CN102321120A - Method for synthesizing alpha-aminophosphonate through water phase cleaning - Google Patents
Method for synthesizing alpha-aminophosphonate through water phase cleaning Download PDFInfo
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- CN102321120A CN102321120A CN201110199445A CN201110199445A CN102321120A CN 102321120 A CN102321120 A CN 102321120A CN 201110199445 A CN201110199445 A CN 201110199445A CN 201110199445 A CN201110199445 A CN 201110199445A CN 102321120 A CN102321120 A CN 102321120A
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Abstract
The invention discloses a method for synthesizing alpha-aminophosphonate through water phase cleaning. Aromatic aldehyde, amine and phosphite ester are used as raw materials, non-ionic surface active agents are used as catalysts, water replaces organic solvents to be used as reaction media, the heating and stirring reaction is carried out at ordinary pressure, and the synthesis of the target compound is realized. Compared with the prior art, the method has the advantages that (1) Tween-20 and Tween-60 non-ionic surface active agents are adopted, raw material resources are wide, the preparation is convenient, and safety and reliability are realized; (2) the catalytic activity is high, the use consumption is little, the stability on the water is realized, the catalysts are not inactivated, and the cyclic use can be realized; and (3) a water phase reaction method is adopted, the environment pollution caused by the organic solvent use is avoided, in addition, the post treatment is convenient, the reaction is safe and stable, the industrial amplification is easy, and energy saving and emission reduction effects are obvious. The method belongs to an efficient and environment-friendly method for synthesizing alpha-aminophosphonate compounds, and the large-scale industrial production is favorably realized.
Description
One technical field
The present invention relates to the method for the synthetic α-An Jilinsuan ester of a kind of water cleaning, belong to the chemical material preparing technical field.Present method is applicable to that with aromatic aldehyde, amine, phosphorous acid ester be raw material, substitutes organic solvent as reaction medium with water, and the heated and stirred reaction realizes the occasion of this target compound under normal pressure.
Two background technologies
The alpha-amino group phosphate compounds has multiple important biological such as good Antiphytoviral, inhibitory enzyme activity, antitumor, weeding, sterilization; Purposes is widely being arranged aspect biological chemistry and the pharmaceutical chemistry; As can be used as stopper enzyme, microbiotic and pharmacologic mediator, weedicide, haptin catalytic antibody etc.; Simultaneously also be a kind of important substrate of synthetic phosphono peptide, so its compound method receive much concern.
Based on the unique physiologically active of alpha-amino group phosphate compounds, the research of relevant this compounds never is interrupted.The researchist constantly makes great efforts to have attempted a lot of methods and improves this synthetic route, and at present the newer technology reported of document comprises methods such as adding the ability field with Lewis acid, protonic acid, solid acid, MOX as the catalysis synthesis process of catalyzer, with microwave, UW radiating.There is following shortcoming more than 1 or 1 in these methods: the Preparation of catalysts process is complicated, cost is higher; The cost that catalyzer can not recycle, its discharging causes the three wastes to handle; Equipment corrosion is serious; Operating procedure is complicated; Can only be suitable for laboratory or small-scale operations, not possess heavy industrialization application etc.
Is to have environment, economical effects with water to replace organic solvent as reaction medium; Because water react has and has traditional chemical technique to react irreplaceable advantage: production cost is lower, reaction conditions is gentle, and side reaction is few; Environmental pollution is little; And the catalyzer easy recovery is applied mechanically and catalytic activity is constant, and water catalysis goal response has the potential industrial applications and is worth, so water react causes people's attention.But the maximum problem of water react is that the solubleness of a lot of organic materialss in water is low; Material can not fully contact; Reaction yield is low, thus one of method of dealing with problems be add cationic, anionic, non-ionics promotes the material contact to improve reaction yield.
Nonionogenic tenside Tween belongs to the polysorbate ester compound, is the safe surface promoting agent of generally acknowledging.Have emulsification, diffusion, solubilising, effect such as stable.In industry such as pharmacy, daily use chemicals, food, weaving, be widely used as emulsifying agent, dispersion agent, solubilizing agent, stablizer etc.Wherein to be used to water be the organic synthesis such as nucleophilic substitution, electrophilic substitution of reaction medium to Tween-20.
The method of the synthetic α-An Jilinsuan ester of a kind of water cleaning that the present invention relates to; With aromatic aldehyde, amine, phosphorous acid ester is raw material; Substitute organic solvent as reaction medium with water; Under the effect of nonionogenic tenside Tween, the reaction of normal pressure heated and stirred realizes the synthetic of α-An Jilinsuan ester cpds.
Three summary of the invention
The object of the present invention is to provide and a kind ofly do that reaction medium substitutes organic solvent, catalyzer and product is easily separated, product purity is high, make the method that the nonionogenic tenside raw material sources of catalyzer synthesize the alpha-amino group phosphate compounds widely with water.
The technical solution that realizes the object of the invention is: with aromatic aldehyde, amine, phosphorous acid ester is raw material, and nonionogenic tenside is a catalyzer, substitutes organic solvent as reaction medium with water, and the heated and stirred reaction realizes the synthetic of this target compound under normal pressure.
The method of the synthetic α-An Jilinsuan ester of a kind of water cleaning of the present invention is characterized in that nonionogenic tenside can mix for one or both of Tween-20, Tween-60.
The mol ratio of the used material of the present invention is an aromatic aldehyde: amine: phosphorous acid ester=1: 1: 1～2; The consumption of phase-transfer catalyst is 1～10% of an aromatic aldehyde mole number; The consumption of reaction medium water is 30～300% of a material total mass, and wherein said material, catalyzer proportionally feed intake with water and mix stirring.
The temperature of reaction according to the invention is 30～100 ℃, wherein preferred 60～65 ℃.
The time of reaction according to the invention is 0.2～2.0 hour, wherein preferred 0.5～1.0 hour.
The method of the synthetic α-An Jilinsuan ester of a kind of water cleaning according to the invention; It is characterized in that: aromatic aldehyde, amine, phosphorous acid ester are raw material, use water as reaction medium, heated and stirred under normal pressure; After reaction finishes; Be cooled to room temperature, filtering separation obtains the solids crude product, and crude product is obtained straight product with ethyl alcohol recrystallization after with water washing.Contained nonionogenic tenside need not to separate and purifies in the filtrating, can directly feed intake by former material ratio and carry out the reaction of next batch.
The chemical principle of institute of the present invention foundation is following:
Wherein: R
1Be aromatic group; R
2Be aromatic group or aliphatic group; R
3Be methyl, ethyl; R
4Be H, methyl, ethyl.
According to the method for synthetic alpha-amino group phosphate compounds provided by the invention, its key problem in technology is to adopt Tween-20, Tween-60 series non-ionic surfactants fcc raw material aromatic aldehyde, amine, phosphorous acid ester to react and obtain the alpha-amino group phosphate compounds.The present invention compared with prior art, its advantage is: Tween-20, Tween-60 nonionogenic tenside are adopted in (1), raw material is that wide material sources, preparation are convenient, safe and reliable; (2) catalytic activity is high, consumption is few; Stable to water, the catalyzer non-inactivation can be recycled; (3) adopt the water react method, avoided with an organic solvent environment being polluted, and convenient post-treatment, the reaction safety and steady, industry is amplified easily, and effects of energy saving and emission reduction is remarkable; (4) reaction conditions is gentle, the reaction times is shorter, product yield 80～91%.Be a kind of method of efficient, eco-friendly synthetic alpha-amino group phosphate compounds, help large-scale industrial production.
Four description of drawings
Accompanying drawing is the schema of the method for the synthetic α-An Jilinsuan ester of a kind of water cleaning of the present invention.
Five embodiments
Below through embodiment the present invention is detailed, these embodiment are only for clear open the present invention, not as limitation of the present invention.
Embodiment 1
In the 25mL round-bottomed flask; Add 10mmol (1.06g) phenyl aldehyde, 10mmol (0.93g) aniline, 11mmol (1.83g) triethyl-phosphite, 1mmol Tween-20 and 15ml water successively; Mix stirring 30 minutes down in 60 ℃ of normal pressures; Filter and use cold water washing, ethyl alcohol recrystallization to obtain the pure article of α-phenylamino-phenmethyl diethyl phosphonate, productive rate 91%.
Embodiment 2
In the 25mL round-bottomed flask; Add 10mmol (1.36g) aubepine successively, 10mmol (1.38g) 4-N-methyl-p-nitroaniline, 12mmol (1.32g) trimethyl phosphite, the Tween-20 of 0.5mmol, 5mL water; Mix stirring 60 minutes down in 70 ℃; Filter and use cold water washing, recrystallizing methanol to obtain the pure article of α-(4-oil of mirbane amino)-(4-p-methoxy-phenyl) dimethyl methyl phosphonate, productive rate 86%.
Embodiment 3
In the 25mL round-bottomed flask; Add 10mmol (1.06g) phenyl aldehyde, 10mmol (0.93g) aniline, 20mmol (2.76g) diethyl phosphite, 0.1mmol Tween-20,0.1mmol Tween-60 and 1.5ml water successively; Mix stirring 45 minutes down in 60 ℃ of normal pressures; Filter and use cold water washing, ethyl alcohol recrystallization to obtain the pure article of α-phenylamino-phenmethyl diethyl phosphonate, productive rate 90%.
Embodiment 4
In the 25mL round-bottomed flask; Add 10mmol (1.06g) phenyl aldehyde, 10mmol (0.93g) aniline, 15mmol (2.07g) diethyl phosphite, 0.5mmol Tween-20 and 10ml water successively; Mix stirring 12 minutes down in 100 ℃ of normal pressures; Filter and use cold water washing, ethyl alcohol recrystallization to obtain the pure article of α-phenylamino-phenmethyl diethyl phosphonate, productive rate 86%.
Embodiment 5
In the 25mL round-bottomed flask; Add 10mmol (1.06g) phenyl aldehyde, 10mmol (0.93g) aniline, 15mmol (2.07g) diethyl phosphite, 0.6mmol Tween-20 and 6ml water successively; Mix stirring 2 hours down in 30 ℃ of normal pressures; Filter and use cold water washing, ethyl alcohol recrystallization to obtain the pure article of α-phenylamino-phenmethyl diethyl phosphonate, productive rate 80%.
Embodiment 6
In the 25mL round-bottomed flask; Add 10mmol (1.06g) phenyl aldehyde, 10mmol (0.73g) butylamine, 11mmol (1.52g) diethyl phosphite, 0.5mmol Tween-20 and 3ml water successively; Mix stirring 60 minutes down in 60 ℃ of normal pressures; Filter and use cold water washing, ethyl alcohol recrystallization to obtain the pure article of α-phenylamino-amyl group diethyl phosphonate, productive rate 86%.
Embodiment 7
In the 25mL round-bottomed flask; Add 10mmol (1.06g) phenyl aldehyde, 10mmol (1.85g) amino dodecane, 11mmol (1.52g) diethyl phosphite, 0.5mmol Tween-20 and 5ml water successively; Mix stirring 50 minutes down in 65 ℃ of normal pressures; Filter and use cold water washing, ethyl alcohol recrystallization to obtain the pure article of α-phenylamino-tridecane phosphonic acid diethyl ester, productive rate 86%.
Embodiment 8
In the 250mL round-bottomed flask, add 100mmol (10.6g) phenyl aldehyde successively, 100mmol (16.2g) 3; The 4-dichlorphenamide bulk powder, 100mmol (13.8g) diethyl phosphite, the Tween-20 of 5mmol, 50mL water mix stirring 60 minutes down in 60 ℃; Filter and use cold water washing; Ethyl alcohol recrystallization obtains the pure article of α-(3, the 4-dichlorobenzene is amino)-phenmethyl diethyl phosphonate, productive rate 85%.Filtering aqueous phase contains Tween-20 catalyzer and the intact raw material of a small amount of unreacted; Can not treated repeated use, in aromatic aldehyde: aromatic amine: the ratio of phosphorous acid ester=1: 1: 1 drops into 100mmol (10.6g) phenyl aldehyde, 100mmol (16.2g) 3; The 4-dichlorphenamide bulk powder; 100mmol (13.8g) diethyl phosphite carries out the next batch building-up reactions, and reaction conditions is the same, productive rate 82～88%.
Claims (6)
1. a water cleans the method for synthesizing the α-An Jilinsuan ester; It is characterized in that: with aromatic aldehyde, amine, phosphorous acid ester is raw material; Nonionogenic tenside Tween is as phase-transfer catalyst, and water is reaction medium, and reaction realizes the synthetic of α-An Jilinsuan ester cpds under normal pressure.
2. the method for the synthetic α-An Jilinsuan ester of a kind of water cleaning according to claim 1 is characterized in that nonionogenic tenside can mix for one or both of Tween-20, Tween-60.
3. the method for the synthetic α-An Jilinsuan ester of a kind of water cleaning according to claim 1; It is characterized in that: the mol ratio of used material is an aromatic aldehyde: amine: phosphorous acid ester=1: 1: 1～2; The consumption of phase-transfer catalyst is 1～10% of an aromatic aldehyde mole number; The consumption of reaction medium water is 30～300% of a material total mass, and wherein said material, catalyzer proportionally feed intake with water and mix stirring.
4. the method for the synthetic α-An Jilinsuan ester of a kind of water cleaning according to claim 1, it is characterized in that: the temperature of reaction is 30～100 ℃, wherein preferred 60～65 ℃.
5. the method for the synthetic α-An Jilinsuan ester of a kind of water cleaning according to claim 1, it is characterized in that: the time of reaction is 0.2～2.0 hour, wherein preferred 0.5～1.0 hour.
6. the method for the synthetic α-An Jilinsuan ester of a kind of water cleaning according to claim 1; It is characterized in that: in water, react with nonionogenic tenside catalysis aromatic aldehyde, amine, phosphorous acid ester; After should finishing; Filtering separation obtains the solids crude product, and crude product is obtained straight product with ethyl alcohol recrystallization after with water washing.Contained nonionogenic tenside need not to separate and purifies in the filtrating, can directly feed intake by former material ratio and carry out the reaction of next batch.
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| CN201110199445A CN102321120A (en) | 2011-07-18 | 2011-07-18 | Method for synthesizing alpha-aminophosphonate through water phase cleaning |
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Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103524555A (en) * | 2013-10-12 | 2014-01-22 | 广西师范大学 | Rhein aminophosphonate derivatives, and synthetic method and applications thereof |
| CN103524556A (en) * | 2013-10-12 | 2014-01-22 | 广西师范大学 | Diacerhein aminophosphonate derivatives, and synthetic method and applications thereof |
| CN104744510A (en) * | 2013-12-25 | 2015-07-01 | 广西师范大学 | Alizarin aminophosphonate derivatives and their synthesis method and use |
-
2011
- 2011-07-18 CN CN201110199445A patent/CN102321120A/en active Pending
Non-Patent Citations (5)
| Title |
|---|
| 《Phosphorus, Sulfur, and Silicon》 20121231 Ch. Syama Sundar et al. TWEEN-20: AN EFFICIENT CATALYST FOR ONE-POT SYNTHESIS OF alpha-AMINOPHOSPHONATES IN AQUEOUS MEDIA 第523-534页 1-6 第187卷, * |
| 《化学研究》 20071231 焦崇峻等 One-Pot Three-Component Synthesis of alpha-Amino Phosphonates Catalyzed by Heteropolyacids in H2O/THF and in Ether 1-6 第18卷, 第4期 * |
| ATUL KUMAR ET AL.: "Non-ionic surfactant catalyzed synthesis of Betti base in water", 《TETRAHEDRON LETTERS》 * |
| CH. SYAMA SUNDAR ET AL.: "TWEEN-20: AN EFFICIENT CATALYST FOR ONE-POT SYNTHESIS OF α-AMINOPHOSPHONATES IN AQUEOUS MEDIA", 《PHOSPHORUS, SULFUR, AND SILICON》 * |
| 焦崇峻等: "One-Pot Three-Component Synthesis of α-Amino Phosphonates Catalyzed by Heteropolyacids in H2O/THF and in Ether", 《化学研究》 * |
Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103524555A (en) * | 2013-10-12 | 2014-01-22 | 广西师范大学 | Rhein aminophosphonate derivatives, and synthetic method and applications thereof |
| CN103524556A (en) * | 2013-10-12 | 2014-01-22 | 广西师范大学 | Diacerhein aminophosphonate derivatives, and synthetic method and applications thereof |
| CN103524556B (en) * | 2013-10-12 | 2016-01-13 | 广西师范大学 | SF-277 aminophosphonate ester derivatives and synthetic method thereof and application |
| CN103524555B (en) * | 2013-10-12 | 2016-01-20 | 广西师范大学 | Rhubarb yellow aminophosphonate ester derivatives and synthetic method thereof and application |
| CN104744510A (en) * | 2013-12-25 | 2015-07-01 | 广西师范大学 | Alizarin aminophosphonate derivatives and their synthesis method and use |
| CN104744510B (en) * | 2013-12-25 | 2016-08-17 | 广西师范大学 | Alizarin aminophosphonate ester derivatives and synthetic method thereof and application |
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Application publication date: 20120118 |