CN113045496B - Method for selectively synthesizing dihydrophenanthridine or phenanthridine compounds - Google Patents

Method for selectively synthesizing dihydrophenanthridine or phenanthridine compounds Download PDF

Info

Publication number
CN113045496B
CN113045496B CN202110288940.5A CN202110288940A CN113045496B CN 113045496 B CN113045496 B CN 113045496B CN 202110288940 A CN202110288940 A CN 202110288940A CN 113045496 B CN113045496 B CN 113045496B
Authority
CN
China
Prior art keywords
compound
acid
dihydrophenanthridine
phenanthridine
nmr
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.)
Active
Application number
CN202110288940.5A
Other languages
Chinese (zh)
Other versions
CN113045496A (en
Inventor
张新迎
于彩云
徐园双
范学森
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.)
Henan Normal University
Original Assignee
Henan Normal 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 Henan Normal University filed Critical Henan Normal University
Priority to CN202110288940.5A priority Critical patent/CN113045496B/en
Publication of CN113045496A publication Critical patent/CN113045496A/en
Application granted granted Critical
Publication of CN113045496B publication Critical patent/CN113045496B/en
Active legal-status Critical Current
Anticipated expiration legal-status Critical

Links

Classifications

    • 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
    • C07D221/10—Aza-phenanthrenes
    • C07D221/12—Phenanthridines
    • 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
    • C07D221/18—Ring systems of four or more rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D491/00—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00
    • C07D491/02—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00 in which the condensed system contains two hetero rings
    • C07D491/10—Spiro-condensed systems
    • C07D491/107—Spiro-condensed systems with only one oxygen atom as ring hetero atom in the oxygen-containing ring

Landscapes

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

Abstract

The invention discloses a method for selectively synthesizing a dihydrophenanthridine compound 3 or a phenanthridine compound 4, belonging to the technical field of organic synthesis. Taking an o-aryl aniline compound 1 and an alkynoate compound 2 as raw materials, and carrying out a heating reaction in an organic solvent in the presence of a ruthenium catalyst, an additive and an acid to obtain a dihydrophenanthridine compound 3 or a phenanthridine compound 4; the invention has the following advantages: 1) the synthesis process is simple, and the dihydrophenanthridine or phenanthridine compound can be synthesized with high selectivity by starting from an o-aryl aniline compound and an alkynoate compound and changing the reaction temperature under the catalysis of a ruthenium catalyst; 2) the raw materials are cheap and easy to obtain, the reaction condition is mild, the operation is simple and convenient, and the application range of the substrate is wide.

Description

Method for selectively synthesizing dihydrophenanthridine or phenanthridine compounds
Technical Field
The invention belongs to the technical field of organic synthesis, and particularly relates to a method for selectively synthesizing dihydrophenanthridine or phenanthridine compounds.
Background
As an important nitrogen-containing fused heterocycle, a phenanthridine structural unit is widely existed in molecules of natural products, medicaments and functional materials. For example, chelerythrine, nitidine, and xanthonine are phenanthridine alkaloids, wherein chelerythrine has cytotoxic and antibacterial activities, and nitidine and xanthonine have significant anticancer activities.
In addition, the dihydrophenanthridine and the derivatives thereof are not only important organic synthesis intermediates, but also important components of bioactive natural products such as lycorine and chelidonine, and can be clinically used for emetic, anti-cancer and treatment of gastrointestinal colic, duodenal ulcer, rheumatoid arthritis, trauma, cancer pain and the like.
At present, some reports on synthetic methods of dihydrophenanthridine and phenanthridine compounds exist, but the literature methods still have certain limitations: such as difficult acquisition of raw materials, harsh reaction conditions, long synthesis route, single product structure, no universal applicability and the like.
Therefore, the research and development of a new method for selectively synthesizing the dihydrophenanthridine or phenanthridine compounds by starting from simple and easily available raw materials and changing reaction conditions have very important theoretical significance and practical prospect.
Disclosure of Invention
The invention solves the technical problem of providing a method for selectively synthesizing dihydrophenanthridine or phenanthridine compounds, selectively synthesizing the dihydrophenanthridine or phenanthridine compounds through the series reaction between the easily obtained o-aryl aniline compounds and the acetylenic acid ester compounds, and has the advantages of simple and easily obtained raw materials, simple and convenient operation, mild conditions, good selectivity, wide substrate application range and the like.
The invention adopts the following technical scheme for solving the technical problems, and the method for selectively synthesizing the dihydrophenanthridine 3 or phenanthridine compound 4 comprises the following operations: heating and reacting an o-aryl aniline compound 1 and an alkynoate compound 2 in an organic solvent in the presence of a ruthenium catalyst, an additive and an acid to obtain a dihydrophenanthridine compound 3 or a phenanthridine compound 4; the reaction equation is:
Figure BDA0002981426800000011
wherein R is1Is hydrogen, halogen, trifluoromethyl, benzyloxy, C1-4Alkyl or C1-4Alkoxy radical, R2Is hydrogen, halogen, trifluoromethyl, benzyloxy or C1-4Alkyl or C1-4Alkoxy radical, R3Is C1-6Chain alkyl or C1-6Chain-substituted alkyl, R4Is C1-4An alkyl group.
Further, in the above technical solution, in the substituents, halogen is selected from fluorine, chlorine, bromine or iodine.
Further, in the above technical scheme, the ruthenium catalyst is [ Ru (p-cymene) Cl2]2{ dichlorobis (4-methylisopropylphenyl) ruthenium (II) }. Other metal catalysts are used, such as: [ RhCp Cl ]2]2{ dichloro (pentamethylcyclopentadienyl) rhodium (III) dimer } or Pd (OAc)2{ Palladium acetate } etc., only a small amount of the target product was detected, using [ IrCp Cl ]2]2{ dichloro (pentamethylcyclopentadienyl) iridium (III) dimer } or CoCp (CO) I2{ pentamethylcyclopentadienylcarbonyldiiodocobalt } et al, the desired product was not detected in the reaction.
Further, in the above technical solution, the additive is silver hexafluoroantimonate, silver trifluoromethanesulfonate, silver tetrafluoroborate or bis-trifluoromethanesulfonylimide silver salt. Wherein, when the dihydrophenanthridine compound 3 is synthesized, the additive is preferably silver trifluoromethanesulfonate or silver tetrafluoroborate; when synthesizing the phenanthridine compound 4, the additive is preferably silver trifluoromethanesulfonate.
Further, in the above technical solution, the acid is acetic acid, pivalic acid, trifluoromethanesulfonic acid, 2,4, 6-trimethylbenzoic acid, trifluoroacetic acid, benzoic acid or chloroacetic acid, and preferably, the acid is acetic acid.
Further, in the above technical solution, the organic solvent plays a role of dissolving the raw material, but at the same time, it is also found that: when synthesizing the dihydrophenanthridine compound 3, the preferable solvent is Tetrahydrofuran (THF) or ethylene glycol dimethyl ether (DME); when synthesizing the phenanthridine compound 4, Tetrahydrofuran (THF) is a preferred solvent.
Further, in the technical scheme, the reaction temperature is 40-140 ℃. Research results show that the generation of the phenanthridine compound 4 is facilitated by increasing the temperature. Wherein the temperature is 40-80 deg.C and molecular sieve is added (for example
Figure BDA0002981426800000021
Molecular sieve), the reaction mainly obtains a dihydrophenanthridine compound 3; the temperature is 100-140 ℃, the phenanthridine compound 4 is mainly obtained through the reaction.
Further, in the technical scheme, the feeding molar ratio of the o-aryl aniline compound 1, the alkynoate compound 2, the additive, the acid and the ruthenium catalyst is 1:1-1.5:0.1-0.4:1.5-2: 0.025-0.075.
The invention has the beneficial effects that:
compared with the prior art, the invention has the following advantages: (1) the synthesis process is simple, and the dihydrophenanthridine or phenanthridine compound is synthesized from the o-aryl aniline compound and the acetylenic acid ester compound in a high-selectivity manner by changing the reaction temperature under the catalysis of a ruthenium catalyst; (2) the raw materials are cheap and easy to obtain, the reaction condition is mild, the operation is simple and convenient, and the application range of the substrate is wide.
Detailed Description
The above-mentioned contents of the present invention are further described in detail by the following examples, but it should not be understood that the scope of the above-mentioned subject matter of the present invention is limited to the following examples, and any technique realized based on the above-mentioned contents of the present invention falls within the scope of the present invention.
Example 1
Figure BDA0002981426800000031
To a 15mL pressure tube were added 1a (50.8mg,0.3mmol), 2a (44.1mg,0.45mmol), solvent (2mL), ruthenium catalyst (0.015mmol), additive (0.06mmol), acid (0.6mmol) and
Figure BDA0002981426800000032
and (3) sealing the pressure-resistant pipe under the protection of argon by using a molecular sieve (50mg), and stirring and reacting at a certain temperature. After the reaction is finished, saturated NaHCO is used3The solution is quenched, filtered with suction, extracted with ethyl acetate (10 mL. times.3), the organic phases are combined and washed successively with water and saturated sodium chloride solution, anhydrous Na2SO4Drying, spinning drying and silica gel column separation (petroleum ether/ethyl acetate 20/1 to petroleum ether/ethyl acetate 10/1) to obtain the product 3a and/or 4 a.
A series of reaction results were obtained by changing reaction conditions such as catalyst, additive, acid species, solvent, temperature and equivalent ratio between reactants, and the like, for the reaction, as shown in Table 1.
TABLE 1 Synthesis of 3a and 4a under different reaction conditions a
Figure BDA0002981426800000033
Figure BDA0002981426800000041
Example 2
Adding 1a (50.8mg,0.3mmol) and,2a (44.1mg,0.45mmol), tetrahydrofuran (2mL), dichlorobis (4-methylisopropylphenyl) ruthenium (II) ([ Ru (p-cymene) Cl)2]29.2mg, 0.015mmol), silver trifluoromethanesulfonate (15.4mg,0.06mmol), acetic acid (34.3. mu.L, 0.6mmol) and
Figure BDA0002981426800000042
MS (50mg), then the pressure tube was sealed under argon protection and placed in a 60 ℃ oil bath to stir the reaction for 24 hours. After the reaction is finished, saturated NaHCO is used3The solution was quenched, filtered with suction, extracted with ethyl acetate (10 mL. times.3), the organic phases were combined and washed successively with water and saturated sodium chloride solution, anhydrous Na2SO4Drying, spin-drying and separation on silica gel (petrol ether/ethyl acetate 20/1) gave product 3a as a white solid (50.5mg, 63%). Characterization data for this compound are:1H NMR(CDCl3,400MHz):δ7.73(d,J＝8.0Hz,1H), 7.68(d,J＝7.6Hz,1H),7.32-7.23(m,3H),7.12(t,J＝7.2Hz,1H),6.83(t,J＝7.2 Hz,1H),6.72(d,J＝7.6Hz,1H),4.93(s,1H),3.61(s,3H),2.85(d,J＝15.2Hz,1H), 2.40(d,J＝15.2Hz,1H),1.71(s,3H).13C{1H}NMR(CDCl3,100MHz):δ172.1, 143.0,138.9,130.8,129.1,127.7,127.5,123.4,123.3,122.8,121.3,119.3,116.0, 54.5,51.5,43.3,25.7.HRMS(ESI)m/z:[M+H]+Calcd for C17H18NO2 268.1332； Found 268.1329.
example 3
A variety of dihydrophenanthridines 3 were synthesized by varying reactants 1 and 2 according to the method and procedure of example 2, with the specific results shown in Table 2.
TABLE 2 Synthesis of various dihydrophenanthridines 3a,b
Figure BDA0002981426800000051
aReaction conditions of 1(0.3mmol),2(0.45mmol), [ Ru (p-cymene) Cl2]2(0.015mmol),AgOTf (0.06mmol),AcOH(0.6mmol),
Figure BDA0002981426800000052
MS (50mg), THF (2mL), argon atmosphere, 60 ℃,24h.bThe isolation yield.
Representative product characterization data are as follows:
Methyl 2-(8-methoxy-6-methyl-5,6-dihydrophenanthridin-6-yl)acetate(3d)
Yellowish solid(58.0mg,65％).1H NMR(CDCl3,400MHz):δ7.74(d,J＝8.4Hz, 1H),7.67(dd,J1＝7.6Hz,J2＝0.8Hz,1H),7.15(td,J1＝7.6Hz,J2＝1.2Hz,1H), 6.94(dd,J1＝8.4 Hz,J2＝2.4 Hz,1H),6.90(td,J1＝7.6 Hz,J2＝0.8 Hz,1H),6.86(d, J＝2.4 Hz,1H),6.78(dd,J1＝8.0 Hz,J2＝0.8 Hz,1H),4.95(s,1H),3.89(s,3H), 3.70(s,3H),2.90(d,J＝15.2 Hz,1H),2.46(d,J＝14.8 Hz,1H),1.76(s,3H).13C{1H} NMR(CDCl3,100 MHz):δ172.1,159.3,142.1,140.6,128.2,124.2,123.8,122.6, 121.4,119.4,115.9,112.6,109.7,55.4,54.6,51.5,43.1,25.5.HRMS(ESI)m/z: [M+H]+Calcd for C18H20NO3298.1438；Found 298.1433.
Methyl 2-(8-fluoro-6-methyl-5,6-dihydrophenanthridin-6-yl)acetate(3g)
White solid(46.2 mg,54％).1H NMR(CDCl3,400 MHz):δ7.73-7.69(m,1H),7.63 (d,J＝7.6 Hz,1H),7.15-7.11(m,1H),7.03(td,J1＝8.4 Hz,J2＝2.8 Hz,1H),6.96 (dd,J1＝9.6 Hz,J2＝2.8 Hz,1H),6.88-6.84(m,1H),6.74(d,J＝8.0 Hz,1H),4.92(s, 1H),3.65(s,3H),2.85(d,J＝15.2 Hz,1H),2.40(d,J＝15.2 Hz,1H),1.70(s,3H). 13C{1H}NMR(CDCl3,100 MHz):δ171.9,162.4(d,1JC-F＝244.3 Hz),142.5,141.0 (d,3JC-F＝6.6 Hz),129.1,127.1(d,4JC-F＝3.8 Hz),124.6(d,3JC-F＝8.8 Hz),123.1, 120.7,119.5,116.1,114.7(d,2JC-F＝22.2 Hz),110.6(d,2JC-F＝22.9 Hz),54.5(d, 4JC-F＝2.7 Hz),51.6,42.9,25.5.19F NMR(CDCl3,376 MHz):δ-114.4(td,J1＝10.2 Hz,J2＝5.3 Hz).HRMS(ESI)m/z:[M+H]+Calcd for C17H17FNO2 286.1238；Found 286.1228.
Methyl 2-(8-bromo-6-methyl-5,6-dihydrophenanthridin-6-yl)acetate(3i)
Yellowish solid(59.2 mg,57％).1H NMR(CDCl3,400 MHz):δ7.64(d,J＝7.2 Hz, 1H),7.60(d,J＝8.4 Hz,1H),7.44(dd,J1＝8.4 Hz,J2＝2.0 Hz,1H),7.37(d,J＝2.0 Hz,1H),7.17-7.13(m,1H),6.87-6.83(m,1H),6.73(d,J＝8.0 Hz,1H),4.94(s,1H), 3.64(s,3H),2.85(d,J＝15.2 Hz,1H),2.40(d,J＝15.2 Hz,1H),1.70(s,3H).13C{1H} NMR(CDCl3,100 MHz):δ171.8,142.9,140.8,133.7,129.9,129.6,126.7,124.5, 123.2,121.2,120.3,119.5,116.1,54.4,51.6,43.0,25.5.HRMS(ESI)m/z:[M+H]+ Calcd for C17H17BrNO2346.0437；Found 346.0428.
Methyl 2-(6-methyl-8-(trifluoromethyl)-5,6-dihydrophenanthridin-6-yl)acetate (3j)
White solid(55.3 mg,55％).1H NMR(CDCl3,400 MHz):δ7.83(d,J＝8.4 Hz,1H), 7.71(d,J＝8.0 Hz,1H),7.57(d,J＝8.4 Hz,1H),7.48(s,1H),7.21-7.17(m,1H), 6.87(t,J＝7.6 Hz,1H),6.76(d,J＝8.0 Hz,1H),5.00(s,1H),3.65(s,3H),2.88(d,J ＝15.2 Hz,1H),2.45(d,J＝15.2 Hz,1H),1.76(s,3H).13C{1H}NMR(CDCl3,100 MHz):δ171.7,143.5,139.2,134.4,130.4,129.1(q,2JC-F＝32.1 Hz),124.5(q,3JC-F＝ 4.3 Hz),124.3(q,1JC-F＝269.7 Hz),123.8,123.1,120.5(q,3JC-F＝4.3 Hz),119.9, 119.5,116.2,54.5,51.6,43.2,25.6.19F NMR(CDCl3,565 MHz):δ-62.33(s).HRMS (ESI)m/z:[M+H]+Calcd for C18H17F3NO2 336.1206；Found 336.1204.
Methyl 2-(6,8,9-trimethyl-5,6-dihydrophenanthridin-6-yl)acetate(3m)
Yellowish syrup(49.6 mg,56％).1H NMR(CDCl3,400 MHz):δ7.66(d,J＝7.6 Hz, 1H),7.52(s,1H),7.09(t,J＝7.6 Hz,1H),7.00(s,1H),6.82(t,J＝7.6 Hz,1H),6.70 (d,J＝7.6 Hz,1H),4.90(s,1H),3.64(s,3H),2.84(d,J＝15.2 Hz,1H),2.41(d,J＝ 15.2 Hz,1H),2.30(s,3H),2.28(s,3H),1.69(s,3H).13C{1H}NMR(CDCl3,100 MHz):δ172.2,142.9,136.7,135.9,135.8,128.6,128.3,124.7,123.9 122.9,121.3, 119.1,115.9,54.3,51.4,43.7,25.8,19.8,19.7.HRMS(ESI)m/z:[M+H]+Calcd for C19H22NO2 296.1645；Found 296.1646.
Methyl 2-(6-methyl-5,6-dihydrobenzo[j]phenanthridin-6-yl)acetate(3n)
Yellowish syrup(54.3 mg,57％).1H NMR(CDCl3,600 MHz):δ8.19(s,1H),7.90 (dd,J1＝7.8 Hz,J2＝0.6 Hz,1H),7.85(d,J＝7.8 Hz,1H),7.78(d,J＝7.8 Hz,1H), 7.69(s,1H),7.46-7.40(m,2H),7.17(td,J1＝7.8 Hz,J2＝1.2 Hz,1H),6.91(td,J1＝ 7.8 Hz,J2＝1.2 Hz,1H),6.78(dd,J1＝7.8 Hz,J2＝0.6 Hz,1H),5.01(s,1H),3.64(s, 3H),2.94(d,J＝15.6 Hz,1H),2.51(d,J＝15.0 Hz,1H),1.84(s,3H).13C{1H}NMR (CDCl3,150 MHz):δ172.1,143.4,138.5,133.0,132.8,129.3,129.1,127.9,127.8, 126.3,125.9,123.8,122.2,121.4,121.3,119.6,116.5,54.8,51.6,43.5,25.8.HRMS (ESI)m/z:[M+H]+Calcd for C21H20NO2 318.1489；Found 318.1486.
Methyl 2-(2-methoxy-6-methyl-5,6-dihydrophenanthridin-6-yl)acetate(3p)
Brown syrup(58.0 mg,65％).1H NMR(CDCl3,600 MHz):δ7.71(d,J＝7.8 Hz,1H), 7.35-7.32(m,1H),7.29-7.26(m,3H),6.77(dd,J1＝9.0 Hz,J2＝3.0 Hz,1H),6.70(d, J＝9.0 Hz,1H),4.76(br s,1H),3.82(s,3H),3.64(s,3H),2.85(d,J＝15.0 Hz,1H), 2.38(d,J＝15.6 Hz,1H),1.71(s,3H).13C{1H}NMR(CDCl3,150 MHz):δ172.2, 153.4,139.4,137.1,130.7,127.8,127.7,123.4,122.9,122.4,117.0,115.3,108.7, 55.9,54.7,51.5,42.7,25.4.HRMS(ESI)m/z:[M+H]+Calcd for C18H20NO3 298.1438；Found 298.1434.
Methyl 2-(2-fluoro-6-methyl-5,6-dihydrophenanthridin-6-yl)acetate(3q)
Yellowish solid(43.7 mg,51％).1H NMR(CDCl3,600 MHz):δ7.66(d,J＝7.8 Hz, 1H),7.39(dd,J1＝9.6 Hz,J2＝3.0 Hz,1H),7.34(td,J1＝7.2 Hz,J2＝1.2 Hz,1H), 7.31(td,J1＝7.8 Hz,J2＝1.2 Hz,1H),7.27(t,J＝7.2 Hz,1H),6.86(td,J1＝8.4 Hz, J2＝3.0 Hz,1H),6.69(dd,J1＝8.4 Hz,J2＝4.8 Hz,1H),4.91(s,1H),3.65(s,3H), 2.84(d,J＝15.0 Hz,1H),2.39(d,J＝15.0 Hz,1H),1.71(s,3H).13C{1H}NMR (CDCl3,100 MHz):δ172.1,157.1(d,1JC-F＝234.0 Hz),139.2,130.0(d,4JC-F＝2.2 Hz),128.2,127.8,123.5,123.0,122.4(d,3JC-F＝7.2 Hz),116.8(d,3JC-F＝7.9 Hz), 115.8(d,2JC-F＝23.1 Hz),109.6(d,2JC-F＝23.1 Hz),54.7,51.5,42.9,25.5.19F NMR (CDCl3,565 MHz):δ-125.2–-125.3(m).HRMS(ESI)m/z:[M+H]+Calcd for C17H17FNO2 286.1238；Found 286.1232.
Methyl 2-(6-butyl-5,6-dihydrophenanthridin-6-yl)acetate(3v)
Yellowish solid(52.9 mg,57％).1H NMR(CDCl3,600 MHz):δ7.77-7.56(m,1H), 7.66(dd,J1＝7.8 Hz,J2＝1.2 Hz,1H),7.30(td,J1＝7.8 Hz,J2＝1.2 Hz,1H),7.24 (td,J1＝7.2 Hz,J2＝1.2 Hz,1H),7.17(dd,J1＝7.8 Hz,J2＝1.2 Hz,1H),7.11(td,J1＝7.8 Hz,J2＝1.2 Hz,1H),6.79(td,J1＝7.2 Hz,J2＝0.6 Hz,1H),6.69(dd,J1＝7.8 Hz,J2＝0.6 Hz,1H),4.79(s,1H),3.62(s,3H),2.88(d,J＝15.0 Hz,1H),2.50(d,J＝ 15.0 Hz,1H),2.12-2.07(m,1H),1.90-1.84(m,1H),1.50-1.45(m,1H),1.33-1.24(m, 3H),0.86(t,J＝7.2 Hz,3H).13C{1H}NMR(CDCl3,150 MHz):δ172.1,143.2, 136.6,131.5,129.2,127.5,127.1,124.4,123.1,122.6,120.2,118.7,115.6,58.0,51.5, 44.3,37.7,26.5,23.1,14.1.HRMS(ESI)m/z:[M+H]+Calcd for C20H24NO2 310.1802；Found 310.1792.
Methyl 2-(6-phenethyl-5,6-dihydrophenanthridin-6-yl)acetate(3x)
Yellowish syrup(75.1 mg,70％).1H NMR(CDCl3,400 MHz):δ7.80(d,J＝7.6 Hz, 1H),7.68(d,J＝7.2 Hz,1H),7.35-7.24(m,5H),7.17-7.10(m,4H),6.83-6.79(m, 1H),6.72(d,J＝8.0 Hz,1H),4.93(s,1H),3.59(s,3H),2.93(d,J＝15.2 Hz,1H), 2.88-2.80(m,1H),2.64-2.56(m,1H),2.51(d,J＝15.2 Hz,1H),2.45-2.37(m,1H), 2.26-2.18(m,1H).13C{1H}NMR(CDCl3,100 MHz):δ172.0,143.2,142.4,136.1, 131.7,129.3,128.5,128.4,127.8,127.4,125.9,124.4,123.2,122.8,120.1,118.9, 115.7,58.1,51.6,44.4,39.9,30.9.HRMS(ESI)m/z:[M+H]+Calcd for C24H24NO2 358.1802；Found 358.1800.
Ethyl 2-(6-methyl-5,6-dihydrophenanthridin-6-yl)acetate(3z)
Yellowish syrup(56.6mg,67％).1H NMR(CDCl3,600MHz):δ7.75(d,J＝7.8Hz, 1H),7.70(d,J＝7.8Hz,1H),7.34-7.32(m,1H),7.27-7.25(m,2H),7.15-7.13(m, 1H),6.86(t,J＝7.8Hz,1H),6.74(d,J＝7.8Hz,1H),4.96(s,1H),4.13-4.09(m,2H), 2.86(d,J＝15.0Hz,1H),2.41(d,J＝15.0Hz,1H),1.73(s,3H),1.24(t,J＝7.2Hz, 3H).13C{1H}NMR(CDCl3,150MHz):δ171.7,143.1,139.0,130.8,129.1,127.6, 127.5,123.5,123.3,122.8,121.3,119.3,116.0,60.5,54.6,43.6,25.7,14.2.HRMS (ESI)m/z:[M+H]+Calcd for C18H20NO2 282.1489；Found 282.1486.
example 4
To a 15mL pressure tube were added 1a (50.8mg,0.3mmol), 2a (44.1mg,0.45 m) in that ordermol), tetrahydrofuran (2mL), dichlorobis (4-methylisopropylphenyl) ruthenium (II) ([ Ru (p-cymene) Cl)2]29.2mg, 0.015mmol), silver trifluoromethanesulfonate (15.4mg,0.06mmol) and acetic acid (34.3 μ L,0.6mmol), the pressure tube was then sealed under argon protection and placed in a 120 ℃ oil bath and stirred for reaction for 24 hours. After the reaction is finished, saturated NaHCO is used3The solution is quenched, filtered with suction, extracted with ethyl acetate (10 mL. times.3), the organic phases are combined and washed successively with water and saturated sodium chloride solution, anhydrous Na2SO4Drying, spin-drying and separation on silica gel (petrol ether/ethyl acetate 10/1) gave product 4a as a white solid (34.8mg, 60%). The characterization data for this compound are:1H NMR(CDCl3,400MHz):δ8.58(d,J＝8.4Hz,1H),8.50(dd,J1＝8.0 Hz,J2＝1.2Hz,1H),8.18(dd,J1＝8.0Hz,J2＝0.8Hz,1H),8.09(dd,J1＝8.0Hz,J2＝0.8Hz,1H),7.82-7.78(m,1H),7.71-7.64(m,2H),7.61-7.57(m,1H),3.02(s,3H). 13C{1H}NMR(CDCl3,150MHz):δ158.9,143.7,132.6,130.5,129.4,128.7,127.3, 126.5,126.3,125.9,123.8,122.3,122.0,23.4.HRMS(ESI)m/z:[M+H]+Calcd for C14H12N 194.0964；Found 194.0963.
example 5
Various phenanthridines 4 were synthesized by varying reactants 1 and 2 according to the procedure and procedure of example 4, with the specific results shown in table 3.
TABLE 3 Synthesis of various phenanthridines 4a,b
Figure BDA0002981426800000101
aReaction conditions of 1(0.3mmol),2(0.45mmol), [ Ru (p-cymene) Cl2]2(0.015mmol), AgOTf (0.06mmol), AcOH (0.6mmol), THF (2mL), argon atmosphere, 120 ℃ for 24h.bThe isolation yield.
Representative product characterization data are as follows:
6,8-Dimethylphenanthridine(4b)
Yellowish solid(37.9mg,61％).1H NMR(CDCl3,400MHz):δ8.45-8.42(m,2H), 8.07(dd,J1＝8.0Hz,J2＝0.4Hz,1H),7.91(s,1H),7.67-7.63(m,1H),7.60-7.54(m, 2H),2.98(s,3H),2.56(s,3H).13C{1H}NMR(CDCl3,100MHz):δ158.6,143.4, 137.2,132.1,130.3,129.3,128.2,126.2,126.04,126.01,123.9,122.2,121.8,23.4, 21.8.HRMS(ESI)m/z:[M+H]+Calcd for C15H14N 208.1121；Found 208.1120.
8-Methoxy-6-methylphenanthridine(4d)
Yellowish solid(37.5mg,56％).1H NMR(CDCl3,400MHz):δ8.53(d,J＝8.8Hz, 1H),8.46(d,J＝7.6Hz,1H),8.11(dd,J1＝8.4Hz,J2＝0.8Hz,1H),7.70-7.66(m, 1H),7.64-7.60(m,1H),7.51-7.46(m,2H),4.01(s,3H),3.03(s,3H).13C{1H}NMR (CDCl3,100MHz):δ158.6,157.9,142.9,129.3,127.6,127.2,126.8,126.4,124.0, 123.9,121.5,120.7,106.8,55.5,23.5.HRMS(ESI)m/z:[M+H]+Calcd for C15H14NO 224.1070；Found 224.1067.
8-Fluoro-6-methylphenanthridine(4g)
Yellowish solid(36.8 mg,58％).1H NMR(CDCl3,400 MHz):δ8.54(dd,J1＝9.2 Hz, J2＝5.2 Hz,1H),8.41(d,J＝8.0 Hz,1H),8.08(d,J＝8.0 Hz,1H),7.77(dd,J1＝9.6 Hz,J2＝2.4 Hz,1H),7.71-7.67(m,1H),7.62-7.58(m,1H),7.56-7.51(m,1H),2.96 (s,3H).13C{1H}NMR(CDCl3,100 MHz):δ161.3(d,1JC-F＝247.0 Hz),157.9(d, 4JC-F＝3.6 Hz),143.4,129.5,129.2(d,4JC-F＝2.1 Hz),128.5,127.1(d,3JC-F＝7.2 Hz), 126.7,124.9(d,3JC-F＝8.6 Hz),123.3,121.7,119.5(d,2JC-F＝23.8 Hz),111.1(d, 2JC-F＝21.0 Hz),23.4.19F NMR(CDCl3,376 MHz):δ-112.0(td,J1＝9.8 Hz,J2＝5.6 Hz).HRMS(ESI)m/z:[M+H]+Calcd for C14H11FN 212.0870；Found 212.0868.
8-Bromo-6-methylphenanthridine(4i)
Yellowish solid(53.9 mg,66％).1H NMR(CDCl3,400 MHz):δ8.38-8.33(m,2H), 8.24(d,J＝2.0 Hz,1H),8.05(d,J＝8.4 Hz,1H),7.82(dd,J1＝8.8 Hz,J2＝2.0 Hz, 1H),7.72-7.68(m,1H),7.58(t,J＝8.0 Hz,1H),2.94(s,3H).13C{1H}NMR(CDCl3, 100 MHz):δ157.6,143.6,133.5,131.2,129.5,129.04,129.02,127.1,126.7,124.1, 123.1,121.8,121.3,23.3.HRMS(ESI)m/z:[M+H]+Calcd for C14H11BrN 272.0069； Found 272.0066.
6,8,9-Trimethylphenanthridine(4l)
White solid(33.9 mg,51％).1H NMR(CDCl3,400 MHz):δ8.46(d,J＝8.0 Hz,1H), 8.30(s,1H),8.05(d,J＝8.0 Hz,1H),7.89(s,1H),7.64(t,J＝7.6 Hz,1H),7.56(t,J ＝7.6 Hz,1H),2.98(s,3H),2.51(s,3H),2.47(s,3H).13C{1H}NMR(CDCl3,100 MHz):δ158.4,143.6,140.3,136.7,130.9,129.3,128.0,126.6,126.0,124.6,123.7, 122.5,121.8,23.3,20.7,20.3.HRMS(ESI)m/z:[M+H]+Calcd for C16H16N 222.1277；Found 222.1274.
2-Methoxy-6-methylphenanthridine(4n)
Brown solid(41.5 mg,62％).1H NMR(CDCl3,400 MHz):δ8.49(d,J＝8.0 Hz,1H), 8.15(d,J＝8.0 Hz,1H),8.00(d,J＝8.8 Hz,1H),7.83(d,J＝2.8 Hz,1H),7.80-7.76 (m,1H),7.67-7.63(m,1H),7.32(dd,J1＝8.8 Hz,J2＝2.4 Hz,1H),3.98(s,3H),2.98 (s,3H).13C{1H}NMR(CDCl3,100 MHz):δ157.9,156.2,139.0,132.1,130.7,130.0, 127.3,126.5,126.0,124.7,122.3,118.3,103.1,55.6,23.2.HRMS(ESI)m/z:[M+H]+ Calcd for C15H14NO 224.1070；Found 224.1068.
3,6-Dimethylphenanthridine(4q)
Yellowish solid(37.9 mg,61％).1H NMR(CDCl3,400 MHz):δ8.53(d,J＝8.0 Hz, 1H),8.37(d,J＝8.0 Hz,1H),8.15(d,J＝8.0 Hz,1H),7.88(s,1H),7.77(t,J＝7.6 Hz,1H),7.61(t,J＝7.6 Hz,1H),7.41(d,J＝8.4 Hz,1H),3.00(s,3H),2.56(s,3H). 13C{1H}NMR(CDCl3,150 MHz):δ158.8,143.9,138.7,132.7,130.4,129.0,128.0, 126.8,126.5,125.6,122.1,121.8,121.4,23.4,21.6.HRMS(ESI)m/z:[M+H]+Calcd for C15H14N 208.1121；Found 208.1122.
3-Chloro-6-methylphenanthridine(4r)
White solid(30.7 mg,45％).1H NMR(CDCl3,400 MHz):δ8.50(d,J＝8.0 Hz,1H), 8.38(d,J＝8.8 Hz,1H),8.18(d,J＝8.0 Hz,1H),8.06(d,J＝2.0 Hz,1H),7.82(t,J＝ 8.0 Hz,1H),7.68(t,J＝8.0 Hz,1H),7.53(dd,J1＝8.8 Hz,J2＝2.0 Hz,1H),3.00(s, 3H).13C{1H}NMR(CDCl3,100 MHz):δ160.2,144.4,134.2,132.1,130.8,128.7, 127.6,126.8,126.6,125.8,123.3,122.25,122.21,23.4.HRMS(ESI)m/z:[M+H]+ Calcd for C14H11ClN 228.0575；Found 228.0582.
6-Butylphenanthridine(4t)
Yellowish syrup(37.4 mg,53％).1H NMR(CDCl3,600 MHz):δ8.61(d,J＝8.4 Hz, 1H),8.52-8.51(m,1H),8.23(d,J＝8.4 Hz,1H),8.12(dd,J1＝7.8 Hz,J2＝0.6 Hz, 1H),7.81-7.78(m,1H),7.71-7.65(m,2H),7.61-7.58(m,1H),3.36(t,J＝7.8 Hz, 2H),1.93-1.88(m,2H),1.59-1.53(m,2H),1.00(t,J＝7.2 Hz,3H).13C{1H}NMR (CDCl3,150 MHz):δ162.5,143.8,133.0,130.3,129.6,128.6,127.2,126.4,126.3, 125.3,123.7,122.5,121.9,36.2,31.8,23.2,14.1.HRMS(ESI)m/z:[M+H]+Calcd for C17H18N 236.1434；Found 236.1437.
6-Phenethylphenanthridine(4v)
Yellowish solid(56.1 mg,66％).1H NMR(CDCl3,400 MHz):δ8.63(d,J＝8.4 Hz, 1H),8.54(d,J＝8.4 Hz,1H),8.24(d,J＝8.4 Hz,1H),8.15(d,J＝8.0 Hz,1H),7.81 (t,J＝8.0 Hz,1H),7.74-7.60(m,3H),7.38-7.30(m,4H),7.24-7.21(m,1H), 3.69-3.65(m,2H),3.31-3.27(m,2H).13C{1H}NMR(CDCl3,100 MHz):δ161.0, 143.8,142.1,133.0,130.4,129.7,128.7,128.6,128.5,127.4,126.5,126.1,126.0, 125.3,123.7,122.6,122.0,37.9,35.0.HRMS(ESI)m/z:[M+H]+Calcd for C21H18N 284.1434；Found 284.1432.
example 6
The phenanthridine compound 4 synthesized by the method can be subjected to a series of reactions, so that a further derivative can be synthesized. For example:
Figure BDA0002981426800000131
to a 10mL reaction flask were added 4a (38.6mg,0.2mmol) and SeO in that order2(39.9mg,0.36 mmol), 1, 4-dioxane (3.2mL) and water (0.2mL), and the mixture was stirred in an oil bath under reflux for 5 hours. After the reaction is finished, the solvent is dried by spinning, and then dichloromethane CH is added into a reaction bottle2Cl2(10mL), suction filtration. The filtrate was washed with water (20mL × 3), and the organic phase was dried over anhydrous sodium sulfate, filtered with suction, dried by spinning, and separated by silica gel column (petroleum ether/ethyl acetate: 20/1) to give 5(22.0mg, 53%) as a white solid. The characterization data for this compound are as follows:1H NMR(CDCl3,600MHz):δ10.4(s,1H),9.38-9.37(m,1H), 8.61(d,J＝8.4Hz,1H),8.57-8.55(m,1H),8.30-8.29(m,1H),7.88-7.85(m,1H), 7.82-7.77(m,2H),7.77-7.74(m,1H).13C{1H}NMR(CDCl3,150MHz):δ195.7, 150.2,143.3,133.4,131.3,131.2,129.9,129.2,128.7,126.9,125.6,123.5,122.2, 121.9.HRMS(ESI)m/z:[M+H]+Calcd for C14H10NO 208.0757；Found 208.0758.
Figure BDA0002981426800000132
to a 10mL reaction flask were added 4a (38.6mg,0.2mmol), I in that order2(10.2mg,0.04mmol)、 NH4F (29.6mg,0.8mmol), TBHP (70% by mass of water)Solution, 309.0mg,2.4mmol) and dimethyl sulfoxide (0.5mL), and the mixture was stirred in an oil bath at 70 ℃ for 48 hours under an oxygen atmosphere. After completion of the reaction, the solvent was dried by evaporation, and the mixture was separated by silica gel column (petroleum ether/ethyl acetate: 10/1) to obtain 6(28.6mg, 70%) as a pale yellow solid. The characterization data for this compound are as follows:1H NMR(CDCl3,400MHz):δ 8.64(d,J＝8.4Hz,1H),8.59-8.57(m,1H),8.42(d,J＝8.4Hz,1H),8.25-8.23(m, 1H),8.00-7.96(m,1H),7.87-7.82(m,3H).13C{1H}NMR(CDCl3,150MHz):δ 143.5,135.7,132.6,132.2,131.0,130.0,129.7,128.8,126.6,125.3,124.7,122.4, 122.2,115.8.HRMS(ESI)m/z:[M+H]+Calcd for C14H9N2 205.0760；Found 205.0757.
Figure BDA0002981426800000141
to a 50mL reaction flask were added 4a (38.6mg,0.2mmol) and dichloromethane (5mL) until it was completely dissolved, methyl triflate (67.9. mu.L, 0.6mmol) was slowly added dropwise to the reaction flask, and the mixture was stirred at room temperature overnight. After the reaction was complete, suction was applied and the resulting precipitate was washed with ether and dried under vacuum to give 7(153.7mg, 86%) as a white solid. The characterization data for this compound are as follows:1H NMR(DMSO-d6,400MHz):δ9.16(d,J＝8.4Hz,2H),8.93(d,J＝8.4Hz,1H), 8.65(d,J＝8.4Hz,1H),8.37(t,J＝7.6Hz,1H),8.15-8.05(m,3H),4.60(s,3H), 3.46(s,3H).13C{1H}NMR(DMSO-d6,150MHz):δ166.4,137.3,135.5,133.7, 132.2,131.2,130.7,130.1,125.02,124.96,124.9,123.9,121.2(q,JC-F＝320.3Hz), 120.6,41.8,20.1.19F NMR(DMSO-d6,565MHz):δ-77.7(s).HRMS(ESI)m/z: [M-OTf]+Calcd for C15H14N 208.1121；Found 208.1120.
Figure BDA0002981426800000142
sequentially adding into a 10mL reaction bottleSalicylaldehyde (32.0. mu.L, 0.3mmol), methanol (1.5mL) and piperidine (29.7. mu.L, 0.3mmol) were added and the mixture was heated to reflux. 7(107.2mg,0.3mmol) was dissolved in methanol (1.5mL) and the resulting solution was added four times over 80 minutes to the refluxing mixture and, after the addition was complete, refluxed for another 1 hour, then cooled to room temperature and stirred overnight. After completion of the reaction, suction filtration was carried out to obtain 8(83.1mg, 89%) as a white solid. The characterization data for this compound are as follows:1H NMR (DMSO-d6,400MHz):δ8.18-8.11(m,2H),7.53-7.50(m,1H),7.43-7.38(m,3H), 7.29(d,J＝7.2Hz,1H),7.19(d,J＝10.0Hz,1H),7.11-7.04(m,3H),6.88(t,J＝7.2 Hz,1H),6.49(d,J＝8.4Hz,1H),6.04(d,J＝10.4Hz,1H),3.12(s,3H).13C{1H} NMR(DMSO-d6,150MHz):δ152.4,141.3,131.9,130.6,130.1,129.5,128.7,128.3, 128.0,127.7,127.5,123.6,123.5,122.6,120.9,120.1,119.7,118.9,115.4,114.5,91.6, 33.5.HRMS(ESI)m/z:[M+H]+Calcd for C22H18NO 312.1383；Found 312.1388.
the foregoing embodiments have described the general principles, principal features and advantages of the invention. It will be understood by those skilled in the art that the present invention is not limited to the embodiments described above, which are given by way of illustration of the principles of the present invention, and that various changes and modifications may be made without departing from the scope of the principles of the present invention, and such changes and modifications are within the scope of the present invention.

Claims (3)

1. The method for selectively synthesizing the dihydrophenanthridine 3 or the phenanthridine compound 4 is characterized by comprising the following operations: heating and reacting an o-aryl aniline compound 1 and an alkynoate compound 2 in an organic solvent in the presence of a ruthenium catalyst, an additive and an acid to obtain a dihydrophenanthridine compound 3 or a phenanthridine compound 4; the reaction equation is:
Figure FDA0003539626670000011
wherein R is1Is hydrogen, halogen, trifluoromethylBenzyloxy group, C1-4Alkyl or C1-4Alkoxy radical, R2Is hydrogen, halogen, trifluoromethyl, benzyloxy, C1-4Alkyl or C1-4Alkoxy radical, R3Is C1-6Chain alkyl or C1-6Chain-substituted alkyl, R4Is C1-4An alkyl group; the ruthenium catalyst is [ Ru (p-cymene) Cl2]2(ii) a When synthesizing the dihydrophenanthridine compound 3, the additive is silver trifluoromethanesulfonate or silver tetrafluoroborate, and the organic solvent is tetrahydrofuran or ethylene glycol dimethyl ether; when the phenanthridine compound 4 is synthesized, the additive is silver trifluoromethanesulfonate, and the organic solvent is tetrahydrofuran; the acid is acetic acid, pivalic acid, trifluoromethanesulfonic acid, 2,4, 6-trimethylbenzoic acid, trifluoroacetic acid, benzoic acid or chloroacetic acid; the reaction temperature is 40-140 ℃, and the generation of the phenanthridine compound 4 is facilitated by raising the temperature; when the reaction temperature is 40-80 ℃ and the molecular sieve is added, the dihydrophenanthridine compound 3 is mainly obtained through the reaction; the reaction temperature is 100-140 ℃, and the phenanthridine compound 4 is mainly obtained through the reaction.
2. The method for the selective synthesis of dihydrophenanthridines 3 or 4 according to claim 1, characterized in that: halogen is selected from fluorine, chlorine, bromine or iodine.
3. The method for the selective synthesis of dihydrophenanthridines 3 or 4, according to claim 1 or 2, characterized in that: the molar ratio of the o-aryl aniline compound 1 to the alkynoate compound 2 to the addition agent to the acid to the ruthenium catalyst is 1:1-1.5:0.1-0.4:1.5-2: 0.025-0.075.
CN202110288940.5A 2021-03-18 2021-03-18 Method for selectively synthesizing dihydrophenanthridine or phenanthridine compounds Active CN113045496B (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
CN202110288940.5A CN113045496B (en) 2021-03-18 2021-03-18 Method for selectively synthesizing dihydrophenanthridine or phenanthridine compounds

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
CN202110288940.5A CN113045496B (en) 2021-03-18 2021-03-18 Method for selectively synthesizing dihydrophenanthridine or phenanthridine compounds

Publications (2)

Publication Number Publication Date
CN113045496A CN113045496A (en) 2021-06-29
CN113045496B true CN113045496B (en) 2022-04-26

Family

ID=76513443

Family Applications (1)

Application Number Title Priority Date Filing Date
CN202110288940.5A Active CN113045496B (en) 2021-03-18 2021-03-18 Method for selectively synthesizing dihydrophenanthridine or phenanthridine compounds

Country Status (1)

Country Link
CN (1) CN113045496B (en)

Families Citing this family (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN113845509B (en) * 2021-10-11 2023-01-24 河南师范大学 Synthetic method of indolyl-substituted spiro [ cyclobutane-1,1' -indene ] compound

Family Cites Families (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN105153033A (en) * 2015-10-13 2015-12-16 遵义医学院 Preparation method of 6-H-phenanthridine compound

Also Published As

Publication number Publication date
CN113045496A (en) 2021-06-29

Similar Documents

Publication Publication Date Title
WO2020114025A1 (en) PREPARATION METHOD FOR β-LACTAM DERIVATIVES
CN115010644B (en) Preparation method of 2, 3-disubstituted indoline compound
CN113045496B (en) Method for selectively synthesizing dihydrophenanthridine or phenanthridine compounds
CN110878099B (en) Preparation method of pyrrole [1,2, alpha ] indole alkaloid derivative
CN112300072A (en) High-yield synthesis method of 5-iodoisoquinoline compounds
CN109912492B (en) Synthetic method of 3-benzylidene isoindoline-1-one derivative
CN109810147B (en) Pyrene-labeled benzimidazole nitrogen heterocyclic carbene palladium metal complex, and preparation and application thereof
CN109651385B (en) Preparation method of pyran [3,2-a ] carbazole compound
CN113845509B (en) Synthetic method of indolyl-substituted spiro [ cyclobutane-1,1' -indene ] compound
CN114835652B (en) Method for synthesizing iminobenzotriazole compound under photocatalysis condition
CN113004248B (en) Method for synthesizing carbazole compound by catalyzing hydrocarbon amination reaction with cobalt
CN115160220A (en) Synthesis process of pyridine-N-oxide
CN109912640B (en) Preparation method of 2-pyrrolidone compound
CN110003089B (en) 3-hydroxymethyl-9-substituted carbazole and preparation method thereof
CN114507180B (en) Methyl-substituted azaheterocyclic compound C (sp 3 ) Method for self dehydroalkenylation of H bonds
CN114437092B (en) Chiral tetrahydrocarbazole polycyclic derivative and preparation method and application thereof
CN115970757B (en) Non-metallocene rare earth metal hydrocarbon functionalization reaction catalyst, preparation method and application thereof
EP1539751B1 (en) Process for the preparation of imidazo(1,2-a)pyridine-3-acetamides
CN115304557B (en) Enamine derivative and preparation method thereof
CN108191878B (en) Novel method for preparing summer alkali-free B
CN111499556B (en) Preparation method of carbazole compound
CN113735832B (en) Preparation method of 7-succinimidyl indole compound
CN116199614B (en) N-axis chiral indole-pyrrole compound and synthesis method thereof
CN111808072B (en) Synthetic method of 3-formyl indole derivative
JP5854436B2 (en) Method for producing 2-borated azulene derivative

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
GR01 Patent grant
GR01 Patent grant