A 4-hydroxy-5-phenylaminoimidazole compound and its preparation method and application

Abstract

The present invention relates to a kind of 4-hydroxy-5-phenylaminoimidazole compound and its preparation method and application, comprising the following steps: dissolving sulfur ylide and nitrosobenzene in a solvent and stirring the reaction; adding amidine hydrochloride and alkali, continuing the stirring reaction; suction filtration, washing the filter cake, and obtaining the target compound after drying. The beneficial effects of the present invention are: without any heavy / precious metal catalyst, the reaction conditions are mild, the steps are simple, the time is short, the reaction yield is high, and the separation yield of most products is more than 80%; the substrate applicability range is wide, and a variety of substrate structures can tolerate the reaction conditions, which is conducive to large-scale production; a method for preparing α-carbonyl amide compounds using 4-hydroxy-5-phenylaminoimidazole compounds is proposed, and the reaction can be completed without a catalyst.

Description

Technical Field

[0001] The present invention belongs to the technical field of drug synthesis, and in particular relates to a 4-hydroxy-5-phenylaminoimidazole compound, a preparation method and an application thereof. Background Art

[0002] Imidazole contains two sp 2 Five-membered aromatic rings containing hybridized nitrogen atoms are widely found in various natural products and bioactive compounds. To date, imidazole derivatives have demonstrated therapeutic potential for treating a wide range of diseases, including tropical diseases, cancer, HIV, and microbial infections such as fungi and viruses. Consequently, they have attracted significant attention from medicinal chemists.

[0003] Since most cancer therapeutics contain an imidazole core, imidazole derivatives have become an important anchor for the development of new anticancer drugs. For example, Zhang et al. developed a series of novel 4,5-disubstituted benzyl-1-methyl-1H-imidazol-2-amine compounds and evaluated them biologically using the P-gp-mediated multidrug-resistant breast cancer cell line MDA435 / LCC6MDR. The results showed that one of the compounds exhibited excellent P-gp regulatory activity, low in vitro cytotoxicity, and good safety and efficacy (4,5-Di-substituted benzyl-imidazol-2-substitutedamines as the structure template for the design and synthesis of reversalagents against P-gp-mediated multidrug resistance breast cancer cells. European Journal of Medicinal Chemistry. 2014, 18, 74-83.). Albrecht et al. tested a series of p38 mitogen-activated protein kinase inhibitors, and the most promising compound, CBS-3595, was successfully evaluated in vitro and in vitro and in vivo preclinical studies (Discovery of N-{4-[5-(4-Fluorophenyl)-3-methyl-2-methylsulfanyl-3H-imidazol-4-yl]-pyridin-2-yl}-acetamide (CBS-3595), a Dual p38αMAPK / PDE-4 Inhibitor with Activity against TNFα-Related Diseases. Journal of Medicinal Chemistry. 2017, 60, 5290-5305.). Loksha et al. prepared a series of imidazole derivatives similar to capravirine or S-1153 and screened them against HIV-1. Two of the compounds had extremely low IC50 values ​​and showed strong activity against viral infection (Synthesis of 2-(aminocarbonylmethylthio)-1H-imidazoles as novel Capravirine analogues. Bioorganic & Medicinal Chemistry. 2005, 13, 4209-4220.).

[0004] Currently, many methods for synthesizing imidazole derivatives have been reported, which can be roughly divided into three types. The first method can synthesize imidazole derivatives through a three-component one-pot method using the corresponding diphenylethylenedione, aldehyde or ketone and ammonium acetate; the second method uses Cu2O as a catalyst to react 2-(indol-3-yl)cyclohexanone with amidine through indole-mediated cyclization rearrangement to obtain spiroimidazole derivatives; the third method can be summarized as a [3+2] cyclization strategy. For example, Lei used a single oxygen ( 1 O2)-mediated oxidation of enamines with amidines to synthesize imidazoles in high yields (Lewis Acid-Relayed Singlet Oxygen Reaction with Enamines: Selective Dimerization of Enamines to Pyrrolin-4-ones. J. Am. Chem. Soc. 2022, 144, 16667-16675.). Liu used amidine compounds to bicyclize 4-cyano-1,2-diketone derivatives to synthesize tetrahydro-5H-imidazo[4,5-b]pyridin-5-one (Bicyclization of 4-Cyano-1,2-diketones with Amidines: Synthesis of Tetrahydroimidazo[4,5-b]-5-pyridinones. J. Org. Chem. 2022, 87, 11274-11280.).

[0005] Although these methods have been demonstrated to be effective pathways for the synthesis of imidazole derivatives, they still suffer from the problems of harsh reaction conditions and the need for metal catalysts.

[0006] Therefore, there is an urgent need for a chemical synthesis method with mild reaction conditions, environmental friendliness, strong substrate applicability, and the ability to quickly and efficiently construct imidazole derivatives, as well as an application method of such imidazole derivatives. Summary of the Invention

[0007] The purpose of the present invention is to overcome the deficiencies in the prior art and provide a 4-hydroxy-5-phenylaminoimidazole compound and a preparation method and application thereof.

[0008] This 4-hydroxy-5-phenylaminoimidazole compound has the structural formula:

[0009]

[0010] R1 is phenyl, substituted phenyl, alkyl or heterocyclic aromatic group, R2 is phenyl or substituted phenyl, and R3 is phenyl, substituted phenyl or substituted alkyl.

[0011] The preparation method of the 4-hydroxy-5-phenylaminoimidazole compound comprises the following steps:

[0012] S1, dissolving sulfur ylide and nitrosobenzene in a solvent and stirring to react;

[0013] S2, adding amidine hydrochloride and base to the reaction system obtained in step S1, and continuing to stir the reaction;

[0014] S3. Filter the reaction system obtained in step S3, wash the filter cake, and dry it to obtain a 4-hydroxy-5-phenylaminoimidazole compound.

[0015] Preferably, in step S1, the structural formula of the sulfur ylide is:

[0016]

[0017] The R1 is a phenyl group, a substituted phenyl group, an alkyl group or a heterocyclic aromatic group, and R4 is a phenyl group or an alkyl group.

[0018] Preferably, in step S1, the structural formula of nitrosobenzene is:

[0019]

[0020] The R2 is phenyl or various substituted phenyl groups.

[0021] Preferably, the reaction temperature ranges from 0 to 40° C.; in step 1, the stirring reaction time is 2 to 10 minutes; and in step 2, the stirring reaction time is 1 to 5 hours.

[0022] Preferably, the solvent includes one or more of acetonitrile, tetrahydrofuran, 1,4-dioxane, methanol, dichloromethane and N,N-dimethylformamide.

[0023] Preferably, the base includes one or more of potassium carbonate, sodium bicarbonate, dipotassium hydrogen phosphate, ammonium carbonate and triethylamine.

[0024] Preferably, the concentration of the sulfur ylide in the solvent is 0.1-1 mmol / mL; the amount of nitrosobenzene is 1 equivalent of the sulfur ylide; the amount of base is 1-2 equivalents of the sulfur ylide, and the amount of amidine hydrochloride is 1-2 equivalents of the sulfur ylide.

[0025] A method for preparing an α-carbonylamide compound, wherein the α-carbonylamide compound is obtained by hydrolyzing a 4-hydroxy-5-phenylaminoimidazole compound and boron trifluoride etherate in a solvent. The structure of the α-carbonylamide compound is:

[0026]

[0027] The R1 is a phenyl group or a substituted phenyl group, and R2 is a phenyl group or a substituted phenyl group.

[0028] The beneficial effects of the present invention are:

[0029] 1) The present invention provides a method for preparing 4-hydroxy-5-phenylaminoimidazole compounds, which does not require any heavy / precious metal catalysts, has mild reaction conditions, simple steps, a short reaction time, and a high reaction yield. The isolated yield of most products is above 80%. The substrate applicability range is wide, and various substrate structures can tolerate the reaction conditions, which is conducive to large-scale production.

[0030] 2) The present invention provides a method for preparing α-carbonylamide compounds using 4-hydroxy-5-phenylaminoimidazole compounds. The reaction can also be completed without a catalyst, which facilitates the large-scale production of α-carbonylamide compounds. BRIEF DESCRIPTION OF THE DRAWINGS

[0031] Figure 1 This is the hydrogen spectrum of the product of Example 3;

[0032] Figure 2 This is the carbon spectrum of the product of Example 3;

[0033] Figure 3 This is the hydrogen spectrum of the product of Example 20;

[0034] Figure 4 This is the carbon spectrum of the product of Example 20;

[0035] Figure 5 This is the hydrogen spectrum of the product of Example 28;

[0036] Figure 6 This is the carbon spectrum of the product of Example 28. DETAILED DESCRIPTION

[0037] The present invention will be further described below with reference to the following examples. The following examples are provided only to facilitate understanding of the present invention. It should be noted that, without departing from the principles of the present invention, it is possible for a person skilled in the art to make various modifications to the present invention, and such improvements and modifications fall within the scope of the claims of the present invention.

[0038] Example 1

[0039] As an example, this embodiment 1 provides a 4-hydroxy-5-phenylaminoimidazole compound and a preparation method thereof. The structural formula of the 4-hydroxy-5-phenylaminoimidazole compound is:

[0040]

[0041] R1 is phenyl, substituted phenyl, alkyl or heterocyclic aromatic group, R2 is phenyl or substituted phenyl, and R3 is phenyl, substituted phenyl or substituted alkyl.

[0042] The preparation method of the 4-hydroxy-5-phenylaminoimidazole compound comprises the following steps:

[0043] S1, dissolving sulfur ylide and nitrosobenzene in a solvent and stirring the reaction; wherein:

[0044] The structural formula of sulfur ylide is:

[0045]

[0046] The R1 is a phenyl group, various substituted phenyl groups, an alkyl group or a heterocyclic aromatic group, and R4 is a phenyl group or an alkyl group.

[0047] The structural formula of nitrosobenzene is:

[0048]

[0049] The R2 is phenyl or various substituted phenyl groups.

[0050] The solvent is selected from one or more of acetonitrile, tetrahydrofuran, 1,4-dioxane, methanol, dichloromethane and N,N-dimethylformamide.

[0051] S2, adding amidine hydrochloride and base to the reaction system obtained in step S1, and continuing to stir the reaction;

[0052] The base is selected from one or more of potassium carbonate, sodium bicarbonate, dipotassium hydrogen phosphate, ammonium carbonate and triethylamine.

[0053] S3. The reaction system obtained in step S3 is filtered, the filter cake is washed, and the target compound is obtained after drying.

[0054] The overall reaction formula of this preparation method is:

[0055]

[0056] Example 2

[0057] As another example, this second example proposes, based on the first example, the application of this 4-hydroxy-5-phenylaminoimidazole compound:

[0058] The 4-hydroxy-5-phenylaminoimidazole compound and boron trifluoride etherate are stirred and reacted in a solvent until the 4-hydroxy-5-phenylaminoimidazole compound is completely reacted, thereby obtaining a hydrolysis product, an α-carbonylamide compound. The amount of boron trifluoride etherate used is 10 to 20 times the equivalent of the 4-hydroxy-5-phenylaminoimidazole compound. The solvent is selected from one or more of acetonitrile, 1,4-dioxane, and dichloromethane. The reaction time is 1 to 5 hours.

[0059] The reaction formula of the hydrolysis reaction is:

[0060]

[0061] In this example, 1.0 mmol, 1.0 equivalent of 2,4-diphenyl-5-(phenylamino)-4H-imidazol-4-ol was dissolved in 5 mL of dichloromethane, and the reaction system was cooled to 0° C. Subsequently, 15.0 mmol, 15.0 equivalents of boron trifluoride etherate were added dropwise to the system, stirred at 0° C. for 0.5 hour, and then stirred at room temperature for 2 hours.

[0062] After completion of the reaction, the reaction system was quenched with water and extracted three times with dichloromethane. The organic phase was dried over anhydrous sodium sulfate and rotary evaporated to obtain a crude product. The crude product was purified by column chromatography using 200-300 mesh silica gel and petroleum ether / ethyl acetate = 10:1. After vacuum drying, the α-carbonylamide compound powder was obtained.

[0063]

[0064] The R1 is a phenyl group or various substituted phenyl groups, and R2 is a phenyl group or various substituted phenyl groups.

[0065] It should be noted that the parts in this embodiment that are the same or similar to those in the first embodiment can be referenced to each other and will not be described in detail in this application.

[0066] Example 3

[0067] As another embodiment, this embodiment three proposes, based on the embodiment one, using the preparation method of this 4-hydroxy-5-phenylaminoimidazole compound to obtain a 2,4-diphenyl-5-(phenylamino)-4H-imidazole-4-ol, whose structural formula is:

[0068]

[0069] 1.0 mmol, 1.0 equivalent of 2-(dimethyl-λ 4 -sulfinyl)-1-phenyl-1-one and 1.0 mmol, 1.0 equivalent of nitrosobenzene were dissolved in 5 mL of acetonitrile and stirred at room temperature for 5 minutes.

[0070] After the reaction of the raw materials was complete, 1.0 mmol, 1.0 equivalent of benzamidine hydrochloride and 1.0 mmol, 1.0 equivalent of sodium bicarbonate were added to the system in sequence, and the mixture was stirred at room temperature for 5 hours.

[0071] After the reaction was complete, the reaction system was filtered, and the filter cake was washed sequentially with 10 mL x 3 of petroleum ether and 10 mL x 3 of water. After vacuum drying, 2,4-diphenyl-5-(phenylamino)-4H-imidazole-4-ol was obtained as a white powder with a yield of 86%.

[0072] The melting point of 2,4-diphenyl-5-(phenylamino)-4H-imidazol-4-ol is 155.3-155.8°C.

[0073] like Figure 1 and Figure 2 As shown, this 2,4-diphenyl-5-(phenylamino)-4H-imidazol-4-ol:

[0074] 1 H NMR (400MHz, CDCl3): δ8.29(d,J=6.8Hz,2H),7.68(d,J=7.8Hz,2H),7.45–7.38(m,3H),7.35(m,2H),7.30(m,2H),7.19–7.14(m,2H),7.10(m,2H). 13 C NMR (100MHz, CDCl3): δ181.7,176.0,138.5,138.4,132.0,131.4,129.6,128.9,128.6,128.4,128.4,124.8,124.2,119.7,102.4. HRMS(ESI):m / z calcd for[M+H] + :328.1444,found:328.1442.

[0075] Example 4

[0076] As another example, Example 4, based on Example 3, adjusts the amounts of benzamidine hydrochloride and sodium bicarbonate to 1.5 mmol, or 1.5 equivalents, while maintaining other conditions. After vacuum drying, 2,4-diphenyl-5-(phenylamino)-4H-imidazol-4-ol is obtained as a white powder. The yield is 92%, and the melting point is the same.

[0077] 1H NMR (400MHz, CDCl3): δ8.29(d,J=6.8Hz,2H),7.68(d,J=7.8Hz,2H),7.45–7.38(m,3H),7.35(m,2H),7.30(m,2H),7.19–7.14(m,2H),7.10(m,2H). 13 C NMR (100MHz, CDCl3): δ181.7,176.0,138.5,138.4,132.0,131.4,129.6,128.9,128.6,128.4,128.4,124.8,124.2,119.7,102.4. HRMS(ESI):m / z calcd for[M+H] + :328.1444,found:328.1442.

[0078] Example 5

[0079] As another example, Example 5, based on Example 3, adjusts the amounts of benzamidine hydrochloride and sodium bicarbonate to 2.0 mmol, or 2.0 equivalents, while maintaining other conditions. After vacuum drying, 2,4-diphenyl-5-(phenylamino)-4H-imidazol-4-ol is obtained as a white powder. The yield is 90%, and the melting point is the same.

[0080] 1 H NMR (400MHz, CDCl3): δ8.29(d,J=6.8Hz,2H),7.68(d,J=7.8Hz,2H),7.45–7.38(m,3H),7.35(m,2H),7.30(m,2H),7.19–7.14(m,2H),7.10(m,2H). 13 C NMR (100MHz, CDCl3): δ181.7,176.0,138.5,138.4,132.0,131.4,129.6,128.9,128.6,128.4,128.4,124.8,124.2,119.7,102.4. HRMS(ESI):m / z calcd for[M+H] + :328.1444,found:328.1442.

[0081] Example 6

[0082] As another embodiment, this embodiment 6 proposes, based on the embodiment 3, that 2-(dimethyl-λ 4The amount of 2,4-diphenyl-5-(phenylamino)-4H-imidazol-4-ol was adjusted to 0.5 mmol (1.0 equivalent) for 1-(2-(4-nitro-5-thio)-1-phenyl-1-one and nitrosobenzene, and the amount of benzamidine hydrochloride and sodium bicarbonate was adjusted to 0.75 mmol (1.5 equivalents). Other conditions remained unchanged. After vacuum drying, 2,4-diphenyl-5-(phenylamino)-4H-imidazol-4-ol was obtained as a white powder with an 80% yield and the same melting point.

[0083] 1 H NMR (400MHz, CDCl3): δ8.29(d,J=6.8Hz,2H),7.68(d,J=7.8Hz,2H),7.45–7.38(m,3H),7.35(m,2H),7.30(m,2H),7.19–7.14(m,2H),7.10(m,2H). 13 C NMR (100MHz, CDCl3): δ181.7,176.0,138.5,138.4,132.0,131.4,129.6,128.9,128.6,128.4,128.4,124.8,124.2,119.7,102.4. HRMS(ESI):m / z calcd for[M+H] + :328.1444,found:328.1442.

[0084] Example 7

[0085] As another embodiment, this embodiment 7 proposes, based on the embodiment 3, that 2-(dimethyl-λ 4 The amount of 2,4-diphenyl-5-(phenylamino)-4H-imidazol-4-ol was adjusted to 2.5 mmol (1.0 equivalent) of 1-(2-(4-nitro-5-thio)-1-phenyl-1-one and nitrosobenzene, and the amount of benzamidine hydrochloride and sodium bicarbonate was adjusted to 3.75 mmol (1.5 equivalents). Other conditions remained unchanged. After vacuum drying, 2,4-diphenyl-5-(phenylamino)-4H-imidazol-4-ol was obtained as a white powder with an 88% yield and the same melting point.

[0086] 1 H NMR (400MHz, CDCl3): δ8.29(d,J=6.8Hz,2H),7.68(d,J=7.8Hz,2H),7.45–7.38(m,3H),7.35(m,2H),7.30(m,2H),7.19–7.14(m,2H),7.10(m,2H). 13C NMR (100MHz, CDCl3): δ181.7,176.0,138.5,138.4,132.0,131.4,129.6,128.9,128.6,128.4,128.4,124.8,124.2,119.7,102.4. HRMS(ESI):m / z calcd for[M+H] + :328.1444,found:328.1442.

[0087] Example 8

[0088] As another embodiment, this embodiment eight is based on the embodiment three and 2-(dimethyl-λ 4 -sulfinyl)-1-phenyl-1-one was replaced with 1-(4-chlorophenyl)-2-(dimethyl-λ 4 -sulfinyl)ethan-1-one to obtain a 4-(4-chlorophenyl)-2-phenyl-5-(phenylamino)-4H-imidazole-4-ol, the structural formula of which is:

[0089]

[0090] White powder, yield 92%, melting point 151.9-152.3℃.

[0091] 1 H NMR (400 MHz, DMSO -D6 ): δ10.21(s,1H),8.26(d,J=6.7Hz,2H),8.06(d,J=8.0Hz,2H),7.60–7.50(m,4H),7.42(m,4H),7.36(m,2H),7.09(t,J=7.3Hz,1H). 13 C NMR (100 MHz, DMSO -D6 ): δ182.8,173.0,140.1,139.2,133.0,132.9,131.9,129.2,129.2,129.0,128.6,127.7,123.9,120.2,103.2. HRMS(ESI):m / zcalcd for[M+H] + :362.1055,found:362.1048.

[0092] Embodiment 9

[0093] As another embodiment, this embodiment nine is based on the embodiment three and 2-(dimethyl-λ 4 -sulfinyl)-1-phenyl-1-one was replaced with 2-(dimethyl-λ 4-sulfinyl)-1-(4-fluorophenyl)ethan-1-one to obtain a 4-(4-fluorophenyl)-2-phenyl-5-(phenylamino)-4H-imidazole-4-ol, whose structural formula is:

[0094]

[0095] White powder, yield 88%, melting point 162.4-162.8℃.

[0096] 1 H NMR (400 MHz, DMSO -D6 ): δ10.19(s,1H),8.26(d,J=6.5Hz,2H),8.07(d,J=8.0Hz,2H),7.60–7.50(m,4H) ,7.46(m,2H),7.39(t,J=7.9Hz,2H),7.17(t,J=8.9Hz,2H),7.09(t,J=7.3Hz,1H). 13 C NMR (100 MHz, DMSO -D6 ): δ182.9,172.8,162.3(d,J=242.3Hz),140.2,136.5,132.9,131.9,129.2, 129.1, 129.0, 127.9 (d, J = 8.3Hz), 123.9, 120.2, 115.4 (d, J = 21.4Hz), 103.2. HRMS(ESI):m / z calcd for[M+H] + :346.1351,found:346.1363.

[0097] Example 10

[0098] As another embodiment, this embodiment 10 is based on the embodiment 3 and 2-(dimethyl-λ 4 -sulfinyl)-1-phenyl-1-one is replaced with 2-(dimethyl-L4-sulfinyl)-1-(4-nitrophenyl)ethan-1-one to obtain a 4-(4-nitrophenyl)-2-phenyl-5-(phenylamino)-4H-imidazole-4-ol having the structural formula:

[0099]

[0100] White powder, yield 86%, melting point 173.1-173.6℃.

[0101] 1 H NMR (400 MHz, DMSO -D6): δ10.35(s,1H),8.28(d,J=6.8Hz,2H),8.23(d,J=8.8Hz,2H),8.05(d,J=8.0Hz,2H), 7.67(d,J=8.8Hz,2H),7.61–7.54(m,4H),7.39(t,J=7.9Hz,2H),7.10(t,J=7.3Hz,1H). 13 C NMR (100 MHz, DMSO -D6 ): δ182.4,173.8,147.6,147.2,140.0,132.6,132.1,129.2,129.0,127.1,124.1,124.0,120.2,103.1. HRMS(ESI):m / zcalcd for[M+H] + :373.1296,found:373.1191.

[0102] Example 11

[0103] As another embodiment, this embodiment eleven is based on the embodiment three and 2-(dimethyl-λ 4 -sulfinyl)-1-phenyl-1-one was replaced with 2-(dimethyl-λ 4 -sulfenyl)-1-(4-cyanophenyl)ethane-1-one to obtain a 4-(4-hydroxy-2-phenyl-5-(phenylamino)-4H-imidazol-4-yl)benzonitrile, whose structural formula is:

[0104]

[0105] White powder, yield 85%, melting point: 178.2-179.1℃.

[0106] 1 H NMR (400 MHz, DMSO -D6 ): δ10.28(s,1H),8.26(d,J=6.8Hz,2H),8.04(d,J=8.0Hz,2H),7.83(d,J=8.4Hz,2H), 7.58(d,J=8.0Hz,3H),7.56–7.49(m,3H),7.39(t,J=7.9Hz,2H),7.10(t,J=7.3Hz,1H); 13 C NMR (100 MHz, DMSO -D6): δ182.5,173.7,145.4,140.0,132.8,132.7,132.1,129.3,129.3,129.0,126.7,124.1,120.2,119.2,111.2,103.2. HRMS(ESI):m / z calcd for

[0107] [M+H]+:353.1397,found:353.1262.

[0108] Example 12

[0109] As another embodiment, this embodiment 12 is based on the embodiment 3 and 2-(dimethyl-λ 4 -sulfinyl)-1-phenyl-1-one was replaced with 2-(dimethyl-λ 4 -sulfenyl)-1-(4-trifluoromethylphenyl)ethane-1-one to obtain a 2-phenyl-5-(phenylamino)-4-(4-(trifluoromethyl)phenyl)-4H-imidazol-4-ol, the structural formula of which is:

[0110]

[0111] White powder, yield 68%, melting point: 173.9-174.7℃.

[0112] 1 H NMR (400 MHz, DMSO -D6 ): δ10.27(s,1H),8.27(d,J=7.0Hz,2H),8.07(d,J=8.1Hz,2H),7.74(d,J=8.4Hz,2H),7.6 3(d,J=8.2Hz,2H),7.56(m,3H),7.48(s,1H),7.39(t,J=7.8Hz,2H),7.10(t,J=7.3Hz,1H); 13 C NMR (100 MHz, DMSO -D6 ): δ182.7,173.4,144.7,140.1,132.8,132.0,129.2,129.0,128.7(q,J=22.8Hz ), 127.1, 126.6, 125.7 (q, J = 3.3Hz), 124.4 (q, J = 210.1Hz), 124.0, 120.2, 103.2. HRMS(ESI):m / z calcd for[M+H] + :396.1319,found:396.1212.

[0113] Example 13

[0114] As another embodiment, this embodiment thirteen is based on the embodiment three and 2-(dimethyl-λ 4 -sulfinyl)-1-phenyl-1-one was replaced with 2-(dimethyl-λ 4 -sulfuryl)-1-(4-methylphenyl)ethane-1-one to obtain a 2-phenyl-5-(phenylamino)-4-(p-tolyl)-4H-imidazol-4-ol, whose structural formula is:

[0115]

[0116] White powder, yield 91%, melting point: 167.7-167.9℃.

[0117] 1 H NMR (400 MHz, DMSO -D6 ): δ10.08(s,1H),8.32–8.21(m,2H),8.08(d,J=8.0Hz,2H),7.54(m,3H),7.38(t,J=7.9H z,2H),7.32(d,J=8.1Hz,2H),7.15(t,J=3.9Hz,3H),7.08(t,J=7.3Hz,1H),2.27(s,3H); 13 C NMR (100 MHz, DMSO -D6 ): δ183.2,172.4,140.3,137.5,137.3,133.1,131.7,129.2,129.1,129.1,128.9,125.6,123.8,120.1,103.6,21.2. HRMS(ESI):m / z calcd for[M+H] + :342.1601,found:342.1601.

[0118] Example 14

[0119] As another embodiment, this embodiment 14 is based on the embodiment 3 and 2-(dimethyl-λ 4 -sulfinyl)-1-phenyl-1-one was replaced with 2-(dimethyl-λ 4 -sulfuryl)-1-(4-methoxyphenyl)ethane-1-one to obtain a 4-(4-methoxyphenyl)-2-phenyl-5-(phenylamino)-4H-imidazole-4-ol, whose structural formula is:

[0120]

[0121] White powder, yield 77%, melting point: 168.4-169.3℃.

[0122] 1 H NMR (400 MHz, DMSO -D6 ): δ10.09(s,1H),8.26(d,J=6.3Hz,2H),8.08(d,J=8.0Hz,2H),7.56(d,J=6.2Hz,2H),7.52(d,J=5.9Hz,1H ),7.41–7.36(m,3H),7.34(s,1H),7.13(s,1H),7.08(t,J=7.3Hz,1H),6.90(d,J=8.7Hz,2H),3.72(s,3H); 13 C NMR (100 MHz, DMSO -D6 ): δ188.1,185.2,137.7,136.4,135.9,133.5,129.5,129.5,129.2,127.5,122.2,122.1. HRMS(ESI):m / z calcd for[M+H] + :358.1551,found:358.1550.

[0123] Example 15

[0124] As another embodiment, this embodiment 15 is based on the embodiment 3 and 2-(dimethyl-λ 4 -sulfinyl)-1-phenyl-1-one was replaced with 2-(dimethyl-λ 4 -sulfuryl)-1-(3-methoxyphenyl)ethane-1-one to obtain a 4-(3-methoxyphenyl)-2-phenyl-5-(phenylamino)-4H-imidazole-4-ol, whose structural formula is:

[0125]

[0126] White powder, yield 61%, melting point: 179.9-180.5℃.

[0127] 1 H NMR (400 MHz, DMSO -D6 ): δ10.15(s,1H),8.29(d,J=6.7Hz,2H),8.10(d,J=8.0Hz,2H),7.60–7.54(m,3H),7.40(t,J=7.7Hz ,2H),7.25(d,J=6.2Hz,2H),7.19(s,1H),7.11(t,J=7.3Hz,1H),6.88(t,J=9.6Hz,2H),3.77(s,3H); 13 C NMR (100 MHz, DMSO -D6): δ183.1,172.8,159.6,141.8,140.2,133.0,131.8,129.7,129.2,129.1,129.0,123.8,120.2,117.7,113.5,111.9,103.5,55.5. HRMS(ESI):m / z calcd for[M+H] + :358.1551,found:358.1437.

[0128] Example 16

[0129] As another embodiment, this embodiment 16 is based on the embodiment 3 and 2-(dimethyl-λ 4 -sulfinyl)-1-phenyl-1-one was replaced with 2-(dimethyl-λ 4 -sulfuryl)-1-(2-methoxyphenyl)ethane-1-one to obtain a 4-(2-methoxyphenyl)-2-phenyl-5-(phenylamino)-4H-imidazole-4-ol, whose structural formula is:

[0130]

[0131] White powder, yield 71%, melting point: 163.7-164.7℃.

[0132] 1 H NMR (400 MHz, DMSO -D6 ): δ10.13(s,1H),8.28–8.24(m,2H),8.07(d,J=7.9Hz,2H),7.59–7.55(m,2H),7.54(s,1H),7.38(t,J=7.9Hz,2H),7 .23(d,J=5.4Hz,2H),7.15(d,J=1.7Hz,1H),7.08(t,J=7.3Hz,1H),6.87(m,1H),6.83(d,J=7.9Hz,1H),3.75(s,3H); 13 C NMR (100 MHz, DMSO -D6 ):

[0133] δ183.0,172.8,159.6,141.8,140.2,133.0,131.8,129.7,129.2,129.1,129.0,123.8,120.1,117.6,113.5,111.9,103.5,55.5. HRMS(ESI):m / z calcd for

[0134] [M+H] +:358.1551,found:358.1470.

[0135] Embodiment 17

[0136] As another embodiment, this embodiment 17 is based on the embodiment 3 and replaces the 2-(dimethyl-λ 4 -sulfinyl)-1-phenyl-1-one was replaced with 2-(dimethyl-λ 4 -sulfuryl)-1-(furan-2-yl)ethane-1-one to obtain a 4-(furan-2-yl)-2-phenyl-5-(phenylamino)-4H-imidazol-4-ol, whose structural formula is:

[0137]

[0138] White powder, yield 82%, melting point: 188.1-188.6℃.

[0139] 1 H NMR (400 MHz, DMSO -D6 ): δ10.42(s,1H),8.24(d,J=7.2Hz,2H),8.11(d,J=8.2Hz,2H),7.61(s,1H),7.55 (m,3H),7.40(t,J=7.9Hz,2H),7.36(s,1H),7.11(t,J=7.4Hz,1H),6.46(m,2H).; 13 C NMR (100 MHz, DMSO -D6 ): δ180.8,173.5,152.8,143.3,140.1,132.9,131.9,129.2,129.2,129.0,124.0,120.2,110.9,108.0,100.1. HRMS(ESI):m / zcalcd for[M+H] + :318.1238,found:318.1187.

[0140] Example 18

[0141] As another embodiment, this embodiment 18 is based on the embodiment 3 and 2-(dimethyl-λ 4 -sulfinyl)-1-phenyl-1-one was replaced with 2-(dimethyl-λ 4 -sulfonyldiene)-1-(thiophen-2-yl)ethane-1-one to obtain a 2-phenyl-5-(phenylamino)-4-(thiophen-2-yl)-4H-imidazol-4-ol, whose structural formula is:

[0142]

[0143] White powder, yield 81%, melting point: 166.6-167.1℃.

[0144] 1 H NMR (400 MHz, DMSO -D6 ): δ10.45(s,1H),8.29–8.21(m,2H),8.12(d,J=8.0Hz,2H),7.58–7.52(m,3H),7.48–7. 43(m,2H),7.41(t,J=7.9Hz,2H),7.21–7.17(m,1H),7.11(t,J=7.4Hz,1H),6.99(m,1H); 13 C NMR (100 MHz, DMSO -D6 ): δ181.8,172.8,144.9,140.2,132.9,131.9,129.2,129.1,129.0,127.2,126.3,125.0,124.0,120.3,101.6. HRMS(ESI):m / z calcd for[M+H] + :334.1009,found:334.1009.

[0145] Example 19

[0146] As another embodiment, this embodiment 19 is based on the embodiment 3 and 2-(dimethyl-λ 4 -sulfinyl)-1-phenyl-1-one was replaced with 1-(dimethyl-λ 4 -sulfuryl)-4-phenylbutane-2-one to obtain a 4-phenylethyl-2-phenyl-5-(phenylamino)-4H-imidazole-4-ol, the structural formula of which is:

[0147]

[0148] White powder, yield 93%, melting point: 172.2-173.2℃.

[0149] 1 H NMR (400 MHz, DMSO -D6): δ10.32(s,1H),8.31–8.23(m,2H),8.09(d,J=8.0Hz,2H),7.54(d,J=6.5Hz,3H),7.40(t,J=7.8Hz,2H),7.25–7.20(m,2H),7.13(d ,J=7.1Hz,3H),7.09(d,J=7.3Hz,1H),6.57(s,1H),2.58(dd,J=18.8,6.5Hz,1H),2.45–2.31(m,2H),2.06(dd,J=18.3,6.3Hz,1H).; 13 C NMR (100 MHz, DMSO -D6 ): δ182.5,171.9,142.0,140.4,133.3,131.5,129.2,129.0,128.8,128.7,128.5,126.1,123.7,120.0,103.0,39.6,29.6. HRMS(ESI):m / z calcd for[M+H] + :356.1758,found:356.1753.

[0150] Example 20

[0151] As another embodiment, this embodiment 20 is based on the embodiment 3 and 2-(dimethyl-λ 4 -sulfinyl)-1-phenyl-1-one was replaced with 1-cyclohexyl-2-(dimethyl-λ 4 -sulfonyldiene)ethane-1-one to obtain a 4-cyclohexyl-2-phenyl-5-(phenylamino)-4H-imidazole-4-ol, whose structural formula is:

[0152]

[0153] White powder, yield 95%, melting point: 160.2-160.9℃. Figure 3 and Figure 4 As shown:

[0154] 1 H NMR (400 MHz, DMSO -D6): δ10.14(s,1H),8.25–8.18(m,2H),8.08(d,J=8.0Hz,2H),7.51(d,J=6.6Hz,3H) ,7.38(t,J=7.8Hz,2H),7.07(t,J=7.3Hz,1H),6.31(s,1H),2.30(d,J=12.6Hz,1H) ,1.93(t,J=11.6Hz,1H),1.80(d,J=12.2Hz,1H),1.61–1.52(m,2H),1.41(td,J=13 .0,2.6Hz,1H),1.20(d,J=12.6Hz,1H),1.08(t,J=13.2Hz,3H),0.72–0.56(m,1H); 13 C NMR (100 MHz, DMSO -D6 ): δ183.3,172.0,140.4,133.4,131.4,129.2,129.0,128.8,123.5,119.9,105.2,44.8,27.2,26.5,26.5,25.9,25.7. HRMS(ESI):m / z calcd for[M+H] + :334.1914,found:334.1910.

[0155] Example 21

[0156] As another example, in Example 21, based on Example 3, nitrosobenzene is replaced with 1-chloro-4-nitrosobenzene to obtain 5-((4-chlorophenyl)amino)-2,4-diphenyl-4H-imidazole-4-ol, whose structural formula is:

[0157]

[0158] White powder, yield 75%, melting point: 167.5-168.1℃.

[0159] 1 H NMR (400 MHz, DMSO -D6 ): δ10.30(s,1H),8.26(d,J=6.6Hz,2H),8.12(d,J=8.9Hz,2H),7.59(d,J=7.8Hz,1H),7.55(s,1H),7.54(s,1H ),7.46(s,1H),7.42(d,J=7.3Hz,3H),7.38(d,J=8.2Hz,1H),7.35(s,1H),7.32(d,J=5.5Hz,1H),7.26(s,1H); 13 CNMR (100 MHz, DMSO-D6 ): δ183.1,172.3,140.0,139.2,132.9,131.9,129.1,129.0,128.7,128.50 126.1,125.9,125.7,121.8,103.8. HRMS(ESI):m / z calcd for[M+H] + :362.1055,found:362.1057.

[0160] Example 22

[0161] As another example, in Example 22, based on Example 3, nitrosobenzene is replaced with 1-bromo-4-nitrosobenzene to obtain 5-((4-bromophenyl)amino)-2,4-diphenyl-4H-imidazole-4-ol, whose structural formula is:

[0162]

[0163] White powder, yield 74%, melting point: 182.6-183.1℃.

[0164] 1 H NMR (400 MHz, DMSO -D6 ): δ10.29(s,1H),8.30–8.23(m,2H),8.06(d,J=8.9Hz,2H),7.57(m,4H),7.53(s,1H),7.44–7 .43(m,1H),7.41(s,1H),7.38(d,J=7.8Hz,1H),7.35(s,1H),7.33–7.31(m,1H),7.26(s,1H); 13 C NMR (100 MHz, DMSO -D6 ): δ183.2,172.3,139.9,139.6,132.0,131.4,129.1,129.0,128.7,128.5,126.3,125.7,122.2,115.7,103.8. HRMS(ESI):m / z calcd for[M+H] + :406.0445and 408.0429.

[0165] Example 23

[0166] As another example, in Example 23, based on Example 3, nitrosobenzene is replaced with 1-trifluoromethyl-4-nitrosobenzene to obtain 2,4-diphenyl-5-((4-(trifluoromethyl)phenyl)amino)-4H-imidazole-4-ol, whose structural formula is:

[0167]

[0168] White powder, yield 76%, melting point: 166.7-167.7℃.

[0169] 1 H NMR (400 MHz, DMSO -D6 ): δ10.26(s,1H),8.13(d,J=8.2Hz,2H),8.03(d,J=8.0Hz,2H),7.69–7.63(m,4H),7.53–7.48(m,5H),7.34(t,J=7.4Hz,1H); 13 C NMR (100 MHz, DMSO -D6 ): δ183.5,172.2,143.6,139.7,132.7,132.0,129.3,129.2,129.1,129.0,128. 7(q,J=18.4Hz),126.6(q,J=3.5Hz),125.7,125.0(q,J=207.7Hz),120.3,104.0. HRMS(ESI):m / z calcd for[M+H] + :396.1319,found:396.1255.

[0170] Example 24

[0171] As another example, in Example 24, based on Example 3, nitrosobenzene is replaced with 1-methyl-4-nitrosobenzene to obtain 2,4-diphenyl-5-(p-tolylamino)-4H-imidazole-4-ol, whose structural formula is:

[0172]

[0173] White powder, yield 67%, melting point: 154.7-155.4℃.

[0174] 1 H NMR (400 MHz, DMSO -D6 ): δ10.03(s,1H),8.25(d,J=6.4Hz,2H),7.95(d,J=7.8Hz,2H),7.54(d,J=7.0Hz ,4H),7.43(d,J=7.0Hz,2H),7.38–7.26(m,4H),7.22–7.11(m,4H),2.28(s,3H); 13 C NMR (100 MHz, DMSO -D6): δ182.9,172.7,140.4,137.8,133.2,132.8,131.7,129.6,129.1,128.9,128.6,128.3,125.7,120.2,103.5,20.9. HRMS(ESI):m / zcalcd for[M+H] + :342.1601,found:342.1578.

[0175] Example 25

[0176] As another example, in Example 25, based on Example 3, nitrosobenzene is replaced with 1-methoxy-4-nitrosobenzene to obtain 5-((4-methoxyphenyl)amino)-2,4-diphenyl-4H-imidazole-4-ol, whose structural formula is:

[0177]

[0178] White powder, yield 65%, melting point: 170.7-171.3℃.

[0179] 1 H NMR (400 MHz, DMSO -D6 ): δ10.04(s,1H),8.25(d,J=6.7Hz,2H),8.01(d,J=8.9Hz,2H),7.54(t,J=7.4Hz,3H),7.44(s,1H),7.4 2(s,1H),7.35(t,J=7.3Hz,2H),7.30(d,J=7.0Hz,1H),7.16(s,1H),6.96(d,J=8.9Hz,2H),3.74(s,3H); 13 C NMR (100 MHz, DMSO -D6 ): δ182.7,172.8,155.8,140.6,133.7,133.3,131.7,129.1,128.9,128.6,128.3,125.7,121.6,114.4,103.4,55.7. HRMS(ESI):m / z calcd for[M+H] + :358.1551,found:358.1474.

[0180] Example 26

[0181] As another example, in Example 26, based on Example 3, nitrosobenzene is replaced with 1-ethoxy-4-nitrosobenzene to obtain 5-((4-ethoxyphenyl)amino)-2,4-diphenyl-4H-imidazole-4-ol, whose structural formula is:

[0182]

[0183] White powder, yield 59%, melting point: 162.3-163.1℃.

[0184] 1 H NMR (400 MHz, DMSO -D6 ): δ10.00(s,1H),8.25(d,J=7.3Hz,2H),7.98(d,J=8.8Hz,2H),7.55–7.50(m,3H),7.43(d,J=7.5Hz,2 H),7.32(m,3H),7.12(s,1H),6.95(s,1H),6.93(s,1H),4.01(d,J=6.9Hz,2H),1.32(t,J=6.9Hz,3H).; 13 C NMR (100 MHz, DMSO -D6 ): δ182.6,172.8,155.0,140.6,133.5,133.30,131.6,129.1,128.9,128.6,128.3,125.7,121.5,114.8,103.4,63.6,15.1. HRMS(ESI):m / z calcd for[M+Na] + :372.1707,found:372.1665.

[0185] Example 27

[0186] As another example, in Example 27, based on Example 3, nitrosobenzene is replaced with 1-isopropyl-3-nitrosobenzene to obtain 5-((4-isopropylphenyl)amino)-2,4-diphenyl-4H-imidazole-4-ol, whose structural formula is:

[0187]

[0188] White powder, yield 78%, melting point: 174.4-174.7℃, such as Figure 5 and Figure 6 As shown:

[0189] 1 H NMR (400 MHz, DMSO -D6): δ10.06(s,1H),8.25(d,J=6.4Hz,2H),7.97(d,J=7.8Hz,2H),7.54(d,J=7.1Hz,3H),7.43(d,J=7.0Hz,2H) ,7.36–7.29(m,3H),7.28–7.22(m,2H),7.16(s,1H),2.86(dt,J=13.7,6.9Hz,1H),1.20(s,3H),1.19(s,3H); 13 C NMR (100 MHz, DMSO -D6 ): δ182.9,172.7,143.9,140.5,138.1,133.2,131.7,129.1,128.9,128.5,128.3,126.9,125.7,120.3,103.5,33.3,24.4. HRMS(ESI):370.1914,found:370.1883.

[0190] Example 28

[0191] As another example, in Example 28, based on Example 3, nitrosobenzene is replaced with 1-bromo-3-nitrosobenzene to obtain 5-((3-bromophenyl)amino)-2,4-diphenyl-4H-imidazole-4-ol, whose structural formula is:

[0192]

[0193] White powder, yield 54%, melting point: 164.9-165.9℃.

[0194] 1 H NMR (400 MHz, DMSO -D6 ): δ10.28(s,1H),8.40(s,1H),8.24(d,J=6.6Hz,2H),8.15(d,J=7.5Hz,1H),8.06(d,J=8.0Hz, 1H),7.57(t,J=7.4Hz,3H),7.42(d,J=7.5Hz,2H),7.34(d,J=8.3Hz,3H),7.25(d,J=3.3Hz,2H); 13 CNMR (100 MHz, DMSO -D6 ): δ183.3,172.2,141.7,139.8,131.9,131.2,129.3,129.0,128.7,128.5,126.4,126.1,125.7,122.6,122.0,119.0,103.9. HRMS(ESI):m / zcalcd for[M+H]+ :406.0550,found:406.0510.

[0195] Example 29

[0196] As another example, in Example 29, based on Example 3, nitrosobenzene is replaced with 1-bromo-3-nitrosobenzene to obtain 2,4-diphenyl-5-(m-tolylamino)-4H-imidazole-4-ol, whose structural formula is:

[0197]

[0198] White powder, yield 60%, melting point: 165.3-166.1℃.

[0199] (400MHz,DMSO -D6 ): δ10.02(s,1H),8.27–8.22(m,2H),7.91(d,J=8.3Hz,1H),7.85(s,1H),7.56(d,J=6.8Hz,2H),7.53(s,1H ),7.44–7.40(m,2H),7.33(m,3H),7.26(t,J=7.8Hz,1H),7.17(s,1H),6.90(d,J=7.5Hz,1H),2.32(s,3H); 13 C NMR (100 MHz, DMSO -D6 ): δ183.1,172.6,140.3,140.2,138.3,133.1,131.8,129.1,129.0,128.9,128.6,128.3,125.7,124.5,120.7,117.4,103.6,21.8. HRMS(ESI):m / z calcd for[M+H] + :342.1601,found:342.1605.

[0200] Example 30

[0201] As another example, in Example 3, nitrosobenzene is replaced with 2,4-dichloro-1-nitrosobenzene to obtain 5-((2,4-dichlorophenyl)amino)-2,4-diphenyl-4H-imidazole-4-ol, whose structural formula is:

[0202]

[0203] White powder, yield 50%, melting point: 169.9-170.3℃.

[0204] 1H NMR (400 MHz, DMSO -D6 ): δ10.53(s,1H),8.11(d,J=7.4Hz,2H),7.66(t,J=7.4Hz,1H),7.57(m,4H),7.47 (d,J=2.2Hz,1H),7.39(t,J=7.3Hz,2H),7.36–7.28(m,3H),7.25(d,J=8.6Hz,1H); 13 C NMR (100 MHz, DMSO -D6 ): δ175.4,172.2,147.2,141.4,133.7,129.3,129.1,128.8,128.6,128.4,128.3,127.5,127.4,127.1,126.3,125.3,90.1. HRMS(ESI):m / z calcd for[M+H] + :396.0665,found:396.0669.

[0205] Example 31

[0206] As another example, in Example 31, based on Example 3, nitrosobenzene is replaced with 2,4-dibromo-1-nitrosobenzene to obtain 5-((2,4-dibromophenyl)amino)-2,4-diphenyl-4H-imidazole-4-ol, whose structural formula is:

[0207]

[0208] White powder, yield 76%, melting point: 133.5-134.3℃.

[0209] 1 H NMR (400 MHz, DMSO -D6 ): δ10.53(s,1H),8.11(d,J=7.4Hz,2H),7.72(d,J=2.1Hz,1H),7.66(t,J=7.4Hz,1H),7.61–7.53(m, 4H),7.47(m,1H),7.39(t,J=7.3Hz,2H),7.34(d,J=7.1Hz,1H),7.30(s,1H),7.18(d,J=8.5Hz,1H).; 13 C NMR (100 MHz, DMSO -D6): δ175.1,172.3,148.9,141.2,134.2,133.8,130.9,129.3,129.1,128.6,128.4,128.3,126.4,125.7,118.3,115.0,90.1. HRMS(ESI):m / z calcd for[M+H] + :375.9169, found:375.9195.

[0210] Example 32

[0211] As another example, in Example 32, benzamidine hydrochloride is replaced with p-chlorobenzamidine hydrochloride on the basis of Example 3 to obtain a 2-(4-chlorophenyl)-4-phenyl-5-(phenylamino)-4H-imidazole-4-ol having the structural formula:

[0212]

[0213] White powder, yield 98%, melting point: 166.8-167.1℃.

[0214] 1 H NMR (400 MHz, DMSO -D6 ): δ10.18(s,1H),8.25(d,J=7.8Hz,2H),8.06(d,J=7.4Hz,2H),7.60(d,J=7.8Hz,2H),7.43(d,J=6.7H z,2H),7.37(d,J=10.6Hz,3H),7.33(d,J=5.0Hz,1H),7.30(s,1H),7.22(s,1H),7.09(t,J=6.6Hz,1H); 13 C NMR (100 MHz, DMSO -D6 ): δ183.3,171.7,140.1,140.1,136.5,131.9,130.8,129.2,129.1,128.6,128.4,125.7,124.0,103.8. HRMS(ESI):m / z calcd for[M+H] + :362.1055,found:362.1000.

[0215] Example 33

[0216] As another example, in Example 33, benzamidine hydrochloride is replaced with p-bromobenzamidine hydrochloride on the basis of Example 3 to obtain a 2-(4-bromophenyl)-4-phenyl-5-(phenylamino)-4H-imidazole-4-ol having the structural formula:

[0217]

[0218] White powder, yield 96%, melting point: 175.7-176.3℃.

[0219] 1 H NMR (400 MHz, DMSO -D6 ): δ10.18(s,1H),8.18(d,J=8.0Hz,2H),8.06(d,J=7.8Hz,2H),7.74(d,J=8.1Hz,2H),7.43(d,J=7.2Hz,2 H),7.39–7.34(m,3H),7.32(d,J=5.1Hz,1H),7.28(d,J=14.9Hz,1H),7.22(s,1H),7.09(t,J=7.1Hz,1H); 13 C NMR (100 MHz, DMSO -D6 ): δ183.3,171.8,140.1,140.0,132.3,132.1,131.0,129.2,128.6,128.4,125.7,125.5,124.0,120.3,103.8. HRMS(ESI):m / z calcd for[M+H] + :406.0550and 408.0530,found:406.0442and 408.0444.

[0220] Example 34

[0221] As another example, in Example 34, benzamidine hydrochloride is replaced with cyclopropylformamidine hydrochloride on the basis of Example 3 to obtain a 2-cyclopropyl-4-phenyl-5-(phenylamino)-4H-imidazole-4-ol having the structural formula:

[0222]

[0223] White powder, yield 77%, melting point: 169.6-170.4℃.

[0224] 1 H NMR (400 MHz, DMSO -D6): δ9.79(d,J=12.0Hz,1H),7.88(d,J=7.9Hz,1H),7.45(d,J=7.5Hz,1H),7.36(d,J=7.6Hz,2H),7.33–7.25(m,3H),7.19(t ,J=7.5Hz,1H),7.08(d,J=7.6Hz,1H),6.95–6.90(m,1H),1.85–1.74(m,1H),1.08(d,J=9.8Hz,3H),0.95(d,J=7.7Hz,1H); 13 C NMR (100 MHz, DMSO -D6 ): δ182.7,179.2,150.2,140.5,129.0,128.4,128.1,126.0,123.9,123.0,103.1,13.0,9.9,7.6. HRMS(ESI):m / z calcd for[M+Na] + :292.1445,found:292.1392.

[0225] Example 35

[0226] As another example, this Example 35 proposes, based on Example 2, a preparation of 2-oxo-N,2-diphenylacetamide:

[0227] 1.0 mmol, 1.0 equivalent of 2,4-diphenyl-5-(phenylamino)-4H-imidazol-4-ol was dissolved in 5 mL of dichloromethane, and the reaction system was cooled to 0°C. Subsequently, 15.0 mmol, 15.0 equivalents of boron trifluoride etherate were added dropwise to the system, stirred at 0°C for 0.5 hours, and then stirred at room temperature for 2 hours. The other steps and conditions were the same as in Example 2, and finally 2-oxo-N,2-diphenylacetamide was obtained as a yellow powder.

[0228] Yield: 77%, melting point: 60.3-60.9°C. Its structural formula is:

[0229]

[0230] 1 H NMR (400MHz, CDCl3): δ9.02 (s, 1H), 8.40 (d, J = 7.5Hz, 2H), 7.71 (d, J = 8.1Hz, 2H), 7.65 (m, 1H), 7.50 (m, 2H), 7.40 (m, 2H), 7.19 (m, 1H); 13C NMR (100MHz, CDCl3): δ187.4,158.9,136.6,134.6,133.1,131.5,129.2,128.6,125.3,119.9. HRMS(ESI):m / z calcd for[M+H] + :225.0790,found:225.0795.

[0231] Example 36

[0232] As another embodiment, this embodiment thirty-six proposes, based on embodiment thirty-five, replacing 2,4-diphenyl-5-(phenylamino)-4H-imidazole-4-ol with 2-phenyl-5-(phenylamino)-4-(p-tolyl)-4H-imidazole-4-ol to obtain a brown powder of 2-oxo-N-phenyl-2-(p-tolyl)acetamide with a yield of 80% and a melting point of 115.6-116.4°C.

[0233] Its structural formula is:

[0234]

[0235] 1 H NMR (400MHz, CDCl3): δ8.96 (s, 1H), 8.35 (d, J = 8.1Hz, 2H), 7.70 (d, J = 8.5Hz, 2H), 7.40(t,J=8.5Hz,2H),7.31(d,J=8.1Hz,2H),7.19(t,J=7.4Hz,1H),2.45(s,3H); 13 CNMR (100MHz, CDCl3): δ186.9,159.3,146.2,136.8,131.8,130.7,129.4,129.3,125.4,120.0,22.1. HRMS(ESI):m / z calcd for[M+H] + :240.1020,found:240.1028.

[0236] Example 37

[0237] As another embodiment, this embodiment thirty-seven proposes, based on embodiment thirty-five, replacing 2,4-diphenyl-5-(phenylamino)-4H-imidazole-4-ol with 5-((4-chlorophenyl)amino)-2,4-diphenyl-4H-imidazole-4-ol to obtain a yellow powder of N-(4-chlorophenyl)-2-oxo-2-phenylacetamide with a yield of 72% and a melting point of 129.6-130.4°C.

[0238] Its structural formula is:

[0239]

[0240] 1 H NMR (400MHz, CDCl3) δ9.0 (s, 1H), 8.40 (d, J = 6.7Hz, 2H), 7.66 (d, J = 8.9Hz, 3H), 7.51 (t, J = 7.8Hz, 2H), 7.36 (d, J = 8.8Hz, 2H); 13 C NMR (100MHz, CDCl3) δ187.2,158.9,135.3,134.9,133.0,131.6,130.5,129.4,128.8,121.3. HRMS(ESI):m / z calcd for[M+H] + :260.0473,found:260.0488.

[0241] Example 38

[0242] As another embodiment, this embodiment thirty-eight proposes, based on embodiment thirty-five, replacing 2,4-diphenyl-5-(phenylamino)-4H-imidazole-4-ol with 5-((4-methoxyphenyl)amino)-2,4-diphenyl-4H-imidazole-4-ol to obtain a white powder of N-(4-methoxyphenyl)-2-oxo-2-phenylacetamide with a yield of 68% and a melting point of 102.6-103.4°C.

[0243] Its structural formula is:

[0244]

[0245] 1 H NMR (400MHz, CDCl3) δ8.89(s,1H),8.42(d,J=9.8Hz,1H),7.77–7.55(m,4H),7.51(t,J=7.9Hz,2H),6.93(d,J=9.0Hz,2H),3.83(s,3H); 13 C NMR (100MHz, CDCl3) δ187.7,158.7,157.2,134.7,133.3,131.6,129.9,128.7,121.6,114.5,55.6. HRMS(ESI):m / z calcd for[M+H] + :256.0969,found:256.0952.

[0246] The various embodiments in this specification are described in a progressive manner, and each embodiment focuses on the differences from other embodiments. The same or similar parts between the various embodiments can be referenced to each other and will not be repeated in this application.

Claims

1. A 4-hydroxy-5-phenylaminoimidazole compound, characterized in that: Its structural formula is: The R1 is phenyl, 4-chlorophenyl, 4-fluorophenyl, 4-nitrophenyl, 4-hydroxyphenyl, 4-trifluoromethylphenyl, p-tolyl, 4-methoxyphenyl, 3-methoxyphenyl, 2-methoxyphenyl, furan-2-yl, thien-2-yl or phenethyl, R2 is phenyl, 4-chlorophenyl, 4-bromophenyl, 4-trifluoromethylphenyl, p-tolyl, 4-methoxyphenyl, 4-ethoxyphenyl, 4-isopropylphenyl, 3-bromophenyl, m-tolyl, 2,4-dichlorophenyl or 2,4-dibromophenyl, and R3 is phenyl, 4-chlorophenyl, 4-bromophenyl or cyclopropyl.

2. The method for preparing the 4-hydroxy-5-phenylaminoimidazole compound according to claim 1, wherein The following steps are involved: S1, dissolving sulfur ylide and nitrosobenzene in a solvent and stirring to react; S2, add amidine hydrochloride and alkali to the reaction system obtained in step S1, and continue to stir the reaction; the structural formula of amidine hydrochloride is: , the substituents are defined as shown in right 1; S3, filtering the reaction system obtained in step S3, washing the filter cake, and drying to obtain a 4-hydroxy-5-phenylaminoimidazole compound; In step S1, the structural formula of sulfur ylide is: R1 is phenyl, substituted phenyl, alkyl or heterocyclic aromatic group, and R4 is methyl; In step S1, the structural formula of nitrosobenzene is: The R2 is phenyl or various substituted phenyl groups.

3. The method for preparing 4-hydroxy-5-phenylaminoimidazole compounds according to claim 2, wherein: The reaction temperature range is 0-40° C.; in step 1, the stirring reaction time is 2-10 minutes; in step 2, the stirring reaction time is 1-5 hours.

4. The method for preparing 4-hydroxy-5-phenylaminoimidazole compounds according to claim 2, wherein: Solvents include acetonitrile, tetrahydrofuran, 1,4-dioxane, methanol, dichloromethane and N , N - one or more of dimethylformamide.

5. The method for preparing 4-hydroxy-5-phenylaminoimidazole compounds according to claim 2, wherein: The base includes one or more of potassium carbonate, sodium bicarbonate, dipotassium hydrogen phosphate, ammonium carbonate and triethylamine.

6. The method for preparing 4-hydroxy-5-phenylaminoimidazole compounds according to claim 2, wherein: The concentration of the sulfur ylide in the solvent is 0.1-1 mmol / mL; the amount of nitrosobenzene used is 1 equivalent of the sulfur ylide; the amount of the base used is 1-2 equivalents of the sulfur ylide; and the amount of amidine hydrochloride used is 1-2 equivalents of the sulfur ylide.

7. A α- The preparation method of carbonyl amide compounds is characterized in that: The method is obtained by hydrolyzing the 4-hydroxy-5-phenylaminoimidazole compound according to claim 1 and boron trifluoride etherate in a solvent. α- The structure of carbonyl amide compounds is: The R1 is a phenyl group or a substituted phenyl group, and R2 is a phenyl group or a substituted phenyl group.

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