwise addition for 12 hours, control the reaction temperature at 3°C, and use 254 nm ultraviolet light irradiation during the reaction;

[0088] 3. Reaction: after the dropwise addition is completed, remove the ice bath and let the reaction continue to react at 25°C for 1 hour;

[0089] 4. Purification: filter, remove the solvent methyl tert-butyl ether under reduced pressure at 60°C and a vacuum degree of -0.05 MPa; the crude product is obtained by 80°C and a vacuum degree of 0.2 mabr, to obtain pure 2,2-dichloro-3-isobutoxy cyclobutanone 190.1 g (purity 99.2%, yield 89.4%);

[0090] 5. Halogenation: pass chlorine gas 45.7 L (1.95 mol) into the prepared 2,2-dichloro-3-isobutoxy cyclobutanone 190.1 g (purity 99.2%, 0.89 mol) at 5°C, which needs to be passed for 8 hours, and at the same time, dropwise add triethylamine 202.3 g (2 mol) to remove the generated hydrogen chloride, and after the reaction is completed, filter out the triethylamine hydrochloride to obtain 2,2,4,4-tetrachloro-3-isobutoxy cyclobutanone 220.6 g;

[0091] 6. Elimination reaction: add 10 wt% ethanolic sodium ethoxide solution 520 g (sodium ethoxide 0.8 mol) to 2,2,4,4-tetrachloro-3-isobutoxy cyclobutanone 220.6 g (purity 99.0%, 0.8 mol) to carry out the elimination reaction, filter after the reaction is completed, and evaporate the solvent ethanol to obtain 2,4,4-trichloro-3-isobutoxy cyclobuten-1-one 186.5 g;

[0092] 7. Hydrolysis reaction: add 30 wt% sulfuric acid 300 g to 2,4,4-trichloro-3-isobutoxy cyclobuten-1-one 186.5 g (purity 99.3%, 0.78 mol) and heat to reflux at 110°C for 12 hours; during the reaction process, sulfuric acid continuously crystallizes out, the hydrolysis reaction is completed after standing and cooling to 25°C, and the finished product of sulfuric acid 87.9 g (purity 99.1%, yield 76.4%) is obtained after filtration.

[0093] Example 4

[0094] The embodiment provides a preparation method of squaric acid, which is only different from the embodiment 3 in that no ultraviolet light irradiation is used in step 2, and the specific steps are as follows.

[0095] 1, Preparation: in a dry reaction bottle, isobutyl vinyl ether 101.2g (1mol) and methyl tert-butyl ether 500mL are added, stirring under nitrogen protection and cooling to 0°C;

[0096] 2, dropwise and charging: keep stirring, slowly drop the methyl tert-butyl ether solution of trichloroacetyl chloride (199.5g, 1.1mol of trichloroacetyl chloride dissolved in 100mL of methyl tert-butyl ether) through a dropping funnel; at the same time, 52.3g (0.8mol) of activated zinc powder is carefully added to the reaction bottle in batches under nitrogen replacement; the dropwise adding time is controlled to be 12 hours, and the reaction temperature is controlled to be 5°C; no 254nm ultraviolet light irradiation is used during the reaction.

[0097] 3, reaction: after the dropwise adding is completed, the ice bath is removed, and the reaction is continued at 25°C for 1 hour;

[0098] 4, purification: filtration, removal of the solvent methyl tert-butyl ether under the condition of 60°C and vacuum degree-0.05MPa; the crude product is obtained by 80°C and vacuum degree 0.2mabr, and the pure 2,2-dichloro-3-isobutoxy cyclobutanone 128.7g (purity 80.5%, yield 49.1%) is obtained;

[0099] 5, halogenation: the prepared 2,2-dichloro-3-isobutoxy cyclobutanone 128.7g (purity 80.5%, 0.49mol) is introduced into chlorine 27.4L (1.22mol) at 5°C, and triethylamine 131.5g (1.3mol) is added dropwise to remove the generated hydrogen chloride during the reaction; after the reaction is completed, the triethylamine hydrochloride is removed by filtration, and 2,2,4,4-tetrachloro-3-isobutoxy cyclobutanone 140.5g is obtained;

[0100] 6, elimination reaction: 2,2,4,4-tetrachloro-3-isobutoxy cyclobutanone 140.5g (purity 85.5%, 0.44mol) is added into 10wt% ethanolic sodium ethoxide solution 306.2g (sodium ethoxide 0.45mol) to perform an elimination reaction; after the reaction is completed, the solvent ethanol is removed by filtration, and 2,4,4-trichloro-3-isobutoxy cyclobuten-1-one 98.8g is obtained;

[0101] 7. Hydrolysis reaction: 2,4,4-trichloro-3-isobutoxy cyclobutene-1-one 98.8 g (purity 96.2%, 0.4 mol) was added to 300 g of 30 wt% sulfuric acid, and heated to reflux at 110°C for 12 hours. During the reaction, the sulfuric acid crystallized out. After the hydrolysis reaction was completed, the mixture was cooled to 25°C, and filtered to obtain 39.5 g of the product (purity 96.1%, yield 33.3%).

[0102] Example 5

[0103] The present example provides a method for preparing a square acid, comprising the following steps:

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

[0105] 2. Dropwise addition and charging: While maintaining vigorous stirring, 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) was slowly added through a dropping funnel; at the same time, 52.3 g (0.8 mol) of activated zinc powder was carefully added to the reaction bottle in multiple batches under nitrogen replacement; the dropwise addition was controlled for 8 hours, and the reaction temperature was controlled at 5°C, and ultraviolet light at 254 nm was used for irradiation during the reaction;

[0106] 3. Reaction: After the dropwise addition was completed, the ice bath was removed, and the reaction was allowed to continue at 25°C for 1 hour;

[0107] 4. Purification: The reaction mixture was filtered, and the solvent methyl tert-butyl ether was removed by rotary evaporation under vacuum at 60°C and a vacuum degree of -0.05 MPa; the crude product was purified by rotary evaporation under vacuum at 80°C and a vacuum degree of 0.2 mabr to obtain pure 2,2-dichloro-3-n-propoxy cyclobutanone 165.9 g (purity 99.3%, yield 83.6%);

[0108] 5. Halogenation: The prepared 2,2-dichloro-3-n-propoxy cyclobutanone 165.9 g (purity 99.3%, 0.84 mol) was passed with chlorine gas 47.0 L (2.1 mol) at 5°C for 8 hours, while triethylamine 212.5 g (2.1 mol) was added dropwise to remove the generated hydrogen chloride; after the reaction was completed, the triethylamine hydrochloride was removed by filtration to obtain 2,2,4,4-tetrachloro-3-n-propoxy cyclobutanone 203.9 g;

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

[0110] 7. Hydrolysis reaction: 2,4,4-trichloro-3-n-propoxy cyclobuten-1-one 166.9 g (purity 99.0%, 0.72 mol) was added to 30 wt% sulfuric acid 300 g, and heating reflux reaction was carried out at 110°C for 12 hours. During the reaction, sulfuric acid was continuously crystallized. After the hydrolysis reaction was completed, it was cooled to 25°C, and after filtration, square acid product 81.6 g (purity 98.3%, yield 70.4%) was obtained.

[0111] Example 6

[0112] The present embodiment provides a method for preparing square acid, comprising the following steps:

[0113] 1. Preparation: In a dry reaction bottle, isopropyl vinyl ether 86.1 g (1 mol) and methyl tert-butyl ether 500 mL were added, and stirring was carried out under nitrogen protection and cooling to 0°C;

[0114] 2. Dropwise addition and charging: Under the condition of keeping stirring, methyl tert-butyl ether solution of trichloroacetyl chloride (199.5 g, 1.1 mol of trichloroacetyl chloride dissolved in 100 mL of methyl tert-butyl ether) was slowly added dropwise through a dropping funnel; at the same time, activated zinc powder 52.3 g (0.8 mol) was carefully added to the reaction bottle in multiple batches under nitrogen replacement; the dropwise addition was controlled for 8 hours of reaction time, and the reaction temperature was controlled at 5°C, and ultraviolet light irradiation at 254 nm was used during the reaction;

[0115] 3. Reaction: After the dropwise addition was completed, the ice bath was removed, and the reaction was allowed to rise to 25°C for 1 hour of continuous reaction;

[0116] 4. Purification: Filtration was carried out, and the solvent methyl tert-butyl ether was removed by vacuum rotary evaporation at 60°C and a vacuum degree of -0.05 MPa; the crude product was obtained by vacuum degree 0.2 mbar at 80°C to obtain pure 2,2-dichloro-3-isopropoxy cyclobutanone 165.6 g (purity 99.0%, yield 83.2%);

[0117] 5. Halogenation: 2,2-dichloro-3-isopropoxy cyclobutanone 165.6 g (purity 99.2%, 0.83 mol) was introduced with chlorine 40.0 L (1.76 mol) at 5°C, and the reaction was carried out for 8 hours, while triethylamine 182.2 g (1.8 mol) was added dropwise to remove the hydrogen chloride generated in the reaction. After the reaction was completed, triethylamine hydrochloride was removed by filtration, and 2,2,4,4-tetrachloro-3-isopropoxy cyclobutanone 201.8 g was obtained.

[0118] 6. Elimination reaction: 2,2,4,4-tetrachloro-3-isopropoxy cyclobutanone 201.8 g (purity 98.8%, 0.75 mol) was added to 10 wt% ethanol sodium ethoxide solution 530 g (sodium ethoxide 0.78 mol) to carry out the elimination reaction. After the reaction was completed, the solvent ethanol was removed by filtration and evaporation, and 2,4,4-trichloro-3-isopropoxy cyclobuten-1-one 172.9 g was obtained.

[0119] 7. Hydrolysis reaction: 2,4,4-trichloro-3-isopropoxy cyclobuten-1-one 172.9 g (purity 98.2%, 0.74 mol) was added to 30 wt% sulfuric acid 300 g, and the reaction was carried out at 110°C for 12 hours. During the reaction, sulfuric acid was continuously crystallized. After the hydrolysis reaction was completed, the reaction was cooled to 25°C, and the product 83.9 g (purity 98.5%, yield 72.5%) was obtained by filtration.

[0120] The yield and purity data of the 2,2-dichloro-3-alkoxy cyclobutanone intermediate and the square acid in the preparation method of the square acid provided in the above examples are shown in Table 2.

[0121] Table 2

[0122]

[0123] As can be seen from the test results, the route provided in examples 1-6 of the present application, which is prepared by reacting alkyl vinyl ether, trichloroacetyl chloride and zinc to prepare 2,2-dichloro-3-alkoxy cyclobutanone intermediate, and then chlorinating, eliminating and hydrolyzing to prepare square acid, not only avoids the use of the limited raw material perfluoro-1,3-butadiene, but also has high yield and purity.

[0124] As can be seen from the comparison of example 3 and example 4, ultraviolet irradiation can promote 2+2 enone cyclization, which is beneficial to improve the yield and purity of the reaction.

[0125] As can be seen from the comparison of example 3 and examples 1-2, the first step synthesis temperature should be controlled at about 5°C, and the first step reaction yield is the best. When isobutyl vinyl ether is used as the raw material, the yield and purity are the highest under the same conditions.

[0126] The applicant states that the above description is only a specific embodiment of the present application, but the protection scope of the present application is not limited thereto, and it should be understood by those skilled in the art that any changes or replacements within the technical scope disclosed by the present application can be easily thought out by those skilled in the art, and all of them fall within the protection scope and disclosure scope of the present application.

Claims

1. A method for synthesizing squaric acid, characterized by, The synthesis method comprises the following steps: (1) reacting alkyl vinyl ether, trichloroacetyl chloride and zinc to obtain 2,2-dichloro-3-alkoxyl cyclobutanone; (2) performing chlorination reaction on 2,2-dichloro-3-alkoxyl cyclobutanone in step (1) and chlorine to obtain 2,2,4,4-tetrachloro-3-alkoxyl cyclobutanone; (3) performing elimination reaction on 2,2,4,4-tetrachloro-3-alkoxyl cyclobutanone in step (2) and a base to obtain 2,4,4-trichloro-3-alkoxyl cyclobuten-1-one; (4) performing hydrolysis reaction on 2,4,4-trichloro-3-alkoxyl cyclobuten-1-one in step (3) to obtain the squaric acid.

2. The method of synthesis of claim 1, wherein, The alkyl vinyl ether in step (1) comprises C1-C10 linear or branched alkyl vinyl ether; The molar ratio of the alkyl vinyl ether to trichloroacetyl chloride in step (1) 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°C, the reaction time is 8-14h, and the reaction is performed under ultraviolet light irradiation.

3. The method of synthesis of claim 2, wherein, The alkyl vinyl ether in step (1) comprises 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 method of synthesis of claim 1, wherein, The reaction in step (1) is performed in the presence of a solvent, and specifically comprises: mixing the alkyl vinyl ether and the solvent, then cooling, adding a solution of trichloroacetyl chloride and the solvent after mixing under temperature control, adding zinc, then continuing the reaction, and obtaining 2,2-dichloro-3-alkoxyl cyclobutanone after purification.

5. The method of synthesis of claim 4, wherein, The solvent is methyl tert-butyl ether; The cooling temperature is-5-5°C, the temperature control temperature is 0-10°C, the temperature control time is 8-12h, the continuing reaction temperature is 10-30°C, and the continuing reaction time is 0.5-2h.

6. The method of synthesis of claim 4, wherein, The purification comprises: filtering the reaction system, and distilling the obtained liquid under reduced pressure to obtain 2,2-dichloro-3-alkoxyl cyclobutanone; The distillation under reduced pressure comprises: first distilling off the solvent at 50-70°C and a vacuum degree of-0.01--0.09MPa, and then distilling at 70-85°C and a vacuum degree of 0-5mbar to obtain 2,2-dichloro-3-alkoxyl cyclobutanone.

7. The method of synthesis of claim 1, wherein, The molar ratio of 2,2-dichloro-3-alkoxyl cyclobutanone to chlorine in step (2) is 1:(2.1-3); The chlorination reaction temperature in step (2) is 0-10°C, and the chlorination reaction time is 8-16h.

8. The method of synthesis of claim 1, wherein, The chlorination reaction in step (2) is performed in the presence of a base, and specifically comprises: introducing chlorine into 2,2-dichloro-3-alkoxyl cyclobutanone, and simultaneously adding a base, and then performing reaction to obtain 2,2,4,4-tetrachloro-3-alkoxyl cyclobutanone; The base comprises any one or a combination of at least two of triethylamine, pyridine or N-methylmorpholine, and the molar ratio of chlorine to the base is 1:(1-1.1).

9. The method of synthesis of claim 1, wherein, 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 the 2,2,4,4-tetrachloro-3-alkoxyl cyclobutanone to the base is 1:(1-1.25); The base in step (3) is added in the form of a base solution, and the concentration of the base solution is 5wt%-20wt%; The solvent in the base solution includes ethanol; The temperature of the elimination reaction in step (3) is 30-50°C, and the time of the elimination reaction is 6-12h; Step (3) further includes a post-processing step of filtering the reaction system and evaporating the solvent after the elimination reaction.

10. The method of synthesis of claim 1, wherein, The hydrolysis reaction in step (4) is carried out in the presence of an acid solution, and the acid includes sulfuric acid and / or hydrochloric acid, and the concentration of the acid solution is 10wt%-30wt%; The temperature of the hydrolysis reaction in step (4) is 90-115°C, and the time of the hydrolysis reaction is 8-24h.

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