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

Abstract

The present invention belongs to the technical field of heterocyclic compounds, and specifically relates to a method for recovering 2-mercaptobenzothiazole from a mother liquor produced by the production of cephalosporin active esters. The recovery method comprises the following steps: (1) distilling the mother liquor produced by the production of cephalosporin active esters 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 decolorant, heating the decolorant and adding water, then adjusting the pH, keeping the temperature and crystallizing, and after the crystallization is completed, hot filtering to obtain 2-mercaptobenzothiazole. The present invention suppresses the oxidation of 2-mercaptobenzothiazole by multiple mechanisms by adding an antioxidant prepared from a main antioxidant 2,2,6,6-tetramethylpiperidin-1-oxyl free radical, mercaptoethyl oleate, and 4-dimethylaminopyridine, thereby ensuring the stable presence of 2-mercaptobenzothiazole during the reaction and crystallization process, and avoiding conversion into byproducts such as dibenzothiazole disulfide, thereby improving the recovery rate and purity of MBT.

Description

Technical Field

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

[0002] 2-Mercaptobenzothiazole, abbreviated as MBT, is a pale yellow monoclinic needle-shaped or leaf-shaped crystal at room temperature. The thiazole ring and mercapto group in 2-mercaptobenzothiazole have 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 properties 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 the synthesis of cephalosporin active esters. The synthesis route involves the reaction of DM with cephalosporin side chain acids (such as aminothioxamic acid and ceftazidime side chain acids) in the presence of a catalyst such as triethyl phosphite. Purification and separation yield high-purity cephalosporin active esters and a reaction mother liquor. This reaction mother liquor contains various byproducts, such as residual cephalosporin active esters and 2-mercaptobenzothiazole after purification. The thiol group in 2-mercaptobenzothiazole is highly reactive and can be oxidized to DM under mild conditions. Therefore, direct isolation of 2-mercaptobenzothiazole results in a difficult recovery rate, hindering its industrialization.

[0004] Generally, 2-mercaptobenzothiazole is not directly recovered from the mother liquor of ceftriaxone production. Instead, 2-mercaptobenzothiazole must first be actively oxidized to dibenzothiazole disulfide. The chemical stability of dibenzothiazole disulfide is utilized to avoid various side reactions in the direct recovery of 2-mercaptobenzothiazole. For example, Chinese patent CN110330466A discloses a method for recovering DM from a mother liquor produced by the production of cephalosporin active esters. The method comprises adjusting the pH of the mother liquor produced by the production of cephalosporin active esters to 4.0-6.5, adding activated carbon, heating the mixture for decolorization, filtering, transferring the filtrate to a high-pressure reactor, adding a catalyst, passing oxygen through the reaction, and filtering to obtain DM. The main components of the mother liquor produced by the production of cephalosporin active esters are a mixed solvent consisting of 2-mercaptobenzothiazole, triethyl phosphate, triethyl phosphite, impurities, dichloromethane, and acetonitrile. 2-mercaptobenzothiazole is unstable and can react chemically with the solvent dichloromethane under certain conditions. Therefore, the patent adopts a free radical-induced catalytic oxidation process to oxidize the 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, the recovered dibenzothiazole disulfide is reduced to 2-mercaptobenzothiazole. During this process, the pH and temperature must be strictly controlled, which further increases the difficulty and cost of the operation and is not conducive to industrial production.

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

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

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

[0009] To achieve the above object, the technical solution adopted by the present invention is:

[0010] The method for recovering 2-mercaptobenzothiazole from the mother liquor of cefuroxime active ester production of the present invention comprises the following steps:

[0011] (1) distilling the mother liquor produced by the production of cephalosporin 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;

[0012] (2) The suspension is purified to obtain a decolorized solution, which is heated and water is added, followed by adjusting the pH value and preserving the temperature for crystallization. After the crystallization is completed, hot filtration is performed to obtain 2-mercaptobenzothiazole.

[0013] in:

[0014] The cephalosporin active ester production mother liquor is obtained by reacting a cephalosporin side chain acid with dibenzothiazole disulfide in an organic solvent under the reduction action of triethyl phosphite, and then purifying the cephalosporin active ester product. The cephalosporin active ester production mother liquor contains the cephalosporin active ester, 2-mercaptobenzothiazole, triethyl phosphate and an organic solvent, and the cephalosporin side chain acid is one of aminothioxime acid, cefixime side chain acid or cefdinir side chain acid.

[0015] In the step (1), the distillation time is 20 to 30 minutes.

[0016] In the step (1), the amount of methanol added is greater than that of the cephalosporin active ester in mol; the ratio of the amount of antioxidant added to the amount of the cephalosporin active ester production mother liquor added is (1.5-3):1, the antioxidant is measured in g, and the cephalosporin active ester production mother liquor is measured in L.

[0017] In the step (1), the antioxidant is prepared from 2,2,6,6-tetramethylpiperidin-1-oxyl free radical, oleic acid ethyl mercaptoethyl ester and 4-dimethylaminopyridine, and the molar ratio of 2,2,6,6-tetramethylpiperidin-1-oxyl free radical, oleic acid ethyl mercaptoethyl ester and 4-dimethylaminopyridine is 1:(1.1~1.8):(0.2~0.5).

[0018] In the step (1), the pH is adjusted to 7.5-7.9, the reaction temperature is 65-75°C, and the reaction time is 1.5-2h.

[0019] In the step (2), the refining step includes activated carbon decolorization and filtration, the decolorization temperature is 40-45°C, and the decolorization time is 35-40 minutes.

[0020] In the step (2), the volume ratio of water to decolorizing solution is (1-1.2):1.

[0021] In the step (2), the pH is adjusted to 3-4.

[0022] In the step (2), the crystallization temperature is 45-50° C., and the crystallization time is 1.5-2.5 h.

[0023] The reaction equation of cephalosporin side chain acid (taking aminothioxamic acid as an example) and dibenzothiazyl disulfide is as follows:

[0024] .

[0025] The reaction equation for converting the residual cephalosporin active ester (taking cefixime side chain acid active ester as an example) into 2-mercaptobenzothiazole is as follows:

[0026] .

[0027] The beneficial effects of the present invention are as follows:

[0028] (1) The prior art does not focus on the recovery and utilization of residual cephalosporin active esters. The recovery rate only refers to the recovery rate when free MBT is directly separated. The residual cephalosporin active esters in the mother liquor are not converted, resulting in a waste of resources. The present invention converts the cephalosporin active esters into MBT by designing a reaction between methanol and cephalosporin active esters, which not only further improves the recovery rate of the target product MBT, but also avoids waste and significantly improves the atom economy.

[0029] (2) Existing MBT recovery technologies do not adequately address the risk of MBT being oxidized to DM. Currently, the risk of MBT being oxidized to DM is generally reduced by using inert atmospheres or by adding reducing agents (e.g., sodium sulfite). However, the reducing agents in these methods are generally difficult to recycle, and the cost of large-scale industrial applications is high. Maintaining an inert atmosphere (e.g., nitrogen protection) requires a dedicated sealed reactor or a continuous gas supply system, which increases equipment cost and operational complexity.

[0030] The present invention adds an antioxidant prepared from a main antioxidant, 2,2,6,6-tetramethylpiperidin-1-oxyl (TEMPO), mercaptoethyl oleate, and 4-dimethylaminopyridine (DMAP), to inhibit MBT oxidation through multiple mechanisms, ensuring the stable presence of MBT during the reaction and crystallization process and preventing conversion to DM or other byproducts. This improves the recovery rate of MBT (both residual MBT in the mother liquor and MBT generated by conversion of the cephalosporin active ester are effectively recovered) and the purity. The recovery rate approaches 100%, and the economic benefits of the present invention will be further amplified when applied industrially. In addition, the main antioxidant TEMPO is recyclable, and the residual liquid after recovering MBT can be recycled as an antioxidant, further reducing the cost of industrial production. In addition, the antioxidant of the present invention not only reduces the risk of sulfhydryl oxidation to disulfide bonds, but also catalyzes the conversion of the cephalosporin active ester into MBT, allowing the cephalosporin active ester to be fully converted into MBT, achieving multiple uses with one dose.

[0031] The antioxidant is composed of 2,2,6,6-tetramethylpiperidin-1-oxyl radical (TEMPO), mercaptoethyl oleate and 4-dimethylaminopyridine (DMAP). The three work synergistically through the following mechanisms to inhibit MBT oxidation, achieving multiple uses with one dose:

[0032] 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 of electrons on the pyridine nitrogen in the molecule can activate the nucleophilic reagent methanol, which is deprotonated to produce CH3O - , CH3O -Attack on the active cephalosporin ester, accelerate the disintegration of the thioester bond; at the same time, due to reasons such as raw material purity and production process, heavy metal ions will remain in the mother liquor of cephalosporin chemical ester production. The nitrogen atom in the pyridine ring has a certain function of complexing metal ions, which can inhibit the occurrence of sulfhydryl oxidation reaction in MBT catalyzed by residual heavy metal ions.

[0033] The nitroxide radical (TEMPO·) in TEMPO can capture oxidative free radicals (such as HO·) to form stable adducts, thereby inhibiting oxidation reactions. The nonpolar long-chain alkyl groups of mercaptoethyl oleate tend to be distributed in the nonpolar organic phase (such as the nonpolar organic matter in the mother liquor), while the thiol and ester groups 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 at the interface between the polar and nonpolar phases. The nitroxide radical of TEMPO tends to stay in the polar phase, while the pyridine ring of 4-dimethylaminopyridine can be complexed with the polar end of the self-assembled structure to form an interfacial antioxidant-catalytic microenvironment, significantly increasing the local concentrations of TEMPO and 4-dimethylaminopyridine; at the same time, 4-dimethylaminopyridine is alkaline and can provide an alkaline microenvironment for TEMPO; TEMPO is particularly stable under weakly alkaline conditions. At pH = 7.5~7.9, it will preferentially react with oxidative free radicals, more effectively protecting the sulfhydryl group of MBT from being oxidized to disulfide bonds (-SS-).

[0034] When the pH is adjusted to a weak alkaline state after adding methanol in step (1), a phase interface between the polar phase and the non-polar phase exists, which can easily lead to a phenomenon of excessively strong weak alkalinity in the local area. In addition, both TEMPO and 4-dimethylaminopyridine exhibit polarity, resulting in poor contact with the non-polar organic phase in the generated mother liquor. The oleic acid mercaptoethyl ester molecules of the present invention contain a mercapto group and a long oleate chain, and are amphiphilic. They can act as a surfactant to reduce interfacial tension, promote mixing of the polar phase and the non-polar phase, and avoid the occurrence of excessively high local alkalinity due to poor compatibility between the polar phase and the non-polar phase, thereby avoiding the occurrence of side reactions (MBT undergoes nucleophilic substitution reactions with residual halogenated hydrocarbon solvents in the mother liquor, such as dichloromethane, to generate thioether byproducts). The thiol group in mercaptoethyl oleate acts as a hydrogen donor, reducing the oxidized nitroxide free radical to the hydroxylamine form (TEMPO-H). Subsequently, TEMPO-H can be re-oxidized to active TEMPO· in an oxidizing environment (such as O2), forming a capture-regeneration cycle. The residual liquid after recovering 2-mercaptobenzothiazole can be recycled, reducing the cost of industrial production. BRIEF DESCRIPTION OF THE DRAWINGS

[0035] Figure 1 This is the HPLC chromatogram of the final product in Example 1;

[0036] Figure 2 This is the H NMR spectrum of the final product in Example 1;

[0037] Figure 3 This is the H NMR spectrum of Compound 1 in the mother liquor remaining after crystallization in Example 1; DETAILED DESCRIPTION

[0038] The present invention is described and illustrated in detail below with reference to the embodiments.

[0039] Example 1

[0040] Collect the mother liquor of cephalosporin active ester production (taking AE-active ester as an example):

[0041] In a dichloromethane solvent, aminothioxamic acid reacts with dibenzothiazole disulfide in the presence of triethyl phosphite to separate and obtain AE-active ester. The remaining liquid phase is the mother liquor for the production of cephalosporin-active ester. The main components of the mother liquor for 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 for the production of cephalosporin-active ester was collected, which contained 630 g of free 2-mercaptobenzothiazole and 142 g of 2-mercaptobenzothiazole in the AE-active ester.

[0042] Recovery of 2-mercaptobenzothiazole from the mother liquor of ceftriaxone production:

[0043] 100 g of antioxidant was prepared according to the molar ratio of TEMPO, mercaptoethyl oleate and 4-dimethylaminopyridine of 1: 1.8: 0.5; 10 L of the mother liquor of cephalosporin active ester production was added to a rotary evaporator and distilled under reduced pressure for 25 min to collect the dark red heavy fraction; 250 ml of methanol (6.17 mol 0.79 g / mL) was added to the heavy fraction. The mixture was mixed with 15 g of an antioxidant (32 g / mol), a small amount of liquid alkali was added, the pH was adjusted to 7.5-7.9, the temperature was raised to 70°C, and the mixture was stirred and kept warm for 1.5 h. After the insulation, a yellow suspension was obtained. The suspension was cooled to 40°C and activated carbon was added for decolorization for 40 min. The mixture was cooled to room temperature and filtered to obtain a light yellow decolorized liquid. The decolorized liquid was transferred to a reaction flask, the temperature was raised to above 40°C, and water was added dropwise in a volume ratio of water to decolorized liquid of 1:1. After the addition was completed, the pH of the decolorized liquid was adjusted to 3-4 with hydrochloric acid, and the mixture was kept warm at 48°C for 2 h for crystallization. After the crystallization was completed, hot filtration was performed without cooling to obtain 777.5 g of the final product.

[0044] The final product was tested by high performance liquid chromatography, and the UV-visible spectrum was as follows Figure 1 As shown, nuclear magnetic resonance detection was performed, and the nuclear magnetic hydrogen spectrum was as shown Figure 2 As shown, 1H NMR (600 MHz, DMSO) δ7.31 (s, 2H), δ7.40 (s, H), δ7.70 (s, H), δ13.77 (s, H) confirmed the yield of 2-mercaptobenzothiazole. The purity of 2-mercaptobenzothiazole in the final product was 98.4%, and the calculated recovery rate was 99.1%. The mother liquor remaining after crystallization was purified to obtain compound I. Compound I was subjected to nuclear magnetic resonance (NMR) detection, and the H NMR spectrum was as shown below. Figure 3 shown.

[0045] Example 2

[0046] Collect the mother liquor of cephalosporin active ester production (taking cefixime side chain acid active ester as an example):

[0047] In a dichloromethane solvent, cefixime side chain acid reacts with dibenzothiazole disulfide in the presence of triethyl phosphite to separate the cefixime side chain acid active ester. The remaining liquid phase is the cefixime active ester production mother liquor. The main components of the cefixime active ester production mother liquor are 2-mercaptobenzothiazole, cefixime side chain acid active ester, triethyl phosphate, dichloromethane, and other colored impurities. 10 L of the cefixime active ester production mother liquor was collected, which contained 1624 g of free 2-mercaptobenzothiazole and 393 g of 2-mercaptobenzothiazole from the cefixime side chain acid active ester.

[0048] Recovery of 2-mercaptobenzothiazole from the mother liquor of ceftriaxone production:

[0049] The molar ratio of TEMPO, mercaptoethyl oleate and 4-dimethylaminopyridine is 1: 1.1: The method comprises the following steps: preparing 100 g of an antioxidant at a ratio of 0.4 for standby use; adding 10 L of cephalosporin active ester production mother liquor into a rotary evaporator, performing reduced pressure distillation for 30 min, and collecting a dark red heavy fraction; adding 250 ml of methanol and 30 g of an antioxidant to the heavy fraction, adding a small amount of liquid alkali, adjusting the pH to 7.5-7.9, heating to 75° C., stirring and keeping warm for 1.6 h, and obtaining a yellow suspension after the insulation is completed; cooling the suspension to 45° C., adding activated carbon, decolorizing for 35 min, cooling to room temperature, and filtering to obtain a light yellow decolorized liquid; transferring the decolorized liquid into a reaction flask, heating to above 40° C., and adding water dropwise, wherein the volume ratio of water to the decolorized liquid is 1.1:1; adjusting the pH of the decolorized liquid to 3-4 with hydrochloric acid after the addition is completed, keeping warm at 45° C. for crystallization for 2.5 h, and hot filtering without cooling after the crystallization is completed to obtain 2015 g of the final product.

[0050] The purity of 2-mercaptobenzothiazole in the final product was 98.9% as determined by high performance liquid chromatography, and the recovery rate was calculated to be 98.8%.

[0051] Example 3

[0052] Collect the mother liquor of cefuroxime active ester production (taking cefdinir active ester as an example):

[0053] In a dichloromethane solvent, the cefdinir side chain acid reacts with dibenzothiazole disulfide in the presence of triethyl phosphite to separate the cefdinir active ester. The remaining liquid phase is the cefdinir active ester production mother liquor. The main components of the cefdinir active ester production mother liquor are 2-mercaptobenzothiazole, cefdinir active ester, triethyl phosphate, dichloromethane, and other colored impurities. 10 L of the cefdinir active ester production mother liquor was collected, which contained 1032 g of free 2-mercaptobenzothiazole and 103 g of 2-mercaptobenzothiazole in the cefdinir active ester.

[0054] Recovery of 2-mercaptobenzothiazole from the mother liquor of ceftriaxone production:

[0055] The molar ratio of TEMPO, mercaptoethyl oleate and 4-dimethylaminopyridine is 1: 1.5: The method comprises the following steps: preparing 100 g of an antioxidant at a ratio of 0.2 for standby use; adding 10 L of cephalosporin active ester production mother liquor into a rotary evaporator, performing reduced pressure distillation for 20 min, and collecting a dark red heavy fraction; adding 250 ml of methanol and 28 g of an antioxidant to the heavy fraction, adding a small amount of liquid alkali, adjusting the pH to 7.5-7.9, heating to 65° C., stirring and keeping warm for 2 h, and obtaining a light yellow suspension after the insulation is completed; cooling the suspension to 41° C., adding activated carbon, decolorizing for 39 min, cooling to room temperature, and filtering to obtain an off-white decolorized liquid; transferring the decolorized liquid into a reaction flask, heating to above 40° C., and adding water dropwise, wherein the volume ratio of water to the decolorized liquid is 1.2:1; adjusting the pH of the decolorized liquid to 3-4 with hydrochloric acid after the addition is completed, keeping warm at 50° C. for crystallization for 1.5 h, and hot filtering without cooling after the crystallization is completed to obtain 1139 g of the final product.

[0056] The purity of 2-mercaptobenzothiazole in the final product was 98.2% as determined by high performance liquid chromatography, and the recovery rate was calculated to be 98.5%.

[0057] Comparative Example 1

[0058] The antioxidant was replaced with vitamin C, and the remaining steps and raw materials were the same as in Example 1 to obtain a final product. The purity of 2-mercaptobenzothiazole in the final product was 90.2% when detected by high performance liquid chromatography, and the calculated recovery rate was 80.2%.

[0059] Comparative Example 2

[0060] The antioxidant was replaced by sodium sulfite, and the remaining steps and raw materials were the same as in Example 1 to obtain a final product. The purity of 2-mercaptobenzothiazole in the final product was 91.3% using a high performance liquid chromatography (HPLC) instrument, and the calculated recovery rate was 81.5%.

[0061] Comparative Example 3

[0062] Without adding 2,2,6,6-tetramethylpiperidin-1-oxyl free radical, the remaining steps and raw materials were the same as in Example 1 to obtain a final product. The purity of 2-mercaptobenzothiazole in the final product was 89.6% by high performance liquid chromatography, and the calculated recovery rate was 68.1%.

[0063] Comparative Example 4

[0064] Without adding mercaptoethyl oleate, the remaining steps and raw materials were the same as in Example 1 to obtain a final product. The purity of 2-mercaptobenzothiazole in the final product was 93.2% by high performance liquid chromatography, and the calculated recovery rate was 88.0%.

[0065] Comparative Example 5

[0066] Without adding 4-dimethylaminopyridine, the remaining steps and raw materials were the same as in Example 1 to obtain a final product. The purity of 2-mercaptobenzothiazole in the final product was 95.5% by high performance liquid chromatography, and the calculated recovery rate was 90.9%.

[0067] The present invention only takes AE-active ester, cefixime side chain acid active ester and cefdinir active ester as examples to describe in detail the specific operating steps of the recovery method, and verifies that the recovery method of the present invention can efficiently recover 2-mercaptobenzothiazole with a recovery rate of nearly 100%. However, the present invention is not limited to this and is also applicable to other types of cephalosporin active esters. The operating steps are partially the same as those in the technical solution of the present invention and are not repeated here.

Claims

1. A method for recovering 2-mercaptobenzothiazole from a mother liquor produced by the production of a cefuroxime active ester, characterized in that: The following steps are involved: (1) distilling the mother liquor produced by the production of cephalosporin 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 the solution warm for crystallization, and filtering the solution hot after the crystallization is completed to obtain 2-mercaptobenzothiazole; The mother liquor for producing the cephalosporin active ester is prepared in an organic solvent by reacting the cephalosporin side chain acid with dibenzothiazole disulfide under the reduction action of triethyl phosphite, and then purifying the cephalosporin active ester product; the cephalosporin side chain acid is one of aminothioxime acid, cefixime side chain acid or cefdinir side chain acid; and the antioxidant is prepared from 2,2,6,6-tetramethylpiperidin-1-oxyl free radical, oleic acid mercaptoethyl ester and 4-dimethylaminopyridine.

2. The method for recovering 2-mercaptobenzothiazole from the mother liquor of cefuroxime active ester production according to claim 1, wherein The mother liquor for producing the active cephalosporin ester contains the active cephalosporin ester, 2-mercaptobenzothiazole, triethyl phosphate and an organic solvent.

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

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

5. The method for recovering 2-mercaptobenzothiazole from the mother liquor of cefuroxime active ester production according to claim 1, characterized in that: In step (1), the molar ratio of 2,2,6,6-tetramethylpiperidin-1-oxyl free radical, mercaptoethyl 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 cefuroxime active ester production according to claim 1, characterized in that: In step (1), the pH is adjusted to 7.5-7.9, the reaction temperature is 65-75°C, and the reaction time is 1.5-2h.

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

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

1.

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

10. The method for recovering 2-mercaptobenzothiazole from the mother liquor of cefuroxime 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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