Method for recovering 2-mercaptobenzothiazole from cephalosporin active ester production mother liquor

Abstract

The invention belongs to the technical field of heterocyclic compounds, and particularly relates to a method for recovering 2-mercaptobenzothiazole from cephalosporin active ester production mother liquor. The recovery method comprises the following steps: (1) distilling the cephalosporin active ester production mother liquor to obtain a heavy fraction; adding methanol and an antioxidant into the heavy fraction, adjusting the pH value, and reacting to obtain a suspension; and (2) refining the suspension to obtain a destaining solution, heating the destaining solution, adding water, then adjusting the pH value, carrying out heat preservation crystallization, and carrying out hot filtration after crystallization is completed to obtain the 2-mercaptobenzothiazole. According to the invention, the antioxidant prepared from the main antioxidant 2, 2, 6, 6-tetramethylpiperidine-1-oxygen free radical, oleic acid mercaptoethyl ester and 4-dimethylaminopyridine is added, so that oxidation of 2-mercaptobenzothiazole is inhibited in multiple mechanisms, stable existence of 2-mercaptobenzothiazole in the reaction and crystallization process is ensured, and the stability of 2-mercaptobenzothiazole is ensured. The conversion into byproducts such as dibenzothiazyl disulfide is avoided, so that the recovery rate and the purity of the MBT are improved.

Description

Technical Field

[0001] The present invention belongs to the technical field of heterocyclic compounds, and particularly relates to a method for recovering 2-mercaptobenzothiazole from the mother liquor of cephalosporin active ester production. Background Art

[0002] 2-Mercaptobenzothiazole, abbreviated as MBT, is a light yellow monoclinic needle-like or leaf-like crystal at room temperature. The thiazole ring and mercapto group in 2-mercaptobenzothiazole have relatively high reactivity, and the nitrogen atom on its thiazole ring can coordinate with the empty orbital on the metal surface to form a metal-2-mercaptobenzothiazole complex. These molecular characteristics make 2-mercaptobenzothiazole commonly used as a rubber vulcanization accelerator, metal corrosion inhibitor or metal content detection reagent.

[0003] Dibenzothiazole disulfide, abbreviated as DM, is one of the important raw materials for synthesizing cephalosporin active ester. The synthesis route is that dibenzothiazole disulfide reacts with cephalosporin side chain acid (such as amoxicillin acid, cephalexin side chain acid, etc.) under the action of catalysts such as triethyl phosphite, and high-purity cephalosporin active ester and reaction mother liquor are obtained through purification and separation; there will be various by-products in the reaction mother liquor, such as residual cephalosporin active ester, 2-mercaptobenzothiazole, etc. after purification. Among them, the mercapto group in 2-mercaptobenzothiazole has relatively high reactivity and can be oxidized to dibenzothiazole disulfide even under mild conditions. Therefore, directly separating 2-mercaptobenzothiazole is difficult to ensure the stability of the recovery rate and is not conducive to industrial promotion.

[0004] Generally, 2-mercaptobenzothiazole is not directly recovered from the mother liquor of cephalosporin active ester production, but 2-mercaptobenzothiazole needs to be actively oxidized to dibenzothiazole disulfide first, and the chemical stability of dibenzothiazole disulfide is used to avoid various side reactions in the process of directly recovering 2-mercaptobenzothiazole. For example, Chinese Patent CN110330466A discloses a method for recovering DM from the mother liquor of cephalosporin active ester production. The method is to adjust the pH of the mother liquor of cephalosporin active ester production to 4.0 - 6.5, add activated carbon, raise the temperature for decolorization, filter, transfer the filtrate into a high-pressure reaction kettle, add a catalyst, and react by passing oxygen, and then filter to obtain DM; the main components of the mother liquor of cephalosporin active ester production are 2-mercaptobenzothiazole, triethyl phosphate, triethyl phosphite, impurities and a mixed solvent composed of dichloromethane and acetonitrile. Among them, 2-mercaptobenzothiazole is unstable and can chemically react with the solvent dichloromethane under certain conditions. Therefore, this patent uses a free radical-initiated catalytic oxidation process to oxidize 2-mercaptobenzothiazole in the mother liquor into stable high-purity DM, thereby recovering DM.

[0005] However, this patent is mainly for the recovery of dibenzothiazole disulfide. For manufacturers who want to obtain the final product 2-mercaptobenzothiazole, it is necessary to strictly control the pH and temperature during the process of re-reducing the recovered dibenzothiazole disulfide to 2-mercaptobenzothiazole, which further increases the operation difficulty and cost and is not conducive to industrial production.

[0006] In addition, existing recovery processes mostly focus on the recovery of 2-mercaptobenzothiazole itself and do not utilize the residual cefotaxime active ester in the mother liquor of cefotaxime active ester production, resulting in insufficient atom economy. For example, Chinese Patent CN102351809A discloses a method for recovering 2-mercaptobenzothiazole from the mother liquor of cefotaxime sodium crystallization, which includes the following steps: (1) adjusting the pH of the mother liquor of cefotaxime sodium crystallization to 2.0 - 5.0 with concentrated sulfuric acid with a concentration of 85 - 98%; (2) heating and distilling the mother liquor obtained in step (1) to distill out the solvent, and the volume of the distilled solvent is 75 - 90% of the total volume of the mother liquor, and the remaining solution after distillation is reserved; (3) cooling the remaining solution obtained in step (2) to 0 - 35°C and filtering, and reserving the filtrate; (4) adding water with a volume 1 - 5 times that of the filtrate to the filtrate obtained in step (3) and stirring to precipitate solids; (5) filtering out the solids obtained in step (4), washing with water and drying to obtain the target product 2-mercaptobenzothiazole.

[0007] This patent does not pay attention to the recovery and utilization of the residual cefotaxime active ester (cefotaxime sodium), and the atom economy is relatively poor. Summary of the Invention

[0008] The purpose of the present invention is to provide a method for recovering 2-mercaptobenzothiazole from the mother liquor of cefotaxime active ester production. By converting the residual cefotaxime active ester in the mother liquor into 2-mercaptobenzothiazole, on the one hand, more 2-mercaptobenzothiazole can be obtained; on the other hand, the oxidation side reaction of 2-mercaptobenzothiazole can also be inhibited.

[0009] To achieve the above purpose, the technical solution adopted by the present invention is: The method for recovering 2-mercaptobenzothiazole from the mother liquor of cefotaxime active ester production according to the present invention includes the following steps: (1) Distilling the mother liquor of cefotaxime active ester to obtain a heavy fraction; adding methanol and an antioxidant to the heavy fraction, adjusting the pH, and reacting to obtain a suspension; (2) Refining the suspension to obtain a decolorized solution, heating the decolorized solution and adding water, then adjusting the pH, keeping warm for crystallization, and performing hot filtration after crystallization to obtain 2-mercaptobenzothiazole.

[0010] Among them: The described cefotaxime active ester production mother liquor is obtained in an organic solvent by reacting cephalosporin side chain acid with dibenzothiazole disulfide under the reduction of triethyl phosphite, followed by reaction and purification to obtain the product cefotaxime active ester. The cefotaxime active ester production mother liquor contains cefotaxime active ester, 2-mercaptobenzothiazole, triethyl phosphate, and an organic solvent. The cephalosporin side chain acid is one of aztreonam acid, cefixime side chain acid, or cefdinir side chain acid.

[0011] In the described step (1), the distillation time is 20 - 30 min.

[0012] In the described step (1), in terms of mol, the addition amount of methanol is greater than that of cefotaxime active ester; the ratio of the addition amount of the antioxidant to the cefotaxime active ester production mother liquor is (1.5 - 3):1, with the antioxidant in g and the cefotaxime active ester production mother liquor in L.

[0013] In the described step (1), the antioxidant is prepared from 2,2,6,6-tetramethylpiperidine-1-oxyl radical, 2-mercaptoethyl oleate, and 4-dimethylaminopyridine. The molar ratio of 2,2,6,6-tetramethylpiperidine-1-oxyl radical, 2-mercaptoethyl oleate, and 4-dimethylaminopyridine is 1:(1.1 - 1.8):(0.2 - 0.5).

[0014] In the described step (1), the pH is adjusted to 7.5 - 7.9, the reaction temperature is 65 - 75 °C, and the reaction time is 1.5 - 2 h.

[0015] In the described step (2), the refining step includes decolorization with activated carbon and filtration. The decolorization temperature is 40 - 45 °C, and the decolorization time is 35 - 40 min.

[0016] In the described step (2), the volume ratio of water to the decolorized solution is (1 - 1.2):1.

[0017] In the described step (2), the pH is adjusted to 3 - 4.

[0018] In the described step (2), the crystallization temperature is 45 - 50 °C, and the crystallization time is 1.5 - 2.5 h.

[0019] The reaction equation of cephalosporin side chain acid (taking aztreonam acid as an example) and dibenzothiazole disulfide is as follows: .

[0020] The reaction equation for converting the residual cefotaxime active ester (taking cefixime side chain acid active ester as an example) into 2-mercaptobenzothiazole in the present invention is as follows: .

[0021] The beneficial effects of the present invention are as follows: (1) The prior art did not pay attention to the recycling of residual cefaclor active ester. The recovery rate only refers to the recovery rate when directly separating free MBT, and the residual cefaclor active ester in the untransformed mother liquor was not recycled, resulting in waste of resources. The present invention designs a reaction between methanol and cefaclor active ester to convert cefaclor active ester into MBT, which not only further improves the recovery rate of the target product MBT, but also avoids waste and significantly improves the atom economy.

[0022] (2) The risk of MBT being oxidized to DM was not fully considered in the prior art for recycling MBT. Currently, methods such as inert atmosphere and adding reducing agents (such as sodium sulfite) are generally used to reduce the risk of MBT being oxidized to DM, but the reducing agents in these methods are generally difficult to recycle, and the cost of large-scale industrial application is high. Maintaining an inert atmosphere (such as nitrogen protection) requires a special sealed reaction kettle or a continuous gas supply system, increasing equipment costs and operation complexity.

[0023] The present invention adds an antioxidant prepared from the main antioxidant 2,2,6,6-tetramethylpiperidine-1-oxyl radical (TEMPO), 2-mercaptoethyl oleate, and 4-dimethylaminopyridine (DMAP) to inhibit the oxidation of MBT through multiple mechanisms, ensuring the stable existence of MBT during the reaction and crystallization processes, avoiding conversion to DM or other by-products, thereby improving the recovery rate (both the residual MBT in the mother liquor and the MBT generated by the conversion of cefaclor active ester are effectively recovered) and purity of MBT. The recovery rate is close to 100%, and the economic benefits of the present invention will be further amplified during industrial application. In addition, the main antioxidant TEMPO can be recycled, and the residual liquid after recovering MBT can be recycled as an antioxidant, further reducing the cost during industrial production. In addition, the antioxidant of the present invention not only reduces the risk of oxidation of mercapto groups to disulfide bonds, but also has the effect of catalyzing the conversion of cefaclor active ester to MBT, enabling the full conversion of cefaclor active ester to MBT and realizing multiple functions with one agent.

[0024] The antioxidant is composed of 2,2,6,6-tetramethylpiperidine-1-oxyl radical (TEMPO), 2-mercaptoethyl oleate, and 4-dimethylaminopyridine (DMAP). The three act synergistically through the following mechanisms to inhibit the oxidation of MBT and realize multiple functions with one agent: 4-Dimethylaminopyridine can be used as both a substitution reaction catalyst and a metal chelating agent. Under weak alkaline conditions (pH = 7.5 - 7.9), the lone pair electrons on the pyridine nitrogen in its molecule can activate the nucleophilic reagent methanol, and methanol deprotonates to obtain CH3O - , and CH3O - attacks cefaclor active ester, accelerating the disintegration of the thioester bond. At the same time, due to reasons such as raw material purity and production processes, heavy metal ions will remain in the mother liquor of cefaclor chemical ester production. The nitrogen atom in the pyridine ring has a certain effect of complexing metal ions, which can inhibit the occurrence of the oxidation reaction of the mercapto group in MBT catalyzed by residual heavy metal ions.

[0025] The nitroxide radical (TEMPO·) in TEMPO can capture oxidative free radicals (such as HO·) to form stable adducts, thereby inhibiting the oxidation reaction. The non-polar long-chain alkyl group of 2-(ethylthio)ethyl oleate tends to be distributed in the non-polar organic phase (such as non-polar organic substances in the mother liquor), while the mercapto group and ester group are anchored in the polar phase (i.e., methanol), forming a micelle-like self-assembled structure. This self-assembled structure can guide the enrichment of TEMPO and 4-dimethylaminopyridine in the phase interface region between the polar phase and the non-polar phase. The nitroxide radical of TEMPO tends to stay in the polar phase, while the pyridine ring of 4-dimethylaminopyridine can complex with the polar end of the self-assembled structure, forming an interfacial antioxidant-catalytic microenvironment, significantly increasing the local concentrations of TEMPO and 4-dimethylaminopyridine; at the same time, 4-dimethylaminopyridine is basic and can provide a basic microenvironment for TEMPO; TEMPO has high stability especially under weakly basic conditions. At pH = 7.5 - 7.9, it will preferentially react with oxidative free radicals, more effectively protecting the mercapto group of MBT from being oxidized to a disulfide bond (-S-S-).

[0026] When the pH is adjusted to weakly basic after adding methanol in step (1), there is a phase interface between the polar phase and the non-polar phase, and there is a tendency for the local weak alkalinity to be too strong; in addition, both TEMPO and 4-dimethylaminopyridine show polarity, and there is a problem of poor contact with the non-polar organic phase in the resulting mother liquor. The 2-(ethylthio)ethyl oleate molecule in the present invention contains a mercapto group and an oleic acid ester long chain, has amphiphilicity, and can be used as a surfactant to reduce the interfacial tension, promote the mixing of the polar phase and the non-polar phase, and avoid side reactions caused by poor compatibility between the polar phase and the non-polar phase, resulting in too high local alkalinity (nucleophilic substitution reaction between MBT and residual halogenated hydrocarbon solvents such as dichloromethane in the mother liquor to generate sulfide by-products). The mercapto group in 2-(ethylthio)ethyl oleate acts as a hydrogen donor to reduce the oxidized nitroxide radical to the hydroxylamine form (TEMPO-H). Subsequently, TEMPO-H can be re-oxidized to the active TEMPO· in an oxidative environment (such as O2), forming a capture-regeneration cycle. The residual liquid after recovering 2-mercaptobenzothiazole can be recycled, reducing the cost in industrial production. Description of the Drawings

[0027] Figure 1 It is the high-performance liquid chromatography diagram of the final product in Example 1; Figure 2 It is the 1H NMR spectrum diagram of the final product in Example 1; Figure 3 It is the 1H NMR spectrum diagram of Compound Ι in the residual mother liquor after crystallization is completed in Example 1; Detailed Embodiments

[0028] The present invention will be specifically described and illustrated below in conjunction with examples.

[0029] Example 1 Collect the mother liquor from the production of cephalosporin active ester (take AE - active ester as an example): In dichloromethane solvent, aminothiazole acid reacts with dibenzothiazole disulfide under the action of triethyl phosphite, and AE - active ester is separated. The remaining liquid phase is the mother liquor from the production of cephalosporin active ester. The main components of the mother liquor from the production of cephalosporin active ester are 2 - mercaptobenzothiazole, AE - active ester, triethyl phosphate, dichloromethane and other colored impurities. 10 L of the mother liquor from the production of cephalosporin active ester is collected, which contains 630 g of free 2 - mercaptobenzothiazole and 142 g of 2 - mercaptobenzothiazole equivalent in AE - active ester.

[0030] Recover 2 - mercaptobenzothiazole from the mother liquor of cephalosporin active ester production: Prepare 100 g of antioxidant by mixing TEMPO, 2 - (ethylthio)ethyl oleate and 4 - dimethylaminopyridine in a molar ratio of 1:1.8:0.5 for standby; add 10 L of the mother liquor from the production of cephalosporin active ester to a rotary evaporation kettle, and perform vacuum distillation for 25 min to collect a dark red heavy fraction; add 250 ml of methanol (6.17 mol, 0.79 g / mL, 32 g / mol) and 15 g of antioxidant to the heavy fraction and mix well. Add a small amount of liquid alkali to adjust the pH to 7.5 - 7.9, heat up to 70 °C, stir and keep the temperature for reaction for 1.5 h. After the heat preservation is completed, a yellow suspension is obtained; after the suspension is cooled to 40 °C, add activated carbon and decolorize for 40 min, then cool to room temperature and filter to obtain a light yellow decolorized solution; transfer the decolorized solution to a reaction flask, heat up to above 40 °C and dropwise add water, where the volume ratio of water to the decolorized solution is 1:1. After dropping, adjust the pH of the decolorized solution to 3 - 4 with hydrochloric acid, keep the temperature at 48 °C for crystallization for 2 h. After crystallization is completed, filter while hot without cooling to obtain 777.5 g of the final product.

[0031] The final product is detected by a high - performance liquid chromatograph, and the ultraviolet - visible spectrogram is as Figure 1 shown, and nuclear magnetic resonance detection is carried out. The 1H NMR spectrogram is as Figure 2 shown, 1 1H NMR (600 MHz, DMSO) δ7.31 (s, 2H), δ7.40 (s, H), δ7.70 (s, H), δ13.77 (s, H), which confirms the obtained 2 - mercaptobenzothiazole. The purity of 2 - mercaptobenzothiazole in the final product is 98.4%, and the calculated recovery rate is 99.1%. The residual mother liquor after crystallization is purified to obtain compound Ι, and the 1H NMR spectrogram of compound Ι is as Figure 3 shown.

[0032] Example 2 Collect the mother liquor from the production of cephalosporin active ester (take the active ester of cefixime side chain acid as an example): In dichloromethane solvent, cefixime side chain acid reacts with dibenzothiazole disulfide under the action of triethyl phosphite, and cefixime side chain acid active ester is separated. The remaining liquid phase is the mother liquor for the production of cefactive ester. The main components of the mother liquor for the production of cefactive ester are 2-mercaptobenzothiazole, cefixime side chain acid active ester, triethyl phosphate, dichloromethane and other colored impurities. 10 L of the mother liquor for the production of cefactive ester is collected, which contains 1624 g of free 2-mercaptobenzothiazole and 393 g of 2-mercaptobenzothiazole equivalent in cefixime side chain acid active ester.

[0033] Recovery of 2-mercaptobenzothiazole from the mother liquor for the production of cefactive ester: Prepare 100 g of antioxidant in accordance with the molar ratio of TEMPO, 2-(ethylthio)ethyl oleate and 4-dimethylaminopyridine being 1: 1.1: 0.4 for standby; add 10 L of the mother liquor for the production of cefactive ester to a rotary evaporation kettle, carry out vacuum distillation for 30 min, and collect the dark red heavy distillate; add 250 ml of methanol and 30 g of antioxidant to the heavy distillate for blending, add a small amount of liquid alkali, adjust the pH to 7.5 - 7.9, raise the temperature to 75 °C, stir and keep the temperature for reaction for 1.6 h, and obtain a yellow suspension after the heat preservation ends; after the suspension is cooled to 45 °C, add activated carbon, decolorize for 35 min, cool to room temperature, and filter to obtain a light yellow decolorized solution; transfer the decolorized solution to a reaction flask, raise the temperature above 40 °C and dropwise add water, where the volume ratio of water to the decolorized solution is 1.1:1. After dropping, adjust the pH of the decolorized solution to 3 - 4 with hydrochloric acid, keep the temperature at 45 °C for crystallization for 2.5 h, and filter while hot without cooling after the crystallization is completed to obtain 2015 g of the final product.

[0034] Using a high performance liquid chromatograph for detection, the purity of 2-mercaptobenzothiazole in the final product is 98.9%, and the calculated recovery rate is 98.8%.

[0035] Example 3 Collect the mother liquor for the production of cefactive ester (taking cefdinir active ester as an example): In dichloromethane solvent, cefdinir side chain acid reacts with dibenzothiazole disulfide under the action of triethyl phosphite, and cefdinir active ester is separated. The remaining liquid phase is the mother liquor for the production of cefactive ester. The main components of the mother liquor for the production of cefactive ester are 2-mercaptobenzothiazole, cefdinir active ester, triethyl phosphate, dichloromethane and other colored impurities. 10 L of the mother liquor for the production of cefactive ester is collected, which contains 1032 g of free 2-mercaptobenzothiazole and 103 g of 2-mercaptobenzothiazole equivalent in cefdinir active ester.

[0036] Recovery of 2-mercaptobenzothiazole from the mother liquor for the production of cefactive ester: Prepare 100 g of antioxidant in accordance with the molar ratio of TEMPO, 2-(ethylthio)ethyl oleate and 4-dimethylaminopyridine being 1:1.5:0.2 for standby; add 10 L of cephalosporin active ester production mother liquor into a rotary evaporation kettle, perform vacuum distillation for 20 min, and collect the dark red heavy fraction; add 250 ml of methanol and 28 g of antioxidant to the heavy fraction for blending, add a small amount of liquid alkali, adjust the pH to 7.5 - 7.9, raise the temperature to 65 °C, stir and keep the temperature for reaction for 2 h, and obtain a light yellow suspension after the heat preservation ends; after the suspension cools to 41 °C, add activated carbon, decolorize for 39 min, cool to room temperature, and filter to obtain an off-white decolorized liquid; transfer the decolorized liquid to a reaction flask, raise the temperature to above 40 °C and add water dropwise, where the volume ratio of water to the decolorized liquid is 1.2:1, after dropping, adjust the pH of the decolorized liquid to 3 - 4 with hydrochloric acid, keep the temperature at 50 °C for crystal precipitation for 1.5 h, and obtain 1139 g of the final product by hot filtration without cooling after crystal precipitation is completed.

[0037] Detect using a high performance liquid chromatograph. The purity of 2-mercaptobenzothiazole in the final product is 98.2%, and the calculated recovery rate is 98.5%.

[0038] Comparative Example 1 Replace the antioxidant with vitamin C, and keep the remaining steps and raw materials the same as in Example 1 to obtain the final product. Detect using a high performance liquid chromatograph. The purity of 2-mercaptobenzothiazole in the final product is 90.2%, and the calculated recovery rate is 80.2%.

[0039] Comparative Example 2 Replace the antioxidant with sodium sulfite, and keep the remaining steps and raw materials the same as in Example 1 to obtain the final product. Detect using a high performance liquid chromatograph. The purity of 2-mercaptobenzothiazole in the final product is 91.3%, and the calculated recovery rate is 81.5%.

[0040] Comparative Example 3 Do not add 2,2,6,6-tetramethylpiperidine-1-oxyl radical, and keep the remaining steps and raw materials the same as in Example 1 to obtain the final product. Detect using a high performance liquid chromatograph. The purity of 2-mercaptobenzothiazole in the final product is 89.6%, and the calculated recovery rate is 68.1%.

[0041] Comparative Example 4 Do not add 2-(ethylthio)ethyl oleate, and keep the remaining steps and raw materials the same as in Example 1 to obtain the final product. Detect using a high performance liquid chromatograph. The purity of 2-mercaptobenzothiazole in the final product is 93.2%, and the calculated recovery rate is 88.0%.

[0042] Comparative Example 5 Without adding 4-dimethylaminopyridine, the remaining steps and raw materials are the same as those in Example 1, and the final product is obtained. The purity of 2-mercaptobenzothiazole in the final product is detected by a high-performance liquid chromatograph, and the recovery rate is calculated to be 90.9%.

[0043] In the present invention, only AE-active ester, cefixime side-chain acid active ester and cefdinir active ester are taken as examples to detail the specific operation steps of the recovery method, and it is verified that the recovery method of the present invention can efficiently recover 2-mercaptobenzothiazole with a recovery rate close to 100%. However, the present invention is not limited thereto, and it is also applicable to other types of cephalosporin active esters. The operation steps are the same as those in the technical solution part of the present invention and will not be elaborated here.

Claims

1. A method for recovering 2-mercaptobenzothiazole from the mother liquor of cephalosporin active ester production, characterized in that, It includes the following steps: (1) Distill the mother liquor for cefotaxime active ester production to obtain a heavy fraction; add methanol and an antioxidant to the heavy fraction, adjust the pH, and react to obtain a suspension; (2) Refine the suspension to obtain a decolorized solution, heat the decolorized solution and add water, then adjust the pH, keep warm for crystallization, and after the crystallization is completed, perform hot filtration to obtain 2-mercaptobenzothiazole.

2. The method for recovering 2-mercaptobenzothiazole from the mother liquor of cephalosporin active ester according to claim 1, characterized in that, The mother liquor for cefotaxime active ester production is obtained after reacting cefotaxime side-chain acid with dibenzothiazole disulfide under the reduction of triethyl phosphite in an organic solvent, reacting, and purifying to obtain the product cefotaxime active ester. The mother liquor for cefotaxime active ester production contains cefotaxime active ester, 2-mercaptobenzothiazole, triethyl phosphate, and an organic solvent. The cefotaxime side-chain acid is one of amoxicillin acid, cefixime side-chain acid, or cefdinir side-chain acid.

3. The method for recovering 2-mercaptobenzothiazole from the mother liquor of cephalosporin active ester production according to claim 1, characterized in that, In step (1), the distillation time is 20 - 30 min.

4. The method for recovering 2-mercaptobenzothiazole from the mother liquor of cephalosporin active ester production according to claim 2, characterized in that, In step (1), calculated in mol, the addition amount of methanol is greater than that of cefotaxime active ester; the ratio of the addition amount of the antioxidant to the mother liquor for cefotaxime active ester production is (1.5 - 3):1, with the antioxidant in g and the mother liquor for cefotaxime active ester production in L.

5. The method for recovering 2-mercaptobenzothiazole from the mother liquor of cephalosporin active ester production according to claim 1, characterized in that, In step (1), the antioxidant is prepared from 2,2,6,6-tetramethylpiperidine-1-oxyl radical, ethyl mercapto oleate, and 4-dimethylaminopyridine. The molar ratio of 2,2,6,6-tetramethylpiperidine-1-oxyl radical, ethyl mercapto oleate, and 4-dimethylaminopyridine is 1:(1.1 - 1.8):(0.2 - 0.5).

6. The method for recovering 2-mercaptobenzothiazole from the mother liquor of cephalosporin active ester production according to claim 1, characterized in that, In step (1), adjust the pH to 7.5 - 7.9, the reaction temperature is 65 - 75 °C, and the reaction time is 1.5 - 2 h.

7. The method for recovering 2-mercaptobenzothiazole from the mother liquor of cephalosporin active ester production according to claim 1, characterized in that, In step (2), the refining step includes decolorization with activated carbon and filtration. The decolorization temperature is 40 - 45 °C, and the decolorization time is 35 - 40 min.

8. The method for recovering 2-mercaptobenzothiazole from the mother liquor of cefaclor active ester according to claim 1, characterized in that, In step (2), the volume ratio of water to the decolorized solution is (1 - 1.2):

1.

9. The method for recovering 2-mercaptobenzothiazole from the mother liquor of cephalosporin active ester production according to claim 1, characterized in that, In step (2), adjust the pH to 3 - 4.

10. The method for recovering 2-mercaptobenzothiazole from the mother liquor of cephalosporin active ester production according to claim 1, characterized in that, In step (2), the crystallization temperature is 45 - 50 °C, and the crystallization time is 1.5 - 2.5 h.

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