CN118108623A - Preparation method of organic nitrogen oxide - Google Patents
Preparation method of organic nitrogen oxide Download PDFInfo
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- CN118108623A CN118108623A CN202410479312.9A CN202410479312A CN118108623A CN 118108623 A CN118108623 A CN 118108623A CN 202410479312 A CN202410479312 A CN 202410479312A CN 118108623 A CN118108623 A CN 118108623A
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- MWUXSHHQAYIFBG-UHFFFAOYSA-N nitrogen oxide Inorganic materials O=[N] MWUXSHHQAYIFBG-UHFFFAOYSA-N 0.000 title claims abstract description 56
- 125000001477 organic nitrogen group Chemical group 0.000 title claims abstract description 28
- 238000002360 preparation method Methods 0.000 title abstract description 11
- 238000006243 chemical reaction Methods 0.000 claims abstract description 30
- -1 (tert-butyl peroxy) methyl Chemical group 0.000 claims abstract description 23
- PAYRUJLWNCNPSJ-UHFFFAOYSA-N Aniline Chemical compound NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 claims abstract description 20
- 239000012074 organic phase Substances 0.000 claims abstract description 16
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims abstract description 14
- 150000001875 compounds Chemical class 0.000 claims abstract description 13
- 239000003960 organic solvent Substances 0.000 claims abstract description 13
- 239000000758 substrate Substances 0.000 claims abstract description 13
- 238000004809 thin layer chromatography Methods 0.000 claims abstract description 12
- NIXOWILDQLNWCW-UHFFFAOYSA-M Acrylate Chemical compound [O-]C(=O)C=C NIXOWILDQLNWCW-UHFFFAOYSA-M 0.000 claims abstract description 8
- 239000003513 alkali Substances 0.000 claims abstract description 8
- 239000003054 catalyst Substances 0.000 claims abstract description 7
- 238000004440 column chromatography Methods 0.000 claims abstract description 7
- 238000012544 monitoring process Methods 0.000 claims abstract description 7
- 238000010534 nucleophilic substitution reaction Methods 0.000 claims abstract description 7
- 238000001291 vacuum drying Methods 0.000 claims abstract description 3
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 42
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 24
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 18
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 claims description 15
- HTZCNXWZYVXIMZ-UHFFFAOYSA-M benzyl(triethyl)azanium;chloride Chemical compound [Cl-].CC[N+](CC)(CC)CC1=CC=CC=C1 HTZCNXWZYVXIMZ-UHFFFAOYSA-M 0.000 claims description 14
- 238000000034 method Methods 0.000 claims description 14
- 239000003208 petroleum Substances 0.000 claims description 9
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 6
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 6
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 6
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical group [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 claims description 6
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 6
- PNJWIWWMYCMZRO-UHFFFAOYSA-N pent‐4‐en‐2‐one Natural products CC(=O)CC=C PNJWIWWMYCMZRO-UHFFFAOYSA-N 0.000 claims description 6
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 claims description 6
- LSXWFXONGKSEMY-UHFFFAOYSA-N di-tert-butyl peroxide Chemical compound CC(C)(C)OOC(C)(C)C LSXWFXONGKSEMY-UHFFFAOYSA-N 0.000 claims description 5
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 claims description 4
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 4
- 239000003795 chemical substances by application Substances 0.000 claims description 4
- 239000003480 eluent Substances 0.000 claims description 4
- 238000003756 stirring Methods 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 3
- 150000007529 inorganic bases Chemical class 0.000 claims description 3
- 239000007788 liquid Substances 0.000 claims description 3
- 229910000027 potassium carbonate Inorganic materials 0.000 claims description 3
- 238000010898 silica gel chromatography Methods 0.000 claims description 3
- 229910000029 sodium carbonate Inorganic materials 0.000 claims description 3
- 239000000243 solution Substances 0.000 claims description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 3
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical class O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 claims description 2
- 238000001308 synthesis method Methods 0.000 claims description 2
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 2
- 238000004519 manufacturing process Methods 0.000 claims 3
- 239000002585 base Substances 0.000 claims 2
- AOUSBQVEVZBMNI-UHFFFAOYSA-N 2-bromoethyl 2-methylprop-2-enoate Chemical compound CC(=C)C(=O)OCCBr AOUSBQVEVZBMNI-UHFFFAOYSA-N 0.000 claims 1
- 239000011541 reaction mixture Substances 0.000 claims 1
- 238000003786 synthesis reaction Methods 0.000 description 7
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 4
- 230000015572 biosynthetic process Effects 0.000 description 4
- 239000000543 intermediate Substances 0.000 description 3
- 238000001228 spectrum Methods 0.000 description 3
- 150000004894 1,2-oxazines Chemical class 0.000 description 2
- GQHTUMJGOHRCHB-UHFFFAOYSA-N 2,3,4,6,7,8,9,10-octahydropyrimido[1,2-a]azepine Chemical compound C1CCCCN2CCCN=C21 GQHTUMJGOHRCHB-UHFFFAOYSA-N 0.000 description 2
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 2
- AVXURJPOCDRRFD-UHFFFAOYSA-N Hydroxylamine Chemical compound ON AVXURJPOCDRRFD-UHFFFAOYSA-N 0.000 description 2
- 150000001204 N-oxides Chemical class 0.000 description 2
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
- 229910052799 carbon Inorganic materials 0.000 description 2
- 239000003153 chemical reaction reagent Substances 0.000 description 2
- 230000007547 defect Effects 0.000 description 2
- 125000000524 functional group Chemical group 0.000 description 2
- 230000007246 mechanism Effects 0.000 description 2
- 229910052757 nitrogen Inorganic materials 0.000 description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- 230000000269 nucleophilic effect Effects 0.000 description 2
- 238000005691 oxidative coupling reaction Methods 0.000 description 2
- 150000002923 oximes Chemical class 0.000 description 2
- 238000010791 quenching Methods 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 230000002194 synthesizing effect Effects 0.000 description 2
- 238000012360 testing method Methods 0.000 description 2
- UXXHQJCUQJZRGE-UHFFFAOYSA-N (2-methylpropan-2-yl)oxy 2-methylprop-2-eneperoxoate Chemical compound CC(=C)C(=O)OOOC(C)(C)C UXXHQJCUQJZRGE-UHFFFAOYSA-N 0.000 description 1
- BBVIDBNAYOIXOE-UHFFFAOYSA-N 1,2,4-oxadiazole Chemical compound C=1N=CON=1 BBVIDBNAYOIXOE-UHFFFAOYSA-N 0.000 description 1
- 150000005071 1,2,4-oxadiazoles Chemical class 0.000 description 1
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 1
- 238000005160 1H NMR spectroscopy Methods 0.000 description 1
- NEAQRZUHTPSBBM-UHFFFAOYSA-N 2-hydroxy-3,3-dimethyl-7-nitro-4h-isoquinolin-1-one Chemical class C1=C([N+]([O-])=O)C=C2C(=O)N(O)C(C)(C)CC2=C1 NEAQRZUHTPSBBM-UHFFFAOYSA-N 0.000 description 1
- RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 description 1
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 1
- FQGADRODESNJMV-UHFFFAOYSA-N N1OC=C2C1=NC(NC2=O)=O Chemical class N1OC=C2C1=NC(NC2=O)=O FQGADRODESNJMV-UHFFFAOYSA-N 0.000 description 1
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 1
- ZBIKORITPGTTGI-UHFFFAOYSA-N [acetyloxy(phenyl)-$l^{3}-iodanyl] acetate Chemical compound CC(=O)OI(OC(C)=O)C1=CC=CC=C1 ZBIKORITPGTTGI-UHFFFAOYSA-N 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 150000001408 amides Chemical class 0.000 description 1
- 230000000202 analgesic effect Effects 0.000 description 1
- 230000000843 anti-fungal effect Effects 0.000 description 1
- 230000001387 anti-histamine Effects 0.000 description 1
- 230000003110 anti-inflammatory effect Effects 0.000 description 1
- 229940121375 antifungal agent Drugs 0.000 description 1
- 125000003118 aryl group Chemical group 0.000 description 1
- 238000005815 base catalysis Methods 0.000 description 1
- 150000008316 benzisoxazoles Chemical class 0.000 description 1
- 230000000975 bioactive effect Effects 0.000 description 1
- 238000006555 catalytic reaction Methods 0.000 description 1
- 238000012512 characterization method Methods 0.000 description 1
- 230000000052 comparative effect Effects 0.000 description 1
- 229910052802 copper Inorganic materials 0.000 description 1
- 239000010949 copper Substances 0.000 description 1
- 230000008878 coupling Effects 0.000 description 1
- 238000010168 coupling process Methods 0.000 description 1
- 238000005859 coupling reaction Methods 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 125000004494 ethyl ester group Chemical group 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 239000001257 hydrogen Substances 0.000 description 1
- 229910052739 hydrogen Inorganic materials 0.000 description 1
- 150000002443 hydroxylamines Chemical class 0.000 description 1
- 150000002545 isoxazoles Chemical class 0.000 description 1
- 239000003446 ligand Substances 0.000 description 1
- 239000008204 material by function Substances 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 229930014626 natural product Natural products 0.000 description 1
- 150000002825 nitriles Chemical class 0.000 description 1
- 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 1
- 150000007530 organic bases Chemical class 0.000 description 1
- 150000002894 organic compounds Chemical class 0.000 description 1
- 239000005416 organic matter Substances 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 230000008092 positive effect Effects 0.000 description 1
- VYDGVLUVNDEQCN-UHFFFAOYSA-N pyrazolo[3,4-d]pyrimidine-4,6-dione Chemical class O=C1NC(=O)C2=CN=NC2=N1 VYDGVLUVNDEQCN-UHFFFAOYSA-N 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- 230000000171 quenching effect Effects 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 230000009466 transformation Effects 0.000 description 1
- 238000000844 transformation Methods 0.000 description 1
- 229910052723 transition metal Inorganic materials 0.000 description 1
- 150000003624 transition metals Chemical class 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C239/00—Compounds containing nitrogen-to-halogen bonds; Hydroxylamino compounds or ethers or esters thereof
- C07C239/08—Hydroxylamino compounds or their ethers or esters
- C07C239/20—Hydroxylamino compounds or their ethers or esters having oxygen atoms of hydroxylamino groups etherified
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The invention belongs to the technical field of organic nitrogen oxide preparation, and discloses a preparation method of organic nitrogen oxide, which comprises the steps of adding aniline and ethyl 2- ((tert-butyl peroxy) methyl) acrylate into a container according to a molar ratio of 1:1-3 as standard substrates, adding alkali as a catalyst, adding an organic solvent at room temperature for nucleophilic substitution reaction for 10-14 hours, monitoring the reaction progress degree by using a thin layer chromatography in the reaction process, stopping the reaction when the substrate consumption is monitored, separating an organic phase by using a column chromatography, removing the organic solvent from the collected organic phase by using a rotary evaporator, and vacuum drying the obtained product overnight to obtain an organic nitrogen oxide compound with chain N-O bonds. The preparation method has mild reaction conditions and simple reaction process.
Description
Technical Field
The invention belongs to the technical field of organic nitrogen oxide preparation, and particularly relates to a preparation method of organic nitrogen oxide.
Background
Organic nitrogen oxides containing N-O bonds are a special and important organic matter with a special structure, and have wide functional application and synthetic conversion value. They are not only found in natural products, drug molecules, functional materials and ligands, but also important synthons and intermediates in synthetic chemistry, and can participate in a variety of organic transformations. The N-O bond is a special chemical bond in organic compounds and exists in oxime and derivatives thereof, hydroxylamine and derivatives thereof, oxypyridinium salts, pyridine oxynitride and other compounds. N-O bonds are present in both aromatic nitrogen heterocyclic compounds such as isoxazoles, benzisoxazoles, furazoles, 1, 2-oxazines and 1, 2-oxazines, and non-aromatic chain compounds such as N-hydroxylamines, oximes and N-oxides, some of which appear to have antifungal, antiinflammatory, analgesic and antihistaminic effects. In addition, compounds containing N-O bonds can be used as important synthetic intermediates, such as N-oxides, hydroxylamines, hydroxamic acids, and the like.
Common N-O bond containing compounds employ metal catalyzed and oxidative coupling, for example Hironao Sajiki et al propose the efficient synthesis of pyrazolo [3, 4-d ] pyrimidine-4, 6-dione derivatives by intramolecular N-N bond coupling of 5-iminomethyl-6-aminouracil derivatives using iodobenzene diacetate. Oxidative coupling is also suitable for synthesizing similar N-O bonds to form isoxazolo [3, 4-d ] pyrimidine-4, 6-dione derivatives, the chemical synthesis route is shown as formulaThe following is shown:
/> 。
Sung Young Hong et al reported a novel method for obtaining 1,2, 4-oxadiazole by copper catalyzed oxidation to form N-O bonds using ready-made amides and organic nitriles. The method can tolerate various functional groups and can produce 3, 5-oxadiazole. The method is also successfully applied to the synthesis of bioactive molecule 1,2, 4-oxadiazole derivatives, and the chemical synthesis route is shown as the formulaAs shown in the drawing,
/>。
The prior art has the defects of expensive transition metal, limited substrate range of partial reaction, harsh partial reaction conditions, complex synthesis steps and the like, meanwhile, the method for synthesizing the chain-shaped N-O bond compound is found to be less, and the method for preparing the organic nitrogen oxide containing the chain-shaped N-O bond, which has mild reaction conditions and simple operation, is hoped to be developed.
Disclosure of Invention
The invention aims to overcome the defects of the prior art and provide a preparation method of organic nitrogen oxide, which adopts 2- ((tert-butyl peroxy) methyl) ethyl acrylate which is easy to synthesize as a reaction substrate and carries out nucleophilic substitution reaction with aniline under the action of base catalysis to synthesize the organic nitrogen oxide with chain N-O bond. The preparation method has mild reaction conditions and simple reaction process.
The technical scheme adopted for solving the technical problems is as follows:
A method for preparing an organic nitroxide compound comprising: adding aniline and 2- ((tert-butylperoxy) methyl) ethyl acrylate into a container according to a molar ratio of 1:1-3 as standard substrates, adding alkali as a catalyst, adding an organic solvent at room temperature, carrying out nucleophilic substitution reaction for 10-14 hours, monitoring the reaction progress in the reaction process by using a thin layer chromatography, stopping the reaction when the substrate consumption is monitored, separating an organic phase by using a column chromatography, removing the organic solvent from the collected organic phase by using a rotary evaporator, and vacuum drying the obtained product overnight to obtain an organic nitrogen oxide compound with chain N-O bonds (the chemical formula is shown as formula III)
Formula III.
Chemical synthesis route is shown as the formulaThe following is shown:
/> 。
The mechanism of the method of the invention is as follows: under the catalysis of alkali, aniline is firstly converted into a nucleophilic nitrogen anion intermediate, then 2- ((tert-butyl peroxy) methyl) ethyl acrylate is subjected to nucleophilic attack, tert-butoxy anion is removed, nucleophilic substitution reaction is completed, and a target product is obtained, wherein the mechanism route is shown as the formulaAs shown.
/>。
Further, the molar ratio of the alkali to the aniline is 1.5-2.5:1, the alkali is inorganic alkali, and the inorganic alkali is sodium carbonate or potassium carbonate.
Further, the organic solvent is one or more of ethyl acetate, dichloromethane, chloroform, acetonitrile, tetrahydrofuran, ethanol, toluene and N, N-dimethylformamide, and the ratio of the volume of the organic solvent to the molar mass of aniline is 1.5-2.5 mL/1 mol.
Further, the volume ratio of petroleum ether to ethyl acetate in the developing agent of the thin layer chromatography is 5:1, and the volume ratio of petroleum ether to ethyl acetate in the eluent of the column chromatography is 10:1.
Further, the synthesis method of the 2- ((tert-butyl peroxy) methyl) ethyl acrylate comprises the following steps: sequentially adding ethyl 2-bromomethacrylate, tert-butyl peroxide, benzyl triethyl ammonium chloride (BTEAC) and dichloromethane into a container, stirring at room temperature until the solution is clear, slowly adding potassium hydroxide, stirring for 6 hours, and monitoring the end of the reaction by using a TLC (thin layer chromatography) plate; adding water for quenching reaction, extracting with dichloromethane, collecting organic phase, washing with saturated saline solution, drying the organic phase with anhydrous sodium sulfate, concentrating the organic phase with rotary evaporator, and separating by silica gel column chromatography to obtain colorless transparent liquid 2- ((tert-butylperoxy) methyl) ethyl acrylate, wherein the synthetic route is shown in formulaThe following is shown:
/> 。
Further, the mol ratio of the 2-bromomethacrylic acid ethyl ester, the tert-butyl peroxide and the benzyl triethyl ammonium chloride is 9-11:10-12:1.
Further, the molar ratio of the potassium hydroxide to the ethyl 2-bromomethacrylate is 1-1.5: 1-2.
The invention has the advantages and positive effects that:
According to the method, the organic nitrogen oxide with the chain N-O bond is prepared by using the ethyl 2- ((tert-butyl peroxy) methyl) acrylate which is easy to synthesize as a reaction substrate and using the inorganic base as a catalyst, so that the preparation condition is mild, the functional group compatibility is high, and the operation is simple, convenient and practical.
Drawings
FIG. 1 is a nuclear magnetic resonance spectrum of an organic nitrogen oxide having a chain N-O bond prepared in example 1;
FIG. 2 is a nuclear magnetic carbon spectrum of an organic nitrogen oxide having a chain-like N-O bond prepared in example 1.
Detailed Description
The invention is further illustrated by the following examples, which are intended to be illustrative only and not limiting in any way. The reagents used in the experiments were all commercially available analytically pure reagents unless otherwise specified.
Example 1
A method for preparing an organic nitroxide compound comprising:
(1) Synthesis of ethyl 2- ((tert-butylperoxy) methyl) acrylate: into a 500mL round bottom flask, ethyl 2-bromomethacrylate 50 mmol, tert-butyl peroxide 55 mmol, benzyltriethylammonium chloride (BTEAC) 5mmol and 250mL dichloromethane were added sequentially, stirred at room temperature until the solution was clear, potassium hydroxide 50 mmol was slowly added, stirred at room temperature for 6 hours, and the TLC plate monitored the end of the reaction. 150mL of water was added to quench the reaction, the mixture was extracted 3 times with 50mL of methylene chloride, the organic phase was collected, washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated by a rotary evaporator, and the organic phase was separated by silica gel column chromatography (petroleum ether: ethyl acetate=400:1) to give ethyl 2- ((tert-butylperoxy) methacrylate as a colorless transparent liquid in 66% yield.
(2) Adding 0.4 mmol of ethyl 2- ((tert-butylperoxy) methyl) acrylate prepared in the step (1) and 0.2 mmol aniline serving as standard substrates into a 10mL test tube, adding 2mL of organic solvent ethyl acetate under the room temperature condition with 0.4 mmol potassium carbonate serving as a catalyst, carrying out nucleophilic substitution reaction for 12 hours, and monitoring the reaction progress by using Thin Layer Chromatography (TLC) during the reaction, wherein the developing agent is petroleum ether: ethyl acetate=5:1. When the substrate consumption is monitored, the reaction is stopped, the organic phase is separated by column chromatography, and the eluent is petroleum ether: ethyl acetate=10:1. The organic phase was collected and the organic solvent ethyl acetate was removed by rotary evaporator, and the resulting product was dried overnight in vacuo to give an organic nitrogen oxide having a chain n—o bond in a yield of 38%.
The nuclear magnetic structure characterization of the organic nitrogen oxide prepared in the example 1 is carried out, and the nuclear magnetic hydrogen spectrum of the organic nitrogen oxide is shown in figure 1 ,1H NMR (400 MHz, CDCl3) δ 7.17 (m, 2H), 6.71 (t, J = 7.3 Hz, 1H), 6.60 (d, J = 7.7 Hz, 2H), 6.27 (s, 1H), 5.78 (m, 1H), 4.24 (q, J = 7.1 Hz, 2H), 4.09 (s, 1H), 4.03 (s, 2H), 1.32 (t, J = 7.1 Hz, 3H)..
The nuclear magnetic carbon spectrum of the organic nitrogen oxide is shown in figure 2 ,13C NMR (101 MHz, CDCl3) δ 166.7, 147.7, 137.7, 129.4, 125.8, 117.9, 113.3, 77.5, 77.2, 76.9, 61.0, 45.0, 14.4.
Example 2
A method for preparing an organic nitroxide compound comprising:
(1) The preparation of ethyl 2- ((tert-butylperoxy) methyl) acrylate was carried out as in example 1;
(2) Adding 0.24 mmol of ethyl 2- ((tert-butylperoxy) methyl) acrylate prepared in the step (1) and 0.2mmol aniline serving as standard substrates into a 10mL test tube, adding 2mL of organic solvent ethyl acetate under the room temperature condition with 0.4 mmol sodium carbonate serving as a catalyst, carrying out nucleophilic substitution reaction for 12 hours, and monitoring the reaction progress by using Thin Layer Chromatography (TLC) during the reaction, wherein the developing agent is petroleum ether: ethyl acetate=5:1. When the substrate consumption is monitored, the reaction is stopped, the organic phase is separated by column chromatography, and the eluent is petroleum ether: ethyl acetate=10:1. The collected organic phase was subjected to removal of the organic solvent by means of a rotary evaporator, and the obtained product was dried overnight in vacuo to obtain an organic nitrogen oxide having a chain-like N-O bond in a yield of 38%.
Comparative example 1
The only difference from example 1 is that organic nitrogen oxides having chain N-O bonds were prepared in a yield of 7% using the organic base 1, 8-diazabicyclo [ 5.4.0 ] undec-7-ene (DBU) as catalyst.
The foregoing is merely a preferred embodiment of the present invention, and it should be noted that it will be apparent to those skilled in the art that variations and modifications can be made without departing from the scope of the invention.
Claims (7)
1. A method for preparing an organic nitroxide compound, comprising:
Adding aniline and 2- ((tert-butylperoxy) methyl) ethyl acrylate into a container according to a molar ratio of 1:1-3 as standard substrates, adding alkali as a catalyst, adding an organic solvent at room temperature, carrying out nucleophilic substitution reaction for 10-14 hours, monitoring the reaction progress by using a thin layer chromatography in the reaction process, stopping the reaction when the substrate consumption is monitored, separating an organic phase by using a column chromatography, removing the organic solvent from the collected organic phase by using a rotary evaporator, and vacuum drying the obtained product overnight to obtain the organic nitrogen oxide compound with chain N-O bonds.
2. The method for preparing an organic nitrogen oxide compound according to claim 1, wherein the molar ratio of the base to the aniline is 1.5-2.5:1, the base is an inorganic base, and the inorganic base is sodium carbonate or potassium carbonate.
3. The method for producing an organic nitrogen oxide compound according to claim 1, wherein the organic solvent is one or more of ethyl acetate, methylene chloride, chloroform, acetonitrile, tetrahydrofuran, ethanol, toluene, and N, N-dimethylformamide.
4. The method for producing an organic nitrogen oxide according to claim 1, wherein the volume ratio of petroleum ether to ethyl acetate in the developing agent of the thin layer chromatography is 5:1, and the volume ratio of petroleum ether to ethyl acetate in the eluent of the column chromatography is 10:1.
5. The method for preparing the organic nitrogen oxide compound according to claim 1, wherein the synthesis method of the ethyl 2- ((tert-butyl peroxy) methyl) acrylate is as follows: sequentially adding 2-bromoethyl methacrylate, tert-butyl peroxide, benzyl triethyl ammonium chloride and dichloromethane into a container, stirring at room temperature until the solution is clear, slowly adding potassium hydroxide, stirring for 6 hours, and monitoring the end of the reaction by a TLC (thin layer chromatography) plate; the reaction mixture was quenched with water, extracted with dichloromethane, and the organic phase was collected, washed with saturated brine, dried over anhydrous sodium sulfate, concentrated on a rotary evaporator, and separated by silica gel column chromatography to give ethyl 2- ((t-butylperoxy) methyl) acrylate as a colorless transparent liquid.
6. The method for producing an organic nitrogen oxide compound according to claim 5, wherein the molar ratio of ethyl 2-bromomethacrylate, t-butyl peroxide, and benzyltriethylammonium chloride is 9 to 11:10-12:1.
7. The method for preparing an organic nitrogen oxide compound according to claim 5, wherein the molar ratio of potassium hydroxide to ethyl 2-bromomethacrylate is 1 to 1.5: 1-2.
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| CN202410479312.9A CN118108623A (en) | 2024-04-22 | 2024-04-22 | Preparation method of organic nitrogen oxide |
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| CN202410479312.9A CN118108623A (en) | 2024-04-22 | 2024-04-22 | Preparation method of organic nitrogen oxide |
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| J. PILAR等: ""Photolysis of 2, 6-di-tert-butyl-4-tert-butylperoxy-4-methyl-2, 5-cyclohexadienone"", ORGANIC MAGNETIC RESONANCE, vol. 14, no. 4, 31 December 1980 (1980-12-31), pages 315 - 318 * |
| YOZO MIURA等: ""N-tert-Butoxy-1-aminopyrenyl Radicals. Isolation, Electronic Structure, and Magnetic Characterization"", JOURNAL OF ORGANIC CHEMISTRY, vol. 67, no. 25, 31 December 2002 (2002-12-31), pages 8764 - 8770 * |
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