CN110437113B - Synthesis method of 4-benzenesulfonylbenzoic acid - Google Patents
Synthesis method of 4-benzenesulfonylbenzoic acid Download PDFInfo
- Publication number
- CN110437113B CN110437113B CN201910690752.8A CN201910690752A CN110437113B CN 110437113 B CN110437113 B CN 110437113B CN 201910690752 A CN201910690752 A CN 201910690752A CN 110437113 B CN110437113 B CN 110437113B
- Authority
- CN
- China
- Prior art keywords
- acid
- benzenesulfonylbenzoic
- reaction
- temperature
- pressure
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Active
Links
Images
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C315/00—Preparation of sulfones; Preparation of sulfoxides
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C315/00—Preparation of sulfones; Preparation of sulfoxides
- C07C315/06—Separation; Purification; Stabilisation; Use of additives
Abstract
The invention discloses a synthesis method of 4-benzenesulfonyl benzoic acid, which comprises the following steps:
sodium benzene sulfinate and p-halogenated benzaldehyde are used as raw materials, inorganic matters are used as reaction catalysts, and heating and pressurizing reaction is carried out at the temperature of 150 ℃ and the temperature of 250 ℃ and under the oxygen atmosphere with the pressure of 0.5-50Mpa to obtain the target product 4-benzenesulfonylbenzoic acid. The raw materials adopted by the invention are cheap and easily available, the product cost is low, and the economic benefit is good; the target product obtained by the process has high purity, ideal yield and simple and convenient operation; the catalyst adopted by the process is cheap and easy to obtain, has high catalytic efficiency and stable catalytic effect, and has market popularization value.
Description
Technical Field
The invention relates to the technical field of preparation of medical intermediates, in particular to a synthetic method of 4-benzenesulfonylbenzoic acid.
Background
4-Benzenesulfonylbenzoic acid, British name 4-Benzenesulfonylbenzoic acid, Cas number 5361-54-6, as a white powder solid, melting point 276-78 ℃. 4-benzenesulfonylbenzoic acid is an important fine chemical, has been widely applied in the field of pharmaceutical synthesis in recent years, becomes a very important pharmaceutical intermediate, and has been applied to development of antitumor drugs, antibacterial drugs and the like.
At present, the synthesis method of 4-benzenesulfonyl benzoic acid mainly comprises the following 2 methods:
(1) 4-methyl diphenyl sulfone oxidation (US 2006/19965):
the synthesis method uses potassium permanganate as an oxidant for oxidation, needs a large amount of water as a solvent, generates a lot of wastes, and has the yield of only 26 percent.
(2) 4-acetyldiphenylsulfone haloform (Journal of Medicinal Chemistry 1991,34, 3295-3301.):
in the synthesis method, 4-acetyl diphenyl sulfone is used as a raw material and reacts with chlorine and liquid bromine under an alkaline condition to prepare 4-benzenesulfonyl benzoic acid, or sodium hypochlorite reacts with the 4-benzenesulfonyl benzoic acid; the yield of the reaction can be more than 70 percent, but the raw materials are expensive and the operation risk is high.
In order to overcome the defects of the original synthesis process, the search for a novel synthesis process for producing the 4-benzenesulfonylbenzoic acid is of great significance.
Disclosure of Invention
The invention aims to research and solve the defects of the existing 4-benzenesulfonylbenzoic acid synthesis technology, provides a production method which is simple and convenient to operate and low in cost, can realize the yield of 4-benzenesulfonylbenzoic acid, and can improve the yield and purity of 4-benzenesulfonylbenzoic acid.
In order to solve the technical problems, the invention adopts a technical scheme that:
provides a synthetic method of 4-benzenesulfonyl benzoic acid, which comprises the following synthetic route:
In a preferred embodiment of the invention, the mass ratio of the sodium benzene sulfinate to the p-halogenated benzaldehyde in the reaction is 2.0-3.5: 1.
In a preferred embodiment of the present invention, the mass ratio of the reaction catalyst to the raw material is 1:10 to 100.
In a preferred embodiment of the invention, the solvent used in the reaction is a mixture of one or more of ethanol, isopropanol, acetonitrile, toluene, 1, 4-dioxane, ethylene glycol monomethyl ether, ethylene glycol dimethyl ether, dimethylformamide, 1, 3-dimethyl-2-imidazolidinone, dimethyl sulfoxide, and hexamethylphosphoric triamide.
In a preferred embodiment of the invention, the catalyst is kaolin, diatomaceous earth, calcium hydroxide, calcium carbonate, powdered molecular sieve, 8-hydroxyquinoline copper, alumina, aluminum hydroxide, SiO2-Al2O3、Fe2O3-Cr2O3-K2O and one or more of vanadyl acetylacetonate.
In a preferred embodiment of the present invention, the reaction temperature is 180-220 ℃.
In a preferred embodiment of the invention, the solvent is dimethylformamide, dimethyl sulfoxide, hexamethylphosphoric triamide.
In a preferred embodiment of the invention, the catalyst is calcium carbonate, powdered molecular sieve, 8-hydroxyquinoline copper, Fe2O3-Cr2O3-K2O, vanadyl acetylacetonate.
In a preferred embodiment of the invention, the oxygen pressure is 0.5-10 MPa.
The invention has the beneficial effects that: the synthesis method of the 4-benzenesulfonyl benzoic acid has the advantages of cheap and easily-obtained raw materials, low product cost and good economic benefit; the target product obtained by the process has high purity, ideal yield and simple and convenient operation; the catalyst adopted by the process is cheap and easy to obtain, has high catalytic efficiency and stable catalytic effect, and has market popularization value.
Drawings
FIG. 1 is a nuclear magnetic spectrum of 4-benzenesulfonylbenzoic acid prepared by the method of the present invention.
Detailed Description
The following detailed description of the preferred embodiments of the present invention, taken in conjunction with the accompanying drawings, will make the advantages and features of the invention easier to understand by those skilled in the art, and thus will clearly and clearly define the scope of the invention.
Example 1:
adding 100 g of sodium benzene sulfinate, 30 g of 4-fluorobenzaldehyde, 5 g of 8-hydroxyquinoline copper and 100 mL of dimethyl sulfoxide into a 500mL miniature high-pressure reaction kettle, uniformly stirring, and introducing oxygen until the pressure is 1 MPa; gradually heating to 160 ℃, and keeping the temperature for reaction for 2 hours.
Cooled to room temperature, the reaction was poured into water, extracted with ethyl acetate, the organic solvent was removed, and the residue was recrystallized from ethanol to give 52 g of 4-benzenesulfonylbenzoic acid with a purity of 98.8%, 1H (NMR, d-DMSO): 13.6(brs, 1H), 8.18-8.16(m, 2H), 8.13-8.10(m, 2H), 8.03-8.01(m, 2H), 7.77-7.76(m, 1H), 7.69-7.65(m, 2H).
Example 2:
adding 120 g of sodium benzene sulfinate, 30 g of 4-fluorobenzaldehyde, 8 g of calcium carbonate and 100 mL of dimethylformamide into a 500mL miniature high-pressure reaction kettle, uniformly stirring, and introducing oxygen until the pressure is 10 MPa; gradually heating to 180 ℃, and keeping the temperature for reaction for 4 hours.
The reaction mixture was cooled to room temperature, poured into water, extracted with ethyl acetate, and the organic solvent was removed, and the residue was recrystallized from ethanol to give 34 g of 4-benzenesulfonylbenzoic acid with a purity of 98.1%.
Example 3:
150 g of sodium benzene sulfinate, 60 g of 4-iodobenzaldehyde, 10 g of vanadyl acetylacetonate and 100 mL of dimethyl sulfoxide are put into a 500mL miniature high-pressure reaction kettle and are stirred uniformly, and then oxygen is introduced until the pressure is 0.5 MPa; gradually heating to 200 ℃, and keeping the temperature for reaction for 2 hours.
The reaction mixture was cooled to room temperature, poured into water, extracted with ethyl acetate, and the organic solvent was removed, and the residue was recrystallized from ethanol to give 56 g of 4-benzenesulfonylbenzoic acid with a purity of 99.1%.
Example 4:
adding 110 g of sodium benzene sulfinate, 45 g of 4-bromobenzaldehyde, 5 g of Fe2O3-Cr2O3-K2O and 80 mL of hexamethylphosphoric triamide into a 500mL miniature high-pressure reaction kettle, uniformly stirring, and introducing oxygen until the pressure is 5 MPa; gradually heating to 180 ℃, and keeping the temperature for reaction for 3 hours.
Cooling to room temperature, pouring the reaction product into water, extracting with ethyl acetate, removing the organic solvent, and recrystallizing the residue with ethanol to obtain 52 g of 4-benzenesulfonylbenzoic acid with a purity of 99.2%.
Example 5:
100 g of sodium benzene sulfinate, 35 g of 4-chlorobenzaldehyde, 10 g of calcium hydroxide and 80 mL of hexamethylphosphoric triamide are put into a 500mL miniature high-pressure reaction kettle, and after uniform stirring, oxygen is introduced until the pressure is 15 MPa; gradually heating to 180 ℃, and keeping the temperature for 5 hours.
Cooling to room temperature, pouring the reactant into water, adjusting the pH value to 1 by concentrated hydrochloric acid, performing suction filtration, washing with water, and recrystallizing the solid by using ethanol to obtain 28 g of 4-benzenesulfonylbenzoic acid with the purity of 98.2%.
The above description is only an embodiment of the present invention, and not intended to limit the scope of the present invention, and all modifications of equivalent structures and equivalent processes, which are made by the present specification, or directly or indirectly applied to other related technical fields, are included in the scope of the present invention.
Claims (7)
1. A synthetic method of 4-benzenesulfonylbenzoic acid is characterized in that the synthetic route is as follows:
2. The method for synthesizing 4-benzenesulfonylbenzoic acid as claimed in claim 1, wherein the mass ratio of sodium benzene sulfinate to p-halogenated benzaldehyde in the reaction is 2.0-3.5: 1.
3. The synthesis method of 4-benzenesulfonylbenzoic acid as claimed in claim 1, wherein the mass ratio of the reaction catalyst to the raw material is 1: 10-100.
4. The method for synthesizing 4-benzenesulfonylbenzoic acid as claimed in claim 1, wherein the solvent used in the reaction is one or more selected from ethanol, isopropanol, acetonitrile, toluene, 1, 4-dioxane, ethylene glycol monomethyl ether, ethylene glycol dimethyl ether, dimethylformamide, 1, 3-dimethyl-2-imidazolidinone, dimethyl sulfoxide and hexamethylphosphoric triamide.
5. The method as claimed in claim 1, wherein the reaction temperature is 180-220 ℃.
6. The method according to claim 1 or 4, wherein the solvent is dimethylformamide, dimethylsulfoxide, or hexamethylphosphoric triamide.
7. The method of synthesizing 4-benzenesulfonylbenzoic acid as claimed in claim 1, wherein the oxygen pressure is 0.5-10 Mpa.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201910690752.8A CN110437113B (en) | 2019-07-29 | 2019-07-29 | Synthesis method of 4-benzenesulfonylbenzoic acid |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201910690752.8A CN110437113B (en) | 2019-07-29 | 2019-07-29 | Synthesis method of 4-benzenesulfonylbenzoic acid |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN110437113A CN110437113A (en) | 2019-11-12 |
| CN110437113B true CN110437113B (en) | 2021-02-09 |
Family
ID=68432125
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201910690752.8A Active CN110437113B (en) | 2019-07-29 | 2019-07-29 | Synthesis method of 4-benzenesulfonylbenzoic acid |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN110437113B (en) |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1997028129A1 (en) * | 1996-02-02 | 1997-08-07 | Zeneca Limited | Aminoheterocyclic derivatives as antithrombotic or anticoagulant agents |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE939325C (en) * | 1954-01-31 | 1956-02-23 | Asta Werke Ag Chem Fab | Process for the preparation of p-arylsulfonylbenzaldehydes |
-
2019
- 2019-07-29 CN CN201910690752.8A patent/CN110437113B/en active Active
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1997028129A1 (en) * | 1996-02-02 | 1997-08-07 | Zeneca Limited | Aminoheterocyclic derivatives as antithrombotic or anticoagulant agents |
Non-Patent Citations (5)
| Title |
|---|
| Design, Synthesis, Characterization and Antimicrobial Evaluation of Some Heterocyclic Condensed Systems with Bridgehead Nitrogen from Thiazolotriazole Class;Stefania-Felicia Barbuceanu 等;《Chem. Pharm. Bull.》;20151231;第694-700页 * |
| Synthesis and Biological Activity of a Series of Diaryl-Substituted a-Cyano-/8-hydroxypropenamides, a New Class of Anthelmintic Agents;Eric B. Sjogren 等;《J. Med. Chem.》;19911231;第3295-3301页 * |
| The Synthesis of Some p-Arylsulphonylbenxaldehydes and Related Aldehydes and Ketones;H. BURTON 等;《Journal of the Chemical Society》;19480101;第601-603页 * |
| Visible-Light Photoredox/Nickel Dual Catalysis for the Cross-Coupling of Sulfinic Acid Salts with Aryl Iodides;Nai-Wei Liu 等;《Org. Lett.》;20180116;第760-763页 * |
| 新型二吡咯类有机荧光材料的合成及其性能研究;刘欢 等;《化工新型材料》;20180831;第244-247页 * |
Also Published As
| Publication number | Publication date |
|---|---|
| CN110437113A (en) | 2019-11-12 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN110862310B (en) | Synthesis method of cyclopropyl methyl ketone | |
| JP5873484B2 (en) | Dronedarone and method for producing the salt thereof | |
| CN107848943A (en) | Prepare the new method of chromanone derivatives | |
| CN110437113B (en) | Synthesis method of 4-benzenesulfonylbenzoic acid | |
| WO2022088301A1 (en) | Method for synthesizing m-phenylenediamine | |
| CN115504870B (en) | Preparation method and application of 4-methoxy-2-naphthol | |
| CN108947800B (en) | Synthesis method of (1S) -4, 5-dimethoxy-1- (carbonylaminomethyl) benzocyclobutane | |
| CN108164423B (en) | Preparation method of naftifine hydrochloride | |
| CN113861069B (en) | Preparation method of nitrile compound | |
| US11325922B2 (en) | Process for the preparation of Crisaborole in a stable crystal form | |
| CN109232544B (en) | Preparation method of prucalopride | |
| US20220235010A1 (en) | Synthesis method for 1-methyl-1h-indazole-6-carboxylic acid | |
| CN102173993B (en) | Method for synthesizing 4,6-diamino resorcinol dihydrochloride (DAR) | |
| CN101516817A (en) | Process for the preparation of trifluoroethoxytoluenes | |
| CN116178239B (en) | Synthesis method of 5- (2-fluorophenyl) -1H-pyrrole-3-formaldehyde | |
| CN112552241A (en) | Synthesis method of pyridazinone | |
| CN113354623B (en) | Preparation method of ilaprazole key intermediate 5- (1H-pyrrole-1-yl) -2-mercaptobenzimidazole | |
| CN112266360B (en) | Synthesis method of high-purity histamine dihydrochloride | |
| CN112645799B (en) | Resorcinol post-treatment process | |
| CN104230747B (en) | A kind of preparation method of asymmetry aromatic azo-compound | |
| CN112110824B (en) | Method for preparing 2-bromo-5-fluoroaniline | |
| CN114163417B (en) | Synthesis method of 3-bromodibenzothiophene | |
| CN115650860A (en) | Synthesis method of 2,2', 5' -tetrachlorobenzidine | |
| CN112358380B (en) | Synthesis method of 4- (4' -alkylcyclohexyl) cyclohexanol | |
| CN117903043A (en) | Preparation method of cis-2-pyridine-2-yl cyclohexanol |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant |