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
room temperature
rhodium
phenyl
ruthenium
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)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
  • Catalysts (AREA)

Abstract

本发明公开了一种室温光照促进的3,4‑二取代异喹啉衍生物绿色合成方法，以水与聚乙二醇400作混合溶剂，苯基肟类化合物与非末端炔为原料，在光照下，于室温合成3,4‑二取代异喹啉衍生物。本发明为一类过渡金属催化的C‑H偶联反应，可简单高效地进行异喹啉衍生物的绿色合成。本发明相比于传统方法，更安全经济、环境友好；官能团容忍性好，收率高；无需额外的光催化剂与氧化剂，降低了成本；副产物为H2O，避免了产生大量废弃物，提高了原子利用率；无需进行底物的预活化并且反应室温进行，降低了操作难度。本发明可以简单快速地补充具有生物活性的异喹啉环的衍生物分子库，从而帮助筛选并发现新的药物候选分子。The invention discloses a green synthesis method of 3,4-disubstituted isoquinoline derivatives promoted by room temperature illumination. Water and polyethylene glycol 400 are used as mixed solvents, and phenyl oxime compounds and non-terminal alkynes are used as raw materials. Under illumination, 3,4-disubstituted isoquinoline derivatives were synthesized at room temperature. The invention is a transition metal-catalyzed C-H coupling reaction, which can simply and efficiently conduct green synthesis of isoquinoline derivatives. Compared with the traditional method, the method is safer, more economical and environmentally friendly; the functional group tolerance is good, and the yield is high; no additional photocatalyst and oxidant are needed, and the cost is reduced ; The atom utilization rate is improved; the pre-activation of the substrate is not required and the reaction is carried out at room temperature, which reduces the difficulty of operation. The invention can simply and quickly supplement the molecular library of derivatives of the isoquinoline ring with biological activity, thereby helping to screen and discover 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)

1.一种室温光照促进的3,4-二取代异喹啉衍生物绿色合成方法，其特征在于以水与聚乙二醇400作混合溶剂，苯基肟类化合物与非末端炔为原料，在光照作用下，于室温合成3,4-二取代异喹啉衍生物，其化学反应式为：1. a 3,4-disubstituted isoquinoline derivative green synthetic method promoted by light at room temperature is characterized in that with water and polyethylene glycol 400 as mixed solvent, phenyl oxime compounds and non-terminal alkynes are raw materials, Under the action of light, 3,4-disubstituted isoquinoline derivatives were synthesized at room temperature. The chemical reaction formula is:
Figure 487158DEST_PATH_IMAGE001
Figure 487158DEST_PATH_IMAGE001
 其中，in, R1为氢、卤素、烷基、苯基、烷氧基、羰基、醛基、羧基、氰基、烷酰氧基、酰胺基中的一种；R 1 is one of hydrogen, halogen, alkyl, phenyl, alkoxy, carbonyl, aldehyde, carboxyl, cyano, alkanoyloxy and amide; R2为氢、烷基、苯基、烷氧基中的一种；R 2 is one of hydrogen, alkyl, phenyl and alkoxy; R3、R4为烷基、苄基、苯基、取代芳基、杂芳基中的一种或两种。R 3 and R 4 are one or both of alkyl, benzyl, phenyl, substituted aryl and heteroaryl. 2.根据权利要求1所述的3,4-二取代异喹啉衍生物绿色合成方法，其特征在于采用如下制备步骤：2. 3,4-disubstituted isoquinoline derivatives green synthesis method according to claim 1 is characterized in that adopting following preparation steps: 在洁净的石英反应器中加入苯基肟类化合物、非末端炔类化合物、催化剂、水/聚乙二醇400（1:1），在光化学反应仪中室温搅拌24小时；反应完全后，加入饱和食盐水与乙酸乙酯萃取，乙酸乙酯层经减压蒸馏除去溶剂，残留物采用硅胶柱层析分离纯化即得产品。Add phenyl oxime compound, non-terminal alkyne compound, catalyst, water/polyethylene glycol 400 (1:1) into a clean quartz reactor, and stir at room temperature in a photochemical reactor for 24 hours; after the reaction is complete, add Saturated brine and ethyl acetate were extracted, the ethyl acetate layer was distilled under reduced pressure to remove the solvent, and the residue was separated and purified by silica gel column chromatography to obtain the product. 3.根据权利要求2所述的制备方法，其特征在于所述催化剂为醋酸铑、乙酰丙酮三苯基膦羰基铑、双环辛烯氯化铑二聚体、五甲基环戊二烯基合醋酸铑、二氯（五甲基环戊二烯基）合铑二聚体、二氯（五甲基环戊二烯基）合铑二聚体、三氯化钌、三苯基膦氯化钌、二氯二羰基双三苯基膦钌、双（2-甲基烯丙基）（1,5-环辛二烯）钌、对伞花烃二氯化钌二聚体、乙酰乙酰钴、二氯（五甲基环戊二烯基）合钴二聚体、五甲基环戊二烯基羰基二碘化钴、二(六氟锑酸)三乙腈(五甲基环戊二烯基)钴、三氯化铱、二氯(五甲基环戊二烯)合铱二聚体、双（1,5-环辛二烯）氯化铱二聚体、甲氧基（环辛二烯）合铱二聚体中的一种或一种以上。3. preparation method according to claim 2 is characterized in that described catalyzer is rhodium acetate, triphenylphosphine carbonyl rhodium acetylacetonate, bicyclooctene rhodium chloride dimer, pentamethylcyclopentadienyl compound Rhodium acetate, dichloro(pentamethylcyclopentadienyl) rhodium dimer, dichloro(pentamethylcyclopentadienyl) rhodium dimer, ruthenium trichloride, triphenylphosphine chloride Ruthenium, dichlorodicarbonylbistriphenylphosphine ruthenium, bis(2-methallyl)(1,5-cyclooctadiene)ruthenium, p-cymene ruthenium dichloride dimer, acetoacetyl cobalt , Dichloro (pentamethyl cyclopentadienyl) cobalt dimer, pentamethyl cyclopentadienyl carbonyl cobalt diiodide, bis (hexafluoroantimonic acid) triacetonitrile (pentamethyl cyclopentadiene base) cobalt, iridium trichloride, dichloro(pentamethylcyclopentadiene) iridium dimer, bis(1,5-cyclooctadiene) iridium chloride dimer, methoxy (cyclooctadiene) Diene) one or more of iridium dimers. 4.根据权利要求2所述的制备方法，其特征在于所述光照条件为选用以高压汞灯、氙灯、金卤灯、发光二极管（LED灯）中的一种或一种以上为光发生装置的光化学反应仪。4. The preparation method according to claim 2, wherein the illumination condition is to select one or more of high pressure mercury lamp, xenon lamp, metal halide lamp, light emitting diode (LED lamp) as the light generating device photochemical reactor. 5.根据权利要求2所述的制备方法，其特征在于所述水与聚乙二醇400作混合溶剂的混合比例为1:1。5. preparation method according to claim 2 is characterized in that the mixing ratio that described water and polyethylene glycol 400 make 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 (4)

* 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
CN116693418A (en) * 2023-05-12 2023-09-05 四川大学 Method for C-3 cyanoalkylation of 2-amino-1, 4-naphthoquinone compounds induced 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 (7)

* 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
CN116693418A (en) * 2023-05-12 2023-09-05 四川大学 Method for C-3 cyanoalkylation of 2-amino-1, 4-naphthoquinone compounds induced by visible light
CN116693418B (en) * 2023-05-12 2025-01-03 四川大学 Method for C-3 cyanoalkylation of 2-amino-1, 4-naphthoquinone compounds induced 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
Huang et al. Nickel‐Catalyzed [2+ 2] Cycloaddition of Alkynes with Activated Cyclic Alkenes: Synthesis and Novel Ring Expansion Studies of Cyclobutene Products
CN108276287B (en) Synthesis method of 4-oxo acrylate derivative catalyzed by visible light
CN110117260B (en) Preparation method of 3-alkyl quinoxaline-2 (1H) -ketone compound
Boddaert et al. Organocatalytic Activity of N‐Heterocyclic Carbenes in the Michael Addition of 1, 3‐Dicarbonyl Compounds: Application to a Stereoselective Spirocyclization Sequence
CN106513048A (en) Catalyst for nonterminal olefin hydroformylation reaction and preparation method and application of catalyst
Zhang et al. Cationic Pd (II)-catalyzed arylative cyclization of N-(2-formylaryl) alkynamides: An efficient route to 2-quinolinones
Lang et al. First organophosphorus radical-mediated cyclisations to afford medium-sized rings: eight-membered lactones and seven-and eight-membered lactams
CN111072577B (en) Novel green synthesis method for efficiently synthesizing quinoxaline derivative through transition metal catalyzed carbene insertion/cyclization reaction
CN111718372A (en) Axial chiral phosphine-ene ligand and preparation method and application thereof
Arena et al. Rhodium‐Catalyzed Enantioselective Hydrogenation of (E)‐Enol Acetate Acids
CN108148021A (en) 2- imines (3H) furane derivative or thiophene derivant and its synthesis
Cicco et al. Cu-catalysed Chan–Evans–Lam reaction meets deep eutectic solvents: efficient and selective C–N bond formation under aerobic conditions at room temperature
CN114573512B (en) Method for synthesizing C2-difluoro alkyl benzimidazole derivative
CN109232420B (en) Method for synthesizing 6-sulfone methyl phenanthridine derivatives through visible light catalysis
CN111056890B (en) A method for preparing aryl ketones based on the free radical-radical coupling reaction of iron-catalyzed ketoacid decarboxylation and fatty aldehyde decarbonylation
CN109836383B (en) Method for preparing 3, 4-dihydroquinoline-2 (1H) -ketone compound
CN108191736B (en) 2, 3-disubstituted indole derivatives and preparation method thereof
CN113444041A (en) Method for synthesizing polysubstituted quinoline compound through photocatalysis
CN106349194A (en) Method for performing decarboxylated oxidative coupling on cinnamic acid derivatives and cyclic ethers
Wang et al. Palladium/Norbornene-Cocatalyzed Three-Component Synthesis of ortho-Acylated Benzonitriles
CN114773175B (en) Preparation method of chiral tertiary alcohol benzo-fused bicyclo [ m.3.0] alkanone compound
Yu et al. Rhodium-Catalyzed Aryl Migratory/Decarbonylation of Diaryl Ketones via the Activation of Unstrained C–C Bonds
CN112759616B (en) Tri-discoene carbene palladium compound and application thereof
Kamble et al. A remarkable HBF4-SiO2-catalyzed synthesis of acylals from aldehydes under solvent-free conditions

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
RJ01 Rejection of invention patent application after publication

Application publication date: 20200421