CN108299297A - A kind of novel 6- alkyl phenanthridines and derivative and preparation method thereof - Google Patents
A kind of novel 6- alkyl phenanthridines and derivative and preparation method thereof Download PDFInfo
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- CN108299297A CN108299297A CN201810172198.XA CN201810172198A CN108299297A CN 108299297 A CN108299297 A CN 108299297A CN 201810172198 A CN201810172198 A CN 201810172198A CN 108299297 A CN108299297 A CN 108299297A
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- 0 *Cc1nc(cccc2)c2c2c1cccc2 Chemical compound *Cc1nc(cccc2)c2c2c1cccc2 0.000 description 4
- WZJOUAATHQENHW-UHFFFAOYSA-N CCCC1=C(N)O1 Chemical compound CCCC1=C(N)O1 WZJOUAATHQENHW-UHFFFAOYSA-N 0.000 description 1
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- 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
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/06—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
- C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
- C07D409/06—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
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Abstract
A kind of novel 6 alkyl phenanthridines and derivative and preparation method thereof, with R BF3K is free based precursor, in a nitrogen atmosphere, using dichloromethane as solvent, with silver oxide and water initiated oxidation reduction system, is captured by 2 isocyano group, 1,1 ' biphenyl, 6 alkyl phenanthridines skeleton structures are formed by cyclization process.Three potassium fluoborate simplicity of alkyl in raw material of the present invention is easy to get, and stability is high and nontoxic.The preparation method of radical initiator in the present invention reacts several minutes can be completed at room temperature, fast and simple, and yield is high.In addition the substrate applicability that the present invention uses is wide, aromatic ring, heteroaromatic, ketone carbonyl and ester group can be compatible with, and not by steric interference, to the 1 of big steric hindranceoAlkane, 2oAlkane and 3oAlkane is equally applicable.
Description
Technical field
The invention belongs to technical field of organic synthesis, and in particular to a kind of novel 6- alkyl phenanthridines and derivative and its preparation
Method.
Background technology
The application potential of free-radical chemistry was excavated by chemists in recent years, because its unique chemical property is having
Play the role of in machine synthesis chemistry very important.Currently, how to prepare active higher, the more preceding free radical of compatibility at
For one of the problem of people's challenge.
Conventional obtains free radical by oxidation reaction, such as with organomagnesium reagent, organolithium reagent organometallic reagent
Method, the drawbacks such as that there are reaction conditions is excessively harsh, functional group's tolerance is weak.The present invention is by aoxidizing the organic gold of other types
Belong to reagent and its derivative obtains corresponding free radical.It is deposited with such a can stablize in air of organic three potassium fluoborates salt
, and the higher reagent of reactivity is raw material in organic chemical reactions, by being aoxidized to organic three potassium fluoborates salt
Reaction, obtains corresponding free radical.Isocyano group -1 2-, 1 '-biphenyl is good free radical scavenger, then undergoes cyclization
Construct 6- alkyl phenanthridine derivatives.
6- alkyl phenanthridines skeleton structures frequently appear in natural products, are extremely important organic synthesis intermediates.
Alkyl trifluoroborate, silver oxide and water can be generated free radicals efficiently and rapidly at room temperature in this patent, and
By isocyano group -1 2-, the capture of 1 '-biphenyl, then undergo cyclisation course and can construct 6- alkyl phenanthridines skeleton structures, this is 6- alkyl
Constructing for phenanthridines skeleton provides a kind of novel path.
Invention content
In order to overcome the above-mentioned deficiency of the prior art, the purpose of the present invention is to provide a kind of novel 6- alkyl phenanthridines and spread out
Biology and preparation method thereof passes through isocyano group -1 2-, 1 '-connection using alkyl trifluoroborate, silver oxide and water as initiation system
The free radical that benzene capture reaction generates, to construct 6- alkyl phenanthridines skeleton structures by cyclisation course.In raw material of the present invention
Three potassium fluoborate simplicity of alkyl is easy to get, and stability is high and nontoxic.The preparation method of 6- alkyl phenanthridines in the present invention, at room temperature instead
It answers several minutes and can be completed, it is fast and simple, and yield is high.
To achieve the above object, the technical solution adopted by the present invention is：
A kind of novel 6- alkyl phenanthridines and derivative, general structure (I) are as follows：
In formula, R bases are(X=H, Br, Cl), In one kind；
Its derivative is as follows：
The preparation method of a kind of novel 6- alkyl phenanthridines is raw material as free based precursor using three potassium fluoborate salt of alkyl,
In a nitrogen atmosphere, using dichloromethane as solvent, with silver oxide and water initiated oxidation reduction system, by isocyano group -1 2-, 1 ' -
Biphenyl captures, and constitutes 6- alkyl phenanthridines precursor structures through cyclization, synthetic route is as shown in public formula (I)：
Its specific synthesis step is as follows：
1) R-BF by metering is sequentially added in clean reactor3K, silver oxide and 2- isocyano groups -1,1 '-connection
Benzene, substitutes nitrogen 3 times, injects dichloromethane-water mixed solvent of 10mL/mmol into reaction tube under nitrogen stream environment, close
Seal reactor；
2) it is vigorously mixed at room temperature for 10~30 minutes, stops stirring, obtain reaction solution；
3) metallic residue in above-mentioned reaction solution is filtered out with diatomite, filter cake is washed 3~5 times with ethyl acetate, is merged
Filtrate is spin-dried for solvent, is detached to get to target product by column chromatography chromatogram.
The R-BF3K is three potassium fluoborate salt of alkyl, and general structure is as shown in public formula (II)：R-BF3K(II)
In formula, R bases are(X=H, Br, Cl), In one kind.
The R-BF3K, silver oxide and 2- isocyano groups -1,1 '-biphenyl are with molar ratio 1:1:1 is measured.
Dichloromethane-water mixed solvent in the step 1), by volume ratio 50:1 dichloromethane is made into water.
The beneficial effects of the invention are as follows：
Three potassium fluoborate simplicity of alkyl in raw material of the present invention is easy to get, and stability is high and nontoxic.6- alkyl phenanthrenes in the present invention
The preparation method of pyridine reacts several minutes can be completed at room temperature, fast and simple, and yield is high.
Description of the drawings
Fig. 1 is the schematic diagram of 18 kinds of alkyl trifluoroborate structural formulas；
Fig. 2 is 18 kinds of 6- alkyl phenanthridine derivatives structures that 2- isocyano groups -1,1 '-biphenyl is formed with free radical cyclization；
Fig. 3 is the nucleus magnetic hydrogen spectrum of compound (15)；
Fig. 4 is that the nuclear-magnetism carbon of compound (15) is composed；
Fig. 5 is the nucleus magnetic hydrogen spectrum of compound (16)；
Fig. 6 is that the nuclear-magnetism carbon of compound (16) is composed；
Fig. 7 is the nucleus magnetic hydrogen spectrum of compound (17)；
Fig. 8 is that the nuclear-magnetism carbon of compound (17) is composed；
Fig. 9 is the nucleus magnetic hydrogen spectrum of compound (18)；
Figure 10 is that the nuclear-magnetism carbon of compound (18) is composed；
Specific implementation mode
The present invention is described in detail with reference to the accompanying drawings and examples, but the present invention is not limited to following embodiment.
Embodiment 1：
Three potassium fluoborate salt (22.6mg, 0.1mmol, 1.0eq.) of phenylpropyl is sequentially added in dry 10mL reaction tubes,
Silver oxide (25.4mg, 0.1mmol, 1.0eq.) and isocyano group -1 2-, 1 '-biphenyl (17.9mg, 0.1mmol, 1.0eq.), substitute
Nitrogen three times, injects 1.0mL dichloromethane and 20.0 μ L distilled water into reaction tube under nitrogen stream environment, screws reaction tube
Lid, is vigorously mixed at room temperature for 10 minutes, reacts the formation that silver mirror is clear that on tube wall.Reaction solution uses diatom first
Soil filters out metallic residue, and filter cake is washed three times with dichloromethane, and merging filtrate is detached after being spin-dried for solvent by column chromatography chromatogram
Obtain 28.0 milligrams of colourless oil liquid, yield 94%.
1H NMR (400MHz, CDCl3) δ 8.64 (d, J=8.3Hz, 1H), 8.54 (d, J=8.0Hz, 1H), 8.19 (d, J
=7.7Hz, 1H), 8.12 (d, J=8.1Hz, 1H), 7.84 (t, J=7.3Hz, 1H), 7.68 (m, 2H), 7.45 (s, 1H),
7.27 (m, 4H), 3.44 (t, J=7.9Hz, 2H), 2.87 (t, J=7.6Hz, 2H), 2.29 (m, 2H)；
13C NMR(100MHz,CDCl3)δ161.9,142.2,133.0,130.7,129.1,128.8,128.6,128.4,
127.4,126.4,125.9,125.1,123.7,122.5,121.9,118.6,115.5,35.6,31.0,29.7；
Embodiment 2：
Three potassium fluoborate salt (21.2mg, 0.1mmol, 1.0eq.) of phenethyl is sequentially added in dry 10mL reaction tubes,
Silver oxide (25.4mg, 0.1mmol, 1.0eq.) and isocyano group -1 2-, 1 '-biphenyl (17.9mg, 0.1mmol, 1.0eq.), substitute
Nitrogen three times, injects 1.0mL dichloromethane and 20.0 μ L distilled water into reaction tube under nitrogen stream environment, screws reaction tube
Lid, is vigorously mixed at room temperature for 10 minutes, reacts the formation that silver mirror is clear that on tube wall.Reaction solution uses diatom first
Soil filters out metallic residue, and filter cake is washed three times with dichloromethane, and merging filtrate is detached after being spin-dried for solvent by column chromatography chromatogram
Obtain 27.0 milligrams of colourless oil liquid, yield 95%.
1H NMR (400MHz, CDCl3) δ 8.64 (d, J=8.3Hz, 1H), 8.54 (d, J=8.0Hz, 1H), 8.19 (d, J
=7.7Hz, 1H), 8.12 (d, J=8.1Hz, 1H), 7.84 (t, J=7.3Hz, 1H), 7.68 (m, 2H), 7.45 (s, 1H),
7.27 (m, 4H), 3.44 (t, J=7.9Hz, 2H), 2.87 (t, J=7.6Hz, 2H), 2.29 (m, 2H)；
13C NMR(100MHz,CDCl3)δ161.9,142.2,133.0,130.7,129.1,128.8,128.6,128.4,
127.4,126.4,125.9,125.1,123.7,122.5,121.9,118.6,115.5,35.6,31.0,29.7；
Embodiment 3：
Sequentially added in dry 10mL reaction tubes three potassium fluoborate salt of 4- chlorobenzene ethyls (24.6mg, 0.1mmol,
1.0eq.), silver oxide (25.4mg, 0.1mmol, 1.0eq.) and isocyano group -1 2-, 1 '-biphenyl (17.9mg, 0.1mmol,
1.0eq.), it substitutes nitrogen three times, injects 1.0mL dichloromethane and 20.0 μ L distilled water into reaction tube under nitrogen stream environment,
Reaction lid is screwed, is vigorously mixed at room temperature for 10 minutes, the formation for being clear that silver mirror on tube wall is reacted.Reaction solution
Metallic residue is filtered out with diatomite first, filter cake is washed three times with dichloromethane, merging filtrate, is spin-dried for after solvent through column layer
Analysis chromatographic isolation obtains 29.9 milligrams of colourless oil liquid, yield 94%.
1H NMR (400MHz, CDCl3) δ 8.66 (d, J=8.2Hz, 1H), 8.56 (dd, J=8.1,0.9Hz, 1H),
8.22 (d, J=8.1Hz, 1H), 8.14 (dd, J=8.1,1.0Hz, 1H), 7.84 (t, J=7.6Hz, 1H), 7.69 (m, 3H),
7.28(s,4H),3.65(m,2H),3.28(m,2H)；
13C NMR(100MHz,CDCl3)δ160.5,143.7,140.4,132.9,131.7,130.4,129.9,129.6,
128.7,128.6,127.4,126.5,125.7,125.2,123.7,122.6,121.9,33.2,33.7；
Embodiment 4：
Sequentially added in dry 10mL reaction tubes three potassium fluoborate salt of 4- bromophenylethyls (29.1mg, 0.1mmol,
1.0eq.), silver oxide (25.4mg, 0.1mmol, 1.0eq.) and isocyano group -1 2-, 1 '-biphenyl (17.9mg, 0.1mmol,
1.0eq.), it substitutes nitrogen three times, injects 1.0mL dichloromethane and 20.0 μ L distilled water into reaction tube under nitrogen stream environment,
Reaction lid is screwed, is vigorously mixed at room temperature for 10 minutes, the formation for being clear that silver mirror on tube wall is reacted.Reaction solution
Metallic residue is filtered out with diatomite first, filter cake is washed three times with dichloromethane, merging filtrate, is spin-dried for after solvent through column layer
Analysis chromatographic isolation obtains 33.3 milligrams of colourless oil liquid, yield 92%.
1H NMR (400MHz, CDCl3) δ 8.66 (d, J=8.2Hz, 1H), 8.56 (dd, J=7.6Hz, 1H), 8.27 (d,
J=8.2,1.0Hz, 1H), 8.23 (d, J=8.0Hz, 1H), 8.14 (dd, J=8.0,1.0Hz, 1H), 7.85 (t, J=
7.6Hz, 1H), 7.67 (m, 3H), 7.43 (d, J=8.4Hz, 2H), 7.24 (d, J=8.4Hz, 2H), 3.65 (m, 2H), 3.26
(m,2H)；
13C NMR(100MHz,CDCl3)δ160.5,143.6,140.9,132.8,131.7,130.6,130.5,129.6,
128.8,127.6,126.4,125.7,125.2,123.5,122.5,121.9,119.7,36.9,33.7；
Embodiment 5：
Three potassium fluoborate salt (16.4mg, 0.1mmol, 1.0eq.) of normal-butyl is sequentially added in dry 10mL reaction tubes,
Silver oxide (25.4mg, 0.1mmol, 1.0eq.) and isocyano group -1 2-, 1 '-biphenyl (17.9mg, 0.1mmol, 1.0eq.), substitute
Nitrogen three times, injects 1.0mL dichloromethane and 20.0 μ L distilled water into reaction tube under nitrogen stream environment, screws reaction tube
Lid, is vigorously mixed at room temperature for 10 minutes, reacts the formation that silver mirror is clear that on tube wall.Reaction solution uses diatom first
Soil filters out metallic residue, and filter cake is washed three times with dichloromethane, and merging filtrate is detached after being spin-dried for solvent by column chromatography chromatogram
Obtain 22.2 milligrams of colourless oil liquid, yield 94%.
1H NMR (400MHz, CDCl3) δ 8.65 (d, J=8.3Hz, 1H), 8.54 (d, J=8.2Hz, 1H), 8.26 (d, J
=8.2Hz, 1H), 8.08 (d, J=8.1Hz, 1H), 7.84 (t, J=7.6Hz, 1H), 7.70 (t, J=7.8Hz, 2H), 7.62
(t, J=7.5Hz, 1H), 3.40 (t, J=8.0Hz, 2H), 1.91 (m, 2H), 1.56 (m, 2H), 1.01 (t, J=7.4Hz,
3H)；
13C NMR(100MHz,CDCl3)δ162.4,133.0,130.4,129.4,128.7,127.3,126.5,126.4,
125.2,123.7,122.5,121.9,35.6,31.5,22.9,13.8；
Embodiment 6：
Three potassium fluoborate salt (16.4mg, 0.1mmol, 1.0eq.) of isobutyl group is sequentially added in dry 10mL reaction tubes,
Silver oxide (25.4mg, 0.1mmol, 1.0eq.) and isocyano group -1 2-, 1 '-biphenyl (17.9mg, 0.1mmol, 1.0eq.), substitute
Nitrogen three times, injects 1.0mL dichloromethane and 20.0 μ L distilled water into reaction tube under nitrogen stream environment, screws reaction tube
Lid, is vigorously mixed at room temperature for 10 minutes, reacts the formation that silver mirror is clear that on tube wall.Reaction solution uses diatom first
Soil filters out metallic residue, and filter cake is washed three times with dichloromethane, and merging filtrate is detached after being spin-dried for solvent by column chromatography chromatogram
Obtain 22.1 milligrams of colourless oil liquid, yield 94%.
1H NMR (400MHz, CDCl3) δ 8.66 (d, J=8.3Hz, 2H), 8.56 (d, J=8.0Hz, 1H), 8.28 (d, J
=8.2Hz, 1H), 8.20 (d, J=7.6Hz, 1H), 7.86 (t, J=7.2Hz, 1H), 7.66 (m, 3H), 3.30 (d, J=
4.6Hz, 2H), 2.40 (m, 1H), 1.05 (d, J=6.6Hz, 6H)；
13C NMR(100MHz,CDCl3)δ162.5,133.0,130.4,129.4,128.7,127.3,126.5,126.4,
125.2,123.7,122.5,121.9,29.7,29.4,22.9；
Embodiment 7：
Sequentially added in dry 10mL reaction tubes spiral shell [4,5] decyl -6- methyl trifluoro boric acid sylvite (25.8mg,
0.1mmol, 1.0eq.), silver oxide (25.4mg, 0.1mmol, 1.0eq.) and isocyano group -1 2-, 1 '-biphenyl (17.9mg,
0.1mmol, 1.0eq.), it substitutes nitrogen three times, injects 1.0mL dichloromethane and 20.0 μ into reaction tube under nitrogen stream environment
L distilled water, screws reaction lid, is vigorously mixed at room temperature for 10 minutes, reacts the shape that silver mirror is clear that on tube wall
At.Reaction solution filters out metallic residue with diatomite first, and filter cake is washed three times with dichloromethane, and merging filtrate is spin-dried for solvent
Pass through 31.3 milligrams of the isolated colourless oil liquid of column chromatography chromatogram, yield 95% afterwards.
1H NMR (400MHz, CDCl3) δ 8.64 (d, J=8.3Hz, 1H), 8.54 (d, J=8.0Hz, 1H), 8.26 (d, J
=7.7Hz, 1H), 8.12 (d, J=8.1Hz, 1H), 7.84 (t, J=7.3Hz, 1H), 7.72 (t, J=7.6Hz, 1H), 7.62
(m,2H),3.65(m,1H),3.03(m,1H),2.06(m,1H),1.50(m,16H)；
13C NMR(100MHz,CDCl3)δ162.6,133.1,130.3,129.5,128.6,127.2,126.5,126.3,
125.4,123.7,122.5,121.9,50.5,45.1,37.9,36.4,35.1,30.3,29.8,29.7,26.8,24.2,
22.8,21.5；
Embodiment 8：
Sequentially added in dry 10mL reaction tubes three potassium fluoborate salt of propione base (19.2mg, 0.1mmol,
1.0eq.), silver oxide (25.4mg, 0.1mmol, 1.0eq.) and isocyano group -1 2-, 1 '-biphenyl (17.9mg, 0.1mmol,
1.0eq.), it substitutes nitrogen three times, injects 1.0mL dichloromethane and 20.0 μ L distilled water into reaction tube under nitrogen stream environment,
Reaction lid is screwed, is vigorously mixed at room temperature for 10 minutes, the formation for being clear that silver mirror on tube wall is reacted.Reaction solution
Metallic residue is filtered out with diatomite first, filter cake is washed three times with dichloromethane, merging filtrate, is spin-dried for after solvent through column layer
Analysis chromatographic isolation obtains 23.5.54 milligrams of colourless oil liquid, yield 97%.
1H NMR (400MHz, CDCl3) δ 8.63 (d, J=8.3Hz, 1H), 8.53 (d, J=8.1Hz, 1H), 8.27 (d, J
=8.2Hz, 1H), 8.08 (d, J=8.1Hz, 1H), 7.84 (t, J=7.6Hz, 1H), 7.70 (t, J=7.8Hz, 2H), 7.62
(t, J=7.5Hz, 1H), 3.71 (t, J=6.9Hz, 2H), 3.16 (t, J=6.9Hz, 2H), 2.71 (q, J=14.7,7.4Hz,
2H), 1.05 (t, J=7.4Hz, 3H)；
13C NMR(100MHz,CDCl3)δ211.2,159.6,143.4,132.7,130.4,129.5,128.5,127.4,
126.4,125.8,125.4,123.7,122.4,122.0,42.1,36.5,29.1,8.0；
Embodiment 9：
Sequentially added in dry 10mL reaction tubes three potassium fluoborate salt of methyl propionate base (24.4mg, 0.1mmol,
1.0eq.), silver oxide (25.4mg, 0.1mmol, 1.0eq.) and isocyano group -1 2-, 1 '-biphenyl (17.9mg, 0.1mmol,
1.0eq.), it substitutes nitrogen three times, injects 1.0mL dichloromethane and 20.0 μ L distilled water into reaction tube under nitrogen stream environment,
Reaction lid is screwed, is vigorously mixed at room temperature for 10 minutes, the formation for being clear that silver mirror on tube wall is reacted.Reaction solution
Metallic residue is filtered out with diatomite first, filter cake is washed three times with dichloromethane, merging filtrate, is spin-dried for after solvent through column layer
Analysis chromatographic isolation obtains 25.4 milligrams of colourless oil liquid, yield 96%.
1H NMR (400MHz, CDCl3) δ 8.63 (d, J=8.3Hz, 1H), 8.53 (d, J=8.1Hz, 1H), 8.27 (d, J
=8.2Hz, 1H), 8.08 (d, J=8.1Hz, 1H), 7.84 (t, J=7.6Hz, 1H), 7.70 (t, J=7.8Hz, 2H), 7.62
(t, J=7.5Hz, 1H), 3.70 (m, 5H), 3.09 (t, J=7.4Hz, 2H)；
13C NMR(100MHz,CDCl3)δ174.1,158.9,143.5,132.7,130.4,129.8,128.5,127.4,
126.5,125.6,125.3,123.7,122.5,121.9,51.7,31.5,29.7.
Embodiment 10：
Sequentially added in dry 10mL reaction tubes three potassium fluoborate salt of ethyl propionate base (20.8mg, 0.1mmol,
1.0eq.), silver oxide (25.4mg, 0.1mmol, 1.0eq.) and isocyano group -1 2-, 1 '-biphenyl (17.9mg, 0.1mmol,
1.0eq.), it substitutes nitrogen three times, injects 1.0mL dichloromethane and 20.0 μ L distilled water into reaction tube under nitrogen stream environment,
Reaction lid is screwed, is vigorously mixed at room temperature for 10 minutes, the formation for being clear that silver mirror on tube wall is reacted.Reaction solution
Metallic residue is filtered out with diatomite first, filter cake is washed three times with dichloromethane, merging filtrate, is spin-dried for after solvent through column layer
Analysis chromatographic isolation obtains 23.1 milligrams of colourless oil liquid, yield 95%.
1H NMR (400MHz, CDCl3) δ 8.63 (d, J=8.0Hz, 1H), 8.53 (d, J=8.0Hz, 1H), 8.28 (d, J
=8.0Hz, 1H), 8.09 (d, J=7.6Hz, 1H), 7.84 (t, J=8.0Hz, 1H), 7.62 (m, 3H), 4.19 (q, J=
14.4,7.2Hz, 2H), 3.72 (t, J=7.2Hz, 2H), 3.08 (t, J=7.4Hz, 2H), 1.27 (t, J=7.2Hz, 3H)；
13C NMR(100MHz,CDCl3)δ173.6,159.2,132.8,130.4,129.7,128.6,127.4,126.5,
125.7,125.3,123.7,122.5,121.9,60.4,31.9,29.7,14.3
Embodiment 11：
Sequentially add N in dry 10mL reaction tubes, three potassium fluoborate salt of N- dimethylpropionamides (24.4mg,
0.1mmol, 1.0eq.), silver oxide (25.4mg, 0.1mmol, 1.0eq.) and isocyano group -1 2-, 1 '-biphenyl (17.9mg,
0.1mmol, 1.0eq.), it substitutes nitrogen three times, injects 1.0mL dichloromethane and 20.0 μ into reaction tube under nitrogen stream environment
L distilled water, screws reaction lid, is vigorously mixed at room temperature for 10 minutes, reacts the shape that silver mirror is clear that on tube wall
At.Reaction solution filters out metallic residue with diatomite first, and filter cake is washed three times with dichloromethane, and merging filtrate is spin-dried for solvent
Pass through 26.2 milligrams of the isolated colourless oil liquid of column chromatography chromatogram, yield 94% afterwards.
1H NMR (400MHz, CDCl3) δ 4.00 (t, J=6.4Hz, 2H), 3.70 (s, 3H), 2.52 (t, J=6.4Hz,
2H),1.43(m,4H),1.26(m,2H),1.16(s,6H),1.06(s,6H)；
13C NMR(100MHz,CDCl3)δ172.3,71.6,59.8,51.6,39.7,34.0,33.0,20.0,17.2；
Embodiment 12：
Sequentially added in dry 10mL reaction tubes three potassium fluoborate salt of N- cyclohexyl propionamide (26.1mg, 0.1mmol,
1.0eq.), silver oxide (25.4mg, 0.1mmol, 1.0eq.) and isocyano group -1 2-, 1 '-biphenyl (17.9mg, 0.1mmol,
1.0eq.), it substitutes nitrogen three times, injects 1.0mL dichloromethane and 20.0 μ L distilled water into reaction tube under nitrogen stream environment,
Reaction lid is screwed, is vigorously mixed at room temperature for 10 minutes, the formation for being clear that silver mirror on tube wall is reacted.Reaction solution
Metallic residue is filtered out with diatomite first, filter cake is washed three times with dichloromethane, merging filtrate, is spin-dried for after solvent through column layer
Analysis chromatographic isolation obtains 30.3 milligrams of colourless oil liquid, yield 91%.
1H NMR (400MHz, CDCl3) δ 8.64 (d, J=8.2Hz, 1H), 8.53 (d, J=8.0Hz, 1H), 8.29 (d, J
=8.2Hz, 1H), 8.08 (d, J=8.8Hz, 1H), 7.85 (t, J=7.7Hz, 1H), 7.72 (q, J=13.8,6.8Hz, 2H),
7.65 (t, J=7.6Hz, 1H), 3.75 (m, 3H), 2.94 (t, J=6.9Hz, 2H), 1.85 (m, 4H), 1.65 (m, 6H)；
13C NMR(100MHz,CDCl3)δ172.1,160.1,142.9,132.8,130.8,129.1,128.7,127.6,
126.7,125.9,125.3,123.8,122.5,122.1,48.0,34.3,33.3,33.1,30.0,25.6,24.9,24.8；
Embodiment 13：
Sequentially added in dry 10mL reaction tubes three potassium fluoborate salt of 2- methvl-propionic acid methyl estes base (25.6mg,
0.1mmol, 1.0eq.), silver oxide (25.4mg, 0.1mmol, 1.0eq.) and isocyano group -1 2-, 1 '-biphenyl (17.9mg,
0.1mmol, 1.0eq.), it substitutes nitrogen three times, injects 1.0mL dichloromethane and 20.0 μ into reaction tube under nitrogen stream environment
L distilled water, screws reaction lid, is vigorously mixed at room temperature for 10 minutes, reacts the shape that silver mirror is clear that on tube wall
At.Reaction solution filters out metallic residue with diatomite first, and filter cake is washed three times with dichloromethane, and merging filtrate is spin-dried for solvent
Pass through 25.4 milligrams of the isolated colourless oil liquid of column chromatography chromatogram, yield 93% afterwards.(nucleus magnetic hydrogen spectrum such as attached drawing 3, nuclear-magnetism
Carbon spectrum such as Fig. 4)
1H NMR (400MHz, CDCl3) δ 8.43 (d, J=8.3Hz, 1H), 8.53 (d, J=8.1Hz, 1H), 8.27 (d, J
=8.2Hz, 1H), 8.07 (d, J=8.0Hz, 1H), 7.84 (t, J=7.6Hz, 1H), 7.70 (t, J=7.8Hz, 1H), 7.63
(t, J=7.8Hz, 1H), 3.85 (m, 1H), 3.68 (s, 3H), 3.44 (m, 2H), 1.37 (d, J=6.8Hz, 3H)；
13C NMR(100MHz,CDCl3)δ174.1,159.0,143.5,132.7,130.4,129.8,128.5,127.4,
126.5,125.6,125.3,123.7,122.5,121.9,51.8,38.4,29.4,17.6；
Embodiment 14：
Sequentially added in dry 10mL reaction tubes three potassium fluoborate salt of thienylethyl (21.8mg, 0.1mmol,
1.0eq.), silver oxide (25.4mg, 0.1mmol, 1.0eq.) and isocyano group -1 2-, 1 '-biphenyl (17.9mg, 0.1mmol,
1.0eq.), it substitutes nitrogen three times, injects 1.0mL dichloromethane and 20.0 μ L distilled water into reaction tube under nitrogen stream environment,
Reaction lid is screwed, is vigorously mixed at room temperature for 10 minutes, the formation for being clear that silver mirror on tube wall is reacted.Reaction solution
Metallic residue is filtered out with diatomite first, filter cake is washed three times with dichloromethane, merging filtrate, is spin-dried for after solvent through column layer
Analysis chromatographic isolation obtains 27.4 milligrams of colourless oil liquid, yield 95%.
1H NMR (400MHz, CDCl3) δ 8.67 (d, J=8.3Hz, 1H), 8.56 (d, J=8.0Hz, 1H), 8.25 (d, J
=8.0Hz, 1H), 8.08 (d, J=8.1Hz, 1H), 7.74 (t, J=7.4Hz, 1H), 7.70 (m, 3H), 7.14 (d, J=
4.6Hz, 1H), 6.94 (m, 2H), 3.78 (t, J=8.0Hz, 2H), 3.56 (m, 2H)；
13C NMR(100MHz,CDCl3)δ160.2,137.0,133.0,130.6,129.5,128.8,127.5,126.8,
126.0,125.2,124.6,123.8,123.3,122.6,122.0,29.7,28.7；
Embodiment 15：
Sequentially added in dry 10mL reaction tubes three potassium fluoborate salt of N- butyl phthalimides (30.9mg,
0.1mmol, 1.0eq.), silver oxide (25.4mg, 0.1mmol, 1.0eq.) and isocyano group -1 2-, 1 '-biphenyl (17.9mg,
0.1mmol, 1.0eq.), it substitutes nitrogen three times, injects 1.0mL dichloromethane and 20.0 μ into reaction tube under nitrogen stream environment
L distilled water, screws reaction lid, is vigorously mixed at room temperature for 10 minutes, reacts the shape that silver mirror is clear that on tube wall
At.Reaction solution filters out metallic residue with diatomite first, and filter cake is washed three times with dichloromethane, and merging filtrate is spin-dried for solvent
Pass through 35.3 milligrams of the isolated colourless oil liquid of column chromatography chromatogram, yield 93% afterwards.
1H NMR (400MHz, CDCl3) δ 8.57 (d, J=8.2Hz, 1H), 8.43 (d, J=7.4Hz, 1H), 8.24 (d, J
=8.2Hz, 1H), 8.08 (dd, J=8.1,1Hz, 1H), 7.65 (m, 2H), 7.56 (m, 5H), 3.90 (m, 3H), 2.89 (m,
1H), 2.12 (m, 1H), 1.48 (d, J=6.9Hz, 3H)；
13C NMR(100MHz,CDCl3)δ168.3,163.7,143.6,133.4,133.0,131.9,130.0,130.0,
128.4,127.2,126.2,125.5,124.8,123.2,122.7,122.3,121.6,37.0,35.0,33.4,21.4；
Embodiment 16：
Three potassium fluoborate salt (19.0mg, 0.1mmol, 1.0eq.) of cyclohexyl is sequentially added in dry 10mL reaction tubes,
Silver oxide (25.4mg, 0.1mmol, 1.0eq.) and isocyano group -1 2-, 1 '-biphenyl (17.9mg, 0.1mmol, 1.0eq.), substitute
Nitrogen three times, injects 1.0mL dichloromethane and 20.0 μ L distilled water into reaction tube under nitrogen stream environment, screws reaction tube
Lid, is vigorously mixed at room temperature for 10 minutes, reacts the formation that silver mirror is clear that on tube wall.Reaction solution uses diatom first
Soil filters out metallic residue, and filter cake is washed three times with dichloromethane, and merging filtrate is detached after being spin-dried for solvent by column chromatography chromatogram
Obtain 23.0 milligrams of colourless oil liquid, yield 88%.
1H NMR (400MHz, CDCl3) δ 8.63 (d, J=8.0Hz, 1H), 8.51 (d, J=8.1Hz, 1H), 8.30 (d, J
=8.2Hz, 1H), 8.13 (d, J=7.6Hz, 1H), 7.84 (t, J=7.6Hz, 1H), 7.70 (t, J=7.8Hz, 2H), 7.62
(t, J=7.5Hz, 1H), 3.60 (m, 1H), 2.07 (d, J=10.8Hz, 2H), 1.95 (m, 3H), 1.80 (m, 1H), 1.58 (m,
4H)；
13C NMR(100MHz,CDCl3)δ166.3,143.9,133.1,130.9,129.9,128.4,127.1,126.1,
125.6,124.7,123.4,122.6,121.8,40.0,32.3,26.9,26.3；
Embodiment 17：
Three potassium fluoborate salt (17.6mg, 0.1mmol, 1.0eq.) of cyclopenta is sequentially added in dry 10mL reaction tubes,
Silver oxide (25.4mg, 0.1mmol, 1.0eq.) and isocyano group -1 2-, 1 '-biphenyl (17.9mg, 0.1mmol, 1.0eq.), substitute
Nitrogen three times, injects 1.0mL dichloromethane and 20.0 μ L distilled water into reaction tube under nitrogen stream environment, screws reaction tube
Lid, is vigorously mixed at room temperature for 10 minutes, reacts the formation that silver mirror is clear that on tube wall.Reaction solution uses diatom first
Soil filters out metallic residue, and filter cake is washed three times with dichloromethane, and merging filtrate is detached after being spin-dried for solvent by column chromatography chromatogram
Obtain 21.0 milligrams of colourless oil liquid, yield 85%.(nucleus magnetic hydrogen spectrum such as attached drawing 5, nuclear-magnetism carbon spectrum such as Fig. 6)
1H NMR (400MHz, CDCl3) δ 8.64 (d, J=8.2Hz, 1H), 8.53 (d, J=8.1Hz, 1H), 8.34 (d, J
=8.2Hz, 1H), 8.12 (d, J=8.1Hz, 1H), 7.82 (t, J=7.6Hz, 1H), 7.68 (m, 2H), 7.60 (t, J=
8.4Hz,1H),4.07(m,1H),2.23(m,4H),1.94(m,2H),1.81(m,2H)；
13C NMR(100MHz,CDCl3)δ164.2,143.8,133.0,130.0,129.9,128.4,127.0,126.2,
126.1,125.7,123.5,122.4,121.8,43.6,32.2,26.0；
Embodiment 18：
Three potassium fluoborate salt (16.4mg, 0.1mmol, 1.0eq.) of tertiary butyl is sequentially added in dry 10mL reaction tubes,
Silver oxide (25.4mg, 0.1mmol, 1.0eq.) and isocyano group -1 2-, 1 '-biphenyl (17.9mg, 0.1mmol, 1.0eq.), substitute
Nitrogen three times, injects 1.0mL dichloromethane and 20.0 μ L distilled water into reaction tube under nitrogen stream environment, screws reaction tube
Lid, is vigorously mixed at room temperature for 10 minutes, reacts the formation that silver mirror is clear that on tube wall.Reaction solution uses diatom first
Soil filters out metallic residue, and filter cake is washed three times with dichloromethane, and merging filtrate is detached after being spin-dried for solvent by column chromatography chromatogram
Obtain 19.3 milligrams of colourless oil liquid, yield 82%.(nucleus magnetic hydrogen spectrum such as attached drawing 7, nuclear-magnetism carbon spectrum such as Fig. 8)
1H NMR (400MHz, CDCl3) δ 8.60 (d, J=8.2Hz, 1H), 8.54 (d, J=8.4Hz, 1H), 8.44 (d, J
=8.2Hz, 1H), 8.05 (d, J=7.2 Hz, 1H), 7.69 (t, J=7.6 Hz, 1H), 7.57 (m, 3H), 1.65 (s, 9H)；
13C NMR(100 MHz,CDCl3)δ166.7,142.9,134.1,130.3,129.3,128.4,128.3,
126.5,125.9,124.3,123.4,123.0,121.6,40.2,31.2。
Claims (5)
1. a kind of novel 6- alkyl phenanthridines and derivative, which is characterized in that its general structure (I) is as follows：
In formula, R bases are(X=H, Br, Cl), In one kind；
Its derivative is as follows：
2. it is raw material as free based precursor using three potassium fluoborate salt of alkyl the preparation method of a kind of novel 6- alkyl phenanthridines,
Under nitrogen atmosphere, using dichloromethane as solvent, with silver oxide and water initiated oxidation reduction system, by isocyano group -1 2-, 1 '-connection
Benzene captures, and constitutes 6- alkyl phenanthridines precursor structures through cyclization, synthetic route is as shown in public formula (I)：
Its specific synthesis step is as follows：
1) R-BF by metering is sequentially added in clean reactor3K, silver oxide and isocyano group -1 2-, 1 '-biphenyl are substituted
Nitrogen 3 times injects dichloromethane-water mixed solvent of 10mL/mmol, sealing reaction under nitrogen stream environment into reaction tube
Device；
2) it is vigorously mixed at room temperature for 10~30 minutes, stops stirring, obtain reaction solution；
3) metallic residue in above-mentioned reaction solution being filtered out with diatomite, filter cake is washed 3~5 times with ethyl acetate, merging filtrate,
It is spin-dried for solvent, is detached to get to target product by column chromatography chromatogram.
3. the preparation method of the novel 6- alkyl phenanthridines of one kind according to claim 2, which is characterized in that the R-BF3K
For three potassium fluoborate salt of alkyl, general structure is as shown in public formula (II)：R-BF3K(II)
In formula, R bases are(X=H, Br, Cl), In one kind.
4. the preparation method of the novel 6- alkyl phenanthridines of one kind according to claim 2, which is characterized in that the R-BF3K、
Silver oxide and 2- isocyano groups -1,1 '-biphenyl are with molar ratio 1:1:1 is measured.
5. the preparation method of the novel 6- alkyl phenanthridines of one kind according to claim 2, which is characterized in that the step 1)
In dichloromethane-water mixed solvent, by volume ratio 50:1 dichloromethane is made into water.
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN111320605A (en) * | 2020-03-09 | 2020-06-23 | 吉林工程技术师范学院 | Preparation method of silver-catalyzed fluorine-containing phenanthridine derivative |
| CN114874141A (en) * | 2022-06-02 | 2022-08-09 | 河南大学 | Synthesis method for constructing phenanthridine compound through ring-opening cyclization of alkenyl benzotriazole under catalysis of visible light |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103936661A (en) * | 2014-04-04 | 2014-07-23 | 常州大学 | Synthetic method of 6-alkyl phenanthridine derivative |
| CN106928128A (en) * | 2017-03-13 | 2017-07-07 | 西京学院 | A kind of Novel alkyl free radical and preparation method thereof |
| CN107235900A (en) * | 2017-07-28 | 2017-10-10 | 温州大学 | The synthetic method of 6 benzyl phenanthridines class compounds |
-
2018
- 2018-03-01 CN CN201810172198.XA patent/CN108299297A/en active Pending
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103936661A (en) * | 2014-04-04 | 2014-07-23 | 常州大学 | Synthetic method of 6-alkyl phenanthridine derivative |
| CN106928128A (en) * | 2017-03-13 | 2017-07-07 | 西京学院 | A kind of Novel alkyl free radical and preparation method thereof |
| CN107235900A (en) * | 2017-07-28 | 2017-10-10 | 温州大学 | The synthetic method of 6 benzyl phenanthridines class compounds |
Non-Patent Citations (5)
| Title |
|---|
| C.LION ET AL.: "Synthese Dans La Chimie Des Phenanthridines. II. Preparation D’Une Nouvelle Serie D’ω-(Phenanthridinyl-6)Alcanoates De Methyle Ou D’Ethyle", 《BULLETIN DES SOCIETES CHIMIQUES BELGES》 * |
| CECILE PASCAL ET AL.: "Synthesis and Separation of New Dibenz[b,d]azonine Atropisomers", 《SYNTHETIC COMMUNICATIONS》 * |
| JUN-CHENG YANG ET AL.: "Copper-catalyzed oxidative cyclization of vinyl azides with benzylic Csp3-H bonds for the synthesis of substituted phenanthridines", 《ORGANIC & BIOMOLECULAR CHEMISTRY》 * |
| JUN-CHENG YANG ET AL.: "Metal-Free, Visible-Light-Promoted Decarboxylative Radical Cyclization of Vinyl Azides with N-Acyloxyphthalimides", 《THE JOURNAL OF ORGANIC CHEMISTRY》 * |
| MORTEN LYSEN ET AL.: "Convergent Synthesis of 6-Substituted Phenanthridines via Anionic Ring Closure", 《ORGANIC LETTERS》 * |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN111320605A (en) * | 2020-03-09 | 2020-06-23 | 吉林工程技术师范学院 | Preparation method of silver-catalyzed fluorine-containing phenanthridine derivative |
| CN114874141A (en) * | 2022-06-02 | 2022-08-09 | 河南大学 | Synthesis method for constructing phenanthridine compound through ring-opening cyclization of alkenyl benzotriazole under catalysis of visible light |
| CN114874141B (en) * | 2022-06-02 | 2024-03-29 | 河南大学 | Synthesis method for constructing phenanthridine compounds by ring-opening cyclization of alkenyl benzotriazole under catalysis of visible light |
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