CN113651758B - Synthetic method of benzo-hydrogenated imidazolone framework - Google Patents
Synthetic method of benzo-hydrogenated imidazolone framework Download PDFInfo
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Abstract
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 benzo-hydrogenated imidazolone framework. The method has the advantages of simple operation, easily obtained raw materials, short reaction steps, high efficiency and high reaction yield of 97 percent.
Description
Technical Field
The invention belongs to the technical field of organic chemistry, in particular to a synthesis method of a benzo-hydrogenated imidazolone framework.
Background
The benzo-hydrogenated imidazolone and the derivatives thereof are used as organic intermediates with high biological activity, are found in many natural products and in drug molecules, how to synthesize the skeleton with high efficiency is always a hot topic for organic chemical workers to research.
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, 9017-9021. ) Ureas and (b)Adv. Synth. Catal.2020, 3621977-1981.) etc., the intramolecular cyclization of the free radicals is achieved to construct the hydrogenated imidazolone backbone; 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.), directly synthesizing the hydrogenated imidazolone and the derivatives thereof; 3. and (3) photocatalysis: the intramolecular free radical coupling reaction is realized by the photo-catalytic induction to generate amide nitrogen free radical (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 realize the purpose of the invention, 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 is 1 、R 2 、R 3 Each independently an electron donating group or an electron withdrawing group.
Further, the method can be used for preparing a novel liquid crystal display the ground is a mixture of a plurality of ground, R is 1 Is a methyl group, a phenyl group or a halogen, R 2 <xnotran> (, , , ) , R </xnotran> 3 Is methyl, ethyl an isopropyl group tert-butyl or benzyl.
Further, the phenylurea and its derivatives areN-methoxy-1,1-diphenylurea,N-ethoxy-1,1-diphenylurea,N-isopropoxy-1,1 diphenyl urea,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 derivative thereof to the catalyst to the oxidant is 1: 0.1 to 0.2: 1.1 to 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 is 1 、R 2 、R 3 The 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 m-chloroperoxybenzoic acid (I)mCPBA) = 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:Nthe (E) -methoxyl-1,1-diphenylurea is 4-tert-butyl iodobenzene, and the (E) -m-chloroperoxybenzoic acid is = 1, (0.1) - (0.15) and (1.5) - (1.8).
(2) Will be provided withNThe-ethoxy-1,1-diphenylurea is placed in a reaction bottle, the catalyst 4-tert-butyl iodobenzene, the oxidant m-chloroperoxybenzoic acid and the reaction solvent trifluoroethanol are added, and the reaction is carried out for 8 hours to obtain the high-yield compoundN-ethoxy-3-phenylbenzhydroimidazol-2-one; the molar ratio of the reactants is:N-ethoxy-1,1-4-tert-butyl iodobenzene as diphenylurea and m-chloroperoxybenzoic acid = 1 (0.15 to 0.2) and 1.2 to 1.5.
(3) Will be provided withNPlacing-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;N-isopropoxy-1,1-diphenylurea 4-tert-butyliodobenzene m-chloroperoxybenzoic acid = 1 (0.13 to 0.18) and (1.2 to 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;N-tert-butoxy-1,1-diphenylurea 4-tert-butyliodobenzene m-chloroperoxybenzoic acid = 1 (0.12 to 0.16) 1.1 to 1.3.
(5) Will be provided withNPlacing the-benzyloxy-1,1-diphenylurea, the catalyst 4-tert-butyl iodobenzene and the m-chloroperoxybenzoic acid into a reaction bottle, adding trifluoroethanol as a solvent, and reacting for 8 hours to obtain the compoundN-benzyloxy-3-phenylbenzhydroimidazol-2-one target product;N-benzyloxy-1,1-diphenylurea 4-tert-butyliodobenzene m-chloroperoxybenzoic acid = 1 (0.16) - (0.2) and (1.6) - (2.0).
(6) Will be provided withNPutting the-methoxy-1,1-bis- (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;N-methoxy-1,1-bis- (4-methylphenyl) -urea: 4-tert-butyl iodobenzene, m-chloroperoxybenzoic acid = 1 (0.11 to 0.14) and (1.1 to 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-oneA compound;N4-tert-butyliodobenzene, m-chloroperoxybenzoic acid = 1 (0.14 to 0.18) and (1.2 to 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 to 0.15) and (1.1 to 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 to 0.20) and (1.6 to 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;N-methoxy-1-butyl-1-phenylurea: 4-tert-butyl iodobenzene, m-chloroperoxybenzoic acid = 1 (0.11 to 0.15) (1.3 to 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 to 0.20) and (1.5 to 2.0).
(12) Will be provided withNPutting the (methoxy) -1-methyl-1- (4-methylphenyl) -urea into a reaction bottle, adding catalysts 4-tert-butyliodobenzene and m-chloroperoxybenzoic acid oxidant, taking trifluoroethanol as a solvent, and reacting for 18 hoursCan be obtained in 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 to 0.18) 1.3 to 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 to 0.20) 1.5 to 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;N<xnotran> - - : 4- : = 1: (0.12~0.16): (1.1~1.5). </xnotran>
In the above-mentioned reaction, the reaction is carried out, the reaction temperature range is 20-30 ℃.
Example 1
NSynthesis of (E) -methoxy-3-phenylbenz-hydroimidazol-2-one
Adding into a reaction tube of 10 mLN-methoxy-1,1-diphenylurea (24.2 mg,0.1 mmol), 75% m-chloroperoxybenzoic acid (m-chloroperoxybenzoic acid) ((m-chloroperoxybenzoic acid))mCPBA,37mg,0.16 mmol), 4-tert-butyliodobenzene (2.6mg, 0.01 mmol), and finally 2 mL Trifluoroethanol (TFE) was added to dissolve it and stirred at room temperature overnight. After the reaction was complete, saturated NaHCO was added 3 Solution 5 mL, 3 times extracted with dichloromethane, combined organic phases, anhydrous Na 2 SO 4 Drying, spin-drying, and finally separating and purifying by column chromatography to obtain light yellow solidN-methoxy-3-phenylbenz-hydroimidazol-2-one (23.3 mg, yield 97%).
1 H NMR (400 MHz, CDCl 3 ) 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); 13 C NMR (100 MHz, CDCl 3 ) 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 (C 14 H 12 N 2 O 2 +H) + requires m/z 241.0977, found m/z 241.0977.
Practice of example 2
NSynthesis of (E) -ethoxy-3-phenylbenz-hydroimidazol-2-one
Will be provided withN-ethoxy-1,1-diphenylurea (25.6 mg,0.1 mmol), 75% m-chloroperoxybenzoic acid (R) ((R))mCPBA,35mg,0.15 mmol), 4-tert-butyliodobenzene (3.9 mg,0.015 mmol) were added to a 10 mL reaction tube, finally, 2 mL Trifluoroethanol (TFE) was added and dissolved, and the mixture was stirred at room temperature overnight. After the reaction was complete, saturated NaHCO was added 3 Solution 5 mL, 3 times extracted with dichloromethane, combined organic phases, anhydrous Na 2 SO 4 Drying, spin-drying, and purifying by column chromatography to obtain colorless liquidN-ethoxy-3-phenylbenz-hydroimidazol-2-one (21.6 mg, 85% yield).
1 H NMR (400 MHz, CDCl 3 ) 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); 13 C NMR (100 MHz, CDCl 3 ) 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 (C 15 H 14 N 2 O 2 +H) + requires m/z 255.1133, found m/z 255.1135.
Example 3
NSynthesis of (E) -isopropoxy-3-phenylbenz-hydroimidazol-2-one
Adding into a reaction tube of 10 mLN-isopropoxy-1,1-diphenylurea (27.0 mg,0.1 mmol), 75% m-chloroperoxybenzoic acid (ca.) (ii)mCPBA,30mg,0.13 mmol), 4-tert-butyliodobenzene (4.7mg, 0.018mmol) and finally 2 mL Trifluoroethanol (TFE) were added to dissolve it and stirred at room temperature overnight. After the reaction was complete, saturated NaHCO was added 3 Solution 5 mL, 3 times extracted with dichloromethane, combined organic phases, anhydrous Na 2 SO 4 Drying, 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). 1 H NMR (400 MHz, CDCl 3 ) 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); 13 C NMR (100 MHz, CDCl 3 ) 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 (C 16 H 16 N 2 O 2 +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 (R) ((R))mCPBA,30mg,0.13 mmol), 4-tert-butyliodobenzene (3.9mg, 0.015 mmol) was added to a 10 mL reaction tube, and finally 2 mL Trifluoroethanol (TFE) was added to dissolve it and stirred at room temperature overnight. After the reaction is complete, addSaturated NaHCO is added 3 Solution 5 mL, 3 times extracted with dichloromethane, combined organic phases, anhydrous Na 2 Drying SO4, spin-drying, and finally separating and purifying by column chromatography to obtain colorless liquidN-tert-butoxy-3-phenylbenz-hydroimidazol-2-one (11.9 mg, 42% yield).
1 H NMR (400 MHz, CDCl 3 ) 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); 13 C NMR (100 MHz, CDCl 3 ) 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 (C 17 H 18 N 2 O 2 +H) + requires m/z 283.1446, found m/z 283.1447.
Example 5
NSynthesis of (E) -benzyloxy-3-phenylbenz-hydroimidazol-2-one
Adding into a reaction tube of 10 mLN-benzyloxy-1,1-diphenylurea (31.8 mg,0.1 mmol), 75% m-chloroperoxybenzoic acid (m-chloroperoxybenzoic acid) ((m-chloroperoxybenzoic acid))mCPBA,46mg,0.2 mmol), 4-tert-butyliodobenzene (5.2mg, 0.02 mmol) and finally 2 mL Trifluoroethanol (TFE) were added and dissolved and stirred at room temperature overnight. After the reaction was complete, saturated NaHCO was added 3 The solution 5 5363 is zxft 5363, the dichloromethane is extracted for 3 times, and the obtained solution is subjected to extraction, the organic phases were combined and anhydrous Na 2 SO 4 Drying, spin-drying, and finally separating and purifying by column chromatography to obtain white solidN-benzyloxy-3-phenylbenzohydroimidazol-2-one (27.3 mg, 86% yield).
1 H NMR (400 MHz, CDCl 3 ) 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); 13 C NMR (100 MHz, CDCl 3 ) 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 (C 20 H 16 N 2 O 2 +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% of m-chloroperoxybenzoic acid (m: (m:))mCPBA,30mg,0.13 mmol), 4-tert-butyliodobenzene (3.6mg, 0.014 mmol) was added to a 10 mL reaction tube, and finally 2 mL Trifluoroethanol (TFE) was added to dissolve it and stirred at room temperature overnight. After the reaction was complete, saturated NaHCO was added 3 Solution 5 mL, dichloromethane extraction 3 times, organic phase combination, anhydrous Na 2 Drying SO4, spin-drying, and finally separating and purifying by column chromatography to obtain white solidN-methoxy-1- (4-tolyl) -5- (4-methyl) -benzoimidazol-2-one (23.4 mg, 87% yield).
1 H NMR (400 MHz, CDCl 3 ) 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); 13 C NMR (100 MHz, CDCl 3 ) 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 (C 16 H 16 N 2 O 2 +H) + requires m/z 269.1290, found m/z 269.1291.
Example 7
NSynthesis of (E) -methoxy-3-methylbenzylimidazol-2-one
Reaction to 10 mLIn tubes to be addedN-methoxy-1-methyl-1-phenylurea (18.0 mg,0.1 mmol), 75% of meta-chloroperoxy oxybenzoic acid (b)mCPBA,37mg,0.16 mmol), 4-tert-butyliodobenzene (4.2mg, 0.016 mmol) and finally 2 mL Trifluoroethanol (TFE) were added to dissolve it and stirred at room temperature overnight. After the reaction was complete, saturated NaHCO was added 3 Solution 5 mL, 3 times extracted with dichloromethane, combined organic phases, anhydrous Na 2 SO 4 Drying, spin-drying, and finally separating and purifying by column chromatography to obtain colorless liquidNMethoxy-3-methylbenzylimidazol-2-one (16.4 mg, 92% yield).
1 H NMR (400 MHz, CDCl 3 ) δ 7.16 – 7.07 (m, 3H), 7.02 – 6.95 (m, 1H), 4.08 (s, 3H), 3.41 (s, 3H); 13 C NMR (100 MHz, CDCl 3 ) 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 (C 9 H 10 N 2 O 2 +H) + requires m/z 179.0820, found m/z 179.0825.
Example 8
NSynthesis of (E) -methoxy-3-ethylbenzohydroimidazol-2-one
Will be provided withN-methoxy-1-ethyl-1-phenylurea (19.4 mg,0.1 mmol), 75% m-chloroperoxybenzoic acid (m: (m-chloroperoxybenzoic acid)) (mCPBA,30mg,0.13 mmol), 4-tert-butyliodobenzene (3.6mg, 0.014 mmol) was added to a 10 mL reaction tube, and finally 2 mL Trifluoroethanol (TFE) was added to dissolve it and stirred at room temperature overnight. After the reaction was complete, saturated NaHCO was added 3 Solution 5 mL, dichloromethane extraction 3 times, organic phase combination, anhydrous Na 2 Drying SO4, spin-drying, and finally separating and purifying by column chromatography to obtain colorless liquidN-methoxy-3-ethylbenzohydroimidazol-2-one (17.1 mg, 89% yield).
1 H NMR (400 MHz, CDCl 3 ) 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); 13 C NMR (100 MHz, CDCl 3 ) 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 (C 10 H 12 N 2 O 2 +H) + requires m/z 193.0977, found m/z 193.0979.
Example 9
NSynthesis of (E) -methoxy-3-isopropylphenylglyoxaline-2-one
Adding into a reaction tube of 10 mLN-methoxy-1-isopropyl-1-phenylurea (20.8 mg,0.1 mmol), 75% m-chloroperoxybenzoic acid (m-chloroperbenzoic acid: (m-chloroperbenzoic acid)) (mCPBA,46mg,0.2 mmol), 4-tert-butyliodobenzene (5.2mg, 0.02 mmol) and finally 2 mL Trifluoroethanol (TFE) were added and dissolved and stirred at room temperature overnight. After the reaction was complete, saturated NaHCO was added 3 Solution 5 mL, 3 times extracted with dichloromethane, combined organic phases, anhydrous Na 2 SO 4 Drying, spin-drying, and purifying by column chromatography to obtain colorless liquidNMethoxy-3-isopropylbenzohydroimidazol-2-one (16.4 mg, 92% yield).
1 H NMR (400 MHz, CDCl 3 ) 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); 13 C NMR (100 MHz, CDCl 3 ) 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 (C 11 H 14 N 2 O 2 +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-chloroperbenzoic acid: (m-chloroperbenzoic acid)) (mCPBA,35mg,0.15 mmol), 4-tert-butyliodobenzene (3.6mg, 0.014 mmol) was added to a 10 mL reaction tube, and finally 2 mL Trifluoroethanol (TFE) was added to dissolve it and stirred at room temperature overnight. After the reaction was complete, saturated NaHCO was added 3 Solution 5 mL, 3 times extracted with dichloromethane, combined organic phases, anhydrous Na 2 Drying SO4, spin-drying, and finally separating and purifying by column chromatography to obtain colorless liquidN-methoxy-3-butylbenz-hydroimidazol-2-one (17.4 mg, yield 79%).
1 H NMR (400 MHz, CDCl 3 ) 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); 13 C NMR (100 MHz, CDCl 3 ) 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 (C 12 H 16 N 2 O 2 +H) + requires m/z 221.1290, found m/z 221.1291.
Example 11
N-methoxy-3-cyclohexyl benzene Synthesis of hydrogenated imidazol-2-ones
Adding into a reaction tube of 10 mLN-methoxy-1-cyclohexyl-1-phenylurea (24.8 mg,0.1 mmol), 75% m-chloroperoxybenzoic acid (m: (m-chloroperoxybenzoic acid)) (mCPBA,46mg,0.2 mmol), 4-tert-butyliodobenzene (5.2mg, 0.02 mmol) and finally 2 mL Trifluoroethanol (TFE) were added and dissolved and stirred at room temperature overnight. After the reaction was complete, saturated NaHCO was added 3 Solution 5 mL, dichloromethane extraction 3 times, organic phase combination, anhydrous Na 2 SO 4 Drying, spin-drying, and finally separating and purifying by column chromatography to obtain light yellow liquidN-methoxy-3-cyclohexylbenzohydroimidazol-2-one (20.2 mg, 82% yield).
1 H NMR (400 MHz, CDCl 3 ) 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); 13 C NMR (100 MHz, CDCl 3 ) 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 (C 14 H 18 N 2 O 2 +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: (m-chloroperbenzoic acid) ((m-chloroperbenzoic acid))mCPBA,30mg,0.13 mmol), 4-tert-butyliodobenzene (3.6mg, 0.014 mmol) were added to a 10 mL reaction tube and finally dissolved in 2 mL Trifluoroethanol (TFE) and stirred at room temperature overnight. After the reaction was complete, saturated NaHCO was added 3 Solution 5 mL, dichloromethane extraction 3 times, organic phase combination, anhydrous Na 2 Drying SO4, spin-drying, and finally separating and purifying by column chromatography to obtain a white solid productN-methoxy-3- (4-methylphenyl) -benzohydroimidazol-2-one (13.9 mg, 72% yield).
1 H NMR (400 MHz, CDCl 3 ) 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); 13 C NMR (100 MHz, CDCl 3 ) 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 (C 10 H 12 N 2 O 2 +H) + requires m/z 193.0977, found m/z 193.0979.
Example 13
N-methoxy-3- (4-chlorophenyl) -Synthesis of benzohydroimidazol-2-ones
Adding into a reaction tube of 10 mLN-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 (5.2mg, 0.02 mmol), and finally 2 mL Trifluoroethanol (TFE) were added to dissolve it and stirred at room temperature overnight. After the reaction was complete, saturated NaHCO was added 3 Solution 5 mL, dichloromethane extraction 3 times, organic phase combination, anhydrous Na 2 SO 4 Drying, spin-drying, and finally separating and purifying by column chromatography to obtain pink solidN-methoxy-3- (4-chlorophenyl) -benzohydroimidazol-2-one (18.7 mg, 88% yield).
1 H NMR (400 MHz, CDCl 3 ) 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); 13 C NMR (100 MHz, CDCl 3 ) δ 150.9, 127.4, 127.0, 125.1, 121.8, 108.6, 107.1, 64.8, 27.3; FTMS exact mass calcd for (C 9 H 9 ClN 2 O 2 +H) + requires m/z 213.0431, found m/z 213.0435.
Example 14
NSynthesis of (E) -methoxytetrahydroquinoline benzohydroimidazol-2-one
Will be provided withN-methoxytetrahydroquinolinecarbonyl amide (20.6 mg,0.1 mmol), 75% of meta-chloroperoxy oxybenzoic acid (b)mCPBA,30mg,0.13 mmol), 4-tert-butyliodobenzene (3.6mg, 0.014 mmol) was added to a 10 mL reaction tube, and finally 2 mL Trifluoroethanol (TFE) was added to dissolve it and stirred at room temperature overnight. After the reaction was complete, saturated NaHCO was added 3 Solution 5 mL, 3 times extracted with dichloromethane, combined organic phases, anhydrous Na 2 Drying SO4, spin-drying, and finally separating and purifying by column chromatography to obtain light yellow liquid productN-methoxytetrahydroquinoline benzohydroimidazol-2-one (14.5 mg, 71% yield).
1 H NMR (400 MHz, CDCl 3 ) 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); 13 C NMR (100 MHz, CDCl 3 ) 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 (C 11 H 12 N 2 O 2 +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.
Claims (3)
1. A method for synthesizing a benzo-hydrogenated imidazolone framework is characterized in that: phenyl urea and derivatives thereof are used as reactants, aryl iodine is used as a catalyst, m-chloroperoxybenzoic acid is used as an oxidant, trifluoroethanol is used as a solvent, reacting to obtain a benzo-hydrogenated imidazolone framework;
said phenylurea and its derivatives areN-methoxy-1,1 diphenyl urea,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 radical-1-phenylurea,N-methoxy-1-cyclohexyl-1-phenylurea,NMethoxy group (I)1-methyl-1- (4-methylphenyl) -urea,N-methoxy-1-methyl-1- (4-chlorophenyl) -urea orN-one of methoxy-tetrahydroquinoline carbonamides;
the aryl iodine is 4-tert-butyl iodobenzene;
the benzo-hydrogenated imidazolone skeletons are respectivelyN-methoxy-3-phenylbenzo hydrogenated imidazol-2-one,N-ethoxy-3-phenylbenz-hydroimidazol-2-one,N-isopropoxy-3-phenylbenz-hydrimidazol-2-one,N-tert-butoxy-3-phenylbenz-hydroimidazol-2-one,N-benzyloxy-3-phenylbenz-hydrimidazol-2-one,N-methoxy-1- (4-tolyl) -5- (4-methyl) -benzoimidazol-2-one,N-methoxy-3-methylbenzylimidazol-2-one,N-methoxy-3-ethylbenzohydroimidazol-2-one,N-methoxy-3-isopropylphenylhydroimidazol-2-one,N-methoxy-3-butylbenz-hydroimidazol-2-one,N-methoxy-3-cyclohexylbenzimidazol-2-one,N-methoxy-3- (4-methylphenyl) -benzoimidazol-2-one,N-methoxy-3- (4-chlorophenyl) -benzohydroimidazol-2-one orN-methoxytetrahydroquinoline benzo hydrogenated imidazol-2-one.
2. 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 to 0.2: 1.1 to 2.0.
3. The method of synthesis according to claim 1, characterized in that: the reaction temperature is 20-30 ℃.
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| CN104817484A (en) * | 2015-05-18 | 2015-08-05 | 安徽师范大学 | 2-indolone derivatives and preparation method thereof |
| CN106045916A (en) * | 2016-05-31 | 2016-10-26 | 付正云 | Synthesis method for imidazolone compound |
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| CN104817484A (en) * | 2015-05-18 | 2015-08-05 | 安徽师范大学 | 2-indolone derivatives and preparation method thereof |
| CN106045916A (en) * | 2016-05-31 | 2016-10-26 | 付正云 | Synthesis method for imidazolone compound |
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| Construction of Benzimidazolone Derivatives via Aryl Iodide Catalyzed Intramolecular Oxidative C−H Amination;Yang Wang et al.;《J. Org. Chem.》;20220216;第87卷;第3234-3241页 * |
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