CN105418537A - Synthetic method of 2-methoxy phenothiazine - Google Patents
Synthetic method of 2-methoxy phenothiazine Download PDFInfo
- Publication number
- CN105418537A CN105418537A CN201510964047.4A CN201510964047A CN105418537A CN 105418537 A CN105418537 A CN 105418537A CN 201510964047 A CN201510964047 A CN 201510964047A CN 105418537 A CN105418537 A CN 105418537A
- Authority
- CN
- China
- Prior art keywords
- methoxyl group
- reaction
- solvent
- synthetic method
- add
- 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.)
- Pending
Links
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D279/00—Heterocyclic compounds containing six-membered rings having one nitrogen atom and one sulfur atom as the only ring hetero atoms
- C07D279/10—1,4-Thiazines; Hydrogenated 1,4-thiazines
- C07D279/14—1,4-Thiazines; Hydrogenated 1,4-thiazines condensed with carbocyclic rings or ring systems
- C07D279/18—[b, e]-condensed with two six-membered rings
- C07D279/20—[b, e]-condensed with two six-membered rings with hydrogen atoms directly attached to the ring nitrogen atom
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The invention provides a synthetic method of 2-methoxy phenothiazine, comprising the following steps: step 1, mixing resorcinol and phenylamine evenly, adding a catalyst under stirring heating, dehydrating, and performing an amination reaction to generate an intermediate I; step 2, adding a solvent and alkali into the intermediate I, dropwise adding a methylation reagent under a heating condition, and performing an etherification reaction to generate an intermediate II; step 3, adding the solvent and sulphur into the intermediate II, adding iodine under a heating reflux condition for initiation reaction, and performing a ring closing reaction to generate an initial product 2-methoxy phenothiazine; step 4, recrystallizing the initial product 2-methoxy phenothiazine by using the solvent, thus obtaining the pure 2-methoxy phenothiazine. The single solvent is adopted, thus benefiting separation and purification of the product, effectively lowering the cost of the solvent, improving industrial preparation reaction cleanness and safety, and reducing environment pollution; meanwhile, the separated and recycled solvent can be used cyclically.
Description
Technical field
The invention belongs to technical field of organic synthesis, be specifically related to a kind of synthetic method of 2-methoxyl group thiodiphenylamine.
Background technology
2-methoxyl group thiodiphenylamine is the important representative in phenothiazine compound newly developed in the world in recent years, also be important pharmaceutical intermediate, this product is in great demand in medicine, agricultural chemicals and high polymer monomer stopper etc. simultaneously, has very strong using value.Its molecular formula C
13h
11nOS, fusing point 185-187 DEG C, temporarily also do not have patent report both at home and abroad.
Synthetic method of the prior art is: the first step: with Resorcinol and aniline for raw material, synthesize 3 monohydroxy pentanoic under certain temperature and catalyst action.
Second step: 3-hydroxy diphenylamine methylates, 3-hydroxy diphenylamine and methyl-sulfate generate 3-methoxy diphenylamine under certain condition.
3rd step: 3 one methoxy diphenylamines in a solvent under certain condition and sulfur reaction generate 2-methoxyl group thiodiphenylamine.
4th step: separating-purifying obtains 2-methoxyl group thiodiphenylamine product.
Solvent used in the 3rd step in the method is the mixture containing polysubstituted aromatic hydrocarbons, complicated component, and solvent boiling point is higher, temperature of reaction is at 160 DEG C, meanwhile, each step solvent of the method is all not identical, and second step solvent used is toluene, solvent used in 3rd step is the mixed solvent containing polysubstituted aromatic hydrocarbons, 4th step recrystallization solvent is for using ethanol-water mixed solvent, and these reasons cause material cost higher, and energy consumption is high, also make byproduct of reaction too much, product separation is comparatively difficult.
Therefore, be badly in need of a kind of reaction conditions gentleness, aftertreatment is easy to the synthetic method of 2-methoxyl group thiodiphenylamine to fill up the vacancy of this type of organic synthesis.
Summary of the invention
Goal of the invention: for above-mentioned deficiency of the prior art, the invention provides a kind of synthetic method of 2-methoxyl group thiodiphenylamine.
Technical scheme: the synthetic method that the invention provides a kind of 2-methoxyl group thiodiphenylamine, comprises the steps: step one, Resorcinol and aniline are mixed, adds catalyzer dehydration and amination reaction generation intermediate I occurs under stirring heating; Step 2, intermediate I solubilizing agent and alkali, drip methylating reagent generation etherification reaction in a heated condition and generate intermediate II; Step 3, intermediate II solubilizing agent and sulphur, add iodine initiation reaction under heated reflux condition, carry out ring closure reaction and generate head product 2-methoxyl group thiodiphenylamine; Step 4, head product 2-methoxyl group thiodiphenylamine solvent carry out recrystallization and obtain pure 2-methoxyl group thiodiphenylamine.
Concrete, the catalyzer described in step one is tosic acid, Phenylsulfonic acid, sulfuric acid or phosphoric acid.Alkali described in step 2 is salt of wormwood, sodium carbonate, sodium hydroxide or potassium hydroxide.Methylating reagent described in step 2 is methyl iodide, methyl-sulfate, methylcarbonate or trimethyl orthoformate.
Of the present invention one large feature is selection and the application of solvent, and the solvent described in step 2 of the present invention, step 3, step 4 is lower boiling, inert aprotic solvent.Further, the solvent described in step 2 of the present invention, step 3, step 4 is single solvent, and is same material, both the separating-purifying of product had been conducive to, effectively reduce solvent cost again, also improve spatter property and the security of industrial preparation feedback, decrease environmental pollution.Concrete, the solvent described in step 2 of the present invention, step 3, step 4 can select ethylene dichloride, benzene, toluene, hexanaphthene, methylcyclohexane.Simultaneously, the add-on of solvent also very important in the present invention, the add-on of the solvent described in step 2, step 3, step 4, be respectively the 3-10 of intermediate I amount of substance doubly, the 3-6 of intermediate II amount of substance doubly, the 3-8 of the amount of head product 2-methoxyl group thiophenylamine substance doubly.
The present invention also has a feature to be exactly reaction conditions gentleness, and the temperature of reaction in step 3 of the present invention is 80-130 DEG C.Because temperature of reaction of the present invention is lower, therefore energy consumption is low, side reaction is few, product purity is high.
The synthesis step that the present invention is complete is as follows:
Step one, Resorcinol and aniline are mixed, the ratio of both amount of substances is 1:1.2, at whipped state 185 ~ 195 DEG C, adds catalyzer dehydration and amination reaction occurs generates intermediate I; Step 2, intermediate I solubilizing agent and alkali, the mol ratio of intermediate I and alkali is 1:1 ~ 1:1.5, drips methylating reagent generation etherification reaction at 30-80 DEG C, 3 ~ 8 hours reaction times, generates intermediate II; Step 3, intermediate II solubilizing agent and sulphur, the mol ratio of sulphur and intermediate II is 1:1 ~ 3:1, under heated reflux condition, at being warming up to 80 ~ 130 DEG C, add iodine initiation reaction, 6 ~ 12 hours reaction times, carry out ring closure reaction and generate head product 2-methoxyl group thiodiphenylamine; Step 4, head product 2-methoxyl group thiodiphenylamine solvent carry out recrystallization, obtain pure 2-methoxyl group thiodiphenylamine, dry weighing.
Beneficial effect: the present invention is compared with existing 2-methoxyl group thiodiphenylamine synthetic method, solvent described in step 2, step 3, step 4 is single solvent, and be same material, both the separating-purifying of product had been conducive to, effectively reduce solvent cost again, also improve spatter property and the security of industrial preparation feedback, decrease environmental pollution.Be separated simultaneously, recovered solvent can recycle.
Embodiment:
Embodiment 1
By 44.7g aniline, 44.0g Resorcinol is added in 1000ml there-necked flask, 140 DEG C are warmed up under nitrogen protection, add 1.32g tosic acid until completely dissolved, finish and continue to be warmed up to 185 ~ 195 DEG C, react 6h at this temperature, sampling HPLC detects, react completely and cool to 70 DEG C, after process, obtain intermediate I;
In above-mentioned intermediate I, add 312g hexanaphthene and 29.7g massfraction is the sodium hydroxide solution of 60%, finish reflux water-dividing and separate to anhydrous, cool to 50 DEG C, drip 60.8g methyl-sulfate, after reaction 8h, cooling aftertreatment obtains intermediate II;
In intermediate II, add 140g hexanaphthene and 12.2g sulphur, heating adds 0.42g iodine after dissolving completely, continues to be warming up to 85 DEG C of backflow 10h, solid is separated out in cooling, and filter, solid 137g hexanaphthene recrystallization obtains pure 2-methoxyl group thiodiphenylamine 61.3g, HPLC content 97%, total recovery=67%.
Embodiment 2
By 44.7g aniline, 44.0g Resorcinol is added in 1000ml there-necked flask, 140 DEG C are warmed up under nitrogen protection, add 1.32g tosic acid until completely dissolved, finish and continue to be warmed up to 185 ~ 195 DEG C, react 6h at this temperature, sampling HPLC detects, react completely and cool to 70 DEG C, after process, obtain intermediate I;
In above-mentioned intermediate I, add 86.7g benzene and 24.7g massfraction is the sodium hydroxide solution of 60%, finish reflux water-dividing and separate to anhydrous, cool to 50 DEG C, drip 60.8g methyl-sulfate, after reaction 4.5h, cooling aftertreatment obtains intermediate II;
In intermediate II, add 78g benzene and 31.9g sulphur, heating adds 0.42g iodine after dissolving completely, continues intensification 100 DEG C backflow 10h, solid is separated out in cooling, and filter, solid 108g benzene recrystallization obtains pure 2-methoxyl group thiodiphenylamine 63.6g, HPLC content 97%, total recovery=69.5%.
Embodiment 3
By 44.7g aniline, 44.0g Resorcinol is added in 1000ml there-necked flask, 140 DEG C are warmed up under nitrogen protection, add 1.32g tosic acid until completely dissolved, finish and continue to be warmed up to 185 ~ 195 DEG C, react 6h at this temperature, sampling HPLC detects, react completely and cool to 70 DEG C, after process, obtain intermediate I;
In above-mentioned intermediate I, add 86.7g benzene and 37.1g massfraction is the sodium hydroxide solution of 60%, finish reflux water-dividing and separate to anhydrous, cool to 30 DEG C, drip 60.8g methyl-sulfate, after reaction 8h, cooling aftertreatment obtains intermediate II;
In intermediate II, add 78g benzene and 12.2g sulphur, heating adds 0.085g iodine after dissolving completely, continues intensification 80 DEG C backflow 10h, solid is separated out in cooling, and filter, solid 108g benzene recrystallization obtains pure 2-methoxyl group thiodiphenylamine 61.5g, HPLC content 97%, total recovery=67.2%.
Embodiment 4
By 44.7g aniline, 44.0g Resorcinol is added in 1000ml there-necked flask, 140 DEG C are warmed up under nitrogen protection, add 1.32g tosic acid until completely dissolved, finish and continue to be warmed up to 185 ~ 195 DEG C, react 6h at this temperature, sampling HPLC detects, react completely and cool to 70 DEG C, after process, obtain intermediate I;
In above-mentioned intermediate I, add 102g toluene and 26.5g massfraction is the sodium hydroxide solution of 60%, finish reflux water-dividing and separate to anhydrous, cool to 40 DEG C, drip 65.5g methyl-sulfate, after reaction 3h, cooling aftertreatment obtains intermediate II;
In intermediate II, add 140g toluene and 13.5g sulphur, heating adds 0.085g iodine after dissolving completely, continues to be warming up to 130 DEG C of backflow 8h, solid is separated out in cooling, and filter, solid 100g re crystallization from toluene obtains pure 2-methoxyl group thiodiphenylamine 62.4g, HPLC content 97%, total recovery=68%.
Embodiment 5
By 44.7g aniline, 44.0g Resorcinol is added in 1000ml there-necked flask, 140 DEG C are warmed up under nitrogen protection, add 1.32g tosic acid until completely dissolved, finish and continue to be warmed up to 185 ~ 195 DEG C, react 6h at this temperature, sampling HPLC detects, react completely and cool to 70 DEG C, after process, obtain intermediate I;
In above-mentioned intermediate I, add 290.8g methylcyclohexane and 37.1g massfraction is the sodium hydroxide solution of 60%, finish reflux water-dividing and separate to anhydrous, cool to 80 DEG C, drip 60.8g methyl-sulfate, after reaction 3h, cooling aftertreatment obtains intermediate II;
195.6g methylcyclohexane and 18.0g sulphur is added in intermediate II, heating adds 0.42g iodine after dissolving completely, continue intensification 110 DEG C backflow 12h, solid is separated out in cooling, filter, solid 212.2g methylcyclohexane recrystallization obtains pure 2-methoxyl group thiodiphenylamine 62.0g, HPLC content 97%, total recovery=67.7%.
Embodiment 6
By 44.7g aniline, 44.0g Resorcinol is added in 1000ml there-necked flask, 140 DEG C are warmed up under nitrogen protection, add 1.32g tosic acid until completely dissolved, finish and continue to be warmed up to 185 ~ 195 DEG C, react 6h at this temperature, sampling HPLC detects, react completely and cool to 70 DEG C, after process, obtain intermediate I;
In above-mentioned intermediate I, add 86.7g benzene and 37.1g massfraction is the sodium hydroxide solution of 60%, finish reflux water-dividing and separate to anhydrous, cool to 40 DEG C, drip 40.1g methylcarbonate, after reaction 6h, cooling aftertreatment obtains intermediate II;
In intermediate II, add 78g benzene and 12.2g sulphur, heating adds 0.42g iodine after dissolving completely, continues intensification 100 DEG C backflow 8h, solid is separated out in cooling, and filter, solid 108g benzene recrystallization obtains pure 2-methoxyl group thiodiphenylamine 61.6g, HPLC content 97%, total recovery=67.3%.
Embodiment 7
By 44.7g aniline, 44.0g Resorcinol is added in 1000ml there-necked flask, 140 DEG C are warmed up under nitrogen protection, add 1.32g tosic acid until completely dissolved, finish and continue to be warmed up to 185 ~ 195 DEG C, react 6h at this temperature, sampling HPLC detects, react completely and cool to 70 DEG C, after process, obtain intermediate I;
In above-mentioned intermediate I, add 86.7g benzene and 37.1g massfraction is the sodium hydroxide solution of 60%, finish reflux water-dividing and separate to anhydrous, cool to 30 DEG C, drip 50.1g methylcarbonate, after reaction 8h, cooling aftertreatment obtains intermediate II;
In intermediate II, add 85g benzene and 12.2g sulphur, heating adds 0.42g iodine after dissolving completely, continues intensification 100 DEG C backflow 8h, solid is separated out in cooling, and filter, solid 112g benzene recrystallization obtains pure 2-methoxyl group thiodiphenylamine 62.2g, HPLC content 97%, total recovery=68%.
Embodiment 8
By 44.7g aniline, 44.0g Resorcinol is added in 1000ml there-necked flask, 140 DEG C are warmed up under nitrogen protection, add 1.32g tosic acid until completely dissolved, finish and continue to be warmed up to 185 ~ 195 DEG C, react 6h at this temperature, sampling HPLC detects, react completely and cool to 70 DEG C, after process, obtain intermediate I;
In above-mentioned intermediate I, add 86.7g benzene and 37.1g massfraction is the sodium hydroxide solution of 60%, finish reflux water-dividing and separate to anhydrous, cool to 35 DEG C, drip 47.2g trimethyl orthoformate, after reaction 8h, cooling aftertreatment obtains intermediate II;
In intermediate II, add 82g benzene and 12.2g sulphur, heating adds 0.42g iodine after dissolving completely, continues intensification 100 DEG C backflow 10h, solid is separated out in cooling, and filter, solid 112g benzene recrystallization obtains pure 2-methoxyl group thiodiphenylamine 59.1g, HPLC content 96%, total recovery=64.6%.
Embodiment 9
By 44.7g aniline, 44.0g Resorcinol is added in 1000ml there-necked flask, 140 DEG C are warmed up under nitrogen protection, add 1.32g tosic acid until completely dissolved, finish and continue to be warmed up to 185 ~ 195 DEG C, react 6h at this temperature, sampling HPLC detects, react completely and cool to 70 DEG C, after process, obtain intermediate I;
In above-mentioned intermediate I, add 102g toluene and 26.5g massfraction is the sodium hydroxide solution of 60%, finish reflux water-dividing and separate to anhydrous, cool to 35 DEG C, drip 47.2g trimethyl orthoformate, after reaction 6h, cooling aftertreatment obtains intermediate II;
In intermediate II, add 140g toluene and 21.3g sulphur, heating adds 0.42g iodine after dissolving completely, continues to be warming up to 130 DEG C of backflow 8h, solid is separated out in cooling, and filter, solid 100g re crystallization from toluene obtains pure 2-methoxyl group thiodiphenylamine 62.0g, HPLC content 97%, total recovery=67.8%.
Embodiment 10
By 44.7g aniline, 44.0g Resorcinol is added in 1000ml there-necked flask, 140 DEG C are warmed up under nitrogen protection, add 1.32g tosic acid until completely dissolved, finish and continue to be warmed up to 185 ~ 195 DEG C, react 6h at this temperature, sampling HPLC detects, react completely and cool to 70 DEG C, after process, obtain intermediate I;
In above-mentioned intermediate I, add 86.7g benzene and 41.5g massfraction is the potassium hydroxide solution of 60%, finish reflux water-dividing and separate to anhydrous, cool to 40 DEG C, drip 60.8g methyl-sulfate, after reaction 5h, cooling aftertreatment obtains intermediate II;
In intermediate II, add 78g benzene and 10.6g sulphur, heating adds 0.42g iodine after dissolving completely, continues intensification 90 DEG C backflow 10h, solid is separated out in cooling, and filter, solid 108g benzene recrystallization obtains pure 2-methoxyl group thiodiphenylamine 63.1g, HPLC content 97%, total recovery=68.9%.
Embodiment 11
By 44.7g aniline, 44.0g Resorcinol is added in 1000ml there-necked flask, 140 DEG C are warmed up under nitrogen protection, add 1.32g tosic acid until completely dissolved, finish and continue to be warmed up to 185 ~ 195 DEG C, react 6h at this temperature, sampling HPLC detects, react completely and cool to 70 DEG C, after process, obtain intermediate I;
In above-mentioned intermediate I, add 290.8g methylcyclohexane and 147.6g massfraction is the solution of potassium carbonate of 50%, finish reflux water-dividing and separate to anhydrous, cool to 60 DEG C, drip 60.8g methyl-sulfate, after reaction 6h, cooling aftertreatment obtains intermediate II;
200g methylcyclohexane and 24.5g sulphur is added in intermediate II, heating adds 0.25g iodine after dissolving completely, continue intensification 115 DEG C backflow 11h, solid is separated out in cooling, filter, solid 212g methylcyclohexane recrystallization obtains pure 2-methoxyl group thiodiphenylamine 61.5g, HPLC content 97%, total recovery=67.2%.
Embodiment 12
By 44.7g aniline, 44.0g Resorcinol is added in 1000ml there-necked flask, 140 DEG C are warmed up under nitrogen protection, add 1.32g tosic acid until completely dissolved, finish and continue to be warmed up to 185 ~ 195 DEG C, react 6h at this temperature, sampling HPLC detects, react completely and cool to 70 DEG C, after process, obtain intermediate I;
In above-mentioned intermediate I, add 290.8g methylcyclohexane and 204.5g massfraction is the sodium carbonate solution of 30%, finish reflux water-dividing and separate to anhydrous, cool to 40 DEG C, drip 50.1g methylcarbonate, after reaction 7h, cooling aftertreatment obtains intermediate II;
200g methylcyclohexane and 24.5g sulphur is added in intermediate II, heating adds 0.25g iodine after dissolving completely, continue intensification 115 DEG C backflow 6h, solid is separated out in cooling, filter, solid 212g methylcyclohexane recrystallization obtains pure 2-methoxyl group thiodiphenylamine 61.0g, HPLC content 97%, total recovery=66.7%.
Claims (9)
1. a synthetic method for 2-methoxyl group thiodiphenylamine, is characterized in that comprising the steps:
Step one, Resorcinol and aniline to be mixed, under stirring heating, add catalyzer dehydration amination reaction occurs generate intermediate I;
Step 2, intermediate I solubilizing agent and alkali, drip methylating reagent generation etherification reaction in a heated condition and generate intermediate II;
Step 3, intermediate II solubilizing agent and sulphur, add iodine initiation reaction under heated reflux condition, carry out ring closure reaction and generate head product 2-methoxyl group thiodiphenylamine;
Step 4, head product 2-methoxyl group thiodiphenylamine solvent carry out recrystallization and obtain pure 2-methoxyl group thiodiphenylamine.
2. the synthetic method of 2-methoxyl group thiodiphenylamine as claimed in claim 1, is characterized in that the alkali described in step 2 is salt of wormwood, sodium carbonate, sodium hydroxide or potassium hydroxide.
3. the synthetic method of 2-methoxyl group thiodiphenylamine as claimed in claim 1, is characterized in that the methylating reagent described in step 2 is methyl-sulfate, methylcarbonate or trimethyl orthoformate.
4. the synthetic method of 2-methoxyl group thiodiphenylamine as claimed in claim 1, is characterized in that the solvent described in step 2, step 3, step 4 is single solvent, and is same material.
5. the synthetic method of 2-methoxyl group thiodiphenylamine as claimed in claim 1, is characterized in that the solvent described in step 2, step 3, step 4 is lower boiling inert aprotic solvent.
6. the synthetic method of 2-methoxyl group thiodiphenylamine as claimed in claim 1, is characterized in that the solvent described in step 2, step 3, step 4 is 1,2-ethylene dichloride, benzene, toluene, hexanaphthene or methylcyclohexane.
7. the synthetic method of 2-methoxyl group thiodiphenylamine as claimed in claim 1, it is characterized in that the add-on of the solvent described in step 2, step 3, step 4, be respectively 3 ~ 8 times of amount of intermediate I amount of substance 3 ~ 10 times, intermediate II amount of substance 3 ~ 6 times, head product 2-methoxyl group thiophenylamine substance.
8. the synthetic method of 2-methoxyl group thiodiphenylamine as claimed in claim 1, it is characterized in that the temperature of reaction in described step 2 is 30 ~ 80 DEG C, the reaction times is 3 ~ 8 hours, and the add-on of alkali is 1.0 ~ 1.5 times of intermediate I amount of substance.
9. the synthetic method of 2-methoxyl group thiodiphenylamine as claimed in claim 1, it is characterized in that the temperature of reaction in described step 3 is 80 ~ 130 DEG C, the reaction times is 6 ~ 12 hours; The add-on of sulphur is 1.0 ~ 3.0 times of intermediate II amount of substance; The add-on of iodine is 0.001 ~ 0.005 times of intermediate II amount of substance.
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN201510964047.4A CN105418537A (en) | 2015-12-18 | 2015-12-18 | Synthetic method of 2-methoxy phenothiazine |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN201510964047.4A CN105418537A (en) | 2015-12-18 | 2015-12-18 | Synthetic method of 2-methoxy phenothiazine |
Publications (1)
Publication Number | Publication Date |
---|---|
CN105418537A true CN105418537A (en) | 2016-03-23 |
Family
ID=55497142
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN201510964047.4A Pending CN105418537A (en) | 2015-12-18 | 2015-12-18 | Synthetic method of 2-methoxy phenothiazine |
Country Status (1)
Country | Link |
---|---|
CN (1) | CN105418537A (en) |
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN112724103A (en) * | 2020-12-16 | 2021-04-30 | 广安凯特制药有限公司 | Isopromazine specific impurity and analysis method and removal method thereof |
Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
RO63135A2 (en) * | 1973-02-03 | 1978-06-15 | Medicamente Terapia Fab De | PROCESS FOR THE PREPARATION OF METHOXYPHENOTHIAZINE |
CN101250139A (en) * | 2008-03-25 | 2008-08-27 | 浙江大学 | Method for synthesizing 3,3'-dimethoxy diphenylurea |
CN101508653A (en) * | 2009-03-24 | 2009-08-19 | 浙江寿尔福化学有限公司 | Synthesis of meta-methoxy diphenylamine |
-
2015
- 2015-12-18 CN CN201510964047.4A patent/CN105418537A/en active Pending
Patent Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
RO63135A2 (en) * | 1973-02-03 | 1978-06-15 | Medicamente Terapia Fab De | PROCESS FOR THE PREPARATION OF METHOXYPHENOTHIAZINE |
CN101250139A (en) * | 2008-03-25 | 2008-08-27 | 浙江大学 | Method for synthesizing 3,3'-dimethoxy diphenylurea |
CN101508653A (en) * | 2009-03-24 | 2009-08-19 | 浙江寿尔福化学有限公司 | Synthesis of meta-methoxy diphenylamine |
Non-Patent Citations (1)
Title |
---|
张涛: "2-甲氧基吩噻嗪的合成研究", 《中国优秀硕士学位论文全文数据库工程科技I辑》 * |
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN112724103A (en) * | 2020-12-16 | 2021-04-30 | 广安凯特制药有限公司 | Isopromazine specific impurity and analysis method and removal method thereof |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
CN103288718B (en) | Preparation method of 2-chloro-5-tirfluoromethylpyridine | |
CN106810426A (en) | A kind of synthetic method of cannabidiol | |
CN104262318B (en) | A kind of preparation method of Olopatadine hydrochloride | |
CN103333111A (en) | Preparation method of lorcaserin hydrochloride | |
CN103539744B (en) | One prepares the method for 3-(3,5-dichlorophenyl)-2,4-imidazolidimediones | |
KR20180113970A (en) | Process for producing aryl-substituted para-phenylenediamine-based material | |
CN102633626B (en) | A kind of 2,4,6-Three methyl Benzene Acetyl Chloride 98Min. synthesis technique | |
CN105418537A (en) | Synthetic method of 2-methoxy phenothiazine | |
CN101597243A (en) | The synthetic method of a kind of 2-cyano group-4 '-bromomethylbiphenyl | |
CN102531888A (en) | Chemical synthesis method of 3,4,5-trimethoxy benzoyl chloride | |
CN105566260B (en) | A kind of preparation method of frusemide | |
CN107011128A (en) | One kind 1,2 two(2‑(2,6 dimethoxy phenoxy groups)Ethyoxyl)The preparation method of ethane | |
CN102070650B (en) | Preparation method for levofloxacin-N-oxide | |
CN105461550A (en) | Preparation method of p-anisoyl chloride | |
CN104926599A (en) | Method for preparing high-purity 4,4'-bis(chloromethyl)-1,1'-biphenyl under novel solvent system | |
CN101863782B (en) | Method for synthesizing ultraviolet photoinitiator of p-dimethylamin benzoic ether compounds | |
CN106278983A (en) | A kind of N-Methyl pyrrolidone continuous preparation method | |
CN105523995A (en) | Preparation method for malaridine intermediate 2-methoxy-5-aminopyridine | |
CN101786956B (en) | Method for deacylating N-acylated diphenylamine or ring-substituted derivatives thereof | |
CN111574416B (en) | Method for preparing tiamulin from isothiourea salt and pleuromutilin p-toluenesulfonate | |
CN102633701B (en) | Synthesis method of S-methyl isothiourea salt | |
CN102898858B (en) | Preparation method of 3', 6'-dimethoxy fluorane yellow thermosensitive dye | |
CN105646191B (en) | A kind of method for preparing fragrant dimethyl chloride | |
CN110845371A (en) | Method for synthesizing o-sulfobenzaldehyde under normal pressure | |
CN110028379B (en) | Preparation method of 4, 4' -dichloromethyl biphenyl |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
C06 | Publication | ||
PB01 | Publication | ||
C10 | Entry into substantive examination | ||
SE01 | Entry into force of request for substantive examination | ||
RJ01 | Rejection of invention patent application after publication |
Application publication date: 20160323 |
|
RJ01 | Rejection of invention patent application after publication |