A process for recovering N-hydroxymethyl phthalimide from 4-AA key intermediate residue

Abstract

This invention belongs to the field of chemical intermediate preparation technology, and particularly relates to a method for recovering N-hydroxymethyl phthalimide from the residue of a key intermediate of 4-AA. The method includes the following steps: (1) Distillation: The toluene mother liquor produced from the preparation of methyl 2-(N-phthaliminomethyl)-3-oxobutyrate, a key intermediate of 4-AA, is filtered and distilled to obtain toluene solvent and concentrated residue. The toluene solvent is recovered and reused. (2) Hydrolysis: A hydrolysis reagent is added to the concentrated residue, with a weight ratio of concentrated residue to hydrolysis reagent of 1:(1.1-4). The mixture is heated to 30-100℃ and kept at this temperature for 1-10 hours with stirring to obtain a hydrolysis product. (3) Recovery: The hydrolysis product is cooled, crystallized, filtered, and washed with water to obtain N-hydroxymethyl phthalimide. This invention can recover effective components from hazardous waste, thereby reducing the discharge of hazardous waste and lowering the cost of hazardous waste treatment.

Description

Technical Field

[0001] This invention belongs to the field of chemical intermediate preparation technology, and in particular relates to a method for recovering N-hydroxymethyl phthalimide from 4-AA key intermediate residue. Background Technology

[0002] 4-AA's key intermediate, methyl 2-(N-phthaliminomethyl)-3-oxobutyrate, is an organic compound and a crucial intermediate in the preparation of the carbapenem intermediate 4-AA. It is prepared from chloromethyl phthalimide, methyl acetoacetate, and sodium methoxide as reactants, with a yield of approximately 90%. The remaining 10% is a residue that requires hazardous waste treatment and is environmentally unfriendly. The main components of the residue are methyl 2,2-bis(N-phthaliminomethyl)-3-oxobutyrate (approximately 38%) and methyl 2-(N-phthaliminomethyl)-3-oxobutyrate (approximately 58%). Summary of the Invention

[0003] The purpose of this invention is to provide a method for recovering N-hydroxymethyl phthalimide from 4-AA key intermediate residue, in order to solve the problems existing in the prior art.

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

[0005] A method for recovering N-hydroxymethyl phthalimide from 4-AA key intermediate residue includes the following steps:

[0006] (1) Distillation: The toluene mother liquor produced in the preparation of methyl 2-(N-phthaliminomethyl)-3-oxobutyrate, a key intermediate of 4-AA, was filtered and distilled to obtain toluene solvent and concentrated residue. The toluene solvent was recovered and reused.

[0007] (2) Hydrolysis: Add hydrolysis reagent to the concentrated residue, the weight ratio of concentrated residue to hydrolysis reagent is 1:(1.1~4), heat to 30~100℃, and keep warm for 1~10h with stirring to obtain hydrolysis product;

[0008] (3) Recovery: The hydrolysis product is cooled, crystallized, filtered, and washed with water to obtain N-hydroxymethyl phthalimide, which is then used in the preparation of methyl 2-(N-phthaliminomethyl)-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, or 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 present invention has the following beneficial effects: First, the hazardous waste generated from the preparation of methyl 2-(N-phthaliminomethyl)-3-oxobutyrate, a key intermediate of 4-AA, is recovered by toluene. Then, the effective components 2,2-bis(N-phthaliminomethyl)-3-oxobutyrate (approximately 38%) and methyl 2-(N-phthaliminomethyl)-3-oxobutyrate (approximately 58%) are hydrolyzed to obtain N-hydroxymethyl phthalimide, the starting material for the preparation of methyl 2-(N-phthaliminomethyl)-3-oxobutyrate, a key intermediate of 4-AA. The recovered material is then condensed with thionyl chloride and methyl acetoacetate to obtain methyl 2-(N-phthaliminomethyl)-3-oxobutyrate, a key intermediate of 4-AA. This achieves the reuse of hazardous waste, reduces the discharge of hazardous waste, and lowers the cost of hazardous waste treatment. Detailed Implementation

[0014] To make the objectives, technical solutions, and advantages of this invention clearer, the invention will be further described in detail below with reference to specific embodiments. It should be understood that the specific embodiments described herein are merely illustrative of the invention and are not intended to limit the invention.

[0015] Example 1:

[0016] (1) Distillation: The reaction mechanism for the preparation of methyl 2-(N-phthaliminomethyl)-3-oxobutyrate, a key intermediate of 4-AA, is as follows:

[0017]

[0018] After the reaction, the product and toluene mother liquor were obtained. After filtering the toluene mother liquor, 800 mL was taken and put into a 1000L four-necked flask for distillation. The toluene was recovered by distillation and reused. The residue was a concentrated residue, weighing about 50 g. The main components of the concentrated residue were methyl 2,2-bis(N-phthaliminomethyl)-3-oxobutyrate (content about 38%) and methyl 2-(N-phthaliminomethyl)-3-oxobutyrate (content about 58%).

[0019] The structure of methyl 2,2-bis(N-phthaliminomethyl)-3-oxobutyrate is as follows:

[0020]

[0021] The structure of methyl 2-(N-phthaliminomethyl)-3-oxobutyrate is:

[0022]

[0023] (2) Hydrolysis: Add 150g of liquid alkali to a four-necked flask, heat to 60℃, and keep warm for 2 hours with stirring to obtain the hydrolysis product.

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

[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] Example 2:

[0029] The toluene mother liquor produced during the preparation of methyl 2-(N-phthaliminomethyl)-3-oxobutyrate, a key intermediate for 4-AA, was filtered, and 800 mL was added to a 1000 L four-necked flask for distillation. The distilled toluene was recovered and reused, and the residue, weighing approximately 49.5 g, was concentrated. 198 g of saturated potassium hydroxide solution was added to the four-necked flask, the temperature was raised to 80 °C, and the mixture was stirred for 1 h. Then, the mixture was cooled to allow crystallization, filtered, and dried to obtain 34 g of qualified N-hydroxymethyl phthalimide, with a recovery rate of 88% and a purity of 99.3%. The product was then condensed with thionyl chloride and methyl acetoacetate to regenerate methyl 2-(N-phthaliminomethyl)-3-oxobutyrate, a key intermediate for 4-AA, thus realizing the reuse of hazardous waste and enhancing its value.

[0030] Example 3:

[0031] The toluene mother liquor produced during the preparation of methyl 2-(N-phthaliminomethyl)-3-oxobutyrate, a key intermediate for 4-AA, was filtered, and 800 mL was added to a 1000 L four-necked flask for distillation. The distilled toluene was recovered and reused, and the residue was a concentrated residue weighing approximately 48 g. 141 g of concentrated hydrochloric acid was added to the four-necked flask, the temperature was raised to 30 °C, and the mixture was stirred for 3 h. Then, the mixture was cooled to allow crystallization, filtered, and dried to obtain 30 g of qualified N-hydroxymethyl phthalimide, with a recovery rate of 81% and a purity of 99.0%. The product was then condensed with thionyl chloride and methyl acetoacetate to regenerate methyl 2-(N-phthaliminomethyl)-3-oxobutyrate, a key intermediate for 4-AA, thus realizing the reuse of hazardous waste and enhancing its value.

[0032] Example 4:

[0033] This embodiment provides a method for recovering N-hydroxymethyl phthalimide 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] Example 5:

[0035] This embodiment provides a method for recovering N-hydroxymethyl phthalimide 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] Example 6:

[0037] This embodiment provides a method for recovering N-hydroxymethyl phthalimide 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 merely descriptions of preferred embodiments of the present invention and are not intended to limit the concept and scope of the present invention. Various modifications and improvements made to the technical solutions of the present invention by those skilled in the art without departing from the design concept of the present invention should fall within the protection scope of the present invention.

[0039] The technologies, shapes, and structures not described in detail in this invention are all known technologies.

Claims

1. A method for recovering N-hydroxymethyl phthalimide from 4-AA key intermediate residue, characterized in that, Includes the following steps: (1) Distillation: The toluene mother liquor produced in the preparation of methyl 2-(N-phthaliminomethyl)-3-oxobutyrate, a key intermediate of 4-AA, was filtered and distilled to obtain toluene solvent and concentrated residue. The toluene solvent was recovered and reused. The main components of the concentrated residue are: methyl 2,2-bis(N-phthaliminomethyl)-3-oxobutyrate and methyl 2-(N-phthaliminomethyl)-3-oxobutyrate. The structure of methyl 2,2-bis(N-phthaliminomethyl)-3-oxobutyrate is as follows: ； The structure of methyl 2-(N-phthaliminomethyl)-3-oxobutyrate is: ； The reaction mechanism for the preparation of methyl 2-(N-phthaliminomethyl)-3-oxobutyrate, a key intermediate of 4-AA, is as follows: ； (2) Hydrolysis: Add hydrolysis reagent to the concentrated residue, the weight ratio of concentrated residue to hydrolysis reagent is 1:(1.1~4), heat to 30~100℃, and keep warm for 1~10h with stirring to obtain hydrolysis product; The reaction mechanism is as follows: ； (3) Recovery: The hydrolysis product is cooled, crystallized, filtered, and washed with water to obtain N-hydroxymethyl phthalimide, which is then used in the preparation of methyl 2-(N-phthaliminomethyl)-3-oxobutyrate, a key intermediate of 4-AA.

2. The method for recovering N-hydroxymethyl phthalimide 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-hydroxymethyl phthalimide from 4-AA key intermediate residue according to claim 1, characterized in that, The hydrolysis reagent mentioned 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-hydroxymethyl phthalimide 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-hydroxymethyl phthalimide from 4-AA key intermediate residue according to claim 1, characterized in that, The duration of the heat preservation hydrolysis in step (2) is 2 hours.

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