CN111138359A - Method for preparing 3-carbonyl-4-azido-N-benzenesulfonyl-1, 2,3, 4-tetrahydroisoquinoline compounds - Google Patents

Method for preparing 3-carbonyl-4-azido-N-benzenesulfonyl-1, 2,3, 4-tetrahydroisoquinoline compounds Download PDF

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CN111138359A
CN111138359A CN202010059470.0A CN202010059470A CN111138359A CN 111138359 A CN111138359 A CN 111138359A CN 202010059470 A CN202010059470 A CN 202010059470A CN 111138359 A CN111138359 A CN 111138359A
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benzenesulfonyl
azido
carbonyl
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tetrahydroisoquinoline
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徐润生
韩鸿宽
熊飞翔
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Jiyang College of Zhejiang A&F University
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D217/00—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems
    • C07D217/22—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to carbon atoms of the nitrogen-containing ring
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Abstract

The invention discloses a method for preparing 3-carbonyl-4-azido-N-benzenesulfonyl-1, 2,3, 4-tetrahydroisoquinoline compounds by iron catalysis, which comprises the following steps: the 2-methylamino benzoyl formic acid compound, sodium azide and benzene sulfonyl chloride compound take an organic solvent as a medium, and fully react under the promotion of a catalyst and cesium carbonate as alkali to prepare a target product, and the product is subjected to post-treatment to prepare the 3-carbonyl-4-azido-N-benzenesulfonyl-1, 2,3, 4-tetrahydroisoquinoline compound; in the formula, R1Selected from one of the following: hydrogen, fluoro, chloro, bromo, methyl, methoxy; r2Selected from one of the following: hydrogen, methyl, methoxy; the method has good yield and saves the cost; the catalyst is efficient without post-treatment, and meets the requirement of environmental protection; the catalytic system has wide adaptability and is suitable for the large-scale industrialized production of the intermediate of the tetrahydroquinoline compound.
Figure DDA0002373971160000011

Description

Method for preparing 3-carbonyl-4-azido-N-benzenesulfonyl-1, 2,3, 4-tetrahydroisoquinoline compounds
Technical Field
The invention belongs to the technical field of pharmaceutical and chemical intermediate preparation, and particularly relates to a method for preparing 3-carbonyl-4-azido-N-benzenesulfonyl-1, 2,3, 4-tetrahydroisoquinoline compounds by iron catalysis.
Background
3-carbonyl-4-azido-N-benzenesulfonyl-1, 2,3, 4-tetrahydroisoquinoline compounds are important tetrahydroisoquinoline organic intermediates. The tetrahydroisoquinoline organic intermediate is used for producing products such as pesticides, medicines, rubber accelerators, color film sensitizers, dyes and the like. After oxidation, pyridine carboxylic acid can be prepared, and its derivative can be used for preparing colour film and dye. The tetrahydroisoquinoline organic intermediate is used as raw materials of medicines, dyes, pesticides, anion exchange resins and the like, iron preservatives, curing agents of soluble phenolic resins and the like. The addition compound formed by the tetrahydroisoquinoline organic intermediate and the metal can be used for quantitative determination of nickel and cadmium and qualitative determination of noble metal, and has wide and important application in the chemical field.
The reported preparation method of the 3-carbonyl-4-azido-N-benzenesulfonyl-1, 2,3, 4-tetrahydroisoquinoline compound is mainly obtained by multi-step coupling and condensation under the catalysis of transition metal, and has the defects of more reaction steps, low reaction efficiency, serious pollution and the like. The method adopts cheap ferric chloride as a catalyst to realize the efficient preparation of the 3-carbonyl-4-azido-N-methyl benzenesulfonyl-1, 2,3, 4-tetrahydroisoquinoline compound. Has the advantages of low cost, simple operation, low requirement on equipment, excellent yield and the like. Has important application prospect in the field of isoquinoline related drug intermediate synthesis industry.
Disclosure of Invention
In view of the problems in the prior art, the present invention aims to provide a method for preparing 3-carbonyl-4-azido-N-benzenesulfonyl-1, 2,3, 4-tetrahydroisoquinoline compounds.
The invention is realized by the following technical scheme:
the method for preparing the 3-carbonyl-4-azido-N-benzenesulfonyl-1, 2,3, 4-tetrahydroisoquinoline compound shown in the formula (IV) by iron catalysis is characterized by comprising the following steps: the preparation method comprises the following steps of (1) sufficiently reacting a 2-methylamino benzoyl formic acid compound shown in a formula (I), sodium azide shown in a formula (II) and a benzene sulfonyl chloride compound shown in a formula (III) in an organic solvent serving as a medium under the promotion of cesium carbonate serving as alkali by taking a transition metal salt as a catalyst to prepare a target product, and carrying out aftertreatment on the product to prepare a 3-carbonyl-4-azido-N-benzenesulfonyl-1, 2,3, 4-tetrahydroisoquinoline compound; the transition metal salt catalyst is 10 mol% equivalent ferric chloride, and the organic solvent is Tetrahydrofuran (THF);
Figure BDA0002373971140000021
in the reaction formula, R1Selected from one of the following: hydrogen, fluoro, chloro, bromo, methyl, methoxy; r2Selected from one of the following: hydrogen, methyl, methoxy.
The method for preparing the 3-carbonyl-4-azido-N-benzenesulfonyl-1, 2,3, 4-tetrahydroisoquinoline compound by iron catalysis is characterized in that the ratio of the 2-methylamino benzoyl formic acid compound, the sodium azide and the solvent tetrahydrofuran is 5 mmol: 6 mmol: 30 mL.
The method for preparing the 3-carbonyl-4-azido-N-benzenesulfonyl-1, 2,3, 4-tetrahydroisoquinoline compound by iron catalysis is characterized in that the ratio of the 2-methylamino benzoyl formic acid to the benzene sulfonyl chloride compound to the sodium azide is 5 mmol: 5 mmol: 6 mmol.
The method for preparing the 3-carbonyl-4-azido-N-benzenesulfonyl-1, 2,3, 4-tetrahydroisoquinoline compound by iron catalysis is characterized in that the ratio of the 2-methylamino benzoyl formic acid to the benzene sulfonyl chloride compound to the ferric chloride is 5 mmol: 5 mmol: 0.5 mmol.
The method for preparing the 3-carbonyl-4-azido-N-benzenesulfonyl-1, 2,3, 4-tetrahydroisoquinoline compound by silver catalysis is characterized in that the equivalent ratio of the 2-methylamino benzoyl formic acid to the benzene sulfonyl chloride compound to the sodium azide is 1:1:1.2-1:1: 1.4.
The method for preparing the 3-carbonyl-4-azido-N-benzenesulfonyl-1, 2,3, 4-tetrahydroisoquinoline compound by iron catalysis is characterized in that the reaction temperature is 120 ℃, and the reaction time is 24 hours.
The method for preparing the 3-carbonyl-4-azido-N-benzenesulfonyl-1, 2,3, 4-tetrahydroisoquinoline compound by iron catalysis is characterized by comprising the following steps:
1) and (3) extraction: after the reactant is cooled to room temperature at normal temperature, 20mL of saturated sodium chloride aqueous solution is added into the reactant, then ethyl acetate is used for extraction for 3 times, 20mL of the saturated sodium chloride aqueous solution is used for each time, and the extraction liquid is combined;
2) concentration: drying the extract with anhydrous sodium sulfate, and rotary drying with rotary evaporator to obtain concentrate;
3) adsorbing the concentrate with column chromatography silica gel, adding into 200-300 mesh chromatography silica gel column, and purifying with n-hexane: performing flash column chromatography on ethyl acetate according to a certain proportion, combining eluent, performing rotary drying by a rotary evaporator, and pumping by an oil pump to obtain the product 3-carbonyl-4-azido-N-benzenesulfonyl-1, 2,3, 4-tetrahydroisoquinoline compound.
The method for preparing the 3-carbonyl-4-azido-N-benzenesulfonyl-1, 2,3, 4-tetrahydroisoquinoline compound by iron catalysis is characterized in that the drying time in the step 2) is 5 hours.
The method for preparing the 3-carbonyl-4-azido-N-benzenesulfonyl-1, 2,3, 4-tetrahydroisoquinoline compound by iron catalysis is characterized in that the ratio of N-hexane to ethyl acetate in the step 3) is 1:1-2: 1.
Drawings
FIG. 1 is a drawing of product 4a of the present invention1H NMR spectrum;
FIG. 2 shows the product 4a of the present invention13C NMR spectrum;
FIG. 3 shows the product 4b of the present invention1H NMR spectrum;
FIG. 4 shows the product 4b of the present invention13C-NMR spectrum;
FIG. 5 shows the preparation of 4c according to the invention1H NMR spectrum;
FIG. 6 shows the preparation of 4c according to the invention13C-NMR spectrum;
FIG. 7 shows the product 4d of the present invention1H NMR spectrum;
FIG. 8 is a drawing showing the production of 4d in the present invention13C NMR spectrum;
FIG. 9 shows the preparation of 4e according to the invention1H NMR spectrum;
FIG. 10 shows the preparation of 4e according to the invention13C-NMR spectrum;
FIG. 11 shows the preparation of 4f of the present invention1H NMR spectrum;
FIG. 12 shows the preparation of 4f of the present invention13C NMR spectrum;
FIG. 13 shows 4g of the product of the present invention1H NMR spectrum;
FIG. 14 shows 4g of the product of the present invention13C NMR spectrum;
FIG. 15 shows 4h of the product of the present invention1H NMR spectrum;
FIG. 16 shows 4h of the product of the present invention13C NMR spectrum.
Detailed Description
The present invention will be described in more detail with reference to specific examples.
The synthesis method comprises the steps of respectively adding 5mmol of 2-methylaminobenzoyl formic acid compound 1, 6mmol of sodium azide compound 2 and 5mmol of benzenesulfonyl chloride compound 3 into a 50mL round-bottom flask, then sequentially adding 30mL of THF, 0.5mmol of ferric chloride and 10mmol of cesium carbonate, and reacting at 120 ℃ for 24 hours under stirring. After cooling, 20mL of saturated sodium chloride aqueous solution is added into the system, extraction is carried out for 3 times by ethyl acetate, 20mL of saturated sodium chloride aqueous solution is carried out for each time, organic phases are combined, after drying by anhydrous sodium sulfate, solvent is evaporated, and silica gel column chromatography with 200 meshes and 300 meshes is carried out to obtain 4 pure products of the 3-carbonyl-4-azido-N-benzenesulfonyl-1, 2,3, 4-tetrahydroisoquinoline compound, wherein the yield is 91-96 percent. Specific examples and characterization data all product structures were determined by comparison of nuclear magnetic resonance and mass spectrometry results as follows.
Figure BDA0002373971140000051
Figure BDA0002373971140000061
Example 1: 4a preparation of the product
Figure BDA0002373971140000062
895mg (5mmol) of 2-methylaminobenzoylcarboxylic acid 1a, 390mg (6mmol) of sodium azide 2 and 950mg (5mmol) of 4-methylbenzenesulfonyl chloride 3a were charged in a 50mL round-bottomed flask, respectively, at room temperature, followed by 30mL of tetrahydrofuran, 81mg (0.5mmol) of ferric chloride and 652mg (10mmol) of cesium carbonate in this order, and the reaction was stirred at 120 ℃ for 24 hours. After cooling, 10mL of saturated aqueous sodium chloride solution was added to the system, extraction was performed 3 times with ethyl acetate (20 mL each time), the organic phases were combined, dried over anhydrous sodium sulfate, the solvent was evaporated, and 200-mesh 300-mesh silica gel column chromatography was performed to obtain pure 4a (1472mg, yield 90%, yellow powder). 4a1The H NMR spectrum is shown in FIGS. 1 and 4a13The C NMR spectrum is shown in FIG. 2.
1H NMR(400MHz,CDCl3)δ7.98(d,J＝8.3Hz,2H),7.35-7.32(m, 3H),7.25(d,J＝7.3Hz,1H),7.17(td,J＝7.6,1.2Hz,1H),6.87(dd,J＝ 7.8,1.1Hz,1H),5.05(s,2H),2.44(s,3H).
13C NMR(100MHz,CDCl3)δ163.0,145.1,135.6,129.5,128.8,128.6, 126.4,125.7,125.0,122.5,119.0,66.7,48.4,21.7.
HRMS(ESI)m/z calcd for C16H13N3NaO3S+[M+Na]+:350.0570,found: 350.0557.
IR(film):3068,2958,2093,1666,1596,1495,1358,1258,1171,1082, 1003,814,753cm-1.
Example 2: 4b preparation of the product
Figure BDA0002373971140000071
890mg (5mmol) of 4-methoxy-2-methylaminobenzoylcarboxylic acid 1b, 390mg (6mmol) of sodium azide 2 and 955mg (5mmol) of 4-methylbenzenesulfonyl chloride 3a were added, respectively, to a 50mL round-bottomed flask at room temperature, followed by 30mL of tetrahydrofuran, 81mg (0.5mmol) of ferric chloride and 652mg (10mmol) of cesium carbonate in that order, and the reaction was stirred at 120 ℃ for 24 hours. Cooling, adding 10mL saturated sodium chloride aqueous solution, extracting with ethyl acetate for 3 times (20 mL each time), mixing organic phases, and adding anhydrous sulfurAfter drying the sodium salt, the solvent was evaporated and purified by 200-mesh 300-mesh silica gel column chromatography to give pure 4b (1642 mg, 92% yield, yellow powder). 4b1The H NMR spectrum is shown in FIGS. 3 and 4b13The C NMR spectrum is shown in FIG. 4.
1H NMR(400MHz,CDCl3)δ7.98(d,J＝8.3Hz,2H),7.34(d,J＝8.1 Hz,2H),6.90(dd,J＝8.5,2.6Hz,1H),6.83(d,J＝2.5Hz,1H),6.79(d, J＝8.5Hz,1H),5.02(s,2H),3.82(s,3H),2.44(s,3H).
13C NMR(100MHz,CDCl3)δ163.5,157.9,145.1,135.6,129.5,128.6, 126.5,120.4,114.8,113.8,112.2,66.1,55.5,48.5,21.7.
HRMS(ESI)m/z calcd for C17H15N3NaO4S+[M+Na]+:380.0675,found: 380.0664.
IR(KBr):3071,2925,2096,1698,1600,1504,1455,1259,1293,1170, 1086,1031,814,736cm-1.
Example 3: preparation of 4c product
Figure BDA0002373971140000081
1070mg (5mmol) of 4-chloro-2-methylaminobenzoylcarboxylic acid 1c, 390mg (6mmol) of sodium azide 2 and 955mg (5mmol) of 4-methylbenzenesulfonyl chloride 3a are added to a 50mL round-bottomed flask, respectively, at room temperature, followed by 30mL of tetrahydrofuran, 81mg (0.5mmol) of ferric chloride and 652mg (10mmol) of cesium carbonate in that order, and the reaction is stirred at 120 ℃ for 24 hours. After cooling, 10mL of saturated aqueous sodium chloride solution was added to the system, extraction was performed 3 times with ethyl acetate (20 mL each time), the organic phases were combined, dried over anhydrous sodium sulfate, the solvent was evaporated, and 200-mesh 300-mesh silica gel column chromatography was performed to obtain pure 4c (1665mg, yield 91%, yellow powder). 4c1The H NMR spectrum is shown in FIGS. 5 and 4c13The C NMR spectrum is shown in FIG. 6.
1H NMR(400MHz,CDCl3)δ7.97(d,J＝8.3Hz,2H),7.35(d,J＝8.1 Hz,2H),7.31(dd,J＝8.3,2.1Hz,1H),7.27–7.24(m,1H),6.81(d,J＝ 8.3Hz,1H),5.01(s,2H),2.44(s,3H).
13C NMR(100MHz,CDCl3)δ162.5,145.3,135.4,131.3,129.5,129.0, 128.7,126.7,126.6,121.3,120.2,47.9,21.7.
HRMS(ESI):calcd for C16H12ClN3NaO3S+[M+Na]+:384.0180,found: 384.0178.
IR(film):3068,2922,2096,1666,1595,1493,1359,1301,1255,1170, 1077,813,727,660cm-1.
Example 4: preparation of 4d product
Figure BDA0002373971140000091
985mg (5mmol) of 4-fluoro-2-methylaminobenzoylcarboxylic acid 1d, 390mg (6mmol) of sodium azide 2 and 955mg (5mmol) of 4-methylbenzenesulfonyl chloride 3a are added to a 50mL round-bottomed flask, respectively, at room temperature, followed by 30mL of tetrahydrofuran, 81mg (0.5mmol) of ferric chloride and 652mg (10mmol) of cesium carbonate in that order, and the reaction is stirred at 120 ℃ for 24 hours. After cooling, 10mL of saturated aqueous sodium chloride solution was added to the system, extraction was performed 3 times with ethyl acetate (20 mL each time), the organic phases were combined, dried over anhydrous sodium sulfate, the solvent was evaporated, and 200-mesh 300-mesh silica gel column chromatography was performed to obtain pure 4d (1587mg, yield 91%, yellow powder). 4d1The H NMR spectrum is shown in FIGS. 7 and 4d13The C NMR spectrum is shown in FIG. 8.
1H NMR(400MHz,CDCl3)δ7.98(d,J＝8.3Hz,2H),7.35(d,J＝8.1Hz, 2H),7.07(td,J＝8.5,2.6Hz,1H),7.01(dd,J＝8.4,2.6Hz,1H),6.84(dd,J ＝8.6,4.8Hz,1H),5.02(s,2H),2.44(s,3H).
13C NMR(100MHz,CDCl3)δ162.8,160.7(d,J＝247.3Hz),145.3, 135.4,129.5,128.7,127.0(d,J＝7.7Hz),120.6(d,J＝8.2Hz),118.4(d, J＝3.1Hz),116.1(d,J＝22.6Hz),114.0(d,J＝23.6Hz),48.0(d,J＝ 2.3Hz),21.7.
HRMS(ESI):calcd for C16H12FN3NaO3S+[M+Na]+:368.0476,found: 368.0470.
IR(film):3068,2923,2093,1667,1505,1359,1273,1225,1170,1079, 953,813cm-1.
Example 5: preparation of 4e product
Figure BDA0002373971140000101
895mg (5mmol) of 2-methylaminobenzoylcarboxylic acid 1a, 390mg (6mmol) of sodium azide 2 and 1110mg (5mmol) of 4-nitrobenzenesulfonyl chloride 3b were respectively added to a 50mL round-bottomed flask at room temperature, followed by 30mL of tetrahydrofuran, 81mg (0.5mmol) of ferric chloride and 652mg (10mmol) of cesium carbonate in that order, and the reaction was stirred at 120 ℃ for 24 hours. After cooling, 10mL of saturated aqueous sodium chloride solution was added to the system, extraction was performed 3 times with ethyl acetate (20 mL each time), the organic phases were combined, dried over anhydrous sodium sulfate, the solvent was evaporated, and silica gel column chromatography was performed using 200-mesh 300-mesh column to obtain pure 4e (1665mg, yield 93%, yellow powder). 4e1The H NMR spectrum is shown in FIGS. 9 and 4e13The C NMR spectrum is shown in FIG. 10.1H NMR(400MHz,CDCl3)δ8.39(d,J＝9.0Hz,2H),8.30(d,J＝8.9 Hz,2H),7.38(td,J＝7.7,1.4Hz,1H),7.29(d,J＝8.1Hz,1H),7.21(td, J＝7.5,1.2Hz,1H),6.91(dd,J＝7.8,1.2Hz,1H),5.08(s,2H).
13C NMR(100MHz,CDCl3)δ163.0,150.7,144.1,130.1,129.1,126.5, 126.1,124.5,124.0,122.1,119.1,48.6.
HRMS(ESI):calcd for C16H12N4NaO5S+[M+Na]+:381.0264,found: 381.0251.
IR(film):3107,2924,2097,1667,1605,1531,1463,1349,1308,1258, 1177,1086,854,805,739cm-1.
Example 6: preparation of 4f product
Figure BDA0002373971140000111
895mg (5mmol) of 2-methylaminobenzoylcarboxylic acid 1a, 390mg (6mmol) of sodium azide 2 and 975mg (5mmol) of 4-fluorobenzenesulfonyl chloride 3c are respectively added to a 50mL round-bottomed flask at room temperature, followed by 30mL of tetrahydrofuran, 81mg (0.5mmol) of ferric chloride and 652mg (10mmol) of cesium carbonate in that order, and the reaction is carried out at 120 ℃Stirred for 24 hours. After cooling, 10mL of saturated aqueous sodium chloride solution was added to the system, and the mixture was extracted with ethyl acetate for 3 times (20 mL each time), the organic phases were combined, dried over anhydrous sodium sulfate, the solvent was evaporated, and the purified product 4f (1539mg, yield 95%, yellow powder) was obtained by 200-mesh 300-mesh silica gel column chromatography. 4f1The H NMR spectrum is shown in FIGS. 11 and 4f13The C NMR spectrum is shown in FIG. 12.
1H NMR(400MHz,CDCl3)δ8.16-8.11(m,2H),7.35(td,J＝7.6,1.3 Hz,1H),7.26(d,J＝6.8Hz,1H),7.25-7.17(m,3H),6.89(dd,J＝7.8, 1.0Hz,1H),5.05(s,2H).
13C NMR(101MHz,CDCl3)δ165.9(d,J＝255.4Hz),163.0,134.4(d,J＝ 3.2Hz),131.7(d,J＝9.8Hz),128.9,126.4,125.9,124.8,122.3,119.0, 116.1(d,J＝22.6Hz),66.8,48.4.
HRMS(ESI):calcd for C15H10FN3NaO3S+[M+Na]+:354.0319,found: 354.0313.
IR(film):3107,3067,2096,1663,1590,1493,1464,1381,1364,1308, 1260,1177,1156,1086,1004,837,753,671cm-1.
Example 7: preparation of 4g of product
Figure BDA0002373971140000121
895mg (5mmol) of 2-methylaminobenzoylcarboxylic acid 1a, 390mg (6mmol) of sodium azide 2 and 1105mg (5mmol) of 4-chlorobenzenesulfonyl chloride 3d were charged in a 50mL round-bottomed flask, respectively, at room temperature, followed by 30mL of tetrahydrofuran, 81mg (0.5mmol) of ferric chloride and 652mg (10mmol) of cesium carbonate in this order, and the reaction was stirred at 120 ℃ for 24 hours. After cooling, 10mL of saturated aqueous sodium chloride solution was added to the system, extraction was performed 3 times with ethyl acetate (20 mL each time), the organic phases were combined, dried over anhydrous sodium sulfate, the solvent was evaporated, and 200-mesh 300-mesh silica gel column chromatography was performed to obtain 4g of a pure product (1583mg, yield 91%, yellow powder). 4g1The H NMR spectrum is shown in FIG. 13, 4g13The C NMR spectrum is shown in FIG. 14.
1H NMR(400MHz,CDCl3)δ8.07-8.02(m,2H),7.55-7.49(m,2H), 7.35(td,J＝7.6,1.3Hz,1H),7.26(d,J＝7.3Hz,1H),7.18(td,J＝7.5, 1.2Hz,1H),6.89(dd,J＝7.9,1.1Hz,1H),5.04(s,2H).
13C NMR(100MHz,CDCl3)δ163.0,140.7,136.9,130.1,129.2,128.9, 126.5,125.9,124.8,122.3,119.1,66.8,48.4.
HRMS(ESI):calcd for C15H9ClN3O3S[M-H]+:346.0059,found: 346.0064.
IR(film):3094,2094,1666,1584,1497,1363,1259,1171,1084,973, 804,755cm-1.
Example 8: preparation of the 4h product
Figure BDA0002373971140000131
895mg (5mmol) of 2-methylaminobenzoylcarboxylic acid 1a, 390mg (6mmol) of sodium azide 2 and 1035mg (5mmol) of 4-methoxybenzenesulfonyl chloride 3e were charged in a 50mL round-bottomed flask, respectively, at room temperature, followed by 30mL of tetrahydrofuran, 81mg (0.5mmol) of ferric chloride and 652mg (10mmol) of cesium carbonate in this order, and the reaction was stirred at 120 ℃ for 24 hours. After cooling, 10mL of saturated aqueous sodium chloride solution was added to the system, extraction was performed 3 times with ethyl acetate (20 mL each time), the organic phases were combined, dried over anhydrous sodium sulfate, the solvent was evaporated, and 200-mesh 300-mesh silica gel column chromatography was performed to obtain a pure product for 4h (1629mg, yield 95%, yellow powder). 4h1The H NMR spectrum is shown in FIG. 15, 4H13The C NMR spectrum is shown in FIG. 16.1H NMR(400MHz,CDCl3)δ8.06–8.02(m,2H),7.34(td,J＝7.6,1.3 Hz,1H),7.25(d,J＝8.0,1H),7.17(td,J＝7.5,1.1Hz,1H),7.02–6.98 (m,2H),6.88(dd,J＝7.8,1.2Hz,1H),5.05(s,2H),3.88(s,3H).
13C NMR(100MHz,CDCl3)δ163.9,163.0,131.0,129.8,128.8,126.4, 125.7,125.1,122.5,119.0,114.0,66.7,55.7,48.4.

Claims (9)

1. A method for preparing a 3-carbonyl-4-azido-N-benzenesulfonyl-1, 2,3, 4-tetrahydroisoquinoline compound represented by the formula (IV), which is characterized by comprising the following steps: the preparation method comprises the following steps of (1) sufficiently reacting a 2-methylamino benzoyl formic acid compound shown in a formula (I), sodium azide shown in a formula (II) and a benzene sulfonyl chloride compound shown in a formula (III) in an organic solvent serving as a medium under the promotion of cesium carbonate serving as alkali by taking a transition metal salt as a catalyst to prepare a target product, and carrying out aftertreatment on the product to prepare a 3-carbonyl-4-azido-N-benzenesulfonyl-1, 2,3, 4-tetrahydroisoquinoline compound; the transition metal salt catalyst is 10 mol% equivalent ferric chloride, and the organic solvent is Tetrahydrofuran (THF);
Figure FDA0002373971130000011
in the reaction formula, R1Selected from one of the following: hydrogen, fluoro, chloro, bromo, methyl, methoxy; r2Selected from one of the following: hydrogen, methyl, methoxy.
2. The method for preparing 3-carbonyl-4-azido-N-benzenesulfonyl-1, 2,3, 4-tetrahydroisoquinoline compound according to claim 1, wherein the ratio of the 2-methylaminobenzoyl carboxylic acid compound, sodium azide and solvent tetrahydrofuran is 5 mmol: 6 mmol: 30 mL.
3. The method for preparing 3-carbonyl-4-azido-N-benzenesulfonyl-1, 2,3, 4-tetrahydroisoquinoline compound according to claim 1, wherein the ratio of the 2-methylaminobenzoyl carboxylic acid, benzenesulfonyl chloride compound and sodium azide is 5 mmol: 5 mmol: 6 mmol.
4. The method for preparing 3-carbonyl-4-azido-N-benzenesulfonyl-1, 2,3, 4-tetrahydroisoquinoline compound according to claim 1, wherein the ratio of the 2-methylaminobenzoyl carboxylic acid, benzenesulfonyl chloride compound and ferric chloride is 5mmol/5mmol/0.5 mmol.
5. The method for preparing 3-carbonyl-4-azido-N-benzenesulfonyl-1, 2,3, 4-tetrahydroisoquinoline compound according to claim 1, wherein the equivalent ratio of the 2-methylaminobenzoyl carboxylic acid, benzenesulfonyl chloride compound and sodium azide is 1:1:1.2-1:1: 1.4.
6. The method for preparing 3-carbonyl-4-azido-N-benzenesulfonyl-1, 2,3, 4-tetrahydroisoquinoline compound according to claim 1, wherein the reaction temperature is 120 ℃ and the reaction time is 24 hours.
7. The method for preparing 3-carbonyl-4-azido-N-benzenesulfonyl-1, 2,3, 4-tetrahydroisoquinoline compound according to claim 1, characterized in that the specific method of post-treatment consists of the following steps:
1) and (3) extraction: after the reactant is cooled to room temperature at normal temperature, 20mL of saturated sodium chloride aqueous solution is added into the reactant, then ethyl acetate is used for extraction for 3 times, 20mL of the saturated sodium chloride aqueous solution is used for each time, and the extraction liquid is combined;
2) concentration: drying the extract with anhydrous sodium sulfate, and rotary drying with rotary evaporator to obtain concentrate;
3) adsorbing the concentrate with column chromatography silica gel, adding into 200-300 mesh chromatography silica gel column, and purifying with n-hexane: performing flash column chromatography on ethyl acetate according to a certain proportion, combining eluent, performing rotary drying by a rotary evaporator, and pumping by an oil pump to obtain the product 3-carbonyl-4-azido-N-benzenesulfonyl-1, 2,3, 4-tetrahydroisoquinoline compound.
8. The method for preparing 3-carbonyl-4-azido-N-benzenesulfonyl-1, 2,3, 4-tetrahydroisoquinoline compound according to claim 7, wherein the drying time in step 2) is 5 hours.
9. The method for preparing 3-carbonyl-4-azido-N-benzenesulfonyl-1, 2,3, 4-tetrahydroisoquinoline compound according to claim 7, wherein the ratio of N-hexane to ethyl acetate in step 3) is 1:1-2: 1.
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Citations (2)

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Publication number Priority date Publication date Assignee Title
CN1255124A (en) * 1997-03-18 2000-05-31 史密丝克莱恩比彻姆有限公司 Substituted isoquinoline derivatives and their use as anticonulsants
CN103772279A (en) * 2012-10-18 2014-05-07 邵阳学院 Preparation method for 4-bromoisoquinolone and derivative thereof

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Publication number Priority date Publication date Assignee Title
CN1255124A (en) * 1997-03-18 2000-05-31 史密丝克莱恩比彻姆有限公司 Substituted isoquinoline derivatives and their use as anticonulsants
CN103772279A (en) * 2012-10-18 2014-05-07 邵阳学院 Preparation method for 4-bromoisoquinolone and derivative thereof

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