CN101792427A - Method for combining polysubstituted furan - Google Patents
Method for combining polysubstituted furan Download PDFInfo
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- CN101792427A CN101792427A CN 201010132417 CN201010132417A CN101792427A CN 101792427 A CN101792427 A CN 101792427A CN 201010132417 CN201010132417 CN 201010132417 CN 201010132417 A CN201010132417 A CN 201010132417A CN 101792427 A CN101792427 A CN 101792427A
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- alcohol
- triphenyl phosphorus
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- 150000002240 furans Chemical class 0.000 title claims abstract description 30
- 238000000034 method Methods 0.000 title claims abstract description 27
- 238000006243 chemical reaction Methods 0.000 claims abstract description 31
- IFPWCRBNZXUWGC-UHFFFAOYSA-M gold(1+);triphenylphosphane;chloride Chemical compound [Cl-].[Au+].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 IFPWCRBNZXUWGC-UHFFFAOYSA-M 0.000 claims abstract description 22
- TVDSBUOJIPERQY-UHFFFAOYSA-N prop-2-yn-1-ol Chemical compound OCC#C TVDSBUOJIPERQY-UHFFFAOYSA-N 0.000 claims abstract description 13
- 238000007363 ring formation reaction Methods 0.000 claims abstract description 7
- 239000002994 raw material Substances 0.000 claims abstract description 6
- 238000006555 catalytic reaction Methods 0.000 claims abstract description 5
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 claims description 42
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 32
- CZKMPDNXOGQMFW-UHFFFAOYSA-N chloro(triethyl)germane Chemical compound CC[Ge](Cl)(CC)CC CZKMPDNXOGQMFW-UHFFFAOYSA-N 0.000 claims description 21
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 18
- 229910021595 Copper(I) iodide Inorganic materials 0.000 claims description 17
- LSXDOTMGLUJQCM-UHFFFAOYSA-M copper(i) iodide Chemical compound I[Cu] LSXDOTMGLUJQCM-UHFFFAOYSA-M 0.000 claims description 17
- 125000003963 dichloro group Chemical group Cl* 0.000 claims description 17
- RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 claims description 17
- 125000000217 alkyl group Chemical group 0.000 claims description 9
- 125000003118 aryl group Chemical group 0.000 claims description 8
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 claims description 6
- 238000004440 column chromatography Methods 0.000 claims description 6
- 238000001035 drying Methods 0.000 claims description 6
- 241000208140 Acer Species 0.000 claims description 5
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 4
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 4
- 239000012141 concentrate Substances 0.000 claims description 4
- 229910052739 hydrogen Inorganic materials 0.000 claims description 4
- 239000001257 hydrogen Substances 0.000 claims description 4
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical class [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 claims description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 3
- 239000013067 intermediate product Substances 0.000 claims description 2
- 229910052757 nitrogen Inorganic materials 0.000 claims description 2
- 150000003333 secondary alcohols Chemical class 0.000 claims description 2
- 150000003509 tertiary alcohols Chemical class 0.000 claims description 2
- 230000002194 synthesizing effect Effects 0.000 claims 3
- 239000003153 chemical reaction reagent Substances 0.000 abstract description 12
- BQCADISMDOOEFD-UHFFFAOYSA-N Silver Chemical compound [Ag] BQCADISMDOOEFD-UHFFFAOYSA-N 0.000 abstract 1
- 238000003477 Sonogashira cross-coupling reaction Methods 0.000 abstract 1
- 239000002253 acid Substances 0.000 abstract 1
- 229910052709 silver Inorganic materials 0.000 abstract 1
- 239000004332 silver Substances 0.000 abstract 1
- 125000001424 substituent group Chemical group 0.000 abstract 1
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 40
- 239000000047 product Substances 0.000 description 15
- 239000000758 substrate Substances 0.000 description 12
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 10
- 239000007788 liquid Substances 0.000 description 10
- 229910052763 palladium Inorganic materials 0.000 description 5
- 239000000243 solution Substances 0.000 description 5
- 238000003756 stirring Methods 0.000 description 5
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 3
- 229910052751 metal Inorganic materials 0.000 description 3
- 239000002184 metal Substances 0.000 description 3
- 101100391174 Dictyostelium discoideum forC gene Proteins 0.000 description 2
- YLQBMQCUIZJEEH-UHFFFAOYSA-N Furan Chemical group C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- 230000003197 catalytic effect Effects 0.000 description 2
- 239000003480 eluent Substances 0.000 description 2
- 238000000605 extraction Methods 0.000 description 2
- 238000007306 functionalization reaction Methods 0.000 description 2
- 239000012074 organic phase Substances 0.000 description 2
- XBWDXHUNQPXBQU-UHFFFAOYSA-N 1-iodoprop-2-en-1-ol Chemical class OC(I)C=C XBWDXHUNQPXBQU-UHFFFAOYSA-N 0.000 description 1
- GQRPHMXAHRRFQF-UHFFFAOYSA-N 2-(furan-2-yl)-4,5-dihydro-1,3-thiazole Chemical class S1CCN=C1C1=CC=CO1 GQRPHMXAHRRFQF-UHFFFAOYSA-N 0.000 description 1
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
- 239000004593 Epoxy Substances 0.000 description 1
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 1
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical class [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 1
- 239000003905 agrochemical Substances 0.000 description 1
- XXROGKLTLUQVRX-UHFFFAOYSA-N allyl alcohol Chemical class OCC=C XXROGKLTLUQVRX-UHFFFAOYSA-N 0.000 description 1
- HFEHLDPGIKPNKL-UHFFFAOYSA-N allyl iodide Chemical group ICC=C HFEHLDPGIKPNKL-UHFFFAOYSA-N 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 239000003054 catalyst Substances 0.000 description 1
- BIPUHAHGLJKIPK-UHFFFAOYSA-N dicyclopropylmethanone Chemical compound C1CC1C(=O)C1CC1 BIPUHAHGLJKIPK-UHFFFAOYSA-N 0.000 description 1
- 125000000118 dimethyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 125000000524 functional group Chemical group 0.000 description 1
- PCHJSUWPFVWCPO-UHFFFAOYSA-N gold Chemical compound [Au] PCHJSUWPFVWCPO-UHFFFAOYSA-N 0.000 description 1
- 229910052737 gold Inorganic materials 0.000 description 1
- 239000010931 gold Substances 0.000 description 1
- 229910052740 iodine Inorganic materials 0.000 description 1
- 239000011630 iodine Substances 0.000 description 1
- 150000002561 ketenes Chemical class 0.000 description 1
- 150000002576 ketones Chemical class 0.000 description 1
- NSPJNIDYTSSIIY-UHFFFAOYSA-N methoxy(methoxymethoxy)methane Chemical compound COCOCOC NSPJNIDYTSSIIY-UHFFFAOYSA-N 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 229930014626 natural product Natural products 0.000 description 1
- 230000037081 physical activity Effects 0.000 description 1
- 229910052703 rhodium Inorganic materials 0.000 description 1
- 239000010948 rhodium Substances 0.000 description 1
- MHOVAHRLVXNVSD-UHFFFAOYSA-N rhodium atom Chemical compound [Rh] MHOVAHRLVXNVSD-UHFFFAOYSA-N 0.000 description 1
- 239000012266 salt solution Substances 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 238000010189 synthetic method Methods 0.000 description 1
- 125000002769 thiazolinyl group Chemical group 0.000 description 1
Landscapes
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Catalysts (AREA)
Abstract
The invention relates to a method for combining polysubstituted furan; polysubstituted 3-iodine-2-propylene-1-alcohol and propargyl alcohol at tail end carry out Sonogashira coupling reaction to generate 4-alkyne-2-hexene-1, and 6-glycol carries out isomerism cyclization reaction to generate a series of polysubstituted furan compounds under the common catalysis of triphenylphosphine-gold chloride and silver trifloromethanesulfonic acid; the method has simple operation and is easy to obtain raw material and reagents, the reaction has high yield, multiple substituent groups can be introduced, the product is easy to separate and purify, therefore, the method is suitable for combining various polysubstituted furan compounds.
Description
Technical field
The present invention relates to a kind of method of combining polysubstituted furan, with terminal propargyl alcohol the Sogashira linked reaction takes place by 3-iodo-propylene-1-alcohol promptly, generate 4-alkynes-2-hexene-1, the method that the isomery cyclization generates a series of furane derivatives takes place in 6-glycol again under the common catalysis of triphenyl phosphorus gold monochloride and silver trifluoromethanesulfonate.
Background technology
Furans is one of most important intermediate in the organic synthesis, also is one of modal structural unit in the natural product, has multiple important physical activity, and at biological technical field, there is huge value of exploiting and utilizing aspects such as medicine and agricultural chemicals.Bibliographical information be a substrate structure furans skeleton with the epoxy of connection ketenes, acetylenic ketone, cyclopropyl ketone, functionalization etc. in the past.Just to have developed with eneyne alcohol recently be raw material under metal catalyst effects such as highly basic or gold, palladium, rhodium, and the isomery cyclisation makes up furan nucleus, but the furans that generally can only Synthetic 2-alkyl replaces, and also some reaction pair conditional request is relatively harsher.(Marshall, J.A. in the document; DuBay, W.J.J.Org.Chem.1993,58,3435.) though reported the example of a Synthetic 2-thiazolinyl furans, alkaline reaction system is leavings group to much unfavorable to the responsive groups of alkalescence with the methoxymethyl ether, substrate compatible relatively poor.For combining polysubstituted furan widely, can obtain 3,4, the furane derivative of 5-position functionalization will provide and select the space widelyr for optionally the furans skeleton being introduced more rich functional groups.
Summary of the invention
Purpose of the present invention just provides a kind of method of using the effective combining polysubstituted furan of isomery cyclization of metal catalytic, reaction can be respectively at 3 of furans, 4, two different substituting groups are introduced in the 5-position, and the substituting group on the 2-position is expanded to thiazolinyl from the past alkyl.
The method of combining polysubstituted furan provided by the invention, the Sonogashira linked reaction takes place with propargyl alcohol in logical 3-iodo-propylene-1-alcohol, generate 4-alkynes-2-hexene-1, the isomery cyclization takes place and generates a series of furane derivatives in 6-glycol again under the common catalysis of triphenyl phosphorus gold monochloride and silver trifluoromethanesulfonate.Reaction formula is as follows:
R
1=hydrogen, alkyl, aryl; R
2=alkyl, aryl; R
3=hydrogen, alkyl, aryl, R
4=alkyl, aryl.The steps include:
(1) 3-iodo-propylene-1-alcohol 1 and terminal propargyl alcohol 2 generation Sonogashira linked reactions generation 4-alkynes-2-hexenes-1; 6-glycol 3: at room temperature; nitrogen protection; press 3-iodo-propylene-1-alcohol 1/ propargyl alcohol 2/ dichloro two triphenyl phosphorus palladium/cuprous iodide/triethylamine/N; the inferior maple of N-dimethyl=1 mmole/0.5-6 mmole/0.005-0.1 mmole/0.01-0.1 mmole/1～5 milliliter/0.2-3 milliliter; with 3-iodo-propylene-1-alcohol 1; terminal propargyl alcohol 2; dichloro two triphenyl phosphorus palladiums; cuprous iodide; triethylamine; N; inferior maple joins in the reaction flask N-dimethyl; be heated to 40-45 ℃, reacted 0.5～12 hour.
(2) after step (2) reacts completely, add the cancellation of 5mL saturated ammonium chloride solution, extracted with diethyl ether, anhydrous sodium sulfate drying filters, and concentrates, and rapid column chromatography obtains intermediate product 4-alkynes-2-hexene-1,6-glycol 3.
(3) after step (2) finishes, press 4-alkynes-2-hexene-1,6-glycol 3/ triphenyl phosphorus gold monochloride/silver trifluoromethanesulfonate/methylene dichloride=1 mmole/0.01-0.1 mmole/0.01-0.1 mmole/0.5-8 milliliter, with 4-alkynes-2-hexene-1,6-glycol 3, triphenyl phosphorus gold monochloride, silver trifluoromethanesulfonate, methylene dichloride add reaction flask, and room temperature reaction stirred 1-4 hour.
(4) after step (3) reacts completely, add 5mL water termination reaction, use extracted with diethyl ether, anhydrous sodium sulfate drying filters, and concentrates, and rapid column chromatography obtains furane derivative 4.
The equivalence ratio of dichloro two triphenyl phosphorus palladiums of the present invention and cuprous iodide is 1: 1; The equivalence ratio of triphenyl phosphorus gold monochloride and silver trifluoromethanesulfonate is 1: 1.
3-iodo-propylene of the present invention-1-alcohol is primary alconol, secondary alcohol.Propargyl alcohol of the present invention is the tertiary alcohol.
The present invention relates to a kind of furane derivative and synthetic method thereof, promptly Sonogashira linked reaction generation 4-alkynes-2-hexene-1 takes place with the propargyl alcohol of end in the vinyl carbinols of 3 iodine replacements, the 6-glycol, the isomery cyclization takes place under the common catalysis of triphenyl phosphorus gold monochloride and silver trifluoromethanesulfonate again generate a series of furane derivatives, present method is simple to operate, raw material and reagent are easy to get, reaction yield is higher, can introduce a plurality of substituting groups simultaneously, the easily separated purifying of product is applicable to the furane derivative that synthesizes multiple replacement.
It will be the very quantum jump that reacts in the past that the present invention introduces the synthetic furans of a plurality of substituting groups at different positions.
The present invention has overcome the drawback of traditional method, has the following advantages: 1) be applicable to polysubstituted iodo vinyl carbinol; 2) reaction conditions gentleness, productive rate height; 3) can introduce a plurality of substituting groups simultaneously; 4) the easily separated purifying of product.
Innovative point of the present invention has been to develop a kind of methodology of isomery cyclization combining polysubstituted furan of metal catalytic.
The productive rate of the corresponding furane derivative of present method gained is 68-87%.
Embodiment
Following examples help to understand the present invention, but are not limited to content of the present invention.
Embodiment 1
In an exsiccant reaction tubes, add cuprous iodide (3.0mg, 0.015mmol, 6mol%), dichloro two triphenyl phosphorus palladiums (7.0mg, 0.010mmol, 4mol%), 4-phenyl-3-n-pentyl-4-iodo-3-butyne-2-alcohol (85.5mg, 0.25mmol), triethylamine (1mL), 2-methyl-3-butyne-2-alcohol (124.1mg, 1.5mmol, 6.0equiv), the inferior maple (1mL) of dimethyl, 40 ℃ were reacted 3 hours, added 5 milliliters of saturated ammonium chloride solution cancellation, ether (3x 15mL) extraction.Organic phase 5% hydrochloric acid, saturated sodium bicarbonate solution, salt solution is respectively washed once, and anhydrous sodium sulfate drying filters, be spin-dried for, rapid column chromatography (eluent petrol ether/ethyl acetate=2/1) is with the thick product 7-methyl-4-phenyl-3-n-pentyl-5-alkynes-3-octene-2 that obtains, 7-glycol, be collected in the bottle, in other bottle, once add 1 milliliter of methylene dichloride, triphenyl phosphorus gold monochloride (2.5mg, 0.005mmol, 2mol%), silver trifluoromethanesulfonate (1.6mg, 0.006mmol, 2mol%), stirring at room 5 minutes adds above-mentioned thick product with the gained mixing solutions and is dissolved in the solution of 1 milliliter of methylene dichloride.Stirring at room 2 hours adds 5 ml water cancellation, ether (3x 15mL) extraction, and organic phase is washed once with salt, and anhydrous sodium sulfate drying filters, and is spin-dried for rapid column chromatography (eluent sherwood oil).Obtain product 2-methyl-5-(2-methacrylic-1-yl)-3-n-pentyl-4-benzofurane, productive rate 56.2mg, 80%, colourless liquid.
1H?NMR(300MHz，CDCl
3)δ7.41-7.34(m，2H)，7.32-7.22(m，3H)，5.85(s，1H)，2.34-2.27(m，5H)，2.05(s，3H)，1.80(s，3H)，1.32-1.08(m，6H)，0.78(t，J＝6.6Hz，3H)；
13C?NMR(CDCl
3，75MHz)δ147.4，145.9，134.4，133.4，129.7，128.2，126.4，124.2，119.7，112.4，31.4，29.8，27.3，23.3，22.3，20.2，14.0，12.0；IR(neat，cm
-1)3028，2957，2927，2858，1655，1604，1547，1491，1445，1376，1272，1191，1055，1005；MS(m/z)283(M
++1，23.2)，282(M
+，100)；HRMS?calcd?forC
20H
26O：282.1984，found：282.1984.
Embodiment 2
Press embodiment 1 described method, different is that used substrate and reagent are: cuprous iodide (11.0mg, 0.058mmol, 2mol%), dichloro two triphenyl phosphorus palladiums (3.7mg, 0.005mmol, 2mol%), 2-butyl-3-hexyl-4-iodo-2-propylene-1-alcohol (80.0mg, 0.25mmol)/triethylamine (1mL), 2-methyl-3-butyne-2-alcohol (43.3mg, 0.52mmol, 2equiv)/and dimethyl sulfoxide (DMSO) (1mL), 40 ℃ were reacted 3 hours.Second step: two milliliters of methylene dichloride, the triphenyl phosphorus gold monochloride (7.2mg, 0.015mmol, 6mol%)/(6mol%), stirring at room 3 hours obtains product 46.5mg to silver trifluoromethanesulfonate, 72% productive rate, colourless liquid for 4.0mg, 0.015mmol.
1H?NMR(300MHz，CDCl
3)δ7.08(s，1H)，5.91(s，1H)，2.36-2.28(m，4H)，2.04(s，3H)，1.88(s，3H)，1.59-1.24(m，12H)，0.98-0.84(m，6H)；
13C?NMR(CDCl
3，75MHz)δ149.3，136.6，133.2，126.0，121.5，112.2，31.7，31.6，30.6，29.2，27.3，23.5，23.4，22.7，22.6，20.0，14.1，13.9；IR(neat，cm
-1)2957，2927，2858，2732，1662，1534，1465，1376，1344，1284，1233，1202，1136，1099，1059，1020；MS(m/z)263(M
++1，14.3)，262(M
+，65.5)，205(100)；HRMS?calcd?for?C
18H
30O：262.2297，found：262.2296.
Embodiment 3
Press embodiment 1 described method, different is that used substrate and reagent are: cuprous iodide (1.0mg, 0.005mmol, 2mol%), dichloro two triphenyl phosphorus palladiums (3.6mg, 0.005mmol, 2mol%), 2-n-pentyl-1-p-methylphenyl-3-iodo-2-propylene-1-alcohol (85.2mg, 0.25mmol)/triethylamine (1mL), 2-methyl-3-butyne-2-alcohol (45.1mg, 0.54mmol, 2equiv)/and dimethyl sulfoxide (DMSO) (1mL), 40 ℃ were reacted 10 hours.Second step: two milliliters of methylene dichloride, the triphenyl phosphorus gold monochloride (2.4mg, 0.005mmol, 2mol%)/(2mol%), stirring at room 1 hour obtains product 61.1mg to silver trifluoromethanesulfonate, 87% productive rate, colourless liquid for 1.4mg, 0.005mmol.
1H?NMR(300MHz，CDCl
3)δ7.50(d，J＝7.8Hz，2H)，7.19(d，J＝8.1Hz，2H)，6.13(s，1H)，6.05(s，1H)，2.62(t，J＝7.8Hz，2H)，2.35(s，3H)，2.06(s，3H)，1.91(s，3H)，1.70-1.55(m，2H)，1.44-1.27(m，4H)，0.94-0.85(m，3H)；
13C?NMR(CDCl
3，75MHz)δ151.5，146.5，136.1，134.6，129.2，125.1，122.7，114.2，111.5，31.7，29.7，27.1，25.9，22.6，21.2，20.2，14.1；IR(neat，cm
-1)3025，2957，2926，2859，1658，1614，1593，1530，1501，1455，1376，1341，1296，1186，1108，1058，1005；MS(m/z)283(M
++1，21.6)，282(M
+，100)；HRMS?calcd?for?C
20H
26O：282.1984，found：282.1983.
Embodiment 4
Press embodiment 1 described method, different is that used substrate and reagent are: cuprous iodide (1.1mg, 0.005mmol, 2mol%), dichloro two triphenyl phosphorus palladiums (3.3mg, 0.005mmol, 2mol%), 4-phenyl-3-sec.-propyl-4-iodo-3-butyne-2-alcohol (79.1mg, 0.25mmol)/triethylamine (1mL), 2-methyl-3-butyne-2-alcohol (121.3mg, 1.5mmol, 6equiv)/and dimethyl sulfoxide (DMSO) (1mL)., 45 ℃ were reacted 5 hours.Second step: two milliliters of methylene dichloride, the triphenyl phosphorus gold monochloride (2.5mg, 0.005mmol, 2mol%)/(2mol%), stirring at room 1.5 hours obtains product 49.5mg to silver trifluoromethanesulfonate, 78% productive rate, colourless liquid for 1.4mg, 0.005mmol.
1H?NMR(300MHz，CDCl
3)δ7.41-7.34(m，2H)，7.33-7.26(m，1H)，7.26-7.20(m，2H)，5.73(s，1H)，2.73(septet，J＝7.1Hz，1H)，2.37(s，3H)，2.05(s，3H)，1.77(s，3H)，1.13(d，J＝7.1Hz，6H)；
13C?NMR(CDCl
3，75MHz)δ147.2，144.8，134.5，133.1，130.5，128.0，126.6，125.3，124.3，112.2，27.3，24.1，22.7，20.1，13.4；IR(neat，cm
-1)3021，2962，2925，1658，1603，1545，1444，1375，1363，1273，1186，1076，1027，1005；MS(m/z)255(M
++1，20.1)，254(M
+，100)；HRMScalcd?for?C
18H
22O：254.1671，found：254.1671.
Embodiment 5
Press embodiment 1 described method, different is that used substrate and reagent are: cuprous iodide (1.4mg, 0.006mmol, 3mol%), dichloro two triphenyl phosphorus palladiums (3.8mg, 0.005mmol, 2mol%), 4-hexyl-3-phenyl-4-iodo-3-butene-2-alcohol (88.5mg, 0.25mmol)/triethylamine (1mL), 2-methyl-3-butyne-2-alcohol (44.0mg, 0.52mmol, 2equiv)/and dimethyl sulfoxide (DMSO) (1mL), reacted 2 hours.Second step: two milliliters of methylene dichloride, the triphenyl phosphorus gold monochloride (2.5mg, 0.005mmol, 2mol%)/silver trifluoromethanesulfonate (3mol%), stirred 2 hours, obtains product 56.3mg, 77% productive rate, colourless liquid for 1.7mg, 0.007mmol by reaction.
1H?NMR(300MHz，CDCl
3)δ7.42-7.34(m，2H)，7.32-7.21(m，3H)，5.96(s，1H)，2.36(t，J＝7.5Hz，2H)，2.26(s，3H)，2.09(s，3H)，1.91(s，3H)，1.33-1.08(m，8H)，0.81(t，J＝6.6Hz，3H)；
13C?NMR(CDCl
3，75MHz)δ147.1，146.3，134.3，132.7，129.4，128.2，126.4，122.8，121.8，111.9，31.4，30.4，29.0，27.4，23.5，22.5，20.1，14.0，12.4；IR(neat，cm
-1)2926，2857，1621，1599，1549，1495，1444，1376，1309，1250，1202，1109，1069，1011；MS(m/z)297(M
++1，22.7)，296(M
+，100)；HRMS?calcd?for?C
21H
28O：296.2140，found：296.2141.
Embodiment 6
Press embodiment 1 described method, different is that used substrate and reagent are: cuprous iodide (1.3mg, 0.006mmol, 3mol%), dichloro two triphenyl phosphorus palladiums (3.7mg, 0.005mmol, 2mol%), 4-phenyl-3-p-methoxyphenyl-4-iodo-3-butyne-2-alcohol (95.1mg, 0.25mmol)/triethylamine (1mL), 2-methyl-3-butyne-2-alcohol (43.3mg, 0.52mmol, 2equiv)/and dimethyl sulfoxide (DMSO) (1mL). reacted 6 hours, second step: two milliliters of methylene dichloride, triphenyl phosphorus gold monochloride (2.4mg, 0.005mmol, 2mol%)/silver trifluoromethanesulfonate (1.5mg, 0.006mmol 2mol%), reaction was stirred 1 hour, obtain product 59.4mg, 75% productive rate.Solid, fusing point: 111.4-111.8 ℃.
1H?NMR(300MHz，CDCl
3)δ7.30-7.16(m，3H)，7.13-7.06(m，2H)，7.01-6.94(m，2H)，6.83-6.76(m，2H)，5.99(s，1H)，3.78(s，3H)，2.37(s，3H)，2.09(s，3H)，1.85(s，3H)；
13C?NMR(CDCl
3，75MHz)δ158.0，147.8，146.6，134.9，133.5，130.7，130.1，127.9，126.2，125.6，123.0，121.4，113.5，112.4，55.1，27.3，20.3，12.6；IR(KBr，cm
-1)3035，2914，2835，1655，1602，1573，1549，1511，1443，1376，1321，1288，1246，1176，1106，1041，1021；MS(m/z)319(M
++1，24.2)，318(M
+，100)；Elemental?analysis?calcd?for?C
22H
22O
2：C，82.99，H，6.96；Found：C，82.82，H，6.91.
Embodiment 7
Press embodiment 1 described method, different is that used substrate and reagent are: and cuprous iodide (1.3mg, 0.006mmol, 3mol%), dichloro two triphenyl phosphorus palladium (3.6mg, 0.005mmol, 2mol%), 3-butyl-4-hexyl-4-iodo-3-butene-2-alcohol (84.2mg, 0.25mmol)/triethylamine (1mL), 2-methyl-3-butyne-2-alcohol (43.0mg, 0.51mmol, 2equiv)/and dimethyl sulfoxide (DMSO) (1mL). reacted 8 hours.Second step: two milliliters of methylene dichloride, the triphenyl phosphorus gold monochloride (2.6mg, 0.005mmol, 2mol%)/silver trifluoromethanesulfonate (3mol%), stirred 3 hours, obtains product 46.9mg, 68% productive rate, colourless liquid for 1.8mg, 0.006mmol by reaction.
1H?NMR(300MHz，CDCl
3)δ5.88(s，1H)，2.32-2.23(m，4H)，2.20(s，3H)，2.04(s，3H)，1.87(s，3H)，1.48-1.24(m，12H)，0.95-0.84(m，6H)；
13C?NMR(CDCl
3，75MHz)δ146.6，145.4，131.4，122.4，119.8，112.1，32.9，31.7，31.0，29.3，27.3，23.7，23.2，22.7，22.6，20.0，14.1，14.0，11.9；IR(neat，cm
-1)2955，2926，2857，1622，1547，1457，1376，1296，1251，1198，1154，1107，1064，1035；MS(m/z)277(M
++1，21.6)，276(M
+，100)；HRMS?calcd?for?C
19H
32O：276.2453，found：276.2451.
Embodiment 8
Press embodiment 1 described method, different is that used substrate and reagent are: cuprous iodide (2.4mg, 0.012mmol, 4mol%), dichloro two triphenyl phosphorus palladiums (11.5mg, 0.015mmol, 6mol%), 3-n-pentyl-4-iodo-3-butene-2-alcohol (67.1mg, 0.25mmol)/triethylamine (1mL), 2-methyl-3-butyne-2-alcohol (42.2mg, 0.50mmol, 2equiv)/and dimethyl sulfoxide (DMSO) (1mL), reacted 0.5 hour.Second step: two milliliters of methylene dichloride, the triphenyl phosphorus gold monochloride (2.6mg, 0.005mmol, 2mol%)/silver trifluoromethanesulfonate (2mol%), stirred 3 hours, obtains product 42.6mg, 83% productive rate, colourless liquid for 1.6mg, 0.006mmol by reaction.
1H?NMR(300MHz，CDCl
3)δ5.98(s，2H)，2.28(t，J＝7.5，2H)，2.20(s，3H)，1.96(s，3H)，1.87(s，3H)，1.55-1.43(m，2H)，1.39-1.22(m，4H)，0.89(t，J＝6.9Hz，3H)；
13C?NMR(CDCl
3，75MHz)δ150.7，145.2，133.1，120.6，114.4，109.4，31.4，30.1，26.9，24.8，22.5，20.1，14.1，11.5；IR(neat，cm
-1)2958，2926，2857，1662，1624，1542，1450，1376，1340，1295，1241，1200，1158，1060；MS(m/z)207(M
++1，12.4)，206(M
+，79.0)，150((M-C
4H
8)
+，100)；HRMS?calcd?for?C
14H
22O：206.1671，found：206.1672.
Embodiment 9
Press embodiment 1 described method, different is that used substrate and reagent are: cuprous iodide (1.1mg, 0.006mmol, 2mol%), dichloro two triphenyl phosphorus palladium (3.5mg, 0.005mmol, 2mol%), and 3-n-pentyl-4-iodo-3-butene-2-alcohol (66.1mg, 0.25mmol)/Et
3N (1mL), and 3-butyl-1-hexin-3-alcohol (71.7mg, 0.51mmol, 2equiv)/and dimethyl sulfoxide (DMSO) (1mL), reacted 3 hours.Second step: two milliliters of methylene dichloride, the triphenyl phosphorus gold monochloride (2.3mg, 0.005mmol, 2mol%)/silver trifluoromethanesulfonate (2mol%), stirred 2 hours, obtains product 54.6mg, 84% productive rate, colourless liquid for 1.6mg, 0.006mmol by reaction.
1H?NMR(300MHz，CDCl
3)δ5.96(s，1H)，5.94(s，1H)，2.36-2.24(m，4H)，2.20(s，3H)，2.09(t，J＝7.2Hz，2H)，1.57-1.41(m，6H)，1.38-1.22(m，4H)，1.01-0.84(m，9H)；
13C?NMR(CDCl
3，75MHz)δ150.6，145.2，141.4，120.6，113.9，109.3，40.3，34.1，31.5，30.1，24.7，22.5，21.36，21.34，14.4，14.1，13.9，11.5；IR(neat，cm
-1)2958，2929，2871，1651，1623，1540，1465，1378，1338，1296，1211，1102；MS(m/z)263(M
++1，14.3)，262(M
+，76.3)，233(M-C
2H
5)
+，100)；HRMScalcd?for?C
18H
30O：262.2297，found：262.2296.
Embodiment 10
Press embodiment 1 described method, different is that used substrate and reagent are: cuprous iodide (1.0mg, 0.005mmol, 2mol%), dichloro two triphenyl phosphorus palladiums (3.4mg, 0.005mmol, 2mol%), 3-n-pentyl-4-iodo-3-butene-2-alcohol (66.5mg, 0.25mmol)/triethylamine (1mL), 1-acetylene-1-hexalin (58.2mg, 0.47mmol, 2equiv)/and dimethyl sulfoxide (DMSO) (1mL)., reacted 2 hours.Second step: two milliliters of methylene dichloride, the triphenyl phosphorus gold monochloride (2.5mg, 0.005mmol, 2mol%)/silver trifluoromethanesulfonate (2mol%), stirred 2 hours, obtains product 48.8mg, 80% productive rate, colourless liquid for 1.3mg, 0.005mmol by reaction.
1H?NMR(300MHz，CDCl
3)δ5.97(s，1H)，5.87(s，1H)，2.61-2.54(m，2H)，2.27(t，J＝7.5Hz，2H)，2.22-2.16(m，5H)，1.64-1.54(m，6H)，1.54-1.42(m，2H)，1.38-1.22(m，4H)，0.88(t，J＝6.9Hz，3H)；
13C?NMR(CDCl
3，75MHz)δ150.4，145.3，141.4，120.5，111.2，109.9，37.6，31.4，30.1，30.0，28.6，27.5，26.5，24.7，22.5，14.1，11.5；IR(neat，cm
-1)2927，2854，1659，1624，1543，1447，1378，1342，1296，1233，1213，1002；MS(m/z)247(M
++1，18.9)，246(M
+，100)；HRMScalcd?for?C
17H
26O：246.1984，found：246.1986.
Embodiment 11
Press embodiment 1 described method, different is that used substrate and reagent are: cuprous iodide (1.3mg, 0.006mmol, 3mol%), dichloro two triphenyl phosphorus palladium (3.8mg, 0.005mmol, 2mol%), 3-n-pentyl-4-iodo-3-butene-2-alcohol (67.3mg, 0.25mmol)/triethylamine (1mL), 1,1-phenylbenzene-2-propine-1-alcohol (101.1mg, 0.49mmol, 2equiv)/and dimethyl sulfoxide (DMSO) (1mL), reacted 4 hours.Second step: two milliliters of methylene dichloride, the triphenyl phosphorus gold monochloride (12.1mg, 0.025mmol, 10mol%)/silver trifluoromethanesulfonate (10mol%), stirred 4 hours, obtains product 61.6mg, 73% productive rate, colourless liquid for 6.5mg, 0.025mmol by reaction.
1H?NMR(300MHz，CDCl
3)δ7.47-7.35(m，3H)，7.34-7.18(m，7H)，6.89(s，1H)，5.23(s，1H)，2.16-2.09(m，5H)，1.37-1.10(m，6H)，0.86(t，J＝6.9Hz，3H)；
13C?NMR(CDCl
3，75MHz)δ150.2，146.6，141.9，140.5，137.9，129.7，128.8，128.2，127.4，127.0，126.6，121.5，116.3，111.5，31.2，29.8，24.5，22.4，14.1，11.5；IR(neat，cm
-1)3057，2956，2927，2856，1593，1531，1491，1444，1375，1277，1186，1145，1073，1031，1001；MS(m/z)331(M
++1，26.2)，330(M
+，100)；HRMS?calcd?forC
24H
26O330.1984，found?330.1974.
Claims (4)
1. the method for a combining polysubstituted furan, it is characterized in that by 3-iodo-propylene-1-alcohol and terminal propargyl alcohol generation Sogashira linked reaction, generate 4-alkynes-2-hexene-1, the 6-glycol, the isomery cyclization takes place under the common catalysis of triphenyl phosphorus gold monochloride and silver trifluoromethanesulfonate again generate furane derivative, reaction formula is as follows:
R
1=hydrogen, alkyl, aryl; R
2=alkyl, aryl; R
3=hydrogen, alkyl, aryl, R
4=alkyl, aryl; The steps include:
(1) 3-iodo-propylene-1-alcohol 1 and terminal propargyl alcohol 2 generation Sonogashira linked reactions, generate 4-alkynes-2-hexene-1,6-glycol 3: at room temperature, nitrogen protection, with raw material 3-iodo-propylene-1-alcohol 1, propargyl alcohol 2, dichloro two triphenyl phosphorus palladiums, cuprous iodide, triethylamine and N, inferior maple joins in the reaction flask N-dimethyl, be heated to 40-45 ℃, reacted 0.5～12 hour, described proportioning raw materials is: 3-iodo-propylene-1-alcohol 1: propargyl alcohol 2: dichloro two triphenyl phosphorus palladiums: cuprous iodide: triethylamine: N, the inferior maple of N-dimethyl=1 mmole: 0.5-6 mmole: 0.005-0.1 mmole: 0.01-0.1 mmole: 1～5 milliliter: 0.2-3 milliliter;
(2) after step (2) reacts completely, add the cancellation of 5mL saturated ammonium chloride solution, extracted with diethyl ether, anhydrous sodium sulfate drying filters, and concentrates, and rapid column chromatography obtains intermediate product 4-alkynes-2-hexene-1,6-glycol 3;
(3) combining polysubstituted furan 4: after step (2) finishes, with 4-alkynes-2-hexene-1,6-glycol 3, triphenyl phosphorus gold monochloride, silver trifluoromethanesulfonate, methylene dichloride add reaction flask, room temperature reaction 1-4 hour, described proportioning raw materials is: 4-alkynes-2-hexene-1,6-glycol 3: triphenyl phosphorus gold monochloride: silver trifluoromethanesulfonate: methylene dichloride=1 mmole: 0.01-0.1 mmole: 0.01-0.1 mmole: 0.5-8 milliliter;
(4) after step (3) reacts completely, add 5mL water termination reaction, use extracted with diethyl ether, anhydrous sodium sulfate drying filters, and concentrates, and rapid column chromatography obtains furane derivative 4.
2. the method for synthesizing polysubstituted furan compounds according to claim 1 is characterized in that the equivalence ratio of described dichloro two triphenyl phosphorus palladiums and cuprous iodide is 1: 1.
3. the method for synthesizing polysubstituted furan compounds according to claim 1, the equivalence ratio that it is characterized in that described triphenyl phosphorus gold monochloride and silver trifluoromethanesulfonate is 1: 1.
4. the method for synthesizing polysubstituted furan compounds according to claim 1 is characterized in that described 3-iodo-propylene-1-alcohol is primary alconol, secondary alcohol, and propargyl alcohol is the tertiary alcohol.
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Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102417493A (en) * | 2011-10-11 | 2012-04-18 | 浙江师范大学 | Method for preparing 2.5-dimethyl furan through glucose by adopting single-step method |
| CN103880790A (en) * | 2014-03-13 | 2014-06-25 | 西北大学 | Synthetic method for furan coupling compound |
| CN104163824A (en) * | 2014-07-04 | 2014-11-26 | 南开大学 | Gold-{2-(9-anthracene phenyl)dicyclohexylphosphine}-acetonitrile complex synthesis and application thereof |
| CN105001145A (en) * | 2015-07-14 | 2015-10-28 | 华南理工大学 | Synthesizing method for bicyclo cyclopropane compound |
| CN108623543A (en) * | 2018-03-21 | 2018-10-09 | 中山大学 | The class photochromic material of triaryl-ethylene containing furan derivatives and its synthetic method and application |
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| 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 |
| CN101580498A (en) * | 2009-05-26 | 2009-11-18 | 西南大学 | Green synthesis method of furane derivative |
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| 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 |
| CN101580498A (en) * | 2009-05-26 | 2009-11-18 | 西南大学 | Green synthesis method of furane derivative |
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Cited By (7)
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|---|---|---|---|---|
| CN102417493A (en) * | 2011-10-11 | 2012-04-18 | 浙江师范大学 | Method for preparing 2.5-dimethyl furan through glucose by adopting single-step method |
| CN102417493B (en) * | 2011-10-11 | 2014-07-30 | 浙江师范大学 | Method for preparing catalysts |
| CN103880790A (en) * | 2014-03-13 | 2014-06-25 | 西北大学 | Synthetic method for furan coupling compound |
| CN103880790B (en) * | 2014-03-13 | 2016-08-24 | 西北大学 | A kind of synthetic method of furan coupling compound |
| CN104163824A (en) * | 2014-07-04 | 2014-11-26 | 南开大学 | Gold-{2-(9-anthracene phenyl)dicyclohexylphosphine}-acetonitrile complex synthesis and application thereof |
| CN105001145A (en) * | 2015-07-14 | 2015-10-28 | 华南理工大学 | Synthesizing method for bicyclo cyclopropane compound |
| CN108623543A (en) * | 2018-03-21 | 2018-10-09 | 中山大学 | The class photochromic material of triaryl-ethylene containing furan derivatives and its synthetic method and application |
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