CN111499592B

CN111499592B - Synthesis method of 5-aminomethylsaccharin

Info

Publication number: CN111499592B
Application number: CN202010178642.6A
Authority: CN
Inventors: 刘晓佳; 刘超; 邹佩佩; 孙永辉; 孔繁蕾
Original assignee: Nanjing Gaoheng Biotechnology Co ltd; Jiangsu Agrochem Laboratory Co ltd
Current assignee: Nanjing Gaoheng Biotechnology Co ltd; Jiangsu Agrochem Laboratory Co ltd
Priority date: 2020-03-14
Filing date: 2020-03-14
Publication date: 2023-06-23
Anticipated expiration: 2040-03-14
Also published as: CN111499592A

Abstract

The invention discloses a synthesis method of 5-aminomethyl saccharin, which comprises the following steps: (1) adding 5-carbamoylsaccharin into tetrahydrofuran and stirring for dissolution; (2) dropwise adding a tetrahydrofuran solution of borane into the solution in the step (1) at room temperature, heating until reflux is completed, and reacting until the reaction is completed; (3) cooling the material reacted in the step (2) to room temperature, slowly dropwise adding trifluoroacetic acid solution, heating to reflux after the dropwise adding is finished, and reacting to completion; (4) and (3) post-treating the material reacted in the step (3) to obtain the 5-aminomethyl saccharin. The method has the advantages of shorter synthetic route, lower production cost, higher safety and higher yield, and is particularly suitable for industrialized mass production.

Description

Synthesis method of 5-aminomethylsaccharin

Technical Field

The invention belongs to the technical field of synthesis of herbicide intermediates, and particularly relates to a synthesis method of 5-aminomethyl saccharin.

Background

The 5-aminomethyl saccharin is an important intermediate for synthesizing sulfonylurea herbicide methyl disulfuron, and has the following structural formula:

。

chinese patent document CN103333120A discloses a method for preparing methyl disulfuron, and specifically discloses a method for preparing 5-aminomethyl saccharin by taking p-toluic acid as a starting material and performing chlorosulfonation-ammonolysis, oxidation, dehydration, reduction and other steps. The method has the following defects: (1) The synthetic route is long, even if calculated as 5-carbamoyl saccharin, two steps are required; (2) The total yield is low, and even if calculated by 5-carbamyl saccharin, the two-step yield is only about 70 percent; (3) The last reduction reaction requires the use of noble metal catalysts with higher price, resulting in higher production cost; (4) is not suitable for industrial mass production.

Chinese patent document CN104610167a discloses a method for preparing 5 (6) -aminomethyl saccharin by catalytic hydrogenation reduction reaction, diazotization reaction+substitution reaction, and reduction reaction using 5 (6) -nitrosaccharin as starting material. The method has the following defects: (1) the synthetic route is still long, requiring three steps; (2) The total yield is low, especially the diazotization reaction and substitution reaction yield is not more than 70%; (3) The first step of catalytic hydrogenation reduction needs to adopt a noble metal catalyst with higher price, and the last step of reduction reaction has the best effect under the condition of adopting the noble metal catalyst with higher price, so that the production cost is higher as well; (4) is not suitable for industrial mass production.

Chinese patent document CN106243046A discloses a preparation method of methyl disulfone, and specifically discloses a method for preparing 5-aminomethyl saccharin by taking 4-chloro-2-aminobenzoic acid as a starting material and performing the steps of esterification, diazotization, sulfur dioxide introduction, oxychlorination, ammoniation into a ring, nitrogen methylation, cyanidation, reduction and the like. The method has the following defects: (1) The synthetic route is longer, and even in 5-chlorosaccharin, three steps are required; (2) The total yield is low, especially the cyanide reaction yield is only about 70%; (3) The last reduction reaction not only needs to use noble metal catalysts with higher price, but also has higher production cost; the method is also required to be carried out under high pressure, and has higher requirements on equipment and lower safety; (4) is not suitable for industrial mass production.

Chinese patent document CN110483439A, CN110483497A, CN110627706a and the like both disclose a synthesis method of 6-aminomethyl-1, 1-dioxo-1, 2-benzothiazol-3-one [ i.e. 5 (6) -aminomethyl saccharin ], and specifically disclose that p-methylbenzyl chloride and phthalimide are used as starting materials, intermediate compound 3 is prepared by condensation, substitution, chlorination, ammoniation and oxidation into a ring, and finally the intermediate compound is reacted with hydrazine hydrate to prepare 5-aminomethyl saccharin. The method has the following defects: (1) the synthetic route is longer; (2) lower overall yield; (3) is not suitable for industrial mass production.

Disclosure of Invention

The invention aims to solve the problems and provide a synthesis method of 5-aminomethyl saccharin, which has the advantages of shorter synthesis route, lower production cost, higher safety and higher yield, and is suitable for industrial mass production.

The technical conception of the invention is as follows: since 5-carbamoyl saccharin contains two amides, the preparation of 5-aminomethylsaccharin by the method of reducing amides is not easily conceivable to those skilled in the art, and the applicant has found through a number of experiments that: the borane/trifluoroacetic acid reduction system is capable of directionally reducing amides on carbamoyl groups without reducing amides on saccharin.

The technical scheme for realizing the aim of the invention is as follows: a synthesis method of 5-aminomethyl saccharin comprises the following steps: (1) adding 5-carbamoylsaccharin into tetrahydrofuran and stirring for dissolution; (2) dropwise adding a tetrahydrofuran solution of borane into the solution in the step (1) at room temperature (15-25 ℃ and the same below), heating until reflux is completed, and reacting until the reaction is completed; (3) cooling the material reacted in the step (2) to room temperature, slowly dropwise adding trifluoroacetic acid solution, heating to reflux after the dropwise adding is finished, and reacting to completion; (4) and (3) post-treating the material reacted in the step (3) to obtain the 5-aminomethyl saccharin.

The molar ratio of the 5-carbamoylsaccharin in the step (1) to the borane in the step (2) is 1:2 to 1:5.

The weight ratio of the 5-carbamoylsaccharin in the step (1) to the trifluoroacetic acid in the step (3) is 1:2 to 1:5.

The post-treatment in the step (4) is reduced pressure distillation, water addition, suction filtration and drying.

The invention has the positive effects that: the method has the advantages of shorter synthetic route, lower production cost, higher safety and higher yield, and is particularly suitable for industrialized mass production.

Detailed Description

Example 1

The synthesis method of the 5-aminomethyl saccharin in the embodiment specifically comprises the following steps:

(1) 50g of 5-carbamoyl saccharin was added to 150mL of tetrahydrofuran and dissolved with stirring.

(2) 600mL of borane in tetrahydrofuran (1 mol/L) was added dropwise to the solution of step (1) at room temperature, and the reaction was completed (about 3 h) after the dropwise addition was completed to reflux.

(3) The material after the reaction in step (2) was cooled to room temperature, 300g of trifluoroacetic acid solution (50 wt%) was slowly added dropwise, and the temperature was raised to reflux after the completion of the dropwise addition, and the reaction was completed (about 1 h).

(4) After the reaction, tetrahydrofuran and trifluoroacetic acid were distilled off under reduced pressure, 30g of water was added, suction filtration was carried out, and drying was carried out at 70℃to obtain 43.7g of 5-aminomethylsaccharin with a purity of 97% (HPLC) and a yield of 93.2%.

Example 2 to example 5

The preparation method of each example was basically the same as that of example 1, except that table 1 was shown.

TABLE 1

	Example 1	Example 2	Example 3	Example 4	Example 5
						1mol/L borane in tetrahydrofuran	600mL	450mL	750mL	600mL	600mL
50wt% trifluoroacetic acid solution	300g	300g	300g	200g	500g
						Weight of the product	43.7g	41.6g	44.0g	41.9g	43.9g
Purity of	96.8%	95.3%	96.5%	95.2%	96.6%
						Yield is good	93.2%	88.7%	93.8%	89.3%	93.6%

Comparative example 1

This comparative example 1 differs from example 1 in that: without adding trifluoroacetic acid solution, the target product could not be obtained.

Claims

1. A synthesis method of 5-aminomethyl saccharin comprises the following steps: (1) adding 5-carbamoylsaccharin into tetrahydrofuran and stirring for dissolution; (2) dropwise adding a tetrahydrofuran solution of borane into the solution in the step (1) at room temperature, heating until reflux is completed, and reacting until the reaction is completed; (3) cooling the material reacted in the step (2) to room temperature, slowly dropwise adding trifluoroacetic acid solution, heating to reflux after the dropwise adding is finished, and reacting to completion; (4) and (3) post-treating the material reacted in the step (3) to obtain the 5-aminomethyl saccharin.

2. The method for synthesizing 5-aminomethyl saccharin according to claim 1, wherein: the molar ratio of the 5-carbamoylsaccharin in the step (1) to the borane in the step (2) is 1:2 to 1:5.

3. The method for synthesizing 5-aminomethyl saccharin according to claim 1, wherein: the weight ratio of the 5-carbamoylsaccharin in the step (1) to the trifluoroacetic acid in the step (3) is 1:2 to 1:5.

4. The method for synthesizing 5-aminomethyl saccharin according to claim 1, wherein: the post-treatment in the step (4) is reduced pressure distillation, water addition, suction filtration and drying.