CN104610167A - Mesosul furon-methyl synthesis method - Google Patents
Mesosul furon-methyl synthesis method Download PDFInfo
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- CN104610167A CN104610167A CN201510026964.8A CN201510026964A CN104610167A CN 104610167 A CN104610167 A CN 104610167A CN 201510026964 A CN201510026964 A CN 201510026964A CN 104610167 A CN104610167 A CN 104610167A
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- asccharin
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
- C07D239/02—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings
- C07D239/24—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members
- C07D239/28—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to ring carbon atoms
- C07D239/46—Two or more oxygen, sulphur or nitrogen atoms
- C07D239/52—Two oxygen atoms
Abstract
The invention discloses a mesosul furon-methyl synthesis method. The mesosul furon-methyl synthesis method comprises steps as follows: 1), 6-nitrosaccharin is reduced to 6-aminosaccharin in the presence of a reduction catalyst; 2), 6-aminosaccharin has diazotization and substitution reactions to obtain 6-oxime methylsaccharin; 3), 6-oxime methylsaccharin is reduced to obtain 6-amine methylsaccharin in the presence of a reduction catalyst; 4), 6-amine methylsaccharin and methanesulfonyl chloride react to obtain 6-methylmethanesulfonamide saccharide; 5),5-methylmethanesulfonamide-2-(methylformate) benzenesulfonamide is obtained through ring opening; 6), 5-methylmethanesulfonamide-2-(methylformate) benzenesulfonamide and ethyl chlorocarbonate have a reaction and then react with 4, 6-dimethoxy pyrimidine-2-amine to obtain mesosul furon-methyl. The mesosul furon-methyl synthesis method has the benefits as follows: (1), 6-nitrosaccharin is taken as a synthesis starting material which is simple and easy to obtain; (2), according to the method, reagents used in reaction processes are common and environment-friendly reagents, the pollution is small, the cost is low, reaction steps are shorter, and the method is applicable to industrial production.
Description
Technical field
The present invention relates to the production method of a kind of weedicide mesosulfuron (Mesosul furon-methyl)
Background technology
Mesosulfuron is the ultra-high efficiency weedicide developed by Bayer agriculture section, belongs to the inhibitor of sulfonylurea acetolactate synthestase (ALS).After being absorbed by weeds root and leaf, conduct in plant, weeds are stopped growing and withered.Be mainly used in cereal and non-crop prevents and kill off annual gramineous weed and some broadleaf weedss.
Mesosulfuron synthesis report comparatively is early found in patent DE4335297, this patent take para-totuidine as starting raw material, mesosulfuron is obtained by reacting through 9 steps, azido reaction is related in synthesis, danger coefficient is higher, use trifluoroacetic acid may heavy corrosion production unit, and intermediate needs through column chromatography purification, thus the industrialization of this synthetic route is had little significance.
Existing mesosulfuron synthetic technology is based on the patent of Bayer agriculture section mostly, relates generally to the synthesis of the key intermediate 5-methanesulfonamido methyl-2-methoxycarbonyl benzsulfamide of mesosulfuron.As US6538150, CN1159732C etc. patent discloses with 4-cyano group-2-nitrobenzene methyl as starting raw material, 3-amino-4-methoxyl carbonyl benzyl amine is obtained through the catalyst such as platinum dioxide or palladium hydroxide hydrogenation, and then with N, N-N,N-DIMETHYLACETAMIDE is solvent, triethylamine is acid binding agent, be obtained by reacting 4-methanesulfonamido methyl-2-amino methyl benzoate under condition of ice bath with methylsulfonyl chloride, then under ice bath, carry out diazotization-sulfonamide substitutions be obtained by reacting intermediate 5-methanesulfonamido methyl-2-methoxycarbonyl benzsulfamide.Employ expensive catalyzer in patent and carry out catalytic hydrogenation, and catalyzer cannot realize recovery, thus constrain the possibility of suitability for industrialized production.The patent that the people such as people, Li Jixing such as Liu Anchang continue to use Bayer carries out study on the synthesis, with to methyl cyanophenyl for raw material, through the Reactive Synthesis mesosulfuron such as nitrated, oxidation, esterification, reduction, but nitration reaction produces in a large amount of spent acid, oxidizing reaction and uses the reagent such as potassium bichromate to environment, thus can also counteracts that industrialized development.
The people such as Ma Changpeng with to methyl cyanophenyl for raw material; 5-cyano group-2-methoxycarbonyl benzene sulfonyl chloride is generated through chlorsulfonic acid; then mesosulfuron is obtained by reacting through ammonification, oxidation, reduction, Mesylation etc.; synthesis step is shorter; but still use potassium bichromate in synthesis, easily cause environmental pollution.The synthesis related in patent CN103755603A faces the problem that potassium dichromate oxidation easily causes environmental pollution equally.
The people such as Qin Zhenwei disclose a patent of invention CN103524386A; take dimethyl terephthalate (DMT) as starting raw material; relevant intermediate 2-amino-4-Toluidrin the methyl-toluate of mesosulfuron is obtained by reacting through nitrated, amidation, dehydration, reduction, Mesylation etc.; avoid the environmental pollution of oxygenant; but the spent acid of nitrated generation and dehydration use a large amount of phosphorus oxychloride, make the industrialization difficulty of this synthetic route larger.
Summary of the invention
6-nitrosaccharin is adopted to obtain 6-isonitrosomethyl asccharin through reduction, diazotization, substitution reaction, then continue reduction and obtain 6-amine methyl saccharine, react with Methanesulfonyl chloride again, open loop obtains 5-Toluidrin methyl-2-methoxycarbonyl benzsulfamide, then under the existence of Vinyl chloroformate, mesosulfuron is obtained by reacting with 4,6-dimethoxypyridin-2-amine.Solve environmental pollution in mesosulfuron and the synthesis of relevant intermediate thereof large, high in cost of production problem, the invention provides the synthetic method that mesosulfuron is new.
Technical scheme of the present invention is as follows:
A synthetic method for mesosulfuron, is characterized in that it comprises the following steps:
Step 1. reacts to obtain the amino asccharin of 6-by 6-nitrosaccharin through catalytic hydrogen reduction;
The 6-aminosugar that step 1 obtains by step 2. progresses greatly row diazotization reaction, then carries out substitution reaction with 10% formoxime solution in neutral conditions and generates 6-isonitrosomethyl asccharin;
The 6-isonitrosomethyl asccharin that step 2 obtains by step 3. obtains 6-aminomethyl asccharin through reduction reaction;
Drip Methanesulfonyl chloride in the 6-aminomethyl asccharin that step 4. obtains in step 3 and obtain 6-methylsulfonyl aminomethyl sugar;
The 6-Toluidrin methyl saccharine that step 4 obtains by step 5. carries out ring-opening reaction in methanol hydrochloride solution, obtains 5-Toluidrin methyl-2-methoxycarbonyl benzsulfamide;
The 5-Toluidrin methyl-2-methoxycarbonyl benzsulfamide that step 5 obtains by step 6. and methyl-chloroformate react, and then carry out being obtained by reacting mesosulfuron with 4,6-dimethoxypyridin-2-amine.
The synthetic method of above-mentioned mesosulfuron, it is characterized in that: in step 2, the diazo reagent of described diazotization reaction is the one in Sodium Nitrite or nitrosyl-sulfuric acid, the mol ratio of its Sodium Nitrite charging capacity and the amino asccharin of 6-is 1.1:1 ~ 1.5:1, preferred 1.1:1, the mol ratio of nitrosyl-sulfuric acid charging capacity and the amino asccharin of 6-is 1.2:1, described diazotization reaction solvent is water, a kind of in acetic acid or 35% concentrated hydrochloric acid or their mixture, diazotizing temperature is 0 ~ 15 DEG C, with sodium-acetate after diazotization reaction completes, a kind of neutralization reaction liquid in ammonium chloride or sodium carbonate is to pH=4-7, then substitution reaction is carried out with 10% formoxime solution, the molar feed ratio of 10% formoxime and the amino asccharin of 6-is 1:1 ~ 4:1, preferably 3:1, at Salzburg vitriol with the substitution reaction of formoxime, S-WAT, carry out in sodium-acetate and 10% formoxime solution, the mol ratio of Salzburg vitriol and the amino asccharin of 6-is 1:20 ~ 1:5, preferably 1:10, the mol ratio of S-WAT and the amino asccharin of 6-is 1:100 ~ 1:20, preferably 1:33.
The synthetic method of above-mentioned mesosulfuron, it is characterized in that: in step 3, described reduction reaction can with reductive agent or catalytic hydrogenating reduction, reduction reaction reductive agent is the one in zinc powder/acetic acid, sodium borohydride/copper sulfate, 5% palladium carbon/ammonium formiate or 10% palladium carbon/ammonium formiate system, reduction system is zinc powder/acetic acid, the mass ratio of zinc powder and 6-isonitrosomethyl asccharin charging capacity is 2:1 ~ 4:1, and temperature is 60 ~ 100 DEG C, and the reaction times is 4 ~ 10h; Reduction system is sodium borohydride/copper sulfate, and the mass ratio of sodium borohydride and 6-isonitrosomethyl asccharin charging capacity is 1:4 ~ 1:2, and the mass ratio of anhydrous cupric sulfate and 6-isonitrosomethyl asccharin charging capacity is 1:1 ~ 1:3, and reflux time is 3 ~ 8h; Reduction system is 5% palladium carbon/ammonium formiate or 10% palladium carbon/ammonium formiate, and the mass ratio of 5% palladium carbon or 10% palladium carbon and 6-isonitrosomethyl asccharin is 1:50 ~ 1:4, and the mass ratio of ammonium formiate and 6-isonitrosomethyl asccharin is 2:1 ~ 4:1, and the reaction times is 4 ~ 10h; The catalyzer of catalytic hydrogenation is the one in 5% palladium carbon, 10% palladium carbon or Raney's nickel, and the mass ratio of catalyzer and 6-isonitrosomethyl asccharin is 1:50 ~ 1:10, preferably 5% palladium carbon; Solvent is the one in methyl alcohol, ethanol or ethyl acetate, preferably methyl alcohol; Temperature of reaction is 25 ~ 80 DEG C, and the hydrogen pressure needed for reaction is 0.5 ~ 4.0Mpa, and the reaction times is 4 ~ 10h.
The synthetic method of above-mentioned mesosulfuron, is characterized in that: step 4 drips in Methanesulfonyl chloride to the dichloromethane solution of 6-aminomethyl asccharin to be obtained by reacting 6-methylsulfonyl aminomethyl asccharin under triethylamine exists.
The synthetic method of above-mentioned mesosulfuron, is characterized in that: in step 5, and the solvent of described asccharin ring-opening reaction is saturated hydrochloric acid-methanol (35%) solution.
The synthetic method of above-mentioned mesosulfuron, it is characterized in that: in step 6, described 5-Toluidrin methyl-2-methoxycarbonyl benzsulfamide and methyl-chloroformate react, reaction solvent is toluene or acetonitrile, and acid binding agent is salt of wormwood, and reflux temperature carries out, then with 4,6-dimethoxypyridin-2-amine reacts, and solvent is toluene, and temperature of reaction is 60-120 DEG C.
The invention has the beneficial effects as follows: (1) uses 6-nitrosaccharin to be synthesis starting raw material, avoid the chemical reagent that the environmental pollutions such as nitrated, oxidation are larger, starting raw material is cheap, wide material sources, simple and easy to get; (2) synthetic method of mesosulfuron of the present invention, the reagent used in reaction process is common, environmental friendliness reagent, pollute little, cost is low, reactions steps is shorter, be applicable to suitability for industrialized production.
Embodiment
Below in conjunction with specific examples, mesosulfuron invention is further described:
Equation:
Embodiment 1 (reference Wang Zhi is quick. the synthesis [D] of weedicide iodosulfuron methyl sodium. and University Of Suzhou, 2008)
Get 6-nitrosaccharin 15.4g, 5% palladium carbon 1.6g, ethanol 250mL is in 500mL autoclave, air 3 times in nitrogen replacement still, be filled with hydrogen to 0.5MPa, be warming up to 35 degree, ensure that hydrogen pressure is 0.3-0.5MPa, stirring reaction 6-8 hour, incline and reaction solution, filter, filtrate concentrates to obtain the amino asccharin 12.5g of 6-, productive rate 93.4%, HPLC detects purity 98%;
Embodiment 2
Get 250mL reaction flask, add the amino asccharin 10g of 6-, concentrated hydrochloric acid 18mL, Glacial acetic acid 92mL, add water 72mL, is cooled to 0-5 DEG C after stirring at room temperature 0.5h, drip the Sodium Nitrite 3.55g being dissolved in 20mL water, in ensureing, temperature is no more than 15 DEG C, drips after rear 0-5 DEG C of ice bath continues to stir 15min and adds 30% sodium acetate aqueous solution adjustment pH to 4-5, for subsequent use; Separately getting 1.3g copper sulfate, 0.2g S-WAT, 36ml water and 32g sodium-acetate is mixed in 85mL 10% formoxime solution, the diazonium salt of above-mentioned preparation is slowly dripped under formoxime mixing liquid level under room temperature, drip completely and continue to stir 2h under room temperature, again by reaction solution ice bath to 0-5 degree, adding 10% hydrochloric acid, reaction solution to be slowly adjusted to pH be about 3, filter, filtrate adds extraction into ethyl acetate repeatedly, merge organic relevant dry, concentrated, then add re crystallization from toluene, obtain 6-isonitrosomethyl asccharin 8g (productive rate 70%, purity 97%);
In embodiment 3 ~ embodiment 5, the method for each embodiment is substantially the same manner as Example 2, and difference is in table 1
Table 1
Embodiment 6
Get 150mL reaction flask, add the amino asccharin 5g of 6-, water 30mL, ice bath is cooled to 0-5 degree and stirs 0.5h, slowly drip 40% nitrosyl-sulfuric acid (40% nitrosyl-sulfuric acid prepare China of reference literature Dong state .2-(the bromo-2-[4-morpholinodithio azo of 6-)-5-diethylaminophenol synthesising process research [J]. Tianjin chemical industry, 2002,06:18-19.) 9.62g, drips and finishes, and continues to stir 10min under ice bath, add appropriate ammonium chloride and regulate pH to 6-7, for subsequent use, separately get 0.65g copper sulfate, 0.1g S-WAT, 18ml water and 15g sodium-acetate are mixed in 42mL 10% formoxime solution, the diazonium salt of above-mentioned preparation is slowly dripped under formoxime mixing liquid level under room temperature, drip completely and continue to stir 2h under room temperature, again by reaction solution ice bath to 0-5 DEG C, adding 10% hydrochloric acid, reaction solution to be slowly adjusted to pH be about 3, stirring reaction 1h under ice bath, filter, filtrate adds extraction into ethyl acetate repeatedly, merge organic relevant dry, concentrated, then re crystallization from toluene is added, obtain 6-isonitrosomethyl asccharin 3.8g (productive rate 66%, purity 97%),
Embodiment 7
Get 250mL reaction flask, add 6-amino asccharin 10g, concentrated hydrochloric acid 18mL, 0-5 DEG C is cooled to after stirring at room temperature 0.5h, drip the Sodium Nitrite 3.55g being dissolved in 20mL water, at dripping rear 0-5 DEG C, ice bath adds sodium carbonate solid adjustment pH to 5 in batches after continuing to stir 15min, for subsequent use, separately get 1.3g copper sulfate, 0.2g S-WAT, 36ml water and 32g sodium-acetate are mixed in 85mL 10% formoxime solution, the diazonium salt of above-mentioned preparation is slowly dripped under formoxime mixing liquid level under room temperature, drip completely and continue to stir 2h under room temperature, again by reaction solution ice bath to 0-5 DEG C, adding 10% hydrochloric acid, reaction solution to be slowly adjusted to pH be about 3, stirring reaction 1h under ice bath, filter, filtrate adds extraction into ethyl acetate repeatedly, merge organic relevant dry, concentrated, then re crystallization from toluene is added, obtain 6-isonitrosomethyl asccharin 7.5g (productive rate 65.6%, purity 97%),
Embodiment 8
Get 6-isonitrosomethyl asccharin 4.5g, 5% palladium carbon 1g, methyl alcohol 50mL, ammonium formiate 12.5g, intensification stirring and refluxing reaction 8h, filter, filtrate concentrates to obtain 6-aminomethyl asccharin 4g (productive rate 94%, purity 96%);
In embodiment 9 ~ embodiment 11, the method for each embodiment is substantially the same manner as Example 8, and difference is in table 2
Table 2
Embodiment 12
Get 6-isonitrosomethyl asccharin 4.5g, add acetic acid 50mL, zinc powder 13g, slowly be heated to 80 degree of reaction 6h, suction filtration, filtrate adds after sodium-acetate regulates about pH to 5 and adds extraction into ethyl acetate, organic phase concentrates to obtain 6-aminomethyl asccharin 3.9g (productive rate 93%, purity 96%);
In embodiment 13 ~ embodiment 15, the method for each embodiment is substantially the same manner as Example 12, and difference is in table 3
Table 3
Embodiment 16
Get 6-isonitrosomethyl asccharin 5g, add methyl alcohol 10mL, tetrahydrofuran (THF) 20mL, copper sulfate 8.2g, sodium borohydride 1.84g is added under stirring at room temperature, stirring at room temperature reaction 1h post-heating return stirring reaction 4h, concentration of reaction solution, adds water filtration, solid adds ethyl acetate and fully dissolves rear filtration, filtrate concentrates to obtain 6-aminomethyl asccharin 4g, yield 85.2%, purity 97%;
In embodiment 17 ~ embodiment 19, the method for each embodiment is substantially the same manner as Example 16, and difference is in table 4
Table 4
Embodiment 20
Get 6-isonitrosomethyl asccharin 5g, 5% palladium carbon 0.5g, methyl alcohol 150mL is in 250mL autoclave, and air 2-3 time in nitrogen replacement still, is filled with hydrogen to pressure 2.5MPa, be warming up between 40 degree of reaction period, ensure hydrogen pressure 2.0-2.5MPa, stirring reaction 8h hypsokinesis goes out reaction solution, filters, 6-aminomethyl asccharin 4.5g (productive rate 95%, purity 97%) is obtained after filtrate is concentrated;
In embodiment 21 ~ embodiment 23, the method for each embodiment is substantially the same manner as Example 20, and difference is in table 5
Table 5
Embodiment 24
Get 6-amine methyl saccharine 5.0g and be dissolved in 50mL methylene dichloride, add triethylamine 3mL, ice bath is cooled to 0-5 DEG C, drips Methanesulfonyl chloride 2.5g, drip and finish, normal-temperature reaction 1h, saturated common salt water washing, collects organic phase drying, remove solvent under reduced pressure, obtain 6-Toluidrin methyl saccharine 5.2g, yield 76.5%, purity 96%;
Embodiment 25 examines document Ma Changpeng, Han Bangyou, Qian Shengli, etc. the synthesis [J] of weedicide mesosulfuron. fine chemistry industry, 2013,03:353-356)
5.0g 6-Toluidrin methyl saccharine is dissolved in the saturated methanol hydrochloride solution of 30mL (35%) at 25 DEG C, slowly be warming up to backflow, continue reaction 5h, concentrate and desolventize, add saturated sodium bicarbonate aqueous solution washing after adding acetic acid ethyl dissolution to neutral or weakly alkaline, aqueous phase adds extraction into ethyl acetate 1-2 time, collection organic phase is dry, concentrating under reduced pressure obtains 5-Toluidrin methyl-2-methoxycarbonyl benzsulfamide 5g, yield 90.0%, purity 99%;
Embodiment 26
Get 5-Toluidrin methyl-2-methoxycarbonyl benzsulfamide 6.4g, acetonitrile 50mL, salt of wormwood 4.2g, in 150mL reaction flask, drip Vinyl chloroformate 3.2g under stirring at room temperature, drip and finish, be warming up to return stirring reaction 2h after continuing to stir 1h under room temperature, concentrated except acetonitrile after being chilled to room temperature, add water 20mL, add 10% dilute hydrochloric acid and regulate pH to 3, filter, collect solid drying, for subsequent use; 4,6-dimethoxypyridins of the solid and 3.1g of getting previous step gained are dissolved in 50mL toluene, after heating reflux reaction 1h, steam except toluene and alcohol mixeding liquid, add equal-volume (30-40mL) toluene simultaneously, repeatedly after 2-3 time, be down to room temperature, concentrate and desolventize, filter to obtain solid after adding water, then add isopropyl ether and fully stir rear filtration, collect solid vacuum-drying and obtain mesosulfuron 8.5g, yield 85%, purity 96%.
Embodiment 27
Get 5-Toluidrin methyl-2-methoxycarbonyl benzsulfamide 6.4g, toluene 50mL, salt of wormwood 4.2g, in 150mL reaction flask, drip Vinyl chloroformate 3.2g under stirring at room temperature, drip and finish, be warming up to return stirring reaction 2-3h after continuing to stir 1h under room temperature, concentrated except toluene after being chilled to room temperature, add water 20mL, add 10% dilute hydrochloric acid and regulate pH to 3, filter, collect solid drying, for subsequent use; 4,6-dimethoxypyridins of the solid and 3.1g of getting previous step gained are dissolved in 50mL toluene, after heating reflux reaction 1h, steam except toluene and alcohol mixeding liquid, add equal-volume (30-40mL) toluene simultaneously, repeatedly after 2-3 time, be down to room temperature, concentrate and desolventize, filter to obtain solid after adding water, then add isopropyl ether and fully stir rear filtration, collect solid vacuum-drying and obtain mesosulfuron 8.5g, yield 85%, purity 96%.
Claims (8)
1. a synthetic method for mesosulfuron, is characterized in that it comprises the following steps:
Step 1. reacts to obtain the amino asccharin of 6-by 6-nitrosaccharin through catalytic hydrogen reduction;
The 6-aminosugar that step 1 obtains by step 2. progresses greatly row diazotization reaction, then carries out substitution reaction with 10% formoxime solution in neutral conditions and generates 6-isonitrosomethyl asccharin;
The 6-isonitrosomethyl asccharin that step 2 obtains by step 3. obtains 6-aminomethyl asccharin through reduction reaction;
Drip Methanesulfonyl chloride in the 6-aminomethyl asccharin that step 4. obtains in step 3 and obtain 6-methylsulfonyl aminomethyl sugar;
The 6-Toluidrin methyl saccharine that step 4 obtains by step 5. carries out ring-opening reaction in methanol hydrochloride solution, obtains 5-Toluidrin methyl-2-methoxycarbonyl benzsulfamide;
The 5-Toluidrin methyl-2-methoxycarbonyl benzsulfamide that step 5 obtains by step 6. and methyl-chloroformate react, and then carry out being obtained by reacting mesosulfuron with 4,6-dimethoxypyridin-2-amine.
2. the synthetic method of mesosulfuron according to claim 1, it is characterized in that: in step 2, the diazo reagent of described diazotization reaction is the one in Sodium Nitrite or nitrosyl-sulfuric acid, and the mol ratio of its Sodium Nitrite charging capacity and the amino asccharin of 6-is 1.1:1 ~ 1.5:1, the mol ratio of nitrosyl-sulfuric acid charging capacity and the amino asccharin of 6-is 1.2:1, described diazotization reaction solvent is water, a kind of in acetic acid or 35% concentrated hydrochloric acid or their mixture, diazotizing temperature is 0 ~ 15 DEG C, with sodium-acetate after diazotization reaction completes, a kind of neutralization reaction liquid in ammonium chloride or sodium carbonate is to pH=4-7, then substitution reaction is carried out with 10% formoxime solution, the molar feed ratio of 10% formoxime and the amino asccharin of 6-is 1:1 ~ 4:1, the substitution reaction of the amino asccharin of 6-and formoxime is at Salzburg vitriol, S-WAT, carry out in sodium-acetate and 10% formoxime solution, the mol ratio of Salzburg vitriol and the amino asccharin of 6-is 1:20 ~ 1:5, the mol ratio of S-WAT and the amino asccharin of 6-is 1:100 ~ 1:20.
3. the synthetic method of mesosulfuron according to claim 2, is characterized in that: the mol ratio of step 2 Sodium Nitrite charging capacity and the amino asccharin of 6-is 1.1:1; The molar feed ratio of 10% formoxime and the amino asccharin of 6-is 3:1; The mol ratio of Salzburg vitriol and the amino asccharin of 6-is 1:10; The mol ratio of S-WAT and the amino asccharin of 6-is 1:33.
4. the synthetic method of mesosulfuron according to claim 1, it is characterized in that: in step 3, described reduction reaction reductive agent or catalytic hydrogenating reduction, reduction reaction reductive agent is the one in zinc powder/acetic acid, sodium borohydride/copper sulfate, 5% palladium carbon/ammonium formiate or 10% palladium carbon/ammonium formiate system, when reduction system is zinc powder/acetic acid, the mass ratio of zinc powder and 6-isonitrosomethyl asccharin charging capacity is 2:1 ~ 4:1, and temperature is 60 ~ 100 DEG C, and the reaction times is 4 ~ 10h; When reduction system is sodium borohydride/copper sulfate, the mass ratio of sodium borohydride and 6-isonitrosomethyl asccharin charging capacity is 1:4 ~ 1:2, and the mass ratio of anhydrous cupric sulfate and 6-isonitrosomethyl asccharin charging capacity is 1:1 ~ 1:3, and reflux time is 3 ~ 8h; Reduction system be 5% palladium carbon/ammonium formiate or 10% palladium carbon/ammonium formiate time, the mass ratio of 5% palladium carbon or 10% palladium carbon and 6-isonitrosomethyl asccharin is 1:50 ~ 1:4, and the mass ratio of ammonium formiate and 6-isonitrosomethyl asccharin is 2:1 ~ 4:1, and the reaction times is 4 ~ 10h; The reduction reaction one that to be the catalyzer of catalytic hydrogenation reaction be in 5% palladium carbon, 10% palladium carbon or Raney's nickel, the mass ratio of catalyzer and 6-isonitrosomethyl asccharin is 1:50 ~ 1:10; Solvent is the one in methyl alcohol, ethanol or ethyl acetate, and temperature of reaction is 25 ~ 80 DEG C, and the hydrogen pressure needed for reaction is 0.5 ~ 4.0Mpa, and the reaction times is 4 ~ 10h.
5. the synthetic method of mesosulfuron according to claim 4, is characterized in that: the reduction reaction described in step 3 is catalytic hydrogenation reaction, and solvent is methyl alcohol.
6. the synthetic method of mesosulfuron according to claim 1, is characterized in that: step 4 drips in Methanesulfonyl chloride to the dichloromethane solution of 6-aminomethyl asccharin to be obtained by reacting 6-methylsulfonyl aminomethyl asccharin under triethylamine exists.
7. the synthetic method of mesosulfuron according to claim 1, is characterized in that: in step 5, and the solvent of described asccharin ring-opening reaction is saturated hydrochloric acid-methanol (35%) solution.
8. the synthetic method of mesosulfuron according to claim 1, it is characterized in that: in step 6, described 5-Toluidrin methyl-2-methoxycarbonyl benzsulfamide and methyl-chloroformate react, reaction solvent is toluene or acetonitrile, and acid binding agent is salt of wormwood, and reflux temperature carries out, then with 4,6-dimethoxypyridin-2-amine reacts, and solvent is toluene, and temperature of reaction is 60-120 DEG C.
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| WO2017115134A1 (en) | 2016-01-01 | 2017-07-06 | Adama Agan Ltd. | Process for preparing 1.1.3-trioxo-1.2-benzothiazole-6-carboxamide |
| WO2017115137A1 (en) | 2016-01-01 | 2017-07-06 | Adama Agan Ltd. | Process for preparing 1,1,3-trioxo-1,2-benzothiazole-6-carboxamide |
| CN111807997A (en) * | 2020-06-27 | 2020-10-23 | 南京合创药业有限公司 | Synthesis method of N- (4-methoxycarbonyl-3-aminosulfonylbenzyl) methanesulfonamide |
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| WO2017115134A1 (en) | 2016-01-01 | 2017-07-06 | Adama Agan Ltd. | Process for preparing 1.1.3-trioxo-1.2-benzothiazole-6-carboxamide |
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| CN106243046B (en) * | 2016-08-02 | 2019-07-05 | 南京工业大学 | A kind of preparation method of mesosulfuron |
| CN111807997A (en) * | 2020-06-27 | 2020-10-23 | 南京合创药业有限公司 | Synthesis method of N- (4-methoxycarbonyl-3-aminosulfonylbenzyl) methanesulfonamide |
| CN111807997B (en) * | 2020-06-27 | 2022-09-23 | 南京合创药业有限公司 | Synthesis method of N- (4-methoxycarbonyl-3-aminosulfonylbenzyl) methanesulfonamide |
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