Method for preparing 3-(phosphoryl)-1-alkyl-3, 4-dihydroquinoxaline-2 (1H)-ketone compound

Abstract

The invention provides a method for efficiently synthesizing 3-(phosphoryl)-1-alkyl-3, 4-dihydroquinoxaline-2 (1H)-ketone compounds containing different substituted functional groups with high selectivity under the assistance of an ultrasonic technology, quinoxaline-2 (1H)-ketone and a phosphorus-hydrogen compound are used as reaction substrates, an organic solvent is added into a reaction system, and the 3-(phosphoryl)-1-alkyl-3, 4-dihydroquinoxaline-2 (1H)-ketone compounds with different substituted functional groups are prepared through a one-pot method. The reaction can be completed within 5 minutes under the assistance of ultrasonic conditions. The method has the advantages that the substrate applicability is high; reaction conditions are mild, reaction time is short, and safety and reliability are achieved; the selectivity of the obtained target product is close to 100%, and the yield is high. The method overcomes the defects of poor reaction selectivity, tedious reaction steps, low yield, need of a noble metal catalyst and reagents harmful to the environment and the like in the traditional synthesis of the 3-(phosphoryl)-1-alkyl-3, 4-dihydroquinoxaline-2 (1H)-ketone compound, and has a good industrial application prospect. The invention also provides a corresponding 3-(phosphoryl)-1-alkyl-3, 4-dihydroquinoxaline-2 (1H)-ketone derivative containing different substituted functional groups at the same time, and also provides a preparation method of the 3-(phosphoryl)-1-alkyl-3, 4-dihydroquinoxaline-2 (1H)-ketone derivative.

Description

Technical Field

[0001] This invention relates to the field of catalytic synthesis of 3-(phosphoryl)-1-alkyl-3,4-dihydroquinoxaline-2(1H)-one compounds, and more specifically to a method for the efficient preparation of 3-(phosphoryl)-1-alkyl-3,4-dihydroquinoxaline-2(1H)-one derivatives by phosphorylation reaction of quinoxaline-2(1H)-one and phosphorus compounds under the assistance of ultrasonic technology. Background Technology

[0002] Phosphoryl-substituted quinoxaline-2(1H)-ones are an important class of organic synthesis intermediates. Especially those containing both a nitrogen-containing heterocycle and a phosphoryl group, these compounds have wide applications in pesticides, insecticides, pharmaceutical intermediates, biological agents, flame-retardant materials, optoelectronic materials, and organic synthesis due to their unique properties. Furthermore, the NH bond and carbonyl group in these compounds can be further modified through post-functionalization reactions to transform them into corresponding functional organophosphorus small molecule compounds.

[0003] Currently, only one method for synthesizing phosphoryl-substituted dihydroquinoxaline-2(1H)-one has been reported in the literature. The main method reported in the industry is the synthesis of phosphoryl-substituted dihydroquinoxaline-2(1H)-one, as follows: (1) Electrocatalytic oxidative dehydrogenation coupling reaction: Quinoxaline-2(1H)-one and phosphorus hydride compounds undergo dehydrogenation coupling reaction under the catalysis of C / Pt electrode. The resulting 3-(phosphoryl)-1-alkyl-3,4-dihydroquinoxaline-2(1H)-one compounds are reaction intermediates with the target product. The reaction is difficult to control. The above reaction has defects such as poor reaction selectivity, high toxicity (requiring the use of lithium perchlorate) and high cost. Moreover, the functional groups of the reaction have poor tolerance, and the salt content of the reaction waste liquid is high, which often requires special treatment (free radical mechanism; Green Chemistry, 2019, 21, 4412); (2) Fluorine reagent-promoted free radical cross-coupling reaction: using quinoxaline-2(1H)-one and phosphorus compounds as starting materials, under the promoting effect of 1-chloromethyl-4-fluoro-1,4-diazobicyclo[2.2.2]octanebis(tetrafluoroborate) salt and air atmosphere to promote the formation of phosphoryl free radicals, and then construct the corresponding C(sp2)-P bond compound by cross-coupling reaction. However, the above methods generally use environmentally unfriendly reagents (fluorine reagents, etc.), and also have drawbacks such as complicated experimental steps, expensive and difficult-to-recycle fluorine reagents, harsh reaction conditions, overlapping substrate applicability, low selectivity and yield, and significant environmental pollution. They cannot effectively prepare 3-(phosphoryl)-1-alkyl-3,4-dihydroquinoxaline-2(1H)-one compounds (free radical mechanism; ChemistrySelect, 2019, 4, 11066); (3) Singh et al. reported in 2025 the direct phosphorylation reaction of quinoxaline-2(1H)-one with diphenylphosphine catalyzed by Thioxanthone (TXO) under visible light catalysis. The target product obtained was a phosphoryl-substituted dihydroquinoxaline-2(1H)-one compound (only 2 cases). However, 5 mol% TXO needs to be added as a photocatalyst during the reaction (the catalyst is expensive and difficult to prepare). Using a white lamp as the light source, acetonitrile as the reaction solvent, and an additional 1.3 equivalents of cesium carbonate as a promoter, 1.3 times the equivalent of acetonitrile is added. In the above system, the molar ratio of quinoxaline-2(1H)-one to diphenylphosphine oxide is close to 2:1, resulting in poor reaction economy. The reaction system also belongs to a free radical reaction mechanism.

[0004] To date, the efficient synthesis of 3-(phosphoryl)-1-alkyl-3,4-dihydroquinoxaline-2(1H)-one compounds faces several challenges, including raw material quality, production safety, and product stability and purity, making the synthesis technology quite difficult.

[0005] To address the shortcomings of existing synthetic processes, the industry is focusing on new methods for synthesizing the corresponding 3-(phosphoryl)-1-alkyl-3,4-dihydroquinoxaline-2(1H)-one compounds. Summary of the Invention

[0006] The purpose of this invention is to provide a new method for the efficient and selective synthesis of corresponding 3-(phosphoryl)-1-alkyl-3,4-dihydroquinoxaline-2(1H)-one compounds using inexpensive and readily available quinoxaline-2(1H)-one and phosphohydrogen compounds as raw materials with the aid of ultrasonic technology, in order to overcome the above-mentioned defects in the prior art.

[0007] This invention comprises the following steps: taking reaction amounts of quinoxaline-2(1H)-one, phosphate compound, and organic solvent, mixing them in a reaction vessel under nitrogen atmosphere, and then sonicating at 25-100°C. o Reacting at step C for 5 minutes yields the corresponding 3-(phosphoryl)-1-alkyl-3,4-dihydroquinoxaline-2(1H)-one compounds with different substituted functional groups. The specific reaction formulas are as follows: （I） in, The ultrasonic power is 800 W, and the organic solvent is ethyl acetate; R 1 Selected from hydrogen and fluorine; R 2 Selected from hydrogen, fluorine, chlorine, bromine, nitro, and trifluoromethyl; R 3 Selected from methyl, ethyl, propyl, butyl, isobutyl, pentyl, hexyl, cyclopropylmethyl, cyclopentylmethyl, cyclohexylmethyl, 3-methoxypropyl, but-2-yn-1-yl, but-3-en-1-yl, benzyl, 4-(trifluoromethyl)benzyl, 4-(tert-butyl)benzyl; R 4 Selected from phenyl, 4-methylphenyl, 3-methylphenyl, 2-methylphenyl, 4-ethylphenyl, 4-methoxyphenyl, 2,5-dimethylphenyl, 3,5-dimethylphenyl, 4-chlorophenyl, 4-fluorophenyl, 3-fluorophenyl, 2-naphthyl, benzyloxy, phenoxy; R 5 It is selected from phenyl, 4-methylphenyl, 3-methylphenyl, 2-methylphenyl, 4-ethylphenyl, 4-methoxyphenyl, 2,5-dimethylphenyl, 3,5-dimethylphenyl, 4-chlorophenyl, 4-fluorophenyl, 3-fluorophenyl, 2-naphthyl, benzyloxy, and phenoxy.

[0008] In the above method for synthesizing 3-(phosphoryl)-1-alkyl-3,4-dihydroquinoxaline-2(1H)-one compounds from quinoxaline-2(1H)-one and phosphorus compounds, the quinoxaline-2(1H)-one is selected from 1-methylquinoxaline-2(1H)-one, 1-ethylquinoxaline-2(1H)-one, 1-propylquinoxaline-2(1H)-one, 1-butylquinoxaline-2(1H)-one, 1-isobutylquinoxaline-2(1H)-one, 1-pentylquinoxaline-2(1H)-one, 1-hexylquinoxaline-2(1H)-one, 1-(cyclopropylmethyl)quinoxaline-2(1H)-one, 1-(cyclopentylmethyl)quinoxaline-2(1H)-one, and 1-(cyclohexylmethyl)quinoxaline-2(1H)-one. 1-(3-methoxypropyl)quinoxaline-2(1H)-one, 1-(but-2-yn-1-yl)quinoxaline-2(1H)-one, 1-(but-3-en-1-yl)quinoxaline-2(1H)-one, 1-benzylquinoxaline-2(1H)-one, 1-[4-(trifluoromethyl)benzyl]quinoxaline-2(1H)-one, 1-[4-(tert-butyl)benzyl]quinoxaline-2(1H)-one, 6-chloro-1-methylquinoxaline-2(1H)-one, 6-bromo-1-methylquinoxaline-2(1H)-one, 1-methyl-6-nitroquinoxaline-2(1H)-one, 1-methyl-6-(trifluoromethyl)quinoxaline-2(1H)-one, 6,7-difluoro-1-methylquinoxaline-2(1H)-one.

[0009] In the above method for synthesizing 3-(phosphoryl)-1-alkyl-3,4-dihydroquinoxaline-2(1H)-one compounds from quinoxaline-2(1H)-one and phosphate compounds, the phosphate compound is selected from diphenylphosphine oxide, di(4-methylphenyl)phosphine oxide, di(3-methylphenyl)phosphine oxide, di(2-methylphenyl)phosphine oxide, di(4-ethylphenyl)phosphine oxide, di(4-methoxyphenyl)phosphine oxide, di(2,5-dimethylphenyl)phosphine oxide, di(3,5-dimethylphenyl)phosphine oxide, di(4-chlorophenyl)phosphine oxide, di(4-fluorophenyl)phosphine oxide, di(3-fluorophenyl)phosphine oxide, di(2-naphthyl)phosphine oxide, dibenzyl phosphite, diphenyl phosphite, and (4-fluorophenyl)phenylphosphine oxide.

[0010] In the above method for synthesizing 3-(phosphoryl)-1-alkyl-3,4-dihydroquinoxaline-2(1H)-one compounds from quinoxaline-2(1H)-one and phosphorus compounds, the molar ratio of quinoxaline-2(1H)-one to phosphorus compounds is 1:[1.0~2.0].

[0011] This invention provides a highly efficient and selective method for synthesizing 3-(phosphoryl)-1-alkyl-3,4-dihydroquinoxaline-2(1H)-one compounds from quinoxaline-2(1H)-ones and phosphorus compounds. The reaction process is mild and easily controlled. While achieving high yields and 100% selectivity, this method is simple to implement and has promising prospects for industrial applications. Detailed Implementation

[0012] The present invention will be further described below with reference to embodiments thereof: I. Testing and Analysis In the following embodiments of the present invention, the structural analysis of the reaction products was performed using an Agilent GC / MS (6890N / 5973N) system equipped with an HP-5MS capillary column (30m × 0.45mm × 0.8μm) and a Bruker Avance-III 500 NMR analyzer. The selectivity and yield of the target products were analyzed using a Bruker Avance-III 500 NMR analyzer. II. Implementation Examples Example 1

[0013] 32 mg (0.2 mmol) of 1-methylquinoxalin-2(1H)-one and 40.4 mg (0.2 mmol) of diphenylphosphine oxide were added to a Schlenk tube under a nitrogen atmosphere, followed by 1.0 mL of ethyl acetate. The mixture was then incubated at 40 °C. o The reaction was stirred at C for 6 hours. After the reaction was completed, the product was purified by column chromatography, and the yield of the target product was 91%. Example 2

[0014] 32 mg (0.2 mmol) of 1-methylquinoxalin-2(1H)-one and 40.4 mg (0.2 mmol) of diphenylphosphine oxide were added to a Schlenk tube under a nitrogen atmosphere, followed by 1.0 mL of ethyl acetate. The mixture was then incubated at 25 °C. o C was placed in an ultrasonic (800W) reactor and reacted for 5 minutes. After the reaction was completed, the product was purified by column chromatography, and the yield of the target product was 98%. Example 3

[0015] 34.8 mg (0.2 mmol) of 1-ethylquinoxaline-2(1H)-one and 40.4 mg (0.2 mmol) of diphenylphosphine oxide were added to a Schlenk tube under a nitrogen atmosphere, followed by 1.0 mL of ethyl acetate. The mixture was then incubated at 25 °C. oC was placed in an ultrasonic (800 W) reactor and reacted for 5 minutes. After the reaction was completed, the product was purified by column chromatography, and the yield of the target product was 95%. Example 4

[0016] 37.6 mg (0.2 mmol) of 1-propylquinoxalin-2(1H)-one and 40.4 mg (0.2 mmol) of diphenylphosphine oxide were added to a Schlenk tube under a nitrogen atmosphere, followed by 1.0 mL of ethyl acetate. The mixture was then incubated at 25 °C. o C was placed in an ultrasonic (800 W) reactor and reacted for 5 minutes. After the reaction was completed, the product was purified by column chromatography, and the yield of the target product was 89%. Example 5

[0017] 40.4 mg (0.2 mmol) of 1-butylquinoxalin-2(1H)-one and 40.4 mg (0.2 mmol) of diphenylphosphine oxide were added to a Schlenk tube under a nitrogen atmosphere, followed by 1.0 mL of ethyl acetate. The mixture was then incubated at 25 °C. o C was placed in an ultrasonic (800 W) reactor and reacted for 5 minutes. After the reaction was completed, the product was purified by column chromatography, and the yield of the target product was 94%. Example 6

[0018] 40.4 mg (0.2 mmol) of 1-isobutylquinoxalin-2(1H)-one and 40.4 mg (0.2 mmol) of diphenylphosphine oxide were added to a Schlenk tube under a nitrogen atmosphere, followed by 1.0 mL of ethyl acetate. The mixture was then incubated at 25 °C. o C was placed in an ultrasonic (800 W) reactor and reacted for 5 minutes. After the reaction was completed, the product was purified by column chromatography, and the yield of the target product was 93%. Example 7

[0019] 43.2 mg (0.2 mmol) of 1-pentylquinoxalin-2(1H)-one and 40.4 mg (0.2 mmol) of diphenylphosphine oxide were added to a Schlenk tube under a nitrogen atmosphere, followed by 1.0 mL of ethyl acetate. The mixture was then incubated at 25 °C. o C was placed in an ultrasonic (800 W) reactor and reacted for 5 minutes. After the reaction was completed, the product was purified by column chromatography, and the yield of the target product was 92%. Example 8

[0020] 46 mg (0.2 mmol) of 1-hexylquinoxalin-2(1H)-one and 40.4 mg (0.2 mmol) of diphenylphosphine oxide were added to a Schlenk tube under a nitrogen atmosphere, followed by 1.0 mL of ethyl acetate. The mixture was then incubated at 25 °C. o C was placed in an ultrasonic (800W) reactor and reacted for 5 minutes. After the reaction was completed, the product was purified by column chromatography, and the yield of the target product was 88%. Example 9

[0021] 40 mg (0.2 mmol) of 1-(cyclopropylmethyl)quinoxalin-2(1H)-one and 40.4 mg (0.2 mmol) of diphenylphosphine oxide were added to a Schlenk tube under a nitrogen atmosphere, followed by 1.0 mL of ethyl acetate. The mixture was then incubated at 25 °C. o C was placed in an ultrasonic (800 W) reactor and reacted for 5 minutes. After the reaction was completed, the product was purified by column chromatography, and the yield of the target product was 95%. Example 10

[0022] 45.6 mg (0.2 mmol) of 1-(cyclopentylmethyl)quinoxalin-2(1H)-one and 40.4 mg (0.2 mmol) of diphenylphosphine oxide were added to a Schlenk tube under a nitrogen atmosphere, followed by 1.0 mL of ethyl acetate. The mixture was then incubated at 25 °C. o C was placed in an ultrasonic (800 W) reactor and reacted for 5 minutes. After the reaction was completed, the product was purified by column chromatography, and the yield of the target product was 93%. Example 11

[0023] 48.4 mg (0.2 mmol) of 1-(cyclohexylmethyl)quinoxalin-2(1H)-one and 40.4 mg (0.2 mmol) of diphenylphosphine oxide were added to a Schlenk tube under a nitrogen atmosphere, followed by the addition of 1.0 mL of ethyl acetate. The mixture was then incubated at 25 °C. o C was placed in an ultrasonic (800 W) reactor and reacted for 5 minutes. After the reaction was completed, the product was purified by column chromatography, and the yield of the target product was 96%. Example 12

[0024] 43.6 mg (0.2 mmol) of 1-(3-methoxypropyl)quinoxalin-2(1H)-one and 40.4 mg (0.2 mmol) of diphenylphosphine oxide were added to a Schlenk tube under a nitrogen atmosphere, followed by the addition of 1.0 mL of ethyl acetate. The mixture was then incubated at 25 °C. oC was placed in an ultrasonic (800 W) reactor and reacted for 5 minutes. After the reaction was completed, the product was purified by column chromatography, and the yield of the target product was 90%. Example 13

[0025] 39.6 mg (0.2 mmol) of 1-(but-2-yn-1-yl)quinoxalin-2(1H)-one and 40.4 mg (0.2 mmol) of diphenylphosphine oxide were added to a Schlenk tube under a nitrogen atmosphere, followed by the addition of 1.0 mL of ethyl acetate. The mixture was then incubated at 25 °C. o C was placed in an ultrasonic (800 W) reactor and reacted for 5 minutes. After the reaction was completed, the product was purified by column chromatography, and the yield of the target product was 94%. Example 14

[0026] 40 mg (0.2 mmol) of 1-(but-3-en-1-yl)quinoxalin-2(1H)-one and 40.4 mg (0.2 mmol) of diphenylphosphine oxide were added to a Schlenk tube under a nitrogen atmosphere, followed by the addition of 1.0 mL of ethyl acetate. The mixture was then incubated at 25 °C. o C was placed in an ultrasonic (800 W) reactor and reacted for 5 minutes. After the reaction was completed, the product was purified by column chromatography, and the yield of the target product was 95%. Example 15

[0027] 47.2 mg (0.2 mmol) of 1-benzylquinoxaline-2(1H)-one and 40.4 mg (0.2 mmol) of diphenylphosphine oxide were added to a Schlenk tube under a nitrogen atmosphere, followed by 1.0 mL of ethyl acetate. The mixture was then incubated at 25 °C. o C was placed in an ultrasonic (800 W) reactor and reacted for 5 minutes. After the reaction was completed, the product was purified by column chromatography, and the yield of the target product was 90%. Example 16

[0028] 60.8 mg (0.2 mmol) of 1-[4-(trifluoromethyl)benzyl]quinoxalin-2(1H)-one and 40.4 mg (0.2 mmol) of diphenylphosphine oxide were added to a Schlenk tube under a nitrogen atmosphere, followed by 1.0 mL of ethyl acetate. The mixture was then incubated at 25 °C. o C was placed in an ultrasonic (800 W) reactor and reacted for 5 minutes. After the reaction was completed, the product was purified by column chromatography, and the yield of the target product was 93%. Example 17

[0029] 58.4 mg (0.2 mmol) of 1-[4-(tert-butyl)benzyl]quinoxalin-2(1H)-one and 40.4 mg (0.2 mmol) of diphenylphosphine oxide were added to a Schlenk tube under a nitrogen atmosphere, followed by the addition of 1.0 mL of ethyl acetate. The mixture was then incubated at 25 °C. o C was placed in an ultrasonic (800 W) reactor and reacted for 5 minutes. After the reaction was completed, the product was purified by column chromatography, and the yield of the target product was 92%. Example 18

[0030] 38.8 mg (0.2 mmol) of 6-chloro-1-methylquinoxalin-2(1H)-one and 40.4 mg (0.2 mmol) of diphenylphosphine oxide were added to a Schlenk tube under a nitrogen atmosphere, followed by 1.0 mL of ethyl acetate. The mixture was then incubated at 25 °C. o C was placed in an ultrasonic (800 W) reactor and reacted for 5 minutes. After the reaction was completed, the product was purified by column chromatography, and the yield of the target product was 96%. Example 19

[0031] 47.8 mg (0.2 mmol) of 6-bromo-1-methylquinoxalin-2(1H)-one and 40.4 mg (0.2 mmol) of diphenylphosphine oxide were added to a Schlenk tube under a nitrogen atmosphere, followed by 1.0 mL of ethyl acetate. The mixture was then incubated at 25 °C. o C was placed in an ultrasonic (800 W) reactor and reacted for 5 minutes. After the reaction was completed, the product was purified by column chromatography, and the yield of the target product was 92%. Example 20

[0032] 41 mg (0.2 mmol) of 1-methyl-6-nitroquinoxalin-2(1H)-one and 40.4 mg (0.2 mmol) of diphenylphosphine oxide were added to a Schlenk tube under a nitrogen atmosphere, followed by 1.0 mL of ethyl acetate. The mixture was then incubated at 25 °C. o C was placed in an ultrasonic (800 W) reactor and reacted for 5 minutes. After the reaction was completed, the product was purified by column chromatography, and the yield of the target product was 93%. Example 21

[0033] 45.6 mg (0.2 mmol) of 1-methyl-6-(trifluoromethyl)quinoxalin-2(1H)-one and 40.4 mg (0.2 mmol) of diphenylphosphine oxide were added to a Schlenk tube under a nitrogen atmosphere, followed by the addition of 1.0 mL of ethyl acetate. The mixture was then incubated at 25 °C. oC was placed in an ultrasonic (800 W) reactor and reacted for 5 minutes. After the reaction was completed, the product was purified by column chromatography, and the yield of the target product was 97%. Example 22

[0034] 39.2 mg (0.2 mmol) of 6,7-difluoro-1-methylquinoxalin-2(1H)-one and 40.4 mg (0.2 mmol) of diphenylphosphine oxide were added to a Schlenk tube under a nitrogen atmosphere, followed by 1.0 mL of ethyl acetate. The mixture was then incubated at 25 °C. o C was placed in an ultrasonic (800 W) reactor and reacted for 5 minutes. After the reaction was completed, the product was purified by column chromatography, and the yield of the target product was 96%. Example 23

[0035] 32 mg (0.2 mmol) of 1-methylquinoxalin-2(1H)-one and 46 mg (0.2 mmol) of di(4-methylphenyl)phosphine were added to a Schlenk tube under a nitrogen atmosphere, followed by 1.0 mL of ethyl acetate. The mixture was then incubated at 25 °C. o C was placed in an ultrasonic (800 W) reactor and reacted for 5 minutes. After the reaction was completed, the product was purified by column chromatography, and the yield of the target product was 95%. Example 24

[0036] 32 mg (0.2 mmol) of 1-methylquinoxalin-2(1H)-one and 46 mg (0.2 mmol) of di(3-methylphenyl)phosphine were added to a Schlenk tube under a nitrogen atmosphere, followed by 1.0 mL of ethyl acetate. The mixture was then incubated at 25 °C. o C was placed in an ultrasonic (800 W) reactor and reacted for 5 minutes. After the reaction was completed, the product was purified by column chromatography, and the yield of the target product was 93%. Example 25

[0037] 32 mg (0.2 mmol) of 1-methylquinoxalin-2(1H)-one and 46 mg (0.2 mmol) of di(2-methylphenyl)phosphine were added to a Schlenk tube under a nitrogen atmosphere, followed by 1.0 mL of ethyl acetate. The mixture was then incubated at 25 °C. o C was placed in an ultrasonic (800 W) reactor and reacted for 5 minutes. After the reaction was completed, the product was purified by column chromatography, and the yield of the target product was 92%. Example 26

[0038] 32 mg (0.2 mmol) of 1-methylquinoxalin-2(1H)-one and 51.6 mg (0.2 mmol) of di(4-ethylphenyl)phosphine were added to a Schlenk tube under a nitrogen atmosphere, followed by 1.0 mL of ethyl acetate. The mixture was then incubated at 25 °C. o C was placed in an ultrasonic (800 W) reactor and reacted for 5 minutes. After the reaction was completed, the product was purified by column chromatography, and the yield of the target product was 96%. Example 27

[0039] 32 mg (0.2 mmol) of 1-methylquinoxalin-2(1H)-one and 52.4 mg (0.2 mmol) of bis(4-methoxyphenyl)phosphine were added to a Schlenk tube under a nitrogen atmosphere, followed by 1.0 mL of ethyl acetate. The mixture was then incubated at 25 °C. o C was placed in an ultrasonic (800 W) reactor and reacted for 5 minutes. After the reaction was completed, the product was purified by column chromatography, and the yield of the target product was 92%. Example 28

[0040] 32 mg (0.2 mmol) of 1-methylquinoxalin-2(1H)-one and 51.6 mg (0.2 mmol) of bis(2,5-dimethylphenyl)phosphine were added to a Schlenk tube under a nitrogen atmosphere, followed by 1.0 mL of ethyl acetate. The mixture was then incubated at 25 °C. o C was placed in an ultrasonic (800 W) reactor and reacted for 5 minutes. After the reaction was completed, the product was purified by column chromatography, and the yield of the target product was 95%. Example 29

[0041] 32 mg (0.2 mmol) of 1-methylquinoxalin-2(1H)-one and 51.6 mg (0.2 mmol) of bis(3,5-dimethylphenyl)phosphine were added to a Schlenk tube under a nitrogen atmosphere, followed by 1.0 mL of ethyl acetate. The mixture was then incubated at 25 °C. o C was placed in an ultrasonic (800 W) reactor and reacted for 5 minutes. After the reaction was completed, the product was purified by column chromatography, and the yield of the target product was 94%. Example 30

[0042] 32 mg (0.2 mmol) of 1-methylquinoxalin-2(1H)-one and 54.2 mg (0.2 mmol) of di(4-chlorophenyl)phosphine oxide were added to a Schlenk tube under a nitrogen atmosphere, followed by 1.0 mL of ethyl acetate. The mixture was then incubated at 25 °C. oC was placed in an ultrasonic (800 W) reactor and reacted for 5 minutes. After the reaction was completed, the product was purified by column chromatography, and the yield of the target product was 96%. Example 31

[0043] 32 mg (0.2 mmol) of 1-methylquinoxalin-2(1H)-one and 47.6 mg (0.2 mmol) of di(4-fluorophenyl)phosphine oxide were added to a Schlenk tube under a nitrogen atmosphere, followed by 1.0 mL of ethyl acetate. The mixture was then incubated at 25 °C. o C was placed in an ultrasonic (800 W) reactor and reacted for 5 minutes. After the reaction was completed, the product was purified by column chromatography, and the yield of the target product was 97%. Example 32

[0044] 32 mg (0.2 mmol) of 1-methylquinoxalin-2(1H)-one and 47.6 mg (0.2 mmol) of di(3-fluorophenyl)phosphine oxide were added to a Schlenk tube under a nitrogen atmosphere, followed by 1.0 mL of ethyl acetate. The mixture was then incubated at 25 °C. o C was placed in an ultrasonic (800 W) reactor and reacted for 5 minutes. After the reaction was completed, the product was purified by column chromatography, and the yield of the target product was 93%. Example 33

[0045] 32 mg (0.2 mmol) of 1-methylquinoxalin-2(1H)-one and 60.4 mg (0.2 mmol) of di(2-naphthyl)oxophosphine were added to a Schlenk tube under a nitrogen atmosphere, followed by 1.0 mL of ethyl acetate. The mixture was then incubated at 25 °C. o C was placed in an ultrasonic (800 W) reactor and reacted for 5 minutes. After the reaction was completed, the product was purified by column chromatography, and the yield of the target product was 84%. Example 34

[0046] 32 mg (0.2 mmol) of 1-methylquinoxaloline-2(1H)-one and 52.4 mg (0.2 mmol) of dibenzyl phosphite were added to a Schlenk tube under a nitrogen atmosphere, followed by 1.0 mL of ethyl acetate. The mixture was then incubated at 25 °C. o C was placed in an ultrasonic (800 W) reactor and reacted for 5 minutes. After the reaction was completed, the product was purified by column chromatography, and the yield of the target product was 94%. Example 35

[0047] 32 mg (0.2 mmol) of 1-methylquinoxalin-2(1H)-one and 46.8 mg (0.2 mmol) of diphenyl phosphite were added to a Schlenk tube under a nitrogen atmosphere, followed by 1.0 mL of ethyl acetate. The mixture was then incubated at 25 °C. o C was placed in an ultrasonic (800 W) reactor and reacted for 5 minutes. After the reaction was completed, the product was purified by column chromatography, and the yield of the target product was 92%. Example 36

[0048] 32 mg (0.2 mmol) of 1-methylquinoxalin-2(1H)-one and 44 mg (0.2 mmol) of (4-fluorophenyl)phenylphosphine oxide were added to a Schlenk tube under a nitrogen atmosphere, followed by 1.0 mL of ethyl acetate. The mixture was then incubated at 25 °C. o C was placed in an ultrasonic (800 W) reactor and reacted for 5 minutes. After the reaction was completed, the product was purified by column chromatography, and the yield of the target product was 89%.

[0049] As can be seen from the above examples, the method used in this invention for preparing corresponding 3-(phosphoryl)-1-alkyl-3,4-dihydroquinoxaline-2(1H)-one compounds with different substituted functional groups through efficient reaction with quinoxaline-2(1H)-ones has advantages such as mild reaction conditions and simple preparation. Furthermore, this method also has advantages such as wide substrate applicability and high yield, providing an efficient method for synthesizing 3-(phosphoryl)-1-alkyl-3,4-dihydroquinoxaline-2(1H)-one derivatives with different substituted functional groups.

[0050] The embodiments described above are merely illustrative of several implementations of the present invention, and while the descriptions are specific and detailed, they should not be construed as limiting the scope of the present invention. It should be noted that those skilled in the art can make various modifications and improvements without departing from the concept of the present invention, and these modifications and improvements all fall within the scope of protection of the present invention. Therefore, the scope of protection of this patent should be determined by the appended claims.

Claims

1. A method for preparing a compound with the structural formula [structure not specified] by ultrasound-assisted reaction of quinoxaline-2(1H)-one with a phosphohydrin. （I） The preparation method of 3-(phosphoryl)-1-alkyl-3,4-dihydroquinoxaline-2(1H)-one compounds is shown in the following reaction formula: （I） Its features are, Includes the following steps: The reaction mixture, consisting of quinoxaline-2(1H)-one, phosphate compound, and organic solvent, was placed in a reaction vessel under nitrogen atmosphere and mixed. The mixture was then subjected to ultrasonic treatment at 25–100 °C. o After reacting at C for 5 minutes, the corresponding 3-(phosphoryl)-1-alkyl-3,4-dihydroquinoxaline-2(1H)-one compounds with different substituted functional groups were obtained. in, The ultrasonic power is 800 W, and the organic solvent is ethyl acetate; R 1 Selected from hydrogen and fluorine; R 2 Selected from hydrogen, fluorine, chlorine, bromine, nitro, and trifluoromethyl; R 3 Selected from methyl, ethyl, propyl, butyl, isobutyl, pentyl, hexyl, cyclopropylmethyl, cyclopentylmethyl, cyclohexylmethyl, 3-methoxypropyl, but-2-yn-1-yl, but-3-en-1-yl, benzyl, 4-(trifluoromethyl)benzyl, 4-(tert-butyl)benzyl; R 4 Selected from phenyl, 4-methylphenyl, 3-methylphenyl, 2-methylphenyl, 4-ethylphenyl, 4-methoxyphenyl, 2,5-dimethylphenyl, 3,5-dimethylphenyl, 4-chlorophenyl, 4-fluorophenyl, 3-fluorophenyl, 2-naphthyl, benzyloxy, phenoxy; R 5 It is selected from phenyl, 4-methylphenyl, 3-methylphenyl, 2-methylphenyl, 4-ethylphenyl, 4-methoxyphenyl, 2,5-dimethylphenyl, 3,5-dimethylphenyl, 4-chlorophenyl, 4-fluorophenyl, 3-fluorophenyl, 2-naphthyl, benzyloxy, and phenoxy.

2. The preparation method according to claim 1, characterized in that, The quinoxaline-2(1H)-one is selected from 1-methylquinoxaline-2(1H)-one, 1-ethylquinoxaline-2(1H)-one, 1-propylquinoxaline-2(1H)-one, 1-butylquinoxaline-2(1H)-one, 1-isobutylquinoxaline-2(1H)-one, 1-pentylquinoxaline-2(1H)-one, 1-hexylquinoxaline-2(1H)-one, 1-(cyclopropylmethyl)quinoxaline-2(1H)-one, 1-(cyclopentylmethyl)quinoxaline-2(1H)-one, 1-(cyclohexylmethyl)quinoxaline-2(1H)-one, 1-(3-methoxypropyl)quinoxaline-2(1H)-one, 1-(but-2 -Alyn-1-yl)quinoxalin-2(1H)-one, 1-(but-3-en-1-yl)quinoxalin-2(1H)-one, 1-benzylquinoxalin-2(1H)-one, 1-[4-(trifluoromethyl)benzyl]quinoxalin-2(1H)-one, 1-[4-(tert-butyl)benzyl]quinoxalin-2(1H)-one, 6-chloro-1-methylquinoxalin-2(1H)-one, 6-bromo-1-methylquinoxalin-2(1H)-one, 1-methyl-6-nitroquinoxalin-2(1H)-one, 1-methyl-6-(trifluoromethyl)quinoxalin-2(1H)-one, 6,7-difluoro-1-methylquinoxalin-2(1H)-one.

3. The preparation method according to claim 1, characterized in that, The phosphate compound is selected from diphenylphosphine oxide, di(4-methylphenyl)phosphine oxide, di(3-methylphenyl)phosphine oxide, di(2-methylphenyl)phosphine oxide, di(4-ethylphenyl)phosphine oxide, di(4-methoxyphenyl)phosphine oxide, di(2,5-dimethylphenyl)phosphine oxide, di(3,5-dimethylphenyl)phosphine oxide, di(4-chlorophenyl)phosphine oxide, di(4-fluorophenyl)phosphine oxide, di(3-fluorophenyl)phosphine oxide, di(2-naphthyl)phosphine oxide, dibenzyl phosphite, diphenyl phosphite, and (4-fluorophenyl)phenylphosphine oxide.

4. The preparation method according to claim 1, characterized in that, The molar ratio of the quinoxaline-2(1H)-one to the phosphorus compound is 1:[1.0~2.0].

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