A process for the preparation of a tetrahydrobenzo[f]isoindole compound

Abstract

The application discloses a preparation method of a tetrahydrobenzo[f]isoindole compound. The tetrahydrobenzo[f]isoindole compound is prepared by taking 1,6-alkynyl compound as raw material, taking alkaline substance as additive, and performing a cyclization reaction in an organic solvent. The structural formula of the 1,6-alkynyl compound is R is one of phenyl, p-fluorophenyl, p-chlorophenyl, p-bromophenyl, p-tert-butylphenyl, p-benzophenyl, p-methoxyphenyl, p-trifluoromethylphenyl, m-chlorophenyl, m-methoxyphenyl, m-cyanophenyl, m-formylphenyl, 3,5-dimethoxyphenyl, o-methoxyphenyl, o-methylphenyl, 1-naphthyl, 2-thienyl, 3-thienyl and p-methylphenyl. The preparation method of the tetrahydrobenzo[f]isoindole compound is characterized by using cheap and easily obtained alkaline substance as additive, using green and low-toxicity solvent, simple and mild reaction condition, high regioselectivity and the ability to be used for the development of heterocyclic drug molecules.

Description

TECHNICAL FIELD

[0001] The present application relates to the technical field of organic synthesis, and particularly relates to a preparation method of a tetrahydrobenzo[f]isoindole compound. BACKGROUND

[0002] The tetrahydrobenzo[f]isoindole compound is an important intermediate in organic synthesis, widely exists in natural products and bioactive molecules, and is mainly applied in the fields of medicine, agriculture, photoelectric materials and the like. However, currently, there are very limited examples of selectively synthesizing the benzo[f]isoindole from simple and easily available enyne raw materials, and recently, Ozawa's group synthesized the benzo[f]isoindole by the dehydrogenation cycloaddition reaction of the enyne compound under high temperature conditions (Org. Lett. 2011, 13, 5390), but the excessively high reaction temperature and the complex synthesis steps of the raw material limit the further application of the reaction. In addition, with the continuous improvement of environmental protection consciousness, the green and sustainable synthesis method is more and more welcomed. Therefore, it is of important research significance to develop a method for simply, efficiently and mildly synthesizing the tetrahydrobenzo[f]isoindole compound.

[0003] The [4+2] cycloaddition reaction of the enyne compound is one of important means for constructing polycyclic compounds, has high atom economy, and can construct multiple ring structures through one-step reaction. Generally, the cycloaddition reaction is divided into intermolecular cyclization method and intramolecular cyclization method. At present, many transition metal catalysts (for example, Ru, Rh, Pd, Au and the like) and non-metal catalysts have been developed for the [4+2] cycloaddition reaction, but they often have the defects of expensive price and complex preparation. It is necessary to develop new cheap and efficient [4+2] cycloaddition reagents. SUMMARY

[0004] The technical problem to be solved by the present application is how to simply and efficiently prepare the tetrahydrobenzo[f]isoindole compound.

[0005] The present application solves the above technical problems by the following technical means:

[0006] The present application provides a preparation method of a tetrahydrobenzo[f]isoindole compound. R is an aryl substituent; the aryl substituent is phenyl, p-fluorophenyl, p-chlorophenyl, p-bromophenyl, p-tert-butylphenyl, p-tolyl, p-methoxyphenyl, p-trifluoromethylphenyl, m-chlorophenyl, m-methoxyphenyl, m-cyanophenyl, m-formylphenyl, 3,5-dimethoxyphenyl, o-methoxyphenyl, o-methylphenyl, 1-naphthyl, 2-thienyl, 3-thienyl, p-methylphenyl, One of them, in which Indicates the position where it is attached to the acetylene group.

[0007] Preferably, the structural formula of the 1,6-enyne compound is as follows:

[0008] One of them.

[0009] Preferably, the alkaline substance is one or a mixture of KOH, Cs2CO3, K2CO3, and tBuOK.

[0010] Preferably, the alkaline substance is Cs2CO3.

[0011] Preferably, the organic solvent is one or a mixture of acetonitrile, isopropanol, and tert-butanol.

[0012] Preferably, the molar ratio of the alkaline substance to the 1,6-enyne compound is 0.5-2:1.

[0013] Preferably, the molar ratio of the alkaline substance to the 1,6-enyne compound is 1.01:1.

[0014] Preferably, the ratio of the 1,6-enyne compound to the organic solvent is 50 mmol: 20 mL.

[0015] Preferably, the reaction is carried out in an inert gas atmosphere.

[0016] Preferably, the reaction is carried out under heating conditions.

[0017] Preferably, the reaction temperature is 40-100℃ and the time is 3-24 hours.

[0018] Preferably, the organic solvent is isopropanol, and the reaction time is 3 hours.

[0019] Preferably, the organic solvent is tert-butanol, and the reaction time is 6 hours.

[0020] Preferably, the method for preparing the tetrahydrobenzo[f]isoindole compound includes the following steps: mixing a 1,6-enyne compound with a basic substance, and then adding an organic solvent to react and obtain the tetrahydrobenzo[f]isoindole compound.

[0021] Preferably, the method further includes a step of separating and purifying the product after the reaction; the separation and purification method includes at least one of column chromatography, vacuum distillation and recrystallization.

[0022] Preferably, the compound prepared by the present invention has the structural formula of either Formula I or Formula II:

[0023]

[0024] Preferably, in formulas I and II, R 1 R 2 All of them are one of hydrogen atoms, alkyl substituents, and aryl substituents.

[0025] Preferably, R in Formula I 1 It is one of hydrogen atom, 6-chloro atom, 6-methyl, 6-methoxy, 7-methoxy, 8-methoxy, 7-chloro atom, 7-formyl, 5,7-dimethoxy, and 8-methoxy.

[0026] Preferably, R in formula II 2 It is one of the following: hydrogen atom, 6-chloro atom, 6-bromine atom, 6-methyl, 6-tert-butyl, 6-phenyl, 6-methoxy, 6-trifluoromethyl, 7-chloro atom, 7-methoxy, 8-methyl, and 6,8-dimethoxy.

[0027] Basic substances, as widely available compounds, can promote intermolecular / intramolecular cycloaddition reactions of unsaturated or multisubstituted compounds to construct multi-carbon heterocyclic compounds. In the preparation method of this invention, a 1,6-enyne compound is used as a raw material, and a basic substance is used as an additive. A cyclization reaction is carried out in an organic solvent to obtain the tetrahydrobenzo[f]isoindole compound. The method can construct a multisubstituted tetrahydrobenzo[f]isoindole compound in one step through a base-promoted 1,6-enyne [4+2] cycloaddition reaction. Furthermore, the basic substance used is inexpensive and readily available, the solvent is green and low in toxicity, and the reaction conditions are simple and mild with high regioselectivity, making it suitable for the development of heterocyclic drug molecules.

[0028] The advantages of this invention are:

[0029] (1) The alkaline substances used in this invention are inexpensive, readily available, widely sourced, low in toxicity, and easy to handle;

[0030] (2) The reaction conditions of this invention are mild and simple;

[0031] (3) The present invention can obtain tetrahydrobenzo[f]isoindole compounds with two configurations of formula I or formula II, with high regioselectivity and good yield;

[0032] (4) The synthesis method used in this invention is green and environmentally friendly;

[0033] (5) The method described in this invention is easy to mass-produce, and the yield and selectivity can be maintained after scale-up;

[0034] (6) The present invention obtains two configuration products by changing the solvent, and the control method is simple and convenient;

[0035] (7) The synthesis method described in this invention has a wide range of applications and can synthesize various tetrahydrobenzo[f]isoindole compounds with different substitutions, which can be used for the development of heterocyclic drug molecules. Attached Figure Description

[0036] Figure 1 The hydrogen NMR spectrum of the product prepared in Example 2 of this invention;

[0037] Figure 2 The carbon NMR spectrum of the product prepared in Example 2 of this invention;

[0038] Figure 3 The hydrogen NMR spectrum of the product prepared in Example 3 of this invention;

[0039] Figure 4 The carbon NMR spectrum of the product prepared in Example 3 of this invention;

[0040] Figure 5 The hydrogen NMR spectrum of the product prepared in Example 4 of this invention;

[0041] Figure 6 The carbon NMR spectrum of the product prepared in Example 4 of this invention;

[0042] Figure 7 The hydrogen NMR spectrum of the product prepared in Example 5 of this invention;

[0043] Figure 8 The carbon NMR spectrum of the product prepared in Example 5 of this invention;

[0044] Figure 9 The hydrogen NMR spectrum of the product prepared in Example 6 of this invention;

[0045] Figure 10 The carbon NMR spectrum of the product prepared in Example 6 of this invention;

[0046] Figure 11 The hydrogen NMR spectrum of the product prepared in Example 7 of this invention;

[0047] Figure 12 The carbon NMR spectrum of the product prepared in Example 7 of this invention;

[0048] Figure 13 The hydrogen NMR spectrum of the product prepared in Example 8 of this invention;

[0049] Figure 14 The carbon NMR spectrum of the product prepared in Example 8 of this invention;

[0050] Figure 15 The hydrogen NMR spectrum of the product prepared in Example 14 of this invention;

[0051] Figure 16 The carbon NMR spectrum of the product prepared in Example 14 of this invention;

[0052] Figure 17 The hydrogen NMR spectrum of the product prepared in Example 18 of this invention;

[0053] Figure 18 The image shows the carbon NMR spectrum of the product prepared in Example 18 of this invention. Detailed Implementation

[0054] To make the objectives, technical solutions, and advantages of the embodiments of the present invention clearer, the technical solutions of the embodiments of the present invention will be clearly and completely described below in conjunction with the embodiments of the present invention. Obviously, the described embodiments are only some embodiments of the present invention, not all embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those skilled in the art without creative effort are within the scope of protection of the present invention.

[0055] Unless otherwise specified, all test materials and reagents used in the following examples are commercially available.

[0056] Unless otherwise specified in the embodiments, the techniques or conditions described in the literature in this field or in accordance with the product manual may be followed.

[0057] Example 1

[0058] Preparation of alkenyne compounds:

[0059] Enyne compounds were synthesized according to previously reported methods (J. Am. Chem. Soc. 2020, 142, 9510; Org. Chem. Front., 2021, 8, 4785), and the experimental procedures were basically consistent with those reported in the literature; among which The preparation method includes the following steps:

[0060]

[0061] Under an ice-water bath at 0°C, K₂CO₃ (38.0 mmol) and allyl bromide (40.0 mmol) were added to a Ts (p-toluenesulfonyl)-protected propargylamine (25.0 mmol) solution in acetonitrile (25 mL). The mixture was heated under reflux for 24 hours. The solvent was removed by rotary evaporation, and the resulting solid was dissolved in ethyl acetate, washed with water, extracted, and dried to obtain a crude product for direct use in the next step. Under a nitrogen atmosphere, iodobenzene (11.0 mmol), Pd(PPh₃)₂Cl₂ (0.2 mmol), CuI (0.2 mmol), and tetrahydrofuran (20 mL) were added to a 10.0 mmol solution of the obtained crude product in Et₃N (20 mL). The mixture was stirred under a nitrogen atmosphere for 16 hours, and the resulting product was washed with water, dried, and separated by column chromatography to obtain the final product.

[0062] Other enyne compounds used in the embodiments of this invention were all prepared by the above method.

[0063] Example 2

[0064] Preparation of tetrahydrobenzo[f]isoindole compounds

[0065] Prepared according to the reaction equation shown below:

[0066]

[0067] 1,6-enyne 50 mmol of Cs2CO3 and 50.5 mmol of Cs2CO3 were added to a round-bottom flask, followed by 20 mL of isopropanol solvent. The mixture was stirred for 3 hours at 80 °C. The target product, tetrahydrobenzo[f]isoindole, was obtained by column chromatography (petroleum ether PE: ethyl acetate EA volume ratio = 10:1) with a yield of 66%.

[0068] The corresponding NMR spectra of the products are as follows Figure 1 and Figure 2 As shown, the data is as follows: 1 H NMR (600MHz, CDCl3) δ7.74(d,J=8.0Hz,2H),7.34(d,J=7.9Hz,2H),7.13(t,J= 7.2Hz,1H),7.08(q,J=7.5Hz,2H),6.98(d,J=7.3Hz,1H),6.28(s,1H),4.24(dt ,J=15.2,2.3Hz,1H),3.96(t,J=8.6Hz,1H),3.87(dt,J=15.1,2.3Hz,1H),2.96 (h,J=8.6,7.5Hz,1H),2.86–2.77(m,2H),2.49(t,J=15.3Hz,1H),2.43(s,3H).13 C NMR (126MHz, CDCl3) δ143.9,140.4,134.0,133.3,133.1,129.9,127.93,127.87,127.2,127.1,126.2,119.7,54.7,50.8,38.6,32.3,21.7.

[0069] Example 3

[0070] Preparation of tetrahydrobenzo[f]isoindole compounds

[0071] Prepared according to the reaction equation shown below:

[0072]

[0073] 1,6-enyne 50 mmol of Cs2CO3 and 50.5 mmol of Cs2CO3 were added to a round-bottom flask, followed by 20 mL of isopropanol solvent. The mixture was stirred at 80 °C for 3 hours. The target product, tetrahydrobenzo[f]isoindole, was obtained by column chromatography (PE:EA volume ratio = 10:1) with a yield of 57%.

[0074] The corresponding NMR spectra of the products are as follows Figure 3 and Figure 4 As shown, the data is as follows: 1 H NMR (600MHz, CDCl3) δ7.74(d,J=8.3Hz,2H),7.34(d,J=8.0Hz,2H),7.10(dd, J=8.1,2.4Hz,1H),7.05(s,1H),6.90(d,J=8.1Hz,1H),6.24(d,J=2.6Hz,1H), 4.23(dt,J=15.2,1.7Hz,1H),3.98–3.93(m,1H),3.88–3.83(m,1H),2.94(dt ,J=17.6,8.8Hz,1H),2.84–2.75(m,2H),2.48(d,J=15.4Hz,1H),2.43(s,3H). 13 C NMR (151MHz, CDCl3) δ144.0,140.9,135.2,133.1,132.5,132.4,130.0,128.1,127.9,127.2,127.1,118.9,54.5,50.7,38.4,32.1,21.7.

[0075] Example 4

[0076] Preparation of tetrahydrobenzo[f]isoindole compounds

[0077] Prepared according to the reaction equation shown below:

[0078]

[0079] 1,6-enyne 50 mmol of Cs2CO3 and 50.5 mmol of Cs2CO3 were added to a round-bottom flask, followed by 20 mL of isopropanol solvent. The mixture was stirred at 80 °C for 3 hours. The target product, tetrahydrobenzo[f]isoindole, was obtained by column chromatography (PE:EA volume ratio = 10:1) with a yield of 65%.

[0080] The corresponding NMR spectra of the products are as follows Figure 5 and Figure 6 As shown, the data is as follows: 1 H NMR (600MHz, CDCl3) δ7.75(d,J=7.9Hz,2H),7.34(d,J=7.9Hz,2H),6.95(d,J=7.9Hz,1H),6.90–6.87(m,2H),6.25(s,1H),4.23(dd,J=15.2,2 .4Hz,1H),3.96(t,J=8.5Hz,1H),3.89–3.84(m,1H),2.98–2.90(m,1H),2.81–2.77(m,2H),2.48(d,J=15.2Hz,1H),2.43(s,3H),2.28(s,3H). 13 C NMR (151MHz, CDCl3) δ143.8,139.2,137.0,133.3,133.2,131.4,129.9,128.9,127.9,127.6,126.1,119.5,54.7,50.8,38.7,32.4,21.7,21.3.

[0081] Example 5

[0082] Preparation of tetrahydrobenzo[f]isoindole compounds

[0083] Prepared according to the reaction equation shown below:

[0084]

[0085] 1,6-enyne 50 mmol of Cs2CO3 and 50.5 mmol of Cs2CO3 were added to a round-bottom flask, followed by 20 mL of isopropanol solvent. The mixture was stirred at 80 °C for 3 hours. The target product, tetrahydrobenzo[f]isoindole, was obtained by column chromatography (PE:EA volume ratio = 9:1) with a yield of 58%.

[0086] The corresponding NMR spectra of the products are as follows Figure 7 and Figure 8 As shown, the data is as follows: 1 H NMR (600MHz, CDCl3) δ7.68 (d, J=8.3Hz, 2H), 7.31 (d, J=8.0Hz, 2H), 6.99 (d, J= 8.4Hz,1H),6.71(dd,J=8.5,2.7Hz,1H),6.51(d,J=2.7Hz,1H),6.23(s,1H),3. 74(s,4H),3.49(q,J=19.2Hz,2H),3.29(dd,J=10.9,5.5Hz,1H),2.90(td,J=1 0.8,5.4Hz,1H),2.81(dd,J=15.2,5.8Hz,1H),2.41(s,3H),2.31–2.26(m,1H). 13 C NMR (151MHz, CDCl3) δ168.7,157.8,143.9,136.5,132.9,129.8,127.9,126.9,126.0,122.6,114.1,112.8,55.4,53.2,40.6,37.9,27.4,21.7.

[0087] Example 6

[0088] Preparation of tetrahydrobenzo[f]isoindole compounds

[0089] Prepared according to the reaction equation shown below:

[0090]

[0091] 1,6-enyne 50 mmol of Cs2CO3 and 50.5 mmol of Cs2CO3 were added to a round-bottom flask, followed by 20 mL of isopropanol solvent. The mixture was stirred at 80 °C for 3 hours. The target product, tetrahydrobenzo[f]isoindole, was obtained by column chromatography (PE:EA volume ratio = 8:1) with a yield of 60%.

[0092] The corresponding NMR spectra of the products are as follows Figure 9 and Figure 10 As shown, the data is as follows: 1H NMR (600MHz, CDCl3) δ7.67 (dd, J=8.2, 1.4Hz, 2H), 7.30 (d, J=7.9Hz, 2H), 7.10 (t, J= 7.9Hz,1H),6.70(d,J=7.7Hz,1H),6.64(d,J=8.1Hz,1H),6.22(s,1H),3.81–3.77(m, 1H),3.76(d,J=1.3Hz,3H),3.54(s,2H),3.30(ddd,J=10.8,5.9,1.3Hz,1H),3.17(dd ,J=16.1,6.4Hz,1H),2.91–2.82(m,1H),2.41(s,3H),1.88(dd,J=16.2,11.2Hz,1H). 13 C NMR (101MHz, CDCl3) δ157.6,143.8,136.1,132.6,129.8,127.9,126.9,125.4,124.3,122.2,121.0,107.3,55.4,53.7,40.0,30.7,28.2,21.7.

[0093] Example 7

[0094] Preparation of tetrahydrobenzo[f]isoindole compounds

[0095] Prepared according to the reaction equation shown below:

[0096]

[0097] 1,6-enyne 50 mmol of Cs2CO3 and 50.5 mmol of Cs2CO3 were added to a round-bottom flask, followed by 20 mL of isopropanol solvent. The mixture was stirred at 80 °C for 3 hours. The target product, tetrahydrobenzo[f]isoindole, was obtained by column chromatography (PE:EA volume ratio = 7:1) with a yield of 62%.

[0098] The corresponding NMR spectra of the products are as follows Figure 11 and Figure 12 As shown, the data is as follows: 1H NMR (600MHz, CDCl3) δ7.73(d,J=7.9Hz,2H),7.33(d,J=8.0Hz,2H),6.31(s,1H),6.19(d,J=5.6Hz,2H),4.23(d,J=15.3Hz,1H),3.94(t,J=8.0Hz,1H),3 .86(d,J=15.0Hz,1H),3.77(d,J=3.8Hz,6H),3.19(dd,J=15.5,7.0Hz,1H), 2.89–2.82(m,1H),2.82–2.78(m,1H),2.42(s,3H),1.98(t,J=15.1Hz,1H). 13 C NMR (151MHz, CDCl3) δ159.4,157.2,143.9,141.1,135.5,129.9,127.8,12 7.3,119.6,113.3,103.4,97.5,55.6,55.5,54.8,50.8,38.5,23.9,21.7.

[0099] Example 8

[0100] Preparation of tetrahydrobenzo[f]isoindole compounds

[0101] Prepared according to the reaction equation shown below:

[0102]

[0103] 1,6-enyne 50 mmol of Cs2CO3 and 50.5 mmol of Cs2CO3 were added to a round-bottom flask, followed by 20 mL of isopropanol solvent. The mixture was stirred at 80 °C for 3 hours. The target product, tetrahydrobenzo[f]isoindole, was obtained by column chromatography (PE:EA volume ratio = 7:1) with a yield of 66%.

[0104] The corresponding NMR spectra of the products are as follows Figure 13 and Figure 14 As shown, the data is as follows: 1H NMR (600MHz, CDCl3) δ7.76–7.71(m,2H),7.33(d,J=8.0Hz,2H),7.05(t,J=7.8Hz,1H),6.70(t,J=8.1Hz,2H),6.65(s,1H),4.24(d,J=15.2Hz ,1H),3.98–3.93(m,1H),3.90(d,J=15.1Hz,1H),3.80(s,3H),2.91(q,J=7.6Hz,1H),2.83–2.78(m,2H),2.46(d,J=15.3Hz,1H),2.42(s,3H). 13 CNMR (151MHz, CDCl3) δ154.9,143.8,139.3,134.8,133.3,129.9,127.9,127.7,122.9,120.5,113.9,109.4,55.7,54.8,51.0,38.2,32.6,21.7.

[0105] Example 9

[0106] Preparation of tetrahydrobenzo[f]isoindole compounds

[0107] Prepared according to the reaction equation shown below:

[0108]

[0109] 1,6-enyne 50 mmol of Cs2CO3 and 50.5 mmol of Cs2CO3 were added to a round-bottom flask, followed by 20 mL of isopropanol solvent. The mixture was stirred at 80 °C for 3 hours. The target product, tetrahydrobenzo[f]isoindole, was obtained by column chromatography (PE:EA volume ratio = 10:1) with a yield of 67%.

[0110] The corresponding NMR data of the products are as follows: 1H NMR (400MHz, CDCl3) δ7.99(d,J=8.4Hz,1H),7.79(d,J=8.3Hz,3H),7.63(d,J=8.3Hz ,1H),7.48(ddd,J=8.4,6.8,1.6Hz,1H),7.42(t,J=7.5Hz,1H),7.36(d,J=8.1Hz,2H ),7.24(d,J=8.3Hz,1H),7.05(s,1H),4.36(d,J=15.4Hz,1H),4.05–3.98(m,2H),3. 05(dt,J=17.0,8.6Hz,1H),2.98–2.87(m,2H),2.66(t,J=15.7Hz,1H),2.43(s,3H). 13 C NMR (101MHz, CDCl3) δ143.9,141.2,133.1,133.0,130.9,129.9,129.4,129.3,128 .6,127.9,127.1,126.8,126.3,125.3,122.5,115.3,54.8,51.2,38.4,33.3,21.7.

[0111] Example 10

[0112] Preparation of tetrahydrobenzo[f]isoindole compounds

[0113] Prepared according to the reaction equation shown below:

[0114]

[0115] 1,6-enyne 50 mmol of Cs2CO3 and 50.5 mmol of Cs2CO3 were added to a round-bottom flask, followed by 20 mL of isopropanol solvent. The mixture was stirred at 80 °C for 3 hours. The target product, tetrahydrobenzo[f]isoindole, was obtained by column chromatography (PE:EA volume ratio = 8:1) with a yield of 58%.

[0116] The corresponding NMR data of the products are as follows: 1H NMR (600MHz, CDCl3) δ8.04(d,J=7.9Hz,1H),7.73(d,J=7.9Hz,2H),7.59(t,J=7.7Hz,2H ),7.50–7.46(m,3H),7.37(s,2H),7.27(t,J=8.4Hz,3H),7.19(d,J=8.4Hz,1H),7.12(d ,J=8.4Hz,1H),6.32(s,1H),3.91(t,J=10.3Hz,1H),3.79–3.71(m,3H),3.52(dd,J=11. 0,5.2Hz,1H),3.10(tt,J=11.1,6.2Hz,1H),2.55(dd,J=15.6,10.9Hz,1H),2.27(s,3H). 13 C NMR (101MHz, CDCl3) δ144.0,141.1,137.5,132.6,130.6,130.2,130.0,129.8,127.9,127.8,127.5,127 .2,126.8,126.2,125.4,123.4,122.8,122.3,121.2,119.9,109.8,108.2,53.9,40.2,35.6,28.5,21.6.

[0117] Example 11

[0118] Preparation of tetrahydrobenzo[f]isoindole compounds

[0119] Prepared according to the reaction equation shown below:

[0120]

[0121] 1,6-enyne 50 mmol of Cs2CO3 and 50.5 mmol of Cs2CO3 were added to a round-bottom flask, followed by 20 mL of isopropanol solvent. The mixture was stirred at 80 °C for 3 hours. The target product, tetrahydrobenzo[f]isoindole, was obtained by column chromatography (PE:EA volume ratio = 8:1) with a yield of 65%.

[0122] The corresponding NMR data of the products are as follows: 1H NMR (600MHz, CDCl3) δ7.67(d,J=8.1Hz,2H),7.31(d,J=8.0Hz,2H),6.53(s,1H),6.44(s,1H),6.22(s,1H),5.87(s,2H),3.72(t,J=10.3H z,1H),3.50–3.41(m,2H),3.27(dd,J=10.8,5.5Hz,1H),2.89(s,1H),2.73(dd,J=15.0,5.9Hz,1H),2.42(s,3H),2.22(t,J=13.3Hz,1H). 13 C NMR (101MHz, CDCl3) δ145.4,144.0,138.2,135.2,132.3,130.0,128.7,127.1,126.9,125.9,125.7,121.8,115.8,52.9,37.0,36.2,26.2,21.7.

[0123] Example 12

[0124] Preparation of tetrahydrobenzo[f]isoindole compounds

[0125] Prepared according to the reaction equation shown below:

[0126]

[0127] 1,6-enyne 50 mmol of Cs2CO3 and 50.5 mmol of Cs2CO3 were added to a round-bottom flask, followed by 20 mL of isopropanol solvent. The mixture was stirred at 80 °C for 3 hours. The target product, tetrahydrobenzo[f]isoindole, was obtained by column chromatography (PE:EA volume ratio = 15:1) with a yield of 42%.

[0128] The corresponding NMR data of the products are as follows: 1 H NMR (600MHz, CDCl3) δ7.73(d,J=7.9Hz,2H),7.34(d,J=7.8Hz,2H),7.05(d, J=5.0Hz,1H),6.79(d,J=5.0Hz,1H),6.25(s,1H),4.22(d,J=15.3Hz,1H),3. 94(t,J=8.6Hz,1H),3.84(d,J=15.3Hz,1H),3.14–3.06(m,1H),2.91(dd,J=1 5.4,8.1Hz,1H),2.80(t,J=9.8Hz,1H),2.43(s,3H),2.34(t,J=16.1Hz,1H). 13CNMR(101MHz, CDCl3)δ144.0,144.0,134.3,133.5,132.8,129.8,127.9,127.4,124.4,123.6,123.2,53.1,40.6,33.2,24.9,21.7.

[0129] Example 13

[0130] Preparation of tetrahydrobenzo[f]isoindole compounds

[0131] Prepared according to the reaction equation shown below:

[0132]

[0133] 1,6-enyne 50 mmol of Cs2CO3 and 50.5 mmol of Cs2CO3 were added to a round-bottom flask, followed by 20 mL of isopropanol solvent. The mixture was stirred at 80 °C for 3 hours. The target product, tetrahydrobenzo[f]isoindole, was obtained by column chromatography (PE:EA volume ratio = 15:1) with a yield of 51%.

[0134] The corresponding NMR data of the products are as follows: 1 H NMR (600MHz, CDCl3) δ7.70–7.66(m,2H),7.31(d,J=8.0Hz,2H),7.06(d,J=5.1 Hz,1H),6.74(d,J=5.2Hz,1H),6.30(s,1H),3.77–3.73(m,1H),3.44(d,J=18. 6Hz,1H),3.34(d,J=20.9Hz,1H),3.29(dd,J=10.9,5.5Hz,1H),3.04(tt,J=10 .7,6.1Hz,1H),2.95(dd,J=15.1,6.3Hz,1H),2.42(s,3H),2.23–2.17(m,1H). 13 C NMR (151MHz, CDCl3) δ144.0,133.6,133.3,132.8,129.8,127.9,126.9,124.6,123.9,123.2,52.9,41.2,32.3,25.3,21.7.

[0135] Example 14

[0136] Preparation of tetrahydrobenzo[f]isoindole compounds

[0137] Prepared according to the reaction equation shown below:

[0138]

[0139] 1,6-enyne 50 mmol of Cs2CO3 and 50.5 mmol of Cs2CO3 were added to a round-bottom flask, followed by 20 mL of tert-butanol solvent. The mixture was stirred at 80 °C for 6 hours. The target product, tetrahydrobenzo[f]isoindole, was obtained by column chromatography (PE:EA volume ratio = 10:1) with a yield of 58%.

[0140] The corresponding NMR spectra of the products are as follows Figure 15 and Figure 16 As shown, the data is as follows: 1 H NMR (600MHz, CDCl3) δ7.68(d,J=8.0Hz,2H),7.33(d,J=7.9Hz,2H),7.24(t,J= 7.2Hz,1H),7.11(d,J=7.5Hz,2H),6.97(d,J=7.3Hz,1H),6.25(s,1H),3.74(d t,J=15.2,2.3Hz,1H),3.52(d,J=8.6Hz,2H),3.29(dt,J=15.1,2.3Hz,1H),2. 91–2.94(m,1H),2.84(dd,J=10.3,4.2Hz,1H),2.41(s,3H),2.28–2.33(m,1H). 13 C NMR (151MHz, CDCl3) δ143.9,135.4,134.8,132.9,129.8,129.4,128.9,127.9,126.6,126.0,125.6,122.6,53.2,40.6,37.6,28.1,21.7.

[0141] Example 15

[0142] Preparation of tetrahydrobenzo[f]isoindole compounds

[0143] Prepared according to the reaction equation shown below:

[0144]

[0145] 1,6-enyne 50 mmol of Cs2CO3 and 50.5 mmol of Cs2CO3 were added to a round-bottom flask, followed by 20 mL of tert-butanol solvent. The mixture was stirred at 80 °C for 6 hours. The target product, tetrahydrobenzo[f]isoindole, was obtained by column chromatography (PE:EA volume ratio = 10:1) with a yield of 55%.

[0146] The corresponding NMR data of the products are as follows: 1H NMR (600MHz, CDCl3) δ7.67(d,J=7.9Hz,2H),7.31(d,J=7.9Hz,2H),7.09(d,J =8.2Hz,1H),6.99(d,J=8.3Hz,1H),6.96(s,1H),6.25(s,1H),3.74(t,J=10.3 Hz,1H),3.51(q,J=19.6Hz,2H),3.29(dd,J=11.0,5.5Hz,1H),2.89(dt,J=11 .0,5.4Hz,1H),2.81(dd,J=15.3,5.8Hz,1H),2.41(s,3H),2.33–2.18(m,1H). 13 CNMR (151MHz, CDCl3) δ144.0,137.2,133.2,132.7,131.5,130.2,129.8,129.1,127.9,127.8,126.7,124.8,123.0,53.0,40.2,37.3,27.7,21.7.

[0147] Example 16

[0148] Preparation of tetrahydrobenzo[f]isoindole compounds

[0149] Prepared according to the reaction equation shown below:

[0150]

[0151] 1,6-enyne 50 mmol of Cs2CO3 and 50.5 mmol of Cs2CO3 were added to a round-bottom flask, followed by 20 mL of tert-butanol solvent. The mixture was stirred at 80 °C for 6 hours. The target product, tetrahydrobenzo[f]isoindole, was obtained by column chromatography (PE:EA volume ratio = 10:1) with a yield of 51%.

[0152] The corresponding NMR data of the products are as follows: 1H NMR (600MHz, CDCl3) δ7.71–7.63(m,2H),7.31(d,J=8.0Hz,2H),7.24(dt,J=8.0,3. 6Hz,1H),7.16–7.07(m,1H),6.94(dd,J=8.4,3.9Hz,1H),6.25(t,J=2.3Hz,1H),3. 74(td,J=10.7,3.1Hz,1H),3.49(q,J=19.8Hz,2H),3.29(dt,J=10.9,4.8Hz,1H),2 .89(s,1H),2.80(dd,J=15.5,5.9Hz,1H),2.42(d,J=3.6Hz,3H),2.31–2.21(m,1H). 13 C NMR (151MHz, CDCl3) δ144.0,137.6,133.8,132.8,132.1,130.5,129.8,129.6,127.8,124.6,123.1,119.6,53.0,40.3,37.3,27.8,21.7.

[0153] Example 17

[0154] Preparation of tetrahydrobenzo[f]isoindole compounds

[0155] Prepared according to the reaction equation shown below:

[0156]

[0157] 1,6-enyne 50 mmol of Cs2CO3 and 50.5 mmol of Cs2CO3 were added to a round-bottom flask, followed by 20 mL of tert-butanol solvent. The mixture was stirred at 80 °C for 6 hours. The target product, tetrahydrobenzo[f]isoindole, was obtained by column chromatography (PE:EA volume ratio = 10:1) with a yield of 57%.

[0158] The corresponding NMR data of the products are as follows: 1 H NMR (600MHz, CDCl3) δ7.72–7.65(m,2H),7.30(d,J=7.8Hz,2H),6.96(t,J=7.3Hz,2H),6.80(s,1H),6.27–6.19(m,1H),3.80–3.70(m, 1H),3.51(q,J=19.3Hz,2H),3.28(dd,J=10.9,5.6Hz,1H),2.94–2.86(m,1H),2.80(dd,J=15.0,5.9Hz,1H),2.41(s,3H),2.25(s,3H).13 C NMR (151MHz, CDCl3) δ143.9,135.6,135.2,132.8,131.7,123.0,129.8,128.8,127.9,127.5,126.0,122.5,53.2,40.7,37.6,27.8,21.7,21.0.

[0159] Example 18

[0160] Preparation of tetrahydrobenzo[f]isoindole compounds

[0161] Prepared according to the reaction equation shown below:

[0162]

[0163] 1,6-enyne 50 mmol of Cs2CO3 and 50.5 mmol of Cs2CO3 were added to a round-bottom flask, followed by 20 mL of tert-butanol solvent. The mixture was stirred at 80 °C for 6 hours. The target product, tetrahydrobenzo[f]isoindole, was obtained by column chromatography (PE:EA volume ratio = 10:1) with a yield of 46%.

[0164] The corresponding NMR spectra of the products are as follows Figure 17 and Figure 18 As shown, the data is as follows: 1 H NMR (600MHz, CDCl3) δ7.69(d,J=8.0Hz,2H),7.32(d,J=7.9Hz,2H),7.18(d,J=7 .1Hz,1H),7.04(d,J=8.1Hz,1H),7.01(s,1H),6.24(s,1H),3.76(t,J=10.3Hz, 1H),3.58–3.49(m,2H),3.30(dd,J=10.8,5.6Hz,1H),2.93(td,J=10.9,5.5Hz, 1H), 2.86 (dd, J=15.1, 5.8Hz, 1H), 2.42 (s, 3H), 2.35–2.29 (m, 1H), 1.28 (s, 9H). 13 C NMR (151MHz, CDCl3) δ149.0,143.8,134.9,132.7,131.9,129.8,128.6,12 7.9,126.2,125.9,123.8,122.5,53.3,40.7,38.0,34.4,31.5,27.7,21.7.

[0165] Example 19

[0166] Preparation of tetrahydrobenzo[f]isoindole compounds

[0167] Prepared according to the reaction equation shown below:

[0168]

[0169] 1,6-enyne 50 mmol of Cs2CO3 and 50.5 mmol of Cs2CO3 were added to a round-bottom flask, followed by 20 mL of tert-butanol solvent. The mixture was stirred at 80 °C for 6 hours. The target product, tetrahydrobenzo[f]isoindole, was obtained by column chromatography (PE:EA volume ratio = 10:1) with a yield of 64%.

[0170] The corresponding NMR data of the products are as follows: 1 H NMR(600MHz, CDCl3)δ7.69(d,J=8.2Hz,2H),7.54–7.51(m,2H),7.41(t,J=7.4Hz,2 H),7.37(d,J=7.8Hz,1H),7.32(d,J=8.1Hz,3H),7.21(s,1H),7.16(d,J=8.0Hz,1H) ,6.27(s,1H),3.77(t,J=10.2Hz,1H),3.62(t,J=17.9Hz,2H),3.33(dd,J=11.1,5. 0Hz,1H),2.97(t,J=5.3Hz,1H),2.95–2.91(m,1H),2.42(s,3H),2.39–2.34(m,1H). 13 C NMR (151MHz, CDCl3) δ143.9,140.8,139.1,135.8,134.0,129.8,129.4,128.9, 128.1,127.9,127.4,127.1,125.5,125.5,122.8,53.2,40.6,37.8,27.9,21.8.

[0171] Example 20

[0172] Preparation of tetrahydrobenzo[f]isoindole compounds

[0173] Prepared according to the reaction equation shown below:

[0174]

[0175] 1,6-enyne 50 mmol of Cs2CO3 and 50.5 mmol of Cs2CO3 were added to a round-bottom flask, followed by 20 mL of tert-butanol solvent. The mixture was stirred at 80 °C for 6 hours. The target product, tetrahydrobenzo[f]isoindole, was obtained by column chromatography (PE:EA volume ratio = 10:1) with a yield of 62%.

[0176] The corresponding NMR data of the products are as follows: 1 H NMR (600MHz, CDCl3) δ7.74(d,J=8.0Hz,2H),7.33(d,J=8.0Hz,2H),6.91(d, J=8.1Hz,1H),6.70–6.62(m,2H),6.22(d,J=2.7Hz,1H),4.24–4.17(m,1H),3 .94(t,J=8.5Hz,1H),3.85(dd,J=14.9,2.6Hz,1H),3.76(d,J=1.1Hz,3H),2. 93(d,J=7.2Hz,1H),2.83–2.75(m,2H),2.48(t,J=15.2Hz,1H),2.42(s,3H). 13 C NMR (151MHz, CDCl3) δ158.8,143.9,137.6,135.1,133.1,129.9,127.9,127.1,127.1,119.1,114.5,111.5,55.4,54.7,50.7,38.4,32.7,21.7.

[0177] Example 21

[0178] Preparation of tetrahydrobenzo[f]isoindole compounds

[0179] Prepared according to the reaction equation shown below:

[0180]

[0181] 1,6-enyne 50 mmol of Cs2CO3 and 50.5 mmol of Cs2CO3 were added to a round-bottom flask, followed by 20 mL of tert-butanol solvent. The mixture was stirred at 80 °C for 6 hours. The target product, tetrahydrobenzo[f]isoindole, was obtained by column chromatography (PE:EA volume ratio = 10:1) with a yield of 56%.

[0182] The corresponding NMR data of the products are as follows: 1H NMR (600MHz, CDCl3) δ7.68(d,J=7.9Hz,2H),7.31(d,J=8.0Hz,2H),7.08(d,J= 8.5Hz,1H),6.98(d,J=8.9Hz,1H),6.84(s,1H),6.26(s,1H),3.74(t,J=10.3Hz ,1H),3.54(dd,J=19.5,5.4Hz,2H),3.30(dd,J=10.9,5.4Hz,1H),2.91(dd,J=1 0.7,5.8Hz,1H),2.85(dd,J=15.3,5.7Hz,1H),2.41(s,3H),2.32–2.26(m,1H). 13 C NMR (101MHz, CDCl3) δ144.0,139.0,136.2,132.9,130.1(d,J=31.6Hz),129.8,129.4,128.3,12 7.9,127.6,126.3(q,J=3.4Hz),124.2(d,J=273.2Hz),123.4,53.1,40.4,37.5,28.2,21.7.19F NMR(564MHz, CDCl3)δ-54.75(s,1F).

[0183] Example 22

[0184] Preparation of tetrahydrobenzo[f]isoindole compounds

[0185] Prepared according to the reaction equation shown below:

[0186]

[0187] 1,6-enyne 50 mmol of Cs2CO3 and 50.5 mmol of Cs2CO3 were added to a round-bottom flask, followed by 20 mL of tert-butanol solvent. The mixture was stirred at 80 °C for 6 hours. The target product, tetrahydrobenzo[f]isoindole, was obtained by column chromatography (PE:EA volume ratio = 10:1) with a yield of 64%.

[0188] The corresponding NMR data of the products are as follows: 1H NMR (600MHz, CDCl3) δ7.67(d,J=7.6Hz,2H),7.30(d,J=7.7Hz,2H),7.16(d,J=8.2Hz,1H),7.06(t,J=7.9Hz,1H),6.98(d,J=7.7Hz,1H),6.24(s,1H) ,3.80(t,J=10.4Hz,1H),3.56(s,2H),3.35–3.32(m,1H),3.20(dd,J=16.4 ,6.1Hz,1H),2.91–2.86(m,1H),2.42(d,J=9.9Hz,4H),1.98–1.92(m,1H). 13 C NMR (151MHz, CDCl3) δ144.0,137.1,134.7,133.3,132.7,129.8,127.9,127.4,127.2,127.0,124.5,122.8,53.5,40.2,34.6,28.5,21.7.

[0189] Example 23

[0190] Preparation of tetrahydrobenzo[f]isoindole compounds

[0191] Prepared according to the reaction equation shown below:

[0192]

[0193] 1,6-enyne 50 mmol of Cs2CO3 and 50.5 mmol of Cs2CO3 were added to a round-bottom flask, followed by 20 mL of tert-butanol solvent. The mixture was stirred at 80 °C for 6 hours. The target product, tetrahydrobenzo[f]isoindole, was obtained by column chromatography (PE:EA volume ratio = 10:1) with a yield of 69%.

[0194] The corresponding NMR data of the products are as follows: 1H NMR (600MHz, CDCl3) δ7.78–7.71(m,2H),7.33(d,J=8.0Hz,2H),7.12–7.08(m,1H),6.72(d,J =8.2Hz,1H),6.64(d,J=7.5Hz,1H),6.24(d,J=2.5Hz,1H),4.23(dt,J=15.2,2.1Hz,1H),3.9 7(dd,J=8.6,7.2Hz,1H),3.88(dt,J=15.3,2.3Hz,1H),3.80(s,3H),3.30(dd,J=15.6,6.9Hz ,1H),2.91–2.85(m,1H),2.82(dd,J=10.0,8.7Hz,1H),2.43(s,3H),2.04(t,J=15.2Hz,1H). 13 C NMR (151MHz, CDCl3) δ156.4,143.9,140.4,135.1,133.1,129.9,127.8,127 .4,121.0,119.6,119.5,119.1,109.9,55.6,54.9,50.8,38.2,24.2,21.7.

[0195] Example 24

[0196] Preparation of tetrahydrobenzo[f]isoindole compounds

[0197] Prepared according to the reaction equation shown below:

[0198]

[0199] 1,6-enyne 50 mmol of Cs2CO3 and 50.5 mmol of Cs2CO3 were added to a round-bottom flask, followed by 20 mL of tert-butanol solvent. The mixture was stirred at 80 °C for 6 hours. The target product, tetrahydrobenzo[f]isoindole, was obtained by column chromatography (PE:EA volume ratio = 10:1) with a yield of 35%.

[0200] The corresponding NMR data of the products are as follows: 1H NMR (600MHz, CDCl3) δ7.68(d,J=8.0Hz,2H),7.32(d,J=8.0Hz,2H),7.06(d,J=5 .1Hz,1H),6.64(d,J=5.1Hz,1H),6.30(s,1H),3.74(t,J=10.4Hz,1H),3.58(d,J =18.7Hz,1H),3.50(d,J=18.8Hz,1H),3.28(dd,J=10.8,5.6Hz,1H),3.00(tt,J= 10.6, 6.1Hz, 1H), 2.86 (dd, J=15.0, 6.4Hz, 1H), 2.42 (s, 3H), 2.12–2.06 (m, 1H). 13 C NMR (151MHz, CDCl3) δ144.0,137.1,134.6,133.0,129.9,129.5,127.9,127.0,122.7,113.2,54.2,50.5,40.0,27.7,21.7.

[0201] Example 25

[0202] Preparation of tetrahydrobenzo[f]isoindole compounds

[0203] Prepared according to the reaction equation shown below:

[0204]

[0205] 1,6-enyne 50 mmol of Cs2CO3 and 50.5 mmol of Cs2CO3 were added to a round-bottom flask, followed by 20 mL of tert-butanol solvent. The mixture was stirred at 80 °C for 6 hours. The target product, tetrahydrobenzo[f]isoindole, was obtained by column chromatography (PE:EA volume ratio = 10:1) with a yield of 41%.

[0206] The corresponding NMR data of the products are as follows: 1 H NMR (600MHz, CDCl3) δ7.67(d,J=8.0Hz,2H),7.30(d,J=8.0Hz,2H),6.24(s,1H),6.21(s,2H),3.78(s,1H),3.76(s,3H),3.74(s,3H),3.5 0(s,2H),3.28(dd,J=10.8,5.9Hz,1H),3.07(dd,J=15.8,6.4Hz,1H),2.85(p,J=4.3Hz,1H),2.40(s,3H),1.81(dd,J=15.8,11.2Hz,1H). 13C NMR (101MHz, CDCl3) δ147.2,143.9,137.2,133.4,130.0,129.7,127.7,12 7.1,124.5,123.1,121.5,119.2,52.9,40.1,37.3,27.6,22.7,21.6,14.1.

[0207] Example 26

[0208] Preparation of tetrahydrobenzo[f]isoindole compounds

[0209] Prepared according to the reaction equation shown below:

[0210]

[0211] 1,6-enyne 50 mmol of Cs2CO3 and 50.5 mmol of Cs2CO3 were added to a round-bottom flask, followed by 20 mL of tert-butanol solvent. The mixture was stirred at 80 °C for 6 hours. The target product, tetrahydrobenzo[f]isoindole, was obtained by column chromatography (PE:EA volume ratio = 10:1) with a yield of 45%.

[0212] The corresponding NMR data of the products are as follows: 1 H NMR (600MHz, CDCl3) δ7.87(d,J=8.5Hz,1H),7.79(d,J=8.0Hz,1H),7.72(d,J=7.9Hz,2H),7.6 1(d,J=8.4Hz,1H),7.54–7.51(m,1H),7.46(t,J=7.4Hz,1H),7.32(d,J=7.9Hz,2H),7.09(d,J= 8.4Hz,1H),6.36(t,J=1.8Hz,1H),3.94(d,J=19.2Hz,1H),3.81(dd,J=21.0,11.3Hz,2H),3.40 (dd,J=10.7,4.8Hz,1H),3.00(ddd,J=20.4,14.0,5.5Hz,2H),2.50–2.45(m,1H),2.41(s,3H). 13 C NMR (101MHz, CDCl3) δ143.8,132.6,132.4,131.9,130.0,129.7,128.5,127.9,127 .8,127.3,126.5,126.4,125.6,125.3,122.8,122.6,53.1,40.3,38.3,25.7,21.6.

[0213] Example 27

[0214] Preparation of tetrahydrobenzo[f]isoindole compounds

[0215] Prepared according to the reaction equation shown below:

[0216]

[0217] 1,6-enyne 50 mmol of Cs2CO3 and 50.5 mmol of Cs2CO3 were added to a round-bottom flask, followed by 20 mL of isopropanol solvent. The mixture was stirred at 80 °C for 3 hours. The target product, tetrahydrobenzo[f]isoindole, was obtained by column chromatography (PE:EA volume ratio = 7:1) with a yield of 70%.

[0218] The corresponding NMR data of the products are as follows: 1 H NMR (600MHz, CDCl3) δ7.75(d,J=7.9Hz,2H),7.34(d,J=7.9Hz,2H),6.99(d,J=5.9Hz,2H),6.92(d,J=4.6Hz,1H),6.48(d,J=2.8Hz,1H),4.26(d,J=15 .1Hz,1H),3.96(t,J=8.6Hz,1H),3.91(d,J=15.1Hz,1H),2.95–2.88(m,1H ),2.81(t,J=9.2Hz,2H),2.47(d,J=15.2Hz,1H),2.43(s,3H),2.27(s,3H). 13 C NMR (151MHz, CDCl3) δ143.9,140.6,133.4,133.3,133.0,132.3,129.9,128.9,127.9,126.8,125.7,116.7,54.7,51.1,38.2,33.0,21.7,19.2.

[0219] Example 28

[0220] Preparation of tetrahydrobenzo[f]isoindole compounds

[0221] Prepared according to the reaction equation shown below:

[0222]

[0223] 1,6-enyne 50 mmol of tBuOK and 50.5 mmol of tBuOK were added to a round-bottom flask, followed by 20 mL of isopropanol solvent. The mixture was stirred at 80 °C for 3 hours. The target product, tetrahydrobenzo[f]isoindole, was obtained by column chromatography (PE:EA volume ratio = 8:1) with a yield of 16%.

[0224] Example 29

[0225] Preparation of tetrahydrobenzo[f]isoindole compounds

[0226] Prepared according to the reaction equation shown below:

[0227]

[0228] 1,6-enyne 50 mmol of KOH and 50.5 mmol of KOH were added to a round-bottom flask, followed by 20 mL of isopropanol solvent. The mixture was stirred at 80 °C for 3 hours. The target product, tetrahydrobenzo[f]isoindole, was obtained by column chromatography (PE:EA volume ratio = 8:1) with a yield of 12%.

[0229] Comparative Example 1

[0230] Preparation of tetrahydrobenzo[f]isoindole compounds

[0231] Prepared according to the reaction equation shown below:

[0232]

[0233] 1,6-enyne 50 mmol of Cs2CO3 and 50.5 mmol of Cs2CO3 were added to a round-bottom flask, followed by 20 mL of isopropanol solvent. The mixture was stirred at 80 °C for 3 hours, but no product was obtained.

[0234] Comparative Example 2

[0235] Preparation of tetrahydrobenzo[f]isoindole compounds

[0236] Prepared according to the reaction equation shown below:

[0237]

[0238] 1,6-enyne 50 mmol of Cs2CO3 and 50.5 mmol of Cs2CO3 were added to a round-bottom flask, followed by 20 mL of isopropanol solvent. The mixture was stirred at 80 °C for 3 hours, but no product was obtained.

[0239] The alkenyne used in Comparative Example 1 is not very stable, and the alkenyne in Comparative Example 2 has great steric hindrance, so neither of them can react.

[0240] The above embodiments are only used to illustrate the technical solutions of the present invention, and are not intended to limit it. Although the present invention has been described in detail with reference to the foregoing embodiments, those skilled in the art should understand that modifications can still be made to the technical solutions described in the foregoing embodiments, or equivalent substitutions can be made to some of the technical features. Such modifications or substitutions do not cause the essence of the corresponding technical solutions to deviate from the spirit and scope of the technical solutions of the embodiments of the present invention.

Claims

1. A tetrahydrobenzo[ f A method for preparing isoindole compounds, characterized in that: It uses 1,6-enyne compounds as raw materials and basic substances as additives, and carries out a cyclization reaction in an organic solvent to obtain the tetrahydrobenzo[ f [Isoindole compound; wherein, the structural formula of the 1,6-enyne compound is] R represents an aryl substituent; the aryl substituent is phenyl, p-fluorophenyl, p-chlorophenyl, p-bromophenyl, p-tert-butylphenyl, p-phenylenephenyl, p-methoxyphenyl, p-trifluoromethylphenyl, m-chlorophenyl, m-methoxyphenyl, m-cyanophenyl, m-formylphenyl, 3,5-dimethoxyphenyl, o-methoxyphenyl, o-methylphenyl, 1-naphthyl, 2-thienyl, 3-thienyl, p-methylphenyl, , One of them, in which Indicates the position where it is attached to the alkynyl group; the alkaline substance is Cs2CO3.

2. The tetrahydrobenzo[] according to claim 1 f A method for preparing isoindole compounds, characterized in that: The structural formula of the 1,6-enyne compound is as follows: , , , , , , , , , , , , , , , , , , One of them.

3. The tetrahydrobenzo[] according to claim 1 f A method for preparing isoindole compounds, characterized in that: The organic solvent is one or a mixture of acetonitrile, isopropanol, and tert-butanol.

4. The tetrahydrobenzo[] according to claim 1 f A method for preparing isoindole compounds, characterized in that: The molar ratio of the alkaline substance to the 1,6-enyne compound is 0.5-2:

1.

5. The tetrahydrobenzo[] according to claim 1 f A method for preparing isoindole compounds, characterized in that: The ratio of the 1,6-enyne compound to the organic solvent is 50 mmol: 20 mL.

6. The tetrahydrobenzo[] according to claim 1 f A method for preparing isoindole compounds, characterized in that: The reaction temperature is 40-100°C. o C, the time is 3-24 hours.

7. The tetrahydrobenzo[] according to claim 1 f A method for preparing isoindole compounds, characterized in that: The organic solvent is isopropanol, and the reaction time is 3 hours.

8. The tetrahydrobenzo[] according to claim 1 f A method for preparing isoindole compounds, characterized in that: The organic solvent is tert-butanol, and the reaction time is 6 hours.

9. The tetrahydrobenzo[] according to any one of claims 1-8 f A method for preparing isoindole compounds, characterized in that: Includes the following steps: A 1,6-enyne compound is mixed with a basic substance, and then an organic solvent is added to react and obtain the tetrahydrobenzo[ f Isoindole compounds.

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