CN114163385B - Method for promoting oxidation of tetrahydroisoquinoline compounds to lactam compounds by using surfactant - Google Patents
Method for promoting oxidation of tetrahydroisoquinoline compounds to lactam compounds by using surfactant Download PDFInfo
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- CN114163385B CN114163385B CN202111318078.4A CN202111318078A CN114163385B CN 114163385 B CN114163385 B CN 114163385B CN 202111318078 A CN202111318078 A CN 202111318078A CN 114163385 B CN114163385 B CN 114163385B
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- -1 lactam compounds Chemical class 0.000 title claims abstract description 25
- 239000004094 surface-active agent Substances 0.000 title claims abstract description 19
- 238000000034 method Methods 0.000 title claims abstract description 16
- 230000003647 oxidation Effects 0.000 title claims abstract description 9
- 238000007254 oxidation reaction Methods 0.000 title claims abstract description 9
- 230000001737 promoting effect Effects 0.000 title claims abstract description 9
- 125000003039 tetrahydroisoquinolinyl group Chemical class C1(NCCC2=CC=CC=C12)* 0.000 title abstract 4
- 238000006243 chemical reaction Methods 0.000 claims abstract description 36
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 18
- 239000000758 substrate Substances 0.000 claims abstract description 15
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims abstract description 14
- 239000003960 organic solvent Substances 0.000 claims abstract description 12
- 125000003118 aryl group Chemical group 0.000 claims abstract description 8
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims abstract description 8
- 239000001301 oxygen Substances 0.000 claims abstract description 8
- 229910052760 oxygen Inorganic materials 0.000 claims abstract description 8
- 229910052757 nitrogen Inorganic materials 0.000 claims abstract description 7
- 239000000047 product Substances 0.000 claims description 15
- 239000012043 crude product Substances 0.000 claims description 13
- 239000012298 atmosphere Substances 0.000 claims description 11
- 238000004440 column chromatography Methods 0.000 claims description 10
- 238000003756 stirring Methods 0.000 claims description 10
- 150000003526 tetrahydroisoquinolines Chemical class 0.000 claims description 8
- XRWMGCFJVKDVMD-UHFFFAOYSA-M didodecyl(dimethyl)azanium;bromide Chemical compound [Br-].CCCCCCCCCCCC[N+](C)(C)CCCCCCCCCCCC XRWMGCFJVKDVMD-UHFFFAOYSA-M 0.000 claims description 7
- PSLWZOIUBRXAQW-UHFFFAOYSA-M dimethyl(dioctadecyl)azanium;bromide Chemical compound [Br-].CCCCCCCCCCCCCCCCCC[N+](C)(C)CCCCCCCCCCCCCCCCCC PSLWZOIUBRXAQW-UHFFFAOYSA-M 0.000 claims description 5
- UWYZHKAOTLEWKK-UHFFFAOYSA-N tetrahydro-isoquinoline Natural products C1=CC=C2CNCCC2=C1 UWYZHKAOTLEWKK-UHFFFAOYSA-N 0.000 claims description 5
- 239000002202 Polyethylene glycol Substances 0.000 claims description 4
- 229920001223 polyethylene glycol Polymers 0.000 claims description 4
- 239000012467 final product Substances 0.000 claims description 3
- 238000010438 heat treatment Methods 0.000 claims description 3
- 239000012495 reaction gas Substances 0.000 claims description 3
- 230000035484 reaction time Effects 0.000 claims description 3
- 125000001637 1-naphthyl group Chemical group [H]C1=C([H])C([H])=C2C(*)=C([H])C([H])=C([H])C2=C1[H] 0.000 claims 1
- 125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 claims 1
- 125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 claims 1
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims 1
- 150000003951 lactams Chemical group 0.000 abstract description 10
- 239000007800 oxidant agent Substances 0.000 abstract description 8
- 238000003786 synthesis reaction Methods 0.000 abstract description 8
- 230000015572 biosynthetic process Effects 0.000 abstract description 6
- 230000001590 oxidative effect Effects 0.000 abstract description 6
- 238000001308 synthesis method Methods 0.000 abstract description 6
- VDBNYAPERZTOOF-UHFFFAOYSA-N isoquinolin-1(2H)-one Chemical class C1=CC=C2C(=O)NC=CC2=C1 VDBNYAPERZTOOF-UHFFFAOYSA-N 0.000 abstract description 3
- 239000003513 alkali Substances 0.000 abstract description 2
- 239000003446 ligand Substances 0.000 abstract 1
- 239000002904 solvent Substances 0.000 abstract 1
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 17
- 239000012295 chemical reaction liquid Substances 0.000 description 7
- 239000007789 gas Substances 0.000 description 7
- 238000002360 preparation method Methods 0.000 description 7
- NQUKHFQYUSVVBI-UHFFFAOYSA-N 2-phenyl-3,4-dihydroisoquinolin-1-one Chemical compound C1CC2=CC=CC=C2C(=O)N1C1=CC=CC=C1 NQUKHFQYUSVVBI-UHFFFAOYSA-N 0.000 description 6
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 6
- 239000000203 mixture Substances 0.000 description 5
- ONQBUHWENXKHHP-UHFFFAOYSA-N 2-phenyl-3,4-dihydro-1h-isoquinoline Chemical compound C1CC2=CC=CC=C2CN1C1=CC=CC=C1 ONQBUHWENXKHHP-UHFFFAOYSA-N 0.000 description 3
- LRFDXMJJNFQGFF-UHFFFAOYSA-N N1=C(C=CC=C1)N1CC2=CC=CCC2CC1 Chemical compound N1=C(C=CC=C1)N1CC2=CC=CCC2CC1 LRFDXMJJNFQGFF-UHFFFAOYSA-N 0.000 description 3
- 239000002585 base Substances 0.000 description 3
- AWJUIBRHMBBTKR-UHFFFAOYSA-N iso-quinoline Natural products C1=NC=CC2=CC=CC=C21 AWJUIBRHMBBTKR-UHFFFAOYSA-N 0.000 description 3
- 238000011160 research Methods 0.000 description 3
- 230000002194 synthesizing effect Effects 0.000 description 3
- 239000004215 Carbon black (E152) Substances 0.000 description 2
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 2
- 239000003242 anti bacterial agent Substances 0.000 description 2
- 125000006615 aromatic heterocyclic group Chemical group 0.000 description 2
- 150000004945 aromatic hydrocarbons Chemical class 0.000 description 2
- 229930195733 hydrocarbon Natural products 0.000 description 2
- 239000011941 photocatalyst Substances 0.000 description 2
- 125000005575 polycyclic aromatic hydrocarbon group Chemical group 0.000 description 2
- SUKJFIGYRHOWBL-UHFFFAOYSA-N sodium hypochlorite Chemical compound [Na+].Cl[O-] SUKJFIGYRHOWBL-UHFFFAOYSA-N 0.000 description 2
- VZSRBBMJRBPUNF-UHFFFAOYSA-N 2-(2,3-dihydro-1H-inden-2-ylamino)-N-[3-oxo-3-(2,4,6,7-tetrahydrotriazolo[4,5-c]pyridin-5-yl)propyl]pyrimidine-5-carboxamide Chemical compound C1C(CC2=CC=CC=C12)NC1=NC=C(C=N1)C(=O)NCCC(N1CC2=C(CC1)NN=N2)=O VZSRBBMJRBPUNF-UHFFFAOYSA-N 0.000 description 1
- NOJZAPPYYLAMOP-UHFFFAOYSA-N 2-(4-chlorophenyl)-3,4,4a,5-tetrahydro-1H-isoquinoline Chemical compound ClC1=CC=C(C=C1)N1CC2=CC=CCC2CC1 NOJZAPPYYLAMOP-UHFFFAOYSA-N 0.000 description 1
- OCSDAIWZTJTJCY-UHFFFAOYSA-N 2-(4-chlorophenyl)-3,4-dihydroisoquinolin-1-one Chemical compound ClC1=CC=C(C=C1)N1C(C2=CC=CC=C2CC1)=O OCSDAIWZTJTJCY-UHFFFAOYSA-N 0.000 description 1
- VNLNPESPGZRXQK-UHFFFAOYSA-N 2-(4-methoxyphenyl)-3,4-dihydroisoquinolin-1-one Chemical compound COc1ccc(cc1)N1CCc2ccccc2C1=O VNLNPESPGZRXQK-UHFFFAOYSA-N 0.000 description 1
- CKUVBYWYHMUQNQ-UHFFFAOYSA-N 2-naphthalen-1-yl-3,4-dihydroisoquinolin-1-one Chemical compound C1(=CC=CC2=CC=CC=C12)N1C(C2=CC=CC=C2CC1)=O CKUVBYWYHMUQNQ-UHFFFAOYSA-N 0.000 description 1
- AZXUGPFLZWWHJZ-UHFFFAOYSA-N 2-pyridin-2-yl-3,4-dihydroisoquinolin-1-one Chemical compound O=C(C1=CC=CC=C1CC1)N1C1=NC=CC=C1 AZXUGPFLZWWHJZ-UHFFFAOYSA-N 0.000 description 1
- ZTIZKPDPDXRVNU-UHFFFAOYSA-N C1(=CC=CC2=CC=CC=C12)N1CC2=CC=CCC2CC1 Chemical compound C1(=CC=CC2=CC=CC=C12)N1CC2=CC=CCC2CC1 ZTIZKPDPDXRVNU-UHFFFAOYSA-N 0.000 description 1
- OIEJRNJUMBYQSL-UHFFFAOYSA-N C1=CC(OC)=CC=C1N1CC2=CC=CCC2CC1 Chemical compound C1=CC(OC)=CC=C1N1CC2=CC=CCC2CC1 OIEJRNJUMBYQSL-UHFFFAOYSA-N 0.000 description 1
- MYMOFIZGZYHOMD-UHFFFAOYSA-N Dioxygen Chemical compound O=O MYMOFIZGZYHOMD-UHFFFAOYSA-N 0.000 description 1
- 229930182555 Penicillin Natural products 0.000 description 1
- 239000003905 agrochemical Substances 0.000 description 1
- 229940088710 antibiotic agent Drugs 0.000 description 1
- 239000003472 antidiabetic agent Substances 0.000 description 1
- 229940125708 antidiabetic agent Drugs 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 239000003054 catalyst Substances 0.000 description 1
- 210000003169 central nervous system Anatomy 0.000 description 1
- 238000012512 characterization method Methods 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 238000010276 construction Methods 0.000 description 1
- 238000010586 diagram Methods 0.000 description 1
- 229910001882 dioxygen Inorganic materials 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 230000007613 environmental effect Effects 0.000 description 1
- SEACYXSIPDVVMV-UHFFFAOYSA-L eosin Y Chemical compound [Na+].[Na+].[O-]C(=O)C1=CC=CC=C1C1=C2C=C(Br)C(=O)C(Br)=C2OC2=C(Br)C([O-])=C(Br)C=C21 SEACYXSIPDVVMV-UHFFFAOYSA-L 0.000 description 1
- 239000000543 intermediate Substances 0.000 description 1
- 239000012046 mixed solvent Substances 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 150000002960 penicillins Chemical class 0.000 description 1
- 102000004196 processed proteins & peptides Human genes 0.000 description 1
- 108090000765 processed proteins & peptides Proteins 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- 238000000425 proton nuclear magnetic resonance spectrum Methods 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 239000012429 reaction media Substances 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 238000010189 synthetic method Methods 0.000 description 1
Classifications
-
- 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
- C07D217/24—Oxygen atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
Abstract
The invention relates to a method for promoting oxidation of tetrahydroisoquinoline compounds into lactam compounds by using a surfactant, belonging to the technical field of organic synthesis. The synthesis of lactam compounds is to take aryl substituted tetrahydroisoquinoline compounds on nitrogen as reaction substrates, pure water as solvent, oxygen as oxidant, and heat under the promotion of surfactant to react, thereby preparing the isoquinolinone compounds containing lactam fragments. The synthesis method of the invention does not need to adopt equivalent oxidant, ligand and alkali, does not need to adopt organic solvent, is green and environment-friendly, has simple synthesis steps, mild reaction conditions, simple and easy operation, high reaction yield up to 95 percent and wide applicable substrate range, provides a new way for converting tetrahydroisoquinoline compounds into corresponding lactam compounds, and has stronger industrial application prospect.
Description
Technical Field
The invention belongs to the technical field of organic synthesis, and particularly relates to a method for promoting oxidation of tetrahydroisoquinoline compounds into lactam compounds by using a surfactant.
Background
Since amide bonds are commonly present in compounds having biological activity, such as peptides, proteins, penicillins, and the like, particularly lactam fragments, they are of interest as important components of antibacterial agents, antidiabetic agents, antibiotics, and drugs directed to the central nervous system. Furthermore, lactam fragments are also widely present in chemical raw materials, synthetic intermediates and agrochemicals. Therefore, the construction of amide bonds is a relatively important research direction in synthetic chemistry. And because of the important application of the lactam compound, the synthesis research of the isoquinolinone compound containing the lactam fragment is very necessary. Aiming at the synthesis method of isoquinoline ketone compounds containing lactam fragments, students at home and abroad have conducted extensive researches.
In 2012, the relaxation group of university of south Kokai was NaClO 2 Is an oxidizing agent in a mixed solvent (Cl 3 CMe/H 2 O=4:1) successfully oxidizes N-substituted tetrahydroisoquinoline derivatives to N-substituted 3, 4-dihydroisoquinolinones in reaction yields up to 94% (a.—r.song et al synthesis 2012,44,2903-2909).
In 2019, anna Lee group used Eosin Y as a photocatalyst under irradiation of blue light, K was used 2 CO 3 And NaN 3 At O 2 N-phenyl tetrahydroisoquinoline was successfully oxidized to N-phenyl-3, 4-dihydro-isoquinolone in an atmosphere, and the reaction was carried out in an organic solvent DMSO in a yield of up to 95% (A. Lee et al. Adv. Synth. Catalyst. 2019,361, 1124-1129).
In 2019, tsogaeva group of Ellangen-Nerenberg university uses Rose Bengal as a photocatalyst, and N-phenyl tetrahydroisoquinoline is oxidized into N-phenyl-3, 4-dihydroisoquinolinone by molecular oxygen oxidation under irradiation of green light using NaOAc as a base, and the reaction is similarly carried out in an organic solvent DMSO, and the yield reaches 72% (A.A. Guryev et al. Chem. Eur. J.2019,25, 4062-4066).
The above is about the synthesis of isoquinolinones containing lactam fragmentsIn the reports, it is often necessary to use environmentally unfriendly oxidizing agents, such as NaClO 2 Or requires an equivalent amount of base to promote the reaction, e.g. K 2 CO 3 ，NaN 3 NaOAc. In addition, the above reported synthetic methods generally employ organic solvents as the reaction medium. At present, few reports are made on synthesizing isoquinoline ketone compounds containing lactam fragments under the conditions of no environment-friendly oxidant, no equivalent base and no organic solvent. Therefore, the development of an environment-friendly synthesis method for synthesizing the isoquinolinone compound containing the lactam fragment has extremely important significance.
Disclosure of Invention
The invention aims to provide a method for promoting tetrahydroisoquinoline compounds to be oxidized into lactam compounds by using a surfactant, which is used for solving the technical problems that the existing synthesis method of isoquinoline ketone compounds containing lactam fragments often needs to adopt an oxidant which is not friendly to the environment, needs equivalent alkali and organic solvent, and does not meet the development requirements of green and environment protection.
A method for promoting the oxidation of tetrahydroisoquinoline compounds to lactam compounds by using a surfactant, wherein the reaction formula is as follows, and the method comprises the following steps:
step (1): taking an aryl substituted tetrahydroisoquinoline compound on nitrogen as a reaction substrate, dissolving a surfactant in pure water, then adding the reaction substrate, stirring and heating to react, wherein the reaction gas atmosphere is oxygen;
step (2): after the reaction is finished, the reaction system is restored to room temperature, an organic solvent is added to extract a crude product of the organic product, then the organic solvent is concentrated, and the obtained crude product of the organic product is separated and purified by column chromatography to obtain a final product.
Preferably, the aryl substituent is any one of aromatic hydrocarbon, heterocyclic aromatic hydrocarbon and polycyclic aromatic hydrocarbon.
Preferably, the amount of the surfactant is 5-10% of the mass fraction of the aryl-substituted tetrahydroisoquinoline compounds on nitrogen.
Preferably, the surfactant is any one of didodecyl dimethyl ammonium bromide, dioctadecyl dimethyl ammonium bromide and D-alpha-tocopheryl polyethylene glycol.
Preferably, the oxidant used in the reaction system is oxygen, the pressure of which is 0.1-0.5MPa.
Preferably, the reaction temperature in the step (1) is 60-110 ℃ and the reaction time is 4-24h.
The invention has the beneficial effects that: the method has the advantages of simple synthesis steps, mild reaction conditions, simple post-treatment, higher reaction yield, wide application range and stronger industrial application prospect compared with the traditional synthesis method, and the method has the advantages of environmental protection compared with the traditional synthesis method.
Drawings
FIG. 1 is N-phenyl-3, 4-dihydroisoquinolinone prepared in example 1 1 H NMR spectrum;
FIG. 2 is a diagram of N-phenyl-3, 4-dihydroisoquinolinone prepared in example 1 13 CNMR spectra.
Detailed Description
The following describes in detail the examples of the present invention, which are implemented on the premise of the technical solution of the present invention, and detailed embodiments and specific operation procedures are given, but the scope of protection of the present invention is not limited to the following examples.
A method for promoting the oxidation of tetrahydroisoquinoline compounds to lactam compounds by using a surfactant, which is characterized by comprising the following steps: the method comprises the following steps:
step (1): taking an aryl substituted tetrahydroisoquinoline compound on nitrogen as a reaction substrate, dissolving a surfactant in pure water, then adding the reaction substrate, stirring and heating to react, wherein the reaction gas atmosphere is oxygen;
step (2): after the reaction is finished, the reaction system is restored to room temperature, an organic solvent is added to extract a crude product of the organic product, then the organic solvent is concentrated, and the obtained crude product of the organic product is separated and purified by column chromatography to obtain a final product.
The aryl substituent is any one of aromatic hydrocarbon, heterocyclic aromatic hydrocarbon and polycyclic aromatic hydrocarbon.
The dosage of the surfactant is 5-10% of the mass fraction of the tetrahydroisoquinoline compound substituted by the aryl on nitrogen.
The surfactant is any one of didodecyl dimethyl ammonium bromide, dioctadecyl dimethyl ammonium bromide and D-alpha-tocopheryl polyethylene glycol.
The oxidant used in the reaction system is oxygen, and the pressure of the oxygen is 0.1-0.5MPa.
The reaction temperature in the step (1) is 60-110 ℃ and the reaction time is 4-24h.
Example 1
Preparation method of N-phenyl-3, 4-dihydro-isoquinolone with structural formula as follows
To a 25mL pressure-resistant tube was added magneton, 1mL of pure water, 2.1mg (10 w.t.%) of didodecyl dimethyl ammonium bromide was dissolved in water, followed by 20.9mg (0.1 mmol) of the substrate N-phenyltetrahydroisoquinoline, and the mixture was added under 0.3MPa O 2 Stirring and reacting for 12h in an oil bath at 110 ℃ in a gas atmosphere, extracting the reaction liquid by using dichloromethane after the reaction is finished, and separating and purifying the crude product by column chromatography to obtain 21.2mg of target product. The product was found to have a structure of N-phenyl-3, 4-dihydroisoquinolinone by NMR and a yield of 95%. Target product characterization data: white solid. 1 H NMR(400MHz,CDCl 3 )δ8.19(dd,J＝7.7,1.1Hz,1H),7.53–7.33(m,6H),7.32–7.23(m,2H),4.07–3.90(m,2H),3.17(t,J＝6.4Hz,2H). 13 C NMR(101MHz,CDCl 3 )δ164.25,143.13,138.34,132.08,129.73,128.95,128.77,127.23,126.99,126.29,125.36,49.45,28.65.MS(EI)m/z calcd for C 15 H 13 NO[M] + :223,found 223.
Example 2
Preparation method of N- (4-chloro-phenyl) -3, 4-dihydro-isoquinolone with structural formula as follows
To a 25mL pressure-resistant tube was added magneton, 1mL of pure water, 2.4mg (10 w.t.%) of didodecyl dimethyl ammonium bromide was dissolved in water, followed by 24.3mg (0.1 mmol) of the substrate N- (4-chloro-phenyl) tetrahydroisoquinoline, and the mixture was added under 0.3MPa O 2 Stirring and reacting for 24 hours in an oil bath at 110 ℃ in a gas atmosphere, extracting a reaction liquid by using methylene dichloride after the reaction is finished, and separating and purifying a crude product by column chromatography to obtain 17.9mg of a target product, wherein the yield is 70%.
Example 3
Preparation method of N- (4-methoxy-phenyl) -3, 4-dihydro-isoquinolone with structural formula as follows
To a 25mL pressure-resistant tube was added magneton, 1mL of pure water, 1.9mg (8 w.t.%) of dioctadecyl dimethyl ammonium bromide was dissolved in water, followed by 23.9mg (0.1 mmol) of the substrate N- (4-methoxy-phenyl) tetrahydroisoquinoline, at 0.2MPa O 2 Stirring and reacting for 8 hours in an oil bath at 90 ℃ in a gas atmosphere, extracting a reaction liquid by using methylene dichloride after the reaction is finished, and separating and purifying a crude product by column chromatography to obtain 18.2mg of a target product, wherein the yield is 72%.
Example 4
Preparation method of N-naphthyl-3, 4-dihydroisoquinolinone with structural formula as follows
To a 25mL pressure-resistant tube was added magneton, 1mL of pure water, 2.6mg (10 w.t.%) of didodecyl dimethyl ammonium bromide was dissolved in water, followed by 25.9mg (0.1 mmol) of the substrate N-naphthyl tetrahydroisoquinoline, and the mixture was added under 0.3MPa O 2 Stirring and reacting for 12h in an oil bath at 100 ℃ in a gas atmosphere, extracting the reaction liquid by using dichloromethane after the reaction is finished, and separating and purifying the crude product by column chromatography to obtain the target product 19.9mg, wherein the yield is 73%.
Example 5
Preparation method of N-pyridyl-3, 4-dihydro-isoquinolone with structural formula as follows
To a 25mL pressure-resistant tube was added magneton, 1mL of pure water, 1.1mg (5 w.t.%) of D-alpha-tocopheryl polyethylene glycol was dissolved in water, followed by 21mg (0.1 mmol) of the substrate N-pyridyltetrahydroisoquinoline, at 0.3MPa O 2 Stirring and reacting for 24 hours in an oil bath at 60 ℃ in a gas atmosphere, extracting a reaction liquid by using methylene dichloride after the reaction is finished, and separating and purifying a crude product by column chromatography to obtain 13.4mg of a target product, wherein the yield is 60%.
Example 6
Preparation method of N-pyridyl-3, 4-dihydro isoquinolone with structural formula as follows
To a 25mL pressure-resistant tube was added magneton, 1mL of pure water, 1.3mg (6w.t.%) of didodecyl dimethyl ammonium bromide was dissolved in water, followed by 21mg (0.1 mmol) of the substrate N-pyridyltetrahydroisoquinoline, and the mixture was added under 0.1MPa O 2 Stirring and reacting for 16h in an oil bath at 100 ℃ in a gas atmosphere, extracting the reaction liquid by using dichloromethane after the reaction is finished, and separating and purifying the crude product by column chromatography to obtain 14.6mg of a target product with the yield of 65%.
Example 7
Preparation method of N-pyridyl-3, 4-dihydro isoquinolone with structural formula as follows
To a 25mL pressure-resistant tube was added magneton, 1mL of pure water, 1.5mg (7w.t.%) of dioctadecyl dimethyl ammonium bromide was dissolved in water, followed by 21mg (0.1 mmol) of the substrate N-pyridyltetrahydroisoquinoline, and the mixture was stirred under 0.5MPa O 2 Stirring and reacting for 4 hours in an oil bath at 90 ℃ in a gas atmosphere, extracting a reaction liquid by using methylene dichloride after the reaction is finished, and separating and purifying a crude product by column chromatography to obtain 15.2mg of a target product, wherein the yield is 68%.
The reaction results of synthesizing isoquinolinones containing lactam fragments under different reaction conditions are shown in Table 1:
TABLE 1
What has been described above is merely some embodiments of the present invention. It will be apparent to those skilled in the art that various modifications and improvements can be made without departing from the spirit of the invention.
Claims (2)
1. A method for promoting the oxidation of tetrahydroisoquinoline compounds to lactam compounds by using a surfactant, which is characterized by comprising the following steps: the method comprises the following steps:
step (1): taking an aryl substituted tetrahydroisoquinoline compound on nitrogen as a reaction substrate, dissolving a surfactant in pure water, then adding the reaction substrate, stirring and heating to react, wherein the reaction gas atmosphere is oxygen;
step (2): after the reaction is finished, the reaction system is restored to room temperature, an organic solvent is added to extract a crude product of the organic product, then the organic solvent is concentrated, and the obtained crude product of the organic product is separated and purified by column chromatography to obtain a final product;
ar is any one of phenyl, p-chlorophenyl, p-methoxyphenyl, 1-naphthyl and 1-pyridyl;
the dosage of the surfactant is 5-10% of the mass fraction of the tetrahydroisoquinoline compound substituted by the aryl on nitrogen;
the surfactant is any one of didodecyl dimethyl ammonium bromide, dioctadecyl dimethyl ammonium bromide and D-alpha-tocopheryl polyethylene glycol;
the pressure of the oxygen is 0.1-0.5MPa.
2. The method for promoting the oxidation of tetrahydroisoquinoline compounds to lactam compounds by using the surfactant according to claim 1, wherein the method comprises the following steps: the reaction temperature of the step (1) is 60-110 ℃ and the reaction time is 4-24h.
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Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105153029A (en) * | 2015-08-27 | 2015-12-16 | 陕西师范大学 | Method for synthesizing isoquinoline ketone compounds |
| CN106588965A (en) * | 2015-10-15 | 2017-04-26 | 北京大学 | Urea peptidomimetic boric acid compound as well as pharmaceutical composition, preparation method and application thereof |
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2021
- 2021-11-05 CN CN202111318078.4A patent/CN114163385B/en active Active
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105153029A (en) * | 2015-08-27 | 2015-12-16 | 陕西师范大学 | Method for synthesizing isoquinoline ketone compounds |
| CN106588965A (en) * | 2015-10-15 | 2017-04-26 | 北京大学 | Urea peptidomimetic boric acid compound as well as pharmaceutical composition, preparation method and application thereof |
Non-Patent Citations (3)
| Title |
|---|
| Isoindolinone Synthesis: Selective Dioxane-Mediated Aerobic Oxidation of Isoindolines;Pawan Thapa，等;《The Journal of Organic Chemistry》;第84卷;第1025-1034页 * |
| Reaction of N-nitroaryl-1,2,3,4-tetrahydroisoquinoline derivatives with oxygen;Shawcross, A. P.，等;《Journal of Heterocyclic Chemistry》;第27卷(第2期);第367-369页 * |
| Thiyl radical promoted iron-catalyzed-selective oxidation of benzylic sp3 C–H bonds with molecular oxygen;Shasha Geng，等;《Chem. Commun.》;第55卷;第12699-12702页 * |
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