An improved process for the synthesis of oxalyl chloride

Abstract

This invention relates to the field of organic chemistry, specifically to an improved synthesis process for oxalyl chloride. The provided synthesis process for oxalyl chloride includes the following steps: S1. Adding oxalic acid dihydrate to a reaction vessel and stirring to dissolve; S2. Slowly adding a composite catalyst to the molten liquid from step S1 and stirring until the mixture is homogeneous; S3. Adding triphosgene to the mixture obtained in step S2, while simultaneously introducing nitrogen gas from the bottom of the reaction vessel, and reacting at a temperature between 102 and 108°C for 2-3 hours; S4. Condensing the nitrogen gas overflowing from the reaction vessel in step S3 to obtain crude oxalyl chloride; S5. Releasing the nitrogen gas overflowing from the circulating water condenser after absorption by water and alkali; S6. Purifying the crude oxalyl chloride obtained in step S4 to obtain pure oxalyl chloride. The preparation method of this application is simple, easy to industrialize, and the product yield can reach over 95%, with a product purity of over 99.0%.

Description

Technical Field

[0001] This invention relates to the field of organic chemistry, and more specifically to an improved process for the synthesis of oxalyl chloride. Background Technology

[0002] Oxaloyl chloride, chemically known as oxaloyl chloride, is an important organic synthesis intermediate and acyl chloride reagent. In the pharmaceutical industry, oxaloyl chloride is a key raw material for the synthesis of third-generation cephalosporins (such as ceftriaxone sodium and cefotaxime sodium) and some sulfonylurea hypoglycemic drugs; in the pesticide field, it is an important precursor for the synthesis of highly effective herbicides and plant growth regulators; in the field of polymer materials, oxaloyl chloride can be used to prepare high-temperature resistant polyamides and functional polyesters.

[0003] The traditional synthesis processes of oxalyl chloride mainly involve the following technical routes:

[0004] Oxalic acid and phosphorus pentachloride process: This was the earliest industrialized method, using oxalic acid and phosphorus pentachloride as raw materials and reacting them in a phosphorus oxychloride medium. However, this process generates a large amount of byproducts, phosphorus oxychloride and hydrogen chloride, has a lengthy post-processing flow, and phosphorus pentachloride is highly hygroscopic, requiring stringent storage and feeding equipment. The product yield is typically only 70%-75%.

[0005] Oxalate chlorination method: Using dimethyl oxalate or diethyl oxalate as raw materials, chlorine gas is introduced under light or heating conditions to carry out a chlorination reaction. This method has a high reaction temperature (>160℃), extremely high energy consumption, and low chlorine utilization rate. During the reaction, deep chlorination is prone to occur, producing tar-like byproducts, making it difficult to achieve a product purity of over 95%.

[0006] Ethylene glycol chlorination-rearrangement method: Although the yield is relatively high, the process is too long, involving three chemical reactions, making intermediate separation difficult, and the investment cost for industrialization is high.

[0007] CN108409558A relates to a method for preparing oxalyl chloride. The method includes: S1, adding 250 ml of solvent, 90-110 g of oxalic acid, and 2-5 g of catalyst to a reaction flask, and mixing and stirring for 30-40 min to form solution A; S2, heating solution A to 50-60℃ under stirring, and adding a certain amount of byproduct inhibitor, 200-210 g of bis(trichloromethyl) carbonate, and 300 ml of solvent to form solution B; S3, while reacting in solution B, distilling off the crude product in the system until the reactor temperature reaches 110℃. The gas generated during the reaction is absorbed by water in multiple stages, and the resulting aqueous solution is a hydrochloric acid base, which, after neutralization, yields sodium chloride. The provided method for preparing oxalyl chloride uses readily available raw materials, simple post-processing, and safe operation. Using organic amines as catalysts and thiourea derivatives as byproduct inhibitors, the chlorination reaction is controllable, with high product yield and few byproducts. The water absorbed by the waste gas during the reaction forms hydrochloric acid, or after neutralization, forms industrial salt, thus preventing secondary pollution. It uses organic amines as catalysts; however, the process has a long reaction time and uses a large amount of solvent, which increases the burden and cost of post-processing. There is still room for improvement in terms of industrial production efficiency and economy. Summary of the Invention

[0008] This invention provides an improved synthesis process for oxalyl chloride, comprising the following steps:

[0009] S1. Add oxalic acid dihydrate to the reaction vessel, gradually heat to 101~105℃, stir to dissolve, and make the oxalic acid dihydrate lose its water of crystallization. The raw material is industrial grade oxalic acid dihydrate, which does not require oxalic acid, thus significantly reducing the cost.

[0010] S2. Slowly add the composite catalyst to the molten liquid from step S1, stir, and mix the liquid evenly;

[0011] S3. Add triphosgene to the mixture obtained in step S2, and simultaneously blow nitrogen gas into the bottom of the reactor. React at a temperature of 102~108℃ for 2~3 hours. The particle size of the triphosgene is between 2~6 mm.

[0012] S4. The nitrogen gas overflowing from the reactor in step S3 is first condensed using a circulating water condenser to obtain crude oxalyl chloride;

[0013] S5. Nitrogen gas overflowing from the circulating water condenser will be absorbed by water and alkali before being discharged.

[0014] S6. Purify the crude oxaloyl chloride obtained in step S4 to obtain pure oxaloyl chloride.

[0015] In this application, triphosgene is used as a chlorinating agent and carbonylating reagent. Under the action of a catalyst, it can controllably decompose and release triphosgene or directly form an active electrophilic intermediate with the catalyst to achieve the chlorination of the oxalic acid hydroxyl group. Compared with phosgene, triphosgene is easier to store and transport, has higher safety, and produces no sulfur- or phosphorus-containing waste residue, making it environmentally friendly. The synthesis process in this application does not add a solvent. It cleverly utilizes the melting point of oxalic acid, then selects a high-boiling-point catalyst, and finally adds triphosgene with an appropriate particle size to ensure efficient reaction by sinking below the liquid surface. If the particle size is too large, it will easily settle to the bottom of the reactor due to gravity, failing to fully contact the molten oxalic acid and affecting the reaction efficiency. If the particle size is too small, it will easily float above the reaction liquid, similarly reducing the reaction yield. Simultaneously, nitrogen gas is blown into the reactor, which serves both as a stirrer and as a gaseous carrier to remove the generated oxalyl chloride from the reactor for subsequent condensation and collection.

[0016] Furthermore, the molar ratio of oxalic acid dihydrate in step S1 to triphosgene in step S3 is 3:(1.9~2.0). The amount of triphosgene added is slightly lower than the theoretical amount to ensure complete reaction of the triphosgene and avoid excessive addition leading to decomposition and the generation of phosgene that could enter subsequent processing and cause safety hazards.

[0017] Furthermore, the mass ratio of oxalic acid dihydrate in step S1 to the composite catalyst in step S2 is (10~30):1.

[0018] Further, in step S2, the composite catalyst is composed of N,N-dimethylformamide (DMF) and 4-dimethylaminopyridine (DMAP), with a mass ratio of (10~20):1. DMF reacts with triphosgene or in-situ generated phosgene to form a highly active reagent intermediate. This intermediate exhibits strong electrophilicity and can rapidly react with the carboxyl group of oxalic acid to undergo chlorination. 4-Dimethylaminopyridine is an electron-rich, super-strong nucleophilic catalyst that can directly attack the carboxyl group of oxalic acid to form an active intermediate, greatly activating the carboxyl carbon and making it more susceptible to nucleophilic attack by chloride ions. Simultaneously, 4-dimethylaminopyridine also activates the intermediate, accelerating the chlorination process. DMF primarily functions as a "chlorination reagent activator," converting stable BTC into a highly active intermediate. DMAP primarily acts as a "carboxyl activator," converting the inert oxalate carboxyl group into a highly reactive acyl DMAP intermediate. When both coexist, a "dual activation" mechanism is formed: the reaction barrier between the highly reactive intermediate (generated from DMF + triphosgene) and the activated oxalate intermediate (generated from oxalate + DMAP) is significantly lowered. This synergistic catalytic effect allows the reaction to proceed rapidly and quantitatively, avoiding side reactions caused by insufficient activation capacity in single-catalyst systems, thus achieving a dual improvement in yield and purity.

[0019] Further, in step S2, the composite catalyst is composed of N,N-dimethylformamide, 4-dimethylaminopyridine, N-methylpyrrolidone, and 2,6-di-tert-butyl-4-methylphenol, with a mass ratio of (10~20):1:(3~5):(0.1~0.3). The addition of N-methylpyrrolidone to the catalyst, due to its strong polarity and electron-donating ability, enables it to form hydrogen bonds or dipole interactions with reaction intermediates and products, stabilizing the active species in the reaction system, inhibiting the decomposition of oxalyl chloride, and improving the yield. 2,6-di-tert-butyl-4-methylphenol, as a free radical scavenger, can capture free radical species that may be generated during the reaction, blocking free radical chain reactions, fundamentally reducing side reactions, and improving the yield. These four components exhibit a deep synergistic effect, and their combined use is far superior to any two-component combination, demonstrating "unexpected technical results." The quaternary system forms a complete "catalysis-activation-stabilization-capture" closed loop. DMF and DMAP are responsible for highly efficient catalysis, N-methylpyrrolidone stabilizes reaction intermediates and products, preventing non-target reactions, and 2,6-di-tert-butyl-4-methylphenol captures potential free radicals, blocking side reaction pathways. All four are indispensable, enabling precise control of the reaction pathway.

[0020] Further, in step S2, the composite catalyst is composed of N,N-dimethylformamide and an ionic liquid, with a mass ratio of N,N-dimethylformamide to ionic liquid of (10~20):1. The ionic liquid is 1-butyl-3-methylimidazolium chloroaluminate. 1-Butyl-3-methylimidazolium chloroaluminate exhibits strong Lewis acidity. This Lewis acidity can coordinate with the carboxyl oxygen atom of oxalic acid to form an Al-carboxylic acid complex, significantly enhancing the electrophilicity of the carboxyl carbon and making it more susceptible to nucleophilic attack by chloride ions. This activation mechanism complements the activation mechanism of DMF. DMF activates the chlorinated reagent, while the ionic liquid activates the carboxyl base. At the same time, the high polarity of the ionic liquid can stabilize the polar transition state and ionic intermediates formed during the reaction, reducing the activation energy and accelerating the reaction process. Finally, the Lewis acidity of the ionic liquid can preferentially combine with trace amounts of water that may be present in the reaction system, acting as an in-situ dehydrating agent to prevent the hydrolysis of oxalyl chloride. Meanwhile, the significant polarity difference between the ionic liquid and the product oxalyl chloride facilitates the timely separation of the product from the catalytic system, avoiding excessive reaction or decomposition of the product.

[0021] Furthermore, the purification method in step S6 is distillation.

[0022] Furthermore, the purification method in step S6 is recrystallization, and the solvent used for recrystallization is diethyl ether and dichloromethane.

[0023] Furthermore, the preparation method of the 1-butyl-3-methylimidazolium chloride aluminate ionic liquid is as follows: 1-methylimidazolium is reacted with chlorobutane to synthesize 1-butyl-3-methylimidazolium chloride, which is then mixed with anhydrous aluminum trichloride at a molar ratio of 1:1.7 and stirred under an inert atmosphere for 1 to 3 hours to obtain the product.

[0024] Further, the recrystallization process is as follows: The crude oxaloyl chloride obtained in step S4 is added to 4 times its mass of diethyl ether, heated to 30°C, stirred to dissolve, and then 0.5 times its mass of dichloromethane is added dropwise. The temperature is gradually lowered to -18 to -12°C and maintained for 1 to 2 hours. The mixture is filtered, washed twice with diethyl ether at a temperature of -12 to -10°C, and then vacuum dried at -10°C to obtain solid oxaloyl chloride. Upon cooling to room temperature, pure oxaloyl chloride is obtained as a colorless liquid. First, the crude oxaloyl chloride is dissolved in diethyl ether, which has low polarity, and then dichloromethane, which has high polarity, is added to reduce the solubility of the crude oxaloyl chloride in the mixed solvent. Simultaneously, the temperature is lowered to a precise temperature to precipitate the solid product. Two washings are necessary to obtain a high-purity product.

[0025] Compared with the prior art, the present invention has the following significant advantages:

[0026] (1) High yield and high purity: Through the synergistic effect of composite catalysts, the reaction rate and selectivity are significantly improved, the yield of oxalyl chloride can reach more than 95%, and the product purity is as high as 99.0%.

[0027] (2) Intrinsic safety and environmental protection: The reaction process does not use solvents, and the hydrogen chloride gas produced by the reaction is easily absorbed to produce industrial hydrochloric acid. There is no waste acid or waste residue discharge, and the process is green and environmentally friendly.

[0028] (3) Simple operation and easy to scale up: This process achieves precise parameter control and stable product quality, providing a reliable technical path for industrial production. Detailed Implementation

[0029] The technical solutions in the embodiments of the present invention will be clearly and completely described below. Obviously, the described embodiments are only some embodiments of the present invention, and not all embodiments.

[0030] Example 1

[0031] An improved process for the synthesis of oxalyl chloride includes the following steps:

[0032] S1. Add 378g of oxalic acid dihydrate to the reaction vessel, gradually heat to 101~105℃, stir to dissolve, and cause the oxalic acid dihydrate to lose its water of crystallization;

[0033] S2. Slowly add 25g of the composite catalyst to the molten liquid in step S1, stir, and mix the liquid evenly;

[0034] S3. Add 598g of triphosgene in batches to the mixture obtained in step S2, while simultaneously blowing nitrogen gas into the bottom of the reactor. React at a temperature between 102 and 108°C for 3 hours. The particle size of the triphosgene is between 2 and 6 mm.

[0035] S4. The nitrogen gas overflowing from the reactor in step S3 is first condensed using a circulating water condenser to obtain crude oxalyl chloride;

[0036] S5. Nitrogen gas overflowing from the circulating water condenser will be absorbed by water and alkali before being discharged.

[0037] S6. Purify the crude oxaloyl chloride obtained in step S4 to obtain pure oxaloyl chloride.

[0038] The composite catalyst in step S2 consists of 23g N,N-dimethylformamide and 2g 4-dimethylaminopyridine.

[0039] The purification method in step S6 is distillation, and the product purity after distillation is 99.2% and the yield is 96.3%.

[0040] Example 2

[0041] An improved process for the synthesis of oxalyl chloride includes the following steps:

[0042] S1. Add 378g of oxalic acid dihydrate to the reaction vessel, gradually heat to 101~105℃, stir to dissolve, and cause the oxalic acid dihydrate to lose its water of crystallization;

[0043] S2. Slowly add 25g of the composite catalyst to the molten liquid in step S1, stir, and mix the liquid evenly;

[0044] S3. Add 598g of triphosgene in batches to the mixture obtained in step S2, while simultaneously blowing nitrogen gas into the bottom of the reactor. React at a temperature between 102 and 108°C for 3 hours. The particle size of the triphosgene is between 2 and 6 mm.

[0045] S4. The nitrogen gas overflowing from the reactor in step S3 is first condensed using a circulating water condenser to obtain crude oxalyl chloride;

[0046] S5. Nitrogen gas overflowing from the circulating water condenser will be absorbed by water and alkali before being discharged.

[0047] S6. Purify the crude oxaloyl chloride obtained in step S4 to obtain pure oxaloyl chloride.

[0048] The composite catalyst in step S2 consists of 23g N,N-dimethylformamide and 2g 4-dimethylaminopyridine.

[0049] The purification method in step S6 is recrystallization. The solvents used for recrystallization are diethyl ether and dichloromethane. The recrystallization process is as follows: the crude oxaloyl chloride obtained in step S4 is added to 4 times its mass of diethyl ether, heated to 30°C, stirred and dissolved, then 0.5 times its mass of dichloromethane of crude oxaloyl chloride is added dropwise, and the temperature is gradually lowered to -18~-15°C and maintained for 1 hour. After filtration, the product is washed twice with diethyl ether at a temperature of -12~-10°C, and then vacuum dried at -10°C to obtain solid oxaloyl chloride product. After being placed at room temperature, pure oxaloyl chloride is obtained, which is a colorless liquid. After recrystallization, the product purity is 99.4% and the yield is 95.1%.

[0050] Example 3

[0051] An improved process for the synthesis of oxalyl chloride includes the following steps:

[0052] S1. Add 378g of oxalic acid dihydrate to the reaction vessel, gradually heat to 101~105℃, stir to dissolve, and cause the oxalic acid dihydrate to lose its water of crystallization;

[0053] S2. Slowly add 25g of the composite catalyst to the molten liquid in step S1, stir, and mix the liquid evenly;

[0054] S3. Add 598g of triphosgene in batches to the mixture obtained in step S2, while simultaneously blowing nitrogen gas into the bottom of the reactor. React at a temperature between 102 and 108°C for 3 hours. The particle size of the triphosgene is between 2 and 6 mm.

[0055] S4. The nitrogen gas overflowing from the reactor in step S3 is first condensed using a circulating water condenser to obtain crude oxalyl chloride;

[0056] S5. Nitrogen gas overflowing from the circulating water condenser will be absorbed by water and alkali before being discharged.

[0057] S6. Purify the crude oxaloyl chloride obtained in step S4 to obtain pure oxaloyl chloride.

[0058] In step S2, the composite catalyst consists of 23g N,N-dimethylformamide and 2g ionic liquid. The ionic liquid is 1-butyl-3-methylimidazolium chloride aluminate. The preparation method of the 1-butyl-3-methylimidazolium chloride ionic liquid is as follows: 1-methylimidazolium is reacted with n-chlorobutane to synthesize 1-butyl-3-methylimidazolium chloride, which is then mixed with anhydrous aluminum trichloride at a molar ratio of 1:1.7. The mixture is stirred and reacted for 2 hours under an inert atmosphere to obtain the product.

[0059] The purification method in step S6 is distillation, and the product purity after distillation is 99.5% with a yield of 96.6%.

[0060] Example 4

[0061] An improved process for the synthesis of oxalyl chloride includes the following steps:

[0062] S1. Add 378g of oxalic acid dihydrate to the reaction vessel, gradually heat to 101~105℃, stir to dissolve, and cause the oxalic acid dihydrate to lose its water of crystallization;

[0063] S2. Slowly add 25g of the composite catalyst to the molten liquid in step S1, stir, and mix the liquid evenly;

[0064] S3. Add 598g of triphosgene in batches to the mixture obtained in step S2, while simultaneously blowing nitrogen gas into the bottom of the reactor. React at a temperature between 102 and 108°C for 3 hours. The particle size of the triphosgene is between 2 and 6 mm.

[0065] S4. The nitrogen gas overflowing from the reactor in step S3 is first condensed using a circulating water condenser to obtain crude oxalyl chloride;

[0066] S5. Nitrogen gas overflowing from the circulating water condenser will be absorbed by water and alkali before being discharged.

[0067] S6. Purify the crude oxaloyl chloride obtained in step S4 to obtain pure oxaloyl chloride.

[0068] The composite catalyst in step S2 consists of 17.18g N,N-dimethylformamide, 1.56g 4-dimethylaminopyridine, 5.94g N-methylpyrrolidone and 0.32g 2,6-di-tert-butyl-4-methylphenol.

[0069] The purification method in step S6 is distillation, and the product purity after distillation is 99.6% and the yield is 97.2%.

[0070] Comparative Example 1

[0071] The only difference was that 2g of 4-dimethylaminopyridine in the composite catalyst of Example 1 was replaced with 2g of N,N-dimethylformamide. Everything else was the same as in Example 1 and will not be repeated here. The purity of the product after distillation was 97.2% and the yield was 93.4%.

[0072] Comparative Example 2

[0073] The only difference was that 2g of ionic liquid in the composite catalyst of Example 3 was replaced with 2g of N,N-dimethylformamide. Everything else was the same as in Example 1, and will not be repeated here. After purification, the product purity was 96.9% and the yield was 94.6%.

[0074] The data comparison above shows that the yield of oxalyl chloride prepared by this invention can reach over 95%, and the product purity is over 99.0%. A comparison of the data from Examples 1 and 2 indicates that, compared to distillation, recrystallization produces a higher product purity, but the recrystallization yield is slightly lower. Data from Examples 1, 3, and then 4 show that the introduction of both the quaternary catalyst and the ionic liquid can improve both product purity and yield. Data from Comparative Examples 1 and 2 show that the lack of synergistic effect between the composite catalysts significantly reduces both yield and purity.

Claims

1. An improved process for synthesizing oxalyl chloride, characterized in that, Includes the following steps: S1. Add oxalic acid dihydrate to the reaction vessel, gradually heat to 101~105℃, stir to dissolve, and cause the oxalic acid dihydrate to lose its water of crystallization; S2. Slowly add the composite catalyst to the molten liquid from step S1, stir, and mix the liquid evenly; S3. Add triphosgene to the mixture obtained in step S2, and simultaneously blow nitrogen gas into the bottom of the reactor. React at a temperature of 102~108℃ for 2~3 hours. The particle size of the triphosgene is between 2~6 mm. S4. The nitrogen gas overflowing from the reactor in step S3 is first condensed using a circulating water condenser to obtain crude oxalyl chloride; S5. Nitrogen gas overflowing from the circulating water condenser will be absorbed by water and alkali before being discharged. S6. Purify the crude oxaloyl chloride obtained in step S4 to obtain pure oxaloyl chloride.

2. The improved synthesis process of oxalyl chloride according to claim 1, characterized in that, The molar ratio of oxalic acid dihydrate in step S1 to triphosgene in step S3 is 3: (1.9~2.0).

3. The improved synthesis process of oxalyl chloride according to claim 1, characterized in that, The mass ratio of oxalic acid dihydrate in step S1 to the composite catalyst in step S2 is (10~30):

1.

4. The improved synthesis process of oxalyl chloride according to claim 1, characterized in that, In step S2, the composite catalyst is composed of N,N-dimethylformamide and 4-dimethylaminopyridine, with a mass ratio of (10~20):

1.

5. The improved synthesis process of oxalyl chloride according to claim 1, characterized in that, The composite catalyst in step S2 is composed of N,N-dimethylformamide, 4-dimethylaminopyridine, N-methylpyrrolidone and 2,6-di-tert-butyl-4-methylphenol, and the mass ratio of N,N-dimethylformamide, 4-dimethylaminopyridine, N-methylpyrrolidone and 2,6-di-tert-butyl-4-methylphenol is (10~20):1:(3~5):(0.1~0.3).

6. The improved synthesis process of oxalyl chloride according to claim 1, characterized in that, In step S2, the composite catalyst is composed of N,N-dimethylformamide and an ionic liquid, with a mass ratio of N,N-dimethylformamide to ionic liquid of (10~20):1, and the ionic liquid is 1-butyl-3-methylimidazolium chloroaluminate.

7. The improved synthesis process of oxalyl chloride according to claim 1, characterized in that, The purification method in step S6 is distillation.

8. The improved synthesis process of oxalyl chloride according to claim 1, characterized in that, The purification method in step S6 is recrystallization, and the solvents used for recrystallization are diethyl ether and dichloromethane.

9. The improved synthesis process of oxalyl chloride according to claim 6, characterized in that, The preparation method of the 1-butyl-3-methylimidazolium chloride aluminate ionic liquid is as follows: 1-methylimidazolium is reacted with chlorobutane to synthesize 1-butyl-3-methylimidazolium chloride, which is then mixed with anhydrous aluminum trichloride at a molar ratio of 1:1.7 and stirred under an inert atmosphere for 1 to 3 hours to obtain the product.

10. The improved synthesis process of oxalyl chloride according to claim 8, characterized in that, The recrystallization process is as follows: the crude oxaloyl chloride obtained in step S4 is added to 4 times its mass of diethyl ether, heated to 30°C, stirred and dissolved, then 0.5 times its mass of dichloromethane is added dropwise, and the temperature is gradually lowered to -18~-12°C and maintained for 1~2 hours. After filtration, the product is washed twice with diethyl ether at a temperature of -12~-10°C, and then vacuum dried at -10°C to obtain solid oxaloyl chloride product. After being placed at room temperature, pure oxaloyl chloride is obtained, which is a colorless liquid.