CN107793357A - A kind of preparation method of 6 substitution phenanthridines class compound - Google Patents
A kind of preparation method of 6 substitution phenanthridines class compound Download PDFInfo
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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
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Abstract
The invention discloses the preparation method of 6 substitution phenanthridines class compounds of the one kind as shown in formula (I), the preparation method is using N [biphenyl of 1 phenyl 1 '] benzenesulfonamides shown in formula (II) as raw material, is reacted in organic solvent in the presence of [Se]/Selectfluor catalytic body agent and corresponding target product formula (II) is made.The present invention preparation method have the present invention synthetic method have it is small to environmental hazard, reaction condition is relatively mild, saving energy resource consumption, selectivity of product height, it is easy to operate the advantages that.
Description
(1) technical field
The present invention relates to a kind of preparation method of organic compound, and in particular to a kind of system of 6- substitutions phenanthridines class compound
Preparation Method.
(2) background technology
Phenanthridines is core texture essential in a variety of natural prodcuts and other important molecules, and it has extensive biology living
Property and application, including antibacterial, antiprotozoan and anticancer etc..Wherein famous phenanthridines class members Ethidium, is common and general
DNA/RNA intercalators, so that the synthetic method for the phenanthridine derivatives that development is efficiently easy to get causes the broad interest of chemist.Cause
This, the related synthetic technology of research and development phenanthridines analog derivative 6- substitution phenanthridines has broad prospect of application.
At present, the synthetic method for the relevant 6- substitution phenanthridines reported both at home and abroad mainly has following several method：(1) with aryl
Triflate and N- trimethyl silicon substrates imines be raw material in palladium catalyst be catalyzed lower synthesis (referring to Org.Lett.2011,
13,1486), this method makes using transition metal-catalyzed cyclisation imines method, and it is using expensive noble metal catalyst and needs to add
Containing virose organic phosphorus compound as part, the more harsh accessory substance of condition；(2) diazobenzene -2- carboxylic acid, ethyl esters, benzene are passed through
Amine and aromatic aldehyde are raw material by Aryne intermediates one pot process (referring to J.Org.Chem.2006,71,9241-9243), the party
Method is only applicable to the synthesis of specific phenanthridines class compound, limits the expansion of substrate；(3) using alkynes and nitrile as raw material, pass through
[2+2+2] cycloaddition synthesis (referring to Chem.Commun.2008,2992.), the Raney nickel that this method uses is expensive and anti-
It is longer between seasonable；(4) using isocyanates as raw material, by be catalyzed aza-Wittig Cyclizations (referring to Org.Lett.2008,
10,2589), this method uses virose organophosphorus compound phospholene oxides and method limits substrate expansion；(5) with
The cyclic ketones of O- phenylalanines and related derivative is raw material, synthesized by hydro-thermal reaction (referring to Org.Lett.2003,5,
1605.), reaction temperature needed for this method is high (being more than 200 degrees Celsius), severe reaction conditions.
In view of above-mentioned problem, develop that a kind of raw material is simple and easy to get, the reaction time is short, simple to operate, reaction is gentle
Syntheti c route come prepare 6- substitution phenanthridines class prepared product be extremely necessary.
(3) content of the invention
For the deficiencies in the prior art, the present invention is intended to provide a kind of 6- substitution phenanthridines and its derivative of preparing
Method, the shortcomings that overcoming prior art, expensive noble metal is substituted, with N- [1- phenyl -1 '-connection simple and easy to get with base metal
Benzene] benzenesulfonamides replace multi-component feedstock and realization is reacted under the conditions of relatively mild.
The present invention is achieved by the following technical solutions：
A kind of preparation method of 6- substitution phenanthridines and its derivative as shown in formula (I), the reaction equation of the preparation method
It is as follows：
Using N- [1- phenyl -1 '-biphenyl] benzenesulfonamides shown in formula (II) as starting material, in selenium catalyst
Under effect, at a temperature of 60~110 DEG C, after reacting 12~36 hours, reaction solution is through isolating and purifying place with oxidant in a solvent
The 6- substitution phenanthridines class compounds shown in formula (I) are made in reason；Described selenium catalyst is one kind in selenium or selenium dioxide；It is described
Oxidant is one kind in Selectfluor, DDQ or Oxone, and the Selectfluor oxidants are that 1- chloromethyls -4- is fluoro-
(tetrafluoro boric acid) salt of Isosorbide-5-Nitrae-diazabicyclo [2.2.2] octane two, the DDQ oxidants are chloro- 5,6- dicyano -1 of 2,3- bis-,
4- benzoquinones, the Oxone are ammonium persulfate-sodium bisulfate；
In formula (I) or formula (II), R1Represent H, fluorine or chlorine, R2Represent H, fluorine, chlorine, the tert-butyl group or trifluoromethoxy.
Raw material N- [1- phenyl -1 '-biphenyl] benzenesulfonamides that the present invention uses, those skilled in the art can be with
Voluntarily prepared according to method is descended：3mmol neighbour's aryl benzenesulfonimide is dissolved in 8mL tetrahydrofurans (anhydrous) solution, used
The solution is injected into two mouthfuls of flasks of 25mL under nitrogen protection by 10mL syringes, and room temperature agitating solution, same with this after having injected
When 2-3 times of equivalent (6-9mL) phenylmagnesium bromide solution (1mmo l/mL) is taken with 10mL syringes, it is and slow under agitation
Phenylmagnesium bromide solution is added dropwise, reaction is moved into magnetic stirrer over night in 65 DEG C of oil cauldrons after being added dropwise., will be anti-after reaction terminates
Liquid 5mol/L ammonium chloride solutions are answered to post-process, reaction solution is transferred in 125mL separatory funnels while added after terminating by post processing
Enter 30mL dichloromethane to be extracted, extract 3 times, take the organic layer containing extractant and target product, i.e. extract, and wherein
A spoon (150~250mg) column chromatography silica gel (100-200 mesh) is added, by being evaporated under reduced pressure (vacuum 0.08kPa), then
Pure product is obtained (with petrol ether/ethyl acetate=5 by pillar layer separation:1 is used as eluant, eluent).
Reaction temperature of the present invention is 60~110 DEG C, is preferably carried out under the conditions of 100 DEG C, of the present invention anti-
It is 12~36 hours, preferably 24 hours between seasonable.
Selenium catalyst of the present invention is preferably selenium, is characterized in cheap and easy to get, and low toxicity is efficient, and auxiliary without extra ligand
Help；The amount ratio of the catalyst and described N- [1- phenyl -1 '-biphenyl] benzenesulfonamides material is 0.1~0.3：
1, preferably 0.2：1.
Oxidant of the present invention is preferably Selectfluor, the oxidant and described N- [1- phenyl -1 '-connection
Benzene] benzenesulfonamides material amount ratio be 2~4：1, preferably 3:1.
Solvent of the present invention is one in acetonitrile, DMF (N,N-dimethylformamide), 1,4- dioxane or toluene
Kind；The volumetric usage of the solvent is with the amount of N- [1- phenyl -1 '-biphenyl] benzenesulfonamides material shown in formula (II)
It is calculated as 3~10mL/mmol.
The specific preparation method for recommending described 6- substitution phenanthridine derivatives of the invention comprises the following steps：By raw material N-
[1- phenyl -1 '-biphenyl] benzsulfamide, oxidant, selenium catalyst, solvent are added in reaction vessel, are stirred at 60~110 DEG C
Reaction 12~36 hours, gained reaction solution obtains target product through isolating and purifying.
Separation and purification treatment method of the present invention is：Reaction is extracted after adding extractant in reaction solution after terminating
Take, take the organic layer containing extractant and target product, i.e. extract, and add column chromatography silica gel wherein, and steam by depressurizing
Solvent is removed in distillation, by residue by pillar layer separation, using petroleum ether and ethyl acetate volume ratio as 10：1 mixed liquor conduct
Eluent, the eluent containing target product is collected, solvent is evaporated off and obtains the 6- substitution phenanthridines class compounds shown in formula (I).
The extractant is dichloromethane or ethyl acetate, and the volumetric usage of the extractant is with the adjacent aryl benzene sulfonyl shown in formula (II)
The amount of imine compound material is calculated as 20~50mL/mmol.Described column chromatography silica gel is 100~200 mesh, its quality and institute
The mass ratio for the 6- substitution phenanthridines class compounds stated is 2：1.
Specifically, the 6- substitutions phenanthridines class compound shown in formula (I) of the present invention is preferably：
The present invention by N- [1- phenyl -1 '-biphenyl] benzsulfamides [Se]/Selectfluor catalyst system and catalyzings effect under,
6- is made by the oxidation/cyclisation aromatization process of this sulfonamide and substitutes phenanthridines and its derivative, beneficial effect：Taken with existing 6-
Compared for the preparation method of phenanthridines and its derivative, raw material is simple and easy to get；Non-metallic catalyst toxicity is relatively low；Reaction condition temperature
With saving energy resource consumption；In addition, also there is the features such as yield is high, and substrate universality is strong, easy to operate.
(4) embodiment
The present invention is described in further detail with reference to specific embodiment, but protection scope of the present invention is not limited to
This：
Embodiment 1
By 119.7mg (0.3mmol) N- [1- phenyl -1 '-biphenyl] benzsulfamide, 212.6mg (0.6mmol)
Selectfluor and 2.4mg (0.03mmol) Se are added in 25mL heavy wall pressure pipes, acetonitrile as solvents, dosage 3mL.Then,
Magnetic agitation 12 hours at 60 DEG C.Then, by reaction solution be transferred in 25mL separatory funnels and meanwhile add 8mL dichloromethane and
8mL water is extracted, and is extracted 3 times, is taken the organic layer containing dichloromethane and target product, i.e. extract, and at last every time
239.4mg column chromatography silica gels (100-200 mesh) are added in secondary extract, solvent is removed by being evaporated under reduced pressure (vacuum is
0.08kPa), by residue by pillar layer separation, using petroleum ether and ethyl acetate volume ratio as 10：1 mixed liquor is used as and washed
De- agent elution, collects the eluent containing target product, and it is 65.5mg that solvent, which is evaporated off, and obtains the quality of pure product
(0.255mmol).The material is white solid, and chemical name is 6- phenylphenanthridineands, yield 85%.
Characterize data：1H NMR(CDCl3,500MHz):δ 8.68 (d, J=8.5Hz, 1H), 8.61 (d, J=8.0Hz,
1H), 8.31 (d, J=8.0Hz, 1H), 8.13 (d, J=8.0Hz, 1H), 7.84 (t, J=7.0Hz, 1H), 7.79 (t, J=
6.0Hz, 1H), 7.69 (t, J=7.0Hz, 1H), 7.63-7.54 (m, 1H)；13C NMR(CDCl3,125MHz):δ161.2,
143.8,139.8,133.4,130.5,130.3,129.7,128.9,128.8,128.7,128.4,127.1,126.9,
125.2,123.7,122.2,121.9.
Embodiment 2
By 136.5g (0.3mmol) N- [1- phenyl -1 '-biphenyl (4 '-tertiary butyl)] benzsulfamide, 204.4mg
(0.9mmol) DDQ and 3.4mg (0.03mmol) SeO2It is added in 25mL heavy wall pressure pipes, DMF makees solvent, dosage 1mL.
Then, magnetic agitation 24 hours at 100 DEG C.Then, reaction solution is transferred in 25mL separatory funnels while adds 6mL acetic acid
Ethyl ester and 8mL water are extracted, and are extracted 3 times, are taken the organic layer containing ethyl acetate and target product, i.e. extract every time, and
273mg column chromatography silica gels (100-200 mesh) are added in last time extract, solvent is removed by being evaporated under reduced pressure (vacuum is
0.08kPa), by residue by pillar layer separation, using petroleum ether and ethyl acetate volume ratio as 10：1 mixed liquor is used as and washed
De- agent elution, collects the eluent containing target product, and it is 71.4mg that solvent, which is evaporated off, and obtains the quality of pure product
(0.228mmol).The material is white solid, and chemical name is 3- tertiary butyl -6- phenylphenanthridineands, yield 76%.
Characterize data：1H NMR(CDCl3,500MHz):δ 8.68 (d, J=8.5Hz, 1H), 8.56 (d, J=8.5Hz,
1H), 8.30 (d, J=2.0Hz, 1H), 8.10 (d, J=8.0Hz, 1H), 7.86-7.83 (m, 1H), 7.79 (J1=8.5Hz, J2
=2.0Hz, 1H), 7.56 (J1=8.5Hz, J2=1.5Hz, 1H), 7.61-7.53 (m, 4H), 1.51 (s, 1H)；13C NMR
(CDCl3,125MHz):δ161.2,152.2,143.7,139.9,133.4,130.5,129.7,128.8,128.6,128.4,
126.7,126.3,125.2,125.0,122.0,121.6,121.4.
Embodiment 3
By 129.9mg (0.3mmol) N- [1- phenyl -1 '-biphenyl (4 '-chlorine)] benzsulfamide, 737.7mg (1.2mmol)
Oxone and 4.7mg (0.06mmol) Se are added in 25mL heavy wall pressure pipes, and Isosorbide-5-Nitrae-dioxane makees solvent, dosage 3mL.
Then, magnetic agitation 36 hours at 110 DEG C.Then, reaction solution is transferred in 25mL separatory funnels while adds 15mL bis-
Chloromethanes and 8mL water are extracted, and are extracted 3 times, are taken the organic layer containing dichloromethane and target product, i.e. extract every time, and
259.8mg column chromatography silica gels (100-200 mesh) are added in last time extract, solvent (vacuum is removed by being evaporated under reduced pressure
Spend for 0.08kPa), by residue by pillar layer separation, using petroleum ether and ethyl acetate volume ratio as 10：1 mixed liquor is made
For eluent, the eluent containing target product is collected, it is 59.9mg that solvent, which is evaporated off, and obtains the quality of pure product
(0.201mmol).The material is white solid, and chemical name is 3- chloro-6-phenyl phenanthridines, yield 67%.
Characterize data：1H NMR(CDCl3,500MHz):δ 8.79 (d, J=8.5Hz, 1H), 8.37 (d, J=9.0Hz,
1H), 8.23 (d, J=1.5Hz, 1H), 8.09 (d, J=8.0Hz, 1H), 7.78 (t, J=7.5Hz, 1H), 7.73 (d, J=
6.5Hz,2H),7.59-7.53(m,5H)；13C NMR(CDCl3,125MHz):δ162.2,144.3,139.2,134.2,
132.8,130.7,129.6,129.3,128.8,128.3,127.22,127.16,124.8,123.1,122.0,121.9.
Embodiment 4
By 125.1mg (0.3mmol) N- [1- phenyl -1 '-biphenyl (4 '-fluorine)] benzsulfamide, 318.8mg (0.9mmol)
Selectfluor and 6.7mg (0.06mmol) SeO2It is added in 25mL heavy wall pressure pipes, toluene makees solvent, dosage 1mL.Connect
, magnetic agitation 36 hours at 100 DEG C.Then, reaction solution is transferred in 25mL separatory funnels while adds 8mL dichloromethanes
Alkane and 8mL water are extracted, and are extracted 3 times, are taken the organic layer containing dichloromethane and target product, i.e. extract, and most every time
250.2mg column chromatography silica gels (100-200 mesh) are added in an extract afterwards, solvent is removed by being evaporated under reduced pressure (vacuum is
0.08kPa), by residue by pillar layer separation, using petroleum ether and ethyl acetate volume ratio as 10：1 mixed liquor is used as and washed
De- agent elution, collects the eluent containing target product, and it is 56.9mg that solvent, which is evaporated off, and obtains the quality of pure product
(0.207mmol).The material is white solid, and chemical name is the fluoro- 6- phenylphenanthridineands of 3-, yield 69%.
Characterize data：1H NMR(CDCl3,500MHz):δ 8.57 (d, J=8.0Hz, 1H), 8.53 (dd, J1=9.0Hz,
J2=6.0Hz, 1H), 8.11 (d, J=8.0Hz, 1H), 7.91 (dd, J1=10.0Hz, J2=2.5Hz, 1H), 7.83 (t, J=
7.5Hz, 1H), 7.75 (d, J=6.5Hz, 2H), 7.61-7.54 (m, 4H)；13C NMR(CDCl3,125MHz):(the J=of δ 162.7
246.3Hz), 162.5,150.0 (J=11.3Hz), 139.4,133.2,129.7,129.0,128.9,128.4,126.9,
124.7,123.8 (J=10.0Hz), 122.0,129.70,120.65 (J=1.5Hz), 119.6.
Embodiment 5
By 144.3mg (0.3mmol) N- [1- phenyl -1 '-biphenyl (4 '-trifluoromethoxy)] benzenesulfonamides,
737.7mg (1.2mmol) Oxone and 7.1mg (0.09mmol) Se is added in 25mL heavy wall pressure pipes, and toluene makees solvent, is used
Measure as 3mL.Then, magnetic agitation 12 hours at 110 DEG C.Then, reaction solution is transferred in 25mL separatory funnels while added
Enter 8mL dichloromethane and 8mL water is extracted, extract 3 times, take the organic layer containing dichloromethane and target product every time, that is, extract
Liquid is taken, and 288.6mg column chromatography silica gels (100-200 mesh) are added in last time extract, it is molten by being evaporated under reduced pressure removing
Agent (vacuum 0.08kPa), by residue by pillar layer separation, using petroleum ether and ethyl acetate volume ratio as 10：1 it is mixed
Liquid is closed as eluent, collects the eluent containing target product, it is 69.2mg that solvent, which is evaporated off, and obtains the quality of pure product
(0.204mmol).The material is white solid, and chemical name is 3- trifluoromethoxy -6- phenylphenanthridineands, yield 68%.
Characterize data：1H NMR(CDCl3,500MHz):δ 8.56-8.53 (m, 2H), 8.15 (d, J=1.5Hz, 1H),
8.12 (d, J=8.5Hz, 1H), 7.82 (t, J=7.0Hz, 1H), 7.74 (d, J=6.0Hz, 2H), 7.63-7.55 (m, 4H),
7.51 (d, J=9.0Hz, 1H)；13C NMR(CDCl3,125MHz):δ 162.6,149.2 (J=1.5Hz), 144.4,139.3,
132.8,130.9,129.6,128.9,128.4,127.4,125.0,123.6,122.1,12 2.0,120.70,120.65 (J=
1.5Hz), 120.6 (J=256.3Hz), 119.6.
Embodiment 6
By 125.1mg (0.3mmol) N- [1- phenyl -1 '-biphenyl (4- fluorine)] benzsulfamide, 212.6mg (0.6mmol)
Selectfluor and 7.1mg (0.09mmol) Se are added in 25mL heavy wall pressure pipes, acetonitrile as solvents, dosage 0.9mL.Connect
, magnetic agitation 12 hours at 60 DEG C.Then, reaction solution is transferred in 25mL separatory funnels while adds 8mL dichloromethanes
Alkane and 8mL water are extracted, and are extracted 3 times, are taken the organic layer containing dichloromethane and target product, i.e. extract, and most every time
250.2mg column chromatography silica gels (100-200 mesh) are added in an extract afterwards, by being evaporated under reduced pressure (vacuum 0.08kPa)
Solvent is removed, by residue by pillar layer separation, using petroleum ether and ethyl acetate volume ratio as 10：1 mixed liquor is used as and washed
De- agent elution, collects the eluent containing target product, and it is 62.7mg that solvent, which is evaporated off, and obtains the quality of pure product
(0.228mmol).The material is white solid, and chemical name is 6- phenyl -9- fluorine phenanthridines, yield 76%.
Characterize data：1H NMR(CDCl3,500MHz):δ 8.43 (d, J=7.5Hz, 1H), 8.27-8.22 (m, 2H),
8.11(dd,J1=9.0Hz, J2=6.0Hz, 1H), 7.80-7.65 (m, 4H), 7.60-7.53 (m, 3H)；13C NMR(CDCl3,
125MHz):δ 163.7 (J=250Hz), 160.5,144.0,139.5,135.8 (J=8.8Hz), 131.8 (J=8.8Hz),
(130.3,129.4,128.8,128.4,126.9,123.2 J=3.8Hz), 122.1 (J=1.3Hz), 122.0,116.1 (J=
23.8Hz), 107.3 (J=22.5Hz)
Embodiment 7
By 129.9mg (0.3mmol) N- [1- phenyl -1 '-biphenyl (4- chlorine)] benzsulfamide, 204.3mg (0.9mmol)
DDQ and 3.4mg (0.03mmol) SeO2It is added in 25mL heavy wall pressure pipes, acetonitrile as solvents, dosage 3mL.Then, in 100
Magnetic agitation 24 hours at DEG C.Then, reaction solution is transferred in 25mL separatory funnels while adds 8mL dichloromethane and 8mL
Water is extracted, and is extracted 3 times, takes the organic layer containing dichloromethane and target product, i.e. extract every time, and extract in last time
Take and 259.8mg column chromatography silica gels (100-200 mesh) added in liquid, solvent (vacuum 0.08kPa) is removed by being evaporated under reduced pressure,
By residue by pillar layer separation, using petroleum ether and ethyl acetate volume ratio as 10：1 mixed liquor as eluent,
The eluent containing target product is collected, it is 69mg (0.237mmol) that solvent, which is evaporated off, and obtains the quality of pure product.The material is white
Color solid, chemical name are 6- phenyl -9- chlorine phenanthridines, yield 79%.
Characterize data：1H NMR(CDCl3,500MHz):δ 8.62 (d, J=2.0Hz, 1H), 8.49 (d, J=8.0Hz,
1H), 8.26 (d, J=8.0Hz, 1H), 8.04 (d, J=8.5Hz, 1H), 7.80-7.67 (m, 4H), 7.60-7.53 (m, 4H)；13C NMR(CDCl3,125MHz):δ160.7,144.2,139.3,137.1,134.8,130.5,130.4,129.7,129.5,
128.9,128.5,127.7,127.2,123.5,122.7,121.96,121.92.
Embodiment 8
By 135.3mg (0.3mmol) N- [1- phenyl -1 '-biphenyl (the fluoro- 4 '-chlorine of 4-)] benzsulfamide, 737.7mg
(1.2mmol) Oxone and 4.8mg (0.06mmol) Se are added in 25mL heavy wall pressure pipes, acetonitrile as solvents, dosage 3mL.
Then, magnetic agitation 24 hours at 110 DEG C.Then, reaction solution is transferred in 25mL separatory funnels while adds 8mL dichloros
Methane and 8mL water are extracted, and are extracted 3 times, are taken the organic layer containing dichloromethane and target product, i.e. extract every time, and
270.6mg column chromatography silica gels (100-200 mesh) are added in last time extract, solvent (vacuum is removed by being evaporated under reduced pressure
For 0.08kPa), by residue by pillar layer separation, using petroleum ether and ethyl acetate volume ratio as 10：1 mixed liquor conduct
Eluent, the eluent containing target product is collected, it is 79.7mg that solvent, which is evaporated off, and obtains the quality of pure product
(0.258mmol).The material is white solid, and chemical name is 3- chloro-6-phenyl -9- fluorine phenanthridines, yield 86%.
Characterize data：1H NMR(CDCl3,500MHz):δ8.39(dd,J1=9.5Hz, J2=6.0Hz, 1H), 8.16-
8.10(m,2H),7.89(dd,J1=9.5Hz, J2=2.5Hz, 1H), 7.72-7.69 (m, 2H), 7.59-7.55 (m, 3H),
7.43-7.39(m,1H),7.33-7.28(m,1H)；13C NMR(CDCl3,125MHz):δ 165.0,163.1 (J=
247.5Hz), 162.9,161.8,145.3 (J=12.5Hz), 139.1,135.6 (J=10.0Hz), 132.1 (J=8.8Hz),
(129.6,129.1,128.5,124.1 J=10.0Hz), 121.7,120.0,116.1 (J=23.8Hz), 114.8 (J=
20.0Hz), 107.1 (J=22.5Hz)
Embodiment 9
By 141.9mg (0.3mmol) N- [1- phenyl -1 '-biphenyl (the fluoro- 4 '-tertiary butyls of 4-)] benzsulfamide, 318.8mg
(0.9mmol) Selectfluor and 2.4mg (0.03mmol) Se are added in 25mL heavy wall pressure pipes, acetonitrile as solvents, dosage
For 3mL.Then, magnetic agitation 12 hours at 100 DEG C.Then, reaction solution is transferred in 25mL separatory funnels while added
8mL dichloromethane and 8mL water are extracted, and are extracted 3 times, are taken the organic layer containing dichloromethane and target product every time, that is, extract
Liquid, and 283.8mg column chromatography silica gels (100-200 mesh) are added in last time extract, remove solvent by being evaporated under reduced pressure
(vacuum 0.08kPa), by residue by pillar layer separation, using petroleum ether and ethyl acetate volume ratio as 10：1 mixing
Liquid collects the eluent containing target product as eluent, and it is 77.5mg that solvent, which is evaporated off, and obtains the quality of pure product
(0.234mmol).The material is white solid, and chemical name is 3- tertiary butyl -6- phenyl -9- fluorine phenanthridines, yield 78%.
Characterize data：1H NMR(CDCl3,500MHz):δ 8.40 (d, J=8.5Hz, 1H), 8.30 (d, J=1.5Hz,
1H),8.23(dd,J1=10.5Hz, J2=2.5Hz, 1H), 8.09 (dd, J1=9.0Hz, J2=6.0Hz, 1H), 7.79
(dd,J1=8.5Hz, J2=2.0Hz, 1H), 7.60-7.53 (m, 3H), 7.32-7.28 (m, 1H), 1.40 (s, 9H)；13C NMR
(CDCl3,125MHz):δ 163.8 (J=251.3Hz), 160.7,153.1,143.9,139.5,135.8 (J=8.8Hz),
131.8 (J=10.0Hz), 129.6,128.8,128.5,126.3,125.3,122.0,121.8,120.9 (J=5.0Hz),
115.8 (J=22.5Hz), 107.1 (J=22.5Hz)
Embodiment 10
By 125.1mg (0.3mmol) N- [1- phenyl -1 '-biphenyl (5- fluorine)] benzsulfamide, 212.6mg (0.6mmol)
Selectfluor and 10.0mg (0.09mmol) SeO2It is added in 25mL heavy wall pressure pipes, Isosorbide-5-Nitrae-dioxane makees solvent, uses
Measure as 3mL.Then, magnetic agitation 24 hours at 60 DEG C.Then, reaction solution is transferred in 25mL separatory funnels while added
8mL dichloromethane and 8mL water are extracted, and are extracted 3 times, are taken the organic layer containing dichloromethane and target product every time, that is, extract
Liquid, and 250.2mg column chromatography silica gels (100-200 mesh) are added in last time extract, by being evaporated under reduced pressure, (vacuum is
0.08kPa), by residue by pillar layer separation, using petroleum ether and ethyl acetate volume ratio as 10：1 mixed liquor is used as and washed
De- agent elution, collects the eluent containing target product, and it is 48.7mg that solvent, which is evaporated off, and obtains the quality of pure product
(0.177mmol).The material is white solid, and chemical name is 6- phenyl -8- fluorine phenanthridines, yield 59%.
Characterize data：1H NMR(CDCl3,500MHz):δ8.54(dd,J1=9.0Hz, J2=5.0Hz, 1H), 8.52 (d,
J=8.5Hz, 1H), 8.29 (dd, J1=8.0Hz, J2=0.5Hz, 1H), 7.78-7.74 (m, 4H), 7.69 (t, J=
7.0Hz,1H),7.61-7.55(m,4H)；13C NMR(CDCl3,125MHz):δ 161.2 (J=246.3Hz), 160.3 (J=
3.8Hz), 143.4,139.1,130.4,130.1 (J=1.3Hz), 129.0,128.7,128.6,127.3,126.4 (J=
7.5Hz), 124.5 (J=7.5Hz), 123.3,121.7,119.7 (J=23.8Hz), 113.3 (J=22.5Hz)
Embodiment 11
By 135.3mg (0.3mmol) N- [1- phenyl -1 '-biphenyl (the fluoro- 4 '-chlorine of 5-)] benzsulfamide, 318.8mg
(0.9mmol) Selectfluor and 7.2mg (0.09mmol) Se are added in 25mL heavy wall pressure pipes, and Isosorbide-5-Nitrae-dioxane is made
Solvent, dosage 3mL.Then, magnetic agitation 36 hours at 100 DEG C.Then, reaction solution is transferred in 25mL separatory funnels
Add 8mL dichloromethane and 8mL water is extracted simultaneously, extract 3 times, take every time organic containing dichloromethane and target product
Layer, i.e. extract, and 270.6mg column chromatography silica gels (100-200 mesh) are added in last time extract, pass through vacuum distillation
Solvent (vacuum 0.08kPa) is removed, using petroleum ether and ethyl acetate volume ratio as 10：1 mixed liquor is washed as eluant, eluent
It is de-, the eluent containing target product is collected, it is 68.6mg (0.222mmol) that solvent, which is evaporated off, and obtains the quality of pure product.The thing
Matter is white solid, and chemical name is 3- chloro-6-phenyl -9- fluorine phenanthridines, yield 74%.
Characterize data：1H NMR(CDCl3,500MHz):δ8.60(dd,J1=9.0Hz, J2=5.5Hz, 1H), 8.43 (d,
J=8.5Hz, 1H), 8.26 (d, J=1.5Hz, 1H), 7.77-7.72 (m, 3H), 7.63-7.56 (m, 5H)；13C NMR
(CDCl3,125MHz):δ 161.5 (J=3.8Hz), 161.3 (J=247.5Hz), 144.0,138.7,134.4,129.8 (J=
1.5Hz), 129.6,129.5,129.3,128.7,127.9,126.4 (J=7.5Hz), 124.8 (J=8.8Hz), 123.1,
(121.8,120.3 J=23.8Hz), 113.5 (J=22.5Hz)
Embodiment 12
By 141.9mg (0.3mmol) N- [1- phenyl -1 '-biphenyl (the fluoro- 4 '-tertiary butyls of 5-)] benzsulfamide, 425.1mg
(1.2mmol) Selectfluor and 4.8mg (0.06mmol) Se powder are added in 25mL heavy wall pressure pipes, and DMF makees solvent, are used
Measure as 3mL.Then, magnetic agitation 36 hours at 100 DEG C.Then, reaction solution is transferred in 25mL separatory funnels while added
Enter 8mL dichloromethane and 8mL water is extracted, extract 3 times, take the organic layer containing dichloromethane and target product every time, that is, extract
Liquid is taken, and 283.8mg column chromatography silica gels (100-200 mesh) are added in last time extract, it is molten by being evaporated under reduced pressure removing
Agent (vacuum 0.08kPa), by residue by pillar layer separation, using petroleum ether and ethyl acetate volume ratio as 10：1 it is mixed
Liquid is closed as eluent, collects the eluent containing target product, it is 85.4mg that solvent, which is evaporated off, and obtains the quality of pure product
(0.258mmol).The material is yellow liquid, and chemical name is 3- tertiary butyl -6- phenyl -8- fluorine phenanthridines, yield 86%.
Characterize data：1H NMR(CDCl3,500MHz):δ8.63(dd,J1=9.0Hz, J2=5.5Hz, 1H), 8.47 (d,
J=9.0Hz, 1H), 8.30 (d, J=1.5Hz, 1H), 7.79 (dd, J1=8.5Hz, J2=2.0Hz, 1H), 7.75-7.71
(m,3H),7.61-7.54(m,4H),149(s,9H)；13C NMR(CDCl3,125MHz):δ 160.9 (J=246.3Hz),
160.3 (J=3.8Hz), 152.2,143.4,139.3,130.1 (J=1.3Hz), 129.5,128.9,128.6,126.4,
126.2 (J=7.5Hz), 125.6,124.6 (J=8.8Hz), 121.4,120.9,119.8 (J=23.8Hz), 113.3 (J=
21.3Hz),35.0,31.3.
Embodiment 13
By 129.9mg (0.3mmol) N- [1- phenyl -1 '-biphenyl (3 '-chlorine)] benzsulfamide, 368.9mg (0.6mmol)
Oxnoe and 7.2mg (0.09mmol) Se are added in 25mL heavy wall pressure pipes, acetonitrile as solvents, dosage 3mL.Then, in
Magnetic agitation 36 hours at 100 DEG C.Then, by reaction solution be transferred in 25mL separatory funnels and meanwhile add 8mL dichloromethane and
8mL water is extracted, and is extracted 3 times, is taken the organic layer containing dichloromethane and target product, i.e. extract, and at last every time
259.8mg column chromatography silica gels (100-200 mesh) are added in secondary extract, solvent is removed by being evaporated under reduced pressure (vacuum is
0.08kPa), by residue by pillar layer separation, using petroleum ether and ethyl acetate volume ratio as 10：1 mixed liquor is used as and washed
De- agent elution, collects the eluent containing target product, and it is 56.7mg that solvent, which is evaporated off, and obtains the quality of pure product
(0.195mmol).The material is white solid, and chemical name is 4- chloro-6-phenyl phenanthridines, yield 65%.
Characterize data：1H NMR(CDCl3,500MHz):δ 8.62 (d, J=8.5Hz, 1H), 8.58 (d, J=2.5Hz,
1H), 8.22 (d, J=9.0Hz, 1H), 8.14 (d, J=8.5Hz, 1H), 7.91-7.88 (m, 1H), 7.76-7.74 (m, 2H),
7.71(dd,J1=9.0Hz, J2=2.5Hz, 1H), 7.69-7.65 (m, 1H), 7.61-7.54 (m, 3H)；13C NMR(CDCl3,
125MHz):δ161.5,142.0,139.2,132.9,132.5,131.7,131.0,129.8,129.4,129.1,129.0,
128.5,127.9,125.4,124.9,122.3,121.6.
Claims (10)
- A kind of 1. preparation method of 6- substitution phenanthridines class compounds as shown in formula (I), it is characterised in that described preparation method For：Using N- [1- phenyl -1 '-biphenyl] benzenesulfonamides shown in formula (II) as starting material, in the effect of selenium catalyst Under, at a temperature of 60~110 DEG C, after reacting 12~36 hours, reaction solution is through separation and purification treatment system with oxidant in a solvent Obtain the 6- substitution phenanthridines class compounds shown in formula (I)；Described selenium catalyst is one kind in selenium or selenium dioxide；The oxidation Agent be Selectfluor, DDQ or Oxone in one kind, the Selectfluor oxidants be the fluoro- Isosorbide-5-Nitraes of 1- chloromethyls -4- - (tetrafluoro boric acid) salt of diazabicyclo [2.2.2] octane two, the DDQ oxidants are chloro- 5, the 6- dicyanos-Isosorbide-5-Nitrae-benzene of 2,3- bis- Quinone, the Oxone are ammonium persulfate-sodium bisulfate；In formula (I) or formula (II), R1Represent H, fluorine or chlorine, R2Represent H, fluorine, chlorine, the tert-butyl group or trifluoromethoxy.
- 2. preparation method as claimed in claim 1, it is characterised in that：The selenium catalyst and described N- [1- phenyl -1 ' - Biphenyl] benzenesulfonamides material amount ratio be 0.1~0.3：1.
- 3. preparation method as claimed in claim 1, it is characterised in that：The oxidant and described N- [1- phenyl -1 '-connection Benzene] benzenesulfonamides material amount ratio be 2~4：1.
- 4. preparation method as claimed in claim 1, it is characterised in that：Described reaction temperature is 100 DEG C.
- 5. preparation method as claimed in claim 1, it is characterised in that：The solvent is acetonitrile, DMF (N, N- dimethyl formyls Amine), one kind in 1,4- dioxane or toluene.
- 6. preparation method as claimed in claim 1, it is characterised in that：N- of the volumetric usage of the solvent shown in formula (II) The amount of [1- phenyl -1 '-biphenyl] benzenesulfonamides material is calculated as 3~10mL/mmol.
- 7. preparation method as claimed in claim 1, it is characterised in that：The separation and purification treatment method is：After reaction terminates Extracted after adding extractant in reaction solution, take the organic layer containing extractant and target product, i.e. extract, and wherein Column chromatography silica gel is added, solvent is removed by being evaporated under reduced pressure, by residue by pillar layer separation, with petroleum ether and ethyl acetate Volume ratio is 10：1 mixed liquor collects the eluent containing target product, solvent is evaporated off and obtains formula (I) institute as eluent The 6- substitution phenanthridines class compounds shown.
- 8. preparation method as claimed in claim 7, it is characterised in that：The extractant is dichloromethane or ethyl acetate.
- 9. preparation method as claimed in claim 7, it is characterised in that：Described column chromatography silica gel is 100~200 mesh.
- 10. preparation method as claimed in claim 7, it is characterised in that：The quality of the column chromatography silica gel takes with described 6- Mass ratio for phenanthridines class compound is 2：1.
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Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107778240A (en) * | 2016-08-29 | 2018-03-09 | 浙江工业大学 | A kind of preparation method of 6 phenylphenanthridinewith |
| CN107778239A (en) * | 2016-08-29 | 2018-03-09 | 浙江工业大学 | A kind of synthetic method of phenanthridines and its derivative |
| CN107793358A (en) * | 2016-08-29 | 2018-03-13 | 浙江工业大学 | A kind of synthetic method of 6 substitution phenanthridines class compound |
| CN109422689A (en) * | 2017-08-25 | 2019-03-05 | 浙江工业大学 | A kind of 6- replaces the synthetic method of phenanthridines class compound |
| CN109422687A (en) * | 2017-08-25 | 2019-03-05 | 浙江工业大学 | A method of synthesis 6- cyano phenanthridines class compound |
Citations (3)
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| CN107778240A (en) * | 2016-08-29 | 2018-03-09 | 浙江工业大学 | A kind of preparation method of 6 phenylphenanthridinewith |
| CN107778239A (en) * | 2016-08-29 | 2018-03-09 | 浙江工业大学 | A kind of synthetic method of phenanthridines and its derivative |
| CN107793358A (en) * | 2016-08-29 | 2018-03-13 | 浙江工业大学 | A kind of synthetic method of 6 substitution phenanthridines class compound |
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| CN107778240A (en) * | 2016-08-29 | 2018-03-09 | 浙江工业大学 | A kind of preparation method of 6 phenylphenanthridinewith |
| CN107778239A (en) * | 2016-08-29 | 2018-03-09 | 浙江工业大学 | A kind of synthetic method of phenanthridines and its derivative |
| CN107793358A (en) * | 2016-08-29 | 2018-03-13 | 浙江工业大学 | A kind of synthetic method of 6 substitution phenanthridines class compound |
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107778240A (en) * | 2016-08-29 | 2018-03-09 | 浙江工业大学 | A kind of preparation method of 6 phenylphenanthridinewith |
| CN107778239A (en) * | 2016-08-29 | 2018-03-09 | 浙江工业大学 | A kind of synthetic method of phenanthridines and its derivative |
| CN107793358A (en) * | 2016-08-29 | 2018-03-13 | 浙江工业大学 | A kind of synthetic method of 6 substitution phenanthridines class compound |
| CN109422689A (en) * | 2017-08-25 | 2019-03-05 | 浙江工业大学 | A kind of 6- replaces the synthetic method of phenanthridines class compound |
| CN109422687A (en) * | 2017-08-25 | 2019-03-05 | 浙江工业大学 | A method of synthesis 6- cyano phenanthridines class compound |
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