CN101580498A - Green synthesis method of furane derivative - Google Patents
Green synthesis method of furane derivative Download PDFInfo
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- CN101580498A CN101580498A CNA2009101039629A CN200910103962A CN101580498A CN 101580498 A CN101580498 A CN 101580498A CN A2009101039629 A CNA2009101039629 A CN A2009101039629A CN 200910103962 A CN200910103962 A CN 200910103962A CN 101580498 A CN101580498 A CN 101580498A
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Abstract
The invention discloses a green synthesis method of furane derivative; 1, 4 dicarbonyl compound is in water, catalyzed by highly acid positive ion-exchange resin, and is heated to obtain the furane derivative. The method takes water as solvent and highly acid positive ion-exchange resin as heterogeneous catalyst which are safe and nontoxic; the highly acid positive ion-exchange resin is easy to be recycled, thus not only reducing the environment pollution, but also reducing the manufacture cost; in addition, the method has simple operation, short reaction time, high yield and extensive application prospect, and is suitable for commercial process; and the products are easy to be separated and purified.
Description
Technical field
The present invention relates to the synthetic method of compound, particularly the green synthesis method of furane derivative.
Background technology
Furans extensively is present in occurring in nature as typical case's representative of five member ring heterocyclic compound.Many furane derivatives are structural units of natural product and important drugs, demonstrate very strong biology and pharmaceutical activity.Therefore, the synthetic great interest that causes numerous chemists of furane derivative.Paal-Knorr reaction is one of important method of synthetic furan compound, and by 1,4-dicarbonyl compound cyclodehydration under anhydrous, acidic conditions generates furan compound.In recent years, because 1, the study on the synthesis of 4-dicarbonyl compound is obtained bigger progress, and Paal-Knorr furans synthesis method also is used widely.But in the method, usually be solvent with benzene or toluene, with tosic acid, polyphosphoric acid, zinc chloride/diacetyl oxide, hydrochloric acid/ethanol or boron trifluoride diethyl etherate/chloroform is catalyzer, relates to the use of toxic organic solvent, strong acid or metal, does not meet the demand for development of Green Chemistry now.
Summary of the invention
In view of this, the object of the present invention is to provide a kind of green synthesis method of furane derivative, solvent safe in utilization and reagent, and be easy to recycling, not only reduce environmental pollution, and reduce production costs; In addition, easy and simple to handle, the reaction times is short, and product is easy to purifying, yield height, is fit to suitability for industrialized production.
For reaching this purpose, the invention provides a kind of green synthesis method of furane derivative, by 1,4-dicarbonyl compound reacting by heating in water, under the storng-acid cation exchange resin catalysis makes furane derivative.
Further, described storng-acid cation exchange resin is that 200～400 orders, degree of crosslinking are 8% sulfonic acid ion exchange resin;
Further, described 1, the mol ratio of 4-dicarbonyl compound and Zeo-karb is 1: 10～12;
Further, described reacting by heating is 100 ℃ of back flow reaction of temperature;
Further, described reacting by heating is 130 ℃ of cappings of temperature;
Further, the mixture that reaction is finished is cooled to room temperature, filters, and collects filtrate and filter residue respectively; Filtrate is used extracted with diethyl ether, collects ether layer, water and salt water washing successively, and anhydrous sodium sulfate drying filters, and filtrate is reclaimed solvent, and resistates convection drying or with drying again after the flash column chromatography separation and purification promptly gets furane derivative; Filter residue is that storng-acid cation exchange resin is removed organic impurity with the ether washing earlier, reuses with hydrochloric acid soln regeneration back again.
Beneficial effect of the present invention is: the green synthesis method that the invention provides a kind of furane derivative, with water is that solvent, storng-acid cation exchange resin are heterogeneous catalyst, safety non-toxic, and storng-acid cation exchange resin is easy to recycling, not only reduce environmental pollution, and reduce production costs; In addition, easy and simple to handle, the reaction times is short, and product is easy to purifying, yield height, is fit to suitability for industrialized production, has a extensive future.
Embodiment
In order to make the purpose, technical solutions and advantages of the present invention clearer, below the preferred embodiments of the present invention are described in detail.
In a preferred embodiment, raw material 1,4-dicarbonyl compound 1a, 3a～5a and 8a～10a prepare according to the pertinent literature method: 1a (Nakazaki J et al.J.Mater.Chem., 2003,13,1011.), 3a, 4a and 8a (Ceylan M et al.Synthesis, 2004,1750.), 5a (Joczyk A et al.Tetrahedron, 1990,46,1025.), 9a (Gatezowski M et al.J.Org.Chem., 2006,71,5942.), 10a (Wu AX et al.Synth.Commun., 1997,27,331.); 2a, 6a and 7a are available from Alfa Aesar company; Reagent is commercially available product and without being further purified; Adopt tlc (GF254 silica-gel plate) monitoring reaction process in the reaction, the gained target product adopt the X-4 micro-fusing point instrument of type (digital display) measure fusing point (temperature is not proofreaied and correct), Bruker AV-300 type nmr determination proton nmr spectra (
1H NMR, 300MHz) and carbon-13 nmr spectra (
13CNMR, 75MHz) (is interior mark with TMS); Flash column chromatography adopts 200～300 order silica gel.
The synthetic logical method of furane derivative: get 1,4-dicarbonyl compound (1mmol), add entry (2mL) and storng-acid cation exchange resin Dowex 50W * 8-200 (10～12mmol), 100 ℃ of back flow reaction of temperature (oil bath heating) or 130 ℃ of cappings of temperature (seal reaction tubes in the rearmounted loft drier and to heat, need not to stir), reaction finishes postcooling to room temperature, filters, and collects filtrate and filter residue respectively; Filtrate is used extracted with diethyl ether, collects ether layer, water and salt water washing successively, anhydrous sodium sulfate drying filters, and filtrate is reclaimed solvent, resistates convection drying (single product) or with dry again (two kinds of products) after the flash column chromatography separation and purification promptly gets furane derivative; Filter residue is that organic impurity is removed with the ether washing by storng-acid cation exchange resin elder generation, is the hydrochloric acid soln regeneration back repeated use of 1mol/L again with concentration.
According to above-mentioned synthetic logical method, the present invention is with 1 of two, three or four replacements (alkyl, aryl and/or ester group replace), and the 4-dicarbonyl compound is a raw material, makes multiple furane derivative, its fusing point,
1H NMR and
13CNMR and pertinent literature report consistent (seeing Table 1).
The synthesis condition of table 1. furane derivative and result
Annotate:
aThe yield of numbering 2～5 and 7～8 is a crude product yield of identifying purity＞95% through NMR, and the yield of numbering 1,6,9 and 10 is the product yield after the flash column chromatography separation and purification; [1] Adriano C et al.Tetrahedron, 1985,41,1919; [2] Ken T et al.Eur.J.Org.Chem., 2007,16,2687; [3] Rao HSP et al.J.Org.Chem., 2003,68,5392.[4] Stanley W et al.J.Org.Chem., 1976,41,310; [5] Forgione P et al.J.Am.Chem.Soc., 2006,128,11350; [6] Dudnik S et al.J.Am.Chem.Soc., 2008,130,1440; [7] Amarnath V et al.J.Org.Chem., 1995,60,301; [8] Fales HM et al.J.Org.Chem., 1980,45,169; [9] Michael HS et al.Org.Lett., 2005,7,3925; [10] Pohmakotr M et al.Tetrahedron Lett., 2003,44,7937; [11] Clawson P et al.J.Chem.Soc., Perkin Trans.1,1990,1,153.
As shown in Table 1: (1) 1,4-dicarbonyl compound is in water, under the storng-acid cation exchange resin catalysis, and when 100 ℃ of back flow reaction of temperature, speed of response is slower, and the reaction times is grown (12～56 hours); And when 130 ℃ of cappings of temperature (because of thermolysis easily takes place when temperature is higher than 140 ℃ storng-acid cation exchange resin, so raising temperature to 130 ℃), speed of response is very fast, and the reaction times is lacked (6～9 hours); (2) when with two, three or four replace (non-ester group replacement) 1, (get single product during 1a～8a) for raw material, wherein, 2a～5a and 7a～8a adopts two kinds of type of heating can Quantitative yield generation furane derivative to the 4-dicarbonyl compound; Though 1a only had 42% transformation efficiency in 56 hours in 100 ℃ of back flow reaction of temperature, it can reach 100% transformation efficiency in 9 hours at 130 ℃ of cappings of temperature; 6a is respectively 81% and 78% in 100 ℃ of back flow reaction of temperature with at the product yield of 130 ℃ of cappings of temperature, and thin-layer chromatography shows that no raw material is residual but unknown by product generation is arranged; (3) when with four replace (replacement of two ester groups) 1,4-dicarbonyl compound (9a and 10a) gets two kinds of products during for raw material, be respectively not decarboxylate (9b and 10b) and single decarboxylate (9c and 10c), trace it to its cause: 9a and 10a have two reaction schemes, article one, route is for directly generating 9b and 10b through the Paal-Knorr cyclodehydration, another route is that first decarboxylation generates 9c and 10c through the Paal-Knorr cyclodehydration again, the yield of two kinds of products depends primarily on the speed of decarboxylation and Paal-Knorr cyclodehydration, when Paal-Knorr cyclodehydration speed during faster than decarboxylation speed, 9a and 10a directly are dehydrated into ring and form stable conjugated system with carbonyl, stop the generation of decarboxylation subsequently, then decarboxylate is not a principal product, otherwise then single decarboxylate is a principal product.
Supposition reaction mechanism of the present invention is as follows:
The storng-acid cation exchange resin conduct
Acid provides proton-catalyzed reaction, and 1, a carbonylic oxygen atom in the 4-dicarbonyl compound is changed into enol-type structure by after protonated, again another carbonylic carbon atom is initiated the intramolecularly nucleophilic attack, and dehydration at last generates furane derivative.(J.Org.Chem., 1995,60,301) such as Amarnath V reported once that the rate-limiting step of Paal-Knorr reaction was the intramolecularly nucleophilic reaction, and when carbonyl was connected with electron-withdrawing group, the positive polarity of carbonylic carbon atom increased, and reactive behavior strengthens.Because of the electrophilic of phenyl is better than thienyl, thus infer according to supposition reaction mechanism of the present invention, with 1,4-dithienyl butane-1,4-diketone (1a) is compared, and 1,4-diphenyl butane-1, the speed of response of 4-diketone (2a) is very fast, and the reaction times is shorter.This estimation result and experimental result and bibliographical information (J.Org.Chem., 2003,68,5392) unanimity.
The present invention verifies the catalytic of storng-acid cation exchange resin and the feasibility of recycling, found that, under the situation that does not add storng-acid cation exchange resin, no furane derivative generates; And storng-acid cation exchange resin recycling 3 times, its catalytic efficiency only has a little reduction, is shown below.
Certainly, except that Dowex 50W * 8-200, the present invention can also use other storng-acid cation exchange resin, can reach the object of the invention.
Explanation is at last, above embodiment is only unrestricted in order to technical scheme of the present invention to be described, although by invention has been described with reference to the preferred embodiments of the present invention, but those of ordinary skill in the art is to be understood that, can make various changes to it in the form and details, and the spirit and scope of the present invention that do not depart from appended claims and limited.
Claims (6)
1, the green synthesis method of furane derivative is characterized in that: by 1,4-dicarbonyl compound reacting by heating in water, under the storng-acid cation exchange resin catalysis makes furane derivative.
2, the green synthesis method of furane derivative according to claim 1 is characterized in that: described storng-acid cation exchange resin is that 200～400 orders, degree of crosslinking are 8% sulfonic acid ion exchange resin.
3, the green synthesis method of furane derivative according to claim 2 is characterized in that: described 1, the mol ratio of 4-dicarbonyl compound and storng-acid cation exchange resin is 1: 10～12.
4, the green synthesis method of furane derivative according to claim 3 is characterized in that: described reacting by heating is 100 ℃ of back flow reaction of temperature.
5, the green synthesis method of furane derivative according to claim 3 is characterized in that: described reacting by heating is 130 ℃ of cappings of temperature.
6, according to the green synthesis method of the described furane derivative of the arbitrary claim of claim 1 to 5, it is characterized in that: the mixture that reaction is finished is cooled to room temperature, filters, and collects filtrate and filter residue respectively; Filtrate is used extracted with diethyl ether, collects ether layer, water and salt water washing successively, and anhydrous sodium sulfate drying filters, and filtrate is reclaimed solvent, and resistates convection drying or with drying again after the flash column chromatography separation and purification promptly gets furane derivative; Filter residue is that storng-acid cation exchange resin is removed organic impurity with the ether washing earlier, reuses with hydrochloric acid soln regeneration back again.
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Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101792427A (en) * | 2010-03-25 | 2010-08-04 | 浙江大学 | Method for combining polysubstituted furan |
| CN101805317A (en) * | 2010-03-25 | 2010-08-18 | 浙江大学 | Method for synthesizing polysubstituted furan compounds |
| JP2011116709A (en) * | 2009-12-04 | 2011-06-16 | National Institute Of Advanced Industrial Science & Technology | Method for producing furans |
| CN107311963A (en) * | 2017-06-20 | 2017-11-03 | 重庆医科大学 | Using four carbonyls as the method for the substituted furan compound of Material synthesis four |
-
2009
- 2009-05-26 CN CN200910103962A patent/CN101580498B/en not_active Expired - Fee Related
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2011116709A (en) * | 2009-12-04 | 2011-06-16 | National Institute Of Advanced Industrial Science & Technology | Method for producing furans |
| CN101792427A (en) * | 2010-03-25 | 2010-08-04 | 浙江大学 | Method for combining polysubstituted furan |
| CN101805317A (en) * | 2010-03-25 | 2010-08-18 | 浙江大学 | Method for synthesizing polysubstituted furan compounds |
| CN107311963A (en) * | 2017-06-20 | 2017-11-03 | 重庆医科大学 | Using four carbonyls as the method for the substituted furan compound of Material synthesis four |
| CN107311963B (en) * | 2017-06-20 | 2020-04-21 | 重庆医科大学 | Method for synthesizing tetra-substituted furan compound by using tetracarbonyl compound as raw material |
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