A method for the photo-oxidative reduction catalytic preparation of aromatic nitro compounds

Abstract

The application discloses a method for preparing aromatic nitro compounds through photo-oxidation and reduction catalysis, and the method comprises the following steps: irradiating a compound of formula I with a nitrite and a photo-catalyst under LED light source to perform photo-oxidation and reduction catalysis reaction, so as to obtain the aromatic nitro compound. 5 The method has mild reaction conditions, can construct ¹ N-labeled aromatic nitro compounds in one step, and has good yield, thereby providing a convenient way for drug metabolism tracking and isotope labeling. The method has wide application prospects in the fields of organic synthesis, drug research and development and isotope labeling.

Description

Technical Field

[0001] This invention relates to the field of photocatalytic redox, specifically to a method for the photo-redox catalytic preparation of aromatic nitro compounds. Background Technology Aromatic nitro compounds are important structural units in pharmaceuticals, organic dyes, and functional materials, and are also widely used intermediates in organic synthesis, participating in various chemical transformations. Traditionally, the preparation of aromatic nitro compounds mainly relies on electrophilic aromatic substitution reactions involving nitric acid and strong acids (such as sulfuric acid). However, this classic method has several inherent drawbacks: First, the reaction conditions are harsh, requiring high concentrations of strong acids and high temperatures, leading to severe equipment corrosion and safety risks; second, regioselectivity is difficult to control, often resulting in mixtures of multiple isomers that are difficult to separate; third, they have poor tolerance to various functional groups (such as halogens, esters, and aldehydes), limiting their application in the later stages of complex molecule modification.

[0002] To overcome these problems, researchers have developed several improved methods. For example, sodium nitrite (NaNO2) is used as the nitrating agent, and strong oxidants (such as m-chloroperoxybenzoic acid, hydrogen peroxide, etc.) are used to promote the direct nitration of aromatic hydrocarbons (CH) (M. Reitti, P. Villo, B. Olofsson, Angew. Chem. Int. Ed. 2016, 55, 8928-8932; Angew. Chem. 2016, 128, 9074-9078). Although these methods avoid the use of mixed acids, they still require an excess of strong oxidants, and the functional group compatibility and regioselectivity need to be improved. Another strategy involves regio-specific nitration of aryl halides with sodium nitrite catalyzed by transition metals (such as palladium and copper) (a) BP Fors, SL Buchwald, J. Am.Chem. Soc. 2009, 131, 12898-12899.; b) S. Li, D. Ma, J. Org. Chem. 2024, 89, 6626-6630. This method can efficiently synthesize the target nitro compound, but it usually requires a high reaction temperature (>100℃) to overcome the energy barrier, resulting in high energy consumption and being unfavorable to heat-sensitive functional groups.

[0003] In recent years, photoredox catalysis has attracted widespread attention due to its advantages such as mild reaction conditions, good selectivity, and broad tolerance to functional groups. Single-electron transfer (SET) processes achieved through photoexcitation can generate radical intermediates at room temperature and pressure, leading to the construction of various chemical bonds. However, to date, there are no reports on the regio-specific nitration of aryl (pseudo)halides using photoredox catalysis. The main challenge lies in how to effectively oxidize the aryl radicals generated by photocatalysis to sodium nitrite to form nitro groups; a suitable photocatalytic system is still lacking.

[0004] Therefore, developing a method to achieve regio-specific nitration of aromatic compounds under mild conditions is a technical challenge in this field, with significant academic value and application prospects. Summary of the Invention

[0005] The purpose of this invention is to provide a method for preparing aromatic nitro compounds, which aims to achieve mild reaction conditions and broad substrate adaptability.

[0006] To achieve the above objectives, the present invention provides a method for preparing aromatic nitro compounds, comprising the following steps: The compound of formula I, nitrite, and photocatalyst are mixed in an organic solvent and subjected to a photo-oxidation-reduction catalytic reaction under LED light source irradiation to obtain the aromatic nitro compound shown in formula II.

[0007] Wherein, a is 0, 1, 2, or 3, and when a is 2 or 3, R1 is the same or different substituents, independently selected from halogens, alkyl groups, alkoxy groups, and acyl groups. Here, those skilled in the art will understand that when a is 0, it indicates no substituents, and when a is 1, it indicates the presence of one substituent.

[0008] Wherein, P is S or Se, and Q is selected from one of OTf, BF4, PF6 and Cl.

[0009] Among them, the It is one of the following: benzene ring, pyrrole ring, and N-methylpyrrole ring.

[0010] The photocatalyst is a phenothiazine compound or a phenothiazine compound.

[0011] Preferably, R1 is selected from chlorine, bromine, methyl, ethyl, isopropyl, tert-butyl, cyclohexyl, methoxy, ethoxy, aldehyde, methoxycarbonyl, acetyl, benzoyl, 3-acetoxypropyl, benzoyloxymethyl, and... .

[0012] Preferably, the structure of the photocatalyst is as follows: Wherein, X is S or Se, b is 0, 1, or 2, and when b is 2, R2 is the same or different substituents; R2 is selected from ethyl, n-butyl, nitro, fluorine, and methoxycarbonyl, preferably, the photocatalyst is .

[0013] Further, the second organic solvent is selected from one or more of N,N-dimethylacetamide, N,N-dimethylformamide, DMSO, acetone and toluene.

[0014] Further, the second organic solvent is a mixed solvent of N,N-dimethylacetamide and acetone, and the volume ratio of N,N-dimethylacetamide to acetone is (2.5~2.9):(0.1~0.5); preferably, the volume ratio of N,N-dimethylacetamide to acetone is 2.8:0.2.

[0015] Furthermore, the wavelength of the light source is 400-460 nm; preferably, the wavelength is 427 nm.

[0016] Further, the nitrite is sodium nitrite or potassium nitrite; the amount of the nitrite used is 3.0-4.0 equivalents of the molar amount of the compound represented by Formula I; preferably, it is 3.5 equivalents.

[0017] Furthermore, the reaction temperature in step two is 20-40℃; preferably, the reaction temperature in step two is 35℃.

[0018] Furthermore, the reaction time for step two is 13-24 hours; preferably, the reaction time for step two is 18 hours.

[0019] Furthermore, the nitrite is 15 N-labeled nitrites are used to prepare 15 N-labeled aromatic nitro compounds.

[0020] Furthermore, the compound of formula I is prepared by reacting the compound of formula III, the dibenzoxanone heterocyclic oxide, and the trifluoromethanesulfonic anhydride in a solvent under low temperature conditions to generate the compound of formula I. The beneficial technical effects of this invention are reflected in at least the following aspects: 1) The reaction conditions are very mild. This invention can be carried out efficiently under visible light (such as 427 nm LED) irradiation and a mild temperature of 35°C, avoiding the safety risks and equipment corrosion problems caused by strong acids and high temperatures in traditional mixed acid nitration methods, and also eliminating the need for strong oxidants such as peroxides. 2) It has broad functional group compatibility. This invention exhibits good tolerance to a variety of functional groups, including electron-donating groups (methyl, ethyl, isopropyl, tert-butyl, methoxy, ethoxy, methyl benzoate, etc.) and electron-withdrawing groups (chlorine, bromine, aldehyde, methyl formate, ketone, amide, etc.), especially showing good compatibility with halogen atoms such as chlorine and bromine, providing synthetic convenience for subsequent transition metal-catalyzed coupling reactions. 3) It can achieve¹ 5 High-efficiency labeling with N: This invention uses inexpensive and readily available Na¹ 5 Using NO2 as a nitrogen source, it is possible to construct¹ in one step under the same conditions. 5 N-labeled aromatic nitro compounds were obtained in good yields (38%–67%), avoiding the limitations of traditional¹ 5 The limitations of N-labeling, which requires de novo synthesis and stringent reaction conditions, provide a convenient synthetic tool for drug metabolism tracking and bioimaging applications. 4) The reaction mechanism is highly innovative. This invention effectively promotes the single-electron transfer process through modified photocatalysts (such as nitro-substituted 10-phenylphenthiazide), realizing the oxidative coupling of aryl radicals and nitrites, and providing a novel reaction pathway for photoredox catalytic aryl nitration. Attached Figure Description

[0021] Figure 1 The hydrogen nuclear magnetic spectrum of the compound prepared in Example 1.

[0022] Figure 2 Carbon NMR spectrum of the compound prepared in Example 1.

[0023] Figure 3 The hydrogen nuclear magnetic spectrum of the compound prepared in Example 29.

[0024] Figure 4 Carbon NMR spectrum of the compound prepared in Example 29. Detailed Implementation

[0025] The technical solutions of the embodiments of this application will be clearly and completely described below with reference to the accompanying drawings. All other embodiments obtained by those skilled in the art based on the embodiments of this application without inventive effort are within the scope of protection of this application.

[0026] Example 1 The first step involved the following steps: Trifluoromethanesulfonic anhydride (Tf₂O, 0.3 mmol, 84.6 mg, 1.5 equivalents) was added dropwise to an anhydrous dichloromethane (3.0 mL) solution of dibenzothiophene sulfoxide (DBTO, 0.24 mmol, 48.1 mg, 1.2 equivalents) and the aromatic base methyl p-methoxybenzoate (0.20 mmol, 1 equivalent, the standard for this reaction) at -78 °C, and the mixture was stirred at this temperature for 30 minutes. The reaction was then continued with stirring for 2 hours while maintaining the temperature. The reaction mixture was concentrated, and the resulting product was purified by silica gel column chromatography (eluent: 5% methanol / dichloromethane). The filtrate was concentrated to give a white product.

[0027] The second step involved the following steps: The aforementioned white product, sodium nitrite (0.6 mmol, 3 equivalents), and the photocatalyst 10-phenylphenthiazide (0.012 mmol, 6.0 mol%) were placed in a dry reaction tube equipped with a magnetic stirrer. Then, N,N-dimethylacetamide (3 mL) was added under an argon atmosphere. The reaction tube was screw-sealed and stirred at room temperature at a distance of 1.0 inch from an LED lamp (440 nm) for 13 hours. The reaction mixture was poured into water (20.0 mL) and extracted with ethyl acetate (3 × 15 mL). The organic phase was washed with saturated brine (15.0 mL), dried over anhydrous sodium sulfate, filtered, and concentrated. The residue was purified by silica gel column chromatography (petroleum ether / ethyl acetate = 20:1) to give the target aromatic nitro compound in 18% yield (based on aromatic base). Figure 1-2 The 1H and 1C NMR spectra of the target product.

[0028] .

[0029] Example 2 The operation is the same as in Example 1, except that in the second step, N,N-dimethylacetamide is replaced with N,N-dimethylformamide. The target aromatic nitro compound is obtained in 14% yield.

[0030] Example 3 The operation is the same as in Example 1, except that in the second step, N,N-dimethylacetamide is replaced with dimethyl sulfoxide. The target aromatic nitro compound is obtained in 5% yield.

[0031] Example 4 The operation is the same as in Example 1, except that in the second step, N,N-dimethylacetamide is replaced with acetone. The target aromatic nitro compound is obtained in 10% yield.

[0032] As can be seen from Examples 1-4, polar aprotic solvents are good solvents for this reaction, but overall, the yield is relatively low.

[0033] Example 5 The procedure was the same as in Example 1, except that in the second step, the N,N-dimethylacetamide was replaced with a mixed solution of N,N-dimethylacetamide and toluene (2.8 mL N,N-dimethylacetamide, 0.2 mL toluene). The target aromatic nitro compound was obtained in 19% yield.

[0034] Example 6 The procedure was the same as in Example 1, except that in the second step, the N,N-dimethylacetamide was replaced with a mixed solution of N,N-dimethylacetamide and acetone (2.5 mL N,N-dimethylacetamide, 0.5 mL acetone). The target aromatic nitro compound was obtained in 21% yield.

[0035] Example 7 The procedure was the same as in Example 1, except that in the second step, the N,N-dimethylacetamide was replaced with a mixed solution of N,N-dimethylacetamide and acetone (2.8 mL N,N-dimethylacetamide, 0.2 mL acetone). The target aromatic nitro compound was obtained in 25% yield.

[0036] Example 8 The procedure was the same as in Example 1, except that in the second step, the N,N-dimethylacetamide was replaced with a mixed solution of N,N-dimethylacetamide and toluene (2.9 mL N,N-dimethylacetamide, 0.1 mL acetone). The target aromatic nitro compound was obtained in 23% yield.

[0037] As shown in Examples 5-8, a single solvent system is insufficient to simultaneously achieve both substrate solubility and a suitable microenvironment for the photocatalytic radical process. Using a binary mixed solvent significantly improves reaction efficiency. Adding a small amount of toluene to N,N-dimethylacetamide only slightly increased the yield from 18% to 19%, a limited improvement. However, adding a small amount of acetone significantly improved the yield. Further optimization of the acetone volume fraction revealed that when the volume ratio of N,N-dimethylacetamide to acetone was 2.8:0.2 (acetone accounting for approximately 6.7%), the target product yield reached 25% (Example 7), an increase of approximately 39% compared to the 18% of the pure N,N-dimethylacetamide system (Example 1). Continuing to increase the acetone content (e.g., 2.5:0.5, acetone accounting for 16.7%) resulted in a decrease in yield to 21%, indicating that there is an optimal range for the mixed solvent ratio. The above results indicate that by introducing an appropriate amount of acetone to finely adjust the polarity and microenvironment of the polar aprotic solvent, the single-electron transfer process can be effectively promoted, and side reactions such as the protonation of aryl sulfonium salts can be suppressed, thereby improving the reaction yield. Therefore, using a mixed solvent system of N,N-dimethylacetamide and acetone, especially with a volume ratio of (2.5–2.9):(0.1–0.5), can provide a better reaction medium for photoredox catalytic aromatic nitration reactions, significantly improving the yield of the target product. Among these, a volume ratio of N,N-dimethylacetamide to acetone of 2.8:0.2 yields the best results.

[0038] Example 9 The operation is the same as in Example 7, except that in the second step, the wavelength of the LED light is adjusted from 440 nm to 456 nm. The target aromatic nitro compound is obtained in a yield of 23%.

[0039] Example 10 The operation is the same as in Example 7, except that in the second step, the wavelength of the LED light is adjusted from 440nm to 427nm. The target aromatic nitro compound is obtained, with a product content of 29%.

[0040] As can be seen from Examples 7, 9 and 10, the excitation efficiency of the photocatalyst is highly sensitive to the wavelength of the light source. Blue light at 427 nm is more compatible with the absorption spectrum of the photocatalyst (10-phenylphenthiazide or its derivative) in this system, which can drive the single electron transfer process more efficiently, thereby obtaining a higher reaction yield.

[0041] Example 11 The operation is the same as that in Example 10, except that in the second step, a photocatalyst is used. Replacing the 10-phenylphenthiazine yielded the target aromatic nitro compound in 33% yield.

[0042] Example 12 The operation is the same as that in Example 10, except that in the second step, a photocatalyst is used. Replacing the 10-phenylphenthiazine yielded the target aromatic nitro compound in 26% yield.

[0043] Example 13 The operation is the same as that in Example 10, except that in the second step, a photocatalyst is used. Replacing the 10-phenylphenthiazine yielded the target aromatic nitro compound in 56% yield.

[0044] Example 14 The operation is the same as that in Example 10, except that in the second step, a photocatalyst is used. Replacing the 10-phenylphenthiazine yielded the target aromatic nitro compound in 53% yield.

[0045] Example 15 The operation is the same as that in Example 10, except that in the second step, a photocatalyst is used. Replacing the 10-phenylphenthiazine yielded the target aromatic nitro compound in 49% yield.

[0046] Example 16 The operation is the same as that in Example 10, except that in the second step, a photocatalyst is used. Replacing the 10-phenylphenthiazine yielded the target aromatic nitro compound in 18% yield.

[0047] Example 17 The operation is the same as that in Example 10, except that in the second step, a photocatalyst is used. Replacing the 10-phenylphenthiazine yielded the target aromatic nitro compound in 26% yield.

[0048] Example 18 The operation is the same as that in Example 10, except that in the second step, a photocatalyst is used. Replacing the 10-phenylphenthiazine yielded the target aromatic nitro compound in 48% yield.

[0049] Example 19 The operation is the same as that in Example 10, except that in the second step, a photocatalyst is used. Replacing the 10-phenylphenthiazine yielded the target aromatic nitro compound in 45% yield.

[0050] Example 20 The operation is the same as that in Example 10, except that in the second step, a photocatalyst is used. Replacing the 10-phenylphenthiazine yielded the target aromatic nitro compound in 43% yield.

[0051] Example 21 The operation is the same as that in Example 10, except that in the second step, a photocatalyst is used. Replacing the 10-phenylphenthiazine yielded the target aromatic nitro compound in 46% yield.

[0052] Comparative Example 1 The operation is the same as that in Example 10, except that no photocatalyst is added in the second step, and the target aromatic nitro compound cannot be obtained in the end.

[0053] Comparative Example 2 The operation is the same as that in Example 10, except that in the second step, no LED light is used for irradiation, and the target aromatic nitro compound cannot be obtained in the end.

[0054] Referring to Examples 11-21, it was found that substituent modification of the phenyl group in the photocatalyst 10-phenylphenthiazine improved the catalytic effect by introducing electron-withdrawing groups, with the introduction of nitro groups significantly enhancing the catalyst's performance. More specifically, the catalyst... It exhibits optimal catalytic efficiency. As can be seen from Comparative Examples 1-2, catalyst and LED irradiation are necessary conditions for the reaction to occur.

[0055] Example 22 The operation is the same as that in Example 13, except that in the second step, a photocatalyst is used. Replace The target aromatic nitro compound was obtained in 50% yield.

[0056] As can be seen from Example 22, the reaction can also be achieved by replacing the sulfur atom in phenothiazine with a selenium atom, i.e., by using phenothiazine as a photocatalyst.

[0057] Example 23 The operation is the same as that in Example 13, except that in the second step, the amount of NaNO2 is increased from 3 equivalents to 3.5 equivalents to obtain the target aromatic nitro compound with a yield of 59%.

[0058] Example 24 The operation is the same as that in Example 23, except that in the second step, the reaction time is increased from 13 hours to 18 hours to obtain the target aromatic nitro compound with a yield of 62%.

[0059] Example 25 The operation is the same as that in Example 23, except that in the second step, the reaction time is increased from 13 hours to 24 hours to obtain the target aromatic nitro compound with a yield of 61%.

[0060] As can be seen from Examples 24-25, the maximum yield can be obtained with a reaction time of 18 hours.

[0061] Example 26 The operation is the same as that in Example 24, except that in the second step, the reaction temperature is adjusted from room temperature to 35°C to obtain the target aromatic nitro compound with a yield of 67%.

[0062] Example 27 The operation is the same as that in Example 24, except that in the second step, the reaction temperature is adjusted from room temperature to 40°C to obtain the target aromatic nitro compound with a yield of 60% [yz1].

[0063] As can be seen from Examples 13 and 26-27, the maximum yield can be obtained by setting the reaction temperature at 35°C.

[0064] Example 28 The operation is the same as that in Example 26, except that in the second step, the NaNO2 is replaced with an equivalent amount of KNO2 to obtain the target aromatic nitro compound, with a product content of 65%.

[0065] As can be seen from the above examples, Example 26 achieved the optimal yield. The optimal reaction conditions were determined to be: irradiation with a 427 nm wavelength LED lamp, a mixed solution of N,N-dimethylacetamide and acetone, a reaction time of 18 hours, and the use of 3.5 equivalents of NaNO2. The photocatalyst was... .

[0066] To further explore the universality of this reaction, we will further expand the range of aromatic substrates below.

[0067] Example 29 The first step involved the following steps: Trifluoromethanesulfonic anhydride (Tf₂O, 0.3 mmol, 84.6 mg, 1.5 equivalents) was added dropwise to an anhydrous dichloromethane (3.0 mL) solution of dibenzothiophene sulfoxide (DBTO, 0.24 mmol, 48.1 mg, 1.2 equivalents) and benzene (0.20 mmol, 1 equivalent, standard for this reaction) at -78 °C, and the mixture was stirred at this temperature for 30 minutes. The reaction was then continued with stirring for 2 hours while maintaining the temperature. The reaction mixture was concentrated, and the resulting product was purified by silica gel column chromatography (eluent: 5% methanol / dichloromethane). The filtrate was concentrated to give a white product.

[0068] The second step includes the following operations: adding the above white product, sodium nitrite (0.7 mmol, 3.5 equivalents), and a photocatalyst... (0.012 mmol, 6.0 mol%) was placed in a dry reaction tube equipped with a magnetic stirrer. A mixed solution of N,N-dimethylacetamide and acetone (2.8 mL N,N-dimethylacetamide, 0.2 mL acetone) was then added under an argon atmosphere. The reaction tube was screw-sealed and stirred at 35°C at a distance of 1.0 inch from an LED lamp (427 nm) for 18 hours. The reaction mixture was poured into water (20.0 mL) and extracted with ethyl acetate (3 × 15 mL). The organic phase was washed with saturated brine (15.0 mL), dried over anhydrous sodium sulfate, filtered, and concentrated. The residue was purified by silica gel column chromatography (petroleum ether / ethyl acetate = 20:1) to give the target product nitrobenzene in 50% yield (based on benzene). Figure 3-4 The 1H and 1C NMR spectra of the target product are shown below, and the overall reaction process is as follows.

[0069] .

[0070] Example 30 The operation is the same as that in Example 29, except that in the first step, the benzene is replaced with an equivalent amount of ethylbenzene to obtain the target aromatic nitro compound p-ethylnitrobenzene with a yield of 42%.

[0071] Example 31 The operation is the same as that in Example 29, except that in the first step, the benzene is replaced with an equivalent amount of cumene to obtain the target aromatic nitro compound p-isopropylnitrobenzene with a yield of 45%.

[0072] Example 32 The operation is the same as that in Example 29, except that in the first step, the benzene is replaced with an equivalent amount of tert-butylbenzene to obtain the target aromatic nitro compound p-tert-butylnitrobenzene with a yield of 58%.

[0073] Example 33 The operation is the same as that in Example 29, except that in the first step, the benzene is replaced with an equivalent amount of cyclohexylbenzene to obtain the target aromatic nitro compound p-cyclohexylnitrobenzene with a yield of 46%.

[0074] Example 34 The operation is the same as that in Example 29, except that in the first step, the benzene is replaced with an equivalent amount of phenylpropyl acetate to obtain the target aromatic nitro compound 4-phenylpropyl nitrate. The yield was 49%.

[0075] Example 35 The operation is the same as that in Example 29, except that in the first step, the benzene is replaced with an equivalent amount of benzene benzoate to obtain the target aromatic nitro compound 4-nitrobenzoate. The yield was 43%.

[0076] Example 36 The operation described is consistent with that in Example 29, except that in the first step, an equivalent amount is used. Replacing the benzene with the target aromatic nitro compound yields the desired aromatic nitro compound. The yield was 53%.

[0077] Example 37 The operation is the same as that in Example 29, except that in the first step, the benzene is replaced with an equivalent amount of m-xylene to obtain the target aromatic nitro compound 2,4-dimethylnitrobenzene with a yield of 46%.

[0078] Example 38 The operation is the same as that in Example 29, except that in the first step, the benzene is replaced with an equivalent amount of p-xylene to obtain the target aromatic nitro compound 2,5-dimethylnitrobenzene in a yield of 44%.

[0079] Example 39 The operation is the same as that in Example 29, except that in the first step, the benzene is replaced with an equivalent amount of o-xylene to obtain the target aromatic nitro compound 3,4-dimethylnitrobenzene with a yield of 39%.

[0080] Example 40 The operation is the same as that in Example 29, except that in the first step, the benzene is replaced with an equivalent amount of m-trimethylbenzene to obtain the target aromatic nitro compound 2,4,6-trimethylnitrobenzene in a yield of 40%.

[0081] Example 41 The operation is the same as that in Example 29, except that in the first step, the benzene is replaced with an equivalent amount of chlorobenzene to obtain the target aromatic nitro compound 4-nitrochlorobenzene, with a yield of 53%.

[0082] Example 42 The operation is the same as that in Example 29, except that in the first step, the benzene is replaced with an equivalent amount of bromobenzene to obtain the target aromatic nitro compound 4-nitrobromobenzene, with a yield of 52%.

[0083] Example 43 The operation is the same as that in Example 29, except that in the first step, the benzene is replaced with an equivalent amount of 4-methoxybenzaldehyde to obtain the target aromatic nitro compound 4-methoxy-3-nitrobenzaldehyde, with a yield of 65%.

[0084] Example 44 The operation is the same as that in Example 29, except that in the first step, the benzene is replaced with an equivalent amount of 4-methoxybenzophenone to obtain the target aromatic nitro compound 4-methoxy-2-nitrobenzophenone. The yield was 66%.

[0085] Example 45 The operation is the same as that in Example 29, except that in the first step, the benzene is replaced with an equivalent amount of methyl 2-methoxybenzoate to obtain the target aromatic nitro compound methyl 2-methoxy-5-nitrodibenzoate. The yield was 43%.

[0086] Example 46 The operation is the same as that in Example 29, except that in the first step, the benzene is replaced with an equivalent amount of methyl 2-ethoxybenzoate to obtain the target aromatic nitro compound methyl 2-ethoxy-5-nitrodibenzoate. The yield was 41%.

[0087] Example 47 The operation is the same as that in Example 29, except that in the first step, the benzene is replaced with an equivalent amount of 2-methoxybenzaldehyde to obtain the target aromatic nitro compound 2-methoxy-4-nitrobenzaldehyde. The yield was 50%.

[0088] Example 48 The operation is the same as that in Example 29, except that in the first step, the benzene is replaced with an equivalent amount of methyl 2,4-dimethylbenzoate to obtain the target aromatic nitro compound methyl 2,4-dimethyl-5-nitrobenzene. The yield was 49%.

[0089] Example 49 The operation is the same as that in Example 29, except that in the first step, the benzene is replaced with an equivalent amount of 2-acetyl-N-methylpyrrole to obtain the target aromatic nitro compound 2-acetyl-5-nitro-N-methylpyrrole. The yield was 55%.

[0090] Example 50 The operation is the same as that in Example 29, except that in the first step, the benzene is replaced with an equivalent amount of 2-ethyl-N-methylpyrrole to obtain the target aromatic nitro compound 2-ethyl-5-nitro-N-methylpyrrole. The yield was 50%.

[0091] As can be seen from Examples 29-50, the nitration method described in this invention has broad substrate applicability and excellent functional group compatibility. This method is applicable to a variety of aromatic substrates, specifically including: monosubstituted alkylbenzenes (such as toluene, ethylbenzene, cumene, tert-butylbenzene, and cyclohexylbenzene) can yield nitro products in moderate yields; ortho-, meta-, and para-substituted dimethylbenzenes, as well as trisubstituted aromatics, can also react smoothly; anisole substrates containing electron-donating groups (methoxy, ethoxy, methyl benzoate), including 1,4-disubstituted and 1,2-disubstituted anisoles, can all yield the target product in good yields; aromatics containing electron-withdrawing groups (chlorine, bromine, aldehyde, methyl formate, and ketone groups) also exhibit good tolerance, and the nitration products of chlorobenzene and bromobenzene can be further used in transition metal-catalyzed coupling reactions. The above reactions fully demonstrate the good adaptability of the reaction.

[0092] For the substrates and reactions involved in Examples 29-50, in the second step, a photocatalyst is used. Replace Both methods can yield the target aromatic nitro compound.

[0093] As can be seen from Example 22, the reaction can also be achieved by replacing the sulfur atom in phenothiazine with a selenium atom, i.e., by using phenothiazine as a photocatalyst.

[0094] Based on the good reactivity of this nitration reaction, we will explore its application in the synthesis of pharmaceutical intermediates to investigate its reactivity in complex reactant systems.

[0095] Example 51 The operation is the same as that in Example 29, except that in the first step, an equivalent amount of pharmaceutical intermediate is used. Replacing the benzene with the target aromatic nitro compound yields the desired aromatic nitro compound. The yield was 52%.

[0096] Example 52 The operation is the same as that in Example 29, except that in the first step, an equivalent amount of pharmaceutical intermediate is used. Replacing the benzene with the target aromatic nitro compound yields the desired aromatic nitro compound. The yield was 46%.

[0097] Example 53 The operation is the same as that in Example 29, except that in the first step, an equivalent amount of pharmaceutical intermediate is used. Replacing the benzene with the target aromatic nitro compound yields the desired aromatic nitro compound. The yield was 50%.

[0098] Example 54 The operation is the same as that in Example 29, except that in the first step, an equivalent amount of pharmaceutical intermediate is used. Replacing the benzene with the target aromatic nitro compound yields the desired aromatic nitro compound. The yield was 40%.

[0099] Example 55 The operation described herein is consistent with that in implementation 29, except that in the first step, an equivalent amount of pharmaceutical intermediate is used. Replacing the benzene with the target aromatic nitro compound yields the desired aromatic nitro compound. The yield was 68%.

[0100] See Examples 51-55. This nitration reaction can still proceed smoothly even with structurally complex drug intermediate molecules.

[0101] Nitrogen is an important element in drug molecules and is crucial for studying their metabolic pathways in organisms. It is commonly used in [the following context is missing from the original text]. 15 N is used as a marker element. Added to the traditional composition path 15 Nitrogen (N) is expensive and has strict requirements for the synthetic route. However, the nitration method disclosed in this patent uses nitrogen in the reaction... 15 N-labeled nitrites can be obtained quickly. 15 N-labeled molecules.

[0102] Example 56 The operation described is consistent with that in Example 29, except that in the second step, an equivalent amount is used.15 By replacing the sodium nitrite with N-labeled sodium nitrite, we can obtain... 15 N-labeled nitrobenzene, with a yield of 52%.

[0103] Example 57 The operation is the same as that in Example 29, except that the dibenzothiophene sulfoxide is replaced with an equivalent amount of dibenzoselenide-5-oxide (CAS classification number 30467-70-0) to obtain the target product nitrobenzene, with a product content of 45%.

[0104] Example 58 The operation is the same as that in Example 29, except that, through in-situ ion exchange, the corresponding products in which the OTf anion group in step one is replaced by the anions of BF4, PF6 and Cl can be obtained, and the yields of the target product nitrobenzene are 47%, 51% and 48%, respectively.

[0105] The above description is merely a preferred embodiment of the present invention and is illustrative rather than restrictive. Those skilled in the art will understand that many changes, modifications, and even equivalents can be made within the spirit and scope defined by the claims of the present invention, all of which will fall within the protection scope of the present invention.

Claims

1. A method for preparing aromatic nitro compounds, characterized in that, Includes the following steps: The compound of formula I, nitrite and photocatalyst are mixed in an organic solvent and subjected to a photo-oxidation-reduction catalytic reaction under LED light source to obtain the aromatic nitro compound shown in formula II. Wherein, a is 0, 1, 2 or 3, and when a is 2 or 3, R1 is the same or different substituents, and is independently selected from halogen, alkyl, alkoxy and acyl groups; Wherein, P is S or Se, and Q is selected from one of OTf, BF4, PF6 and Cl; Among them, It is one of the following: benzene ring, pyrrole ring, and N-methylpyrrole ring; The photocatalyst is a phenothiazine compound or a phenothiazine compound.

2. The method according to claim 1, characterized in that, R1 is selected from chlorine, bromine, methyl, ethyl, isopropyl, tert-butyl, cyclohexyl, methoxy, ethoxy, aldehyde, methoxycarbonyl, acetyl, benzoyl, 3-acetoxypropyl, benzoyloxymethyl, and... .

3. The method according to claim 1, characterized in that, The structure of the photocatalyst is as follows: Wherein, X is S or Se, b is 0, 1, or 2, and when b is 2, R2 is the same or different substituents; R2 is selected from ethyl, n-butyl, nitro, fluorine, and methoxycarbonyl, preferably, the photocatalyst is .

4. The method according to claim 1, characterized in that, The organic solvent is selected from one or more of N,N-dimethylacetamide, N,N-dimethylformamide, DMSO, acetone and toluene.

5. The method according to claim 4, characterized in that, The organic solvent is a mixture of N,N-dimethylacetamide and acetone, and the volume ratio of N,N-dimethylacetamide to acetone is (2.5~2.9):(0.1~0.5); preferably, the volume ratio of N,N-dimethylacetamide to acetone is 2.8:0.

2.

6. The method according to claim 1, characterized in that, The wavelength of the light source is 400-460 nm; preferably, the wavelength is 427 nm.

7. The method according to claim 1, characterized in that, The nitrite is sodium nitrite or potassium nitrite; the amount of the nitrite is 3.0-4.0 equivalents of the molar amount of the compound of Formula I; preferably, it is 3.5 equivalents.

8. The method according to claim 1, characterized in that, The reaction temperature in step two is 20-40℃; preferably, the reaction temperature in step two is 35℃.

9. The method according to claim 1, characterized in that, The reaction time for step two is 13-24 hours; preferably, the reaction time for step two is 18 hours.

10. The method according to claim 1, characterized in that, The nitrite is 15 N-labeled nitrites are used to prepare 15 N-labeled aromatic nitro compounds.

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