CN113845466A - alpha-oxo-N-phenyl-3-butenamide compound and preparation method and application thereof - Google Patents
alpha-oxo-N-phenyl-3-butenamide compound and preparation method and application thereof Download PDFInfo
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- CN113845466A CN113845466A CN202111274158.4A CN202111274158A CN113845466A CN 113845466 A CN113845466 A CN 113845466A CN 202111274158 A CN202111274158 A CN 202111274158A CN 113845466 A CN113845466 A CN 113845466A
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Abstract
The invention discloses an alpha-oxo-N-phenyl-3-butenamide compound, and a preparation method and application thereof. The invention takes high-valence iodine reagent as an oxidant to carry out oxidation reaction on alpha position of N-phenylbut-3-enamine to synthesize the alpha-oxo-N-phenyl-3-crotonamide compound. The method has the advantages of mild reaction conditions, high selectivity, high yield (up to 87 percent) and environmental friendliness, and can be used in the field of synthesis of medicines, pesticides and chemical intermediates.
Description
Technical Field
The invention belongs to the field of organic synthesis, and particularly relates to an alpha-oxo-N-phenyl-3-butenamide compound, and a preparation method and application thereof.
Background
The N-phenyl-3-crotonamide compound is an important chemical intermediate and a product, and the compound is widely applied to the fields of medicines, pesticides, coatings, dyes and the like. For example: aromatic amine compounds such as 4-vinylaniline are intermediates for producing important chemical products such as medicines, dyes, stabilizers, bactericides, insecticides, herbicides, developers, antioxidants, petroleum additives and the like.
The main production methods at present include aniline derivative electrolytic reduction method, catalytic hydrogenation method, iron powder reduction method, biological fermentation and the like. The nitrobenzene derivative electrolytic reduction method has high technical difficulty, strict production control requirements and high power consumption, and China does not realize industrialization; the biological fermentation process is green and environment-friendly, but the production time is long, the efficiency needs to be improved, and a large amount of aniline derivatives and a small amount of other impurities exist in the product, so that the production efficiency and the product quality of the process are influenced. The iron powder reduction method has high production cost, small production scale and serious pollution, and is eliminated by most countries. The catalytic hydrogenation method obtains the phenylamine derivative by hydrogenation reduction under the action of the catalyst, and has the advantages of simple process, high product quality, small environmental pollution and wide development prospect.
Disclosure of Invention
Aiming at the defects of the prior art, the invention aims to provide the alpha-oxo-N-phenyl-3-butenamide compound which has simple process, mild reaction and environmental friendliness, and the preparation method and the application thereof.
The purpose of the invention is realized by the following technical scheme:
an α -oxo-N-phenyl-3-butenamide compound having the structure:
the preparation method of the alpha-oxo-N-phenyl-3-butenamide compound comprises the following steps:
mixing a high-valence iodine reagent, N-phenyl-3-butenamide, N-hydroxyphthalimide and an organic solvent to obtain a mixture, stirring and heating the mixture for 8-24 hours in an oil bath at the temperature of 40-100 ℃, taking reaction liquid after heating, adding water into the reaction liquid, extracting, spinning the extracted organic phase to obtain a crude product, and separating and purifying the crude product to obtain the alpha-oxo-N-phenyl-3-butenamide compound.
Preferably, the organic solvent is at least one of dichloroethane, dichloromethane, acetic acid, ethylene glycol dimethyl ether and dimethyl sulfoxide; more preferably dichloroethane.
Preferably, the molar weight ratio of the high-valence iodine reagent to the N-phenyl-3-butenamine is 0.02-200: 1; more preferably 200: 1.
Preferably, the molar weight ratio of the N-phenyl-3-butenamide to the N-hydroxyphthalimide is 0.005-50: 1; more preferably 0.005: 1.
Preferably, the adding amount ratio of the N-hydroxyphthalimide to the organic solution is 0.002-20 mmol/mL; more preferably 20 mmol/mL.
Preferably, the high-valence iodine reagent is p-chloro (dibenzoic acid) iodobenzene with a chemical formula of 4-Cl-C6H4(OCOPh)2。
Preferably, the p-chloro (dibenzoic acid) iodobenzene is prepared by the following steps: adding 4-chloroiodobenzene diacetic acid 6mmol and benzoic acid 12mmol into a 25mL round-bottom flask, adding methanol 5mL to fully dissolve, heating to 45 ℃, reacting for 0.5h, carrying out reduced pressure distillation, rotationally evaporating the solvent, pouring the reaction liquid and the solid into a Buchner funnel, and washing with methanol 15mL for three times to obtain a white solid, namely p-chloro (dibenzoic acid) iodobenzene.
The 4-chloroiodobenzene diacetic acid is prepared by the following steps: adding 10.3mmol of sodium orthoperiodate and 22mmol of sodium acetate into a mixed solution of 13.5mL of glacial acetic acid and 1.5mL of acetic anhydride, stirring, adding 10mmol of 4-chloroiodobenzene, heating to 120 ℃, stirring and boiling the mixture in a reflux condenser for 2h, cooling to room temperature, extracting reaction liquid by using dichloromethane, distilling under reduced pressure, grinding obtained residual liquid in 15mL of n-hexane until solidification, filtering and collecting solids, washing with the n-hexane for three times, and naturally air-drying in the dark to obtain a white solid, namely the 4-chloroiodobenzene diacetic acid.
Preferably, the N-phenyl-3-butenamine is prepared by the following steps: taking 7mmol of 3-butenoic acid in a solanaceous bottle, adding 5mL of dichloromethane, adding 1mL of triethylamine in the container, adding 5mmol of aniline in ice bath, finally adding 1mL of phosphorus oxychloride, reacting for 2h at normal temperature after ice bath for 0.5h, and purifying the reaction liquid by column chromatography to obtain a white solid, namely the product N-phenyl-3-butenylamine; the operating conditions of the chromatographic column are as follows: the mobile phase is ethyl acetate: n-hexane ═ 1: 8, the stationary phase is column chromatography silica gel.
Preferably, the solvent used for the extraction is at least one of ethyl acetate and dichloromethane.
Preferably, the separation and purification mode is as follows: separating and purifying by column chromatography.
Preferably, the stirring speed is 400-1000 r/s, and more preferably 600 r/s.
Preferably, the oil bath is silicone oil.
The application of the alpha-oxo-N-phenyl-3-crotonamide compound in the preparation of medicines, pesticides and chemical intermediates.
Compared with the prior art, the invention has the beneficial effects that:
the invention takes high-valence iodine reagent as an oxidant to carry out oxidation reaction on alpha position of N-phenylbut-3-enamine to synthesize the alpha-oxo-N-phenyl-3-crotonamide compound. The method has the advantages of mild reaction conditions, high selectivity, high yield and environmental friendliness, and can be used in the field of synthesis of medicines, pesticides and chemical intermediates.
Drawings
FIG. 1 is a nuclear magnetic resonance spectrum of a pale yellow solid product obtained in example 1.
Detailed Description
In order to make the objects, technical solutions and advantages of the present invention more apparent, the present invention is further described in detail with reference to the following embodiments. It should be understood that the specific embodiments described herein are merely illustrative of the invention and are not intended to limit the invention.
The specific operating method for the column chromatography separation in the examples is as follows: the mobile phase is ethyl acetate: n-hexane ═ 1: 8, the stationary phase is column chromatography silica gel, and the operation steps are as follows by using a 300mL column: the reaction mixture was extracted three times with 25mL of water and 10mL of dichloromethane, the organic phase was collected, dried over anhydrous magnesium sulfate, and the organic solvent was removed in vacuo, followed by column chromatography (ethyl acetate: n-hexane ═ 1: 8) to obtain a pure product. The by-products are separated from the target product during column chromatography.
The p-chloro (dibenzoic acid) iodobenzene described in the examples was prepared as follows: adding 6mmol of 4-chloroiodobenzene diacetic acid and 12mmol of benzoic acid into a 25mL round-bottom flask, adding 5mL of methanol to fully dissolve the 4-chloroiodobenzene diacetic acid and the 12mmol of benzoic acid, heating to 45 ℃, reacting for 0.5h, carrying out reduced pressure distillation, rotationally evaporating the solvent to dryness, pouring the reaction liquid and the solid into a Buchner funnel, and washing with 15mL of methanol for three times to obtain a white solid, namely p-chloro (dibenzoic acid) iodobenzene; the purity of the prepared p-chloro (dibenzoic acid) iodobenzene is 99%.
The N-phenyl-3-butenamine is prepared according to the following steps: taking 7mmol of 3-butenoic acid in a solanaceous bottle, adding 5mL of dichloromethane, adding 1mL of triethylamine in the container, adding 5mmol of aniline in ice bath, finally adding 1mL of phosphorus oxychloride, reacting for 2h at normal temperature after ice bath for 0.5h, and purifying the reaction liquid by column chromatography to obtain a white solid, namely the product N-phenyl-3-butenylamine; the column chromatography conditions are as follows: the mobile phase is ethyl acetate: n-hexane ═ 1: 8, the stationary phase is column chromatography silica gel, and the operation steps are as follows by using a 300mL column: the reaction mixture was extracted three times with 25mL of water and 10mL of dichloromethane, the organic phase was collected, dried over anhydrous magnesium sulfate, and the organic solvent was removed in vacuo, followed by column chromatography (ethyl acetate: n-hexane ═ 1: 8) to obtain a pure product.
Example 1
A preparation method of alpha-oxo-N-phenyl-3-crotonamide compound comprises the following steps:
adding one of 0.4mmol of p-chloro (dibenzoic acid) iodobenzene, 0.2mmol of N-phenyl-3-butenamide, 0.4mmol of N-hydroxyphthalimide, 2mL of dichloroethane and 5 # magneton (the stirring speed is 600r/s) into a reactor in sequence; and (2) introducing condensed water into a condenser pipe from bottom to top, placing the reactor into a 60 ℃ oil bath kettle, heating while stirring for reaction for 12 hours, adding 15mL of water into reaction liquid after the reaction is finished, extracting with 10mL of ethyl acetate for three times each time, combining obtained organic phases, carrying out spin drying by a rotary evaporator, and separating and purifying a crude product by column chromatography to obtain a 46.4mg light yellow solid product, namely alpha-oxo-N-phenyl-3-butenamide, wherein the yield is 72%.
The chemical reaction formula of example 1 is as follows:
the nmr hydrogen spectrum data of the pale yellow solid product obtained in example 1 are: 1H NMR (400MHz, CDCl)3):δ9.70(s,1H),7.85-7.89(m,2H),7.79-7.82(m,2H),7.73-7.76(m,2H),7.34-7.39(m,2H),7.13-7.17(m,1H),6,08-6.16(m,1H),5.73-5.78(m,1H),5.54-5.57(m,1H).
Example 2
A preparation method of alpha-oxo-N-phenyl-3-crotonamide compound comprises the following steps:
adding 20mmol of p-chloro (dibenzoic acid) iodobenzene, 0.1mmol of N-phenyl-3-butenamide, 20mmol of N-hydroxyphthalimide, 1mL of dichloroethane and one of No. 5 magnetons (stirring speed is 400r/s) into a reactor in sequence; and (2) introducing condensed water into a condenser pipe from bottom to top, placing the reactor into a 60 ℃ oil bath kettle, heating while stirring for reaction for 12 hours, adding 15mL of water into reaction liquid after the reaction is finished, extracting with 10mL of ethyl acetate for three times each time, combining obtained organic phases, carrying out spin drying by a rotary evaporator, and separating and purifying a crude product by column chromatography to obtain a 36mg light yellow solid product, namely alpha-oxo-N-phenyl-3-butenamide, wherein the yield is 87%.
Example 3
A preparation method of alpha-oxo-N-phenyl-3-crotonamide compound comprises the following steps:
adding 0.2mmol of p-chloro (dibenzoic acid) iodobenzene, 10mmol of N-phenyl-3-butenamide, 0.2mmol of N-hydroxyphthalimide, 100mL of dichloroethane and one of No. 5 magnetons (the stirring speed is 1000r/s) into a reactor in sequence; and (2) introducing condensed water into a condenser pipe from bottom to top, placing the reactor into a 60 ℃ oil bath kettle, heating while stirring for reaction for 12 hours, adding 50mL of water into reaction liquid after the reaction is finished, extracting with 50mL of ethyl acetate for three times each time, combining obtained organic phases, carrying out spin drying by a rotary evaporator, and separating and purifying a crude product by column chromatography to obtain 2.4g of a light yellow solid product, namely alpha-oxo-N-phenyl-3-butenamide, wherein the yield is 76%.
The nmr spectra of the products obtained in examples 2 and 3 are substantially the same as those of example 1 and are not given here, and the nmr spectra of both examples 2 and 3 indicate that the desired product was successfully prepared.
The above-described embodiments of the present invention should not be construed as limiting the scope of the present invention. Any other corresponding changes and modifications made according to the technical idea of the present invention should be included in the protection scope of the claims of the present invention.
Claims (10)
1. An α -oxo-N-phenyl-3-butenamide compound having the following structure:
2. a method of preparing an α -oxo-N-phenyl-3-butenamide compound according to claim 1, which comprises the steps of:
mixing a high-valence iodine reagent, N-phenyl-3-butenamide, N-hydroxyphthalimide and an organic solvent to obtain a mixture, stirring and heating the mixture for 8-24 hours in an oil bath at the temperature of 40-100 ℃, taking reaction liquid after heating, adding water into the reaction liquid, extracting, spinning the extracted organic phase to obtain a crude product, and separating and purifying the crude product to obtain the alpha-oxo-N-phenyl-3-butenamide compound.
3. The method for preparing the alpha-oxo-N-phenyl-3-butenamide compound according to claim 2, wherein the molar weight ratio of the high-valence iodine reagent to the N-phenyl-3-butenamide is 0.02 to 200: 1.
4. The method for preparing an α -oxo-N-phenyl-3-butenamide compound according to claim 2 or 3, wherein the molar weight ratio of N-phenyl-3-butenamide to N-hydroxyphthalimide is 0.005 to 50: 1.
5. The method for preparing an α -oxo-N-phenyl-3-butenamide compound according to claim 4, wherein the addition amount ratio of N-hydroxyphthalimide to the organic solution is 0.002 to 20 mmol/mL.
6. The method for producing an α -oxo-N-phenyl-3-butenamide compound according to claim 2 or 3, wherein the organic solvent is at least one of dichloroethane, dichloromethane, acetic acid, ethylene glycol dimethyl ether and dimethyl sulfoxide.
7. A process for the preparation of an α -oxo-N-phenyl-3-butenamide compound according to claim 2 or 3, wherein the higher iodine reagent is iodobenzene p-chloro (dibenzoate) and has the formula 4-Cl-C6H4(OCOPh)2。
8. The method for producing an α -oxo-N-phenyl-3-butenamide compound according to claim 2 or 3, wherein the solvent used for the extraction is at least one of ethyl acetate and methylene chloride; the oil bath adopts silicone oil.
9. The method for producing an α -oxo-N-phenyl-3-butenamide compound according to claim 2 or 3, wherein the separation and purification are carried out by: separating and purifying by column chromatography; the stirring speed is 400-1000 r/s.
10. The use of an α -oxo-N-phenyl-3-butenamide compound according to claim 1 in the preparation of pharmaceuticals, pesticides and chemical intermediates.
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Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN111646917A (en) * | 2020-06-01 | 2020-09-11 | 湖北工业大学 | Preparation method of iodobenzene para-aminated compound promoted by m-chloroperoxybenzoic acid |
| CN113248396A (en) * | 2021-05-25 | 2021-08-13 | 湖北工业大学 | Preparation method of chlorobenzene para-aminated compound mediated by high-valence iodine reagent |
| CN113336665A (en) * | 2021-05-25 | 2021-09-03 | 湖北工业大学 | Preparation method of bromobenzene para-aminated compound mediated by high-valence iodine reagent |
| CN113698337A (en) * | 2021-09-29 | 2021-11-26 | 湖北工业大学 | Preparation method of alpha-oxo acetophenone compound |
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- 2021-10-29 CN CN202111274158.4A patent/CN113845466A/en active Pending
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN111646917A (en) * | 2020-06-01 | 2020-09-11 | 湖北工业大学 | Preparation method of iodobenzene para-aminated compound promoted by m-chloroperoxybenzoic acid |
| CN113248396A (en) * | 2021-05-25 | 2021-08-13 | 湖北工业大学 | Preparation method of chlorobenzene para-aminated compound mediated by high-valence iodine reagent |
| CN113336665A (en) * | 2021-05-25 | 2021-09-03 | 湖北工业大学 | Preparation method of bromobenzene para-aminated compound mediated by high-valence iodine reagent |
| CN113698337A (en) * | 2021-09-29 | 2021-11-26 | 湖北工业大学 | Preparation method of alpha-oxo acetophenone compound |
Non-Patent Citations (1)
| Title |
|---|
| PENG-CHENG QIAN，等: "(Diacetoxyiodo)benzene-Mediated Oxygenation of Benzylic C(sp3)–H Bonds with N-Hydroxyamides at Room Temperature", 《EUR. J. ORG. CHEM》 * |
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