CN105646295A - Method for preparing 2-methoxy-5-sulfamoyl methyl benzoate - Google Patents
Method for preparing 2-methoxy-5-sulfamoyl methyl benzoate Download PDFInfo
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- CN105646295A CN105646295A CN201511010526.9A CN201511010526A CN105646295A CN 105646295 A CN105646295 A CN 105646295A CN 201511010526 A CN201511010526 A CN 201511010526A CN 105646295 A CN105646295 A CN 105646295A
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- methyl ester
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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
- C07C303/40—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 by reactions not involving the formation of sulfonamide groups
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- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
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Abstract
The invention provides a method for preparing 2-methoxy-5-sulfamoyl methyl benzoate. The method comprises the following steps: adding 2-methoxy-5-chlorobenzene methyl formate and sodium aminosulfinate at the mol ratio of 1:1-1.1 and a solvent and a catalyst into a reactor, controlling temperature at 40-65 DEG C and reacting for 8-16 h; carrying out decoloration by adding active carbon after the reaction, filtering to remove active carbon, the catalyst and a by-product sodium chloride; and carrying out vacuum concentration on a filtrate so as to obtain 2-methoxy-5-sulfamoyl methyl benzoate. The method for preparing 2-methoxy-5-sulfamoyl methyl benzoate has advantages of short original process flow, high yield and good quality. In addition, ''three wastes (waste gas, waste water and industrial residue)'' which pollute the environment are not generated. The method is very environmentally friendly and is suitable for large-scale industrial production.
Description
Technical field
The invention belongs to organic compound synthesis technical field, in particular it relates to a kind of method preparing 2-methoxyl group-5-sulfamoylbenzoic acid methyl ester.
Background technology
2-methoxyl group-5-sulfamoylbenzoic acid methyl ester 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 salicylic acid through methylating, chlorosulfonation, amination, be esterified to obtain this product, its process route is long, the quantity of three wastes that each step produces is big, especially high chemical oxygen demand (COD), high salt, high ammonia nitrogen, composite waste etc., intractability is big, and processing cost is high, seriously constrains this product large-scale industrial production. The present invention adopts brand-new technique with line, under adopting a small amount of catalyst of amino sulfinic acid sodium and 2-methoxy-5-chlorobenzoic acid methyl ester to exist, direct polycondensation and obtain this product, substantially reduce its synthetic route, overcome the shortcoming that above-mentioned three wastes generation amount is big, except purge process produces a small amount of activated carbon residue, 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 method preparing 2-methoxyl group-5-sulfamoylbenzoic acid methyl ester; substantially reduce synthetic route; except purge process produces a small amount of activated carbon residue; produce without other three wastes free from environmental pollution; and product yield is high, quality is good, it is simple to advantages such as industrialized production.
Technical scheme: the invention provides a kind of method preparing 2-methoxyl group-5-sulfamoylbenzoic acid methyl ester, it is that the 2-methoxy-5-chlorobenzoic acid methyl ester of 1:1��1.1 and amino sulfinic acid sodium and solvent and catalyst join reaction unit by mol ratio, controls temperature and react 8��16 hours at 40��65 DEG C; Reaction terminates, and adds activated carbon decolorizing, filters and removes activated carbon, catalyst and byproduct sodium chloride; Filtrate obtains 2-methoxyl group-5-sulfamoylbenzoic acid methyl ester through concentrating under reduced pressure.
Further, the above-mentioned method preparing 2-methoxyl group-5-sulfamoylbenzoic acid methyl ester, described filtrate after concentrating under reduced pressure in 60 DEG C of vacuum dryings.
Further, the above-mentioned method preparing 2-methoxyl group-5-sulfamoylbenzoic acid methyl ester, described reaction unit is the reaction unit equipped with reflux.
Further, the above-mentioned method preparing 2-methoxyl group-5-sulfamoylbenzoic acid methyl ester, described 2-methoxy-5-chlorobenzoic acid methyl ester, amino sulfinic acid sodium, solvent and catalyst are warming up to backflow in reaction unit, and being warming up to temperature is 40��65 DEG C.
Further, the above-mentioned method preparing 2-methoxyl group-5-sulfamoylbenzoic acid methyl ester, described catalyst is cuprous bromide.
Further, the above-mentioned method preparing 2-methoxyl group-5-sulfamoylbenzoic acid methyl ester, the mol ratio of described 2-methoxy-5-chlorobenzoic acid methyl ester and cuprous bromide is 1:0.05��0.1.
Further, the above-mentioned method preparing 2-methoxyl group-5-sulfamoylbenzoic acid methyl ester, it is characterised in that: described solvent is oxolane.
Beneficial effect: compared with prior art; the invention have the advantages that the method preparing 2-methoxyl group-5-sulfamoylbenzoic acid methyl ester of the present invention; advantage of the present invention is that former technological process is short; yield is high; quality is good; and the three wastes of nonpollution environment produce, very environmental protection, it is suitable for large-scale industrial production.
Accompanying drawing explanation
Fig. 1 is the synthetic route chart of traditional handicraft 2-methoxyl group-5-sulfamoylbenzoic acid methyl ester of the present invention;
Fig. 2 is the synthetic route chart of 2-methoxyl group-5-sulfamoylbenzoic acid methyl ester of the present invention.
Detailed description of the invention
Following by several specific embodiments, being further elucidated with the present invention, these embodiments, simply to illustrate that problem, are not a kind of restriction.
Embodiment 1
Synthetic route as shown in Figure 2, 300g oxolane will be added in equipped with the 1000ml reaction bulb of reflux, 50g(0.25mol) 2-methoxy-5-chlorobenzoic acid methyl ester, 1.8g cuprous bromide (0.0125mol), 25.7g(0.25mol) amino sulfinic acid sodium, it is warming up to 65 DEG C, and keep 12 hours at this temperature, insulation terminates, reactant liquor adds 2 grams of activated carbons and takes 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 ester white crystals powder 57.9g(0.236mol), yield 94.5%, content 99.51%(HPLC).
Wherein HPLC testing conditions: mobile phase: 700 milliliters of water; Methanol 200 milliliters. Detection wavelength: 240nm, flow velocity 1.0ml/min, 0.01 gram of sample, it is diluted to 25 milliliters with mobile phase, sample size 5 �� l.
Embodiment 2
Synthetic route as shown in Figure 2, 300g oxolane will be added in equipped with the 1000ml reaction bulb of reflux, 50g(0.25mol) 2-methoxy-5-chlorobenzoic acid methyl ester, 3.6g(0.025mol) cuprous bromide, 26.8g(0.26mol) amino sulfinic acid sodium, it is warming up to 45 DEG C, and keep 16 hours at this temperature, insulation terminates, reactant liquor adds 2 grams of activated carbons and takes 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 ester white crystals powder 58.3g(0.238mol), yield 95.09%, content 99.66%(HPLC).
Wherein HPLC testing conditions: mobile phase: 700 milliliters of water; Methanol 200 milliliters. Detection wavelength: 240nm, flow velocity 1.0ml/min, 0.01 gram of sample, it is diluted to 25 milliliters with mobile phase, sample size 5 �� l.
Embodiment 3
Synthetic route as shown in Figure 2, 300g oxolane will be added in equipped with the 1000ml reaction bulb of reflux, 50g(0.25mol) 2-methoxy-5-chlorobenzoic acid methyl ester, 2.9g(0.02mol) cuprous bromide, 28.3g(0.275mol) amino sulfinic acid sodium, it is warming up to 40 DEG C, and keep 8 hours at this temperature, insulation terminates, reactant liquor adds 2 grams of activated carbons and takes 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 ester white crystals powder 59.2g(0.241mol), yield 96.55%, content 99.51%(HPLC).
Wherein HPLC testing conditions: mobile phase: 700 milliliters of water; Methanol 200 milliliters. Detection wavelength: 240nm, flow velocity 1.0ml/min, 0.01 gram of sample, it is diluted to 25 milliliters with mobile phase, sample size 5 �� l.
From embodiment 1-3 it can be seen that advantage of the present invention is that former technological process is short, yield is high, reaches more than 90%. And good product quality, can obtain content more than 99% after traditional handicraft need are purified, and the present invention can be stably obtained content and all reach more than 99.5% product.
The above is only several embodiments of invention, it is noted that for those skilled in the art, under the premise without departing from inventive principle, it is also possible to make some improvement, these improvement also should be regarded as protection scope of the present invention.
Claims (7)
1. the method preparing 2-methoxyl group-5-sulfamoylbenzoic acid methyl ester, it is characterized in that: be that the 2-methoxy-5-chlorobenzoic acid methyl ester of 1:1��1.1 and amino sulfinic acid sodium and solvent and catalyst join reaction unit by mol ratio, control temperature and react 8��16 hours at 40��65 DEG C; Reaction terminates, and adds activated carbon decolorizing, filters and removes activated carbon, catalyst and byproduct sodium chloride; Filtrate obtains 2-methoxyl group-5-sulfamoylbenzoic acid methyl ester through concentrating under reduced pressure.
2. the method preparing 2-methoxyl group-5-sulfamoylbenzoic acid methyl ester according to claim 1, it is characterised in that: described filtrate after concentrating under reduced pressure in 60 DEG C of vacuum dryings.
3. the method preparing 2-methoxyl group-5-sulfamoylbenzoic acid methyl ester according to claim 1, it is characterised in that: described reaction unit is the reaction unit equipped with reflux.
4. the method preparing 2-methoxyl group-5-sulfamoylbenzoic acid methyl ester according to claim 3, it is characterised in that: described 2-methoxy-5-chlorobenzoic acid methyl ester, amino sulfinic acid sodium, solvent and catalyst are warming up to 40��65 DEG C in reaction unit.
5. the method preparing 2-methoxyl group-5-sulfamoylbenzoic acid methyl ester according to claim 1 or 4, it is characterised in that: described catalyst is cuprous bromide.
6. the method preparing 2-methoxyl group-5-sulfamoylbenzoic acid methyl ester according to claim 5, it is characterised in that: the mol ratio of described 2-methoxy-5-chlorobenzoic acid methyl ester and cuprous bromide is 1:0.05��0.1.
7. the method preparing 2-methoxyl group-5-sulfamoylbenzoic acid methyl ester according to claim 1, it is characterised in that: described solvent is oxolane.
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| CN201511010526.9A CN105646295A (en) | 2015-12-30 | 2015-12-30 | Method for preparing 2-methoxy-5-sulfamoyl methyl benzoate |
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| CN201511010526.9A CN105646295A (en) | 2015-12-30 | 2015-12-30 | Method for preparing 2-methoxy-5-sulfamoyl methyl benzoate |
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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 |
-
2015
- 2015-12-30 CN CN201511010526.9A patent/CN105646295A/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 (1)
| Title |
|---|
| 王福兰等: "舒比利的合成", 《中国医药工业杂志》 * |
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