CN106380429A - Method for synthesizing 2-nitro-methylsulfonylbenzoic acid - Google Patents

Method for synthesizing 2-nitro-methylsulfonylbenzoic acid Download PDF

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Publication number
CN106380429A
CN106380429A CN201610777987.7A CN201610777987A CN106380429A CN 106380429 A CN106380429 A CN 106380429A CN 201610777987 A CN201610777987 A CN 201610777987A CN 106380429 A CN106380429 A CN 106380429A
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Prior art keywords
acid
nitro
nitric acid
methylsulfonyltoluene
content
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CN201610777987.7A
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Chinese (zh)
Inventor
李仁峰
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Jujube Guipu Material Ltd Company
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Jujube Guipu Material Ltd Company
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Priority to CN201610777987.7A priority Critical patent/CN106380429A/en
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    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07CACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C315/00Preparation of sulfones; Preparation of sulfoxides
    • C07C315/04Preparation of sulfones; Preparation of sulfoxides by reactions not involving the formation of sulfone or sulfoxide groups

Abstract

The invention discloses a method for synthesizing 2-nitro-methylsulfonylbenzoic acid. The production materials are p-toluene sulfonic acid, nitric acid, sulfuric acid and vanadic anhydride. According to the invention, under existence condition of nitric acid and oxygen, catalytic oxidation dual effects of vanadic anhydride are employed to increase the reaction conversion rate and the yield of the product 2-nitro-methylsulfonylbenzoic acid; dropping of mixed acid replaces the single dropping of nitric acid, massive nitric acid decomposition and volatilization can be prevented, the nitric acid concentration in a reaction solution is kept in a certain scope, and nitric acid utilization rate is greatly increased.

Description

A kind of 2- nitro-to thiamphenicol benzoic acid synthesis technique
Technical field
The present invention relates to chemical products manufacture field, specially a kind of 2- nitro-to thiamphenicol benzoic acid synthesis technique.
Background technology
2- nitryl-4-thiamphenicol benzoic acid, also known as adjacent nitro is to thiamphenicol benzoic acid, CAS No. is 110964-79-9; English name is 2-Nitro-4-methylsulfonylbenzoic acid or O-Nitro-P-Methylsulfonyl Benzoic Acid (referred to as NMSBA);Molecular formula is C8H7NO6S, and molecular weight is 245.21, is white or yellowish under normal temperature Color crystalline powder.2- nitryl-4-thiamphenicol benzoic acid is important organic synthesis intermediate, be widely used in dyestuff, medicine and The production of agricultural chemicals.2- nitro is a kind of important medicinal intermediate to thiamphenicol benzoic acid.The benzene of 2- nitro -4- methylsulfonyltoluene Two strong electron-withdrawing groups group is had on ring so that methyl oxidation is relatively difficult for carboxyl, and to the control of degree of oxidation also very Difficult.At present, existing report is mainly divided by the method that 2- nitro -4- methylsulfonyltoluene prepares 2- nitryl-4-thiamphenicol benzoic acid For chemical oxidization method and liquid phase oxygen (air) oxidizing process.Prepare this kind of benzoic acid containing multiple electron-withdrawing groups, generally will use The toluene of the corresponding substituent of strong oxidizer nitric acid oxidation and obtain, because the difficult oxidation of the toluene containing electron-withdrawing group is still needed in five oxidations Just can carry out under two vanadium catalysis.
But existing 2- nitro-in thiamphenicol benzoic acid synthesis technique, purity and poor yields, and a large amount of nitric acid is with tail The discharge of gas, pollutes environment, wastes substantial amounts of resource.
Content of the invention
It is an object of the invention to provide a kind of 2- nitro-to thiamphenicol benzoic acid synthesis technique, to solve above-mentioned background The problem proposing in technology.
For achieving the above object, the present invention provides following technical scheme:A kind of 2- nitro-work is synthesized to thiamphenicol benzoic acid Skill, is to methylsulfonyltoluene, nitric acid, sulfuric acid, vanadic anhydride including 2- nitro-to thiamphenicol benzoic acid production material, described 2- nitro-be to thiamphenicol benzoic acid production synthetic process step:
(1) by the concentrated sulfuric acid with methylsulfonyltoluene is sequentially placed in reactor, and be sufficiently stirred for;
(2) when reactor temperature is at 0~10 DEG C, drip nitration mixture;
(3) after acid adding finishes, stir 2-2.5h at 10-12 DEG C, subsequently will rise to 15-25 DEG C, continue stirring 2- 2.5h;
(4), stopped when content is less than 0.1% to methylsulfonyltoluene content with high performance liquid chromatograph analysis raw material Reaction;
(5) catalyst, then heating mixture are added in reactant;
(6) when reactor internal temperature is 30-40 DEG C, it is passed through oxygen, meanwhile, continue dropping in reactant necessarily dense The nitration mixture of degree, the time is 6.5-7.5h;
(7), stopped when content is less than 0.1% to methylsulfonyltoluene content with high performance liquid chromatograph analysis raw material Reaction;
(8) reaction mixture is cooled to 20-25 DEG C, carries out vacuum filtration, and filter cake is washed with water to neutrality, be dried.
Further, described to methylsulfonyltoluene, nitric acid, vanadic anhydride content be followed successively by 98.5%, 65%, 99.5%.
Further, described nitration mixture is that sulfuric acid is formed with nitric acid fusion, and proportioning is, sulfuric acid: nitric acid=50ml: 20ml.
Further, described catalyst is vanadic anhydride.
Compared with prior art, the invention has the beneficial effects as follows:
A kind of 2- nitro of the present invention-and to thiamphenicol benzoic acid synthesis technique, under conditions of nitric acid and oxygen exist, adopt With the catalysis oxidation double action of vanadic anhydride, improve the conversion ratio of reaction and product 2- nitro-to methylsulfonyl benzene The yield of formic acid;Replaced using dropping mixed acid and individually drip nitric acid it is therefore prevented that the decomposition of a large amount of nitric acid and volatilization, keep reaction In liquid, the concentration of nitric acid maintains in certain scope, substantially increases the utilization rate of nitric acid.
Specific embodiment
Below in conjunction with the accompanying drawing in the embodiment of the present invention, the technical scheme in the embodiment of the present invention is carried out clear, complete Site preparation description is it is clear that described embodiment is only a part of embodiment of the present invention, rather than whole embodiments.It is based on Embodiment in the present invention, it is every other that those of ordinary skill in the art are obtained under the premise of not making creative work Embodiment, broadly falls into the scope of protection of the invention.
Embodiment 1
A kind of 2- nitro-to thiamphenicol benzoic acid synthesis technique, including 2- nitro-be to thiamphenicol benzoic acid production material To methylsulfonyltoluene, nitric acid, sulfuric acid, vanadic anhydride, described 2- nitro-thiamphenicol benzoic acid production synthetic process is walked Suddenly it is:
(1) by the concentrated sulfuric acid with methylsulfonyltoluene is sequentially placed in reactor, and be sufficiently stirred for;
(2) when reactor temperature is at 0 DEG C, drip nitration mixture;
(3) after acid adding finishes, stir 2h at 10 DEG C, subsequently will rise to 15 DEG C, continue stirring 2h;
(4), stopped when content is less than 0.1% to methylsulfonyltoluene content with high performance liquid chromatograph analysis raw material Reaction;
(5) catalyst, then heating mixture are added in reactant;
(6) when reactor internal temperature is 30 DEG C, it is passed through oxygen, meanwhile, continue dropping finite concentration in reactant Nitration mixture, the time be 6.5h;
(7), stopped when content is less than 0.1% to methylsulfonyltoluene content with high performance liquid chromatograph analysis raw material Reaction;
(8) reaction mixture is cooled to 20-25 DEG C, carries out vacuum filtration, and filter cake is washed with water to neutrality, be dried.
The described content to methylsulfonyltoluene, nitric acid, vanadic anhydride is followed successively by 98.5%, 65%, 99.5%.
Described nitration mixture is that sulfuric acid is formed with nitric acid fusion, and proportioning is, sulfuric acid: nitric acid=50ml: 20ml.
Described catalyst is vanadic anhydride.
Embodiment 2
A kind of 2- nitro-to thiamphenicol benzoic acid synthesis technique, including 2- nitro-be to thiamphenicol benzoic acid production material To methylsulfonyltoluene, nitric acid, sulfuric acid, vanadic anhydride, described 2- nitro-thiamphenicol benzoic acid production synthetic process is walked Suddenly it is:
(1) by the concentrated sulfuric acid with methylsulfonyltoluene is sequentially placed in reactor, and be sufficiently stirred for;
(2) when reactor temperature is at 5 DEG C, drip nitration mixture;
(3) after acid adding finishes, stir 2.3h at 11 DEG C, subsequently will rise to 20 DEG C, continue stirring 2.3h;
(4), stopped when content is less than 0.1% to methylsulfonyltoluene content with high performance liquid chromatograph analysis raw material Reaction;
(5) catalyst, then heating mixture are added in reactant;
(6) when reactor internal temperature is 35 DEG C, it is passed through oxygen, meanwhile, continue dropping finite concentration in reactant Nitration mixture, the time be 7h;
(7), stopped when content is less than 0.1% to methylsulfonyltoluene content with high performance liquid chromatograph analysis raw material Reaction;
(8) reaction mixture is cooled to 23 DEG C, carries out vacuum filtration, and filter cake is washed with water to neutrality, be dried.
The described content to methylsulfonyltoluene, nitric acid, vanadic anhydride is followed successively by 98.5%, 65%, 99.5%.
Described nitration mixture is that sulfuric acid is formed with nitric acid fusion, and proportioning is, sulfuric acid: nitric acid=50ml: 20ml.
Described catalyst is vanadic anhydride.
Embodiment 3
A kind of 2- nitro-to thiamphenicol benzoic acid synthesis technique, including 2- nitro-be to thiamphenicol benzoic acid production material To methylsulfonyltoluene, nitric acid, sulfuric acid, vanadic anhydride, described 2- nitro-thiamphenicol benzoic acid production synthetic process is walked Suddenly it is:
(1) by the concentrated sulfuric acid with methylsulfonyltoluene is sequentially placed in reactor, and be sufficiently stirred for;
(2) when reactor temperature is at 10 DEG C, drip nitration mixture;
(3) after acid adding finishes, stir 2.5h at 12 DEG C, subsequently will rise to 25 DEG C, continue stirring 2.5h;
(4), stopped when content is less than 0.1% to methylsulfonyltoluene content with high performance liquid chromatograph analysis raw material Reaction;
(5) catalyst, then heating mixture are added in reactant;
(6) when reactor internal temperature is 40 DEG C, it is passed through oxygen, meanwhile, continue dropping finite concentration in reactant Nitration mixture, the time be 7.5h;
(7), stopped when content is less than 0.1% to methylsulfonyltoluene content with high performance liquid chromatograph analysis raw material Reaction;
(8) reaction mixture is cooled to 25 DEG C, carries out vacuum filtration, and filter cake is washed with water to neutrality, be dried.
The described content to methylsulfonyltoluene, nitric acid, vanadic anhydride is followed successively by 98.5%, 65%, 99.5%.
Described nitration mixture is that sulfuric acid is formed with nitric acid fusion, and proportioning is, sulfuric acid: nitric acid=50ml: 20ml.
Described catalyst is vanadic anhydride.
In sum, under conditions of nitric acid and oxygen exist, the catalysis oxidation using vanadic anhydride is dual for the present invention Effect, improves the yield of the conversion ratio of reaction and product 2- nitro-to thiamphenicol benzoic acid;Taken using dropping mixed acid Generation independent dropping nitric acid, it is therefore prevented that the decomposition of a large amount of nitric acid and volatilization, keeps the concentration of nitric acid in reactant liquor to maintain certain In the range of, substantially increase the utilization rate of nitric acid.
Although an embodiment of the present invention has been shown and described, for the ordinary skill in the art, permissible Understand and can carry out multiple changes, modification, replacement to these embodiments without departing from the principles and spirit of the present invention And modification, the scope of the present invention be defined by the appended.

Claims (4)

1. a kind of 2- nitro-to thiamphenicol benzoic acid synthesis technique it is characterised in that:Including 2- nitro-to thiamphenicol benzoic acid Production material is to methylsulfonyltoluene, nitric acid, sulfuric acid, vanadic anhydride, described 2- nitro-produce synthesis to thiamphenicol benzoic acid Process step is:
(1) by the concentrated sulfuric acid with methylsulfonyltoluene is sequentially placed in reactor, and be sufficiently stirred for;
(2) when reactor temperature is at 0~10 DEG C, drip nitration mixture;
(3) after acid adding finishes, stir 2-2.5h at 10-12 DEG C, subsequently will rise to 15-25 DEG C, continue stirring 2-2.5h;
(4) when content is less than 0.1%, stop reaction with high performance liquid chromatograph analysis raw material to methylsulfonyltoluene content;
(5) catalyst, then heating mixture are added in reactant;
(6) when reactor internal temperature is 30-40 DEG C, it is passed through oxygen, meanwhile, continue dropping in reactant certain density Nitration mixture, the time is 6.5-7.5h;
(7) when content is less than 0.1%, stop reaction with high performance liquid chromatograph analysis raw material to methylsulfonyltoluene content;
(8) reaction mixture is cooled to 20-25 DEG C, carries out vacuum filtration, and filter cake is washed with water to neutrality, be dried.
2. a kind of 2- nitro according to claim 1-to thiamphenicol benzoic acid synthesis technique it is characterised in that:Described right Methylsulfonyltoluene, nitric acid, the content of vanadic anhydride are followed successively by 98.5%, 65%,
99.5%.
3. a kind of 2- nitro according to claim 1-to thiamphenicol benzoic acid synthesis technique it is characterised in that:Described mixed Acid is formed with nitric acid fusion for sulfuric acid, and proportioning is, sulfuric acid: nitric acid=50ml: 20ml.
4. a kind of 2- nitro according to claim 1-to thiamphenicol benzoic acid synthesis technique it is characterised in that:Described urge Agent is vanadic anhydride.
CN201610777987.7A 2016-08-30 2016-08-30 Method for synthesizing 2-nitro-methylsulfonylbenzoic acid Pending CN106380429A (en)

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Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4781750A (en) * 1985-08-27 1988-11-01 Rohm And Haas Company Herbicidally active enols
CN1038584C (en) * 1992-10-19 1998-06-03 Basf公司 Preparation of methylsulfonylbenzoic acids
CN101921215A (en) * 2010-08-20 2010-12-22 安吉豪森药业有限公司 Method for producing 2-nitro-p-methylsullfonyl benzoic acid

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4781750A (en) * 1985-08-27 1988-11-01 Rohm And Haas Company Herbicidally active enols
CN1038584C (en) * 1992-10-19 1998-06-03 Basf公司 Preparation of methylsulfonylbenzoic acids
CN101921215A (en) * 2010-08-20 2010-12-22 安吉豪森药业有限公司 Method for producing 2-nitro-p-methylsullfonyl benzoic acid

Non-Patent Citations (3)

* Cited by examiner, † Cited by third party
Title
张园园 等: "2-硝基-4-对甲砜基苯甲酸合成工艺的优化", 《湖北农业科学》 *
杨剑波 等: "硝磺酮的合成与除草效果", 《农药》 *
高学彦 等: "2-硝基-4-甲磺酰基苯甲酸的合成研究", 《化学试剂》 *

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Application publication date: 20170208