IES87007B2 - Drug intermediates o-nitrobenzenesulfonyl chloride synthesis method - Google Patents
Drug intermediates o-nitrobenzenesulfonyl chloride synthesis method Download PDFInfo
- Publication number
- IES87007B2 IES87007B2 IES20180199A IES20180199A IES87007B2 IE S87007 B2 IES87007 B2 IE S87007B2 IE S20180199 A IES20180199 A IE S20180199A IE S20180199 A IES20180199 A IE S20180199A IE S87007 B2 IES87007 B2 IE S87007B2
- Authority
- IE
- Ireland
- Prior art keywords
- solution
- nitrobenzenesulfonyl chloride
- washed
- synthesis method
- added
- Prior art date
Links
Classifications
-
- 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
- C07C303/02—Preparation of esters or amides of sulfuric acids; Preparation of sulfonic acids or of their esters, halides, anhydrides or amides of sulfonic acids or halides thereof
- C07C303/16—Preparation of esters or amides of sulfuric acids; Preparation of sulfonic acids or of their esters, halides, anhydrides or amides of sulfonic acids or halides thereof by oxidation of thiols, sulfides, hydropolysulfides, or polysulfides with formation of sulfo or halosulfonyl groups
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Detergent Compositions (AREA)
Abstract
The present invention discloses o-nitrobenzenesulfonyl chloride synthesis method, comprises the following steps: 5-hydroxy-6-thiomethyl-nitrobenzene and potassium chloride solution were added to the reaction vessel, the temperature of the solution was raised, the reaction was carried out, and then trichloroacetic acid solution is added in batches, controlled the stirring speed; triiron dodecacarbonyl is added within in batches, raises the temperature, continues to react, reduces the temperature, precipitated the solid, filtered, washed with sodium sulfate solution for several times, washed with triethylamine solution for several times, washed with nonane solution for several times, recrystallizes from the p-methoxybenzyl alcohol solution, dehydrates with dehydration, gets the finished o-nitrobenzenesulfonyl chloride. <Figure 1>
Description
Drug intermediates o-nitrobenzenesulfonyl chloride synthesis method
FIELD OF THE INVENTION
The present invention relates to a method for preparing a pharmaceutical intermediate which belongs to the field of organic synthesis, more particularly, relates to drug intermediates o-nitrobenzenesulfonyl chloride synthesis method.
GENERAL BACKGROUND
O-nitrobenzenesulfonyl chloride is mainly used as medicine, dye intermediates, the existing synthesis methods are mostly using the method that leads the chlorine gas into the bis(o-nitrophenyl)disulfide, the mixture of concentrated hydrochloric acid and concentrated nitric acid, the reaction temperature to 70°C, continues to heat and leading the chlorine into for lh, dumps the supernatant, the product is washed with water at 70 °C, cools it to solidification, dry, gets the o-nitrobenzenesulfonyl chloride. However, this synthesis method requires concentrated hydrochloric acid and concentrated nitric acid, chlorine as reactants, due to strong corrosion of concentrated hydrochloric acid and concentrated nitric acid, the equipment requires high corrosion resistance ability, the cost of reaction increases; chlorine is a kind of toxic gas, it is harmful to the synthesis operator health, the risk coefficient is higher, and the synthesis method is complicated and the final yield is not very high. Therefore, it is necessary to propose a new synthesis method.
SUMMARY
Based on the technical problems of the background technology, the purpose of the present invention is to provide drug intermediates o-nitrobenzenesulfonyl chloride synthesis method, comprises the following steps:
A. 5-hydroxy-6-thiomethyl-nitrobenzene and potassium chloride solution were added to the reaction vessel, the temperature of the solution was raised to 40-46 ° C, the reaction was carried out for 150-180 min, and then trichloroacetic acid solution is added in batches, controlled the stirring speed at 210-230 rpm;
B: triiron dodecacarbonyl is added within 60-80 min in batches, raises the temperature to 50-56 °C within 20-30 min, continues to react for 1-2 h, reduces the temperature to 5-11 °C, precipitated the solid, filtered, washed with sodium sulfate solution for several times, washed with triethylamine solution for several times, washed with nonane solution for several times, recrystallizes from the p-methoxybenzyl alcohol solution, dehydrates with dehydration, gets the finished o-nitrobenzenesulfonyl chloride.
Preferably, the potassium chloride solution has a mass fraction of 10-17%.
Preferably, the mass fraction of the trichloroacetic acid solution is 30-36%.
Preferably, the sodium sulfate solution has a mass fraction of 15-22%.
Preferably, the triethylamine solution has a mass fraction of 40-45%.
Preferably, the mass fraction of nonane solution is 60-67%.
Preferably, the p-methoxybenzyl alcohol solution has a mass fraction of 80-86%.
Throughout the reaction process can be the following reaction formula:
CjHClxO, + Fej(CO)12
NO,
Compared with the synthesis method disclosed in the background art, the invention provides drug intermediates o-nitrobenzenesulfonyl chloride synthesis method, it is unnecessary to use concentrated hydrochloric acid and concentrated nitric acid, chlorine as reactants, avoiding the concentrated hydrochloric acid and concentrated nitric acid corrosion to the equipment, reducing the cost of the reaction, avoiding the chlorine gas harmful to synthesis operators’ health, reducing the risk factor, reducing intermediate links reaction, decreasing the reaction time and improving the reaction yield, at the same time, the present invention provides a new synthetic route which has laid a good foundation for further enhancing the yield of the reaction.
DESCRIPTION OF THE DRAWINGS
Figure 1 is the infrared analysis spectrum of finished product o-nitrobenzenesulfonyl chloride.
DETAILED DESCRIPTION OF PREFERRED EMBODIMENTS
The following examples with reference to specific embodiments of the present invention are further illustrated:
Embodiment 1
Drug intermediates o-nitrobenzenesulfonyl chloride synthesis method, comprises the following steps:
A: 3mol 5-hydroxy-6-thiomethyl-nitrobenzene and 1.6L potassium chloride solution with a mass fraction of 10% were added to the reaction vessel, the temperature of the solution was raised to 40 ° C, the reaction was carried out for 150 min, and then 6 mol trichloroacetic acid solution with a mass fraction of 30% is added in 2 times, controlled the stirring speed at 210 rpm;
B: 3 mol triiron dodecacarbonyl is added within 60 min in 2 times, raises the temperature to 50 °C within 20 min, continues to react for 1 h, reduces the temperature to 5 °C, precipitated the solid, filtered, washed with sodium sulfate solution with a mass fraction of 15% for 3 times, washed with triethylamine solution with a mass fraction of 40% for 2 times, washed with nonane solution with a mass fraction of 60% for 3 times, recrystallizes from the p-methoxybenzyl alcohol solution with a mass fraction of 80%, dehydrates with activated alumina dehydration, gets the finished o-nitrobenzenesulfonyl chloride 590.07g, yield of 89%.
Embodiment 2
Drug intermediates o-nitrobenzenesulfonyl chloride synthesis method, comprises the following steps:
A: 3mol 5-hydroxy-6-thiomethyl-nitrobenzene and 1.6L potassium chloride solution with a mass fraction of 13.5% were added to the reaction vessel, the temperature of the solution was raised to 43 °C, the reaction was carried out for 165 min, and then 7 mol trichloroacetic acid solution with a mass fraction of 33% is added in 3 times, controlled the stirring speed at 220 rpm;
B: 3.5 mol triiron dodecacarbonyl is added within 70 min in 3 times, raises the temperature to 53 °C within 25 min, continues to react for 1.5 h, reduces the temperature to 5.5 °C, precipitated the solid, filtered, washed with sodium sulfate solution with a mass fraction of 17.5% for 4 times, washed with triethylamine solution with a mass fraction of 42.5% for 3 times, washed with nonane solution with a mass fraction of 63.5% for 4 times, recrystallizes from the p-methoxybenzyl alcohol solution with a mass fraction of 83%, dehydrates with anhydrous calcium sulphate dehydration, gets the finished o-nitrobenzenesulfonyl chloride 609.96g, yield of 92%.
Embodiment 3
Drug intermediates o-nitrobenzenesulfonyl chloride synthesis method, comprises the following steps:
A: 3mol 5-hydroxy-6-thiomethyl-nitrobenzene and 1.6L potassium chloride solution with a mass fraction of 17% were added to the reaction vessel, the temperature of the solution was raised to 46 °C, the reaction was carried out for 180 min, and then 8 mol trichloroacetic acid solution with a mass fraction of 36% is added in 4 times, controlled the stirring speed at 230 rpm;
B: 4 mol triiron dodecacarbonyl is added within 80 min in 4 times, raises the temperature to 56 °C within 30 min, continues to react for 2 h, reduces the temperature to 11°C, precipitated the solid, filtered, washed with sodium sulfate solution with a mass fraction of 22% for 5 times, washed with triethylamine solution with a mass fraction of 45% for 4 times, washed with nonane solution with a mass fraction of 67% for 5 times, recrystallizes from the p-methoxybenzyl alcohol solution with a mass fraction of 86%, dehydrates with phosphorus pentoxide dehydration, gets the finished o-nitrobenzenesulfonyl chloride 636.48g, yield of 96%.
Infrared analysis of finished product o-nitrobenzenesulfonyl chloride, infrared spectrum is shown in figure 1, the analysis of data is shown in table 1.
Table 1 Peak data
Serial Peak position Transmittance Half width Peak difference number (cm-1) (%) (cm'1) (%) 1 414 65 26 16 2 548 56 25 9 3 561 45 14 18 4 584 47 32 20 5 615 47 26 28
6 645 37 10 47 7 698 44 12 42 8 723 27 13 41 9 735 29 11 37 10 777 26 12 67 11 844 45 10 52 12 1052 66 11 22 13 1124 47 16 31 14 1145 51 17 18 15 1187 20 45 50 16 1268 60 35 12 17 1307 41 32 29 18 1363 23 41 22 19 1389 19 31 34 20 1463 25 44 46 21 1539 19 53 60 22 2854 9 56 7 23 2931 9 172 15 24 3099 27 193 19 25 3964 43 735 47
The embodiments of the present invention are merely preferred embodiments of the present invention, but the range of the present invention is not limited this, and any person who is familiar with those skilled in the arts, within the technical range of the present invention. It is intended that the technical solution and its inventive concept be replaced or modified equivalently with reference to the range of the invention.
Claims (4)
1. O-nitrobenzenesulfonyl chloride synthesis method, comprises the following steps: A: 5-hydroxy-6-thiomethyl-nitrobenzene and potassium chloride solution were added to the reaction vessel, the temperature of the solution was raised to 40-46 0 C, the reaction was carried out for 150-180 min, and then trichloroacetic acid solution is added in batches, controlled the stirring speed at 210-230 rpm; B: triiron dodecacarbonyl is added within 60-80 min in batches, raises the temperature to 50-56 °C within 20-30 min, continues to react for 1-2 h, reduces the temperature to 5-11 °C, precipitated the solid, filtered, washed with sodium sulfate solution for several times, washed with triethylamine solution for several times, washed with nonane solution for several times, recrystallizes from the p-methoxybenzyl alcohol solution, dehydrates with dehydration, gets the finished o-nitrobenzenesulfonyl chloride.
2. O-nitrobenzenesulfonyl chloride synthesis method according to claim 1 wherein the potassium chloride solution has a mass fraction of 10-17%.
3. O-nitrobenzenesulfonyl chloride synthesis method according to claim 1 wherein the mass fraction of the trichloroacetic acid solution is 30-36%.
4. O-nitrobenzenesulfonyl chloride synthesis method according to claim 1 wherein the sodium sulfate solution has a mass fraction of 15-22%.
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201710715097.8A CN108238986A (en) | 2017-08-19 | 2017-08-19 | The synthetic method of pharmaceutical intermediate ortho-nitrophenyl sulfonic acid chloride |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| IES20180199A2 IES20180199A2 (en) | 2019-05-01 |
| IES87007B2 true IES87007B2 (en) | 2019-05-01 |
Family
ID=60037065
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| IES20180199A IES87007B2 (en) | 2017-08-19 | 2018-06-26 | Drug intermediates o-nitrobenzenesulfonyl chloride synthesis method |
Country Status (4)
| Country | Link |
|---|---|
| CN (1) | CN108238986A (en) |
| AU (1) | AU2018100848A4 (en) |
| GB (1) | GB201713881D0 (en) |
| IE (1) | IES87007B2 (en) |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN113666848A (en) * | 2021-08-18 | 2021-11-19 | 山东同成医药股份有限公司 | Preparation method of o-nitrobenzenesulfonyl chloride |
-
2017
- 2017-08-19 CN CN201710715097.8A patent/CN108238986A/en active Pending
- 2017-08-30 GB GBGB1713881.9A patent/GB201713881D0/en not_active Ceased
-
2018
- 2018-06-21 AU AU2018100848A patent/AU2018100848A4/en not_active Ceased
- 2018-06-26 IE IES20180199A patent/IES87007B2/en unknown
Also Published As
| Publication number | Publication date |
|---|---|
| AU2018100848A4 (en) | 2018-08-02 |
| IES20180199A2 (en) | 2019-05-01 |
| CN108238986A (en) | 2018-07-03 |
| GB201713881D0 (en) | 2017-10-11 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| Li et al. | Rapid synthesis of metal-organic frameworks MIL-53 (Cr) | |
| CN104387311A (en) | Synthetic method of 3-arylselanyl indole compound | |
| AU2018100848A4 (en) | Drug intermediates o-nitrobenzenesulfonyl chloride synthesis method | |
| Wu et al. | A new acentric metal borate Mg [B6O9 (OH) 2]· 4H2O: Synthesis, structure and optical property | |
| Zhao et al. | Syntheses, structures and photocatalytic properties of a series of cobalt coordination polymers based on flexible bis (triazole) and dicarboxylate ligands | |
| Bhat et al. | First structurally characterized anion exchange product of noval cyclohexane containing substituted thio piperazinium chloride [C6H11S (CH2) 3C4H9N2C6H5Cl (L1Cl)]: synthesis, crystal structure and supramolecularity of (L1NO3) | |
| US3340299A (en) | Tetrasubstituted ethylene diamines | |
| CN106957255B (en) | Methylisoindoline of 5 bromines of one kind (R) N Boc 1 and its preparation method and application | |
| CN108912043B (en) | Synthetic method of 2,3, 5-trichloropyridine | |
| CN104610310B (en) | A kind of benzimidizole derivatives-cadmium (II) complex with fluorescence property and synthetic method thereof | |
| CN104557768A (en) | Synthesis method of benzothiazole derivatives | |
| AU2018100526A4 (en) | Drug intermediates p-benzoylbenzoic acid synthesis method | |
| CN106565603B (en) | A kind of synthetic method of 5,7- dinitro -8- amide groups quinolines | |
| CN111499622B (en) | Preparation method of medicine for treating bile duct cancer | |
| AU2018100827A4 (en) | Drug intermediates 4-benzyloxy-3-methoxy-4'-methylbenzophenone synthesis method | |
| AU2018100845A4 (en) | Trienegolinone intermediates dichlorobenzoquinone synthesis method | |
| AU2018100832A4 (en) | Drug intermediates 4-nitro-4'-ethyl amide diphenyl sulfone synthesis method | |
| AU2018100822A4 (en) | Antitumor drug intermediates 3, 5-tert-butyl-4-hydroxy benzoic acid synthesis method | |
| Niewahner et al. | Improved synthesis of Geodken's macrocycle through the synthesis of the dichloride salt | |
| AU2018100846A4 (en) | Anti-amoebic dysentery drug phenidone synthesis method | |
| CN108349870B (en) | Process for the preparation of intermediates of compounds which modulate kinase activity | |
| AU2018100818A4 (en) | Hormone drug intermediates 9(11)–pregnene-16beta-methyl-17alpha, 21-glycol-3,20-diketone-21-acetate synthesis method | |
| AU2018100532A4 (en) | Anti-arrhythmic drug intermediate 1-(2,6-dimethoxy)-2-acetone synthesis method | |
| AU2018100847A4 (en) | Anti-clavicular spirochete drugs ethyl imidazole synthesis method | |
| AU2018100821A4 (en) | Flavones glycoside drug intermediates acetylene carboxylic acid synthesis method |