CN113264877A

CN113264877A - Method for preparing azide-substituted quinoline-2, 4-diketone through metal-free catalytic free radical series carbon cyclization reaction

Info

Publication number: CN113264877A
Application number: CN202110511213.0A
Authority: CN
Inventors: 孙凯; 王薪; 张震; 李立梅; 刘颖杰
Original assignee: Yantai University
Current assignee: Yantai University
Priority date: 2021-05-11
Filing date: 2021-05-11
Publication date: 2021-08-17

Abstract

The invention discloses a method for preparing azido-substituted quinoline-2, 4-dione by free radical series carbon cyclization reaction without metal catalysis, relates to the field of chemical preparation, and relates to a preparation method of quinolinedione. The invention aims to solve the problems of high production cost, increased probability of side reaction and environmental pollution caused by metal catalysis. The method comprises the following steps: under the condition of room temperature, methacrylamide, preactivated azidotrimethylsilane solution and dimethyl sulfoxide react, and after the reaction is finished, the mixture is treated with H₂Quenching with O and CH₂Cl₂The extraction is carried out for 3 times, then the organic solvent is concentrated in vacuum, and the residue is purified by flash column chromatography to obtain the azido-substituted quinoline-2, 4-dione. The invention solves the technical problems of high production cost, increased probability of side reaction and environmental pollution caused by metal catalysis, and the compound prepared by the method has the function of inhibiting the plant growthThe activity of the phytopathogen can be applied to the control of the phytopathogen and the preparation of the medicine for resisting the phytopathogen.

Description

Method for preparing azide-substituted quinoline-2, 4-diketone through metal-free catalytic free radical series carbon cyclization reaction

Technical Field

The invention relates to the field of chemical preparation, in particular to a preparation method of quinolinedione.

Background

Green sustainable chemistry has been proposed to solve global chemical pollution and resource exhaustion problems by creating cleaner chemical production flows. The use of expensive metals and high temperature lead to problems of high production cost, increased occurrence probability of side reactions, serious environmental pollution and the like, in this case, no metal participates in the organic reaction under room temperature condition, which is an ideal strategy for green chemistry, but the reaction efficiency under mild condition is a high concern for chemists. The search for a synthetic method with high selectivity and high efficiency of chemical reaction to construct a series of valuable chemical structure frameworks is a great challenge.

The organic azide has wide application in the fields of fine chemical industry and pharmaceutical industry. The azide group is not only a good functional group for organic synthesis and transformation, but also a functional group in the medicine. carbon-N₃Bonds are important synthetic methods that provide a means for the introduction of nitrogen atoms into a variety of organic molecules. Thus how to combine N₃The introduction of organic molecules has been a hot spot for organic chemists to study. Thus, there is a continuing need in synthetic organic chemistry to develop sustainable and practical methods to form carbon-N₃A key. On the other hand, nitrogen-containing heterocycles are key backbone structures of many drug molecules, and in particular, structurally diverse quinoline-2, 4-diones are widely found in many natural products, pharmaceuticals, and agrochemicals. Although some methods for constructing quinoline-2, 4-dione have been reported, most methods adopt metal catalysis, which leads to the use of expensive metal and causes problems of high production cost, increased occurrence probability of side reaction, serious environmental pollution and the like due to high temperature.

Disclosure of Invention

The invention aims to solve the technical problems of high production cost, increased probability of side reaction and environmental pollution caused by metal catalysis, and provides a metal-free-radical series carbocyclization reaction for preparing azide-substituted quinoline-2, 4-diketone.

The method for preparing the azide-substituted quinoline-2, 4-diketone by the metal-free catalyzed free radical series carbon cyclization reaction comprises the following steps:

to the reaction tube were added N- (2-cyanophenyl) -N-methylacrylamide (1a)60mg and diphenyldiselenide (PhSe) in this order at room temperature₂46.8mg, 145mg of iodobenzene diethyl ester and 127. mu.L of azidotrimethylsilane (93% specification) were finally reacted in 2mL of dimethyl sulfoxide (DMSO), the reaction tube was stirred at room temperature for 12 hours until complete consumption of the starting material was monitored by TLC analysis, and after completion of the reaction, the mixture was treated with H₂Quenching with O (15mL) and CH₂Cl₂(3 × 5mL) and the organic solvent was then concentrated in vacuo and the residue was purified by flash column chromatography using a mixture of petroleum ether and ethyl acetate as eluent, Rf ═ 0.44, to give 3- (azidomethyl) -1, 3-dimethylquinoline-2, 4(1H, 3H) -dione (2 a).

to a reaction tube were added in this order N- (2-cyano-3-fluorophenyl) -N-methacrylamide (1b)65mg, diphenyldiselenide 46.8mg, diethyliodobenzene 145mg and 127. mu.L azidotrimethylsilane (93% of specification) at room temperature, and finally the reaction was carried out in 2mL dimethyl sulfoxide (DMSO), the reaction tube was stirred at room temperature for 12 hours until the complete consumption of the starting material was monitored by TLC analysis, and after completion of the reaction, the mixture was treated with H₂Quenching with O (15mL) and CH₂Cl₂(3 × 5mL) and the organic solvent was then concentrated in vacuo and the residue was purified by flash column chromatography with a mixture of petroleum ether and ethyl acetate as eluent, Rf ═ 0.29, to give 3- (azidomethyl) -5-fluoro-1, 3-dimethylquinoline-2, 4(1H, 3H) -dione (2 b).

to a reaction tube were added, in this order, 70mg of N- (3-chloro-2-cyanophenyl) -N-methacrylamide (1c), 46.8mg of diphenyldiselenide, 145mg of diethyliodobenzene and 127. mu.L of azido trisulfide at room temperatureMethylsilane (specification 93%), finally in 2mL of dimethyl sulfoxide (DMSO), the reaction tube was stirred at room temperature for 12 hours until complete consumption of starting material was monitored by TLC analysis, after completion of the reaction the mixture was washed with H₂Quenching with O (15mL) and CH₂Cl₂(3 × 5mL) and the organic solvent was then concentrated in vacuo and the residue was purified by flash column chromatography with a mixture of petroleum ether and ethyl acetate as eluent, Rf ═ 0.31, to give 3- (azidomethyl) -5-chloro-1, 3-dimethylquinoline-2, 4(1H, 3H) -dione (2 c).

to a reaction tube were added 83mg of N- (3-bromo-2-cyano) -N-methacrylamide (1d), 46.8mg of diphenyldiselenide, 145mg of diethyliodobenzene and 127. mu.L of azidotrimethylsilane (93% specification) in this order at room temperature, and finally the reaction was carried out in 2mL of dimethyl sulfoxide (DMSO), and the reaction tube was stirred at room temperature for 12 hours until the complete consumption of the starting material was monitored by TLC analysis, and after completion of the reaction, the mixture was treated with H₂Quenching with O (15mL) and CH₂Cl₂(3 × 5mL) and the organic solvent was then concentrated in vacuo and the residue was purified by flash column chromatography with a mixture of petroleum ether and ethyl acetate as eluent, Rf ═ 0.34, to give 3- (azidomethyl) -5-bromo-1, 3-dimethylquinoline-2, 4(1H, 3H) -dione (2 d).

to a reaction tube were added 65mg of N- (2-cyano-4-fluorophenyl) -N-methacrylamide (1e), 46.8mg of diphenyldiselenide, 145mg of diethyliodobenzene and 127. mu.L of azidotrimethylsilane (93% specification) at room temperature, and finally the reaction was carried out in 2mL of dimethyl sulfoxide (DMSO), the reaction tube was stirred at room temperature for 12 hours until the complete consumption of the starting material was monitored by TLC analysis, and after completion of the reaction, the mixture was treated with H₂Quenching with O (15mL) and CH₂Cl₂(3X 5mL), then the organic solvent is concentrated in vacuo and the residue is passed throughPurification by flash column chromatography using a mixture of petroleum ether and ethyl acetate as eluent, Rf ═ 0.34, yielded 3- (azidomethyl) -6-fluoro-1, 3-dimethylquinoline-2, 4(1H, 3H) -dione (2 e).

to a reaction tube were added 70mg of N- (4-chloro-2-cyanophenyl) -N-methacrylamide (1f), 46.8mg of diphenyldiselenide, 145mg of diethyliodobenzene and 127. mu.L of azidotrimethylsilane (93% specification) at room temperature, and finally the reaction was carried out in 2mL of dimethyl sulfoxide (DMSO), and then the reaction tube was stirred at room temperature for 12 hours until the complete consumption of the starting material was monitored by TLC analysis, and after completion of the reaction, the mixture was treated with H₂Quenching with O (15mL) and CH₂Cl₂(3 × 5mL) and the organic solvent was then concentrated in vacuo and the residue was purified by flash column chromatography with a mixture of petroleum ether and ethyl acetate as eluent, Rf ═ 0.46, to give 3- (azidomethyl) -6-chloro-1, 3-dimethylquinoline-2, 4(1H, 3H) -dione (2 f).

to a reaction tube were added 83mg of N- (4-bromo-2-cyanophenyl) -N-methacrylamide (1g), 46.8mg of diphenyldiselenide, 145mg of diethyliodobenzene and 127. mu.L of azidotrimethylsilane (93% specification) at room temperature, and finally the reaction was carried out in 2mL of dimethyl sulfoxide (DMSO), and then the reaction tube was stirred at room temperature for 12 hours until the complete consumption of the starting material was monitored by TLC analysis, and after completion of the reaction, the mixture was treated with H₂Quenching with O (15mL) and CH₂Cl₂(3 × 5mL) and the organic solvent was then concentrated in vacuo and the residue was purified by flash column chromatography using a mixture of petroleum ether and ethyl acetate as eluent, Rf ═ 0.43, to give 3- (azidomethyl) -6-bromo-1, 3-dimethylquinoline-2, 4(1H, 3H) -dione (2 g).

to a reaction tube were added N- (2-cyano-4-methylphenyl) -N-methacrylamide (1H)64mg, diphenyl diselenide 46.8mg, diethyl iodobenzene 145mg and 127. mu.L azidotrimethylsilane (93% specification) in this order at room temperature, and finally the reaction was carried out in 2mL dimethyl sulfoxide (DMSO), and then the reaction tube was stirred at room temperature for 12 hours until the complete consumption of the starting material was monitored by TLC analysis, and after completion of the reaction, the mixture was treated with H₂Quenching with O (15mL) and CH₂Cl₂(3 × 5mL) was extracted, the organic solvent was then concentrated in vacuo and the residue was purified by flash column chromatography with a mixture of petroleum ether and ethyl acetate as eluent, Rf ═ 0.41, to give 3- (azidomethyl) -1,3, 6-trimethylquinoline-2, 4(1H, 3H) -dione (compound 2H).

to a reaction tube were added N- (2-cyano-5-fluorophenyl) -N-methacrylamide (1i)65mg, diphenyldiselenide 46.8mg, diethyliodobenzene 145mg and 127. mu.L azidotrimethylsilane (93% of specification) at room temperature, and finally the reaction was carried out in 2mL dimethyl sulfoxide (DMSO), and then the reaction tube was stirred at room temperature for 12 hours until the complete consumption of the starting material was monitored by TLC analysis, after the completion of the reaction, the mixture was treated with H₂Quenching with O (15mL) and CH₂Cl₂(3 × 5mL) and the organic solvent was then concentrated in vacuo and the residue was purified by flash column chromatography with a mixture of petroleum ether and ethyl acetate as eluent, Rf ═ 0.51, to give 3- (azidomethyl) -7-fluoro-1, 3-dimethylquinoline-2, 4(1H, 3H) -dione (2 i).

to a reaction tube were added, in this order, N- (5-bromo-2-cyano) -N-methacrylamide (1k)83mg, diphenyldiselenide 46.8mg, diethyliodobenzene 145mg, 127. mu.L azidotrimethylsilane at room temperature, and finally the reaction was carried out in 2mL of dimethyl sulfoxide (DMSO), and then the reaction tube was stirred at room temperature for 12 hours until monitoring by TLC analysisUntil the raw materials are completely consumed, after the reaction is completed, the mixture is treated with H₂Quenching with O (15mL) and CH₂Cl₂(3 × 5mL) and the organic solvent was then concentrated in vacuo and the residue was purified by flash column chromatography using a mixture of petroleum ether and ethyl acetate as eluent, Rf ═ 0.55, to give 3- (azidomethyl) -7-bromo-1, 3-dimethylquinoline-2, 4(1H, 3H) -dione (2 k).

to a reaction tube were added in this order N- (2-cyano-5-methylphenyl) -N-methacrylamide (1L)64mg, diphenyl diselenide 46.8mg, diethyl iodobenzene 145mg, 127. mu.L azidotrimethylsilane (93% specification) at room temperature, and finally the reaction was carried out in 2mL dimethyl sulfoxide (DMSO), and then the reaction tube was stirred at room temperature for 12 hours until the complete consumption of the starting material was monitored by TLC analysis, and after completion of the reaction, the mixture was treated with H₂Quenching with O (15mL) and CH₂Cl₂(3 × 5mL) and the organic solvent was then concentrated in vacuo and the residue was purified by flash column chromatography with a mixture of petroleum ether and ethyl acetate as eluent, Rf ═ 0.50, to give 3- (azidomethyl) -1,3, 7-trimethylquinoline-2, 4(1H, 3H) -dione (2 l).

to a reaction tube were added in this order N- (2-cyano-5-methoxyphenyl) -N-methacrylamide (1m)69mg, diphenyldiselenide 46.8mg, diethyliodobenzene 145mg, 127. mu.L azidotrimethylsilane (93% specification) at room temperature, and finally the reaction was carried out in 2mL dimethyl sulfoxide (DMSO), and then the reaction tube was stirred at room temperature for 12 hours until the complete consumption of the starting material was monitored by TLC analysis, and after completion of the reaction, the mixture was treated with H₂Quenching with O (15mL) and CH₂Cl₂(3X 5mL), followed by concentration of the organic solvent in vacuo, and purification of the residue by flash column chromatography using a mixture of petroleum ether and ethyl acetate as eluent, Rf ═ 0.33, to give 3- (azidomethyl) -7-methylOxy-1, 3-dimethylquinoline-2, 4(1H, 3H) -dione (2 m).

The reaction mechanism of the invention is as follows: the azido group was originally formed by ligand exchange and PhI (OAc)₂And TMSN₃Weak I-N bonds between the interactions. The azide group then attacks the activated alkenyl moiety of substrate 1 to give the group intermediate a. Subsequently, intermediate a is subjected to intramolecular 6-exocyclic cyclization with an alkynyl fast to give imine group B. Imine group B undergoes hydrogen abstraction (pathway A) to give imine C. Finally, imine C is substituted by H₂Hydrolysis of O gives the corresponding product 2.

The compound prepared by the method has the activity of inhibiting phytopathogen, can be applied to the control of the phytopathogen and can be applied to the preparation of the medicine for resisting the phytopathogen.

Drawings

FIG. 1 is a drawing of Compound 2a according to one embodiment¹H NMR spectrum; FIG. 2 is a drawing of Compound 2a in accordance with one embodiment¹³C NMR spectrum; FIG. 3 is an HR-ESI-MS spectrum of compound 2a according to the first embodiment; FIG. 4 is a drawing of Compound 2b according to second embodiment¹H NMR spectrum; FIG. 5 is a drawing of Compound 2b according to second embodiment¹³C NMR spectrum; FIG. 6 is an HR-ESI-MS spectrum of Compound 2b, according to a second embodiment; FIG. 7 is a drawing of Compound 2c in accordance with a third embodiment¹H NMR spectrum; FIG. 8 is a drawing of Compound 2c in accordance with a third embodiment¹³C NMR spectrum; FIG. 9 is an HR-ESI-MS spectrum of compound 2c, according to a third embodiment; FIG. 10 is a drawing of Compound 2d according to the fourth embodiment¹H NMR spectrum; FIG. 11 is a drawing of Compound 2d according to the fourth embodiment¹³C NMR spectrum; FIG. 12 is an HR-ESI-MS spectrum of Compound 2d, according to fourth embodiment; FIG. 13 is a drawing of Compound 2e of the fifth embodiment¹H NMR spectrum; FIG. 14 is a drawing of Compound 2e of the fifth embodiment¹³C NMR spectra(ii) a FIG. 15 is an HR-ESI-MS spectrum of compound 2e, according to fifth embodiment; FIG. 16 is a drawing of Compound 2f according to the sixth embodiment¹H NMR spectrum; FIG. 17 is a drawing of Compound 2f in accordance with the sixth embodiment¹³C NMR spectrum; FIG. 18 is an HR-ESI-MS spectrum of Compound 2f, according to the sixth embodiment; FIG. 19 is a drawing showing 2g of Compound No. seven¹H NMR spectrum; FIG. 20 is a drawing of 2g of Compound No. seven¹³C NMR spectrum; FIG. 21 is an HR-ESI-MS spectrum of compound 2g, according to seventh embodiment; FIG. 22 is a drawing of Compound 2h of embodiment eight¹H NMR spectrum; FIG. 23 is a drawing of Compound 2h of embodiment eight¹³C NMR spectrum; FIG. 24 is an HR-ESI-MS spectrum of compound 2h in accordance with example eight; FIG. 25 is a drawing of Compound 2i according to a fifth embodiment¹H NMR spectrum; FIG. 26 is a drawing of Compound 2i according to a fifth embodiment¹³C NMR spectrum; FIG. 27 is an HR-ESI-MS spectrum of Compound 2i, according to embodiment nine; FIG. 28 is a drawing of Compound 2k of the tenth embodiment¹H NMR spectrum; FIG. 29 is a drawing of Compound 2k of the tenth embodiment¹³C NMR spectrum; FIG. 30 is an HR-ESI-MS spectrum of compound 2k, according to ten embodiments; FIG. 31 is a drawing of 2l compound of the eleventh embodiment¹H NMR spectrum; FIG. 32 is a drawing of 2l compound of the eleventh embodiment¹³C NMR spectrum; FIG. 33 is an HR-ESI-MS spectrum of compound 2l according to eleventh embodiment; FIG. 34 is a drawing of compound 2m in accordance with the twelfth embodiment¹H NMR spectrum; FIG. 35 is a drawing of compound 2m in accordance with the twelfth embodiment¹³C NMR spectrum; FIG. 36 is an HR-ESI-MS spectrum of compound 2m, example twelve.

Detailed Description

The technical solution of the present invention is not limited to the following specific embodiments, but includes any combination of the specific embodiments.

The first embodiment is as follows: the method for preparing azide-substituted quinoline-2, 4-dione by the metal-free catalyzed free radical tandem carbocyclization reaction in the embodiment is as follows:

to the reaction tube were added N- (2-cyanophenyl) -N-methylacrylamide (1a)60mg and diphenyldiselenide (PhSe) in this order at room temperature₂46.8mg、Diethyliodobenzene 145mg and 127. mu.L azidotrimethylsilane (93% specification) were finally reacted in 2mL dimethyl sulfoxide (DMSO), the reaction tube was stirred at room temperature for 12 hours until complete consumption of the starting material was monitored by TLC analysis, and after completion of the reaction, the mixture was treated with H₂Quenching with O (15mL) and CH₂Cl₂(3 × 5mL) and the organic solvent was then concentrated in vacuo and the residue was purified by flash column chromatography using a mixture of petroleum ether and ethyl acetate as eluent, Rf ═ 0.44, to give 3- (azidomethyl) -1, 3-dimethylquinoline-2, 4(1H, 3H) -dione (2 a). The yield was: 90%, 66 mg.

The equation for the reaction is:

of Compound 2a¹H NMR、¹³The structure of the compound is known by C NMR and HR-ESI-MS spectra. Specifically, the method comprises the following steps: compound 2a is a red liquid, Rf (petroleum ether: ethyl acetate ═ 3:1): 0.44.¹H NMR(400MHz,CDCl₃):δ8.03(d,J＝7.8Hz,1H),7.65(t,J＝7.8Hz, 1H),7.19(t,J＝7.4Hz,2H),3.97(s,2H),3.49(s,3H),1.38(s,3H)。¹³C NMR(150MHz,CDCl₃) Delta 195.47, 171.89,143.19,136.60,128.31,123.40,119.77,115.07,57.11,55.68,29.97,23.21 HRMS (ESI) calculated to give a molecular formula C₁₂H₁₂N₄O₂[M+Na]⁺:267.0632,found:267.0631。

The reaction mechanism is as follows: the azido group was originally formed by ligand exchange and PhI (OAc)₂And TMSN₃Weak I-N bonds between the interactions. The azide group then attacks the activated alkenyl moiety of substrate 1a to give the group intermediate a. Subsequently, intermediate a is subjected to intramolecular 6-exocyclic cyclization with an alkynyl fast to give imine group B. Imine group B undergoes hydrogen abstraction (pathway A) to give imine C. Finally, imine C is substituted by H₂Hydrolysis of O gives the corresponding product 2 a.

The second embodiment is as follows: the method for preparing azide-substituted quinoline-2, 4-dione by the metal-free catalyzed free radical tandem carbocyclization reaction in the embodiment is as follows:

to a reaction tube were added in this order N- (2-cyano-3-fluorophenyl) -N-methacrylamide (1b)65mg, diphenyldiselenide 46.8mg, diethyliodobenzene 145mg and 127. mu.L azidotrimethylsilane (93% of specification) at room temperature, and finally the reaction was carried out in 2mL dimethyl sulfoxide (DMSO), the reaction tube was stirred at room temperature for 12 hours until the complete consumption of the starting material was monitored by TLC analysis, and after completion of the reaction, the mixture was treated with H₂Quenching with O (15mL) and CH₂Cl₂Extraction (3 × 5mL) followed by concentration of the organic solvent in vacuo and purification of the residue by flash column chromatography with a mixture of petroleum ether and ethyl acetate as eluent, Rf ═ 0.29, gave 3- (azidomethyl) -5-fluoro-1, 3-dimethylquinoline-2, 4(1H, 3H) -dione (compound 2b) in the following yield: 70%, 55 mg.

The equation for the reaction is:

of Compound 2b¹H NMR、¹³The structure of the compound is known by C NMR and HR-ESI-MS spectra. Specifically, the method comprises the following steps: compound 2b is a red liquid, Rf (petroleum ether: EtOAc ═ 3:1): 0.29;¹H NMR(600MHz,CDCl₃)δ7.60–7.56(m,1H),6.99(d,J＝8.5 Hz,1H),6.91–6.87(m,1H),3.94(dd,J＝33.3,11.5Hz,2H),3.49(s,3H),1.40(s,3H)；¹³C NMR(151 MHz,CDCl₃)δ192.59,171.27,162.23(d,J＝267.1Hz),144.17(d,J＝3.0Hz),136.64(d,J＝11.9Hz), 111.61(d,J＝21.2Hz),110.85(d,J＝3.3Hz),109.72(d,J＝9.5Hz),57.99,54.80,30.79,22.73；HRMS (ESI)calcd for C₁₂H₁₁FN₄O₂[M+Na]⁺:285.0758,found:285.0754.

the third concrete implementation mode: the method for preparing azide-substituted quinoline-2, 4-dione by the metal-free catalyzed free radical tandem carbocyclization reaction in the embodiment is as follows:

sequentially adding N- (3-chloro-2-cyanophenyl) -N-methyl into a reaction tube at room temperatureAcrylamide (1c)70mg, diphenyldiselenide 46.8mg, diethyliodobenzene 145mg and 127. mu.L azidotrimethylsilane (93% specification), finally reacted in 2mL dimethyl sulfoxide (DMSO), the reaction tube was stirred at room temperature for 12 hours until complete consumption of the starting material was monitored by TLC analysis, and after completion of the reaction, the mixture was treated with H₂Quenching with O (15mL) and CH₂Cl₂Extraction (3 × 5mL) followed by concentration of the organic solvent in vacuo and purification of the residue by flash column chromatography with a mixture of petroleum ether and ethyl acetate as eluent, Rf ═ 0.31, gave 3- (azidomethyl) -5-chloro-1, 3-dimethylquinoline-2, 4(1H, 3H) -dione (compound 2c) in the following yield: 43%, 36 mg.

The equation for the reaction is:

of Compound 2c¹H NMR、¹³The structure of the compound is known by C NMR and HR-ESI-MS spectra. Specifically, the method comprises the following steps: compound 2c is a red liquid, Rf (petroleum ether: ethyl acetate ═ 3:1): 0.31.¹H NMR(600MHz,CDCl₃):δ7.49(t,J＝8.2Hz,1H),7.23(dd,J＝8.0, 0.8Hz,1H),7.12(dd,J＝8.4,0.6Hz,1H),3.92(dd,J＝28.5,11.7Hz,2H),3.48(s,3H),1.39(s,3H).¹³C NMR(150MHz,CDCl₃):δ193.30,170.64,144.51,135.62,134.69,126.76,118.18,113.87,58.25,54.19, 30.87,21.77.HRMS(ESI)calcd for C₁₂H₁₁ClN₄O₂[M+Na]⁺:301.0463,found:301.0460。

the fourth concrete implementation mode: the method for preparing azide-substituted quinoline-2, 4-dione by the metal-free catalyzed free radical tandem carbocyclization reaction in the embodiment is as follows:

to a reaction tube were added 83mg of N- (3-bromo-2-cyano) -N-methacrylamide (1d), 46.8mg of diphenyldiselenide, 145mg of diethyliodobenzene and 127. mu.L of azidotrimethylsilane (93% specification) in this order at room temperature, and finally the reaction was carried out in 2mL of dimethyl sulfoxide (DMSO), and the reaction tube was stirred at room temperature for 12 hours until TLC analysisThe reaction is completed, and the mixture is treated with H₂Quenching with O (15mL) and CH₂Cl₂Extraction (3 × 5mL) followed by concentration of the organic solvent in vacuo and purification of the residue by flash column chromatography with a mixture of petroleum ether and ethyl acetate as eluent, Rf ═ 0.34, gave 3- (azidomethyl) -5-bromo-1, 3-dimethylquinoline-2, 4(1H, 3H) -dione (compound 2d) in the following yield: 63%, 61 mg.

The equation for the reaction is:

of Compound 2d¹H NMR、¹³The structure of the compound is known by C NMR and HR-ESI-MS spectra. Specifically, the method comprises the following steps: compound 2d is a red liquid, Rf (petroleum ether: ethyl acetate ═ 3:1): 0.34.¹H NMR(600MHz,CDCl₃):δ7.44(dd,J＝8.0,0.8Hz,1H),7.38(t,J＝ 8.1Hz,1H),7.16(d,J＝8.3Hz,1H),3.90(q,J＝11.7Hz,2H),3.46(s,3H),1.37(s,3H).¹³C NMR(150 MHz,CDCl₃):δ193.60,170.48,144.59,134.86,130.33,123.13,119.37,114.60,58.03,54.13,30.81,21.59. HRMS(ESI)calcd for C₁₂H₁₁BrN₄O₂[M+Na]⁺:344.9958,found:344.9955。

the fifth concrete implementation mode: the method for preparing azide-substituted quinoline-2, 4-dione by the metal-free catalyzed free radical tandem carbocyclization reaction in the embodiment is as follows:

to a reaction tube were added 65mg of N- (2-cyano-4-fluorophenyl) -N-methacrylamide (1e), 46.8mg of diphenyldiselenide, 145mg of diethyliodobenzene and 127. mu.L of azidotrimethylsilane (93% specification) at room temperature, and finally the reaction was carried out in 2mL of dimethyl sulfoxide (DMSO), the reaction tube was stirred at room temperature for 12 hours until the complete consumption of the starting material was monitored by TLC analysis, and after completion of the reaction, the mixture was treated with H₂Quenching with O (15mL) and CH₂Cl₂(3X 5mL), then the organic solvent is concentrated in vacuo and the residue is purified by flash column chromatography using petroleum ether and ethyl acetateA mixture of ethyl esters of acids was used as eluent, Rf ═ 0.34, to give 3- (azidomethyl) -6-fluoro-1, 3-dimethylquinoline-2, 4(1H, 3H) -dione (compound 2e) in yield: 66%, 52 mg.

The equation for the reaction is:

of Compound 2e¹H NMR、¹³The structure of the compound is known by C NMR and HR-ESI-MS spectra. Specifically, the method comprises the following steps: compound 2e is a red liquid, Rf (petroleum ether: ethyl acetate ═ 3:1): 0.34.¹H NMR(600MHz,CDCl₃):δ7.71(dd,J＝7.9,3.1Hz,1H),7.39-7.36(m, 1H),7.18(dd,J＝9.1,4.0Hz,1H),4.00-3.95(m,2H),3.50(s,3H),1.39(s,3H).¹³C NMR(150MHz, CDCl₃):δ194.76,171.47,158.60(d,J＝245.6Hz),139.64,123.56(d,J＝23.8Hz),120.94(d,J＝5.9Hz), 116.93(d,J＝7.5Hz),114.03(d,J＝23.2Hz),57.00,55.81,30.26,23.14.HRMS(ESI)calcd for C₁₂H₁₁FN₄O₂[M+Na]⁺:285.0758,found:285.0755.

the sixth specific implementation mode: the method for preparing azide-substituted quinoline-2, 4-dione by the metal-free catalyzed free radical tandem carbocyclization reaction in the embodiment is as follows:

to a reaction tube were added 70mg of N- (4-chloro-2-cyanophenyl) -N-methacrylamide (1f), 46.8mg of diphenyldiselenide, 145mg of diethyliodobenzene and 127. mu.L of azidotrimethylsilane (93% specification) at room temperature, and finally the reaction was carried out in 2mL of dimethyl sulfoxide (DMSO), and then the reaction tube was stirred at room temperature for 12 hours until the complete consumption of the starting material was monitored by TLC analysis, and after completion of the reaction, the mixture was treated with H₂Quenching with O (15mL) and CH₂Cl₂Extraction (3 × 5mL) followed by concentration of the organic solvent in vacuo and purification of the residue by flash column chromatography with a mixture of petroleum ether and ethyl acetate as eluent, Rf ═ 0.46, gave 3- (azidomethyl) -6-chloro-1, 3-dimethylquinoline-2, 4(1H, 3H) -dione (compound 2f) in the following yield: 70% and 58 mg.

The equation for the reaction is:

of compound 2f¹H NMR、¹³The structure of the compound is known by C NMR and HR-ESI-MS spectra. Specifically, the method comprises the following steps: compound 2f is a white solid, Rf (petroleum ether: ethyl acetate ═ 3:1): 0.46.¹H NMR(400MHz,CDCl₃):δ7.96(d,J＝2.6Hz,1H),7.57(dd,J＝8.9, 2.6Hz,1H),7.12(d,J＝8.9Hz,1H),3.95(s,2H),3.46(s,3H),1.36(s,3H).¹³C NMR(150MHz,CDCl₃):δ 194.51,171.58,141.71,136.17,129.27,127.74,120.75,116.71,57.18,55.74,30.16,23.10.HRMS(ESI) calcd for C₁₂H₁₁ClN₄O₂[M+Na]⁺:301.0463,found:301.0462.

the seventh embodiment: the method for preparing azide-substituted quinoline-2, 4-dione by the metal-free catalyzed free radical tandem carbocyclization reaction in the embodiment is as follows:

to a reaction tube were added 83mg of N- (4-bromo-2-cyanophenyl) -N-methacrylamide (1g), 46.8mg of diphenyldiselenide, 145mg of diethyliodobenzene and 127. mu.L of azidotrimethylsilane (93% specification) at room temperature, and finally the reaction was carried out in 2mL of dimethyl sulfoxide (DMSO), and then the reaction tube was stirred at room temperature for 12 hours until the complete consumption of the starting material was monitored by TLC analysis, and after completion of the reaction, the mixture was treated with H₂Quenching with O (15mL) and CH₂Cl₂Extraction (3 × 5mL) followed by concentration of the organic solvent in vacuo and purification of the residue by flash column chromatography with a mixture of petroleum ether and ethyl acetate as eluent, Rf ═ 0.43, gave 3- (azidomethyl) -6-bromo-1, 3-dimethylquinoline-2, 4(1H, 3H) -dione (compound 2g) in the following yield: 81%, 78.5 mg.

The equation for the reaction is:

of compound 2g¹H NMR、¹³The structure of the compound is known by C NMR and HR-ESI-MS spectra. Specifically, the method comprises the following steps: compound 2g was a white solid, Rf (petroleum ether: ethyl acetate ═ 3:1): 0.43.¹H NMR(600MHz,CDCl₃)δ8.12(d,J＝2.5Hz,1H),7.73(dd,J＝8.8, 2.5Hz,1H),7.08(d,J＝8.8Hz,1H),3.97(s,2H),3.48(s,3H),1.39(s,3H)；¹³C NMR(151MHz,CDCl₃)δ 194.40,171.58,142.17,139.03,130.77,121.05,116.98,116.49,57.21,55.74,30.13,23.11；HRMS(ESI) calcd for C₁₂H₁₁BrN₄O₂[M+Na]⁺:344.9958,found:344.9958.

the specific implementation mode is eight: the method for preparing azide-substituted quinoline-2, 4-dione by the metal-free catalyzed free radical tandem carbocyclization reaction in the embodiment is as follows:

to a reaction tube were added N- (2-cyano-4-methylphenyl) -N-methacrylamide (1H)64mg, diphenyl diselenide 46.8mg, diethyl iodobenzene 145mg and 127. mu.L azidotrimethylsilane (93% specification) in this order at room temperature, and finally the reaction was carried out in 2mL dimethyl sulfoxide (DMSO), and then the reaction tube was stirred at room temperature for 12 hours until the complete consumption of the starting material was monitored by TLC analysis, and after completion of the reaction, the mixture was treated with H₂Quenching with O (15mL) and CH₂Cl₂Extraction (3 × 5mL) followed by concentration of the organic solvent in vacuo and purification of the residue by flash column chromatography with a mixture of petroleum ether and ethyl acetate as eluent, Rf ═ 0.41, gave 3- (azidomethyl) -1,3, 6-trimethylquinoline-2, 4(1H, 3H) -dione (compound 2H) in the following yield: 80%, 62 mg.

The equation for the reaction is:

of Compound 2h¹H NMR、¹³The structure of the compound is known by C NMR and HR-ESI-MS spectra. Specifically, the method comprises the following steps: compound 2h was a red liquid, Rf (petroleum ether: ethyl acetate ═ 3:1): 0.41.¹H NMR(600MHz,CDCl₃):δ7.83(d,J＝1.8Hz,1H),7.46(dd,J＝8.4, 1.9Hz,1H),7.08(d,J＝8.4Hz,1H),3.97(s,2H),3.48(s,3H),2.36(s,3H),1.38(s,3H).¹³C NMR(150 MHz,CDCl₃):δ195.70,171.77,141.04,137.38,133.20,128.23,119.59,115.04,56.99,55.75,29.94,23.22, 20.33.HRMS(ESI)calcd for C₁₃H₁₄N₄O₂[M+Na]⁺:281.1009,found:281.1004.

the specific implementation method nine: the method for preparing azide-substituted quinoline-2, 4-dione by the metal-free catalyzed free radical tandem carbocyclization reaction in the embodiment is as follows:

to a reaction tube were added N- (2-cyano-5-fluorophenyl) -N-methacrylamide (1i)65mg, diphenyldiselenide 46.8mg, diethyliodobenzene 145mg and 127. mu.L azidotrimethylsilane (93% of specification) at room temperature, and finally the reaction was carried out in 2mL dimethyl sulfoxide (DMSO), and then the reaction tube was stirred at room temperature for 12 hours until the complete consumption of the starting material was monitored by TLC analysis, after the completion of the reaction, the mixture was treated with H₂Quenching with O (15mL) and CH₂Cl₂Extraction (3 × 5mL) followed by concentration of the organic solvent in vacuo and purification of the residue by flash column chromatography with a mixture of petroleum ether and ethyl acetate as eluent, Rf ═ 0.51, gave 3- (azidomethyl) -7-fluoro-1, 3-dimethylquinoline-2, 4(1H, 3H) -dione (compound 2i) in the following yield: 77%, 60.5 mg.

The equation for the reaction is:

of Compound 2i¹H NMR、¹³The structure of the compound is known by C NMR and HR-ESI-MS spectra. Specifically, the method comprises the following steps: compound 2i is a yellow liquid, Rf (petroleum ether: ethyl acetate ═ 3:1): 0.51.¹H NMR(400MHz,CDCl₃):δ8.12-8.06(m,1H),6.93-6.87(m,2H), 4.01-3.95(m,2H),3.48(s,3H),1.40(s,3H).¹³C NMR(100MHz,CDCl₃):δ193.93,172.09,167.85(d,J＝ 256.8Hz),145.55(d,J＝11.7Hz),131.36(d,J＝11.4Hz),116.39(d,J＝2.3Hz),110.83(d,J＝22.4Hz), 102.74(d,J＝27.6Hz),56.98,56.87,30.14,23.20.HRMS(ESI)calcd for C₁₂H₁₁FN₄O₂[M+Na]⁺:285.0758, found:285.0753.

the detailed implementation mode is ten: the method for preparing azide-substituted quinoline-2, 4-dione by the metal-free catalyzed free radical tandem carbocyclization reaction in the embodiment is as follows:

to a reaction tube were added 83mg of N- (5-bromo-2-cyano) -N-methacrylamide (1k), 46.8mg of diphenyldiselenide, 145mg of diethyliodobenzene, 127. mu.L of azidotrimethylsilane in this order at room temperature, and finally the reaction was carried out in 2mL of dimethyl sulfoxide (DMSO), and then the reaction tube was stirred at room temperature for 12 hours until the complete consumption of the starting material was monitored by TLC analysis, after the completion of the reaction, the mixture was treated with H₂Quenching with O (15mL) and CH₂Cl₂Extraction (3 × 5mL), followed by concentration of the organic solvent in vacuo, purification of the residue by flash column chromatography with a mixture of petroleum ether and ethyl acetate as eluent, Rf ═ 0.55, gave 3- (azidomethyl) -7-bromo-1, 3-dimethylquinoline-2, 4(1H, 3H) -dione (2k) in the following yield: 80%, 77.5 mg.

The equation for the reaction is:

of Compound 2k¹H NMR、¹³The structure of the compound is known by C NMR and HR-ESI-MS spectra. Specifically, the method comprises the following steps: compound 2k is a yellow liquid, Rf (petroleum ether: ethyl acetate ═ 3:1): 0.55.¹H NMR(600MHz,CDCl₃):δ7.88(d,J＝8.3Hz,1H),7.36(d,J＝1.6 Hz,1H),7.33(dd,J＝8.3,1.6Hz,1H),3.96(s,2H),3.48(s,3H),1.38(s,3H).¹³C NMR(150MHz,CDCl₃): δ194.59,171.90,144.02,134.08,131.76,129.63,127.21,126.65,118.48,118.35,57.18,55.83,30.12,23.12. HRMS(ESI)calcd for C₁₂H₁₁BrN₄O₂[M+Na]⁺:344.9958,found:344.9953.

the concrete implementation mode eleven: the method for preparing azide-substituted quinoline-2, 4-dione by the metal-free catalyzed free radical tandem carbocyclization reaction in the embodiment is as follows:

to a reaction tube were added in this order N- (2-cyano-5-methylphenyl) -N-methacrylamide (1L)64mg, diphenyl diselenide 46.8mg, diethyl iodobenzene 145mg, 127. mu.L azidotrimethylsilane (93% specification) at room temperature, and finally the reaction was carried out in 2mL dimethyl sulfoxide (DMSO), and then the reaction tube was stirred at room temperature for 12 hours until the complete consumption of the starting material was monitored by TLC analysis, and after completion of the reaction, the mixture was treated with H₂Quenching with O (15mL) and CH₂Cl₂Extraction (3 × 5mL) followed by concentration of the organic solvent in vacuo and purification of the residue by flash column chromatography with a mixture of petroleum ether and ethyl acetate as eluent, Rf ═ 0.50, gave 3- (azidomethyl) -1,3, 7-trimethylquinoline-2, 4(1H, 3H) -dione (compound 2l) in the following yield: 85% and 65.8 mg.

The equation for the reaction is:

of Compound 2l¹H NMR、¹³The structure of the compound is known by C NMR and HR-ESI-MS spectra. Specifically, the method comprises the following steps: compound 2l was a yellow liquid, Rf (petroleum ether: ethyl acetate ═ 3:1): 0.50.¹H NMR(600MHz,CDCl₃):δ7.93(dd,J＝7.9,1.7Hz,1H),7.01(d,J ＝7.9Hz,1H),6.98(s,1H),3.99-3.94(m,2H),3.49(d,J＝1.2Hz,3H),2.46(s,3H),1.38(d,J＝1.2Hz,3H). ¹³C NMR(150MHz,CDCl₃):δ195.02,172.22,148.16,143.27,128.40,124.44,117.64,115.52,56.86,55.86, 29.91,23.28,22.48.HRMS(ESI)calcd for C₁₃H₁₄N₄O₂[M+Na]⁺:281.1009,found:281.1004.

the specific implementation mode twelve: the method for preparing azide-substituted quinoline-2, 4-dione by the metal-free catalyzed free radical tandem carbocyclization reaction in the embodiment is as follows:

sequentially adding N- (2-cyanogen) into a reaction tube at room temperature69mg of phenyl-5-methoxyphenyl) -N-methacrylamide (1m), 46.8mg of diphenyldiselenide, 145mg of diethyliodobenzene, 127. mu.L of azidotrimethylsilane (93% specification), the reaction was finally carried out in 2mL of dimethyl sulfoxide (DMSO), the reaction tube was then stirred at room temperature for 12 hours until complete consumption of the starting material was monitored by TLC analysis, and after completion of the reaction, the mixture was treated with H₂Quenching with O (15mL) and CH₂Cl₂Extraction (3 × 5mL) followed by concentration of the organic solvent in vacuo and purification of the residue by flash column chromatography with a mixture of petroleum ether and ethyl acetate as eluent, Rf ═ 0.33, gave 3- (azidomethyl) -7-methoxy-1, 3-dimethylquinoline-2, 4(1H, 3H) -dione (compound 2m) in the following yield: 82%, 67.5 mg.

The equation for the reaction is:

of Compound 2m¹H NMR、¹³The structure of the compound is known by C NMR and HR-ESI-MS spectra. Specifically, the method comprises the following steps: compound 2m is a red liquid, Rf (petroleum ether: ethyl acetate ═ 3:1): 0.33.¹H NMR(600MHz,CDCl₃):δ8.01(d,J＝8.7Hz,1H),6.71(dd,J＝8.7, 2.2Hz,1H),6.62(d,J＝2.2Hz,1H),3.97(d,J＝11.3Hz,1H),3.93(d,J＝11.3Hz,1H),3.91(s,3H),3.46 (s,3H),1.37(s,3H).¹³C NMR(150MHz,CDCl₃):δ193.75,172.49,166.37,145.20,130.88,113.67,108.54, 101.11,56.49,56.05,55.85,29.91,23.37.HRMS(ESI)calcd for C₁₃H₁₄N₄O₃[M+Na]⁺:267.0710,found: 297.0710.

experiment one:

the compounds prepared in the first to the twelfth embodiments are subjected to an activity test for inhibiting phytopathogen:

4 pathogenic bacteria were selected, including blueberry canker pathogen (Botryosphaeria dothidea), spruce verticillium (Fusarium verticillioides), poplar canker pathogen (Dothiorella gregaria), and poplar canker pathogen (Cytospora chrysosperma).

Culturing the four pathogenic bacteria in a PDA plate constant temperature biochemical incubator at 28 deg.C for 5d, allowing a large amount of spores to grow on the surface of the colony, washing the spores with sterile water to obtain spore suspension, and observing the spore concentration under the microscope to obtain 1x10⁷one/mL. The confrontation experiment adopts a cup-dish method, 100mL of PDA is uniformly mixed with 5mL of spore suspension, the mixture is poured into a rectangular glass culture dish, and an Oxford cup is placed. 12 compounds were diluted to 10mg/mL with dichloromethane, 200uL was added to the Oxford cup, and dichloromethane was used as a control. Culturing at 28 deg.C for 3 days, and measuring the diameter of the bacteria-inhibiting agent in mm (see Table 1).

Table 1.12 compounds inhibit phytopathogen activity (n ═ 3)

As can be seen from Table 1, the compounds prepared by the method of the present invention have activity of inhibiting plant pathogenic bacteria, and can be applied to the control of plant pathogenic bacteria.

Experiment two:

the process for the preparation of azido-substituted quinoline-2, 4-diones is as follows:

to the reaction tube were added 0.3mmol (60mg) of N- (2-cyanophenyl) -N-methylacrylamide (1a) and diphenyldiselenide (PhSe) at room temperature₂0.15mmol (46.8mg), diethyliodobenzene PhI (OAc)₂0.45mmol (145mg) and 127. mu.L of azidotrimethylsilane (93% specification) were mixed and finally reacted in 2mL of acetonitrile, then the reaction tube was stirred at room temperature for 12 hours until complete consumption of starting material was monitored by TLC analysis, after completion of the reaction, the mixture was washed with H₂Quenching with O (15mL) and CH₂Cl₂Extract 3 times (5 mL each time), then there will beThe organic solvent was concentrated in vacuo and the residue was purified by flash column chromatography with Rf ═ 0.44 using a mixture of petroleum ether and ethyl acetate as eluent to give 3- (azidomethyl) -1, 3-dimethylquinoline-2, 4(1H, 3H) -dione. The yield was: 82 percent.

Experiment three:

to the reaction tube were added 0.3mmol (60mg) of N- (2-cyanophenyl) -N-methylacrylamide (1a) and diphenyldiselenide (PhSe) at room temperature₂0.15mmol (46.8mg), diethyliodobenzene PhI (OAc)₂0.45mmol (145mg) and 127. mu.L of azidotrimethylsilane (93% specification) were mixed and finally reacted in 2ml of DMF, then the reaction tube was stirred at room temperature for 12 hours until complete consumption of starting material was monitored by TLC analysis, after completion of the reaction, the mixture was washed with H₂Quenching with O (15mL) and CH₂Cl₂Extraction was carried out 3 times (5 mL each), the organic solvent was then concentrated in vacuo and the residue was purified by flash column chromatography, Rf ═ 0.44, using a mixture of petroleum ether and ethyl acetate as eluent, to give 3- (azidomethyl) -1, 3-dimethylquinoline-2, 4(1H, 3H) -dione. The yield was: 82 percent.

Experiment four:

to the reaction tube were added 0.3mmol (60mg) of N- (2-cyanophenyl) -N-methylacrylamide (1a) and diphenyldiselenide (PhSe) at room temperature₂0.15mmol (46.8mg), diethyliodobenzene PhI (OAc)₂0.45mmol (145mg) and 127. mu.L of azidotrimethylsilane solution (93% of specification) were finally reacted in 2mLEtOAc, the reaction tube was then stirred at room temperature for 12 hours until complete consumption of starting material was monitored by TLC analysis, and after completion of the reaction, the mixture was washed with H₂Quenching with O (15mL) and CH₂Cl₂Extraction was carried out 3 times (5 mL each), the organic solvent was then concentrated in vacuo and the residue was purified by flash column chromatography, Rf ═ 0.44, using a mixture of petroleum ether and ethyl acetate as eluent, to give 3- (azidomethyl) -1, 3-dimethylQuinoline-2, 4(1H, 3H) -dione. The yield was: 82 percent.

Experiment five:

to the reaction tube were added 0.3mmol (60mg) of N- (2-cyanophenyl) -N-methylacrylamide (1a) and diphenyldiselenide (PhSe) at room temperature₂0.15mmol (46.8mg), diethyliodobenzene PhI (OAc)₂0.45mmol (145mg) and 127. mu.L azidotrimethylsilane (93% of specification) were finally reacted in 2mL DCE, and then the reaction tube was stirred at room temperature for 12 hours until complete consumption of the starting material was monitored by TLC analysis, after completion of the reaction, the mixture was washed with H₂Quenching with O (15mL) and CH₂Cl₂Extraction was carried out 3 times (5 mL each), the organic solvent was then concentrated in vacuo and the residue was purified by flash column chromatography, Rf ═ 0.44, using a mixture of petroleum ether and ethyl acetate as eluent, to give 3- (azidomethyl) -1, 3-dimethylquinoline-2, 4(1H, 3H) -dione. The yield was: 82 percent.

Experiment six:

to the reaction tube were added 0.3mmol (60mg) of N- (2-cyanophenyl) -N-methylacrylamide (1a) and diphenyldiselenide (PhSe) at room temperature₂0.15mmol (46.8mg), diethyliodobenzene PhI (OAc)₂0.45mmol (145mg) and 127. mu.L azidotrimethylsilane (93% of specification) were finally reacted in 2mL dioxane, the reaction tube was then stirred at room temperature for 12 hours until complete consumption of the starting material was monitored by TLC analysis, and after completion of the reaction, the mixture was washed with H₂Quenching with O (15mL) and CH₂Cl₂Extraction was carried out 3 times (5 mL each), the organic solvent was then concentrated in vacuo and the residue was purified by flash column chromatography, Rf ═ 0.44, using a mixture of petroleum ether and ethyl acetate as eluent, to give 3- (azidomethyl) -1, 3-dimethylquinoline-2, 4(1H, 3H) -dione. The yield was: 82 percent.

Experiment seven:

to the reaction tube were added 0.3mmol (60mg) of N- (2-cyanophenyl) -N-methylacrylamide (1a) and diphenyldiselenide (PhSe) at room temperature₂0.15mmol (46.8mg), diethyliodobenzene PhI (OAc)₂0.45mmol (145mg) and 127. mu.L azidotrimethylsilane (93% of specification) were finally reacted in 2mL DCM, then the reaction tube was stirred at room temperature for 12 hours until complete consumption of starting material was monitored by TLC analysis, after completion of the reaction, the mixture was washed with H₂Quenching with O (15mL) and CH₂Cl₂Extraction was carried out 3 times (5 mL each), the organic solvent was then concentrated in vacuo and the residue was purified by flash column chromatography, Rf ═ 0.44, using a mixture of petroleum ether and ethyl acetate as eluent, to give 3- (azidomethyl) -1, 3-dimethylquinoline-2, 4(1H, 3H) -dione. The yield was: 82 percent.

Experiment eight:

the azide-substituted quinoline-2, 4-dione method is as follows:

0.3mmol (60mg) of N- (2-cyanophenyl) -N-methylacrylamide (1a) and diphenyldiselenide (PhSe) were added to the reaction tube at 60 ℃₂0.15mmol (46.8mg), diethyliodobenzene PhI (OAc)₂0.45mmol (145mg) and 127. mu.L azidotrimethylsilane (93% of specification) were finally reacted in 2mL dimethyl sulfoxide (DMSO), the reaction tube was then stirred at room temperature for 12 hours until complete consumption of starting material was monitored by TLC analysis, and after completion of the reaction, the mixture was washed with H₂Quenching with O (15mL) and CH₂Cl₂Extraction was carried out 3 times (5 mL each), the organic solvent was then concentrated in vacuo and the residue was purified by flash column chromatography, Rf ═ 0.44, using a mixture of petroleum ether and ethyl acetate as eluent, to give 3- (azidomethyl) -1, 3-dimethylquinoline-2, 4(1H, 3H) -dione. The yield was: 74 percent.

From experiments two to seven, the solvents DMF, EtOAc, DCE, dioxane, and DCM did not increase the yield. From the eighth experiment, the yield is reduced due to the increase of the temperature, and when the temperature is increased to 60 ℃, the reaction yield is reduced to 74%.

Claims

1. A method for preparing azide-substituted quinoline-2, 4-diketone by free-radical tandem carbocyclization reaction without metal catalysis is characterized in that the method for preparing azide-substituted quinoline-2, 4-diketone comprises the following steps:

to a reaction tube were added in this order 60mg of N- (2-cyanophenyl) -N-methacrylamide, 46.8mg of diphenyldiselenide, 145mg of diethyliodobenzene and 127. mu.L of azidotrimethylsilane at room temperature, and finally the reaction was carried out in 2mL of dimethyl sulfoxide, and the reaction tube was stirred at room temperature for 12 hours until the complete consumption of the starting material was monitored by TLC analysis, and after completion of the reaction, the mixture was treated with H₂Quenching with O and CH₂Cl₂Extraction was followed by concentration of the organic solvent in vacuo and the residue was purified by flash column chromatography with a mixture of petroleum ether and ethyl acetate as eluent, Rf ═ 0.44, to give 3- (azidomethyl) -1, 3-dimethylquinoline-2, 4(1H, 3H) -dione.

2. A method for preparing azide-substituted quinoline-2, 4-diketone by free-radical tandem carbocyclization reaction without metal catalysis is characterized in that the method for preparing azide-substituted quinoline-2, 4-diketone comprises the following steps:

to a reaction tube were added in this order 65mg of N- (2-cyano-3-fluorophenyl) -N-methacrylamide, 46.8mg of diphenyldiselenide, 145mg of diethyliodobenzene and 127. mu.L of azidotrimethylsilane at room temperature, and finally the reaction was carried out in 2mL of dimethyl sulfoxide, and the reaction tube was stirred at room temperature for 12 hours until the complete consumption of the starting material was monitored by TLC analysis, after completion of the reaction, the mixture was treated with H₂Quenching with O and CH₂Cl₂Extraction was followed by concentration of the organic solvent in vacuo and the residue was purified by flash column chromatography with a mixture of petroleum ether and ethyl acetate as eluent, Rf ═ 0.29, to give 3- (azidomethyl) -5-fluoro-1, 3-dimethylquinoline-2, 4(1H, 3H) -dione.

3. A method for preparing azide-substituted quinoline-2, 4-diketone by free-radical tandem carbocyclization reaction without metal catalysis is characterized in that the method for preparing azide-substituted quinoline-2, 4-diketone comprises the following steps:

to a reaction tube were added N- (3-chloro-2-cyanophenyl) -N-methacrylamide 70mg, diphenyldiselenide 46.8mg, diethyliodobenzene 145mg and 127. mu.L azidotrimethylsilane in this order at room temperature, and finally a reaction was carried out in 2mL dimethyl sulfoxide, and the reaction tube was stirred at room temperature for 12 hours until the complete consumption of the starting material was monitored by TLC analysis, after completion of the reaction, the mixture was treated with H₂Quenching with O and CH₂Cl₂Extraction was followed by concentration of the organic solvent in vacuo and the residue was purified by flash column chromatography with a mixture of petroleum ether and ethyl acetate as eluent, Rf ═ 0.31, to give 3- (azidomethyl) -5-chloro-1, 3-dimethylquinoline-2, 4(1H, 3H) -dione.

4. A method for preparing azide-substituted quinoline-2, 4-diketone by free-radical tandem carbocyclization reaction without metal catalysis is characterized in that the method for preparing azide-substituted quinoline-2, 4-diketone comprises the following steps:

to a reaction tube were added 83mg of N- (3-bromo-2-cyano) -N-methacrylamide, 46.8mg of diphenyldiselenide, 145mg of diethyliodobenzene and 127. mu.L of azidotrimethylsilane in this order at room temperature, and finally a reaction was carried out in 2mL of dimethyl sulfoxide, and the reaction tube was stirred at room temperature for 12 hours until the complete consumption of the starting material was monitored by TLC analysis, and after completion of the reaction, the mixture was treated with H₂Quenching with O and CH₂Cl₂Extraction was followed by concentration of the organic solvent in vacuo and the residue was purified by flash column chromatography with a mixture of petroleum ether and ethyl acetate as eluent, Rf ═ 0.34, to give 3- (azidomethyl) -5-bromo-1, 3-dimethylquinoline-2, 4(1H, 3H) -dione.

5. A method for preparing azide-substituted quinoline-2, 4-diketone by free-radical tandem carbocyclization reaction without metal catalysis is characterized in that the method for preparing azide-substituted quinoline-2, 4-diketone comprises the following steps:

at room temperature, 65mg of N- (2-cyano-4-fluorophenyl) -N-methacrylamide, 46.8mg of diphenyl diselenide,145mg of diethyliodobenzene and 127. mu.L of azidotrimethylsilane were finally reacted in 2mL of dimethyl sulfoxide, the reaction tube was stirred at room temperature for 12 hours until complete consumption of the starting material was monitored by TLC analysis, and after completion of the reaction, the mixture was treated with H₂Quenching with O and CH₂Cl₂Extraction was followed by concentration of the organic solvent in vacuo and the residue was purified by flash column chromatography with a mixture of petroleum ether and ethyl acetate as eluent, Rf ═ 0.34, to give 3- (azidomethyl) -6-fluoro-1, 3-dimethylquinoline-2, 4(1H, 3H) -dione.

6. A method for preparing azide-substituted quinoline-2, 4-diketone by free-radical tandem carbocyclization reaction without metal catalysis is characterized in that the method for preparing azide-substituted quinoline-2, 4-diketone comprises the following steps:

to a reaction tube were added N- (4-chloro-2-cyanophenyl) -N-methacrylamide 70mg, diphenyldiselenide 46.8mg, diethyliodobenzene 145mg and 127. mu.L azidotrimethylsilane at room temperature, and finally the reaction was carried out in 2mL of dimethyl sulfoxide, and then the reaction tube was stirred at room temperature for 12 hours until the complete consumption of the starting material was monitored by TLC analysis, after the completion of the reaction, the mixture was treated with H₂Quenching with O and CH₂Cl₂Extraction was followed by concentration of the organic solvent in vacuo and the residue was purified by flash column chromatography with a mixture of petroleum ether and ethyl acetate as eluent, Rf ═ 0.46, to give 3- (azidomethyl) -6-chloro-1, 3-dimethylquinoline-2, 4(1H, 3H) -dione.

7. A method for preparing azide-substituted quinoline-2, 4-diketone by free-radical tandem carbocyclization reaction without metal catalysis is characterized in that the method for preparing azide-substituted quinoline-2, 4-diketone comprises the following steps:

to a reaction tube were added 83mg of N- (4-bromo-2-cyanophenyl) -N-methacrylamide, 46.8mg of diphenyldiselenide, 145mg of diethyliodobenzene and 127. mu.L of azidotrimethylsilane at room temperature, and finally the reaction was carried out in 2mL of dimethyl sulfoxide, and then the reaction tube was stirred at room temperature for 12 hours until the crude was monitored by TLC analysisUntil the material is completely consumed, after the reaction is finished, the mixture is added with H₂Quenching with O and CH₂Cl₂Extraction was followed by concentration of the organic solvent in vacuo and the residue was purified by flash column chromatography with a mixture of petroleum ether and ethyl acetate as eluent, Rf ═ 0.43, to give 3- (azidomethyl) -6-bromo-1, 3-dimethylquinoline-2, 4(1H, 3H) -dione.

8. A method for preparing azide-substituted quinoline-2, 4-diketone by free-radical tandem carbocyclization reaction without metal catalysis is characterized in that the method for preparing azide-substituted quinoline-2, 4-diketone comprises the following steps:

to a reaction tube were added N- (2-cyano-4-methylphenyl) -N-methacrylamide 64mg, diphenyldiselenide 46.8mg, diethyliodobenzene 145mg and 127. mu.L azidotrimethylsilane in this order at room temperature, and finally the reaction was carried out in 2mL dimethyl sulfoxide, and then the reaction tube was stirred at room temperature for 12 hours until the complete consumption of the starting material was monitored by TLC analysis, after the completion of the reaction, the mixture was treated with H₂Quenching with O and CH₂Cl₂The organic solvent was then concentrated in vacuo and the residue was purified by flash column chromatography with a mixture of petroleum ether and ethyl acetate as eluent, Rf ═ 0.41, to give 3- (azidomethyl) -1,3, 6-trimethylquinoline-2, 4(1H, 3H) -dione.

9. A method for preparing azide-substituted quinoline-2, 4-diketone by free-radical tandem carbocyclization reaction without metal catalysis is characterized in that the method for preparing azide-substituted quinoline-2, 4-diketone comprises the following steps:

to a reaction tube were added 65mg of N- (2-cyano-5-fluorophenyl) -N-methacrylamide, 46.8mg of diphenyldiselenide, 145mg of diethyliodobenzene and 127. mu.L of azidotrimethylsilane at room temperature, and finally the reaction was carried out in 2mL of dimethyl sulfoxide, and then the reaction tube was stirred at room temperature for 12 hours until the complete consumption of the raw materials was monitored by TLC analysis, after the completion of the reaction, the mixture was treated with H₂Quenching with O and CH₂Cl₂Extracting, vacuum concentrating the organic solvent, and collecting the residueThe product was purified by flash column chromatography using a mixture of petroleum ether and ethyl acetate as eluent, Rf ═ 0.51, to give 3- (azidomethyl) -7-fluoro-1, 3-dimethylquinoline-2, 4(1H, 3H) -dione.

10. A method for preparing azide-substituted quinoline-2, 4-diketone by free-radical tandem carbocyclization reaction without metal catalysis is characterized in that the method for preparing azide-substituted quinoline-2, 4-diketone comprises the following steps:

to a reaction tube were added 83mg of N- (5-bromo-2-cyano) -N-methacrylamide, 46.8mg of diphenyldiselenide, 145mg of diethyliodobenzene, 127. mu.L of azidotrimethylsilane in this order at room temperature, and finally the reaction was carried out in 2mL of dimethyl sulfoxide, and then the reaction tube was stirred at room temperature for 12 hours until the complete consumption of the starting material was monitored by TLC analysis, after completion of the reaction, the mixture was treated with H₂Quenching with O and CH₂Cl₂Extraction, followed by concentration of the organic solvent in vacuo and purification of the residue by flash column chromatography with a mixture of petroleum ether and ethyl acetate as eluent, Rf ═ 0.55, to give 3- (azidomethyl) -7-bromo-1, 3-dimethylquinoline-2, 4(1H, 3H) -dione;

to a reaction tube were added in this order N- (2-cyano-5-methylphenyl) -N-methacrylamide 64mg, diphenyldiselenide 46.8mg, diethyliodobenzene 145mg, and 127. mu.L azidotrimethylsilane at room temperature, and finally the reaction was carried out in 2mL dimethyl sulfoxide, and then the reaction tube was stirred at room temperature for 12 hours until the complete consumption of the starting material was monitored by TLC analysis, after the completion of the reaction, the mixture was treated with H₂Quenching with O and CH₂Cl₂Extraction, followed by concentration of the organic solvent in vacuo, purification of the residue by flash column chromatography with a mixture of petroleum ether and ethyl acetate as eluent, Rf ═ 0.50, to give 3- (azidomethyl) -1,3, 7-trimethylquinoline-2, 4(1H, 3H) -dione;

to a reaction tube were added in this order N- (2-cyano-5-methoxyphenyl) -N-methacrylamide 69mg, diphenyldiselenide 46.8mg, diethyliodobenzene 145mg, and 127. mu.L azidotrimethylsilane at room temperature, and finally the reaction was carried out in 2mL of dimethyl sulfoxide, and then the reaction tube was stirred at room temperature for 12 hours until the complete consumption of the starting material was monitored by TLC analysis, and after completion of the reaction, the mixture was treated with H₂Quenching with O and CH₂Cl₂Extraction was followed by concentration of the organic solvent in vacuo and the residue was purified by flash column chromatography with a mixture of petroleum ether and ethyl acetate as eluent, Rf ═ 0.33, to give 3- (azidomethyl) -7-methoxy-1, 3-dimethylquinoline-2, 4(1H, 3H) -dione.