CN105884724B - A kind of preparation method of benzofuran compounds - Google Patents
A kind of preparation method of benzofuran compounds Download PDFInfo
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- CN105884724B CN105884724B CN201410795833.1A CN201410795833A CN105884724B CN 105884724 B CN105884724 B CN 105884724B CN 201410795833 A CN201410795833 A CN 201410795833A CN 105884724 B CN105884724 B CN 105884724B
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- AYLTZXUHICTWHA-UHFFFAOYSA-N COc(cc1)cc(C2)c1OC2c1ccccc1 Chemical compound COc(cc1)cc(C2)c1OC2c1ccccc1 AYLTZXUHICTWHA-UHFFFAOYSA-N 0.000 description 1
Abstract
The present invention provides a kind of preparation method of benzofuran compounds, including：In a nitrogen atmosphere, in the presence of persulfate and organic solvent, the p methoxy phenol class compound of trimethyl silicane radical protection is made to be reacted with aromatics olefin(e) compound.The method starting material of the present invention is simple, is not necessarily to metal catalytic, and reaction condition is mild; it is easy to operate; belong to environmentally protective chemical technology, can be widely applied to the preparation of benzofuran compounds, and one step of method that can be through the invention completes the synthesis of natural products corsifuran A.
Description
Technical field
The present invention relates to a kind of preparation methods of benzofuran compounds.
Background technology
Benzofuran compounds are the important heterocyclic compounds of a kind of various structures, be widely present in natural products and
In synthetic drug, there is potential bioactivity and pharmacological property, such as anti-inflammatory, anticancer, anti-oxidant physiological function.It is wherein outstanding
It is 2,3- Dihydrobenzofuranes skeletons, represents many nuclear structures with biology and pharmaceutically active compounds, following institute
Compound 1-4 shown etc., therefore more and more people are dedicated to the study on the synthesis of benzofuran compound.
Currently, being reported much about the method for preparing Dihydrobenzofuranes compound, but still have many disadvantages, example
Such as, reaction starting material is complicated, multistep is needed to synthesize, and severe reaction conditions need metal catalytic etc..Therefore, seek to one kind
The preparation method of environmentally protective, easy to operate and efficient benzofuran compounds is in accordance with people's demand.
Invention content
Problems to be solved by the invention
Present invention aims at a kind of preparation method of benzofuran compounds is provided, this method solve existing benzos
Furfuran compound preparation method is complicated, condition is harsh, feature of environmental protection difference problem.
The solution to the problem
To solve the above-mentioned problems, a kind of preparation method of benzofuran compounds is provided, including：In nitrogen atmosphere
Under, in the presence of persulfate and organic solvent, make the p methoxy phenol class compound and virtue of trimethyl silicane radical protection
Fragrant class olefin(e) compound reaction.
The present invention also provides a kind of method preparing formula (I) compound,
Wherein,
R1Indicate H or halogen,
R2Indicate H, methyl or cyclopropyl,
R3Indicate H, halogen, methyl, methoxyl group or tertiary butyl,
R4Indicate H, methyl or propyl,
Alternatively, R3With R4It can be bonded to each other to form ring,
The method includes：In a nitrogen atmosphere, in the presence of persulfate and organic solvent, make following formula (II) institutes
The compound shown is reacted with following formula (III) compounds represented,
In formula (II), R1Indicate H or halogen；TMS indicates trimethyl silicane group,
In formula (III), R2Indicate H, methyl or cyclopropyl；R3Indicate H, halogen, methyl, methoxyl group or tertiary butyl；R4It indicates
H, methyl or propyl；Alternatively, R3With R4It can be bonded to each other to form ring.
In the present invention, the persulfate is sodium peroxydisulfate, potassium peroxydisulfate or ammonium persulfate.
In the present invention, change shown in the p methoxy phenol class compound of the trimethyl silicane radical protection or formula (II)
The molar ratio for closing object and the persulfate is 1:2~1:3, preferably 1:3.
In the present invention, the p methoxy phenol class compound of the trimethyl silicane radical protection or the formula (II) are shown
Compound and the aromatics olefin(e) compound or the molar ratio of the formula (III) compound represented be 1:2~1:4, it is excellent
It is selected as 1:4.
In the present invention, the organic solvent includes acetonitrile, dichloromethane, methanol, tetrahydrofuran or N, N- dimethyl methyls
Amide.
In the present invention, the amount of the organic solvent is every mM of trimethyl silicane radical protection to methoxybenzene
Phenolic compound or (II) compound represented use 5~10ml.
In the present invention, the p methoxy phenol class compound of the trimethyl silicane radical protection or the formula (II) are shown
Compound and the aromatics olefin(e) compound or the formula (III) compound represented in room temperature to reacting at 70 DEG C, it is excellent
It is selected at 50 DEG C and reacts.
In the present invention, the reaction time is 48~72h.
In the present invention, further comprise using by volume is 20:1~30:1 petroleum ether：Ethyl acetate is used as and washes
De- agent, carries out column chromatography for separation.
The effect of invention
In the method for the invention, under nitrogen atmosphere, appropriate heating can react, and charging sequence is arbitrary, easy to operate
It is convenient.In addition, the reaction raw materials in the method for the present invention need not move through complicated synthesis, part even commercially available, the oxygen used
Agent such as sodium peroxydisulfate is cheap and easily-available and pollution-free, and the reaction raw materials of the present invention is applied widely, can utilize reaction
The change of substituent group in raw material brings the preparation for realizing different substitution benzofuran compounds.In the present invention, entire reaction
Process safety environmental protection, at low cost, high financial profit belongs to green chemistry process, can be widely applied to prepare benzofurans
Object is closed, and one step of preparation method of the present invention can be utilized to prepare natural products corsifuran A.
Specific implementation mode
According to an aspect of the present invention, a kind of preparation method of benzofuran compounds is provided, this method includes：In nitrogen
Under gas atmosphere, in presence of organic solvent, using persulfate as oxidant, trimethyl silicane radical protection to methoxybenzene
Phenolic compound is stirred to react in a heated condition with aromatics olefin(e) compound, is reacted after a certain period of time, by isolating and purifying
Obtain benzofuran compounds.
In the present invention, the example of described " halogen " includes F, Cl, Br, I etc., preferably F, Cl, Br.
The embodiment of the present invention is given below.It should be noted that these embodiments are merely illustrative, the present invention is unlimited
In these embodiments.
The measurement of the product in embodiment is carried out using following instrument.
Determining instrument：Switzerland's Bruker AV-400 nuclear magnetic resonance chemical analysers.
Determination condition：It rear products therefrom will be isolated and purified will be dissolved in deuterochloroform and test.
Embodiment 1
40mg 4- methoxyl group phenol oxygroup trimethyl silanes, 145mg sodium peroxydisulfates and 85mg are added into 10mL round-bottomed flasks
Styrene seals flask and replaces 3 nitrogen, 2ml acetonitriles are added into reaction bulb with syringe needle, react 72h at 50 DEG C.Reaction knot
Shu Hou, reaction solution after filtering and concentrating and be spin-dried for, then with volume ratio be 30:1 petroleum ether：The mixed solution conduct of ethyl acetate
Eluant, eluent carries out silica gel column chromatography purifies and separates, obtains 2- phenyl -5- methoxyl group -2,3- Dihydrobenzofuranes, structural formula
For：
Obtained 2- phenyl -5- methoxyl group -2,3- Dihydrobenzofuranes are colourless liquid, yield 72%, nuclear-magnetism number
According to for：1H NMR(400MHz,CDCl3) δ 7.42-7.30 (m, 5H), 6.83-6.73 (m, 2H), 6.70 (dd, J=8.6,
2.6Hz, 1H), 5.74 (t, J=8.8Hz, 1H), 3.77 (s, 3H), 3.60 (dd, J=15.7,9.3Hz, 1H), 3.20 (dd, J
=15.7,8.2Hz, 1H).
13C NMR(100MHz,CDCl3)δ154.33,153.81,142.04,128.63,127.99,127.51,
125.77,113.04,111.23,109.21,84.24,56.06,38.89。
Embodiment 2
40mg 4- methoxyl group phenol oxygroup trimethyl silanes, 97mg sodium peroxydisulfates and 85mg are added into 10mL round-bottomed flasks
Styrene seals flask and replaces 3 nitrogen, 2ml acetonitriles are added into reaction bulb with syringe needle, react 72h at 50 DEG C.Reaction knot
Shu Hou, reaction solution after filtering and concentrating and be spin-dried for, then with volume ratio be 30:1 petroleum ether：The mixed solution conduct of ethyl acetate
Eluant, eluent carries out silica gel column chromatography purifies and separates, obtains 2- phenyl -5- methoxyl group -2,3- Dihydrobenzofuranes, structural formula
For：
Obtained 2- phenyl -5- methoxyl group -2,3- Dihydrobenzofuranes are colourless liquid, yield 29%, nuclear-magnetism number
According to for：1H NMR(400MHz,CDCl3) δ 7.42-7.30 (m, 5H), 6.83-6.73 (m, 2H), 6.70 (dd, J=8.6,
2.6Hz, 1H), 5.74 (t, J=8.8Hz, 1H), 3.77 (s, 3H), 3.60 (dd, J=15.7,9.3Hz, 1H), 3.20 (dd, J
=15.7,8.2Hz, 1H).
13C NMR(100MHz,CDCl3)δ154.33,153.81,142.04,128.63,127.99,127.51,
125.77,113.04,111.23,109.21,84.24,56.06,38.89。
Embodiment 3
40mg 4- methoxyl group phenol oxygroup trimethyl silanes, 145mg sodium peroxydisulfates and 43mg are added into 10mL round-bottomed flasks
Styrene seals flask and replaces 3 nitrogen, 2ml acetonitriles are added into reaction bulb with syringe needle, react 72h at 50 DEG C.Reaction knot
Shu Hou, reaction solution after filtering and concentrating and be spin-dried for, then with volume ratio be 30:1 petroleum ether：The mixed solution conduct of ethyl acetate
Eluant, eluent carries out silica gel column chromatography purifies and separates, obtains 2- phenyl -5- methoxyl group -2,3- Dihydrobenzofuranes, structural formula
For：
Obtained 2- phenyl -5- methoxyl group -2,3- Dihydrobenzofuranes are colourless liquid, yield 34%, nuclear-magnetism number
According to for：1H NMR(400MHz,CDCl3) δ 7.42-7.30 (m, 5H), 6.83-6.73 (m, 2H), 6.70 (dd, J=8.6,
2.6Hz, 1H), 5.74 (t, J=8.8Hz, 1H), 3.77 (s, 3H), 3.60 (dd, J=15.7,9.3Hz, 1H), 3.20 (dd, J
=15.7,8.2Hz, 1H).
13C NMR(100MHz,CDCl3)δ154.33,153.81,142.04,128.63,127.99,127.51,
125.77,113.04,111.23,109.21,84.24,56.06,38.89。
Embodiment 4
40mg 4- methoxyl group phenol oxygroup trimethyl silanes, 139mg ammonium persulfates and 85mg are added into 10mL round-bottomed flasks
Styrene seals flask and replaces 3 nitrogen, 2ml acetonitriles are added into reaction bulb with syringe needle, react 72h at 50 DEG C.Reaction knot
Shu Hou, reaction solution after filtering and concentrating and be spin-dried for, then with volume ratio be 30:1 petroleum ether：The mixed solution conduct of ethyl acetate
Eluant, eluent carries out silica gel column chromatography purifies and separates, obtains 2- phenyl -5- methoxyl group -2,3- Dihydrobenzofuranes, structural formula
For：
Obtained 2- phenyl -5- methoxyl group -2,3- Dihydrobenzofuranes are colourless liquid, yield 14%, nuclear-magnetism number
According to for：1H NMR(400MHz,CDCl3) δ 7.42-7.30 (m, 5H), 6.83-6.73 (m, 2H), 6.70 (dd, J=8.6,
2.6Hz, 1H), 5.74 (t, J=8.8Hz, 1H), 3.77 (s, 3H), 3.60 (dd, J=15.7,9.3Hz, 1H), 3.20 (dd, J
=15.7,8.2Hz, 1H).
13C NMR(100MHz,CDCl3)δ154.33,153.81,142.04,128.63,127.99,127.51,
125.77,113.04,111.23,109.21,84.24,56.06,38.89。
Embodiment 5
40mg 4- methoxyl group phenol oxygroup trimethyl silanes, 145mg sodium peroxydisulfates and 85mg are added into 10mL round-bottomed flasks
Styrene seals flask and replaces 3 nitrogen, 2ml acetonitriles are added into reaction bulb with syringe needle, react 72h at room temperature.Reaction knot
Shu Hou, reaction solution after filtering and concentrating and be spin-dried for, then with volume ratio be 30:1 petroleum ether：The mixed solution conduct of ethyl acetate
Eluant, eluent carries out silica gel column chromatography purifies and separates, obtains 2- phenyl -5- methoxyl group -2,3- Dihydrobenzofuranes, structural formula
For：
Obtained 2- phenyl -5- methoxyl group -2,3- Dihydrobenzofuranes are colourless liquid, yield 9%, nuclear magnetic data
For：1H NMR(400MHz,CDCl3) δ 7.42-7.30 (m, 5H), 6.83-6.73 (m, 2H), 6.70 (dd, J=8.6,2.6Hz,
1H), 5.74 (t, J=8.8Hz, 1H), 3.77 (s, 3H), 3.60 (dd, J=15.7,9.3Hz, 1H), 3.20 (dd, J=15.7,
8.2Hz,1H)。
13C NMR(100MHz,CDCl3)δ154.33,153.81,142.04,128.63,127.99,127.51,
125.77,113.04,111.23,109.21,84.24,56.06,38.89。
Embodiment 6
40mg 4- methoxyl group phenol oxygroup trimethyl silanes, 145mg sodium peroxydisulfates and 85mg are added into 10mL round-bottomed flasks
Styrene seals flask and replaces 3 nitrogen, 2ml acetonitriles are added into reaction bulb with syringe needle, react 72h at 70 DEG C.Reaction knot
Shu Hou, reaction solution after filtering and concentrating and be spin-dried for, then with volume ratio be 30:1 petroleum ether：The mixed solution conduct of ethyl acetate
Eluant, eluent carries out silica gel column chromatography purifies and separates, obtains 2- phenyl -5- methoxyl group -2,3- Dihydrobenzofuranes, structural formula
For：
Obtained 2- phenyl -5- methoxyl group -2,3- Dihydrobenzofuranes are colourless liquid, yield 50%, nuclear-magnetism number
According to for：1H NMR(400MHz,CDCl3) δ 7.42-7.30 (m, 5H), 6.83-6.73 (m, 2H), 6.70 (dd, J=8.6,
2.6Hz, 1H), 5.74 (t, J=8.8Hz, 1H), 3.77 (s, 3H), 3.60 (dd, J=15.7,9.3Hz, 1H), 3.20 (dd, J
=15.7,8.2Hz, 1H).
13C NMR(100MHz,CDCl3)δ154.33,153.81,142.04,128.63,127.99,127.51,
125.77,113.04,111.23,109.21,84.24,56.06,38.89。
Embodiment 7
40mg 4- methoxyl group phenol oxygroup trimethyl silanes, 145mg sodium peroxydisulfates and 95mg are added into 10mL round-bottomed flasks
2-methyl styrene seals flask and replaces 3 nitrogen, 2ml acetonitriles are added into reaction bulb with syringe needle, react 72h at 50 DEG C.
After reaction, reaction solution is after filtering and concentrating and be spin-dried for, then with volume ratio for 30:1 petroleum ether：The mixing of ethyl acetate is molten
Liquid carries out silica gel column chromatography purifies and separates, obtains 2- o-methyl-phenyl -5- methoxyl group -2,3- dihydrobenzo furans as eluant, eluent
It mutters, structural formula is：
Obtained 2- o-methyl-phenyl -5- methoxyl group -2,3- Dihydrobenzofuranes be white solid, yield 65%,
Nuclear magnetic data is：1H NMR(400MHz,CDCl3) δ 7.48-7.42 (m, 1H), 7.19 (d, J=3.6Hz, 3H), 6.80 (d, J=
8.6Hz, 1H), 6.76 (s, 1H), 6.71 (dd, J=8.5,2.6Hz, 1H), 5.92 (t, J=8.8Hz, 1H), 3.76 (s, 3H),
3.63 (dd, J=15.6,9.5Hz, 1H), 3.07 (dd, J=15.5,8.2Hz, 1H), 2.36 (s, 3H).
13C NMR(100MHz,CDCl3)δ154.31,153.87,140.29,134.19,130.50,127.60,
127.35,126.26,124.99,113.06,111.29,109.21,81.74,56.06,37.90,19.22。
Embodiment 8
Into 10mL round-bottomed flasks be added 40mg 4- methoxyl group phenol oxygroup trimethyl silanes, 145mg sodium peroxydisulfates and
130mg p-tert-butylstyrenes seal flask and replace 3 nitrogen, 2ml acetonitriles are added into reaction bulb with syringe needle, at 50 DEG C
React 72h.After reaction, reaction solution is after filtering and concentrating and be spin-dried for, then with volume ratio for 30:1 petroleum ether：Ethyl acetate
Mixed solution as eluant, eluent, carry out silica gel column chromatography purifies and separates, obtain 2- (4- tert-butyl-phenyls) methoxyl group-2-5-,
3- Dihydrobenzofuranes, structural formula are：
Obtained 2- (4- tert-butyl-phenyls) -5- methoxyl group -2,3- Dihydrobenzofuranes are white solid, and yield is
52%, nuclear magnetic data is：1H NMR(400MHz,CDCl3) δ 7.39 (d, J=8.3Hz, 2H), 7.33 (d, J=8.3Hz,
2H), 6.80-6.73 (m, 2H), 6.72-6.67 (m, 1H), 5.71 (t, J=8.7Hz, 1H), 3.76 (d, J=6.2Hz, 3H),
3.57 (dd, J=15.7,9.3Hz, 1H), 3.22 (dd, J=15.7,8.2Hz, 1H), 1.31 (s, 9H).
13C NMR(100MHz,CDCl3)δ154.25,153.83,151.07,138.84,127.70,125.68,
125.55,113.00,111.22,109.19,84.21,56.06,38.61,34.58,31.33。
Embodiment 9
Into 10mL round-bottomed flasks be added 40mg 4- methoxyl group phenol oxygroup trimethyl silanes, 145mg sodium peroxydisulfates and
108mg seals flask and replaces 3 nitrogen, 2ml acetonitriles are added into reaction bulb with syringe needle, at 50 DEG C to methoxy styrene
React 48h.After reaction, reaction solution is after filtering and concentrating and be spin-dried for, then with volume ratio for 20:1 petroleum ether：Ethyl acetate
Mixed solution as eluant, eluent, carry out silica gel column chromatography purifies and separates, obtain 2- (4- methoxyphenyls) methoxyl group-2-5-,
3- Dihydrobenzofuranes (natural products corsifuran A), structural formula is：
Obtained 2- (4- methoxyphenyls) -5- methoxyl group -2,3- Dihydrobenzofuranes are colourless liquid, and yield is
38%, nuclear magnetic data is：1H NMR(400MHz,CDCl3) δ 7.33 (d, J=8.6Hz, 2H), 6.90 (d, J=8.6Hz,
2H), 6.83-6.63 (m, 3H), 5.68 (t, J=8.8Hz, 1H), 3.81 (s, 3H), 3.77 (s, 3H), 3.55 (dd, J=
15.8,9.2Hz, 1H), 3.19 (dd, J=15.7,8.3Hz, 1H).
13C NMR(100MHz,CDCl3)δ159.48,154.25,153.75,133.95,127.72,127.30,
114.02,113.00,111.20,109.18,84.19,56.06,55.33,38.73。
Embodiment 10
Into 10mL round-bottomed flasks be added 40mg 4- methoxyl group phenol oxygroup trimethyl silanes, 145mg sodium peroxydisulfates and
148mg seals flask and replaces 3 nitrogen, 2ml acetonitriles are added into reaction bulb with syringe needle, are reacted at 50 DEG C to bromstyrol
72h.After reaction, reaction solution is after filtering and concentrating and be spin-dried for, then with volume ratio for 30:1 petroleum ether：Ethyl acetate mixes
Solution is closed as eluant, eluent, silica gel column chromatography purifies and separates is carried out, obtains 2- (4- bromophenyls) -5- methoxyl group -2,3- dihydrobenzenes
And furans, structural formula are：
Obtained 2- (4- bromophenyls) -5- methoxyl group -2,3- Dihydrobenzofuranes be colourless liquid, yield 35%,
Nuclear magnetic data is：1H NMR(400MHz,CDCl3) δ 7.75 (dd, J=24.5,8.4Hz, 2H), 7.52 (d, J=8.4Hz, 2H),
7.31 (s, 1H), 6.79 (s, 1H), 6.76-6.70 (m, 1H), 5.72 (t, J=8.7Hz, 1H), 3.79 (s, 3H), 3.63 (dd,
J=15.4,9.2Hz, 1H), 3.15 (dd, J=15.5,8.1Hz, 1H).
13C NMR(100MHz,CDCl3)δ154.47,153.58,141.17,132.47,131.74,130.98,
127.44,113.16,111.24,109.28,83.43,56.05,38.87。
Embodiment 11
40mg 4- methoxyl group phenol oxygroup trimethyl silanes, 145mg sodium peroxydisulfates and 99mg are added into 10mL round-bottomed flasks
Pfluorostyrene seals flask and replaces 3 nitrogen, 2ml acetonitriles are added into reaction bulb with syringe needle, react 72h at 50 DEG C.Instead
After answering, reaction solution after filtering and concentrating and be spin-dried for, then with volume ratio be 30:1 petroleum ether：The mixed solution of ethyl acetate
As eluant, eluents, silica gel column chromatography purifies and separates are carried out, 2- (4- fluorophenyls) -5- methoxyl group -2,3- Dihydrobenzofuranes are obtained,
Its structural formula is：
Obtained 2- (4- fluorophenyls) -5- methoxyl group -2,3- Dihydrobenzofuranes be colourless liquid, yield 41%,
Nuclear magnetic data is：1H NMR(400MHz,CDCl3) δ 7.37 (dd, J=8.6,5.4Hz, 2H), 7.03 (s, 2H), 6.77 (d, J=
8.6Hz, 2H), 6.70 (dd, J=8.5,2.2Hz, 1H), 5.71 (t, J=8.8Hz, 1H), 3.77 (s, 3H), 3.59 (dd, J=
15.7,9.3Hz, 1H), 3.16 (dd, J=15.7,8.2Hz, 1H).
13C NMR(100MHz,CDCl3)δ163.70,154.40,153.59,127.60,127.52,115.62,
115.40,113.09,111.21,109.25,83.61,56.05,38.93。
Embodiment 12
40mg 4- methoxyl group phenol oxygroup trimethyl silanes, 145mg sodium peroxydisulfates and 94mg are added into 10mL round-bottomed flasks
Indenes seals flask and replaces 3 nitrogen, 2ml acetonitriles are added into reaction bulb with syringe needle, react 72h at 50 DEG C.Reaction terminates
Afterwards, reaction solution is after filtering and concentrating and be spin-dried for, then with volume ratio for 30:1 petroleum ether：The mixed solution of ethyl acetate is used as and washes
De- agent, carries out silica gel column chromatography purifies and separates, obtains 8- methoxyl groups -9b, 10- dihydro -4bH- benzos [b] indeno [2,1-d] furan
It mutters, structural formula is：
Obtained 8- methoxyl groups -9b, 10- dihydro -4bH- benzos [b] indeno [2,1-d] furans is colourless liquid, and yield is
38%, nuclear magnetic data is：1H NMR(400MHz,CDCl3) δ 7.55 (t, J=8.60Hz, 1H), 7.28-7.21 (m, 3H),
6.81 (s, 1H), 6.65-6.64 (m, 2H), 6.18 (d, J=8.23Hz, 1H), 4.28 (t, J=17.23Hz, 1H), 3.75 (s,
3H), 3.51 (dd, J=8.58,8.56Hz, 1H), 3.20 (dd, J=1.34,1.38Hz, 1H).
13C NMR(100MHz,CDCl3)δ154.38,152.99,142.17,140.91,131.83,129.23,
127.26,125.90,125.09,113.51,110.88,109.81,90.73,56.06,45.27,38.97。
Embodiment 13
Into 10mL round-bottomed flasks be added 40mg 4- methoxyl group phenol oxygroup trimethyl silanes, 145mg sodium peroxydisulfates and
116mg α-cyclopropyl-phenyl ethylene seal flask and replace 3 nitrogen, 2ml acetonitriles are added into reaction bulb with syringe needle, at 50 DEG C
React 72h.After reaction, reaction solution is after filtering and concentrating and be spin-dried for, then with volume ratio for 30:1 petroleum ether：Ethyl acetate
Mixed solution as eluant, eluent, carry out silica gel column chromatography purifies and separates, obtain 2- phenyl -2- cyclopropyl -5- methoxyl groups -2,3-
Dihydrobenzofuranes, structural formula are：
Obtained 2- phenyl 2- cyclopropyl -5- methoxyl group -2,3- Dihydrobenzofuranes be colourless liquid, yield 70%,
Its nuclear magnetic data is：1H NMR(400MHz,CDCl3) δ 7.49 (d, J=7.6Hz, 2H), 7.33 (t, J=7.6Hz, 2H),
7.26-7.22 (m, 1H), 6.80-6.55 (m, 3H), 3.73 (s, 3H), 3.45 (d, J=15.7Hz, 1H), 3.39 (d, J=
16.0Hz,1H),1.51–1.40(m,1H),0.57–0.48(m,2H),0.48–0.40(m,2H)。
13C NMR(100MHz,CDCl3)δ154.07,153.41,146.15,128.12,127.59,127.05,
125.23,112.89,111.15,109.00,90.33,55.99,43.24,21.63,1.79,1.35。
Embodiment 14
Into 10mL round-bottomed flasks be added 40mg 4- methoxyl group phenol oxygroup trimethyl silanes, 145mg sodium peroxydisulfates and
108mg meta-methoxy styrene seals flask and replaces 3 nitrogen, 2ml acetonitriles is added into reaction bulb with syringe needle, at 50 DEG C
React 72h.After reaction, reaction solution is after filtering and concentrating and be spin-dried for, then with volume ratio for 20:1 petroleum ether：Ethyl acetate
Mixed solution as eluant, eluent, carry out silica gel column chromatography purifies and separates, obtain 2- (3- methoxyphenyls) methoxyl group-2-5-,
3- Dihydrobenzofuranes, structural formula are：
Obtained 2- (3- methoxyphenyls) -5- methoxyl group -2,3- Dihydrobenzofuranes are colourless liquid, and yield is
42%, nuclear magnetic data is：1H NMR(400MHz,CDCl3) δ 7.29 (d, J=7.9Hz, 1H), 6.97 (d, J=8.5Hz,
2H), 6.87-6.83 (m, 1H), 6.78 (d, J=8.2Hz, 2H), 6.70 (d, J=8.6Hz, 1H), 5.71 (t, J=8.7Hz,
1H), 3.80 (s, 3H), 3.77 (s, 3H), 3.59 (dd, J=14.9,10.2Hz, 1H), 3.19 (dd, J=15.7,8.2Hz,
1H)。
13C NMR(100MHz,CDCl3)δ159.86,154.34,153.78,143.68,129.72,127.47,
118.01,113.45,113.05,111.22,111.26,109.23,84.09,56.06,55.27,38.88。
Embodiment 15
40mg 2- chloro-4-methoxy phenol oxygroup trimethyl silanes, 124mg sodium peroxydisulfates are added into 10mL round-bottomed flasks
With 110mg p-tert-butylstyrenes, seals flask and replace 3 nitrogen, 2ml acetonitriles are added into reaction bulb with syringe needle, at 50 DEG C
Lower reaction 72h.After reaction, reaction solution is after filtering and concentrating and be spin-dried for, then with volume ratio for 20:1 petroleum ether：Acetic acid second
The mixed solution of ester carries out silica gel column chromatography purifies and separates, obtains 5- methoxyl groups -7- chloro- 2- (4- tert-butyl benzenes as eluant, eluent
Base) -2,3- Dihydrobenzofuranes, structural formula is：
The obtained chloro- 2- of 5- methoxyl groups -7- (4- tert-butyl-phenyls) -2,3- Dihydrobenzofuranes are faint yellow solid, production
Rate is 42%, and nuclear magnetic data is：1H NMR(400MHz,CDCl3) δ 7.39 (d, J=8.4Hz, 2H), 7.33 (d, J=
8.3Hz, 2H), 6.71 (d, J=2.3Hz, 1H), 6.68 (s, 1H), 5.79 (t, J=8.6Hz, 1H), 3.75 (s, 3H), 3.63
(dd, J=16.1,9.0Hz, 1H), 3.28 (dd, J=15.9,8.0Hz, 1H), 1.31 (s, 9H).
13C NMR(100MHz,CDCl3)δ154.49,151.29,149.92,138.10,128.98,125.71,
125.58,113.18,110.21,84.70,56.17,39.26,31.32。
Embodiment 16
40mg 4- methoxyl group phenol oxygroup trimethyl silanes, 124mg sodium peroxydisulfates and 96mg are added into 10mL round-bottomed flasks
α-methylstyrene seals flask and replaces 3 nitrogen, 2ml acetonitriles are added into reaction bulb with syringe needle, react 72h at 50 DEG C.
After reaction, reaction solution is after filtering and concentrating and be spin-dried for, then with volume ratio for 20:1 petroleum ether：The mixing of ethyl acetate is molten
Liquid carries out silica gel column chromatography purifies and separates, obtains 2- methyl -2- phenyl -5- methoxyl group -2,3- dihydrobenzo furans as eluant, eluent
It mutters, structural formula is：
Obtained 2- methyl -2- phenyl -5- methoxyl group -2,3- Dihydrobenzofuranes be colourless liquid, yield 61%,
Nuclear magnetic data is：1H NMR(400MHz,CDCl3) δ 7.46 (d, J=7.4Hz, 2H), 7.34 (t, J=7.6Hz, 2H), 7.25
(d, J=4.8Hz, 1H), 6.79 (d, J=8.5Hz, 1H), 6.69 (dd, J=12.4,3.9Hz, 2H), 3.74 (s, 3H), 3.41
(d, J=15.6Hz, 1H), 3.34 (d, J=15.5Hz, 1H), 1.76 (s, 3H).
13C NMR(100MHz,CDCl3)δ154.16,153.07,146.90,128.35,127.47,127.01,
124.54,113.03,111.38,109.40,89.19,56.03,45.17,29.23。
Embodiment 17
Into 10mL round-bottomed flasks be added 40mg 4- methoxyl group phenol oxygroup trimethyl silanes, 124mg sodium peroxydisulfates and
The amyl- 1- alkene benzene of 119mg seals flask and replaces 3 nitrogen, 2ml acetonitriles are added into reaction bulb with syringe needle, are reacted at 50 DEG C
72h.After reaction, reaction solution is after filtering and concentrating and be spin-dried for, then with volume ratio for 20:1 petroleum ether：Ethyl acetate mixes
Solution is closed as eluant, eluent, silica gel column chromatography purifies and separates is carried out, obtains 2- phenyl -3- propyl -5- methoxyl group -2,3- dihydrobenzenes
And furans, structural formula are：
Obtained 2- phenyl -3- propyl -5- methoxyl group -2,3- Dihydrobenzofuranes be colourless liquid, yield 45%,
Nuclear magnetic data is：1H NMR(400MHz,CDCl3) δ 7.33 (dd, J=13.1,3.7Hz, 5H), 6.74 (dt, J=8.5,
7.3Hz, 3H), 5.31 (d, J=6.3Hz, 1H), 3.77 (s, 3H), 3.38 (dd, J=13.1,6.6Hz, 1H), 1.77 (ddd, J
=22.7,11.6,6.3Hz, 2H), 1.47 (dd, J=14.3,7.2Hz, 2H), 0.94 (t, J=7.3Hz, 3H).
13C NMR(100MHz,CDCl3)δ154.30,153.57,142.12,131.62,128.61,127.99,
125.93,112.98,110.92,109.18,90.18,56.06,50.93,37.23,20.12,14.17。
By embodiment 1 to 17 it is found that the present invention under nitrogen atmosphere, appropriate heating can react, simple to operate.This
Outside, the reaction raw materials that the present invention uses need not move through complicated synthesis, part even commercially available, the oxidant such as persulfuric acid of use
Sodium is cheap and easily-available and pollution-free, and the present invention can be brought by the change of substituent group in reaction raw materials and realize different substituted benzene
The preparation of benzofuran compound.
The preparation method of the present invention is not necessarily to metal catalytic, and reaction condition is mild, reaction process safety and environmental protection, at low cost, warp
Ji high efficiency, belongs to green chemistry process, can be widely applied to prepare benzofuran compounds, and can be through the invention
One step of preparation method complete the preparation of natural products corsifuran A.
Claims (12)
1. a kind of method preparing formula (I) compound,
Wherein,
R1Indicate H or halogen,
R2Indicate H, methyl or cyclopropyl,
R3Indicate H, halogen, methyl, methoxyl group or tertiary butyl,
R4Indicate H, methyl or propyl,
Alternatively, R3With R4It can be bonded to each other to form ring,
The method includes：In a nitrogen atmosphere, in the presence of persulfate and organic solvent, make shown in following formula (II)s
Compound is reacted with following formula (III) compounds represented,
In formula (II), R1Indicate H or halogen；TMS indicates trimethyl silicane group,
In formula (III), R2Indicate H, methyl or cyclopropyl；R3Indicate H, halogen, methyl, methoxyl group or tertiary butyl；R4Indicate H, first
Base or propyl；Alternatively, R3With R4It can be bonded to each other to form ring.
2. according to the method described in claim 1, it is characterized in that, the persulfate is sodium peroxydisulfate, potassium peroxydisulfate or mistake
Ammonium sulfate.
3. method according to claim 1 or 2, which is characterized in that formula (II) compound represented and the over cure
The molar ratio of hydrochlorate is 1:2~1:3.
4. according to the method described in claim 3, it is characterized in that, the formula (II) compound represented and the persulfate
Molar ratio be 1:3.
5. method according to claim 1 or 2, which is characterized in that formula (II) compound represented and the formula
(III) molar ratio of compound represented is 1:2~1:4.
6. according to the method described in claim 5, it is characterized in that, the formula (II) compound represented and the formula (III)
The molar ratio of compound represented is 1:4.
7. method according to claim 1 or 2, which is characterized in that the organic solvent includes acetonitrile, dichloromethane, first
Alcohol, tetrahydrofuran or N,N-dimethylformamide.
8. method according to claim 1 or 2, which is characterized in that the amount of the organic solvent is described in every mM
(II) compound represented uses 5~10ml.
9. method according to claim 1 or 2, which is characterized in that formula (II) compound represented and the formula
(III) compound represented in room temperature to reacting at 70 DEG C.
10. according to the method described in claim 9, it is characterized in that, the formula (II) compound represented and the formula (III)
Compound represented is reacted at 50 DEG C.
11. method according to claim 1 or 2, which is characterized in that the reaction time is 48~72h.
12. method according to claim 1 or 2, which is characterized in that it is 20 to further comprise using by volume:1~
30:1 petroleum ether：Ethyl acetate carries out column chromatography for separation as eluant, eluent.
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Non-Patent Citations (5)
| Title |
|---|
| [3+2] Coupling of Quinone Monoacetals by Combined Acid-Hydrogen Bond Donor;Toshifumi Dohi et al.;《Org. Lett.》;20110815;第13卷(第18期);第4814-4817页 * |
| Bronsted Acid-Controlled [3 + 2] Coupling Reaction of Quinone Monoacetals with Alkene Nucleophiles: A Catalytic System of Perfluorinated Acids and Hydrogen Bond Donor for the Construction of Benzofurans;Yinjun Hu et al.;《The Journal of Organic Chemistry》;20130514;第78卷;第5530-5543页 * |
| Dihydrobenzofuran Synthesis by an Anodic [3 + 2] Cycloaddition of Phenols and Unactivated Alkenes;Kazuhiro Chiba et al.;《J. Org. Chem.》;19990911;第64卷;第7654-7656页 * |
| Iron-Catalyzed Oxidative Cross-Coupling of Phenols and Alkenes;Umesh A. Kshirsagar et al.;《Org. Lett.》;20130611;第15卷(第12期);第3174-3177页 * |
| Photocatalytic Synthesis of Dihydrobenzofurans by Oxidative [3+2] Cycloaddition of Phenols;Travis R. Blum et al.;《Angew. Chem. Int. Ed.》;20140825;第53卷;第11056-11059页 * |
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