CN111039867A - Green synthesis method of 3, 4-disubstituted isoquinoline derivative promoted by room-temperature illumination - Google Patents

Green synthesis method of 3, 4-disubstituted isoquinoline derivative promoted by room-temperature illumination Download PDF

Info

Publication number
CN111039867A
CN111039867A CN201911262771.7A CN201911262771A CN111039867A CN 111039867 A CN111039867 A CN 111039867A CN 201911262771 A CN201911262771 A CN 201911262771A CN 111039867 A CN111039867 A CN 111039867A
Authority
CN
China
Prior art keywords
dimer
pentamethylcyclopentadienyl
room temperature
cobalt
phenyl
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Pending
Application number
CN201911262771.7A
Other languages
Chinese (zh)
Inventor
海俐
吴勇
管玫
吕松洋
贺茂遥
杨增豹
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Sichuan University
Original Assignee
Sichuan University
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Sichuan University filed Critical Sichuan University
Priority to CN201911262771.7A priority Critical patent/CN111039867A/en
Publication of CN111039867A publication Critical patent/CN111039867A/en
Pending legal-status Critical Current

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D217/00—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems
    • C07D217/02—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems with only hydrogen atoms or radicals containing only carbon and hydrogen atoms, directly attached to carbon atoms of the nitrogen-containing ring; Alkylene-bis-isoquinolines
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D217/00—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems
    • C07D217/12—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems with radicals, substituted by hetero atoms, attached to carbon atoms of the nitrogen-containing ring
    • C07D217/14—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems with radicals, substituted by hetero atoms, attached to carbon atoms of the nitrogen-containing ring other than aralkyl radicals
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D221/00—Heterocyclic compounds containing six-membered rings having one nitrogen atom as the only ring hetero atom, not provided for by groups C07D211/00 - C07D219/00
    • C07D221/02—Heterocyclic compounds containing six-membered rings having one nitrogen atom as the only ring hetero atom, not provided for by groups C07D211/00 - C07D219/00 condensed with carbocyclic rings or ring systems
    • C07D221/04—Ortho- or peri-condensed ring systems
    • C07D221/06—Ring systems of three rings
    • C07D221/14—Aza-phenalenes, e.g. 1,8-naphthalimide

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Catalysts (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)

Abstract

The invention discloses a green synthesis method of a 3, 4-disubstituted isoquinoline derivative promoted by room temperature illumination, which takes water and polyethylene glycol 400 as a mixed solvent, and a phenyl oxime compound and a non-terminal alkyne as raw materials to synthesize the 3, 4-disubstituted isoquinoline derivative at room temperature under illumination. The invention relates to a C-H coupling reaction catalyzed by transition metal, which can simply and efficiently carry out green synthesis of isoquinoline derivatives. Compared with the traditional method, the method is safer, more economical and more environment-friendly; the tolerance of the functional group is good, and the yield is high; extra photocatalyst and oxidant are not needed, so that the cost is reduced; the by-product is H2O, avoids generating a large amount of waste, and improves the atom utilization rate; the preactivation of the substrate is not needed and the reaction is carried out at room temperature, thus reducing the operation difficulty. The invention can be simple and quickThe library of biologically active isoquinoline ring derivative molecules is supplemented to aid in the screening and discovery of new drug candidate molecules.

Description

Green synthesis method of 3, 4-disubstituted isoquinoline derivative promoted by room-temperature illumination
Technical Field
The invention belongs to the technical field of organic synthetic chemistry, and relates to a green synthesis method of a 3, 4-disubstituted isoquinoline derivative promoted by room-temperature illumination.
Background
Isoquinoline and derivatives thereof are important N-heterocyclic compounds, and are a very important class of medicines, natural products, active biomolecules and the like. The research on the synthetic method is highly valued by the academic and industrial circles at home and abroad [ see: (a) g, O' Donnell, R. Poeschl, O. Zimhony, M. Gunaratnam, J.B.C. Moreira, S.Neidle, D. Evangelopoulos, S. Bhakta, J.P. Malkinson, H.I. Boshoff, A.Lenaerts and S. Gibbons,J. Nat. Prod., 2009,72, 360；(b) J. A. Bull, J. J.Mousseau, G. Pelletier and A. B. Charette,Chem. Rev., 2012,112, 2642.]. At present, the transition metal catalyzed C-H coupling reaction is an excellent method for synthesizing isoquinoline in organic chemistry due to its stepwise high efficiency and atom economy [ see: (a) r, He, Z.T. Huang, Q.Y. Zheng and C. Wang,Angew. Chem., Int. Ed., 2014,53, 4950；(b) D. Zhao, F. Lied and F. Glorius,Chem. Sci., 2014,5, 2869；(c) X. L. Wu and L. Dong,Org. Lett., 2018,20, 6990.]. However, most of these studies have so far focused on the search for novel catalysts or the development of distinctive substrates. However, studies on the environmental friendliness of the reaction, such as avoiding the use or recycling of a catalyst, avoiding the use of an oxidizing agent, avoiding the use of an organic solvent, and the like, have been rarely reported. In current chemical synthesis, chemists are increasingly concerned about the development of environmental protection and sustainable technologies. Therefore, the development of a green, simple and efficient isoquinoline synthesis strategy is urgently needed. Methods for green synthesis of isoquinoline that have been reported so far include: (1) the Li topic group reports a novel cobalt catalyst and its use in the photoreaction synthesis of isoquinoline derivatives [ see: W.F. Tian, D.P. Wang, S.F. Wang, K.H. He, X.P. Caoand Y. Li,Org. Lett., 2018,20, 1421.]the Sundararaju subject group successfully synthesizes isoquinolone derivatives under photoreaction by cobalt catalysis [ see: D. kalsi, S. Dutta, N. Barsu, M. Rueping and dB. Sundararaju,ACS Catal., 2018,8, 8115.](3) Kotora topic group developed a method for synthesizing benzisoquinoline derivatives under microwave conditions [ see: D.Frejka, J. Ulč, E. A. B. Kantchev, I. Císařová and M. Kotora,ACS Catal., 2018,8, 10290.]the Bhanage group synthesizes isoquinoline derivatives and isoquinolinone derivatives using polyethylene glycol as a solvent under microwave conditions, and realizes the recycling of the ruthenium catalyst [ see: D.S. Deshmukh, N. Gangwar and B.M. Bhanage,Eur. J. Org. Chem., 2019,2919.]. However, there is still a need to develop a safe, simple, efficient, low-cost, and environmentally friendly coupling reaction to construct isoquinoline derivatives.
Disclosure of Invention
Aiming at the problems in the prior art, the invention aims to provide an efficient, mild and environment-friendly green synthesis method of a 3, 4-disubstituted isoquinoline derivative. The green synthesis method of the 3, 4-disubstituted isoquinoline derivative promoted by room temperature illumination comprises the steps of taking water and polyethylene glycol 400 as a mixed solvent, taking phenyl oxime compounds and non-terminal alkyne as raw materials, and carrying out transition metal catalyzed C-H coupling reaction at room temperature under illumination to synthesize the 3, 4-disubstituted isoquinoline derivative. The invention solves the problems of long steps, harsh reaction conditions, low atom utilization rate, toxic organic solvent use, environmental pollution, high cost and the like in the traditional isoquinoline derivative synthesis, provides a preparation method which is milder, more effective and more environment-friendly than the existing reports, and the byproduct is only water, thereby greatly improving the atom utilization rate and having good application prospect.
The technical route of the invention takes phenyl oxime compound and non-terminal alkyne as raw materials, and the phenyl oxime compound and the non-terminal alkyne are directly coupled in one step under the conditions of illumination and room temperature. The chemical reaction formula is shown as follows:
Figure 808788DEST_PATH_IMAGE001
R1is one of hydrogen, halogen, alkyl, phenyl, alkoxy, carbonyl, aldehyde group, carboxyl, cyano, alkanoyloxy and amide; r2Is one of hydrogen, alkyl, phenyl and alkoxy; r3、R4Of alkyl, benzyl, phenyl, substituted aryl, heteroarylOne or two.
The green synthesis method of the 3, 4-disubstituted isoquinoline derivative is characterized by comprising the following preparation steps: adding a phenyl oxime compound, a non-terminal alkyne compound, a catalyst and water/polyethylene glycol 400 (1: 1) into a clean quartz reactor, and stirring for 24 hours at room temperature in a photochemical reactor; after completion of the reaction, saturated brine and ethyl acetate were added to conduct extraction. And distilling the ethyl acetate layer under reduced pressure to remove the solvent, and separating and purifying the residue by silica gel column chromatography to obtain the product.
Wherein the catalyst is rhodium acetate, acetylacetonatocarbonyltriphenylphosphine rhodium, dicyclooctenylrhodium chloride dimer, pentamethylcyclopentadienylrhodium acetate, dichloro (pentamethylcyclopentadienyl) rhodium dimer, ruthenium trichloride, triphenylphosphine ruthenium chloride, dichlorobis-triphenylphosphine ruthenium, bis (2-methylallyl) (1, 5-cyclooctadiene) ruthenium, one or more of p-cymene ruthenium dichloride dimer, cobalt acetoacetoxide, dichloro (pentamethylcyclopentadienyl) cobalt dimer, pentamethylcyclopentadienyl cobalt carbonyl diiodide, bis (hexafluoroantimonic acid) triethylenenitrile (pentamethylcyclopentadienyl) cobalt, iridium trichloride, dichloro (pentamethylcyclopentadienyl) iridium dimer, bis (1, 5-cyclooctadiene) iridium chloride dimer and methoxy (cyclooctadiene) iridium dimer.
Wherein, the illumination condition is a photochemical reaction instrument which takes one or more than one of a high-pressure mercury lamp, a xenon lamp, a metal halide lamp and a light-emitting diode (LED) lamp as a light generating device.
Wherein the mixing ratio of the water and the polyethylene glycol 400 as the mixed solvent is 1: 1.
Compared with the traditional reaction conditions, the invention is a green method for synthesizing the 3, 4-disubstituted isoquinoline derivative by taking water and polyethylene glycol 400 as a mixed solvent, a phenyl oxime compound and non-terminal alkyne as raw materials and carrying out a transition metal catalyzed C-H coupling reaction at room temperature under illumination, has a plurality of unique advantages and is embodied as follows:
1. the C-H coupling reaction is carried out at room temperature, and isoquinoline derivatives can be simply, conveniently and efficiently obtained;
2. the C-H coupling reaction takes water and polyethylene glycol as green solvents, and compared with the traditional organic solvent, the C-H coupling reaction has the advantages of low toxicity, incombustibility, good thermal stability and chemical stability, no generation of vapor pressure, excellent solubility and the like, and improves the reaction safety;
3. the synthetic route of the invention uses phenyl oxime compounds as raw materials, the reagent has higher safety and stability, and the byproduct generated in the reaction process is only water, thereby avoiding generating a large amount of waste and having higher atom economy and environmental friendliness.
Detailed description of the invention
The present invention will be further described with reference to specific embodiments to assist in understanding the invention. It is not intended that the scope of the invention be limited thereby, but rather that the invention be defined by the claims appended hereto.
Example 1: synthesis of 1-methyl-3, 4-diphenylisoquinoline
Figure 725929DEST_PATH_IMAGE002
Acetophenone oxime (27.0 mg, 0.20 mmol), tolane (42.7 mg, 0.24 mmol), pentamethylcyclopentadienyl rhodium (II) acetate (6.7 mg, 0.01 mmol), water (0.5 mL), polyethylene glycol 400 (0.5 mL), and a high-pressure mercury lamp as a light generator were sequentially added to a clean quartz reactor and stirred at room temperature for 24 hours in a photochemical reactor. After completion of the reaction, saturated brine (10 mL) and ethyl acetate (5 mL. times.3) were added to conduct extraction. The ethyl acetate layer was collected, the solvent was removed under reduced pressure, and the residue was separated and purified by silica gel column chromatography (petroleum ether/ethyl acetate = 50/1, v/v) to give the objective product 51.3 mg as a white solid in a yield of 87%. Melting point: 155-156oC；1H NMR (400 MHz, Chloroform-d) δ 8.23 – 8.18(m, 1H), 7.69 – 7.63 (m, 1H), 7.62 – 7.57 (m, 2H), 7.40 – 7.30 (m, 5H), 7.24– 7.15 (m, 5H), 3.08 (s, 3H).13C NMR (100 MHz, Chloroform-d) δ 157.7, 149.4,140.9, 137.5, 136.0, 131.4, 130.3, 129.9, 129.2, 128.2, 127.6, 127.1, 126.9,126.5, 126.2, 126.1, 125.5, 22.7. HRMS (ESI):m/zcalculated for C22H17NH+:296.1434, found: 296.1432。
Example 2: 1, 6-dimethyl-3, 4-diphenylisoquinoline
Figure 505666DEST_PATH_IMAGE003
4-methyl acetophenone oxime (33.0 mg, 0.20 mmol), tolane (42.7 mg, 0.24 mmol), acetic acid (pentamethylcyclopentadienyl) rhodium (II) (6.7 mg, 0.01 mmol), water (0.5 mL), polyethylene glycol 400 (0.5 mL), and a high-pressure mercury lamp as a light generator were sequentially added to a clean quartz reactor and stirred at room temperature in a photochemical reactor for 24 hours. After completion of the reaction, saturated brine (10 mL) and ethyl acetate (5 mL. times.3) were added to conduct extraction. The ethyl acetate layer was collected, the solvent was removed under reduced pressure, and the residue was separated and purified by silica gel column chromatography (petroleum ether/ethyl acetate = 50/1, v/v) to give the objective product 54.8 mg as a white solid in a yield of 89%. Melting point: 159-160oC；1H NMR (400 MHz, Chloroform-d) δ 8.08(d,J= 8.9 Hz, 1H), 7.42 – 7.38 (m, 2H), 7.37 – 7.29 (m, 5H), 7.23 – 7.13(m, 5H), 3.04 (d,J= 1.5 Hz, 3H), 2.42 (s, 3H).13C NMR (100 MHz, Chloroform-d) δ 157.4, 149.6, 141.2, 140.2, 137.8, 136.2, 131.5, 128.8, 128.7, 128.2,127.6, 127.0, 126.8, 125.5, 125.1, 124.6, 22.7, 22.2. HRMS (ESI):m/zcalculated for C23H19NH+: 310.1590, found: 310.1588。
Example 3: 6-chloro-1-methyl-3, 4-diphenylisoquinoline
Figure 838558DEST_PATH_IMAGE004
4-chloro-acetophenone oxime (3) is added into a clean quartz reactor in sequence3.8 mg, 0.20 mmol), tolane (42.7 mg, 0.24 mmol), dichloro (pentamethylcyclopentadienyl) rhodium (III) dimer (6.2 mg, 0.01 mmol), water (0.5 mL), polyethylene glycol 400 (0.5 mL), and a photochemical reaction apparatus with a high-pressure mercury lamp as the light generator, the chamber was stirred at room temperature for 24 hours. After completion of the reaction, saturated brine (10 mL) and ethyl acetate (5 mL. times.3) were added to conduct extraction. The ethyl acetate layer was collected, the solvent was removed under reduced pressure, and the residue was separated and purified by silica gel column chromatography (petroleum ether/ethyl acetate = 50/1, v/v) to give the objective product 54.2 mg as a pale yellow solid in a yield of 83%. Melting point: 172-173oC；1H NMR (400 MHz, Chloroform-d) δ8.13 (d,J= 8.9 Hz, 1H), 7.62 (d,J= 1.9 Hz, 1H), 7.52 (dd,J= 8.9, 2.1Hz, 1H), 7.38 – 7.32 (m, 5H), 7.19 (dtt,J= 6.5, 4.9, 2.6 Hz, 5H), 3.05 (s,3H).13C NMR (100 MHz, Chloroform-d) δ 157.7, 150.6, 140.5, 137.1, 136.8,136.4, 131.3, 130.2, 128.4, 127.6, 127.5, 127.4, 127.3, 127.2, 125.1, 124.4,22.7. HRMS (ESI):m/zcalculated for C22H17ClNH+: 330.1044, found: 330.1043。
Example 4: 2, 3-diphenyl-8, 9-dihydro-7H-benzo [ de ]]Quinolines
Figure 652931DEST_PATH_IMAGE005
The method comprises the steps of sequentially adding benzocyclohexane-1-ketoxime (32.2 mg, 0.20 mmol), tolane (42.7 mg, 0.24 mmol), dichloro (pentamethylcyclopentadienyl) rhodium (III) dimer (6.2 mg, 0.01 mmol), water (0.5 mL), polyethylene glycol 400 (0.5 mL) and a high-pressure mercury lamp into a clean quartz reactor, and stirring the mixture for 24 hours in a photochemical reaction instrument chamber of a light generation device at a constant temperature. After completion of the reaction, saturated brine (10 mL) and ethyl acetate (5 mL. times.3) were added to conduct extraction. The ethyl acetate layer was collected, the solvent was removed under reduced pressure, and the residue was separated and purified by silica gel column chromatography (petroleum ether/ethyl acetate = 50/1, v/v) to give the objective product 50.2 mg as a bright yellow solid in a yield of 79%. Melting point: 147-148oC；1H NMR (400 MHz, Chloroform-d)δ 7.49 (d,J= 3.9 Hz, 1H), 7.48 (s, 1H), 7.40 – 7.28 (m, 6H), 7.23 (dt,J=7.1, 1.8 Hz, 2H), 7.21 – 7.13 (m, 3H), 3.43 – 3.37 (m, 2H), 3.21 (t,J= 6.1Hz, 2H), 2.29 (p,J= 6.3 Hz, 2H).13C NMR (100 MHz, Chloroform-d) δ 159.3,149.5, 141.1, 138.5, 137.8, 136.3, 131.4, 130.3, 130.0, 129.1, 128.2, 127.6,127.0, 126.9, 124.8, 123.9, 123.6, 34.8, 30.8, 23.5. HRMS (ESI):m/zcalculated for C24H19NH+: 322.1596, found: 322.1596。
Example 5: 1,3, 4-triphenylisoquinoline
Figure 475393DEST_PATH_IMAGE006
Benzophenone oxime (39.4 mg, 0.20 mmol), tolane (42.7 mg, 0.24 mmol), bis (hexafluoroantimonic acid) triacetonitrile (pentamethylcyclopentadienyl) cobalt (III) (5.6 mg, 0.01 mmol), water (0.5 mL), polyethylene glycol 400 (0.5 mL), and a high-pressure mercury lamp were sequentially added to a clean quartz reactor and stirred at room temperature for 24 hours in a photochemical reactor of a light generator. After completion of the reaction, saturated brine (10 mL) and ethyl acetate (5 mL. times.3) were added to conduct extraction. The ethyl acetate layer was collected, the solvent was removed under reduced pressure, and the residue was separated and purified by silica gel column chromatography (petroleum ether/ethyl acetate = 50/1, v/v) to give the objective product 56.6 mg as a yellow solid in a yield of 80%. Melting point: 169-171oC；1H NMR (400 MHz, Chloroform-d) δ8.20 (d,J= 8.4 Hz, 1H), 7.87 – 7.82 (m, 2H), 7.74 (d,J= 8.2 Hz, 1H), 7.63– 7.49 (m, 5H), 7.46 – 7.35 (m, 5H), 7.32 (dd,J= 7.5, 1.5 Hz, 2H), 7.23 –7.15 (m, 3H).13C NMR (100 MHz, Chloroform-d) δ 158.8, 148.6, 139.8, 138.7,136.5, 135.9, 130.3, 129.4, 129.2, 128.9, 128.7, 127.5, 127.3, 127.3, 126.5,126.5, 126.3, 126.0, 125.6, 125.0, 124.4. HRMS (ESI):m/zcalculated forC27H19NH+: 358.1596, found: 358.1596。
Example 6: 3, 4-bis (4-methoxyphenyl) -1-methylisoquinoline
Figure 742426DEST_PATH_IMAGE007
Acetophenone oxime (27.0 mg, 0.20 mmol), bis (4-methoxyphenyl) acetylene (57.1 mg, 0.24 mmol), bis (2-methallyl) (1, 5-cyclooctadiene) ruthenium (II) (3.2 mg, 0.01 mmol), water (0.5 mL), polyethylene glycol 400 (0.5 mL), and a high-pressure mercury lamp were sequentially added to a clean quartz reactor and stirred at an internal chamber of a photochemical reactor of a light generator for 24 hours. After completion of the reaction, saturated brine (10 mL) and ethyl acetate (5 mL. times.3) were added to conduct extraction. The ethyl acetate layer was collected, the solvent was removed under reduced pressure, and the residue was separated and purified by silica gel column chromatography (petroleum ether/ethyl acetate = 50/1, v/v) to give the objective product 62.9 mg as a yellow solid in a yield of 89%. Melting point: 115-116oC；1H NMR (400 MHz,Chloroform-d) δ 8.18 (dd,J= 5.6, 3.8 Hz, 1H), 7.72 – 7.64 (m, 1H), 7.61 –7.53 (m, 2H), 7.34 (d,J= 8.7 Hz, 2H), 7.15 (d,J= 8.5 Hz, 2H), 6.92 (d,J= 8.5 Hz, 2H), 6.76 (d,J= 8.7 Hz, 2H), 3.85 (s, 3H), 3.77 (s, 3H), 3.07 (s,3H).13C NMR (100 MHz, Chloroform-d) δ 158.6, 158.6, 157.4, 149.1, 136.5,133.6, 132.4, 131.5, 129.9, 129.8, 128.3, 126.3, 126.2, 126.0, 125.5, 113.8,113.2, 55.2, 55.2, 22.7. HRMS (ESI):m/zcalculated for C24H21NO2H+: 356.1651,found: 356.1652。
Example 7: 1-methyl-3, 4-diethylisoquinoline
Figure 128277DEST_PATH_IMAGE008
Acetophenone oxime (27.0 mg, 0.20 mmol), 3-decyne (19.7 mg, 0.24 mmol), dichloro (pentamethylcyclopentadienyl) iridium (III) dimer (8.0 mg, 0.01 mmol), water (0.5 mL), and polyethylene glycol were added sequentially to a clean quartz reactorAlcohol 400 (0.5 mL), high pressure mercury lamp as light generator photochemical reaction instrument chamber temperature stirring 24 hours. After completion of the reaction, saturated brine (10 mL) and ethyl acetate (5 mL. times.3) were added to conduct extraction. The ethyl acetate layer was collected, the solvent was removed under reduced pressure, and the residue was separated and purified by silica gel column chromatography (petroleum ether/ethyl acetate = 50/1, v/v) to give the objective product 29.9mg as a yellow solid in a yield of 75%. Melting point: 123-124oC；1H NMR (400 MHz, Chloroform-d) δ 8.07 (d,J= 8.3 Hz, 1H), 7.97 (d,J= 8.5 Hz, 1H), 7.65 (ddd,J= 8.4, 6.8, 1.2 Hz,1H), 7.49 (ddd,J= 8.1, 6.9, 1.0 Hz, 1H), 3.04 (q,J= 7.6 Hz, 2H), 2.97 (q,J= 7.6 Hz, 2H), 2.91 (s, 3H), 1.34 (t,J= 7.6 Hz, 3H), 1.28 (t,J= 7.6 Hz,3H).13C NMR (100 MHz, Chloroform-d) δ 155.8, 152.6, 135.2, 129.5, 127.2,126.2, 126.1, 125.3, 123.4, 28.5, 22.4, 20.7, 15.3, 15.0. HRMS (ESI):m/zcalculated for C14H17NH+: 200.1439, found: 200.1439。

Claims (5)

1. A room temperature illumination-promoted green synthesis method of 3, 4-disubstituted isoquinoline derivatives is characterized in that water and polyethylene glycol 400 are used as mixed solvents, phenyl oxime compounds and non-terminal alkyne are used as raw materials, and the 3, 4-disubstituted isoquinoline derivatives are synthesized at room temperature under the illumination effect, and the chemical reaction formula is as follows:
Figure 487158DEST_PATH_IMAGE001
wherein,
R1is one of hydrogen, halogen, alkyl, phenyl, alkoxy, carbonyl, aldehyde group, carboxyl, cyano, alkanoyloxy and amide;
R2is one of hydrogen, alkyl, phenyl and alkoxy;
R3、R4is one or two of alkyl, benzyl, phenyl, substituted aryl and heteroaryl.
2. The green synthesis method of 3, 4-disubstituted isoquinoline derivatives as claimed in claim 1, characterized by the following preparation steps:
adding a phenyl oxime compound, a non-terminal alkyne compound, a catalyst and water/polyethylene glycol 400 (1: 1) into a clean quartz reactor, and stirring for 24 hours at room temperature in a photochemical reactor; after the reaction is completed, adding saturated salt water and ethyl acetate for extraction, removing the solvent from an ethyl acetate layer through reduced pressure distillation, and separating and purifying the residue by silica gel column chromatography to obtain the product.
3. The process according to claim 2, wherein the catalyst is rhodium acetate, triphenylphosphine carbonyl rhodium acetylacetonate, dicyclooctene rhodium chloride dimer, pentamethylcyclopentadienyl rhodium acetate, dichloro (pentamethylcyclopentadienyl) rhodium dimer, ruthenium trichloride, triphenylphosphine ruthenium chloride, dichlorobis-triphenylphosphine ruthenium, bis (2-methylallyl) (1, 5-cyclooctadiene) ruthenium, p-cymene ruthenium dichloride dimer, cobalt acetoacetoxide, dichloro (pentamethylcyclopentadienyl) cobalt dimer, pentamethylcyclopentadienyl cobalt diiodide, bis (hexafluoroantimonate) triethylenenitrile (pentamethylcyclopentadienyl) cobalt, iridium trichloride, dichloro (pentamethylcyclopentadienyl) iridium dimer, bis (1, 5-cyclooctadiene) iridium chloride dimer, cobalt trichloride, or a mixture thereof, One or more of methoxyl (cyclooctadiene) iridium dimer.
4. The method according to claim 2, wherein the light irradiation condition is a photochemical reaction apparatus using one or more light generating devices selected from a high-pressure mercury lamp, a xenon lamp, a metal halide lamp, and a light emitting diode (LED lamp).
5. The method according to claim 2, wherein the mixing ratio of the water to the polyethylene glycol 400 as the mixed solvent is 1: 1.
CN201911262771.7A 2019-12-11 2019-12-11 Green synthesis method of 3, 4-disubstituted isoquinoline derivative promoted by room-temperature illumination Pending CN111039867A (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
CN201911262771.7A CN111039867A (en) 2019-12-11 2019-12-11 Green synthesis method of 3, 4-disubstituted isoquinoline derivative promoted by room-temperature illumination

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
CN201911262771.7A CN111039867A (en) 2019-12-11 2019-12-11 Green synthesis method of 3, 4-disubstituted isoquinoline derivative promoted by room-temperature illumination

Publications (1)

Publication Number Publication Date
CN111039867A true CN111039867A (en) 2020-04-21

Family

ID=70235534

Family Applications (1)

Application Number Title Priority Date Filing Date
CN201911262771.7A Pending CN111039867A (en) 2019-12-11 2019-12-11 Green synthesis method of 3, 4-disubstituted isoquinoline derivative promoted by room-temperature illumination

Country Status (1)

Country Link
CN (1) CN111039867A (en)

Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN113402516A (en) * 2021-06-04 2021-09-17 四川大学 Method for synthesizing isoquinolone derivative by room-temperature C-H activation/cyclization cascade reaction of N-chloroamide
CN114014807A (en) * 2021-12-02 2022-02-08 天津力生制药股份有限公司 Preparation method of key intermediate of roxasistat
CN114957089A (en) * 2022-06-27 2022-08-30 兰州大学 Method for green synthesis of aza spiro oxime compound driven by visible light

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB1457186A (en) * 1973-02-24 1976-12-01 Hoechst Ag Isoquinoline derivatives and process for their manufacture
CN107382856A (en) * 2017-07-04 2017-11-24 江苏理工学院 New multi-substituted isoquinoline derivative and its synthetic method
CN110066246A (en) * 2019-06-05 2019-07-30 哈尔滨工业大学 A method of preparing isoquinoline-1-ketone derivative

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB1457186A (en) * 1973-02-24 1976-12-01 Hoechst Ag Isoquinoline derivatives and process for their manufacture
CN107382856A (en) * 2017-07-04 2017-11-24 江苏理工学院 New multi-substituted isoquinoline derivative and its synthetic method
CN110066246A (en) * 2019-06-05 2019-07-30 哈尔滨工业大学 A method of preparing isoquinoline-1-ketone derivative

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
RAFAEL ALONSO等: "New Light-Induced Iminyl Radical Cyclization Reactions of Acyloximes to Isoquinolines", 《ORGANIC LETTERS》 *

Cited By (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN113402516A (en) * 2021-06-04 2021-09-17 四川大学 Method for synthesizing isoquinolone derivative by room-temperature C-H activation/cyclization cascade reaction of N-chloroamide
CN113402516B (en) * 2021-06-04 2022-11-01 四川大学 Method for synthesizing isoquinolone derivative by room-temperature C-H activation/cyclization cascade reaction of N-chloroamide
CN114014807A (en) * 2021-12-02 2022-02-08 天津力生制药股份有限公司 Preparation method of key intermediate of roxasistat
CN114014807B (en) * 2021-12-02 2023-01-17 天津力生制药股份有限公司 Preparation method of key intermediate of roxasistat
CN114957089A (en) * 2022-06-27 2022-08-30 兰州大学 Method for green synthesis of aza spiro oxime compound driven by visible light

Similar Documents

Publication Publication Date Title
CN111039867A (en) Green synthesis method of 3, 4-disubstituted isoquinoline derivative promoted by room-temperature illumination
CN108276287B (en) Synthesis method of 4-oxo acrylate derivative catalyzed by visible light
CN110105305B (en) Transition metal catalyzed C-H activation/cyclization synthesis 1,2-benzothiazine derivative green synthesis method
CN109988117A (en) The preparation method of a kind of 3- methyl-quinoxaline -2 (1H) -one analog derivative
CN108299296B (en) Preparation method of phenanthridine heterocyclic compound
Zhang et al. Recyclable alkylated Ru (bpy) 32+ complex as a visible-light photoredox catalyst for perfluoroalkylation
CN114031542A (en) Novel preparation method of azabicyclo medical intermediate
Lang et al. First organophosphorus radical-mediated cyclisations to afford medium-sized rings: eight-membered lactones and seven-and eight-membered lactams
CN108059610B (en) Preparation method of 3-acyl spiro-trienone compound
KR20180120730A (en) Method for producing fluorine-containing compound
CN111808023B (en) Method for preparing 3-aryl isoquinoline derivative
CN108148021B (en) 2-imine (3H) polysubstituted furan or thiophene derivative and synthesis thereof
CN115215814A (en) Synthetic method of isoxazolidine compounds
CN113214273B (en) Synthesis method of tetrahydrofuran indole compound
CN114573512A (en) Method for synthesizing C2-difluoroalkyl benzimidazole derivative
CN111362795B (en) Preparation method of substituted butyrate derivatives
CN109232420B (en) Method for synthesizing 6-sulfone methyl phenanthridine derivatives through visible light catalysis
CN108191736B (en) 2, 3-disubstituted indole derivatives and preparation method thereof
CN106349194A (en) Method for performing decarboxylated oxidative coupling on cinnamic acid derivatives and cyclic ethers
CN107445835B (en) Synthesis method of 1, 2-dihydro cyclobuteno [ a ] naphthalene derivative and precursor thereof
CN114773175B (en) Preparation method of chiral tertiary alcohol benzo-fused bicyclo [ m.3.0] alkanone compound
CN110540516A (en) Preparation method of 1-sulfonylmethyl-3, 4-dihydronaphthalene
CN114773229B (en) 1,6 Diene compound and preparation method and application thereof
CN111732508B (en) Synthesis method of spiro compound
CN112441935B (en) Synthesis method of beta-aminoketone compound

Legal Events

Date Code Title Description
PB01 Publication
PB01 Publication
SE01 Entry into force of request for substantive examination
SE01 Entry into force of request for substantive examination
RJ01 Rejection of invention patent application after publication

Application publication date: 20200421

RJ01 Rejection of invention patent application after publication