CN102964317B - New preparation method of tetrasubstituted furan compound - Google Patents
New preparation method of tetrasubstituted furan compound Download PDFInfo
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- CN102964317B CN102964317B CN201110257311.2A CN201110257311A CN102964317B CN 102964317 B CN102964317 B CN 102964317B CN 201110257311 A CN201110257311 A CN 201110257311A CN 102964317 B CN102964317 B CN 102964317B
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- reaction
- acetate
- water
- pdcl
- dimethylacetamide
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- PWATWSYOIIXYMA-UHFFFAOYSA-N CCCCCc1ccccc1 Chemical compound CCCCCc1ccccc1 PWATWSYOIIXYMA-UHFFFAOYSA-N 0.000 description 1
- NPEVGJNMRHDOBZ-UHFFFAOYSA-N COc(cc1)ccc1-c1c(-c(cc2)ccc2OC)[o]c(-c(cc2)ccc2OC)c1-c(cc1)ccc1OC Chemical compound COc(cc1)ccc1-c1c(-c(cc2)ccc2OC)[o]c(-c(cc2)ccc2OC)c1-c(cc1)ccc1OC NPEVGJNMRHDOBZ-UHFFFAOYSA-N 0.000 description 1
- UYQZNJVPAAQIHU-UHFFFAOYSA-N COc(cc1)ccc1C#Cc(cc1)ccc1[O](C)C Chemical compound COc(cc1)ccc1C#Cc(cc1)ccc1[O](C)C UYQZNJVPAAQIHU-UHFFFAOYSA-N 0.000 description 1
- YUUNYTYPYPDGRI-UHFFFAOYSA-N Fc(cc1)ccc1-c1c(-c2ccccc2)[o]c(-c2ccccc2)c1-c(cc1)ccc1F Chemical compound Fc(cc1)ccc1-c1c(-c2ccccc2)[o]c(-c2ccccc2)c1-c(cc1)ccc1F YUUNYTYPYPDGRI-UHFFFAOYSA-N 0.000 description 1
- RCOPXPNGDKPSLU-UHFFFAOYSA-N Fc(cc1)ccc1C#Cc1ccccc1 Chemical compound Fc(cc1)ccc1C#Cc1ccccc1 RCOPXPNGDKPSLU-UHFFFAOYSA-N 0.000 description 1
- FWLFKBDHSBFSMW-UHFFFAOYSA-N c(cc1)ccc1-c1c(-c2ccccc2)[o]c(-c2ccccc2)c1-c1ccccc1 Chemical compound c(cc1)ccc1-c1c(-c2ccccc2)[o]c(-c2ccccc2)c1-c1ccccc1 FWLFKBDHSBFSMW-UHFFFAOYSA-N 0.000 description 1
- JRXXLCKWQFKACW-UHFFFAOYSA-N c(cc1)ccc1C#Cc1ccccc1 Chemical compound c(cc1)ccc1C#Cc1ccccc1 JRXXLCKWQFKACW-UHFFFAOYSA-N 0.000 description 1
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- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
- Catalysts (AREA)
Abstract
The invention provides a method for preparing tetrasubstituted furan by direct oxidation of 1, 2-diaryl acetylene. The method includes: taking a metal palladium compound as a catalyst, adopting an acetate as an alkaline additive, and employing oxygen (or air) as an oxidant, oxidizing 1, 2-diaryl acetylene in a mixed solution of N, N-dimethylacetamide (DMA) and water so as to generate a tetrasubstituted furan compound. The catalyst involved in the invention is easily available, the reagents needed by the reaction are inexpensive, and the reaction conditions are mild.
Description
Technical field
The present invention relates to the preparation of furans, specifically a kind of method being used for the oxidation of 1,2-diaryl acetylene and preparing furans.
Background technology
Furans is the important five member ring heterocyclic compound of a class, is extensively present in and has in bioactive natural product.Furans is again the very important synthetic intermediate of a class, is widely used in organic synthesis.Because furfuran compound presents diversified biological function and pharmaceutical activity, therefore this compounds has attracted people to study interest greatly.For organic chemist, synthesizing this compounds is a valuable and challenging problem.
Traditional furans synthetic method mainly contains two kinds: a kind of is carry out structure of modification to the furan nucleus existed; Another kind is then be that precursor is to construct furan structure unit with non-ring compound, because the method for furan nucleus transformation has certain limitation, so be that raw material is to prepare the many of furans research with non-ring compound, wherein again with the cyclized condensation reaction of Isosorbide-5-Nitrae-dicarbonyl compound under acid catalysis (Paa l-Knorr synthesis) and methods involving comparatively ripe.It is raw material that Jiang Huanfeng reports with tolane, Pd (OAc)
2with Zn (OTf)
2for catalyzer, 7.6bar O
2in 100 DEG C of methanol solutions, react 24h, the product (Synlett 2009, No.6,929932) of 50%-80% productive rate can be obtained.This reaction is that " one kettle way " completes, and is also first generate Isosorbide-5-Nitrae-dicarbonyl compound in the reaction, then at Lewis acid Zn (OTf)
2effect under cyclisation generate furan compound (see formula 1).It is high to there is temperature of reaction in reaction, and pressure is large, the shortcoming that the time is long.
Summary of the invention
It is feed metal palladium compound is catalyzer that the object of the invention is to provide with 1,2-diaryl acetylene, and alkaline additive acetate is promotor, and oxygen (or air) is oxygenant, and catalyzed oxidation prepares the novel method of furans.
Alkaline additive acetate involved in the present invention is M (CH
3cOO)
n(during n=1, when M=Li, Na, K, n=2, M=Mg, Ca, Ba), is preferably sodium acetate and potassium acetate.Alkali plays a very important role in the reaction, and when not adding alkali, it is bad that reaction is carried out.A small amount of product is only had to generate.
Palladium metal compound involved in the present invention is PdCl
2, Pd (CH
3cN)
2cl
2, (C
6h
5cN)
2pdCl
2.
Oxygen (or air) pressure involved in the present invention is 0.1-0.5Mpa.
The molecular formula of 1,2-diaryl acetylene of the present invention is:
(X, Y=H, Cl, CH
3, OCH
3, Br, F, NO
2).
The ratio of palladium catalyst of the present invention and acetate mole dosage is 1: 1-1: 10, and the ratio of palladium catalyst and substrate 1,2-diaryl acetylene mole dosage is 1: 100-10: 100.
Temperature of reaction of the present invention is 45 DEG C-120 DEG C.Reaction is carried out under liquid phase state.
The mass ratio of N,N-dimethylacetamide of the present invention and water is 40: 1-1: 10, preferably 20: 1-1: 2.The effect of water to reaction is most important, does not have adding reaction and can not carrying out of water, and not having DMA to react can carry out, but result is bad.The effect of DMA is solvent and stable Pd catalyzer.
Due to the utilization of above-mentioned technology, the present invention compared with prior art has following advantages:
1, the oxidizing reaction of this catalyst system, uses green inexpensive oxygen (or air) to be oxygen source; Reaction conditions is gentle, and the air of 0.1MPa just can make reaction carry out, and improves operability and the security of reaction.
2, due to oxygen, the use of catalyzer and promotor makes reaction conditions gentle, and selectivity is high, and product is easily separated.Simultaneously involved in the present inventionly be easy to get to catalyzer, needed for reaction, reagent is cheap.
3, some substrate only uses water as solvent, and reaction also can be carried out, and decreases the pollution problem that organic solvent brings.
Embodiment
Specific embodiment of the invention step is described in detail below by some embodiments, should by these embodiments as scope of the invention restriction.All oxidizing reactions are all carry out in the 50mL stainless steel cauldron of polytetrafluoro liner.
Embodiment 1-17
The investigation of table 1 reaction conditions
a
areaction conditions: tolane (2.0mmol), catalyzer (0.1mmol), alkali (0.1mmol) solvent (m/m mass ratio): 2/0.1,80 DEG C, 1atm O
2, 6h.
b1a tm air in 6h
c1a tm air in 12h
Table 1 is visible, and the effect of catalyzer to reaction is apparent, does not add metal palladium catalyst reaction and does not carry out, do not have product to generate.Pd catalyzer is with PdCl
2, Pd (CH
3cN)
2cl
2, (C
6h
5cN)
2pdCl
2as well, consider cheap and easy to get, PdCl
2as well.Solvent is best with the mixing solutions result of DMA and water, and yield reaches 82%.In order to obtain similar reaction result, the reaction times required when air is oxygenant compared with oxygen is longer.The effect of alkali is also very important, does not have adding of alkali, and it is bad that reaction is carried out.Only has the product yield of 10%.Sodium acetate and potassium acetate are for the product yield obtained during alkali is higher than other acetate.
Embodiment 18-23
The consumption of table 2 water is on the impact of reaction
a
| Embodiment | DMA/H 2O(m/m) | Yield (%) |
| 18 | 2/0.05 | 35 |
| 19 | 2/0.1 | 83 |
| 20 | 2/0.5 | 84 |
| 21 | 2/1 | 79 |
| 22 | 1/2 | 80 |
| 23 | 0/2 | 45 |
areaction conditions: tolane (2.0mmol), PdCl
2(0.1mmol), NaOAc (0.2mmol) 60 DEG C, 1atm O
2, 12h.
Contribute to improving the yield reacted from adding of the known water of reacting phenomenon, also have promoter action to improve speed of response to reaction simultaneously.But the water yield is increased to the solvability that to a certain degree can affect substrate, and makes reaction result bad.Under the condition added not having DMA, the yield of product only has 45%.DMA and H as can be known from the results of Table 2
2the mass ratio of O with 20: 1-1: 2 as well.
Embodiment 24
By 1mmol 1,2-dibenzenyl (1a), 0.05mmol PdCl
2, 0.2mmol NaOAc, 10mL (mass ratio 9: 1) N,N-dimethylacetamide and the aqueous solution add in 50mL teflon-lined autoclave pressure, closed reactor, with air by still pressurising power to 0.3MPa, 80 DEG C reaction 16h.Reaction terminates rear cool to room temperature, careful bleed.Reaction solution adds 20mL water, and with extracted with diethyl ether 3 times (30mLx3), ether layer anhydrous sodium sulfate drying, except desolventizing, obtain oxidation products 2a through silica gel column chromatography, yield is 84%.
1H NMR(CDCl
3，400MHz)δ7.157.19(m，4H)，7.207.28(m，12H)，7.517.53(m，4H)。
Embodiment 25
By 1mmol substituted diphenylamine ethyl-acetylene 1b, 0.02mmol PdCl
2, 0.05mmol KOAc, 10mL (mass ratio 7: 3) N,N-dimethylacetamide and the aqueous solution add in 50mL teflon-lined autoclave pressure, closed reactor, with oxygen by still pressurising power to 0.1MPa, 60 DEG C reaction 6h.Reaction terminates rear cool to room temperature, careful bleed.Reaction solution adds 20mL water, and with extracted with diethyl ether 3 times (30mLx3), ether layer anhydrous sodium sulfate drying, except desolventizing, obtain oxidation products 2b through silica gel column chromatography, yield is 75%.
1H NMR(CDCl
3，400MHz)δ2.32(s，12H)，7.04(s，8H)，7.06(d，J＝8.0Hz，4H)，7.40(d，J＝8.4Hz，4H)
Embodiment 26
By 2mmo l substituted diphenylamine ethyl-acetylene 1c, 0.06mmol Pd (CH
3cN)
2cl
2, 0.6mmol KOAc, 15mL (mass ratio 8: 2) N,N-dimethylacetamide and the aqueous solution add in 50mL teflon-lined autoclave pressure, closed reactor, with air by still pressurising power to 0.4MPa, 60 DEG C reaction 5h.Reaction terminates rear cool to room temperature, careful bleed.Reaction solution adds 30mL water, and with extracted with diethyl ether 3 times (40mLx3), ether layer anhydrous sodium sulfate drying, except desolventizing, obtain oxidation products 2c through silica gel column chromatography, yield is 60%.
1H NMR(CDCl
3，400MHz)δ6.96-7.00(m，8H)，7.087.11(m，4H)，7.437.47(m，4H)
Embodiment 27
By 1mmol substituted diphenylamine ethyl-acetylene 1d, 0.01mmol PdCl
2, 0.1mmol NaOAc, 10mL (mass ratio 6: 4) N,N-dimethylacetamide and the aqueous solution add in 50mL teflon-lined autoclave pressure, closed reactor, with oxygen by still pressurising power to 0.1MPa, 50 DEG C reaction 12h.Reaction terminates rear cool to room temperature, careful bleed.Reaction solution adds 20mL water, and with extracted with diethyl ether 3 times (30mLx3), ether layer anhydrous sodium sulfate drying, except desolventizing, obtain oxidation products 2d through silica gel column chromatography, yield is 50%.
1H NMR(CDCl
3，400MHz)δ3.81(s，12H)，6.80-6.84(m，8H)，7.08(d，J＝8.4Hz，4H)，7.46(d，J＝8.8Hz，4H)
Embodiment 28
By 1mmol substituted diphenylamine ethyl-acetylene 1e, 0.01mmol (C
6h
5cN)
2pdCl
2, 0.05mmol NaOAc, 10mL (mass ratio 5: 5) N,N-dimethylacetamide and the aqueous solution add in 50mL teflon-lined autoclave pressure, closed reactor, with air by still pressurising power to 0.5MPa, 80 DEG C reaction 12h.Reaction terminates rear cool to room temperature, careful bleed.Reaction solution adds 20mL water, and with extracted with diethyl ether 3 times (30mLx3), ether layer anhydrous sodium sulfate drying, except desolventizing, obtain oxidation products 2e through silica gel column chromatography, yield is 60%.
1H NMR(400MHz，CDCl
3)：δ＝1.30(s，36H)，7.07(d，4H，J＝7.6Hz)，7.23(d，4H，J＝8.4Hz)，7.28(d，4H，J＝8.0Hz)，7.48(d，4H，J＝8.0Hz).
Embodiment 29
By 1mmol substituted diphenylamine ethyl-acetylene 1f, 0.04mmol PdCl
2, 0.2mmol NaOAc, 10mL (mass ratio 1: 9) N,N-dimethylacetamide and the aqueous solution add in 50mL teflon-lined autoclave pressure, closed reactor, with air by still pressurising power to 0.2MPa, 120 DEG C reaction 10h.Reaction terminates rear cool to room temperature, careful bleed.Reaction solution adds 10mL water, and with extracted with diethyl ether 3 times (20mLx3), ether layer anhydrous sodium sulfate drying, except desolventizing, obtain oxidation products 2e through silica gel column chromatography, yield is 76%.
1H NMR(CDCl
3，400MHz)δ2.25(s，6H)，2.32(s，6H)，7.44(s，2H)，7.267.28(d，2H)，7.137.16(t，J＝8.0Hz，4H)，6.96-7.06(m，8H)
Embodiment 30
By 3mmol substituted diphenylamine ethyl-acetylene 1g, 0.27mmol PdCl
2, 0.9mmol NaOAc, 30mL (mass ratio 9.5: 0.5) N,N-dimethylacetamide and the aqueous solution add in 50mL teflon-lined autoclave pressure, closed reactor, with oxygen by still pressurising power to 0.3MPa, 75 DEG C reaction 8h.Reaction terminates rear cool to room temperature, careful bleed.Reaction solution adds 30mL water, and with extracted with diethyl ether 3 times (40mLx3), ether layer anhydrous sodium sulfate drying, except desolventizing, obtain oxidation products 2g through silica gel column chromatography, yield is 63%.
1H NMR(CDCl
3，400MHz)δ6.93-6.99(m，4H)，7.107.14(m，4H)，7.227.31(m，6H)7.467.51(m，4H)。
Claims (6)
1. prepare the method for four substituted furans for one kind, it is characterized in that: under the existence of alkaline additive acetate, 1,2-diaryl acetylene is under the effect of palladium metal compound catalyst, with oxygen or air for oxygenant is under liquid-phase condition, in N,N-dimethylacetamide (DMA) and water mixed solution, reaction directly generates four substituted furans;
The molecular formula of 1,2-diaryl acetylene is:
one of, wherein X, Y=H, Cl, CH
3, OCH
3, Br, F, NO
2;
The palladium metal compound catalyst molecular formula used is PdCl
2, Pd (CH
3cN)
2cl
2or (C
6h
5cN)
2pdCl
2.
2. method according to claim 1, is characterized in that: the molecular formula of acetate is M (CH
3cOO)
n, during n=1, M=Li, Na or K, during n=2, M=Mg, Ca or Ba.
3. method according to claim 1, is characterized in that: the ratio of palladium catalyst and acetate mole dosage is 1:1 ~ 1:10; The ratio of palladium catalyst and substrate 1,2-diaryl acetylene mole dosage is 1:100 ~ 10:100.
4. method according to claim 1, is characterized in that: the pressure of oxygen or air is 0.1 ~ 0.5Mpa.
5. method according to claim 1, is characterized in that: temperature of reaction is 45 DEG C ~ 120 DEG C.
6. method according to claim 1, is characterized in that: the mass ratio of N,N-dimethylacetamide and water is 40:1 ~ 1:10.
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|---|---|---|---|
| CN201110257311.2A CN102964317B (en) | 2011-09-01 | 2011-09-01 | New preparation method of tetrasubstituted furan compound |
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Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101121718A (en) * | 2006-08-08 | 2008-02-13 | 中国科学院上海药物研究所 | Polysubstituted furanpyrimidine compounds and synthetic method thereof |
| JP2009196975A (en) * | 2008-01-23 | 2009-09-03 | Tosoh Corp | Heteroacene derivative, its precursor compound and their production methods |
-
2011
- 2011-09-01 CN CN201110257311.2A patent/CN102964317B/en not_active Expired - Fee Related
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101121718A (en) * | 2006-08-08 | 2008-02-13 | 中国科学院上海药物研究所 | Polysubstituted furanpyrimidine compounds and synthetic method thereof |
| JP2009196975A (en) * | 2008-01-23 | 2009-09-03 | Tosoh Corp | Heteroacene derivative, its precursor compound and their production methods |
Non-Patent Citations (2)
| Title |
|---|
| Palladium-Catalyzed Oxidation and Cyclization of Carbon–Carbon Triple Bonds in Fluorous Media Using Molecular Oxygen;Wen, Yanmei，等;《Synlett》;20110329(第7期);第1024页表1、1025页图1 * |
| Synthesis of tetrasubstituted furans via sequential Pd(OAc)2/Zn(OTf)2-catalyzed oxidation and cyclization of aromatic alkynes with molecular oxygen;Wang, Azhong，等;《Synlett》;20090316(第6期);第929-930页 * |
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