Preparation method of 1-cyano-2-acyl-1,2,3,4-tetrahydroisoquinoline compounds

Abstract

A method for preparing 1-cyano-2-acyl-1,2,3,4-tetrahydroisoquinoline compounds, which are shown by formula III. In the presence of light, a photosensitizer and a desiccant, the compound shown by the general formula of structure I first undergoes a photoredox reaction, and then the compound shown by the general formula of structure II is added in situ, and then a Reissert-type reaction is carried out to obtain the 1-cyano-2-acyl-1,2,3,4-tetrahydroisoquinoline compound shown by the general formula of structure III. The present invention uses simple and readily available 1,2,3,4-tetrahydroisoquinoline compounds and acyl nitriles as raw materials; the acyl nitrile serves as both an acyl source and a cyano source, on the one hand avoiding highly toxic cyano sources, and on the other hand having high atom economy; under blue light irradiation, air can be used as an oxidant, with high environmental friendliness; the 1-cyano-2-acyl-1,2,3,4-tetrahydroisoquinoline compound is constructed through a "one-pot" reaction cascade of photoredox and Reissert-type reactions, with mild reaction conditions, simple operation, high step economy, and good application prospects.

Description

Technical Field

[0001] The present invention relates to the technical field of chemistry and relates to a method for preparing 1-cyano-2-acyl-1,2,3,4-tetrahydroisoquinoline compounds. Background Art

[0002] 1-Substituted 1,2,3,4-tetrahydroisoquinolines are an important class of bioactive alkaloids, and their skeletons are present in many natural products and bioactive compounds, such as the alkaloids (-)-trolline and (R)-coclaurine, and 1CTIQ with monoamine oxidase inhibitory activity (Life Sci. 1997, 60, 1719.), the antiparasitic drug praziquantel, and the urinary system drug solifenacin, etc. Among them, since the α-cyanoamide structure in 1-cyano-2-acyl-1,2,3,4-tetrahydroisoquinoline compounds can be very easily converted into structures such as α-cyanoamine, α-amido carboxylic acid, α-amido aldehyde or ketone, and β-amidoamide, 1-cyano-2-acyl-1,2,3,4-tetrahydroisoquinoline compounds are very important compounds among 1-substituted 1,2,3,4-tetrahydroisoquinoline compounds. Therefore, developing new and efficient synthetic methods to construct structurally novel and diverse 1-cyano-2-acyl-1,2,3,4-tetrahydroisoquinoline compounds is of great significance for enriching organic synthesis methodology and deeply carrying out chemical biology research in this field.

[0003]

[0004] At present, there are very few synthetic methods for 1-cyano-2-acyl-1,2,3,4-tetrahydroisoquinoline compounds. One method is to use 3,4-dihydroisoquinoline compounds as substrates and prepare them through Reissert-type reactions (Synthesis 2020, 52, 3337.). However, on the one hand, this type of method requires the pre-preparation of 3,4-dihydroisoquinoline compounds, and on the other hand, highly toxic cyanide sources such as hydrogen cyanide and sodium cyanide need to be used, and its application scope is limited. Another method is to use 2-acyl-1,2,3,4-tetrahydroisoquinoline compounds as substrates and prepare them through α-cyanation reactions (RSC Adv. 2014, 4, 60075; Molecules 2018, 23, 3223). However, on the one hand, this type of method requires the pre-preparation of 2-acyl-1,2,3,4-tetrahydroisoquinoline compounds, and on the other hand, an excessive amount of oxidant needs to be used, and its step economy and environmental friendliness are poor. Therefore, there is an urgent need to develop efficient and green methods for synthesizing 1-cyano-2-acyl-1,2,3,4-tetrahydroisoquinoline compounds. Summary of the Invention

[0005] In view of the deficiencies of the prior art, the present invention provides a method for preparing 1-cyano-2-acyl-1,2,3,4-tetrahydroisoquinoline compounds. This preparation method involves a "one-pot" reaction cascade of photoredox and Reissert-type reactions. The raw materials are simple and easily available, the operation is convenient, the reaction conditions are mild, and the atomic and step economy is high.

[0006] The technical solution of the present invention:

[0007] A method for preparing 1-cyano-2-acyl-1,2,3,4-tetrahydroisoquinoline compounds. In the presence of light, a photosensitizer, an oxidant, and a desiccant, a compound represented by the general formula of formula I is used as a raw material. First, a photoredox reaction is carried out in a solvent, and then a compound represented by the general formula of formula II is added in situ, and then a Reissert-type reaction is carried out to obtain a 1-cyano-2-acyl-1,2,3,4-tetrahydroisoquinoline compound represented by the general formula of formula III.

[0008]

[0009] In the general formula of formula I or formula III, R 1 , R 2 , R 3 , R 4 each independently selected from any one of the following groups: a hydrogen atom, fluorine, chlorine, bromine, iodine, trifluoromethyl, difluoromethyl, nitro, cyano, ester group, amino group, N-substituted amino group, N,N-disubstituted amino group, C1-C6 straight-chain or branched-chain alkyl or cycloalkyl, C1-C6 alkoxy group, naphthyl group, phenyl group, and naphthalene or phenyl group with substituents; in the general formula of formula II or formula III, R 5 selected from any one of the following groups: C1-C6 straight-chain or branched-chain alkyl or cycloalkyl, naphthyl group, phenyl group, and naphthalene or phenyl group with substituents; in the N-substituted amino group and N,N-disubstituted amino group, the substituent is selected from at least one of C1-C6 straight-chain or branched-chain alkyl or cycloalkyl, naphthyl group, phenyl group, and naphthalene or phenyl group with substituents; in the naphthalene or phenyl group with substituents, the substituent is selected from at least one of fluorine, chlorine, bromine, iodine, trifluoromethyl, difluoromethyl, nitro, cyano, ester group, amino group, N-substituted amino group, N,N-disubstituted amino group, C1-C6 straight-chain or branched-chain alkyl or cycloalkyl, and C1-C6 alkoxy group.

[0010] In the above technical solution, the photosensitizer is a porphyrin-based photosensitizer, Eosin Y photosensitizer, Ir(ppy)3-based photosensitizer, Ru(bpy)3Cl2-based photosensitizer, preferably a porphyrin-based photosensitizer;

[0011] In the above technical solution, the oxidant is hydrogen peroxide, tert-butyl hydroperoxide, iodosylbenzene, m-chloroperoxybenzoic acid, (diacetoxyiodo)benzene, oxygen, air, preferably air and oxygen;

[0012] In the above technical solution, the desiccant is molecular sieve, molecular sieve, molecular sieve, anhydrous sodium sulfate, anhydrous magnesium sulfate, preferably and molecular sieve;

[0013] In the above technical solution, the dosage of the photosensitizer is 0.1%-100% of the molar dosage of the compound represented by the general formula of the formula I structure, preferably 1%-20%;

[0014] In the above technical solution, if the oxidant is air or oxygen, an air or oxygen balloon is used. If it is not a gas, the dosage of the oxidant is 10%-400% of the molar dosage of the compound represented by the general formula of the formula I structure, preferably 50%-200%;

[0015] In the above technical solution, the dosage of the desiccant is 1 mg - 200 mg of desiccant per 0.1 mmol of the compound represented by the general formula of the formula I structure, preferably 10 mg - 100 mg;

[0016] In the above technical solution, the solvent is selected from at least one or a mixture of two or more of dichloromethane, chloroform, carbon tetrachloride, 1,2-dichloroethane, ethyl acetate, benzene, toluene, xylene, mesitylene, ether, tetrahydrofuran, 1,4-dioxane, dimethyl sulfoxide, N,N-dimethylformamide, acetonitrile and water, preferably 1,2-dichloroethane and toluene;

[0017] In the above technical solution, the dosage of the solvent is 0.05 mL - 10.0 mL of solvent per 0.1 mmol of the compound represented by the general formula of the formula I structure, preferably 0.2 mL - 1.0 mL;

[0018] In the above technical solution, the light irradiation is blue light irradiation, purple light irradiation or white light irradiation, with a wattage of 4 watts - 50 watts, preferably blue light irradiation with a wattage of 8 watts - 24 watts;

[0019] In the above technical solution, the temperature is -20°C to 110°C, preferably 0°C to 40°C;

[0020] In the above technical solution, the molar ratio of the compound represented by the general formula of the formula II structure to the compound represented by the general formula of the formula I structure is 1:0.5 - 1:4.0, preferably 1:0.8 - 1:2.0;

[0021] In the above technical solution, the photo-redox reaction time is 1 hour to 120 hours, preferably 4 hours to 48 hours, and the Reissert type reaction time is 0.5 hour to 120 hours, preferably 1 hour to 24 hours.

[0022] Advantages of the present invention: Using easily available 1,2,3,4-tetrahydroisoquinoline compounds and acyl nitriles as raw materials; acyl nitriles serve as both acyl sources and cyano sources, on the one hand avoiding highly toxic cyano sources, and on the other hand having high atom economy; under blue light irradiation, air can be used as an oxidant, showing high environmental friendliness; constructing 1-cyano-2-acyl-1,2,3,4-tetrahydroisoquinoline compounds through a "one-pot" reaction cascade of photo-redox and Reissert type reactions, with mild reaction conditions, simple operation, and high step economy. Description of the Drawings

[0023] Figure 1 Single crystal-X-ray diffraction structure of the compound of formula IIIa prepared in Example 1 of the present invention.

[0024] Figure 2 For the compound of formula IIIa prepared in Example 1 of the present invention 1 1H-NMR spectrum.

[0025] Figure 3 For the compound of formula IIIa prepared in Example 1 of the present invention 13 13C-NMR spectrum. Detailed Embodiments

[0026] The present invention will be further described below in conjunction with specific embodiments, but the present invention is not limited to the following embodiments. The methods are conventional methods unless otherwise specified. The reactants can be obtained from public commercial channels unless otherwise specified.

[0027] Example 1. Preparation of the compound shown in the structure of formula IIIa

[0028] The reaction formula is as follows

[0029]

[0030] Add 1,2,3,4-tetrahydroisoquinoline (0.5 mmol), Meso-tetra(4-chlorophenyl)porphyrin (0.01 mmol), The molecular sieve (0.250 g) and toluene (2.5 mL) were added to a reaction flask, and then an air balloon was connected. The reaction was carried out at room temperature under irradiation with 12 W blue light. After 24 hours, the blue light irradiation was removed, and then benzonitrile (0.55 mmol) was added to the above reaction. After completion of the addition, the reaction was continued at room temperature for 12 hours, and then filtered through diatomaceous earth. After the filtrate was evaporated to dryness, silica gel column chromatography was carried out to obtain 121 mg of the compound shown in the structure of formula IIIa, with a yield of 92%. 1 1H NMR (400 MHz, CDCl3) δ 7.58–7.27 (m, 8H), 7.25–7.19 (m, 1H), 6.50 (brs, 1H), 4.04 (brs, 1H), 3.60 (brs, 1H), 3.14–3.03 (m, 1H), 2.95–2.79 (m, 1H); 13 13C NMR (100 MHz, CDCl3) δ 171.2, 134.0, 133.8, 131.9, 131.1, 129.7, 129.2, 129.0, 128.2, 127.7, 127.3, 117.9, 44.6, 43.4, 28.8; HRMS (ESI): calcd for C17H14N2NaO [M+Na] + : 285.1004, found: 285.1000.

[0031] Example 2. Preparation of the compound shown in the structural formula IIIb

[0032] The reaction formula is as follows:

[0033]

[0034] According to a similar method as described in Example 1, the compound shown in formula IIIb was prepared to obtain 157 mg, with a yield of 92%. 1 1H NMR (400 MHz, CDCl3) δ 7.68–7.37 (m, 6H), 7.31–7.15 (m, 2H), 6.61 (s, 1H), 4.04 (s, 1H), 3.64 (s, 1H), 3.11 (s, 1H), 3.02–2.79 (m, 1H); 13C NMR (100 MHz, CDCl3) δ 171.0, 136.4, 133.7, 131.8, 131.2, 130.4, 129.0, 128.9, 127.9, 127.3, 123.4, 116.5, 45.8, 43.1, 28.8; HRMS (ESI): calcd for C17H14BrN2O [M+H] + : 341.0284, found: 341.0286.

[0035] Example 3. Preparation of the compound represented by the structural formula IIIc

[0036] The reaction formula is as follows:

[0037]

[0038] The compound represented by the formula IIIc was prepared according to a similar method to that described in Example 1, giving 119 mg in a yield of 70%. 1 HNMR(400MHz,CDCl3)δ7.61–7.43(m,7H),7.11(d,J=8.2Hz,1H),6.46(brs,1H),4.04(brs,1H),3.56(brs,1H),3.07–2.94(m,1H),2.88–2.76(m,1H); 13 C NMR(100MHz,CDCl3)δ171.2,133.6,132.7,132.4,131.2,130.4,130.1,129.0,127.3,121.0,117.4,110.1,44.1,43.1,28.3;HRMS(ESI):calcd for C17H13BrN2NaO[M+Na] + :363.0103,found:363.0107。

[0039] Example 4. Preparation of the compound represented by the structural formula IIId

[0040] The reaction formula is as follows:

[0041]

[0042] The compound represented by the formula IIId was prepared according to a similar method to that described in Example 1, giving 81 mg in a yield of 56%. 1 HNMR(400MHz,CDCl3)δ7.71(brs,1H),7.63(d,J=8.0Hz,1H),7.58–7.44(m,5H),7.37(d,J=8.0Hz,1H),6.52(brs,1H),4.11(brs,1H),3.59(brs,1H),3.21–3.03(m,1H),2.95(m,1H); 1313C NMR (101 MHz, CDCl3) δ 171.2, 139.5, 133.4, 132.4, 131.4, 131.3, 130.8, 129.9, 129.1, 127.3, 117.8, 117.0, 111.8, 44.2, 42.7, 28.0; HRMS (ESI): calcd for C 18 H 13 N3NaO [M+Na] + : 310.0951, found: 310.0954。

[0043] Example 5, Preparation of the compound represented by the structural formula IIIe

[0044] The reaction formula is as follows:

[0045]

[0046] According to a similar method as described in Example 1, the compound represented by formula IIIe was prepared to obtain 115 mg with a yield of 68%. 1 1H NMR (400 MHz, CDCl3) δ 7.60–7.42 (m, 6H), 7.40 (s, 1H), 7.28 (s, 1H), 6.44 (brs, 1H), 4.04 (brs, 1H), 3.55 (brs, 1H), 3.05 (brs, 1H), 2.84 (d, J = 16.3 Hz, 1H); 13 13C NMR (100 MHz, CDCl3) δ 171.1, 135.9, 133.7, 132.5, 131.2, 130.82, 129.1, 129.0, 127.3, 127.2, 123.1, 117.4, 44.3, 43.0, 28.5; HRMS (ESI): calcd for C 17 H 13 BrN2NaO [M+Na] + : 363.0103, found: 363.0103。

[0047] Example 6, Preparation of the compound represented by the structural formula IIIf

[0048] The reaction formula is as follows:

[0049]

[0050] According to a similar method as described in Example 1, the compound represented by formula IIIf was prepared to obtain 99 mg with a yield of 66%. 1HNMR(400MHz,CDCl3)δ7.58–7.45(m,2H),7.45–7.38(m,1H),7.38–7.25(m,3H),7.24–7.08(m,2H),6.55and 5.51(2s,1H),4.93–4.83and 3.91–3.77(2m,1H),3.70–3.55and 3.51–3.39(2m,1H),3.21–3.02(m,1H),3.00–2.91and 2.90–2.79(2m,1H); 13 C NMR((100MHz,CDCl3)δ166.4,158.5(d,J=248Hz),133.8,132.5(d,J=8Hz),129.74,129.53,129.12,127.89,127.69,127.58,125.1(d,J=3Hz),122.4(d,J=16Hz),117.70,116.1(d,J=21Hz),44.24,42.82,28.65;HRMS(ESI):calcd for C 17 H 13 FN2NaO[M+Na] + :303.0910,found:303.0905。

[0051] Example 7, preparation of the compound represented by the structural formula IIIg

[0052] The reaction formula is as follows:

[0053]

[0054] According to the similar method described in Example 1, the compound represented by formula IIIg was prepared to obtain 124 mg with a yield of 73%. 1 HNMR(400MHz,CDCl3)δ7.73–7.60(m,2H),7.54–7.29(m,5H),7.26–7.16(m,1H),6.46(s,1H),3.99(s,1H),3.63(s,1H),3.16–2.99(m,1H),2.89(d,J=16.3Hz,1H); 13 C NMR(100MHz,CDCl3)δ169.4 135.8,134.0,133.4,130.4,130.2,129.5,129.1,127.8,127.6,127.5,125.6,122.9,117.5,44.5,43.3,28.5;HRMS(ESI):calcd for C 17 H13 BrN2NaO [M+Na] + : 363.0103, found: 363.0101。

[0055] Example 8. Preparation of the compound represented by the structural formula IIIh

[0056] The reaction formula is as follows:

[0057]

[0058] According to a similar method as described in Example 1, the compound represented by formula IIIh was prepared, obtaining 92 mg with a yield of 50%. 1 HNMR(400 MHz, CDCl3) δ 7.71–7.60 (m, 2H), 7.44 (d, J = 6.9 Hz, 1H), 7.36 (t, J = 8.1 Hz, 1H), 7.31 (s, 1H), 6.88 (s, 1H), 6.73 (s, 1H), 6.40 (s, 1H), 3.93 (s, 1H), 3.82 (s, 3H), 3.61 (s, 1H), 3.03 (s, 1H), 2.85 (d, J = 17.0 Hz, 1H); 13 C NMR(100 MHz, CDCl3) δ 169.3, 159.9, 135.9, 134.8, 133.9, 130.4, 130.2, 128.6, 125.7, 122.9, 119.8, 117.7, 114.1, 113.9, 55.4, 44.2, 43.3, 28.8; HRMS(ESI): calcd for C 18 H 15 BrN2NaO2 [M+Na] + : 393.0209, found: 393.0210。

[0059] Example 9. Preparation of the compound represented by the structural formula IIIi

[0060] The reaction formula is as follows:

[0061]

[0062] According to a similar method as described in Example 1, the compound represented by formula IIIi was prepared, obtaining 69 mg with a yield of 35%. 1HNMR(400MHz,CDCl3)δ8.03–7.85(m,3H),7.80–7.30(m,6H),7.16and 7.08(2d,1H),6.85–6.70and 5.47–5.33(2m,1H),5.10–5.01and 3.72–3.61(2m,1H),3.58–3.44(m,1H),3.21–2.62(m,2H); 13 C NMR(100MHz,CDCl3)δ170.5,133.6,132.7(brs),132.4,131.9(brs),131.5(brs),131.3,130.5(brs),129.7(brs),128.8(brs),128.1(brs),127.1(brs),125.1(brs),124.8(brs),124.4(brs),123.8(brs),121.2,117.4,49.2and 43.4,42.5and 37.9,28.4and 27.5;HRMS(ESI):calcd for C 21 H 16 BrN2O[M+H] + :391.0441,found:391.0443。

[0063] Example 10, preparation of the compound represented by the structural formula IIIj

[0064] The reaction formula is as follows:

[0065]

[0066] According to the similar method described in Example 1, the compound represented by formula IIIj was prepared to obtain 52 mg with a yield of 44%. 1 HNMR(400MHz,CDCl3)δ7.27–7.21(m,1H),6.90–6.81(m,1H),6.73(s,1H),6.42(s,1H),3.91(dt,J = 12.7,4.8Hz,1H),3.81(s,3H),3.77–3.65(m,1H),3.05–2.90(m,2H),2.31and 2.22(2s,3H); 13 C NMR(100MHz,CDCl3)δ169.7,159.9,135.3,128.7,120.7,118.1,114.0,113.7,55.5,43.2,42.2,28.9,21.5;HRMS(ESI):calcd for C 13 H14 N2NaO2[M+Na] + : 253.0947, found: 253.0947。

[0067] Example 11, preparation of the compound represented by the structural formula IIIk

[0068] The reaction formula is as follows:

[0069]

[0070] According to a similar method as described in Example 1, the compound represented by formula IIIk was prepared, obtaining 94 mg with a yield of 94%. 1 HNMR(400 MHz, CDCl3) δ 7.36–7.27 (m, 3H), 7.25–7.17 (m, 1H), 6.47 (s, 1H), 3.94 (dt, J = 13.2, 4.8 Hz, 1H), 3.76–3.65 (m, 1H), 3.06–2.92 (m, 2H), 2.31 and 2.22 (2s, 3H); 13 C NMR(100 MHz, CDCl3) δ 169.7, 133.9, 129.3, 129.1, 128.6, 127.7, 127.5, 117.9, 43.5, 42.3, 28.6, 21.5; HRMS(ESI): calcd for C 12 H 12 N2NaO[M+Na] + : 223.0842, found: 223.0843。

[0071] Example 12, preparation of the compound represented by the structural formula IIIl

[0072] The reaction formula is as follows:

[0073]

[0074] According to a similar method as described in Example 1, the compound represented by formula IIIl was prepared, obtaining 65 mg with a yield of 46%. 1 HNMR(400 MHz, CDCl3) δ 7.58 (d, J = 7.9 Hz, 1H), 7.31 (d, J = 7.7 Hz, 1H), 7.19 (t, J = 7.9 Hz, 1H), 6.51 (s, 1H), 4.05 (m, 1H), 3.74–3.62 (m, 1H), 3.06 (dt, J = 17.2, 3.4 Hz, 1H), 2.90 (ddd, J = 21.4, 10.6, 5.2 Hz, 1H), 2.29 and 2.23 (2s, 3H); 1313C NMR (100 MHz, CDCl3) δ 169.5, 133.7, 133.1, 130.8, 128.8, 126.7, 125.5, 117.5, 43.4, 41.8, 29.4, 21.3; HRMS (ESI): calcd for C 12 H 11 BrN2NaO [M+Na] + : 300.9947, found: 300.9946。

[0075] Example 13. Preparation of the compound represented by the structural formula IIIm

[0076] The reaction formula is as follows:

[0077]

[0078] According to a similar method as described in Example 1, the compound represented by formula IIIm was prepared to obtain 28 mg, with a yield of 25%. 1 1H NMR (400 MHz, CDCl3) δ 7.25–7.15 (m, 3H), 6.48 (s, 1H), 4.03 (dt, J = 13.8, 4.4 Hz, 1H), 3.77–3.66 (m, 1H), 2.91–2.82 and 2.81–2.74 (2m, 2H), 2.29 and 2.23 (2s, 3H), 2.27 (s, 3H); 13 13C NMR (100 MHz, CDCl3) δ 169.5, 137.1, 132.2, 130.4, 128.5, 127.3, 125.3, 118.1, 43.8, 42.0, 26.0, 21.3, 19.3; HRMS (ESI): calcd for C 13 H 14 N2NaO [M+Na] + : 237.0998, found: 237.0998。

[0079] Example 14. Preparation of the compound represented by the structural formula IIIn

[0080] The reaction formula is as follows:

[0081]

[0082] According to a similar method as described in Example 1, the compound represented by formula IIIn was prepared to obtain 85 mg, with a yield of 61%. 1HNMR(400MHz,CDCl3)δ7.49(s,1H),7.44(dd,J=8.2,1.7Hz,1H),7.10(d,J=8.2Hz,1H),6.45(s,1H),3.96(dt,J=13.4,4.5Hz,1H),3.73–3.60(m,1H),2.97–2.90(m,2H),2.29 and2.22(2s,3H); 13 C NMR(100MHz,CDCl3)δ169.7,132.8,132.3,130.9,130.5,130.4,121.1,117.4,43.0,41.9,28.2,21.5;HRMS(ESI):calcd for C 12 H 11 BrN2NaO[M+Na] + :300.9947,found:300.9947。

[0083] Example 15. Preparation of the compound represented by the structural formula IIIo

[0084] The reaction formula is as follows:

[0085]

[0086] According to a similar method as described in Example 1, the compound represented by formula IIIo was prepared to obtain 78 mg with a yield of 64%. 1 HNMR(400MHz,CDCl3)δ8.27(s,1H),8.20(d,J=8.5Hz,1H),7.44(d,J=8.4Hz,1H),6.63(s,1H),4.05(dt,J=9.2,4.4Hz,1H),3.82–3.67(m,1H),3.17–3.07(m,2H),2.34 and 2.26(2s,3H); 13 C NMR(100MHz,CDCl3)δ169.6,141.3,130.7,130.6,130.3,124.0,123.0,116.9,43.3,43.2,41.5,28.9,21.5;HRMS(ESI):calcd for C 12 H 12 N3O3[M+H] + :246.0879,found:246.0873。

[0087] Example 16. Preparation of the compound represented by the structural formula IIIp

[0088] The reaction formula is as follows:

[0089]

[0090] According to a similar method as described in Example 1, the compound shown in Formula IIIp was prepared to obtain 17 mg with a yield of 16%. 1 HNMR(400MHz,CDCl3)δ7.17–7.06(m,3H),6.43(s,1H),3.93(dt,J=13.3,4.6Hz,1H),3.74–3.60(m,1H),3.01–2.89(m,2H),2.36 and 2.35(2s,3H),2.30 and 2.22(2s,3H); 13 C NMR(100MHz,CDCl3)δ169.7,137.6,130.7,129.9,129.1,128.4,127.8,118.1,43.6,42.4,28.2,21.5,21.1; HRMS(ESI):calcd for C 13 H 14 N2NaO[M+Na] + :237.0998,found:237.0999.

Claims

1. A method for preparing 1-cyano-2-acyl-1,2,3,4-tetrahydroisoquinoline compounds, characterized in that, In the presence of Meso-tetra(p-chlorophenyl)porphyrin photosensitizer, air and molecular sieve desiccant under blue light irradiation, the compound represented by the general formula I first undergoes a photoredox reaction in a solvent at room temperature for 24 hours, then the compound represented by the general formula II is added in situ, and then a Reissert-type reaction is carried out at room temperature for 12 hours to obtain a 1-cyano-2-acyl-1,2,3,4-tetrahydroisoquinoline compound represented by the general formula III; In the general formula structure of Formula I or the general formula structure of Formula III, R 1 , R 2 , R 3 , R 4 are each independently selected from any one of the following groups: hydrogen atom, fluorine, chlorine, bromine, iodine, trifluoromethyl, difluoromethyl, nitro, cyano, ester group, amino group, N-substituted amino group, N,N-disubstituted amino group, C1-C6 straight-chain or branched-chain alkyl or cycloalkyl, C1-C6 straight-chain or branched-chain alkoxy group, naphthyl group, phenyl group, and naphthalene or phenyl containing a substituent; in the general formula structure of Formula II or the general formula structure of Formula III, R 5 is selected from any one of the following groups: C1-C6 straight-chain or branched-chain alkyl or cycloalkyl, naphthyl group, phenyl group, and naphthalene or phenyl containing a substituent; in the N-substituted amino group and the N,N-disubstituted amino group, the substituent is selected from at least one of C1-C6 straight-chain or branched-chain alkyl or cycloalkyl, naphthyl group, phenyl group, and naphthalene or phenyl containing a substituent; in the naphthalene or phenyl containing a substituent, the substituent is selected from at least one of fluorine, chlorine, bromine, iodine, trifluoromethyl, difluoromethyl, nitro, cyano, ester group, amino group, N-substituted amino group, N,N-disubstituted amino group, C1-C6 straight-chain or branched-chain alkyl or cycloalkyl, and C1-C6 straight-chain or branched-chain alkoxy group.

2. The method according to claim 1, characterized in that: The molecular sieve desiccant is molecular sieve, molecular sieve or molecular sieve.

3. The method according to claim 1, wherein: The dosage of the Meso-tetra(p-chlorophenyl)porphyrin photosensitizer is 0.1%-100% of the molar dosage of the compound represented by the general formula I.

4. The method according to claim 1, characterized in that: The dosage of the molecular sieve desiccant is 1 mg - 200 mg of desiccant per 0.1 mmol of the compound represented by the general formula I.

5. The method according to claim 1, characterized in that: The solvent is selected from at least one or two or more of dichloromethane, chloroform, carbon tetrachloride, 1,2-dichloroethane, ethyl acetate, benzene, toluene, xylene, mesitylene, diethyl ether, tetrahydrofuran, 1,4-dioxane, dimethyl sulfoxide, N,N-dimethylformamide, acetonitrile and water, or a mixed solvent thereof.

6. The method according to claim 1, wherein: The dosage of the solvent is 0.05 mL - 10.0 mL of solvent per 0.1 mmol of the compound represented by the general formula I.

7. The method according to claim 1, characterized in that: The blue light is blue light of 4 W - 50 W.

8. The method according to claim 1, wherein: The molar ratio of the compound represented by the general formula II to the compound represented by the general formula I is 1:0.5 - 1:4.0.

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