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CN110003166B - Method for synthesizing tetraoxaheterocyclic by utilizing aryne and tetrahydrofuran - Google Patents

Method for synthesizing tetraoxaheterocyclic by utilizing aryne and tetrahydrofuran Download PDF

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CN110003166B
CN110003166B CN201910293194.1A CN201910293194A CN110003166B CN 110003166 B CN110003166 B CN 110003166B CN 201910293194 A CN201910293194 A CN 201910293194A CN 110003166 B CN110003166 B CN 110003166B
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tetrahydrofuran
aryne
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CN110003166A (en
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戚朝荣
程瑞祥
江焕峰
熊文芳
汪露
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South China University of Technology SCUT
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Abstract

The invention belongs to the technical field of organic synthesis, and discloses a method for synthesizing tetraoxaheterocycle by utilizing aryne and tetrahydrofuran. Taking 2-trimethylsilyl-1, 3-bis (trifluoromethanesulfonyloxy) benzene or derivatives thereof as an aryne precursor, taking anhydrous tetrahydrofuran as a reactant and a solvent, adding alkali as an accelerator, stirring and reacting at a certain temperature under the protection of an inert atmosphere, and separating and purifying a product after the reaction is finished to obtain the tetraoxaheterocyclic compounds. The synthesis method of the tetraoxaheterocyclic compounds is different from the traditional high dilution method and template method, and has the advantages of easily obtained raw materials, simple reaction operation, high yield, wide substrate applicability, high functional group tolerance and the like. Is beneficial to industrial production and has potential application prospect in a plurality of fields such as organic synthesis, catalysis, analytical chemistry and the like.

Description

Method for synthesizing tetraoxaheterocyclic by utilizing aryne and tetrahydrofuran
Technical Field
The invention belongs to the technical field of organic synthesis, and particularly relates to a method for synthesizing tetraoxaheterocycle by utilizing aryne and tetrahydrofuran.
Background
Macrocyclic compounds have attracted the attention of chemists and biologists since the 1967 s when Pedersen synthesized crown ethers and reported the property of complexing alkali metal ions. The artificially synthesized macrocyclic compound mainly comprises cyclophane, calixarene, porphyrin, cyclodextrin and the like. Wherein, the ring is a compound which connects two non-adjacent atoms on the aromatic ring through a bridge chain formed by linear atoms with various numbers, and the number of the linear bridge chain or the aromatic ring contained in the ring can be one or more. The compounds have wide application in various fields such as catalysis, analysis, pharmaceutical chemistry and material chemistry due to the properties of macrocyclic effect, hydrogen bond, van der Waals force, pi-pi stacking and the like, and are widely applied by the scientists (D.J.cram, J.M.cram, Acc.chem.Res.1971,4,204 213; A.D.Cort, L.Mandolini, B.Masci, J.Org.chem.1980,45, 3923. Buck 3925; R.M.Izatt, J.S.Chedshaw, K.Pawlak, R.L.Bruening, B.J.Tarbet, chem.Rem.1992, 92, 1261. Buck 1354; S.Bartoli, S.Roels, J.Am.Bracci.2002. Talbot.83127; Soglc.136J.1364, S.Bartoc.13631, S.R.J.Chec.31, S.Chevre.31, J..
The synthesis of cyclopoly macrocycles traditionally requires either a highly diluted solvent (P. Rajakumar, R. Padmanahan, Tetrahedron Lett.2010,51, 1059-. However, the high dilution method is troublesome to operate, has a long reaction time, requires a large amount of solvent, and has a low yield; the template method has short reaction time and high yield, but needs to introduce and remove a template, thereby increasing the steps and difficulty of synthesis. With the development of organic synthesis and cyclophane chemistry, methods of cyclophane synthesis are emerging, such as by pyrolysis of sulfones (z.pechlivantiis, h.hopf, l.ernst, eur.j.org.chem.2009,223-237), Suzuki-Miyaura cross-coupling and olefin metathesis (s.kotha, a.s.chavan, m.shaikh, j.org.chem.2012,77,482-,
Figure BDA0002025606040000022
chem.commun.2012,48,2855-2857), and the like.
Arynes are a class of highly active reaction intermediates with special structures and are widely used in organic synthesis (S.S. Bhojgude, A.T. Biju, Angew.chem.Int.Ed.2012,51, 1520-. Reactions involving arynes include multicomponent reactions with nucleophilic and electrophilic reagents (Z.Liu, R.C.Larock, J.org.chem.2006,71, 3198-. However, at present, no document is reported for synthesizing cycloparaffin by directly using aryne as a raw material.
Disclosure of Invention
Aiming at the defects and shortcomings of the prior art, the invention aims to provide a method for synthesizing tetraoxaheterocycle by utilizing aryne and tetrahydrofuran. The method takes 2-trimethylsilyl-1, 3-bis (trifluoromethanesulfonyloxy) benzene and derivatives thereof as an aryne precursor, the aryne precursor is decomposed in situ under the action of alkali to generate aryne, and the aryne precursor and tetrahydrofuran are subjected to domino reaction to construct tetraoxaheterocycle in one step.
The purpose of the invention is realized by the following technical scheme:
a method for synthesizing tetraoxaheterocyclic by utilizing aryne and tetrahydrofuran comprises the following steps:
taking 2-trimethylsilyl-1, 3-bis (trifluoromethanesulfonyloxy) benzene or a derivative thereof as an aryne precursor, taking anhydrous tetrahydrofuran as a reactant and a solvent, adding alkali as an accelerator, stirring and reacting at a certain temperature under the protection of an inert atmosphere, and separating and purifying a product after the reaction is finished to obtain a tetraoxaheterocyclic compound;
the reaction equation of the above synthesis method is shown as the following formula:
Figure BDA0002025606040000021
wherein R is hydrogen, 4-methyl, 4-ethyl, 5-methyl, 5-chloro, 5-fluoro, 5-phenyl, 5-naphthyl, 5-p-methylphenyl, 5-p-ethylphenyl, 5-p-trifluoromethylphenyl, 5-p-methoxyphenyl, 5-p-chlorophenyl, 5-m-methylphenyl, 5-o-methylphenyl, 5-m-methoxyphenyl, 5-o-methoxyphenyl or 5- (2, 4-dimethyl) phenyl; TMS means trimethylsilyl and OTf means trifluoromethanesulfonyloxy.
Preferably, the base is at least one of cesium fluoride and potassium fluoride.
Preferably, the molar ratio of the aryne precursor to the tetrahydrofuran is 1 (60-240).
Preferably, the molar ratio of the aryne precursor to the base is 1 (1-8).
Preferably, the solvent is anhydrous tetrahydrofuran or a mixed solvent of the anhydrous tetrahydrofuran and any one of anhydrous acetonitrile, anhydrous dimethyl sulfoxide and anhydrous toluene according to a volume ratio of 1: 1.
Preferably, the inert atmosphere refers to a nitrogen atmosphere.
Preferably, the reaction temperature is 80-130 ℃, and the reaction time is 4-24 h.
Preferably, the steps of separating and purifying are: and cooling the reaction liquid to room temperature, washing with water, extracting with ethyl acetate, drying with anhydrous magnesium sulfate, filtering, concentrating under reduced pressure to obtain a crude product, and purifying by column chromatography to obtain the tetraoxaheterocyclic compounds. The column chromatography eluent is a mixed solvent of petroleum ether and ethyl acetate with the volume ratio of (10-30): 1.
The preparation method of the invention has the following advantages and beneficial effects:
the synthesis method of the tetraoxaheterocyclic compounds is different from the traditional high dilution method and template method, and has the advantages of easily obtained raw materials, simple reaction operation, high yield, wide substrate applicability, high functional group tolerance and the like. Is beneficial to industrial production and has potential application prospect in a plurality of fields such as organic synthesis, catalysis, analytical chemistry and the like.
Drawings
FIG. 1, FIG. 2 and FIG. 3 are a hydrogen spectrum, a carbon spectrum and a fluorine spectrum, respectively, of a target product obtained in example 9;
FIG. 4, FIG. 5 and FIG. 6 are a hydrogen spectrum, a carbon spectrum and a fluorine spectrum of the objective product obtained in example 10, respectively;
FIG. 7, FIG. 8 and FIG. 9 are a hydrogen spectrum, a carbon spectrum and a fluorine spectrum, respectively, of the objective product obtained in example 11;
FIG. 10, FIG. 11 and FIG. 12 are a hydrogen spectrum, a carbon spectrum and a fluorine spectrum, respectively, of the objective product obtained in example 12;
FIG. 13, FIG. 14 and FIG. 15 are a hydrogen spectrum, a carbon spectrum and a fluorine spectrum, respectively, of the objective product obtained in example 13;
FIG. 16, FIG. 17 and FIG. 18 are a hydrogen spectrum, a carbon spectrum and a fluorine spectrum, respectively, of a target product obtained in example 14;
FIG. 19, FIG. 20 and FIG. 21 are a hydrogen spectrum, a carbon spectrum and a fluorine spectrum, respectively, of the objective product obtained in example 15;
FIG. 22, FIG. 23 and FIG. 24 are a hydrogen spectrum, a carbon spectrum and a fluorine spectrum, respectively, of a target product obtained in example 16;
FIG. 25, FIG. 26 and FIG. 27 are a hydrogen spectrum, a carbon spectrum and a fluorine spectrum, respectively, of a target product obtained in example 17;
fig. 28, 29 and 30 are a hydrogen spectrum, a carbon spectrum and a fluorine spectrum of the objective product obtained in example 18, respectively.
Detailed Description
The present invention will be described in further detail with reference to examples and drawings, but the present invention is not limited thereto.
Example 1
0.2 mmol of 2-trimethylsilyl-1, 3-bis (trifluoromethanesulfonyloxy) benzene, 0.8 mmol of cesium fluoride and 2 ml of anhydrous tetrahydrofuran were added to a reaction tube, and the mixture was stirred at 120 ℃ for 10 hours; after the reaction is finished, cooling the reaction liquid to room temperature, adding 4mL of water, extracting with ethyl acetate (5mL multiplied by 3), combining organic phases, drying by using anhydrous magnesium sulfate, filtering, concentrating under reduced pressure to obtain a crude product, and separating and purifying by column chromatography, wherein the eluent of the column chromatography is a mixed solvent of petroleum ether and ethyl acetate in a volume ratio of 10:1 to obtain a target product, and the yield is 32%.
Example 2
Adding 0.2 mmol of 2-trimethylsilyl-1, 3-bis (trifluoromethanesulfonyloxy) benzene, 0.8 mmol of potassium fluoride and 2 ml of anhydrous tetrahydrofuran into a reaction tube, and stirring at 80 ℃ for reaction for 10 hours; after the reaction is finished, cooling the reaction liquid to room temperature, adding 4mL of water, extracting with ethyl acetate (5mL multiplied by 3), combining organic phases, drying by using anhydrous magnesium sulfate, filtering, concentrating under reduced pressure to obtain a crude product, and separating and purifying by column chromatography, wherein the eluent of the column chromatography is a mixed solvent of petroleum ether and ethyl acetate in a volume ratio of 10:1 to obtain a target product, and the yield is 32%.
Example 3
0.2 mmol of 2-trimethylsilyl-1, 3-bis (trifluoromethanesulfonyloxy) benzene, 0.8 mmol of potassium fluoride and 2 ml of anhydrous tetrahydrofuran are added into a reaction tube, and the mixture is stirred and reacted for 10 hours at 130 ℃; after the reaction is finished, cooling the reaction liquid to room temperature, adding 4mL of water, extracting with ethyl acetate (5mL multiplied by 3), combining organic phases, drying by using anhydrous magnesium sulfate, filtering, concentrating under reduced pressure to obtain a crude product, and separating and purifying by column chromatography, wherein the eluent of the column chromatography is a mixed solvent of petroleum ether and ethyl acetate in a volume ratio of 10:1 to obtain a target product, and the yield is 69%.
Example 4
Adding 0.2 mmol of 2-trimethylsilyl-1, 3-bis (trifluoromethanesulfonyloxy) benzene and 0.8 mmol of potassium fluoride into a reaction tube, and stirring at 120 ℃ for reaction for 4 hours; after the reaction is finished, cooling the reaction liquid to room temperature, adding 4mL of water, extracting with ethyl acetate (5mL multiplied by 3), combining organic phases, drying by using anhydrous magnesium sulfate, filtering, concentrating under reduced pressure to obtain a crude product, and separating and purifying by column chromatography, wherein the eluent of the column chromatography is a mixed solvent of petroleum ether and ethyl acetate in a volume ratio of 10:1, so that the target product is obtained, and the yield is 34%.
Example 5
Adding 0.2 mmol of 2-trimethylsilyl-1, 3-bis (trifluoromethanesulfonyloxy) benzene and 0.8 mmol of potassium fluoride into a reaction tube, and stirring at 120 ℃ for reaction for 24 hours; after the reaction is finished, cooling the reaction liquid to room temperature, adding 4mL of water, extracting with ethyl acetate (5mL multiplied by 3), combining organic phases, drying by using anhydrous magnesium sulfate, filtering, concentrating under reduced pressure to obtain a crude product, and separating and purifying by column chromatography, wherein the eluent of the column chromatography is a mixed solvent of petroleum ether and ethyl acetate in a volume ratio of 10:1 to obtain a target product, and the yield is 69%.
Example 6
0.2 mmol of 2-trimethylsilyl-1, 3-bis (trifluoromethanesulfonyloxy) benzene, 1 ml of anhydrous tetrahydrofuran containing 0.8 mmol of potassium fluoride and 1 ml of anhydrous ethyl acetate were added to a reaction tube, and the mixture was stirred at 120 ℃ for 10 hours; after the reaction is finished, cooling the reaction liquid to room temperature, adding 4mL of water, extracting with ethyl acetate (5mL multiplied by 3), combining organic phases, drying by using anhydrous magnesium sulfate, filtering, concentrating under reduced pressure to obtain a crude product, and separating and purifying by column chromatography, wherein the eluent of the column chromatography is a mixed solvent of petroleum ether and ethyl acetate in a volume ratio of 10:1 to obtain a target product, and the yield is 23%.
Example 7
Adding 0.2 mmol of 2-trimethylsilyl-1, 3-bis (trifluoromethanesulfonyloxy) benzene, 0.2 mmol of potassium fluoride and 2 ml of anhydrous tetrahydrofuran into a reaction tube, and stirring at 80 ℃ for reaction for 10 hours; after the reaction is finished, cooling the reaction liquid to room temperature, adding 4mL of water, extracting with ethyl acetate (5mL multiplied by 3), combining organic phases, drying by using anhydrous magnesium sulfate, filtering, concentrating under reduced pressure to obtain a crude product, and separating and purifying by column chromatography, wherein the eluent of the column chromatography is a mixed solvent of petroleum ether and ethyl acetate in a volume ratio of 10:1 to obtain a target product, and the yield is 25%.
Example 8
Adding 0.2 mmol of 2-trimethylsilyl-1, 3-bis (trifluoromethanesulfonyloxy) benzene, 0.8 mmol of potassium fluoride and 2 ml of anhydrous tetrahydrofuran into a reaction tube, and stirring at 80 ℃ for reaction for 10 hours; after the reaction is finished, cooling the reaction liquid to room temperature, adding 4mL of water, extracting with ethyl acetate (5mL multiplied by 3), combining organic phases, drying by using anhydrous magnesium sulfate, filtering, concentrating under reduced pressure to obtain a crude product, and separating and purifying by column chromatography, wherein the eluent of the column chromatography is a mixed solvent of petroleum ether and ethyl acetate in a volume ratio of 10:1 to obtain a target product, and the yield is 31%.
Example 9
Adding 0.2 mmol of 2-trimethylsilyl-1, 3-bis (trifluoromethanesulfonyloxy) benzene and 0.8 mmol of potassium fluoride into a reaction tube, and stirring at 120 ℃ for reaction for 10 hours; after the reaction is finished, cooling the reaction liquid to room temperature, adding 4mL of water, extracting with ethyl acetate (5mL multiplied by 3), combining organic phases, drying by using anhydrous magnesium sulfate, filtering, concentrating under reduced pressure to obtain a crude product, and separating and purifying by column chromatography, wherein the eluent of the column chromatography is a mixed solvent of petroleum ether and ethyl acetate in a volume ratio of 10:1 to obtain a target product, and the yield is 66%.
The obtained hydrogen spectrogram, carbon spectrogram and fluorine spectrogram of the target product are respectively shown in fig. 1, fig. 2 and fig. 3, and the structural characterization data are shown as follows:
1H NMR(400MHz,CDCl3)δ＝7.50(t,J＝8.4Hz,1H),6.62(d,J＝8.4Hz,2H),4.44-4.40(m,2H),4.26–4.22(m,2H),3.55–3.51m,2H),3.43-3.38(m,2H),3.24-3.21(m,2H),3.17-3.15(m,2H),2.04–1.93(m,4H),1.83-1.80(m,2H),1.59-1.54(m,2H),1.27–1.18(m,4H)；
13C NMR(100MHz,CDCl3)δ＝161.03,137.33,120.21(q,J＝326.9Hz),110.34,106.23,70.28,70.14,69.69,26.36,25.65,25.41；
19F NMR(376MHz,CDCl3)δ＝-75.93.
HRMS(ESI)Calcd for C25H32ClN2Si[M+Na]+,463.1378,found 463.1373。
the structure of the target product is deduced from the above data as follows:
Figure BDA0002025606040000071
example 10
Adding 0.2 mmol of 4-methyl-2-trimethylsilyl-1, 3-bis (trifluoromethanesulfonyloxy) benzene and 0.8 mmol of potassium fluoride into a reaction tube, taking 2 ml of anhydrous tetrahydrofuran as a solvent and a reactant, and stirring at the rotating speed of 630rpm at 120 ℃ for reaction for 10 hours; after the reaction is finished, cooling the reaction liquid to room temperature, adding 4mL of water, extracting with ethyl acetate (5mL multiplied by 3), combining organic phases, drying by using anhydrous magnesium sulfate, filtering, concentrating under reduced pressure to obtain a crude product, and separating and purifying by column chromatography, wherein the eluent of the column chromatography is a mixed solvent of petroleum ether and ethyl acetate in a volume ratio of 20:1 to obtain a target product, and the yield is 38%.
The obtained hydrogen spectrogram, carbon spectrogram and fluorine spectrogram of the target product are respectively shown in fig. 4, 5 and 6, and the structural characterization data are shown as follows:
1H NMR(400MHz,CDCl3)δ＝7.41(d,J＝8.4Hz,1H),6.73(d,J＝8.4Hz,1H),4.35-4.23(m,2H),4.20-4.15(m,1H),4.09-4.03(m,1H),3.51-3.34(m,5H),3.28-3.25(m,3H),2.23(s,3H),1.95-1.82(m,5H),1.59-1.35(m,7H)；
13C NMR(100MHz,CDCl3)δ＝159.4,158.2,139.0,125.4,120.2(q,J＝327.5Hz),109.6,77.2,70.69,70.65,70.58,70.34,70.21,27.29,26.62,26.35,26.15,25.69,25.45,15.93；
19F NMR(376MHz,CDCl3)δ＝-74.41.
IR(KBr)νmax 2932,2860,1580,1470,1376,1288,1197,1105cm-1；
HRMS(ESI)Calcd for C20H29F3O6S[M+Na]+,477.1530,found 477.1529。
the structure of the target product is deduced from the above data as follows:
Figure BDA0002025606040000081
example 11
Adding 0.2 mmol of 5-methyl-2-trimethylsilyl-1, 3-bis (trifluoromethanesulfonyloxy) benzene and 0.8 mmol of potassium fluoride into a reaction tube, taking 2 ml of anhydrous tetrahydrofuran as a solvent and a reactant, and stirring at the rotating speed of 630rpm at 120 ℃ for reaction for 10 hours; after the reaction is finished, cooling the reaction liquid to room temperature, adding 4mL of water, extracting with ethyl acetate (5mL multiplied by 3), combining organic phases, drying by using anhydrous magnesium sulfate, filtering, concentrating under reduced pressure to obtain a crude product, and separating and purifying by column chromatography, wherein the eluent of the column chromatography is a mixed solvent of petroleum ether and ethyl acetate in a volume ratio of 10:1, so that the target product is obtained, and the yield is 57%.
The obtained hydrogen spectrogram, carbon spectrogram and fluorine spectrogram of the target product are respectively shown in fig. 7, 8 and 9, and the structural characterization data are shown as follows:
1H NMR(400MHz,CDCl3)δ＝6.43(s,2H),4.43–4.38(m,2H),4.24–4.19(m,2H),3.60–3.52(m,2H),3.46-3.40(m,2H),3.29–3.24(m,2H),3.19–3.14(m,2H),2.36(s,3H),2.06–1.89(m,4H),1.84-1.77(m,2H),1.60–1.53(m,2H),1.30–1.22(m,4H)；
13C NMR(100MHz,CDCl3)δ＝160.85,149.26,120.5(q,J＝326.8),107.34,107.17,70.29,70.18,69.58,26.38,25.71,25.42,22.67；
19F NMR(376MHz,CDCl3)δ＝-76.34.
IR(KBr)νmax 2925,2857,1583,1445,1362,1199,1177,673cm-1；
HRMS(ESI)Calcd for C20H29F3O6S[M+Na]+,477.1533,found 477.1529。
the structure of the target product is deduced from the above data as follows:
Figure BDA0002025606040000091
example 12
Adding 0.2 mmol of 5-phenyl-2-trimethylsilyl-1, 3-bis (trifluoromethanesulfonyloxy) benzene and 0.8 mmol of potassium fluoride into a reaction tube, taking 2 ml of anhydrous tetrahydrofuran as a solvent and a reactant, and stirring at the rotating speed of 630rpm at 120 ℃ for reaction for 10 hours; after the reaction is finished, cooling the reaction liquid to room temperature, adding 4mL of water, extracting with ethyl acetate (5mL multiplied by 3), combining organic phases, drying by using anhydrous magnesium sulfate, filtering, concentrating under reduced pressure to obtain a crude product, and separating and purifying by column chromatography, wherein the eluent of the column chromatography is a mixed solvent of petroleum ether and ethyl acetate in a volume ratio of 10:1 to obtain the target product, and the yield is 53%.
The obtained hydrogen, carbon and fluorine spectra of the target product are shown in fig. 10, 11 and 12, respectively, and the structural characterization data are as follows:
1H NMR(400MHz,CDCl3)δ＝7.56(d,J＝7.6Hz,2H),7.49-7.42(m,3H),6.78(s,2H),4.54-4.50(m,2H),4.32-4.27(m,2H),3.56–3.53(m,2H),3.45-3.40(m,2H),3.27–3.22(m,2H),3.17-3.12(m,2H),2.09–1.98(m,4H),1.88-1.81(m,2H),1.61–1.56(m,2H),1.28–1.20(m,4H)；
13C NMR(100MHz,CDCl3)δ＝161.12,150.61,139.38,129.13,128.98,127.15,120.23(q,J＝326.7Hz),108.61,105.23,70.19,70.13,69.72,26.33,25.55,25.45；
19F NMR(376MHz,CDCl3)δ＝-76.08.
IR(KBr)νmax 2942,2860,1582,1445,1363,1205,1111,677cm-1；
HRMS(ESI)Calcd for C25H31F3O6S[M+Na]+,539.1688,found 539.1686。
the structure of the target product is deduced from the above data as follows:
Figure BDA0002025606040000101
example 13
Adding 0.2 mmol of 5-p-methylphenyl-2-trimethylsilyl-1, 3-bis (trifluoromethanesulfonyloxy) benzene and 0.8 mmol of potassium fluoride into a reaction tube, taking 2 ml of anhydrous tetrahydrofuran as a solvent and a reactant, and stirring at the rotating speed of 630rpm at 120 ℃ for reaction for 10 hours; after the reaction is finished, cooling the reaction liquid to room temperature, adding 4mL of water, extracting with ethyl acetate (5mL multiplied by 3), combining organic phases, drying by using anhydrous magnesium sulfate, filtering, concentrating under reduced pressure to obtain a crude product, and separating and purifying by column chromatography, wherein the eluent of the column chromatography is a mixed solvent of petroleum ether and ethyl acetate in a volume ratio of 10:1 to obtain a target product, and the yield is 55%.
The obtained hydrogen, carbon and fluorine spectra of the target product are shown in fig. 13, 14 and 15, respectively, and the structural characterization data are as follows:
1H NMR(400MHz,CDCl3)δ＝7.46(d,J＝8.0Hz,2H),7.28(d,J＝8.0Hz,2H),6.78(s,2H),4.54-4.48(m,2H),4.31-4.26(m,2H),3.57–3.52(m,2H),3.45–3.40(m,2H),3.26-3.21(m,2H),3.17–3.12(m,2H),2.41(s,3H),2.07–1.94(m,4H),1.88–1.82(m,2H),1.62–1.54(m,2H),1.30–1.18(m,4H)；
13C NMR(100MHz,CDCl3)δ＝161.13,150.55,139.33,136.44,129.68,126.99,120.26(q,J＝326.8Hz),108.39,105.04,70.19,70.13,69.70,26.34,25.55,25.47,21.13；
19F NMR(376MHz,CDCl3)δ＝-76.14.
IR(KBr)νmax 2928,2859,1591,1549,1463,1366,1200,1116cm-1；
HRMS(ESI)Calcd for C26H33F3O6S[M+Na]+,553.1846,found 553.1842。
the structure of the target product is deduced from the above data as follows:
Figure BDA0002025606040000102
example 14
Adding 0.2 mmol of 5-p-ethylphenyl-2-trimethylsilyl-1, 3-bis (trifluoromethanesulfonyloxy) benzene and 0.8 mmol of potassium fluoride into a reaction tube, taking 2 ml of anhydrous tetrahydrofuran as a solvent and a reactant, and stirring at the rotating speed of 630rpm at 120 ℃ for reaction for 10 hours; after the reaction is finished, cooling the reaction liquid to room temperature, adding 4mL of water, extracting with ethyl acetate (5mL multiplied by 3), combining organic phases, drying by using anhydrous magnesium sulfate, filtering, concentrating under reduced pressure to obtain a crude product, and separating and purifying by column chromatography, wherein the eluent of the column chromatography is a mixed solvent of petroleum ether and ethyl acetate in a volume ratio of 10:1, so that the target product is obtained, and the yield is 47%.
The obtained hydrogen, carbon and fluorine spectra of the target product are shown in fig. 16, 17 and 18, respectively, and the structural characterization data are as follows:
1H NMR(400MHz,CDCl3)δ＝7.49(d,J＝7.6Hz,2H),7.31(d,J＝8.0Hz,2H),6.78(s,2H),4.54–4.49(m,2H),4.31–4.26(m,2H),3.57–3.52(m,2H),3.45–3.40(m,2H),3.26-.21(m,2H),3.17–3.12(m,2H),2.72(q,J＝7.6Hz,2H),2.07–1.94(m,4H),1.88-1.80(m,2H),1.62–1.54(m,2H),1.30–1.20(m,7H)；
13C NMR(100MHz,CDCl3)δ161.13,150.60,145.66,136.72,128.51,127.11,120.27(q,J＝326.8Hz),108.42,105.09,70.19,70.13,69.70,28.53,26.35,25.56,25.48,15.41；
19F NMR(376MHz,CDCl3)δ＝-76.14.
IR(KBr)νmax 2935,2862,1589,1442,1371,1206,1116,672cm-1；
HRMS(ESI)Calcd for C27H35F3O6S[M+Na]+,567.2001,found 567.1999。
the structure of the target product is deduced from the above data as follows:
Figure BDA0002025606040000111
example 15
Adding 0.2 mmol of 5-p-trifluoromethylphenyl-2-trimethylsilyl-1, 3-bis (trifluoromethanesulfonyloxy) benzene and 0.8 mmol of potassium fluoride into a reaction tube, taking 2 ml of anhydrous tetrahydrofuran as a solvent and a reactant, and stirring at the rotating speed of 630rpm at 120 ℃ for reaction for 10 hours; after the reaction is finished, cooling the reaction liquid to room temperature, adding 4mL of water, extracting with ethyl acetate (5mL multiplied by 3), combining organic phases, drying by using anhydrous magnesium sulfate, filtering, concentrating under reduced pressure to obtain a crude product, and separating and purifying by column chromatography, wherein the eluent of the column chromatography is a mixed solvent of petroleum ether and ethyl acetate in a volume ratio of 30:1 to obtain a target product, and the yield is 34%.
The obtained hydrogen, carbon and fluorine spectra of the target product are shown in fig. 19, 20 and 21, respectively, and the structural characterization data are as follows:
1H NMR(400MHz,CDCl3)δ＝7.73(d,J＝8.4Hz,2H),7.66(d,J＝8.4Hz,2H),6.76(s,2H),4.54–4.48(m,2H),4.33–4.28(m,2H),3.57–3.52(m,2H),3.45–3.40(m,2H),3.27–3.22(m,2H),3.18–3.13(m,2H),2.09–1.95(m,4H),1.90-1.82(m,2H),1.63-1.55(m,2H),1.27-1.16(m,4H)；
13C NMR(100MHz,CDCl3)δ＝161.35,148.96,143.03,131.12(q,J＝32.5Hz),127.66,125.97(q,J＝3.7Hz),123.91(q,J＝270.7Hz),120.25(q,J＝326.7Hz),109.72,105.43,70.35,70.23,69.95,26.40,25.64,25.59；
19F NMR(376MHz,CDCl3)δ＝-62.70,-75.96.
IR(KBr)νmax 2932,2862,1587,1442,1371,1328,1202,1119cm-1；
HRMS(ESI)Calcd for C20H26F6O6S[M+Na]+,607.1566,found 607.1559。
the structure of the target product is deduced from the above data as follows:
Figure BDA0002025606040000121
example 16
Adding 0.2 mmol of 5-p-methoxyphenyl-2-trimethylsilyl-1, 3-bis (trifluoromethanesulfonyloxy) benzene and 0.8 mmol of potassium fluoride into a reaction tube, taking 2 ml of anhydrous tetrahydrofuran as a solvent and a reactant, and stirring at the rotating speed of 630rpm at 120 ℃ for reaction for 10 hours; after the reaction is finished, cooling the reaction liquid to room temperature, adding 4mL of water, extracting with ethyl acetate (5mL multiplied by 3), combining organic phases, drying by using anhydrous magnesium sulfate, filtering, concentrating under reduced pressure to obtain a crude product, and separating and purifying by column chromatography, wherein the eluent of the column chromatography is a mixed solvent of petroleum ether and ethyl acetate in a volume ratio of 10:1, so that the target product is obtained, and the yield is 57%.
The obtained hydrogen, carbon and fluorine spectra of the target product are shown in fig. 22, 23 and 24, respectively, and the structural characterization data are as follows:
1H NMR(400MHz,CDCl3)δ＝7.51(d,J＝8.0Hz,2H),6.98(d,J＝8.4Hz,2H),6.74(s,2H),4.52–4.48(m,2H),4.30–4.25(m,2H),3.85(s,3H),3.55–3.51(m,2H),3.44–3.39(m,2H),3.25–3.20(m,2H),3.16–3.11(m,2H),2.05–1.97(m,4H),1.86–1.81(m,2H),1.59–1.54(m,2H),1.27–1.19(m,4H)；
13C NMR(101MHz,CDCl3)δ＝161.10,160.5,150.15,131.52,128.35,120.23(q,J＝326.7Hz),114.36,107.85,104.65,70.14,70.09,69.63,55.33,26.30,25.51,25.40；
19F NMR(376MHz,CDCl3)δ＝-76.20；
IR(KBr)νmax 2934,2853,1542,1446,1361,1198,1110,1034cm-1；
HRMS(ESI)Calcd for C26H33F3O7S[M+Na]+,569.1793,found 569.1791。
the structure of the target product is deduced from the above data as follows:
Figure BDA0002025606040000131
example 17
Adding 0.2 mmol of 5-m-methylphenyl-2-trimethylsilyl-1, 3-bis (trifluoromethanesulfonyloxy) benzene and 0.8 mmol of potassium fluoride into a reaction tube, taking 2 ml of anhydrous tetrahydrofuran as a solvent and a reactant, and stirring at the rotating speed of 630rpm at 120 ℃ for reaction for 10 hours; after the reaction is finished, cooling the reaction liquid to room temperature, adding 4mL of water, extracting with ethyl acetate (5mL multiplied by 3), combining organic phases, drying by using anhydrous magnesium sulfate, filtering, concentrating under reduced pressure to obtain a crude product, and separating and purifying by column chromatography, wherein the eluent of the column chromatography is a mixed solvent of petroleum ether and ethyl acetate in a volume ratio of 10:1 to obtain a target product, and the yield is 51%.
The obtained hydrogen, carbon and fluorine spectra of the target product are shown in fig. 25, 26 and 27, respectively, and the structural characterization data are as follows:
1H NMR(400MHz,CDCl3)δ＝7.35(s,3H),7.26(s,1H),6.77(s,2H),4.54-4.50(m,2H),4.30–4.28(m,2H),3.57–3.54(m,2H),3.46-3.41(m,2H),3.25-3.23(m,2H),3.18-3.11(m,2H),2.44(s,3H),2.05–1.98(m,4H),1.87-1.79(m,2H),1.61-1.56(m,2H),1.29–1.21(m,4H)；
13C NMR(100MHz,CDCl3)δ＝161.10,150.84,139.42,138.76,129.90,128.90,127.80,124.32,120.27(q,J＝326.7Hz),108.61,105.30,70.22,70.18,69.76,26.36,25.58,25.51,21.43；
19F NMR(376MHz,CDCl3)δ＝-76.08.
IR(KBr)νmax 2926,2858,1592,1555,1436,1368,1199,1116cm-1；
HRMS(ESI)Calcd for C26H33F3O6S[M+Na]+,553.1847,found 553.1842。
the structure of the target product is deduced from the above data as follows:
Figure BDA0002025606040000141
example 18
Adding 0.2 mmol of 5-o-methylphenyl-2-trimethylsilyl-1, 3-bis (trifluoromethanesulfonyloxy) benzene and 0.8 mmol of potassium fluoride into a reaction tube, taking 2 ml of anhydrous tetrahydrofuran as a solvent and a reactant, and stirring at the rotating speed of 630rpm at 120 ℃ for reaction for 10 hours; after the reaction is finished, cooling the reaction liquid to room temperature, adding 4mL of water, extracting with ethyl acetate (5mL multiplied by 3), combining organic phases, drying by using anhydrous magnesium sulfate, filtering, concentrating under reduced pressure to obtain a crude product, and separating and purifying by column chromatography, wherein the eluent of the column chromatography is a mixed solvent of petroleum ether and ethyl acetate in a volume ratio of 10:1 to obtain a target product, and the yield is 50%.
The obtained hydrogen, carbon and fluorine spectra of the target product are shown in fig. 28, 29 and 30, respectively, and the structural characterization data are as follows:
1H NMR(400MHz,CDCl3)δ＝7.34–7.25(m,3H),7.20(d,J＝7.2Hz,2H),6.55(s,2H),4.46–4.42(m,2H),4.27-4.23(m,2H),3.59–3.54(m,2H),3.44-3.40(m,2H),3.29–3.25(m,2H),3.20–3.16(m,2H),2.30(s,3H),2.07–1.95(m,4H),1.83–1.76(m,2H),1.60–1.55(m,2H),1.34-1.24(m,4H).
13C NMR(100MHz,CDCl3)δ＝160.62,151.65,140.22,134.86,130.62,128.73,128.46,125.99,120.29(q,J＝326.8Hz),108.48,107.29,70.29,70.17,69.67,26.52,25.67,25.38,20.24；
19F NMR(376MHz,CDCl3)δ＝-76.09.
IR(KBr)νmax 2927,2859,1592,1553,1428,1367,1202,1116cm-1；
HRMS(ESI)Calcd for C26H33F3O6S[M+Na]+,553.1844,found 553.1842。
the structure of the target product is deduced from the above data as follows:
Figure BDA0002025606040000151
the above embodiments are preferred embodiments of the present invention, but the present invention is not limited to the above embodiments, and any other changes, modifications, substitutions, combinations, and simplifications which do not depart from the spirit and principle of the present invention should be construed as equivalents thereof, and all such changes, modifications, substitutions, combinations, and simplifications are intended to be included in the scope of the present invention.

Claims (8)

1. A method for synthesizing tetraoxaheterocyclic by utilizing aryne and tetrahydrofuran is characterized by comprising the following steps:
taking 2-trimethylsilyl-1, 3-bis (trifluoromethanesulfonyloxy) benzene or a derivative thereof as an aryne precursor, taking anhydrous tetrahydrofuran as a reactant and a solvent, adding alkali as an accelerator, stirring and reacting at a certain temperature under the protection of an inert atmosphere, and separating and purifying a product after the reaction is finished to obtain a tetraoxaheterocyclic compound;
the reaction equation of the above synthesis method is shown as the following formula:
Figure FDA0003144578260000011
wherein R is hydrogen, 4-methyl, 4-ethyl, 5-methyl, 5-chloro, 5-fluoro, 5-phenyl, 5-naphthyl, 5-p-methylphenyl, 5-p-ethylphenyl, 5-p-trifluoromethylphenyl, 5-p-methoxyphenyl, 5-p-chlorophenyl, 5-m-methylphenyl, 5-o-methylphenyl, 5-m-methoxyphenyl, 5-o-methoxyphenyl or 5- (2, 4-dimethyl) phenyl; TMS means trimethylsilyl, OTf means trifluoromethanesulfonyloxy;
the alkali is at least one of cesium fluoride and potassium fluoride.
2. The method for synthesizing tetraoxaheterocycle using aryne and tetrahydrofuran as claimed in claim 1, wherein: the molar ratio of the aryne precursor to the tetrahydrofuran is 1 (60-240).
3. The method for synthesizing tetraoxaheterocycle using aryne and tetrahydrofuran as claimed in claim 1, wherein: the molar ratio of the aryne precursor to the alkali is 1 (1-8).
4. The method for synthesizing tetraoxaheterocycle using aryne and tetrahydrofuran as claimed in claim 1, wherein: the solvent is anhydrous tetrahydrofuran or a mixed solvent of the anhydrous tetrahydrofuran and any one of anhydrous acetonitrile, anhydrous dimethyl sulfoxide and anhydrous toluene according to the volume ratio of 1: 1.
5. The method for synthesizing tetraoxaheterocycle using aryne and tetrahydrofuran as claimed in claim 1, wherein: the inert atmosphere refers to a nitrogen atmosphere.
6. The method for synthesizing tetraoxaheterocycle using aryne and tetrahydrofuran as claimed in claim 1, wherein: the reaction temperature is 80-130 ℃, and the reaction time is 4-24 h.
7. The method for synthesizing tetraoxaheterocycle using aryne and tetrahydrofuran as claimed in claim 1, wherein the step of separating and purifying comprises: and cooling the reaction liquid to room temperature, washing with water, extracting with ethyl acetate, drying with anhydrous magnesium sulfate, filtering, concentrating under reduced pressure to obtain a crude product, and purifying by column chromatography to obtain the tetraoxaheterocyclic compounds.
8. The method of claim 7, wherein the synthesis of tetraoxaheterocyclic using aryne and tetrahydrofuran is as follows: the column chromatography eluent is a mixed solvent of petroleum ether and ethyl acetate with the volume ratio of (10-30): 1.
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Citations (1)

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US4638097A (en) * 1985-04-23 1987-01-20 Basf Aktiengesellschaft Reducing the content of cyclic oligomeric ethers in polytetramethylene ether glycols or polyoxybutylene polyoxyalkylene glycols

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Publication number Priority date Publication date Assignee Title
US4638097A (en) * 1985-04-23 1987-01-20 Basf Aktiengesellschaft Reducing the content of cyclic oligomeric ethers in polytetramethylene ether glycols or polyoxybutylene polyoxyalkylene glycols

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Binding of Acetylcholine and Tetramethylammonium to a Cyclophane Receptor: Anion’s Contribution to the Cation Interaction;Sandra Bartoli等;《JACS》;20020613;第8307-8315页 *
Metathesis Reaction of Formaldehyde Acetals: An Easy Entry into the Dynamic Covalent Chemistry of Cyclophane Formation;Roberta Cacciapaglia等;《JACS》;20050908;第13666-13671页 *

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