A method for preparing a hydroxyalkyl-substituted phenanthridine derivative

Abstract

This invention relates to a visible light-mediated method for preparing hydroxyalkyl-substituted phenanthridine derivatives from biphenyl isonitriles and furans via free radical coupling cyclization. Under the influence of a photocatalyst and blue light radiation in an argon atmosphere, this invention achieves a technical solution for synthesizing structurally diverse hydroxyalkyl-substituted phenanthridine compounds from biphenyl isonitriles and furans, resulting in stable molecular structures and excellent chemical properties. The synthetic method utilizes inexpensive and readily available reactants, requiring only a photocatalyst, additives, and blue light, thus saving raw materials and reducing reaction costs. The reaction system is simple, the reaction conditions are mild, the required equipment is minimal, the experimental operation is simple, and the atom economy is high, with excellent yields. The method for synthesizing hydroxyalkyl-substituted phenanthridine derivatives of this invention can be applied to multiple industrial production fields, including pharmaceuticals, pesticides, and organic functional materials.

Description

TECHNICAL FIELD

[0001] The present application relates to a kind of hydroxyalkyl substituted phenanthridine compound and its synthesis method, belong to the field of organic synthesis. BACKGROUND

[0002] Phenanthridine derivative is a very important organic nitrogen-containing heterocyclic compound. The compound containing phenanthridine skeleton structure usually has unique physiological and pharmacological activity, for example: they have regulating immunity, anti-inflammatory, fungicidal, analgesic, antibacterial, antitumor, anxiolytic, hypolipidemic, herbicidal and insecticidal activities. Some phenanthridine-containing core skeleton often exists in drug molecules, such as Trispheridine, Decarine, Asiatcumine A. In addition, phenanthridine derivatives are also widely used in the synthesis of valuable organic functional materials, chemical dyes, polymers and fluorescent probes. Therefore, it has theoretical significance and practical application value to develop a simple and fast method for synthesizing phenanthridine derivatives.

[0003] SUMMARY

[0004] Therefore, in order to make up for the defects of the prior art, the present application provides a synthesis method of hydroxyalkyl substituted phenanthridine compound and its derivative with stable molecular structure and excellent chemical properties.

[0005] The technical scheme adopted by the present application to solve its technical problems is: the present application provides a kind of hydroxyalkyl substituted phenanthridine compound and its derivative, its general formula is formula I:

[0006]

[0007] Among them

[0008] R 1 selected from:

[0009] hydrogen atom, halogen group, alkyl group, methoxy group, cyano group

[0010] R 2 selected from:

[0011] hydrogen atom, halogen group, alkyl group, alkoxy group, cyano group, ester group, trifluoromethyl group, methylthio group

[0012] R 3 selected from:

[0013] hydrogen atom, alkyl group

[0014] The present application also provides a method for synthesizing hydroxyalkyl substituted phenanthridine compound and its derivative, under the irradiation of blue light and photocatalyst, comprising the following steps:

[0015] (I) adding biphenyl isonitrile compound and furan compound, catalyst, additive in a reaction container;

[0016] (II) mixing the reactants well, and carrying out the reaction under the conditions of blue light irradiation and heating under argon protection;

[0017] (III) purifying the product by column chromatography after the reaction is completed.

[0018] Preferably, the method of the present application, the biphenyl isonitrile compound has a general formula of formula II:

[0019]

[0020] wherein

[0021] R 1 is selected from:

[0022] a hydrogen atom, a halogen group, an alkyl group, a methoxy group, a cyano group

[0023] R 2 is selected from:

[0024] a hydrogen atom, a halogen group, an alkyl group, an alkoxy group, a cyano group, an ester group, a trifluoromethyl group, a methylthio group

[0025] Preferably, the method of the present application, the biphenyl isonitrile compound has a general formula of formula III:

[0026]

[0027] wherein

[0028] R 3 is selected from:

[0029] a hydrogen atom, an alkyl group

[0030] Preferably, the method of the present application, the photocatalyst is one of Ir(ppy)3, Ir(dFCF3ppy)2(dtbbpy)PF6, 4CzIPN, Rose Bengal, Ru(bpy)3(PF6)2, Eosin Y.

[0031] Preferably, the method of the present application, the additive I is selected from one of lithium bromide, sodium bromide, potassium bromide, ammonium bromide.

[0032] Preferably, the method of the present application, the amount of water of the additive II is 0-40 equivalents.

[0033] Preferably, in the method of the present invention, the atmosphere of the reaction vessel is: argon atmosphere; the molar ratio of biphenyl isonitrile compound to photocatalyst to additive is 1.0:0.005-0.01:0.2-1.2; the reaction temperature is 50℃-65℃; and the reaction time is 24h-36h.

[0034] The beneficial effects of this invention compared to the prior art are as follows:

[0035] (I) This invention provides a technical solution for converting biphenyl isonitrile compounds and furan compounds into a hydroxyalkyl-substituted phenanthridine compound under photocatalysis and blue light irradiation in an argon atmosphere. The reaction adopts a "one-pot" method to directly and selectively synthesize the target product with a moderate to high yield, overcoming the huge waste of manpower, financial resources, and materials caused by existing multi-step synthesis methods, and saving a lot of research and development time and production cycle; (II) The technical solution for converting biphenyl isonitrile compounds and furan compounds into a hydroxyalkyl-substituted phenanthridine compound under photocatalysis and blue light irradiation in an argon atmosphere has the advantages of simple reaction system, mild reaction conditions, wide availability of raw materials, high atom economy, and significant increase in product added value and high usability, with foreseeable market commercialization prospects; (III) The technical solution for converting biphenyl isonitrile compounds and furan compounds into a hydroxyalkyl-substituted phenanthridine compound under photocatalysis and blue light irradiation in an argon atmosphere has a scientific and reasonable reaction process, simple and convenient operation, few reaction steps, and few required equipment. The hydroxyalkyl-substituted phenanthridine derivatives and their synthesis methods of the present invention can be used in multiple fields such as chemical dyes, pharmaceuticals, and functional materials; they are particularly suitable for the research and development of efficient and selective one-pot synthesis of hydroxyalkyl-substituted phenanthridine compounds. Attached Figure Description

[0036] To demonstrate the product of this invention, the present invention provides hydrogen NMR and carbon NMR spectra of some embodiments.

[0037] Figure 1 a and 1b NMR spectrum of the product of Example 1.

[0038] Figure 2a and 2b NMR spectrum of the product in Example 3.

[0039] Figure 3a and 3b NMR spectrum of the product in Example 9.

[0040] Where a is the proton spectrum and b is the carbon spectrum.

[0041] Figure 4 This is the chemical reaction principle equation of this application. Detailed Implementation

[0042] The present invention will now be described in further detail with reference to the accompanying drawings. These drawings are simplified schematic diagrams, illustrating only the basic structure of the invention, and therefore only show the components relevant to the invention.

[0043]

[0044] Examples 1-10

[0045] Step 1: Add the biphenyl isonitrile compound, additives, photocatalyst, and furan compound to the reaction vessel;

[0046] Step 2: After stirring the reactants evenly, argon gas is introduced, and the reaction is carried out under blue light irradiation and heating conditions;

[0047] Step 3: After the reaction is complete, column chromatography is performed to purify the product.

[0048] Table 1 shows the biphenyl isonitrile compounds, furan compounds, reaction conditions, reaction products, and yields.

[0049] Table 1: Reactants and reaction conditions in Examples 1-10.

[0050]

[0051]

[0052]

[0053] The NMR data of the products from some embodiments are as follows:

[0054] The NMR data of the product from Example 1 are as follows:

[0055] 1 H NMR (400MHz, CDCl3) δ8.58(d,J=8.2Hz,1H),8.49(d,J=7.7Hz,1H),8.21(d,J=8.2Hz,1H),8.09(d,J=8.0Hz,1H),7.82–7.76(m,1H),7.71 –7.62(m,2H),7.62–7.56(m,1H),3.74(t,J=6.2Hz,2H),3.60(s,1H),3.39(t,J=7.5Hz,2H),2.06(p,J=7.3Hz,2H),1.78(p,J=6.5Hz,2H); 13C NMR (100MHz, CDCl3) δ161.7,143.2,132.9,130.5,129.2,128.7,127.4,126.5,126.2,125.2,123.6,122.5,121.9,62.2,34.9,32.3,24.4.

[0056] The NMR data of the product in Example 3 are as follows:

[0057] 1 H NMR (400MHz, CDCl3) δ8.50(d,J=8.2Hz,1H),8.18(d,J=8.2Hz,1H),7.99(d,J=9.0Hz,1H),7.81(d,J=2.7Hz,1H),7.79–7.74(m,1H),7.67–7.61( m,1H),7.29(dd,J=9.0,2.7Hz,1H),3.97(s,3H),3.72(t,J=6.1Hz,2H),3.35(t,J=7.5Hz,2H),2.04(p,J=8.2,7.4Hz,2H),1.77(p,J=6.5Hz,2H); 13 C NMR (100MHz, CDCl3) δ159.1,157.9,138.3,132.4,130.4,130.0,127.3,126.1,125.2,124.5,122.4,118.3,102.9,61.9,55.5,34.6,32.3,24.7.

[0058] The NMR data of the product from Example 9 are as follows:

[0059] 1 H NMR (400MHz, CDCl3) δ8.52(d,J=8.9Hz,1H),8.44(d,J=7.8Hz,1H),8.18(d,J=2.0Hz,1H),8.08(d,J=7.5Hz,1H),7.78–7. 68(m,2H),7.64–7.58(m,1H),3.74(t,J=6.1Hz,2H),3.36(t,J=7.4Hz,2H),2.08(p,J=7.3Hz,2H),1.78(p,J=6.4Hz,2H); 13 C NMR (100MHz, CDCl3) δ160.6,143.1,133.2,131.2,131.0,129.3,129.0,126.9,126.1,125.4,124.2,123.0,121.8,62.0,34.7,32.3,24.2.

[0060] Based on the above-described preferred embodiments of the present invention, and through the foregoing description, those skilled in the art can make various changes and modifications without departing from the inventive concept. The technical scope of this invention is not limited to the contents of the specification, but must be determined according to the scope of the claims.

[0061] Note: See the attached diagram in the instruction manual for the NMR spectrum.

Claims

1. A method of synthesizing a hydroxyalkyl-substituted phenanthridine derivative, characterized by, Under the irradiation of blue light and the photocatalyst, the method comprises the following steps: (I) adding a biphenyl isonitrile compound, a furan compound, a catalyst and an additive into a reaction container; (II) stirring the reaction materials uniformly, and performing a reaction under the conditions of argon atmosphere, blue light irradiation and heating; (III) purifying the product through column chromatography; The structures of the biphenyl isonitrile compound, the furan compound and the hydroxyl alkyl substituted phenanthridine derivative are shown in the following table: The photocatalyst is Ir(dFCF3ppy)2(dtbbpy)PF6; The additive is lithium bromide and water, wherein the amount of water is 30 times of the molar amount of the biphenyl isonitrile compound; The molar ratio of the biphenyl isonitrile compound, the photocatalyst and lithium bromide is 1.0:0.01:1.2; the reaction temperature is 50 DEG C; and the reaction time is 24 hours.

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