CN107235900A - The synthetic method of 6 benzyl phenanthridines class compounds - Google Patents
The synthetic method of 6 benzyl phenanthridines class compounds Download PDFInfo
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- 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
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Abstract
The invention discloses the synthetic method of 6 benzyl phenanthridines class compounds, reaction equation is as follows：
Description
Technical field
The present invention relates to the synthetic method of a class organic compound, and in particular to the synthesis side of 6- benzyl phenanthridines class compounds
Method, belongs to technical field of chemistry.
Background technology
6- benzyl phenanthridines class compounds are common construction units in a class natural products, much the construction unit containing phenanthridines
Natural products all shows good pharmacological activity, and representative therein is that trisphaeridine, Nitidine Chloride (have anti-liver cancer and anti-work
Property), fagaronine.Some benzo phenanthridines class compounds have anti-liver cancer and anti-, anti-nasopharyngeal carcinoma and anti-gastric cancer activity, and and calf thymus
DNA has strong interaction.It is reported that benzo phenanthridines class compound can be used as topoisomerase I and type Ⅱ topoisomerase
Inhibitor, so as to play antitumaous effect.
So important just because of 6- benzyl phenanthridines class compounds, people synthesize to it has carried out numerous studies, at present
Through exploring a plurality of synthetic route and method, for example：
(1) RMgBr method：It is anti-under the conditions of copper catalyst using -2 '-bromo biphenyl of 2- cyano group and ethylmagnesium bromide as raw material
Should, obtain 6- benzyl phenanthridines classes；
(2) azidotrimethylsilane method：Using 2- acetyl biphenyls and azidotrimethylsilane as raw material, equivalent is added
Pivalic acid, in trifluoroacetic acid solvent, obtain 6- benzyl phenanthridines classes.
However, either RMgBr method, or azidotrimethylsilane method, there is certain defect, example in them
Such as：
(1) RMgBr method：Need HTHP, severe reaction conditions；Metal catalytic is needed, synthesis cost is higher；Ring
Border pollution is big；
(2) azidotrimethylsilane：Used raw material nitrine is abnormally dangerous, and needs to add greatly in reaction system
The acid of amount, environmental pollution is serious.
It can be seen that, although there are a variety of methods for preparing 6- benzyl phenanthridines class compounds in the prior art, but these methods are all
In the presence of than more serious defect, their application is caused to be restricted.
At present, the synthetic method of phenanthridines is a study hotspot, new phenanthridines parent nucleus synthetic method is studied, especially without gold
The synthetic method of category, can greatly promote the research to the medicine of construction unit containing phenanthridines.
The content of the invention
It is an object of the invention to provide one kind it is easy to operate, be easy to post processing, reaction condition it is gentle, without catalyst,
The synthetic method of green, economic 6- benzyl phenanthridines class compounds.
In order to realize above-mentioned target, the present invention is adopted the following technical scheme that：
The synthetic method of 6- benzyl phenanthridines class compounds, it is characterised in that with toluene and 2- with structure shown in formula (I)
Isocyano group biphenyl is raw material, adds oxidant and alkali, is obtained in reaction dissolvent by radical reaction with formula (II) Suo Shi
The 6- benzyl phenanthridines class compounds of structure, reaction equation is as follows：
Wherein, R=hydrogen, fluorine, chlorine, methyl, methoxyl group or naphthalene nucleus.
The synthetic method of foregoing 6- benzyl phenanthridines class compounds, it is characterised in that specifically include following steps：
Step1：The alkali of reaction dissolvent and catalytic amount is added in reaction vessel, then reaction vessel is carried out continuously 3 times
Pumping-inflated with nitrogen operation；
Step2：Continue to add oxidant into reaction vessel, join with the toluene of structure shown in formula (I) and 2- isocyano groups
Benzene, reacts a period of time in oil bath；
Step3：After reaction terminates, the mixture obtained by reaction is isolated and purified.
The synthetic method of foregoing 6- benzyl phenanthridines class compounds, it is characterised in that foregoing 2- isocyano groups biphenyl is with having
The mol ratio of the toluene of structure shown in formula (I) is 1:1~65.
The synthetic method of foregoing 6- benzyl phenanthridines class compounds, it is characterised in that aforementioned oxidizer be chrome green,
Manganese dioxide, 2,2,6,6- tetramethyl piperidine oxides, 2,3-Dichloro-5,6-dicyano-1,4-benzoquinone, two (trifluoroacetic acid) iodine
Benzene, di-tert-butyl hydrogen peroxide, silver carbonate, silver acetate, silver nitrate, silver sulfate, iodobenzene diacetate, ammonium persulfate, potassium peroxydisulfate
At least one of with sodium peroxydisulfate.
The synthetic method of foregoing 6- benzyl phenanthridines class compounds, it is characterised in that with molar amount, aforementioned oxidizer
The amount ratio of consumption and foregoing 2- isocyano groups biphenyl is 1：1~3.
The synthetic method of foregoing 6- benzyl phenanthridines class compounds, it is characterised in that aforementioned bases are 1,8- diazabicylos
In 11 carbon -7- alkene, Isosorbide-5-Nitrae-diazabicylo (2,2,2) octane, diethylamine, triethylamine, diethanol amine and triethanolamine extremely
Few one kind, with molar amount, the consumption of aforementioned bases is the 1%~10% of foregoing 2- isocyano groups biphenyl consumption.
The synthetic method of foregoing 6- benzyl phenanthridines class compounds, it is characterised in that aforementioned bases be potassium carbonate, sodium carbonate,
At least one of potassium acetate and sodium acetate, with molar amount, the consumption of aforementioned bases is the 1% of foregoing 2- isocyano groups biphenyl consumption
~10%.
The synthetic method of foregoing 6- benzyl phenanthridines class compounds, it is characterised in that previous reaction solvent is toluene, 4- chlorine
Toluene, 4- methoxy toluenes, 4- toluene bromides, 3- toluene bromides, 3- chlorotoluenes ortho-xylene, meta-xylene, paraxylene, 2,3,4,
At least one of the toluene fluorides of 5,6- five and mesitylene.
The synthetic method of foregoing 6- benzyl phenanthridines class compounds, it is characterised in that the temperature of reaction is 0 DEG C~120 DEG C.
The synthetic method of foregoing 6- benzyl phenanthridines class compounds, it is characterised in that the time of reaction is 12h~24h.
It should be noted that：
(1) reaction temperature
In the synthetic method of the present invention, reaction temperature is 0 DEG C~120 DEG C, in non-limiting manner for example：0℃、20℃、40
DEG C, 60 DEG C, 80 DEG C, 100 DEG C or 120 DEG C.
(2) reaction time
In the synthetic method of the present invention, the reaction time, there is no particular limitation, for example, can pass through liquid chromatographic detection mesh
Product or raw material residual percentage and determine the suitable reaction time, usually 12h~24h, in non-limiting manner for example：
12h, 14h, 16h, 18h, 20h, 22h or 24h.
(3) isolate and purify
The mixture of gained after reaction can be isolated and purified further, can to obtain purer final products
To use isolation and purification method well known within the skill of those ordinarily skilled, for example：Extraction, column chromatography, distillation, recrystallization, decantation,
Filtering, centrifugation, washing, evaporation, stripping or adsorb, or at least two isolation and purification methods combination, for example：Extraction and post layer
The combination of analysis.
Certainly, the reactant mixture of acquisition can also be introduced directly into the directly reaction of other processes if desired to produce
Other products.Optionally, before other processes are incorporated into, can to reaction mixing pre-process, for example concentrate, extract and
One or more in vacuum distillation, to obtain crude product or pure product, are then incorporated into other processes.
The present invention is advantageous in that：
(1) preparation process is easy to operate, and products therefrom is easy to post processing；
(2) HTHP is not needed, reaction condition is gentle；
(3) catalyst, synthesis cost reduction are not needed；
(4) reaction substrate functional group tolerance is high, and substrate spectrum is wide, easily prepare；
(5) oxidant is cheap and easy to get, more economical；
(6) efficient, high income is reacted；
(7) it is free from environmental pollution, environmental protection.
Embodiment
The synthetic method of the present invention, using 2- isocyano groups biphenyl and toluene as raw material, using without metal activation toluene benzyl position carbon
The method of hydrogen bond, 6- benzyl phenanthridines class compounds are obtained by radical reaction, and experimental implementation is simple, no metal catalytic, to ring
Border does not produce pollution.
In order to illustrate more clearly of the synthetic method of the present invention, the present invention is made below in conjunction with specific preferred embodiment
It is specific to introduce.
Embodiment 1
The synthesis of 6- benzyl phenanthridines：
Under room temperature (25 DEG C), by organic base Isosorbide-5-Nitrae-diazabicylo of reaction dissolvent toluene (2mL) and catalytic amount (2,2,
2) octane (DABCO, 0.03mmol, 0.1equiv) is added in reaction tube, and 3 pumping-inflated with nitrogen are carried out continuously to reaction tube
Operation, then proceedes to add oxidant di-tert-butyl hydrogen peroxide (DTBP, 0.75mmol, 2.5equiv), original into reaction tube
Expect toluene (2mL) and raw material 2- isocyano groups biphenyl (0.3mmol, 1equiv), stirred afterwards in oil bath under 120 DEG C of reaction temperatures
24h, after question response terminates, directly spins off reaction dissolvent, (300 mesh silica gel is filled in post, with petroleum ether and acetic acid second through column chromatography
Ester volume ratio 40：1 is eluant, eluent) separation after obtain product, product is yellow solid, yield 80%.
The data of the proton nmr spectra of products therefrom are as follows：
1H NMR(500MHz,CDCl3)δ8.59(1H,d),8.53(1H,d),8.19(2H,t),7.71-7.77(2H,m),
7.63(1H,t),7.55(1H,t),7.30-7.32(2H,m),7.21-7.25(2H,m),7.16(1H,d),4.75(2H,s)。
The data of the carbon-13 nmr spectra of products therefrom are as follows：
13C NMR(125MHz,CDCl3)δ160.2,143.6,139.0,133.2,130.3,129.8,128.6,128.5,
127.2,127.0,126.6,125.3,123.9,122.3,121.9,43.0。
The theoretical calculation and experimental result analyzed product are as follows：
Anal.Calcd.For C20H15N：C,89.19；H,5.61；N,5.20；
Found：C,89.20；H,5.72；N,5.21.
Embodiment 2
The synthesis of 6- (4- methyl-benzyls) phenanthridines：
Under room temperature (25 DEG C), by reaction dissolvent paraxylene (2mL) and organic base Isosorbide-5-Nitrae-diazabicylo of catalytic amount
(2,2,2) octane (DABCO, 0.03mmol, 0.1equiv) is added in reaction tube, and 3 times are carried out continuously to reaction tube and is evacuated-fills
Operating under nitrogen, then proceed to add into reaction tube oxidant di-tert-butyl hydrogen peroxide (DTBP, 0.75mmol,
2.5equiv), raw material paraxylene (2mL) and raw material 2- isocyano groups biphenyl (0.3mmol, 1equiv), afterwards 120 in oil bath
Stir 24h under DEG C reaction temperature, after question response terminates, directly spin off reaction dissolvent, through column chromatography (300 mesh silica gel of filling in post,
With petroleum ether and ethyl acetate volume ratio 40：1 is eluant, eluent) separation after obtain product, product is yellow solid, yield 78%.
The data of the proton nmr spectra of products therefrom are as follows：
1H NMR(500MHz,CDCl3)δ8.58(1H,d),8.52(1H,d),8.18-8.20(m,2H),7.71-7.76
(m,2H),7.61-7.64(m,1H),7.53-7.57(m,1H),7.19-7.23(m,2H),7.02-7.04(m,2H),4.70
(s,2H),2.25(s,3H)。
The data of the carbon-13 nmr spectra of products therefrom are as follows：
13C NMR(125MHz,CDCl3)δ160.3,143.7,136.0,135.7,133.2,130.2,129.8,129.6,
129.2,128.6,128.3,127.2,127.0,126.5,125.3,123.9,122.3,121.9,42.6,20.9。
The theoretical calculation and experimental result analyzed product are as follows：
Anal.Calcd.For C21H17N：C,89.01；H,6.05；N,4.94；
Found：C,89.02；H,6.06；N,4.95.
Embodiment 3
The synthesis of 6- (3- methyl-benzyls) phenanthridines：
Under room temperature (25 DEG C), by reaction dissolvent meta-xylene (2mL) and organic base Isosorbide-5-Nitrae-diazabicylo of catalytic amount
(2,2,2) octane (DABCO, 0.03mmol, 0.1equiv) is added in reaction tube, and 3 times are carried out continuously to reaction tube and is evacuated-fills
Operating under nitrogen, then proceed to add into reaction tube oxidant di-tert-butyl hydrogen peroxide (DTBP, 0.75mmol,
2.5equiv), raw material meta-xylene (2mL) and raw material 2- isocyano groups biphenyl (0.3mmol, 1equiv), afterwards 120 in oil bath
Stir 24h under DEG C reaction temperature, after question response terminates, directly spin off reaction dissolvent, through column chromatography (300 mesh silica gel of filling in post,
With petroleum ether and ethyl acetate volume ratio 40：1 is eluant, eluent) separation after obtain product, product is yellow solid, yield 73%.
The data of the proton nmr spectra of products therefrom are as follows：
1H NMR(500MHz,CDCl3)δ:8.59(d,1H),8.54(d,1H),8.18-8.22(m,2H),7.72-7.77
(m,2H),7.62-7.66(m,1H),7.54-7.58(m,1H),7.11-7.12(m,3H),6.97(d,1H),4.71(s,2H),
2.24(s,3H)。
The data of the carbon-13 nmr spectra of products therefrom are as follows：
13CNMR(125MHz,CDCl3)δ：160.2,143.6,139.0,138.1,133.2,130.3,129.8,128.6,
128.3,127.3,127.1,126.6,125.5,125.4,123.9,121.9,43.0,21.3。
The theoretical calculation and experimental result analyzed product are as follows：
Anal.Calcd.For C21H17N：C,89.01；H,6.05；N,4.94；
Found：C,89.02；H,6.06；N,4.95.
Embodiment 4
The synthesis of 6- (2- methyl-benzyls) phenanthridines：
Under room temperature (25 DEG C), by reaction dissolvent ortho-xylene (2mL) and organic base Isosorbide-5-Nitrae-diazabicylo of catalytic amount
(2,2,2) octane (DABCO, 0.03mmol, 0.1equiv) is added in reaction tube, and 3 times are carried out continuously to reaction tube and is evacuated-fills
Operating under nitrogen, then proceed to add into reaction tube oxidant di-tert-butyl hydrogen peroxide (DTBP, 0.75mmol,
2.5equiv), raw material ortho-xylene (2mL) and raw material 2- isocyano groups biphenyl (0.3mmol, 1equiv), afterwards 120 in oil bath
Stir 24h under DEG C reaction temperature, after question response terminates, directly spin off reaction dissolvent, through column chromatography (300 mesh silica gel of filling in post,
With petroleum ether and ethyl acetate volume ratio 40：1 is eluant, eluent) separation after obtain product, product is yellow solid, yield 70%.
The data of the proton nmr spectra of products therefrom are as follows：
1H NMR(500MHz,CDCl3)δ8.62(1H,d),8.55(1H,d),8.15(1H,d),8.01(1H,d),7.70-
7.78(2H,m),7.61-7.65(1H,m),7.54(1H,t),7.20-7.22(2H,m),7.08(t,1H),6.91-6.95(m,
1H),6.74(1H,d),4.68(2H,s),2.49(3H,s)。
The data of the carbon-13 nmr spectra of products therefrom are as follows：
13C NMR(125MHz,CDCl3)δ:160.1,143.8,137.6,136.0,133.0,130.3,130.0,
129.8,128.6,128.4,127.3,126.9,126.2,125.9,125.6,123.8,122.4,121.9,40.2,20.0。
The theoretical calculation and experimental result analyzed product are as follows：
Anal.Calcd.For C21H17N：C,89.01；H,6.05；N,4.94；
Found：C,89.02；H,6.06；N,4.95.
Embodiment 5
The synthesis of 6- (4- methoxy-benzyls) phenanthridines：
Under room temperature (25 DEG C), by reaction dissolvent 4- methoxy toluenes (2mL) and organic base Isosorbide-5-Nitrae-diaza of catalytic amount
Two rings (2,2,2) octane (DABCO, 0.03mmol, 0.1equiv) is added in reaction tube, and 3 times are carried out continuously to reaction tube and is taken out
The operation of gas-inflated with nitrogen, then proceed to add into reaction tube oxidant di-tert-butyl hydrogen peroxide (DTBP, 0.75mmol,
2.5equiv), raw material 4- methoxy toluenes (2mL) and raw material 2- isocyano groups biphenyl (0.3mmol, 1equiv), afterwards in oil bath
In stir 24h under 120 DEG C of reaction temperatures, after question response terminates, reaction dissolvent is directly spun off, through column chromatography (300 mesh of filling in post
Silica gel, with petroleum ether and ethyl acetate volume ratio 40：1 is eluant, eluent) separation after obtain product, product is yellow solid, yield
68%.
The data of the proton nmr spectra of products therefrom are as follows：
1H NMR(500MHz,CDCl3)δ：8.53(1H,d),8.46(1H,d),8.12(2H,2H),7.64-7.70(2H,
m),7.55-7.58(1H,m),7.48-7.51(1H,m),7.14-7.16(2H,m),6.70(2H,d),6.70(2H,d),4.61
(2H,s),3.64(3H,s)。
The data of the carbon-13 nmr spectra of products therefrom are as follows：
13C NMR(125MHz,CDCl3)δ：160.5,158.1,133.3,131.2,130.4,129.8,129.5,
128.7,127.3,126.7,125.4,124.0,122.4,122.0,114.0,55.2,42.2。
The theoretical calculation and experimental result analyzed product are as follows：
Anal.Calcd.For C21H17NO：C,84.25；H,5.72；N,4.68；O,5.34；
Found：C,84.26；H,5.73；N,4.69；O,5.35.
Embodiment 6
The synthesis of 6- (4- chlorobenzyls) phenanthridines：
Under room temperature (25 DEG C), by reaction dissolvent 4- chlorotoluenes (2mL) and organic base Isosorbide-5-Nitrae-diazabicylo of catalytic amount
(2,2,2) octane (DABCO, 0.03mmol, 0.1equiv) is added in reaction tube, and 3 times are carried out continuously to reaction tube and is evacuated-fills
Operating under nitrogen, then proceed to add into reaction tube oxidant di-tert-butyl hydrogen peroxide (DTBP, 0.75mmol,
2.5equiv), raw material 4- chlorotoluenes (2mL) and raw material 2- isocyano groups biphenyl (0.3mmol, 1equiv), afterwards 120 in oil bath
Stir 24h under DEG C reaction temperature, after question response terminates, directly spin off reaction dissolvent, through column chromatography (300 mesh silica gel of filling in post,
With petroleum ether and ethyl acetate volume ratio 40：1 is eluant, eluent) separation after obtain product, product is yellow solid, yield 70%.
The data of the proton nmr spectra of products therefrom are as follows：
1H NMR(500MHz,d6-DMSO)δ:8.61(1H,d),8.54(1H,d),8.18(1H,d),8.10(1H,d),
7.72-7.79(2H,m),7.65(1H,t),7.58(1H,t),7.19-7.24(4H,m),4.70(2H,s)。
The data of the carbon-13 nmr spectra of products therefrom are as follows：
13CNMR(100MHz,d6-DMSO)δ:159.5,137.5,133.2,132.0,130.4,129.8,129.8,
128.7,127.3,126.7,125.1,123.8,122.4,121.9,42.2。
The theoretical calculation and experimental result analyzed product are as follows：
Anal.Calcd.For C20H14ClN：C,79.07；H,4.65；Cl,11.67；N,4.61；
Found：C,79.08；H,4.66；Cl,11.68；N,4.62.
Embodiment 7
The synthesis of 6- (2,3,4,5,6- PFBBRs) phenanthridines：
Under room temperature (25 DEG C), by the organic base Isosorbide-5-Nitrae of the toluene fluoride (2mL) of reaction dissolvent 2,3,4,5,6- five and catalytic amount-
Diazabicylo (2,2,2) octane (DABCO, 0.03mmol, 0.1equiv) is added in reaction tube, and reaction tube is carried out continuously
3 pumpings-inflated with nitrogen operation, then proceed to add into reaction tube oxidant di-tert-butyl hydrogen peroxide (DTBP,
0.75mmol, 2.5equiv), the toluene fluoride (2mL) of raw material 2,3,4,5,6- five and raw material 2- isocyano groups biphenyl (0.3mmol,
1equiv), 24h is stirred under 120 DEG C of reaction temperatures in oil bath afterwards, after question response terminates, reaction dissolvent is directly spun off, through post
Chromatography (fills 300 mesh silica gel, with petroleum ether and ethyl acetate volume ratio 40 in post：1 is eluant, eluent) separation after obtain product, produce
Thing is yellow solid, yield 75%.
The data of the proton nmr spectra of products therefrom are as follows：
1H NMR(500MHz,CDCl3)δ：8.66(1H,d),8.51-8.54(1H,m),8.28(1H,d),7.92(1H,
d),7.87(1H,t),7.74(1H,t),7.60-7.67(2H,m),4.76(2H,s)。
The data of the carbon-13 nmr spectra of products therefrom are as follows：
13C NMR(1120MHz,CDCl3)δ：155.4,143.7,133.2,130.8,130.4,128.9,127.8,
127.3,127.1,125.3,125.2,124.0,122.9,122.1,29.1。
The theoretical calculation and experimental result analyzed product are as follows：
Anal.Calcd.For C20H10F5N：C,66.86；H,2.81；F,26.44；N,3.90；
Found：C,66.87；H,2.82；F,26.45；N,3.91.
Embodiment 8
The synthesis of 6- (2- menaphthyls) phenanthridines：
Under room temperature (25 DEG C), by reaction dissolvent 2- methyl naphthalenes (2mL) and organic base Isosorbide-5-Nitrae-diazabicylo of catalytic amount
(2,2,2) octane (DABCO, 0.03mmol, 0.1equiv) is added in reaction tube, and 3 times are carried out continuously to reaction tube and is evacuated-fills
Operating under nitrogen, then proceed to add into reaction tube oxidant di-tert-butyl hydrogen peroxide (DTBP, 0.75mmol,
2.5equiv), raw material 2- methyl naphthalenes (2mL) and raw material 2- isocyano groups biphenyl (0.3mmol, 1equiv), afterwards 120 in oil bath
Stir 24h under DEG C reaction temperature, after question response terminates, directly spin off reaction dissolvent, through column chromatography (300 mesh silica gel of filling in post,
With petroleum ether and ethyl acetate volume ratio 40：1 is eluant, eluent) separation after obtain product, product is yellow solid, yield 83%.
The data of the proton nmr spectra of products therefrom are as follows：
1H NMR(500MHz,CDCl3)δ:8.61(1H,d),8.56(1H,d),8.22-8.25(2H,m),7.64-7.78
(7H,m),7.53(1H,t),7.48(1H,d),7.37-7.39(2H,m),4.92(2H,s)。
The data of the carbon-13 nmr spectra of products therefrom are as follows：
13C NMR(125MHz,CDCl3)δ:160.3,143.9,136.9,133.8,133.6,132.4,130.7,
129.0,128.4,127.8,127.6,127.4,127.3,127.1,127.0,126.2,125.7,124.3,122.7,
122.2,43.4。
The theoretical calculation and experimental result analyzed product are as follows：
Anal.Calcd.For C24H17N：C,90.25；H,5.36；N,4.39；
Found：C,90.26；H,5.37；N,4.40.
Embodiment 9
The synthesis of 6- (3,5- dimethyl benzyl) phenanthridines：
Under room temperature (25 DEG C), by reaction dissolvent mesitylene (2mL) and organic base Isosorbide-5-Nitrae-diazabicylo of catalytic amount
(2,2,2) octane (DABCO, 0.03mmol, 0.1equiv) is added in reaction tube, and 3 times are carried out continuously to reaction tube and is evacuated-fills
Operating under nitrogen, then proceed to add into reaction tube oxidant di-tert-butyl hydrogen peroxide (DTBP, 0.75mmol,
2.5equiv), raw material mesitylene (2mL) and raw material 2- isocyano groups biphenyl (0.3mmol, 1equiv), afterwards 120 in oil bath
Stir 24h under DEG C reaction temperature, after question response terminates, directly spin off reaction dissolvent, through column chromatography (300 mesh silica gel of filling in post,
With petroleum ether and ethyl acetate volume ratio 40：1 is eluant, eluent) separation after obtain product, product is yellow solid, yield 87%.
The data of the proton nmr spectra of products therefrom are as follows：
1H NMR(500MHz,d6-DMSO)δ8.79(1H,dd),8.73(1H,dd),8.31(1H,d)；8.12(1H,d),
7.85(1H,t),7,77(1H,t),7.68(2H,m),6.92(2H,s),6.74(1H,s),4.62(2H,s),2.12(6H,s)。
The data of the carbon-13 nmr spectra of products therefrom are as follows：
13C NMR(125MHz,DMSO-d6)δ160.1,143.2,139.0,137.3,132.6,130.7,128.8,
127.7,126.9,126.7,126.1,124.7,123.3,122.7,122.5,41.8,20.8。
The theoretical calculation and experimental result analyzed product are as follows：
Anal.Calcd.For C22H19N：C,88.85；H,6.44；N,4.71；
Found：C,88.86；H,6.45；N,4.72.
Embodiment 10 is to embodiment 20
In addition to organic base DABCO is replaced with into following alkali respectively, with identical with the embodiment 1 with highest products collection efficiency
Mode implement embodiment 10 respectively to embodiment 20, the yield of used alkali and corresponding product is as shown in the table：
As seen from the above table, when using other alkali, such as：Organic base 1, the carbon -7- alkene of 8- diazabicylos 11
(DBU) highly basic potassium carbonate, in triethylamine, diethylamine, triethanolamine, diethanol amine and inorganic base, sodium carbonate, potassium acetate and
Sodium acetate, can react, but yield has obvious reduction compared with DABCO, and this illustrates the appropriately selected to reaction of alkali
Yield have significant impact.
In addition, through experiment, when reaction dissolvent is from 3- chlorotoluenes, 4- toluene bromides or 3- toluene bromides, also can occur anti-
Should, and the yield of product is all higher, is at least attained by more than 70%, even more high.
By above-mentioned all embodiments it will be evident that the use of toluene and 2- isocyano groups biphenyl being raw material, oxidant is added
And alkali, 6- benzyl phenanthridines class compounds are obtained with high yield and high-purity by radical reaction in reaction dissolvent, this is
The efficient quick synthesis of such compound provides brand-new synthetic route.
It should be noted that the invention is not limited in any way for above-described embodiment, all use equivalent substitutions or equivalent change
The technical scheme that the mode changed is obtained, all falls within protection scope of the present invention.
Claims (10)
- The synthetic method of 1.6- benzyl phenanthridines class compounds, it is characterised in that different with toluene and 2- with structure shown in formula (I) Cyanobiphenyl is raw material, adds oxidant and alkali, is obtained in reaction dissolvent by radical reaction with knot formula (II) Suo Shi The 6- benzyl phenanthridines class compounds of structure, reaction equation is as follows：Wherein, R=hydrogen, fluorine, chlorine, methyl, methoxyl group or naphthalene nucleus.
- 2. the synthetic method of 6- benzyls phenanthridines class compound according to claim 1, it is characterised in that specifically include following Step：Step1：The alkali of reaction dissolvent and catalytic amount is added in reaction vessel, then reaction vessel is carried out continuously 3 pumpings- Inflated with nitrogen is operated；Step2：Continue to add oxidant into reaction vessel, with the toluene of structure shown in formula (I) and 2- isocyano group biphenyl, A period of time is reacted in oil bath；Step3：After reaction terminates, the mixture obtained by reaction is isolated and purified.
- 3. the synthetic method of 6- benzyls phenanthridines class compound according to claim 1 or 2, it is characterised in that the 2- is different Cyanobiphenyl is 1 with the mol ratio with the toluene of structure shown in formula (I):1~65.
- 4. the synthetic method of 6- benzyls phenanthridines class compound according to claim 1 or 2, it is characterised in that the oxidation Agent is chrome green, manganese dioxide, 2, chloro- 5, the 6- dicyanos-Isosorbide-5-Nitrae-benzene of 2,6,6- tetramethyl piperidine oxides, 2,3- bis- Quinone, two (trifluoroacetic acid) iodobenzenes, di-tert-butyl hydrogen peroxide, silver carbonate, silver acetate, silver nitrate, silver sulfate, iodobenzene diacetate, At least one of ammonium persulfate, potassium peroxydisulfate and sodium peroxydisulfate.
- 5. the synthetic method of 6- benzyls phenanthridines class compound according to claim 4, it is characterised in that with molar amount, The amount ratio of the consumption of the oxidant and the 2- isocyano groups biphenyl is 1：1~3.
- 6. the synthetic method of 6- benzyls phenanthridines class compound according to claim 1 or 2, it is characterised in that the alkali is Carbon -7- the alkene of 1,8- diazabicylo 11, Isosorbide-5-Nitrae-diazabicylo (2,2,2) octane, diethylamine, triethylamine, diethanol amine and At least one of triethanolamine, with molar amount, the consumption of the alkali for the 2- isocyano groups biphenyl consumption 1%~ 10%.
- 7. the synthetic method of 6- benzyls phenanthridines class compound according to claim 1 or 2, it is characterised in that the alkali is At least one of potassium carbonate, sodium carbonate, potassium acetate and sodium acetate, with molar amount, the consumption of the alkali is the 2- isocyanides The 1%~10% of base biphenyl consumption.
- 8. the synthetic method of 6- benzyls phenanthridines class compound according to claim 1 or 2, it is characterised in that the reaction Solvent be toluene, 4- chlorotoluenes, 4- methoxy toluenes, 4- toluene bromides, 3- toluene bromides, 3- chlorotoluenes ortho-xylene, meta-xylene, At least one of paraxylene, the toluene fluorides of 2,3,4,5,6- five and mesitylene.
- 9. the synthetic method of 6- benzyls phenanthridines class compound according to claim 1 or 2, it is characterised in that the temperature of reaction Spend for 0 DEG C~120 DEG C.
- 10. the synthetic method of 6- benzyls phenanthridines class compound according to claim 1 or 2, it is characterised in that reaction when Between be 12h~24h.
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| CN113651681A (en) * | 2021-08-11 | 2021-11-16 | 中山大学 | Method for preparing aldehyde/ketone by breaking C-C bond |
| CN114940663A (en) * | 2022-05-31 | 2022-08-26 | 暨南大学 | Phenanthridine compound and synthesis method thereof |
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| CN108299297A (en) * | 2018-03-01 | 2018-07-20 | 西京学院 | A kind of novel 6- alkyl phenanthridines and derivative and preparation method thereof |
| CN108341779A (en) * | 2018-04-24 | 2018-07-31 | 温州大学苍南研究院 | The preparation method of 6- acetonitrile-base phenanthridines |
| CN113651681A (en) * | 2021-08-11 | 2021-11-16 | 中山大学 | Method for preparing aldehyde/ketone by breaking C-C bond |
| CN113651681B (en) * | 2021-08-11 | 2022-07-22 | 中山大学 | Method for preparing aldehyde/ketone by breaking C-C bond |
| CN114940663A (en) * | 2022-05-31 | 2022-08-26 | 暨南大学 | Phenanthridine compound and synthesis method thereof |
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