CN102558089B - Method for preparation and purification of 2-(4-methyl-1-piperazinyl)-4- thiazolinone - Google Patents
Method for preparation and purification of 2-(4-methyl-1-piperazinyl)-4- thiazolinone Download PDFInfo
- Publication number
- CN102558089B CN102558089B CN201210008859.8A CN201210008859A CN102558089B CN 102558089 B CN102558089 B CN 102558089B CN 201210008859 A CN201210008859 A CN 201210008859A CN 102558089 B CN102558089 B CN 102558089B
- Authority
- CN
- China
- Prior art keywords
- methyl
- room temperature
- methylene dichloride
- add
- thiazolinone
- 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.)
- Expired - Fee Related
Links
Landscapes
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention discloses a method for preparation and purification of 2-(4-methyl-1-piperazinyl)-4- thiazolinone. [Emim] SCN (sulfocyanic acid) is used as raw materials and a solvent, ethyl chloroacetate is added at the room temperature, and reaction is carried out for 1.5-2 hours. Then acetic acid is added, the mixture is stirred for 5-7min at the room temperature, N-methyl piperazine is added, the mixture is stirred under magnetic force at the room temperature, and the reaction is continuously carried out for 1.5-2 hours. The reaction is stopped, the products are cooled to the room temperature, the extractant dichloromethane and water are added for extraction, the lower organic layer is collected, the water layer is extractor twice to three time with dichloromethane, the dichloromethane layers are combined, the solvent is evaporated after drying with anhydrous magnesium sulfate, and the white solid product is prepared via separation and purification of coarse products in a method of column chromatography. The prepared 2-(4-methyl-1-piperazinyl)-4- thiazolinone is a novel compound, the used raw materials can be obtained easily and are inexpensive, the operation is simple, the efficiency is high, the yield reaches 73-76 percent, and the preparation method is suitable for industrial production.
Description
Technical field
The present invention relates to a kind of 2-(4
-methyl
-1
-piperazinyl) preparation and the method for purification of-4-thiazolinone, particularly methylene dichloride and water are that extraction agent extracts and obtains crude product, methyl alcohol, methylene dichloride and triethylamine are that eluent carries out column chromatography and separates and obtain new compound 2-(4
-methyl
-1
-piperazinyl)-4-thiazolinone.
Background technology
2-(
n,
n-disubstituted amido)-4-thiazolinone compounds is as the important heterogeneous ring compound of a class, has good biology and physiologically active, is also a kind of well organic synthesis intermediate simultaneously, can be used for synthetic liquid crystal material and dyestuff etc.About the research of 4-thiazolinone has become one of current hot subject, obtain investigator's extensive concern.Therefore the synthetic new 4-thiazolinone compounds of exploitation, for the kind of enriching 4-thiazolinone compounds, expands its purposes significant.
2-(
n,
n-disubstituted amido) if-contain heteroatoms on the substituent structure of 4-thiazolinone, can increase the polarity of thiazolinone compounds, its structure division fragment and ionic liquid have similarity, and there is certain difficulty in both separating-purifyings therefore.At present about 2-(
n,
n-disubstituted amido) aftertreatment of-4-thiazolinone normally extracts by ethyl acetate, carries out column chromatogram chromatography with ethyl acetate and sherwood oil.On post-treating method, exist when extraction incomplete, in column chromatography, adsorb morely, cause the shortcomings such as productive rate reduction.
Summary of the invention
The object of the invention is to overcome the deficiencies in the prior art, a kind of 2-(4 is provided
-methyl
-1
-piperazinyl) preparation and the method for purification of-4-thiazolinone.
2-(4
-methyl
-1
-piperazinyl) preparation and the method for purification of-4-thiazolinone be: taking [Emim] SCN as raw material and solvent, under room temperature, add ethyl chloroacetate, reaction 1.5～2h, then add acetic acid, under room temperature, stir 5～7min, add again N methyl piperazine, mixture continues reaction 1.5～2h under magnetic agitation room temperature, stopped reaction, be cooled to after room temperature, add extraction agent methylene dichloride and water to extract, collect lower floor's organic layer, water layer is used dichloromethane extraction 2～3 times again, combined dichloromethane layer, with boiling off solvent after anhydrous magnesium sulfate drying, crude product obtains white solid product through column chromatography separating-purifying, the mol ratio of described N methyl piperazine and [Emim] SCN is 1:5～1:9, the mol ratio of N methyl piperazine and ethyl chloroacetate is 1:1～1:1.2, described N methyl piperazine and the mol ratio of acetic acid are 1:1～1:1.2, described extraction agent water and the volume ratio of methylene dichloride are 1:1～1:1.3, the volume ratio of methyl alcohol, methylene dichloride and triethylamine that described crude product separates through column chromatography is that 1:40:0.1～1:45:0.2 makes eluent.
The mol ratio of described N methyl piperazine and [Emim] SCN is 1:5～1:7; The mol ratio of N methyl piperazine and ethyl chloroacetate is 1:1～1:1.1; Described N methyl piperazine and the mol ratio of acetic acid are 1:1～1:1.1; Described extraction agent water and the volume ratio of methylene dichloride are 1:1～1:1.2; The volume ratio of methyl alcohol, methylene dichloride and triethylamine that described crude product separates through column chromatography is that 1:40:0.1～1:45:0.15 makes eluent.
4-thiazolinone compounds has good biological activity, will in the fields such as medicine, novel pesticide, macromolecular material, dyestuff, have a wide range of applications.Research and development new compound 2-(4
-methyl
-1
-piperazinyl)-4-thiazolinone has very important academic significance, practical value and wide market outlook.
2-(4 prepared by the present invention
-methyl
-1
-piperazinyl)-4-thiazolinone is a kind of new compound, taking methylene dichloride and water as extraction agent, obtain taking methyl alcohol, methylene dichloride and triethylamine as eluent column chromatography, the present invention's target product loss in extraction and column chromatography process reduces, productive rate reaches 73～76%, is the preparation method who is applicable to suitability for industrialized production.
Embodiment
2-(4
-methyl
-1
-piperazinyl) preparation and the method for purification of-4-thiazolinone be: taking [Emim] SCN as raw material and solvent, under room temperature, add ethyl chloroacetate, reaction 1.5～2h, then add acetic acid, under room temperature, stir 5～7min, add again N methyl piperazine, mixture continues reaction 1.5～2h under magnetic agitation room temperature, stopped reaction, be cooled to after room temperature, add extraction agent methylene dichloride and water to extract, collect lower floor's organic layer, water layer is used dichloromethane extraction 2～3 times again, combined dichloromethane layer, with boiling off solvent after anhydrous magnesium sulfate drying, crude product obtains white solid product through column chromatography separating-purifying, the mol ratio of described N methyl piperazine and [Emim] SCN is 1:5～1:9, the mol ratio of N methyl piperazine and ethyl chloroacetate is 1:1～1:1.2, described N methyl piperazine and the mol ratio of acetic acid are 1:1～1:1.2, described extraction agent water and the volume ratio of methylene dichloride are 1:1～1:1.3, the volume ratio of methyl alcohol, methylene dichloride and triethylamine that described crude product separates through column chromatography is that 1:40:0.1～1:45:0.2 makes eluent.
The mol ratio of described N methyl piperazine and [Emim] SCN is 1:5～1:7; The mol ratio of N methyl piperazine and ethyl chloroacetate is 1:1～1:1.1; Described N methyl piperazine and the mol ratio of acetic acid are 1:1～1:1.1; Described extraction agent water and the volume ratio of methylene dichloride are 1:1～1:1.2; The volume ratio of methyl alcohol, methylene dichloride and triethylamine that described crude product separates through column chromatography is that 1:40:0.1～1:45:0.15 makes eluent.
[Emim] SCN is that a kind of negatively charged ion is thiocyanate ion, and positively charged ion is the ionic liquid of 1-ethyl-3-methylimidazole.Its preparation process is as follows: in round-bottomed flask, add 32 mmol monobromethanes, add 30 mmol Methylimidazoles again, load onto reflux condensing tube, mixture reacts 24h at 70 DEG C of magnetic agitation, after cooling, wash solid with ethyl acetate and ether respectively, dissolution of solid, in acetone, is added to 31mmol potassium sulfocyanate, under magnetic agitation room temperature, react 24h, decompression, except acetone, is crossed filtering solid, and vacuum-drying obtains [Emim] SCN.At preparation 2-(4
-methyl
-1
-piperazinyl) in the reaction of-4-thiazolinone, [Emim] SCN, both as reactant, provides thiocyanate ion negatively charged ion, again as reaction solvent.So [Emim] SCN is relatively more excessive.
Reaction equation of the present invention is:
Below in conjunction with embodiment, the present invention is further illustrated.
Embodiment 1:
In round-bottomed flask bottle, add 2.5 mL [Emim] SCN, ethyl chloroacetate 2.2 mmol, react 2h under room temperature.Then add 2 mmol acetic acid, under room temperature, stir 7min, then add 2 mmol N methyl piperazines, mixture continues reaction 2h under magnetic agitation room temperature.Stopped reaction, be cooled to room temperature, add 12 mL methylene dichloride and 10 mL water to extract, collect lower floor's organic layer, water layer is used 12 mL dichloromethane extraction 3 times again, combined dichloromethane layer, with boiling off solvent after anhydrous magnesium sulfate drying, crude product separates through column chromatography, and the volume ratio of methyl alcohol and methylene dichloride, triethylamine is that 1:45:0.15 makes eluent, purification obtains white solid product 0.302 g, productive rate 76 %.The structure of product through M.p., FTIR,
1h NMR, HRMS confirmation.
2-(4
-methyl
-1
-piperazinyl)-4-thiazolinone: M.p.:96.5～97.5 DEG C; FTIR (KBr pellet, cm
-1): 2984,2946,2929,2802,1685,1540,1450,1385,1346,1295,1263,1215,999,858;
1h NMR (400 MHz, CDCl
3): 4.00 (t,
j=4.8Hz, 2H), 3.96 (s, 2H), 3.55 (t,
j=4.8Hz, 2H), 2.53 (t,
j=4.8Hz, 2H), 2.49 (t,
j=4.8Hz, 2H), 2.35 (s, 3H); HRMS (m/z): Calcd. for C
8h
13n
3oS, 199.0779, found 199.0778.
Embodiment 2:
In round-bottomed flask bottle, add 2 mL [Emim] SCN, ethyl chloroacetate 2 mmol, react 2h under room temperature.Then add 2.2 mmol acetic acid, under room temperature, stir 7min, then add 2 mmol N methyl piperazines, mixture continues reaction 2h under magnetic agitation room temperature.Stopped reaction, be cooled to room temperature, add 10 mL methylene dichloride and 10 mL water to extract, collect lower floor's organic layer, water layer is used 10 mL dichloromethane extraction 2 times again, combined dichloromethane layer, with boiling off solvent after anhydrous magnesium sulfate drying, crude product separates through column chromatography, and the volume ratio of methyl alcohol and methylene dichloride, triethylamine is that 1:40:0.1 makes eluent, purification obtains white solid product 0.298 g, productive rate 75 %.The structure of product through M.p., FTIR,
1h NMR, HRMS confirmation.
Embodiment 3:
In round-bottomed flask bottle, add 1.5 mL [Emim] SCN, ethyl chloroacetate 2 mmol, react 1.5h under room temperature.Then add 2 mmol acetic acid, under room temperature, stir 5min, then add 2 mmol N methyl piperazines, mixture continues reaction 1.5h under magnetic agitation room temperature.Stopped reaction, be cooled to room temperature, add 10 mL methylene dichloride and 10 mL water to extract, collect lower floor's organic layer, water layer is used 10 mL dichloromethane extraction 2 times again, combined dichloromethane layer, with boiling off solvent after anhydrous magnesium sulfate drying, crude product separates through column chromatography, and the volume ratio of methyl alcohol and methylene dichloride, triethylamine is that 1:45:0.15 makes eluent, purification obtains white solid product 0.291 g, productive rate 73 %.The structure of product through M.p., FTIR,
1h NMR, HRMS confirmation.
Embodiment 4:
In round-bottomed flask bottle, add 2.5 mL [Emim] SCN, ethyl chloroacetate 2.2 mmol, react 2h under room temperature.Then add 2 mmol acetic acid, under room temperature, stir 5min, then add 2 mmol N methyl piperazines, mixture continues reaction 2h under magnetic agitation room temperature.Stopped reaction, be cooled to room temperature, add 10 mL methylene dichloride and 10 mL water to extract, collect lower floor's organic layer, water layer is used 10 mL dichloromethane extraction 2 times again, combined dichloromethane layer, with boiling off solvent after anhydrous magnesium sulfate drying, crude product separates through column chromatography, and the volume ratio of methyl alcohol and methylene dichloride, triethylamine is that 1:40:0.15 makes eluent, purification obtains white solid product 0.295 g, productive rate 74 %.The structure of product through M.p., FTIR,
1h NMR, HRMS confirmation.
Embodiment 5:
In round-bottomed flask bottle, add 1.5 mL [Emim] SCN, ethyl chloroacetate 2.4 mmol, react 2h under room temperature.Then add 2.4 mmol acetic acid, under room temperature, stir 5min, then add 2 mmol N methyl piperazines, mixture continues reaction 2h under magnetic agitation room temperature.Stopped reaction, be cooled to room temperature, add 13 mL methylene dichloride and 10 mL water to extract, collect lower floor's organic layer, water layer is used 13 mL dichloromethane extraction 2 times again, combined dichloromethane layer, with boiling off solvent after anhydrous magnesium sulfate drying, crude product separates through column chromatography, and the volume ratio of methyl alcohol and methylene dichloride, triethylamine is that 1:40:0.2 makes eluent, purification obtains white solid product 0.295 g, productive rate 74 %.The structure of product through M.p., FTIR,
1h NMR, HRMS confirmation.
Embodiment 6:
In round-bottomed flask bottle, add 1.5 mL [Emim] SCN, ethyl chloroacetate 2.4 mmol, react 2h under room temperature.Then add 2.4 mmol acetic acid, under room temperature, stir 5min, then add 2 mmol N methyl piperazines, mixture continues reaction 2h under magnetic agitation room temperature.Stopped reaction, be cooled to room temperature, add 12 mL methylene dichloride and 10 mL water to extract, collect lower floor's organic layer, water layer is used 12 mL dichloromethane extraction 3 times again, combined dichloromethane layer, with boiling off solvent after anhydrous magnesium sulfate drying, crude product separates through column chromatography, and the volume ratio of methyl alcohol and methylene dichloride, triethylamine is that 1:45:0.2 makes eluent, purification obtains white solid product 0.291 g, productive rate 73 %.The structure of product through M.p., FTIR,
1h NMR, HRMS confirmation.
Claims (2)
1. a 2-(4
-methyl
-1
-piperazinyl) preparation and the method for purification of-4-thiazolinone, it is characterized in that: taking [Emim] SCN as raw material and solvent, under room temperature, add ethyl chloroacetate, reaction 1.5～2h, then add acetic acid, under room temperature, stir 5～7min, add again N methyl piperazine, mixture continues reaction 1.5～2h under magnetic agitation room temperature, stopped reaction, be cooled to after room temperature, add extraction agent methylene dichloride and water to extract, collect lower floor's organic layer, water layer is used dichloromethane extraction 2～3 times again, combined dichloromethane layer, with boiling off solvent after anhydrous magnesium sulfate drying, crude product obtains white solid product through column chromatography separating-purifying, the mol ratio of described N methyl piperazine and [Emim] SCN is 1:5～1:9, the mol ratio of N methyl piperazine and ethyl chloroacetate is 1:1～1:1.2, described N methyl piperazine and the mol ratio of acetic acid are 1:1～1:1.2, described extraction agent water and the volume ratio of methylene dichloride are 1:1～1:1.3, the volume ratio of methyl alcohol, methylene dichloride and triethylamine that described crude product separates through column chromatography is that 1:40:0.1～1:45:0.2 makes eluent.
2. a kind of 2-(4 according to claim 1
-methyl
-1
-piperazinyl) preparation and the method for purification of-4-thiazolinone, it is characterized in that: the mol ratio of described N methyl piperazine and [Emim] SCN is 1:5～1:7; The mol ratio of N methyl piperazine and ethyl chloroacetate is 1:1～1:1.1; Described N methyl piperazine and the mol ratio of acetic acid are 1:1～1:1.1; Described extraction agent water and the volume ratio of methylene dichloride are 1:1～1:1.2; The volume ratio of methyl alcohol, methylene dichloride and triethylamine that described crude product separates through column chromatography is that 1:40:0.1～1:45:0.15 makes eluent.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201210008859.8A CN102558089B (en) | 2012-01-12 | 2012-01-12 | Method for preparation and purification of 2-(4-methyl-1-piperazinyl)-4- thiazolinone |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201210008859.8A CN102558089B (en) | 2012-01-12 | 2012-01-12 | Method for preparation and purification of 2-(4-methyl-1-piperazinyl)-4- thiazolinone |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN102558089A CN102558089A (en) | 2012-07-11 |
| CN102558089B true CN102558089B (en) | 2014-07-09 |
Family
ID=46404850
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201210008859.8A Expired - Fee Related CN102558089B (en) | 2012-01-12 | 2012-01-12 | Method for preparation and purification of 2-(4-methyl-1-piperazinyl)-4- thiazolinone |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN102558089B (en) |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1556107A (en) * | 2003-12-30 | 2004-12-22 | 中国药科大学 | Preparation method of 2-(hydrocarbon) imido (amine)-4-thiazolidone hydrochloride |
| CN1556106A (en) * | 2003-12-30 | 2004-12-22 | 中国药科大学 | Preparation method of 2-(hydrocarbon) imido (amine)-4-thiazolidone |
-
2012
- 2012-01-12 CN CN201210008859.8A patent/CN102558089B/en not_active Expired - Fee Related
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1556107A (en) * | 2003-12-30 | 2004-12-22 | 中国药科大学 | Preparation method of 2-(hydrocarbon) imido (amine)-4-thiazolidone hydrochloride |
| CN1556106A (en) * | 2003-12-30 | 2004-12-22 | 中国药科大学 | Preparation method of 2-(hydrocarbon) imido (amine)-4-thiazolidone |
Non-Patent Citations (2)
| Title |
|---|
| Dmytro Havrylyuk et al..Synthesis of novel thiazolone-based compounds containing pyrazoline moiety and evaluation of their anticancer activity.《European Journal of Medicinal Chemistry》.2008,第44卷第1396—1404页. |
| Synthesis of novel thiazolone-based compounds containing pyrazoline moiety and evaluation of their anticancer activity;Dmytro Havrylyuk et al.;《European Journal of Medicinal Chemistry》;20081007;第44卷;第1396—1404页 * |
Also Published As
| Publication number | Publication date |
|---|---|
| CN102558089A (en) | 2012-07-11 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN105330598A (en) | Preparing method for pirfenidone | |
| CN102391128B (en) | Production method of antibiotic pharmaceutical intermediate mono-p-nitro benzyl malonate | |
| CN107892654B (en) | Isolongifolane-based fluorescent acid-base indicator and synthetic method and application thereof | |
| CN103788010B (en) | Febuxostat intermediate and preparation method thereof | |
| CN104311485A (en) | Preparation method of medicine bosutinib for treating leukemia | |
| CN103772189B (en) | Synthesis method of diethylstilbestrol compound methyl pigeon pea ketonic acid A | |
| CN102558089B (en) | Method for preparation and purification of 2-(4-methyl-1-piperazinyl)-4- thiazolinone | |
| CN106883192B (en) | The synthetic method of the benzoic acid derivative of nitrogenous class heterocyclic antineoplastic pharmaceutical actives oxazolyl modification | |
| CN110105294A (en) | A kind of preparation method of polysubstituted tetrahydroquinoxaline derivative | |
| CN107382877A (en) | A kind of synthetic method of 4 amino 2 methyl 5 (bromomethyl) pyrimidine hydrobromate | |
| CN107868033B (en) | Preparation method of phenylalanine compound | |
| CN101671299A (en) | Method for synthesizing Nexavar | |
| CN104402728A (en) | Preparation method for 5-chlorine-2-hydroxyl-3-nitroacetophenone | |
| CN113045583B (en) | Preparation method of pinoxaden metabolite | |
| CN106588786A (en) | Preparation method of high purity favipiravir impurity | |
| CN104072495B (en) | The preparation method of natural product alkaloid A aptamine | |
| CN100453515C (en) | Method for synthesizing methyl azulenoids | |
| CN108840806B (en) | Preparation method of benzamide compound | |
| CN102702175A (en) | Preparation method of indole-3-succinimide | |
| CN101555248B (en) | Method for preparing poly-substituted 1, 5-naphthyridine compound | |
| CN110563721A (en) | Preparation method of azasetron hydrochloride | |
| Ikai et al. | Synthesis of polysaccharide derivatives bearing bromobenzoate pendants for use as chiral auxiliaries | |
| CN103408439A (en) | Chemical synthetic method of norbelladine | |
| CN112457243B (en) | Synthesis method of 7-bromo-5-methoxyquinoline | |
| CN108822060B (en) | 3-aryl substituted oxetane and preparation method thereof |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C14 | Grant of patent or utility model | ||
| GR01 | Patent grant | ||
| CF01 | Termination of patent right due to non-payment of annual fee |
Granted publication date: 20140709 Termination date: 20190112 |
|
| CF01 | Termination of patent right due to non-payment of annual fee |