阅读说明：本技术 一种高效氮化试剂及其应用 (Efficient nitriding reagent and application thereof ) 是由 焦宁 刘建忠 张�诚 于 2020-09-30 设计创作，主要内容包括：本发明公开了一种高效氮化试剂及其应用。所述的氮化试剂包括氮氧化物、活性剂、还原剂及有机溶剂。应用该氮化试剂可生产酰胺及腈等含氮化合物,并且方法条件简单、废弃物排放量少、反应设备简单。(The invention discloses a high-efficiency nitriding reagent and application thereof. The nitriding reagent comprises nitrogen oxide, an active agent, a reducing agent and an organic solvent. The application of the nitriding reagent can produce amide, nitrile and other nitrogen-containing compounds, and has the advantages of simple process conditions, less waste discharge and simple reaction equipment.)

1. The efficient nitriding reagent comprises a nitrogen oxide, an active agent, a reducing agent and an organic solvent; or the nitriding reagent comprises nitrogen oxide, an active agent, an acidic reagent and an organic solvent, and does not comprise a reducing agent;

here, the nitrogen oxide is R¹-NO₂Nitrate, nitrite, hydroxylamine and its derivatives, or hydroxylamine acid salts; here, R¹Is C1-C6 alkane or aromatic hydrocarbon radical; the C1-C6 alkane can be methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, tert-butyl, n-pentyl, or n-hexyl; the aromatic hydrocarbon group is phenyl or naphthyl; the nitrate may be an alkali metal or ammonium salt, such as potassium nitrate, sodium nitrate or ammonium nitrate; the nitrite may be an alkali metal or ammonium salt, such as potassium nitrite, sodium nitrite or ammonium nitrite; hydroxylamine derivatives are hydroxylamine compounds with a leaving group on the hydroxylamine oxygen atom, such as oxyacetylhydroxylamine; the hydroxylamine acid salt is an inorganic acid salt, such as hydroxylamine acid salt; preferably, the nitrogen oxide is nitromethane, nitroethane, nitropropane, nitrobutane, 2-nitropropane, 2-methyl-2-nitropropane, nitrobenzene, alkali metal nitrate, alkali metal nitrite, hydroxylamine, or hydroxylamine hydrochloride; more preferably, the nitrogen oxides are nitromethane;

the activating agent is one or a mixture of more of trifluoromethanesulfonic anhydride, acetyl chloride, trifluoromethanesulfonic acid, sulfonyl chloride, chlorosulfonic acid, sulfuric acid and trifluoromethanesulfonic silicone grease; preferably, the activator is trifluoromethanesulfonic anhydride, sulfonyl chloride, chlorosulfonic acid, sulfuric acid, or trifluoromethanesulfonic silicone grease;

the reducing agent is selected from one or more of formic acid, sodium formate and ammonium formate; preferably, the reducing agent is formic acid;

the organic solvent is selected from 1, 2-dichloroethane, 1, 2-dibromoethane, dichloromethane, chloroform, carbon tetrachloride, ethyl acetate, methyl acetate, butyl acetate, acetone, nitromethane, nitroethane, toluene, o-xylene, m-xylene, p-xylene, benzene, chlorobenzene, nitrobenzene, N-pentane, N-hexane, N-heptane, N-octane, cyclopentane, cyclohexane, cycloheptane, cyclooctane, diethyl ether, butyl ether, tetrahydrofuran, methyltetrahydrofuran, 1, 4-dioxane, tert-butyl methyl ether and N, n-dimethylformamide, N, a mixture of one or more of N-dimethylacetamide, dimethylsulfoxide, methanol, N-propanol, isopropanol, N-butanol, isobutanol, cyclopentanol, cyclohexanol, formic acid, acetic anhydride, trifluoroethanol, trifluoroacetic acid, and methanesulfonic acid; preferably, acetic acid;

the acidic reagent is selected from one or more of sulfuric acid, trifluoromethanesulfonic acid and acidic solid acid, and the acidic solid acid can be heteropoly acid or acidic cation exchanger.

2. The high efficiency nitriding reagent according to claim 1, wherein the molar ratio of nitrogen oxide, active agent and reducing agent is (1-50): (0.5-10): (0.5-20), preferably (2-50): (1-5): (1-8), more preferably (4-40): (2-3): (2-5), particularly preferably (4-40):2: 2.5;

alternatively, the molar ratio of nitrogen oxide, active agent to acidic agent is (1-50): 0.01-0.5): 0.01-1, preferably (2-50): 0.05-0.3): 0.05-0.5), more preferably (4-40): 0.08-0.2): 0.1-0.3, especially preferably (4-40):0.1: 0.2.

3. The high efficiency nitriding reagent according to claim 1, wherein said high efficiency nitriding reagent further comprises a lewis acid selected from the group consisting of, but not limited to, ferric triflate, copper triflate, zinc triflate, scandium triflate, indium triflate, aluminum trichloride, boron trifluoride etherate, and mixtures of one or more thereof, preferably ferric triflate.

4. The high efficiency nitriding reagent according to any one of claims 1 to 3, comprising nitromethane, triflic anhydride and formic acid; more preferably, nitromethane, trifluoromethanesulfonic anhydride, formic acid, and acetic acid;

alternatively, nitromethane, sulfonyl chloride and formic acid; more preferably, nitromethane, sulfonyl chloride, formic acid, and acetic acid;

alternatively, nitromethane, sulfuric acid and formic acid; more preferably, nitromethane, sulfuric acid, formic acid, and acetic acid;

alternatively, nitromethane, chlorosulfonic acid and formic acid; more preferably, nitromethane, trifluoromethanesulfonic anhydride, formic acid, and acetic acid;

alternatively, nitromethane, a silyl triflate (e.g., tert-butyldimethylsilyl triflate, trimethylsilyl triflate, triethylsilyltriflate, or triisopropylsilyltriflate), and an acidic reagent (e.g., sulfuric acid, trifluoromethanesulfonic acid, phosphotungstic acid, or an acidic cation exchanger); more preferably, nitromethane, trifluoromethanesulfonic acid silyl ester (e.g., tert-butyldimethylsilyltrifluoromethanesulfonate, trimethylsilyltrifluoromethanesulfonate, triethylsilyltrifluoromethanesulfonate, or triisopropylsilyltrifluoromethanesulfonate), sulfuric acid, and acetic acid; or, include nitromethane, silyl triflates (e.g., tert-butyldimethylsilyl triflate, trimethylsilyl triflate, triethylsilyl triflate, or triisopropylsilyl triflate), trifluoromethanesulfonic acid, and acetic acid; or, including nitromethane, silyl triflates (e.g., tert-butyldimethylsilyl triflate, trimethylsilyl triflate, triethylsilyl triflate, or triisopropylsilyl triflate), phosphotungstic acid, and acetic acid; or, including nitromethane, silyl triflates (e.g., tert-butyldimethylsilyl triflate, trimethylsilyl triflate, triethylsilyl triflate, or triisopropylsilyl triflate), Amberlyst, and acetic acid; or, include nitromethane, silyl triflates (e.g., tert-butyldimethylsilyl triflate, trimethylsilyl triflate, triethylsilyl triflate, or triisopropylsilyl triflate), Dowex, and acetic acid.

5. Use of the high efficiency nitriding reagent according to any one of claims 1-4, comprising nitriding a substrate in the presence of the high efficiency nitriding reagent to obtain a nitrided substrate; here, the substrate includes, but is not limited to: ketones, aldehydes, acetylenes, alkylaromatics, or aromatics.

6. Use according to claim 5, wherein the ketone compound is preferably a compound of formula (I):

obtaining a corresponding nitrified substrate as shown in a formula (II) or a formula (III):

here, R in the formulae (I), (II) and (III)₁Selected from the group consisting of alkyl, unsubstituted arylalkyl, substituted arylalkyl, unsubstituted heteroaryl, and substituted heteroaryl; r in the formulae (I) and (II)₂Selected from the group consisting of unsubstituted C1-C6 alkyl, substituted C1-C6 alkyl, unsubstituted aryl, substituted aryl, unsubstituted heteroaryl, and substituted heteroaryl; or R₁And R₂Are connected with each otherTo form a C4-C16 alkylene group; alternatively, said R₁And R₂Or NH₂Is the residue of an organic compound which at least simultaneously comprises R as defined above₁And R₂。

7. Use according to claim 5, wherein the aldehyde compound is a compound of formula (IV):

obtaining a corresponding nitrified substrate as shown in formula (V) or as shown in formula (VI):

here, R in the formulae (IV), (V) and (VI)₃Selected from the group consisting of alkyl, unsubstituted arylalkyl, substituted arylalkyl, unsubstituted heteroaryl, and substituted heteroaryl; alternatively, said R₃Is the residue of an organic compound comprising at least R as defined above₃。

8. Use according to claim 5, wherein the acetylenic compound is of formula (VII):

obtaining the corresponding nitrified substrate as a compound of formula (VIII):

here, R in the formulae (VII) and (VIII)₄Selected from the group consisting of alkyl, unsubstituted arylalkyl, substituted arylalkyl, unsubstituted heteroaryl, and substituted heteroaryl; r in the formulae (VII) and (VIII)₅Selected from the group consisting of unsubstituted C1-C6 alkyl, substituted C1-C6 alkyl, unsubstituted aryl, substituted aryl, unsubstituted heteroaryl, and substituted heteroaryl; or R₄And R₅Linked to form a C11-C16 alkylene group; alternatively, said R₄And R₅Is the residue of an organic compound which at least simultaneously comprises R as defined above₄And R₅。

9. Use of the high efficiency nitriding reagent according to any one of claims 1-4, comprising oxidizing a substrate in a one-pot process and nitriding in the presence of the high efficiency nitriding reagent to obtain an oxidatively nitrided substrate; here, the substrate is a compound represented by the formula (IX):

the substrate of oxidative nitridation is a compound shown as a formula (X) or a compound shown as a formula (XI):

wherein Ar in formula (IX), formula (X) and formula (XI) is selected from the group consisting of alkyl, unsubstituted aryl, substituted aryl, unsubstituted heteroaryl, and substituted heteroaryl; r in the formulae (IX) and (X)₆Selected from the group consisting of hydrogen, unsubstituted C1-C6 alkyl, substituted C1-C6 alkyl, unsubstituted aryl, substituted aryl, unsubstituted heteroaryl, and substituted heteroaryl; optionally, Ar and R are₆Is the residue of an organic compound comprising at least Ar and R as defined above simultaneously₆。

Technical Field

The present application relates to, but is not limited to, the field of organic chemistry technology, and more particularly to a high efficiency nitridation reagent and its application.

Background

Amide and nitrile compounds are important organic synthons and are also important organic chemical raw materials and chemical intermediates, and are widely applied to the industries of materials, medicines, pesticides and the like. For example, marketed drugs such as bicalutamide, panthenol, iopamidol, alfuzosin hydrochloride, tolvaptan, etc. contain an amide structure. Therefore, the method has important scientific significance and application value for the efficient synthesis research of amide and nitrile compounds.

However, the conventional method for synthesizing amide compounds mainly comprises a condensation reaction of carboxylic acids and amines, and an oxidative coupling reaction of amines with alcohols and aldehydes. The current method is relatively universal but has high cost price, and needs to consume equivalent activating reagent and generate equivalent waste; oxidative coupling requires the use of equivalent amounts of oxidizing agents as well as complex and expensive pincer chelated transition metals. The american society for chemistry green chemistry institute (consisting of members of the major pharmaceutical industry worldwide) has therefore pointed out in 2007 that avoiding the use of low atom economy reagents to synthesize amides is the greatest challenge facing organic chemistry. [ (a) v.r.pattabiiraman, j.w.bode, Nature 480,471(2011) - (b) J.D.G.Brown,R.J.Young,G.M.Keserü,Nat.Rev.Drug.Discovery 17,709(2018).(c)D.G.Brown,JonasJ.Med.Chem.59,4443(2016).(d)S.D.Roughley,A.M.Jordan,Morofuji,J.Med.Chem.54,3451(2011)]. The biggest limitation of the traditional synthetic methods is that the equivalent amount of carboxylic acid activating reagent is needed, a large amount of waste is caused, the large-scale application is difficult, and most of oxidative coupling methods depend on transition metal catalysts, so that the residue of the transition metal in the product is difficult to remove; further limiting the application of conventional methods.

Disclosure of Invention

The following is a summary of the subject matter described in detail herein. This summary is not intended to limit the scope of the claims.

The invention provides a novel and high-efficiency nitriding reagent, which can be used for producing amide and nitrile nitrogen-containing compounds, and has the advantages of simple method conditions, less waste discharge and simple reaction equipment.

The application provides a high-efficiency nitriding reagent, which comprises a nitrogen oxide, an active agent, a reducing agent and an organic solvent; or the nitriding reagent comprises nitrogen oxide, an active agent, an acidic reagent and an organic solvent, and does not comprise a reducing agent;

here, the nitrogen oxide is R¹-NO₂Nitrate, nitrite, hydroxylamine and its derivatives, or hydroxylamine acid salts; here, R¹Is C1-C6 alkane or aromatic hydrocarbon radical; the C1-C6 alkane can be methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, tert-butyl, n-pentyl, or n-hexyl; the aromatic hydrocarbon group is phenyl or naphthyl; the nitrate may be an alkali metal or ammonium salt, such as potassium nitrate, sodium nitrate or ammonium nitrate; the nitrite may be an alkali metal or ammonium salt, such as potassium nitrite, sodium nitrite or ammonium nitrite; hydroxylamine derivatives are hydroxylamine compounds with a leaving group on the hydroxylamine oxygen atom, such as oxyacetylhydroxylamine; the hydroxylamine acid salt is an inorganic acid salt, such as hydroxylamine acid salt; preferably, the nitrogen oxide is nitroMethane, nitroethane, nitropropane, nitrobutane, 2-nitropropane, 2-methyl-2-nitropropane, nitrobenzene, alkali metal nitrate, alkali metal nitrite, hydroxylamine, or hydroxylamine hydrochloride; more preferably, the nitrogen oxides are nitromethane;

the activating agent is one or a mixture of more of trifluoromethanesulfonic anhydride, acetyl chloride, trifluoromethanesulfonic acid, sulfonyl chloride, chlorosulfonic acid, sulfuric acid and trifluoromethanesulfonic silicone grease; preferably, the activator is trifluoromethanesulfonic anhydride, sulfonyl chloride, chlorosulfonic acid, sulfuric acid, or trifluoromethanesulfonic silicone grease;

the reducing agent is selected from one or more of formic acid, sodium formate and ammonium formate; preferably, the reducing agent is formic acid;

the organic solvent is selected from 1, 2-dichloroethane, 1, 2-dibromoethane, dichloromethane, chloroform, carbon tetrachloride, ethyl acetate, methyl acetate, butyl acetate, acetone, nitromethane, nitroethane, toluene, o-xylene, m-xylene, p-xylene, benzene, chlorobenzene, nitrobenzene, N-pentane, N-hexane, N-heptane, N-octane, cyclopentane, cyclohexane, cycloheptane, cyclooctane, diethyl ether, butyl ether, tetrahydrofuran, methyltetrahydrofuran, 1, 4-dioxane, tert-butyl methyl ether and N, n-dimethylformamide, N, a mixture of one or more of N-dimethylacetamide, dimethylsulfoxide, methanol, N-propanol, isopropanol, N-butanol, isobutanol, cyclopentanol, cyclohexanol, formic acid, acetic anhydride, trifluoroethanol, trifluoroacetic acid, and methanesulfonic acid; preferably, acetic acid;

the acidic reagent is selected from one or more of sulfuric acid, trifluoromethanesulfonic acid and acidic solid acid, and the acidic solid acid can be heteropolyacid (such as phosphotungstic acid) or acidic cation exchanger.

In embodiments herein, the acidic cation exchanger may be of H⁺Acidic groups in the form of, for example, polystyrene-based, which comprise copolymers of styrene and divinylbenzene as carrier matrix, having H⁺A sulfonic acid group in its form; can be selected from Amberlyst, Amberlite, Dowex, Lewatit, POne or more of urolite and Serdolit, e.g., Amberlyst 15, Serdolit,50WX2 hydrogen form.

In embodiments herein, the sulfuric acid may be dilute sulfuric acid or concentrated sulfuric acid, and the concentrated sulfuric acid may be selected from 95 wt% to 99.9 wt% concentrated sulfuric acid, preferably 98 wt% concentrated sulfuric acid.

In embodiments herein, the silicone triflate includes, but is not limited to, tris (C1-C6 alkyl) silyl triflate, where the C1-C6 alkyl groups are each independently selected from methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, tert-butyl, n-pentyl, and neopentyl; for example, the trifluoromethanesulfonate silicone grease may be tert-butyldimethylsilyl trifluoromethanesulfonate, trimethylsilyl trifluoromethanesulfonate, triethylsilyltriflate or triisopropylsilyltrifluoromethanesulfonate.

In embodiments of the present application, a high efficiency nitriding reagent is provided, wherein the molar ratio of nitrogen oxide, active agent to reducing agent is (1-50): 0.5-10): 0.5-20, preferably, (2-50): 1-5): 1-8, more preferably, (4-40): 2-3): 2-5, particularly preferably (4-40):2: 2.5; optionally, the molar ratio of the nitrogen oxide to the organic solvent is (1-8): (10-50), preferably, (1-2): (10-20).

In embodiments of the present application, a high efficiency nitriding reagent is provided, wherein the molar ratio of nitrogen oxide, active agent to acidic agent is (1-50): 0.01-0.5): 0.01-1, preferably (2-50): 0.05-0.3): 0.05-0.5, more preferably (4-40): 0.08-0.2): 0.1-0.3, particularly preferably (4-40):0.1: 0.2; optionally, the molar ratio of the nitrogen oxide to the organic solvent is (1-5): (1-10), preferably, (1-2): (1-5).

In an embodiment of the present application, the high efficiency nitriding reagent further comprises a lewis acid selected from one or more of, but not limited to, iron triflate, copper triflate, zinc triflate, scandium triflate, indium triflate, aluminum trichloride, boron trifluoride etherate, preferably, iron triflate.

In some embodiments herein, a high efficiency nitriding reagent provided herein comprises nitromethane, triflic anhydride, and formic acid; more preferably, nitromethane, trifluoromethanesulfonic anhydride, formic acid and acetic acid are included.

In some embodiments of the present application, a high efficiency nitrating reagent is provided wherein the molar ratio of nitromethane, triflic anhydride, and formic acid is (4-40):2: 2.5.

In some embodiments herein, a high efficiency nitriding reagent provided herein comprises nitromethane, sulfonyl chloride, and formic acid; more preferably, nitromethane, sulfonyl chloride, formic acid and acetic acid are included.

In some embodiments of the present application, a high efficiency nitriding reagent is provided, wherein the molar ratio of nitromethane, sulfonyl chloride, and formic acid is (4-40):2: 2.5.

In some embodiments herein, a high efficiency nitriding reagent provided herein comprises nitromethane, sulfuric acid, and formic acid; more preferably, nitromethane, sulfuric acid, formic acid, and acetic acid are included.

In some embodiments herein, a high efficiency nitriding reagent is provided, wherein the molar ratio of nitromethane, sulfuric acid to formic acid is (4-40):2: 2.5.

In some embodiments herein, a high efficiency nitriding reagent provided herein comprises nitromethane, chlorosulfonic acid, and formic acid; more preferably, nitromethane, trifluoromethanesulfonic anhydride, formic acid and acetic acid are included.

In some embodiments herein, a high efficiency nitriding reagent is provided, wherein the molar ratio of nitromethane, chlorosulfonic acid, and formic acid is (4-40):2: 2.5.

In some embodiments of the present application, a high potency nitriding reagent provided herein comprises nitromethane, a silyl triflate (e.g., tert-butyldimethylsilyl triflate, trimethylsilyl triflate, triethylsilyltriflate, or triisopropylsilyltriflate), and an acidic reagent (e.g., sulfuric acid, trifluoromethanesulfonic acid, phosphotungstic acid, or an acidic cation exchanger);

more preferably, nitromethane, trifluoromethanesulfonic acid silyl ester (e.g., tert-butyldimethylsilyltrifluoromethanesulfonate, trimethylsilyltrifluoromethanesulfonate, triethylsilyltrifluoromethanesulfonate, or triisopropylsilyltrifluoromethanesulfonate), sulfuric acid, and acetic acid;

including nitromethane, silyl triflates (e.g., tert-butyldimethylsilyl triflate, trimethylsilyl triflate, triethylsilyl triflate, or triisopropylsilyl triflate), trifluoromethanesulfonic acid, and acetic acid;

including nitromethane, silyl triflates (e.g., tert-butyldimethylsilyl triflate, trimethylsilyl triflate, triethylsilyl triflate, or triisopropylsilyl triflate), phosphotungstic acid, and acetic acid;

including nitromethane, silyl triflates (e.g., tert-butyldimethylsilyl triflate, trimethylsilyl triflate, triethylsilyl triflate, or triisopropylsilyl triflate), Amberlyst, and acetic acid;

including nitromethane, silyl triflates (e.g., tert-butyldimethylsilyl triflate, trimethylsilyl triflate, triethylsilyl triflate, or triisopropylsilyl triflate), Dowex, and acetic acid.

In some embodiments of the present application, a high efficiency nitriding reagent is provided, wherein the molar ratio of nitromethane, silicon triflate to acidic reagent is (4-40):0.1: 0.2.

In some embodiments herein, a high efficiency nitriding reagent provided herein comprises nitromethane, trifluoromethanesulfonic anhydride, formic acid, and ferric trifluoromethanesulfonate; preferably, the compound comprises nitromethane, trifluoromethanesulfonic anhydride, formic acid, acetic acid and ferric trifluoromethanesulfonate, wherein the molar ratio of the nitromethane to the trifluoromethanesulfonic anhydride to the formic acid to the ferric trifluoromethanesulfonate is (2-20) to (1-5) to (1-10): (1:30): (0.02-0.5), preferably (2-10): 1-4): 1-6): (1:20): (0.02-0.3) more preferably, is (2-6): 1-3): 1-4): (1:15): (0.02-0.4), particularly preferably (2-4): 1-2): 1-3): (1:10): (0.02-0.2).

In another aspect, the present application provides the use of a high efficiency nitriding reagent as described above, said use comprising nitriding a substrate in the presence of a high efficiency nitriding reagent as described above to obtain a nitrided substrate; here, the substrate includes, but is not limited to: ketones, aldehydes, acetylenes, alkylaromatics, or aromatics.

In some embodiments of the present application, the ketone compound is preferably a compound of formula (I):

obtaining a corresponding nitrified substrate as shown in a formula (II) or a formula (III):

here, R in the formulae (I), (II) and (III)₁Selected from the group consisting of alkyl, unsubstituted arylalkyl, substituted arylalkyl, unsubstituted heteroaryl, and substituted heteroaryl; r in the formulae (I) and (II)₂Selected from the group consisting of unsubstituted C1-C6 alkyl, substituted C1-C6 alkyl, unsubstituted aryl, substituted aryl, unsubstituted heteroaryl, and substituted heteroaryl; or R₁And R₂Linked to form a C4-C16 alkylene group; alternatively, said R₁And R₂Or NH₂Is the residue of an organic compound which at least simultaneously comprises R as defined above₁And R₂。

In some embodiments of the present application, the aldehyde compound is a compound of formula (IV):

obtaining a corresponding nitrified substrate as shown in formula (V) or as shown in formula (VI):

here, R in the formulae (IV), (V) and (VI)₃Selected from the group consisting of alkyl, unsubstituted arylalkyl, substituted arylalkyl, unsubstituted heteroaryl, and substituted heteroaryl; alternatively, said R₃Is the residue of an organic compound comprising at least R as defined above₃。

In some embodiments of the present application, the acetylenic compound is a compound of formula (VII):

obtaining the corresponding nitrified substrate as a compound of formula (VIII):

here, R in the formulae (VII) and (VIII)₄Selected from the group consisting of alkyl, unsubstituted arylalkyl, substituted arylalkyl, unsubstituted heteroaryl, and substituted heteroaryl; r in the formulae (VII) and (VIII)₅Selected from the group consisting of unsubstituted C1-C6 alkyl, substituted C1-C6 alkyl, unsubstituted aryl, substituted aryl, unsubstituted heteroaryl, and substituted heteroaryl; or R₄And R₅Linked to form a C11-C16 alkylene group; alternatively, said R₄And R₅Is the residue of an organic compound which at least simultaneously comprises R as defined above₄And R₅。

In an embodiment of the present application, the use of the above high efficiency nitriding reagent further comprises oxidizing the substrate using a one-pot process and nitriding in the presence of the above high efficiency nitriding reagent, thereby obtaining an oxidatively nitrided substrate; here, the substrate is a compound represented by the formula (IX):

the substrate of oxidative nitridation is a compound shown as a formula (X) or a compound shown as a formula (XI):

wherein Ar in formula (IX), formula (X) and formula (XI) is selected from the group consisting of alkyl, unsubstituted aryl, substituted aryl, unsubstituted heteroaryl, and substituted heteroaryl; r in the formulae (IX) and (X)₆Selected from the group consisting of hydrogen, unsubstituted C1-C6 alkyl, substituted C1-C6 alkyl, unsubstituted aryl, substituted aryl, unsubstituted heteroaryl, and substituted heteroaryl; optionally, Ar and R are₆Is the residue of an organic compound comprising at least Ar and R as defined above simultaneously₆。

In the method, the reaction substrate reacts for 4 to 36 hours at 40 to 120 ℃ in the atmosphere of the nitriding reagent, the activating reagent and the reducing agent in the organic solvent solution in air.

In an embodiment of the present application, said R₁And R₂Or NH₂、R₃With CN or NH₂、R₄And R₅And Ar and R₆Or NH₂Optionally a residue of a pharmaceutical compound or intermediate compound thereof, or of an organic catalyst or intermediate compound thereof, which pharmaceutical compound or intermediate compound, or of an organic catalyst or intermediate compound thereof, comprises at least simultaneously R₁And R₂、R₃、R₄And R₅Or Ar and R₆；

For example,

in embodiments herein, the alkyl group may be a C1-C22 alkyl group, substituted or unsubstituted; for example, unsubstituted C1-C6 alkyl groups or substituted C1-C6 alkyl groups.

In embodiments herein, the unsubstituted C1-C6 alkanyl group refers to methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, tert-butyl, n-pentyl, or n-hexyl.

The substituted C1-C6 alkyl refers to the C1-C6 alkyl is substituted by one or more of the following groups: halogen, nitro, hydroxy, carboxyl, C1-C3 alkoxy, and the like.

The unsubstituted aromatic hydrocarbon group is phenyl or naphthyl;

the substituted aryl radical refers to phenyl or naphthyl, and is substituted by one or more of the following groups at any position on the benzene ring: halogen, nitro, hydroxy, carboxyl, C1-C3 alkoxy, and the like.

The unsubstituted heteroaryl group refers to an aryl group including one or more ring heteroatoms selected from nitrogen, oxygen, and sulfur, and illustrative examples include, but are not limited to: pyrrole, furan, thiophene, thiazole, isothiazole, imidazole, triazole, tetrazole, pyrazole, oxazole, isoxazole, pyridine, pyrazine, pyridazine, pyrimidine, and the like.

The substituted heteroaryl refers to the unsubstituted heteroaryl substituted at any position on the ring with one or more of the following groups: halogen, nitro, hydroxy, carboxyl, C1-C3 alkoxy, and the like.

Additional features and advantages of the invention will be set forth in the description which follows, and in part will be obvious from the description, or may be learned by practice of the invention. The objectives and other advantages of the invention will be realized and attained by the structure particularly pointed out in the written description and claims hereof.

Detailed Description

Hereinafter, embodiments of the present invention will be described in detail in order to make the objects, technical solutions and advantages of the present invention more apparent. It should be noted that the embodiments and features of the embodiments in the present application may be arbitrarily combined with each other without conflict.

Determination of MS using an agilent (esi) mass spectrometer, manufacturer: agilent, model: the high resolution mass spectrum prepared by Agilent 6120B is recorded by a PE SCLEX QSTAR spectrometer.

Nuclear magnetic hydrogen and carbon spectra were recorded using a Bruker avil-400 spectrometer.

Purifying by thin layer chromatography using GF254(0.4-0.5nm) silica gel plate.

The reaction was monitored by Thin Layer Chromatography (TLC) using a developing reagent system including, but not limited to: the volume ratio of the solvent is adjusted according to the compound, but a small amount of triethylamine and the like can be added for adjustment.

The sodium hydroxide solution in the examples is a 2M aqueous sodium hydroxide solution, unless otherwise specified; the amount of ethyl acetate used for extraction can be 5ml each time; the brine was saturated aqueous sodium chloride.

The reagents used in the examples were purchased from Acros, Aldrich Chemical Company or carbofuran, among others.

EXAMPLE 1 Synthesis of N-Phenylisobutylamides

a) A reaction tube was charged with 60-100mg (1.2mmol) of nitromethane, 40-60mg (0.3mmol) of isobutyrophenone, 0.5mL of carbon tetrachloride, 169mg of trifluoromethanesulfonic anhydride and 35mg of formic acid, and the mixture was stirred at 100 ℃ for 12 hours. After the reaction is finished, 10mL of sodium hydroxide solution is added to quench the reaction, ethyl acetate is used for extraction for 3 times, 5mL of saline is added to the organic phase for washing, the organic phase is combined, and column chromatography separation is carried out to obtain 17.6mg of N-phenyl isobutyl amide with the yield of 36%.

b) A reaction tube is taken, 60-100mg (1.2mmol) of nitromethane, 40-60mg (0.3mmol) of isobutyrophenone, 0.5mL of carbon tetrachloride, 61mg of acetic anhydride and 35mg of formic acid are added, and stirring is carried out at 100 ℃ for 12 hours. After the reaction is finished, 10mL of sodium hydroxide solution is added to quench the reaction, ethyl acetate is used for extraction for 3 times, 5mL of organic phase saline is added for washing, organic phases are combined, and the N-phenyl isobutyl amide is obtained by column chromatography separation, wherein the yield is 0 mg.

c) A reaction tube is taken, 60-100mg (1.2mmol) of nitromethane, 40-60mg (0.3mmol) of isobutyrophenone, 0.5mL of carbon tetrachloride, 126mg of trifluoroacetic anhydride and 35mg of formic acid are added, and stirring is carried out at 100 ℃ for 12 hours. After the reaction is finished, 10mL of sodium hydroxide solution is added to quench the reaction, ethyl acetate is used for extraction for 3 times, 5mL of organic phase saline is added for washing, organic phases are combined, and the N-phenyl isobutyl amide is obtained by column chromatography separation, wherein the yield is 0 mg.

d) A reaction tube is taken, 60-100mg (1.2mmol) of nitromethane, 40-60mg (0.3mmol) of isobutyrophenone, 0.5mL of carbon tetrachloride, 68.4mg of trifluoroacetic acid and 35mg of formic acid are added, and the mixture is stirred at 100 ℃ for 12 hours. After the reaction is finished, 10mL of sodium hydroxide solution is added to quench the reaction, ethyl acetate is used for extraction for 3 times, 5mL of organic phase saline is added for washing, organic phases are combined, and the N-phenyl isobutyl amide is obtained by column chromatography separation, wherein the yield is 0 mg.

e) A reaction tube was charged with 60-100mg (1.2mmol) of nitromethane, 40-60mg (0.3mmol) of isobutyrophenone, 0.5mL of carbon tetrachloride, 57.6mg of methanesulfonic acid and 35mg of formic acid, and the mixture was stirred at 100 ℃ for 12 hours. After the reaction is finished, 10mL of sodium hydroxide solution is added to quench the reaction, ethyl acetate is used for extraction for 3 times, 5mL of organic phase saline is added for washing, organic phases are combined, and the N-phenyl isobutyl amide is obtained by column chromatography separation, wherein the yield is 0 mg.

f) A reaction tube was taken, 60-100mg (1.2mmol) of nitromethane, 40-60mg (0.3mmol) of isobutyrophenone, 0.5mL of carbon tetrachloride, 90mg of trifluoromethanesulfonic acid and 35mg of formic acid were added, and the mixture was stirred at 100 ℃ for 12 hours. After the reaction is finished, 10mL of sodium hydroxide solution is added to quench the reaction, ethyl acetate is used for extraction for 3 times, 5mL of organic phase saline is added for washing, organic phases are combined, and the N-phenyl isobutyl amide is obtained by column chromatography separation, wherein the yield is 10%.

g) A reaction tube was charged with 60-100mg (1.2mmol) of nitromethane, 40-60mg (0.3mmol) of isobutyrophenone, 0.5mL of carbon tetrachloride, 76.2mg of oxalyl chloride and 35mg of formic acid, and the mixture was stirred at 100 ℃ for 12 hours. After the reaction is finished, 10mL of sodium hydroxide solution is added to quench the reaction, ethyl acetate is used for extraction for 3 times, 5mL of organic phase saline is added for washing, organic phases are combined, and the N-phenyl isobutyl amide is obtained by column chromatography separation, wherein the yield is 0 mg.

h) A reaction tube is taken, 60-100mg (1.2mmol) of nitromethane, 40-60mg (0.3mmol) of isobutyrophenone, 0.5mL of carbon tetrachloride and 35mg of formic acid are added, and the mixture is stirred at 100 ℃ for 12 hours. After the reaction is finished, 10mL of sodium hydroxide solution is added to quench the reaction, ethyl acetate is used for extraction for 3 times, 5mL of organic phase saline is added for washing, organic phases are combined, and the N-phenyl isobutyl amide is obtained by column chromatography separation, wherein the yield is 0 mg.

i) A reaction tube is taken, 60-100mg (1.2mmol) of nitromethane, 40-60mg (0.3mmol) of isobutyrophenone, 0.5mL of carbon tetrachloride, 169mg of trifluoromethanesulfonic anhydride and 51mg of sodium formate are added, and stirring is carried out at 100 ℃ for 12 hours. After the reaction is finished, 10mL of sodium hydroxide solution is added to quench the reaction, ethyl acetate is used for extraction for 3 times, 5mL of organic phase saline is added for washing, organic phases are combined, and column chromatography separation is carried out to obtain 9mg of N-phenyl isobutyl amide with the yield of 18%.

j) A reaction tube was charged with 60-100mg (1.2mmol) of nitromethane, 40-60mg (0.3mmol) of isobutyrophenone, 0.5mL of carbon tetrachloride, 169mg of trifluoromethanesulfonic anhydride, and 81mg of phenylsilicone, and the mixture was stirred at 100 ℃ for 12 hours. After the reaction is finished, 10mL of sodium hydroxide solution is added to quench the reaction, ethyl acetate is used for extraction for 3 times, 5mL of organic phase saline is added for washing, organic phases are combined, and the N-phenyl isobutyl amide is obtained by column chromatography separation, wherein the yield is 0 mg.

k) A reaction tube was charged with 60 to 100mg (1.2mmol) of nitromethane, 40 to 60mg (0.3mmol) of isobutyrophenone, 0.5mL of carbon tetrachloride, 169mg of trifluoromethanesulfonic anhydride, and 87mg of triethylsilane hydride, and stirred at 100 ℃ for 12 hours. After the reaction is finished, 10mL of sodium hydroxide solution is added to quench the reaction, ethyl acetate is used for extraction for 3 times, 5mL of organic phase saline is added for washing, organic phases are combined, and the N-phenyl isobutyl amide is obtained by column chromatography separation, wherein the yield is 0 mg.

l) A reaction tube was charged with 60 to 100mg (1.2mmol) of nitromethane, 40 to 60mg (0.3mmol) of isobutyrophenone, 0.5mL of carbon tetrachloride, 169mg of trifluoromethanesulfonic anhydride, 28.5mg of sodium borohydride, and stirred at 100 ℃ for 12 hours. After the reaction is finished, 10mL of sodium hydroxide solution is added to quench the reaction, ethyl acetate is used for extraction for 3 times, 5mL of organic phase saline is added for washing, organic phases are combined, and the N-phenyl isobutyl amide is obtained by column chromatography separation, wherein the yield is 0 mg.

m) taking a reaction tube, adding 60-100mg (1.2mmol) of nitromethane, 40-60mg (0.3mmol) of isobutyrophenone, 0.5mL of carbon tetrachloride, 169mg of trifluoromethanesulfonic anhydride and 47.3mg of ammonium formate, and stirring at 100 ℃ for 12 hours. After the reaction is finished, 10mL of sodium hydroxide solution is added to quench the reaction, ethyl acetate is used for extraction for 3 times, 5mL of organic phase saline is added for washing, organic phases are combined, and the N-phenyl isobutyl amide 10mg and the yield are 20% are obtained through column chromatography separation.

n) taking a reaction tube, adding 60-100mg (1.2mmol) of nitromethane, 40-60mg (0.3mmol) of isobutyrophenone, 0.5mL of carbon tetrachloride, 169mg of trifluoromethanesulfonic anhydride, 190mg of 2, 6-dimethyl-1, 4-dihydropyridine-3, 5-dicarboxylic acid ethyl ester acetic acid, and stirring at 100 ℃ for 12 hours. After the reaction is finished, 10mL of sodium hydroxide solution is added to quench the reaction, ethyl acetate is used for extraction for 3 times, 5mL of organic phase saline is added for washing, organic phases are combined, and the N-phenyl isobutyl amide is obtained by column chromatography separation, wherein the yield is 0 mg.

o) A reaction tube was charged with 60 to 100mg (1.2mmol) of nitromethane, 40 to 60mg (0.3mmol) of isobutyrophenone, 0.5mL of carbon tetrachloride and 169mg of trifluoromethanesulfonic anhydride, and the mixture was stirred at 100 ℃ for 12 hours. After the reaction is finished, 10mL of sodium hydroxide solution is added to quench the reaction, ethyl acetate is used for extraction for 3 times, 5mL of organic phase saline is added for washing, organic phases are combined, and the N-phenyl isobutyl amide is obtained by column chromatography separation, wherein the yield is 0 mg.

p) A reaction tube was charged with 60 to 100mg (1.2mmol) of nitromethane, 40 to 60mg (0.3mmol) of isobutyrophenone, 0.5mL of hexafluoroisopropanol, 169mg of trifluoromethanesulfonic anhydride, and 35mg of formic acid, and the mixture was stirred at 100 ℃ for 12 hours. After the reaction is finished, 10mL of sodium hydroxide solution is added to quench the reaction, ethyl acetate is used for extraction for 3 times, 5mL of organic phase saline is added for washing, organic phases are combined, and column chromatography separation is carried out to obtain 11mg of N-phenyl isobutyl amide with the yield of 22%.

q) taking a reaction tube, adding 60-100mg (1.2mmol) of nitromethane, 40-60mg (0.3mmol) of isobutyrophenone, 0.5mL of trifluoroethanol, 169mg of trifluoromethanesulfonic anhydride and 35mg of formic acid, and stirring at 100 ℃ for 12 hours. After the reaction is finished, 10mL of sodium hydroxide solution is added to quench the reaction, ethyl acetate is used for extraction for 3 times, 5mL of saline is added to the organic phase for washing, the organic phase is combined, and column chromatography separation is carried out to obtain 4.4mg of N-phenyl isobutyl amide with the yield of 9%.

r) A reaction tube was charged with 60 to 100mg (1.2mmol) of nitromethane, 40 to 60mg (0.3mmol) of isobutyrophenone, 0.5mL of 1, 2-dichloroethane, 169mg of trifluoromethanesulfonic anhydride, 35mg of formic acid, and stirred at 100 ℃ for 12 hours. After the reaction is finished, 10mL of sodium hydroxide solution is added to quench the reaction, ethyl acetate is used for extraction for 3 times, 5mL of organic phase saline is added for washing, organic phases are combined, and the N-phenyl isobutyl amide is obtained by column chromatography separation, wherein the yield is 28%.

s) A reaction tube was charged with 60 to 100mg (1.2mmol) of nitromethane, 40 to 60mg (0.3mmol) of isobutyrophenone, 0.5mL of acetonitrile, 169mg of trifluoromethanesulfonic anhydride and 35mg of formic acid, and the mixture was stirred at 100 ℃ for 12 hours. After the reaction is finished, 10mL of sodium hydroxide solution is added to quench the reaction, ethyl acetate is used for extraction for 3 times, 5mL of organic phase saline is added for washing, organic phases are combined, and the N-phenyl isobutyl amide is obtained by column chromatography separation, wherein the yield is 0 mg.

t) A reaction tube was charged with 60 to 100mg (1.2mmol) of nitromethane, 40 to 60mg (0.3mmol) of isobutyrophenone, 0.5mL of nitromethane, 169mg of trifluoromethanesulfonic anhydride and 35mg of formic acid, and the mixture was stirred at 100 ℃ for 12 hours. After the reaction is finished, 10mL of sodium hydroxide solution is added to quench the reaction, ethyl acetate is used for extraction for 3 times, 5mL of organic phase saline is added for washing, organic phases are combined, and the N-phenyl isobutyl amide is obtained through column chromatography separation, wherein the yield is 27%.

u) A reaction tube was charged with 60 to 100mg (1.2mmol) of nitromethane, 40 to 60mg (0.3mmol) of isobutyrophenone, 0.5mL of chlorobenzene, 169mg of trifluoromethanesulfonic anhydride, 35mg of formic acid, and stirred at 100 ℃ for 12 hours. After the reaction is finished, 10mL of sodium hydroxide solution is added to quench the reaction, ethyl acetate is used for extraction for 3 times, 5mL of organic phase saline is added for washing, organic phases are combined, and column chromatography separation is carried out to obtain 13mg of N-phenyl isobutyl amide with the yield of 26%.

v) taking a reaction tube, adding 60-100mg (1.2mmol) of nitromethane, 40-60mg (0.3mmol) of isobutyrophenone, 0.5mL of ethanol, 169mg of trifluoromethanesulfonic anhydride and 35mg of formic acid, and stirring at 100 ℃ for 12 hours. After the reaction is finished, 10mL of sodium hydroxide solution is added to quench the reaction, ethyl acetate is used for extraction for 3 times, 5mL of organic phase saline is added for washing, organic phases are combined, and the N-phenyl isobutyl amide is obtained by column chromatography separation, wherein the yield is 0 mg.

w) taking a reaction tube, adding 60-100mg (1.2mmol) of nitromethane, 40-60mg (0.3mmol) of isobutyrophenone, 0.5mL of carbon tetrachloride, 169mg of trifluoromethanesulfonic anhydride and 35mg of formic acid, and stirring at 100 ℃ for 12 hours. After the reaction is finished, 10mL of sodium hydroxide solution is added to quench the reaction, ethyl acetate is used for extraction for 3 times, 5mL of saline is added to the organic phase for washing, the organic phase is combined, and column chromatography separation is carried out to obtain 24.5mg of N-phenyl isobutyl amide with the yield of 50%.

Example 2 acetanilide

A reaction tube is taken, 60-100mg (1.2mmol) of nitromethane, 30-40mg (0.3mmol) of acetophenone, 0.5mL of acetic acid, 150 mg (0.6mmol) of trifluoromethanesulfonic anhydride and 30-60mg (0.75mmol) of formic acid are added, and the mixture is stirred for 1-72 hours at 80-120 ℃. After the reaction is finished, 10mL of sodium hydroxide solution is added to quench the reaction, ethyl acetate is used for extraction for 3 times, 5mL of saline is added to the organic phase for washing, the organic phase is combined, and the acetanilide 28.4mg is obtained through column chromatography separation, wherein the yield is 70%.

Example 3 Paramethylacetanilide

a) The method comprises the following steps A reaction tube is taken, 60-100mg (1.2mmol) of nitromethane, 35-45mg (0.3mmol) of p-methylacetophenone, 0.5mL of acetic acid, 150 mg (0.6mmol) of trifluoromethanesulfonic anhydride and 30-60mg (0.75mmol) of formic acid are added, and the mixture is stirred for 1-72 hours at 80-120 ℃. After the reaction is finished, 10mL of sodium hydroxide solution is added to quench the reaction, ethyl acetate is used for extraction for 3 times, 5mL of saline is added to the organic phase for washing, the organic phase is combined, and column chromatography separation is carried out to obtain 31.3mg of p-methylacetanilide with the yield of 70%.

b) Taking a reaction tube, adding 60-100mg (1.2mmol) of nitromethane, 35-45mg (0.3mmol) of p-methylacetophenone, 0.5mL of acetic acid, 70-100mg (0.6mmol) of sulfonyl chloride and 30-60mg (0.75mmol) of formic acid, and stirring at 80-120 ℃ for 1-72 hours. After the reaction is finished, 10mL of sodium hydroxide solution is added to quench the reaction, ethyl acetate is used for extraction for 3 times, 5mL of organic phase saline is added for washing, organic phases are combined, and column chromatography separation is carried out to obtain 9mg of p-methylacetanilide with the yield of 20%.

c) Taking a reaction tube, adding 60-100mg (1.2mmol) of nitromethane, 35-45mg (0.3mmol) of p-methylacetophenone, 0.5mL of acetic acid, 60-100mg (0.6mmol) of chlorosulfonic acid and 30-60mg (0.75mmol) of formic acid, and stirring at 80-120 ℃ for 1-72 hours. After the reaction is finished, 10mL of sodium hydroxide solution is added to quench the reaction, ethyl acetate is used for extraction for 3 times, 5mL of organic phase saline is added for washing, organic phases are combined, and column chromatography separation is carried out to obtain 22mg of p-methylacetanilide with the yield of 50%.

d) Taking a reaction tube, adding 60-100mg (1.2mmol) of nitromethane, 35-45mg (0.3mmol) of p-methylacetophenone, 0.5mL of acetic acid, 60-100mg (0.6mmol) of 98% concentrated sulfuric acid and 30-60mg (0.75mmol) of formic acid, and stirring at 80-120 ℃ for 1-72 hours. After the reaction is finished, 10mL of sodium hydroxide solution is added to quench the reaction, ethyl acetate is used for extraction for 3 times, 5mL of organic phase saline is added for washing, organic phases are combined, and column chromatography separation is carried out to obtain 22mg of p-methylacetanilide with the yield of 50%.

e) Adding 35-45mg (0.3mmol) of p-methylacetophenone, 0.5mL of nitromethane, 60-100mg (0.6mmol) of 98% concentrated sulfuric acid and 30-60mg (0.75mmol) of formic acid into a reaction tube, and stirring at 80-120 ℃ for 1-72 hours. After the reaction is finished, 10mL of sodium hydroxide solution is added to quench the reaction, ethyl acetate is used for extraction for 3 times, 5mL of saline is added to the organic phase for washing, the organic phase is combined, column chromatography separation is carried out to obtain 35mg of p-methylacetanilide, and the yield is 78%.

Example 4 p-n-butylacetanilide

A reaction tube was taken, and 60-100mg (1.2mmol) of nitromethane, 50-60mg (0.3mmol) of p-n-butylacetophenone, 0.5mL of acetic acid, 200mg (0.6mmol) of trifluoromethanesulfonic anhydride, 30-60mg (0.75mmol) of formic acid were added, and the mixture was stirred at 80-120 ℃ for 1-72 hours. After the reaction is finished, 10mL of sodium hydroxide solution is added to quench the reaction, ethyl acetate is used for extraction for 3 times, 5mL of organic phase saline is added for washing, organic phases are combined, and column chromatography separation is carried out to obtain 40.1mg of n-butylacetanilide with the yield of 70%.

Example 5P-Phenylacetanilide

a) Taking a reaction tube, adding 0.5mL of nitromethane, 53-63mg (0.3mmol) of p-phenylacetophenone, 0.5mL of acetic acid, 5-15mg (0.03mmol) of tert-butyldimethylsilyl trifluoromethanesulfonate and 1545-55mg of Amberlyst, and stirring at 80-120 ℃ for 1-72 hours. After the reaction is finished, 10mL of sodium hydroxide solution is added to quench the reaction, ethyl acetate is used for extraction for 3 times, 5mL of organic phase saline is added for washing, organic phases are combined, column chromatography separation is carried out to obtain 55.8mg of p-phenylacetanilide, and the yield is 88%.

b) Taking a reaction tube, adding 0.5mL of nitromethane, 53-63mg (0.3mmol) of p-phenylacetophenone, 0.5mL of acetic acid and 5-15mg (0.03mmol) of tert-butyldimethylsilyl trifluoromethanesulfonate into the reaction tube,45-55mg of 50WX2 hydrogen type acidic cation exchange resin is stirred for 1-72 hours at 80-120 ℃. After the reaction, 10mL of sodium hydroxide solution was added to quench the reaction, which was extracted 3 times with ethyl acetate and washed with 5mL of organic phase brineWashing, combining organic phases, and performing column chromatography separation to obtain 52.6mg of p-phenylacetanilide with the yield of 83%.

c) Taking a reaction tube, adding 0.5mL of nitromethane, 53-63mg (0.3mmol) of p-phenylacetophenone, 0.5mL of acetic acid, 5-15mg (0.03mmol) of tert-butyldimethylsilyl trifluoromethanesulfonate and 45-55mg (0.06mmol) of phosphotungstic acid, and stirring at 80-120 ℃ for 1-72 hours. After the reaction is finished, 10mL of sodium hydroxide solution is added to quench the reaction, ethyl acetate is used for extraction for 3 times, 5mL of organic phase saline is added for washing, organic phases are combined, and column chromatography separation is carried out to obtain 44.3mg of p-phenylacetanilide, wherein the yield is 70%.

d) Taking a reaction tube, adding 0.5mL of nitromethane, 53-63mg (0.3mmol) of p-phenylacetophenone, 0.5mL of acetic acid, 5-15mg (0.03mmol) of tert-butyldimethylsilyl trifluoromethanesulfonate and 5-15mg (0.06mmol) of trifluoromethanesulfonate into the reaction tube, and stirring the mixture at the temperature of 80-120 ℃ for 1-72 hours. After the reaction is finished, 10mL of sodium hydroxide solution is added to quench the reaction, ethyl acetate is used for extraction for 3 times, 5mL of organic phase saline is added for washing, organic phases are combined, and column chromatography separation is carried out to obtain 40.5mg of p-phenylacetanilide with the yield of 64%.

e) Taking a reaction tube, adding 0.5mL of nitromethane, 53-63mg (0.3mmol) of p-phenylacetophenone, 0.5mL of acetic acid, 5-15mg (0.03mmol) of tert-butyldimethylsilyl trifluoromethanesulfonate and 5-15mg (0.06mmol) of 98% concentrated sulfuric acid, and stirring at 80-120 ℃ for 1-72 hours. After the reaction is finished, 10mL of sodium hydroxide solution is added to quench the reaction, ethyl acetate is used for extraction for 3 times, 5mL of organic phase saline is added for washing, organic phases are combined, and column chromatography separation is carried out to obtain 31.6mg of p-phenylacetanilide with the yield of 50%.

f) Taking a reaction tube, adding 0.5mL of nitromethane, 53-63mg (0.3mmol) of p-phenylacetophenone, 0.5mL of acetic acid, 5-15mg (0.03mmol) of trimethylsilyl trifluoromethanesulfonate and 1545-55mg of Amberlyst, and stirring at 80-120 ℃ for 1-72 hours. After the reaction is finished, 10mL of sodium hydroxide solution is added to quench the reaction, ethyl acetate is used for extraction for 3 times, 5mL of saline is added to the organic phase for washing, the organic phase is combined, and column chromatography separation is carried out to obtain 45.5mg of p-phenylacetanilide with the yield of 72%.

g) Taking a reaction tube, adding 0.5mL of nitromethane, 53-63mg (0.3mmol) of p-phenylacetophenone, 0.5mL of acetic acid, 5-15mg (0.03mmol) of triethylsilyl trifluoromethanesulfonate and 1545-55mg of Amberlyst, and stirring at 80-120 ℃ for 1-72 hours. After the reaction is finished, 10mL of sodium hydroxide solution is added to quench the reaction, ethyl acetate is used for extraction for 3 times, 5mL of organic phase saline is added for washing, organic phases are combined, and column chromatography separation is carried out to obtain 40.5mg of p-phenylacetanilide with the yield of 64%.

h) Taking a reaction tube, adding 0.5mL of nitromethane, 53-63mg (0.3mmol) of p-phenylacetophenone, 0.5mL of acetic acid, 5-15mg (0.03mmol) of triisopropylsilyl trifluoromethanesulfonate and 1545-55mg of Amberlyst, and stirring at 80-120 ℃ for 1-72 hours. After the reaction is finished, 10mL of sodium hydroxide solution is added to quench the reaction, ethyl acetate is used for extraction for 3 times, 5mL of organic phase saline is added for washing, organic phases are combined, and column chromatography separation is carried out to obtain 31.5mg of p-phenylacetanilide with the yield of 50%.

i) Taking a reaction tube, adding 60-100mg (1.2mmol) of nitromethane, 50-60mg (0.3mmol) of p-phenylacetophenone, 0.5mL of acetic acid, 150 mg (0.6mmol) of trifluoromethanesulfonic anhydride and 30-60mg (0.75mmol) of formic acid, and stirring at 80-120 ℃ for 1-72 hours. After the reaction is finished, 10mL of sodium hydroxide solution is added to quench the reaction, ethyl acetate is used for extraction for 3 times, 5mL of organic phase saline is added for washing, organic phases are combined, and column chromatography separation is carried out to obtain 40.1mg of p-phenylacetanilide, wherein the yield is 70%.

Example 6 Paramethoxyacetanilide

A reaction tube is taken, 60-100mg (1.2mmol) of nitromethane, 40-50mg (0.3mmol) of p-methoxyacetophenone, 0.5mL of acetic acid, 200mg (0.6mmol) of trifluoromethanesulfonic anhydride and 30-60mg (0.75mmol) of formic acid are added, and the mixture is stirred for 1-72 hours at 80-120 ℃. After the reaction is finished, 10mL of sodium hydroxide solution is added to quench the reaction, ethyl acetate is used for extraction for 3 times, 5mL of saline is added to the organic phase for washing, the organic phase is combined, column chromatography separation is carried out to obtain 39.1mg of p-methoxyacetanilide, and the yield is 79%.

Example 7 Bromoacetanilide

A reaction tube is taken, 60-100mg (1.2mmol) of nitromethane, 55-65mg (0.3mmol) of p-bromoacetophenone, 0.5mL of acetic acid, 200mg (0.6mmol) of trifluoromethanesulfonic anhydride and 30-60mg (0.75mmol) of formic acid are added, and the mixture is stirred for 1-72 hours at 80-120 ℃. After the reaction is finished, 10mL of sodium hydroxide solution is added to quench the reaction, ethyl acetate is used for extraction for 3 times, 5mL of saline is added to the organic phase for washing, the organic phase is combined, column chromatography separation is carried out to obtain 39.6mg of p-bromoacetanilide, and the yield is 62%.

Example 8 Parafluoroacetanilides

A reaction tube is taken, 60-100mg (1.2mmol) of nitromethane, 35-45mg (0.3mmol) of p-fluoroacetophenone, 0.5mL of acetic acid, 150 mg (0.6mmol) of trifluoromethanesulfonic anhydride and 30-60mg (0.75mmol) of formic acid are added, and the mixture is stirred at 80-120 ℃ for 1-72 hours. After the reaction is finished, 10mL of sodium hydroxide solution is added to quench the reaction, ethyl acetate is used for extraction for 3 times, 5mL of saline is added to the organic phase for washing, the organic phase is combined, and column chromatography separation is carried out to obtain 34.4mg of p-fluoroacetanilide with the yield of 75%.

Example 9 Paracetanilide

A reaction tube is taken, 60-100mg (1.2mmol) of nitromethane, 35-45mg (0.3mmol) of p-aminoacetophenone, 0.5mL of acetic acid, 150 mg (0.6mmol) of trifluoromethanesulfonic anhydride and 30-60mg (0.75mmol) of formic acid are added, and the mixture is stirred for 1-72 hours at 80-120 ℃. After the reaction is finished, 10mL of sodium hydroxide solution is added to quench the reaction, ethyl acetate is used for extraction for 3 times, 5mL of saline is added to the organic phase for washing, the organic phase is combined, and column chromatography separation is carried out to obtain 22.5mg of p-aminoacetanilide with the yield of 50%.

Example 10 Parahydroxyacetanilide

A reaction tube is taken, 60-100mg (1.2mmol) of nitromethane, 35-45mg (0.3mmol) of p-hydroxyacetophenone, 0.5mL of acetic acid, 150 mg (0.6mmol) of trifluoromethanesulfonic anhydride and 30-60mg (0.75mmol) of formic acid are added, and the mixture is stirred for 1-72 hours at 80-120 ℃. After the reaction is finished, 10mL of sodium hydroxide solution is added to quench the reaction, ethyl acetate is used for extraction for 3 times, 5mL of saline is added to the organic phase for washing, the organic phase is combined, column chromatography separation is carried out to obtain 38.5mg of p-hydroxyacetanilide, and the yield is 85%.

Example 11 Paramethylthioacetanilide

A reaction tube is taken, 60-100mg (1.2mmol) of nitromethane, 45-55mg (0.3mmol) of p-methylthioacetophenone, 0.5mL of acetic acid, 150 mg (0.6mmol) of trifluoromethanesulfonic anhydride and 30-60mg (0.75mmol) of formic acid are added, and the mixture is stirred at 80-120 ℃ for 1-72 hours. After the reaction is finished, 10mL of sodium hydroxide solution is added to quench the reaction, ethyl acetate is used for extraction for 3 times, 5mL of organic phase saline is used for washing, organic phases are combined, and column chromatography separation is carried out to obtain 21.7mg of p-methylthioacetanilide with the yield of 40%.

Example 12 o-Methoxyacetanilide

A reaction tube is taken and added with 60-100mg (1.2mmol) of nitromethane, 40-50mg (0.3mmol) of o-methoxyacetophenone, 0.5mL of acetic acid, 200mg (0.6mmol) of trifluoromethanesulfonic anhydride and 30-60mg (0.75mmol) of formic acid, and stirred for 1-72 hours at 80-120 ℃. After the reaction is finished, 10mL of sodium hydroxide solution is added to quench the reaction, ethyl acetate is used for extraction for 3 times, 5mL of saline is added to the organic phase for washing, the organic phase is combined, and column chromatography separation is carried out to obtain 14.9mg of o-methoxyacetanilide with the yield of 30%.

Example 13 o-methylacetanilide

A reaction tube is taken, 60-100mg (1.2mmol) of nitromethane, 35-45mg (0.3mmol) of o-methylacetophenone, 0.5mL of acetic acid, 150 mg (0.6mmol) of trifluoromethanesulfonic anhydride and 30-60mg (0.75mmol) of formic acid are added, and the mixture is stirred for 1-72 hours at 80-120 ℃. After the reaction is finished, 10mL of sodium hydroxide solution is added to quench the reaction, ethyl acetate is used for extraction for 3 times, 5mL of saline is added to the organic phase for washing, the organic phase is combined, and column chromatography separation is carried out to obtain 32.2mg of o-methylacetanilide with the yield of 72%.

Example 14 o-Bromoacetylphenylamine

A reaction tube is taken and added with 60-100mg (1.2mmol) of nitromethane, 55-65mg (0.3mmol) of o-bromoacetophenone, 0.5mL of acetic acid, 200mg (0.6mmol) of trifluoromethanesulfonic anhydride, 30-60mg (0.75mmol) of formic acid, and stirred for 1-72 hours at 80-120 ℃. After the reaction is finished, 10mL of sodium hydroxide solution is added to quench the reaction, ethyl acetate is used for extraction for 3 times, 5mL of organic phase saline is added for washing, organic phases are combined, column chromatography separation is carried out to obtain 28.8mg of o-bromoacetamidine, and the yield is 45%.

Example 15O-fluoroacetanilides

A reaction tube is taken, 60-100mg (1.2mmol) of nitromethane, 35-45mg (0.3mmol) of o-fluoroacetophenone, 0.5mL of acetic acid, 150 mg (0.6mmol) of trifluoromethanesulfonic anhydride and 30-60mg (0.75mmol) of formic acid are added, and the mixture is stirred at 80-120 ℃ for 1-72 hours. After the reaction is finished, 10mL of sodium hydroxide solution is added to quench the reaction, ethyl acetate is used for extraction for 3 times, 5mL of saline is added to the organic phase for washing, the organic phase is combined, column chromatography separation is carried out to obtain 23.4mg of o-fluoroacetanilide, and the yield is 51%.

Example 16 m-methoxyacetanilide

A reaction tube is taken, 60-100mg (1.2mmol) of nitromethane, 40-50mg (0.3mmol) of m-methoxyacetophenone, 0.5mL of acetic acid, 200mg (0.6mmol) of trifluoromethanesulfonic anhydride and 30-60mg (0.75mmol) of formic acid are added, and the mixture is stirred for 1-72 hours at 80-120 ℃. After the reaction is finished, 10mL of sodium hydroxide solution is added to quench the reaction, ethyl acetate is used for extraction for 3 times, 5mL of saline is added to the organic phase for washing, the organic phase is combined, and column chromatography separation is carried out to obtain 13.9mg of m-methoxyacetanilide with the yield of 28%.

Example 17 m-fluoroacetanilide

A reaction tube is taken, 60-100mg (1.2mmol) of nitromethane, 35-45mg (0.3mmol) of m-fluoroacetophenone, 0.5mL of acetic acid, 150 mg (0.6mmol) of trifluoromethanesulfonic anhydride and 30-60mg (0.75mmol) of formic acid are added, and the mixture is stirred at 80-120 ℃ for 1-72 hours. After the reaction is finished, 10mL of sodium hydroxide solution is added to quench the reaction, ethyl acetate is used for extraction for 3 times, 5mL of saline is added to the organic phase for washing, the organic phase is combined, and the m-fluoroacetanilide 25.3mg and the yield is 55% are obtained through column chromatography separation.

Example 18 Metamethylacetanilide

A reaction tube is taken, 60-100mg (1.2mmol) of nitromethane, 35-45mg (0.3mmol) of m-methylacetophenone, 0.5mL of acetic acid, 200mg (0.6mmol) of trifluoromethanesulfonic anhydride and 30-60mg (0.75mmol) of formic acid are added, and the mixture is stirred for 1-72 hours at 80-120 ℃. After the reaction is finished, 10mL of sodium hydroxide solution is added to quench the reaction, ethyl acetate is used for extraction for 3 times, 5mL of organic phase saline is added for washing, organic phases are combined, and column chromatography separation is carried out to obtain 15.2mg of m-methylacetanilide with the yield of 34%.

Example 19M-Chloropropioanilide

Taking a reaction tube, adding 60-100mg (1.2mmol) of nitromethane, 45-55mg (0.3mmol) of m-chloropropiophenone, 0.5mL of acetic acid, 200mg (0.6mmol) of trifluoromethanesulfonic anhydride, 30-60mg (0.75mmol) of formic acid, and stirring at 80-120 ℃ for 1-72 hours. After the reaction is finished, 10mL of sodium hydroxide solution is added to quench the reaction, ethyl acetate is used for extraction for 3 times, 5mL of saline is added to the organic phase for washing, the organic phase is combined, and column chromatography separation is carried out to obtain 34mg of m-chloropropionaniline with the yield of 62%.

¹H NMR(CDCl₃,400MHz):δ7.84(s,1H),7.64(s,1H),7.35(d,J＝8.0Hz,1H),7.19(t,J＝8.1Hz,1H),7.05(d,J＝7.9Hz,1H),2.38(q,J＝7.6Hz,2H),1.22(t,J＝7.6Hz,3H)；¹³C NMR(CDCl₃100MHz) delta 172.59,139.13,134.46,129.84,124.11,120.02,117.86,30.58,9.56 ppm; HRMS m/z (ESI) theoretical value C₉H₁₁NOCl(M+H)⁺184.0529, found 184.0532.

Example 20N- (3, 4-dichlorophenyl) acetamide

A reaction tube is taken, 60-100mg (1.2mmol) of nitromethane, 50-60mg (0.3mmol) of 3, 4-dichloroacetophenone, 0.5mL of acetic acid, 200mg (0.6mmol) of trifluoromethanesulfonic anhydride and 30-60mg (0.75mmol) of formic acid are added, and the mixture is stirred for 1-72 hours at 80-120 ℃. After the reaction is finished, 10mL of sodium hydroxide solution is added to quench the reaction, ethyl acetate is used for extraction for 3 times, 5mL of saline is added to the organic phase for washing, the organic phase is combined, and column chromatography separation is carried out to obtain 37.1mg of N- (3, 4-dichlorophenyl) acetamide with the yield of 61%.

¹H NMR(CDCl₃,400MHz):δ8.09(s,1H),7.73(s,1H),7.35-7.27(m,2H),2.17(s,3H)；¹³C NMR(CDCl₃,100MHz):δ168.99,137.34,132.61,130.39,127.45,121.67,119.20,24.39. ppm; HRMS m/z (ESI) theoretical value C₈H₈NOCl₂(M+H)⁺203.9983, found 203.9986.

Example 213, 4-dimethylacetanilide

A reaction tube is taken, 60-100mg (1.2mmol) of nitromethane, 40-50mg (0.3mmol) of 3, 4-dimethylacetophenone, 0.5mL of acetic acid, 200mg (0.6mmol) of trifluoromethanesulfonic anhydride and 30-60mg (0.75mmol) of formic acid are added, and the mixture is stirred for 1-72 hours at 80-120 ℃. After the reaction is finished, 10mL of sodium hydroxide solution is added to quench the reaction, ethyl acetate is used for extraction for 3 times, 5mL of saline is added to the organic phase for washing, the organic phase is combined, and the 3, 4-dimethylacetanilide 20.1mg is obtained through column chromatography separation, wherein the yield is 41%.

¹H NMR(CDCl₃,400MHz):δ7.63(s,1H),7.27(s,1H),7.20(d,J＝7.9Hz,1H),7.03(d,J＝8.0Hz,1H),2.20(s,6H),2.12(s,3H)；¹³C NMR(CDCl₃100MHz) delta 168.51,137.05,135.62,132.54,129.82,121.44,117.59,24.34,19.78,19.09. ppm; HRMS m/z (ESI) theoretical value C₁₀H₁₄NO(M+H)⁺164.1075, found 164.1078.

Example 22 Pentanylanilide

A reaction tube was taken, and 60-100mg (1.2mmol) of nitromethane, 40-50mg (0.3mmol) of cyclopentanone, 0.5mL of acetic acid, 200mg (0.6mmol) of trifluoromethanesulfonic anhydride, 30-60mg (0.75mmol) of formic acid were added, followed by stirring at 80-120 ℃ for 1-72 hours. After the reaction is finished, 10mL of sodium hydroxide solution is added to quench the reaction, ethyl acetate is used for extraction for 3 times, 5mL of saline is added to the organic phase for washing, the organic phase is combined, and the valeranilide 44.1mg with the yield of 83% is obtained by column chromatography separation.

Example 23 Octananilide

A reaction tube was taken, and 60-100mg (1.2mmol) of nitromethane, 55-65mg (0.3mmol) of benzophenon, 0.5mL of acetic acid, 200mg (0.6mmol) of trifluoromethanesulfonic anhydride, 30-60mg (0.75mmol) of formic acid were added, followed by stirring at 80-120 ℃ for 1-72 hours. After the reaction is finished, 10mL of sodium hydroxide solution is added to quench the reaction, ethyl acetate is used for extraction for 3 times, 5mL of saline is added to the organic phase for washing, the organic phase is combined, and column chromatography separation is carried out to obtain 44.1mg of the octanoyl aniline with the yield of 67%.

¹H NMR(CDCl₃,400MHz):δ7.75(s,1H),7.52(d,J＝7.9Hz,2H),7.28(t,J＝8.5Hz,2H),7.07(t,J＝7.4Hz,1H),2.33(t,J＝7.6Hz,2H),1.70(p,J＝7.4Hz,2H),1.39–1.17(m,8H),0.87(t,J＝6.7Hz,3H)；¹³C NMR(CDCl₃100MHz) delta 171.80,138.04,128.82,124.04,119.91,37.68,31.62,29.18,28.99,25.65,22.54,13.99. ppm; HRMS m/z (ESI) theoretical value C₁₄H₂₂NO(M+H)⁺220.1701, found 220.1705

EXAMPLE 24 benzanilide

A reaction tube was taken, and 60-100mg (1.2mmol) of nitromethane, 50-60mg (0.3mmol) of benzophenone, 0.5mL of acetic acid, 200mg (0.6mmol) of trifluoromethanesulfonic anhydride and 30-60mg (0.75mmol) of formic acid were added, followed by stirring at 80-120 ℃ for 1-72 hours. After the reaction is finished, 10mL of sodium hydroxide solution is added to quench the reaction, ethyl acetate is used for extraction for 3 times, 5mL of saline is added to the organic phase for washing, the organic phase is combined, column chromatography separation is carried out to obtain 56.2mg of N-benzanilide, and the yield is 95%.

Example 252 Phenylacetanilide

A reaction tube is taken, 60-100mg (1.2mmol) of nitromethane, 50-60mg (0.3mmol) of diphenylethanone, 0.5mL of acetic acid, 150 mg (0.6mmol) of trifluoromethanesulfonic anhydride and 30-60mg (0.75mmol) of formic acid are added, and the mixture is stirred at 80-120 ℃ for 1-72 hours. After the reaction is finished, 10mL of sodium hydroxide solution is added to quench the reaction, ethyl acetate is used for extraction for 3 times, 5mL of saline is added to the organic phase for washing, the organic phase is combined, and column chromatography separation is carried out to obtain 27.2mg of 2-phenylacetanilide with the yield of 43%.

¹H NMR(DMSO-d₆,400MHz):δ10.15(s,1H),7.59(d,J＝7.8Hz,2H),7.38–7.20(m,7H),7.03(t,J＝7.4Hz,1H),3.63(s,2H)；¹³C NMR(DMSO-d₆100MHz) delta 169.05,139.18,135.98,129.06,128.67,128.27,126.49,123.18,119.08,43.30 ppm; HRMS m/z (ESI) theoretical value C₁₄H₁₄NO(M+H)⁺212.1075, found 212.1074.

Example 26 benzamide

A reaction tube was taken, and 60-100mg (1.2mmol) of nitromethane, 45-55mg (0.3mmol) of 2,2, 2-trimethylacetophenone, 0.5mL of acetic acid, 200mg (0.6mmol) of trifluoromethanesulfonic anhydride, 30-60mg (0.75mmol) of formic acid were added, and the mixture was stirred at 80-120 ℃ for 1-72 hours. After the reaction is finished, 10mL of sodium hydroxide solution is added to quench the reaction, ethyl acetate is used for extraction for 3 times, 5mL of saline is added to an organic phase for washing, the organic phase is combined, column chromatography separation is carried out to obtain 28.3mg of benzamide, and the yield is 78%.

Example 27 p-tert-Butylcyanide

A reaction tube was taken, and 600mg (1.2mmol) of nitromethane 500-. Then, 40-60mg (0.3mmol) of p-tert-butylbenzaldehyde (Fe (OTf))₃10-20mg (0.03mmol), triethylamine 50-70mg (0.6mmol), 30-70 deg.CStirring for 1-72 hours. After the reaction is finished, 10mL of sodium hydroxide solution is added to quench the reaction, ethyl acetate is used for extraction for 3 times, 5mL of saline is added to an organic phase for washing, the organic phases are combined, and column chromatography separation is carried out to obtain 34.8mg of p-anisidine with the yield of 73%.

¹H NMR(CDCl₃,400MHz):δ7.58(d,J＝8.5Hz,2H),7.48(d,J＝8.5Hz,2H),1.33(s,9H)；¹³C NMR(CDCl₃,100MHz):δ156.60,131.92,126.13,119.13,109.25,35.22,30.90ppm；MS(70eV):m/z(％)＝159.1

Example 28P-Phenylbenzonitrile

A reaction tube was taken, and 600mg (1.2mmol) of nitromethane 500-. Then 50-70mg (0.3mmol) of p-phenyl benzaldehyde (Fe (OTf))₃10-20mg (0.03mmol), and 50-70mg (0.6mmol) of triethylamine, and stirring at 30-70 deg.C for 1-72 hr. After the reaction is finished, 10mL of sodium hydroxide solution is added to quench the reaction, ethyl acetate is used for extraction for 3 times, 5mL of saline is added to an organic phase for washing, the organic phases are combined, and column chromatography separation is carried out to obtain 42.9mg of p-phenyl benzonitrile with the yield of 73%.

Example 29P-methoxybenzonitrile

A reaction tube was taken, and 600mg (0.5mL) of nitromethane 500-. Then, 30-50mg (0.3mmol) of p-methoxybenzaldehyde (Fe (OTf))₃10-20mg (0.03mmol), and 50-70mg (0.6mmol) of triethylamine, and stirring at 30-70 deg.C for 1-72 hr. After the reaction is finished, 10mL of sodium hydroxide solution is added to quench the reaction, ethyl acetate is used for extraction for 3 times, 5mL of organic phase saline is added for washing, organic phases are combined, and column chromatography separation is carried outYield p-methoxybenzonitrile 29.9mg, 75%.

Example 30 p-chlorobenzonitrile

A reaction tube was taken, and 600mg (0.5mL) of nitromethane 500-. Then, 30-50mg (0.3mmol) of p-chlorobenzaldehyde (Fe (OTf))₃10-20mg (0.03mmol), and 50-70mg (0.6mmol) of triethylamine, and stirring at 30-70 deg.C for 1-72 hr. After the reaction is finished, 10mL of sodium hydroxide solution is added to quench the reaction, ethyl acetate is used for extraction for 3 times, 5mL of saline is added to the organic phase for washing, the organic phase is combined, and the p-chlorobenzonitrile 30.0mg is obtained through column chromatography separation, wherein the yield is 73%.

Example 31 methyl p-cyanobenzoate

A reaction tube was taken, and 600mg (0.5mL) of nitromethane 500-. Subsequently, 40-60mg (0.3mmol) of methyl p-formylbenzoate (Fe (OTf))₃10-20mg (0.03mmol), and 50-70mg (0.6mmol) of triethylamine, and stirring at 30-70 deg.C for 1-72 hr. After the reaction is finished, 10mL of sodium hydroxide solution is added to quench the reaction, ethyl acetate is used for extraction for 3 times, 5mL of saline is added to the organic phase for washing, the organic phase is combined, and column chromatography separation is carried out to obtain 43.4mg of methyl p-cyanobenzoate with the yield of 90%.

Example 32 Paracyanobenzonitrile

Taking a reaction tube, adding 600mg (0.5mL) of nitromethane 500-50-200mg (0.6mmol), 30-60mg (0.75mmol) of formic acid, stirring at 80-120 ℃ for 4 hours. Then, p-cyanobenzaldehyde 30-50mg (0.3mmol), Fe (OTf)₃10-20mg (0.03mmol), and 50-70mg (0.6mmol) of triethylamine, and stirring at 30-70 deg.C for 1-72 hr. After the reaction is finished, 10mL of sodium hydroxide solution is added to quench the reaction, ethyl acetate is used for extraction for 3 times, 5mL of saline is added to the organic phase for washing, the organic phase is combined, and column chromatography separation is carried out to obtain 35.3mg of the cyanobenzene with the yield of 92%.

Example 33 p-Nitrophenylcarbonitrile

A reaction tube was taken, and 600mg (0.5mL) of nitromethane 500-. Then, 30-60mg (0.3mmol) of p-nitrobenzaldehyde (Fe (OTf))₃10-20mg (0.03mmol), and 50-70mg (0.6mmol) of triethylamine, and stirring at 30-70 deg.C for 1-72 hr. After the reaction is finished, 10mL of sodium hydroxide solution is added to quench the reaction, ethyl acetate is used for extraction for 3 times, 5mL of saline is added to an organic phase for washing, the organic phase is combined, and column chromatography separation is carried out to obtain 42.2mg of p-nitrobenzonitrile with the yield of 90%.

Example 34 Paracetamidobenzonitrile

A reaction tube was taken, and 600mg (0.5mL) of nitromethane 500-. 40-60mg (0.3mmol) of p-acetamidobenzaldehyde (OTf)₃10-20mg (0.03mmol), and 50-70mg (0.6mmol) of triethylamine, and stirring at 30-70 deg.C for 1-72 hr. After the reaction is finished, 10mL of sodium hydroxide solution is added to quench the reaction, ethyl acetate is used for extraction for 3 times, 5mL of organic phase saline is added for washing, organic phases are combined, and column chromatography separation is carried out to obtain 32.7mg of p-acetamido benzonitrile with the yield of 68%.

¹H NMR(DMSO-d₆,400MHz):δ10.36(s,1H),7.79–7.68(m,4H),2.08(s,3H)；¹³C NMR(DMSO-d₆,100MHz):δ169.16,143.46,133.21,119.09,118.90,104.68,24.18ppm；MS(70eV):m/z(％)＝160.2.

Example 35 Paradimethylaminobenzonitrile

A reaction tube was taken, and 600mg (0.5mL) of nitromethane 500-. Then, 30-60mg (0.3mmol) of p-dimethylaminobenzaldehyde (Fe), (OTf) was added₃10-20mg (0.03mmol), and 50-70mg (0.6mmol) of triethylamine, and stirring at 30-70 deg.C for 1-72 hr. After the reaction is finished, 10mL of sodium hydroxide solution is added to quench the reaction, ethyl acetate is used for extraction for 3 times, 5mL of saline is added to an organic phase for washing, the organic phase is combined, and the p-nitrobenzonitrile 32.7mg and the yield is 84% are obtained through column chromatography separation.

¹H NMR(CDCl₃,400MHz):δ7.43(d,J＝9.0Hz,2H),6.61(d,J＝8.9Hz,2H),3.01(s,6H)；¹³C NMR(CDCl₃,100MHz):δ152.33,133.20,120.63,111.26,97.04,39.77ppm；MS(70eV):m/z(％)＝146.2.

Example 364- (4-methyl-1-piperazinyl) benzonitrile

A reaction tube was taken, and 600mg (0.5mL) of nitromethane 500-. Then, 50-70mg (0.3mmol) of 4- (4-methyl-1-piperazinyl) benzaldehyde (Fe (OTf))₃10-20mg (0.03mmol), and 50-70mg (0.6mmol) of triethylamine, and stirring at 30-70 deg.C for 1-72 hr. After the reaction is finished, 10mL of sodium hydroxide solution is added to quench the reaction, and the mixture is extracted by ethyl acetate for 3 times and is organicThe mixture was washed with 5mL of additional saline, and the organic phases were combined and separated by column chromatography to give 25.9mg of 4- (4-methyl-1-piperazinyl) benzonitrile in 43% yield.

¹H NMR(CDCl₃,400MHz):δ7.46(d,J＝8.9Hz,2H),6.84(d,J＝9.0Hz,2H),3.32(t,J＝5.2Hz,4H),2.53(t,J＝5.2Hz,4H),2.33(s,3H)；¹³C NMR(CDCl₃,100MHz):δ153.24,133.37,119.95,114.11,100.08,54.46,46.91,45.94ppm；MS(70eV):m/z(％)＝201.2.

Example 373, 4-Dimethoxybenzonitrile

A reaction tube was taken, and 600mg (0.5mL) of nitromethane 500-. Then, 40-60mg (0.3mmol) of 3, 4-dimethoxybenzaldehyde (Fe (OTf))₃10-20mg (0.03mmol), and 50-70mg (0.6mmol) of triethylamine, and stirring at 30-70 deg.C for 1-72 hr. After the reaction is finished, 10mL of sodium hydroxide solution is added to quench the reaction, ethyl acetate is used for extraction for 3 times, 5mL of saline is added to an organic phase for washing, the organic phases are combined, and the 3, 4-dimethoxybenzonitrile 29.8mg is obtained through column chromatography separation, wherein the yield is 61%.

Example 382-Bromobenzonitrile

A reaction tube was taken, and 600mg (0.5mL) of nitromethane 500-. Then, 40-70mg (0.3mmol) of 2-bromobenzaldehyde (Fe (OTf))₃10-20mg (0.03mmol), and 50-70mg (0.6mmol) of triethylamine, and stirring at 30-70 deg.C for 1-72 hr. After the reaction is finished, 10mL of sodium hydroxide solution is added to quench the reaction, ethyl acetate is used for extraction for 3 times, 5mL of saline is added to the organic phase for washing, the organic phase is combined, and the 2-bromobenzonitrile 46.7mg is obtained by column chromatography separation, wherein the yield is 86 percent。

Example 392-nitrobenzonitrile

A reaction tube was taken, and 600mg (0.5mL) of nitromethane 500-. Then 30-60mg (0.3mmol) of 2-nitrobenzaldehyde (Fe (OTf))₃10-20mg (0.03mmol), and 50-70mg (0.6mmol) of triethylamine, and stirring at 30-70 deg.C for 1-72 hr. After the reaction is finished, 10mL of sodium hydroxide solution is added to quench the reaction, ethyl acetate is used for extraction for 3 times, 5mL of brine is added to an organic phase for washing, the organic phase is combined, and the 2-nitrobenzonitrile 42.6mg is obtained through column chromatography separation, wherein the yield is 96%.

Example 401 Naphthalenecarbonitrile

A reaction tube was taken, and 600mg (0.5mL) of nitromethane 500-. Then 30-60mg (0.3mmol) of 1-naphthaldehyde (Fe (OTf))₃10-20mg (0.03mmol), and 50-70mg (0.6mmol) of triethylamine, and stirring at 30-70 deg.C for 1-72 hr. After the reaction is finished, 10mL of sodium hydroxide solution is added to quench the reaction, ethyl acetate is used for extraction for 3 times, 5mL of saline is added to the organic phase for washing, the organic phase is combined, and the 1-naphthanitrile 43.2mg is obtained through column chromatography separation, wherein the yield is 94%.

Example 412 Naphthalenecarbonitrile

A reaction tube was taken, and 600mg (0.5mL) of nitromethane 500-. Followed by addition of 1-Naphthalenecarboxaldehyde 30-60mg (0.3mmol), Fe (OTf)₃10-20mg (0.03mmol), and 50-70mg (0.6mmol) of triethylamine, and stirring at 30-70 deg.C for 1-72 hr. After the reaction is finished, 10mL of sodium hydroxide solution is added to quench the reaction, ethyl acetate is used for extraction for 3 times, 5mL of saline is added to the organic phase for washing, the organic phase is combined, and the 1-naphthanitrile 44.1mg is obtained through column chromatography separation, wherein the yield is 96%.

Example 429 cyanoanthracene

A reaction tube was taken, and 600mg (0.5mL) of nitromethane 500-. Then, 50-70mg (0.3mmol) of 9-formylanthracene (Fe (OTf))₃10-20mg (0.03mmol), and 50-70mg (0.6mmol) of triethylamine, and stirring at 30-70 deg.C for 1-72 hr. After the reaction is finished, 10mL of sodium hydroxide solution is added to quench the reaction, ethyl acetate is used for extraction for 3 times, 5mL of saline is added to the organic phase for washing, the organic phase is combined, and the 9-cyanoanthracene is obtained by column chromatography separation, wherein the yield is 71 mg.

Example 43 Cinnanitrile

A reaction tube was taken, and 600mg (0.5mL) of nitromethane 500-. Then, cinnamic aldehyde 30-50mg (0.3mmol), Fe (OTf) was added₃10-20mg (0.03mmol), and 50-70mg (0.6mmol) of triethylamine, and stirring at 30-70 deg.C for 1-72 hr. After the reaction is finished, 10mL of sodium hydroxide solution is added to quench the reaction, ethyl acetate is used for extraction for 3 times, 5mL of saline is added to the organic phase for washing, the organic phase is combined, and the cinnamonitrile 16.3mg is obtained through column chromatography separation, wherein the yield is 42%.

Example 442-cyanobenzofuran

A reaction tube was taken, and 600mg (0.5mL) of nitromethane 500-. Then 30-60mg (0.3mmol) of 2-formylbenzofuran (Fe (OTf))₃10-20mg (0.03mmol), and 50-70mg (0.6mmol) of triethylamine, and stirring at 30-70 deg.C for 1-72 hr. After the reaction is finished, 10mL of sodium hydroxide solution is added to quench the reaction, ethyl acetate is used for extraction for 3 times, 5mL of organic phase saline is used for washing, organic phases are combined, and column chromatography separation is carried out to obtain 18.9mg of 2-cyanobenzofuran with the yield of 44%.

¹H NMR(CDCl₃,400MHz):δ7.68(d,J＝7.9Hz,1H),7.56(d,J＝8.4Hz,1H),7.51(t,J＝7.7Hz,1H),7.46(s,1H),7.37(t,J＝7.4Hz,1H)；¹³C NMR(CDCl₃,100MHz):δ155.66,128.42,127.30,125.47,124.54,122.56,118.45,112.09,111.82ppm；MS(70eV):m/z(％)＝.143.2

Example 453-cyanobenzothiophenes

A reaction tube was taken, and 600mg (0.5mL) of nitromethane 500-. Then 40-60mg (0.3mmol) of 2-formylbenzothiophene (Fe (OTf))₃10-20mg (0.03mmol), and 50-70mg (0.6mmol) of triethylamine, and stirring at 30-70 deg.C for 1-72 hr. After the reaction is finished, 10mL of sodium hydroxide solution is added to quench the reaction, ethyl acetate is used for extraction for 3 times, 5mL of organic phase saline is added for washing, organic phases are combined, and the 2-cyanobenzothiophene 37.7mg and the yield is 79% are obtained through column chromatography separation.

¹H NMR(CDCl₃,400MHz):δ8.11(s,1H),7.99(d,J＝7.9Hz,1H),7.91(d,J＝7.9Hz,1H),7.57-7.44(m,2H)；¹³C NMR(CDCl₃,100MHz):δ138.41,137.50,137.18,126.11,125.90,122.77,122.44,114.26,107.02ppm；MS(70eV):m/z(％)＝159.2.

Example 462-phenyl, 4-cyanothiazole

A reaction tube was taken, and 600mg (0.5mL) of nitromethane 500-. Then, 40-70mg (0.3mmol) of 2-phenyl, 4-cyanothiazole (OTf)₃10-20mg (0.03mmol), and 50-70mg (0.6mmol) of triethylamine, and stirring at 30-70 deg.C for 1-72 hr. After the reaction is finished, 10mL of sodium hydroxide solution is added to quench the reaction, ethyl acetate is used for extraction for 3 times, 5mL of saline is added to an organic phase for washing, the organic phases are combined, and the 2-phenyl and 4-cyanothiazole 31.8mg and the yield is 57% are obtained through column chromatography separation.

¹H NMR(CDCl₃,400MHz):δ7.97(s,1H),7.94(dd,J＝7.4,1.9Hz,2H),7.53–7.43(m,3H)；¹³C NMR(CDCl₃,100MHz):δ169.81,131.76,131.35,129.84,129.19,127.44,126.84,114.02ppm；MS(70eV):m/z(％)＝.186.2

Example 47 decanonitrile

A reaction tube was taken, and 600mg (0.5mL) of nitromethane 500-. Then 2-phenyl, decanal 30-60mg (0.3mmol), Fe (OTf)₃10-20mg (0.03mmol), and 50-70mg (0.6mmol) of triethylamine, and stirring at 30-70 deg.C for 1-72 hr. After the reaction is finished, 10mL of sodium hydroxide solution is added to quench the reaction, ethyl acetate is used for extraction for 3 times, 5mL of saline is added to an organic phase for washing, the organic phase is combined, and column chromatography separation is carried out to obtain 27.6mg of 2-phenyl decylonitrile with the yield of 60%.

Example 48 benzamide

A reaction tube was taken, and 60-100mg (1.2mmol) of nitromethane, 30-40mg (0.3mmol) of benzaldehyde, 0.5mL of acetic acid, 200mg (0.6mmol) of trifluoromethanesulfonic anhydride and 30-60mg (0.75mmol) of formic acid were added, followed by stirring at 80-120 ℃ for 1-72 hours. After the reaction is finished, 10mL of sodium hydroxide solution is added to quench the reaction, ethyl acetate is used for extraction for 3 times, 5mL of saline is added to an organic phase for washing, the organic phase is combined, and column chromatography separation is carried out to obtain 25.4mg of benzamide, wherein the yield is 70%.

Example 49 Paramethylbenzamide

A reaction tube was taken, and 60-100mg (1.2mmol) of nitromethane, 30-40mg (0.3mmol) of p-tolualdehyde, 0.5mL of acetic acid, 200mg (0.6mmol) of trifluoromethanesulfonic anhydride, 30-60mg (0.75mmol) of formic acid were added, followed by stirring at 80-120 ℃ for 1-72 hours. After the reaction is finished, 10mL of sodium hydroxide solution is added to quench the reaction, ethyl acetate is used for extraction for 3 times, 5mL of saline is added to the organic phase for washing, the organic phase is combined, and column chromatography separation is carried out to obtain 31.2mg of p-methylbenzamide with the yield of 77%.

Example 50P-tert-Butylbenzamide

A reaction tube was taken, and 60-100mg (1.2mmol) of nitromethane, 40-60mg (0.3mmol) of p-t-butylbenzaldehyde, 0.5mL of acetic acid, 200mg (0.6mmol) of trifluoromethanesulfonic anhydride, 30-60mg (0.75mmol) of formic acid were added, followed by stirring at 80-120 ℃ for 1-72 hours. After the reaction is finished, 10mL of sodium hydroxide solution is added to quench the reaction, ethyl acetate is used for extraction for 3 times, 5mL of saline is added to an organic phase for washing, the organic phase is combined, column chromatography separation is carried out to obtain 41.4mg of p-tert-butylbenzoamide, and the yield is 78%.

Example 51 Paraphenylbenzamides

A reaction tube was taken, and 60-100mg (1.2mmol) of nitromethane, 40-70mg (0.3mmol) of p-benzaldehyde, 0.5mL of acetic acid, 200mg (0.6mmol) of trifluoromethanesulfonic anhydride, 30-60mg (0.75mmol) of formic acid were added, and the mixture was stirred at 80-120 ℃ for 1-72 hours. After the reaction is finished, 10mL of sodium hydroxide solution is added to quench the reaction, ethyl acetate is used for extraction for 3 times, 5mL of saline is added to an organic phase for washing, the organic phase is combined, and column chromatography separation is carried out to obtain 47.3mg of p-phenylbenzamide with the yield of 80%.

Example 52 Paramethoxybenzamide

A reaction tube was taken, and 60-100mg (1.2mmol) of nitromethane, 30-50mg (0.3mmol) of p-methoxybenzaldehyde, 0.5mL of acetic acid, 200mg (0.6mmol) of trifluoromethanesulfonic anhydride, 30-60mg (0.75mmol) of formic acid were added, and the mixture was stirred at 80-120 ℃ for 1-72 hours. After the reaction is finished, 10mL of sodium hydroxide solution is added to quench the reaction, ethyl acetate is used for extraction for 3 times, 5mL of saline is added to an organic phase for washing, the organic phase is combined, column chromatography separation is carried out to obtain 34.5mg of p-methoxybenzamide, and the yield is 76%.

Example 53 Parapentoxybenzamide

A reaction tube was taken, and 60-100mg (1.2mmol) of nitromethane, 50-70mg (0.3mmol) of p-pentyloxybenzaldehyde, 0.5mL of acetic acid, 200mg (0.6mmol) of trifluoromethanesulfonic anhydride, 30-60mg (0.75mmol) of formic acid were added, followed by stirring at 80-120 ℃ for 1-72 hours. After the reaction is finished, 10mL of sodium hydroxide solution is added to quench the reaction, ethyl acetate is used for extraction for 3 times, 5mL of saline is added to an organic phase for washing, the organic phase is combined, and column chromatography separation is carried out to obtain 20.5mg of p-pentyloxybenzamide with the yield of 33%.

¹H NMR(DMSO-d₆,400MHz):δ7.86–7.78(m,3H),7.16(s,1H),7.02–6.85(m,2H),4.00(t,J＝6.5Hz,2H),1.77–1.65(m,2H),1.44–1.28(m,4H),0.89(t,J＝7.1Hz,3H)；¹³C NMR(DMSO-d₆100MHz) delta 167.51,161.07,129.37,126.31,113.82,67.63,28.30,27.68,21.89,13.92 ppm; HRMS M/z (ESI) theoretical C12H18NO2(M + H) +,208.1338, found 208.1342.

Example 54P-hydroxybenzamide

A reaction tube is taken, 60-100mg (1.2mmol) of nitromethane, 30-40mg (0.3mmol) of p-hydroxybenzaldehyde, 0.5mL of acetic acid, 200mg (0.6mmol) of trifluoromethanesulfonic anhydride and 30-60mg (0.75mmol) of formic acid are added, and the mixture is stirred at 80-120 ℃ for 1-72 hours. After the reaction is finished, 10mL of sodium hydroxide solution is added to quench the reaction, ethyl acetate is used for extraction for 3 times, 5mL of saline is added to the organic phase for washing, the organic phase is combined, and the p-hydroxybenzamide 32.9mg is obtained through column chromatography separation with the yield of 80%.

Example 55P-Phenyloxybenzamides

A reaction tube is taken, 60-100mg (1.2mmol) of nitromethane, 50-70mg (0.3mmol) of p-phenoxybenzaldehyde, 0.5mL of acetic acid, 200mg (0.6mmol) of trifluoromethanesulfonic anhydride and 30-60mg (0.75mmol) of formic acid are added, and the mixture is stirred for 1-72 hours at 80-120 ℃. After the reaction is finished, 10mL of sodium hydroxide solution is added to quench the reaction, ethyl acetate is used for extraction for 3 times, 5mL of saline is added to the organic phase for washing, the organic phase is combined, and column chromatography separation is carried out to obtain 23mg of p-phenoxy benzamide, wherein the yield is 36%.

¹H NMR(DMSO-d₆,400MHz):δ7.93(s,1H),7.91(t,J＝2.1Hz,1H),7.89(t,J＝2.1Hz,1H),7.47–7.39(m,2H),7.31(s,1H),7.24–7.16(m,1H),7.10-7.08(m,1H),7.08-7.05(m,1H),7.01(t,J＝2.1Hz,1H),6.99(t,J＝2.1Hz,1H)；¹³C NMR(DMSO-d₆100 MHz). delta.167.24, 159.51,155.65,130.27,129.73,129.00,124.30,119.52,117.30. ppm; HRMS M/z (ESI) theoretical C13H12NO2(M + H) +,214.0868, found 214.0869.

Example 56 p-chlorobenzamide

A reaction tube was taken, and 60-100mg (1.2mmol) of nitromethane, 40-50mg (0.3mmol) of p-chlorobenzaldehyde, 0.5mL of acetic acid, 200mg (0.6mmol) of trifluoromethanesulfonic anhydride, 30-60mg (0.75mmol) of formic acid were added, followed by stirring at 80-120 ℃ for 1-72 hours. After the reaction is finished, 10mL of sodium hydroxide solution is added to quench the reaction, ethyl acetate is used for extraction for 3 times, 5mL of saline is added to an organic phase for washing, the organic phases are combined, and column chromatography separation is carried out to obtain 39.1mg of p-chlorobenzamide with the yield of 84%.

Example 57 p-fluorobenzamide

A reaction tube was taken, and 60-100mg (1.2mmol) of nitromethane, 30-40mg (0.3mmol) of p-fluorobenzaldehyde, 0.5mL of acetic acid, 200mg (0.6mmol) of trifluoromethanesulfonic anhydride, 30-60mg (0.75mmol) of formic acid were added, followed by stirring at 80-120 ℃ for 1-72 hours. After the reaction is finished, 10mL of sodium hydroxide solution is added to quench the reaction, ethyl acetate is used for extraction for 3 times, 5mL of saline is added to an organic phase for washing, the organic phases are combined, and column chromatography separation is carried out to obtain 33.4mg of p-fluorobenzamide with the yield of 80%.

Example 58 para-bromobenzamide

A reaction tube is taken, 60-100mg (1.2mmol) of nitromethane, 40-70mg (0.3mmol) of p-bromobenzaldehyde, 0.5mL of acetic acid, 200mg (0.6mmol) of trifluoromethanesulfonic anhydride and 30-60mg (0.75mmol) of formic acid are added, and the mixture is stirred for 1-72 hours at 80-120 ℃. After the reaction is finished, 10mL of sodium hydroxide solution is added to quench the reaction, ethyl acetate is used for extraction for 3 times, 5mL of saline is added to the organic phase for washing, the organic phase is combined, column chromatography separation is carried out to obtain 42.4mg of p-bromobenzamide, and the yield is 71%.

Example 59P-iodobenzamide

A reaction tube is taken, 60-100mg (1.2mmol) of nitromethane, 50-70mg (0.3mmol) of p-iodobenzaldehyde, 0.5mL of acetic acid, 200mg (0.6mmol) of trifluoromethanesulfonic anhydride and 30-60mg (0.75mmol) of formic acid are added, and the mixture is stirred for 1-72 hours at 80-120 ℃. After the reaction is finished, 10mL of sodium hydroxide solution is added to quench the reaction, ethyl acetate is used for extraction for 3 times, 5mL of saline is added to an organic phase for washing, the organic phase is combined, column chromatography separation is carried out to obtain 48.2mg of p-iodobenzamide, and the yield is 65%.

Example 60 Paramethylthiobenzamide

A reaction tube was taken, and 60-100mg (1.2mmol) of nitromethane, 40-50mg (0.3mmol) of p-methylthiobenzaldehyde, 0.5mL of acetic acid, 200mg (0.6mmol) of trifluoromethanesulfonic anhydride, 30-60mg (0.75mmol) of formic acid were added, and the mixture was stirred at 80-120 ℃ for 1-72 hours. After the reaction is finished, 10mL of sodium hydroxide solution is added to quench the reaction, ethyl acetate is used for extraction for 3 times, 5mL of organic phase saline is used for washing, organic phases are combined, column chromatography separation is carried out to obtain 28.6mg of p-methylthiobenzamide, and the yield is 57%.

¹H NMR(DMSO-d₆,400MHz):δ7.94(s,1H),7.83(d,J＝8.2Hz,2H),7.30(d,J＝8.0Hz,3H),2.51(s,3H)；¹³C NMR(DMSO-d₆100MHz) delta 167.39,142.47,130.32,127.99,124.78,14.11 ppm; HRMS M/z (ESI) theoretical C8H10NOS (M + H) +,168.0483, found 168.0484.

Example 61 para-Trifluoromethylbenzamide

A reaction tube was taken, and 60-100mg (1.2mmol) of nitromethane, 40-60mg (0.3mmol) of p-trifluoromethylbenzaldehyde, 0.5mL of acetic acid, 200mg (0.6mmol) of trifluoromethanesulfonic anhydride, 30-60mg (0.75mmol) of formic acid were added, followed by stirring at 80-120 ℃ for 1-72 hours. After the reaction is finished, 10mL of sodium hydroxide solution is added to quench the reaction, ethyl acetate is used for extraction for 3 times, 5mL of saline is added to the organic phase for washing, the organic phase is combined, and column chromatography separation is carried out to obtain 40.3mg of p-trifluoromethyl benzamide, wherein the yield is 71%.

¹H NMR(DMSO-d₆,400MHz):δ8.20(s,1H),8.07(d,J＝8.0Hz,2H),7.82(d,J＝8.1Hz,2H),7.62(s,1H)；¹³C NMR(DMSO-d₆,100MHz):δ166.71,138.09,131.17(q,J＝32Hz),128.31,123.95(q,J＝270Hz),125.22(q,J＝4Hz)；¹⁹F NMR(DMSO-d₆377 MHz): delta-61.41 ppm; HRMS M/z (ESI) theoretical C8H7NF3O (M + H) +,190.0480, found 190.0483

Example 622 iodobenzamide

A reaction tube was taken, and 60-100mg (1.2mmol) of nitromethane, 60-80mg (0.3mmol) of 2-iodobenzaldehyde, 0.5mL of acetic acid, 200mg (0.6mmol) of trifluoromethanesulfonic anhydride, 30-60mg (0.75mmol) of formic acid were added, followed by stirring at 80-120 ℃ for 1-72 hours. After the reaction is finished, 10mL of sodium hydroxide solution is added to quench the reaction, ethyl acetate is used for extraction for 3 times, 5mL of saline is added to the organic phase for washing, the organic phase is combined, and the 2-iodobenzamide 44.5mg is obtained through column chromatography separation, wherein the yield is 60%.

Example 632-Bromobenzamide

A reaction tube was taken, and 60-100mg (1.2mmol) of nitromethane, 40-70mg (0.3mmol) of 2-bromobenzaldehyde, 0.5mL of acetic acid, 200mg (0.6mmol) of trifluoromethanesulfonic anhydride, 30-60mg (0.75mmol) of formic acid were added, followed by stirring at 80-120 ℃ for 1-72 hours. After the reaction is finished, 10mL of sodium hydroxide solution is added to quench the reaction, ethyl acetate is used for extraction for 3 times, an organic phase is added, 5mL of saline is used for washing, organic phases are combined, column chromatography separation is carried out, 46.6mg of 2-bromobenzamide is obtained, and the yield is 78%.

Example 642-Methylbenzamide

A reaction tube was taken, and 60-100mg (1.2mmol) of nitromethane, 30-40mg (0.3mmol) of 2-methylbenzaldehyde, 0.5mL of acetic acid, 200mg (0.6mmol) of trifluoromethanesulfonic anhydride, 30-60mg (0.75mmol) of formic acid were added, followed by stirring at 80-120 ℃ for 1-72 hours. After the reaction is finished, 10mL of sodium hydroxide solution is added to quench the reaction, ethyl acetate is used for extraction for 3 times, 5mL of saline is added to an organic phase for washing, the organic phase is combined, and the 2-methylbenzamide 32.4mg is obtained through column chromatography separation, wherein the yield is 80%.

Example 652-hydroxybenzamide

A reaction tube was taken, and 60-100mg (1.2mmol) of nitromethane, 30-40mg (0.3mmol) of 2-hydroxybenzaldehyde, 0.5mL of acetic acid, 200mg (0.6mmol) of trifluoromethanesulfonic anhydride, 30-60mg (0.75mmol) of formic acid were added, followed by stirring at 80-120 ℃ for 1-72 hours. After the reaction is finished, 10mL of sodium hydroxide solution is added to quench the reaction, ethyl acetate is used for extraction for 3 times, 5mL of organic phase saline is added for washing, organic phases are combined, and column chromatography separation is carried out to obtain 23.0mg of 2-hydroxybenzamide with the yield of 56%.

Example 663-bromobenzamide

A reaction tube was taken, and 60-100mg (1.2mmol) of nitromethane, 40-70mg (0.3mmol) of 3-bromobenzaldehyde, 0.5mL of acetic acid, 200mg (0.6mmol) of trifluoromethanesulfonic anhydride, 30-60mg (0.75mmol) of formic acid were added, followed by stirring at 80-120 ℃ for 1-72 hours. After the reaction is finished, 10mL of sodium hydroxide solution is added to quench the reaction, ethyl acetate is used for extraction for 3 times, 5mL of saline is added to an organic phase for washing, the organic phases are combined, and column chromatography separation is carried out to obtain 46.0mg of 3-bromobenzamide with the yield of 77%.

Example 673-Methylbenzamide

A reaction tube was taken, and 60-100mg (1.2mmol) of nitromethane, 30-40mg (0.3mmol) of 3-methylbenzaldehyde, 0.5mL of acetic acid, 200mg (0.6mmol) of trifluoromethanesulfonic anhydride, 30-60mg (0.75mmol) of formic acid were added, followed by stirring at 80-120 ℃ for 1-72 hours. After the reaction is finished, 10mL of sodium hydroxide solution is added to quench the reaction, ethyl acetate is used for extraction for 3 times, 5mL of saline is added to the organic phase for washing, the organic phase is combined, and the 3-methylbenzamide 28.0mg and the yield is 69% are obtained through column chromatography separation.

Example 683-Chlorobenzenecarboxamide

A reaction tube was taken, and 60-100mg (1.2mmol) of nitromethane, 30-40mg (0.3mmol) of 3-chlorobenzaldehyde, 0.5mL of acetic acid, 200mg (0.6mmol) of trifluoromethanesulfonic anhydride, 30-60mg (0.75mmol) of formic acid were added, followed by stirring at 80-120 ℃ for 1-72 hours. After the reaction is finished, 10mL of sodium hydroxide solution is added to quench the reaction, ethyl acetate is used for extraction for 3 times, 5mL of saline is added to an organic phase for washing, the organic phases are combined, and the 3-chlorobenzamide 34.9mg is obtained through column chromatography separation, wherein the yield is 75%.

Example 693-Fluorobenzamide

A reaction tube was taken, and 60-100mg (1.2mmol) of nitromethane, 30-40mg (0.3mmol) of 3-fluorobenzaldehyde, 0.5mL of acetic acid, 200mg (0.6mmol) of trifluoromethanesulfonic anhydride, 30-60mg (0.75mmol) of formic acid were added, followed by stirring at 80-120 ℃ for 1-72 hours. After the reaction is finished, 10mL of sodium hydroxide solution is added to quench the reaction, ethyl acetate is used for extraction for 3 times, 5mL of saline is added to an organic phase for washing, the organic phases are combined, and column chromatography separation is carried out to obtain 27.1mg of 3-fluorobenzamide with the yield of 65%.

Example 703, 4-Dichlorobenzamide

A reaction tube was taken, and 60-100mg (1.2mmol) of nitromethane, 40-60mg (0.3mmol) of 3, 4-dichlorobenzaldehyde, 0.5mL of acetic acid, 200mg (0.6mmol) of trifluoromethanesulfonic anhydride, 30-60mg (0.75mmol) of formic acid were added, followed by stirring at 80-120 ℃ for 1-72 hours. After the reaction is finished, 10mL of sodium hydroxide solution is added to quench the reaction, ethyl acetate is used for extraction for 3 times, 5mL of organic phase saline is added for washing, organic phases are combined, and column chromatography separation is carried out to obtain 45.4mg of 3, 4-dichlorobenzamide, wherein the yield is 80%.

¹H NMR(DMSO-d₆,400MHz):δ8.14(s,1H),8.09(d,J＝2.1Hz,1H),7.84(dd,J＝8.4,2.0Hz,1H),7.72(d,J＝8.4Hz,1H),7.60(s,1H)；¹³C NMR(DMSO-d₆100MHz) delta 165.58,134.65,134.07,131.21,130.59,129.46,127.73 ppm; HRMS M/z (ESI) theoretical C7H6NOCl2(M + H) +,189.9826, found 189.9826.

Example 713, 4-Dimethylbenzamide

A reaction tube was taken, and 60-100mg (1.2mmol) of nitromethane, 30-50mg (0.3mmol) of 3, 4-dimethylbenzaldehyde, 0.5mL of acetic acid, 200mg (0.6mmol) of trifluoromethanesulfonic anhydride, 30-60mg (0.75mmol) of formic acid were added, followed by stirring at 80-120 ℃ for 1-72 hours. After the reaction is finished, 10mL of sodium hydroxide solution is added to quench the reaction, ethyl acetate is used for extraction for 3 times, 5mL of saline is added to the organic phase for washing, the organic phase is combined, and the 3, 4-dimethyl benzamide 35.8mg is obtained through column chromatography separation, wherein the yield is 80%.

¹H NMR(DMSO-d₆,400MHz):δ7.85(s,1H),7.67(d,J＝2.0Hz,1H),7.60(dd,J＝7.8,2.0Hz,1H),7.22(s,1H),7.19(d,J＝7.8Hz,1H),2.25(s,6H)；¹³C NMR(DMSO-d₆100MHz) delta 167.95,139.72,135.97,131.79,129.20,128.59,124.96,19.37,19.30 ppm; HRMS M/z (ESI) theoretical C9H12NO (M + H) +,150.0919, found 150.0921.

Example 72 naphthalene-1-carboxamide

A reaction tube was taken, and 60-100mg (1.2mmol) of nitromethane, 30-60mg (0.3mmol) of naphthalene-1-carbaldehyde, 0.5mL of acetic acid, 200mg (0.6mmol) of trifluoromethanesulfonic anhydride, 30-60mg (0.75mmol) of formic acid were added, followed by stirring at 80-120 ℃ for 1-72 hours. After the reaction is finished, 10mL of sodium hydroxide solution is added to quench the reaction, ethyl acetate is used for extraction for 3 times, 5mL of organic phase saline is added for washing, organic phases are combined, column chromatography separation is carried out to obtain 46.2mg of naphthalene-1-formamide, and the yield is 90%.

Example 73 naphthalene-2-carboxamide

A reaction tube was taken, and 60-100mg (1.2mmol) of nitromethane, 30-60mg (0.3mmol) of naphthalene-2-carbaldehyde, 0.5mL of acetic acid, 200mg (0.6mmol) of trifluoromethanesulfonic anhydride, 30-60mg (0.75mmol) of formic acid were added, followed by stirring at 80-120 ℃ for 1-72 hours. After the reaction is finished, 10mL of sodium hydroxide solution is added to quench the reaction, ethyl acetate is used for extraction for 3 times, 5mL of saline is added to the organic phase for washing, the organic phase is combined, and the naphthalene-2-formamide 38.0mg with the yield of 74% is obtained through column chromatography separation.

Example 74 Cinnanamide

A reaction tube was taken, and 60-100mg (1.2mmol) of nitromethane, 30-50mg (0.3mmol) of cinnamaldehyde, 0.5mL of acetic acid, 200mg (0.6mmol) of trifluoromethanesulfonic anhydride, 30-60mg (0.75mmol) of formic acid were added, followed by stirring at 80-120 ℃ for 1-72 hours. After the reaction is finished, 10mL of sodium hydroxide solution is added to quench the reaction, ethyl acetate is used for extraction for 3 times, 5mL of saline is added to the organic phase for washing, the organic phase is combined, column chromatography separation is carried out to obtain 39.7mg of cinnamamide, and the yield is 90%.

¹H NMR(DMSO-d₆,400MHz):δ7.55(dt,J＝5.7,1.6Hz,3H),7.47–7.33(m,4H),7.11(s,1H),6.61(d,J＝15.9Hz,1H)；¹³C NMR(DMSO-d₆100MHz) delta 166.71,139.20,134.88,129.48,128.95,127.55,122.32 ppm; HRMS M/z (ESI) theoretical C9H10NO (M + H) +,148.0762, found148.0764.

Example 75P-Nitrobenzamide

A reaction tube was taken, and 60-100mg (1.2mmol) of nitromethane, 30-60mg (0.3mmol) of p-nitrobenzaldehyde, 0.5mL of acetic acid, 200mg (0.6mmol) of trifluoromethanesulfonic anhydride, 30-60mg (0.75mmol) of formic acid were added, followed by stirring at 80-120 ℃ for 1-72 hours. After the reaction is finished, 10mL of sodium hydroxide solution is added to quench the reaction, ethyl acetate is used for extraction for 3 times, 5mL of saline is added to an organic phase for washing, the organic phase is combined, and column chromatography separation is carried out to obtain 34.9mg of p-nitrobenzamide with the yield of 70%.

Example 763-Thiophenecarboxamide

A reaction tube is taken, 60-100mg (1.2mmol) of nitromethane, 30-40mg (0.3mmol) of 3-thiophenecarboxaldehyde, 0.5mL of acetic acid, 200mg (0.6mmol) of trifluoromethanesulfonic anhydride and 30-60mg (0.75mmol) of formic acid are added, and the mixture is stirred for 1-72 hours at 80-120 ℃. After the reaction is finished, 10mL of sodium hydroxide solution is added to quench the reaction, ethyl acetate is used for extraction for 3 times, 5mL of saline is added to the organic phase for washing, the organic phase is combined, and the 3-thiophenecarboxamide 19.8mg is obtained through column chromatography separation, wherein the yield is 52%.

¹H NMR(DMSO-d₆,400MHz):δ8.12(d,J＝1.8Hz,1H),7.79(s,1H),7.55(dd,J＝4.9,3.0Hz,1H),7.49–7.46(m,1H),7.24(s,1H)；¹³C NMR(DMSO-d₆,100MHz):δ163.73,138.00,129.05,127.18,126.59ppm；MS(70eV):m/z(％)＝127.2.

Example 772-Thiophenecarboxamide

A reaction tube is taken, 60-100mg (1.2mmol) of nitromethane, 30-40mg (0.3mmol) of 2-thiophenecarboxaldehyde, 0.5mL of acetic acid, 200mg (0.6mmol) of trifluoromethanesulfonic anhydride and 30-60mg (0.75mmol) of formic acid are added, and the mixture is stirred for 1-72 hours at 80-120 ℃. After the reaction is finished, 10mL of sodium hydroxide solution is added to quench the reaction, ethyl acetate is used for extraction for 3 times, 5mL of saline is added to the organic phase for washing, the organic phase is combined, and the 2-thiophenecarboxamide 21.3mg is obtained through column chromatography separation, wherein the yield is 56%.

¹H NMR(DMSO-d₆,400MHz):δ7.97(s,1H),7.74(t,J＝4.2Hz,2H),7.39(s,1H),7.12(dd,J＝4.8,3.8Hz,1H)；¹³C NMR(DMSO-d₆,100MHz):δ162.90,140.34,131.01,128.67,127.91ppm；MS(70eV):m/z(％)＝127.3.

Example 782 Furancarboxamide

A reaction tube was taken, and 60-100mg (1.2mmol) of nitromethane, 20-30mg (0.3mmol) of 2-furaldehyde, 0.5mL of acetic acid, 200mg (0.6mmol) of trifluoromethanesulfonic anhydride, 30-60mg (0.75mmol) of formic acid were added, followed by stirring at 80-120 ℃ for 1-72 hours. After the reaction is finished, 10mL of sodium hydroxide solution is added to quench the reaction, ethyl acetate is used for extraction for 3 times, 5mL of saline is added to the organic phase for washing, the organic phase is combined, and the 2-furancarboxamide 12.0mg and the yield is 36% are obtained through column chromatography separation.

¹H NMR(DMSO-d₆,400MHz):δ7.80(d,J＝1.7Hz,1H),7.76(s,1H),7.37(s,1H),7.09(dd,J＝3.4,0.8Hz,1H),6.60(dd,J＝3.4,1.8Hz,1H)；¹³C NMR(DMSO-d₆,100MHz):δ159.36,148.04,145.00,113.57,111.76ppm；MS(70eV):m/z(％)＝111.2.

Example 792-benzofuran carboxamides

A reaction tube was taken, and 60-100mg (1.2mmol) of nitromethane, 30-50mg (0.3mmol) of 2-benzofurancarboxaldehyde, 0.5mL of acetic acid, 200mg (0.6mmol) of trifluoromethanesulfonic anhydride, 30-60mg (0.75mmol) of formic acid were added, followed by stirring at 80-120 ℃ for 1-72 hours. After the reaction is finished, 10mL of sodium hydroxide solution is added to quench the reaction, ethyl acetate is used for extraction for 3 times, 5mL of organic phase saline is added for washing, organic phases are combined, and column chromatography separation is carried out to obtain 32.4mg of 2-benzofuran carboxamide with the yield of 67%.

¹H NMR(DMSO-d₆,400MHz):δ8.15(s,1H),7.76(d,J＝7.7Hz,1H),7.72(s,1H),7.63(d,J＝8.4Hz,1H),7.55(s,1H),7.44(ddd,J＝8.5,7.2,1.3Hz,1H),7.36–7.27(m,1H)；¹³C NMR(DMSO-d₆,100MHz):δ159.89,154.32,149.34,127.25,126.80,123.66,122.77,111.84,109.62ppm；MS(70eV):m/z(％)＝161.2.

Example 803-Benzothiophenecarboxamide

A reaction tube is taken, and 60-100mg (1.2mmol) of nitromethane, 40-60mg (0.3mmol) of 3-benzothiophenecarboxaldehyde, 0.5mL of acetic acid, 200mg (0.6mmol) of trifluoromethanesulfonic anhydride and 30-60mg (0.75mmol) of formic acid are added, and the mixture is stirred for 1-72 hours at 80-120 ℃. After the reaction is finished, 10mL of sodium hydroxide solution is added to quench the reaction, ethyl acetate is used for extraction for 3 times, 5mL of organic phase saline is added for washing, organic phases are combined, and the 3-benzothiophenecarboxamide 47.3mg is obtained through column chromatography separation, wherein the yield is 89%.

¹H NMR(DMSO-d₆,400MHz):δ8.55(d,J＝8.2Hz,1H),8.41(s,1H),8.01(d,J＝7.5Hz,1H),7.97(s,1H),7.50–7.29(m,3H)；¹³C NMR(DMSO-d₆,100MHz):δ165.01,139.52,137.36,131.29,130.82,124.79,122.70ppm；MS(70eV):m/z(％)＝177.3.

Example 814- (2-pyridinyl) -benzamide

A reaction tube was taken, and 60-100mg (1.2mmol) of nitromethane, 40-70mg (0.3mmol) of 4- (2-pyridyl) -benzaldehyde, 0.5mL of acetic acid, 200mg (0.6mmol) of trifluoromethanesulfonic anhydride, 30-60mg (0.75mmol) of formic acid were added, followed by stirring at 80-120 ℃ for 1-72 hours. After the reaction is finished, 10mL of sodium hydroxide solution is added to quench the reaction, ethyl acetate is used for extraction for 3 times, 5mL of saline is added to the organic phase for washing, the organic phase is combined, and column chromatography separation is carried out to obtain 53.5mg of 4- (2-pyridyl) -benzamide, wherein the yield is 90%.

¹H NMR(DMSO-d₆,400MHz):δ8.69(d,J＝4.3Hz,1H),8.17(d,J＝8.3Hz,2H),8.09(s,1H),8.02(t,J＝8.3Hz,3H),7.89(td,J＝9.1,7.8,1.4Hz,1H),7.45(s,1H),7.38(dd,J＝7.1,5.0Hz,1H)；¹³C NMR(DMSO-d₆,100MHz):δ167.76,155.16,149.76,141.26,137.46,134.56,128.10,126.38,123.22,122.37,120.81,119.17ppm；198.1.

Example 82 acetanilide

A reaction tube is taken, 60-100mg (1.2mmol) of nitromethane, 25-35mg (0.3mmol) of phenylacetylene, 0.5mL of acetic acid, 200mg (0.6mmol) of trifluoromethanesulfonic anhydride and 30-60mg (0.75mmol) of formic acid are added, and the mixture is stirred for 1-72 hours at 80-120 ℃. After the reaction is finished, 10mL of sodium hydroxide solution is added to quench the reaction, ethyl acetate is used for extraction for 3 times, 5mL of saline is added to the organic phase for washing, the organic phase is combined, and the acetanilide 30mg with the yield of 74% is obtained through column chromatography separation.

Example 83 Paramethylacetanilide

A reaction tube is taken, 60-100mg (1.2mmol) of nitromethane, 30-40mg (0.3mmol) of p-methylphenylacetylene, 0.5mL of acetic acid, 200mg (0.6mmol) of trifluoromethanesulfonic anhydride and 30-60mg (0.75mmol) of formic acid are added, and the mixture is stirred for 1-72 hours at 80-120 ℃. After the reaction is finished, 10mL of sodium hydroxide solution is added to quench the reaction, ethyl acetate is used for extraction for 3 times, 5mL of saline is added to the organic phase for washing, the organic phase is combined, and column chromatography separation is carried out to obtain 31.3mg of p-methylacetanilide with the yield of 70%.

Example 84 p-butylacetanilide

A reaction tube is taken and added with 60-100mg (1.2mmol) of nitromethane, 40-50mg (0.3mmol) of n-butyl phenylacetylene, 0.5mL of acetic acid, 200mg (0.6mmol) of trifluoromethanesulfonic anhydride, 30-60mg (0.75mmol) of formic acid, and stirred for 1-72 hours at 80-120 ℃. After the reaction is finished, 10mL of sodium hydroxide solution is added to quench the reaction, ethyl acetate is used for extraction for 3 times, 5mL of organic phase saline is added for washing, organic phases are combined, column chromatography separation is carried out to obtain 39mg of n-butylacetanilide, and the yield is 68%.

Example 85P-Phenylacetanilide

A reaction tube is taken, 60-100mg (1.2mmol) of nitromethane, 50-60mg (0.3mmol) of p-phenyl phenylacetylene, 0.5mL of acetic acid, 200mg (0.6mmol) of trifluoromethanesulfonic anhydride and 30-60mg (0.75mmol) of formic acid are added, and the mixture is stirred for 1-72 hours at 80-120 ℃. After the reaction is finished, 10mL of sodium hydroxide solution is added to quench the reaction, ethyl acetate is used for extraction for 3 times, 5mL of organic phase saline is added for washing, organic phases are combined, and column chromatography separation is carried out to obtain 34.2mg of p-phenylacetanilide, wherein the yield is 54%.

Example 86 Paramethoxyacetanilide

A reaction tube is taken, 60-100mg (1.2mmol) of nitromethane, 35-45mg (0.3mmol) of p-methoxyphenylacetylene, 0.5mL of acetic acid, 200mg (0.6mmol) of trifluoromethanesulfonic anhydride and 30-60mg (0.75mmol) of formic acid are added, and the mixture is stirred at 80-120 ℃ for 1-72 hours. After the reaction is finished, 10mL of sodium hydroxide solution is added to quench the reaction, ethyl acetate is used for extraction for 3 times, 5mL of saline is added to the organic phase for washing, the organic phase is combined, and column chromatography separation is carried out to obtain 31.2mg of p-methoxyacetanilide with the yield of 63%.

Example 87 Bromoacetanilide

A reaction tube is taken, 60-100mg (1.2mmol) of nitromethane, 50-60mg (0.3mmol) of p-bromophenylacetylene, 0.5mL of acetic acid, 200mg (0.6mmol) of trifluoromethanesulfonic anhydride and 30-60mg (0.75mmol) of formic acid are added, and the mixture is stirred for 1-72 hours at 80-120 ℃. After the reaction is finished, 10mL of sodium hydroxide solution is added to quench the reaction, ethyl acetate is used for extraction for 3 times, 5mL of saline is added to the organic phase for washing, the organic phase is combined, column chromatography separation is carried out to obtain 39.6mg of p-bromoacetanilide, and the yield is 62%.

Example 88 Parafluoroacetanilide

A reaction tube is taken, 60-100mg (1.2mmol) of nitromethane, 30-40mg (0.3mmol) of p-fluoroacetylene, 0.5mL of acetic acid, 200mg (0.6mmol) of trifluoromethanesulfonic anhydride and 30-60mg (0.75mmol) of formic acid are added, and the mixture is stirred at 80-120 ℃ for 1-72 hours. After the reaction is finished, 10mL of sodium hydroxide solution is added to quench the reaction, ethyl acetate is used for extraction for 3 times, 5mL of saline is added to the organic phase for washing, the organic phase is combined, column chromatography separation is carried out to obtain 34mg of p-fluoroacetanilide, and the yield is 74%.

Example 89 o-methoxyacetanilide

A reaction tube is taken and added with 60-100mg (1.2mmol) of nitromethane, 35-45mg (0.3mmol) of o-methoxyphenylacetylene, 0.5mL of acetic acid, 200mg (0.6mmol) of trifluoromethanesulfonic anhydride, 30-60mg (0.75mmol) of formic acid, and stirred for 1-72 hours at 80-120 ℃. After the reaction is finished, 10mL of sodium hydroxide solution is added to quench the reaction, ethyl acetate is used for extraction for 3 times, 5mL of saline is added to the organic phase for washing, the organic phase is combined, and column chromatography separation is carried out to obtain 20.8mg of o-methoxyacetanilide with the yield of 42%.

Example 90 o-methylacetanilide

A reaction tube is taken, 60-100mg (1.2mmol) of nitromethane, 30-40mg (0.3mmol) of o-tolylacetylene, 0.5mL of acetic acid, 200mg (0.6mmol) of trifluoromethanesulfonic anhydride and 30-60mg (0.75mmol) of formic acid are added, and the mixture is stirred at 80-120 ℃ for 1-72 hours. After the reaction is finished, 10mL of sodium hydroxide solution is added to quench the reaction, ethyl acetate is used for extraction for 3 times, 5mL of organic phase saline is added for washing, organic phases are combined, and column chromatography separation is carried out to obtain 17.9mg of o-methylacetanilide with the yield of 40%.

Example 91 m-fluoroacetanilide

A reaction tube is taken, 60-100mg (1.2mmol) of nitromethane, 30-40mg (0.3mmol) of m-fluoroacetylene, 0.5mL of acetic acid, 200mg (0.6mmol) of trifluoromethanesulfonic anhydride and 30-60mg (0.75mmol) of formic acid are added, and the mixture is stirred at 80-120 ℃ for 1-72 hours. After the reaction is finished, 10mL of sodium hydroxide solution is added to quench the reaction, ethyl acetate is used for extraction for 3 times, 5mL of saline is added to the organic phase for washing, the organic phase is combined, column chromatography separation is carried out to obtain 26.6mg of m-fluoroacetanilide, and the yield is 58%.

Example 92 Methylacetanilide

A reaction tube is taken, 60-100mg (1.2mmol) of nitromethane, 30-40mg (0.3mmol) of m-methylphenylacetylene, 0.5mL of acetic acid, 200mg (0.6mmol) of trifluoromethanesulfonic anhydride and 30-60mg (0.75mmol) of formic acid are added, and the mixture is stirred for 1-72 hours at 80-120 ℃. After the reaction is finished, 10mL of sodium hydroxide solution is added to quench the reaction, ethyl acetate is used for extraction for 3 times, 5mL of organic phase saline is added for washing, organic phases are combined, and column chromatography separation is carried out to obtain 17.9mg of m-methylacetanilide with the yield of 40%.

Example 93 m-Chloroacetanilide

A reaction tube is taken, 60-100mg (1.2mmol) of nitromethane, 35-45mg (0.3mmol) of m-chlorobenzene acetylene, 0.5mL of acetic acid, 200mg (0.6mmol) of trifluoromethanesulfonic anhydride and 30-60mg (0.75mmol) of formic acid are added, and the mixture is stirred for 1-72 hours at 80-120 ℃. After the reaction is finished, 10mL of sodium hydroxide solution is added to quench the reaction, ethyl acetate is used for extraction for 3 times, 5mL of saline is added to the organic phase for washing, the organic phase is combined, and the m-chloroacetanilide 27.9mg and the yield are obtained through column chromatography separation and 55%.

Example 94 Metahydroxyacetanilide

A reaction tube is taken, 60-100mg (1.2mmol) of nitromethane, 30-40mg (0.3mmol) of m-hydroxy phenylacetylene, 0.5mL of acetic acid, 200mg (0.6mmol) of trifluoromethanesulfonic anhydride and 30-60mg (0.75mmol) of formic acid are added, and the mixture is stirred for 1-72 hours at 80-120 ℃. After the reaction is finished, 10mL of sodium hydroxide solution is added to quench the reaction, ethyl acetate is used for extraction for 3 times, 5mL of organic phase saline is added for washing, organic phases are combined, and the m-hydroxyacetanilide 9.1mg and the yield is 20% are obtained through column chromatography separation.

Example 95N-Acylnaphthylamine

A reaction tube was taken, and 60-100mg (1.2mmol) of nitromethane, 40-50mg (0.3mmol) of 2-ethynylnaphthalene, 0.5mL of acetic acid, 200mg (0.6mmol) of trifluoromethanesulfonic anhydride, 30-60mg (0.75mmol) of formic acid were added, followed by stirring at 80-120 ℃ for 1-72 hours. After the reaction, 10mL of sodium hydroxide solution is added to quench the reaction, ethyl acetate is used for extraction for 3 times, 5mL of saline is added to the organic phase for washing, the organic phase is combined, and column chromatography separation is carried out to obtain 19.4mg of N-acetylnaphthylamine with the yield of 35%.

Example 96 Azidetridecan-2-one

A reaction tube was taken, and 60-100mg (1.2mmol) of nitromethane, 45-55mg (0.3mmol) of alkyne in ring 12, 0.5mL of acetic acid, 200mg (0.6mmol) of trifluoromethanesulfonic anhydride, 30-60mg (0.75mmol) of formic acid were added, followed by stirring at 80-120 ℃ for 1-72 hours. After the reaction is finished, 10mL of sodium hydroxide solution is added to quench the reaction, ethyl acetate is used for extraction for 3 times, 5mL of organic phase saline is added for washing, organic phases are combined, and the azacyclotridecane-2-ketone 24.8mg and the yield is 42% are obtained through column chromatography separation.

¹H NMR(CDCl₃,400MHz):δ6.04(s,1H),3.27(dd,J＝10.8,5.9Hz,2H),2.22–2.15(m,2H),1.71–1.61(m,2H),1.51-1.46(m,2H),1.41–1.22(m,14H)；¹³C NMR(CDCl₃,100MHz):δ173.51,38.94,36.76,28.20,26.67,26.25,26.10,25.64,25.14,24.85,24.54,23.83.ppm；MS(70eV):m/z(％)＝197.3.

Example 97 hexanoanilide

A reaction tube was taken, and 60-100mg (1.2mmol) of nitromethane, 40-50mg (0.3mmol) of 1-phenyl-1-hexyne, 0.5mL of acetic acid, 200mg (0.6mmol) of trifluoromethanesulfonic anhydride, 30-60mg (0.75mmol) of formic acid were added, followed by stirring at 80-120 ℃ for 1-72 hours. After the reaction is finished, 10mL of sodium hydroxide solution is added to quench the reaction, ethyl acetate is used for extraction for 3 times, 5mL of saline is added to the organic phase for washing, the organic phase is combined, and the hexanoyl aniline 36.1mg and the yield is 63% are obtained through column chromatography separation.

Example 98 Methylhexanoanilide

A reaction tube is taken, 60-100mg (1.2mmol) of nitromethane, 45-55mg (0.3mmol) of 1-p-methylbenzene-1-hexyne, 0.5mL of acetic acid, 200mg (0.6mmol) of trifluoromethanesulfonic anhydride and 30-60mg (0.75mmol) of formic acid are added, and the mixture is stirred for 1-72 hours at 80-120 ℃. After the reaction is finished, 10mL of sodium hydroxide solution is added to quench the reaction, ethyl acetate is used for extraction for 3 times, 5mL of saline is added to the organic phase for washing, the organic phase is combined, and column chromatography separation is carried out to obtain 38.8mg of p-formanilide A and the yield is 63%.

Example 99N-Benzenepropanamide

A reaction tube was taken, and 60-100mg (1.2mmol) of nitromethane, 30-40mg (0.3mmol) of 1-phenyl-1-propyne, 0.5mL of acetic acid, 200mg (0.6mmol) of trifluoromethanesulfonic anhydride, 30-60mg (0.75mmol) of formic acid were added, followed by stirring at 80-120 ℃ for 1-72 hours. After the reaction is finished, 10mL of sodium hydroxide solution is added to quench the reaction, ethyl acetate is used for extraction for 3 times, 5mL of saline is added to the organic phase for washing, the organic phase is combined, and the N-phenylacrylamide is obtained by column chromatography separation with 25mg of yield of 56%.

¹H NMR(CDCl₃,400MHz):δ7.52(d,J＝8.0Hz,2H),7.48(s,1H),7.30(t,J＝7.8Hz,2H),7.09(t,J＝7.4Hz,1H),2.38(q,J＝7.6Hz,2H),1.23(t,J＝7.7Hz,3H)；¹³C NMR(CDCl₃100MHz) delta 172.16,137.99,128.91,124.10,119.83,30.67,9.65 ppm; HRMS m/z (ESI) theoretical value C₉H₁₂NO(M+H)⁺150.0919, found 150.0920.

Example 100N, 2-bis (4-methoxyphenyl) acetamide

A reaction tube was taken, and 60-100mg (1.2mmol) of nitromethane, 65-75mg (0.3mmol) of 1, 2-bis (4-methoxyphenyl) acetylene, 0.5mL of acetic acid, 200mg (0.6mmol) of trifluoromethanesulfonic anhydride, 30-60mg (0.75mmol) of formic acid and stirred at 80-120 ℃ for 1-72 hours were added. After the reaction is finished, 10mL of sodium hydroxide solution is added to quench the reaction, ethyl acetate is used for extraction for 3 times, 5mL of saline is added to the organic phase for washing, the organic phase is combined, and the N, 2-bis (4-methoxyphenyl) acetamide 20.3mg is obtained by column chromatography separation with the yield of 25%.

¹H NMR(CDCl₃,400MHz):δ7.31(d,J＝9.0Hz,2H),7.25(d,J＝10.8Hz,2H),7.01(s,1H),6.93(d,J＝8.7Hz,2H),6.82(d,J＝9.0Hz,2H),3.83(s,3H),3.77(s,3H),3.66(s,2H)；¹³C NMR(CDCl₃100MHz) delta 169.37,159.08,156.51,130.75,130.69,126.48,121.71,114.64,114.06,55.45,55.31,43.75 ppm; HRMS m/z (ESI) theoretical value C₁₆H₁₈NO₃(M+H)⁺272.1287, found 272.1289.

Example 1012-Phenylacetanilide

A reaction tube is taken, 60-100mg (1.2mmol) of nitromethane, 50-60mg (0.3mmol) of diphenylacetylene, 0.5mL of acetic acid, 200mg (0.6mmol) of trifluoromethanesulfonic anhydride and 30-60mg (0.75mmol) of formic acid are added, and the mixture is stirred at 80-120 ℃ for 1-72 hours. After the reaction is finished, 10mL of sodium hydroxide solution is added to quench the reaction, ethyl acetate is used for extraction for 3 times, 5mL of organic phase saline is added for washing, organic phases are combined, and column chromatography separation is carried out to obtain 46.2mg of 2-phenylacetanilide with the yield of 73%.

Example 102N, 2-bis (4-bromophenyl) acetamide

A reaction tube was taken, and 60-100mg (1.2mmol) of nitromethane, 95-105mg (0.3mmol) of 1, 2-bis (4-bromophenyl) acetylene, 0.5mL of acetic acid, 200mg (0.6mmol) of trifluoromethanesulfonic anhydride, 30-60mg (0.75mmol) of formic acid and stirred at 80-120 ℃ for 1-72 hours were added. After the reaction is finished, 10mL of sodium hydroxide solution is added to quench the reaction, ethyl acetate is used for extraction for 3 times, 5mL of saline is added to an organic phase for washing, the organic phase is combined, and column chromatography separation is carried out to obtain 55mg of N, 2-bis (4-bromophenyl) acetamide with the yield of 50%.

¹H NMR(DMSO-d₆,400MHz):δ10.30(s,1H),7.56(d,J＝8.8Hz,2H),7.49(dd,J＝16.3,8.6Hz,4H),7.28(d,J＝8.3Hz,2H),3.64(s,2H)；¹³C NMR(DMSO-d₆100MHz) delta 168.78,138.43,135.11,131.51,131.41,131.12,121.01,119.78,114.81,42.43 ppm; HRMS m/z (ESI) theoretical value C₁H₁₂NOBr₂(M+H)⁺367.9286, found 367.9288.

Example 1035-chloro-N- (p-tolyl) pentanamide

A reaction tube was taken, and 60-100mg (1.2mmol) of nitromethane, 50-60mg (0.3mmol) of 1- (5-chloro-1-yn-1-yl) -4-methylbenzene, 0.5mL of acetic acid, 150 mg (0.6mmol) of trifluoromethanesulfonic anhydride, 30-60mg (0.75mmol) of formic acid and stirred at 80-120 ℃ for 1-72 hours were added. After the reaction, 10mL of sodium hydroxide solution was added to quench the reaction, which was extracted 3 times with ethyl acetate, the organic phase was washed with 5mL of brine, the organic phases were combined and separated by column chromatography to give 29.7mg of 5-chloro-N- (p-tolyl) pentanamide in 44% yield.

¹H NMR(CDCl₃,400MHz):δ7.54(s,1H),7.38(d,J＝8.3Hz,2H),7.10(d,J＝8.1Hz,2H),3.54(t,J＝5.8Hz,2H),2.36(t,J＝6.7Hz,2H),2.30(s,3H),1.91–1.77(m,4H)；¹³C NMR(CDCl₃100MHz) delta 170.70,135.21,133.91,129.39,120.06,44.54,36.46,31.86,22.82,20.79 ppm; HRMS m/z (ESI) theoretical value C₁₂H₁₇NOCl(M+H)⁺226.0999, found 226.1003.

Example 1046-oxy-6- (p-toluidino) hexyl acetate

A reaction tube was taken, and 60-100mg (1.2mmol) of nitromethane, 60-70mg (0.3mmol) of 6- (p-tolyl) hexa-5-yn-1-ylacetate, 0.5mL of acetic acid, 200mg (0.6mmol) of trifluoromethanesulfonic anhydride, 30-60mg (0.75mmol) of formic acid and stirred at 80-120 ℃ for 1-72 hours were added. After the reaction is finished, 10mL of sodium hydroxide solution is added to quench the reaction, ethyl acetate is used for extraction for 3 times, 5mL of saline is added to the organic phase for washing, the organic phase is combined, and column chromatography separation is carried out to obtain 40.3mg of 6-oxo-6- (p-toluidino) hexyl acetate with the yield of 51%.

¹H NMR(CDCl₃,400MHz):δ7.52(s,1H),7.38(d,J＝8.3Hz,2H),7.09(d,J＝8.1Hz,2H),4.04(t,J＝6.6Hz,2H),2.33(t,J＝7.5Hz,2H),2.29(s,3H),2.02(s,3H),1.73(p,J＝7.6Hz,2H),1.64(p,J＝6.9Hz,2H),1.49–1.34(m,2H)；¹³C NMR(CDCl₃100MHz) delta 171.20,171.03,135.38,133.71,129.34,119.91,64.23,37.29,28.32,25.53,25.13,20.92,20.76. ppm; HRMS m/z (ESI) theoretical value C₁₅H₂₂NO₃(M+H)⁺264.1600, found 264.1600.

Example 105N 1, N1-dimethyl-N7- (p-tolyl) pimelodiamide

A reaction tube was taken, and 60-100mg (1.2mmol) of nitromethane, 70-80mg (0.3mmol) of N, N-dimethyl-7- (p-tolyl) hept-6-ynylamide, 0.5mL of acetic acid, 200mg (0.6mmol) of trifluoromethanesulfonic anhydride, 30-60mg (0.75mmol) of formic acid and stirred at 80-120 ℃ for 1-72 hours were added. After the reaction, 10mL of sodium hydroxide solution was added to quench the reaction, which was extracted 3 times with ethyl acetate, the organic phase was washed with 5mL of brine, the organic phases were combined and separated by column chromatography to give N1, N1-dimethyl-N7- (p-tolyl) pimelinamide in 50.5mg, 61% yield.

¹H NMR(DMSO-d₆,400MHz):δ9.75(s,1H),7.47(d,J＝8.0Hz,2H),7.07(d,J＝8.0Hz,2H),2.93(s,3H),2.79(s,3H),2.33–2.13(m,7H),1.58(t,J＝7.6Hz,2H),1.50(t,J＝7.6Hz,2H),1.38–1.20(m,2H)；¹³C NMR(DMSO-d₆100MHz) delta 171.84,170.93,136.85,131.70,128.97,119.00,36.66,36.30,34.73,32.21,28.47,25.06,24.44,20.40. ppm; HRMS m/z (ESI) theoretical value C₁₆H₂₅N₂O₂(M+H)⁺277.1916, found 277.1915.

Example 106 acetanilide

A reaction tube is taken, 30-40mg (0.3mmol) of ethyl benzene, 5mg of N-hydroxyphthalimide, 4.0mg of cobalt acetate tetrahydrate and 0.5mL of acetic acid are added, stirring is carried out for 12 hours under the condition of oxygen atmosphere at the temperature of 80 ℃, then 500 mg (0.5mL) of nitromethane, 200mg (0.6mmol) of trifluoromethanesulfonic anhydride, 30-60mg (0.75mmol) of formic acid are added, and stirring is carried out for 1-72 hours at the temperature of 80-120 ℃. After the reaction is finished, 10mL of sodium hydroxide solution is added to quench the reaction, ethyl acetate is used for extraction for 3 times, 5mL of saline is added to the organic phase for washing, the organic phase is combined, and the acetanilide 29.2mg is obtained through column chromatography separation, wherein the yield is 72%.

Example 107 Paramethylacetanilide

A reaction tube is taken, 30-40mg (0.3mmol) of ethyl methyl benzene, 5mg of N-hydroxyphthalimide, 4.0mg of cobalt acetate tetrahydrate and 0.5mL of acetic acid are added, stirring is carried out for 12 hours under the condition of oxygen atmosphere at the temperature of 80 ℃, then 600mg (0.5mL) of nitromethane 500-100, 200mg (0.6mmol) of trifluoromethanesulfonic anhydride, 30-60mg (0.75mmol) of formic acid are added, and stirring is carried out for 1-72 hours at the temperature of 80-120 ℃. After the reaction is finished, 10mL of sodium hydroxide solution is added to quench the reaction, ethyl acetate is used for extraction for 3 times, 5mL of saline is added to the organic phase for washing, the organic phase is combined, column chromatography separation is carried out to obtain 32.7mg of p-methylacetanilide, and the yield is 73%.

Example 108P-Phenylacetanilide

Taking a reaction tube, adding 50-60mg (0.3mmol) of p-phenylethane, 5mg of N-hydroxyphthalimide, 4.0mg of cobalt acetate tetrahydrate and 0.5mL of acetic acid, stirring for 12 hours at 80 ℃ under the oxygen atmosphere, then adding 600mg (0.5mL) of nitromethane, 200mg (0.6mmol) of trifluoromethanesulfonic anhydride, 30-60mg (0.75mmol) of formic acid, and stirring for 1-72 hours at 80-120 ℃. After the reaction is finished, 10mL of sodium hydroxide solution is added to quench the reaction, ethyl acetate is used for extraction for 3 times, 5mL of organic phase saline is added for washing, organic phases are combined, and column chromatography separation is carried out to obtain 41.8mg of p-phenylacetanilide, wherein the yield is 66%.

Example 109 Paramethoxyacetanilide

A reaction tube is taken, 40-50mg (0.3mmol) of p-methoxy ethylbenzene, 5mg of N-hydroxyphthalimide, 4.0mg of cobalt acetate tetrahydrate and 0.5mL of acetic acid are added, and the mixture is stirred for 12 hours under the condition of oxygen atmosphere at the temperature of 80 ℃, then 600mg (0.5mL) of nitromethane, 200mg (0.6mmol) of trifluoromethanesulfonic anhydride, 30-60mg (0.75mmol) of formic acid are added, and the mixture is stirred for 1-72 hours at the temperature of 80-120 ℃. After the reaction is finished, 10mL of sodium hydroxide solution is added to quench the reaction, ethyl acetate is used for extraction for 3 times, 5mL of organic phase saline is added for washing, organic phases are combined, and column chromatography separation is carried out to obtain 40.6mg of p-phenylacetanilide with the yield of 82%.

Example 110 Bromoacetanilide

Taking a reaction tube, adding 50-60mg (0.3mmol) of p-bromoethylbenzene, 5mg of N-hydroxyphthalimide, 4.0mg of cobalt acetate tetrahydrate and 0.5mL of acetic acid, stirring for 12 hours at 80 ℃ under an oxygen atmosphere, then adding 600mg (0.5mL) of nitromethane, 200mg (0.6mmol) of trifluoromethanesulfonic anhydride, 30-60mg (0.75mmol) of formic acid, and stirring for 1-72 hours at 80-120 ℃. After the reaction is finished, 10mL of sodium hydroxide solution is added to quench the reaction, ethyl acetate is used for extraction for 3 times, 5mL of saline is added to the organic phase for washing, the organic phase is combined, column chromatography separation is carried out to obtain 44.7mg of p-bromoacetanilide, and the yield is 70%.

Example 111 Parafluoroacetanilide

A reaction tube is taken, 30-40mg (0.3mmol) of p-fluoroethylbenzene, 5mg of N-hydroxyphthalimide, 4.0mg of cobalt acetate tetrahydrate and 0.5mL of acetic acid are added, and the mixture is stirred for 12 hours under the condition of oxygen atmosphere at the temperature of 80 ℃, then 600mg (0.5mL) of nitromethane, 200mg (0.6mmol) of trifluoromethanesulfonic anhydride and 30-60mg (0.75mmol) of formic acid are added, and the mixture is stirred for 1-72 hours at the temperature of 80-120 ℃. After the reaction is finished, 10mL of sodium hydroxide solution is added to quench the reaction, ethyl acetate is used for extraction for 3 times, 5mL of saline is added to the organic phase for washing, the organic phase is combined, column chromatography separation is carried out to obtain 36.7mg of p-fluoroacetanilide, and the yield is 80%.

Example 112 Paracetanilide

A reaction tube is taken, 40-50mg (0.3mmol) of p-chloro-ethylbenzene, 5mg of N-hydroxyphthalimide, 4.0mg of cobalt acetate tetrahydrate and 0.5mL of acetic acid are added, and the mixture is stirred for 12 hours under the condition of oxygen atmosphere at the temperature of 80 ℃, then 600mg (0.5mL) of nitromethane, 200mg (0.6mmol) of trifluoromethanesulfonic anhydride, 30-60mg (0.75mmol) of formic acid are added, and the mixture is stirred for 1-72 hours at the temperature of 80-120 ℃. After the reaction is finished, 10mL of sodium hydroxide solution is added to quench the reaction, ethyl acetate is used for extraction for 3 times, 5mL of saline is added to the organic phase for washing, the organic phase is combined, column chromatography separation is carried out to obtain 37.5mg of p-chloroacetanilide, and the yield is 74%.

Example 113 o-methoxyacetanilide

A reaction tube is taken, 40-50mg (0.3mmol) of o-methoxyethylbenzene, 5mg of N-hydroxyphthalimide, 4.0mg of cobalt acetate tetrahydrate and 0.5mL of acetic acid are added, stirring is carried out for 12 hours under the oxygen atmosphere condition at the temperature of 80 ℃, then 600mg (0.5mL) of nitromethane 500-100, 200mg (0.6mmol) of trifluoromethanesulfonic anhydride, 30-60mg (0.75mmol) of formic acid are added, and stirring is carried out for 1-72 hours at the temperature of 80-120 ℃. After the reaction is finished, 10mL of sodium hydroxide solution is added to quench the reaction, ethyl acetate is used for extraction for 3 times, 5mL of saline is added to the organic phase for washing, the organic phase is combined, and column chromatography separation is carried out to obtain 29.7mg of o-methoxyacetanilide with the yield of 60%.

Example 114 o-methylacetanilide

A reaction tube is taken, 30-40mg (0.3mmol) of o-methyl ethylbenzene, 5mg of N-hydroxyphthalimide, 4.0mg of cobalt acetate tetrahydrate and 0.5mL of acetic acid are added, stirring is carried out for 12 hours under the condition of oxygen atmosphere at the temperature of 80 ℃, then 600mg (0.5mL) of nitromethane 500-ion, 200mg (0.6mmol) of trifluoromethanesulfonic anhydride, 30-60mg (0.75mmol) of formic acid are added, and stirring is carried out for 1-72 hours at the temperature of 80-120 ℃. After the reaction is finished, 10mL of sodium hydroxide solution is added to quench the reaction, ethyl acetate is used for extraction for 3 times, 5mL of saline is added to the organic phase for washing, the organic phase is combined, and column chromatography separation is carried out to obtain 29.1mg of o-methylacetanilide with the yield of 65%.

Example 115 o-Bromoacetylphenylamine

A reaction tube is taken, 30-40mg (0.3mmol) of o-bromoethylbenzene, 5mg of N-hydroxyphthalimide, 4.0mg of cobalt acetate tetrahydrate and 0.5mL of acetic acid are added, stirring is carried out for 12 hours under the condition of oxygen atmosphere at the temperature of 80 ℃, then 600mg (0.5mL) of nitromethane 500-100, 200mg (0.6mmol) of trifluoromethanesulfonic anhydride, 30-60mg (0.75mmol) of formic acid are added, and stirring is carried out for 1-72 hours at the temperature of 80-120 ℃. After the reaction is finished, 10mL of sodium hydroxide solution is added to quench the reaction, ethyl acetate is used for extraction for 3 times, 5mL of organic phase saline is added for washing, organic phases are combined, column chromatography separation is carried out to obtain 32mg of o-bromoacetamidine, and the yield is 50%.

Example 116 benzamide

A reaction tube is taken, 20-30mg (0.3mmol) of toluene, 5mg of N-hydroxyphthalimide, 2.0mg of cobalt acetate tetrahydrate and 0.6mL of hexafluoroisopropanol are added, and the mixture is stirred for 12 hours under the condition of oxygen atmosphere at the temperature of 25 ℃, and then 600mg (0.5mL) of nitromethane 500-200 mg (0.6mmol), 30-60mg (0.75mmol) of trifluoromethanesulfonic anhydride and 0.5mL of acetic acid are added, and the mixture is stirred for 1-72 hours at the temperature of 80-120 ℃. After the reaction is finished, 10mL of sodium hydroxide solution is added to quench the reaction, ethyl acetate is used for extraction for 3 times, 5mL of saline is added to an organic phase for washing, the organic phase is combined, and column chromatography separation is carried out to obtain 20mg of benzamide, wherein the yield is 55%.

Example 117 Paramethylbenzamide

Taking a reaction tube, adding 25-35mg (0.3mmol) of p-xylene, 5mg of N-hydroxyphthalimide, 2.0mg of cobalt acetate tetrahydrate and 0.6mL of hexafluoroisopropanol, stirring for 12 hours under the oxygen atmosphere condition at 25 ℃, then adding 500 mg (0.5mL) of nitromethane, 200mg (0.6mmol) of trifluoromethanesulfonic anhydride, 30-60mg (0.75mmol) of formic acid and 0.5mL of acetic acid, and stirring for 1-72 hours at 80-120 ℃. After the reaction is finished, 10mL of sodium hydroxide solution is added to quench the reaction, ethyl acetate is used for extraction for 3 times, 5mL of saline is added to the organic phase for washing, the organic phase is combined, and column chromatography separation is carried out to obtain 21.5mg of p-methylbenzamide with the yield of 53%.

Example 118 p-tert-Butylcarboxamide

A reaction tube is taken, 40-50mg (0.3mmol) of p-tert-butyltoluene, 5mg of N-hydroxyphthalimide, 2.0mg of cobalt acetate tetrahydrate and 0.6mL of hexafluoroisopropanol are added, stirring is carried out for 12 hours under the oxygen atmosphere condition at the temperature of 25 ℃, then 500 mg (0.5mL) of nitromethane, 200mg (0.6mmol) of trifluoromethanesulfonic anhydride, 30-60mg (0.75mmol) of formic acid and 0.5mL of acetic acid are added, and stirring is carried out for 1-72 hours at the temperature of 80-120 ℃. After the reaction is finished, 10mL of sodium hydroxide solution is added to quench the reaction, ethyl acetate is used for extraction for 3 times, 5mL of saline is added to an organic phase for washing, the organic phase is combined, column chromatography separation is carried out to obtain 26.6mg of p-tert-butylbenzamide, and the yield is 50%.

Example 119 Paramethoxybenzamide

30-40mg (0.3mmol) of p-methoxytoluene, 5mg of N-hydroxyphthalimide, 2.0mg of cobalt acetate tetrahydrate and 0.6mL of hexafluoroisopropanol are added into a reaction tube, and stirred for 12 hours under the oxygen atmosphere condition at the temperature of 25 ℃, and then 500 mg (0.5mL) of nitromethane, 200mg (0.6mmol) of trifluoromethanesulfonic anhydride, 30-60mg (0.75mmol) of formic acid and 0.5mL of acetic acid are added and stirred for 1-72 hours at the temperature of 80-120 ℃. After the reaction is finished, 10mL of sodium hydroxide solution is added to quench the reaction, ethyl acetate is used for extraction for 3 times, 5mL of saline is added to an organic phase for washing, the organic phase is combined, column chromatography separation is carried out to obtain 31.7mg of p-methoxybenzamide, and the yield is 70%.

Example 120 p-Chlorobenzamide

30-40mg (0.3mmol) of p-chlorotoluene, 5mg of N-hydroxyphthalimide, 2.0mg of cobalt acetate tetrahydrate and 0.6mL of hexafluoroisopropanol are added into a reaction tube, and stirred for 12 hours under the oxygen atmosphere condition at the temperature of 25 ℃, and then 500 mg (0.5mL) of nitromethane, 200mg (0.6mmol) of trifluoromethanesulfonic anhydride, 30-60mg (0.75mmol) of formic acid and 0.5mL of acetic acid are added and stirred for 1-72 hours at the temperature of 80-120 ℃. After the reaction is finished, 10mL of sodium hydroxide solution is added to quench the reaction, ethyl acetate is used for extraction for 3 times, 5mL of saline is added to an organic phase for washing, the organic phases are combined, column chromatography separation is carried out to obtain 24.2mg of p-chlorobenzamide, and the yield is 52%.

Example 121 para-Bromobenzamide

Taking a reaction tube, adding 45-55mg (0.3mmol) of p-bromotoluene, 5mg of N-hydroxyphthalimide, 2.0mg of cobalt acetate tetrahydrate and 0.6mL of hexafluoroisopropanol, stirring for 12 hours under the oxygen atmosphere condition at the temperature of 25 ℃, then adding 500 mg (0.5mL) of nitromethane, 200mg (0.6mmol) of trifluoromethanesulfonic anhydride, 30-60mg (0.75mmol) of formic acid and 0.5mL of acetic acid, and stirring for 1-72 hours at the temperature of 80-120 ℃. After the reaction is finished, 10mL of sodium hydroxide solution is added to quench the reaction, ethyl acetate is used for extraction for 3 times, 5mL of saline is added to the organic phase for washing, the organic phase is combined, and column chromatography separation is carried out to obtain 37.6mg of p-bromobenzamide with the yield of 63%.

Example 122P-iodobenzamide

Taking a reaction tube, adding 60-70mg (0.3mmol) of p-iodotoluene, 5mg of N-hydroxyphthalimide, 2.0mg of cobalt acetate tetrahydrate and 0.6mL of hexafluoroisopropanol, stirring for 12 hours under the oxygen atmosphere condition at 25 ℃, then adding 500 mg (0.5mL) of nitromethane, 200mg (0.6mmol) of trifluoromethanesulfonic anhydride, 30-60mg (0.75mmol) of formic acid and 0.5mL of acetic acid, and stirring for 1-72 hours at 80-120 ℃. After the reaction is finished, 10mL of sodium hydroxide solution is added to quench the reaction, ethyl acetate is used for extraction for 3 times, 5mL of saline is added to the organic phase for washing, the organic phase is combined, and column chromatography separation is carried out to obtain 44.5mg of p-iodobenzamide, wherein the yield is 60%.

Example 123M-Bromobenzamide

Taking a reaction tube, adding 45-55mg (0.3mmol) of m-bromotoluene, 5mg of N-hydroxyphthalimide, 2.0mg of cobalt acetate tetrahydrate and 0.6mL of hexafluoroisopropanol, stirring for 12 hours under the oxygen atmosphere condition at the temperature of 25 ℃, then adding 500 mg (0.5mL) of nitromethane, 200mg (0.6mmol) of trifluoromethanesulfonic anhydride, 30-60mg (0.75mmol) of formic acid and 0.5mL of acetic acid, and stirring for 1-72 hours at the temperature of 80-120 ℃. After the reaction is finished, 10mL of sodium hydroxide solution is added to quench the reaction, ethyl acetate is used for extraction for 3 times, an organic phase is added, 5mL of saline is used for washing, organic phases are combined, column chromatography separation is carried out to obtain 31mg of m-bromobenzamide, and the yield is 52%.

EXAMPLE 124M-methylbenzamide

Taking a reaction tube, adding 25-35mg (0.3mmol) of m-xylene, 5mg of N-hydroxyphthalimide, 2.0mg of cobalt acetate tetrahydrate and 0.6mL of hexafluoroisopropanol, stirring for 12 hours under the oxygen atmosphere condition at 25 ℃, then adding 500 mg (0.5mL) of nitromethane, 200mg (0.6mmol) of trifluoromethanesulfonic anhydride, 30-60mg (0.75mmol) of formic acid and 0.5mL of acetic acid, and stirring for 1-72 hours at 80-120 ℃. After the reaction is finished, 10mL of sodium hydroxide solution is added to quench the reaction, ethyl acetate is used for extraction for 3 times, 5mL of saline is added to the organic phase for washing, the organic phase is combined, and column chromatography separation is carried out to obtain 20.3mg of m-methylbenzamide with the yield of 50%.

EXAMPLE 125 Isoiodobenzamide

Taking a reaction tube, adding 60-70mg (0.3mmol) of m-iodobenzene, 5mg of N-hydroxyphthalimide, 2.0mg of cobalt acetate tetrahydrate and 0.6mL of hexafluoroisopropanol, stirring for 12 hours under the oxygen atmosphere condition at 25 ℃, then adding 500 mg (0.5mL) of nitromethane, 200mg (0.6mmol) of trifluoromethanesulfonic anhydride, 30-60mg (0.75mmol) of formic acid, 0.5mL of acetic acid and stirring for 1-72 hours at 80-120 ℃. After the reaction is finished, 10mL of sodium hydroxide solution is added to quench the reaction, ethyl acetate is used for extraction for 3 times, 5mL of saline is added to the organic phase for washing, the organic phase is combined, and column chromatography separation is carried out to obtain 29.6mg of m-iodobenzamide, wherein the yield is 40%.

Example 1263, 5-Dimethylbenzamide

Taking a reaction tube, adding 30-40mg (0.3mmol) of mesitylene, 5mg of N-hydroxyphthalimide, 2.0mg of cobalt acetate tetrahydrate and 0.6mL of hexafluoroisopropanol, stirring for 12 hours under the oxygen atmosphere condition at 25 ℃, then adding 500 mg (0.5mL) of nitromethane, 200mg (0.6mmol) of trifluoromethanesulfonic anhydride, 30-60mg (0.75mmol) of formic acid and 0.5mL of acetic acid, and stirring for 1-72 hours at 80-120 ℃. After the reaction is finished, 10mL of sodium hydroxide solution is added to quench the reaction, ethyl acetate is used for extraction for 3 times, 5mL of saline is added to the organic phase for washing, the organic phase is combined, and the 3, 5-dimethyl benzamide 20.1mg is obtained through column chromatography separation, wherein the yield is 45%.

¹H NMR(DMSO-d₆,400MHz):δ7.85(s,1H),7.48(s,2H),7.24(s,1H),7.13(s,1H),2.30(s,6H)；¹³C NMR(DMSO-d₆,100MHz):δ168.10,137.20,134.25,132.39,125.23,20.82ppm；MS(70eV):m/z(％)＝.149.2

Example 127 Paramethylacetanilide

A reaction tube is taken and added with 60-100mg (1.2mmol) of hydroxylamine hydrochloride, 35-45mg (0.3mmol) of p-methylacetophenone, 0.5mL of acetic acid, 200mg (0.6mmol) of trifluoromethanesulfonic anhydride, 30-60mg (0.75mmol) of formic acid, and stirred for 1-72 hours at 80-120 ℃. After the reaction is finished, 10mL of sodium hydroxide solution is added to quench the reaction, ethyl acetate is used for extraction for 3 times, 5mL of organic phase saline is added for washing, organic phases are combined, and column chromatography separation is carried out to obtain 9.0mg of o-methylacetanilide with the yield of 20%.

Example 128 Paramethylacetanilide

A reaction tube was taken, and 200mg (1.2mmol) of O-acetylhydroxylamine trifluoromethanesulfonate 100-. After the reaction is finished, 10mL of sodium hydroxide solution is added to quench the reaction, ethyl acetate is used for extraction for 3 times, 5mL of organic phase saline is added for washing, organic phases are combined, column chromatography separation is carried out to obtain 38mg of p-methylacetanilide, and the yield is 85%.

Example 129 Paramethylacetanilide

A reaction tube was taken, and 200mg (1.2mmol) of O-acetylhydroxylamine trifluoromethanesulfonate 100-. After the reaction is finished, 10mL of sodium hydroxide solution is added to quench the reaction, ethyl acetate is used for extraction for 3 times, 5mL of organic phase saline is added for washing, organic phases are combined, column chromatography separation is carried out to obtain 40mg of p-methylacetanilide, and the yield is 90%.

Example 130 Paraphenylbenzamides

A reaction tube was taken, and 200mg (1.2mmol) of O-acetylhydroxylamine trifluoromethanesulfonate 100-. After the reaction is finished, 10mL of sodium hydroxide solution is added to quench the reaction, ethyl acetate is used for extraction for 3 times, 5mL of saline is added to an organic phase for washing, the organic phase is combined, column chromatography separation is carried out to obtain 53mg of p-phenyl benzamide, and the yield is 90%.

Example 131 caprolactam

Adding 0.5mL of nitromethane, 0.5mL of acetic acid, 150 mg of trifluoromethanesulfonic anhydride (0.6mmol) and 30-60mg of formic acid (0.75mmol) into a reaction tube, stirring at 80-120 ℃ for 1-72 hours, then adding 25-40mg of cyclohexanone, stirring at 80-120 ℃ for 1-72 hours, adding 10mL of sodium hydroxide solution after the reaction is finished, quenching the reaction, extracting for 3 times by using ethyl acetate, adding 5mL of saline into an organic phase, washing, combining the organic phases, and separating by column chromatography to obtain 28.8mg of 6-oxo-6- (p-toluidinyl) hexyl acetate with the yield of 51%.

Example 1326-oxo-6-phenylamino-hexanoic acid ethyl ester

Adding 40-50mg (0.3mmol) of cyclohexylbenzene, 5mg of N-hydroxyphthalimide, 4.0mg of cobalt acetate tetrahydrate and 0.5mL of acetic acid into a reaction tube, stirring for 12 hours at 80 ℃ under an oxygen atmosphere, and then adding 500 mg (0.5mL) of nitromethane and 600mg (0.5mL) of trifluoromethanesulfonic acidAcid anhydride 150 mg (0.6mmol), formic acid 30-60mg (0.75mmol), stirring at 80-120 deg.C for 1-72 hours. After the reaction is finished, 10mL of sodium hydroxide solution is added to quench the reaction, ethyl acetate is used for extraction for 3 times, 5mL of saline is added to the organic phase for washing, the organic phase is combined, and the 6-oxo-6-phenylamino-ethyl hexanoate 23.2mg is obtained through column chromatography separation, wherein the yield is 31%.¹H NMR(CDCl₃,400MHz):δ7.73(s,1H),7.54(d,J＝8.0Hz,2H),7.31(t,J＝7.9Hz,2H),7.10(t,J＝7.3Hz,1H),4.06(t,J＝6.6Hz,2H),2.37(t,J＝7.5Hz,2H),2.05(s,3H),1.79-1.1.70(m,2H),1.70–1.60(m,2H),1.46-1.37(m,2H)；¹³C NMR(CDCl₃,100MHz):δ171.33,171.20,138.01,128.79,124.04,119.84,64.20,37.24,28.26,25.48,25.08,20.89.ppm.

Example 133 iloperidone derivative

Taking a reaction tube, adding 60-100mg (1.2mmol) of nitromethane, 200mg (0.3mmol) of p-iloperidone 120-. After the reaction is finished, 10mL of sodium hydroxide solution is added to quench the reaction, ethyl acetate is used for extraction for 3 times, 5mL of saline is added to the organic phase for washing, the organic phase is combined, and column chromatography separation is carried out to obtain 83.3mg of iloperidone derivative with the yield of 63%.¹H NMR(DMSO-d₆,400MHz):δ9.80(s,1H),7.94(dd,J＝8.7,5.3Hz,1H),7.63(dd,J＝9.1,2.0Hz,1H),7.31(d,J＝2.2Hz,1H),7.23(td,J＝9.1,2.0Hz,1H),7.09(dd,J＝8.7,2.2Hz,1H),6.87(d,J＝8.7Hz,1H),3.94(t,J＝6.3Hz,2H),3.73(s,3H),3.09(ddd,J＝11.7,8.2,3.7Hz,1H),2.97(d,J＝11.3Hz,2H),2.48(t,J＝7.1Hz,2H),2.11(t,J＝10.9Hz,2H),2.04–1.97(m,5H),1.91–1.78(m,4H)；¹³C NMR(DMSO-d₆,100MHz):δ167.75,163.59(d,J＝246Hz),162.99(d,J＝14Hz),161.22,148.90,143.89,133.25,123.63(d,J＝12Hz),117.19,113.72,112.37(d,J＝25Hz),110.97,104.47,97.25(d,J＝27Hz),67.04,55.37,54.69,52.93,33.44,30.04,26.45,23.86；¹⁹F NMR(DMSO-d₆,377MHz):δ-109.93ppm.

Example 134 Ezetimibe derivatives

A reaction tube is taken, 60-100mg (1.2mmol) of nitromethane, 200mg (0.3mmol) of the ezetimibe intermediate 120-200, 0.5mL of acetic acid, 200mg (0.6mmol) of trifluoromethanesulfonic anhydride 150-200 and 30-60mg (0.75mmol) of formic acid are added, and the mixture is stirred for 1-72 hours at the temperature of 80-120 ℃. After the reaction is finished, 10mL of sodium hydroxide solution is added to quench the reaction, ethyl acetate is used for extraction for 3 times, 5mL of saline is added to the organic phase for washing, the organic phase is combined, and column chromatography separation is carried out to obtain 28.9mg of the ezetimibe derivative with the yield of 26%.¹H NMR(CDCl₃,400MHz):δ7.88(s,1H),7.46–7.41(m,2H),7.41–7.31(m,3H),7.28(d,J＝6.2Hz,2H),6.96(t,J＝8.7Hz,2H),5.40(dd,J＝8.7,3.6Hz,1H),4.66(t,J＝8.8Hz,1H),4.25(dd,J＝8.9,3.7Hz,1H),3.10–2.95(m,2H),2.41–2.27(m,2H),2.01(p,J＝7.2Hz,2H)；¹³C NMR(CDCl₃,100MHz):δ172.14,170.60,159.11(d,J＝242Hz),153.75,138.93,133.94,129.13,128.67,125.73,121.65(d,J＝8Hz),115.37(d,J＝22Hz)70.03,57.49,35.93,34.68,19.87；¹⁹F NMR(CDCl₃,377MHz):δ-118.23ppm.

Example 135 Fenbufen derivatives

A reaction tube is taken, 60-100mg (1.2mmol) of nitromethane, 60-120mg (0.3mmol) of fenbufen, 0.5mL of acetic acid, 200mg (0.6mmol) of trifluoromethanesulfonic anhydride and 30-60mg (0.75mmol) of formic acid are added, and the mixture is stirred for 1-72 hours at 80-120 ℃. After the reaction is finished, 10mL of sodium hydroxide solution is added to quench the reaction, ethyl acetate is used for extraction for 3 times, 5mL of saline is added to the organic phase for washing, the organic phase is combined, and column chromatography separation is carried out to obtain 28.9mg of the fenbufen derivative with the yield of 26%.¹H NMR(DMSO-d₆,400MHz):δ7.77(d,J＝8.4Hz,2H),7.70(d,J＝7.4Hz,2H),7.49(t,J＝7.6Hz,2H),7.38(dd,J＝17.0,7.9Hz,3H),2.81(s,4H)；¹³C NMR(DMSO-d₆,100MHz):δ176.96,139.93,139.39,132.00,129.01,127.75,127.51,127.09,126.82,28.51ppm.

Example 136 Tunna Musk derivatives

A reaction tube was taken, and 60-100mg (1.2mmol) of nitromethane, 60-120mg (0.3mmol) of musk tonalide, 0.5mL of acetic acid, 200mg (0.6mmol) of trifluoromethanesulfonic anhydride, 30-60mg (0.75mmol) of formic acid were added, followed by stirring at 80-120 ℃ for 1-72 hours. After the reaction is finished, 10mL of sodium hydroxide solution is added to quench the reaction, ethyl acetate is used for extraction for 3 times, 5mL of saline is added to the organic phase for washing, the organic phase is combined, column chromatography separation is carried out to obtain 60.7mg of tonalid derivatives, and the yield is 74%.¹H NMR(CDCl₃,400MHz):δ7.58(s,1H),7.14(s,2H),2.20(s,3H),2.16(s,3H),1.90–1.81(m,2H),1.62(t,J＝13.2Hz,1H),1.30(s,3H),1.28(s,3H),1.24(s,3H),1.04(s,3H),0.98(d,J＝6.7Hz,3H)；¹³C NMR(CDCl₃,100MHz):δ168.43,143.28,143.18,133.09,128.84,127.41,121.73,43.58,37.30,34.48,34.10,32.25,31.94,28.54,24.89,24.00,17.58,16.74ppm.

Example 137 Dacronine derivatives

A reaction tube is taken, 60-100mg (1.2mmol) of nitromethane, 60-120mg (0.3mmol) of dyclonine, 0.5mL of acetic acid, 200mg (0.6mmol) of trifluoromethanesulfonic anhydride and 30-60mg (0.75mmol) of formic acid are added, and the mixture is stirred at 80-120 ℃ for 1-72 hours. After the reaction is finished, 10mL of sodium hydroxide solution is added to quench the reaction, ethyl acetate is used for extraction for 3 times, organic phase is added with 5mL of saline for washing, organic phases are combined, and the dyclonine derivative 77.5mg is obtained through column chromatography separation, wherein the yield is 85%.¹H NMR(DMSO-d₆,400MHz):δ9.99(s,1H),7.48(d,J＝8.8Hz,2H),6.87(d,J＝8.9Hz,2H),3.91(t,J＝6.4Hz,2H),3.31(t,J＝7.0Hz,2H),3.13(s,4H),2.77(t,J＝7.0Hz,2H),1.77–1.61(m,6H),1.53(s,2H),1.46-1.36(m,2H),0.92(t,J＝7.4Hz,3H)；¹³C NMR(DMSO-d₆,100MHz):δ167.37,154.82,131.82,120.79,114.46,67.25,52.47,52.12,30.80,30.50,22.70,21.30,18.74,13.67ppm.

Example 138 Metaxalone derivatives

Taking a reaction tube, 60-120mg (0.3mmol) of metaxalone, 5mg of N-hydroxyphthalimide, 2.0mg of cobalt acetate tetrahydrate and 0.6mL of hexafluoroisopropanol, stirring for 12 hours at 25 ℃ under the oxygen atmosphere, then adding 500 mg (0.5mL) of nitromethane, 200mg (0.6mmol) of trifluoromethanesulfonic anhydride, 30-60mg (0.75mmol) of formic acid and 0.5mL of acetic acid, and stirring for 1-72 hours at 80-120 ℃. After the reaction is finished, 10mL of sodium hydroxide solution is added to quench the reaction, ethyl acetate is used for extraction for 3 times, 5mL of saline is added to the organic phase for washing, the organic phase is combined, and column chromatography separation is carried out to obtain 45mg of metaxalone derivative with the yield of 33.8%.¹H NMR(DMSO-d₆,400MHz):δ7.92(s,1H),7.63(s,1H),7.31(s,2H),7.26(s,1H),6.95(s,1H),4.95–4.84(m,1H),4.31–4.05(m,2H),3.62(t,J＝9.0Hz,1H),3.37–3.30(m,1H),2.31(s,3H)；¹³C NMR(DMSO-d₆,100MHz):δ167.61,158.60,158.01,139.07,135.55,121.05,118.14,110.54,73.44,68.67,41.48,21.01.ppm.

Example 139 Propadone derivatives

A reaction tube is taken, 60-100mg (1.2mmol) of nitromethane, 60-120mg (0.3mmol) of propafenone, 0.5mL of acetic acid, 200mg (0.6mmol) of trifluoromethanesulfonic anhydride and 30-60mg (0.75mmol) of formic acid are added, and the mixture is stirred for 1-72 hours at 80-120 ℃. After the reaction is finished, 10mL of sodium hydroxide solution is added to quench the reaction, ethyl acetate is used for extraction for 3 times, 5mL of organic phase saline is added for washing, organic phases are combined, column chromatography separation is carried out to obtain 102mg of propafenone derivative, and the yield is high82％。¹H NMR(DMSO-d₆,400MHz):δ8.84(s,1H),7.89(d,J＝7.8Hz,1H),7.32–7.25(m,4H),7.23–7.15(m,1H),7.11–7.03(m,2H),6.99–6.90(m,1H),4.94–4.83(m,1H),4.21–4.14(m,2H),3.68(t,J＝9.0Hz,1H),3.45(dd,J＝8.8,6.5Hz,1H),3.21–3.03(m,2H),2.92(t,J＝7.8Hz,2H),2.70(t,J＝7.8Hz,2H),1.49(h,J＝7.3Hz,2H),0.83(t,J＝7.4Hz,3H)；¹³C NMR(DMSO-d₆,100MHz):δ170.30,157.09,148.76,141.11,128.26,128.22,127.63,125.89,124.51,122.53,121.07,113.10,70.81,69.48,45.41,45.00,37.68,30.86,20.01,10.94ppm.

EXAMPLE 140 acebutolol derivatives

A reaction tube is taken, 60-100mg (1.2mmol) of nitromethane, 60-120mg (0.3mmol) of acebutolol, 0.5mL of acetic acid, 200mg (0.6mmol) of trifluoromethanesulfonic anhydride and 30-60mg (0.75mmol) of formic acid are added, and the mixture is stirred for 1-72 hours at 80-120 ℃. After the reaction is finished, 10mL of sodium hydroxide solution is added to quench the reaction, ethyl acetate is used for extraction for 3 times, 5mL of saline is added to the organic phase for washing, the organic phase is combined, column chromatography separation is carried out to obtain 46.7mg of the acebutolol derivative, and the yield is 62%.¹H NMR(DMSO-d₆,400MHz):δ9.77(s,1H),8.82(s,1H),8.04(s,1H),7.45(d,J＝8.6Hz,1H),7.00(d,J＝8.8Hz,1H),4.87(s,1H),4.14(d,J＝3.8Hz,2H),3.89(dt,J＝13.2,6.7Hz,1H),3.63(t,J＝8.8Hz,1H),3.46–3.36(m,1H),2.23(t,J＝7.2Hz,2H),2.07(s,3H),1.59(dd,J＝14.4,7.2Hz,2H),1.12(dd,J＝5.9,3.1Hz,6H),0.90(t,J＝7.2Hz,3H)；¹³C NMR(DMSO-d₆,100MHz):δ170.71,168.13,156.14,144.39,133.02,127.67,115.20,113.90,113.30,71.04,69.93,44.26,40.94,38.16,23.82,19.49,19.28,18.58,13.62ppm.

Example 141 tolperisone derivatives

Taking a reaction tube, adding60-100mg (1.2mmol) of nitromethane, 60-120mg (0.3mmol) of tolperisone, 0.5mL of acetic acid, 150 mg (0.6mmol) of trifluoromethanesulfonic anhydride, 30-60mg (0.75mmol) of formic acid, and stirring at 80-120 ℃ for 1-72 hours. After the reaction is finished, 10mL of sodium hydroxide solution is added to quench the reaction, ethyl acetate is used for extraction for 3 times, 5mL of saline is added to the organic phase for washing, the organic phase is combined, and column chromatography separation is carried out to obtain 62.4mg of tolperisone derivative with the yield of 80%.¹H NMR(DMSO-d₆,400MHz):δ10.13(s,1H),7.47(d,J＝8.4Hz,2H),7.09(d,J＝8.3Hz,2H),2.74–2.64(m,1H),2.58–2.42(m,3H),2.35-2.31(m,2H),2.25(s,3H),2.19(dd,J＝12.2,5.5Hz,1H),1.52-1.46(m,4H),1.40-1.36(m,2H),1.04(d,J＝6.8Hz,3H)；¹³C NMR(DMSO-d₆,100MHz):δ173.40,136.86,131.70,129.00,119.02,62.15,54.07,37.53,25.67,23.96,20.38,15.71.ppm.

Example 142 Aripirrubicin derivatives

A reaction tube is taken, 60-100mg (1.2mmol) of nitromethane, 60-120mg (0.3mmol) of eperepine, 0.5mL of acetic acid, 200mg (0.6mmol) of trifluoromethanesulfonic anhydride and 30-60mg (0.75mmol) of formic acid are added, and the mixture is stirred for 1-72 hours at 80-120 ℃. After the reaction is finished, 10mL of sodium hydroxide solution is added to quench the reaction, ethyl acetate is used for extraction for 3 times, 5mL of saline is added to the organic phase for washing, the organic phase is combined, and the eperexopine derivative 59.2mg and the yield is 72% are obtained through column chromatography separation.¹H NMR(DMSO-d₆,400MHz):δ10.15(s,1H),7.49(d,J＝8.4Hz,2H),7.12(d,J＝8.4Hz,2H),2.76–2.63(m,1H),2.57-2.50(m,3H),2.45(d,J＝4.5Hz,2H),2.31(d,J＝4.9Hz,2H),2.19(dd,J＝12.2,5.5Hz,1H),1.52-1.46(m,4H),1.43–1.34(m,2H),1.15(t,J＝7.6Hz,3H),1.04(d,J＝6.8Hz,3H)；¹³C NMR(DMSO-d₆,100MHz):δ173.39,138.21,137.07,127.80,119.08,62.16,54.07,37.51,27.56,25.68,23.96,15.71.ppm.

Example 143 Katacrine derivatives

A reaction tube is taken, and 60-100mg (1.2mmol) of nitromethane, 60-120mg (0.3mmol) of ketanserin, 0.5mL of acetic acid, 200mg (0.6mmol) of trifluoromethanesulfonic anhydride and 30-60mg (0.75mmol) of formic acid are added, and the mixture is stirred at 80-120 ℃ for 1-72 hours. After the reaction is finished, 10mL of sodium hydroxide solution is added to quench the reaction, ethyl acetate is used for extraction for 3 times, 5mL of saline is added to the organic phase for washing, the organic phase is combined, and the Kataerin derivative 83.7mg is obtained through column chromatography separation, wherein the yield is 72%.¹H NMR(DMSO-d₆,400MHz):δ11.43(s,1H),9.89(s,1H),7.93(d,J＝7.7Hz,1H),7.70–7.54(m,3H),7.23–7.16(m,2H),7.11(t,J＝8.8Hz,2H),4.04(t,J＝6.4Hz,2H),3.01(s,2H),2.52(d,J＝12.1Hz,2H),2.29(s,1H),2.02(s,2H),1.74(d,J＝11.2Hz,2H),1.61(dd,J＝21.9,11.2Hz,2H)；¹³C NMR(DMSO-d₆,100MHz):δ173.36,161.86,157.77(d,J＝238Hz),150.10,139.37,135.75,134.92,127.33,122.45,120.75(d,J＝8Hz),115.21,115.03(d,J＝7Hz),113.70,55.18,52.82,42.78,37.45,28.44；¹⁹F NMR(DMSO-d₆,377MHz):δ-119.78ppm.

Example 144 purine derivatives

A reaction tube was taken, and 60-100mg (1.2mmol) of nitromethane, 60-120mg (0.3mmol) of purine, 0.5mL of acetic acid, 200mg (0.6mmol) of trifluoromethanesulfonic anhydride, 30-60mg (0.75mmol) of formic acid were added, followed by stirring at 80-120 ℃ for 1-72 hours. After the reaction is finished, 10mL of sodium hydroxide solution is added to quench the reaction, ethyl acetate is used for extraction for 3 times, 5mL of saline is added to the organic phase for washing, the organic phase is combined, column chromatography separation is carried out to obtain 46.1mg of purine derivatives, and the yield is 70%.¹H NMR(DMSO-d₆,400MHz):δ9.01(s,1H),8.93–8.80(m,3H),8.16(s,1H),8.09(d,J＝8.4Hz,2H),7.54(s,1H),7.32(ddd,J＝22.8,14.6,7.1Hz,5H),5.55(s,2H)；¹³C NMR(DMSO-d₆,100MHz):δ167.73,152.59,152.09,151.81,146.98,137.92,136.50,136.25,130.66,129.24,128.87,128.06,127.87,127.77,122.37,119.16,46.66ppm.

EXAMPLE 145 Psoralea corylifolia derivatives

Taking a reaction tube, adding 60-100mg (1.2mmol) of nitromethane, 60-120mg (0.3mmol) of fructus psoraleae, 0.5mL of acetic acid, 200mg (0.6mmol) of trifluoromethanesulfonic anhydride and 30-60mg (0.75mmol) of formic acid, and stirring at 80-120 ℃ for 1-72 hours. After the reaction is finished, 10mL of sodium hydroxide solution is added to quench the reaction, ethyl acetate is used for extraction for 3 times, organic phase is added with 5mL of saline for washing, organic phases are combined, and the malaytea scurfpea fruit derivative 52mg is obtained through column chromatography separation, wherein the yield is 80%.¹H NMR(DMSO-d₆,400MHz):δ8.14(d,J＝2.1Hz,1H),8.12(s,1H),8.07(d,J＝8.1Hz,2H),7.78(d,J＝9.9Hz,1H),7.52(d,J＝8.1Hz,2H),7.49(s,1H),6.77(d,J＝2.1Hz,1H),6.40(d,J＝9.9Hz,1H),4.22(s,3H)；¹³C NMR(DMSO-d₆,100MHz):δ167.39,159.32,148.32,146.26,143.06,142.39,137.70,133.92,131.62,130.19,127.96,125.59,125.38,114.51,113.82,106.23,61.07ppm.

Example 146 naproxen derivatives

A reaction tube is taken, 60-100mg (1.2mmol) of nitromethane, 60-120mg (0.3mmol) of naproxen, 0.5mL of acetic acid, 200mg (0.6mmol) of trifluoromethanesulfonic anhydride and 30-60mg (0.75mmol) of formic acid are added, and the mixture is stirred for 1-72 hours at 80-120 ℃. After the reaction is finished, 10mL of sodium hydroxide solution is added to quench the reaction, ethyl acetate is used for extraction for 3 times, 5mL of organic phase saline is added for washing, organic phases are combined, column chromatography separation is carried out to obtain 52mg of naproxen derivative, and the yield is 80%.¹H NMR(DMSO-d₆,400MHz):δ12.29(s,1H),8.07(s,1H),7.99(dd,J＝8.6,4.2Hz,3H),7.80(s,1H),7.52(d,J＝9.2Hz,1H),7.40(s,1H),7.35(dd,J＝9.6,4.9Hz,2H),7.29(dd,J＝18.0,5.2Hz,2H),3.82–3.75(m,4H),1.43(d,J＝7.1Hz,3H)；¹³C NMR(DMSO-d₆,100MHz):δ175.65,168.03,153.35,139.26,136.52,133.08,131.58,130.69,129.41,128.51,127.47,126.85,126.05,124.45,123.38,122.33,119.13,114.22,56.39,44.66,18.40ppm

Although the embodiments disclosed in the present application are described above, the descriptions are only for the convenience of understanding the present application, and are not intended to limit the present application. It will be understood by those skilled in the art that various changes in form and details may be made therein without departing from the spirit and scope of the disclosure as defined by the appended claims.