阅读说明：本技术 一种苯并氢化咪唑酮骨架的合成方法 (Synthetic method of benzo-hydrogenated imidazolone framework ) 是由 王阳 吴正光 崔一墨 于 2021-08-03 设计创作，主要内容包括：本发明公开了一种苯并氢化咪唑酮骨架的合成方法,属于有机化学技术领域。该合成方法以苯基脲及其衍生物作为反应物、芳基碘作为催化剂、间氯过氧苯甲酸作为氧化剂、三氟乙醇作为溶剂,进行反应,即可得到苯并氢化咪唑酮骨架。本发明的方法操作简单,原料易得,反应步骤短、高效,反应产率高达97%。(The invention discloses a synthesis method of a benzo-hydrogenated imidazolone framework, belonging to the technical field of organic chemistry. According to the synthesis method, phenylurea and derivatives thereof are used as reactants, aryl iodine is used as a catalyst, m-chloroperoxybenzoic acid is used as an oxidant, and trifluoroethanol is used as a solvent, and the reaction is carried out to obtain the benzohydroimidazolone skeleton. The method has the advantages of simple operation, easily obtained raw materials, short reaction steps, high efficiency and high reaction yield up to 97 percent.)

1. A method for synthesizing a benzo-hydrogenated imidazolone framework is characterized in that: as shown in the following formula:

taking phenylurea shown as a formula a and derivatives thereof as reactants, taking aryl iodine shown as a formula b as a catalyst, taking m-chloroperoxybenzoic acid as an oxidant and taking trifluoroethanol as a solvent, and reacting to obtain a benzohydroimidazolone skeleton shown as a formula c;

wherein R is¹、R²、R³Each independently an electron donating group or an electron withdrawing group.

2. The method of synthesis according to claim 1, characterized in that: r¹Is methyl, phenyl or halogen, R²Is aliphatic alkyl or aryl, R³Is methyl, ethyl, isopropyl, tert-butyl or benzyl.

3. The method of synthesis according to claim 2, characterized in that: the aliphatic alkyl is methyl, ethyl, isopropyl, n-butyl or cyclohexyl.

4. The method of synthesis according to claim 1, characterized in that: said phenylurea and its derivatives areN-methoxy-1, 1-diphenylurea,N-ethoxy-1, 1-diphenylurea,N-isopropoxy-1, 1-diphenylurea,N-tert-butoxy-1, 1-diphenylurea,N-benzyloxy-1, 1-diphenylurea,N-methoxy-1, 1-bis- (4-methylphenyl) -urea,N-methoxy-1-methyl-1-phenylurea,N-methoxy-1-ethyl-1-phenylurea,N-methoxy-1-isopropyl-1-phenylurea,N-methoxy-1-butyl-1-phenylurea,N-methoxy-1-cyclohexyl-1-phenylurea,N-methoxy-1-methyl-1- (4-methylphenyl) -urea,N-methoxy-1-methyl-1- (4-chlorophenyl) -urea orN-methoxy-tetrahydroquinoline carbonamide.

5. The method of synthesis according to claim 1, characterized in that: the molar ratio of the phenylurea and the derivative thereof to the catalyst to the oxidant is 1: 0.1-0.2: 1.1-2.0.

6. The method of synthesis according to claim 1, characterized in that: the reaction temperature is 20-30 ℃.

Technical Field

The invention belongs to the technical field of organic chemistry, and particularly relates to a synthesis method of a benzo-hydrogenated imidazolone framework.

Background

The benzo-hydrogenated imidazolone and the derivatives thereof as organic intermediates with high biological activity exist in a plurality of natural products and drug molecules, and the research on how to synthesize the frameworks with high efficiency is a hot topic of organic chemical workers.

In recent years, the main strategies for the synthesis of hydrogenated imidazolones are: 1. electrochemical synthesis: by designing novel reaction substrates, e.g. enyne amides (A)Angew. Chem. Int. Ed. 2019, 58, 9017-Adv. Synth. Catal.2020, 3621977-1981.), etc., to implement the cyclization of free radicals in molecules to construct hydrogenated imidazolone frameworks; 2. traditional coupling reaction: catalysis of intramolecular Suzuki coupling reactions with transition metals (Angew. Chem. Int. Ed. 2021, 60, 6314–6319.、Tetrahedron Letters2003, 446073-6077.), direct synthesis of hydrogenated imidazoleOxazolone and its derivatives; 3. and (3) photocatalysis: the free radical coupling reaction in the molecule is realized by generating amide nitrogen free radical through photocatalysis induction (Org. Lett. 2020, 22, 6360−6364.）。

However, the methods of the above synthesis strategies are complex in operation process, too harsh in reaction conditions, and rely too much on metal catalysis to realize the synthesis of target molecules, such routes mostly use noble metal catalysts and long synthesis routes, and the operation is complex and part of the yield is not ideal. At present, the synthesis of the benzo-hydrogenated imidazolone by utilizing a coupling strategy of C-N bond catalytic oxidation of micromolecules is not realized, so that the development of an aryl iodine catalytic oxidation method for efficiently synthesizing the derivatives has important significance for the development of medical intermediates.

Disclosure of Invention

The invention aims to provide a method for synthesizing a benzo-hydrogenated imidazolone framework, which is constructed in a high yield by catalyzing coupling reaction of C-N bonds in molecules with a cheap aryl iodine catalyst.

In order to achieve the purpose, the invention adopts the following technical scheme:

a method for synthesizing a benzo-hydrogenated imidazolone framework is shown as the following formula:

specifically, phenylurea shown as a formula a and derivatives thereof are used as reactants, aryl iodine shown as a formula b is used as a catalyst, m-chloroperoxybenzoic acid is used as an oxidant, and trifluoroethanol is used as a solvent, and the reaction is carried out at the temperature of 20-30 ℃ to obtain the benzohydroimidazolone skeleton shown as a formula c.

Wherein R is¹、R²、R³Each independently an electron donating group or an electron withdrawing group.

Further, R¹Is methyl, phenyl or halogen, R²Is aliphatic alkyl (methyl, ethyl, isopropyl, n-butyl or cyclohexyl) or aryl, R³Is methyl, ethyl, isopropyl,Tert-butyl or benzyl.

Further, the phenylurea and its derivatives areN-methoxy-1, 1-diphenylurea,N-ethoxy-1, 1-diphenylurea,N-isopropoxy-1, 1-diphenylurea,N-tert-butoxy-1, 1-diphenylurea,N-benzyloxy-1, 1-diphenylurea,N-methoxy-1, 1-bis- (4-methylphenyl) -urea,N-methoxy-1-methyl-1-phenylurea,N-methoxy-1-ethyl-1-phenylurea,N-methoxy-1-isopropyl-1-phenylurea,N-methoxy-1-butyl-1-phenylurea,N-methoxy-1-cyclohexyl-1-phenylurea,N-methoxy-1-methyl-1- (4-methylphenyl) -urea,N-methoxy-1-methyl-1- (4-chlorophenyl) -urea orN-methoxy-tetrahydroquinoline carbonamide.

Further, the molar ratio of the phenylurea and the derivatives thereof to the catalyst to the oxidant is 1: 0.1-0.2: 1.1-2.0.

The method has the advantages of simple operation, easily obtained raw materials, short reaction steps, high efficiency and high reaction yield up to 97 percent.

Detailed Description

The application of the chemical synthesis method for synthesizing the benzohydroimidazolone and the derivatives thereof in the medical intermediate has important significance, and how to rapidly and efficiently synthesize the benzohydroimidazolone and the derivatives thereof by the current chemical means is difficult to realize. The inventor has long studied and found that phenylurea derivatives can be efficiently converted into the benzohydroimidazolone by using aryl iodine as a catalyst and m-chloroperoxybenzoic acid as an oxidizing agent.

The synthesis method of the benzo-hydrogenated imidazolone is shown as the following formula:

wherein R is¹、R²、R³The group may be an electron donating group or an electron withdrawing group.

The molar ratio of the reactants is: phenylurea and its derivatives 4-tert-butyliodobenzene and m-chloroperoxybenzoic acidmCPBA) = 1 : (0.1~0.2): (1.1~2.0)。

Still further, the following method may be selected:

(1) will be provided withNPutting the-methoxy-1, 1-diphenylurea into a reaction bottle, adding a catalyst 4-tert-butyl iodobenzene, an oxidant m-chloroperoxybenzoic acid and a reaction solvent trifluoroethanol, and reacting for 8 hours to obtain the compound with high yieldN-methoxy-3-phenylbenz-hydroimidazol-2-one; the molar ratio of the reactants is:N4-tert-butyl iodobenzene, m-chloroperoxybenzoic acid = 1 (0.1-0.15) and (1.5-1.8) as the methoxy-1, 1-diphenylurea.

(2) Will be provided withNThe (E) -ethoxy-1, 1-diphenylurea is placed in a reaction bottle, a catalyst of 4-tert-butyl iodobenzene, an oxidant of m-chloroperoxybenzoic acid and a reaction solvent of trifluoroethanol are added, and the reaction is carried out for 8 hours to obtain the (E) -ethoxy-1, 1-diphenylurea with high yieldN-ethoxy-3-phenylbenzhydroimidazol-2-one; the molar ratio of the reactants is:N4-tert-butyliodobenzene, m-chloroperoxybenzoic acid = 1 (0.15-0.2) and (1.2-1.5).

(3) Will be provided withNPlacing the-isopropoxy-1, 1-diphenylurea into a reaction bottle, adding a catalyst 4-tert-butyl iodobenzene, an oxidant m-chloroperoxybenzoic acid and a reaction solvent trifluoroethanol, and reacting for 8 hours to obtain the compound with high yieldN-isopropoxy-3-phenylbenzhydroimidazol-2-one derivatives;N4-tert-butyliodobenzene, m-chloroperoxybenzoic acid = 1 (0.13-0.18) and (1.2-1.5).

(4) Will be provided withNPutting the (E) -tert-butoxy-1, 1-diphenylurea into a reaction bottle, adding a catalyst 4-tert-butyliodobenzene, an oxidant m-chloroperoxybenzoic acid and trifluoroethanol as a solvent, and reacting for 8 hours to obtain the (E) -tert-butoxy-1, 1-diphenylurea with high yieldN-tert-butoxy-3-phenylbenz-hydroimidazol-2-one compounds;N4-tert-butyliodobenzene, m-chloroperoxybenzoic acid = 1 (0.12-0.16) and (1.1-1.3).

(5) Will be provided withNPutting the (E) -benzyloxy-1, 1-diphenylurea, a catalyst 4-tert-butyliodobenzene and m-chloroperoxybenzoic acid into a reaction bottle, adding trifluoroethanol as a solvent, and reacting for 8 hours to obtain the compound I with high yieldN-benzyloxy-3-phenylbenzhydroimidazol-2-one target product;N-benzyloxy-1, 1-bisThe phenylurea comprises 4-tert-butyl iodobenzene and m-chloroperoxybenzoic acid = 1 (0.16-0.2) and 1.6-2.0).

(6) Will be provided withNPutting the (methoxy) -1, 1-di- (4-methylphenyl) -urea, the catalyst 4-tert-butyl iodobenzene and the m-chloroperoxybenzoic acid into a reaction bottle, adding trifluoroethanol as a solvent, and reacting for 12 hours to obtain the compound I with high yieldN-methoxy-1- (4-tolyl) -5- (4-methyl) -benzoimidazol-2-one target product;Nmethoxy-1, 1-bis- (4-methylphenyl) -urea 4-tert-butyliodobenzene m-chloroperoxybenzoic acid = 1 (0.11-0.14) 1.1-1.4.

(7) Will be provided withNPutting the (E) -methoxy-1-methyl-1-phenylurea into a reaction bottle, adding catalysts 4-tert-butyl iodobenzene and m-chloroperoxybenzoic acid oxidant, and reacting for 12 hours by using trifluoroethanol as a solvent to obtain the (E) -methoxy-1-methyl-1-phenylurea with high yieldN-methoxy-3-methylbenzohydroimidazol-2-one compounds;N4-tert-butyl iodobenzene, m-chloroperoxybenzoic acid = 1 (0.14-0.18) and (1.2-1.6).

(8) Will be provided withNPutting the (E) -methoxy-1-ethyl-1-phenylurea into a reaction bottle, adding catalysts 4-tert-butyl iodobenzene and m-chloroperoxybenzoic acid oxidant, and reacting for 12 hours by using trifluoroethanol as a solvent to obtain the (E) -methoxy-1-ethyl-1-phenylurea with high yieldN-methoxy-3-ethylbenzohydroimidazol-2-one target product;N4-tert-butyl iodobenzene, m-chloroperoxybenzoic acid = 1 (0.10-0.15) and (1.1-1.5).

(9) Will be provided withNPutting the (E) -methoxy-1-isopropyl-1-phenylurea into a reaction bottle, adding catalysts 4-tert-butyl iodobenzene and m-chloroperoxybenzoic acid oxidant, and reacting for 12 hours by using trifluoroethanol as a solvent to obtain the (E) -methoxy-1-isopropyl-1-phenylurea with high yieldN-methoxy-3-isopropylphenylglyoxaline-2-one compounds;N4-tert-butyl iodobenzene, m-chloroperoxybenzoic acid = 1 (0.18-0.20) and (1.6-2.0).

(10) Will be provided withNPutting the (E) -methoxy-1-butyl-1-phenylurea into a reaction bottle, adding catalysts 4-tert-butyliodobenzene and m-chloroperoxybenzoic acid oxidant, and reacting for 16 hours by using trifluoroethanol as a solvent to obtain the (E) -methoxy-1-butyl-1-phenylurea with high yieldN-methoxy-3-butylbenz-hydroimidazol-2-one target product;N4-tert-butyl iodobenzene, m-chloroperoxybenzoic acid = 1 (0.11-0.15) and (1.3-1.6).

(11) Will be provided withNPutting the (E) -methoxy-1-cyclohexyl-1-phenylurea into a reaction bottle, adding catalysts 4-tert-butyliodobenzene and m-chloroperoxybenzoic acid oxidant, and reacting for 16 hours by using trifluoroethanol as a solvent to obtain the (E) -methoxy-1-cyclohexyl-1-phenylurea with high yieldN-methoxy-3-cyclohexylbenzoimidazol-2-one compounds;N4-tert-butyliodobenzene, m-chloroperoxybenzoic acid = 1 (0.15-0.20) and (1.5-2.0).

(12) Will be provided withNPutting the (methoxy) -1-methyl-1- (4-methylphenyl) -urea into a reaction bottle, adding catalysts 4-tert-butyl iodobenzene and m-chloroperoxybenzoic acid oxidant, using trifluoroethanol as a solvent, and reacting for 18 hours to obtain the (methoxy) -1-methyl-1- (4-methylphenyl) -urea with high yieldN-methoxy-3- (4-methylphenyl) -benzoimidazol-2-one target product;N-methoxy-1-methyl-1- (4-methylphenyl) -urea 4-tert-butyliodobenzene m-chloroperoxybenzoic acid = 1 (0.14-0.18): 1.3-1.6.

(13) Will be provided withNPutting the (methoxy) -1-methyl-1- (4-chlorphenyl) -urea into a reaction bottle, adding catalysts of 4-tert-butyl iodobenzene and m-chloroperoxybenzoic acid oxidant, using trifluoroethanol as a solvent, and reacting for 24 hours to obtain the (methoxy) -1-methyl-1- (4-chlorphenyl) -urea with high yieldN-methoxy-3- (4-chlorophenyl) -benzoimidazol-2-one compounds;N-methoxy-1-methyl-1- (4-chlorophenyl) -urea 4-tert-butyliodobenzene m-chloroperoxybenzoic acid = 1 (0.16-0.20) 1.5-2.0.

(14) Will be provided withNPutting the-methoxytetrahydroquinoline carbonylamide into a reaction bottle, adding catalysts 4-tert-butyliodobenzene and m-chloroperoxybenzoic acid oxidant, taking trifluoroethanol as a solvent, and reacting for 24 hours to obtain the compoundN-methoxytetrahydroquinoline benzohydroimidazol-2-one compounds;Nmethoxy-tetrahydroquinoline carbonylamide, 4-tert-butyliodobenzene, m-chloroperoxybenzoic acid = 1 (0.12-0.16) and 1.1-1.5.

In the above reaction, the reaction temperature range is 20-30 ℃.

Example 1

NSynthesis of (E) -methoxy-3-phenylbenz-hydroimidazol-2-one

To a 10 mL reaction tube was addedNMethoxy-1, 1-diphenylurea (24.2 mg, 0.1 mmol), 75% m-chloroperoxybenzoic acid (mmCPBA, 37mg, 0.16 mmol), 4-tert-butyliodobenzene (2.6 mg, 0.01 mmol), and finally 2 mL of Trifluoroethanol (TFE) was added to dissolve it, and stirred at room temperature overnight. After the reaction was complete, saturated NaHCO was added₃5 mL of the solution, extracting with dichloromethane for 3 times, combining the organic phases, and adding anhydrous Na₂SO₄Drying, spin-drying, and finally separating and purifying by column chromatography to obtain light yellow solidN-methoxy-3-phenylbenz-hydroimidazol-2-one (23.3 mg, 97% yield).

¹H NMR (400 MHz, CDCl₃) δ 7.53 (d, J = 4.4 Hz, 4H), 7.45 – 7.38 (m, 1H), 7.24 – 7.16 (m, 2H), 7.13 – 7.04 (m, 2H), 4.16 (s, 3H); ¹³C NMR (100 MHz, CDCl₃) δ 148.9, 133.0, 128.6, 126.9, 125.3, 125.0, 124.9, 121.4, 121.0, 108.1, 105.9, 63.7; ESI FTMS exact mass calcd for (C₁₄H₁₂N₂O₂+H)⁺ requires m/z 241.0977, found m/z 241.0977.

Example 2

NSynthesis of (E) -ethoxy-3-phenylbenz-hydroimidazol-2-one

Will be provided withNEthoxy-1, 1-diphenylurea (25.6 mg, 0.1 mmol), 75% m-chloroperoxybenzoic acid (mmCPBA, 35mg, 0.15 mmol), 4-tert-butyliodobenzene (3.9 mg, 0.015 mmol) was added to a 10 mL reaction tube, which was finally dissolved by addition of 2 mL of Trifluoroethanol (TFE), and stirred at room temperature overnight. After the reaction was complete, saturated NaHCO was added₃5 mL of solution, dichloroExtracting with methane for 3 times, mixing organic phases, and extracting with anhydrous Na₂SO₄Drying, spin-drying, and purifying by column chromatography to obtain colorless liquidN-ethoxy-3-phenylbenz-hydroimidazol-2-one (21.6 mg, 85% yield).

¹H NMR (400 MHz, CDCl₃) δ 7.66 – 7.46 (m, 4H), 7.45 – 7.36 (m, 1H), 7.25 – 7.14 (m, 2H), 7.13 – 6.95 (m, 2H), 4.42 (q, J = 7.1 Hz, 2H), 1.48 (t, J = 7.1 Hz, 3H); ¹³C NMR (100 MHz, CDCl₃) δ 150.4, 134.2, 129.6, 127.8, 127.3, 126.0, 126.0, 122.4, 121.9, 109.0, 107.1, 73.1, 13.9; ESI FTMS exact mass calcd for (C₁₅H₁₄N₂O₂+H)⁺ requires m/z 255.1133, found m/z 255.1135.

Example 3

NSynthesis of (E) -isopropoxy-3-phenylbenz-hydroimidazol-2-one

To a 10 mL reaction tube was addedN-isopropoxy-1, 1-diphenylurea (27.0 mg, 0.1 mmol), 75% m-chloroperoxybenzoic acid ((ii))mCPBA, 30mg, 0.13 mmol), 4-tert-butyliodobenzene (4.7 mg, 0.018 mmol), and finally 2 mL of Trifluoroethanol (TFE) were added to dissolve it, and stirred at room temperature overnight. After the reaction was complete, saturated NaHCO was added₃5 mL of the solution, extracting with dichloromethane for 3 times, combining the organic phases, and adding anhydrous Na₂SO₄Drying, spin-drying, and finally separating and purifying by column chromatography to obtain colorless viscous liquidN-isopropoxy-3-phenylbenz-hydroimidazol-2-one (21.5 mg, 80% yield).¹H NMR (400 MHz, CDCl₃) δ 7.65 – 7.47 (m, 4H), 7.45 – 7.35 (m, 1H), 7.23 – 7.14 (m, 2H), 7.12 – 6.99 (m, 2H), 4.76 (p, J = 6.2 Hz, 1H), 1.45 (d, J = 6.3 Hz, 6H); ¹³C NMR (100 MHz, CDCl₃) δ 151.1, 134.3, 129.5, 128.4, 127.8, 126.0, 126.0, 122.3, 121.8, 108.9, 107.5, 80.1, 21.1; ESI FTMS exact mass calcd for (C₁₆H₁₆N₂O₂+H)⁺requires m/z 269.1290, found m/z 269.1293.

Example 4

NSynthesis of (E) -tert-butoxy-3-phenylbenz-hydroimidazol-2-one

Will be provided withN-tert-butoxy-1, 1-diphenylurea (28.4 mg, 0.1 mmol), 75% m-chloroperoxybenzoic acid (MmCPBA, 30mg, 0.13 mmol), 4-tert-butyliodobenzene (3.9 mg, 0.015 mmol) was added to a 10 mL reaction tube, which was finally dissolved by addition of 2 mL of Trifluoroethanol (TFE), and stirred at room temperature overnight. After the reaction was complete, saturated NaHCO was added₃5 mL of the solution, extracting with dichloromethane for 3 times, combining the organic phases, and adding anhydrous Na₂Drying SO4, spin drying, and purifying by column chromatography to obtain colorless liquidN-tert-butoxy-3-phenylbenz-hydroimidazol-2-one (11.9 mg, 42% yield).

¹H NMR (400 MHz, CDCl₃) δ 7.59 – 7.49 (m, 4H), 7.44 – 7.36 (m, 1H), 7.20 (d, J = 7.8 Hz, 1H), 7.17 – 7.10 (m, 1H), 7.09 – 6.99 (m, 2H), 1.53 (s, 9H); ¹³C NMR (100 MHz, CDCl₃) δ 153.4, 134.4, 130.2, 129.5, 127.7, 126.9, 1260, 122.1, 121.9, 108.9, 108.7, 86.5, 27.7; ESI FTMS exact mass calcd for (C₁₇H₁₈N₂O₂+H)⁺ requires m/z 283.1446, found m/z 283.1447.

Example 5

NSynthesis of (E) -benzyloxy-3-phenylbenz-hydroimidazol-2-one

To a 10 mL reaction tube was addedN-benzyloxy-1, 1-diphenylurea (31.8 mg, 0.1 mmol), 75% m-chloroperoxybenzoic acid (ii)mCPBA, 46mg, 0.2 mmol), 4-tert-butyliodobenzene(5.2 mg, 0.02 mmol), and finally 2 mL of Trifluoroethanol (TFE) was added thereto and dissolved, and the mixture was stirred at room temperature overnight. After the reaction was complete, saturated NaHCO was added₃5 mL of the solution, extracting with dichloromethane for 3 times, combining the organic phases, and adding anhydrous Na₂SO₄Drying, spin-drying, and finally separating and purifying by column chromatography to obtain white solidN-benzyloxy-3-phenylbenz-hydroimidazol-2-one (27.3 mg, 86% yield).

¹H NMR (400 MHz, CDCl₃) δ 7.62 – 7.48 (m, 6H), 7.46 – 7.33 (m, 4H), 7.10 – 6.98 (m, 3H), 6.96 – 6.89 (m, 1H), 5.33 (s, 2H); ¹³C NMR (100 MHz, CDCl₃) δ 149.5, 133.2, 133.1, 129.0, 128.5, 128.3, 127.7 126.8, 126.3, 124.9, 124.8, 121.3, 120.8, 107.9, 106.3, 78.2; ESI FTMS exact mass calcd for (C₂₀H₁₆N₂O₂+H)⁺ requires m/z 317.1290, found m/z 317.1290.

Example 6

NSynthesis of (E) -methoxy-1- (4-tolyl) -5- (4-methyl) -benzoimidazol-2-one

Will be provided withN-methoxy-1, 1-bis- (4-methylphenyl) -urea (27.0 mg, 0.1 mmol), 75% m-chloroperoxybenzoic acid: (m-chloroperbenzoic acid) (m-chloroperbenzoic acid)mCPBA, 30mg, 0.13 mmol), 4-t-butyliodobenzene (3.6 mg, 0.014 mmol) was added to a 10 mL reaction tube, and finally 2 mL of Trifluoroethanol (TFE) was added to dissolve it, and stirred at room temperature overnight. After the reaction was complete, saturated NaHCO was added₃5 mL of the solution, extracting with dichloromethane for 3 times, combining the organic phases, and adding anhydrous Na₂Drying SO4, spin drying, and purifying by column chromatography to obtain white solidN-methoxy-1- (4-tolyl) -5- (4-methyl) -benzoimidazol-2-one (23.4 mg, 87% yield).

¹H NMR (400 MHz, CDCl₃) δ 7.42 – 7.37 (m, 2H), 7.32 (d, J = 8.1 Hz, 2H), 7.02 (s, 1H), 6.94 (d, J = 8.0 Hz, 1H), 6.90 – 6.84 (m, 1H), 4.14 (s, 3H), 2.42 (d, J = 5.4 Hz, 6H); ¹³C NMR (100 MHz, CDCl₃) δ 150.2, 137.7, 132.3, 131.6, 130.2, 126.4, 125.8, 124.0, 122.5, 108.9, 107.4, 64.6, 21.5, 21.2; ESI FTMS exact mass calcd for (C₁₆H₁₆N₂O₂+H)⁺ requires m/z 269.1290, found m/z 269.1291.

Example 7

NSynthesis of (E) -methoxy-3-methylbenzylimidazol-2-one

To a 10 mL reaction tube was addedN-methoxy-1-methyl-1-phenylurea (18.0 mg, 0.1 mmol), 75% m-chloroperoxybenzoic acid (mmCPBA, 37mg, 0.16 mmol), 4-tert-butyliodobenzene (4.2 mg, 0.016 mmol), and finally 2 mL of Trifluoroethanol (TFE) was added to dissolve it, and stirred at room temperature overnight. After the reaction was complete, saturated NaHCO was added₃5 mL of the solution, extracting with dichloromethane for 3 times, combining the organic phases, and adding anhydrous Na₂SO₄Drying, spin-drying, and purifying by column chromatography to obtain colorless liquidNMethoxy-3-methylbenzylimidazol-2-one (16.4 mg, 92% yield).

¹H NMR (400 MHz, CDCl₃) δ 7.16 – 7.07 (m, 3H), 7.02 – 6.95 (m, 1H), 4.08 (s, 3H), 3.41 (s, 3H); ¹³C NMR (100 MHz, CDCl₃) δ 150.0, 125.5, 125.2, 120.8, 120.7, 106.8, 105.6, 63.6, 26.1; ESI FTMS exact mass calcd for (C₉H₁₀N₂O₂+H)⁺ requires m/z 179.0820, found m/z 179.0825.

Example 8

NSynthesis of (E) -methoxy-3-ethylbenzohydroimidazol-2-one

Will be provided withNMethoxy group (I)1-Ethyl-1-phenylurea (19.4 mg, 0.1 mmol), 75% m-chloroperoxybenzoic acid (m: -1mCPBA, 30mg, 0.13 mmol), 4-t-butyliodobenzene (3.6 mg, 0.014 mmol) was added to a 10 mL reaction tube, and finally 2 mL of Trifluoroethanol (TFE) was added to dissolve it, and stirred at room temperature overnight. After the reaction was complete, saturated NaHCO was added₃5 mL of the solution, extracting with dichloromethane for 3 times, combining the organic phases, and adding anhydrous Na₂Drying SO4, spin drying, and purifying by column chromatography to obtain colorless liquidN-methoxy-3-ethylbenzohydroimidazol-2-one (17.1 mg, 89% yield).

¹H NMR (400 MHz, CDCl₃) δ 7.17 – 7.07 (m, 3H), 7.05 – 6.95 (m, 1H), 4.09 (s, 3H), 3.93 (q, J = 7.2 Hz, 2H), 1.34 (t, J = 7.2 Hz, 3H); ¹³C NMR (100 MHz, CDCl₃) δ 150.6, 126.3, 125.6, 121.7, 121.5, 108.0, 106.8, 64.7, 36.0, 13.7; ESI FTMS exact mass calcd for (C₁₀H₁₂N₂O₂+H)⁺ requires m/z 193.0977, found m/z 193.0979.

Example 9

NSynthesis of (E) -methoxy-3-isopropylphenylglyoxaline-2-one

To a 10 mL reaction tube was addedN-methoxy-1-isopropyl-1-phenylurea (20.8 mg, 0.1 mmol), 75% m-chloroperoxybenzoic acid (mmCPBA, 46mg, 0.2 mmol), 4-tert-butyliodobenzene (5.2 mg, 0.02 mmol), and finally 2 mL of Trifluoroethanol (TFE) was added to dissolve it, and stirred at room temperature overnight. After the reaction was complete, saturated NaHCO was added₃5 mL of the solution, extracting with dichloromethane for 3 times, combining the organic phases, and adding anhydrous Na₂SO₄Drying, spin-drying, and purifying by column chromatography to obtain colorless liquidNMethoxy-3-isopropylphenylglyoxalin-2-one (16.4 mg, 92% yield).

¹H NMR (400 MHz, CDCl₃) δ 7.18 – 7.03 (m, 4H), 4.76 – 4.63 (m, 1H), 4.08 (s, 3H), 1.53 (d, J = 7.0 Hz, 6H); ¹³C NMR (100 MHz, CDCl₃) δ 150.3, 126.5, 124.7, 121.5, 121.2, 109.4, 106.8, 64.6, 45.3, 20.3; ESI FTMS exact mass calcd for (C₁₁H₁₄N₂O₂+H)⁺ requires m/z 207.1133, found m/z 207.1130.

Example 10

NSynthesis of (E) -methoxy-3-butylbenz-hydroimidazol-2-one

Will be provided withN-methoxy-1-butyl-1-phenylurea (22.2 mg, 0.1 mmol), 75% m-chloroperoxybenzoic acid (m: -methoxy-1-mCPBA, 35mg, 0.15 mmol), 4-t-butyliodobenzene (3.6 mg, 0.014 mmol) was added to a 10 mL reaction tube, and finally 2 mL of Trifluoroethanol (TFE) was added to dissolve it, and the mixture was stirred at room temperature overnight. After the reaction was complete, saturated NaHCO was added₃5 mL of the solution, extracting with dichloromethane for 3 times, combining the organic phases, and adding anhydrous Na₂Drying SO4, spin drying, and purifying by column chromatography to obtain colorless liquidNMethoxy-3-butylbenz-hydroimidazol-2-one (17.4 mg, 79% yield).

¹H NMR (400 MHz, CDCl₃) δ 7.17 – 7.05 (m, 3H), 7.03 – 6.96 (m, 1H), 4.08 (s, 3H), 3.86 (t, J = 7.3 Hz, 2H), 1.76 – 1.67 (m, 2H), 1.44 – 1.33 (m, 2H), 0.95 (t, J = 7.4 Hz, 3H); ¹³C NMR (100 MHz, CDCl₃) δ 150.9, 126.3, 126.0, 121.7, 121.5, 108.1, 106.7, 64.6, 41.0, 30.5, 20.1, 13.7; ESI FTMS exact mass calcd for (C₁₂H₁₆N₂O₂+H)⁺ requires m/z 221.1290, found m/z 221.1291.

Example 11

NSynthesis of (E) -methoxy-3-cyclohexylbenzohydroimidazol-2-one

To a 10 mL reaction tube was addedN-methoxy-1-cyclohexyl-1-phenylurea (24.8 mg, 0.1 mmol), 75% m-chloroperoxybenzoic acid (mmCPBA, 46mg, 0.2 mmol), 4-tert-butyliodobenzene (5.2 mg, 0.02 mmol), and finally 2 mL of Trifluoroethanol (TFE) was added to dissolve it, and stirred at room temperature overnight. After the reaction was complete, saturated NaHCO was added₃5 mL of the solution, extracting with dichloromethane for 3 times, combining the organic phases, and adding anhydrous Na₂SO₄Drying, spin-drying, and finally separating and purifying by column chromatography to obtain light yellow liquidN-methoxy-3-cyclohexylbenzoimidazol-2-one (20.2 mg, 82% yield).

¹H NMR (400 MHz, CDCl₃) δ 7.21 – 7.16 (m, 1H), 7.15 – 7.03 (m, 3H), 4.33 – 4.19 (m, 1H), 4.08 (s, 3H), 2.17 – 2.03 (m, 2H), 1.95 – 1.82 (m, 4H), 1.80 – 1.69 (m, 1H), 1.51 – 1.37 (m, 2H), 1.34 – 1.24 (m, 1H); ¹³C NMR (100 MHz, CDCl₃) δ 149.3, 125.4, 124.0, 120.3, 120.1, 108.7, 105.7, 63.5, 52.2, 29.2, 24.9, 24.3; ESI FTMS exact mass calcd for (C₁₄H₁₈N₂O₂+H)⁺ requires m/z 247.1446, found m/z 247.1444.

Example 12

NSynthesis of (E) -methoxy-3- (4-methylphenyl) -benzoimidazol-2-one

Will be provided withN-methoxy-1-methyl-1- (4-methylphenyl) -urea (19.4 mg, 0.1 mmol), 75% m-chloroperoxybenzoic acid: (mCPBA, 30mg, 0.13 mmol), 4-t-butyliodobenzene (3.6 mg, 0.014 mmol) was added to a 10 mL reaction tube, and finally 2 mL of Trifluoroethanol (TFE) was added to dissolve it, and stirred at room temperature overnight. After the reaction was complete, saturated NaHCO was added₃5 mL of the solution, extracting with dichloromethane for 3 times, combining the organic phases, and adding anhydrous Na₂Drying SO4, spin drying, and purifying by column chromatography to obtain white pigmentColored solid productN-methoxy-3- (4-methylphenyl) -benzoimidazol-2-one (13.9 mg, 72% yield).

¹H NMR (400 MHz, CDCl₃) δ 6.95 (s, 1H), 6.93 – 6.89 (m, 1H), 6.86 (d, J = 7.9 Hz, 1H), 4.07 (s, 3H), 3.38 (s, 3H), 2.41 (s, 3H); ¹³C NMR (100 MHz, CDCl₃) δ 151.2, 131.7, 126.3, 124.4, 122.3, 107.6, 107.3, 64.6, 27.1, 21.5; FTMS exact mass calcd for (C₁₀H₁₂N₂O₂+H)⁺ requires m/z 193.0977, found m/z 193.0979.

Example 13

NSynthesis of (E) -methoxy-3- (4-chlorophenyl) -benzoimidazol-2-one

To a 10 mL reaction tube was addedN-methoxy-1-methyl-1- (4-chlorophenyl) -urea (21.4 mg, 0.1 mmol), 75% m-chloroperoxybenzoic acid (R) ((R))mCPBA, 46mg, 0.2 mmol), 4-tert-butyliodobenzene (5.2 mg, 0.02 mmol), and finally 2 mL of Trifluoroethanol (TFE) was added to dissolve it, and stirred at room temperature overnight. After the reaction was complete, saturated NaHCO was added₃5 mL of the solution, extracting with dichloromethane for 3 times, combining the organic phases, and adding anhydrous Na₂SO₄Drying, spin-drying, and finally separating and purifying by column chromatography to obtain pink solidN-methoxy-3- (4-chlorophenyl) -benzoimidazol-2-one (18.7 mg, 88% yield).

¹H NMR (400 MHz, CDCl₃) δ 7.12 (d, J = 2.0 Hz, 1H), 7.08 (dd, J = 8.3, 2.0 Hz, 1H), 6.88 (d, J = 8.3 Hz, 1H), 4.07 (s, 3H), 3.39 (s, 3H); ¹³C NMR (100 MHz, CDCl₃) δ 150.9, 127.4, 127.0, 125.1, 121.8, 108.6, 107.1, 64.8, 27.3; FTMS exact mass calcd for (C₉H₉ClN₂O₂+H)⁺ requires m/z 213.0431, found m/z 213.0435.

Example 14

NSynthesis of (E) -methoxytetrahydroquinoline benzohydroimidazol-2-one

Will be provided withNMethoxytetrahydroquinoline carbonylamide (20.6 mg, 0.1 mmol), 75% m-chloroperoxybenzoic acid (MmCPBA, 30mg, 0.13 mmol), 4-t-butyliodobenzene (3.6 mg, 0.014 mmol) was added to a 10 mL reaction tube, and finally 2 mL of Trifluoroethanol (TFE) was added to dissolve it, and stirred at room temperature overnight. After the reaction was complete, saturated NaHCO was added₃5 mL of the solution, extracting with dichloromethane for 3 times, combining the organic phases, and adding anhydrous Na₂Drying SO4, spin drying, and purifying by column chromatography to obtain light yellow liquid productNMethoxytetrahydroquinoline Benzohydroimidazol-2-one (14.5 mg, 71% yield).

¹H NMR (400 MHz, CDCl₃) δ 7.04 – 6.98 (m, 1H), 6.94 (d, J = 7.7 Hz, 1H), 6.90 – 6.83 (m, 1H), 4.07 (s, 3H), 3.92 – 3.74 (m, 2H), 2.85 (t, J = 6.1 Hz, 2H), 2.11 (p, J = 6.0 Hz, 2H); ¹³C NMR (100 MHz, CDCl₃) δ 150.1, 124.6, 122.9, 121.2, 119.9, 119.8, 104.5, 64.7, 38.9, 23.8, 21.7; ESI FTMS exact mass calcd for (C₁₁H₁₂N₂O₂+H)⁺ requires m/z 205.0977, found m/z 205.0980.

The above description is only a preferred embodiment of the present invention, and should not be taken as limiting the invention in any way, and any person skilled in the art can make any simple modification, equivalent replacement, and improvement on the above embodiment without departing from the technical spirit of the present invention, and still fall within the protection scope of the technical solution of the present invention.