Method for recovering N-hydroxymethyl phthalimide from 4-AA key intermediate residues

Abstract

The invention belongs to the technical field of preparation of chemical intermediates, and particularly relates to a method for recovering N-hydroxymethyl phthalimide from 4-AA key intermediate residues. Comprising the following steps: (1) distillation: filtering and distilling toluene mother liquor generated in preparation of 4-AA key intermediate 2-(N-phthalimido methyl)-3-oxobutyric acid methyl ester to obtain a toluene solvent and concentrated residues, and recycling the toluene solvent; (2) hydrolysis: a hydrolysis reagent is added into the concentrated residues, the weight ratio of the concentrated residues to the hydrolysis reagent is 1: (1.1-4), the temperature is increased to 30-100 DEG C, heat preservation hydrolysis is conducted for 1-10 h under stirring, and a hydrolysis product is obtained; and (3) recovery: cooling the hydrolysis product, crystallizing, filtering, and washing with water to obtain the N-hydroxymethyl phthalimide. According to the method, effective components in the hazardous waste can be recovered, so that the discharge of the hazardous waste is reduced, and the hazardous waste treatment cost is reduced.

Description

Technical Field

[0001] The invention belongs to the technical field of chemical intermediate preparation, and in particular relates to a method for recovering N-hydroxymethylphthalimide from 4-AA key intermediate residue. Background Art

[0002] 4-AA key intermediate 2-(N-phthalimidomethyl)-3-oxobutyric acid methyl ester is an organic compound and a key intermediate for preparing carbapenem intermediate 4-AA. It is prepared from chloromethylphthalimide, methyl acetoacetate and sodium methoxide as reactants with a yield of about 90%. The remaining 10% is residue, which needs to be treated as hazardous waste and is not environmentally friendly. The main components of the residue are 2,2-bis(N-phthalimidomethyl)-3-oxobutyric acid methyl ester (about 38%) and 2-(N-phthalimidomethyl)-3-oxobutyric acid methyl ester (about 58%). Summary of the invention

[0003] The object of the present invention is to provide a method for recovering N-hydroxymethylphthalimide from 4-AA key intermediate residue, so as to solve the problems existing in the prior art.

[0004] The technical solution adopted by the present invention to solve its technical problem is:

[0005] A method for recovering N-hydroxymethylphthalimide from 4-AA key intermediate residue comprises the following steps:

[0006] (1) Distillation: Filter and distill the toluene mother liquor produced by the preparation of methyl 2-(N-phthalimidomethyl)-3-oxobutanoate, a key intermediate of 4-AA, to obtain a toluene solvent and a concentrated residue, and recover the toluene solvent for reuse;

[0007] (2) hydrolysis: adding a hydrolysis reagent to the concentrated residue, with the weight ratio of the concentrated residue to the hydrolysis reagent being 1:(1.1-4), heating to 30-100° C., and hydrolyzing for 1-10 hours under stirring to obtain a hydrolyzate;

[0008] (3) Recovery: The hydrolysis product is cooled, crystallized, filtered, and washed with water to obtain N-hydroxymethylphthalimide, which is then used in the preparation of methyl 2-(N-phthalimidomethyl)-3-oxobutyrate, a key intermediate of 4-AA.

[0009] Furthermore, in step (2), the weight ratio of the concentrated residue to the hydrolysis reagent is 1:3.

[0010] Furthermore, in step (2), the hydrolysis reagent is any one of liquid alkali, hydrochloric acid, sulfuric acid, potassium hydroxide aqueous solution, sodium carbonate aqueous solution, and potassium carbonate aqueous solution.

[0011] Furthermore, the hydrolysis temperature in step (2) is 60°C.

[0012] Furthermore, the duration of the hydrolysis in step (2) is 2 hours.

[0013] The invention has the following beneficial effects: the invention firstly recovers toluene from hazardous waste generated by preparing 4-AA key intermediate 2-(N-phthalimidomethyl)-3-oxobutyric acid methyl ester, and then hydrolyzes the effective components 2,2-bis(N-phthalimidomethyl)-3-oxobutyric acid methyl ester (about 38%) and 2-(N-phthalimidomethyl)-3-oxobutyric acid methyl ester (about 58%) to obtain N-hydroxymethylphthalimide, a starting material for preparing 4-AA key intermediate 2-(N-phthalimidomethyl)-3-oxobutyric acid methyl ester, and the recovered material is then chlorinated with thionyl chloride and condensed with methyl acetoacetate to obtain 4-AA key intermediate 2-(N-phthalimidomethyl)-3-oxobutyric acid methyl ester, thereby realizing the reuse of hazardous waste, reducing the emission of hazardous waste, and reducing the cost of hazardous waste treatment. DETAILED DESCRIPTION

[0014] In order to make the purpose, technical solution and advantages of the present invention more clearly understood, the present invention is further described in detail below in conjunction with specific embodiments. It should be understood that the specific embodiments described herein are only used to explain the present invention and are not used to limit the present invention.

[0015] Embodiment 1:

[0016] (1) Distillation: The reaction mechanism for the preparation of 4-AA key intermediate 2-(N-phthalimidomethyl)-3-oxobutyric acid methyl ester is as follows:

[0017]

[0018] After the reaction, the product and toluene mother liquor are obtained. After filtering the toluene mother liquor, 800 mL is taken out and put into a 1000 L four-necked bottle for distillation. The toluene is distilled and recovered and reused. The remainder is a concentrated residue weighing about 50 g. The main components of the concentrated residue are: 2,2-di(N-phthalimidomethyl)-3-oxobutyric acid methyl ester (content of about 38%) and 2-(N-phthalimidomethyl)-3-oxobutyric acid methyl ester (content of about 58%).

[0019] The structure of methyl 2-bis(N-phthalimidomethyl)-3-oxobutanoate is:

[0020]

[0021] The structure of methyl 2-(N-phthalimidomethyl)-3-oxobutanoate is:

[0022]

[0023] (2) Hydrolysis: Add 150 g of liquid alkali into a four-necked bottle, raise the temperature to 60°C, and hydrolyze for 2 h under stirring to obtain a hydrolyzate.

[0024] (3) Recovery: The hydrolysis product was cooled, crystallized, filtered, and dried to obtain 35 g of qualified N-hydroxymethylphthalimide with a recovery rate of 90% and a purity of 99.5%. The product was then chlorinated with thionyl chloride and condensed with methyl acetoacetate to obtain the key intermediate of 4-AA, 2-(N-phthalimidomethyl)-3-oxobutyric acid methyl ester.

[0025] The reaction mechanism of hydrolysis and recovery is as follows:

[0026]

[0027] By recycling the concentrated residue, the emission of hazardous waste is reduced and the value of hazardous waste is increased.

[0028] Embodiment 2:

[0029] The toluene mother liquor produced in the preparation of 4-AA key intermediate 2-(N-phthalimidomethyl)-3-oxobutyric acid methyl ester was filtered, and 800 mL was put into a 1000 L four-necked flask for distillation. The distilled toluene was recovered and reused. The remainder was a concentrated residue weighing about 49.5 g. 198 g of a saturated aqueous solution of potassium hydroxide was added to the four-necked flask, the temperature was raised to 80°C, stirred for 1 hour, then cooled for crystallization, filtered, and dried to obtain 34 g of qualified N-hydroxymethylphthalimide with a recovery rate of 88% and a purity of 99.3%. The product was then chlorinated with dichlorothionyl and condensed with methyl acetoacetate to obtain 4-AA key intermediate 2-(N-phthalimidomethyl)-3-oxobutyric acid methyl ester, thereby realizing the reuse of hazardous waste and improving the value of hazardous waste.

[0030] Embodiment 3:

[0031] After filtering the toluene mother liquor produced in the preparation of 4-AA key intermediate 2-(N-phthalimidomethyl)-3-oxobutyric acid methyl ester, 800 mL was put into a 1000 L four-necked flask for distillation. The distilled toluene was recovered and reused. The remainder was a concentrated residue weighing about 48 g. 141 g of concentrated hydrochloric acid was added to the four-necked flask, the temperature was raised to 30°C, stirred for 3 hours, then cooled for crystallization, filtered, and dried to obtain 30 g of qualified N-hydroxymethylphthalimide with a recovery rate of 81% and a purity of 99.0%. The product was then chlorinated with dichlorothionyl and condensed with methyl acetoacetate to obtain 4-AA key intermediate 2-(N-phthalimidomethyl)-3-oxobutyric acid methyl ester, thereby realizing the reuse of hazardous waste and improving the value of hazardous waste.

[0032] Embodiment 4:

[0033] This embodiment provides a method for recovering N-hydroxymethylphthalimide from 4-AA key intermediate residue. The method steps are basically the same as those in Example 1, except that the hydrolysis reagent used in step (2) is concentrated sulfuric acid.

[0034] Embodiment 5:

[0035] This embodiment provides a method for recovering N-hydroxymethylphthalimide from 4-AA key intermediate residue. The method steps are basically the same as those in Example 1, except that the hydrolysis reagent used in step (2) is a saturated aqueous solution of sodium carbonate.

[0036] Embodiment 6:

[0037] This embodiment provides a method for recovering N-hydroxymethylphthalimide from 4-AA key intermediate residue. The method steps are basically the same as those in Example 1, except that the hydrolysis reagent used in step (2) is a saturated aqueous solution of potassium carbonate.

[0038] The above embodiments are only for describing the preferred implementation of the present invention, and are not intended to limit the concept and scope of the present invention. Without departing from the design concept of the present invention, various modifications and improvements made by ordinary persons in the art to the technical solution of the present invention should fall within the protection scope of the present invention.

[0039] The techniques, shapes, and structural parts not described in detail in the present invention are all well-known techniques.

Claims

1. A method for recovering N-hydroxymethylphthalimide from 4-AA key intermediate residue, characterized in that: The following steps are involved: (1) Distillation: Filter and distill the toluene mother liquor produced by the preparation of methyl 2-(N-phthalimidomethyl)-3-oxobutanoate, a key intermediate of 4-AA, to obtain a toluene solvent and a concentrated residue, and recover the toluene solvent for reuse; (2) hydrolysis: adding a hydrolysis reagent to the concentrated residue, with the weight ratio of the concentrated residue to the hydrolysis reagent being 1:(1.1-4), heating to 30-100° C., and hydrolyzing for 1-10 hours under stirring to obtain a hydrolyzate; (3) Recovery: The hydrolysis product is cooled, crystallized, filtered, and washed with water to obtain N-hydroxymethylphthalimide, which is then used in the preparation of methyl 2-(N-phthalimidomethyl)-3-oxobutyrate, a key intermediate of 4-AA.

2. The method for recovering N-hydroxymethylphthalimide from 4-AA key intermediate residue according to claim 1, characterized in that: The weight ratio of the concentrated residue to the hydrolysis reagent in step (2) is 1:

3.

3. The method for recovering N-hydroxymethylphthalimide from 4-AA key intermediate residue according to claim 1, characterized in that: The hydrolysis reagent in step (2) is any one of liquid alkali, hydrochloric acid, sulfuric acid, potassium hydroxide aqueous solution, sodium carbonate aqueous solution, and potassium carbonate aqueous solution.

4. The method for recovering N-hydroxymethylphthalimide from 4-AA key intermediate residue according to claim 1, characterized in that: The hydrolysis temperature in step (2) is 60°C.

5. The method for recovering N-hydroxymethylphthalimide from 4-AA key intermediate residue according to claim 1, characterized in that: The duration of the hydrolysis in step (2) is 2 hours.

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