CN109879818A - The synthetic method of N- (4,6- dimethoxypyridin -2- base) -4- methylsulfonyl -2- nitrobenzamide - Google Patents
The synthetic method of N- (4,6- dimethoxypyridin -2- base) -4- methylsulfonyl -2- nitrobenzamide Download PDFInfo
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- CN109879818A CN109879818A CN201910271806.7A CN201910271806A CN109879818A CN 109879818 A CN109879818 A CN 109879818A CN 201910271806 A CN201910271806 A CN 201910271806A CN 109879818 A CN109879818 A CN 109879818A
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- China
- Prior art keywords
- dimethoxypyridin
- synthetic method
- methylsulfonyl
- base
- nitrobenzamide
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- CSJLJSGWKXPGRN-UHFFFAOYSA-N 2,4-dimethoxypyridine Chemical compound COC1=CC=NC(OC)=C1 CSJLJSGWKXPGRN-UHFFFAOYSA-N 0.000 title claims abstract description 14
- 238000010189 synthetic method Methods 0.000 title claims abstract description 14
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 claims abstract description 17
- 238000010992 reflux Methods 0.000 claims abstract description 13
- 235000010233 benzoic acid Nutrition 0.000 claims abstract description 12
- 229960003053 thiamphenicol Drugs 0.000 claims abstract description 12
- 238000006482 condensation reaction Methods 0.000 claims abstract description 11
- 239000005711 Benzoic acid Substances 0.000 claims abstract description 9
- 239000012752 auxiliary agent Substances 0.000 claims abstract description 9
- 238000010792 warming Methods 0.000 claims abstract description 9
- 239000003054 catalyst Substances 0.000 claims abstract description 6
- 239000002904 solvent Substances 0.000 claims abstract description 6
- 238000003756 stirring Methods 0.000 claims abstract description 5
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical group CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 15
- 239000012065 filter cake Substances 0.000 claims description 10
- 238000001914 filtration Methods 0.000 claims description 9
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 6
- 239000002253 acid Substances 0.000 claims description 5
- 239000000706 filtrate Substances 0.000 claims description 5
- 239000000463 material Substances 0.000 claims description 5
- FYGHSUNMUKGBRK-UHFFFAOYSA-N 1,2,3-trimethylbenzene Chemical group CC1=CC=CC(C)=C1C FYGHSUNMUKGBRK-UHFFFAOYSA-N 0.000 claims description 4
- LVFRCHIUUKWBLR-UHFFFAOYSA-N 4,6-dimethoxypyrimidin-2-amine Chemical compound COC1=CC(OC)=NC(N)=N1 LVFRCHIUUKWBLR-UHFFFAOYSA-N 0.000 claims description 4
- 238000009833 condensation Methods 0.000 claims description 4
- 230000005494 condensation Effects 0.000 claims description 4
- 238000001816 cooling Methods 0.000 claims description 4
- 238000002425 crystallisation Methods 0.000 claims description 4
- 235000019441 ethanol Nutrition 0.000 claims description 3
- 239000003795 chemical substances by application Substances 0.000 claims description 2
- 238000001035 drying Methods 0.000 claims 1
- 238000000034 method Methods 0.000 abstract description 5
- GOJUJUVQIVIZAV-UHFFFAOYSA-N 2-amino-4,6-dichloropyrimidine-5-carbaldehyde Chemical group NC1=NC(Cl)=C(C=O)C(Cl)=N1 GOJUJUVQIVIZAV-UHFFFAOYSA-N 0.000 abstract description 2
- 239000003344 environmental pollutant Substances 0.000 abstract description 2
- 231100000719 pollutant Toxicity 0.000 abstract description 2
- 230000009979 protective mechanism Effects 0.000 abstract description 2
- 238000002360 preparation method Methods 0.000 abstract 1
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 6
- 150000001875 compounds Chemical class 0.000 description 5
- FFYYHFMMWZGEMB-UHFFFAOYSA-N 4,6-dimethoxypyridin-2-amine Chemical compound COC1=CC(N)=NC(OC)=C1 FFYYHFMMWZGEMB-UHFFFAOYSA-N 0.000 description 4
- 238000006243 chemical reaction Methods 0.000 description 4
- 239000000376 reactant Substances 0.000 description 4
- 238000010606 normalization Methods 0.000 description 3
- 150000005199 trimethylbenzenes Chemical class 0.000 description 3
- 239000005578 Mesotrione Substances 0.000 description 2
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
- KPUREKXXPHOJQT-UHFFFAOYSA-N mesotrione Chemical compound [O-][N+](=O)C1=CC(S(=O)(=O)C)=CC=C1C(=O)C1C(=O)CCCC1=O KPUREKXXPHOJQT-UHFFFAOYSA-N 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 238000003786 synthesis reaction Methods 0.000 description 2
- VHMLWGKIOAZNGG-UHFFFAOYSA-N 2-nitro-n-sulfonylbenzamide Chemical compound [O-][N+](=O)C1=CC=CC=C1C(=O)N=S(=O)=O VHMLWGKIOAZNGG-UHFFFAOYSA-N 0.000 description 1
- YWQPJRWLHFOASL-UHFFFAOYSA-N 4-methylsulfonyl-2-nitrobenzamide Chemical compound CS(=O)(=O)C1=CC=C(C(N)=O)C([N+]([O-])=O)=C1 YWQPJRWLHFOASL-UHFFFAOYSA-N 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 239000002131 composite material Substances 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 230000004224 protection Effects 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- 150000003230 pyrimidines Chemical class 0.000 description 1
- 238000009333 weeding Methods 0.000 description 1
Landscapes
- Pyridine Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The present invention provides N- (4,6- dimethoxypyridin -2- base) -4- methylsulfonyl -2- nitrobenzamide synthetic method, it is in a solvent, 2- nitryl-4-thiamphenicol benzoic acid and 2- amino -4 is added, 6- dimethoxypyridin, in the presence of catalyst and auxiliary agent, stirring is lower and is warming up to micro- reflux, condensation reaction obtains N- (4,6- dimethoxypyridin -2- base) -4- methylsulfonyl -2- nitrobenzamide.Synthetic method of the present invention is easy to operate, and preparation process technique is relatively easy to control, and reduces pollutant kind, so being environmentally protective process route.
Description
Technical field
The invention belongs to technical field of organic synthesis, and in particular to a kind of N- (4,6- dimethoxypyridin -2- base) -4- first
The synthetic method of sulfuryl -2- nitrobenzamide.
Background technique
Mesotrione is by a kind of weeding of inhibition p-hydroxyphenypyruvate dioxydenase of Syngenta Co., Ltd's exploitation
Agent.We are when modifying its molecular structure, with the key intermediate 2- nitryl-4-thiamphenicol benzoic acid of mesotrione
Condensation reaction is carried out with 2- amino-4,6-dimethoxy pyrimidine, is meaningfully composite N- (4,6- dimethoxypyridin -2- base) -
This substance of 4- methylsulfonyl -2- nitrobenzamide.Usually this kind of reaction is first to be prepared into 2- nitryl-4-thiamphenicol benzoic acid
Acyl chlorides, then condensation reaction is carried out with 2- amino-4,6-dimethoxy pyrimidine, but author does not obtain being wanted with this method
Target compound.Therefore we look for another way, and 2- nitryl-4-thiamphenicol benzoic acid and 2- amino -4,6- dimethoxy is phonetic
Pyridine, in the presence of catalyst and auxiliary agent, directly progress condensation reaction, to prepare target compound N- (4,6- dimethoxies
Yl pyrimidines -2- base) -4- methylsulfonyl -2- nitrobenzamide.Have no that document discloses the synthetic method for reporting the substance at present.
Summary of the invention
The purpose of the present invention is to provide a kind of synthesis N- (4,6- dimethoxypyridin -2- base) -4- methylsulfonyl -2- nitre
The synthetic method of yl-benzamide.
Its technical solution is as follows:
The synthetic method of N- (4,6- dimethoxypyridin -2- base) -4- methylsulfonyl -2- nitrobenzamide is added in a solvent
2- nitryl-4-thiamphenicol benzoic acid and 2- amino-4,6-dimethoxy pyrimidine, in the presence of catalyst and auxiliary agent, under stirring simultaneously
It is warming up to micro- reflux, condensation reaction obtains N- (4,6- dimethoxypyridin -2- base) -4- methylsulfonyl -2- nitrobenzamide.
Further scheme, the catalyst are three fluoboric acid, and additional amount and 2- nitryl-4-thiamphenicol benzoic acid are added
Amount mass ratio is 0.05-0.2:13.
Further scheme, the auxiliary agent are n,N-Dimethylformamide, and solvent is trimethylbenzene；The solvent and auxiliary agent
Volume ratio is 250:5-15.Auxiliary agent mainly plays hydrotropy.
Further scheme is down to room temperature after the condensation reaction, carries out first time filtering to reactant；In filter cake
Middle addition ethyl alcohol and the stirring extremely reflux that heats up, then carry out filtering for second while hot；Second of filtered filtrate is carried out cold
But it crystallizes, carries out third time filtering again after material is sufficiently precipitated, gained filter cake dries to obtain N- (4,6- dimethoxypyridin -2-
Base) -4- methylsulfonyl -2- nitrobenzamide.
Further scheme, the condensation reaction are carried out in the reactor of belt stirrer and condenser pipe.
The present invention is directly by 2- nitryl-4-thiamphenicol benzoic acid and 2- amino -4,6- dimethoxypyridin condensation reaction system
Standby to obtain N- (4,6- dimethoxypyridin -2- base) -4- methylsulfonyl -2- nitrobenzamide, synthetic method is easy to operate, and makes
Standby process is relatively easy to control, and reduces pollutant kind, so being environmentally protective process route.
Specific embodiment
The method of the invention is described in detail below with reference to specific embodiment
Embodiment 1:
By 13 grams of 2- nitryl-4-thiamphenicol benzoic acids, 8 grams of 2- amino -4,6- dimethoxypyridin investment belt stirrers and condensation
In 250 milliliters of trimethylbenzenes in the three-necked flask of pipe, 0.10 gram of three fluoboric acid is added, n,N-Dimethylformamide 5ml is being stirred
It descends and is warming up to micro- reflux.It samples gas and composes middle control analysis, to reactant concentration less than 0.5%, stop reaction and be down to room temperature, go forward side by side
Ethyl alcohol is added in row filtering, filter cake, is warming up to reflux, and reflux after five minutes, is filtered, filtrate crystallisation by cooling while hot, sufficiently analysed to material
Refiltered after out, filter cake dries to obtain target compound, and content 99.7%(gas composes normalization method), yield 67.1%.
Embodiment 2:
By 13 grams of 2- nitryl-4-thiamphenicol benzoic acids, 8 grams of 2- amino -4,6- dimethoxypyridin investment belt stirrers and condensation
250 milliliters of trimethylbenzenes in the three-necked flask of pipe are added 0.15 gram, n,N-Dimethylformamide 5ml of three fluoboric acid, under stiring
And it is warming up to micro- reflux.It samples gas and composes middle control analysis, to reactant concentration less than 0.5%, stop reaction and be down to room temperature, and carry out
Methanol is added in filtering, filter cake, is warming up to reflux, and reflux after five minutes, is filtered, filtrate crystallisation by cooling while hot, is sufficiently precipitated to material
After refilter, filter cake dries to obtain target compound, and content 99.4%(gas composes normalization method), yield 67.2%.
Embodiment 3:
By 13 grams of 2- nitryl-4-thiamphenicol benzoic acids, 8 grams of 2- amino -4,6- dimethoxypyridin investment belt stirrers and condensation
In 250 milliliters of trimethylbenzenes in the three-necked flask of pipe, 0.1 gram of three fluoboric acid is added, n,N-Dimethylformamide 10ml is being stirred
It descends and is warming up to micro- reflux.It samples gas and composes middle control analysis, to reactant concentration less than 0.5%, stop reaction and be down to room temperature, go forward side by side
Methanol is added in row filtering, filter cake, is warming up to reflux, and reflux after five minutes, is filtered, filtrate crystallisation by cooling while hot, sufficiently analysed to material
Refiltered after out, filter cake dries to obtain target compound, and content 99.6%(gas composes normalization method), yield 67.3%.
The above is only a preferred embodiment of the present invention, it is noted that for the ordinary skill people of the art
For member, various improvements and modifications may be made without departing from the principle of the present invention, these improvements and modifications are also answered
It is considered as protection scope of the present invention.
Claims (5)
- The synthetic method of 1.N- (4,6- dimethoxypyridin -2- base) -4- methylsulfonyl -2- nitrobenzamide, it is characterised in that: In a solvent, 2- nitryl-4-thiamphenicol benzoic acid and 2- amino-4,6-dimethoxy pyrimidine is added, is deposited in catalyst and auxiliary agent Under, stirring is lower and is warming up to micro- reflux, and condensation reaction obtains N- (4,6- dimethoxypyridin -2- base) -4- methylsulfonyl -2- nitro Benzamide.
- 2. synthetic method according to claim 1, it is characterised in that: the catalyst is three fluoboric acid, additional amount It is 0.05-0.2:13 with 2- nitryl-4-thiamphenicol benzoic acid additional amount mass ratio.
- 3. synthetic method according to claim 1, it is characterised in that: the auxiliary agent is n,N-Dimethylformamide, molten Agent is trimethylbenzene；The volume ratio of the solvent and auxiliary agent is 250:5-15.
- 4. synthetic method according to claim 1, it is characterised in that: after the condensation reaction, room temperature is down to, to anti- Object is answered to carry out first time filtering；Ethyl alcohol is added in filter cake and the stirring that heats up is to flowing back, then carries out filtering for second while hot；It is right Second of filtered filtrate carries out crystallisation by cooling, carries out third time filtering, the drying of gained filter cake again after material is sufficiently precipitated Obtain N- (4,6- dimethoxypyridin -2- base) -4- methylsulfonyl -2- nitrobenzamide.
- 5. synthetic method according to claim 1, it is characterised in that: the condensation reaction is with blender and condensation It is carried out in the reactor of pipe.
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201910271806.7A CN109879818A (en) | 2019-04-04 | 2019-04-04 | The synthetic method of N- (4,6- dimethoxypyridin -2- base) -4- methylsulfonyl -2- nitrobenzamide |
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201910271806.7A CN109879818A (en) | 2019-04-04 | 2019-04-04 | The synthetic method of N- (4,6- dimethoxypyridin -2- base) -4- methylsulfonyl -2- nitrobenzamide |
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Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1680342A (en) * | 2005-01-19 | 2005-10-12 | 南开大学 | Benzothiadiazole derivatives and their synthesis methods and screening of induced disease resistance activity |
| CN101492416A (en) * | 2001-08-17 | 2009-07-29 | 阿斯特拉曾尼卡有限公司 | Compounds effecting glucokinase |
| CN102015660A (en) * | 2008-04-23 | 2011-04-13 | 协和发酵麒麟株式会社 | 2-aminoquinazoline derivatives |
| CN106459072A (en) * | 2014-03-20 | 2017-02-22 | 拜耳制药股份公司 | Inhibitors of the Wnt signaling pathway |
-
2019
- 2019-04-04 CN CN201910271806.7A patent/CN109879818A/en active Pending
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101492416A (en) * | 2001-08-17 | 2009-07-29 | 阿斯特拉曾尼卡有限公司 | Compounds effecting glucokinase |
| CN1680342A (en) * | 2005-01-19 | 2005-10-12 | 南开大学 | Benzothiadiazole derivatives and their synthesis methods and screening of induced disease resistance activity |
| CN102015660A (en) * | 2008-04-23 | 2011-04-13 | 协和发酵麒麟株式会社 | 2-aminoquinazoline derivatives |
| CN106459072A (en) * | 2014-03-20 | 2017-02-22 | 拜耳制药股份公司 | Inhibitors of the Wnt signaling pathway |
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Application publication date: 20190614 |
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