CN102408392A - Green preparation method of 2-(N, N-disubstituted amino)-4-isothiazolinone in water phase - Google Patents
Green preparation method of 2-(N, N-disubstituted amino)-4-isothiazolinone in water phase Download PDFInfo
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- CN102408392A CN102408392A CN2011103538667A CN201110353866A CN102408392A CN 102408392 A CN102408392 A CN 102408392A CN 2011103538667 A CN2011103538667 A CN 2011103538667A CN 201110353866 A CN201110353866 A CN 201110353866A CN 102408392 A CN102408392 A CN 102408392A
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Abstract
The invention discloses a green preparation method of 2-(N, N-disubstituted amino)-4-isothiazolinone in a water phase. The green preparation method comprises the following steps of: taking N, N-disubstituted thiourea a raw material, sodium acetate as a catalyst and water as a solvent, and adopting oil bath heating at 80-90 DEG C to dissolve the solid; then, adding ethyl chloroacetate, and letting the mixture to react for 1-2 h at 80-90 DEG C under magnetic stirring; and stopping the reaction, cooling the solution to room temperature, adding a sodium carbonate solid to neutralize the solution to be neutral, adding extracting agent ethyl acetate and water to extract the solution, collecting the upper organic layer, extracting the water layer for 2-3 times by using ethyl acetate, merging the ethyl acetate layer, evaporating the solvent by using anhydrous magnesium sulfate to dry, and separating and purifying the coarse product to obtain white solid or oily product through column chromatography. The method for synthesizing 2-(N, N-disubstituted amino)-4-isothiazolinone in the water phase is green and has easily acquired raw materials, low cost, easiness in operation and high efficiency, the yield rate reaches 83-93%, and the preparation method is applicable to industrial production.
Description
Technical field
The present invention relates to a kind of aqueous phase prepare 2-(
N,
N-disubstituted amido)-the greenization method of 4-thiazolinone, particularly with
N,
N-two substituting thioureidos and ethyl chloroacetate are raw material, under the condition of aqueous solvent, prepare 2-(
N,
N-disubstituted amido)-the 4-thiazolinone.
Background technology
N,
N-two substituting thioureidos have widely at aspects such as medicine, agricultural chemicals and chemical industry to be used, and still important organic synthesis intermediate can be used as and manyly has that important biomolecule is active five, the synthesis material of 6-membered heterocyclic compound.2-(
N,
N-disubstituted amido)-the 4-thiazolinone usually can by
N,
N-two substituting thioureidos are that starting raw material is synthetic.2-(
N,
N-disubstituted amido)-4-thiazolinone compounds has good biological activity, also is a kind of good organic synthesis intermediate simultaneously, can be used for synthetic liquid crystal material and dyestuff etc.The research of relevant 4-thiazolinone has become one of current hot subject, has obtained investigator's extensive concern.
Present 2-(
N,
N-disubstituted amido)-and the synthetic of 4-thiazolinone carry out in organic solvent usually, and have volatility, inflammableness, contaminate environment, do not meet the shortcomings such as requirement of Green Chemistry.And have on the method that productive rate is lower, conditional request is higher, shortcoming such as the reaction times is long.
Summary of the invention
The objective of the invention is to overcome the deficiency of prior art, provide a kind of aqueous phase prepare 2-(
N,
N-disubstituted amido)-the greenization method of 4-thiazolinone.
Aqueous phase 2-(
N,
N-disubstituted amido)-Pallution-free preparation method of 4-thiazolinone is: with
N,
N-two substituting thioureidos are raw material, and sodium-acetate is made catalyzer, and water is solvent, 80～90 ℃ of following oil bath heating; Make the solid dissolving, add ethyl chloroacetate then, mixture reacted 1～2 hour down for 80～90 ℃ in magnetic agitation; Stopped reaction, be cooled to room temperature after, add the yellow soda ash solid and be neutralized to neutrality; Add extraction agent ETHYLE ACETATE and water and extract, collect the upper strata organic layer, water layer is used ethyl acetate extraction 2～3 times again; The combined ethyl acetate layer, with boiling off solvent behind the anhydrous magnesium sulfate drying, crude product through column chromatography separate purify obtain 2-(
N,
N-disubstituted amido)-the 4-thiazolinone; Described
N,
NThe mol ratio of-two substituting thioureidos and ethyl chloroacetate is 1:1.5～1:2; Described sodium-acetate with
N,
NThe mol ratio of-two substituting thioureidos is 1.5:1～2:1; Described solvent is a water; The volume ratio of described extraction agent ETHYLE ACETATE and water is 1:1～1:1.5; Described crude product is that 1:2～1:2.5 makes eluent through the volume ratio of isolating ETHYLE ACETATE of column chromatography and sherwood oil.
Described
N,
N-two substituting thioureidos are:
N,
N-diethyl thiourea,
N,
N-diallyl thiourea,
N,
N-two n-pentyl thiocarbamides,
N,
N-di-n-octyl thiocarbamide,
The N-methyl-
N-Phenylthiourea,
The N-sec.-propyl-
N-Phenylthiourea.
2-(
N,
N-disubstituted amido)-4-thiazolinone compounds has good biological activity, will in fields such as medicine, novel pesticide, macromolecular material, dyestuff, pigment, fluorescent reagent, have a wide range of applications.Along with the development of society, the greenization compound method is more and more paid close attention to by people.Explore a kind of Synthetic 2-(
N,
N-disubstituted amido)-the green novel method of 4-thiazolinone has crucial academic significance, practical value and vast market prospect.
The present invention aqueous phase prepare 2-(
N,
N-disubstituted amido)-and the 4-thiazolinone, present method meets the requirement of Green Chemistry, and the raw material of use is easy to get, and cost is low, and operation is easy, and efficient is high, and productive rate reaches 83 ~ 93%, is the preparation method who is fit to suitability for industrialized production.
Embodiment
Aqueous phase 2-(
N,
N-disubstituted amido)-Pallution-free preparation method of 4-thiazolinone is: with
N,
N-two substituting thioureidos are raw material, and sodium-acetate is made catalyzer, and water is solvent, 80～90 ℃ of following oil bath heating; Make the solid dissolving, add ethyl chloroacetate then, mixture reacted 1～2 hour down for 80～90 ℃ in magnetic agitation; Stopped reaction, be cooled to room temperature after, add the yellow soda ash solid and be neutralized to neutrality; Add extraction agent ETHYLE ACETATE and water and extract, collect the upper strata organic layer, water layer is used ethyl acetate extraction 2～3 times again; The combined ethyl acetate layer, with boiling off solvent behind the anhydrous magnesium sulfate drying, crude product through column chromatography separate purify obtain 2-(
N,
N-disubstituted amido)-the 4-thiazolinone; Described
N,
NThe mol ratio of-two substituting thioureidos and ethyl chloroacetate is 1:1.5～1:2; Described sodium-acetate with
N,
NThe mol ratio of-two substituting thioureidos is 1.5:1～2:1; Described solvent is a water; The volume ratio of described extraction agent ETHYLE ACETATE and water is 1:1～1:1.5; Described crude product is that 1:2～1:2.5 makes eluent through the volume ratio of isolating ETHYLE ACETATE of column chromatography and sherwood oil.
Described
N,
N-two substituting thioureidos are:
N,
N-diethyl thiourea,
N,
N-diallyl thiourea,
N,
N-two n-pentyl thiocarbamides,
N,
N-di-n-octyl thiocarbamide,
N-Methyl-
N-Phenylthiourea,
The N-sec.-propyl-
N-Phenylthiourea.
Reaction equation of the present invention is:
Below in conjunction with embodiment the present invention is further described.
Embodiment 1:
In the round-bottomed flask bottle, add
N,
N-diethyl thiourea 0.20 mmol, sodium-acetate 0.30 mmol adds 4 mL water, 80 ℃ of following oil bath heating, makes the solid dissolving.Add ethyl chloroacetate 0.30 mmol then, mixture reacted 1 hour down for 80 ℃ in magnetic agitation.Stopped reaction is cooled to room temperature and adds the yellow soda ash solid and be neutralized to neutrality, adds 10 mL ETHYLE ACETATE and 10 mL water extract; Collect the upper strata organic layer, water layer is used 10 mL ethyl acetate extractions 2 times, combined ethyl acetate layer again; With boiling off solvent behind the anhydrous magnesium sulfate drying, crude product separates through column chromatography, and the volume ratio of ETHYLE ACETATE and sherwood oil is that 1:2 makes eluent; Purification obtains reddish-brown oily product 0.032 g, productive rate 93 %.The structure of product through FTIR,
1H NMR conclusive evidence.
2-(
N,
N-diethylin)-4-thiazolinone: FTIR (KBr pellet, cm
-1): 2977,2935,1693,1556,1445,1384,1360,1312,1256,1186,1079,784;
1H NMR (400 MHz, CDCl
3): 3.93 (s, 2H), 3.47 (q,
J=7.2Hz, 2H), 3.45 (q,
J=7.2Hz, 2H), 1.31 (t,
J=7.2Hz, 3H), 1.25 (t,
J=7.2Hz, 3H).
Embodiment 2:
In the round-bottomed flask bottle, add
N,
N-diallyl thiourea 0.20 mmol, sodium-acetate 0.40 mmol adds 6 mL water, 90 ℃ of following oil bath heating, makes the solid dissolving.Add ethyl chloroacetate 0.40 mmol then, mixture reacted 2 hours down for 90 ℃ in magnetic agitation.Stopped reaction is cooled to room temperature and adds the yellow soda ash solid and be neutralized to neutrality, adds 10 mL ETHYLE ACETATE and 15 mL water extract; Collect the upper strata organic layer, water layer is used 10 mL ethyl acetate extractions 3 times, combined ethyl acetate layer again; With boiling off solvent behind the anhydrous magnesium sulfate drying, crude product separates through column chromatography, and the volume ratio of ETHYLE ACETATE and sherwood oil is that 1:2.5 makes eluent; Purification obtains safran oily product 0.034 g, productive rate 87 %.The structure of product through FTIR,
1H NMR conclusive evidence.
Embodiment 3:
In the round-bottomed flask bottle, add
N,
N-two n-pentyl thiocarbamides 0.20 mmol, sodium-acetate 0.30 mmol adds 4 mL water, 90 ℃ of following oil bath heating, makes the solid dissolving.Add ethyl chloroacetate 0.40 mmol then, mixture reacted 1 hour down for 90 ℃ in magnetic agitation.Stopped reaction is cooled to room temperature and adds the yellow soda ash solid and be neutralized to neutrality, adds 10 mL ETHYLE ACETATE and 10 mL water extract; Collect the upper strata organic layer, water layer is used 10 mL ethyl acetate extractions 2 times, combined ethyl acetate layer again; With boiling off solvent behind the anhydrous magnesium sulfate drying, crude product separates through column chromatography, and the volume ratio of ETHYLE ACETATE and sherwood oil is that 1:2 makes eluent; Purification obtains reddish-brown oily product 0.044 g, productive rate 86 %.The structure of product through FTIR,
1H NMR conclusive evidence.
Embodiment 4:
In the round-bottomed flask bottle, add
N,
N-di-n-octyl thiocarbamide 0.20 mmol, sodium-acetate 0.40 mmol adds 6 mL water, 80 ℃ of following oil bath heating, makes the solid dissolving.Add ethyl chloroacetate 0.30 mmol then, mixture reacted 2 hours down for 80 ℃ in magnetic agitation.Stopped reaction is cooled to room temperature and adds the yellow soda ash solid and be neutralized to neutrality, adds 10 mL ETHYLE ACETATE and 15 mL water extract; Collect the upper strata organic layer, water layer is used 10 mL ethyl acetate extractions 3 times, combined ethyl acetate layer again; With boiling off solvent behind the anhydrous magnesium sulfate drying, crude product separates through column chromatography, and the volume ratio of ETHYLE ACETATE and sherwood oil is that 1:2.5 makes eluent; Purification obtains reddish-brown oily product 0.058 g, productive rate 86 %.The structure of product through FTIR,
1H NMR conclusive evidence.
Embodiment 5:
In the round-bottomed flask bottle, add
N-methyl-
N-phenylthiourea 0.20 mmol, sodium-acetate 0.30 mmol adds 4 mL water, 80 ℃ of following oil bath heating, makes the solid dissolving.Add ethyl chloroacetate 0.40 mmol then, mixture reacted 1 hour down for 80 ℃ in magnetic agitation.Stopped reaction is cooled to room temperature and adds the yellow soda ash solid and be neutralized to neutrality, adds 10 mL ETHYLE ACETATE and 10 mL water extract; Collect the upper strata organic layer, water layer is used 10 mL ethyl acetate extractions 2 times, combined ethyl acetate layer again; With boiling off solvent behind the anhydrous magnesium sulfate drying, crude product separates through column chromatography, and the volume ratio of ETHYLE ACETATE and sherwood oil is that 1:2.5 makes eluent; Purification obtains white solid product 0.036 g, productive rate 88 %.The structure of product through m.p., FTIR,
1H NMR conclusive evidence.
Embodiment 6:
In the round-bottomed flask bottle, add
N-sec.-propyl-
N-phenylthiourea 0.20 mmol, sodium-acetate 0.30 mmol adds 6 mL water, 90 ℃ of following oil bath heating, makes the solid dissolving.Add ethyl chloroacetate 0.30 mmol then, mixture reacted 1 hour down for 90 ℃ in magnetic agitation.Stopped reaction is cooled to room temperature and adds the yellow soda ash solid and be neutralized to neutrality, adds 10 mL ETHYLE ACETATE and 15 mL water extract; Collect the upper strata organic layer, water layer is used 10 mL ethyl acetate extractions 2 times, combined ethyl acetate layer again; With boiling off solvent behind the anhydrous magnesium sulfate drying, crude product separates through column chromatography, and the volume ratio of ETHYLE ACETATE and sherwood oil is that 1:2 makes eluent; Purification obtains white solid product 0.039 g, productive rate 83 %.The structure of product through m.p., FTIR,
1H NMR, ultimate analysis conclusive evidence.
Claims (2)
- An aqueous phase 2-( N, N-disubstituted amido)-and the Pallution-free preparation method of 4-thiazolinone, it is characterized in that: with N, N-two substituting thioureidos are raw material, and sodium-acetate is made catalyzer, and water is solvent, 80～90 ℃ of following oil bath heating; Make the solid dissolving, add ethyl chloroacetate then, mixture reacted 1～2 hour down for 80～90 ℃ in magnetic agitation; Stopped reaction, be cooled to room temperature after, add the yellow soda ash solid and be neutralized to neutrality; Add extraction agent ETHYLE ACETATE and water and extract, collect the upper strata organic layer, water layer is used ethyl acetate extraction 2～3 times again; The combined ethyl acetate layer, with boiling off solvent behind the anhydrous magnesium sulfate drying, crude product through column chromatography separate purify obtain 2-( N, N-disubstituted amido)-the 4-thiazolinone; Described N, NThe mol ratio of-two substituting thioureidos and ethyl chloroacetate is 1:1.5～1:2; Described sodium-acetate with N, NThe mol ratio of-two substituting thioureidos is 1.5:1～2:1; Described solvent is a water; The volume ratio of described extraction agent ETHYLE ACETATE and water is 1:1～1:1.5; Described crude product is that 1:2～1:2.5 makes eluent through the volume ratio of isolating ETHYLE ACETATE of column chromatography and sherwood oil.
- A kind of aqueous phase 2-2. according to claim 1 ( N, N-disubstituted amido)-and the Pallution-free preparation method of 4-thiazolinone, it is characterized in that: described N, N-two substituting thioureidos are: N, N-diethyl thiourea, N, N-diallyl thiourea, N, N-two n-pentyl thiocarbamides, N, N-di-n-octyl thiocarbamide, The N-methyl- N-Phenylthiourea, The N-sec.-propyl- N-Phenylthiourea.
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105219119A (en) * | 2015-09-29 | 2016-01-06 | 陕西理工学院 | A kind of thiazolone anthracene amine light-sensitive coloring agent and preparation method thereof |
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|---|---|---|---|---|
| CN1964956A (en) * | 2004-05-24 | 2007-05-16 | 安美基公司 | Inhibitors of 11-beta-hydroxy steroid dehydrogenase type 1 |
| JP2008260725A (en) * | 2007-04-13 | 2008-10-30 | Ohara Yakuhin Kogyo Kk | Method for producing 2-imino-4-thiazolidinone |
| US20100222326A1 (en) * | 2007-04-27 | 2010-09-02 | Ucb Pharma, S.A. | New Heterocyclic Derivatives Useful For The Treatment of CNS Disorders |
-
2011
- 2011-11-10 CN CN2011103538667A patent/CN102408392A/en active Pending
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1964956A (en) * | 2004-05-24 | 2007-05-16 | 安美基公司 | Inhibitors of 11-beta-hydroxy steroid dehydrogenase type 1 |
| JP2008260725A (en) * | 2007-04-13 | 2008-10-30 | Ohara Yakuhin Kogyo Kk | Method for producing 2-imino-4-thiazolidinone |
| US20100222326A1 (en) * | 2007-04-27 | 2010-09-02 | Ucb Pharma, S.A. | New Heterocyclic Derivatives Useful For The Treatment of CNS Disorders |
Non-Patent Citations (1)
| Title |
|---|
| A.M. VIJESH，等: "Synthesis, characterization and anti-microbial studies of some novel 2,4-disubstituted thiazoles", 《EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY》, vol. 45, 6 August 2010 (2010-08-06), pages 5060 - 5061 * |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105219119A (en) * | 2015-09-29 | 2016-01-06 | 陕西理工学院 | A kind of thiazolone anthracene amine light-sensitive coloring agent and preparation method thereof |
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Application publication date: 20120411 |