A method for the aqueous phase synthesis of 2,5-methylene-benzo[d][1,3,6]oxadiazepine compounds

Abstract

The application belongs to the technical field of organic synthesis, and particularly relates to a 2,5-methylene-benzo[ d ][1,3,6]oxadiazocin compound and a preparation method thereof, a derivative of the 2,5-methylene-benzo[ d ][1,3,6]oxadiazocin compound and a preparation method thereof. The application provides a method for efficiently preparing the 2,5-methylene-benzo[ d ][1,3,6]oxadiazocin compound under normal temperature and pressure conditions by using gamma-hydroxy aldehyde and ortho-aryldiamine as reaction raw materials, water as a solvent and p-toluenesulfonic acid monohydrate as a catalyst. The synthesis method has the advantages of simple operation, low cost of raw materials and catalyst, small amount of catalyst, mild reaction conditions, green environmental protection (water medium), wide substrate applicability and good industrial production feasibility. In addition, the obtained product provides a novel heterocyclic bridge ring skeleton construction strategy in the fields of organic synthesis and medicinal chemistry, and has good application prospect and economic and social benefits.

Description

Technical Field

[0001] This invention belongs to the field of organic synthesis technology, specifically relating to a 2,5-methylene-benzo[d][1,3,6]oxadiazacyclooctane compound and its preparation method, as well as derivatives of the 2,5-methylene-benzo[d][1,3,6]oxadiazacyclooctane compound and their preparation methods. Background Technology

[0002] In recent years, driven by the "escape the plane" concept, three-dimensional saturated bridging scaffolds rich in sp³ hybridized carbon atoms have attracted widespread attention as non-classical bioequivalents of planar aromatic rings. These scaffolds can precisely locate pharmacophores, thereby optimizing the interaction between drugs and targets. Among them, bridging heterocyclic skeletons containing oxygen and nitrogen atoms, especially benzo-fused multifunctional heterocyclic octane systems, have become highly attractive structural units in medicinal chemistry due to their unique three-dimensional topology and potential as both hydrogen bond donors and acceptors. 2,5-methylene-benzo[d][1,3,6]oxadiazine octane compounds are such heterocyclic molecules with rigid bridged ring structures, integrating benzene rings, methylene bridges, and oxygen and nitrogen heteroatoms into their skeletons, providing medicinal chemists with novel chemical spaces to explore biological activities. Despite their potential value, the synthetic methods for these scaffolds remain relatively limited. Existing methods are often constrained by low reaction efficiency, limited diversity, or multiple reaction steps, hindering further research in synthetic chemistry and medicinal chemistry. Therefore, developing economical, universal, and efficient synthetic methods for 2,5-methylene-benzo[d][1,3,6]oxadiazacyclooctane compounds is of great significance to organic chemistry and medicinal chemistry. Summary of the Invention

[0003] In view of this, the present invention provides a 2,5-methylene-benzo[d][1,3,6]oxadiazacyclooctane compound and its preparation method, a derivative of the 2,5-methylene-benzo[d][1,3,6]oxadiazacyclooctane compound and its preparation method. The preparation method of the 2,5-methylene-benzo[d][1,3,6]oxadiazacyclooctane compound provided by the present invention is simple and easy to operate, and the yield of the 2,5-methylene-benzo[d][1,3,6]oxadiazacyclooctane compound obtained is relatively high.

[0004] This invention provides a method for preparing 2,5-methylene-benzo[d][1,3,6]oxadiazacyclooctane compounds, comprising the following steps:

[0005] A cyclization reaction was carried out by mixing γ-hydroxy-α,β-unsaturated enaldehyde, o-aryl diamine, protic acid catalyst and solvent to obtain the 2,5-methylene-benzo[d][1,3,6]oxadiazacyclic octane compound;

[0006] The γ-hydroxy-α,β-unsaturated enaldehyde has the structure shown in Formula 1 or is... or or or The o-aryl diamine has the structure shown in Formulas 2-3:

[0007] Formula 1, Equation 2, Formula 3;

[0008] When the γ-hydroxy-α,β-unsaturated enal is When the o-aryl diamine is The 2,5-methylene-benzo[d][1,3,6]oxadiazacyclooctane compound is... ;

[0009] When the γ-hydroxy-α,β-unsaturated enal is When the o-aryl diamine is The 2,5-methylene-benzo[d][1,3,6]oxadiazacyclooctane compound is... ;

[0010] When the γ-hydroxy-α,β-unsaturated enal is When the o-aryl diamine is The 2,5-methylene-benzo[d][1,3,6]oxadiazacyclooctane compound is... ;

[0011] When the γ-hydroxy-α,β-unsaturated enal is When the o-aryl diamine is The 2,5-methylene-benzo[d][1,3,6]oxadiazacyclooctane compound is... ;

[0012] When the γ-hydroxy-α,β-unsaturated enal is When the o-aryl diamine has the structure shown in any of formulas 2-3; when the o-aryl diamine is When the 2,5-methylene-benzo[d][1,3,6]oxadiazacyclooctane compound has the structure shown in Formula I; when the o-aryl diamine is At that time, the 2,5-methylene-benzo[d][1,3,6]oxadiazacyclooctane compound has the structure shown in Formula ⅠI;

[0013] Formula I, Formula II;

[0014] Among them, R 1 and R 2 Independently, they are aryl, phenyl, halogen-substituted phenyl, alkyl-substituted phenyl, alkoxy-substituted phenyl, or alkyl;

[0015] R 3 Independently, they are hydrogen atoms, halogen atoms, or alkyl groups.

[0016] Preferably, the Including γ-hydroxy-γ-diphenyl-α,β-unsaturated enal, (E)-4,4-bis(4-fluorophenyl)-4-hydroxy-2-butenal, (E)-4,4-bis(4-chlorophenyl)-4-hydroxy-2-butenal, (E)-4,4-bis(4-bromophenyl)-4-hydroxy-2-butenal, (E)-4,4-bis(4-methylphenyl)-4-hydroxy-2-butenal, (E)-4,4-bis(4-methoxyphenyl)-4-hydroxy (E)-4,4-bis(3-chlorophenyl)-4-hydroxy-2-butenal, (E)-4-hydroxy-4,4-bis(naphthyl-2-yl)-2-butenal, (E)-4-hydroxy-4,4-bis(thiophen-2-yl)-2-butenal, (E)-4-hydroxy-4-methylpentan-2-enal, (E)-4-benzyl-4-hydroxy-5-phenylpentan-2-enal, (E)-4-hydroxy-4-phenylpentan-2-enal.

[0017] Preferably, the protic acid catalyst includes p-toluenesulfonic acid monohydrate and trifluoroacetic acid;

[0018] The molar ratio of the γ-hydroxy-α,β-unsaturated enaldehyde to the protic acid catalyst is 1:0.01~0.1.

[0019] Preferably, the This includes 1,2-phenylenediamine, 4,5-difluoro-1,2-phenylenediamine, 4,5-dichloro-1,2-phenylenediamine, 4,5-dimethyl-1,2-phenylenediamine, and 3,6-dibromo-1,2-phenylenediamine.

[0020] Preferably, the molar ratio of the γ-hydroxy-α,β-unsaturated enaldehyde and o-aryl diamine is 1:1.3~1.7.

[0021] Preferably, the cyclization reaction is carried out at a temperature of 20-35 °C for 2-24 h.

[0022] This invention also provides 2,5-methylene-benzo[d][1,3,6]oxadiazacyclooctane compounds prepared according to the preparation method described above, having the structure shown in any of Formulas I to II:

[0023] Formula I, Formula II;

[0024] Among them, R 1 and R 2 Independently, they are aryl, phenyl, halogen-substituted phenyl, alkyl-substituted phenyl, alkoxy-substituted phenyl, or alkyl;

[0025] R 3 Independently, they are hydrogen atoms, halogen atoms, or alkyl groups.

[0026] Preferably, it has the structure shown in any of the formulas I-1 to I-24 and II-1:

[0027] Formula I-1 Formula I-2 Formula I-3 Formula I-4 Formula I-5 Formula I-6 Formula I-7 Formula I-8 Formula I-9 Formula I-10 Formula I-11 Formula I-12 Formula I-13 Formula I-14 Formula I-15 Formula I-16 Formula I-17 Formula I-18 Formula I-19 Formula I-20 Formula I-21 Formula I-22 Formula I-23 Formula I-24; Formula II-1.

[0028] This invention also provides derivatives prepared from 2,5-methylene-benzo[d][1,3,6]oxadiazacyclooctane compounds having the structure shown in Formula I in the above-mentioned technical solutions, having the structure shown in any one of Formulas a to d:

[0029] Formula a Formula b Formula c Formula d.

[0030] The present invention also provides a method for preparing the derivatives described in the above technical solution, comprising the following steps:

[0031] The The preparation method includes the following steps: [The following text appears to be a list of steps and is not translated: "to..."] 1-Methyl-1H-indole, bismuth trifluoromethanesulfonate, and a first organic solvent were mixed and subjected to a ring-opening rearrangement / substitution reaction to obtain the [substance name missing]. ;

[0032] The The preparation method includes the following steps: [The following text appears to be a list of steps and is not translated: "to..."] The mixture of 1H-pyrrole, bismuth trifluoromethanesulfonate, and a second organic solvent undergoes a ring-opening rearrangement / substitution reaction to obtain the desired product. ;

[0033] The The preparation method includes the following steps: [The following text appears to be a list of steps and is not translated: "to..."] A mixture of iodomethane, potassium carbonate, and a third organic solvent undergoes a nucleophilic substitution reaction to obtain the desired product. ;

[0034] The The preparation method includes the following steps: [The following text appears to be a list of steps and is not translated: "to..."] Sodium borohydride, acetic acid, and a fourth organic solvent are mixed and then subjected to a reduction reaction to obtain the [substance name missing]. .

[0035] This invention provides a method for the efficient preparation of 2,5-methylene-benzo[d][1,3,6]oxadiazacyclic octane compounds using γ-hydroxyenal and o-aryldiamine as reactants, catalyzed by p-toluenesulfonic acid monohydrate, and in water as a solvent, under ambient temperature and pressure. This synthetic method offers significant advantages, including simple operation, readily available and inexpensive raw materials, low-cost and small-volume catalysts, mild reaction conditions, environmental friendliness (using water as a medium), and broad substrate applicability, demonstrating good feasibility for industrial production. Furthermore, the obtained products provide a novel strategy for constructing heterocyclic bridged ring skeletons in organic synthesis and medicinal chemistry, showing promising application prospects and economic and social benefits.

[0036] This invention provides a method for preparing 2,5-methylene-benzo[d][1,3,6]oxadiazacyclooctane compounds, comprising the following steps:

[0037] A cyclization reaction was carried out by mixing γ-hydroxy-α,β-unsaturated enaldehyde, o-aryl diamine, protic acid catalyst and solvent to obtain the 2,5-methylene-benzo[d][1,3,6]oxadiazacyclic octane compound;

[0038] The γ-hydroxy-α,β-unsaturated enaldehyde has the structure shown in Formula 1 or is... or or or The o-aryl diamine has the structure shown in Formulas 2-3:

[0039] Formula 1, Equation 2, Formula 3;

[0040] When the γ-hydroxy-α,β-unsaturated enal is When the o-aryl diamine is The 2,5-methylene-benzo[d][1,3,6]oxadiazacyclooctane compound is... ;

[0041] When the γ-hydroxy-α,β-unsaturated enal is When the o-aryl diamine is The 2,5-methylene-benzo[d][1,3,6]oxadiazacyclooctane compound is... ;

[0042] When the γ-hydroxy-α,β-unsaturated enal is When the o-aryl diamine is The 2,5-methylene-benzo[d][1,3,6]oxadiazacyclooctane compound is... ;

[0043] When the γ-hydroxy-α,β-unsaturated enal is When the o-aryl diamine is The 2,5-methylene-benzo[d][1,3,6]oxadiazacyclooctane compound is... ;

[0044] When the γ-hydroxy-α,β-unsaturated enal is When the o-aryl diamine has the structure shown in any of formulas 2-3; when the o-aryl diamine is When the 2,5-methylene-benzo[d][1,3,6]oxadiazacyclooctane compound has the structure shown in Formula I; when the o-aryl diamine is At that time, the 2,5-methylene-benzo[d][1,3,6]oxadiazacyclooctane compound has the structure shown in Formula ⅠI;

[0045] Formula I, Formula II;

[0046] In this invention, R 1 The R is an aryl, phenyl, halogen-substituted phenyl, alkyl-substituted phenyl, alkoxy-substituted phenyl, or alkyl compound. 1 The aryl group can be 2-naphthyl or 2-thienyl, wherein R 1 The halogenated phenyl group can be 4-fluorophenyl, 4-chlorophenyl, 4-bromophenyl, or 3-chlorophenyl, wherein R 1 The alkyl-substituted phenyl group can be 4-methylphenyl; the R 1 The alkoxy-substituted phenyl group can be 4-methoxyphenyl; the R 1 The alkyl group can be methyl or benzyl; R 2 The R is an aryl, phenyl, halogen-substituted phenyl, alkyl-substituted phenyl, alkoxy-substituted phenyl, or alkyl compound. 2 The aryl group can be 2-naphthyl or 2-thienyl, wherein R 2 The halogenated phenyl group can be 4-fluorophenyl, 4-chlorophenyl, 4-bromophenyl, or 3-chlorophenyl, wherein R 2 The alkyl-substituted phenyl group can be 4-methylphenyl; the R 2 The alkoxy-substituted phenyl group can be 4-methoxyphenyl; the R 2 The alkyl group can be methyl or benzyl.

[0047] As a specific embodiment of the present invention, R 1 and R 2 It can simultaneously be 2-naphthyl, 2-thienyl, phenyl, 4-fluorophenyl, 4-bromophenyl, 4-chlorophenyl, 3-chlorophenyl, 4-methylphenyl, 4-methoxyphenyl, methyl, and benzyl; when R 1 When R is phenyl 2 It can also be methyl.

[0048] As a specific embodiment of the present invention, the Including γ-hydroxy-γ-diphenyl-α,β-unsaturated enal, (E)-4,4-bis(4-fluorophenyl)-4-hydroxy-2-butenal, (E)-4,4-bis(4-chlorophenyl)-4-hydroxy-2-butenal, (E)-4,4-bis(4-bromophenyl)-4-hydroxy-2-butenal, (E)-4,4-bis(4-methylphenyl)-4-hydroxy-2-butenal, (E)-4,4-bis(4-methoxyphenyl)-4-hydroxy (E)-4,4-bis(3-chlorophenyl)-4-hydroxy-2-butenal, (E)-4-hydroxy-4,4-bis(naphthyl-2-yl)-2-butenal, (E)-4-hydroxy-4,4-bis(thiophen-2-yl)-2-butenal, (E)-4-hydroxy-4-methylpentan-2-enal, (E)-4-benzyl-4-hydroxy-5-phenylpentan-2-enal, (E)-4-hydroxy-4-phenylpentan-2-enal.

[0049] In this invention, R 3 It is a hydrogen atom, a halogen atom, or an alkyl group. The R... 3 The halogen atoms include 4,5-difluorine, 4,5-dichloro, and 3,6-dibromo, wherein R 3 The alkyl group includes 4,5-dimethyl.

[0050] As a specific embodiment of the present invention, the This includes 1,2-phenylenediamine, 4,5-difluoro-1,2-phenylenediamine, 4,5-dichloro-1,2-phenylenediamine, 4,5-dimethyl-1,2-phenylenediamine, and 3,6-dibromo-1,2-phenylenediamine.

[0051] In one specific embodiment of the present invention, the protic acid catalyst includes p-toluenesulfonic acid monohydrate and trifluoroacetic acid. In this invention, the protic acid catalyst possesses multiple activation functions to promote the efficient and highly selective synthesis of the product, enabling the synthesis of 2,5-methylene-benzo[d][1,3,6]oxadiazacyclooctane compounds under ambient pressure. During the reaction, prior activation of the reactants is not required.

[0052] In one specific embodiment of the present invention, the molar ratio of the γ-hydroxy-α,β-unsaturated enal to the protic acid catalyst is 1:0.01~0.1. Reducing the amount of protic acid will result in a longer reaction time and a significantly lower yield.

[0053] In one specific embodiment of the present invention, the solvent may be water; the molar concentration of γ-hydroxy-α,β-unsaturated enal in the reaction solution system of the cyclization reaction may be 0.08~0.12 mol / L, specifically 0.1 mol / L.

[0054] In one specific embodiment of the present invention, the molar ratio of γ-hydroxy-α,β-unsaturated enaldehyde and o-aryl diamine can be 1:1.3~1.7, or specifically 1:1.5.

[0055] In one specific embodiment of the present invention, the cyclization reaction is carried out at a temperature of 20-35 °C for 2-24 h.

[0056] As a specific embodiment of the present invention, preparation The reaction equation is:

[0057] .

[0058] In this invention, the cyclization reaction is followed by: concentrating the cyclization reaction system and then separating and purifying it using silica gel column chromatography to obtain the 2,5-methylene-benzo[d][1,3,6]oxadiazacyclic octane compound. This invention does not have special requirements for the concentration and silica gel column chromatography; conventional methods in the art can be used.

[0059] This invention also provides 2,5-methylene-benzo[d][1,3,6]oxadiazacyclooctane compounds prepared according to the preparation method described above, having the structure shown in any one of Formulas I to II:

[0060] Formula I, Formula II;

[0061] Among them, R 1 and R 2 Independently, they are aryl, phenyl, halogen-substituted phenyl, alkyl-substituted phenyl, alkoxy-substituted phenyl, or alkyl;

[0062] R 3 Independently, they are hydrogen atoms, halogen atoms, or alkyl groups.

[0063] As a specific embodiment of the present invention, the 2,5-methylene-benzo[d][1,3,6]oxadiazacyclooctane compound may have any of the structures shown in Formula I-1 to I-24 and Formula II-1:

[0064] Formula I-1 Formula I-2 Formula I-3 Formula I-4 Formula I-5 Formula I-6 Formula I-7 Formula I-8 Formula I-9 Formula I-10 Formula I-11 Formula I-12 Formula I-13 Formula I-14 Formula I-15 Formula I-16 Formula I-17 Formula I-18 Formula I-19 Formula I-20 Formula I-21 Formula I-22 Formula I-23 Formula I-24; Formula II-1.

[0065] This invention also provides derivatives prepared from 2,5-methylene-benzo[d][1,3,6]oxadiazacyclooctane compounds having the structure shown in Formula I in the above-mentioned technical solutions, having the structure shown in any one of Formulas a to d:

[0066] Formula a Formula b Formula c Formula d.

[0067] As a specific embodiment of the present invention, the It can be The It can be The It can be The It can be .

[0068] The present invention also provides a method for preparing the derivatives described in the above technical solution, comprising the following steps:

[0069] The The preparation method includes the following steps: [The following text appears to be a list of steps and is not translated: "to..."] 1-Methyl-1H-indole, bismuth trifluoromethanesulfonate, and a first organic solvent were mixed and subjected to a ring-opening rearrangement / substitution reaction to obtain the [substance name missing]. ;

[0070] The The preparation method includes the following steps: [The following text appears to be a list of steps and is not translated: "to..."] The mixture of 1H-pyrrole, bismuth trifluoromethanesulfonate, and a second organic solvent undergoes a ring-opening rearrangement / substitution reaction to obtain the desired product. ;

[0071] The The preparation method includes the following steps: [The following text appears to be a list of steps and is not translated: "to..."] A mixture of iodomethane, potassium carbonate, and a third organic solvent undergoes a nucleophilic substitution reaction to obtain the desired product. ;

[0072] The The preparation method includes the following steps: [The following text appears to be a list of steps and is not translated: "to..."] Sodium borohydride, acetic acid, and a fourth organic solvent are mixed and then subjected to a reduction reaction to obtain the [substance name missing]. .

[0073] In this invention, the The preparation method includes the following steps: [The following text appears to be a list of steps and is not translated: "to..."] 1-Methyl-1H-indole, bismuth trifluoromethanesulfonate, and a first organic solvent were mixed and subjected to a ring-opening rearrangement / substitution reaction to obtain the [substance name missing]. As a specific embodiment of the present invention, the first organic solvent may be tetrahydrofuran; The molar ratio of 1-methyl-1H-indole and bismuth trifluoromethanesulfonate can be 1:1.8~2.2:0.1~0.3, specifically 1:2.0:0.2. This invention does not have a specific limitation on the amount of the first organic solvent used, as long as it can dissolve completely. In one specific embodiment of this invention, the ring-opening rearrangement / substitution reaction can be carried out at room temperature, specifically 20~35 °C; the reaction time can be 13~15 h. In another specific embodiment of this invention, the ring-opening rearrangement / substitution can be accompanied by stirring; this invention does not have a specific limitation on the stirring, as long as the reaction is complete.

[0074] In this invention, the equation for the ring-opening rearrangement / substitution reaction is: .

[0075] In this invention, the The preparation method includes the following steps: [The following text appears to be a list of steps and is not translated: "to..."] The mixture of 1H-pyrrole, bismuth trifluoromethanesulfonate, 5Å molecular sieve, and a second organic solvent undergoes a ring-opening rearrangement / substitution reaction to obtain the desired product. As a specific embodiment of the present invention, the second organic solvent may be tetrahydrofuran; The molar ratio of 1H-pyrrole and bismuth trifluoromethanesulfonate can be 1:1.8~2.2:0.1~0.3, specifically 1:2.0:0.2, with 200 mg of 5Å molecular sieve. This invention does not have a specific limitation on the amount of the second organic solvent, as long as it can dissolve completely. In one specific embodiment of this invention, the ring-opening rearrangement / substitution temperature can be room temperature, specifically 20~35 °C; the reaction time can be 11~13 h. In another specific embodiment of this invention, the ring-opening rearrangement / substitution reaction can be accompanied by stirring; this invention does not have a specific limitation on the stirring, as long as the reaction is complete.

[0076] In this invention, the equation for the ring-opening rearrangement / substitution reaction is: .

[0077] In this invention, the preparation method includes the following steps: Will A mixture of iodomethane, potassium carbonate, and a third organic solvent undergoes a nucleophilic substitution reaction to obtain the desired product. As a specific embodiment of the present invention, the third organic solvent can be N,N-dimethylformamide; the N,N-dimethylformamide can be dried N,N-dimethylformamide, and the water content of the dried N,N-dimethylformamide is less than or equal to 50 ppm; The molar ratio of iodomethane and potassium carbonate can be 1:4.8~5.2:2.8~3.2, specifically 1:5.0:3.0. This invention does not have a specific limitation on the amount of the third organic solvent used, as long as it can dissolve completely. In one specific embodiment of this invention, the substitution reaction temperature can be room temperature, specifically 20~35 °C; the substitution reaction time can be 11~13 h. In another specific embodiment of this invention, the substitution reaction can be accompanied by stirring; this invention does not have a specific limitation on the stirring, as long as the reaction is complete.

[0078] In this invention, the equation for the nucleophilic substitution reaction is: .

[0079] In this invention, the The preparation method includes the following steps: [The following text appears to be a list of steps and is not translated: "to..."] Sodium borohydride, acetic acid, and a fourth organic solvent are mixed and then subjected to a reduction reaction to obtain the [substance name missing]. In one specific embodiment of the present invention, the fourth organic solvent may be tetrahydrofuran; The molar ratio of sodium borohydride and acetic acid can be 1:1.8~2.2:1.8~2.2, specifically 1:2.0:2.0. This invention does not have a specific limitation on the amount of the fourth organic solvent used, as long as it can dissolve completely. In one specific embodiment of this invention, the reduction reaction temperature can be room temperature, specifically 20~35 °C; the reduction reaction time can be 22~26 h. In another specific embodiment of this invention, the reduction reaction can be accompanied by stirring; this invention does not have a specific limitation on the stirring, as long as the reaction is complete.

[0080] In this invention, the equation for the reduction reaction is: .

[0081] This invention is based on The method for preparing derivatives from raw materials is simple, easy to operate, has mild reaction conditions, and produces high-purity products.

[0082] To further illustrate the present invention, the technical solutions provided by the present invention will be described in detail below with reference to the embodiments, but they should not be construed as limiting the scope of protection of the present invention.

[0083] After the preparation of each embodiment was completed, in order to further verify that the purified compound was indeed the target product to be prepared in this embodiment, the obtained solid product was analyzed. The analytical methods used were nuclear magnetic resonance and high-resolution mass spectrometry, and the detection results are listed in each embodiment.

[0084] Example 1

[0085] Using R 1 =R 2 It is a γ-hydroxy-γ-diphenyl-α,β-unsaturated enal of phenyl, R 3 Using 1,2-phenylenediamine (containing hydrogen) as a reactant, and catalyzed by p-toluenesulfonic acid monohydrate, the specific process is as follows:

[0086] (E)-4-hydroxy-4,4-diphenylbut-2-enal (95.5 mg, 0.4 mmol), 1,2-phenylenediamine (65.0 mg, 0.6 mmol), and p-toluenesulfonic acid monohydrate (0.8 mg, 0.004 mmol) were dissolved in water (4 mL) and reacted at 25 °C for 2 h. The reaction equation is as follows:

[0087]

[0088] The reaction solution was concentrated and then subjected to silica gel column chromatography to obtain a solid product of 115.6 mg, with a calculated yield of 88%.

[0089] The analysis of the test is as follows:

[0090] 1. Proton and carbon NMR spectra:

[0091] 1 H NMR (300 MHz, DMSO-d6) δ 7.58 (d, J = 7.6 Hz, 2H), 7.38 (d, J = 7.6Hz, 2H), 7.29 (t, J = 7.6 Hz, 2H), 7.16 (t, J = 7.3 Hz, 1H), 7.05 (t, J = 7.5Hz, 2H), 7.00-6.91 (m, 1H), 6.75-6.51 (m, 2H), 6.33 (t, J = 7.4 Hz, 1H), 6.21(t, J = 7.5 Hz, 1H), 6.08 (d, J = 7.9 Hz, 1H), 5.83-5.70 (m, 1H), 5.54 (t, J= 6.2 Hz, 1H), 4.63 (t, J = 5.7 Hz, 1H), 2.22 (dt, J1 = 12.7 Hz, J2 = 6.3 Hz, 1H), 1.55 (d, J = 12.2 Hz, 1H) ppm.

[0092] 13 C NMR (75 MHz, DMSO-d6) δ 147.4, 143.5, 133.8, 131.3, 128.1, 127.1,126.3, 126.1, 125.6, 124.8, 118.6, 118.2, 118.0, 116.9, 86.7, 84.8, 58.9, 41.0 ppm.

[0093] 2. High-resolution mass spectrometry: HRMS (ESI) C 22 H 21 N2O [M+H] + Found: 329.1648, Found: 329.1649.

[0094] The results show that the theoretical mass is 329.1648, while the observed peak value in the actual mass spectrum is 329.1649. Combined with nuclear magnetic resonance, the product structure can be determined as follows:

[0095] This is a product of this embodiment.

[0096] Example 2

[0097] Using R1 =R 2 It is a γ-hydroxy-γ-diphenyl-α,β-unsaturated enal of 4-fluorophenyl, R 3 Using 1,2-phenylenediamine (containing hydrogen) as a reactant, and catalyzed by p-toluenesulfonic acid monohydrate, the specific process is as follows:

[0098] (E)-4,4-bis(4-fluorophenyl)-4-hydroxybut-2-enal (109.9 mg, 0.4 mmol), 1,2-phenylenediamine (64.9 mg, 0.6 mmol), and p-toluenesulfonic acid monohydrate (0.8 mg, 0.004 mmol) were dissolved in water (4 mL) and reacted at 25 °C for 4 h. The reaction equation is as follows:

[0099]

[0100] The reaction solution was concentrated and purified by silica gel column chromatography to obtain a solid product of 125.6 mg, with a calculated yield of 86%.

[0101] The analysis of the test is as follows:

[0102] 1. Proton and carbon NMR spectra:

[0103] 1 H NMR (300 MHz, DMSO-d6) δ 7.69-7.47 (m, 2H), 7.43-7.25 (m, 2H), 7.12(t, J = 8.8 Hz, 2H), 6.84 (t, J = 8.5 Hz, 2H), 6.66 (d, J = 6.0 Hz, 1H), 6.60(d, J = 7.8 Hz, 1H), 6.33 (t, J = 7.8 Hz, 1H), 6.21 (t, J = 7.7 Hz, 1H), 6.07(d, J = 7.9 Hz, 1H), 5.75 (d, J = 6.0 Hz, 1H), 5.54 (t, J = 6.5 Hz, 1H), 4.58(t, J = 6.8 Hz, 1H), 2.32-2.12 (m, 1H), 1.54 (d, J = 12.3 Hz, 1H) ppm.

[0104] 13C NMR (75 MHz, DMSO-d6) δ 161.0 (d, J = 241.5 Hz), 160.5 (d, J =240.0 Hz), 143.4 (d, J = 2.3 Hz), 139.7 (d, J = 3.0 Hz), 133.8, 131.5, 128.1(d, J = 8.3 Hz), 127.1 (d, J = 8.3 Hz), 118.8, 118.5, 118.1, 117.3, 115.0 (d,J = 21.8 Hz), 113.9 (d, J = 21.0 Hz), 86.3, 85.3, 59.2, 41.2 ppm.

[0105] 19 F NMR (282 MHz, DMSO-d6) δ -116.8, -117.4 ppm.

[0106] 2. High-resolution mass spectrometry: HRMS (ESI) C 22 H 19 F2N2O [M+H] + Found: 365.1460, Found: 365.1461.

[0107] The results show that the theoretical mass is 365.1460, while the observed value of the peak in the actual mass spectrum is 365.1461. Combined with nuclear magnetic resonance, the product structure can be determined as follows:

[0108] This is a product of this embodiment.

[0109] Example 3

[0110] Using R 1 =R 2 It is a γ-hydroxy-γ-diphenyl-α,β-unsaturated enal of 4-chlorophenyl, R 3 Using 1,2-phenylenediamine (containing hydrogen) as a reactant, and catalyzed by p-toluenesulfonic acid monohydrate, the specific process is as follows:

[0111] (E)-4,4-bis(4-chlorophenyl)-4-hydroxybut-2-enal (123.0 mg, 0.4 mmol), 1,2-phenylenediamine (65.1 mg, 0.6 mmol), and p-toluenesulfonic acid monohydrate (0.8 mg, 0.004 mmol) were dissolved in water (4 mL) and reacted at 25 °C for 2 h. The reaction equation is as follows:

[0112]

[0113] The reaction solution was concentrated and then subjected to silica gel column chromatography to obtain a solid product of 119.8 mg, with a calculated yield of 75%.

[0114] The analysis of the test is as follows:

[0115] 1. Proton and carbon NMR spectra:

[0116] 1 H NMR (300 MHz, DMSO-d6) δ 7.56 (d, J = 8.2 Hz, 2H), 7.47-7.22 (m,4H), 7.08 (d, J = 8.2 Hz, 2H), 6.67 (d, J = 6.9 Hz, 1H), 6.60 (d, J = 7.8 Hz,1H), 6.35 (t, J = 7.5 Hz, 1H), 6.24 (t, J = 7.5 Hz, 1H), 6.10 (d, J = 7.9 Hz,1H), 5.80 (d, J = 6.4 Hz, 1H), 5.55 (t, J = 6.7 Hz, 1H), 4.59 (t, J = 5.7 Hz,1H), 2.35-2.07 (m, 1H), 1.55 (d, J = 12.4 Hz, 1H) ppm.

[0117] 13 C NMR (75 MHz, DMSO-d6) δ 145.8, 142.1, 133.5, 131.3, 131.2, 130.4,128.2, 128.0, 127.1, 126.9, 118.7, 118.3, 118.0, 117.1, 86.0, 85.2, 58.9, 41.0 ppm.

[0118] 2. High-resolution mass spectrometry: HRMS (ESI) C 22 H 19 Cl2N2O [M+H] + : 397.0869, Found: 397.0872.

[0119] The results show that the theoretical mass is 397.0869, while the observed value of the peak found in the actual mass spectrum is 397.0872. Combined with nuclear magnetic resonance, the product structure can be determined as follows:

[0120] This is a product of this embodiment.

[0121] Example 4

[0122] Using R 1 =R 2 It is a γ-hydroxy-γ-diphenyl-α,β-unsaturated enal of 4-bromophenyl, R 3 Using 1,2-phenylenediamine (hydrogen-containing) as a reactant, and catalyzed by p-toluenesulfonic acid monohydrate, the specific implementation process is as follows:

[0123] (E)-4,4-bis(4-bromophenyl)-4-hydroxybut-2-enal (158.6 mg, 0.4 mmol), 1,2-phenylenediamine (65.1 mg, 0.6 mmol), and p-toluenesulfonic acid monohydrate (0.8 mg, 0.004 mmol) were dissolved in water (4 mL) and reacted at 25 °C for 2 h. The reaction equation is as follows:

[0124]

[0125] The reaction solution was concentrated and then subjected to silica gel column chromatography to obtain a solid product of 161.5 mg, with a calculated yield of 83%.

[0126] The analysis of the test is as follows:

[0127] 1. Proton and carbon NMR spectra:

[0128] 1 H NMR (300 MHz, DMSO-d6) δ 7.59-7.40 (m, 4H), 7.30 (d, J = 7.9 Hz,2H), 7.22 (d, J = 8.2 Hz, 2H), 6.78-6.54 (m, 2H), 6.38 (t, J = 7.4 Hz, 1H), 6.26 (t, J = 7.6 Hz, 1H), 6.13 (d, J = 8.0 Hz, 1H), 5.79 (d, J = 6.0 Hz, 1H), 5.55 (t, J = 5.9 Hz, 1H), 4.60 (t, J = 5.8 Hz, 1H), 2.21 (dt, J1 = 12.6 Hz, J2= 6.3 Hz, 1H), 1.57 (d, J = 12.3 Hz, 1H) ppm.

[0129] 13C NMR (75 MHz, DMSO-d6) δ 146.2, 142.5, 133.5, 131.3, 131.1, 130.1,128.4, 127.3, 119.8, 119.0, 118.7, 118.4, 118.0, 117.2, 86.1, 85.2, 58.9, 41.0 ppm.

[0130] 2. High-resolution mass spectrometry: HRMS (ESI) C 22 H 19 Br2N2O [M+H] + Found: 484.9859, Found: 484.9855.

[0131] The results show that the theoretical mass is 484.9859, while the observed peak value in the actual mass spectrum is 484.9855. Combined with nuclear magnetic resonance, the product structure can be determined as follows:

[0132] This is a product of this embodiment.

[0133] Example 5

[0134] Using R 1 =R 2 It is a γ-hydroxy-γ-diphenyl-α,β-unsaturated enal of 3-chlorophenyl, R 3 Using 1,2-phenylenediamine (hydrogen-containing) as a reactant, and catalyzed by p-toluenesulfonic acid monohydrate, the specific implementation process is as follows:

[0135] (E)-4,4-bis(3-chlorophenyl)-4-hydroxybut-2-enal (123.1 mg, 0.4 mmol), 1,2-phenylenediamine (65.1 mg, 0.6 mmol), and p-toluenesulfonic acid monohydrate (0.8 mg, 0.004 mmol) were dissolved in water (4 mL) and reacted at 25 °C for 2 h. The reaction equation is as follows:

[0136]

[0137] The reaction solution was concentrated and then subjected to silica gel column chromatography to obtain a solid product of 151.1 mg, with a calculated yield of 95%.

[0138] The analysis of the test is as follows:

[0139] 1. Proton and carbon NMR spectra:

[0140] 1H NMR (300 MHz, DMSO-d6) δ 7.76-7.60 (m, 1H), 7.56 (d, J = 7.8 Hz,1H), 7.46-7.28 (m, 3H), 7.23 (d, J = 8.1 Hz, 1H), 7.10 (t, J = 7.7 Hz, 1H), 7.03 (d, J = 8.1 Hz, 1H), 6.73 (d, J = 6.2 Hz, 1H), 6.68 (d, J = 7.7 Hz, 1H), 6.39 (t, J = 7.4 Hz, 1H), 6.27 (t, J = 7.4 Hz, 1H), 6.12 (d, J = 7.9 Hz, 1H),5.79 (d, J = 6.1 Hz, 1H), 5.60 (t, J = 6.5 Hz, 1H), 4.68 (t, J = 5.8 Hz, 1H), 2.21 (dt, J1= 12.8 Hz, J2= 6.4 Hz, 1H), 1.59 (d, J = 12.4 Hz, 1H) ppm.

[0141] 13 C NMR (75 MHz, DMSO-d6) δ 149.2, 145.3, 133.5, 133.2, 132.1, 131.4,130.3, 129.1, 126.7, 125.9, 125.0, 124.9, 123.6, 118.8, 118.5, 118.1, 117.3,86.1, 85.4, 59.0, 41.0 ppm.

[0142] 2. High-resolution mass spectrometry: HRMS (ESI) C 22 H 19 Cl2N2O [M+H] + Found: 397.0869, Found: 397.0871.

[0143] The results show that the theoretical mass is 397.0869, while the observed peak value in the actual mass spectrum is 397.0871. Combined with nuclear magnetic resonance, the product structure can be determined as follows:

[0144] This is a product of this embodiment.

[0145] Example 6

[0146] Using R 1 =R2 It is a γ-hydroxy-γ-diphenyl-α,β-unsaturated enal of 4-methylphenyl, R 3 Using 1,2-phenylenediamine (hydrogen-containing) as a reactant, and catalyzed by p-toluenesulfonic acid monohydrate, the specific implementation process is as follows:

[0147] (E)-4-hydroxy-4,4-di-p-tolylbut-2-enal (106.7 mg, 0.4 mmol), 1,2-phenylenediamine (65.0 mg, 0.6 mmol), and p-toluenesulfonic acid monohydrate (0.9 mg, 0.004 mmol) were dissolved in water (4 mL) and reacted at 25 °C for 4 h. The reaction equation is as follows:

[0148]

[0149] The reaction solution was concentrated and then subjected to silica gel column chromatography to obtain a solid product of 125.9 mg, with a calculated yield of 88%.

[0150] The analysis of the test is as follows:

[0151] 1. Proton and carbon NMR spectra:

[0152] 1 H NMR (300 MHz, DMSO-d6) δ 7.42 (d, J = 7.8 Hz, 2H), 7.24 (d, J = 7.8Hz, 2H), 7.08 (d, J = 7.8 Hz, 2H), 6.85 (d, J = 7.8 Hz, 2H), 6.67-6.51 (m,2H), 6.40-6.30 (m, 1H), 6.29-6.20 (m, 1H), 6.19-6.08 (m, 1H), 5.69 (d, J =5.8 Hz, 1H), 5.50 (t, J = 6.5 Hz, 1H), 4.57 (t, J = 5.6 Hz, 1H), 2.31-2.17(m, 4H), 2.13 (s, 3H), 1.54 (d, J = 12.3 Hz, 1H) ppm.

[0153] 13C NMR (75 MHz, DMSO-d6) δ 144.7, 140.8, 135.1, 134.1, 133.8, 131.1,128.6, 127.6, 126.0, 124.7, 118.6, 118.1, 117.9, 116.7, 86.4, 84.7, 59.0,40.8, 20.5, 20.4 ppm.

[0154] 2. High-resolution mass spectrometry: HRMS (ESI) C 24 H 25 N2O [M+H] + Found: 357.1961, Found: 357.1960.

[0155] The results show that the theoretical mass is 357.1961, while the observed value of the peak in the actual mass spectrum is 357.1960. Combined with nuclear magnetic resonance, the product structure can be determined as follows:

[0156] This is a product of this embodiment.

[0157] Example 7

[0158] Using R 1 =R 2 It is a γ-hydroxy-γ-diphenyl-α,β-unsaturated enal of 4-methoxyphenyl, R 3 Using 1,2-phenylenediamine (hydrogen-containing) as a reactant, and catalyzed by p-toluenesulfonic acid monohydrate, the specific implementation process is as follows:

[0159] (E)-4-hydroxy-4,4-bis(4-methoxyphenyl)but-2-enal (119.5 mg, 0.4 mmol), 1,2-phenylenediamine (64.9 mg, 0.6 mmol), and p-toluenesulfonic acid monohydrate (0.8 mg, 0.004 mmol) were dissolved in water (4 mL) and reacted at 25 °C for 2 h. The reaction equation is as follows:

[0160]

[0161] The reaction solution was concentrated and then subjected to silica gel column chromatography to obtain a solid product of 149.7 mg, with a calculated yield of 96%.

[0162] The analysis of the test is as follows:

[0163] 1. Proton and carbon NMR spectra:

[0164] 1H NMR (300 MHz, DMSO-d6) δ 7.44 (d, J = 8.3 Hz, 2H), 7.24 (d, J = 8.3Hz, 2H), 6.84 (d, J = 8.3 Hz, 2H), 6.74-6.48 (m, 4H), 6.35 (t, J = 7.4 Hz,1H), 6.25 (t, J = 7.5 Hz, 1H), 6.14 (d, J = 7.9 Hz, 1H), 5.74-5.60 (m, 1H),5.50 (t, J = 6.4 Hz, 1H), 4.53 (t, J = 5.6 Hz, 1H), 3.69 (s, 3H), 3.60 (s, 3H), 2.38-2.09 (m, 1H), 1.54 (d, J = 12.2 Hz, 1H) ppm.

[0165] 13 C NMR (75 MHz, DMSO-d6) δ 157.6, 157.0, 139.8, 136.1, 133.9, 131.2,127.2, 126.0, 118.6, 118.2, 118.0, 116.8, 113.4, 112.5, 86.1, 84.8, 59.1,55.0, 54.8, 41.0 ppm.

[0166] 2. High-resolution mass spectrometry: HRMS (ESI) C 24 H 25 N₂O₃ [M+H] + Found: 389.1860, Found: 389.1862.

[0167] The results show that the theoretical mass is 389.1860, while the observed peak value in the actual mass spectrum is 389.1862. Combined with nuclear magnetic resonance, the product structure can be determined as follows:

[0168] This is a product of this embodiment.

[0169] Example 8

[0170] Using R 1 =R 2 It is a naphthyl-γ-hydroxy-γ-diphenyl-α,β-unsaturated enal, R 3 Using 1,2-phenylenediamine (hydrogen-containing) as a reactant, and catalyzed by p-toluenesulfonic acid monohydrate, the specific implementation process is as follows:

[0171] (E)-4-hydroxy-4,4-bis(naphthyl-2-yl)but-2-enal (135.6 mg, 0.4 mmol), 1,2-phenylenediamine (65.1 mg, 0.6 mmol), and p-toluenesulfonic acid monohydrate (0.8 mg, 0.004 mmol) were dissolved in water (4 mL) and reacted at 25 °C for 2 h. The reaction equation is as follows:

[0172]

[0173] The reaction solution was concentrated and then subjected to silica gel column chromatography to obtain a solid product of 164.6 mg, with a calculated yield of 96%.

[0174] The analysis of the test is as follows:

[0175] 1. Proton and carbon NMR spectra:

[0176] 1 H NMR (300 MHz, DMSO-d6) δ 8.28-8.13 (m, 1H), 7.95 (d, J = 6.8 Hz,2H), 7.81 (d, J = 8.0 Hz, 2H), 7.77-7.57 (m, 5H), 7.54-7.40 (m, 2H), 7.40-7.24 (m, 2H), 6.74 (d, J = 6.0 Hz, 1H), 6.65 (d, J = 7.8 Hz, 1H), 6.37-6.22(m, 1H), 6.17-6.01 (m, 2H), 5.94 (d, J = 5.9 Hz, 1H), 5.68 (t, J = 6.3 Hz,1H), 4.92 (t, J = 5.7 Hz, 1H), 2.38 (dt, J1= 12.7 Hz, J2= 6.4 Hz, 1H), 1.65 (d, J = 12.3 Hz, 1H) ppm.

[0177] 13C NMR (75 MHz, DMSO-d6) δ 144.7, 141.0, 133.8, 132.8, 132.5, 131.7,131.4, 131.2, 128.1, 127.82, 127.78, 127.3, 127.1, 126.6, 126.2, 125.8,125.5, 125.3, 124.7, 124.3, 122.8, 118.7, 118.2, 117.9, 116.9, 86.9, 85.2,58.8, 41.2 ppm.

[0178] 2. High-resolution mass spectrometry: HRMS (ESI) C 30 H 25 N2O [M+H] + Found: 429.1961, Found: 429.1964.

[0179] The results show that the theoretical mass is 429.1961, while the observed value of the peak found in the actual mass spectrum is 429.1964. Combined with nuclear magnetic resonance, the product structure can be determined as follows:

[0180] This is a product of this embodiment.

[0181] Example 9

[0182] Using R 1 =R 2 It is a 2-thienyl γ-hydroxy-γ-diphenyl-α,β-unsaturated enal, R 3 Using 1,2-phenylenediamine (hydrogen-containing) as a reactant, and catalyzed by p-toluenesulfonic acid monohydrate, the specific implementation process is as follows:

[0183] (E)-4-hydroxy-4,4-bis(thiophen-2-yl)but-2-enal (100.3 mg, 0.4 mmol), 1,2-phenylenediamine (64.9 mg, 0.6 mmol), and p-toluenesulfonic acid monohydrate (0.8 mg, 0.004 mmol) were dissolved in water (4 mL) and reacted at 25 °C for 6 h. The reaction equation is as follows:

[0184]

[0185] The reaction solution was concentrated and then subjected to silica gel column chromatography to obtain a solid product of 110.3 mg, with a calculated yield of 81%.

[0186] The analysis of the test is as follows:

[0187] 1. Proton and carbon NMR spectra:

[0188] 1 H NMR (300 MHz, DMSO-d6) δ 7.35 (d, J = 5.0 Hz, 1H), 7.19-7.04 (m,2H), 7.03-6.95 (m, 1H), 6.94-6.86 (m, 1H), 6.84-6.77 (m, 1H), 6.72 (d, J =6.0 Hz, 1H), 6.66-6.57 (m, 1H), 6.47-6.25 (m, 3H), 5.88 (d, J = 5.9 Hz, 1H), 5.55 (t, J = 6.7 Hz, 1H), 4.43 (t, J = 5.8 Hz, 1H), 2.48-2.34 (m, 1H), 1.61(d, J = 12.6 Hz, 1H) ppm.

[0189] 13 C NMR (75 MHz, DMSO-d6) δ 153.1, 146.7, 133.4, 130.4, 127.3, 126.1,124.3, 124.1, 124.0, 122.0, 118.8, 118.4, 118.2, 117.0, 86.1, 83.6, 62.6,40.5 ppm.

[0190] 2. High-resolution mass spectrometry: HRMS (ESI) C 18 H 17 N2OS2 [M+H] + : 341.0777, Found: 341.0773.

[0191] The results show that the theoretical mass is 341.0777, while the observed value of the peak in the actual mass spectrum is 341.0773. Combined with nuclear magnetic resonance, the product structure can be determined as follows:

[0192] This is a product of this embodiment.

[0193] Example 10

[0194] (E)-3-(9-hydroxy-9H-fluorene-9-yl)acrylaldehyde ( ), R 3 Using 1,2-phenylenediamine (containing hydrogen) as a reactant, and catalyzed by p-toluenesulfonic acid monohydrate, the specific process is as follows:

[0195] (E)-3-(9-hydroxy-9H-fluorene-9-yl)propenal (95.6 mg, 0.4 mmol), 1,2-phenylenediamine (64.9 mg, 0.6 mmol), and p-toluenesulfonic acid monohydrate (0.8 mg, 0.004 mmol) were dissolved in water (4 mL) and reacted at 25 °C for 2 h. The reaction equation is as follows:

[0196]

[0197] The reaction solution was concentrated and then subjected to silica gel column chromatography to obtain a solid product of 113.9 mg, with a calculated yield of 87%.

[0198] The analysis of the test is as follows:

[0199] 1. Proton and carbon NMR spectra:

[0200] 1 H NMR (300 MHz, DMSO-d6) δ 7.73 (t, J = 7.9 Hz, 2H), 7.57 (d, J = 7.4Hz, 1H), 7.36 (t, J = 7.4 Hz, 1H), 7.32-7.20 (m, 2H), 7.00 (t, J = 7.4 Hz,1H), 6.92 (d, J = 7.6 Hz, 1H), 6.81 (d, J = 7.3 Hz, 2H), 6.66-6.49 (m, 3H), 6.09 (d, J = 5.9 Hz, 1H), 5.86 (t, J = 6.4 Hz, 1H), 3.84 (t, J = 6.1 Hz, 1H),3.20 (dt, J1 = 13.6 Hz, J2 = 6.8 Hz, 1H), 1.81 (d, J = 13.0 Hz, 1H) ppm.

[0201] 13 C NMR (75 MHz, DMSO-d6) δ 150.2, 145.8, 139.5, 138.8, 133.6, 129.1,128.4, 127.5, 126.7, 126.6, 123.3, 119.9, 119.5, 118.8, 117.8, 116.8, 89.8,87.1, 61.9, 39.3 ppm.

[0202] 2. High-resolution mass spectrometry: HRMS (ESI) C 22 H 19 N2O [M+H]+ : 327.1492, Found: 327.1492.

[0203] The results show that the theoretical mass is 327.1492, and the observed value of the peak found in the actual mass spectrum is also 327.1492. Combined with nuclear magnetic resonance, the product structure can be determined as follows:

[0204] This is a product of this embodiment.

[0205] Example 11

[0206] (E)-3-(5-hydroxy-5H-dibenzo[a,d][7]cyclopenten-5-yl)acrylonitrile ( ), R 3 Using 1,2-phenylenediamine (hydrogen-containing) as a reactant, and catalyzed by p-toluenesulfonic acid monohydrate, the specific implementation process is as follows:

[0207] (E)-3-(5-hydroxy-5H-dibenzo[a,d][7]cyclopenten-5-yl)propenal (105.1 mg, 0.4 mmol), 1,2-phenylenediamine (64.8 mg, 0.6 mmol), and p-toluenesulfonic acid monohydrate (0.8 mg, 0.004 mmol) were dissolved in water (4 mL) and reacted at 25 °C for 2 h. The reaction equation is as follows:

[0208]

[0209] The reaction solution was concentrated and then subjected to silica gel column chromatography to obtain a solid product of 136.0 mg, with a calculated yield of 97%.

[0210] The analysis of the test is as follows:

[0211] 1. Proton and carbon NMR spectra:

[0212] 1H NMR (300 MHz, DMSO-d6) δ 7.82 (d, J = 7.8 Hz, 1H), 7.50-7.35 (m,2H), 7.35-7.20 (m, 3H), 7.19-6.97 (m, 3H), 6.81 (t, J = 7.7 Hz, 1H), 6.65 (d,J = 7.6 Hz, 2H), 6.36 (t, J = 7.5 Hz, 1H), 6.14 (t, J = 7.5 Hz, 1H), 5.90 (d,J = 7.9 Hz, 1H), 5.74-5.60 (m, 1H), 4.84 (d, J = 6.1 Hz, 1H), 4.13 (t, J =6.0 Hz, 1H), 1.98 (dt, J1 = 12.9 Hz, J2 = 6.5 Hz, 1H), 1.38 (d, J = 12.3 Hz,1H) ppm.

[0213] 13 C NMR (75 MHz, DMSO-d6) δ 142.5, 138.5, 133.4, 132.4, 132.0, 131.9,131.2, 130.4, 129.0, 128.3, 128.0, 127.0, 126.3, 125.7, 124.9, 124.1, 118.4,118.1, 117.6, 117.0, 86.0, 85.0, 54.6, 39.9 ppm.

[0214] 2. High-resolution mass spectrometry: HRMS (ESI) C 24 H 21 N2O [M+H] + : 353.1648, Found: 353.1648.

[0215] The results show that the theoretical mass is 353.1648, and the observed value of the peak found in the actual mass spectrum is also 353.1648. Combined with nuclear magnetic resonance, the product structure can be determined as follows:

[0216] This is a product of this embodiment.

[0217] Example 12

[0218] Using R 1 =R 2 It is a methyl γ-hydroxy-γ-diphenyl-α,β-unsaturated enal, R 3Using 1,2-phenylenediamine (hydrogen-containing) as a reactant, and catalyzed by p-toluenesulfonic acid monohydrate, the specific implementation process is as follows:

[0219] (E)-4-hydroxy-4-methylpent-2-enal (45.7 mg, 0.4 mmol), 1,2-phenylenediamine (65.0 mg, 0.6 mmol), and p-toluenesulfonic acid monohydrate (0.8 mg, 0.004 mmol) were dissolved in water (4 mL) and reacted at 25 °C for 2 h. The reaction equation is as follows:

[0220]

[0221] The reaction solution was concentrated and then subjected to silica gel column chromatography to obtain a solid product of 48.7 mg, with a calculated yield of 60%.

[0222] The analysis of the test is as follows:

[0223] 1. Proton and carbon NMR spectra:

[0224] 1 H NMR (300 MHz, DMSO-d6) δ 6.65 (d, J = 7.8 Hz, 1H), 6.61-6.55 (m,1H), 6.54-6.34 (m, 2H), 6.34-6.17 (m, 1H), 6.12-5.82 (m, 1H), 5.33-4.98 (m,1H), 3.55-3.36 (m, 1H), 2.78-2.53 (m, 1H), 1.41 (d, J = 12.5 Hz, 1H), 1.08(s, 3H), 0.92 (s, 3H) ppm.

[0225] 13 C NMR (75 MHz, DMSO-d6) δ 134.7, 130.8, 119.1, 118.3, 117.7, 116.5,84.4, 78.5, 59.0, 41.2, 28.6, 23.1 ppm.

[0226] 2. High-resolution mass spectrometry: HRMS (ESI) C 12 H 17 N2O [M+H] + Found: 205.1335, Found: 205.1329.

[0227] The results show that the theoretical mass is 205.1335, while the observed value of the peak in the actual mass spectrum is 205.1329. Combined with nuclear magnetic resonance, the product structure can be determined as follows:

[0228] This is a product of this embodiment.

[0229] Example 13

[0230] Using R 1 =R 2 It is a benzyl γ-hydroxy-γ-diphenyl-α,β-unsaturated enal, R 3 Using 1,2-phenylenediamine (hydrogen-containing) as a reactant, and catalyzed by p-toluenesulfonic acid monohydrate, the specific implementation process is as follows:

[0231] (E)-4-benzyl-4-hydroxy-5-phenylpent-2-enal (106.8 mg, 0.4 mmol), 1,2-phenylenediamine (65.1 mg, 0.6 mmol), and p-toluenesulfonic acid monohydrate (0.8 mg, 0.004 mmol) were dissolved in water (4 mL) and reacted at 25 °C for 4 h. The reaction equation is as follows:

[0232]

[0233] The reaction solution was concentrated and then subjected to silica gel column chromatography to obtain a solid product of 134.7 mg, with a calculated yield of 95%.

[0234] The analysis of the test is as follows:

[0235] 1. Proton and carbon NMR spectra:

[0236] 1 H NMR (300 MHz, DMSO-d6) δ 7.33-7.14 (m, 8H), 7.11 (d, J = 7.3 Hz, 2H), 6.77-6.63 (m, 2H), 6.56-6.39 (m, 3H), 6.05 (d, J = 5.7 Hz, 1H), 5.20 (t,J = 6.2 Hz, 1H), 3.75 (t, J = 6.2 Hz, 1H), 2.84-2.61 (m, 3H), 2.54 (d, J =13.8 Hz, 1H), 1.85 (dt, J1 = 13.2 Hz, J2 = 6.7 Hz, 1H), 1.29 (d, J = 12.6 Hz,1H) ppm.

[0237] 13C NMR (75 MHz, DMSO-d6) δ 138.9, 138.4, 134.2, 130.6, 130.4, 129.8,128.0, 127.7, 126.1, 125.6, 119.1, 118.4, 117.9, 116.7, 85.3, 82.6, 57.9,43.1, 40.5, 40.2 ppm.

[0238] 2. High-resolution mass spectrometry: HRMS (ESI) C 24 H 25 N2O [M+H] + Found: 357.1961, Found: 357.1958.

[0239] The results show that the theoretical mass is 357.1961, while the observed peak value in the actual mass spectrum is 357.1958. Combined with nuclear magnetic resonance, the product structure can be determined as follows:

[0240] This is a product of this embodiment.

[0241] Example 14

[0242] (E)-3-(1-hydroxycyclopentyl)acrylaldehyde ( ), R 3 Using 1,2-phenylenediamine (containing hydrogen) as a reactant, and catalyzed by p-toluenesulfonic acid monohydrate, the specific process is as follows:

[0243] (E)-3-(1-hydroxycyclopentyl)propenal (56.3 mg, 0.4 mmol), 1,2-phenylenediamine (65.1 mg, 0.6 mmol), and p-toluenesulfonic acid monohydrate (0.8 mg, 0.004 mmol) were dissolved in water (4 mL) and reacted at 25 °C for 2 h. The reaction equation is as follows:

[0244]

[0245] The reaction solution was concentrated and purified by silica gel column chromatography to obtain 57.2 mg of solid product, with a calculated yield of 62%.

[0246] The analysis of the test is as follows:

[0247] 1. Proton and carbon NMR spectra:

[0248] 1H NMR (300 MHz, DMSO-d6) δ 6.67 (d, J = 7.7 Hz, 1H), 6.59 (d, J = 7.6Hz, 1H), 6.53-6.35 (m, 2H), 6.27 (d, J = 5.9 Hz, 1H), 6.06 (d, J = 5.7 Hz,1H), 5.11 (t, J = 6.5 Hz, 1H), 3.49-3.40 (m, 1H), 2.49-2.37 (m, 1H), 1.75-1.54 (m, 2H), 1.54-1.33 (m, 6H), 1.20-1.02 (m, 1H) ppm.

[0249] 13 C NMR (75 MHz, DMSO-d6) δ 135.1, 131.3, 119.1, 118.4, 117.9, 116.8,90.5, 83.7, 58.1, 42.5, 39.4, 32.6, 24.2, 23.6 ppm.

[0250] 2. High-resolution mass spectrometry: HRMS (ESI) C 14 H 19 N2O [M+H] + Found: 231.1492, Found: 231.1491.

[0251] The results show that the theoretical mass is 231.1492, while the observed value of the peak found in the actual mass spectrum is 231.1491. Combined with nuclear magnetic resonance, the product structure can be determined as follows:

[0252] This is a product of this embodiment.

[0253] Example 15

[0254] (E)-3-(1-hydroxycyclohexyl)acrylaldehyde ( ), R 3 Using 1,2-phenylenediamine (containing hydrogen) as a reactant, and catalyzed by p-toluenesulfonic acid monohydrate, the specific process is as follows:

[0255] (E)-3-(1-hydroxycyclohexyl)propenal (61.9 mg, 0.4 mmol), 1,2-phenylenediamine (65.1 mg, 0.6 mmol), and p-toluenesulfonic acid monohydrate (0.8 mg, 0.004 mmol) were dissolved in water (4 mL) and reacted at 25 °C for 2 h. The reaction equation is as follows:

[0256]

[0257] The reaction solution was concentrated and then subjected to silica gel column chromatography to obtain a solid product of 78.2 mg, with a calculated yield of 80%.

[0258] The analysis of the test is as follows:

[0259] 1. Proton and carbon NMR spectra:

[0260] 1 H NMR (300 MHz, CDCl3) δ 6.84-6.48 (m, 4H), 5.31 (d, J = 7.2 Hz, 1H), 4.84 (s, 1H), 4.28 (s, 1H), 3.57 (d, J = 6.5 Hz, 1H), 2.64 (dt, J1= 13.2 Hz,J2= 6.7 Hz, 1H), 1.77 (d, J = 12.9 Hz, 1H), 1.73-1.59 (m, 1H), 1.58-1.28 (m,9H) ppm.

[0261] 13 C NMR (75 MHz, CDCl3) δ 133.8, 129.8, 120.1, 119.8, 118.2, 84.9,80.8, 58.5, 40.4, 37.3, 31.8, 25.6, 23.59, 23.55 ppm.

[0262] 2. High-resolution mass spectrometry: HRMS (ESI) C 15 H 21 N2O [M+H] + Found: 245.1648, Found: 245.1641.

[0263] The results show that the theoretical mass is 245.1648, while the observed value of the peak in the actual mass spectrum is 245.1641. Combined with nuclear magnetic resonance, the product structure can be determined as follows:

[0264] This is a product of this embodiment.

[0265] Example 16

[0266] Using R 1 It is a phenyl group, R 2 It is a methyl γ-hydroxy-γ-diphenyl-α,β-unsaturated enal, R 3Using 1,2-phenylenediamine (containing hydrogen) as a reactant, and catalyzed by p-toluenesulfonic acid monohydrate, the specific process is as follows:

[0267] (E)-4-hydroxy-4-phenylpentan-2-enal (70.6 mg, 0.4 mmol), 1,2-phenylenediamine (65.0 mg, 0.6 mmol), and p-toluenesulfonic acid monohydrate (0.8 mg, 0.004 mmol) were dissolved in water (4 mL) and reacted at 25 °C for 2 h. The reaction equation is as follows:

[0268]

[0269] The reaction solution was concentrated and then subjected to silica gel column chromatography to obtain solid product A: 33.0 mg, with a calculated yield of 31%; solid product B: 47.1 mg, with a calculated yield of 44%.

[0270] The analysis of the test is as follows:

[0271] Product A:

[0272] 1. Proton and carbon NMR spectra:

[0273] 1 H NMR (300 MHz, DMSO-d6) δ 7.44-7.27 (m, 4H), 7.25-7.16 (m, 1H), 6.75(d, J = 7.7 Hz, 1H), 6.68 (d, J = 7.6 Hz, 1H), 6.64-6.35 (m, 3H), 6.35-6.12(m, 1H), 5.54-5.31 (m, 1H), 3.89-3.55 (m, 1H), 2.23-1.90 (m, 1H), 1.30 (d, J= 12.4 Hz, 1H), 1.18 (s, 3H) ppm.

[0274] 13 C NMR (75 MHz, DMSO-d6) δ 148.2, 134.4, 130.7, 128.0, 126.2, 124.5,119.3, 118.6, 118.0, 116.9, 84.9, 83.0, 60.6, 40.0, 23.7 ppm.

[0275] 2. High-resolution mass spectrometry: HRMS (ESI) C 17 H 19 N2O [M+H] +Found: 267.1492, Found: 267.1491.

[0276] The results show that the theoretical mass is 267.1492, while the observed value of the peak found in the actual mass spectrum is 267.1491.

[0277] Product B:

[0278] 1. Proton and carbon NMR spectra:

[0279] 1 H NMR (300 MHz, DMSO-d6) δ 7.12 (d, J = 7.0 Hz, 2H), 7.05-6.89 (m,3H), 6.53 (d, J = 7.8 Hz, 1H), 6.49-6.36 (m, 1H), 6.27 (t, J = 7.5 Hz, 1H),6.08 (t, J = 7.6 Hz, 1H), 5.82 (d, J = 7.9 Hz, 1H), 5.54-5.22 (m, 2H), 3.95(t, J = 6.1 Hz, 1H), 2.92-2.67 (m, 1H), 1.58 (d, J = 12.4 Hz, 1H), 1.36 (s, 3H) ppm.

[0280] 13 C NMR (75 MHz, DMSO-d6) δ 144.5, 133.9, 131.6, 126.7, 125.4, 125.3,118.4, 117.9, 117.8, 116.7, 84.9, 83.7, 59.5, 41.5, 30.4 ppm.

[0281] 2. High-resolution mass spectrometry: HRMS (ESI) C 17 H 19 N2O [M+H] + Found: 267.1492, Found: 267.1490.

[0282] The results show that the theoretical mass is 267.1492, while the observed value of the peak in the actual mass spectrum is 267.1490. Combined with nuclear magnetic resonance, the product structure can be determined as follows:

[0283] This is a product of this embodiment.

[0284] Example 17

[0285] Using R1 =R 2 It is a γ-hydroxy-γ-diphenyl-α,β-unsaturated enal of phenyl, R 3 Using 4,5-difluoro-1,2-phenylenediamine as the reactant, and with p-toluenesulfonic acid monohydrate as the catalyst, the specific implementation process is as follows:

[0286] (E)-4-hydroxy-4,4-diphenylbut-2-enal (95.4 mg, 0.4 mmol), 4,5-difluoro-1,2-phenylenediamine (86.7 mg, 0.6 mmol), and p-toluenesulfonic acid monohydrate (0.8 mg, 0.004 mmol) were dissolved in water (4 mL) and reacted at 25 °C for 2 h. The reaction equation is as follows:

[0287]

[0288] The reaction solution was concentrated and then subjected to silica gel column chromatography to obtain a solid product of 130.9 mg, with a calculated yield of 90%.

[0289] The analysis of the test is as follows:

[0290] 1. Proton and carbon NMR spectra:

[0291] 1 H NMR (300 MHz, DMSO-d6) δ 7.59 (d, J = 7.7 Hz, 2H), 7.35 (d, J = 7.6Hz, 2H), 7.29 (t, J = 7.5 Hz, 2H), 7.16 (t, J = 7.2 Hz, 1H), 7.08 (t, J = 7.4Hz, 2H), 7.01 (t, J = 7.0 Hz, 1H), 6.80 (d, J = 6.2 Hz, 1H), 6.60 (dd, J1=12.9 Hz, J2= 8.3 Hz, 1H), 6.22-5.81 (m, 2H), 5.52 (t, J = 6.5 Hz, 1H), 4.61(t, J = 5.7 Hz, 1H), 2.23 (dt, J1 = 12.6 Hz, J2 = 6.3 Hz, 1H), 1.55 (d, J =12.3 Hz, 1H) ppm.

[0292] 13 C NMR (75 MHz, DMSO-d6) δ 147.0, 143.4, 141.8 (dd, J1 = 230.3 Hz, J2= 12.8 Hz), 141.2 (dd, J1 = 229.1 Hz, J2 = 13.1 Hz), 131.0 (d, J = 7.5 Hz), 128.6 (d, J = 6.8 Hz), 128.2, 127.2, 126.4, 126.0, 125.7, 124.9, 105.8 (d, J = 20.3 Hz), 105.1 (d, J = 19.5 Hz), 87.2, 84.6, 58.7, 41.5 ppm.

[0293] 19 F NMR (282 MHz, DMSO-d6) δ -152.7 (d, J = 24.7 Hz), -153.7 (d, J =24.8 Hz) ppm.

[0294] 2. High-resolution mass spectrometry: HRMS (ESI) C 22 H 19 F2N2O [M+H] + : 365.1460, Found: 365.1460.

[0295] The results show that the theoretical mass is 365.1460, and the observed value of the peak found in the actual mass spectrum is also 365.1460. Combined with nuclear magnetic resonance, the product structure can be determined as follows:

[0296] This is a product of this embodiment.

[0297] Example 18

[0298] Using R 1 =R 2 It is a γ-hydroxy-γ-diphenyl-α,β-unsaturated enal of phenyl, R 3 Using 4,5-dichloro-1,2-phenylenediamine as the reactant, and with p-toluenesulfonic acid monohydrate as the catalyst, the specific implementation process is as follows:

[0299] (E)-4-hydroxy-4,4-diphenylbut-2-enal (95.5 mg, 0.4 mmol), 4,5-dichloro-1,2-phenylenediamine (106.3 mg, 0.6 mmol), and p-toluenesulfonic acid monohydrate (0.8 mg, 0.004 mmol) were dissolved in water (4 mL) and reacted at 25 °C for 2 h. The reaction equation is as follows:

[0300]

[0301] The reaction solution was concentrated and then subjected to silica gel column chromatography to obtain a solid product of 133.4 mg, with a calculated yield of 84%.

[0302] The analysis of the test is as follows:

[0303] 1. Proton and carbon NMR spectra:

[0304] 1 H NMR (300 MHz, DMSO-d6) δ 7.58 (d, J = 7.7 Hz, 2H), 7.37 (d, J = 7.6Hz, 2H), 7.29 (t, J = 7.5 Hz, 2H), 7.18 (d, J = 7.3 Hz, 1H), 7.11 (t, J = 7.7Hz, 2H), 7.07-6.95 (m, 2H), 6.89-6.74 (m, 1H), 6.43-6.29 (m, 1H), 6.27 (d, J= 5.9 Hz, 1H), 5.54 (t, J = 6.6 Hz, 1H), 4.64 (t, J = 5.8 Hz, 1H), 2.24 (dt,J1 = 12.9 Hz, J2 = 6.4 Hz, 1H), 1.58 (d, J = 12.5 Hz, 1H) ppm.

[0305] 13 C NMR (75 MHz, DMSO-d6) δ 146.7, 143.1, 134.7, 132.3, 128.2, 127.2,126.4, 126.0, 125.7, 124.8, 118.7, 118.6, 117.9, 117.1, 86.9, 84.3, 58.7, 41.2 ppm.

[0306] 2. High-resolution mass spectrometry: HRMS (ESI) C 22 H 19 Cl2N2O [M+H] + Found: 397.0869, Found: 397.0873.

[0307] The results show that the theoretical mass is 397.0869, while the observed value of the peak found in the actual mass spectrum is 397.0873. Combined with nuclear magnetic resonance, the product structure can be determined as follows:

[0308] This is a product of this embodiment.

[0309] Example 19

[0310] Using R 1 =R 2 It is a γ-hydroxy-γ-diphenyl-α,β-unsaturated enal of phenyl, R 3 Using 4,5-dimethyl-1,2-phenylenediamine as the reactant, and with p-toluenesulfonic acid monohydrate as the catalyst, the specific implementation process is as follows:

[0311] (E)-4-hydroxy-4,4-diphenylbut-2-enal (95.5 mg, 0.4 mmol), 4,5-dimethyl-1,2-phenylenediamine (81.9 mg, 0.6 mmol), and p-toluenesulfonic acid monohydrate (0.8 mg, 0.004 mmol) were dissolved in water (4 mL) and reacted at 25 °C for 2 h. The reaction equation is as follows:

[0312]

[0313] The reaction solution was concentrated and then subjected to silica gel column chromatography to obtain a solid product of 133.0 mg, with a calculated yield of 93%.

[0314] The analysis of the test is as follows:

[0315] 1. Proton and carbon NMR spectra:

[0316] 1 H NMR (300 MHz, DMSO-d6) δ 7.56 (d, J = 7.6 Hz, 2H), 7.39 (d, J = 7.7Hz, 2H), 7.28 (t, J = 7.6 Hz, 2H), 7.14 (t, J = 7.3 Hz, 1H), 7.06 (t, J = 7.5Hz, 2H), 6.97 (t, J = 7.2 Hz, 1H), 6.46-6.27 (m, 2H), 5.88 (s, 1H), 5.60-5.34(m, 2H), 4.59 (t, J = 5.3 Hz, 1H), 2.17 (dt, J1= 12.7 Hz, J2= 6.4 Hz, 1H), 1.94 (s, 3H), 1.81 (s, 3H), 1.52 (d, J = 12.3 Hz, 1H) ppm.

[0317] 13C NMR (75 MHz, DMSO-d6) δ 147.5, 143.7, 131.3, 128.6, 128.1, 127.1,126.1, 125.4, 125.0, 124.8, 123.7, 119.9, 119.2, 86.5, 85.0, 59.3, 40.3,18.3, 18.2 ppm.

[0318] 2. High-resolution mass spectrometry: HRMS (ESI) C 24 H 25 N2O [M+H] + Found: 357.1961, Found: 357.1959.

[0319] The results show that the theoretical mass is 357.1961, while the observed value of the peak found in the actual mass spectrum is 357.1959. Combined with nuclear magnetic resonance, the product structure can be determined as follows:

[0320] This is a product of this embodiment.

[0321] Example 20

[0322] Using R 1 =R 2 It is a γ-hydroxy-γ-diphenyl-α,β-unsaturated enal of phenyl, R 3 Using 3,6-dibromo-1,2-phenylenediamine as the reactant, and with p-toluenesulfonic acid monohydrate as the catalyst, the specific implementation process is as follows:

[0323] (E)-4-hydroxy-4,4-diphenylbut-2-enal (95.5 mg, 0.4 mmol), 3,6-dibromo-1,2-phenylenediamine (159.8 mg, 0.6 mmol), and p-toluenesulfonic acid monohydrate (0.8 mg, 0.004 mmol) were dissolved in water (4 mL) and reacted at 25 °C for 4 h. The reaction equation is as follows:

[0324]

[0325] The reaction solution was concentrated and then subjected to silica gel column chromatography to obtain a solid product of 146.9 mg, with a calculated yield of 76%.

[0326] The analysis of the test is as follows:

[0327] 1. Proton and carbon NMR spectra:

[0328] 1H NMR (300 MHz, DMSO-d6) δ 7.65 (d, J = 7.7 Hz, 2H), 7.41 (d, J = 7.6Hz, 2H), 7.30 (t, J = 7.5 Hz, 2H), 7.17 (t, J = 7.3 Hz, 1H), 7.06 (t, J = 7.4Hz, 2H), 7.01-6.91 (m, 1H), 6.70 (d, J = 8.5 Hz, 1H), 6.59 (d, J = 8.5 Hz, 1H), 6.47 (d, J = 6.3 Hz, 1H), 5.97-5.69 (m, 2H), 5.17 (t, J = 5.7 Hz, 1H),2.22 (dt, J1 = 12.5 Hz, J2 = 6.2 Hz, 1H), 1.67 (d, J = 12.4 Hz, 1H) ppm.

[0329] 13 C NMR (75 MHz, DMSO-d6) δ 146.7, 142.6, 132.4, 130.2, 128.2, 127.5,126.5, 125.8, 125.6, 124.8, 122.6, 121.4, 111.6, 87.5, 84.0, 58.7, 41.2 ppm.

[0330] 2. High-resolution mass spectrometry: HRMS (ESI) C 22 H 19 Br2N2O [M+H] + Found: 484.9859, Found: 484.9857.

[0331] The results show that the theoretical mass is 484.9859, while the observed peak value in the actual mass spectrum is 484.9857. Combined with nuclear magnetic resonance, the product structure can be determined as follows:

[0332] This is a product of this embodiment.

[0333] Example 21

[0334] Using R 1 =R 2 It is a γ-hydroxy-γ-diphenyl-α,β-unsaturated enal of phenyl, 2,3-diaminonaphthalene ( Using p-toluenesulfonic acid monohydrate as a reactant, the reaction is carried out using this catalyst. The specific implementation process is as follows:

[0335] (E)-4-hydroxy-4,4-diphenylbut-2-enal (95.5 mg, 0.4 mmol), 2,3-diaminonaphthalene (95.0 mg, 0.6 mmol), and p-toluenesulfonic acid monohydrate (0.8 mg, 0.004 mmol) were dissolved in water (4 mL) and reacted at 25 °C for 12 h. The reaction equation is as follows:

[0336]

[0337] The reaction solution was concentrated and then subjected to silica gel column chromatography to obtain a solid product of 146.8 mg, with a calculated yield of 97%.

[0338] The analysis of the test is as follows:

[0339] 1. Proton and carbon NMR spectra:

[0340] 1 H NMR (300 MHz, DMSO-d6) δ 7.60 (d, J = 7.7 Hz, 2H), 7.50-7.37 (m,3H), 7.31 (t, J = 7.6 Hz, 2H), 7.25-7.11 (m, 3H), 7.10-6.83 (m, 6H), 6.61-6.48 (m, 1H), 6.33 (d, J = 6.2 Hz, 1H), 5.61 (t, J = 6.5 Hz, 1H), 4.72 (t, J= 5.7 Hz, 1H), 2.26 (dt, J1= 12.8 Hz, J2= 6.4 Hz, 1H), 1.76 (d, J = 12.4 Hz,1H) ppm.

[0341] 13 C NMR (75 MHz, DMSO-d6) δ 147.2, 143.5, 136.5, 134.8, 128.3, 128.2,127.4, 127.3, 126.4, 126.2, 125.7, 124.8, 124.7, 124.4, 122.0, 121.5, 112.2,111.3, 88.2, 84.7, 59.2, 40.7 ppm.

[0342] 2. High-resolution mass spectrometry: HRMS (ESI) C 26 H 23 N2O [M+H] + Found: 379.1805, Found: 379.1807.

[0343] The results show that the theoretical mass is 379.1805, while the observed value of the peak in the actual mass spectrum is 379.1807. Combined with nuclear magnetic resonance, the product structure can be determined as follows:

[0344] This is a product of this embodiment.

[0345] Example 22

[0346] Using R 1 =R 2 It is a methyl γ-hydroxy-γ-diphenyl-α,β-unsaturated enal, R 3 Using 1,2-phenylenediamine of 4,5-difluoropolymer as the reactant, and catalyzed by p-toluenesulfonic acid monohydrate, the specific implementation process is as follows:

[0347] (E)-4-hydroxy-4-methylpent-2-enal (45.9 mg, 0.4 mmol), 4,5-difluoro-1,2-phenylenediamine (86.7 mg, 0.6 mmol), and p-toluenesulfonic acid monohydrate (0.8 mg, 0.004 mmol) were dissolved in water (4 mL) and reacted at 25 °C for 2 h. The reaction equation is as follows:

[0348]

[0349] The reaction solution was concentrated and then subjected to silica gel column chromatography to obtain a solid product of 48.1 mg, with a calculated yield of 50%.

[0350] The analysis of the test is as follows:

[0351] 1. Proton and carbon NMR spectra:

[0352] 1 H NMR (300 MHz, CDCl3) δ 6.54-6.29 (m, 2H), 5.27 (d, J = 7.2 Hz, 1H), 4.72 (brs, 1H), 4.26 (s, 1H), 3.46 (d, J = 6.3 Hz, 1H), 2.69 (dt, J1 = 13.2Hz, J2 = 6.7 Hz, 1H), 1.76 (d, J = 13.0 Hz, 1H), 1.19 (s, 3H), 1.12 (s, 3H)ppm.

[0353] 13 C NMR (75 MHz, CDCl3) δ 143.8 (dd, J1 = 235.9 Hz, J2 = 13.1 Hz),142.8 (dd, J1 = 234.8 Hz, J2 = 12.8 Hz), 129.7 (d, J = 6.8 Hz), 126.1 (d, J =6.8 Hz), 107.8 (d, J = 20.3 Hz), 106.0 (d, J = 20.3 Hz), 85.3, 79.9, 60.2,40.7, 28.4, 22.9 ppm.

[0354] 19 F NMR (282 MHz, CDCl3) δ -150.0 (d, J = 23.2 Hz), -151.7 (d, J =23.4 Hz) ppm.

[0355] 2. High-resolution mass spectrometry: HRMS (ESI) C 12 H 15 F2N2O [M+H] + Found: 241.1147, Found: 241.1144.

[0356] The results show that the theoretical mass is 241.1147, while the observed value of the peak in the actual mass spectrum is 241.1144. Combined with nuclear magnetic resonance, the product structure can be determined as follows:

[0357] This is a product of this embodiment.

[0358] Example 23

[0359] Using R 1 =R 2 It is a methyl γ-hydroxy-γ-diphenyl-α,β-unsaturated enal, R 3 Using 4,5-dichloro-1,2-phenylenediamine as the reactant, and with p-toluenesulfonic acid monohydrate as the catalyst, the specific implementation process is as follows:

[0360] (E)-4-hydroxy-4-methylpentan-2-enal (45.9 mg, 0.4 mmol), 4,5-dichloro-1,2-phenylenediamine (106.5 mg, 0.6 mmol), and p-toluenesulfonic acid monohydrate (0.8 mg, 0.004 mmol) were dissolved in water (4 mL) and reacted at 25 °C for 2 h. The reaction equation is as follows:

[0361]

[0362] The reaction solution was concentrated and purified by silica gel column chromatography to obtain 72.1 mg of solid product, with a calculated yield of 66%.

[0363] The analysis of the test is as follows:

[0364] 1. Proton and carbon NMR spectra:

[0365] 1 H NMR (300 MHz, CDCl3) δ 6.71 (s, 1H), 6.66 (s, 1H), 5.26 (d, J = 7.1Hz, 1H), 4.92 (s, 1H), 4.39 (s, 1H), 3.48 (t, J = 5.2 Hz, 1H), 2.69 (dt, J1 =13.4 Hz, J2 = 6.7 Hz, 1H), 1.76 (d, J = 13.1 Hz, 1H), 1.20 (s, 3H), 1.11 (s,3H) ppm.

[0366] 13 C NMR (75 MHz, CDCl3) δ 133.6, 130.1, 121.9, 120.5, 120.3, 118.8,85.0, 79.9, 60.2, 40.8, 28.4, 23.1 ppm.

[0367] 2. High-resolution mass spectrometry: HRMS (ESI) m / z [M+H] + : 273.0556, Found: 273.0553.

[0368] The results show that the theoretical mass is 273.0556, while the observed value of the peak found in the actual mass spectrum is 273.0553. Combined with nuclear magnetic resonance, the product structure can be determined as follows:

[0369] This is a product of this embodiment.

[0370] Example 24

[0371] Using R 1 =R 2 It is a methyl γ-hydroxy-γ-diphenyl-α,β-unsaturated enal, R 3 Using 4,5-dimethyl-1,2-phenylenediamine as the reactant, and with p-toluenesulfonic acid monohydrate as the catalyst, the specific implementation process is as follows:

[0372] (E)-4-hydroxy-4-methylpentan-2-enal (45.9 mg, 0.4 mmol), 4,5-dimethyl-1,2-phenylenediamine (81.9 mg, 0.6 mmol), and p-toluenesulfonic acid monohydrate (0.8 mg, 0.004 mmol) were dissolved in water (4 mL) and reacted at 25 °C for 2 h. The reaction equation is as follows:

[0373]

[0374] The reaction solution was concentrated and then subjected to silica gel column chromatography to obtain a solid product of 56.7 mg, with a calculated yield of 61%.

[0375] The analysis of the test is as follows:

[0376] 1. Proton and carbon NMR spectra:

[0377] 1 H NMR (300 MHz, CDCl3) δ 6.43 (s, 1H), 6.40 (s, 1H), 5.29 (d, J = 7.3Hz, 1H), 4.66 (s, 1H), 4.21 (s, 1H), 3.60-3.27 (m, 1H), 2.67 (dt, J1 = 13.3Hz, J2 = 6.7 Hz, 1H), 2.09 (s, 6H), 1.76 (d, J = 12.9 Hz, 1H), 1.18 (s, 3H), 1.10 (s, 3H) ppm.

[0378] 13 C NMR (75 MHz, CDCl3) δ 131.1, 127.8, 127.5, 126.3, 121.3, 119.7, 85.5, 79.6, 60.2, 40.5, 28.6, 23.0, 18.6, 18.4 ppm.

[0379] 2. High-resolution mass spectrometry: HRMS (ESI) C 14 H 21 N2O [M+H] + Found: 233.1648, Found: 233.1644.

[0380] The results show that the theoretical mass is 233.1648, while the observed value of the peak found in the actual mass spectrum is 233.1644. Combined with nuclear magnetic resonance, the product structure can be determined as follows:

[0381] This is a product of this embodiment.

[0382] Example 25

[0383] Using R 1 =R 2 It is a methyl γ-hydroxy-γ-diphenyl-α,β-unsaturated enal, R 3 Using 3,6-dibromo-1,2-phenylenediamine as the reactant, and with p-toluenesulfonic acid monohydrate as the catalyst, the specific implementation process is as follows:

[0384] (E)-4-hydroxy-4-methylpent-2-enal (45.6 mg, 0.4 mmol), 3,6-dibromo-1,2-phenylenediamine (160.0 mg, 0.6 mmol), and p-toluenesulfonic acid monohydrate (0.8 mg, 0.004 mmol) were dissolved in water (4 mL) and reacted at 25 °C for 2 h. The reaction equation is as follows:

[0385]

[0386] The reaction solution was concentrated and then subjected to silica gel column chromatography to obtain a solid product of 107.2 mg, with a calculated yield of 74%.

[0387] The analysis of the test is as follows:

[0388] 1. Proton and carbon NMR spectra:

[0389] 1 H NMR (300 MHz, CDCl3) δ 6.89 (d, J = 8.5 Hz, 1H), 6.82 (d, J = 8.5Hz, 1H), 5.67 (d, J = 5.8 Hz, 1H), 5.43 (t, J = 6.3 Hz, 1H), 5.23 (d, J = 6.2Hz, 1H), 3.67 (t, J = 6.1 Hz, 1H), 2.71 (dt, J1 = 13.0 Hz, J2 = 6.5 Hz, 1H), 1.87 (d, J = 12.8 Hz, 1H), 1.22 (s, 3H), 1.05 (s, 3H) ppm.

[0390] 13 C NMR (75 MHz, CDCl3) δ 132.1, 129.3, 123.3, 122.1, 113.1, 111.7, 84.9, 80.0, 60.4, 41.2, 28.3, 22.8 ppm.

[0391] 2. High-resolution mass spectrometry: HRMS (ESI) m / z Calcd for C 12 H 15 Br2N2O [M+H] + Found: 360.9546, Found: 360.9545.

[0392] The results show that the theoretical mass is 360.9546, while the observed peak value in the actual mass spectrum is 360.9545. Combined with nuclear magnetic resonance, the product structure can be determined as follows:

[0393] This is a product of this embodiment.

[0394] Example 26

[0395] Using R 1 =R 2 It is a phenyl group, R 3 Using 4,4-diphenyl-1,4,5,6-tetrahydro-2H-2,5-methanealkylbenzo[d][1,3,6]oxadiazacyclooctane as a reactant and 1-methyl-1H-indole as a catalyst, the reaction was carried out with bismuth trifluoromethanesulfonate as a catalyst. The specific implementation process is as follows:

[0396] 4,4-Diphenyl-1,4,5,6-tetrahydro-2H-2,5-methanealkylbenzo[d][1,3,6]oxazazzicyclooctane (131.6 mg, 0.4 mmol) and bismuth trifluoromethanesulfonate (52.8 mg, 0.08 mmol) were dissolved in tetrahydrofuran (4 mL), and 1-methyl-1H-indole (100.0 μL, 0.8 mmol) was added. The reaction was carried out at 25 °C for 14 h. The reaction equation is as follows:

[0397]

[0398] The reaction solution was concentrated and then subjected to silica gel column chromatography to obtain a solid product of 116.6 mg, with a calculated yield of 63%.

[0399] The analysis of the test is as follows:

[0400] 1. Proton and carbon NMR spectra:

[0401] 1H NMR (300 MHz, CDCl3) δ 7.70 (d, J = 7.7 Hz, 2H), 7.49 (d, J = 7.7Hz, 2H), 7.42-7.29 (m, 3H), 7.29-7.20 (m, 3H), 7.20-7.14 (m, 2H), 7.14-7.05(m, 1H), 6.98 (t, J = 7.5 Hz, 1H), 6.84 (s, 1H), 6.60-6.42 (m, 2H), 6.42-6.34(m, 1H), 4.58 (d, J = 11.1 Hz, 1H), 4.45 (dd, J1= 12.8 Hz, J2= 4.7 Hz, 1H),3.85 (s, 1H), 3.80-3.46 (m, 4H), 3.02 (s, 2H), 2.39 (q, J = 12.5 Hz, 1H),2.04-1.78 (m, 1H) ppm.

[0402] 13 C NMR (75 MHz, CDCl3) δ 145.7, 143.4, 137.0, 133.7, 133.0, 128.9,128.2, 127.8, 127.24, 127.21, 126.8, 126.6, 125.9, 125.4, 121.4, 120.5,119.8, 119.1, 118.6, 117.7, 114.5, 109.2, 78.4, 58.6, 34.9, 32.5, 30.9 ppm.

[0403] 2. High-resolution mass spectrometry: HRMS (ESI) C 31 H 30 N3O [M+H] + Found: 460.2383, Found: 460.2379.

[0404] The results show that the theoretical mass is 460.2383, while the observed value of the peak found in the actual mass spectrum is 460.2379. Combined with nuclear magnetic resonance, the product structure can be determined as follows:

[0405] This is a product of this embodiment.

[0406] Example 27

[0407] Using R 1 =R 2 It is a phenyl group, R3 The reaction was carried out using 4,4-diphenyl-1,4,5,6-tetrahydro-2H-2,5-methanealkylbenzo[d][1,3,6]oxadiazacyclooctane as a reactant, with 1H-pyrrole as the reactant and bismuth trifluoromethanesulfonate as the catalyst. The specific implementation process is as follows:

[0408] 4,4-Diphenyl-1,4,5,6-tetrahydro-2H-2,5-methanealkylbenzo[d][1,3,6]oxazazzicyclooctane (65.8 mg, 0.2 mmol), bismuth trifluoromethanesulfonate (65.6 mg, 0.1 mmol), and 5Å molecular sieve (200 mg) were dissolved in tetrahydrofuran (2 mL), and 1H-pyrrole (28.0 μL, 0.4 mmol) was added. The reaction was carried out at 25 °C for 12 h. The reaction equation is as follows:

[0409]

[0410] The reaction solution was concentrated and then subjected to silica gel column chromatography to obtain a solid product of 43.2 mg, with a calculated yield of 55%.

[0411] The analysis of the test is as follows:

[0412] 1. Proton and carbon NMR spectra:

[0413] 1 H NMR (300 MHz, DMSO-d6) δ 10.55 (s, 1H), 7.77 (d, J = 7.7 Hz, 2H), 7.53 (d, J = 7.7 Hz, 2H), 7.39 (t, J = 7.5 Hz, 2H), 7.33-7.21 (m, 3H), 7.14(t, J = 7.3 Hz, 1H), 6.61-6.51 (m, 1H), 6.45 (d, J = 7.5 Hz, 1H), 6.29 (t, J= 7.6 Hz, 1H), 5.99 (d, J = 7.6 Hz, 1H), 5.93-5.84 (m, 1H), 5.80-5.71 (m, 1H), 5.49 (s, 1H), 4.61 (d, J = 10.9 Hz, 1H), 4.28-4.06 (m, 3H), 3.66 (s,1H), 2.13-1.95 (m, 1H), 1.65-1.41 (m, 1H) ppm.

[0414] 13C NMR (75 MHz, DMSO-d6) δ 146.2, 145.3, 134.7, 134.1, 133.0, 128.2,127.9, 126.7, 126.5, 126.2, 125.4, 124.9, 117.9, 116.6, 116.3, 113.4, 106.8,105.1, 78.2, 57.3, 36.6, 30.4 ppm.

[0415] 2. High-resolution mass spectrometry: HRMS (ESI) C 26 H 26 N3O [M+H] + Found: 396.2070, Found: 396.2059.

[0416] The results show that the theoretical mass is 396.2070, while the observed value of the peak found in the actual mass spectrum is 396.2059. Combined with nuclear magnetic resonance, the product structure can be determined as follows:

[0417] This is a product of this embodiment.

[0418] Example 28

[0419] Using R 1 =R 2 It is a phenyl group, R 3 The reaction involves 4,4-diphenyl-1,4,5,6-tetrahydro-2H-2,5-methanebenzo[d][1,3,6]oxadiazacyclooctane, with iodomethane as the reactant and potassium carbonate as the catalyst. The specific implementation process is as follows:

[0420] 4,4-Diphenyl-1,4,5,6-tetrahydro-2H-2,5-methanealkylbenzo[d][1,3,6]oxazazzicyclooctane (65.9 mg, 0.2 mmol) and potassium carbonate (82.9 mg, 0.6 mmol) were dissolved in dry N,N-dimethylformamide (2 mL), and iodomethane (63.0 μL, 1.0 mmol) was added. The reaction was carried out at 25 °C for 12 h. The reaction equation is as follows:

[0421]

[0422] The reaction solution was concentrated and purified by silica gel column chromatography to obtain 40.1 mg of an oily product, with a calculated yield of 56%.

[0423] The analysis of the test is as follows:

[0424] 1. Proton and carbon NMR spectra:

[0425] 1 H NMR (300 MHz, CDCl3) δ 7.66-7.57 (m, 2H), 7.53-7.46 (m, 2H), 7.45-7.36 (m, 2H), 7.35-7.27 (m, 1H), 7.21-7.10 (m, 3H), 6.93-6.76 (m, 3H), 6.74-6.63 (m, 1H), 5.34 (d, J = 6.7 Hz, 1H), 4.08 (d, J = 5.1 Hz, 1H), 3.28 (s,3H), 2.25 (d, J = 13.4 Hz, 1H), 2.16 (s, 3H), 1.92-1.79 (m, 1H) ppm.

[0426] 13 C NMR (75 MHz, CDCl3) δ 144.9, 141.9, 140.3, 139.5, 129.0, 128.0,127.0, 126.84, 126.78, 126.7, 120.6, 119.9, 117.7, 116.4, 91.6, 90.8, 71.8,40.2, 39.5, 33.2 ppm.

[0427] 2. High-resolution mass spectrometry: HRMS (ESI) C 24 H 25 N2O [M+H] + Found: 357.1961, Found: 357.1947.

[0428] The results show that the theoretical mass is 357.1961, while the observed value of the peak found in the actual mass spectrum is 357.1947. Combined with nuclear magnetic resonance, the product structure can be determined as follows:

[0429] This is a product of this embodiment.

[0430] Example 29

[0431] Using R 1 =R 2 It is a phenyl group, R 3 Using 4,4-diphenyl-1,4,5,6-tetrahydro-2H-2,5-methanealkylbenzo[d][1,3,6]oxadiazacyclooctane as the reactant, sodium borohydride was used as the reducing agent and acetic acid as the catalyst. The specific implementation process is as follows:

[0432] 4,4-Diphenyl-1,4,5,6-tetrahydro-2H-2,5-methanealkylbenzo[d][1,3,6]oxazazzicyclooctane (65.8 mg, 0.2 mmol) and sodium borohydride (15.2 mg, 0.4 mmol) were dissolved in tetrahydrofuran (2 mL), and acetic acid (23.0 μL, 0.4 mmol) was added. The reaction was carried out at 25 °C for 24 h. The reaction equation is as follows:

[0433]

[0434] The reaction solution was concentrated and then subjected to silica gel column chromatography to obtain 58.5 mg of solid product, with a calculated yield of 89%.

[0435] The analysis of the test is as follows:

[0436] 1. Proton and carbon NMR spectra:

[0437] 1 H NMR (300 MHz, CDCl3) δ 7.66 (d, J = 7.3 Hz, 2H), 7.49 (d, J = 7.7Hz, 2H), 7.37 (t, J = 7.5 Hz, 2H), 7.26 (t, J = 7.6 Hz, 3H), 7.16 (t, J = 7.3Hz, 1H), 6.85-6.74 (m, 1H), 6.73-6.61 (m, 2H), 6.37 (d, J = 7.3 Hz, 1H), 3.88(dd, J1= 10.5 Hz, J2= 2.5 Hz, 1H), 3.83-3.45 (m, 3H), 3.43-3.28 (m, 1H),2.83-2.58 (m, 1H), 1.98-1.78 (m, 1H), 1.71-1.56 (m, 1H) ppm.

[0438] 13 C NMR (75 MHz, CDCl3) δ 145.3, 144.4, 140.7, 138.3, 128.8, 128.2,127.4, 126.6, 126.2, 125.3, 121.9, 121.2, 120.6, 119.7, 80.6, 62.7, 45.9,31.4 ppm.

[0439] 2. High-resolution mass spectrometry: HRMS (ESI) C 22 H 23 N2O [M+H]+ Found: 331.1805, Found: 331.1798.

[0440] The results show that the theoretical mass is 331.1805, while the observed value of the peak found in the actual mass spectrum is 331.1798. Combined with nuclear magnetic resonance, the product structure can be determined as follows:

[0441] This is a product of this embodiment.

[0442] Although the above embodiments have provided a detailed description of the present invention, they are only some embodiments of the present invention, and not all embodiments. People can obtain other embodiments based on these embodiments without creative effort, and these embodiments all fall within the protection scope of the present invention.

Claims

1. A method for preparing a 2,5-methylene-benzo[d][1,3,6]oxadiazacyclooctane compound, characterized in that, Includes the following steps: A cyclization reaction was carried out by mixing γ-hydroxy-α,β-unsaturated enaldehyde, o-aryl diamine, protic acid catalyst and solvent to obtain the 2,5-methylene-benzo[d][1,3,6]oxadiazacyclic octane compound; The γ-hydroxy-α,β-unsaturated enaldehyde has the structure shown in Formula 1 or is... or or or The o-aryl diamine has the structure shown in Formulas 2-3: Formula 1, Equation 2, Formula 3; When the γ-hydroxy-α,β-unsaturated enal is When the o-aryl diamine is The 2,5-methylene-benzo[d][1,3,6]oxadiazacyclooctane compound is... ; When the γ-hydroxy-α,β-unsaturated enal is When the o-aryl diamine is The 2,5-methylene-benzo[d][1,3,6]oxadiazacyclooctane compound is... ; When the γ-hydroxy-α,β-unsaturated enal is When the o-aryl diamine is The 2,5-methylene-benzo[d][1,3,6]oxadiazacyclooctane compound is... ; When the γ-hydroxy-α,β-unsaturated enal is When the o-aryl diamine is The 2,5-methylene-benzo[d][1,3,6]oxadiazacyclooctane compound is... ; When the γ-hydroxy-α,β-unsaturated enal is When the o-aryl diamine has the structure shown in any of formulas 2-3; when the o-aryl diamine is When the 2,5-methylene-benzo[d][1,3,6]oxadiazacyclooctane compound has the structure shown in Formula I; when the o-aryl diamine is At that time, the 2,5-methylene-benzo[d][1,3,6]oxadiazacyclooctane compound has the structure shown in Formula ⅠI; Formula I, Formula II; Among them, R 1 and R 2 Independently, they are aryl, phenyl, halogen-substituted phenyl, alkyl-substituted phenyl, alkoxy-substituted phenyl, or alkyl; R 3 Independently, they are hydrogen atoms, halogen atoms, or alkyl groups.

2. The preparation method according to claim 1, characterized in that, The Including γ-hydroxy-γ-diphenyl-α,β-unsaturated enal, (E)-4,4-bis(4-fluorophenyl)-4-hydroxy-2-butenal, (E)-4,4-bis(4-chlorophenyl)-4-hydroxy-2-butenal, (E)-4,4-bis(4-bromophenyl)-4-hydroxy-2-butenal, (E)-4,4-bis(4-methylphenyl)-4-hydroxy-2-butenal, (E)-4,4-bis(4-methoxyphenyl)-4-hydroxy (E)-4,4-bis(3-chlorophenyl)-4-hydroxy-2-butenal, (E)-4-hydroxy-4,4-bis(naphthyl-2-yl)-2-butenal, (E)-4-hydroxy-4,4-bis(thiophen-2-yl)-2-butenal, (E)-4-hydroxy-4-methylpentan-2-enal, (E)-4-benzyl-4-hydroxy-5-phenylpentan-2-enal, (E)-4-hydroxy-4-phenylpentan-2-enal.

3. The preparation method according to claim 1 or 2, characterized in that, The protic acid catalyst includes p-toluenesulfonic acid monohydrate and trifluoroacetic acid; The molar ratio of the γ-hydroxy-α,β-unsaturated enaldehyde and the protic acid catalyst is 1:0.01~0.

1.

4. The preparation method according to claim 1, characterized in that, The This includes 1,2-phenylenediamine, 4,5-difluoro-1,2-phenylenediamine, 4,5-dichloro-1,2-phenylenediamine, 4,5-dimethyl-1,2-phenylenediamine, and 3,6-dibromo-1,2-phenylenediamine.

5. The preparation method according to claim 1 or 4, characterized in that, The molar ratio of the γ-hydroxy-α,β-unsaturated enaldehyde and o-aryl diamine is 1:1.3~1.

7.

6. The preparation method according to claim 1, characterized in that, The cyclization reaction is carried out at a temperature of 20-35°C for 2-24 hours.

7. A 2,5-methylene-benzo[d][1,3,6]oxadiazacyclooctane compound prepared according to the preparation method of any one of claims 1 to 6, characterized in that, It has the structure shown in any of Equations I to II: Formula I, Formula II; Among them, R 1 and R 2 Independently, they are aryl, phenyl, halogen-substituted phenyl, alkyl-substituted phenyl, alkoxy-substituted phenyl, or alkyl; R 3 Independently, they are hydrogen atoms, halogen atoms, or alkyl groups.

8. The 2,5-methylene-benzo[d][1,3,6]oxadiazacyclooctane compound according to claim 7, characterized in that, It has any of the structures shown in Equations I-1 to I-24 and Equation II-1: Formula I-1 Formula I-2 Formula I-3 Formula I-4 Formula I-5 Formula I-6 Formula I-7 Formula I-8 Formula I-9 Formula I-10 Formula I-11 Formula I-12 Formula I-13 Formula I-14 Formula I-15 Formula I-16 Formula I-17 Formula I-18 Formula I-19 Formula I-20 Formula I-21 Formula I-22 Formula I-23 Formula I-24; Formula II-1.

9. A derivative prepared from a 2,5-methylene-benzo[d][1,3,6]oxadiazacyclic octane compound having the structure shown in Formula I as described in claim 7, characterized in that... It has any of the structures shown in equations a to d: Formula a Formula b Formula c Formula d.

10. A method for preparing the derivative of claim 9, comprising the following steps: The The preparation method includes the following steps: [The following text appears to be a list of steps and is not translated: "to..."] 1-Methyl-1H-indole, bismuth trifluoromethanesulfonate, and a first organic solvent were mixed and subjected to a ring-opening rearrangement / substitution reaction to obtain the [substance name missing]. ; The The preparation method includes the following steps: [The following text appears to be a list of steps and is not translated: "to..."] The mixture of 1H-pyrrole, bismuth trifluoromethanesulfonate, and a second organic solvent undergoes a ring-opening rearrangement / substitution reaction to obtain the desired product. ; The aforementioned manufacturing The preparation method includes the following steps: A mixture of iodomethane, potassium carbonate, and a third organic solvent undergoes a nucleophilic substitution reaction to obtain the desired product. ; The The preparation method includes the following steps: [The following text appears to be a list of steps and is not translated: "to..."] Sodium borohydride, acetic acid, and a fourth organic solvent are mixed and then subjected to a reduction reaction to obtain the [substance name missing]. .

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