CN118005650A - Method for synthesizing tetrahydroxazolo isoindolinone by photocatalysis - Google Patents
Method for synthesizing tetrahydroxazolo isoindolinone by photocatalysis Download PDFInfo
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- catechol
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- 238000000034 method Methods 0.000 title claims abstract description 31
- 230000002194 synthesizing effect Effects 0.000 title claims abstract description 21
- 230000001699 photocatalysis Effects 0.000 title claims abstract description 19
- 238000007146 photocatalysis Methods 0.000 title claims abstract description 17
- PXZQEOJJUGGUIB-UHFFFAOYSA-N isoindolin-1-one Chemical compound C1=CC=C2C(=O)NCC2=C1 PXZQEOJJUGGUIB-UHFFFAOYSA-N 0.000 title claims description 5
- YCIMNLLNPGFGHC-UHFFFAOYSA-N catechol Chemical compound OC1=CC=CC=C1O YCIMNLLNPGFGHC-UHFFFAOYSA-N 0.000 claims abstract description 44
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims abstract description 39
- 238000003756 stirring Methods 0.000 claims abstract description 25
- -1 tetrahydrooxazoloisoindolinone Chemical compound 0.000 claims abstract description 25
- 238000006243 chemical reaction Methods 0.000 claims abstract description 23
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 claims abstract description 22
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims abstract description 20
- 229910052700 potassium Inorganic materials 0.000 claims abstract description 17
- 239000011591 potassium Substances 0.000 claims abstract description 17
- XKJCHHZQLQNZHY-UHFFFAOYSA-N phthalimide Chemical compound C1=CC=C2C(=O)NC(=O)C2=C1 XKJCHHZQLQNZHY-UHFFFAOYSA-N 0.000 claims abstract description 16
- 239000012074 organic phase Substances 0.000 claims abstract description 15
- 239000012043 crude product Substances 0.000 claims abstract description 14
- 239000002904 solvent Substances 0.000 claims abstract description 14
- 239000003153 chemical reaction reagent Substances 0.000 claims abstract description 13
- 229910000027 potassium carbonate Inorganic materials 0.000 claims abstract description 11
- TXNLQUKVUJITMX-UHFFFAOYSA-N 4-tert-butyl-2-(4-tert-butylpyridin-2-yl)pyridine Chemical compound CC(C)(C)C1=CC=NC(C=2N=CC=C(C=2)C(C)(C)C)=C1 TXNLQUKVUJITMX-UHFFFAOYSA-N 0.000 claims abstract description 10
- 238000001035 drying Methods 0.000 claims abstract description 10
- 229910052757 nitrogen Inorganic materials 0.000 claims abstract description 10
- 239000000047 product Substances 0.000 claims abstract description 10
- 238000004440 column chromatography Methods 0.000 claims abstract description 9
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 7
- 229920006395 saturated elastomer Polymers 0.000 claims abstract description 7
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 claims abstract description 4
- 238000001914 filtration Methods 0.000 claims abstract description 4
- 239000000376 reactant Substances 0.000 claims abstract description 4
- 238000007789 sealing Methods 0.000 claims abstract description 4
- 238000005406 washing Methods 0.000 claims abstract description 4
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N dimethyl sulfoxide Natural products CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 claims description 18
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 12
- 238000002390 rotary evaporation Methods 0.000 claims description 12
- 239000003795 chemical substances by application Substances 0.000 claims description 6
- 238000002386 leaching Methods 0.000 claims description 6
- 239000011259 mixed solution Substances 0.000 claims description 6
- 239000003208 petroleum Substances 0.000 claims description 6
- 239000000243 solution Substances 0.000 claims description 6
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 claims description 4
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 claims description 4
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 claims description 3
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 claims description 3
- XUIMIQQOPSSXEZ-UHFFFAOYSA-N Silicon Chemical compound [Si] XUIMIQQOPSSXEZ-UHFFFAOYSA-N 0.000 claims description 3
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 3
- 230000015572 biosynthetic process Effects 0.000 claims description 3
- 150000001875 compounds Chemical class 0.000 claims description 3
- 125000004184 methoxymethyl group Chemical group [H]C([H])([H])OC([H])([H])* 0.000 claims description 3
- 239000000741 silica gel Substances 0.000 claims description 3
- 229910002027 silica gel Inorganic materials 0.000 claims description 3
- 229910052710 silicon Inorganic materials 0.000 claims description 3
- 239000010703 silicon Substances 0.000 claims description 3
- 238000003786 synthesis reaction Methods 0.000 claims description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 3
- 238000010025 steaming Methods 0.000 abstract 1
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 12
- 238000007363 ring formation reaction Methods 0.000 description 7
- CHZXTOCAICMPQR-UHFFFAOYSA-N 2-(2-bromoethyl)isoindole-1,3-dione Chemical compound C1=CC=C2C(=O)N(CCBr)C(=O)C2=C1 CHZXTOCAICMPQR-UHFFFAOYSA-N 0.000 description 5
- 238000000926 separation method Methods 0.000 description 4
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 3
- 238000005160 1H NMR spectroscopy Methods 0.000 description 3
- 229920001971 elastomer Polymers 0.000 description 3
- 238000000605 extraction Methods 0.000 description 3
- 239000007788 liquid Substances 0.000 description 3
- 239000011734 sodium Substances 0.000 description 3
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical class O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 3
- 230000008878 coupling Effects 0.000 description 2
- 238000010168 coupling process Methods 0.000 description 2
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- 125000000524 functional group Chemical group 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 238000010189 synthetic method Methods 0.000 description 2
- KAUMDYDNLPQESC-UHFFFAOYSA-N 3-hydroxy-2,3-dihydroisoindol-1-one Chemical compound C1=CC=C2C(O)NC(=O)C2=C1 KAUMDYDNLPQESC-UHFFFAOYSA-N 0.000 description 1
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 238000010523 cascade reaction Methods 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 230000018044 dehydration Effects 0.000 description 1
- 238000006297 dehydration reaction Methods 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 150000002500 ions Chemical class 0.000 description 1
- 229930014626 natural product Natural products 0.000 description 1
- 230000000269 nucleophilic effect Effects 0.000 description 1
- 238000005580 one pot reaction Methods 0.000 description 1
- 125000002734 organomagnesium group Chemical group 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
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Abstract
The invention provides a method for synthesizing tetrahydrooxazoloisoindolinone by photocatalysis, which comprises the following steps: s1: adding a stirrer, N- (2-haloethyl) phthalimide, potassium carbonate and Ir [ dF (CF 3)ppy]2(dtbbpy)PF6 and alkyl bis (catechol) silicate-18-crown ether-6-potassium reagent into a reactor, sealing, S2 adding a dry solvent into the reactant, vacuumizing and recharging nitrogen, S3 placing the reactor under a blue LED lamp for the first time, adding a saturated K 2CO3 solution after finishing the reaction, continuously stirring, extracting by ethyl acetate, merging the organic phases, washing the organic phases by saturated saline solution, collecting the obtained organic phases, further drying, filtering and steaming to remove the solvent soon to obtain a crude product, and S4 separating the crude product by column chromatography to obtain the product.
Description
Technical Field
The invention relates to the technical field of photocatalytic synthesis, in particular to a method for synthesizing tetrahydrooxazoloisoindolinone by photocatalysis.
Background
Isoindolinones are a common class of dominant backbone structures that are ubiquitous in many natural product and drug molecular structures. At present, three main methods for synthesizing related structures of tetrahydrooxazoloisoindolinone are reported in the literature:
(1) Nucleophilic addition-cyclization "one pot" synthesis of N- (2-bromoethyl) phthalimide with organomagnesium reagent (method one):
(2)
(2) Intramolecular dehydration cyclization of 3-hydroxyisoindolinone (method two):
(3) Photo-promoted addition-cyclization reaction of N- (2-bromoethyl) phthalimide and potassium carboxylate salt (method three):
in the first two methods, a magnesium metal reagent is needed to be synthesized, and the anhydrous and anaerobic operation is strict and the functional group compatibility is not strong. In the third method, besides the strong ultraviolet light, the products are always two products of cyclization and non-cyclization, and the dependency on the reaction conditions is strong. Furthermore, compared with the first two methods, the method has not been developed for the universality study of related tetrahydrooxazoloisoindolinone derivatives. Therefore, the development of a synthetic method of the tetrahydrooxazoloisoindolinone derivative with high universality, simplicity, convenience and high efficiency is very important and urgent by combining the problems and the defects in the prior literature report and research.
Disclosure of Invention
The invention aims to provide a method for synthesizing tetrahydrooxazolo isoindolinone by photocatalysis, which solves the problems of strong dependence on reaction conditions, complicated steps, high operation requirement and poor compatibility of the conventional method.
In order to solve the problems, the invention provides a method for synthesizing tetrahydrooxazoloisoindolinone by photocatalysis, which comprises the following steps:
S1: adding a stirrer, N- (2-halogenated ethyl) phthalimide, potassium carbonate and Ir [ dF (CF 3)ppy]2(dtbbpy)PF6 and alkyl bis (catechol) silicate-18-crown ether-6-potassium reagent into a reactor, and sealing the reactor;
S2: adding a dry solvent into the reactant obtained in the step S1, vacuumizing the reactor and recharging nitrogen;
S3: placing the reactor subjected to the S2 treatment under a blue LED lamp for first stirring, adding a saturated K 2CO3 solution after finishing the reaction, continuously stirring to remove catechol, extracting by ethyl acetate, merging organic phases, washing with saturated saline water, collecting the obtained organic phases, further drying, filtering, and removing the solvent by rotary evaporation to obtain a crude product;
S4: and (3) separating the crude product treated in the step (S3) by column chromatography by taking a mixed solution of petroleum ether and ethyl acetate as a leaching agent, and finally performing rotary evaporation to obtain the product tetrahydroxazoloisoindolinone compound.
In a preferred embodiment, in the step S1, the molar ratio of the N- (2-haloethyl) phthalimide to Ir [ dF (CF 3)ppy]2(dtbbpy)PF6) is 1:0.02-0.03.
In a preferred embodiment, in the step S1, the molar ratio of the N- (2-haloethyl) phthalimide to the bis-catechol alkyl high valence silicon reagent is 1:1.5-2.5.
In a preferred embodiment, in the step S1, the molar ratio of the N- (2-haloethyl) phthalimide to the potassium carbonate is 1:1.0-2.0.
Preferably, in the step S1, the alkyl bis (catechol) silicate-18-crown ether-6-potassium reagent includes one of allyl bis (catechol) silicate-18-crown ether-6-potassium, benzyl bis (catechol) silicate-18-crown ether-6-potassium, and methoxymethyl bis (catechol) silicate-18-crown ether-6-potassium.
In a preferred embodiment, in the step S2, the drying solvent is dimethyl sulfoxide, and the molar ratio of the N- (2-haloethyl) phthalimide to the dimethyl sulfoxide is 1:350-450.
In a preferred embodiment, in the step S2, the number of times of vacuumizing and recharging the nitrogen is 3.
In a preferred embodiment, in the step S3, the blue LED lamp is a blue LED lamp with a wavelength of 3-30W, and the condition of the first stirring is stirring at room temperature for 24 hours, and the condition of the continuous stirring is stirring at room temperature for 30 minutes.
Preferably, in the step S3, the drying process conditions are as follows: dried by adding anhydrous sodium sulfate, anhydrous potassium carbonate or anhydrous magnesium sulfate.
As a preferable scheme, the length of the silica gel column in the column chromatography separation is 10cm.
As a preferable scheme, the reaction formula for synthesizing the tetrahydrooxazoloisoindolinone by photocatalysis is as follows:
Compared with the prior art, the invention has the beneficial effects that: the invention provides a preparation method for synthesizing tetrahydroxazolo isoindolinone by photocatalysis free radical-free radical coupling/cyclization tandem, which utilizes a free radical-free radical coupling/ion cyclization tandem reaction strategy to synthesize the tetrahydroxazolo isoindolinone compound for the first time under the mild condition of redox neutrality; the method has the advantages of mild reaction conditions, good functional group compatibility, simple operation, wide substrate application range and the like.
Detailed Description
The following description of the present invention will be made clearly and fully, and it is apparent that the embodiments described are some, but not all, of the embodiments of the present invention. All other embodiments, which can be made by those skilled in the art based on the embodiments of the invention without making any inventive effort, are intended to be within the scope of the invention.
The invention provides a method for synthesizing tetrahydrooxazoloisoindolinone by photocatalysis, which comprises the following steps:
S1: adding a stirrer, N- (2-halogenated ethyl) phthalimide, potassium carbonate and Ir [ dF (CF 3)ppy]2(dtbbpy)PF6 and alkyl bis (catechol) silicate-18-crown ether-6-potassium reagent into a reactor, and sealing the reactor;
S2: adding a dry solvent into the reactant obtained in the step S1, vacuumizing the reactor and recharging nitrogen;
S3: placing the reactor subjected to the S2 treatment under a blue LED lamp for first stirring, adding a saturated K 2CO3 solution after finishing the reaction, continuously stirring to remove catechol, extracting by ethyl acetate, merging organic phases, washing with saturated saline water, collecting the obtained organic phases, further drying, filtering, and removing the solvent by rotary evaporation to obtain a crude product;
S4: and (3) separating the crude product treated in the step (S3) by column chromatography by taking a mixed solution of petroleum ether and ethyl acetate as a leaching agent, and finally performing rotary evaporation to obtain the product tetrahydroxazoloisoindolinone compound.
Preferably, in the step S1, the molar ratio of the N- (2-haloethyl) phthalimide to Ir [ dF (CF 3)ppy]2(dtbbpy)PF6) is 1:0.02-0.03.
Preferably, in the step S1, the molar ratio of the N- (2-haloethyl) phthalimide to the bis-catechol alkyl high valence silicon reagent is 1:1.5-2.5.
Preferably, in the step S1, the molar ratio of the N- (2-haloethyl) phthalimide to the potassium carbonate is 1:1.0-2.0.
Preferably, in the step S1, the alkyl bis (catechol) silicate-18-crown-6-potassium reagent includes one of allyl bis (catechol) silicate-18-crown-6-potassium, benzyl bis (catechol) silicate-18-crown-6-potassium, and methoxymethyl bis (catechol) silicate-18-crown-6-potassium.
Preferably, in the step S2, the drying solvent is dimethyl sulfoxide, and the molar ratio of the N- (2-haloethyl) phthalimide to the dimethyl sulfoxide is 1:350-450.
Preferably, in the step S2, the number of times of vacuumizing and recharging nitrogen is 3.
Preferably, in the step S3, the blue LED lamp is a blue LED lamp with a wavelength of 3-30W, and the condition of the first stirring is stirring at room temperature for 24 hours, and the condition of the continuous stirring is stirring at room temperature for 30 minutes.
Preferably, in the step S3, the drying process conditions are as follows: dried by adding anhydrous sodium sulfate, anhydrous potassium carbonate or anhydrous magnesium sulfate.
Preferably, the length of the silica gel column in the column chromatography separation is 10cm.
Preferably, the reaction formula for synthesizing the tetrahydrooxazoloisoindolinone by photocatalysis is as follows:
The following description of the above technical scheme of the present invention is developed in conjunction with specific reagents and reaction conditions, and provides analytical data of the products prepared in the following examples:
example 1
S1: a10 mL dry reaction tube was taken, and a stirrer, N- (2-bromoethyl) phthalimide (50.6 mg,0.2mmol,1.0 equiv), K 2CO3 (27.6 mg,1.0 equiv) and Ir [ dF (CF 3)ppy]2(dtbbpy)PF6 (4.5 mg, 0.04 mmol,0.02 equiv), a rubber stopper, and a glove box were added.
S2: the reaction tube was removed, dried DMSO (6 mL) was added, and the nitrogen was evacuated and repeated three times.
S3: the reaction tube was placed under a blue LED lamp at room temperature of 9W, stirred, and cooled with a fan. After stirring at room temperature for 24 hours, the reaction was terminated, a saturated K 2CO3 solution (5 mL) was added, stirring was performed for 30 minutes, and after removing a large amount of catechol, extraction was performed with ethyl acetate (4X 5 mL), and the combined organic phases were washed with saturated brine. The organic phase was collected, dried over anhydrous Na 2SO4, filtered and the solvent was removed by rotary evaporation to give the crude product.
S4: and (3) performing column chromatography separation on the crude product by taking a mixed solution of petroleum ether and ethyl acetate as a leaching agent, and finally performing rotary evaporation to obtain 26.3mg of allyl-substituted tetrahydrooxazolo isoindolinone, wherein the yield is 61% and the product is yellow liquid. Analytical data were as follows:
1H NMR(500MHz,CDCl3)δ7.76-7.74(m,1H),7.60-7.54(m,2H),7.52-7.48(m,1H),5.70-5.61(m,1H),5.13-5.09(m,1H),5.06-5.04(m,1H),4.26-4.23(m,1H),4.18-4.14(m,1H),4.05(q,J＝7.8Hz,1H),3.46-3.40(m,1H),2.78(d,J＝7.1Hz,2H);13C NMR(126MHz,CDCl3)δ173.7,146.3,133.0,132.0,131.4,130.0,124.1,122.7,119.7,99.8,69.6,42.6,40.5;HRMS(ESI)[M+H]+:calculated for C13H14NO2:216.1025,found 216.1019.
Example two
S1: a10 mL dry reaction tube was taken, and a stirrer, N- (2-bromoethyl) phthalimide (50.6 mg,0.2mmol,1.0 equiv), K 2CO3 (27.6 mg,1.0 equiv) and Ir [ dF (CF 3)ppy]2(dtbbpy)PF6 (4.5 mg, 0.04 mmol,0.02 equiv), a rubber stopper, and a glove box were added.
S2: the reaction tube was removed, dried DMSO (6 mL) was added, and the nitrogen was evacuated and repeated three times.
S3: the reaction tube was placed under a blue LED lamp at room temperature of 9W, stirred, and cooled with a fan. After stirring at room temperature for 24 hours, the reaction was terminated, a saturated K 2CO3 solution (5 mL) was added, stirring was performed for 30 minutes, and after removing a large amount of catechol, extraction was performed with ethyl acetate (4X 5 mL), and the combined organic phases were washed with saturated brine. The organic phase was collected, dried over anhydrous Na 2SO4, filtered and the solvent was removed by rotary evaporation to give the crude product.
S4: and (3) separating the crude product by column chromatography by taking a mixed solution of petroleum ether and ethyl acetate as a leaching agent, and finally performing rotary evaporation to obtain 18.2mg of benzyl-substituted tetrahydrooxazolo isoindolinone, wherein the yield is 34% and the product is yellow liquid. Analytical data were as follows:
1H NMR(500MHz,CDCl3)δ7.71(d,J＝7.5Hz,1H),7.60-7.57(m,1H),7.51-7.48(m,2H),7.26-7.22(m,5H),4.03-3.97(m,2H),3.94-3.90(m,1H),3.39(d,J＝13.8Hz,1H),3.16(d,J＝13.9Hz,1H),2.84-2.78(m,1H);13CNMR(126MHz,CDCl3)δ173.9,147.1,135.2,133.0,131.8,130.6,130.0,128.1,127.0,124.2,122.6,100.5,69.8,43.2,43.1.
Example III
S1: a10 mL dry reaction tube was taken, and a stirrer, N- (2-bromoethyl) phthalimide (50.6 mg,0.2mmol,1.0 equiv), K 2CO3 (27.6 mg,1.0 equiv) and Ir [ dF (CF 3)ppy]2(dtbbpy)PF6 (4.5 mg, 0.04 mmol,0.02 equiv), a rubber stopper, and a glove box were added.
S2: the reaction tube was removed, dried DMSO (6 mL) was added, and the nitrogen was evacuated and repeated three times.
S3: the reaction tube was placed under a blue LED lamp at room temperature of 9W, stirred, and cooled with a fan. After stirring at room temperature for 24 hours, the reaction was terminated, a saturated K 2CO3 solution (5 mL) was added, stirring was performed for 30 minutes, and after removing a large amount of catechol, extraction was performed with ethyl acetate (4X 5 mL), and the combined organic phases were washed with saturated brine. The organic phase was collected, dried over anhydrous Na 2SO4, filtered and the solvent was removed by rotary evaporation to give the crude product.
S4: and (3) performing column chromatography separation on the crude product by taking a mixed solution of petroleum ether and ethyl acetate as a leaching agent, and finally performing rotary evaporation to obtain 26.3mg of methoxymethyl-substituted tetrahydrooxazolo-isoindolinone, wherein the yield is 60% and the product is yellow liquid. Analytical data were as follows:
1H NMR(500MHz,CDCl3)δ7.77(d,J＝7.5Hz,1H),7.62-7.57(m,2H),7.54-7.51(m,1H),4.33-4.30(m,1H),4.17-4.13(m,1H),4.06(q,J＝7.7Hz,1H),3.78(d,J＝10.5Hz,1H),3.73(d,J＝10.5Hz,1H),3.52-3.47(m,1H),3.43(s,3H);13C NMR(126MHz,CDCl3)δ173.8,144.9,133.1,132.2,130.4,124.3,123.1,98.6,74.8,70.3,59.9,43.2;HRMS(ESI)[M+H]+:calculated for C12H14NO3:220.0974,found 220.0971.
The 9W blue LED lamp adopted in the embodiment can be replaced by a 3-30W blue LED lamp, and anhydrous sodium sulfate can be replaced by anhydrous potassium carbonate and anhydrous magnesium sulfate.
Through the above examples, the invention further proves that the synthetic method of the tetrahydroxazoloisoindolinone derivative has high universality, simplicity, convenience and high efficiency, and has higher commercial value and popularization value.
The above is merely exemplary embodiments of the present invention, and the scope of the present invention is not limited in any way. All technical schemes formed by adopting equivalent exchange or equivalent substitution fall within the protection scope of the invention.
Although the present disclosure is described above, the scope of protection of the present disclosure is not limited thereto. Various changes and modifications may be made by one skilled in the art without departing from the spirit and scope of the disclosure, and these changes and modifications will fall within the scope of the invention.
Claims (10)
1. A method for synthesizing tetrahydrooxazoloisoindolinone by photocatalysis is characterized in that: the method comprises the following steps:
S1: adding a stirrer, N- (2-halogenated ethyl) phthalimide, potassium carbonate and Ir [ dF (CF 3)ppy]2(dtbbpy)PF6 and alkyl bis (catechol) silicate-18-crown ether-6-potassium reagent into a reactor, and sealing the reactor;
S2: adding a dry solvent into the reactant obtained in the step S1, vacuumizing the reactor and recharging nitrogen;
S3: placing the reactor subjected to the S2 treatment under a blue LED lamp for first stirring, adding a saturated K 2CO3 solution after finishing the reaction, continuously stirring to remove catechol, extracting by ethyl acetate, merging organic phases, washing with saturated saline water, collecting the obtained organic phases, further drying, filtering, and removing the solvent by rotary evaporation to obtain a crude product;
S4: and (3) separating the crude product treated in the step (S3) by column chromatography by taking a mixed solution of petroleum ether and ethyl acetate as a leaching agent, and finally performing rotary evaporation to obtain the product tetrahydroxazoloisoindolinone compound.
2. The method for synthesizing the tetrahydrooxazoloisoindolinone by photocatalysis according to claim 1, wherein the method comprises the following steps: in the step S1, the molar ratio of the N- (2-halogenated ethyl) phthalimide to Ir [ dF (CF 3)ppy]2(dtbbpy)PF6) is 1:0.02-0.03.
3. The method for synthesizing the tetrahydrooxazoloisoindolinone by photocatalysis according to claim 1, wherein the method comprises the following steps: in the step S1, the molar ratio of the N- (2-halogenated ethyl) phthalimide to the bis-catechol alkyl high-valence silicon reagent is 1:1.5-2.5.
4. The method for synthesizing the tetrahydrooxazoloisoindolinone by photocatalysis according to claim 1, wherein the method comprises the following steps: in the step S1, the molar ratio of the N- (2-halogenated ethyl) phthalimide to the potassium carbonate is 1:1.0-2.0.
5. The method for synthesizing the tetrahydrooxazoloisoindolinone according to claim 1, wherein in the step S1, the alkyl bis (catechol) silicate-18-crown-6-potassium reagent comprises one of allyl bis (catechol) silicate-18-crown-6-potassium, benzyl bis (catechol) silicate-18-crown-6-potassium, methoxymethyl bis (catechol) silicate-18-crown-6-potassium.
6. The method for synthesizing the tetrahydrooxazoloisoindolinone by photocatalysis according to claim 1, wherein the method comprises the following steps: in the step S2, the drying solvent is dimethyl sulfoxide, and the molar ratio of the N- (2-halogenated ethyl) phthalimide to the dimethyl sulfoxide is 1:350-450.
7. The method for synthesizing the tetrahydrooxazoloisoindolinone according to claim 1, wherein in the step S2, the number of times of vacuumizing and recharging nitrogen is 3.
8. The method for synthesizing the tetrahydrooxazoloisoindolinone by photocatalysis according to claim 1, wherein in the step S3, the blue LED lamp is a blue LED lamp with a weight of 3-30W, the condition of the first stirring is stirring at room temperature for 24 hours, and the condition of the continuous stirring is stirring at room temperature for 30 minutes; the conditions of the drying treatment are as follows: dried by adding anhydrous sodium sulfate, anhydrous potassium carbonate or anhydrous magnesium sulfate.
9. The method for synthesizing the tetrahydrooxazoloisoindolinone according to claim 1, wherein in step S4, the silica gel column is 10cm in length.
10. The method for photocatalytic synthesis of tetrahydrooxazoloisoindolinone according to any one of claims 1 to 9, wherein: the reaction general formula for synthesizing the tetrahydroxazolo isoindolinone by photocatalysis is as follows:
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