CN105439915A - Preparation method of methyl 2-methoxy-5-sulfamoylbenzoate - Google Patents
Preparation method of methyl 2-methoxy-5-sulfamoylbenzoate Download PDFInfo
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- CN105439915A CN105439915A CN201511010518.4A CN201511010518A CN105439915A CN 105439915 A CN105439915 A CN 105439915A CN 201511010518 A CN201511010518 A CN 201511010518A CN 105439915 A CN105439915 A CN 105439915A
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- acid methyl
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C303/00—Preparation of esters or amides of sulfuric acids; Preparation of sulfonic acids or of their esters, halides, anhydrides or amides
- C07C303/36—Preparation of esters or amides of sulfuric acids; Preparation of sulfonic acids or of their esters, halides, anhydrides or amides of amides of sulfonic acids
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Abstract
The invention provides a preparation method of methyl 2-methoxy-5-sulfamoylbenzoate. The preparation method comprises the following steps: 2-methoxy-5-methyl chlorobenzoate and sodium amino sulfinate in a mole ratio being 1: (1.05-1.2) as well as a solvent and a catalyst are added to a reactor and react for 10-14 h when the temperature is controlled to be 45-60 DEG C; after reaction, activated carbon is added for decoloration, and the activated carbon, the catalyst and a by-product sodium chloride are removed through filtering; a filtrate is subjected to reduced-pressure concentration, and methyl 2-methoxy-5-sulfamoylbenzoate is obtained. The preparation method of methyl 2-methoxy-5-sulfamoylbenzoate has the advantages that an original process is short, the yield is high, the quality is good, three wastes contaminating the environment are avoided, environmental protection is realized, and the method is suitable for large-scale industrial production.
Description
Technical field
The invention belongs to organic compound synthesis technical field, particularly, relate to a kind of preparation method of 2-methoxyl group-5-sulfamoylbenzoic acid methyl esters.
Background technology
2-methoxyl group-5-sulfamoylbenzoic acid methyl esters is the important intermediate of anti-antipsychotics Sulpiride and left-handed Sulpiride.As shown in Figure 1, its synthesis all adopts at present both at home and abroad Whitfield's ointment through methylating, chlorosulphonation, amination, esterification must this product, its operational path is long, the quantity of three wastes that each step produces is large, especially high chemical oxygen demand (COD), high salt, high ammonia nitrogen, composite waste etc., intractability is large, and processing cost is high, seriously constrains this product large-scale industrial production.The present invention adopts brand-new technique with line, under adopting amino-sulfinic acid sodium and a small amount of catalyzer of 2-methoxy-5-chlorobenzoic acid methyl esters to exist, direct polycondensation and obtain this product, substantially reduce its synthetic route, overcome the shortcoming that above-mentioned three wastes generation is large, except producing a small amount of gac residue in purge process, produce without other three wastes free from environmental pollution, and its quality and yield exceed existing technique indices.
Summary of the invention
Goal of the invention: for the deficiencies in the prior art; the invention provides a kind of preparation method of 2-methoxyl group-5-sulfamoylbenzoic acid methyl esters; substantially reduce synthetic route; except producing a small amount of gac residue in purge process; produce without other three wastes free from environmental pollution; and product yield is high, quality is good, is convenient to the advantages such as suitability for industrialized production.
Technical scheme: the preparation method that the invention provides a kind of 2-methoxyl group-5-sulfamoylbenzoic acid methyl esters, be that the 2-methoxy-5-chlorobenzoic acid methyl esters of 1:1.05 ~ 1.2 and amino-sulfinic acid sodium and solvent and catalyzer join reaction unit by mol ratio, control temperature was 45 ~ 60 DEG C of reactions 10 ~ 14 hours; Reaction terminates, and adds activated carbon decolorizing, filters and removes gac, catalyzer and byproduct sodium chloride; Filtrate obtains 2-methoxyl group-5-sulfamoylbenzoic acid methyl esters through concentrating under reduced pressure.
Further, the preparation method of above-mentioned 2-methoxyl group-5-sulfamoylbenzoic acid methyl esters, described filtrate after concentrating under reduced pressure in 60 DEG C of vacuum-dryings.
Further, the preparation method of above-mentioned 2-methoxyl group-5-sulfamoylbenzoic acid methyl esters, described reaction unit is the reaction unit that reflux is housed.
Further, the preparation method of above-mentioned 2-methoxyl group-5-sulfamoylbenzoic acid methyl esters, described 2-methoxy-5-chlorobenzoic acid methyl esters, amino-sulfinic acid sodium, solvent and catalyzer are warming up to backflow in reaction unit, and being warming up to temperature is 45 ~ 60 DEG C.
Further, the preparation method of above-mentioned 2-methoxyl group-5-sulfamoylbenzoic acid methyl esters, described catalyzer is cuprous bromide.
Further, the preparation method of above-mentioned 2-methoxyl group-5-sulfamoylbenzoic acid methyl esters, the mol ratio of described 2-methoxy-5-chlorobenzoic acid methyl esters and cuprous bromide is 1:0.05 ~ 0.1.
Further, the preparation method of above-mentioned 2-methoxyl group-5-sulfamoylbenzoic acid methyl esters, is characterized in that: described solvent is tetrahydrofuran (THF).
Beneficial effect: compared with prior art; the present invention has the following advantages: the preparation method of 2-methoxyl group-5-sulfamoylbenzoic acid methyl esters of the present invention; advantage of the present invention is that former technical process is short; yield is high; quality is good; and the three wastes of nonpollution environment produce, very environmental protection, is applicable to large-scale industrial production.
Accompanying drawing explanation
Fig. 1 is the synthetic route chart of traditional technology 2-methoxyl group-5-sulfamoylbenzoic acid methyl esters of the present invention;
Fig. 2 is the synthetic route chart of 2-methoxyl group-5-sulfamoylbenzoic acid methyl esters of the present invention.
Embodiment
By several specific embodiment, will illustrate the present invention further below, these embodiments, just in order to describe the problem, are not a kind of restriction.
Embodiment 1
Synthetic route as shown in Figure 2, 300g tetrahydrofuran (THF) will be added in the 1000ml reaction flask that reflux is housed, 50g(0.25mol) 2-methoxy-5-chlorobenzoic acid methyl esters, 1.8g cuprous bromide (0.0125mol), 31g(0.3mol) amino-sulfinic acid sodium, be warming up to 60 DEG C, and keep 12 hours at this temperature, insulation terminates, in reaction solution, add 2 grams of gacs take advantage of heat filtering, filtrate reduced in volume is to dry, 60 DEG C of vacuum-dryings obtain, obtain 2-methoxyl group-5-sulfamoylbenzoic acid methyl esters white crystals powder 57.9g(0.236mol), yield 94.5%, content 99.51%(HPLC).
Wherein HPLC testing conditions: moving phase: 700 ml waters; Methyl alcohol 200 milliliters.Determined wavelength: 240nm, flow velocity 1.0ml/min, 0.01 gram, sample, is diluted to 25 milliliters by moving phase, sample size 5 μ l.
Embodiment 2
Synthetic route as shown in Figure 2, 300g tetrahydrofuran (THF) will be added in the 1000ml reaction flask that reflux is housed, 50g(0.25mol) 2-methoxy-5-chlorobenzoic acid methyl esters, 3.6g(0.025mol) cuprous bromide, 26.8g(0.26mol) amino-sulfinic acid sodium, be warming up to 45 DEG C, and keep 14 hours at this temperature, insulation terminates, in reaction solution, add 2 grams of gacs take advantage of heat filtering, filtrate reduced in volume is to dry, 60 DEG C of vacuum-dryings obtain, obtain 2-methoxyl group-5-sulfamoylbenzoic acid methyl esters white crystals powder 58.3g(0.238mol), yield 95.09%, content 99.66%(HPLC).
Wherein HPLC testing conditions: moving phase: 700 ml waters; Methyl alcohol 200 milliliters.Determined wavelength: 240nm, flow velocity 1.0ml/min, 0.01 gram, sample, is diluted to 25 milliliters by moving phase, sample size 5 μ l.
Embodiment 3
Synthetic route as shown in Figure 2, 300g tetrahydrofuran (THF) will be added in the 1000ml reaction flask that reflux is housed, 50g(0.25mol) 2-methoxy-5-chlorobenzoic acid methyl esters, 2.9g(0.02mol) cuprous bromide, 28.3g(0.275mol) amino-sulfinic acid sodium, be warming up to 50 DEG C, and keep 10 hours at this temperature, insulation terminates, in reaction solution, add 2 grams of gacs take advantage of heat filtering, filtrate reduced in volume is to dry, 60 DEG C of vacuum-dryings obtain, obtain 2-methoxyl group-5-sulfamoylbenzoic acid methyl esters white crystals powder 59.2g(0.241mol), yield 96.55%, content 99.51%(HPLC).
Wherein HPLC testing conditions: moving phase: 700 ml waters; Methyl alcohol 200 milliliters.Determined wavelength: 240nm, flow velocity 1.0ml/min, 0.01 gram, sample, is diluted to 25 milliliters by moving phase, sample size 5 μ l.
From embodiment 1-3, advantage of the present invention is that former technical process is short, and yield is high, reaches more than 90%.And good product quality, traditional technology need purified after can obtain content more than 99%, what the present invention can be stable obtain content all reaches more than 99.5% product.
The above is only several embodiments of invention, and it should be pointed out that for those skilled in the art, under the prerequisite not departing from inventive principle, can also make some improvement, these improvement also should be considered as protection scope of the present invention.
Claims (7)
1. the preparation method of a 2-methoxyl group-5-sulfamoylbenzoic acid methyl esters, it is characterized in that: be that the 2-methoxy-5-chlorobenzoic acid methyl esters of 1:1.05 ~ 1.2 and amino-sulfinic acid sodium and solvent and catalyzer join reaction unit by mol ratio, control temperature was 45 ~ 60 DEG C of reactions 10 ~ 14 hours; Reaction terminates, and adds activated carbon decolorizing, filters and removes gac, catalyzer and byproduct sodium chloride; Filtrate obtains 2-methoxyl group-5-sulfamoylbenzoic acid methyl esters through concentrating under reduced pressure.
2. the preparation method of 2-methoxyl group-5-sulfamoylbenzoic acid methyl esters according to claim 1, is characterized in that: described filtrate after concentrating under reduced pressure in 60 DEG C of vacuum-dryings.
3. the preparation method of 2-methoxyl group-5-sulfamoylbenzoic acid methyl esters according to claim 1, is characterized in that: described reaction unit is the reaction unit that reflux is housed.
4. the preparation method of 2-methoxyl group-5-sulfamoylbenzoic acid methyl esters according to claim 3, is characterized in that: described 2-methoxy-5-chlorobenzoic acid methyl esters, amino-sulfinic acid sodium, solvent and catalyzer are warming up to 45 ~ 60 DEG C in reaction unit.
5. the preparation method of the 2-methoxyl group-5-sulfamoylbenzoic acid methyl esters according to claim 1 or 4, is characterized in that: described catalyzer is cuprous bromide.
6. the preparation method of 2-methoxyl group-5-sulfamoylbenzoic acid methyl esters according to claim 5, is characterized in that: the mol ratio of described 2-methoxy-5-chlorobenzoic acid methyl esters and cuprous bromide is 1:0.05 ~ 0.1.
7. the preparation method of 2-methoxyl group-5-sulfamoylbenzoic acid methyl esters according to claim 1, is characterized in that: described solvent is tetrahydrofuran (THF).
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Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1884259A (en) * | 2006-06-08 | 2006-12-27 | 南开大学 | Process for preparing 2-methoxyl-5-amino sulfonyl methyl benzoate |
| CN103553990A (en) * | 2013-11-08 | 2014-02-05 | 苏州诚和医药化学有限公司 | Method for synthesizing 2-methoxyl-4-amino-5-ethylsulfonyl methyl benzoate by utilizing halogenation of halogen |
| CN105017098A (en) * | 2015-07-17 | 2015-11-04 | 大连奇凯医药科技有限公司 | Preparation technology of alkyloxybenzsulfamide and its derivatives |
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2015
- 2015-12-30 CN CN201511010518.4A patent/CN105439915A/en active Pending
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1884259A (en) * | 2006-06-08 | 2006-12-27 | 南开大学 | Process for preparing 2-methoxyl-5-amino sulfonyl methyl benzoate |
| CN103553990A (en) * | 2013-11-08 | 2014-02-05 | 苏州诚和医药化学有限公司 | Method for synthesizing 2-methoxyl-4-amino-5-ethylsulfonyl methyl benzoate by utilizing halogenation of halogen |
| CN105017098A (en) * | 2015-07-17 | 2015-11-04 | 大连奇凯医药科技有限公司 | Preparation technology of alkyloxybenzsulfamide and its derivatives |
Non-Patent Citations (2)
| Title |
|---|
| 张广良等: "4,4-二甲基-3-异噁唑酮衍生物的合成与表征", 《有机化学》 * |
| 王福兰等: "舒必利的合成", 《中国医药工业杂志》 * |
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