CN1962626A - 1-methylamino-1- methylthio-2-nitroethylene synthesis method - Google Patents
1-methylamino-1- methylthio-2-nitroethylene synthesis method Download PDFInfo
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Abstract
The invention discloses a new chemical synthesizing method of 1-motol-1-methylmercapto-2-nitroethylene as one intermediate of ulcer drug ranitidine, which comprises the following steps: adopting nitromethane, carbon bisulphide and potassium hydroxide as initial reacting material; synthesizing 1, 1-dimethyldisulphide-2-nitro ethylene to dissolve in the water; reacting with aminomethane to synthesize new intermediate product; filtering to obtain the product.
Description
Technical field
The present invention relates to the chemical pharmaceutical field, relate to a kind of chemosynthesis novel method of one of intermediate 1-methylamino--1-methylthio group-2-nitroethylene of synthetic digestive ulcer medicament Ranitidine HCL specifically.
Background technology
1-methylamino--1-methylthio group-2-nitroethylene is an important intermediate of preparation digestive ulcer medicament Ranitidine HCL, and its production directly influences the quality and the cost of Ranitidine HCL.For synthesizing of N-methyl isophthalic acid-methylthio group-2-nitroethylene amine, document has more report, but the ubiquitous weak point of these methods is: by product is more, and yield is too low; Because use inflammable and explosive chemical solvents production process poor stability in a large number; Operational path is longer, complicated operation.Now several routes with bibliographical information are described below respectively:
(1) chemical solvents method [Chinese Academy of Sciences's Chengdu organic chemistry research, Huang Hui, 1994]: at first under the effect of highly basic potassium hydroxide, Nitromethane 99Min. and dithiocarbonic anhydride react and produce 1,1-two potassium and sulfenyl 3s-2-nitroethylene, serve as the reaction mixed solvent with ethanol or methyl alcohol then, carry out methylation reaction with potassiumiodide alkane or methyl-sulfate and obtain 1,1-diformazan sulfenyl-2-nitroethylene; Because 1,1-diformazan sulfenyl-2-nitroethylene is water insoluble, so in polar aprotic solvent such as DMF, react with monomethylamine aqueous solution, obtain 1-methylamino-1-methylthio group-2-nitroethylene crude product, at last with Iso Butyl Acetate or ethyl acetate to crude product 1-methylamino-1-methylthio group-2-nitroethylene recrystallization, obtain yellow crystals, 112～114 ℃ of yields 39.4% of fusing point.Synthetic route is as follows:
The main drawback of this route is: (a) reaction process need be carried out in organic solvent methyl alcohol, ethanol, DMF, and the discharging of chemical solvents causes environmental pollution; (b) methyl alcohol, ethanol are hazardous chemical, and is inflammable and explosive, the production process poor stability.(c) intermediates 1, and 1-diformazan sulfenyl-2-nitroethylene is water insoluble, need react the cost recovery height of solvent DMF after reaction is finished in molten as DMF in that aprotic, polar is organic.(d) 1, when 1-diformazan sulfenyl-2-nitroethylene and Monomethylamine prepared in reaction 1-methylamino-1-methylthio group-2-nitroethylene, side reaction takes place easily generate 1,1-dimethylin-2-nitroethylene, cause product 1-methylamino-1-methylthio group-2-nitroethylene purification difficult, quality product descends.(e) reaction yield is lower, less than 40%.
(2) phase-transfer catalyst method (US4,967,007):
The synthesis technique of this route: in the cold mixt that contains NaOH, water, benzene and four butyl bromation amine, slowly add methylamine hydrochloride.Under 10～15 ℃ of stirrings, in mixture, add CS2, continue to stir 15min then.Under 10～15 ℃, in mixture, drip methyl-sulfate.Mixture at room temperature stirred 3 hours, removed the benzene layer, used the benzene aqueous layer extracted again, can obtain compound carbon imines disulfide except that after desolvating.This compound is faint yellow oily thing, boiling point: 187～190 ℃.To contain mixture heating up to 90～100 ℃ of Nitromethane 99Min., carbon imines disulfide, rare earth modified zeolite (RE70NaY) then, heat 72 hours after-filtration, and filtrate be distilled remove solvent and promptly get product 1-potassium and sulfenyl 3-1-methylamino-2-nitroethylene.Fusing point: 112～114 ℃
The main drawback of this operational path is: yield low (about 36%); Operating process condition harshness, complexity; Technological process is used carcinogenic chemical solvents benzene; Catalyzer Tetrabutyl amonium bromide and rare earth modified zeolite cost an arm and a leg, the cost height; The cycle of technological process is long, is unwell to industrial production.
Summary of the invention
The present invention is for overcoming problems of the prior art, the new synthetic method of a kind of 1-methylamino--1-methylthio group-2-nitroethylene is provided, this synthetic method significantly reduces the use of the minimizing of reaction process unit operation, chemical solvents, safer, environmental protection, energy consumption reduce, and yield improves, and production cost reduces.
The present invention is achieved by the following technical solutions:
Thinking of the present invention is an initial reactant with Nitromethane 99Min., dithiocarbonic anhydride, potassium hydroxide, synthesizes 1 earlier, 1-two potassium and sulfenyl 3s-2-nitroethylene; It is dissolved in the water, with water is solvent and the reaction of Monomethylamine generation methylamino-, synthetic new intermediate product 1-potassium and sulfenyl 3-1-methylamino-2-nitroethylene, this intermediate product is water-soluble, do not separate directly and methyl-sulfate carries out methylation reaction, generate water-fast 1-methylamino-1-methylthio group-2-nitroethylene, obtain solid phase prod 1-methylamino-1-methylthio group-2-nitroethylene after filtration.Reaction principle of the present invention is as follows:
The synthetic method of 1-methylamino-of the present invention-1-methylthio group-2-nitroethylene may further comprise the steps:
(1) preparation of potassium hydroxide-ethanol solution
KOH and dehydrated alcohol are joined in the enamel or stainless steel cauldron that molten alkali uses, stir down and be heated to 30～70 ℃ of dissolvings, it is stand-by to drop to room temperature after dissolving is complete; KOH and dehydrated alcohol are 1.5～2.1: 3.5～4.5 by weight;
The preparation of the two potassium and sulfenyl 3s of (2) 1,1--2-nitroethylene
In enamel or stainless steel addition reaction still, add Nitromethane 99Min., dithiocarbonic anhydride and dehydrated alcohol, stir 15～30 ℃ down, add potassium hydroxide-ethanol solution, reacted 1～5 hour down, cool to below the room temperature at 35～45 ℃, filter, obtain brick-red solid 1,1-two potassium and sulfenyl 3s-2-nitroethylene, wherein the weight ratio of Nitromethane 99Min., dithiocarbonic anhydride, dehydrated alcohol and potassium hydroxide-ethanol solution is 1.3～1.7: 2.5～3.9: 1.3～1.7: 10.5～13.6;
(3) preparation of 1-methylamino--1-methylthio group-2-nitroethylene
In enamel reaction still with solid di-potassium 1, the dissolving of blunging of 1-two potassium and sulfenyl 3s-2-nitroethylene, be heated to about 35 ℃, the monomethylamine aqueous solution of adding 40%, insulation reaction is 2～7 hours under this temperature, adds methyl-sulfate then and carries out methylation reaction 1～6 hour, below the cool to room temperature, filter, obtain crude product 1-methylamino--1-methylthio group-2-nitroethylene; Wherein 1,1-two potassium and sulfenyl 3s-2-nitroethylene, water, 40% monomethylamine aqueous solution, methyl-sulfate are by weight than being 1.0～1.4: 2.2～3.0: 0.4～0.7: 1.1～1.5;
(4) recrystallization
In enamel or stainless steel cauldron, add activated carbon, 60～80% aqueous ethanol and crude product 1-methylamino--1-methylthio group-2-nitroethylene, its weight ratio is 1～2: 42～65: 8～15, be heated to 60～80 ℃ of dissolvings, refluxed 1～3 hour, and removed by filter activated carbon, cool to room temperature, remove by filter etoh solvent, with 60～80% aqueous ethanols washing solid, remove the mother liquor that is adsorbed on the solid, get light yellow solid 1-methylamino--1-methylthio group-2-nitroethylene.
Preferably, the synthetic method of above-mentioned 1-methylamino--1-methylthio group-2-nitroethylene, it may further comprise the steps:
(1) preparation of potassium hydroxide-ethanol solution
KOH and dehydrated alcohol are joined in 1000 liters of enamel or the stainless steel cauldron, be heated to 58～62 ℃ of dissolvings under stirring, it is stand-by to drop to room temperature after the dissolving fully; KOH and dehydrated alcohol are 1.9: 4 by weight;
The preparation of (2) 1,1-two potassium and sulfenyl 3s-2-nitroethylene
In 2000 liters of enamel or stainless steel cauldron, add Nitromethane 99Min., dithiocarbonic anhydride and dehydrated alcohol, stir 18～22 ℃ down, add potassium hydroxide-ethanol solution, reacted 1 hour down, cool to room temperature at 38～42 ℃, filter, obtain brick-red solid 1,1-two potassium and sulfenyl 3s-2-nitroethylene, wherein the weight ratio of Nitromethane 99Min., dithiocarbonic anhydride, dehydrated alcohol and potassium hydroxide-ethanol solution is 1.3: 2.5: 1.5: 10.5;
(3) preparation of 1-first An Ji-1-methylthio group-2-nitroethylene
Give birth in enamel or the stainless steel cauldron solid di-potassium 1 2000, the dissolving of blunging of 1-two potassium and sulfenyl 3s-2-nitroethylene, be heated to about 35 ℃, the monomethylamine aqueous solution of adding 40%, insulation reaction is 3～6 hours under this temperature, adds methyl-sulfate then and carries out methylation reaction 1.5～2.5 hours, below the cool to room temperature, filter, obtain crude product 1-methylamino--1-methylthio group-2-nitroethylene; Wherein 1,1-two potassium and sulfenyl 3s-2-nitroethylene, water, 40% monomethylamine aqueous solution, methyl-sulfate are by weight than being 1.2: 2.3: 0.55: 1.15;
(4) recrystallization
In 1000 liters of enamel or stainless steel cauldron, add activated carbon, dehydrated alcohol and crude product 1-methylamino--1-methylthio group-2-nitroethylene, its weight ratio is 1.5: 50: 12, be heated to 60～75 ℃ of dissolvings, refluxed 1～3 hour, remove by filter activated carbon, cool to below the room temperature, remove by filter etoh solvent, remove the mother liquor that is adsorbed on the solid with the washing of 60～80% aqueous ethanols, get light yellow solid 1-methylamino--1-methylthio group-2-nitroethylene.
Preferably, the synthetic method of above-mentioned 1-methylamino--1-methylthio group-2-nitroethylene, it may further comprise the steps:
(1) preparation of potassium hydroxide-ethanol solution
190kgKOH and 400kg dehydrated alcohol are added in 1000 liters of enamel or the molten alkali reaction still of stainless steel, stir down and be heated to 60 ℃ of dissolvings, it is stand-by to be reduced to room temperature after dissolving is complete;
The preparation of (2) 1,1-two potassium and sulfenyl 3s-2-nitroethylene
In 2000 liters of enamel or the stainless steel cauldron, add 150kg Nitromethane 99Min., 170kg dithiocarbonic anhydride and 150kg dehydrated alcohol, stir following 20 ℃, begin to drip potassium hydroxide-ethanol solution 590kg, dropwise, reacted 1 hour down at 40 ℃, cool to below the room temperature, filter, obtain brick-red solid di-potassium 1,1-two potassium and sulfenyl 3s-2-nitroethylene 380kg;
(3) preparation of 1-methylamino--1-methylthio group-2-nitroethylene
In 2000 liters of enamel or stainless steel cauldron with 1,1-two potassium and sulfenyl 3s-2-nitroethylene 380kg 800kg water stirring and dissolving, be heated to 35 ℃ and add 40% monomethylamine aqueous solution 100kg, insulation reaction is 5 hours under this temperature, (synthesized new intermediate product 1-potassium and sulfenyl 3-1-methylamino-2-nitroethylene, this intermediate product is water-soluble, do not separate directly and methyl-sulfate carries out methylation reaction,) add the 400kg methyl-sulfate and carried out methylation reaction 2 hours, below the cool to room temperature, filter, obtain crude product 1-methylamino--1-methylthio group-2-nitroethylene;
(4) recrystallization
Add activated carbon 350kg, dehydrated alcohol 600kg and 200kg crude product 1-methylamino--1-methylthio group-2-nitroethylene heating for dissolving in 1000 liters of enamel or the stainless steel cauldron, refluxed 1～3 hour, remove by filter activated carbon, cool to room temperature, remove by filter etoh solvent, remove the mother liquor that is adsorbed on the solid with the washing of 60～70% aqueous ethanols, get light yellow solid 1-methylamino--1-methylthio group-2-nitroethylene.
The present invention compared with prior art has following significant advantage:
(1) ammoxidation and methylation reaction are reaction solvent with water, do not use inflammable and explosive and poisonous and hazardous chemical solvents, and technological process is safer, and the discharging of chemical solvents reduces 70%, more environmental protection; Production cost lower (compare US4,967,007 and the technical costs of the yellow intelligent exploitation of Chengdu Organic Chemistry Inst., Chinese Academy of Sciences reduce by 40%).
(2) novel process intermediates 1-potassium and sulfenyl 3-1-methylamino-2-nitroethylene is the water-soluble (intermediates 1 of the synthetic method of the yellow intelligent exploitation of Chengdu Organic Chemistry Inst., Chinese Academy of Sciences, 1-diformazan sulfenyl-2-nitroethylene is water insoluble, need in aprotic polar solvent such as DMF, to carry out), can obtain product 1-methylamino-1-methylthio group-2-nitroethylene without separating directly to react with methyl-sulfate, so, ammoxidation and methylation reaction are realized " one pot of change " operation, reduce unit operation and equipment.
(3) ammoxidation of novel process and methylation reaction be at room temperature reaction, and reaction process does not need heating, the process milder, energy expenditure reduce (patent US4, ammoxidation and methylation reaction temperature are 10～15 ℃ in 967,007; Ammoxidation and methylation reaction temperature in the technology of the yellow intelligent exploitation of Chengdu Organic Chemistry Inst., Chinese Academy of Sciences are 75 ℃).
(4) aqueous ethanol of the crude product 1-potassium and sulfenyl 3 of novel process-1-methylamino-2-nitroethylene recrystallization employing 65～95% is as recrystallization solvent, cost is lower, and obtaining purity through recrystallization is 98.5 qualified product (yellow intelligent ethyl acetate or the Iso Butyl Acetate with costliness of Chengdu Organic Chemistry Inst., Chinese Academy of Sciences is recrystallization solvent).
(5) product yield brings up to 65% by the deficiencies in the prior art 40%, and production cost reduces greatly.
Embodiment
Below the present invention is further illustrated.
The synthetic method of a kind of 1-methylamino--1-methylthio group-2-nitroethylene may further comprise the steps:
(1) preparation of potassium hydroxide-ethanol solution
190kgKOH and 400kg dehydrated alcohol are added in the enamel or stainless steel cauldron that 1000 liters of molten alkali use, stir down and be heated to 40～80 ℃ of dissolvings, it is stand-by to be reduced to room temperature after dissolving is complete.
The preparation of (2) 1,1-two potassium and sulfenyl 3s-2-nitroethylene
In 2000 liters of enamel or the stainless steel addition reaction still, add 150kg Nitromethane 99Min., 170kg dithiocarbonic anhydride and 150kg dehydrated alcohol, stir following 20 ℃ and begin to drip potassium hydroxide-ethanol solution, dropwise, reacted 1～5 hour down, cool to below the room temperature then at 40 ℃, filter, obtain brick-red solid 1,1-two potassium and sulfenyl 3s-2-nitroethylene, the recycle and reuse of filtrate ethanol.
(3) preparation of 1-methylthio group-1-methylamino--2-nitroethylene
The 2000L enamel reaction still is interior with solid di-potassium 1,1-two potassium and sulfenyl 3s-2-nitroethylene is with 400～800kg water stirring and dissolving, add 40% Monomethylamine 100kg about 35 ℃, insulation reaction is 2～7 hours under this temperature, it is ammoxidation, synthesized new intermediate product 1-potassium and sulfenyl 3-1-methylamino-2-nitroethylene, this intermediate product is water-soluble, do not separate directly and methyl-sulfate carries out methylation reaction, add the 400kg methyl-sulfate then and carried out methylation reaction 1～6 hour, filter, obtain crude product 1-methylamino--1-methylthio group-2-nitroethylene.
(4) recrystallization
Adding activated carbon 350kg, dehydrated alcohol 600kg and 200kg crude product 1-methylamino--1-methylthio group-2-nitroethylene are heated to 75 ℃ of dissolvings in the 1000L enamel recrystallization still, refluxed 1～3 hour, remove by filter activated carbon, drop to room temperature, remove by filter etoh solvent, remove the mother liquor that is adsorbed on the crystal with the washing of 60～80% aqueous ethanols, get pale yellow crystals 1-methylamino--1-methylthio group-2-nitroethylene, purity is 98.5%.
Production process of the present invention is simple, operates safer, environmental protection, energy consumption reduces, and yield improves, and production cost reduces, and is suitable for suitability for industrialized production.
Claims (3)
1, the synthetic method of 1-methylamino--1-methylthio group-2-nitroethylene is characterized in that it may further comprise the steps:
(1) preparation of potassium hydroxide-ethanol solution
KOH and dehydrated alcohol are joined in the enamel or stainless steel cauldron that molten alkali uses, stir down and be heated to 30～70 ℃ of dissolvings, it is stand-by to drop to room temperature after dissolving is complete; KOH and dehydrated alcohol are 1.5～2.1: 3.5～4.5 by weight;
The preparation of the two potassium and sulfenyl 3s of (2) 1,1--2-nitroethylene
In enamel or stainless steel addition reaction still, add Nitromethane 99Min., dithiocarbonic anhydride and dehydrated alcohol, stir 15～30 ℃ down, add potassium hydroxide-ethanol solution, reacted 1～5 hour down, cool to below the room temperature at 35～45 ℃, filter, obtain brick-red solid 1,1-two potassium and sulfenyl 3s-2-nitroethylene, wherein the weight ratio of Nitromethane 99Min., dithiocarbonic anhydride, dehydrated alcohol and potassium hydroxide-ethanol solution is 1.3～1.7: 2.5～3.9: 1.3～1.7: 10.5～13.6;
(3) preparation of 1-methylamino--1-methylthio group-2-nitroethylene
In enamel reaction still with solid di-potassium 1, the dissolving of blunging of 1-two potassium and sulfenyl 3s-2-nitroethylene, be heated to about 35 ℃, the monomethylamine aqueous solution of adding 40%, insulation reaction is 2～7 hours under this temperature, adds methyl-sulfate then and carries out methylation reaction 1～6 hour, below the cool to room temperature, filter, obtain crude product 1-methylamino--1-methylthio group-2-nitroethylene; Wherein 1,1-two potassium and sulfenyl 3s-2-nitroethylene, water, 40% monomethylamine aqueous solution, methyl-sulfate are by weight than being 1.0～1.4: 2.2～3.0: 0.4～0.7: 1.1～1.5;
(4) recrystallization
In enamel or stainless steel cauldron, add activated carbon, 60～80% aqueous ethanol and crude product 1-methylamino--1-methylthio group-2-nitroethylene, its weight ratio is 1～2: 42～65: 8～15, be heated to 60～80 ℃ of dissolvings, refluxed 1～3 hour, and removed by filter activated carbon, cool to room temperature, remove by filter etoh solvent, with 60～80% aqueous ethanols washing solid, remove the mother liquor that is adsorbed on the solid, get light yellow solid 1-methylamino--1-methylthio group-2-nitroethylene.
2, the synthetic method of 1-methylamino-as claimed in claim 1-1-methylthio group-2-nitroethylene is characterized in that it may further comprise the steps:
(1) preparation of potassium hydroxide-ethanol solution
KOH and dehydrated alcohol are joined in 1000 liters of enamel or the stainless steel cauldron, be heated to 58～62 ℃ of dissolvings under stirring, it is stand-by to drop to room temperature after the dissolving fully; KOH and dehydrated alcohol are 1.9: 4 by weight;
The preparation of (2) 1,1-two potassium and sulfenyl 3s-2-nitroethylene
In 2000 liters of enamel or stainless steel cauldron, add Nitromethane 99Min., dithiocarbonic anhydride and dehydrated alcohol, stir 18～22 ℃ down, add potassium hydroxide-ethanol solution, reacted 1 hour down, cool to room temperature at 38～42 ℃, filter, obtain brick-red solid 1,1-two potassium and sulfenyl 3s-2-; Nitroethylene, wherein the weight ratio of Nitromethane 99Min., dithiocarbonic anhydride, dehydrated alcohol and potassium hydroxide-ethanol solution is 1.3: 2.5: 1.5: 10.5;
(3) preparation of 1-first An Ji-1-methylthio group-2-nitroethylene
Give birth in enamel or the stainless steel cauldron solid di-potassium 1 2000, the dissolving of blunging of 1-two potassium and sulfenyl 3s-2-nitroethylene, be heated to about 35 ℃, the monomethylamine aqueous solution of adding 40%, insulation reaction is 3～6 hours under this temperature, adds methyl-sulfate then and carries out methylation reaction 1.5～2.5 hours, below the cool to room temperature, filter, obtain crude product 1-methylamino--1-methylthio group-2-nitroethylene; Wherein 1,1-two potassium and sulfenyl 3s-2-nitroethylene, water, 40% monomethylamine aqueous solution, methyl-sulfate are by weight than being 1.2: 2.3: 0.55: 1.15;
(4) recrystallization
In 1000 liters of enamel or stainless steel cauldron, add activated carbon, dehydrated alcohol and crude product 1-methylamino--1-methylthio group-2-nitroethylene, its weight ratio is 1.5: 50: 12, be heated to 60～75 ℃ of dissolvings, refluxed 1～3 hour, remove by filter activated carbon, cool to below the room temperature, remove by filter etoh solvent, remove the mother liquor that is adsorbed on the solid with the washing of 60～80% aqueous ethanols, get light yellow solid 1-methylamino--1-methylthio group-2-nitroethylene.
3, the synthetic method of 1-methylamino-as claimed in claim 1-1-methylthio group-2-nitroethylene is characterized in that it may further comprise the steps:
(1) preparation of potassium hydroxide-ethanol solution
190kgKOH and 400kg dehydrated alcohol are added in 1000 liters of enamel or the molten alkali reaction still of stainless steel, stir down and be heated to 60 ℃ of dissolvings, it is stand-by to be reduced to room temperature after dissolving is complete;
The preparation of (2) 1,1-two potassium and sulfenyl 3s-2-nitroethylene
In 2000 liters of enamel or the stainless steel cauldron, add 150kg Nitromethane 99Min., 170kg dithiocarbonic anhydride and 150kg dehydrated alcohol, stir following 20 ℃, begin to drip potassium hydroxide-ethanol solution 590kg, dropwise, reacted 1 hour down at 40 ℃, cool to below the room temperature, filter, obtain brick-red solid di-potassium 1,1-two potassium and sulfenyl 3s-2-nitroethylene 380kg;
(3) preparation of 1-methylamino--1-methylthio group-2-nitroethylene
In 2000 liters of enamel or stainless steel cauldron with 1,1-two potassium and sulfenyl 3s-2-nitroethylene 380kg 800kg water stirring and dissolving, be heated to 35 ℃ and add 40% monomethylamine aqueous solution 100kg, insulation reaction is 5 hours under this temperature, (synthesized new intermediate product 1-potassium and sulfenyl 3-1-methylamino-2-nitroethylene, this intermediate product is water-soluble, do not separate directly and methyl-sulfate carries out methylation reaction,) add the 400kg methyl-sulfate and carried out methylation reaction 2 hours, below the cool to room temperature, filter, obtain crude product 1-methylamino--1-methylthio group-2-nitroethylene;
(4) recrystallization
Add activated carbon 350kg, dehydrated alcohol 600kg and 200kg crude product 1-methylamino--1-methylthio group-2-nitroethylene heating for dissolving in 1000 liters of enamel or the stainless steel cauldron, refluxed 1～3 hour, remove by filter activated carbon, cool to room temperature, remove by filter etoh solvent, remove the mother liquor that is adsorbed on the solid with the washing of 60～70% aqueous ethanols, get light yellow solid 1-methylamino--1-methylthio group-2-nitroethylene.
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104119257A (en) * | 2013-04-26 | 2014-10-29 | 郭铭 | Preparation method for 1-methylamino-1-methylthio-2-nitroethylene |
| CN109851532A (en) * | 2019-03-18 | 2019-06-07 | 苏州大学 | Application of the ytterbium in catalysis azepine Henle reaction |
-
2006
- 2006-11-16 CN CN 200610102159 patent/CN1962626A/en active Pending
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104119257A (en) * | 2013-04-26 | 2014-10-29 | 郭铭 | Preparation method for 1-methylamino-1-methylthio-2-nitroethylene |
| CN104119257B (en) * | 2013-04-26 | 2016-08-03 | 石家庄康坦福化工科技有限公司 | A kind of preparation method of 1-methylamino-1-methyl mercapto-2-nitroethylene |
| CN109851532A (en) * | 2019-03-18 | 2019-06-07 | 苏州大学 | Application of the ytterbium in catalysis azepine Henle reaction |
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