A method for nitrating aromatic compounds

Abstract

This application belongs to the technical field of organic synthesis, and specifically discloses a method for nitrating aromatic compounds. Using unactivated aromatic compounds as raw materials, hexafluoroisopropanol which is easy to recycle as a solvent, and nitrate as a nitrating reagent, a nitrated aromatic compound can be obtained under relatively simple and mild conditions. In particular, this application can also be applied to the synthesis of dinitroaromatic compounds and the late-stage nitration modification of various drug molecules. This application avoids the use of corrosive acids and additional catalysts, and directly uses inexpensive and readily available nitrate as a nitrating reagent to achieve green nitration of unactivated aromatic compounds, which has important application prospects in the field of synthesizing aromatic nitro compounds, and also provides a new method for large-scale industrial production of nitroarenes.

Description

Technical Field

[0001] This application belongs to the technical field of organic synthesis, and more specifically, relates to a nitration method for aromatic compounds. Background Art

[0002] The nitration reaction of aromatic compounds is an important type of organic reaction and has wide application value in the fields of medicine, pesticides, dyes, fragrances, explosives, etc. The traditional nitration reaction method is the mixed acid method, that is, under the catalysis of concentrated sulfuric acid, concentrated nitric acid is used as the nitrating reagent for the nitration reaction. This traditional synthesis method has a mature process and low cost, but there are also problems such as many side reactions, low selectivity, high requirements for reaction equipment, and serious environmental pollution. Therefore, it is of great research significance to develop and explore new, efficient and "green" nitration reactions for aromatic compounds.

[0003] In recent years, many new nitration methods have been developed (ChemistrySelect 2021, 6, 1337-1356). (1) Transition metal catalysis, such as the cross-coupling reaction of aryl halides and sodium nitrite catalyzed by transition metal Pd reported by the S.L. Buchwald research group to synthesize nitroarenes (J. Am. Chem. Soc. 2009, 131, 12898-12899), and the research group of Jiaoning used tert-butyl nitrite (TBN) as the nitrating reagent and Pd-catalyzed activation of the carbon-hydrogen bond of aromatic hydrocarbons to achieve nitration of aromatic hydrocarbons (ACS Catal. 2015, 5, 1956-1963). The research group of Zou Jianping reported the nitration of special heterocyclic aromatic hydrocarbons with N-directed groups catalyzed by transition metal Cu (Org. Chem. Front. 2021, 8, 5821-5830). Transition metal catalysis generally has the problems of using expensive transition metals or being limited to aromatic hydrocarbons with directing groups. (2) When using nitrate as the nitrating reagent, an equivalent amount or more of an oxidant or ionic liquid acid is required as a co-catalyst (ChemSusChem 2021, 14, 5340-5358, ChemistrySelect 2021, 6, 1337-1356). For example, when using iron(III) nitrate nonahydrate as the nitrating reagent and TEMPO as the co-oxidant, the nitration of indazole rings can be achieved (Org. Biomol. Chem., 2018, 16, 5113-5118). (3) When using only nitrate as the nitrating reagent without adding an additional co-catalyst, only the nitration of special substrates such as highly activated aromatic hydrocarbons can be achieved (J. Org. Chem. 2023, 88, 4649-4661). For example, Patent CN1854114A discloses using only nitrate as the nitrating reagent, but the method of this patent is limited to electron-rich aromatic hydrocarbons such as phenol, benzenediol, substituted phenol, and naphthol. (4) New organic nitrating reagents (Nat. Commun. 2019, 10, 3410, JACS Au. 2022, 2, 2152-2161) generally require additional steps to synthesize the organic nitrating reagent and additional catalysts, increasing the cost of the reaction system, so they are not very suitable for large-scale production. (5) Electrochemical methods, such as using tetrabutylammonium nitrite as the nitrating reagent to achieve the nitration of electron-rich aromatic hydrocarbons under electrochemical conditions (ChemSusChem, 2021, 14, 4936-4940). (6) Photocatalytic nitration to achieve the nitration modification of proteins under light irradiation (Angew. Chem. Int. Ed, 2021, 60, 13414-13422). (7) Biochemical nitration (Chem. Rev, 2018, 118, 1338-1408). (8) Flow chemistry nitration (Beilstein J. Org. Chem, 2014, 10, 405-424).

[0004] The above methods usually have relatively high catalyst costs, poor substrate generality, strong pollution or corrosiveness, or require additional steps to synthesize nitrating reagents, etc. Based on the existing nitration systems, it is still of great industrial application value to develop and explore new green and economical nitration synthesis methods. Summary of the Invention

[0005] Aiming at the defects of the prior art, the purpose of this application is to provide a nitration method for aromatic compounds, aiming to solve the problems of large substrate limitations, harsh reaction conditions, low atom economy, and high environmental pollution existing in the nitration methods of aromatic compounds in the prior art.

[0006] To achieve the above purpose, this application provides a nitration method for aromatic compounds. Using aromatic compounds as raw materials and nitrates as nitrating reagents, after a nitration reaction occurs in a solvent system containing hexafluoroisopropanol, the aromatic nitro compounds are obtained through purification and separation; the aromatic compounds are substituted or unsubstituted aromatic rings with 6 - 60 carbon atoms or substituted or unsubstituted heteroaromatic rings with 6 - 60 carbon atoms.

[0007] Preferably, for the substituted aromatic rings and substituted heteroaromatic rings, they are all mono - substituted or poly - substituted, and their substituents are independently selected from hydrogen, halogen, trifluoromethyl, trifluoromethoxy, nitro, cyano, phenolic hydroxyl, aldehyde group, carbonyl group, carboxyl group, sulfonic acid group, amino group, acetylamino group, C1 - C10 alkyl groups, C1 - C10 alkoxy groups, C6 - C30 aryloxy groups, C1 - C10 alkyl chains containing carbonyl groups, C6 - C30 aryl carbonyl groups, C1 - C10 ester groups, C6 - C30 aryl groups, and C6 - C30 heteroaromatic groups.

[0008] More preferably, the aromatic rings are selected from benzene, biphenyl, fluorene, naphthalene, anthracene, phenanthrene, pyrene, piperonal (1,2 - methylenedioxybenzene), and binaphthyl skeletons; the heteroaromatic rings are selected from furan, thiophene, pyridine, and indole.

[0009] Preferably, the substituted heteroaromatic rings are selected from furan, thiophene, pyridine, and indole with electron - withdrawing groups, and the electron - withdrawing groups are further preferably halogen, ester group, carbonyl group, aldehyde group, carboxyl group, sulfonic acid group, trifluoromethyl, trifluoromethoxy, nitro.

[0010] Preferably, the aromatic compounds are drug molecules with aromatic rings, amino acids with aromatic rings, or glycosides with aromatic rings, and the drug molecules with aromatic rings are selected from ibuprofen, adapalene, naproxen, nabumetone, estrone, estradiol, paracetamol, chrysin, diclofenac, pyriproxyfen, clofibrate, fenofibrate, bifendate, indomethacin, arbutin, and rofecoxib;

[0011] The amino acids with aromatic rings are selected from tyrosine and phenylalanine.

[0012] The glycosides with aromatic rings are selected from arbutin and lactoside.

[0013] Preferably, the nitrate is one or more of iron nitrate, bismuth nitrate, bismuth nitrate pentahydrate, iron nitrate nonahydrate, gallium nitrate, gallium nitrate hydrate, aluminum nitrate, aluminum nitrate nonahydrate, and ammonium cerium nitrate.

[0014] More preferably, the nitrate is bismuth nitrate pentahydrate, iron nitrate nonahydrate, gallium nitrate hydrate.

[0015] Generally speaking, compared with the prior art, the above technical solutions conceived by this application mainly have the following technical advantages:

[0016] (1) This application provides a new type of green and economic preparation method for nitration of aromatic compounds, which can realize the direct nitration of unactivated aromatic compounds by using nitrates such as iron nitrate and bismuth nitrate as nitrating agents in hexafluoroisopropanol solvent, as well as the late nitration modification of various drug molecules. Using simple aromatic hydrocarbons as raw materials, hexafluoroisopropanol as a solvent, and cheap and easily available nitrates as nitrating agents, after sufficient reaction under simple and mild conditions, the reaction solvent is removed, and the nitrated aromatic compounds are obtained by purification and separation. This preparation method has the advantages of high reaction efficiency, mild reaction conditions, cheap and easily available raw materials, simple, safe operation, wide substrate generality, easy separation of products, and high atomic and step economy of the reaction.

[0017] (2) This application provides a nitrating agent for the nitration reaction of aromatic compounds by using cheap nitrates containing crystal water such as iron nitrate, bismuth nitrate, and gallium nitrate. Compared with the nitration system using sulfuric acid as a catalyst and nitric acid as a nitrating agent in the traditional method, its advantages are that it does not use a strong acid system, does not require the use of an additional catalyst, has mild reaction conditions, fast reaction speed, simple and safe reaction operation. In addition, the prices of these inorganic salts are very low, they are easy to obtain, have stable chemical properties, and are easy to store. Using nitrates such as iron nitrate and bismuth nitrate as nitrating agents can be simply treated with nitric acid after the nitration reaction and then recycled as a nitrating agent, without generating waste, and the only by-product is water, which is a "green" reaction system.

[0018] (3) The nitration reaction of aromatic compounds provided by this application utilizes the characteristic of hexafluoroisopropanol as a solvent to enhance the inherent nitration ability of metal nitrates, and provides a simple and generally applicable C-H nitration. After the reaction, the solvent hexafluoroisopropanol can be recovered by simple distillation, and the recovered solvent can be reused for the nitration reaction of aromatic compounds multiple times.

[0019] (4) The aromatic compounds in the nitration preparation method provided by this application have a wide range of universality. They can be electron-rich aromatic compounds such as benzene, toluene, piperylene (1,2-methylenedioxybenzene), polysubstituted alkylbenzenes, polysubstituted alkoxybenzenes, phenol, substituted phenols, naphthalene, substituted naphthalenes, anthracene, substituted anthracenes, phenanthrene, substituted phenanthrenes, pyrene, substituted pyrenes, etc. The aromatic compounds can also be electron-deficient aromatic compounds such as chlorobenzene, bromobenzene, fluorobenzene, iodobenzene, dichlorobenzene, dibromobenzene, difluorobenzene, diiodobenzene, benzotrifluoride, nitrobenzene, p-toluenesulfonic acid, piperonylic acid, benzene with electron-withdrawing substituents, phenol with strong electron-withdrawing groups, naphthalene with electron-withdrawing substituents, anthracene with electron-withdrawing substituents, phenanthrene with electron-withdrawing substituents, pyrene with electron-withdrawing substituents, etc. The aromatic compounds can also be heterocyclic aromatic hydrocarbons with electron-withdrawing substituents such as 2-acetylfuran, 5-bromoindole, etc.

[0020] (5) The nitration preparation method of aromatic compounds provided by this application has a wide range of applications. It can be applied to the nitration modification of various drug molecules, such as the nitration of the aromatic ring in any one of the drug molecules such as ibuprofen, adapalene, naproxen, nabumetone, estrone, estradiol, paracetamol (p-acetaminophen), chrysin, diclofenac, pyriproxyfen, clofibrate, fenofibrate, bifendate, indomethacin, arbutin, rofecoxib, etc. It can also be applied to the nitration of amino acid molecules, such as the nitration of the aromatic ring in any one of the amino acid molecules such as tyrosine, phenylalanine, tyrosine derivatives, phenylalanine derivatives, etc. This nitration preparation method can also be used for the nitration of glycoside molecule derivatives, such as the nitration of the aromatic ring in any one of the arbutin and lactoside derivative molecules.

[0021] (6) The nitration preparation method of aromatic compounds provided by this application can prepare dinitrated aromatic compounds. When the substituents on the aromatic ring of the aromatic compound are electron-donating groups such as hydroxyl or alkoxy groups, dinitrated aromatic hydrocarbons can be obtained by controlling the reaction time and the equivalent of the nitrating reagent.

[0022] (7) The nitration preparation method of aromatic compounds provided by this application can be scaled up to reactions above the gram level. In large-scale production, the solvent hexafluoroisopropanol in the reaction system can be recovered by distillation, and the nitrate used can be simply treated with dilute nitric acid after the reaction and then recycled as a nitrating agent. No waste is generated, and the only by-product is water. It has an important application prospect in the field of synthesizing aromatic nitro compounds and also provides a new idea for the large-scale industrial production of nitroarenes.

[0023] (8) The nitration preparation method of aromatic compounds provided by this application can completely react most aromatic compounds and drug molecules under mild conditions through the screening of nitrating reagents and reaction conditions. In the preferred embodiments, the yields of the synthesized nitrated aromatic compounds are mostly above 90%, and the synthesis efficiency is relatively high. Detailed implementation manners

[0024] In order to make the objectives, technical solutions and advantages of this application clearer, the following further elaborates on this application in combination with embodiments. It should be understood that the specific embodiments described herein are only used to explain this application and are not used to limit this application.

[0025] This application provides a novel green and economical nitration method for aromatic compounds, which can also be applied to the late-stage nitration modification of various drug molecules. Using unactivated aromatic compounds as raw materials and nitrates as nitrating reagents, after a nitration reaction occurs in a solvent system containing hexafluoroisopropanol, the solvent is removed and the product is purified and separated to obtain mono-nitrated or multi-nitrated aromatic nitro compounds (aromatic compounds with nitro groups on the aromatic ring), that is, the nitration of C-H on the aromatic ring of aromatic compounds can be achieved.

[0026] The aromatic compounds described in this application can be substituted or unsubstituted aromatic rings with 6 to 60 carbon atoms, or substituted or unsubstituted heteroaromatic rings with 4 to 60 carbon atoms. Preferably, they are substituted or unsubstituted aromatic rings with 6 to 50 carbon atoms, substituted or unsubstituted heteroaromatic rings with 4 to 50 carbon atoms; more preferably, they are substituted or unsubstituted aromatic rings with 6 to 30 carbon atoms, substituted or unsubstituted heteroaromatic rings with 4 to 30 carbon atoms.

[0027] In some embodiments, the above-mentioned substituted aromatic rings and substituted heteroaromatic rings are all mono-substituted or multi-substituted, and their substituents are independently selected from hydrogen, halogen, trifluoromethyl, trifluoromethoxy, nitro, cyano, phenolic hydroxyl, aldehyde group, carbonyl group, carboxyl group, sulfonic acid group, amino group, acetylamino group, C1-C10 alkyl group, C1-C10 alkoxy group, C6-C30 aryloxy group, C1-C10 alkyl chain containing a carbonyl group, C6-C30 arylcarbonyl group, C1-C10 ester group, C6-C30 aryl group and C4-C30 heteroaromatic group.

[0028] In some embodiments, the aromatic rings are selected from benzene, biphenyl, fluorene, naphthalene, anthracene, phenanthrene, pyrene, piperylene (1,2-methylenedioxybenzene) and binaphthyl skeletons; the heteroaromatic rings are selected from furan, thiophene, pyridine and indole.

[0029] In some embodiments of this application, the aromatic compound is an aromatic hydrocarbon represented by Formula I, and its nitration reaction is as follows:

[0030]

[0031] R is one or more substituents, each independently selected from hydrogen, halogen, trifluoromethyl, trifluoromethoxy, nitro, cyano, phenolic hydroxyl, aldehyde, carboxyl, carbonyl, sulfonic acid group, amino, acetylamino, C1-C10 alkyl (preferably C1-C5 alkyl), C1-C10 alkoxy (preferably C1-C5 alkoxy), C6-C30 aryloxy (preferably C6-C18 aryloxy), C1-C10 alkyl chain containing carbonyl (preferably C1-C5 alkyl chain containing carbonyl), C6-C30 arylcarbonyl (preferably C6-C18 alkylarylcarbonyl), C1-C10 ester group (preferably C1-C5 ester group), and C6-C30 aryl (preferably C6-C18 aryl).

[0032] In some preferred embodiments, the aromatic compound is selected from benzene, toluene, piperylene (1,2-methylenedioxybenzene), polysubstituted benzene with C1-C5 alkyl, polysubstituted benzene with C1-C5 alkoxy, phenol, polysubstituted phenol with C1-C5 alkyl, naphthalene, polysubstituted naphthalene with C1-C5 alkyl, anthracene, substituted anthracene with C1-C5 alkyl, phenanthrene, substituted phenanthrene with C1-C5 alkyl, pyrene, substituted pyrene with C1-C5 alkyl and other electron-rich aromatic compounds, or it can also be electron-deficient aromatic compounds such as chlorobenzene, bromobenzene, fluorobenzene, iodobenzene, dichlorobenzene, dibromobenzene, difluorobenzene, diiodobenzene, trifluorotoluene, nitrobenzene, p-toluenesulfonic acid, piperic acid, benzene with electron-withdrawing substituents, phenol with electron-withdrawing group, naphthalene with electron-withdrawing substituents, anthracene with electron-withdrawing substituents, phenanthrene with electron-withdrawing substituents, pyrene with electron-withdrawing substituents. The electron-withdrawing group is selected from halogen, trifluoromethyl, trifluoromethoxy, nitro, cyano, aldehyde, carboxyl, sulfonic acid group, etc.

[0033] In some other embodiments, the aromatic compound is a substituted or unsubstituted heteroaromatic ring. The substituted heteroaromatic ring is selected from furan, thiophene, pyridine and indole with electron-withdrawing groups, and the electron-withdrawing groups include but are not limited to halogen, ester group, carbonyl, aldehyde, carboxyl, sulfonic acid group, trifluoromethyl, trifluoromethoxy, nitro. For example, in some embodiments, the heteroaromatic hydrocarbon is 2-acetylfuran, 5-bromoindole, etc.

[0034] Some embodiments confirm that for aromatic compounds containing complex functional groups, such as complex drug molecules with aromatic rings, amino acids and their derivatives, glycosides and their derivatives, etc., when using the nitration method of the present application as a substrate, nitration of the target position - aromatic ring can also be achieved, reflecting the universality of the nitration method of the present application. The drug molecules with aromatic rings include but are not limited to ibuprofen, adapalene, naproxen, nabumetone, estrone, estradiol, paracetamol (p-acetaminophenol), chrysin, diclofenac, pyriproxyfen, clofibrate, fenofibrate, bifendate, indomethacin, arbutin, and rofecoxib. The amino acids with aromatic rings include but are not limited to tyrosine, phenylalanine, tyrosine derivatives, and phenylalanine derivatives. The glycoside molecule derivatives with aromatic rings include but are not limited to arbutin and lactoside derivative molecules.

[0035] In some embodiments, when the substituent on the aromatic compound is an electron-donating group such as a hydroxyl group or an alkoxy group, dinitrated aromatics can be obtained by controlling the reaction time and the equivalent of the nitrating reagent. In particular, when the reaction activity of the aromatic compound substrate is high, other solvents such as DCE (dichloroethane), DCM (dichloromethane), etc. can be introduced in addition to the HFIP solvent to reduce the reaction substrate activity to obtain a mononitro compound, and the volume ratio of HFIP to other solvents is 1:(1 - 20). The solvents in the system can be recovered by distillation and reused in the nitration system of aromatic compounds. For aromatic compounds with high reaction activity, using HFIP as a single solvent tends to produce polynitro compounds.

[0036] In some embodiments, the nitrate is one or more of iron nitrate, bismuth nitrate, bismuth nitrate pentahydrate, iron nitrate nonahydrate, gallium nitrate, gallium nitrate hydrate, aluminum nitrate, aluminum nitrate nonahydrate, and ammonium cerium nitrate. The nitrate in the system can be reused after being treated with dilute nitric acid at the end of the reaction. In a preferred embodiment, the nitrate is bismuth nitrate pentahydrate, iron nitrate nonahydrate, or gallium nitrate hydrate.

[0037] In some embodiments, the molar ratio of the aromatic compound to the nitrate is 1:(0.33 - 1). The concentration of the aromatic compound in the reaction system is 0.25 - 0.5 M. The reaction temperature is 0°C - 120°C, preferably 25°C - 60°C, and the reaction time is 1 - 36 h, preferably 1 - 24 h. The reaction temperature and reaction time can be adjusted according to the type of substrate.

[0038] The nitration reaction of this application is a liquid-phase system, and the reaction operation is simple, including the following steps: adding a nitrating reagent and an aromatic compound in a corresponding molar ratio (0.33 - 1:1), and the solvent hexafluoroisopropanol (0.25 - 0.5 M) into a tube reactor, stirring and reacting at 0 °C to 120 °C for 1 - 36 hours. After the reaction, the solvent is removed by rotary evaporation, and after separation, the nitration product of the aromatic hydrocarbon compound is obtained.

[0039] The nitration reaction of the aromatic compound in this application can achieve production on a scale above the gram level. The solvent hexafluoroisopropanol in the reaction system can be recovered by distillation. The nitrate used can be simply treated with nitric acid after the reaction and then recycled as a nitrating agent, without generating waste. The only by-product is water.

[0040] Compared with nitric acid, metal nitrates or nitrites are easier to handle and have higher functional group tolerance. Under appropriate catalysts, they are often used as nitro sources in C(sp 2 )-H nitration reactions. However, in the nitration reaction of unactivated aromatic compounds in this application, metal salts such as iron nitrate and bismuth nitrate are directly used as nitrating reagents without additional additives and catalysts, unexpectedly achieving the purpose of green nitration synthesis.

[0041] In the traditional method, a nitration system using sulfuric acid as a catalyst and nitric acid as a nitrating reagent uses the acidity of concentrated sulfuric acid to dehydrate nitric acid to generate nitronium ions for electrophilic substitution reactions. While in this application, a nitrate containing cheap hydrated iron nitrate, bismuth nitrate, gallium nitrate, etc. is used as a nitrating reagent for the nitration reaction of aromatic compounds, mainly using the strong hydrogen bond action of the solvent hexafluoroisopropanol to enhance the nitration ability of the nitrate. Compared with the traditional concentrated acid reaction system, the advantages of the nitration reaction system in this application are that it does not use a strong acid system, does not require the use of additional catalysts, has mild reaction conditions, fast reaction speed, simple and safe reaction operation, wide substrate universality, and the only by-product is water, making it a "green" reaction system.

[0042] The present application provides a novel preparation method for the nitration of aromatic hydrocarbons in the green economy, which can achieve the direct nitration of unactivated aromatic compounds using nitrates such as iron nitrate and bismuth nitrate as nitrating reagents in hexafluoroisopropanol solvent, as well as the late-stage nitration modification of various drug molecules. This preparation method has the advantages of high reaction efficiency, mild reaction conditions, inexpensive and easily available raw materials, simple, safe, wide substrate generality, easy separation of products, and high atomic and step economy of the reaction. It avoids the use of corrosive acids and additional catalysts, and realizes the green nitration of unactivated aromatic compounds directly using inexpensive and easily available nitrates, having important application prospects in the field of synthesizing nitroaromatic hydrocarbons and providing a new method for large-scale industrial production of nitroaromatic hydrocarbons. In some embodiments, the specific experiments include the following steps: In a 10 ml reaction tube, add a magnetic stir bar, add the aromatic compound, the nitrating reagent nitrate, and the solvent hexafluoroisopropanol in the corresponding proportions, and seal the tube mouth with a stopper. The reaction mixture is stirred at 0 - 120 °C. The progress of the reaction is monitored by thin-layer chromatography (TLC). When there is no raw material remaining in the system, cool the reaction mixture to room temperature and remove the solvent under reduced pressure. Then purify the crude mixture by flash column chromatography to provide the nitration product. The eluent used in the column chromatography separation and purification step is a mixture of petroleum ether and ethyl acetate or dichloromethane and methanol. The volume ratio range of petroleum ether to ethyl acetate is 20:1 to 1:1, and the volume ratio range of dichloromethane to methanol is 20:1 to 1:4.

[0043] The following are examples:

[0044] Example 1

[0045] Add a magnetic stir bar, substrate 1a (79 mg, 0.5 mmol, 1.0 equivalent), HFIP (1.0 mL), and Fe(NO3)3·9H2O (202 mg, 0.5 mmol, 1.0 equivalent) into a 10 ml transparent glass reaction tube, seal the tube mouth with a stopper, and react at 100 °C for 12 hours. Cool the reaction mixture to room temperature and remove the solvent under reduced pressure. Then purify the crude mixture by flash column chromatography to provide the nitration product 2a (white solid, 95 mg, yield 94%). 1 H NMR (600 MHz, CDCl3) δ 8.13 - 8.07 (m, 2.2H), 7.84 (dd, J = 1.9, 7.8 Hz, 1H), 7.74 (dd, J = 1.7, 7.7 Hz, 1H), 7.71 - 7.66 (m, 2.2H), 7.49 - 7.40 (m, 2H). 1313C NMR (101 MHz, CDCl3) δ 146.40, 135.21, 133.32, 132.76, 130.11, 128.38, 125.72, 125.13, 114.59.

[0046] Examples 2 to 12

[0047] Examples 2 to 12 are the same as Example 1 in the preparation method of aromatic nitration. The only difference lies in the nitrating reagent nitrate and the reaction temperature used, resulting in different NMR yields of the products. The specific conditions and reaction yields are shown in Table 1 below:

[0048] Table 1 Screening of Nitrating Reagents

[0049] Example Nitrating reagent Equivalent of nitrating reagent Solvent Time (h) Temperature (°C) Yield (%) 2 Iron(III) nitrate nonahydrate 1.0 HFIP 12 100 99 3 Bismuth(III) nitrate pentahydrate 1.0 HFIP 12 100 93 4 Gallium(III) nitrate hydrate 1.0 HFIP 12 100 82 5 Aluminum(III) nitrate nonahydrate 1.0 HFIP 12 100 33 6 Copper(II) nitrate trihydrate 1.5 HFIP 12 100 39 7 Ammonium cerium(IV) nitrate 0.5 HFIP 12 100 22 8 Silver nitrate 3.0 HFIP 12 100 trace 9 Sodium nitrate 3.0 HFIP 12 100 trace 10 Potassium nitrate 3.0 HFIP 12 100 trace 11 Sodium nitrite 3.0 HFIP 12 100 trace 12 tert-Butyl nitrite 3.0 HFIP 12 100 trace

[0050] It can be seen from comparing with Example 1 that when using nitrate as the nitrating reagent, there are also significant differences in the yields of nitroarenes obtained with different nitrates in the solvent hexafluoroisopropanol (HFIP). Using nitrates such as iron(III) nitrate nonahydrate, bismuth(III) nitrate pentahydrate, and gallium(III) nitrate hydrate as nitrating reagents gives a better yield in the hexafluoroisopropanol solvent. Using nitrates such as aluminum(III) nitrate nonahydrate, copper(II) nitrate trihydrate, and ammonium cerium(IV) nitrate as nitrating reagents gives a medium yield in the hexafluoroisopropanol solvent. Using nitrates such as silver nitrate, sodium nitrate, potassium nitrate, sodium nitrite, and tert-butyl nitrite as nitrating reagents gives fewer nitrated products in the hexafluoroisopropanol solvent.

[0051] It can be seen from Examples 2 - 4 that using nitrates such as iron(III) nitrate nonahydrate, bismuth(III) nitrate pentahydrate, and gallium(III) nitrate hydrate as nitrating reagents can all give a better yield. In the following examples, iron(III) nitrate nonahydrate is selected as the nitrating reagent.

[0052] Examples 13 to 19

[0053] Examples 13 to 19 are the same as Example 1 in the preparation method of aromatic nitration. The only difference lies in the different equivalents of the nitrating reagent, reaction time, and reaction temperature, resulting in different yields of the products. The specific conditions and reaction yields are shown in Table 2 below:

[0054] Table 2 Screening of Equivalents of Nitrating Reagents

[0055] Example Nitrating reagent Equivalent of nitrating reagent Solvent Time (h) Temperature (°C) Yield (%) 13 Iron(III) nitrate nonahydrate 1.0 HFIP 12 60 54 14 Iron(III) nitrate nonahydrate 1.0 HFIP 24 60 77 15 Iron(III) nitrate nonahydrate 1.0 HFIP 36 60 94 16 Iron(III) nitrate nonahydrate 1.0 HFIP 12 80 79 17 Iron(III) nitrate nonahydrate 0.5 HFIP 12 100 79 18 Iron(III) nitrate nonahydrate 0.5 HFIP 24 100 94 19 Iron(III) nitrate nonahydrate 0.75 HFIP 12 100 91

[0056] Examples 20 to 31

[0057] Examples 20 to 31 are the same as Example 1 in the preparation method of aromatic nitration. The only difference lies in the different solvents used, resulting in different yields of the products. The specific conditions and reaction yields are shown in Table 3 below:

[0058] Table 3 Screening of Solvents for Nitration Reaction

[0059]

[0060] It can be seen from a comparison with Example 1 that when ferric nitrate nonahydrate is used as the nitrating reagent, using HFIP as the solvent results in a significant difference in yield compared to other solvents such as dichloromethane, toluene, ethyl acetate, 1,4-dioxane, DMF, acetonitrile, and methanol.

[0061] Example 32

[0062] A magnetic stir bar, substrate 1b (56 mg, 0.5 mmol, 1.0 equiv), HFIP (1.0 mL), and Fe(NO3)3·9H2O (202 mg, 0.5 mmol, 1.0 equiv) were added to a 10 mL transparent glass reaction tube. The tube was sealed with a stopper and reacted at 100 °C for 12 h. The reaction mixture was cooled to room temperature, and the solvent was removed under reduced pressure. Then the crude mixture was purified by flash column chromatography to give the nitration product 2b (colorless liquid, 69 mg, 87% yield). 1 H NMR (600 MHz, CDCl3) δ 8.18 (d, J = 8.5 Hz, 2.4H), 7.87 (d, J = 8.1 Hz, 1H), 7.63 - 7.47 (m, 4.4H), 7.42 (t, J = 7.7 Hz, 1H). 13 C NMR (101 MHz, CDCl3) δ 146.65, 141.51, 133.30, 132.02, 129.71, 127.72, 127.18, 125.70, 125.06.

[0063] Example 33

[0064] A magnetic stir bar, substrate 1c (49 mg, 0.5 mmol, 1.0 equiv), HFIP (1.0 mL), and Fe(NO3)3·9H2O (202 mg, 0.5 mmol, 1.0 equiv) were added to a 10 mL transparent glass reaction tube. The tube was sealed with a stopper and reacted at 100 °C for 12 h. The reaction mixture was cooled to room temperature, and the solvent was removed under reduced pressure. Then the crude mixture was purified by flash column chromatography to give the nitration product 2c (colorless liquid, 69 mg, 94% yield). 1 H NMR (600 MHz, CDCl3) δ 8.33 - 8.19 (m, 6.2H), 8.10 - 8.04 (m, 1H), 7.67 - 7.62 (m, 1H), 7.33 - 7.28 (m, 2H), 7.24 - 7.18 (m, 6.2H). 13CNMR(151MHz,CDCl3)δ166.42(d, 1 J CF =258.0Hz),135.69(d, 3 J CF =8.3Hz),126.47(d, 3 J CF =10.0Hz),126.31(d, 4 J CF =2.8Hz),124.69(d, 4 J CF =4.5Hz),118.60(d, 2 J CF =20.7Hz),116.56(d, 2 J CF =23.6Hz). 19 F NMR(565MHz,CDCl3)δ-102.00。

[0065] Example 34

[0066] A magnetic stir bar, substrate 1d (102 mg, 0.5 mmol, 1.0 equiv), HFIP (1.0 mL), and Fe(NO3)3·9H2O (202 mg, 0.5 mmol, 1.0 equiv) were added to a 10 mL clear glass reaction tube. The tube was sealed with a stopper and reacted at 100 °C for 12 hours. The reaction mixture was cooled to room temperature and the solvent was removed under reduced pressure. The crude mixture was then purified by flash column chromatography to afford the nitration product 2d (white solid, 123 mg, 99% yield). 1 H NMR(600MHz,CDCl3)δ8.03(dd,J=1.3,7.9Hz,1H),7.95 - 7.88(m,6.4H),7.84(dd,J=1.6,8.1Hz,1H),7.51 - 7.46(m,1H),7.28 - 7.24(m,1H). 13 C NMR(151MHz,CDCl3)δ153.1,147.8,141.99,138.76,133.49,129.16,125.52,124.94,102.82,86.31。

[0067] Example 35

[0068] A magnetic stir bar, substrate 1e (118 mg, 0.5 mmol, 1.0 equiv), HFIP (1.0 mL), and Fe(NO3)3·9H2O (202 mg, 0.5 mmol, 1.0 equiv) were added to a 10 mL transparent glass reaction tube. The tube was sealed with a stopper and reacted at 100 °C for 36 h. The reaction mixture was cooled to room temperature, and the solvent was removed under reduced pressure. Then, the crude mixture was purified by flash column chromatography to afford the nitration product 2e (white solid, 131 mg, 93% yield). 1 1H NMR (600 MHz, CDCl3) δ 7.95 (dd, J = 1.0, 1.9 Hz, 1H), 7.79 (d, J = 8.6 Hz, 1H), 7.65 - 7.61 (m, 1H). 13 13C NMR (151 MHz, CDCl3) δ 137.73, 131.63, 127.51, 126.91, 115.89.

[0069] Example 36

[0070] A magnetic stir bar, substrate 1f (73 mg, 0.5 mmol, 1.0 equiv), HFIP (1.0 mL), and Fe(NO3)3·9H2O (202 mg, 0.5 mmol, 1.0 equiv) were added to a 10 mL transparent glass reaction tube. The tube was sealed with a stopper and reacted at 100 °C for 24 h. The reaction mixture was cooled to room temperature, and the solvent was removed under reduced pressure. Then, the crude mixture was purified by flash column chromatography to afford the nitration product 2f (colorless liquid, 77 mg, 78% yield). 1 1H NMR (600 MHz, CDCl3) δ 7.88 (d, J = 8.8 Hz, 1H), 7.58 (d, J = 2.2 Hz, 1H), 7.40 (dd, J = 2.2, 8.7 Hz, 1H). 13 13C NMR (101 MHz, CDCl3) δ 139.46, 131.92, 128.66, 128.06, 126.89.

[0071] Example 37

[0072] A magnetic stir bar, substrate 1g (57 mg, 0.5 mmol, 1.0 equiv), HFIP (1.0 mL), and Fe(NO3)3·9H2O (202 mg, 0.5 mmol, 1.0 equiv) were added to a 10 mL transparent glass reaction tube. The tube was sealed with a stopper and reacted at 100 °C for 24 h. The reaction mixture was cooled to room temperature, and the solvent was removed under reduced pressure. Then, the crude mixture was purified by flash column chromatography to afford the nitration product 2g (colorless liquid, 69 mg, 87% yield). 11H NMR (600 MHz, CDCl3) δ 8.16 (td, J = 5.7, 9.1 Hz, 1H), 7.07 - 7.01 (m, 2H). 13 13C NMR (151 MHz, CDCl3) δ 165.85 (d, 1 J = 259.7 Hz, 3 J = 11.1 Hz), 156.93 (d, 1 J = 255.2 Hz, 3 J = 13.2 Hz), 128.39 (d, 3 J = 8.7 Hz, 4 J = 2.2 Hz), 112.32 (d, 2 J = 18.8 Hz, 4 J = 4.3 Hz), 106.68 (d, 2 J = 24.3 Hz, 4 J = 4.2 Hz). 19 19F NMR (565 MHz, CDCl3) δ -97.64, -110.99。

[0073] Example 38

[0074] A magnetic stir bar, substrate 1h (165 mg, 0.5 mmol, 1.0 equiv), HFIP (1.0 mL), and Fe(NO3)3·9H2O (202 mg, 0.5 mmol, 1.0 equiv) were added to a 10 mL transparent glass reaction tube. The tube was sealed with a stopper and reacted at 100 °C for 24 h. The reaction mixture was cooled to room temperature and the solvent was removed under reduced pressure. Then the crude mixture was purified by flash column chromatography to give the nitration product 2h (white solid, 163 mg, 87% yield). 1 1H NMR (600 MHz, CDCl3) δ 8.41 (d, J = 1.8 Hz, 1H), 7.81 (dd, J = 1.8, 8.5 Hz, 1H), 7.58 (d, J = 8.5 Hz, 1H). 13 13C NMR (151 MHz, CDCl3) δ 149.74, 138.30, 126.51, 100.39, 87.77。

[0075] Example 39

[0076] A magnetic stir bar, substrate 1i (40 mg, 0.5 mmol, 1.0 equiv), HFIP (1.0 mL), and Fe(NO3)3·9H2O (202 mg, 0.5 mmol, 1.0 equiv) were added to a 10 mL transparent glass reaction tube. The tube was sealed with a stopper and reacted at 60 °C for 12 h. The reaction mixture was cooled to room temperature and the solvent was removed under reduced pressure. Then the crude mixture was purified by flash column chromatography to give the nitration product 2i (colorless liquid, 60 mg, 98% yield). 1 H NMR (600 MHz, CDCl3) δ 8.19 (d, J = 8.7 Hz, 2H), 7.68 (t, J = 7.4 Hz, 1H), 7.52 (t, J = 8.0 Hz, 2H). 13 C NMR (151 MHz, CDCl3) δ 148.19, 134.66, 129.35, 123.46.

[0077] Example 40

[0078] A magnetic stir bar, substrate 1j (46 mg, 0.5 mmol, 1.0 equiv), HFIP (1.0 mL), and Fe(NO3)3·9H2O (202 mg, 0.5 mmol, 1.0 equiv) were added to a 10 mL transparent glass reaction tube. The tube was sealed with a stopper and reacted at 60 °C for 12 h. The reaction mixture was cooled to room temperature and the solvent was removed under reduced pressure. Then the crude mixture was purified by flash column chromatography to give the nitration product 2j (colorless liquid, 71 mg, 99% yield). 1 H NMR (600 MHz, CDCl3) δ 8.09 (d, J = 8.7 Hz, 2H), 7.94 (d, J = 8.3 Hz, 1.2H), 7.49 (t, J = 8.2 Hz, 1.2H), 7.33 (d, J = 5.0 Hz, 2H), 7.30 (d, J = 8.6 Hz, 2.4H). 13 C NMR (151 MHz, CDCl3) δ 146.07, 133.62, 133.09, 132.84, 129.89, 126.96, 124.69, 123.57, 21.67, 20.47.

[0079] Example 41

[0080] A magnetic stir bar, substrate 1k (53 mg, 0.5 mmol, 1.0 equiv), HFIP (1.0 mL), and Fe(NO3)3·9H2O (202 mg, 0.5 mmol, 1.0 equiv) were added to a 10 mL transparent glass reaction tube. The tube was sealed with a stopper and reacted at 60 °C for 12 h. The reaction mixture was cooled to room temperature, and the solvent was removed under reduced pressure. The crude mixture was then purified by flash column chromatography to afford the nitration product 2k (colorless liquid, 59 mg, 76% yield). Colorless liquid. 1 H NMR (600 MHz, CDCl3) δ 8.16 - 8.11 (m, 2.6H), 7.86 (dd, J = 1.4, 8.1 Hz, 1H), 7.52 (td, J = 1.4, 7.5 Hz, 1H), 7.36 (dd, J = 1.4, 7.7 Hz, 1H), 7.34 - 7.31 (m, 3.6H), 2.91 (q, J = 7.5 Hz, 2H), 2.76 (q, J = 7.6 Hz, 2.6H), 1.28 (td, J = 5.0, 7.6 Hz, 7H). 13 C NMR (151 MHz, CDCl3) δ 152.15, 139.05, 133.05, 131.28, 128.77, 126.90, 124.62, 123.76, 28.98, 26.25, 15.17, 15.03。

[0081] Example 42

[0082] A magnetic stir bar, substrate 1l (67 mg, 0.5 mmol, 1.0 equiv), HFIP (1.0 mL), and Fe(NO3)3·9H2O (202 mg, 0.5 mmol, 1.0 equiv) were added to a 10 mL transparent glass reaction tube. The tube was sealed with a stopper and reacted at 60 °C for 12 h. The reaction mixture was cooled to room temperature, and the solvent was removed under reduced pressure. The crude mixture was then purified by flash column chromatography to afford the nitration product 2l (colorless liquid, 79 mg, 88% yield). 1 H NMR (600 MHz, CDCl3) δ 8.20 - 8.14 (m, 7.2H), 7.59 - 7.53 (m, 8.2H), 7.49 - 7.44 (m, 1H), 7.35 - 7.29 (m, 2H), 1.43 (s, 9H), 1.39 (s, 32.4H). 13 C NMR (151 MHz, CDCl3) δ 158.99, 146.13, 130.88, 128.73, 126.97, 126.37, 124.00, 123.48, 35.53, 31.18, 30.80。

[0083] Example 43

[0084] A magnetic stir bar, substrate 1m (54 mg, 0.5 mmol, 1.0 equiv), HFIP (1.0 mL), and Fe(NO3)3·9H2O (202 mg, 0.5 mmol, 1.0 equiv) were added to a 10 mL transparent glass reaction tube. The tube was sealed with a stopper and reacted at room temperature (25 °C) for 18 hours. The reaction mixture was cooled to room temperature, and the solvent was removed under reduced pressure. Then, the crude mixture was purified by flash column chromatography to give the nitration product 2m (colorless liquid, 64 mg, 85% yield). 1 H NMR (400 MHz, CDCl3) δ 7.74 (s, 1H), 7.31 - 7.23 (d, J = 7.8 Hz, 1H), 7.18 (d, J = 7.8 Hz, 1H), 2.51 (s, 3H). 13 C NMR (101 MHz, CDCl3) δ 149.10, 137.14, 133.89, 132.60, 130.50, 124.92, 20.69, 20.01。

[0085] Example 44

[0086] A magnetic stir bar, substrate 1n (60 mg, 0.5 mmol, 1.0 equiv), HFIP (1.0 mL), and Fe(NO3)3·9H2O (202 mg, 0.5 mmol, 1.0 equiv) were added to a 10 mL transparent glass reaction tube. The tube was sealed with a stopper and reacted at room temperature (25 °C) for 18 hours. The reaction mixture was cooled to room temperature, and the solvent was removed under reduced pressure. Then, the crude mixture was purified by flash column chromatography to give the nitration product 2n (colorless liquid, 79 mg, 63% yield). 1 H NMR (600 MHz, CDCl3) δ 6.92 (s, 2H), 2.31 (s, 3H), 2.28 (s, 6H). 13 C NMR (151 MHz, CDCl3) δ 149.92, 140.43, 129.74, 129.57, 21.18, 17.68。

[0087] Example 45

[0088] A magnetic stir bar, substrate 1o (67 mg, 0.5 mmol, 1.0 equiv), HFIP (1.0 mL), and Fe(NO3)3·9H2O (202 mg, 0.5 mmol, 1.0 equiv) were added to a 10 mL transparent glass reaction tube. The tube was sealed with a stopper and reacted at room temperature (25 °C) for 18 h. The reaction mixture was cooled to room temperature and the solvent was removed under reduced pressure. The crude mixture was then purified by flash column chromatography to afford the nitration product 2o (white solid, 69 mg, 77% yield). 1 H NMR (600 MHz, CDCl3) δ 7.04 (s, 1H), 2.25 (s, 6H), 2.12 (s, 6H). 13 C NMR (151 MHz, CDCl3) δ 153.32, 135.44, 132.56, 124.50, 19.74, 14.02.

[0089] Example 46

[0090] A magnetic stir bar, substrate 1p (74 mg, 0.5 mmol, 1.0 equiv), HFIP (1.0 mL), and Fe(NO3)3·9H2O (202 mg, 0.5 mmol, 1.0 equiv) were added to a 10 mL transparent glass reaction tube. The tube was sealed with a stopper and reacted at room temperature (25 °C) for 18 h. The reaction mixture was concentrated under reduced pressure. The crude mixture was then purified by flash column chromatography to afford the nitration product 2p (white solid, 69 mg, 71% yield). 1 H NMR (600 MHz, CDCl3) δ 2.24 (s, 3H), 2.22 (s, 6H), 2.15 (s, 6H). 13 C NMR (151 MHz, CDCl3) δ 151.79, 137.03, 134.06, 123.71, 17.02, 16.55, 15.09.

[0091] Example 47

[0092] A magnetic stir bar, substrate 1q (47 mg, 0.5 mmol, 1.0 equiv), HFIP / DCE = 1:19 (1.0 mL), and Fe(NO3)3·9H2O (202 mg, 0.5 mmol, 1.0 equiv) were added to a 10 mL transparent glass reaction tube. The tube was sealed with a stopper and reacted at room temperature (25 °C) for 18 h. The reaction mixture was concentrated under reduced pressure. The crude mixture was then purified by flash column chromatography to afford the nitration product 2q (yellow solid, 50 mg, 72% yield). 11H NMR (600 MHz, CDCl3) δ 8.23 - 8.10 (m, 2H), 6.98 - 6.86 (m, 2H), 6.30 (s, 1H). 13 13C NMR (151 MHz, CDCl3) δ 161.66, 141.71, 126.42, 115.84。

[0093] Example 48

[0094] A magnetic stir bar, substrate 1q (47 mg, 0.5 mmol, 1.0 equiv), HFIP (1.0 mL), and Fe(NO3)3·9H2O (202 mg, 0.5 mmol, 1.0 equiv) were added to a 10 mL clear glass reaction tube. The tube was sealed with a stopper and reacted at room temperature (25 °C) for 18 h. The reaction mixture was concentrated under reduced pressure. The crude mixture was then purified by flash column chromatography to afford the nitration product 2q’ (white solid, 78 mg, 85% yield). 1 1H NMR (600 MHz, CDCl3) δ 11.02 (s, 1H), 9.07 (d, J = 2.8 Hz, 1H), 8.46 (dd, J = 2.7, 9.3 Hz, 1H), 7.34 (d, J = 9.2 Hz, 1H). 13 13C NMR (151 MHz, CDCl3) δ 159.19, 131.78, 122.03, 121.39。

[0095] Example 49

[0096] A magnetic stir bar, substrate 2q (70 mg, 0.5 mmol, 1.0 equiv), HFIP (1.0 mL), and Fe(NO3)3·9H2O (202 mg, 0.5 mmol, 1.0 equiv) were added to a 10 mL clear glass reaction tube. The tube was sealed with a stopper and reacted at room temperature (25 °C) for 12 h. The reaction mixture was concentrated under reduced pressure. The crude mixture was then purified by flash column chromatography to afford the nitration product 2q’ (white solid, 91 mg, 99% yield). 1 1H NMR (600 MHz, CDCl3) δ 11.02 (s, 1H), 9.07 (d, J = 2.8 Hz, 1H), 8.46 (dd, J = 2.7, 9.3 Hz, 1H), 7.34 (d, J = 9.2 Hz, 1H). 13 13C NMR (151 MHz, CDCl3) δ 159.19, 131.78, 122.03, 121.39。

[0097] Example 50

[0098] A magnetic stir bar, substrate 1r (54 mg, 0.5 mmol, 1.0 equiv), HFIP / DCE = 1:19 (1.0 mL), and Fe(NO3)3·9H2O (202 mg, 0.5 mmol, 1.0 equiv) were added to a 10 mL transparent glass reaction tube. The tube was sealed with a stopper and reacted at room temperature (25 °C) for 3 hours. The reaction mixture was concentrated under reduced pressure to remove the solvent. The crude mixture was then purified by flash column chromatography to afford the nitration product 2r (yellow solid, 66 mg, 86% yield). 1 H NMR (600 MHz, CDCl3) δ 10.42 (s, 1H), 7.87 (s, 1H), 7.38 (d, J = 7.7 Hz, 1H), 7.04 (d, J = 8.6 Hz, 1H), 2.33 (s, 3H). 13 C NMR (101 MHz, CDCl3) δ 153.22, 138.87, 133.26, 130.20, 124.45, 119.73, 20.35.

[0099] Example 51

[0100] A magnetic stir bar, substrate 1r' (54 mg, 0.5 mmol, 1.0 equiv), HFIP (1.0 mL), and Fe(NO3)3·9H2O (202 mg, 0.5 mmol, 1.0 equiv) were added to a 10 mL transparent glass reaction tube. The tube was sealed with a stopper and reacted at room temperature (25 °C) for 12 hours. The reaction mixture was concentrated under reduced pressure to remove the solvent. The crude mixture was then purified by flash column chromatography to afford the nitration product 2r' (yellow solid, 94 mg, 95% yield). 1 H NMR (600 MHz, CDCl3) δ 11.27 (s, 1H), 8.14 (s, 2H), 2.45 (s, 3H). 13 C NMR (151 MHz, CDCl3) δ 147.57, 137.39, 131.85, 129.55, 20.41.

[0101] Example 52

[0102] A magnetic stir bar, substrate 1s (62 mg, 0.5 mmol, 1.0 equiv), HFIP (1.0 mL), and Fe(NO3)3·9H2O (202 mg, 0.5 mmol, 1.0 equiv) were added to a 10 mL transparent glass reaction tube. The tube was sealed with a stopper and reacted at room temperature (25 °C) for 6 hours. The reaction mixture was concentrated under reduced pressure to remove the solvent. The crude mixture was then purified by flash column chromatography to afford the nitration product 2s (white solid, 83 mg, 99% yield). 11H NMR (600 MHz, CDCl3) δ 11.01 (s, 1H), 9.94 (s, 1H), 8.63 (s, 1H), 8.13 (d, J = 8.8 Hz, 1H), 7.31 (d, J = 8.7 Hz, 1H). 13 13C NMR (151 MHz, CDCl3) δ 188.68, 159.38, 136.46, 129.42, 128.68, 121.40。

[0103] Example 53

[0104] A magnetic stir bar, substrate 1t (81 mg, 0.5 mmol, 1.0 equiv), HFIP (1.0 mL), and Fe(NO3)3·9H2O (202 mg, 0.5 mmol, 1.0 equiv) were added to a 10 mL clear glass reaction tube. The tube was sealed with a stopper and reacted at room temperature (25 °C) for 12 h. The reaction mixture was concentrated under reduced pressure. The crude mixture was then purified by flash column chromatography to afford the nitration product 2t (pale yellow solid, 88 mg, 85% yield). 1 1H NMR (600 MHz, CDCl3) δ 10.79 (s, 1H), 8.43 (d, J = 1.1 Hz, 1H), 7.82 (dd, J = 2.3, 8.8 Hz, 1H), 7.31 (d, J = 8.8 Hz, 1H). 13 13C NMR (151 MHz, CDCl3) δ 157.30, 133.87 (q, 3 J = 3.3 Hz), 133.24, 123.26 (q, 3 J = 4.5 Hz), 122.20 (q, 2 J = 34.6 Hz). 123.05 (q, 1 J = 271.7 Hz), 121.36. 19 19F NMR (565 MHz, CDCl3) δ -62.35。

[0105] Example 54

[0106] A magnetic stir bar, substrate 1u (60 mg, 0.5 mmol, 1.0 equiv), HFIP (1.0 mL), and Fe(NO3)3·9H2O (202 mg, 0.5 mmol, 1.0 equiv) were added to a 10 mL clear glass reaction tube. The tube was sealed with a stopper and reacted at room temperature (25 °C) for 12 h. The reaction mixture was concentrated under reduced pressure. The crude mixture was then purified by flash column chromatography to afford the nitration product 2u (yellow solid, 81 mg, 99% yield). 11H NMR (600 MHz, CDCl3) δ 10.89 (s, 1H), 8.47 (d, J = 2.6 Hz, 1H), 7.82 (d, J = 8.6 Hz, 1H), 7.30 (d, J = 8.9 Hz, 1H). 13 13C NMR (151 MHz, CDCl3) δ 157.91, 139.70, 130.23, 121.88, 116.73, 104.62。

[0107] Example 55

[0108] A magnetic stir bar, substrate 1v (69 mg, 0.5 mmol, 1.0 equiv), HFIP (1.0 mL), and Fe(NO3)3·9H2O (202 mg, 0.5 mmol, 1.0 equiv) were added to a 10 mL clear glass reaction tube. The tube was sealed with a stopper and reacted at room temperature (25 °C) for 12 h. The reaction mixture was concentrated under reduced pressure to remove the solvent. The crude mixture was then purified by flash column chromatography to afford the nitration product 2v (yellow solid, 85 mg, 93% yield). 1 1H NMR (600 MHz, CD3OD) δ 8.80 (d, J = 3.1 Hz, 7H), 8.02 (dd, J = 3.1, 9.6 Hz, 9H), 6.68 (d, J = 9.6 Hz, 9H). 13 13C NMR (151 MHz, CD3OD) δ 172.22, 137.85, 132.53, 129.40, 126.90, 125.47。

[0109] Example 56

[0110] A magnetic stir bar, substrate 1w (54 mg, 0.5 mmol, 1.0 equiv), HFIP (1.0 mL), and Fe(NO3)3·9H2O (202 mg, 0.5 mmol, 1.0 equiv) were added to a 10 mL clear glass reaction tube. The tube was sealed with a stopper and reacted at room temperature (25 °C) for 12 h. The reaction mixture was concentrated under reduced pressure to remove the solvent. The crude mixture was then purified by flash column chromatography to afford the nitration product 2w (colorless liquid, 60 mg, 77% yield). 1 1H NMR (400 MHz, CDCl3) δ 8.30 - 8.12 (m, 2H), 7.01 - 6.84 (m, 2H), 3.91 (s, 3H). 13 13C NMR (151 MHz, CDCl3) δ 164.72, 141.67, 126.03, 114.13, 56.09。

[0111] Example 57

[0112] A magnetic stir bar, substrate 1x (69 mg, 0.5 mmol, 1.0 equiv), HFIP (1.0 mL), and Fe(NO3)3·9H2O (202 mg, 0.5 mmol, 1.0 equiv) were added to a 10 mL transparent glass reaction tube. The tube was sealed with a stopper and reacted at room temperature (25 °C) for 12 hours. The reaction mixture was concentrated under reduced pressure to remove the solvent. The crude mixture was then purified by flash column chromatography to afford the nitration product 2x (yellow solid, 83 mg, 91% yield). 1 H NMR (600 MHz, CDCl3) δ 7.39 (d, J = 3.2 Hz, 1H), 7.11 (dd, J = 3.1, 9.1 Hz, 1H), 7.03 (d, J = 9.1 Hz, 1H), 3.92 (s, 3H), 3.81 (s, 3H). 13 C NMR (151 MHz, CDCl3) δ 153.02, 147.53, 121.07, 115.28, 110.11, 57.25, 56.19。

[0113] Example 58

[0114] A magnetic stir bar, substrate 1y (63 mg, 0.5 mmol, 1.0 equiv), HFIP (1.0 mL), and Fe(NO3)3·9H2O (202 mg, 0.5 mmol, 1.0 equiv) were added to a 10 mL transparent glass reaction tube. The tube was sealed with a stopper and reacted at 60 °C for 12 hours. The reaction mixture was cooled to room temperature and concentrated under reduced pressure to remove the solvent. The crude mixture was then purified by flash column chromatography to afford the nitration product 2y (colorless liquid, 68 mg, 79% yield). 1 H NMR (600 MHz, CDCl3) δ 8.01 (d, J = 2.3 Hz, 1.2H), 7.71 (dd, J = 0.9, 2.1 Hz, 1H), 7.50 (dd, J = 2.3, 8.2 Hz, 1.2H), 7.44 (d, J = 8.2 Hz, 1H), 7.34 (ddt, J = 0.7, 2.1, 7.5 Hz, 1H), 7.32 (d, J = 8.2 Hz, 1.2H), 2.60 (s, 3.6H), 2.44 (d, J = 0.8 Hz, 3H). 13 C NMR (151 MHz, CDCl3) δ 138.43, 134.11, 133.99, 133.21, 132.60, 132.21, 131.65, 126.04, 124.89, 124.08, 20.86, 20.16。

[0115] Example 59

[0116] A magnetic stir bar, substrate 1z (131 mg, 0.5 mmol, 1.0 equiv), HFIP (1.0 mL), and Fe(NO3)3·9H2O (202 mg, 0.5 mmol, 1.0 equiv) were added to a 10 mL transparent glass reaction tube. The tube was sealed with a stopper and reacted at room temperature (25 °C) for 24 h. The reaction mixture was concentrated under reduced pressure to remove the solvent. The crude mixture was then purified by flash column chromatography to afford the nitration product 2z (yellow solid, 113 mg, 74% yield). 1 H NMR (600 MHz, CDCl3) δ 9.62 (s, 1H), 7.87 (dd, J = 0.9, 2.0 Hz, 1H), 7.73 (d, J = 8.5 Hz, 1H), 7.70 - 7.64 (m, 2H), 7.39 (dd, J = 2.1, 8.5 Hz, 1H), 7.23 (d, J = 7.9 Hz, 2H), 2.37 (s, 3H), 2.33 (s, 3H). 13 C NMR (151 MHz, CDCl3) δ 144.78, 137.40, 136.86, 135.79, 134.62, 131.40, 130.07, 127.32, 126.04, 121.74, 21.71, 20.60. HRMS m / z (ESI): calcd. for C 14 H 15 N2O4S [M + H] + : 307.0747, found: 307.07471.

[0117] Example 60

[0118] A magnetic stir bar, substrate 1aa (120 mg, 0.5 mmol, 1.0 equiv), HFIP (1.0 mL), and Fe(NO3)3·9H2O (202 mg, 0.5 mmol, 1.0 equiv) were added to a 10 mL transparent glass reaction tube. The tube was sealed with a stopper and reacted at 120 °C for 24 h. The reaction mixture was cooled to room temperature and concentrated under reduced pressure to remove the solvent. The crude mixture was then purified by flash column chromatography to afford the nitration product 2aa (colorless liquid, 82 mg, 57% yield). 1 H NMR (600 MHz, CDCl3) δ 8.56 (d, J = 2.7 Hz, 2.8H), 8.25 (dd, J = 2.7, 9.1 Hz, 2.8H), 8.18 (dq, J = 1.3, 2.6 Hz, 1H), 8.07 (dd, J = 2.5, 8.8 Hz, 1H), 7.87 (d, J = 8.8 Hz, 1H), 7.48 (dq, J = 1.5, 9.0 Hz, 2.8H). 1313C NMR (151 MHz, CDCl3) δ 152.35, 134.96, 129.80, 124.23, 122.76, 121.54, 121.16, 117.43, 116.66. 19 19F NMR (565 MHz, CDCl3) δ -57.36, -57.68. HRMS m / z (ESI): calcd. for C7H4BrF3NO3 [M+H] + : 285.9321, found: 285.93206。

[0119] Example 61

[0120] A magnetic stir bar, substrate 1bb (70 mg, 0.5 mmol, 1.0 equiv), HFIP (1.0 mL), and Fe(NO3)3·9H2O (202 mg, 0.5 mmol, 1.0 equiv) were added to a 10 mL clear glass reaction tube. The tube was sealed with a stopper and reacted at room temperature (25 °C) for 18 h. The reaction mixture was cooled to room temperature, the solvent was removed under reduced pressure, and the crude mixture was purified by flash column chromatography to give the nitration product 2bb (colorless liquid, 91 mg, 99% yield). 1 1H NMR (600 MHz, CDCl3) δ 7.87 (d, J = 11.1 Hz, 1H), 6.82 (d, J = 8.2 Hz, 1H), 3.96 (s, 3H), 2.62 (s, 3H). 13 13C NMR (151 MHz, CDCl3) δ 151.80 (d, 3 J = 10.5 Hz), 149.52 (d, 1 J = 248.7 Hz), 140.66 (d, 3 J = 7.0 Hz), 132.50 (d, 4 J = 3.7 Hz), 115.92 (d, 4 J = 1.9 Hz), 113.61 (d, 2 J = 22.6 Hz), 56.64, 21.50. 19 19F NMR (565 MHz, CDCl3) δ -135.44. HRMS m / z (ESI): calcd. for C8H9FNO3 [M+H] + : 186.0561, found: 186.05613。

[0121] Example 62

[0122] A magnetic stir bar, substrate 1cc (135 mg, 0.5 mmol, 1.0 equiv), HFIP (1.0 mL), and Fe(NO3)3·9H2O (202 mg, 0.5 mmol, 1.0 equiv) were added to a 10 mL transparent glass reaction tube. The tube was sealed with a stopper and reacted at room temperature (25 °C) for 12 hours. The reaction mixture was cooled to room temperature, the solvent was removed under reduced pressure, and the crude mixture was purified by flash column chromatography to give the nitration product 2cc (white solid, 127 mg, 81% yield). 1 1H NMR (600 MHz, CDCl3) δ 7.50 (d, J = 1.9 Hz, 1H), 7.49 (d, J = 1.9 Hz, 1H), 1.38 (s, 9H), 1.32 (s, 9H). 13 13C NMR (151 MHz, CDCl3) δ 153.98, 142.16, 128.78, 124.68, 114.47, 36.56, 35.33, 31.18, 30.97.

[0123] Example 63

[0124] A magnetic stir bar, substrate 1dd (103 mg, 0.5 mmol, 1.0 equiv), HFIP (1.0 mL), and Fe(NO3)3·9H2O (202 mg, 0.5 mmol, 1.0 equiv) were added to a 10 mL transparent glass reaction tube. The tube was sealed with a stopper and reacted at 100 °C for 18 hours. The reaction mixture was cooled to room temperature, the solvent was removed under reduced pressure, and the crude mixture was purified by flash column chromatography to give the nitration product 2dd (colorless liquid, 114 mg, 91% yield). 1 1H NMR (600 MHz, CDCl3) δ 7.79 (s, 1H), 7.74 (s, 1H), 2.41 (s, 3H). 13 13C NMR (151 MHz, CDCl3) δ 139.57, 137.32, 134.97, 127.60, 112.27, 19.89.

[0125] Example 64

[0126] A magnetic stir bar, substrate 1ee (102 mg, 0.5 mmol, 1.0 equiv), HFIP (1.0 mL), and Fe(NO3)3·9H2O (202 mg, 0.5 mmol, 1.0 equiv) were added to a 10 mL transparent glass reaction tube. The tube was sealed with a stopper and reacted at 120 °C for 24 hours. The reaction mixture was cooled to room temperature, the solvent was removed under reduced pressure, and the crude mixture was purified by flash column chromatography to give the nitration product 2ee (colorless liquid, 82 mg, 66% yield). 11H NMR (600 MHz, CDCl3) δ 7.57 (dd, J = 3.1, 7.2 Hz, 1H), 7.53 (dd, J = 3.1, 7.4 Hz, 1H), 4.00 (s, 3H). 13 13C NMR (151 MHz, CDCl3) δ 157.29 (d, 1 J = 252.4 Hz), 147.78 (d, 4 J = 3.8 Hz), 125.41, 125.32, 120.63 (d, 3 J = 9.8 Hz), 112.00 (d, 2 J = 27.0 Hz), 63.01. 19 19F NMR (565 MHz, CDCl3) δ -113.27. HRMS m / z (ESI): calcd. for C7H6BrFNO3 [M+H] + : 249.9510, found: 249.95102。

[0127] Example 65

[0128] A magnetic stir bar, substrate 1ff (82 mg, 0.5 mmol, 1.0 equiv), HFIP (1.0 mL), and Fe(NO3)3·9H2O (202 mg, 0.5 mmol, 1.0 equiv) were added to a 10 mL transparent glass reaction tube. The tube was sealed with a stopper and reacted at room temperature (25 °C) for 12 hours. The reaction mixture was concentrated under reduced pressure to remove the solvent. The crude mixture was then purified by flash column chromatography to afford the nitration product 2ff (pale yellow solid, 96 mg, 92% yield). 1 1H NMR (600 MHz, CDCl3) δ 7.49 (s, 1H), 6.72 (s, 1H), 6.16 (s, 2H), 2.46 (s, 3H). 13 13C NMR (151 MHz, CDCl3) δ 199.30, 152.81, 148.95, 140.16, 135.16, 106.24, 104.84, 103.78, 30.26。

[0129] Example 66

[0130] A magnetic stir bar, substrate 1gg (136 mg, 1 mmol, 1.0 equiv), TfOH (455 mg, 3.0 mmol), and Fe(NO3)3·9H2O (162 mg, 0.4 mmol, 0.4 equiv) were added to a 10 mL transparent glass reaction tube. The tube was sealed with a stopper and reacted at room temperature (25 °C) for 1 hour. The reaction mixture was concentrated under reduced pressure, and the crude mixture was purified by flash column chromatography to afford the nitration product 2gg (white solid, 163 mg, 92% yield). 1 H NMR (400 MHz, CDCl3) δ 8.80 (s, 3H), 8.37 (ddd, J = 1.1, 2.4, 8.2 Hz, 3H), 8.32 (dt, J = 1.4, 7.7 Hz, 3H), 7.87 (dd, J = 1.5, 7.8 Hz, 1H), 7.72 - 7.67 (m, 1H), 7.65 - 7.61 (m, 4H), 3.95 (s, 9H), 3.88 (s, 3H). 13 C NMR (101 MHz, CDCl3) δ 165.83, 164.95, 148.29, 135.28, 132.97, 131.89, 131.85, 129.88, 129.71, 127.39, 124.55, 123.93, 53.25, 52.80。

[0131] Example 67

[0132] A magnetic stir bar, substrate 1hh (146 mg, 1 mmol, 1.0 equiv), TfOH (455 mg, 3.0 mmol, 3.0 equiv), and Fe(NO3)3·9H2O (162 mg, 0.4 mmol, 0.4 equiv) were added to a 10 mL transparent glass reaction tube. The tube was sealed with a stopper and reacted at room temperature (25 °C) for 1 hour. The reaction mixture was concentrated under reduced pressure, and the crude mixture was purified by flash column chromatography to afford the nitration product 2hh (colorless liquid, 198 mg, 99% yield). 1 H NMR (600 MHz, CDCl3) δ 8.50 (s, 1H), 8.44 (d, J = 8.3 Hz, 1H), 7.98 (d, J = 7.8 Hz, 1H), 7.74 (t, J = 8.1 Hz, 1H). 13 C NMR (151 MHz, CDCl3) δ 148.42, 132.45 (q, 2 J = 34.2 Hz), 131.27 (q, J = 3.6 Hz), 130.50, 126.81, 122.99 (d, 1 J = 272.8 Hz), 120.98 (q, 3J = 3.9 Hz).

[0133] Example 68

[0134] A magnetic stir bar, substrate 1ii (225 mg, 1 mmol, 1.0 equiv), TfOH (455 mg, 3.0 mmol, 3.0 equiv), and Fe(NO3)3·9H2O (162 mg, 0.4 mmol, 0.4 equiv) were added to a 10 mL transparent glass reaction tube. The tube was sealed with a stopper and reacted at room temperature (25 °C) for 12 hours. The reaction mixture was concentrated under reduced pressure, and the crude mixture was purified by flash column chromatography to afford the nitration product 2ii (colorless liquid, 261 mg, 97% yield). 1 1H NMR (600 MHz, CDCl3) δ 8.11 (s, 1H), 7.92 (d, J = 8.4 Hz, 1H), 7.69 (d, J = 8.4 Hz, 1H). 13 13C NMR (151 MHz, CDCl3) δ 150.16, 136.28, 131.31 (q, 2 J = 34.7 Hz), 129.74 (q, 3 J = 3.5 Hz), 123.00 (q, 3 J = 3.9 Hz), 122.65 (q, 4 J = 273.0 Hz), 118.90. 19 19F NMR (565 MHz, CDCl3) δ -63.06.

[0135] Example 69

[0136] A magnetic stir bar, substrate 1jj (86 mg, 1 mmol, 1.0 equiv), TfOH (455 mg, 3.0 mmol, 3.0 equiv), and Fe(NO3)3·9H2O (162 mg, 0.4 mmol, 0.4 equiv) were added to a 10 mL transparent glass reaction tube. The tube was sealed with a stopper and reacted at room temperature (25 °C) for 12 hours. The reaction mixture was concentrated under reduced pressure, and the crude mixture was purified by flash column chromatography to afford the nitration product 2jj (white solid, 104 mg, 96% yield). 1 1H NMR (600 MHz, CD3OD) δ 8.30 (s, 1H), 7.92 (d, J = 7.9 Hz, 1H), 7.51 (d, J = 7.7 Hz, 1H), 2.56 (s, 3H). 13 13C NMR (151 MHz, CD3OD) δ 150.05, 136.65, 134.26, 131.04, 122.91, 19.97.

[0137] Example 70

[0138] A magnetic stir bar, substrate 1kk (100 mg, 0.5 mmol, 1.0 equiv), HFIP (1.0 mL), and Fe(NO3)3·9H2O (202 mg, 0.5 mmol, 1.0 equiv) were added to a 10 mL clear glass reaction tube. The tube was sealed with a stopper and reacted at room temperature (25 °C) for 12 h. The reaction mixture was concentrated under reduced pressure, and the crude mixture was purified by flash column chromatography to afford the nitration product 2kk (pale yellow solid, 82 mg, 67% yield). 1 1H NMR (600 MHz, CDCl3) δ 7.74 (d, J = 2.3 Hz, 1H), 7.28 (dd, J = 2.3, 8.6 Hz, 1H), 7.15 (d, J = 8.3 Hz, 2H), 6.93 - 6.89 (m, 3H), 2.38 (s, 3H), 2.34 (s, 3H). 13 13C NMR (151 MHz, CDCl3) δ 153.99, 148.81, 141.00, 134.89, 133.94, 133.28, 130.51, 125.73, 120.49, 118.89, 20.78, 20.48.

[0139] Example 71

[0140] A magnetic stir bar, substrate 1ll (105 mg, 0.5 mmol, 1.0 equiv), HFIP (1.0 mL), and Fe(NO3)3·9H2O (202 mg, 0.5 mmol, 1.0 equiv) were added to a 10 mL clear glass reaction tube. The tube was sealed with a stopper and reacted at 120 °C for 24 h. The reaction mixture was cooled to room temperature and concentrated under reduced pressure. The crude mixture was purified by flash column chromatography to afford the nitration product 2ll (white solid, 97 mg, 74% yield). 1 1H NMR (600 MHz, CDCl3) δ 8.35 (d, J = 1.8 Hz, 1H), 7.94 (dd, J = 1.8, 7.9 Hz, 1H), 7.73 - 7.67 (m, 2H), 7.48 (d, J = 7.9 Hz, 1H), 7.32 (d, J = 7.9 Hz, 2H), 2.69 (s, 3H), 2.46 (s, 3H). 13 13C NMR (151 MHz, CDCl3) δ 193.93, 149.09, 144.28, 137.76, 137.06, 133.98, 133.84, 133.13, 130.30, 129.49, 126.25, 21.87, 20.74. HRMS m / z (ESI): calcd. for C15 H 14 NO3[M+H] + : 256.0968, found: 256.09673。

[0141] Example 72

[0142] A magnetic stir bar, substrate 1mm (77 mg, 0.5 mmol, 1.0 eq), HFIP (1.0 mL), and Fe(NO3)3·9H2O (202 mg, 0.5 mmol, 1.0 eq) were added to a 10 mL clear glass reaction tube. The tube was sealed with a stopper and reacted at 60 °C for 12 hours. The reaction mixture was cooled to room temperature and the solvent was removed under reduced pressure. Then, the crude mixture was purified by flash column chromatography to give the nitration product 2mm (white solid, 98 mg, 98% yield). 1 H NMR (600 MHz, CDCl3) δ 8.35 - 8.28 (m, 3.2H), 7.88 (dd, J = 1.3, 8.1 Hz, 1H), 7.78 - 7.74 (m, 3.2H), 7.66 (dt, J = 1.3, 6.1 Hz, 3.2H), 7.64 (dd, J = 1.3, 7.6 Hz, 1H), 7.56 - 7.51 (m, 4H), 7.50 - 7.43 (m, 5.8H), 7.37 - 7.35 (m, 2H). 13 C NMR (151 MHz, CDCl3) δ 149.80, 148.10, 147.56, 139.22, 136.81, 132.79, 132.45, 129.67, 129.44, 129.18, 128.72, 128.67, 128.39, 128.28, 127.88, 124.59, 124.56。

[0143] Example 73

[0144] A magnetic stir bar, substrate 1nn (156 mg, 0.5 mmol, 1.0 eq), HFIP (1.0 mL), and Fe(NO3)3·9H2O (202 mg, 0.5 mmol, 1.0 eq) were added to a 10 mL clear glass reaction tube. The tube was sealed with a stopper and reacted at 120 °C for 24 hours. The reaction mixture was cooled to room temperature and the solvent was removed under reduced pressure. Then, the crude mixture was purified by flash column chromatography to give the nitration product 2nn (white solid, 176 mg, 99% yield). 11H NMR (600 MHz, CDCl3) δ 8.03 (d, J = 2.0 Hz, 1H), 7.76 (dd, J = 2.0, 8.2 Hz, 1H), 7.58 - 7.53 (m, 2H), 7.29 (d, J = 8.2 Hz, 1H), 7.18 - 7.11 (m, 2H). 13 13C NMR (151 MHz, CDCl3) δ 149.38, 135.71, 135.43, 134.27, 133.17, 132.17, 129.55, 127.42, 123.21, 121.98. HRMS m / z (ESI): calcd. for C 12 10H8Br2NO2 [M + H] + : 355.8916, found: 355.89158。

[0145] Example 74

[0146] A magnetic stir bar, substrate 1oo (64 mg, 0.5 mmol, 1.0 equiv), HFIP (1.0 mL), and Fe(NO3)3·9H2O (202 mg, 0.5 mmol, 1.0 equiv) were added to a 10 mL clear glass reaction tube. The tube was sealed with a stopper and reacted at room temperature (25 °C) for 18 h. The reaction mixture was concentrated under reduced pressure to remove the solvent. The crude mixture was then purified by flash column chromatography to afford the nitration product 2oo (yellow solid, 86 mg, 99% yield). 1 1H NMR (600 MHz, CDCl3) δ 8.56 (d, J = 8.7 Hz, 1H), 8.22 (dd, J = 1.2, 7.6 Hz, 1H), 8.11 (d, J = 8.0 Hz, 1H), 7.95 (d, J = 9.5 Hz, 1H), 7.71 (ddd, J = 1.3, 6.9, 8.6 Hz, 1H), 7.62 (ddd, J = 1.1, 6.8, 8.1 Hz, 1H), 7.53 (t, J = 7.9 Hz, 1H). 13 13C NMR (151 MHz, CDCl3) δ 134.78, 134.45, 129.56, 128.72, 127.46, 125.23, 124.24, 124.12, 123.22。

[0147] Example 75

[0148] A magnetic stir bar, substrate 1pp (71 mg, 0.5 mmol, 1.0 equiv), HFIP (1.0 mL), and Fe(NO3)3·9H2O (202 mg, 0.5 mmol, 1.0 equiv) were added to a 10 mL transparent glass reaction tube. The tube was sealed with a stopper and reacted at room temperature (25 °C) for 12 h. The reaction mixture was concentrated under reduced pressure to remove the solvent. The crude mixture was then purified by flash column chromatography to afford the nitration product 2pp (pale yellow solid, 73 mg, 78% yield). 1 H NMR (600 MHz, CDCl3) δ 8.60 (d, J = 8.7 Hz, 1H), 8.12 (d, J = 7.8 Hz, 1H), 8.08 (d, J = 8.5 Hz, 1H), 7.71 (ddd, J = 1.3, 6.9, 8.5 Hz, 1H), 7.64 (ddd, J = 1.3, 6.9, 8.3 Hz, 1H), 7.37 (d, J = 7.9 Hz, 1H), 2.77 (s, 3H). 13 C NMR (151 MHz, CDCl3) δ 142.37, 133.13, 128.96, 127.17, 125.18, 125.02, 124.72, 123.86, 123.68, 20.25。

[0149] Example 76

[0150] A magnetic stir bar, substrate 1qq (79 mg, 0.5 mmol, 1.0 equiv), (HFIP:DCE = 1:9) (1.0 mL), and Fe(NO3)3·9H2O (202 mg, 0.5 mmol, 1.0 equiv) were added to a 10 mL transparent glass reaction tube. The tube was sealed with a stopper and reacted at room temperature (25 °C) for 12 h. The reaction mixture was concentrated under reduced pressure to remove the solvent. The crude mixture was then purified by flash column chromatography to afford the nitration product 2qq (pale yellow solid, 95 mg, 94% yield). 1 H NMR (600 MHz, CDCl3) δ 8.77 (d, J = 8.8 Hz, 1H), 8.38 (d, J = 8.7 Hz, 1H), 8.35 (d, J = 8.5 Hz, 1H), 7.75 - 7.70 (m, 1H), 7.58 (t, J = 7.7 Hz, 1H), 6.79 (d, J = 8.7 Hz, 1H), 4.09 (s, 3H). 13 C NMR (101 MHz, CDCl3) δ 160.69, 139.25, 130.15, 127.33, 126.93, 126.64, 125.66, 123.54, 122.86, 101.98, 56.38。

[0151] Example 77

[0152] A magnetic stir bar, substrate 1qq’ (79 mg, 0.5 mmol, 1.0 equiv), HFIP (1.0 mL), and Fe(NO3)3·9H2O (202 mg, 0.5 mmol, 1.0 equiv) were added to a 10 mL transparent glass reaction tube. The tube was sealed with a stopper and reacted at room temperature (25 °C) for 12 h. The reaction mixture was concentrated under reduced pressure to remove the solvent. The crude mixture was then purified by flash column chromatography to afford the nitration product 2qq’ (yellow solid, 102 mg, 82% yield). 1 H NMR (600 MHz, CDCl3) δ 8.81 (s, 1H), 8.71 (d, J = 8.7 Hz, 1H), 8.48 (d, J = 8.5 Hz, 1H), 7.93 (ddd, J = 1.3, 6.9, 8.6 Hz, 1H), 7.84 - 7.75 (m, 1H), 4.22 (s, 3H). 13 C NMR (151 MHz, CDCl3) δ 156.23, 132.93, 129.81, 129.12, 128.15, 125.08, 124.18, 120.91, 64.45. HRMS m / z (ESI): calcd. for C 11 H9N2O5 [M+H] + : 249.0506, found: 249.05060.

[0153] Example 78

[0154] A magnetic stir bar, substrate 1rr (104 mg, 0.5 mmol, 1.0 equiv), HFIP (1.0 mL), and Fe(NO3)3·9H2O (202 mg, 0.5 mmol, 1.0 equiv) were added to a 10 mL transparent glass reaction tube. The tube was sealed with a stopper and reacted at room temperature (25 °C) for 24 h. The reaction mixture was concentrated under reduced pressure to remove the solvent. The crude mixture was then purified by flash column chromatography to afford the nitration product 2rr (light yellow solid, 101 mg, 80% yield). 11H NMR (600 MHz, CDCl3) δ 8.61 (d, J = 8.6 Hz, 1H), 8.55 (d, J = 8.0 Hz, 5.5H), 8.47 (d, J = 8.8 Hz, 1H), 8.40 (d, J = 7.5 Hz, 5.5H), 8.23 (d, J = 7.5 Hz, 1H), 8.05 (d, J = 8.2 Hz, 5.5H), 7.94 (dd, J = 1.0, 7.5 Hz, 1H), 7.89 (d, J = 8.2 Hz, 5.5H), 7.81 - 7.71 (m, 11H), 7.69 - 7.63 (m, 1H), 7.54 (dd, J = 7.5, 8.8 Hz, 1H). 13 13C NMR (151 MHz, CDCl3) δ 146.6, 133.69, 132.76, 131.81, 130.26, 130.06, 129.55, 128.93, 128.59, 128.23, 126.15, 124.48, 123.90, 123.71。

[0155] Example 79

[0156] A magnetic stir bar, substrate 1ss (143 mg, 0.5 mmol, 1.0 equiv), HFIP (1.0 mL), and Fe(NO3)3·9H2O (202 mg, 0.5 mmol, 1.0 equiv) were added to a 10 mL clear glass reaction tube. The tube was sealed with a stopper and reacted at room temperature (25 °C) for 18 hours. The reaction mixture was concentrated under reduced pressure to remove the solvent. The crude mixture was then purified by flash column chromatography to afford the nitration product 2ss (yellow solid, 152 mg, 92% yield). 1 1H NMR (600 MHz, CDCl3) δ 8.34 (dd, J = 1.2, 8.7 Hz, 1H), 8.11 (dd, J = 1.2, 7.5 Hz, 1H), 8.04 (d, J = 8.2 Hz, 1H), 7.82 (d, J = 8.2 Hz, 1H), 7.48 (dd, J = 7.5, 8.7 Hz, 1H). 13 13C NMR (151 MHz, CDCl3) δ 137.18, 133.85, 129.81, 129.32, 128.48, 126.21, 123.61, 122.95, 121.02. HRMS m / z (ESI): calcd. for C 10 H6Br2NO2 [M + H] + : 329.8760, found: 329.87607。

[0157] Example 80

[0158] A magnetic stir bar, substrate 1tt (78 mg, 0.5 mmol, 1.0 equiv), HFIP (1.0 mL), and Fe(NO3)3·9H2O (202 mg, 0.5 mmol, 1.0 equiv) were added to a 10 mL transparent glass reaction tube. The tube was sealed with a stopper and reacted at room temperature (25 °C) for 12 hours. The reaction mixture was concentrated under reduced pressure to remove the solvent. The crude mixture was then purified by flash column chromatography to afford the nitration product 2tt (pale yellow solid, 89 mg, 89% yield). 2tt 1 H NMR (600 MHz, CDCl3) δ 10.16 (s, 1H), 8.17 (d, J = 8.1 Hz, 3H), 8.14 (d, J = 7.2 Hz, 1H), 7.76 (s, 1H), 7.67 (t, J = 7.9 Hz, 1H). 13 C NMR (151 MHz, CDCl3) δ 190.06, 148.07, 135.06, 135.05, 134.26, 134.04, 132.97, 126.76, 126.06, 125.68, 120.90。

[0159] Example 81

[0160] A magnetic stir bar, substrate 1uu (89 mg, 0.5 mmol, 1.0 equiv), (HFIP:DCE = 1:9) (1.0 mL), and Fe(NO3)3·9H2O (202 mg, 0.5 mmol, 1.0 equiv) were added to a 10 mL transparent glass reaction tube. The tube was sealed with a stopper and reacted at room temperature (25 °C) for 12 hours. The reaction mixture was concentrated under reduced pressure to remove the solvent. The crude mixture was then purified by flash column chromatography to afford the nitration product 2uu (pale yellow solid, 89 mg, 80% yield). 1 H NMR (600 MHz, CDCl3) δ 8.60 (s, 1H), 8.05 (d, J = 8.5 Hz, 2H), 7.94 (d, J = 8.9 Hz, 2H), 7.67 - 7.61 (m, 2H), 7.55 (t, J = 7.6 Hz, 2H). 13 C NMR (151 MHz, CDCl3) δ 130.94, 130.51, 129.02, 128.52, 126.35, 122.80, 121.53。

[0161] Example 82

[0162] A magnetic stir bar, substrate 1vv (89 mg, 0.5 mmol, 1.0 equiv), (HFIP:DCE = 1:9) (1.0 mL), and Fe(NO3)3·9H2O (202 mg, 0.5 mmol, 1.0 equiv) were added to a 10 mL clear glass reaction tube. The tube was sealed with a stopper and reacted at room temperature (25 °C) for 12 h. The reaction mixture was concentrated under reduced pressure to remove the solvent. The crude mixture was then purified by flash column chromatography to afford the nitration product 2vv (pale yellow solid, 80 mg, 71% yield). 1 H NMR (600 MHz, CDCl3) δ 9.51 (d, J = 1.9 Hz, 1H), 8.91 (J = 4.2 Hz, 1H), 8.73 - 8.69 (m, 7.6H), 8.65 (d, J = 8.4 Hz, 7.6H), 8.51 - 8.47 (m, 7.6H), 8.43 (s, 7.6H), 8.34 (dd, J = 2.2, 8.7 Hz, 1H), 8.27 (d, J = 9.3 Hz, 1H), 8.19 - 8.16 (m, 1H), 7.97 (d, J = 7.9 Hz, 7.6H), 7.95 - 7.89 (m, 3H), 7.83 - 7.79 (m, 7.6H), 7.78 - 7.72 (m, 15.2H), 7.72 - 7.66 (m, 8.6H).

[0163] Example 83

[0164] A magnetic stir bar, substrate 1ww (137 mg, 0.5 mmol, 1.0 equiv), (HFIP:DCE = 1:9) (1.0 mL), and Fe(NO3)3·9H2O (202 mg, 0.5 mmol, 1.0 equiv) were added to a 10 mL clear glass reaction tube. The tube was sealed with a stopper and reacted at 60 °C for 12 h. The reaction mixture was cooled to room temperature and concentrated under reduced pressure to remove the solvent. The crude mixture was then purified by flash column chromatography to afford the nitration product 2ww (pale yellow solid, 137 mg, 86% yield). 1 H NMR (600 MHz, CDCl3) δ 8.31 - 8.24 (m, 2H), 7.79 (d, J = 8.2 Hz, 1H), 7.66 (d, J = 8.1 Hz, 1H), 7.63 (d, J = 1.8 Hz, 1H), 7.54 (dd, J = 1.8, 8.1 Hz, 1H), 1.53 (s, 6H). 1313C NMR (151 MHz, CDCl3) δ 157.08, 154.39, 147.58, 144.74, 135.96, 131.02, 126.74, 123.80, 123.69, 122.88, 120.41, 118.51, 47.71, 26.78. HRMS m / z (ESI): calcd. for C 15 H 13 BrNO2 [M+H] + : 318.0124, found: 318.01245。

[0165] Example 84

[0166] A magnetic stir bar, substrate 1xx (101 mg, 0.5 mmol, 1.0 equiv), (HFIP:DCE = 1:9) (1.0 mL), and Fe(NO3)3·9H2O (202 mg, 0.5 mmol, 1.0 equiv) were added to a 10 mL clear glass reaction tube. The tube was sealed with a stopper and reacted at room temperature (25 °C) for 12 h. The reaction mixture was concentrated under reduced pressure. The crude mixture was then purified by flash column chromatography to afford the nitration product 2xx (yellow solid, 101 mg, 82% yield). 1 1H NMR (600 MHz, CDCl3) δ 8.71 (dd, J = 3.7, 9.4 Hz, 1H), 8.52 (d, J = 8.4 Hz, 1H), 8.19 (dd, J = 7.5, 16.8 Hz, 2H), 8.12 (d, J = 9.5 Hz, 1H), 8.08 (d, J = 8.9 Hz, 1H), 8.03 (t, J = 7.6 Hz, 1H), 7.97 (d, J = 8.5 Hz, 1H), 7.91 (d, J = 9.0 Hz, 1H). 13 13C NMR (151 MHz, CDCl3) δ 142.58, 134.94, 131.40, 130.74, 130.70, 129.95, 127.64, 127.13, 127.04, 126.76, 124.64, 124.61, 124.04, 123.44, 122.61, 121.58。

[0167] Example 85

[0168] A magnetic stir bar, substrate 1yy (157 mg, 0.5 mmol, 1.0 equiv), (HFIP:DCE = 1:9) (1.0 mL), and Fe(NO3)3·9H2O (202 mg, 0.5 mmol, 1.0 equiv) were added to a 10 mL transparent glass reaction tube. The tube was sealed with a stopper and reacted at room temperature (25 °C) for 24 h. The reaction mixture was concentrated under reduced pressure to remove the solvent. The crude mixture was then purified by flash column chromatography to afford the nitration product 2yy (pale yellow solid, 127 mg, 71% yield). 1 H NMR (600 MHz, CDCl3) δ 8.85 (d, J = 2.4 Hz, 1H), 8.17 (d, J = 9.1 Hz, 1H), 8.02 (d, J = 9.1 Hz, 1H), 7.96 (dd, J = 2.4, 9.4 Hz, 1H), 7.90 (d, J = 8.2 Hz, 1H), 7.60 (d, J = 9.1 Hz, 1H), 7.47 (d, J = 9.1 Hz, 1H), 7.35 (ddd, J = 1.2, 6.7, 8.1 Hz, 1H), 7.25 - 7.23 (m, 1H), 7.21 (d, J = 9.3 Hz, 1H), 7.03 (d, J = 7.6 Hz, 1H), 3.83 (s, 3H), 3.78 (s, 3H). 13 C NMR (101 MHz, CDCl3) δ 158.23, 155.01, 143.81, 137.00, 133.73, 131.98, 130.21, 129.28, 128.30, 127.31, 126.85, 126.83, 125.30, 124.72, 123.85, 119.82, 117.96, 115.56, 113.92, 56.81, 56.70。

[0169] Example 86

[0170] A magnetic stir bar, substrate 1zz (194 mg, 0.5 mmol, 1.0 equiv), HFIP (1.0 mL), and Fe(NO3)3·9H2O (202 mg, 0.5 mmol, 1.0 equiv) were added to a 10 mL transparent glass reaction tube. The tube was sealed with a stopper and reacted at room temperature (25 °C) for 12 h. The reaction mixture was concentrated under reduced pressure to remove the solvent. The crude mixture was then purified by flash column chromatography to afford the nitration product 2zz (pale yellow solid, 165 mg, 76% yield). 2zz-1: 11H NMR (600 MHz, CDCl3) δ 8.74 (d, J = 2.3 Hz, 1H), 8.07 (d, J = 8.4 Hz, 1H), 8.02 (dd, J = 8.7, 5.9 Hz, 2H), 7.97 (dd, J = 9.4, 2.4 Hz, 1H), 7.69 (d, J = 8.4 Hz, 1H), 7.58 (t, J = 7.5 Hz, 1H), 7.52 (d, J = 6.8 Hz, 2H), 7.41 - 7.35 (m, 2H), 7.30 (d, J = 9.1 Hz, 1H), 7.26 - 7.18 (m, 4H), 3.64 (s, 3H). 13 13C NMR (151 MHz, CDCl3) δ 157.42, 143.77, 138.21, 137.65, 137.09, 134.44, 132.71, 132.60, 129.60, 128.59, 128.28, 127.92, 127.47, 127.30, 127.18, 126.78, 126.69, 125.36, 125.11, 120.77, 120.10, 114.42, 56.02. HRMS m / z (ESI): calcd. for C 28 H 20 NO4[M + H] + : 434.1387, found: 434.13887。2zz - 2: 1 1H NMR (600 MHz, CDCl3) δ 7.99 - 7.93 (m, 3H), 7.90 (d, J = 9.1 Hz, 1H), 7.56 (dd, J = 8.4, 18.9 Hz, 4H), 7.41 (dt, J = 7.5, 15.0 Hz, 4H), 7.31 (t, J = 7.8 Hz, 1H), 7.25 - 7.20 (m, 3H), 3.61 (s, 3H). 13 13C NMR (151 MHz, CDCl3) δ 197.33, 156.45, 148.41, 138.32, 136.36, 134.14, 133.61, 132.91, 132.68, 132.18, 131.14, 130.30, 129.42, 128.39, 128.23, 127.74, 127.38, 127.08, 126.74, 126.11, 125.78, 124.42, 122.02, 117.97, 113.78, 56.04. HRMS m / z (ESI): calcd. for C 28 H 20 NO4[M + H] + : 434.1387, found: 434.13887。

[0171] Example 87

[0172] A magnetic stir bar, substrate 1aaa (61 mg, 0.5 mmol, 1.0 equiv), HFIP (1.0 mL), and Fe(NO3)3·9H2O (202 mg, 0.5 mmol, 1.0 equiv) were added to a 10 mL transparent glass reaction tube. The tube was sealed with a stopper and reacted at room temperature (25 °C) for 12 hours. The reaction mixture was concentrated under reduced pressure to remove the solvent. The crude mixture was then purified by flash column chromatography to afford the nitration product 2aaa (white solid, 98 mg, 92% yield). 1 H NMR (600 MHz, CDCl3) δ 7.88 (d, J = 8.5 Hz, 1H), 7.65 (s, 1H), 6.86 (d, J = 8.7 Hz, 1H), 6.14 (s, 2H). 13 C NMR (151 MHz, CDCl3) δ: 153.42, 148.41, 120.11, 107.82, 104.73, 103.30.

[0173] Example 88

[0174] A magnetic stir bar, substrate 1bbb (89 mg, 0.5 mmol, 1.0 equiv), HFIP (1.0 mL), and Fe(NO3)3·9H2O (202 mg, 0.5 mmol, 1.0 equiv) were added to a 10 mL transparent glass reaction tube. The tube was sealed with a stopper and reacted at room temperature (25 °C) for 12 hours. The reaction mixture was concentrated under reduced pressure to remove the solvent. The crude mixture was then purified by flash column chromatography to afford the nitration product 2bbb (pale yellow solid, 165 mg, 96% yield). 1 H NMR (600 MHz, CD3OD) δ 7.44 (s, 1H), 7.20 (s, 1H), 6.24 (s, 2H). 13 C NMR (151 MHz, CD3OD) δ 199.10, 152.71, 148.85, 140.27, 135.11, 106.24, 104.84, 103.78。

[0175] Example 89

[0176] A magnetic stir bar, substrate 1ccc (55 mg, 0.5 mmol, 1.0 equiv), HFIP (1.0 mL), and Fe(NO3)3·9H2O (202 mg, 0.5 mmol, 1.0 equiv) were added to a 10 mL transparent glass reaction tube. The tube was sealed with a stopper and reacted at 120 °C for 24 h. The reaction mixture was cooled to room temperature and the solvent was removed under reduced pressure. The crude mixture was then purified by flash column chromatography to give the nitration product 2ccc (pale yellow solid, 69 mg, 86% yield). 1 H NMR (400 MHz, CDCl3) δ 7.30 (s, 1H), 7.20 (s, 1H), 2.54 (s, 3H); 13 C NMR (101 MHz, CDCl3) δ 186.8, 151.9, 151.5, 116.7, 111.9, 26.3.

[0177] Example 90

[0178] A magnetic stir bar, substrate 1ddd (60 mg, 0.5 mmol, 1.0 equiv), HFIP (1.0 mL), and Fe(NO3)3·9H2O (202 mg, 0.5 mmol, 1.0 equiv) were added to a 10 mL transparent glass reaction tube. The tube was sealed with a stopper and reacted at 120 °C for 24 h. The reaction mixture was cooled to room temperature and the solvent was removed under reduced pressure. The crude mixture was then purified by flash column chromatography to give the nitration product 2ddd (pale yellow solid, 71 mg, 81% yield). 1 H NMR (400 MHz, CDCl3) δ 7.80 (s, 1H), 7.50 (s, 1H), 2.51 (s, 3H); 13 C NMR (101 MHz, CDCl3) δ 187.1, 152.4, 151.9, 116.9, 112.5, 26.8.

[0179] Example 91

[0180] A magnetic stir bar, substrate 1eee (86 mg, 0.5 mmol, 1.0 equiv), HFIP (1.0 mL), and Fe(NO3)3·9H2O (202 mg, 0.5 mmol, 1.0 equiv) were added to a 10 mL transparent glass reaction tube. The tube was sealed with a stopper and reacted at room temperature (25 °C) for 12 h. The reaction mixture was removed the solvent under reduced pressure. The crude mixture was then purified by flash column chromatography to give the nitration product 2eee (pale yellow solid, 97 mg, 86% yield). 11H NMR (400 MHz, CDCl3): δ 8.13 - 8.09 (m, 2H), 8.07 (s, 1H), 7.52 (d, J = 1.0 Hz, 1H), 4.02 (s, 3H); 13 13C NMR (100 MHz, CDCl3): δ 158.8, 153.0, 150.3, 131.6, 128.6, 112.4, 110.6, 109.1, 53.1.

[0181] Example 92

[0182] A magnetic stir bar, substrate 1fff (76 mg, 0.5 mmol, 1.0 equiv), HFIP (1.0 mL), and Fe(NO3)3·9H2O (202 mg, 0.5 mmol, 1.0 equiv) were added to a 10 mL transparent glass reaction tube. The tube was sealed with a stopper and reacted at room temperature (25 °C) for 12 h. The reaction mixture was concentrated under reduced pressure to remove the solvent. The crude mixture was then purified by flash column chromatography to afford the nitration product 2fff (pale yellow solid, 65 mg, 66% yield). 1 1H NMR (400 MHz, CD3CN) δ 8.36 (d, J = 8.4 Hz, 1H), 7.63 (d, J = 8.5 Hz, 1H); 13 13C NMR (75 MHz, CD3CN) δ 152.4, 143.5, 142.1, 137.3, 124.3, 116.9.

[0183] This preparation method can also be applied to the late-stage nitration modification of various drug molecules, amino acids, amino acid derivatives, saccharides, and saccharide derivatives. The generality of the substrate aims to demonstrate the wide application scope of this preparation method. The following experiments are for the late-stage nitration of complex molecules such as drug molecules, amino acids, and saccharides under this preparation method.

[0184] Example 93

[0185] A magnetic stir bar, substrate 3a (103 mg, 0.5 mmol, 1.0 equiv), HFIP (1.0 mL), and Fe(NO3)3·9H2O (202 mg, 0.5 mmol, 1.0 equiv) were added to a 10 mL transparent glass reaction tube. The tube was sealed with a stopper and reacted at 60 °C for 6 h. The reaction mixture was cooled to room temperature and concentrated under reduced pressure to remove the solvent. The crude mixture was then purified by flash column chromatography to afford the nitration product 4a (colorless liquid, 112 mg, 89% yield). 11H NMR (600 MHz, CD3OD) δ 7.84 (s, 3H), 7.74 (s, 1H), 7.56 (d, J = 7.9 Hz, 3H), 7.36 (d, J = 7.7 Hz, 3H), 7.23 (d, J = 7.6 Hz, 1H), 7.11 (d, J = 7.7 Hz, 1H), 2.77 (d, J = 7.4 Hz, 6H), 2.59 (d, J = 6.7 Hz, 2H), 1.96 - 1.90 (m, 1H), 1.89 (dd, J = 6.7, 13.2 Hz, 3H), 1.57 (d, J = 6.9 Hz, 3H), 1.51 (d, J = 6.8 Hz, 9H), 1.39 - 1.27 (m, 4H), 0.97 - 0.94 (m, 6H), 0.94 - 0.90 (m, 18H). 13 13C NMR (151 MHz, CD3OD) δ 217.37, 201.45, 151.28, 150.41, 143.47, 142.64, 135.44, 135.02, 133.92, 132.81, 130.24, 128.25, 125.81, 124.43, 45.24, 42.08, 31.22, 30.74, 22.50, 22.69, 18.33, 18.94. HRMS m / z (ESI): calcd. for C 13 H 16 NO4[M - H] - : 250.1085, found: 250.10860。

[0186] Example 94

[0187] A magnetic stir bar, substrate 3b (58 mg, 0.25 mmol, 1.0 equiv), HFIP (1.0 mL), and Fe(NO3)3·9H2O (101 mg, 0.25 mmol, 1.0 equiv) were added to a 10 - mL transparent glass reaction tube. The tube was sealed with a stopper and reacted at room temperature (25 °C) for 2 hours. The reaction mixture was concentrated under reduced pressure to remove the solvent. Then the crude mixture was purified by flash column chromatography to give the nitration product 4b (pale yellow solid, 68 mg, 99% yield). 1 1H NMR (600 MHz, CD3OD) δ 7.90 (d, J = 9.1 Hz, 1H), 7.79 (s, 1H), 7.59 (d, J = 8.8 Hz, 1H), 7.54 (d, J = 8.8 Hz, 1H), 7.40 (d, J = 9.1 Hz, 1H), 3.97 (s, 3H), 3.89 (t, J = 7.0 Hz, 1H), 1.54 (d, J = 7.1 Hz, 3H). 1313C NMR (151 MHz, CD3OD) δ 177.76, 149.73, 139.30, 136.96, 133.14, 130.23, 129.52, 127.49, 125.62, 121.31, 114.71, 57.56, 46.26, 18.73. HRMS m / z (ESI): calcd. for C 14 H 12 NO5[M - H] - : 274.0721, found: 274.07218。

[0188] Example 95

[0189] A magnetic stir bar, substrate 3c (103 mg, 0.25 mmol, 1.0 equiv), HFIP (1.0 mL), and Fe(NO3)3·9H2O (101 mg, 0.25 mmol, 1.0 equiv) were added to a 10 - mL clear glass reaction tube. The tube was sealed with a stopper and reacted at room temperature (25 °C) for 12 h. The reaction mixture was concentrated under reduced pressure to remove the solvent. The crude mixture was then purified by flash column chromatography to afford the nitration product 4c (white solid, 112 mg, 98% yield). 1 1H NMR (600 MHz, CD3OD) δ 8.64 (s, 4.5H), 8.28 (d, J = 8.7 Hz, 9H), 7.97 (s, 1H), 7.81 (s, 3.5H), 7.74 (d, J = 8.5 Hz, 7H), 7.65 (d, J = 8.8 Hz, 4.5H), 7.63 (s, 4.5H), 7.44 (d, J = 8.3 Hz, 2H), 4.05 (s, 3H), 3.88 (s, 10.5H), 2.16 (s, 27H), 2.13 (s, 13.5H), 1.86 (s, 27H). 13 13C NMR (151 MHz, CD3OD) δ 178.17, 145.98, 138.94, 134.42, 133.21, 132.68, 132.18, 131.02, 130.34, 128.23, 126.26, 124.43, 121.91, 62.20, 42.20, 39.41, 37.82, 30.43. HRMS m / z (ESI): calcd. for C 28 H 26 NO5[M - H] - : 456.1816, found: 456.18177。

[0190] Example 96

[0191] A magnetic stir bar, substrate 3d (58 mg, 0.25 mmol, 1.0 equiv), HFIP (1.0 mL), and Fe(NO3)3·9H2O (101 mg, 0.25 mmol, 1.0 equiv) were added to a 10 mL transparent glass reaction tube. The tube was sealed with a stopper and reacted at room temperature (25 °C) for 24 h. The reaction mixture was concentrated under reduced pressure to remove the solvent. The crude mixture was then purified by flash column chromatography to afford the nitration product 4d (pale yellow solid, 61 mg, 89% yield). 1 H NMR (600 MHz, CDCl3) δ 7.88 (d, J = 9.1 Hz, 1H), 7.62 (s, 1H), 7.60 (d, J = 8.8 Hz, 1H), 7.44 (d, J = 8.7 Hz, 1H), 7.31 (d, J = 9.1 Hz, 1H), 4.01 (s, 3H), 3.04 (t, J = 7.4 Hz, 2H), 2.83 (t, J = 7.4 Hz, 2H), 2.15 (s, 3H). 13 C NMR (151 MHz, CDCl3) δ 207.58, 148.42, 138.19, 136.15, 131.86, 130.50, 128.58, 126.80, 124.43, 120.89, 113.42, 57.23, 44.80, 30.28, 29.51. HRMS m / z (ESI): calcd. for C 15 H 16 NO4 [M + H] + : 274.1074, found: 274.10742。

[0192] Example 97

[0193] A magnetic stir bar, substrate 3e (91 mg, 0.5 mmol, 1.0 equiv), HFIP (1.0 mL), and Fe(NO3)3·9H2O (202 mg, 0.5 mmol, 1.0 equiv) were added to a 10 mL transparent glass reaction tube. The tube was sealed with a stopper and reacted at room temperature (25 °C) for 2 h. The reaction mixture was concentrated under reduced pressure to remove the solvent. The crude mixture was then purified by flash column chromatography to afford the nitration product 4e (yellow solid, 97 mg, 86% yield). 1 H NMR (600 MHz, CD3OD) δ 7.83 (s, 1H), 7.27 (d, J = 8.7 Hz, 1H), 6.84 (d, J = 8.6 Hz, 1H), 3.58 (dd, J = 4.4, 8.8 Hz, 1H), 3.13 (d, J = 14.4 Hz, 1H), 2.79 (dd, J = 8.7, 14.4 Hz, 1H). 1313C NMR (151 MHz, CD3OD) δ 175.35, 137.68, 137.54, 131.45, 127.30, 125.65, 116.48, 58.08, 39.17. HRMS m / z (ESI): calcd. for C9H9N2O5 [M-H] - : 225.0517, found: 225.05160。

[0194] Example 98

[0195] A magnetic stir bar, substrate 3f (112 mg, 0.5 mmol, 1.0 equiv), HFIP (1.0 mL), and Fe(NO3)3·9H2O (202 mg, 0.5 mmol, 1.0 equiv) were added to a 10 mL clear glass reaction tube. The tube was sealed with a stopper and reacted at room temperature (25 °C) for 1.5 h. The reaction mixture was concentrated under reduced pressure. The crude mixture was then purified by flash column chromatography to afford the nitration product 4f (yellow solid, 109 mg, 81% yield). 1 1H NMR (600 MHz, CD3OD) δ 7.94 (s, 1H), 7.50 (d, J = 8.6 Hz, 1H), 7.04 (d, J = 2.9 Hz, 1H), 4.48 (p, J = 3.5 Hz, 1H), 3.21 (dt, J = 4.2, 14.0 Hz, 1H), 2.94 (dd, J = 7.5, 14.5 Hz, 1H), 1.93 (s, 3H). 13 13C NMR (151 MHz, CD3OD) δ 172.45, 154.74, 139.42, 135.38, 131.70, 129.08, 126.45, 120.73, 57.26, 38.19, 22.72. HRMS m / z (ESI): calcd. for C 11 H 11 N2O6 [M-H] - : 267.0623, found: 267.06228.

[0196] Example 99

[0197] A magnetic stir bar, substrate 3f (112 mg, 0.5 mmol, 1.0 equiv), HFIP (1.0 mL), and Fe(NO3)3·9H2O (202 mg, 0.5 mmol, 1.0 equiv) were added to a 10 mL clear glass reaction tube. The tube was sealed with a stopper and reacted at room temperature (25 °C) for 3 h. The reaction mixture was concentrated under reduced pressure. The crude mixture was then purified by flash column chromatography to afford the nitration product 4f' (yellow solid, 144 mg, 92% yield).1 1H NMR (600 MHz, CD3OD) δ 8.14 (s, 2H), 4.75 - 4.61 (m, 1H), 3.26 (d, J = 14.0 Hz, 1H), 3.05 - 2.93 (m, 1H), 1.96 (s, 3H). 13 13C NMR (151 MHz, CD3OD) δ 174.18, 173.16, 154.39, 139.08, 135.35, 132.26, 130.75, 126.38, 120.85, 54.70, 37.18, 22.32. HRMS m / z (ESI): calcd. for C 11 H 11 N2O6 [M - H] - : 267.0623, found: 267.06228.

[0198] Example 100

[0199] A magnetic stir bar, the substrate 3 g (135 mg, 0.5 mmol, 1.0 equiv), (HFIP:DCE = 1:9) (1.0 mL), and Fe(NO3)3·9H2O (202 mg, 0.5 mmol, 1.0 equiv) were added to a 10 mL clear glass reaction tube. The tube was sealed with a stopper and reacted at room temperature (25 °C) for 4 h. The reaction mixture was concentrated under reduced pressure to remove the solvent. The crude mixture was then purified by flash column chromatography to afford the nitration product 4 g (yellow solid, 59 mg, 37% yield). 1 1H NMR (400 MHz, CDCl3) δ 10.41 (s, 1H), 7.98 (d, J = 1.5 Hz, 1H), 6.86 (s, 1H), 3.03 - 2.83 (m, 2H), 2.58 - 2.46 (m, 1H), 2.46 - 2.38 (m, 1H), 2.27 - 1.96 (m, 5H), 1.67 - 1.44 (m, 6H), 0.91 (s, 3H). 13 13C NMR (101 MHz, CDCl3) δ 153.03, 148.93, 133.23, 131.88, 121.66, 119.10, 50.48, 47.94, 43.57, 37.84, 35.89, 31.39, 29.74, 26.01, 25.81, 21.66, 13.89.

[0200] Example 101

[0201] A magnetic stir bar, substrate 3g (135 mg, 0.5 mmol, 1.0 equiv), (HFIP:DCE = 1:9) (1.0 mL), and Fe(NO3)3·9H2O (202 mg, 0.5 mmol, 1.0 equiv) were added to a 10 mL transparent glass reaction tube. The tube was sealed with a stopper and reacted at room temperature (25 °C) for 24 h. The reaction mixture was concentrated under reduced pressure to remove the solvent. The crude mixture was then purified by flash column chromatography to afford the nitration product 4g' (yellow solid, 164 mg, 91% yield). 1 H NMR (600 MHz, CDCl3) δ 10.62 (s, 1H), 8.16 (s, 1H), 2.89 (dd, J = 3.5, 8.0 Hz, 2H), 2.56 - 2.49 (m, 1H), 2.48 - 2.41 (m, 1H), 2.28 (td, J = 4.4, 11.1 Hz, 1H), 2.17 (dd, J = 9.6, 18.7 Hz, 1H), 2.14 - 2.01 (m, 3H), 1.67 - 1.55 (m, 3H), 1.55 - 1.45 (m, 3H), 0.91 (s, 3H). 13 C NMR (151 MHz, CDCl3) δ 144.95, 141.77, 139.21, 133.64, 132.24, 122.79, 50.13, 47.77, 43.55, 37.11, 35.81, 31.24, 25.87, 24.96, 24.86, 21.55, 13.82. HRMS m / z (ESI): calcd. for C 18 H 19 N2O6 [M - H] - : 359.1249, found: 359.12490.

[0202] Example 102

[0203] A magnetic stir bar, substrate 3h (135 mg, 0.5 mmol, 1.0 equiv), (HFIP:DCE = 1:9) (1.0 mL), and Fe(NO3)3·9H2O (202 mg, 0.5 mmol, 1.0 equiv) were added to a 10 mL transparent glass reaction tube. The tube was sealed with a stopper and reacted at room temperature (25 °C) for 12 h. The reaction mixture was concentrated under reduced pressure to remove the solvent. The crude mixture was then purified by flash column chromatography to afford the nitration product 4h (yellow solid, 65 mg, 41% yield). 11H NMR (600 MHz, CD3OD) δ 7.91 (s, 1H), 6.78 (s, 1H), 3.68 (t, J = 8.8 Hz, 1H), 2.99 - 2.77 (m, 2H), 2.31 (d, J = 13.3 Hz, 1H), 2.13 (d, J = 9.9 Hz, 1H), 2.10 - 2.03 (m, 1H), 2.00 (d, J = 13.0 Hz, 1H), 1.94 - 1.87 (m, 1H), 1.71 (q, J = 8.4 Hz, 1H), 1.58 - 1.46 (m, 2H), 1.39 - 1.30 (m, 4H), 1.19 (q, J = 11.4 Hz, 1H), 0.79 (s, 3H). 13 13C NMR (151 MHz, CD3OD) δ 155.78, 149.23, 134.07, 133.23, 122.55, 121.02, 82.34, 51.28, 44.75, 44.28, 39.83, 37.71, 30.67, 30.58, 27.89, 27.27, 23.95, 11.60. HRMS m / z (ESI): calcd. for C 18 H 22 NO4[M - H] - : 316.1554, found: 316.15523.

[0204] Example 103

[0205] A magnetic stir bar, substrate 3h (135 mg, 0.5 mmol, 1.0 equiv), (HFIP:DCE = 1:9) (1.0 mL), and Fe(NO3)3·9H2O (202 mg, 0.5 mmol, 1.0 equiv) were added to a 10 mL transparent glass reaction tube. The tube was sealed with a stopper and reacted at room temperature (25 °C) for 24 hours. The reaction mixture was concentrated under reduced pressure to remove the solvent. The crude mixture was then purified by flash column chromatography to afford the nitration product 4h' (yellow solid, 143 mg, 79% yield). 11H NMR (600 MHz, CD3OD) δ 7.91 (s, 1H), 3.68 (t, J = 8.8 Hz, 1H), 2.73 - 2.62 (m, 2H), 2.31 (d, J = 15.9 Hz, 1H), 2.11 (d, J = 9.9 Hz, 1H), 2.10 - 2.02 (m, 1H), 2.00 (d, J = 12.8 Hz, 1H), 1.91 (d, J = 8.7 Hz, 1H), 1.71 (q, J = 9.7 Hz, 1H), 1.52 (q, J = 14.6, 16.6 Hz, 2H), 1.44 - 1.34 (m, 2H), 1.35 - 1.26 (m, 2H), 1.24 - 1.15 (m, 1H), 0.80 (s, 3H). 13 13C NMR (151 MHz, CD3OD) δ 149.70, 135.98, 124.42, 124.29, 82.35, 51.06, 44.63, 44.29, 39.69, 37.69, 30.67, 27.49, 27.36, 25.62, 23.89, 11.60. HRMS m / z (ESI): calcd. for C 18 H 21 N2O6 [M - H] - : 361.1405, found: 361.14018.

[0206] Example 104

[0207] A magnetic stir bar, substrate 3i (76 mg, 0.5 mmol, 1.0 equiv), (HFIP:DCE = 1:9) (1.0 mL), and Fe(NO3)3·9H2O (202 mg, 0.5 mmol, 1.0 equiv) were added to a 10 mL clear glass reaction tube. The tube was sealed with a stopper and reacted at room temperature (25 °C) for 1 hour. The reaction mixture was concentrated under reduced pressure to remove the solvent. The crude mixture was then purified by flash column chromatography to afford the nitration product 4i (yellow solid, 39 mg, 40% yield). 1 1H NMR (600 MHz, CD3OD) δ 8.37 (d, J = 2.7 Hz, 1H), 7.60 (dd, J = 2.6, 9.1 Hz, 1H), 7.04 (d, J = 9.0 Hz, 1H), 2.13 (s, 3H). 13 13C NMR (151 MHz, CD3OD) δ 171.66, 154.34, 135.43, 131.04, 130.37, 122.03, 116.99, 23.60. HRMS m / z (ESI): calcd. for C8H7N2O4 [M - H] -:195.0411,found:195.04110.

[0208] Example 105

[0209] A magnetic stir bar, substrate 3i (76 mg, 0.5 mmol, 1.0 equiv), HFIP (1.0 mL), and Fe(NO3)3·9H2O (202 mg, 0.5 mmol, 1.0 equiv) were added to a 10 mL transparent glass reaction tube. The tube was sealed with a stopper and reacted at room temperature (25 °C) for 12 h. The reaction mixture was concentrated under reduced pressure to remove the solvent. The crude mixture was then purified by flash column chromatography to afford the nitration product 4i' (yellow solid, 96 mg, 80% yield). 1 H NMR (600 MHz, DMSO) δ 10.38 (s, 1H), 8.40 (s, 2H), 2.06 (s, 3H). 13 C NMR (151 MHz, DMSO) δ 171.40, 168.77, 139.77, 139.71, 120.37, 120.31, 23.77. HRMS m / z (ESI): calcd. for C8H6N3O6 [M-H] - :240.0262,found:240.02613.

[0210] Example 106

[0211] A magnetic stir bar, substrate 3j (127 mg, 0.5 mmol, 1.0 equiv), HFIP (1.0 mL), and Fe(NO3)3·9H2O (202 mg, 0.5 mmol, 1.0 equiv) were added to a 10 mL transparent glass reaction tube. The tube was sealed with a stopper and reacted at room temperature (25 °C) for 2 h. The reaction mixture was concentrated under reduced pressure to remove the solvent. The crude mixture was then purified by flash column chromatography to afford the nitration product 4j (yellow solid, 136 mg, 91% yield). 1 H NMR (600 MHz, CDCl3) δ 14.10 (s, 1H), 12.02 (s, 1H), 8.10 (d, J = 7.4 Hz, 2H), 7.65 - 7.53 (m, 3H), 6.92 (s, 1H), 6.48 (s, 1H). 13 C NMR (151 MHz, CDCl3) δ 181.83, 167.60, 165.15, 153.44, 133.08, 129.86, 129.61, 126.97, 118.29, 106.80, 100.87. HRMS m / z (ESI): calcd. for C 15 H8NO6 [M-H] -: 298.0357, found: 298.03579.

[0212] Example 107

[0213] A magnetic stir bar, substrate 3k (148 mg, 0.5 mmol, 1.0 equiv), HFIP (1.0 mL), and Fe(NO3)3·9H2O (202 mg, 0.5 mmol, 1.0 equiv) were added to a 10 mL transparent glass reaction tube. The tube was sealed with a stopper and reacted at room temperature (25 °C) for 3 hours. The reaction mixture was concentrated under reduced pressure to remove the solvent. The crude mixture was then purified by flash column chromatography to afford the nitration product 4k (yellow-orange solid, 145 mg, 85% yield). 1 1H NMR (600 MHz, CD3OD) δ 8.17 (s, 1H), 7.97 - 7.91 (m, 1H), 7.50 (d, J = 8.1 Hz, 2H), 7.22 (t, J = 8.1 Hz, 1H), 6.35 (d, J = 8.9 Hz, 1H), 3.69 (s, 2H). 13 13C NMR (151 MHz, CD3OD) δ 189.02, 151.49, 141.40, 137.40, 133.29, 130.19, 127.77, 127.38, 124.21, 115.07, 44.23. HRMS m / z (ESI): calcd. for C 14 H9Cl2N2O4 [M-H] - : 338.9945, found: 338.99450.

[0214] Example 108

[0215] A magnetic stir bar, substrate 3l (161 mg, 0.5 mmol, 1.0 equiv), HFIP (1.0 mL), and Fe(NO3)3·9H2O (202 mg, 0.5 mmol, 1.0 equiv) were added to a 10 mL transparent glass reaction tube. The tube was sealed with a stopper and reacted at room temperature (25 °C) for 12 hours. The reaction mixture was concentrated under reduced pressure to remove the solvent. The crude mixture was then purified by flash column chromatography to afford the nitration product 4l (pale yellow solid, 180 mg, 99% yield). 11H NMR (600 MHz, CDCl3) δ 8.17 (s, 1.3H), 8.13 (s, 1H), 7.66 (s, 1.3H), 7.56 (q, J = 7.7 Hz, 2.3H), 7.47 (s, 1H), 7.32 (dd, J = 7.9, 16.0 Hz, 4.6H), 7.21 - 7.07 (m, 5.6H), 7.01 (d, J = 8.9 Hz, 1.3H), 6.96 (dd, J = 8.0, 14.5 Hz, 4.6H), 6.86 (d, J = 6.1 Hz, 2.3H), 6.73 (t, J = 9.3 Hz, 2.3H), 5.69 - 5.52 (m, 2.3H), 4.34 (d, J = 11.3 Hz, 1H), 4.28 (d, J = 7.5 Hz, 1.3H), 4.20 (d, J = 17.5 Hz, 1H), 4.12 (d, J = 12.2 Hz, 1.3H), 1.51 (d, J = 6.6 Hz, 3H), 1.49 (d, J = 6.3 Hz, 4H). 13 13C NMR (151 MHz, CDCl3) δ 162.94, 157.23, 154.75, 146.84, 146.75, 142.02, 138.86, 138.81, 130.04, 129.86, 124.65, 123.93, 123.60, 123.34, 121.82, 118.59, 117.72, 117.01, 116.96, 116.78, 115.76, 111.55, 110.63, 72.52, 71.38, 68.86, 68.74, 17.00, 16.98. HRMS m / z (ESI): calcd. for C 20 H 19 N2O5 [M + H] + : 367.1288, found: 367.12896.

[0216] Example 109

[0217] A magnetic stir bar, substrate 3m (122 mg, 0.5 mmol, 1.0 equiv), HFIP (1.0 mL), and Fe(NO3)3·9H2O (202 mg, 0.5 mmol, 1.0 equiv) were added to a 10 mL clear glass reaction tube. The tube was sealed with a stopper and reacted at room temperature (25 °C) for 18 h. The reaction mixture was concentrated under reduced pressure to remove the solvent. The crude mixture was then purified by flash column chromatography to afford the nitration product 4m (colorless liquid, 143 mg, 99% yield). 11H NMR (600 MHz, CDCl3) δ 7.73 (s, 1H), 7.38 (d, J = 9.1 Hz, 1H), 6.95 (d, J = 8.8 Hz, 1H), 4.24 (q, J = 7.1 Hz, 2H), 1.63 (s, 6H), 1.25 (t, J = 6.2 Hz, 3H). 13 13C NMR (151 MHz, CDCl3) δ 173.31, 147.65, 143.32, 132.92, 127.22, 125.24, 121.51, 82.17, 62.03, 25.16, 14.16.

[0218] Example 110

[0219] A magnetic stir bar, substrate 3n (181 mg, 0.5 mmol, 1.0 equiv), HFIP (1.0 mL), and Fe(NO3)3·9H2O (202 mg, 0.5 mmol, 1.0 equiv) were added to a 10 mL transparent glass reaction tube. The tube was sealed with a stopper and reacted at 80 °C for 24 h. The reaction mixture was cooled to room temperature and the solvent was removed under reduced pressure. Then the crude mixture was purified by flash column chromatography to give the nitration product 4n (colorless liquid, 187 mg, 92% yield). 1 1H NMR (600 MHz, CDCl3) δ 8.18 (s, 1H), 7.90 (d, J = 9.0 Hz, 1H), 7.70 (d, J = 8.2 Hz, 2H), 7.48 (d, J = 8.1 Hz, 2H), 6.98 (d, J = 8.7 Hz, 1H), 5.08 (d, J = 6.2 Hz, 1H), 1.70 (s, 6H), 1.22 (d, J = 6.2 Hz, 6H). 13 13C NMR (101 MHz, CDCl3) δ 192.23, 172.24, 152.48, 141.81, 139.47, 135.14, 134.25, 131.21, 130.20, 129.08, 127.40, 118.38, 82.25, 69.98, 25.28, 21.61.

[0220] Example 111

[0221] A magnetic stir bar, substrate 3o (209 mg, 0.5 mmol, 1.0 equiv), HFIP (1.0 mL), and Fe(NO3)3·9H2O (202 mg, 0.5 mmol, 1.0 equiv) were added to a 10 mL transparent glass reaction tube. The tube was sealed with a stopper and reacted at 60 °C for 12 h. The reaction mixture was cooled to room temperature and the solvent was removed under reduced pressure. Then the crude mixture was purified by flash column chromatography to afford the nitration product 4o (white solid, 251 mg, 99% yield). 1 H NMR (600 MHz, DMSO) δ 6.23 (s, 4H), 4.07 (s, 6H), 3.58 (s, 6H). 13 C NMR (151 MHz, DMSO) δ 162.90, 149.18, 138.65, 135.52, 119.62, 107.39, 104.25, 61.07, 53.14. HRMS m / z (ESI): calcd. for C 20 H 17 N2O 14 [M + H] + : 509.0674, found: 509.06768.

[0222] Example 112

[0223] A magnetic stir bar, substrate 3p (179 mg, 0.5 mmol, 1.0 equiv), HFIP (1.0 mL), and Fe(NO3)3·9H2O (202 mg, 0.5 mmol, 1.0 equiv) were added to a 10 mL transparent glass reaction tube. The tube was sealed with a stopper and reacted at room temperature (25 °C) for 1 h. The reaction mixture was concentrated under reduced pressure. Then the crude mixture was purified by flash column chromatography to afford the nitration product 4p (yellow solid, 108 mg, 54% yield). 1 H NMR (600 MHz, CDCl3) δ 7.67 (s, 1H), 7.66 (d, J = 8.1 Hz, 2H), 7.51 (d, J = 8.1 Hz, 2H), 7.08 (s, 1H), 3.98 (s, 3H), 3.72 (s, 2H), 2.38 (s, 3H). 13 C NMR (151 MHz, CDCl3) δ 175.25, 167.82, 150.08, 141.17, 140.60, 136.72, 133.73, 132.68, 131.37, 129.67, 128.80, 112.36, 111.67, 101.78, 57.12, 29.93, 13.83. HRMS m / z (ESI): calcd. for C 19 H14 ClN2O6[M-H] - :401.0546, found:401.05471.

[0224] Example 113

[0225] A magnetic stir bar, substrate 3q (136 mg, 0.5 mmol, 1.0 equiv), HFIP (1.0 mL), and Fe(NO3)3·9H2O (202 mg, 0.5 mmol, 1.0 equiv) were added to a 10 mL clear glass reaction tube. The tube was sealed with a stopper and reacted at room temperature (25 °C) for 1 hour. The reaction mixture was concentrated under reduced pressure to remove the solvent. The crude mixture was then purified by flash column chromatography to afford the nitration product 4q (pale yellow solid, 111 mg, 70% yield). 1 1H NMR (600 MHz, CDCl3). δ 7.83 (d, J = 3.0 Hz, 1H), 7.46 (dd, J = 2.9, 9.2 Hz, 1H), 7.12 (d, J = 9.1 Hz, 1H), 4.70 - 4.54 (m, 1H), 3.92 (d, J = 9.9 Hz, 1H), 3.73 (dd, J = 5.7, 12.1 Hz, 1H), 3.51 - 3.45 (m, 3H), 3.43 - 3.36 (m, 1H). 13 13C NMR (151 MHz, CDCl3) δ 151.60, 151.12, 135.19, 128.63, 121.54, 113.13, 103.28, 78.28, 77.85, 74.79, 71.28, 62.44. HRMS m / z (ESI): calcd. for C 12 H 16 NO9[M+H] + :318.0820, found:318.08219。

[0226] Example 114

[0227] A magnetic stir bar, substrate 3q (136 mg, 0.5 mmol, 1.0 equiv), HFIP (1.0 mL), and Fe(NO3)3·9H2O (202 mg, 0.5 mmol, 1.0 equiv) were added to a 10 mL clear glass reaction tube. The tube was sealed with a stopper and reacted at room temperature (25 °C) for 12 hours. The reaction mixture was concentrated under reduced pressure to remove the solvent. The crude mixture was then purified by flash column chromatography to afford the nitration product 4q' (yellow - orange solid, 156 mg, 86% yield). 11H NMR (600 MHz, CD3OD) δ 8.02 (s, 2H), 3.92 (d, J = 12.0 Hz, 1H), 3.76 - 3.68 (m, 1H), 3.47 (q, J = 10.4, 10.8 Hz, 3H), 3.41 (t, J = 8.9 Hz, 1H), 3.34 - 3.28 (m, 1H). 13 13C NMR (151 MHz, CD3OD) δ 141.07, 140.98, 137.66, 121.65, 103.73, 98.03, 93.90, 78.29, 77.72, 74.69, 71.21, 62.38. HRMS m / z (ESI): calcd. for C 12 H 13 N2O 11 [M - H] - : 361.0525, found: 361.05236。

[0228] Example 115

[0229] A magnetic stir bar, substrate 3r (227 mg, 0.5 mmol, 1.0 equiv), HFIP (1.0 mL), and Fe(NO3)3·9H2O (202 mg, 0.5 mmol, 1.0 equiv) were added to a 10 mL clear glass reaction tube. The tube was sealed with a stopper and reacted at room temperature (25 °C) for 12 h. The reaction mixture was concentrated under reduced pressure. The crude mixture was then purified by flash column chromatography to afford the nitration product 4r (pale yellow liquid, 247 mg, 99% yield). 1 1H NMR (600 MHz, CDCl3) δ 7.57 - 7.52 (m, 1H), 7.21 - 7.16 (m, 1H), 7.00 (d, J = 9.1 Hz, 1H), 5.46 - 5.39 (m, 2H), 5.07 (d, J = 8.1 Hz, 1H), 4.99 (d, J = 7.9 Hz, 1H), 4.15 (d, J = 6.0 Hz, 2H), 4.07 (t, J = 6.1 Hz, 1H), 3.89 (s, 3H), 2.14 (s, 3H), 2.05 (s, 3H), 2.03 (s, 3H), 1.97 (s, 3H). 1313C NMR (101 MHz, CDCl3) δ 170.56, 170.19, 170.04, 169.37, 149.61, 149.24, 139.37, 124.02, 114.81, 114.12, 100.10, 77.36, 71.51, 70.71, 68.50, 67.04, 61.76, 57.02, 20.74, 20.64, 20.58, 20.56. HRMS m / z (ESI): calcd. for C 21 H 26 NO 13 [M + H] + : 500.1399, found: 500.13996.

[0230] This preparation method can be scaled up to reactions above the gram scale. The gram-scale reaction experiments are designed to prove that this preparation method can achieve large-scale production, and the solvent used in the nitration system can be recovered, and the nitration reagent nitrate can be recovered by simple post-treatment with dilute nitric acid. The following experiments are for the large-scale synthesis of some nitroarenes from some substrates under this preparation method.

[0231] Example 116

[0232] A magnetic stir bar, substrate 1a (2.34 g, 15.0 mmol, 1.0 equiv.), Fe(NO3)3·9H2O (2.43 g, 6.0 mmol, 0.4 equiv.), and HFIP (15 mL) were added to a 50 mL round-bottom flask. The round-bottom flask was connected to a reflux condenser and refluxed at 100 °C for 72 hours. After the reaction was completed (monitored by thin-layer chromatography), the mixture was cooled to room temperature. The solvent HFIP was recovered from the reaction mixture by distillation. Then, the crude mixture was purified through a short silica gel column to give the nitration product 2a (2.90 g, 98%).

[0233] Example 117

[0234] A magnetic stir bar, substrate 1u (3.639 g, 30.5 mmol, 1.0 equiv.), Fe(NO3)3·9H2O (4.937 g, 12.2 mmol, 0.4 equiv.), and HFIP (20 mL) were added to a 50 mL round-bottom flask. The round-bottom flask was stirred at room temperature for 24 hours. After the reaction was completed (monitored by thin-layer chromatography), the mixture was cooled to room temperature. The solvent HFIP was recovered from the reaction mixture by distillation. Then, the crude mixture was purified through a short silica gel column to give the nitration product 2u (4.705 g, 94%).

[0235] Comparative Example 1

[0236] A magnetic stir bar, substrate 3k (148 mg, 0.5 mmol, 1.0 equiv), HFIP (1.0 mL), and concentrated HNO3 (35 mg, 0.5 mmol, 1.0 equiv) were added to a 10 mL transparent glass reaction tube. The tube was sealed with a stopper and reacted at room temperature (25 °C) for 3 hours. The reaction mixture was concentrated under reduced pressure to remove the solvent. The crude mixture was then purified by flash column chromatography to afford the nitration product 4k (yellow-orange solid, 71 mg, 42% yield).

[0237] Comparative Example 2

[0238] A magnetic stir bar, substrate 3l (161 mg, 0.5 mmol, 1.0 equiv), HFIP (1.0 mL), and concentrated HNO3 (35 mg, 0.5 mmol, 1.0 equiv) were added to a 10 mL transparent glass reaction tube. The tube was sealed with a stopper and reacted at room temperature (25 °C) for 12 hours. The reaction mixture was concentrated under reduced pressure to remove the solvent. The crude mixture was then purified by flash column chromatography to afford only a small amount of the nitration product 4l (yield < 20%).

[0239] The structural formulas of products 2a - 2fff and 4a - 4r in Specific Examples 1 - 115 of the present application are as follows:

[0240]

[0241]

[0242]

[0243]

[0244] It is readily understood by those skilled in the art that the above are merely preferred embodiments of the present application and are not intended to limit the present application. Any modifications, equivalent substitutions, and improvements made within the spirit and principles of the present application shall be included within the protection scope of the present application.

Claims

1. A method for nitrating an aromatic compound, characterized in that: Aromatic compounds are used as raw materials and nitrates are used as nitrating agents. Nitration reaction occurs in a solvent system containing hexafluoroisopropanol, and aromatic nitro compounds are obtained by purification and separation; the aromatic compounds are substituted or unsubstituted aromatic rings of C6-C60, or substituted or unsubstituted heterocyclic aromatic rings of C4-C60; The aromatic ring is selected from benzene, biphenyl, fluorene, naphthalene, anthracene, phenanthrene, pyrene, piperonyl (1,2-methylenedioxybenzene) and binaphthyl skeleton; The heterocyclic aromatic ring is selected from furan, thiophene, pyridine and indole; When the aromatic compound is a C6-C60 substituted aromatic ring or a C4-C60 substituted heterocyclic aromatic ring, it is monosubstituted or polysubstituted, and its substituents are each independently selected from halogen, trifluoromethyl, trifluoromethoxy, nitro, cyano, phenolic hydroxyl, aldehyde, carbonyl, carboxyl, sulfonic acid, amino, acetylamino, C1-C10 alkyl, C1-C10 alkoxy, C6-C30 aryloxy, C1-C10 alkyl chain containing carbonyl, C6-C30 arylcarbonyl, C1-C10 ester, C6-C30 aryl and C4-C30 heterocyclic aromatic; The nitrate is one or more of ferric nitrate, bismuth nitrate, bismuth nitrate pentahydrate, ferric nitrate nonahydrate, gallium nitrate and gallium nitrate hydrate.

2. The nitration method according to claim 1, characterized in that: The substituted heterocyclic aromatic ring is selected from furan, thiophene, pyridine and indole with an electron withdrawing group, wherein the electron withdrawing group is selected from halogen, C1-C10 ester group, carbonyl group, aldehyde group, carboxyl group, sulfonic acid group, trifluoromethyl group, trifluoromethoxy group, and nitro group.

3. The nitration method according to claim 1, characterized in that: The solvent for the nitration reaction is hexafluoroisopropanol; or The solvent for the nitration reaction is a mixed solvent of hexafluoroisopropanol and other organic solvents, the other solvents are dichloromethane and / or dichloroethane, and the volume ratio of the hexafluoroisopropanol to the other solvents is 1:(1-20).

4. The nitration method according to claim 1, characterized in that: The molar ratio of the aromatic compound to the nitrate is 1:(0.33-1).

5. The nitration method according to claim 1, characterized in that: The concentration of the aromatic compound in the reaction system is 0.25-0.5M.

6. The nitration method according to claim 1, characterized in that: The reaction temperature of the reaction is 0°C-120°C, and the reaction time is 1-36h.

7. The nitration method according to claim 6, characterized in that: The reaction temperature of the reaction is 25°C-60°C.

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