Method for preparing naphthopyran compound without transition metal catalysis

Abstract

The invention develops an efficient strategy for realizing synthesis of a naphthopyran ring skeleton by carrying out enyne double decomposition reaction on a 1-((2-aryl) vinyl) naphthalene-2-phenol compound and alkyne-containing imine by taking binaphthol phosphate as a catalyst. The synthesis of a series of novel product structures which are not reported in literatures is expected to provide important technical support and early theoretical basis for the creation of new drugs of the compounds. The naphthol is simple in structure, easy to prepare, wide in derivation range and low in price, and the structural diversity of naphthopyran compounds can be better enriched. The method disclosed by the invention can be prepared by a one-pot method, is efficient and rapid, simple to operate, short in reaction step, good in substrate tolerance, mild in reaction condition and wide in application range, and overcomes the defects of complex operation, harsh reaction conditions, substrate limitation, intolerant substrate functional groups, tedious steps and the like in the traditional reaction.

Description

Technical Field

[0001] The invention relates to the field of synthetic pharmaceutical chemistry, and in particular to a method for synthesizing naphthopyran compounds without transition metal catalysis. Background Art

[0002] Naphthopyran structures are present in large quantities in natural products, drug molecules or optoelectronic materials. There are currently several main methods for the synthesis of naphthopyran rings. Expensive metal-catalyzed two-component or multi-component reactions, rearrangement reactions and microwave-assisted reactions are used to construct this biologically active skeleton. However, since metals, especially transition metals and noble metals, are toxic, expensive, and rare, and non-commercial ligands are required in pharmaceuticals, metal-free catalytic reactions have attracted attention in recent years due to their selectivity, recyclability, increased yield, simple operation and low sensitivity to air and moisture. Summary of the invention

[0003] The invention provides an ene-yne ​​metathesis reaction using binaphthol phosphate as a catalyst, realizing an efficient strategy for synthesizing naphthopyran ring skeletons, and synthesizing a series of novel product structures that have not been reported in the literature. The method has the advantages of simple operation, wide application range of functional groups, simple and easy-to-obtain raw materials, high yield, etc.

[0004] The present invention is achieved through the following technical solutions:

[0005] The present invention provides a multifunctional naphthopyran derivative 3, characterized in that: under an inert gas and / or nitrogen atmosphere, compound 1, compound 2, a catalyst, an additive, and a solvent are mixed to generate a product having a structure of: Where R 1 represents C1-C12 straight chain alkyl, C1-C12 branched chain alkyl, R 2 , R 3 represents phenyl, naphthyl or monosubstituted phenyl, disubstituted phenyl, the substituents are halogen, alkyl, cyano, trifluoromethyl or alkoxy independently substituted at each position of the ortho, meta or para of the benzene ring, R 4 , R 5 is halogen, alkyl, cyano, trifluoromethyl or alkoxy substituted independently at each position;

[0006] The method for preparing naphthopyran compounds without transition metal catalysis of the present invention is characterized in that the synthesis route is as shown in Formula I: Wherein Pg represents an amino protecting group, such as: -Cbz, -Boc.

[0007] The catalyst is selected from one of (±)-binaphthol phosphate, diphenyl phosphate, xylene phosphate, and (±)-spirocyclic diphenol phosphate, and is preferably (±)-binaphthol phosphate.

[0008] The synthesis reaction time is 1-48h.

[0009] The solvent is one of trifluoroethanol and a mixed solvent of trifluoroethanol and other solvents, preferably trifluoroethanol.

[0010] The additive is one of anhydrous sodium sulfate, anhydrous magnesium sulfate, and no additive, preferably anhydrous sodium sulfate.

[0011] Furthermore, the reaction temperature is 0°C-120°C, preferably 25°C.

[0012] Furthermore, the molar amount of compound 2 is 1-5 times the molar amount of compound 1, preferably 1-3 times, and more preferably 1.2 times.

[0013] The beneficial effects of the present invention are:

[0014] (1) The present invention has developed an ene-yne ​​metathesis reaction of 1-((2-aryl)vinyl)naphthalene-2-phenol compounds and acetylene imines using binaphthol phosphate as a catalyst, realizing an efficient strategy for synthesizing naphthopyran ring skeletons, and synthesizing a series of novel product structures that have not been reported in the literature, in order to provide important technical support and preliminary theoretical basis for the creation of new drugs for this type of compound.

[0015] (2) The naphthol in the present invention has a simple structure, is easy to prepare, has a wide range of derivatization, is cheap, and can better enrich the structural diversity of naphthopyran compounds.

[0016] (3) The method of the present invention can be prepared by a one-pot process, which is efficient and fast, simple to operate, and has a short reaction step. At the same time, the substrate tolerance is good, the reaction conditions are mild, and the application range is wide. It solves the shortcomings of traditional reactions such as complex operation, harsh reaction conditions, substrate limitations, substrate functional group intolerance, and cumbersome steps. DETAILED DESCRIPTION

[0017] The technical solution of the present invention is described clearly and completely below. Obviously, the embodiments described here are only a part of the present invention rather than all the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without creative work belong to the protection scope of the present invention.

[0018] Compound 1 in the present invention can be synthesized by existing technology, reference:

[0019] [1] Zhang, W; Angew Chem, Int Ed, Org Lett, Nat Commun, 2022, 13, 400.

[0020] Compound 2 in the present invention can be synthesized by existing technology, reference:

[0021] [2] Yang, D; Adv Synth Catal, 10.1002 / adsc.201600082, 2016, 358, 1731.

[0022] Example 1

[0023] The synthesis of naphthopyran compounds is as follows

[0024] 0.24mmol of alkynyl imine compound 1, 0.2mmol of naphthol compound 2, 0.02mmol of binaphthol phosphate, 100mg of anhydrous sodium sulfate and a stirring bar were added to a 10ml reaction tube, and vacuum was replaced with nitrogen three times. 2ml of trifluoroethanol was injected into the reaction tube under nitrogen. The reaction tube was placed under 18-W visible light band and stirred on a magnetic stirrer. The reaction progress was detected using a TLC plate, and the reaction was stopped when the raw material 2 was completely consumed. The solvent was removed with a rotary evaporator, and a pale yellow solid product (yield: 62%) was obtained by silica gel (200-300 mesh) column chromatography.

[0025] Product testing data are as follows: 1 H NMR (400MHz, CDCl3) δ7.77 (dd, J=8.5, 3.2Hz, 2H), 7.70 (d, J=8.3Hz, 1H), 7.46-7. 40 (m, 1H), 7.40-7.35 (m, 4H), 7.32 (dt, J = 6.5, 3.3Hz, 2H), 7.23 (d, J = 8.9Hz, 1H), 7.15 (s, 1H), 7.13-7.04 (m, 4H), 6.89 (dd, J=6.6, 2.9Hz, 2H), 4.48 (dq, J=11.8, 8. 6Hz, 1H), 4.38 (dq, J = 10.8, 7.1Hz, 1H), 4.33-4.18 (m, 2H), 1.25 (t, J = 7.1Hz, 3H).

[0026] Embodiment 2:

[0027] The synthesis of naphthopyran compounds is as follows:

[0028] 0.24mmol of alkynyl imine compound 1, 0.2mmol of naphthol compound 2, 0.02mmol of binaphthol phosphate, 100mg of anhydrous sodium sulfate and a stirring bar were added to a 10ml reaction tube, and vacuum was replaced with nitrogen three times. 2ml of trifluoroethanol was injected into the reaction tube under nitrogen. The reaction tube was placed under 18-W visible light band and stirred on a magnetic stirrer. The reaction progress was detected using a TLC plate, and the reaction was stopped when the raw material 2 was completely consumed. The solvent was removed with a rotary evaporator, and a pale yellow solid product (yield: 63%) was obtained by silica gel (200-300 mesh) column chromatography.

[0029] Product testing data are as follows: 1 H NMR (400MHz, CDCl3) δ7.75-7.67 (m, 2H), 7.65 (d, J = 8.4Hz, 1H), 7.38 (t, J = 7.1Hz, 1H), 7.32 (t, J = 7.4Hz, 1H), 7.24-7.19 (m, 2H), 7.16 (d, J = 8.9Hz, 1H ), 7.03 (ddd, J=20.7, 14.1, 7.5Hz, 7H), 6.87-6.78 (m, 2H), 4.42 (dq, J=11. 8, 8.6Hz, 1H), 4.34-4.23 (m, 1H), 4.23-4.08 (m, 2H), 1.16 (d, J = 7.1Hz, 3H).

[0030] Embodiment 3:

[0031] The synthesis of naphthopyran compounds is as follows

[0032] 0.24mmol of alkynyl imine compound 1, 0.2mmol of naphthol compound 2, 0.02mmol of binaphthol phosphate, 100mg of anhydrous sodium sulfate and a stirring bar were added to a 10ml reaction tube, and vacuum was replaced with nitrogen three times. 2ml of trifluoroethanol was injected into the reaction tube under nitrogen. The reaction tube was placed under 18-W visible light band and stirred on a magnetic stirrer. The reaction progress was detected using a TLC plate, and the reaction was stopped when the raw material 2 was completely consumed. The solvent was removed with a rotary evaporator, and a pale yellow solid product (yield: 60%) was obtained by silica gel (200-300 mesh) column chromatography.

[0033] Product testing data are as follows: 1H NMR (400MHz, CDCl3) δ7.79 (d, J=8.9Hz, 2H), 7.74 (t, J=7.1Hz, 1H), 7.49-7.43 ( m, 1H), 7.40 (dd, J=9.0, 2.0Hz, 1H), 7.38-7.34 (m, 1H), 7.24 (d, J=8.9Hz, 1H), 7 .15-7.06 (m, 7H), 7.06-7.02 (m, 1H), 6.95-6.87 (m, 2H), 4.50 (dq, J=11.8, 8.6H z, 1H), 4.38 (dq, J = 10.8, 7.1Hz, 1H), 4.32-4.19 (m, 2H), 1.29 (t, J = 3.6Hz, 3H).

[0034] Embodiment 4:

[0035] The synthesis of naphthopyran compounds is as follows

[0036] 0.24mmol of alkynyl imine compound 1, 0.2mmol of naphthol compound 2, 0.02mmol of binaphthol phosphate, 100mg of anhydrous sodium sulfate and a stirring bar were added to a 10ml reaction tube, and vacuum was replaced with nitrogen three times. 2ml of trifluoroethanol was injected into the reaction tube under nitrogen. The reaction tube was placed under 18-W visible light band and stirred on a magnetic stirrer. The reaction progress was detected using a TLC plate, and the reaction was stopped when the raw material 2 was completely consumed. The solvent was removed with a rotary evaporator, and a pale yellow solid product (yield: 62%) was obtained by silica gel (200-300 mesh) column chromatography.

[0037] Product testing data are as follows: 1 H NMR (400MHz, CDCl3) δ7.76 (dd, J=8.2, 4.0Hz, 2H), 7.68 (d, J=8.4Hz, 1H), 7.42 (qd, J= 3.9, 2.1Hz, 2H), 7.37 (dt, J=7.9, 2.0Hz, 1H), 7.28 (dd, J=8.6, 4.4Hz, 1H), 7.26 (s, 1H) ,7.24-7.19(m,2H),7.18-7.09(m,5H),6.98-6.89(m,2H),4.44(dt,J=15.0,6.0Hz,1 H), 4.36 (ddd, J=14.2, 8.9, 5.4Hz, 1H), 4.32-4.20 (m, 2H), 1.28 (t, J=9.7, 4.2Hz, 3H).

[0038] Embodiment 5:

[0039] The synthesis of naphthopyran compounds is as follows

[0040] 0.24mmol of alkynyl imine compound 1, 0.2mmol of naphthol compound 2, 0.02mmol of binaphthol phosphate, 100mg of anhydrous sodium sulfate and a stirring bar were added to a 10ml reaction tube, and vacuum was replaced with nitrogen three times. 2ml of trifluoroethanol was injected into the reaction tube under nitrogen. The reaction tube was placed under 18-W visible light band and stirred on a magnetic stirrer. The reaction progress was detected using a TLC plate, and the reaction was stopped when the raw material 2 was completely consumed. The solvent was removed with a rotary evaporator, and a pale yellow solid product (yield: 94%) was obtained by silica gel (200-300 mesh) column chromatography.

[0041] Product testing data are as follows: 1 H NMR (400MHz, CDCl3) δ7.73-7.62 (m, 3H), 7.35 (t, J = 7.3Hz, 1H), 7.28 (dd, J = 14.1, 7.0Hz, 1H), 7.18-7.12 (m, 2H), 7.09 (d, J = 8.4Hz, 4H), 7.0 6-6.96 (m, 4H), 6.91-6.75 (m, 2H), 4.47-4.35 (m, 1H), 4.29 (dq, J=10.8, 7.2Hz, 1H), 4.24-4.08 (m, 2H), 2.34 (s, 3H), 1.15 (t, J=7.1Hz, 3H).

[0042] Embodiment 6:

[0043] The synthesis of naphthopyran compounds is as follows

[0044] 0.24mmol of alkynyl imine compound 1, 0.2mmol of naphthol compound 2, 0.02mmol of binaphthol phosphate, 100mg of anhydrous sodium sulfate and a stirring bar were added to a 10ml reaction tube, and vacuum was replaced with nitrogen three times. 2ml of trifluoroethanol was injected into the reaction tube under nitrogen. The reaction tube was placed under 18-W visible light band and stirred on a magnetic stirrer. The reaction progress was detected using a TLC plate, and the reaction was stopped when the raw material 2 was completely consumed. The solvent was removed with a rotary evaporator, and a pale yellow solid product (yield: 61%) was obtained by silica gel (200-300 mesh) column chromatography.

[0045] Product testing data are as follows: 1H NMR (400MHz, CDCl3) δ7.80-7.69 (m, 3H), 7.42 (t, J = 7.5Hz, 1H), 7.36 (t, J = 7.4Hz, 1H), 7.22 (dt, J = 13.7, 5.9Hz, 6H), 7.13-7.04 (m, 4H), 6.95-6.8 7(m, 2H), 4.49(tt, J=17.3, 8.6Hz, 1H), 4.42-4.31(m, 1H), 4.31-4.16(m, 2H), 2.71(q, J=7.6Hz, 2H), 1.29(t,J=7.2Hz, 3H), 1.23(t,J=7.1Hz, 3H).

[0046] Embodiment 7:

[0047] The synthesis of naphthopyran compounds is as follows

[0048] 0.24mmol of alkynyl imine compound 1, 0.2mmol of naphthol compound 2, 0.02mmol of binaphthol phosphate, 100mg of anhydrous sodium sulfate and a stirring bar were added to a 10ml reaction tube, and vacuum was replaced with nitrogen three times. 2ml of trifluoroethanol was injected into the reaction tube under nitrogen. The reaction tube was placed under 18-W visible light band and stirred on a magnetic stirrer. The reaction progress was detected using a TLC plate, and the reaction was stopped when the raw material 2 was completely consumed. The solvent was removed with a rotary evaporator, and a pale yellow solid product (yield: 40%) was obtained by silica gel (200-300 mesh) column chromatography.

[0049] Product testing data are as follows: 1 H NMR (400MHz, CDCl3) δ7.73-7.62 (m, 3H), 7.36 (dd, J = 11.2, 4.1Hz, 1H), 7.29 (dd, J=10.9, 4.6Hz, 3H), 7.18-7.14 (m, 2H), 7.12 (d, J=9.8Hz, 2H), 7.03-6.96 (m, 4H) , 6.81 (dd, J=6.4, 2.9Hz, 2H), 4.41 (dq, J=11.8, 8.6Hz, 1H), 4.28 (ddd, J=14.3, 1 0.8, 7.2Hz, 1H), 4.23-4.08 (m, 2H), 1.30 (d, J=2.9Hz, 9H), 1.16 (t, J=7.1Hz, 3H).

[0050] Embodiment 8:

[0051] The synthesis of naphthopyran compounds is as follows

[0052] 0.24mmol of alkynyl imine compound 1, 0.2mmol of naphthol compound 2, 0.02mmol of binaphthol phosphate, 100mg of anhydrous sodium sulfate and a stirring bar were added to a 10ml reaction tube, and vacuum was replaced with nitrogen three times. 2ml of trifluoroethanol was injected into the reaction tube under nitrogen. The reaction tube was placed under 18-W visible light band and stirred on a magnetic stirrer. The reaction progress was detected using a TLC plate, and the reaction was stopped when the raw material 2 was completely consumed. The solvent was removed with a rotary evaporator, and a pale yellow solid product (yield: 28%) was obtained by silica gel (200-300 mesh) column chromatography.

[0053] Product testing data are as follows: 1 H NMR (400MHz, CDCl3) δ7.82-7.68 (m, 3H), 7.44 (t, J=7.2Hz, 1H), 7.37 (dd, J=13.2, 5.8Hz, 1H), 7.27-7.19 (m, 4H), 7.14-7.03 (m, 4H), 6.92 ( dd, J=11.9, 5.2Hz, 4H), 4.48 (dq, J=11.8, 8.6Hz, 1H), 4.36 (tt, J=13.5, 4.9Hz, 1H), 4.31-4.16 (m, 2H), 3.86 (s, 3H), 1.22 (t, J=7.1Hz, 3H).

[0054] Embodiment 9:

[0055] The synthesis of naphthopyran compounds is as follows

[0056] 0.24mmol of alkynyl imine compound 1, 0.2mmol of naphthol compound 2, 0.02mmol of binaphthol phosphate, 100mg of anhydrous sodium sulfate and a stirring bar were added to a 10ml reaction tube, and vacuum was replaced with nitrogen three times. 2ml of trifluoroethanol was injected into the reaction tube under nitrogen. The reaction tube was placed under 18-W visible light band and stirred on a magnetic stirrer. The reaction progress was detected using a TLC plate, and the reaction was stopped when the raw material 2 was completely consumed. The solvent was removed with a rotary evaporator, and a pale yellow solid product (yield: 79%) was obtained by silica gel (200-300 mesh) column chromatography.

[0057] Product testing data are as follows: 1H NMR (400MHz, CDCl3) δ7.92-7.81 (m, 3H), 7.79-7.73 (m, 3H), 7.66-7.59 (m, 1H), 7.5 6-7.45 (m, 2H), 7.43 (dd, J=8.4, 1.5Hz, 1H), 7.36-7.30 (m, 2H), 7.23 (d, J=5.1Hz, 1H ), 7.20 (d, J = 5.4Hz, 1H), 7.19 (s, 1H), 7.07-7.00 (m, 3H), 6.92 (dd, J = 6.5, 2.8Hz, 2 H), 4.59-4.45 (m, 1H), 4.45-4.35 (m, 1H), 4.34-4.19 (m, 2H), 1.27 (t, J = 4.3Hz, 3H).

[0058] Embodiment 10:

[0059] The synthesis of naphthopyran compounds is as follows

[0060] 0.24mmol of alkynyl imine compound 1, 0.2mmol of naphthol compound 2, 0.02mmol of binaphthol phosphate, 100mg of anhydrous sodium sulfate and a stirring bar were added to a 10ml reaction tube, and vacuum was replaced with nitrogen three times. 2ml of trifluoroethanol was injected into the reaction tube under nitrogen. The reaction tube was placed under 18-W visible light band and stirred on a magnetic stirrer. The reaction progress was detected using a TLC plate, and the reaction was stopped when the raw material 2 was completely consumed. The solvent was removed with a rotary evaporator, and a pale yellow solid product (yield: 43%) was obtained by silica gel (200-300 mesh) column chromatography.

[0061] Product testing data are as follows: 1 H NMR (400MHz, CDCl3) δ7.67 (dd, J=8.1, 5.1Hz, 2H), 7.61 (d, J=8.3Hz, 1H), 7. 36-7.26 (m, 5H), 7.27-7.22 (m, 2H), 7.14 (d, J=8.7Hz, 1H), 7.07-6.95 (m, 2H ), 6.82 (d, J = 8.0Hz, 2H), 6.70 (d, J = 8.1Hz, 2H), 4.40 (dq, J = 11.8, 8.6Hz, 1H ), 4.34-4.25(m, 1H), 4.25-4.07(m, 2H), 2.16(s, 3H), 1.15t, J=7.1Hz, 3H).

[0062] Embodiment 11:

[0063] The synthesis of naphthopyran compounds is as follows

[0064] 0.24mmol of alkynyl imine compound 1, 0.2mmol of naphthol compound 2, 0.02mmol of binaphthol phosphate, 100mg of anhydrous sodium sulfate and a stirring bar were added to a 10ml reaction tube, and vacuum was replaced with nitrogen three times. 2ml of trifluoroethanol was injected into the reaction tube under nitrogen. The reaction tube was placed under 18-W visible light band and stirred on a magnetic stirrer. The reaction progress was detected using a TLC plate, and the reaction was stopped when the raw material 2 was completely consumed. The solvent was removed with a rotary evaporator, and a pale yellow solid product (yield: 58%) was obtained by silica gel (200-300 mesh) column chromatography.

[0065] Product testing data are as follows: 1 H NMR (400MHz, CDCl3) δ7.69 (d, J=8.7Hz, 2H), 7.60 (d, J=8.3Hz, 1H), 7.36-7.26 (m, 5H), 7.21 (dd, J=6.4, 2.9Hz, 2H), 7.15 (d, J=8.7Hz, 1H), 7.08 (s, 1 H), 7.01-6.95 (m, 3H), 6.72 (d, J=8.5Hz, 2H), 4.41 (dq, J=11.8, 8.6Hz, 1H ), 4.30 (dq, J=10.8, 7.1Hz, 1H), 4.24-4.09 (m, 2H), 1.15 (t, J=7.1Hz, 3H).

[0066] Embodiment 12:

[0067] The synthesis of naphthopyran compounds is as follows

[0068] 0.24mmol of alkynyl imine compound 1, 0.2mmol of naphthol compound 2, 0.02mmol of binaphthol phosphate, 100mg of anhydrous sodium sulfate and a stirring bar were added to a 10ml reaction tube, and vacuum was replaced with nitrogen three times. 2ml of trifluoroethanol was injected into the reaction tube under nitrogen. The reaction tube was placed under 18-W visible light band and stirred on a magnetic stirrer. The reaction progress was detected using a TLC plate, and the reaction was stopped when the raw material 2 was completely consumed. The solvent was removed with a rotary evaporator, and a pale yellow solid product (yield: 56%) was obtained by silica gel (200-300 mesh) column chromatography.

[0069] Product testing data are as follows: 1H NMR (400MHz, CDCl3) δ7.69 (d, J=8.7Hz, 2H), 7.60 (d, J=8.4Hz, 1H), 7.37-7 .26 (m, 5H), 7.25-7.19 (m, 2H), 7.17-7.13 (m, 1H), 7.09 (d, JJ=5.2Hz, 1H), 6 .99-6.95 (m, 2H), 6.94-6.88 (m, 1H), 6.76 (s, 1H), 6.67 (d, J=7.6Hz, 1H), 4 .46-4.35(m,1H), 4.34-4.25(m,1H), 4.25-4.10(m,2H), 1.22-1.17(t,3H).

[0070] Embodiment 13:

[0071] The synthesis of naphthopyran compounds is as follows

[0072] 0.24mmol of alkynyl imine compound 1, 0.2mmol of naphthol compound 2, 0.02mmol of binaphthol phosphate, 100mg of anhydrous sodium sulfate and a stirring bar were added to a 10ml reaction tube, and vacuum was replaced with nitrogen three times. 2ml of trifluoroethanol was injected into the reaction tube under nitrogen. The reaction tube was placed under 18-W visible light band and stirred on a magnetic stirrer. The reaction progress was detected using a TLC plate, and the reaction was stopped when the raw material 2 was completely consumed. The solvent was removed with a rotary evaporator, and a pale yellow solid product (yield: 72%) was obtained by silica gel (200-300 mesh) column chromatography.

[0073] Product testing data are as follows: 1 H NMR (400MHz, CDCl3) δ7.70 (d, J=9.2Hz, 2H), 7.64 (d, J=8.4Hz, 1H), 7.34 (dd, J=12.6, 5.3Hz, 1H), 7.32-7.26 (m, 1H), 7.26-7.13 (m, 9H), 6. 94(t,J=7.6Hz,1H), 6.74(t,J=7.5Hz,1H), 6.54(d,J=7.7Hz,1H), 4.41(dq,J=11.7,8.6Hz,1H), 4.33-4.12(m,3H), 1.21(t,J=4.5Hz,3H).

[0074] Embodiment 14:

[0075] The synthesis of naphthopyran compounds is as follows

[0076] 0.24mmol of alkynyl imine compound 1, 0.2mmol of naphthol compound 2, 0.02mmol of binaphthol phosphate, 100mg of anhydrous sodium sulfate and a stirring bar were added to a 10ml reaction tube, and vacuum was replaced with nitrogen three times. 2ml of trifluoroethanol was injected into the reaction tube under nitrogen. The reaction tube was placed under 18-W visible light band and stirred on a magnetic stirrer. The reaction progress was detected using a TLC plate, and the reaction was stopped when the raw material 2 was completely consumed. The solvent was removed with a rotary evaporator, and a pale yellow solid product (yield: 49%) was obtained by silica gel (200-300 mesh) column chromatography.

[0077] Product testing data are as follows: 1 H NMR (400MHz, CDCl3) δ7.79-7.72(m, 2H), 7.68(d, J=8.3Hz, 1H), 7.44-7.39(m , 4H), 7.37-7.31 (m, 3H), 7.25-7.20 (m, 1H), 7.11 (d, J=4.5Hz, 2H), 7.09 (d, J =5.1Hz, 2H), 6.82 (d, J = 8.4Hz, 2H), 4.48 (dq, J = 11.8, 8.6Hz, 1H), 4.41-4.31 (m, 1H), 4.32-4.16 (m, 2H), 1.28 (t, J = 8.7, 2.0Hz, 3H), 1.24 (s, J = 2.3Hz, 9H).

[0078] Embodiment 15:

[0079] The synthesis of naphthopyran compounds is as follows

[0080] 0.24mmol of acetylene imine compound 1, 0.2mmol of naphthol compound 2, 0.02mmol of binaphthol phosphate, 100mg of anhydrous sodium sulfate and a stirrer were added to a 10ml reaction tube, and the mixture was evacuated and replaced with nitrogen three times. 2ml of trifluoroethanol was injected into the reaction tube under nitrogen. The reaction tube was placed under 18-W visible light band and stirred on a magnetic stirrer. The reaction progress was monitored using a TLC plate, and the reaction was stopped when the raw material 2 was completely consumed. The solvent was removed using a rotary evaporator, and a pale yellow solid product was obtained by silica gel (200-300 mesh) column chromatography (yield: 49%).

[0081] Product testing data are as follows: 1H NMR (400MHz, CDCl3) δ7.70 (dd, J=8.4, 3.2Hz, 2H), 7.61 (d, J=8.3Hz, 1H), 7.38-7.29 (m, 5H), 7.23 (ddd, J=7.9, 7.2, 2.6Hz, 4H), 7.18-7.14 (m, 1 H), 7.11 (s, 1H), 7.04 (s, 1H), 6.90 (t, J = 6.2Hz, 2H), 4.43 (dq, J = 11.7, 8.6Hz, 1H), 4.29 (tt, J = 13.6, 4.9Hz, 1H), 4.25-4.10 (m, 2H), 1.16 (t, J = 7.1Hz,3H).

[0082] Embodiment 16:

[0083] The synthesis of naphthopyran compounds is as follows

[0084] 0.24mmol of acetylene imine compound 1, 0.2mmol of naphthol compound 2, 0.02mmol of binaphthol phosphate, 100mg of anhydrous sodium sulfate and a stirrer were added to a 10ml reaction tube, and the mixture was evacuated and replaced with nitrogen three times. 2ml of trifluoroethanol was injected into the reaction tube under nitrogen. The reaction tube was placed under 18-W visible light band and stirred on a magnetic stirrer. The reaction progress was monitored using a TLC plate, and the reaction was stopped when the raw material 2 was completely consumed. The solvent was removed using a rotary evaporator, and a pale yellow solid product was obtained by silica gel (200-300 mesh) column chromatography (yield: 71%).

[0085] Product testing data are as follows: 1 H NMR (400MHz, CDCl3) δ8.19 (dd, J = 5.5, 4.1Hz, 1H), 7.73-7.66 (m, 1H), 7.60 (s, 1H), 7.52-7.43 (m, 2H), 7.42-7.34 (m, 3H), 7.32-7.27 (m, 2H) ), 7.14-7.05 (m, 5H), 6.93-6.84 (m, 2H), 4.53 (dq, J=11.7, 8.6Hz, 1H), 4.37 (tt, J=13.2, 4.8Hz, 1H), 4.31-4.17 (m, 2H), 1.26-1.22 (t, 3H).

[0086] Embodiment 17:

[0087] The synthesis of naphthopyran compounds is as follows

[0088] 0.24mmol of acetylene imine compound 1, 0.2mmol of naphthol compound 2, 0.02mmol of binaphthol phosphate, 100mg of anhydrous sodium sulfate and a stirrer were added to a 10ml reaction tube, and the mixture was evacuated and replaced with nitrogen three times. 2ml of trifluoroethanol was injected into the reaction tube under nitrogen. The reaction tube was placed under 18-W visible light band and stirred on a magnetic stirrer. The reaction progress was monitored using a TLC plate, and the reaction was stopped when the raw material 2 was completely consumed. The solvent was removed using a rotary evaporator, and a pale yellow solid product was obtained by silica gel (200-300 mesh) column chromatography (yield: 47%).

[0089] Product testing data are as follows: 1 H NMR (400MHz, CDCl3) δ7.84 (d, J=1.9Hz, 1H), 7.59 (t, J=7.4Hz, 1H), 7.47 (dd, J=8.3, 4.3Hz, 1H), 7 .39 (dd, J=9.0, 2.0Hz, 1H), 7.34-7.28 (m, 3H), 7.25-7.20 (m, 2H), 7.18-7.15 (m, 1H), 7.01 (dddd, J=17.1, 8.5, 6.0Hz, 5H), 6.85-6.79 (m, 2H), 4.44 (dq, J=11.9, 8.6Hz, 1H), 4.36-4.26 (m, 1H), 4.26-4.09 (m, 2H), 1.17 (t, J=4.6Hz, 3H).

[0090] Embodiment 18:

[0091] The synthesis of naphthopyran compounds is as follows

[0092] 0.24mmol of acetylene imine compound 1, 0.2mmol of naphthol compound 2, 0.02mmol of binaphthol phosphate, 100mg of anhydrous sodium sulfate and a stirrer were added to a 10ml reaction tube, and the mixture was evacuated and replaced with nitrogen three times. 2ml of trifluoroethanol was injected into the reaction tube under nitrogen. The reaction tube was placed under 18-W visible light band and stirred on a magnetic stirrer. The reaction progress was monitored using a TLC plate, and the reaction was stopped when the raw material 2 was completely consumed. The solvent was removed using a rotary evaporator, and a pale yellow solid product was obtained by silica gel (200-300 mesh) column chromatography (yield: 69%).

[0093] Product testing data are as follows: 1H NMR (400MHz, CDCl3) δ7.75 (d, J=1.3Hz, 1H), 7.62 (d, J=8.9Hz, 1H), 7.53 (d, J=8. 7Hz, 1H), 7.40-7.33 (m, 1H), 7.33-7.27 (m, 3H), 7.23 (ddd, J=5.6, 4.8, 3.4Hz, 2H) ,7.18-7.12(m,1H),7.05-6.98(m,4H),6.96(s,1H),6.86-6.77(m,2H),4.42(dq, J=11.9, 8.6Hz, 1H), 4.33-4.23 (m, 1H), 4.22-4.06 (m, 2H), 1.16 (t, J=5.3Hz, 3H).

[0094] Embodiment 19:

[0095] The synthesis of naphthopyran compounds is as follows

[0096] 0.24mmol of acetylene imine compound 1, 0.2mmol of naphthol compound 2, 0.02mmol of binaphthol phosphate, 100mg of anhydrous sodium sulfate and a stirrer were added to a 10ml reaction tube, and the mixture was evacuated and replaced with nitrogen three times. 2ml of trifluoroethanol was injected into the reaction tube under nitrogen. The reaction tube was placed under 18-W visible light band and stirred on a magnetic stirrer. The reaction progress was monitored using a TLC plate, and the reaction was stopped when the raw material 2 was completely consumed. The solvent was removed using a rotary evaporator, and a pale yellow solid product was obtained by silica gel (200-300 mesh) column chromatography (yield: 51%).

[0097] Product testing data are as follows: 1 H NMR (400MHz, CDCl3) δ7.78 (d, J=9.2Hz, 2H), 7.68 (d, J=8.3Hz, 1H), 7.47-7.35 (m, 5 H), 7.29 (dt, J=7.4, 3.6Hz, 2H), 7.23 (d, J=8.9Hz, 1H), 7.18 (s, 1H), 7.12 (t, J=8.0 Hz, 1H), 6.96 (dd, J=18.4, 3.6Hz, 2H), 6.66 (dd, J=8.4, 1.9Hz, 1H), 4.49 (dq, J=11. 9, 8.6Hz, 1H), 4.38 (dq, J=10.8, 7.1Hz, 1H), 4.33-4.17 (m, 2H), 1.29-1.26 (t, 3H).

[0098] Embodiment 20:

[0099] The synthesis of naphthopyran compounds is as follows

[0100] 0.24mmol of acetylene imine compound 1, 0.2mmol of naphthol compound 2, 0.02mmol of binaphthol phosphate, 100mg of anhydrous sodium sulfate and a stirrer were added to a 10ml reaction tube, and the mixture was evacuated and replaced with nitrogen three times. 2ml of trifluoroethanol was injected into the reaction tube under nitrogen. The reaction tube was placed under 18-W visible light band and stirred on a magnetic stirrer. The reaction progress was monitored using a TLC plate, and the reaction was stopped when the raw material 2 was completely consumed. The solvent was removed using a rotary evaporator, and a pale yellow solid product was obtained by silica gel (200-300 mesh) column chromatography (yield: 46%).

[0101] Product testing data are as follows: 1 H NMR (400MHz, CDCl3) δ7.75 (dt, J=13.5, 6.3Hz, 2H), 7.68 (t, J=7.9Hz, 1H), 7.47-7 .34 (m, 5H), 7.31 (ddd, J=5.6, 4.8, 3.4Hz, 2H), 7.25-7.18 (m, 1H), 7.13 (dd, J=16. 3, 7.4Hz, 2H), 7.11-7.05 (m, 3H), 6.94-6.85 (m, 2H), 4.47 (dq, J=11.8, 8.6Hz, 1H) , 4.33-4.19 (m, 2H), 4.18-4.09 (m, 1H), 1.71-1.60 (m, 2H), 0.88 (t, J = 7.4Hz, 3H).

[0102] Embodiment 21

[0103] The synthesis of naphthopyran compounds is as follows

[0104] 0.24mmol of acetylene imine compound 1, 0.2mmol of naphthol compound 2, 0.02mmol of binaphthol phosphate, 100mg of anhydrous sodium sulfate and a stirrer were added to a 10ml reaction tube, and the mixture was evacuated and replaced with nitrogen three times. 2ml of trifluoroethanol was injected into the reaction tube under nitrogen. The reaction tube was placed under 18-W visible light band and stirred on a magnetic stirrer. The reaction progress was monitored using a TLC plate, and the reaction was stopped when the raw material 2 was completely consumed. The solvent was removed using a rotary evaporator, and a pale yellow solid product was obtained by separation using a silica gel (200-300 mesh) column chromatography (yield: 62%).

[0105] Product testing data are as follows: 1H NMR (400MHz, CDCl3) δ7.39-7.32(m, 3H), 7.28-7.22(m, 3H), 7.10-7.05(m, 4H), 7.04-6.95(m, 3H), 6.88-6.81(m, 2H) , 6.40 (s, 1H), 4.52 (dq, J=11.8, 8.6Hz, 1H), 4.36 (dq, J=10.8, 7.1Hz, 1H), 4.30-4.15 (m, 2H), 1.23 (t, J=7.1Hz, 3H).

[0106] Although embodiments of the present invention have been shown and described, it will be appreciated by those skilled in the art that various changes, modifications, substitutions and variations may be made to the embodiments without departing from the principles and spirit of the present invention, and that the scope of the present invention is defined by the appended claims and their equivalents.

Claims

1. A method for preparing a naphthopyran derivative 3, characterized in that In an inert gas and / or nitrogen atmosphere, compound 1, compound 2, a catalyst, an additive, and a solvent are mixed to generate a product having a structure of: R 1 represents C1-C12 straight chain alkyl, C1-C12 branched chain alkyl, R 2 , R 3 represents phenyl, naphthyl or monosubstituted phenyl, disubstituted phenyl, the substituents are halogen, alkyl, cyano, trifluoromethyl or alkoxy independently substituted at each position of the ortho, meta or para of the benzene ring, R 4 , R 5 is a halogen, alkyl, cyano, trifluoromethyl or alkoxy group independently substituted at each position; its synthetic route is as shown in Formula I Wherein Pg represents an amino protecting group, such as: -Cbz, -Boc.

2. The preparation method according to claim 1, characterized in that: The catalyst is selected from one of (±)-binaphthol phosphate, diphenyl phosphate, xylene phosphate, and (±)-spirocyclic diphenol phosphate, and is preferably (±)-binaphthol phosphate.

3. The preparation method according to claim 1, characterized in that: The synthesis reaction time is 1-48h.

4. The preparation method according to claim 1, characterized in that: The solvent is trifluoroethanol or a mixed solvent of trifluoroethanol and other solvents, preferably trifluoroethanol.

5. The preparation method according to claim 1, characterized in that: The additive is one of anhydrous sodium sulfate, anhydrous magnesium sulfate, and no additive, preferably anhydrous sodium sulfate.

6. The preparation method according to claim 1, characterized in that: The temperature is 0°C-120°C, preferably 25°C.

7. The preparation method according to claim 1, characterized in that: The molar amount of the compound 2 is 1-5 times the molar amount of the compound 1, preferably 1-3 times, more preferably 1.2 times.

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