CN110483439B - Method for synthesizing 6-aminomethyl-1, 1-dioxo-1, 2-benzothiazole-3-one - Google Patents
Method for synthesizing 6-aminomethyl-1, 1-dioxo-1, 2-benzothiazole-3-one Download PDFInfo
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
- C07D209/44—Iso-indoles; Hydrogenated iso-indoles
- C07D209/48—Iso-indoles; Hydrogenated iso-indoles with oxygen atoms in positions 1 and 3, e.g. phthalimide
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D275/00—Heterocyclic compounds containing 1,2-thiazole or hydrogenated 1,2-thiazole rings
- C07D275/04—Heterocyclic compounds containing 1,2-thiazole or hydrogenated 1,2-thiazole rings condensed with carbocyclic rings or ring systems
- C07D275/06—Heterocyclic compounds containing 1,2-thiazole or hydrogenated 1,2-thiazole rings condensed with carbocyclic rings or ring systems with hetero atoms directly attached to the ring sulfur atom
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
- C07D417/06—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
Abstract
The invention provides a method for synthesizing 6-aminomethyl-1, 1-dioxo-1, 2-benzothiazole-3-ketone, which comprises the following steps: a step of synthesizing 2- (3-sulfonic acid group-4-methylbenzyl) -1H-isoindole-1, 3-dione, 2- (3-chlorosulfonyl-4-methylbenzyl) -1H-isoindole-1, 3-dione, 2- (3-aminosulfonyl-4-methylbenzyl) -1H-isoindole-1, 3-dione, 2- (1, 1-dioxo-1, 2-benzothiazol-3-on-6-ylmethyl) -1H-isoindole-1, 3-dione, and a target compound. The synthesis method is a new synthesis method of the mesosulfuron intermediate 4-methanesulfonamido methyl-2-sulfamoyl methyl benzoate, the synthesis method does not need hydrogenation reduction, the reaction condition is mild, various raw materials are easy to obtain, the yield is high, the production cost can be effectively reduced, and the method has a strong industrial application prospect.
Description
Technical Field
The invention belongs to the field of organic drug synthesis, and particularly relates to a synthesis method of 6-aminomethyl-1, 1-dioxo-1, 2-benzothiazole-3-ketone.
Background
The methyl disulfonsulfuron, also called mesosulfuron, the chemical name 2- [ (4, 6-dimethoxypyrimidine 2-aminocarbonyl) aminosulfonyl ] -a- (methylsulfonylamino) methyl p-toluate is a novel sulfonylurea herbicide developed by German Bayer company in 2002, and the sulfonylurea herbicide is the largest herbicide in the world and mainly acts by inhibiting acetolactate synthase, is absorbed by roots and leaves of weeds and is conducted in plants, so that the weeds are promoted to stop growing to achieve the weeding effect. The herbicide mainly prevents and removes gramineous weeds and part of broad-leaved weeds in wheat fields, including alopecurus, wild oats, club grass, bluegrass, stiff grass, arthroncus, beckmark beckmannia, wheatgrass, shepherd's purse, descurainia sophia, caraway marigold and the like, and shows a rising trend in the market demand of the herbicide in China.
Currently, methyldisulfuron is mainly prepared by condensing 4-methylsulfonylaminomethyl-2-sulfamoylbenzoic acid methyl ester (intermediate I) and 4, 6-dimethoxy-2- (phenoxycarbonyl) aminopyrimidine (intermediate II), and the reaction route is shown as follows:
synthesis route of mesosulfuron-methyl
The precursor compounds of the intermediate I mainly comprise two compounds: methyl 2-amino-4-aminomethylbenzoate (Compound 1) or 6-aminomethyl-1, 1-dioxo-1, 2-benzothiazol-3-one (Compound 2), the conventional synthesis method of Compound 2 is troublesome and has a low yield. Therefore, it is necessary to develop a novel synthesis method of compound 2.
Disclosure of Invention
In view of the above, it is necessary to provide a method for synthesizing 6-aminomethyl-1, 1-dioxo-1, 2-benzothiazol-3-one, which is an intermediate of mesosulfuron, and which is simple and has high yield.
Therefore, the invention provides a method for synthesizing 6-aminomethyl-1, 1-dioxo-1, 2-benzothiazole-3-ketone, which comprises the following steps:
synthesizing a compound 6 by using 2- (4-methylbenzyl) -1H-isoindole-1, 3-diketone and chlorosulfonic acid as raw materials to synthesize 2- (3-sulfonic acid group-4-methylbenzyl) -1H-isoindole-1, 3-diketone (the compound 6);
the compound 5 is synthesized by taking the compound 6 and phosphorus oxychloride as raw materials, and synthesizing 2- (3-chlorosulfonyl-4-methylbenzyl) -1H-isoindole-1, 3-diketone (compound 5) at 0-80 ℃ under the action of alkaline substances;
synthesizing a compound 4 by using the compound 5 and ammonia water as raw materials to synthesize 2- (3-aminosulfonyl-4-methylbenzyl) -1H-isoindole-1, 3-diketone (compound 4) at the temperature of 40-100 ℃;
synthesizing a compound 3 by using the compound 4 and an oxidant as raw materials, and synthesizing 2- (1, 1-dioxo-1, 2-benzothiazole-3-ketone-6-ylmethyl) -1H-isoindole-1, 3-diketone (compound 3) at 0-120 ℃ under the action of a catalyst;
synthesizing the target compound by using the compound 3 and hydrazine hydrate as raw materials to synthesize 6-aminomethyl-1, 1-dioxo-1, 2-benzothiazole-3-ketone (compound 2) at the temperature of 0-100 ℃.
The synthesis method of the target compound comprises: and reacting the compound 3 with hydrazine hydrate in a first solvent at the temperature of 0-100 ℃ for 1-3 h to obtain the target compound 6-aminomethyl-1, 1-dioxo-1, 2-benzothiazole-3-one, wherein the molar ratio of the compound 3 to the hydrazine hydrate is 1-3. The hydrazine hydrate used in the synthesis reaction may be pure hydrazine hydrate or a hydrazine hydrate solution, for example, a hydrazine hydrate solution having a mass percentage of 30% to 80%. The molar ratio of the compound 3 to the hydrazine hydrate is defined as 1 to 3, which is beneficial to improving the utilization rate and the yield of reactants.
In the synthesis process of the target compound, an amide group on an isoindole group in the compound 3 is subjected to a hydrazinolysis reaction under the action of hydrazine hydrate, and the compound 2 can be obtained without involving a reduction reaction, wherein the specific synthetic route is as follows:
the first solvent is mainly used for dissolving the compound 3, and may be dichloroethane, dichloromethane, chloroform, acetone, tetrahydrofuran or N, N-dimethylformamide. And after the synthesis reaction of the target compound is finished, the method also comprises a purification treatment step. Specifically, the purification treatment comprises the following steps: and after the synthesis reaction is finished, removing the first solvent, and then recrystallizing with ethanol to obtain the compound 2.
The synthesis method of the compound 3 comprises: and (2) reacting the compound 4, the oxidant, the defoaming agent and a vanadium pentoxide catalyst in a second solvent at 0-120 ℃ for 1-3 h to obtain the compound 3, wherein the molar ratio of the compound 4 to the oxidant to the vanadium pentoxide is 1.5-3. In the synthesis process of the compound 3, the structural formula of the compound 4 is shown in the specification
Under the action of catalyst vanadium pentoxide, oxidizingOxidizing methyl of benzyl in the compound 4 into carboxyl by using an agent, and then carrying out cyclization reaction on the carboxyl and an adjacent sulfonamide group on a benzene ring connected with the carboxyl to form lactam; as the reaction can generate more foams, the excessive foams influence the reaction and the industrial production is unsafe, the antifoaming agent can be added in the reaction process to reduce the influence of the foams on the reaction and increase the safety of the industrial production. Thus, the synthetic route for said compound 3 is shown below:
therefore, the molar ratio of the compound 4 to the oxidant to the vanadium pentoxide is in the range of 1.5-3.
Wherein, the second solvent is mainly used for dissolving the compound 4 and can be one or more of N, N-dimethylformamide, N-dimethylacetamide, dimethyl sulfoxide, pyridine, N-methylpyrrolidone, dichloroethane and chloroform. The oxidant is mainly used for oxidizing benzyl on the compound 4 into benzene carboxyl under the action of a catalyst vanadium pentoxide, and can be potassium dichromate, potassium permanganate or a combination of the potassium dichromate and the potassium permanganate. The defoaming agent is emulsified silicone oil, a high-alcohol fatty acid ester compound, polyoxyethylene polyoxypropylene pentaerythritol ether, polyoxyethylene polyoxypropylene amine ether, polyoxypropylene glycerol ether, polyoxypropylene polyoxyethylene glycerol ether and polydimethylsiloxane.
The synthesis method of the compound 4 comprises: and dissolving the compound 5 and excessive ammonia water in tetrahydrofuran, and reacting at 40-100 ℃ for 1-3 h to obtain the compound 4. Wherein the structural formula of the compound 5 is shown in the specification
The compound 4 is mainly prepared by the substitution reaction of the compound 5 and ammonia water, so that excessive ammonia water is added in the synthesis process, and the substitution reaction can be ensuredThe forward reaction is carried out, which is beneficial to improving the yield of the compound 4. Specifically, the synthetic route of the compound 4 is as follows:
the synthesis method of the compound 5 comprises: and (2) reacting the compound 6, phosphorus oxychloride and an alkaline substance in a third solvent at 0-80 ℃ for 1-3 h to obtain the compound 5, wherein the molar ratio of the compound 6, the phosphorus oxychloride and the alkaline substance is (1.33-1). The structural formula of the compound 6 is
The compound 6 and phosphorus oxychloride undergo substitution reaction in an alkaline environment to prepare a compound 5; the synthetic route is as follows:
wherein the third solvent is mainly used for dissolving the compound 6, and can be chloroform, dichloroethane or acetone. The alkaline substance mainly provides an alkaline environment for the normal proceeding of the substitution reaction, and can be sodium carbonate, potassium carbonate, sodium bicarbonate, potassium bicarbonate, triethylamine, sodium hydroxide or potassium hydroxide. The method further comprises the following steps after the synthesis reaction of the compound 5 is finished: putting the reacted system into a large amount of ice water, stirring for 10-30 min, collecting an organic layer, and removing the third solvent to obtain the purified compound 5.
The synthesis method of the compound 6 comprises：
Synthesizing 2- (4-methylbenzyl) -1H-isoindole-1, 3-diketone, under the action of an alkaline catalyst and a phase transfer catalyst, reacting p-methylbenzyl chloride and phthalimide in a fourth solvent at 0-100 ℃ for 1-3H to obtain 2- (4-methylbenzyl) -1H-isoindole-1, 3-diketone, wherein the molar ratio of the alkaline catalyst to the phase transfer catalyst to the methylbenzyl chloride to the phthalimide is 1 (0.2-1) to (1-3);
the synthetic compound 6- (4-methylbenzyl) -1H-isoindole-1, 3-diketone and chlorosulfonic acid react in a fifth solvent at the temperature of 0-100 ℃ to obtain the compound 6, wherein the molar ratio of the 2- (4-methylbenzyl) -1H-isoindole-1, 3-diketone to the chlorosulfonic acid is 1 (1-3).
As can be seen from the above reaction steps: the compound 6 is mainly prepared by the substitution reaction of simple and easily obtained raw materials of p-methylbenzyl chloride and phthalimide to synthesize 2- (4-methylbenzyl) -1H-isoindole-1, 3-diketone and the substitution reaction of the 2- (4-methylbenzyl) -1H-isoindole-1, 3-diketone and chlorosulfonic acid. The synthesis process is simple, the reaction condition is mild, and the yield is high. Specifically, the synthetic route of the compound 6 is as follows:
the alkaline catalyst mainly provides an alkaline environment for the substitution reaction of p-methylbenzyl chloride and phthalimide, and is sodium carbonate, potassium carbonate, sodium bicarbonate, potassium bicarbonate, triethylamine, sodium hydroxide or potassium hydroxide. The phase transfer catalyst is benzyltriethylammonium chloride, tetrabutylammonium bromide, tetrabutylammonium chloride, tetrabutylammonium hydrogen sulfate, trioctylmethylammonium chloride, dodecyltrimethylammonium chloride, tetradecyltrimethylammonium chloride or tributylamine. The fourth solvent is mainly used for dissolving p-methylbenzyl chloride and can be one or a combination of at least two of N, N-dimethylformamide, N-dimethylacetamide, dimethyl sulfoxide, pyridine and N-methylpyrrolidone; the fifth solvent is mainly used for dissolving the 2- (4-methylbenzyl) -1H-isoindole-1, 3-dione, and can be dichloroethane or chloroform.
The invention also provides a synthetic method of the 6-aminomethyl-1, 1-dioxo-1, 2-benzothiazole-3-ketone, which comprises the following steps:
synthesizing a compound 6 by using 2- (4-methylbenzyl) -1H-isoindole-1, 3-diketone and chlorosulfonic acid as raw materials to synthesize 2- (3-sulfonic acid group-4-methylbenzyl) -1H-isoindole-1, 3-diketone (the compound 6);
the compound 4 is synthesized by taking the compound 6, ammonium iodide and ammonia water as raw materials to carry out electrolytic reaction to prepare 2- (3-aminosulfonyl-4-methylbenzyl) -1H-isoindole-1, 3-diketone (compound 4);
synthesizing a compound 3 by using the compound 4 and an oxidant as raw materials, and synthesizing 2- (1, 1-dioxo-1, 2-benzothiazole-3-ketone-6-ylmethyl) -1H-isoindole-1, 3-diketone (compound 3) at 0-120 ℃ under the action of a catalyst;
the target compound is synthesized by taking the compound 3 and hydrazine hydrate as raw materials and synthesizing 6-aminomethyl-1, 1-dioxo-1, 2-benzothiazole-3-ketone at the temperature of 0-100 ℃.
The synthesis method of the compound 4 comprises the following steps: dissolving the compound 6 in methanol, adding 0.3-1 equivalent of ammonium iodide, then introducing excessive ammonia gas, and carrying out electrolytic reaction for 1-5 h at the temperature of 0-50 ℃ to obtain the compound 4. Further, after the completion of the synthesis reaction, the compound 4 is purified by washing with water and removing the solvent. The synthetic route of the compound 4 is shown as follows:
compared with the prior art, the synthesis method of the 6-aminomethyl-1, 1-dioxo-1, 2-benzothiazole-3-ketone is a new synthesis method of a mesosulfuron-methyl intermediate, a new route for synthesizing the compound 6-aminomethyl-1, 1-dioxo-1, 2-benzothiazole-3-ketone is designed, the synthesis method does not need hydrogenation reduction, mainly generates substitution reaction and oxidation reaction, has mild reaction conditions, easily obtained raw materials and high yield, can effectively reduce the production cost of the mesosulfuron-methyl intermediate 4-methanesulfonamido methyl-2-sulfamoyl methyl benzoate, and has stronger industrial application prospect.
Detailed Description
The technical solution of the present invention is further described in detail by the following embodiments.
Example 1
This example provides a method for synthesizing 6-aminomethyl-1, 1-dioxo-1, 2-benzothiazol-3-one, which comprises the steps of sequentially synthesizing compound 6, compound 5, compound 4, compound 3, and a target compound. The specific synthetic method of each compound is shown below.
Synthesis of compound 6:2- (3-sulfo-4-methylbenzyl) -1H-isoindole-1, 3-dione
Weighing 7g of p-methylbenzyl chloride, dissolving the p-methylbenzyl chloride with a proper amount of N, N-dimethylformamide, sequentially adding 7.35g of phthalimide, 8.1g of tetrabutylammonium bromide and 5.3g of sodium carbonate into a system, and reacting for 2 hours at the temperature of 50 ℃; after the reaction, the mixture was extracted with water, and the organic layer was collected and the solvent was removed to obtain 12.3g of 2- (4-methylbenzyl) -1H-isoindole-1, 3-dione;
dissolving 12.3g of 2- (4-methylbenzyl) -1H-isoindole-1, 3-dione in chloroform, adding 8.7g of chlorosulfonic acid, and reacting at 80 ℃ for 3H; after the reaction was completed, it was washed with water and the solvent was removed to obtain 15.75g of Compound 6 with a yield of 95%.
NMR measurements on Compound 6, 1H NMR (400MHz, DMSO). Delta.7.89 (m, 4H), delta.7.65 (s, 1H), delta.7.16 (m, 2H), delta.4.72 (s, 2H), delta.2.50 (d, 3H); the structural formula of the compound 6 can be judged from the test result
In other embodiments, the reaction solvent N, N-dimethylformamide may be replaced with N, N-dimethylacetamide, dimethylsulfoxide, pyridine, or N-methylpyrrolidone; the reaction solvent chloroform can be replaced by dichloroethane; the alkaline catalyst sodium carbonate can be replaced by potassium carbonate, sodium bicarbonate, potassium bicarbonate, triethylamine, sodium hydroxide or potassium hydroxide; the phase transfer catalyst tetrabutylammonium bromide can be replaced by benzyltriethylammonium chloride (TEBA), tetrabutylammonium chloride, tetrabutylammonium hydrogen sulfate, trioctylmethylammonium chloride, dodecyltrimethylammonium chloride, tetradecyltrimethylammonium chloride or tributylamine; the molar ratio of p-methylbenzyl chloride, phthalimide, tetrabutylammonium bromide and basic catalyst can be adjusted in the range of 1; the molar ratio of 2- (4-methylbenzyl) -1H-isoindole-1, 3-dione to chlorosulfonic acid is 1 to 3, preferably 1; the two reaction temperatures can be adjusted at 0-100 ℃, preferably 100 ℃, 50 ℃, 0 ℃,40 ℃ and 60 ℃; the two reaction times can be adjusted within 1-3 h, preferably 1h, 2h and 2.5h.
Synthesis of Compound 5:2- (3-chlorosulfonyl-4-methylbenzyl) -1H-isoindole-1, 3-dione
Dissolving 15.75g of compound 6 in a proper amount of chloroform, adding 3.6g of phosphorus oxychloride and 5.8g of triethylamine, and reacting for 1h at the temperature of 50 ℃; after the reaction, the reaction mixture was poured into a large amount of ice water, stirred for 10 to 30min, and the organic layer was collected to remove the solvent, whereby 15.95g of Compound 5 was obtained, which was found to have a yield of 96%.
Nuclear magnetic resonance assay was performed on Compound 5, 1H NMR (400MHz, DMSO): delta 7.88 (m, 4H), delta 7.65 (s, 1H), delta 7.15 (m, 2H), delta 4.72 (s, 2H), delta 2.51 (d, 3H); the structural formula of the compound 5 can be judged from the test result
In other embodiments, the reaction solvent chloroform may be replaced with dichloroethane or acetone; the basic catalyst triethylamine can be replaced by sodium carbonate, potassium carbonate, sodium bicarbonate, potassium bicarbonate, triethylamine, sodium hydroxide or potassium hydroxide; the molar ratio of compound 1, phosphorus oxychloride and basic catalyst is in the range of 1.33 to 1; the reaction temperature can be selected from 0 deg.C, 10 deg.C, 20 deg.C, 30 deg.C, 40 deg.C, 60 deg.C, 70 deg.C or 80 deg.C; the reaction time can be selected to be 3h, 2.5h, 2h or 1.5h.
Synthesis of compound 4:2- (3-aminosulfonyl-4-methylbenzyl) -1H-isoindole-1, 3-dione
15.95g of the compound 5 is dissolved by a small amount of tetrahydrofuran, is dripped into excessive ammonia water, reacts for 3 hours at the temperature of 80 ℃, and after the reaction is finished, 14.46g of the compound 4 is obtained by filtration, wherein the yield is 96%.
NMR measurements on Compound 4, 1H NMR (400MHz, DMSO). Delta.7.88 (d, 4H), delta.7.79 (s, 1H), delta.7.46 (d, 1H), delta.7.35 (m, 3H), delta.4.80 (s, 2H), delta.2.51 (d, 3H); the structural formula of the compound 4 can be judged from the test result
In other embodiments, the reaction temperature may be selected to be 40 ℃, 50 ℃,60 ℃, 70 ℃, 90 ℃, or 100 ℃; the reaction time can be selected to be 1h, 1.5h, 2h or 2.5h.
Synthesis of compound 3:2- (1, 1-dioxo-1, 2-benzothiazol-3-on-6-ylmethyl) -1H-isoindole-1, 3-di
Ketones
14.46g of the compound 4 is dissolved in a proper amount of solvent N, N-dimethylformamide, an organic silicon defoaming agent is added, then 7.73g of potassium dichromate and 3.2g of vanadium pentoxide are added to react for 2 hours at 60 ℃, water washing is carried out after the reaction is finished, an organic layer is collected, the solvent is removed, and then 14.24g of the compound 3 is obtained by ethanol recrystallization, wherein the yield is 95%.
Nuclear magnetic resonance assay of compound 3, 1H NMR (400MHz, DMSO): delta 8.22 (s, 1H), delta 7.79-8.08 (m, 6H), delta 4.99 (s, 2H); the structural formula of the compound 3 can be judged from the test result
In other embodiments, the reaction temperature may be 0 ℃, 10 ℃, 20 ℃, 30 ℃, 50 ℃, 70 ℃,80 ℃, 90 ℃, 100 ℃ or 120 ℃; the reaction time can be selected to be 3h, 2.5h, 2h or 1.5h; the reaction solvent N, N-dimethylformamide can be replaced by N, N-dimethylacetamide, dimethyl sulfoxide, pyridine, N-methylpyrrolidone, dichloroethane or trichloromethane; the oxidizing agent potassium dichromate can be replaced by potassium permanganate; the organic silicon defoamer is emulsified silicone oil, polydimethylsiloxane, a higher alcohol fatty acid ester compound, polyoxyethylene polyoxypropylene pentaerythritol ether, polyoxyethylene polyoxypropylene amine ether, polyoxypropylene glycerol ether and polyoxypropylene polyoxyethylene glycerol ether; preferably silicone emulsion or polydimethylsiloxane; the molar ratio of 2- (3-aminosulfonyl-4-methylbenzyl) -1H-isoindole-1, 3-dione, oxidizing agent and vanadium pentoxide can be adjusted in the range of 1.
Synthesizing a target compound: 6-aminomethyl-1, 1-dioxo-1, 2-benzothiazol-3-one
14.24g of the compound 3 is dissolved in N, N-dimethylformamide, 9g of 40% hydrazine hydrate is dropwise added into the reaction system, the reaction is carried out for 2 hours at 60 ℃ after the dropwise addition is finished, the solvent is removed after the reaction is finished, and the ethanol is used for recrystallization to obtain 8.56g of the target compound, wherein the yield is 97%.
Subjecting the target compound to nuclear magnetic resonance, 1H NMR (400MHz, DMSO): delta 3.91 (s, 2H), delta 7.91 (s, 1H), delta 8.11 (d, 1H), delta 7.2 (d, 1H); the structural formula of the target compound can be judged from the test result
In other embodiments, dichloroethane as solvent may be replaced with dichloroethane, dichloromethane, chloroform, acetone, tetrahydrofuran, or N, N-dimethylformamide; the hydrazine hydrate can be selected from commercial hydrazine hydrate with the mass fraction of 30%, 80%, 50% or between 30% and 80% as required, and the molar ratio of 2- (1, 1-dioxo-1, 2-benzothiazol-3-on-6-ylmethyl) -1H-isoindole-1, 3-dione to hydrazine hydrate is 1 (1-3), preferably the molar ratio of 2- (1, 1-dioxo-1, 2-benzothiazol-3-on-6-ylmethyl) -1H-isoindole-1, 3-dione to hydrazine hydrate is 1.
Example 2
This example provides a method for synthesizing 6-aminomethyl-1, 1-dioxo-1, 2-benzothiazol-3-one, which comprises the steps of sequentially synthesizing compound 6, compound 5, compound 4, compound 3, and a target compound. The method of synthesis of each compound provided in this example is substantially the same as the corresponding compound provided in example 1.
Synthesis of compound 6:2- (3-sulfonic acid group-4-methylbenzyl) -1H-isoindole-1, 3-diketones
The method for synthesizing the compound 6 in this example is basically the same as the method for synthesizing the compound 6 provided in example 1, and mainly differs in the reaction solvent, the basic catalyst, the reaction parameters, and the like. Specifically, in this example, 7g of p-methylbenzyl chloride was weighed and dissolved with an appropriate amount of pyridine, and 7.35g of phthalimide, 16g of tetrabutylammonium bromide and 6g of sodium hydroxide were sequentially added to the system, and reacted at 100 ℃ for 1 hour; after the reaction, extracting with water, collecting an organic layer, and removing the solvent to obtain 12.1g of 2- (4-methylbenzyl) -1H-isoindole-1, 3-dione;
dissolving 12.1g of 2- (4-methylbenzyl) -1H-isoindole-1, 3-dione in dichloroethane, adding 15g of chlorosulfonic acid, and reacting at 60 ℃ for 2H; after the reaction was completed, the reaction mixture was washed with water and the solvent was removed to obtain 14.9g of Compound 6 in a yield of 90%.
Synthesis of compound 5:2- (3-chlorosulfonyl-4-methylbenzyl) -1H-isoindole-1, 3-dione
The method for synthesizing the compound 5 in this example is basically the same as the method for synthesizing the compound 5 provided in example 1, and the main difference is that the reaction solvent, the basic catalyst, the reaction parameters and the like are different. Specifically, in the present embodiment, the first and second electrodes,
dissolving 14.9g of compound 6 in a proper amount of dichloroethane, adding 6.8g of phosphorus oxychloride and 5g of sodium hydroxide, and reacting at 30 ℃ for 1.5h; after completion of the reaction, the reaction mixture was poured into a large amount of ice water, stirred for 20min, and the organic layer was collected to remove the solvent, whereby 14.5g of Compound 5 was obtained in 92% yield.
Synthesis of compound 4:2- (3-aminosulfonyl-4-methylbenzyl) -1H-isoindole-1, 3-dione
14.5g of Compound 5 was dissolved in a small amount of tetrahydrofuran, added dropwise to an excess of aqueous ammonia, reacted at 40 ℃ for 2.5 hours, and after completion of the reaction, filtered to obtain 12.9g of Compound 4, the yield was 94%.
Synthesis of compound 3:2- (1, 1-dioxo-1, 2-benzothiazol-3-on-6-ylmethyl) -1H-isoindole-1, 3-di
Ketones
The method for synthesizing the compound 3 in this embodiment is basically the same as the method for synthesizing the compound 3 provided in embodiment 1, and mainly differs in the reaction solvent, the antifoaming agent, the oxidizing agent, the reaction parameters, and the like. Specifically, in this example, 12.9g of compound 4 is dissolved in an appropriate amount of dichloroethane, a silicone emulsion defoaming agent is added, then 9.2g of potassium dichromate and 3.5g of vanadium pentoxide are added to react at 120 ℃ for 1 hour, water washing is performed after the reaction is completed, an organic layer is collected to remove the solvent, and recrystallization is performed with ethanol to obtain 11.85g of compound 3, where the yield is 89%.
Synthesizing a target compound: 6-aminomethyl-1, 1-dioxo-1, 2-benzothiazol-3-one
The method for synthesizing the compound 3 in this example is basically the same as the method for synthesizing the compound 3 provided in example 1, and the main difference is that the reaction solvent, the reaction parameters and the like are different. Specifically, in this example, 11.85g of compound 3 was dissolved in dichloroethane, 9.4g of 40% hydrazine hydrate was added dropwise to the reaction system, the reaction was carried out at 60 ℃ for 2 hours after the addition was completed, the solvent was removed after the reaction was completed, and recrystallization was carried out with ethanol to obtain 6.98g of the objective compound with a yield of 94%.
Example 3
This example provides a method for synthesizing 6-aminomethyl-1, 1-dioxo-1, 2-benzothiazol-3-one, which comprises the steps of sequentially synthesizing compound 6, compound 4, compound 3, and a target compound. The specific synthetic method of each compound is shown below.
Synthesis of compound 6:2- (3-sulfo-4-methylbenzyl) -1H-isoindole-1, 3-dione
The method for synthesizing compound 6 in this example is basically the same as the method for synthesizing compound 6 provided in example 1, and the main difference is that the reaction solvent, the basic catalyst, the reaction parameters, and the like are different. Specifically, in this embodiment, 7g of p-methylbenzyl chloride is weighed and dissolved with an appropriate amount of dimethyl sulfoxide, and 7.35g of phthalimide, 3.5g of tetrabutylammonium bromide and 6g of triethylamine are sequentially added to the system to react for 1.5 hours at a temperature of 70 ℃; after the reaction, extracting with water, collecting an organic layer, and removing the solvent to obtain 12.2g of 2- (4-methylbenzyl) -1H-isoindole-1, 3-dione;
dissolving 12.2g of 2- (4-methylbenzyl) -1H-isoindole-1, 3-dione in dichloroethane, adding 8g of chlorosulfonic acid, and reacting at 80 ℃ for 3 hours; after the reaction was completed, the reaction mixture was washed with water and the solvent was removed to obtain 14.25g of Compound 6, which was 86% in yield.
Synthesis of compound 4:2- (3-aminosulfonyl-4-methylbenzyl) -1H-isoindole-1, 3-dione
14.25g of compound 6 is dissolved in a proper amount of methanol, 7g of ammonium iodide is added into a reaction system, then excessive ammonia gas is introduced, electrolytic reaction is carried out for 4 hours at the temperature of 20 ℃, and after the reaction is finished, the compound 4 is washed by water and the solvent is removed, so that 12.08g of compound 4 is obtained, and the yield is 85%.
NMR measurements on Compound 4, 1H NMR (400MHz, DMSO). Delta.8.23 (s, 1H), delta.7.79-8.09 (m, 6H), delta.4.98 (s, 2H); the structural formula of the compound 4 can be judged from the test result
In other embodiments, the electrolysis reaction temperature may be selected to be 0, 10 ℃, 30 ℃,40 ℃ or 50 ℃, and the reaction time may be selected to be 5h, 4.5h, 3.5h, 3h, 2.5h, 2h, 1.5h or 1h.
Synthesis of Compound 3:2- (1, 1-dioxo-1, 2-benzothiazol-3-on-6-ylmethyl) -1H-isoindole-1, 3-di
Ketones
The method for synthesizing the compound 3 in this example is basically the same as the method for synthesizing the compound 3 provided in example 1, and the main difference is that the reaction solvent, the antifoaming agent, the oxidizing agent, the reaction parameters and the like are different. Specifically, in this embodiment, 12.08g of the compound 4 is dissolved in an appropriate amount of a solvent, which is dimethyl sulfoxide, a polyoxyethylene polyoxypropylene amine ether defoaming agent is added, then 6g of potassium permanganate and 2g of vanadium pentoxide are added to react at 10 ℃ for 3 hours, water washing is performed after the reaction is completed, an organic layer is collected, the solvent is removed, and then ethanol is used for recrystallization to obtain 9.5g of the compound 3, wherein the yield is 75%.
Synthesizing a target compound: 6-aminomethyl-1, 1-bisOxy-1, 2-benzothiazol-3-ones
The method for synthesizing compound 3 in this example is basically the same as the method for synthesizing compound 3 provided in example 1, and the main difference is that the reaction solvent, the reaction parameters, and the like are different. Specifically, in this example, 9.5g of compound 3 was dissolved in tetrahydrofuran, 10g of 30% hydrazine hydrate was added dropwise to the reaction system, reaction was carried out at 100 ℃ for 1.5 hours after completion of the addition, the solvent was removed after the completion of the reaction, and recrystallization was carried out with ethanol to obtain 5.35g of the objective compound, with a yield of 90%.
Finally, it should be noted that: the above examples are only intended to illustrate the technical solution of the present invention and not to limit it; although the present invention has been described in detail with reference to preferred embodiments, those skilled in the art will understand that: modifications of the embodiments of the invention or equivalent substitutions for parts of the technical features are possible; without departing from the spirit of the present invention, it is intended to cover all aspects of the invention as defined by the appended claims.
Claims (12)
1. A method for synthesizing 6-aminomethyl-1, 1-dioxo-1, 2-benzothiazol-3-one comprises the following steps:
synthesis of compound 6: taking 2- (4-methylbenzyl) -1H-isoindole-1, 3-diketone and chlorosulfonic acid as raw materials, carrying out substitution reaction to synthesize a compound 6, wherein the compound 6 is 2- (3-sulfonic group-4-methylbenzyl) -1H-isoindole-1, 3-diketone;
synthesis of Compound 5: taking the compound 6 and phosphorus oxychloride as raw materials, and synthesizing a compound 5 at 0-80 ℃ under the action of alkaline substances, wherein the compound 5 is 2- (3-chlorosulfonyl-4-methylbenzyl) -1H-isoindole-1, 3-diketone;
synthesis of compound 4: taking the compound 5 and ammonia water as raw materials to synthesize a compound 4 at the temperature of 40-100 ℃, wherein the compound 4 is 2- (3-aminosulfonyl-4-methylbenzyl) -1H-isoindole-1, 3-dione;
synthesis of compound 3: taking the compound 4 and an oxidant as raw materials, and synthesizing a compound 3 at 0-120 ℃ under the action of a catalyst, wherein the compound 3 is 2- (1, 1-dioxo-1, 2-benzothiazole-3-ketone-6-ylmethyl) -1H-isoindole-1, 3-diketone;
synthesizing a target compound: the compound 3 and hydrazine hydrate are used as raw materials to synthesize 6-aminomethyl-1, 1-dioxo-1, 2-benzothiazole-3-ketone at the temperature of 0-100 ℃.
2. The method of synthesizing 6-aminomethyl-1, 1-dioxo-1, 2-benzothiazol-3-one according to claim 1, characterized in that said method of synthesis of the target compound comprises: reacting the compound 3 with hydrazine hydrate in a first solvent at the temperature of 0-100 ℃ for 1-3 h to obtain the target compound 6-aminomethyl-1, 1-dioxo-1, 2-benzothiazole-3-ketone, wherein the molar ratio of the compound 3 to the hydrazine hydrate is 1: 1-3.
3. The method of synthesizing 6-aminomethyl-1, 1-dioxo-1, 2-benzothiazol-3-one according to claim 2, wherein said first solvent is dichloroethane, dichloromethane, chloroform, acetone, tetrahydrofuran, or N, N-dimethylformamide.
4. The method of synthesizing 6-aminomethyl-1, 1-dioxo-1, 2-benzothiazol-3-one according to claim 1,2 or 3, characterized in that said method of synthesizing compound 3 comprises: and (2) reacting the compound 4, the oxidant, the defoaming agent and a vanadium pentoxide catalyst in a second solvent at 0-120 ℃ for 1-3 h to obtain the compound 3, wherein the molar ratio of the compound 4 to the oxidant to the vanadium pentoxide is 1: 0.5-3: 0.2-0.5.
5. The method for synthesizing 6-aminomethyl-1, 1-dioxo-1, 2-benzothiazol-3-one according to claim 4, characterized in that said oxidizing agent is potassium dichromate, potassium permanganate or a combination of both, said antifoaming agent is silicone emulsion, higher alcohol fatty acid ester complex, polyoxyethylene polyoxypropylene pentaerythritol ether, polyoxyethylene polyoxypropylene amine ether, polyoxypropylene glycerol ether and polyoxypropylene polyoxyethylene glycerol ether, polydimethylsiloxane, and said second solvent is one or more of N, N-dimethylformamide, N-dimethylacetamide, dimethyl sulfoxide, pyridine, N-methylpyrrolidone, dichloroethane and chloroform.
6. The method of synthesizing 6-aminomethyl-1, 1-dioxo-1, 2-benzothiazol-3-one according to claim 1, characterized in that said method of synthesizing compound 4 comprises: and dissolving the compound 5 and excessive ammonia water in tetrahydrofuran, and reacting at 40-100 ℃ for 1-3 h to obtain the compound 4.
7. The method of synthesizing 6-aminomethyl-1, 1-dioxo-1, 2-benzothiazol-3-one according to claim 1, characterized in that said method of synthesizing compound 5 comprises: and (2) reacting the compound 6, phosphorus oxychloride and an alkaline substance in a third solvent at 0-80 ℃ for 1-3 h to obtain the compound 5, wherein the molar ratio of the compound 6, the phosphorus oxychloride and the alkaline substance is 1: 0.33-1: 1-3.
8. The method of synthesizing 6-aminomethyl-1, 1-dioxo-1, 2-benzothiazol-3-one according to claim 7, characterized in that said third solvent is chloroform, dichloroethane or acetone and said basic substance is sodium carbonate, potassium carbonate, sodium bicarbonate, potassium bicarbonate, triethylamine, sodium hydroxide or potassium hydroxide.
9. The method of synthesizing 6-aminomethyl-1, 1-dioxo-1, 2-benzothiazol-3-one according to claim 1, characterized in that said method of synthesizing compound 6 comprises:
under the action of an alkaline catalyst and a phase transfer catalyst, p-methylbenzyl chloride and phthalimide react in a fourth solvent at the temperature of 0-100 ℃ for 1-3H to synthesize 2- (4-methylbenzyl) -1H-isoindole-1, 3-dione, wherein the molar ratio of the alkaline catalyst to the phase transfer catalyst to the methylbenzyl chloride to the phthalimide is 1:1 (0.2-1) to (1-3);
reacting 2- (4-methylbenzyl) -1H-isoindole-1, 3-dione with chlorosulfonic acid in a fifth solvent at 0-100 ℃ to synthesize the compound 6, wherein the molar ratio of the 2- (4-methylbenzyl) -1H-isoindole-1, 3-dione to the chlorosulfonic acid is 1 (1-3).
10. The method for synthesizing 6-aminomethyl-1, 1-dioxo-1, 2-benzothiazol-3-one according to claim 9, characterized in that said basic catalyst is sodium carbonate, potassium carbonate, sodium bicarbonate, potassium bicarbonate, triethylamine, sodium hydroxide or potassium hydroxide, said phase transfer catalyst is benzyltriethylammonium chloride, tetrabutylammonium bromide, tetrabutylammonium chloride, tetrabutylammonium hydrogen sulfate, trioctylmethylammonium chloride, dodecyltrimethylammonium chloride, tetradecyltrimethylammonium chloride or tributylamine, said fourth solvent is one of N, N-dimethylformamide, N-dimethylacetamide, dimethylsulfoxide, pyridine and N-methylpyrrolidone or a combination of at least two thereof, and said fifth solvent is dichloroethane or chloroform.
11. A method for synthesizing 6-aminomethyl-1, 1-dioxo-1, 2-benzothiazole-3-ketone comprises the following steps:
synthesis of compound 6: taking 2- (4-methylbenzyl) -1H-isoindole-1, 3-diketone and chlorosulfonic acid as raw materials to synthesize a compound 6, wherein the compound 6 is 2- (3-sulfonic acid group-4-methylbenzyl) -1H-isoindole-1, 3-diketone;
synthesis of Compound 4: carrying out an electrolytic reaction on the compound 6, ammonium iodide and ammonia water serving as raw materials to obtain a compound 4, wherein the compound 4 is 2- (3-aminosulfonyl-4-methylbenzyl) -1H-isoindole-1, 3-dione;
synthesis of compound 3: taking the compound 4 and an oxidant as raw materials, and synthesizing a compound 3 under the action of a catalyst at the temperature of 0-120 ℃, wherein the compound 3 is 2- (1, 1-dioxo-1, 2-benzothiazole-3-keto-6-ylmethyl) -1H-isoindole-1, 3-dione;
synthesizing a target compound: the compound 3 and hydrazine hydrate are used as raw materials to synthesize 6-aminomethyl-1, 1-dioxo-1, 2-benzothiazole-3-ketone at the temperature of 0-100 ℃.
12. The method of synthesizing 6-aminomethyl-1, 1-dioxo-1, 2-benzothiazol-3-one according to claim 11, wherein said method of synthesizing compound 4 comprises: dissolving the compound 6 in methanol, adding 0.3-1 equivalent of ammonium iodide, then introducing excessive ammonia gas, and carrying out electrolytic reaction for 1-5 h at the temperature of 0-50 ℃ to obtain the compound 4.
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