CN109678810B - 1,2-oxygen nitrogen heterocyclic butane compound and preparation method and application thereof - Google Patents
1,2-oxygen nitrogen heterocyclic butane compound and preparation method and application thereof Download PDFInfo
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Abstract
The invention discloses a 1,2-oxygen nitrogen heterocyclic butane compound and a preparation method and application thereof. The compound III is obtained by reacting N-hydroxyphthalimide with 1,2-dibromoethane and triethylamine; reacting the compound III with hydrobromic acid to obtain a yellow compound IV; compound IV, pyridine and halide R 1 Reacting X to obtain a compound V; and reacting the compound V with sodium hydride to obtain 1,2-oxazacyclobutane compounds. The 1,2-oxygen nitrogen heterocyclic butane compound can be used for aminomethylation or hydroxymethylation of a 1-pyrimidyl indole compound, and the reaction process has the advantages of good regioselectivity, high yield, simple process conditions, mild and green reaction conditions, high atom economy, wide substrate application range and the like.
Description
Technical Field
The invention belongs to the technical field of organic synthesis methodology, and particularly relates to a 1,2-oxazacyclobutane compound, and a preparation method and application thereof.
Background
Aminomethyl and hydroxymethyl fragment aromatic compounds widely exist in natural products, drug molecules and functional materials with biological activity, and a method for efficiently and accurately introducing aminomethyl and hydroxymethyl into an aromatic system needs to be found in the field of organic synthesis.
Current methods for introducing aminomethyl and hydroxymethyl groups into aromatic compounds include: (1) Mannich reaction; (2) Nucleophilic addition reaction of high activity aryl organic metal reagent to imine or aldehyde; (3) The transition metal catalyzes the cross-coupling reaction of the aryl halide with the activated amine or aldehyde. However, these three types of reactions have certain limitations. For example, the substrate range of the Mannich reaction is limited to aromatic compounds containing electron donating groups, and the chemoselectivity is poor; the preparation of aryl organometallic reagents requires strict anhydrous and oxygen-free operation and the functional group tolerance of the substrate is poor; the transition metal catalyzed cross-coupling reaction requires the preparation of aryl halides, and the reaction ends up producing waste of halides, which is less economical to atom.
Therefore, the prior art is lack of a reagent for selectively aminomethylating and hydroxymethylating aromatic compounds, which has the advantages of high efficiency, atom economy, mild conditions and wide substrate application range.
Disclosure of Invention
The invention aims to provide 1,2-oxazetidine compounds.
The invention also aims to provide a preparation method of the 1,2-oxazacyclobutane compound.
The invention further aims to provide the application of the 1,2-oxazacyclobutanes compound in aminomethylation of 1-pyrimidyl indole compound.
The invention further aims to provide the application of the 1,2-oxazacyclobutanes compound in the hydroxymethylation of the 1-pyrimidyl indole compound.
The invention is realized by the following steps of providing a 1,2-oxazacyclobutane compound, wherein the chemical structural formula of the compound is shown as the following formula (I):
in the formula (I), R 1 Is p-toluenesulfonyl, benzenesulfonyl, p-fluorobenzenesulfonyl, p-chlorobenzenesulfonyl, p-bromobenzenesulfonyl, p-trifluoromethylbenzenesulfonyl, p-methoxybenzenesulfonyl, p-tert-butylbenzenesulfonyl, m-bromobenzenesulfonyl, 2,4,6-trimethylbenzenesulfonyl, 2-naphthalenesulfonyl, tert-butoxycarbonyl or benzyloxycarbonyl.
Preferably, the method comprises the steps of:
(1) Adding 1,2-dibromoethane and triethylamine into an N, N-dimethylformamide solution containing a compound II, stirring at room temperature until a reaction solution becomes colorless, collecting a solid precipitated from the reaction solution, and recrystallizing to obtain a compound III; wherein the compound II is N-hydroxyphthalimide, and the molar volume ratio of the N-hydroxyphthalimide to the N, N-dimethylformamide solution to the dibromoethane to the triethylamine is 60mmol:80mL of: 120mmol:120mmol of the total weight of the solution;
(2) Adding hydrobromic acid with the mass concentration of 48% into a glacial acetic acid solution of the compound III, stirring and reacting for 5 minutes at 130 ℃, cooling, filtering, and concentrating the filtrate to obtain a yellow compound IV; wherein the molar volume ratio of the compound III to the glacial acetic acid solution to the hydrobromic acid is 120mmol:10mL of: 15mL;
(3) Pyridine is added into the compound IV, the mixture is stirred and reacted for 5 minutes at room temperature, and then the halogenated substance R is added into the reaction liquid 1 X, stirring for 5 hours at room temperature, dropwise adding 1.0M hydrochloric acid solution into the reaction solution to neutrality, extracting, and purifying by column chromatography to obtain a compound V; wherein the molar volume ratio of the compound IV to pyridine to halide is 8.7mmol:15mL of: 20.9mmol; the halogen compound R 1 In X, R 1 Is p-toluenesulfonyl, benzenesulfonyl, p-fluorobenzenesulfonyl, p-chlorobenzenesulfonyl, p-bromobenzenesulfonyl, p-trifluoromethylbenzenesulfonyl, p-methoxybenzenesulfonyl, p-tert-butylbenzenesulfonyl, m-bromobenzenesulfonyl, 2,4,6-trimethylbenzenesulfonyl, 2-naphthalenesulfonyl, tert-butoxycarbonyl or benzyloxycarbonyl, and X is a halogen element;
(4) Adding 2-3 batches of mineral oil with the mass concentration of 60% of sodium hydride into the anhydrous tetrahydrofuran solution of the compound V, stirring for 1.5 hours at room temperature, dropwise adding 1.0M hydrochloric acid solution into the reaction mixture until the reaction mixture is neutral, and extracting and purifying by column chromatography to obtain a compound I; wherein the molar volume ratio of the compound V, the anhydrous tetrahydrofuran solution and the sodium hydride is 0.83mmol:20mL of: 1.87mmol.
Preferably, in the step (1), the collecting and recrystallizing of the solid precipitated in the reaction solution are specifically: filtering out precipitated solid from the reaction solution, diluting the filtrate with ice water, filtering out the precipitated solid, combining the precipitated solid, and recrystallizing the precipitate with ethanol;
in the step (3), the organic matter is extracted by ethyl acetate, and the mass ratio of ethyl acetate/petroleum ether in column chromatography is 1:3;
in the step (4), the organic matter is extracted by ethyl acetate, and the mass ratio of ethyl acetate/petroleum ether in column chromatography is 1:2.
the invention further discloses application of the 1,2-oxygen nitrogen heterocyclic butane compound in aminomethylation or hydroxymethylation of a 1-pyrimidyl indole compound.
Preferably, the chemical structural formula of the 1-pyrimidyl indole compound is shown as the following formula:
in the above formula, R 2 Is methyl, methoxy, ester group, halogen, nitro or amino.
Preferably, the aminomethylation process comprises the steps of: adding a 1-pyrimidyl indole compound and a 1,2-oxazacyclobutane compound into an organic solvent, adding a catalyst and an additive, stirring and reacting at 40-80 ℃ for 0.5-3 hours, concentrating a reaction solution, removing the organic solvent from the concentrated solution, and performing column chromatography to obtain a 1-pyrimidyl-2-aminomethyl compound; wherein the catalyst is a cobalt complex; the additive is alkali;
the molar volume ratio of the 1-pyrimidyl indole compound to 1,2-oxazacyclobutane compound, the organic solvent, the catalyst and the additive is 1.0mmol:2.0mmol:10mL of: 0.05mmol:0.1mmol.
Preferably, the 1-pyrimidyl indole compound is at least one of 1- (2-pyrimidyl) indole, 1- (2-pyrimidyl) 2-methylindole, 1- (2-pyrimidyl) -4-bromoindole, 1- (2-pyrimidyl) -4-methoxyindole, 1- (2-pyrimidyl) -4-benzyloxyindole, 1- (2-pyrimidyl) -4-aminoindole, 1- (2-pyrimidyl) -4-nitroindole, 4- (1- (2-pyrimidyl)) methyl indole carboxylate, 1- (2-pyrimidyl) -5-fluoroindole, 1- (2-pyrimidyl) -5-chloroindole, 1- (2-pyrimidyl) -5-iodoindole, 1- (2-pyrimidyl) -6-fluoroindole, and 1- (2-pyrimidyl) -6-methoxyindole.
Preferably, the hydroxymethylation process is specifically as follows: adding a 1-pyrimidyl indole compound and a 1,2-oxazacyclobutane compound into an organic solvent, adding a catalyst and an additive, stirring and reacting at 40-80 ℃ for 0.5-3 hours, concentrating a reaction solution, removing the organic solvent from the concentrated solution, and performing column chromatography to obtain a 1-pyrimidyl-2-aminomethyl compound; wherein the catalyst is a cobalt complex; the additive is alkali;
the molar volume ratio of the 1-pyrimidyl indole compound to 1,2-oxazacyclobutane compound, the organic solvent, the catalyst and the additive is 1.0mmol:1.1mmol:10mL of: 0.05mmol:0.1mmol.
Preferably, the organic solvent is at least one of acetonitrile, 1,2-dichloroethane, dichloromethane, chloroform, chlorobenzene, dimethyl sulfoxide, toluene, trifluorotoluene, mesitylene, ethanol, acetic acid, 1,4-dioxane and tetrahydrofuran;
the cobalt complex is Co (OAc) 2 、Co(acac) 3 、CoCl 2 、[Cp*Co(CO)I 2 ]、[Cp*Co(C 6 H 6 )](PF 6 ) 2 At least one of;
the alkali is at least one of potassium acetate, sodium carbonate, potassium carbonate, cesium carbonate, sodium bicarbonate, potassium phosphate, lithium phosphate, dipotassium hydrogen phosphate, potassium dihydrogen phosphate, sodium benzoate, sodium hydroxide and lithium hydroxide.
Preferably, the organic solvent is toluene or ethanol; the cobalt complex is pentamethylcyclopentadienyl carbonyl diiodo cobalt; the base is potassium acetate.
The invention overcomes the defects of the prior art and provides 1,2-oxygen nitrogen heterocyclic butane compounds, a preparation method and application thereof. The 1,2-oxygen nitrogen heterocyclic butane compound of the present invention has the structural formula shown in the following formula (I):
in the formula (I), R 1 Is p-toluenesulfonyl, benzenesulfonyl, p-fluorobenzenesulfonyl or p-chloroBenzenesulfonyl, p-bromobenzenesulfonyl, p-trifluoromethylbenzenesulfonyl, p-methoxybenzenesulfonyl, p-tert-butylbenzenesulfonyl, m-bromobenzenesulfonyl, 2,4,6-trimethylbenzenesulfonyl, 2-naphthalenesulfonyl, tert-butoxycarbonyl, or benzyloxycarbonyl.
The preparation process of the 1,2-oxygen nitrogen heterocyclic butane compound is shown as the following reaction equation:
the invention further discloses an application of the 1,2-oxazacyclobutane compound in aminomethylation or hydroxymethylation of the 1-pyrimidyl indole compound, wherein the structural formula of the 1-pyrimidyl indole compound is shown as the following formula:
in the above formula, R 2 Is methyl, methoxy, ester group, halogen, nitro or amino.
The aminomethylation process of the 1-pyrimidyl indole compound is shown as the following reaction equation:
the hydroxymethylation process of the 1-pyrimidyl indole compound is shown as the following reaction equation:
compared with the defects and shortcomings of the prior art, the invention has the following beneficial effects: the invention provides a reagent for efficiently and selectively aminomethylating and hydroxymethylating aromatic compounds, provides potential value for the synthesis of bioactive molecules containing aminomethylating and hydroxymethyl, and has the advantages of good regioselectivity, high yield, simple process condition, mild reaction condition, greenness, high atom economy, wide substrate application range and the like.
Drawings
FIG. 1 is a NMR spectrum of N-p-toluenesulfonyl-1,2-oxetane in example 1 of this invention;
FIG. 2 is a NMR spectrum of N-p-toluenesulfonyl-1,2-oxetane in example 1 of this invention;
FIG. 3 is a NMR spectrum of 1- (-2-pyrimidinyl) -2-p-toluenesulfonamide methylindole in example 4 of the present invention;
FIG. 4 is a NMR spectrum of 1- (-2-pyrimidinyl) -2-p-toluenesulfonamide methylindole in example 4 of the present invention;
FIG. 5 is a NMR spectrum of 1- (2-pyrimidinyl) -2-hydroxymethyl indole in example 7 of the present invention;
FIG. 6 is a NMR spectrum of 1- (2-pyrimidinyl) -2-hydroxymethyl indole in example 7 of the present invention.
Detailed Description
In order to make the objects, technical solutions and advantages of the present invention more apparent, the present invention is described in further detail below with reference to the accompanying drawings and embodiments. It should be understood that the specific embodiments described herein are merely illustrative of the invention and do not limit the invention.
The amount relationship of each substance involved in each step in the following examples is obtained by conversion of reaction equations, and there may be slight variations in the actual operation process, and should not be used to limit only the amount of each substance.
Example 1,2 preparation of Oxetane Compounds
(1) Adding 120mmol 1, 2-dibromoethane and 120mmol triethylamine into 80mL N, N-dimethylformamide solution containing 60mmol N-hydroxyphthalimide, stirring at room temperature until the reaction solution becomes colorless, collecting the solid separated out from the reaction solution, diluting the filtrate with ice water, filtering out the solid separated out, combining the solid separated out, and recrystallizing the precipitate with ethanol to obtain a compound III;
(2) Adding 15mL of hydrobromic acid with the mass concentration of 48% into 10mL of glacial acetic acid solution of 120mmol of compound III, stirring and reacting for 5 minutes at 130 ℃, cooling, filtering, and concentrating the filtrate to obtain a yellow compound IV;
(3) Adding 5mL of pyridine into 8.7mmol of the compound IV, stirring at room temperature for reaction for 5 minutes, adding 20.9mmol of 4-methylbenzenesulfonyl chloride into the reaction solution, stirring at room temperature for 5 hours, dropwise adding a 1.0M hydrochloric acid solution into the reaction solution until the solution is neutral, extracting by ethyl acetate, and purifying by column chromatography (the mass ratio of ethyl acetate to petroleum ether is 1:3) to obtain a compound V;
(4) Adding 2-3 batches of mineral oil with the mass concentration of 60% of sodium hydride, the amount of which is 1.87mmol, into 20mL of anhydrous tetrahydrofuran solution of 0.83mmol of the compound V, stirring at room temperature for 1.5 hours, dropwise adding 1.0M hydrochloric acid solution into the reaction mixture until the mixture is neutral, extracting by ethyl acetate, and purifying by column chromatography (the mass ratio of ethyl acetate to petroleum ether is 1:2) to obtain the compound N-p-toluenesulfonyl-1,2-oxetane I.
As shown in FIGS. 1-2, the compound I is N-p-toluenesulfonyl-1,2-oxetane as shown in FIGS. 1 and 2.
Example 2
(1) Adding 120mmol 1, 2-dibromoethane and 120mmol triethylamine into 80mL N, N-dimethylformamide solution containing 60mmol N-hydroxyphthalimide, stirring at room temperature until the reaction solution becomes colorless, collecting the solid separated out from the reaction solution, diluting the filtrate with ice water, filtering out the solid separated out, merging the solid separated out, and recrystallizing the precipitate with ethanol to obtain a compound III;
(2) Adding 15mL of hydrobromic acid with the mass concentration of 48% into 10mL of glacial acetic acid solution of 120mmol of compound III, stirring and reacting for 5 minutes at 130 ℃, cooling, filtering, and concentrating the filtrate to obtain a yellow compound IV;
(3) Adding 5mL of pyridine into 8.7mmol of compound IV, stirring at room temperature for reaction for 5 minutes, adding 20.9mmol of benzenesulfonyl chloride into the reaction solution, stirring at room temperature for 5 hours, dropwise adding 1.0M hydrochloric acid solution into the reaction solution until the solution is neutral, extracting by using ethyl acetate, and purifying by using column chromatography (the mass ratio of ethyl acetate to petroleum ether is 1:3) to obtain compound V;
(4) Mineral oil with the sodium hydride mass concentration of 60 percent is added into 2 to 3 batches of 0.83mmol of compound V in 20mL of anhydrous tetrahydrofuran solution, the sodium hydride amount is 1.87mmol, 1.0M hydrochloric acid solution is added into the reaction mixture dropwise after stirring for 1.5 hours at room temperature until the reaction mixture is neutral, extraction is carried out through ethyl acetate, and benzenesulfonyl-1,2-oxetane I is obtained through column chromatography (the mass ratio of ethyl acetate/petroleum ether is 1:2).
Example 3
(1) Adding 120mmol 1, 2-dibromoethane and 120mmol triethylamine into 80mL N, N-dimethylformamide solution containing 60mmol N-hydroxyphthalimide, stirring at room temperature until the reaction solution becomes colorless, collecting the solid separated out from the reaction solution, diluting the filtrate with ice water, filtering out the solid separated out, merging the solid separated out, and recrystallizing the precipitate with ethanol to obtain a compound III;
(2) Adding 15mL of hydrobromic acid with the mass concentration of 48% into 10mL of glacial acetic acid solution of 120mmol of a compound III, stirring and reacting for 5 minutes at 130 ℃, cooling, filtering, and concentrating the filtrate to obtain a yellow compound IV;
(3) Adding 5mL of pyridine into 8.7mmol of the compound IV, stirring at room temperature for reaction for 5 minutes, adding 20.9mmol of p-fluorobenzenesulfonyl into the reaction liquid, stirring at room temperature for 5 hours, dropwise adding 1.0M hydrochloric acid solution into the reaction liquid until the solution is neutral, extracting by using ethyl acetate, and purifying by using column chromatography (the mass ratio of ethyl acetate to petroleum ether is 1:3) to obtain a compound V;
(4) Adding 2-3 batches of mineral oil with the mass concentration of 60% of sodium hydride in 1.87mmol of sodium hydride into 20mL of anhydrous tetrahydrofuran solution of 0.83mmol of compound V, stirring at room temperature for 1.5 hours, dropwise adding 1.0M hydrochloric acid solution into the reaction mixture until the mixture is neutral, extracting by ethyl acetate, and purifying by column chromatography (the mass ratio of ethyl acetate to petroleum ether is 1:2) to obtain p-fluorobenzenesulfonyl-1,2-oxetane I.
Example 4
1.0mmol of 1- (2-pyrimidinyl) indole and 2.0mmol of N-p-toluenesulfonyl-1,2-oxetane I prepared in example 1 were added to 10mL of acetonitrile, 0.05mmol of pentamethylcyclopentadienyl cobalt hexafluorophosphate and 0.1mmol of potassium acetate were added, and a reaction was stirred at 40 to 80 ℃ for 0.5 to 3 hours, and the reaction solution was concentrated, and the concentrated solution was subjected to column chromatography after removal of the organic solvent to obtain 1- (-2-pyrimidinyl) -2-p-toluenesulfonylaminomethylindole.
When the compound is analyzed, as shown in figures 3-4, as can be seen from figures 3 and 4, the compound I is 1- (-2-pyrimidinyl) -2-p-toluenesulfonamide methylindole.
Example 5
1.0mmol of 1- (2-pyrimidinyl) -4-bromoindole and 2.0mmol of N-p-toluenesulfonyl-1,2-oxetane I prepared in example 2 are added into 10mL of dimethyl sulfoxide, 0.05mmol of cobalt acetate (divalent cobalt) and 0.1mmol of cesium carbonate are added, the mixture is stirred and reacted for 0.5 to 3 hours at the temperature of between 40 and 80 ℃, reaction liquid is concentrated, and the concentrated solution is subjected to column chromatography after organic solvent is removed to obtain 1-pyrimidinyl-2-p-toluenesulfonylmethyl-4-bromoindole.
Example 6
1.0mmol of 1- (2-pyrimidinyl) indole and 2.0mmol of p-fluorobenzenesulfonyl-1,2-oxetane I prepared in example 3 are added into 10mL1, 4-dioxane, 0.05mmol of cobalt acetylacetonate (trivalent cobalt) and 0.1mmol of cesium carbonate are added, the mixture is stirred and reacted for 0.5 to 3 hours at the temperature of between 40 and 80 ℃, reaction liquid is concentrated, and the concentrated solution is subjected to column chromatography after an organic solvent is removed to obtain the 1-pyrimidinyl-2-p-fluorobenzenesulfonamide methylindole.
Example 7
1.0mmol of 1- (2-pyrimidinyl) indole and 1.1mmol of the compound I prepared in example 1 were added to 10mL of acetonitrile, 0.05mmol of pentamethylcyclopentadienylcarbonyl cobalt diiodide and 0.1mmol of potassium acetate were then added, the reaction was stirred at 40-80 ℃ for 0.5-3 hours, the reaction solution was concentrated, and the concentrated solution was subjected to column chromatography after removal of the organic solvent to obtain 1- (2-pyrimidinyl-) 2-hydroxymethylindole.
When the compound is analyzed, as shown in figures 5 to 6, as can be seen from figures 5 and 6, the compound I is 1- (2-pyrimidinyl) -2-hydroxymethyl indole.
Example 8
1.0mmol of 1- (2-pyrimidinyl) -4-bromoindole and 1.1mmol of the compound I prepared in example 2 are added into 10mL of chlorobenzene, then 0.05mmol of cobalt chloride (divalent cobalt) and 0.1mmol of sodium bicarbonate are added, the mixture is stirred and reacted for 0.5 to 3 hours at the temperature of between 40 and 80 ℃, reaction liquid is concentrated, and the concentrated solution is subjected to column chromatography after organic solvent is removed to obtain the 1- (2-pyrimidinyl) -2-hydroxymethyl 4-bromoindole.
Example 9
1.0mmol of 1- (2-pyrimidinyl) -4-methylindole and 1.1mmol of the compound I prepared in example 2 were added to 10mL1, 4-dioxane, 0.05mmol of cobalt acetylacetonate (trivalent cobalt) and 0.1mmol of sodium benzoate were then added, the mixture was stirred at 40 to 80 ℃ for reaction for 0.5 to 3 hours, the reaction mixture was concentrated, and the concentrated solution was subjected to column chromatography after removal of the organic solvent to obtain 1- (2-pyrimidinyl) -2-hydroxymethyl-4-methylindole.
The above description is only for the purpose of illustrating the preferred embodiments of the present invention and is not to be construed as limiting the invention, and any modifications, equivalents and improvements made within the spirit and principle of the present invention are intended to be included within the scope of the present invention.
Claims (4)
1. The application of 1,2-oxygen nitrogen heterocyclic butane compounds in aminomethylation or hydroxymethylation of 1-pyrimidyl indole compounds;
the chemical structural formula of the 1,2-oxygen nitrogen heterocyclic butane compound is shown as the following formula (I):
in the formula (I), R 1 Is p-toluenesulfonyl, benzenesulfonyl, p-fluorobenzenesulfonyl, p-chlorobenzenesulfonyl, p-bromobenzenesulfonyl, p-trifluoromethylbenzenesulfonyl, p-methoxybenzenesulfonyl, p-tert-butylbenzenesulfonyl, m-bromobenzenesulfonyl, 2,4,6-trimethylbenzenesulfonyl, 2-naphthalenesulfonyl, tert-butoxycarbonyl or benzyloxycarbonyl;
the chemical structural formula of the 1-pyrimidyl indole compound is shown as the following formula:
in the above formula, R 2 Is methyl, methoxy, ester group, halogen, nitro or amino;
the aminomethylation process comprises the following steps: adding a 1-pyrimidyl indole compound and a 1,2-oxygen nitrogen heterocyclic butane compound into an organic solvent, adding a catalyst and an additive, stirring and reacting at 40-80 ℃ for 0.5-3 hours, concentrating a reaction solution, removing the organic solvent from the concentrated solution, and performing column chromatography to obtain a 1-pyrimidyl-2-aminomethyl compound; wherein the catalyst is a cobalt complex; the additive is alkali; the molar volume ratio of the 1-pyrimidyl indole compound to 1,2-oxazacyclobutane compound, the organic solvent, the catalyst and the additive is 1.0mmol:2.0mmol:10mL of: 0.05mmol:0.1mmol;
the hydroxymethylation process comprises the following steps: adding a 1-pyrimidyl indole compound and a 1,2-oxazacyclobutane compound into an organic solvent, adding a catalyst and an additive, stirring and reacting at 40-80 ℃ for 0.5-3 hours, concentrating a reaction solution, removing the organic solvent from the concentrated solution, and performing column chromatography to obtain a 1-pyrimidyl-2-aminomethyl compound; wherein the catalyst is a cobalt complex; the additive is alkali; the molar volume ratio of the 1-pyrimidyl indole compound to 1,2-oxazacyclobutane compound, the organic solvent, the catalyst and the additive is 1.0mmol:1.1mmol:10mL of: 0.05mmol:0.1mmol.
2. The use of claim 1, wherein the 1-pyrimidyl indole compound is at least one of 1- (2-pyrimidyl) indole, 1- (2-pyrimidyl) -2-methylindole, 1- (2-pyrimidyl) -4-bromoindole, 1- (2-pyrimidyl) -4-methoxyindole, 1- (2-pyrimidyl) -4-benzyloxyindole, 1- (2-pyrimidyl) -4-aminoindole, 1- (2-pyrimidyl) -4-nitroindole, 4- (1- (2-pyrimidyl)) methyl indole carboxylate, 1- (2-pyrimidyl) -5-fluoroindole, 1- (2-pyrimidyl) -5-chloroindole, 1- (2-pyrimidyl) -5-iodoindole, 1- (2-pyrimidyl) -6-fluoroindole, and 1- (2-pyrimidyl) -6-methoxyindole.
3. The use of claim 1, wherein the organic solvent is at least one of acetonitrile, 1,2-dichloroethane, dichloromethane, chloroform, chlorobenzene, dimethyl sulfoxide, toluene, trifluorotoluene, mesitylene, ethanol, acetic acid, 1,4-dioxane, tetrahydrofuran;
the cobalt complex is Co (OAc) 2 、Co(acac) 3 、CoCl 2 、[Cp*Co(CO)I 2 ]、[Cp*Co(C 6 H 6 )](PF 6 ) 2 At least one of;
the alkali is at least one of potassium acetate, sodium carbonate, potassium carbonate, cesium carbonate, sodium bicarbonate, potassium phosphate, lithium phosphate, dipotassium hydrogen phosphate, potassium dihydrogen phosphate, sodium benzoate, sodium hydroxide and lithium hydroxide.
4. Use according to claim 3, wherein the organic solvent is toluene or ethanol; the cobalt complex is pentamethylcyclopentadienyl carbonyl diiodo cobalt; the base is potassium acetate.
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| Tomas Javorskis et al.，.N-Protected 1,2-Oxazetidines as a Source of Electrophilic Oxygen: Straightforward Access to Benzomorpholines and Related Heterocycles by Using a Reactive Tether.《Chemistry - A European Journal》.2015,第21卷(第25期),第9157-9164页. * |
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