CN109020814A - A kind of polysubstituted 10- hydroxyl is luxuriant and rich with fragrance and its derivative and its synthetic method - Google Patents

A kind of polysubstituted 10- hydroxyl is luxuriant and rich with fragrance and its derivative and its synthetic method Download PDF

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CN109020814A
CN109020814A CN201710433212.2A CN201710433212A CN109020814A CN 109020814 A CN109020814 A CN 109020814A CN 201710433212 A CN201710433212 A CN 201710433212A CN 109020814 A CN109020814 A CN 109020814A
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CN109020814B (en
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王彬
江雅婷
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Nankai University
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C67/00—Preparation of carboxylic acid esters
    • C07C67/30—Preparation of carboxylic acid esters by modifying the acid moiety of the ester, such modification not being an introduction of an ester group
    • C07C67/333—Preparation of carboxylic acid esters by modifying the acid moiety of the ester, such modification not being an introduction of an ester group by isomerisation; by change of size of the carbon skeleton
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C45/00—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds
    • C07C45/61—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups
    • C07C45/67—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups by isomerisation; by change of size of the carbon skeleton
    • C07C45/68—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups by isomerisation; by change of size of the carbon skeleton by increase in the number of carbon atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C67/00—Preparation of carboxylic acid esters
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C69/00—Esters of carboxylic acids; Esters of carbonic or haloformic acids
    • C07C69/76—Esters of carboxylic acids having a carboxyl group bound to a carbon atom of a six-membered aromatic ring
    • C07C69/94—Esters of carboxylic acids having a carboxyl group bound to a carbon atom of a six-membered aromatic ring of polycyclic hydroxy carboxylic acids, the hydroxy groups and the carboxyl groups of which are bound to carbon atoms of six-membered aromatic rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
    • C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
    • C07D471/04—Ortho-condensed systems

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Abstract

The present invention provides a kind of polysubstituted 10- hydroxyl phenanthrene and its derivative and its synthetic methods, this method comprises: formula (2) compound is made in formula (1) compound under the action of bromine catalyst, additive, peroxide and organic solvent, reaction formula is as follows:Wherein, R1For hydrogen, halogen, aryl, alkyl or alkoxy, binding site is 3 or 4 or 5 or 6；R2For hydrogen, halogen, aryl, alkyl, alkoxy or ester group, 2 ' position of binding site or 3 ' positions or 4 ' positions or 5 ' positions or 6 ' positions；EWG be cyano, methoxy for formoxyl, ethoxy for formoxyl or N- phenyl formamide base.The synthetic route of the method for the present invention is short, starting material is simple, reaction condition is mild, catalyst is inexpensive pollution-free, and substrate spectrum is wide, and product is easily separated.

Description

A kind of polysubstituted 10- hydroxyl is luxuriant and rich with fragrance and its derivative and its synthetic method
Technical field
The invention belongs to pharmaceutical-chemical intermediate and related chemistry technical fields, and in particular to arrive a kind of polysubstituted 10- hydroxyl Base phenanthrene and its derivative and its green synthesis method.
Background technique
Polycyclic aromatic hydrocarbon is the basic framework of organic molecule, is widely used in chemical field.Organic light of the structure containing polycyclic aromatic hydrocarbon Electric material has received widespread attention.It is concerned comprising luxuriant and rich with fragrance or phenanthryl derivative material with its higher photo and thermal stability, It is widely used in pigment, field of photovoltaic materials.Meanwhile polycyclic system skeleton can make overall structure more steady since π-π stacking acts on Surely synthetic ligands are also used for, in the large biological molecules such as DNA in conjunction with and be used for medicine.Luxuriant and rich with fragrance basic framework is also used for natural activity production The synthesis of object, if the skeleton structure of phenanthrenecarboxylic acid ethyl ester is the key intermediate that phenanthroindolizididerivative pyridine alkaloid synthesizes.It can be seen that Building phenanthrene and its polycyclic aromatic hydrocarbon skeleton of derivative species have wide scientific research value and market prospects.
Luxuriant and rich with fragrance skeleton there are many production method, more typically there are four types of, first is that being existed with diarylethene base nitrile by iodine Phenanthrene ring is constructed by freely cyclization under illumination condition；Or using diarylethene nitrile in trifluoroacetic acid as solvent, trifluoro vanadyl (VOF3) to be coupled to obtain luxuriant and rich with fragrance acetonitrile by internal oxidation under conditions of oxidant；Third is that two virtues replaced with fragrant bromine in ring Base vinylformic acid methyl esters is substrate, generates aryl radical under radical initiator induction, is then carried out freely cyclization Obtain polysubstituted phenanthrenecarboxylic acid methyl esters；Fourth is that obtaining bromine by metal catalytic for substrate with 2- (bromoacetylene base) -1,1'- biphenyl Substituted phenanthrene ring.But have that method reaction step is more above, substrate difficulty is made and substrate spectrum and selectivity etc. lack It falls into and is needed mostly using transition metal as catalyst, there are many defects such as environmental pollution.In last several steps of pharmaceutical synthesis It often to avoid having an impact using transition metal to prevent from testing lytic activity, so its application is restricted.
Therefore, it how by simple starting material, less reaction step, mild reaction condition, and uses honest and clean The research work of the free of contamination catalyst preparation polysubstituted triphenylene of valence and its derivative is very necessary.
Summary of the invention
The problem to be solved by the invention is to provide a kind of efficient polysubstituted 10- hydroxyl is luxuriant and rich with fragrance and its derivative and its green Color synthetic method.
In order to achieve the above objectives, the technical scheme of the present invention is realized as follows:
A kind of polysubstituted 10- hydroxyl is luxuriant and rich with fragrance and its synthetic method of derivative, this method comprises: by formula (1) compound in bromine Formula (2) compound is made under the action of catalyst, additive, peroxide and organic solvent, reaction formula is as follows:
Wherein, R1For hydrogen, halogen, aryl, alkyl or alkoxy, binding site is 3 or 4 or 5 or 6；R2For Hydrogen, halogen, aryl, alkyl, alkoxy or ester group, 2 ' position of binding site or 3 ' positions or 4 ' positions or 5 ' positions or 6 ' positions；EWG is Cyano, methoxy are for formoxyl, ethoxy for formoxyl or N- phenyl formamide base.
Further, formula (2) compound synthesis method Chinese style (1) compound, containing bromine catalyst, peroxide and additive Molar ratio is 1:(0.05~0.8): (1~5): (0.4~3).
Further, the bromine catalyst that contains is N- bromo-succinimide, N- bromine phthalimide, tetrabutylammonium bromide, bromination Lithium, sodium bromide, potassium bromide, hydrobromic acid, triphenyl phosphorus hydrobromate, bromine ethylamine hydrobromide, bromobenzene, bromodiphenyl methane, benzyl The mixture of one or more of amine in bromine, dibromo isocyanurate, N- bromo acetamide or N- bromo hexamethylene；It is preferred that , it is described containing bromine catalyst be N- bromo-succinimide, N- bromine phthalimide, amine in N- bromo hexamethylene, dibromo isocyanurate or The mixture of one or more of bromine ethylamine hydrobromide；It is furthermore preferred that the bromine catalyst that contains is N- bromo fourth two Acid imide.
Further, the peroxide is tert-butyl hydroperoxide, hydrogen peroxide, di-tert-butyl peroxide, isopropylbenzene Base hydrogen peroxide, metachloroperbenzoic acid, peroxidized t-butyl perbenzoate, ammonium persulfate-sodium bisulfate, potassium peroxydisulfate or acetic acid The mixture of one or more of iodobenzene；Preferably, the peroxide is tert-butyl hydroperoxide.
Further, the additive in formula (2) compound synthesis method is sodium dihydrogen phosphate and its hydrate, acetic acid, triphen The mixture of one or more of base phosphorus, citric acid, pyridine, sodium acetate or DBU；Preferably, the additive is phosphorus The mixture of one or more of acid dihydride sodium, acetic acid or citric acid；It is furthermore preferred that the additive is biphosphate Sodium.
Further, the additional amount of the organic solvent in formula (2) compound synthesis method be formula (1) compound by weight 4~ 100 times.
Further, the reaction temperature of formula (2) compound synthesis method is 60~100 DEG C, and the reaction time is 0.5~15 small When.
Further, the reaction temperature of formula (2) compound synthesis method is 80~90 DEG C, and the reaction time is 7~15 hours.
Further, when EWG is cyano, the synthetic method of formula (1) compound is as follows:
When EWG be methoxy for formoxyl or ethoxy for formoxyl when, the synthetic method of formula (1) compound is as follows:
When EWG is N- phenyl formamide base, the synthetic method of formula (1) compound is as follows:
Further, the organic solvent in formula (1) compound synthesis method is toluene, Isosorbide-5-Nitrae-dioxane, N, N '-dimethyl The mixture of one or more of formamide, ethyl alcohol or methanol；
It is ethyl alcohol, methanol, glycol dinitrate by the organic solvent in the method for formula (1) compound synthesis formula (2) compound Ether, 1,4- dioxane, tetrahydrofuran, 1,2- methylene chloride, carbon tetrachloride or N, one of N '-dimethyl formamide or two Kind or more mixture；Preferably, organic solvent is tetrahydrofuran.
Further, the alkalinity additive in formula (1) compound synthesis method be natrium carbonicum calcinatum, it is Anhydrous potassium carbonate, anhydrous The mixture of one or more of potassium phosphate or barium hydroxide；The palladium catalyst is that four-(triphenyl phosphorus) change palladium, 1, One of 1'- bis(diphenylphosphino) ferrocene dichloropalladium (II) or bis- (triphenylphosphine) palladium chlorides (II).
Further, when EWG be cyano or methoxy for formoxyl or ethoxy for formoxyl when, the synthesis of formula (1) compound is anti- The reaction time for the first step answered is 8~12 hours, and reaction temperature is 80~165 DEG C；The reaction time of second step is 1~5 small When, reaction temperature is 80 DEG C.
Further, when EWG is N- phenyl formamide base, the reaction time of the synthetic reaction of formula (1) compound is 8~12 Hour, reaction temperature is 165 DEG C.
The present invention also provides a kind of polysubstituted 10- hydroxyl phenanthrene and its derivative, which has changes shown in formula (2) Learn structure:
Wherein, R1For hydrogen, halogen, aryl, alkyl or alkoxy, binding site is 3 or 4 or 5 or 6；R2For Hydrogen, halogen, aryl, alkyl, alkoxy or ester group, 2 ' position of binding site or 3 ' positions or 4 ' positions or 5 ' positions or 6 ' positions；EWG is Cyano, methoxy are for formoxyl, ethoxy for formoxyl or N- phenyl formamide base.
Compared with the existing technology, polysubstituted 10- hydroxyl phenanthrene and its derivative of the present invention and its synthetic method have Following advantage:
The synthetic route of the method for the present invention is short, starting material is simple, reaction condition is mild, catalyst is inexpensive pollution-free, bottom Object range is wide, and product is easily separated.
Detailed description of the invention
The attached drawing for constituting a part of the invention is used to provide further understanding of the present invention, schematic reality of the invention It applies example and its explanation is used to explain the present invention, do not constitute improper limitations of the present invention.In the accompanying drawings:
Fig. 1 is embodiment 1-4 compound 1a1H nuclear-magnetism,13C nuclear magnetic spectrogram, high resolution mass spectrum figure；
Fig. 2 is 5 compound 2a of embodiment1H nuclear-magnetism,13C nuclear magnetic spectrogram；
Fig. 3 is 6 compound 3a of embodiment1H nuclear-magnetism,13C nuclear magnetic spectrogram；
Fig. 4 is 7 compound 4a of embodiment1H nuclear-magnetism,13C nuclear magnetic spectrogram；
Fig. 5 is 8 compound 5a of embodiment1H nuclear-magnetism,13C nuclear magnetic spectrogram；
Fig. 6 is 8 compound 5b of embodiment1H nuclear-magnetism,13C nuclear magnetic spectrogram；
Fig. 7 is 9 compound 6a of embodiment1H nuclear-magnetism,13C nuclear magnetic spectrogram；
Fig. 8 is 10 compound 7a of embodiment1H nuclear-magnetism,13C nuclear magnetic spectrogram；
Fig. 9 is 11 compound 8a of embodiment1H nuclear-magnetism,13C nuclear magnetic spectrogram；
Figure 10 is 12 compound 9a of embodiment1H nuclear-magnetism,13C nuclear magnetic spectrogram；
Figure 11 is 13 compound 10a of embodiment1H nuclear-magnetism,13C nuclear magnetic spectrogram；
Figure 12 is 14 compound 11a of embodiment1H nuclear-magnetism,13C nuclear magnetic spectrogram；
Figure 13 is 15 compound 12a of embodiment1H nuclear-magnetism,13C nuclear magnetic spectrogram；
Figure 14 is 16 compound 13a of embodiment1H nuclear-magnetism,13C nuclear magnetic spectrogram.
Specific embodiment
In addition to being defined, technical term used in following embodiment has universal with those skilled in the art of the invention The identical meanings of understanding.Test reagent used in following embodiment is unless otherwise specified conventional biochemical reagent；It is described Experimental method is unless otherwise specified conventional method.
Below with reference to embodiment, the present invention will be described in detail.
The synthesis of embodiment 1:ethyl 10-hydroxyphenanthrene-9-carboxylate (1a)
The method of synthesis formula (1) compound includes the following steps:
Step 1: four (triphenyl phosphorus) palladiums (0.3mmol, 346.7mg), Anhydrous potassium carbonate are added in three-neck flask (9mmol, 1.24g) after sealing, air in bottle is taken out and is filled with nitrogen to the greatest extent, repeatedly once.It is sequentially added again into three-neck flask 2 '-bromoacetophenones (3mmol, 405 μ L), are dissolved in phenyl boric acid (3.6mmol, 435mg) mixed liquor of 3mL ethyl alcohol, full through nitrogen Toluene 12mL with after.By reaction mixture under the conditions of 110 DEG C back flow reaction 11 hours, intermediate product biphenyl second can be obtained Ketone.Almost convert.Pass through silica gel column separating purification (petroleum ether: ethyl acetate=100:1).
Step 2: 10mL anhydrous tetrahydro furan is added in three-neck flask, adds sodium hydride and (be scattered in kerosene, contain Amount is 60%, 8.4mmol, 0.336g), diethyl carbonate (8.4mmol, 0.72mL).Sealing is placed on oil bath pan and returns for 80 DEG C Stream heating.4-acetylbiphenyl is dissolved in 10mL anhydrous tetrahydro furan, is added drop-wise in reaction mixture dropwise under reflux conditions.Directly It is totally consumed to 4-acetylbiphenyl, stops reaction, almost convert.Changed by the way that formula (1) can be obtained after silica gel column separating purification Close object ethyl 3- ([1,1'-biphenyl] -2-yl) -3-oxopropanoate.
Its reaction equation is as follows:
The method of synthesis formula (2) compound includes the following steps:
Formula (1) compound ethyl 3- ([1,1'-biphenyl] -2-yl) -3- is added in the reactor Oxopropanoate (0.25mmol, 67mg), N- bromo-succinimide (0.1mmol, 17.8mg), tert-butyl hydroperoxide (0.875mmol, 78.86mg), sodium dihydrogen phosphate dihydrate (0.25mmol, 39mg), tetrahydrofuran 2mL, sealing, at 80 DEG C Under be stirred to react 15 hours.It is cooled to room temperature, after solvent is removed under reduced pressure, passes through column chromatographic isolation and purification (eluant, eluent is petroleum ether) Obtain formula (2) compound ethyl 10-hydroxyphenanthrene-9-carboxylate (1a) 63.7mg, yield 96%.
1H NMR (400MHz, Chloroform-d) δ 13.32 (s, 1H), 8.77 (d, J=8.5Hz, 1H), 8.64-8.45 (m, 3H), 7.73 (t, J=7.7Hz, 1H), 7.65-7.41 (m, 3H), 4.58 (q, J=6.8Hz, 2H), 1.53 (t, J= 7.0Hz,3H)；13C NMR(101MHz,CDCl3)δ172.96,162.75,133.67,130.44,129.47,127.61, 126.88,126.08,126.00,125.26,124.98,124.23,122.87,122.45,101.56,62.09,14.39.[M +H]+:267.1016,found 267.1016.
The synthesis of embodiment 2:ethyl 10-hydroxyphenanthrene-9-carboxylate (1a)
The method of synthesis formula (1) compound is as described in Example 1.
The method of synthesis formula (2) compound includes the following steps:
Formula (1) compound ethyl 3- ([1,1'-biphenyl] -2-yl) -3- is added in the reactor Oxopropanoate (0.25mmol, 67mg), N- bromo-succinimide (0.1mmol, 17.8mg), tert-butyl hydroperoxide (0.875mmol, 78.86mg), sodium dihydrogen phosphate dihydrate (0.25mmol, 39mg), tetrahydrofuran 2mL, sealing, at 90 DEG C Under be stirred to react 15 hours.It is cooled to room temperature, after solvent is removed under reduced pressure, passes through column chromatographic isolation and purification (eluant, eluent is petroleum ether) Obtain formula (2) compound ethyl 10-hydroxyphenanthrene-9-carboxylate (1a) 57.2mg, yield 86%.
The synthesis of embodiment 3:ethyl 10-hydroxyphenanthrene-9-carboxylate (1a)
The method of synthesis formula (1) compound is as described in Example 1.
The method of synthesis formula (2) compound includes the following steps:
Formula (1) compound ethyl 3- ([1,1'-biphenyl] -2-yl) -3- is added in the reactor Oxopropanoate (0.25mmol, 67mg), N- bromo-succinimide (0.1mmol, 17.8mg), bromine ethylamine hydrobromide (0.1mmol, 20.5mg), tert-butyl hydroperoxide (0.875mmol, 78.86mg), sodium dihydrogen phosphate dihydrate (0.25mmol, 39mg), tetrahydrofuran 2mL, sealing, is stirred to react 15 hours at 80 DEG C.It is cooled to room temperature, is removed under reduced pressure molten After agent, formula (2) compound ethyl 10- is obtained by column chromatographic isolation and purification (eluant, eluent is petroleum ether) Hydroxyphenanthrene-9-carboxylate (1a) 61.9mg, yield 93%.
The synthesis of embodiment 4:ethyl 10-hydroxyphenanthrene-9-carboxylate (1a)
The method of synthesis formula (1) compound is as described in Example 1.
The method of synthesis formula (2) compound includes the following steps:
Formula (1) compound ethyl 3- ([1,1'-biphenyl] -2-yl) -3- is added in the reactor Oxopropanoate (0.25mmol, 67mg), dibromo isocyanurate (0.05mmol, 14.8mg), tert-butyl hydroperoxide (0.875mmol, 78.86mg), tetrahydrofuran 2mL, sealing, is stirred to react 15 hours at 90 DEG C.It is cooled to room temperature, decompression removes After removing solvent, formula (2) compound ethyl 10- is obtained by column chromatographic isolation and purification (eluant, eluent is petroleum ether) Hydroxyphenanthrene-9-carboxylate (1a) 49mg, yield 74%.
The conjunction of embodiment 5:ethyl 10-hydroxy-7-methoxyphenanthrene-9-carboxylate (2a) At
The method of synthesis formula (1) compound includes the following steps:
By the phenyl boric acid (3.6mmol, 435mg) in embodiment 1 replace with to methoxyphenylboronic acid (3.6mmol, 548mg), with embodiment 1, that finally obtain is formula (1) compound ethyl3- (4'-methoxy- for other methods and condition [1,1'-biphenyl]-2-yl)-3-oxopropanoate。
The method of synthesis formula (2) compound includes the following steps:
Formula (1) compound ethyl 3- (4'-methoxy- [1,1'-biphenyl] -2-yl) -3- is added in reactor Oxopropanoate (0.25mmol, 75mg), N- bromo-succinimide (0.1mmol, 17.8mg), tert-butyl hydroperoxide (0.875mmol, 78.86mg), sodium dihydrogen phosphate dihydrate (0.25mmol, 39mg), tetrahydrofuran 2mL, sealing, at 80 DEG C Under be stirred to react 15 hours.It is cooled to room temperature, after solvent is removed under reduced pressure, passes through column chromatographic isolation and purification (eluant, eluent is petroleum ether) Obtain formula (2) compound ethyl 10-hydroxy-7-methoxyphenanthrene-9-carboxylate (2a) 68.9mg, yield 92%.
1H NMR (400MHz, Chloroform-d) δ 13.44 (s, 1H), 8.49 (d, J=8.2Hz, 1H), 8.43 (d, J =8.9Hz, 2H), 8.30 (d, J=2.6Hz, 1H), 7.70 (d, J=7.7Hz, 1H), 7.54 (t, J=7.6Hz, 1H), 7.08 (dd, J=9.1,2.6Hz, 1H), 4.57 (q, J=7.1Hz, 2H), 3.92 (s, 3H), 1.55 (t, J=7.1Hz, 3H)；13C NMR(101MHz,CDCl3)δ173.00,163.69,159.05,133.84,131.02,130.55,125.79,125.02, 124.29,124.16,121.93,120.20,113.58,108.03,101.15,77.37,77.05,76.73,61.97, 55.15,14.35.
The synthesis of embodiment 6:ethyl 7-fluoro-10-hydroxyphenanthrene-9-carboxylate (3a)
The method of synthesis formula (1) compound includes the following steps:
Phenyl boric acid (3.6mmol, 435mg) in embodiment 1 is replaced with to fluorobenzoic boric acid (3.6mmol, 504mg), With embodiment 1, that finally obtain is formula (1) compound ethyl3- (4'-fluoro- [1,1'- for his method and condition biphenyl]-2-yl)-3-oxopropanoate。
The method of synthesis formula (2) compound includes the following steps:
Formula (1) compound ethyl 3- (4'-fluoro- [1,1'-biphenyl] -2-yl) -3- is added in reactor Oxopropanoate (0.25mmol, 71.0mg), N- bromo-succinimide (0.1mmol, 17.8mg), tert-butyl hydroperoxide Hydrogen (0.875mmol, 78.86mg), sodium dihydrogen phosphate dihydrate (0.25mmol, 39mg), tetrahydrofuran 2mL, sealing, 80 It is stirred to react at DEG C 15 hours.It is cooled to room temperature, after solvent is removed under reduced pressure, by column chromatographic isolation and purification, (eluant, eluent is petroleum Ether) formula (2) compound Ethyl 4- (4-bromophenyl) -1-hydroxy-2-naphthoate (3a) 59.0mg is obtained, it produces Rate 84%.
1H NMR (400MHz, Chloroform-d) δ 13.50 (s, 1H), 8.41 (ddd, J=23.3,15.5,8.2Hz, 4H), 7.70 (t, J=7.6Hz, 1H), 7.56 (t, J=7.6Hz, 1H), 7.14 (t, J=8.2Hz, 1H), 4.57 (q, J= 7.1Hz, 2H), 1.54 (t, J=7.1Hz, 3H)；13C NMR(101MHz,CDCl3)δ172.64,163.97,163.39, 160.97,133.27,131.18,131.08,130.70,126.56,125.06,124.82,124.73,124.69,122.51, 122.49,122.17,112.59,112.36,111.56,111.31,100.91,100.88,77.37,77.05,76.73, 62.28,14.29
The synthesis of embodiment 7:ethyl 10-hydroxy-7-methylphenanthrene-9-carboxylate (4a)
The method of synthesis formula (1) compound includes the following steps:
Phenyl boric acid (3.6mmol, 435mg) in embodiment 1 is replaced with to methylphenylboronic acid (3.6mmol, 490mg), With embodiment 1, that finally obtain is formula (1) compound ethyl3- (4'-methyl- [1,1'- for other methods and condition biphenyl]-2-yl)-3-oxopropanoate。
The method of synthesis formula (2) compound includes the following steps:
Formula (1) compound ethyl 3- (4'-methyl- [1,1'-biphenyl] -2-yl) -3- is added in the reactor Oxopropanoate (0.25mmol, 70.0mg), N- bromo-succinimide (0.1mmol, 17.8mg), tert-butyl hydroperoxide Hydrogen (0.875mmol, 78.86mg), sodium dihydrogen phosphate dihydrate (0.25mmol, 39mg), tetrahydrofuran 2mL, sealing, 80 It is stirred to react at DEG C 15 hours.It is cooled to room temperature, after solvent is removed under reduced pressure, by column chromatographic isolation and purification, (eluant, eluent is petroleum Ether) obtain formula (2) compound ethyl 10-hydroxy-7-methylphenanthrene-9-carboxylate (4a) 65.5mg, yield 94%.
1H NMR (400MHz, Chloroform-d) δ 13.26 (s, 1H), 8.55 (s, 1H), 8.49 (t, J=8.4Hz, 2H), 8.39 (d, J=8.3Hz, 1H), 7.70 (t, J=7.6Hz, 1H), 7.57 (t, J=7.6Hz, 1H), 7.26 (d, J= 8.4Hz, 1H), 4.57 (q, J=7.1Hz, 2H), 2.50 (s, 3H), 1.53 (t, J=7.1Hz, 3H)；13C NMR(101MHz, CDCl3)δ172.93,162.74,137.25,133.73,130.34,129.53,126.38,125.98,125.71,124.94, 124.86,123.88,122.73,122.23,101.37,77.41,77.09,76.77,61.98,22.19,14.30
Embodiment 8:ethyl 10-hydroxy-8-methylphenanthrene-9-carboxylate (5a) and The synthesis of ethyl 10-hydroxy-6-methylphenanthrene-9-carboxylate (5b)
The method of synthesis formula (1) compound includes the following steps:
Phenyl boric acid (3.6mmol, 435mg) in embodiment 1 is replaced with into 3- methylphenylboronic acid (3.6mmol, 490mg), With embodiment 1, that finally obtain is formula (1) compound ethyl3- (3'-methyl- [1,1'- for other methods and condition biphenyl]-2-yl)-3-oxopropanoate。
The method of synthesis formula (2) compound includes the following steps:
Formula (1) compound ethyl 3- (3'-methyl- [1,1'-biphenyl] -2-yl) -3- is added in the reactor Oxopropanoate (0.25mmol, 70.5mg), N- bromo-succinimide (0.1mmol, 17.8mg), tert-butyl hydroperoxide Hydrogen (0.875mmol, 78.86mg), sodium dihydrogen phosphate dihydrate (0.25mmol, 39mg), tetrahydrofuran 2mL, sealing, 80 It is stirred to react at DEG C 15 hours.It is cooled to room temperature, after solvent is removed under reduced pressure, by column chromatographic isolation and purification, (eluant, eluent is petroleum Ether) obtain ethyl 10-hydroxy-8-methylphenanthrene-9-carboxylate (5a) 37mg, yield 53%, And ethyl 10-hydroxy-6-methylphenanthrene-9-carboxylate (5b) 27.9mg, yield 40%, always Yield is 93%.
(5a)1H NMR (400MHz, Chloroform-d) δ 13.23 (s, 1H), 8.68 (d, J=8.6Hz, 1H), 8.62- 8.50 (m, 2H), 8.36 (s, 1H), 7.75 (t, J=7.8Hz, 1H), 7.63 (t, J=7.5Hz, 1H), 7.40 (d, J= 8.6Hz, 1H), 4.61 (q, J=7.1Hz, 2H), 2.56 (s, 3H), 1.55 (t, J=7.1Hz, 3H)；13C NMR(101MHz, CDCl3)δ172.94,162.07,133.60,133.44,130.21,129.16,127.12,126.70,126.15,125.88, 125.35,124.93,122.73,122.40,101.54,77.36,77.05,76.73,61.95,21.49,14.37.
(5b)1H NMR (600MHz, Chloroform-d) δ 10.89 (s, 1H), 8.57 (d, J=8.3Hz, 1H), 8.44 (dd, J=17.8,8.0Hz, 2H), 7.74 (t, J=8.3Hz, 1H), 7.63 (t, J=8.0Hz, 1H), 7.43 (dt, J= 14.6,7.0Hz, 2H), 4.45 (q, J=7.1Hz, 2H), 2.53 (s, 3H), 1.37 (t, J=7.2Hz, 3H)；13C NMR (151MHz,CDCl3)δ171.70,158.24,134.18,133.75,130.44,130.02,128.78,127.21, 126.85,124.55,124.53,122.76,120.28,103.63,77.25,77.03,76.82,61.78,22.96, 14.14.
Embodiment 9:ethyl 7- (tert-butyl) -10-hydroxyphenanthrene-9-carboxylate (6a) Synthesis
The method of synthesis formula (1) compound includes the following steps:
By the phenyl boric acid (3.6mmol, 435mg) in embodiment 1 replace with to tert-butylbenzeneboronic acid (3.6mmol, 642mg), with embodiment 1, that finally obtain is formula (1) compound ethyl7- (tert-butyl)-for other methods and condition 10-hydroxyphenanthrene-9-carboxylate。
The method of synthesis formula (2) compound includes the following steps:
Formula (1) compound ethyl 7- (tert-butyl) -10-hydroxyphenanthrene- is added in the reactor 9-carboxylate (0.25mmol, 83.0mg), N- bromo-succinimide (0.1mmol, 17.8mg), tert-butyl hydroperoxide Hydrogen (0.875mmol, 78.86mg), sodium dihydrogen phosphate dihydrate (0.25mmol, 39mg), tetrahydrofuran 2mL, sealing, 80 It is stirred to react at DEG C 15 hours.It is cooled to room temperature, after solvent is removed under reduced pressure, by column chromatographic isolation and purification, (eluant, eluent is petroleum Ether) obtain formula (2) compound ethyl 7- (tert-butyl) -10-hydroxyphenanthrene-9-carboxylate (6a) 76.7mg, yield 95%.
1H NMR(400MHz,Chloroform-d)δ13.39(s,1H),8.86(s,1H),8.62–8.41(m,3H), 7.73 (t, J=7.6Hz, 1H), 7.64-7.51 (m, 2H), 4.59 (q, J=7.1Hz, 2H), 1.57 (t, J=7.1Hz, 3H), 1.44(s,9H)；13C NMR(101MHz,CDCl3)δ173.20,162.99,150.28,133.62,130.41,129.24, 126.46,125.00,124.96,123.85,122.59,122.33,122.30,101.68,77.38,77.07,76.75, 62.00,35.25,31.51,14.46.
The synthesis of embodiment 10:diethyl 9-hydroxyphenanthrene-2,10-dicarboxylate (7a)
The method of synthesis formula (1) compound includes the following steps:
By the phenyl boric acid (3.6mmol, 435mg) in embodiment 1 replace with to ethoxycarbonyl phenyl boric acid (3.6mmol, 699mg), with embodiment 1, that finally obtain is formula (1) compound ethyl2'- (3-ethoxy-3- for other methods and condition oxopropanoyl)-[1,1'-biphenyl]-4-carboxylate。
The method of synthesis formula (2) compound includes the following steps:
Formula (1) compound ethyl 2'- (3-ethoxy-3-oxopropanoyl)-[1,1'- is added in the reactor Biphenyl] -4-carboxylate (0.25mmol, 85.0mg), N- bromo-succinimide (0.1mmol, 17.8mg), uncle Butylhydroperoxide (0.875mmol, 78.86mg), sodium dihydrogen phosphate dihydrate (0.25mmol, 39mg), tetrahydrofuran 2mL, sealing, is stirred to react 15 hours at 80 DEG C.It is cooled to room temperature, after solvent is removed under reduced pressure, passes through column chromatographic isolation and purification (eluant, eluent is petroleum ether than ethyl acetate 200:1) obtains formula (2) compound diethyl 9-hydroxyphenanthrene- 2,10-dicarboxylate (7a) 76..0mg, yield 90%.
1H NMR (400MHz, Chloroform-d) δ 13.45 (s, 1H), 9.49 (s, 1H), 8.48 (t, J=8.5Hz, 3H), 7.75 (t, J=7.7Hz, 1H), 7.65 (t, J=7.5Hz, 1H), 4.58 (q, J=7.1Hz, 2H), 4.44 (q, J= 7.1Hz, 2H), 1.60 (t, J=7.1Hz, 3H), 1.46 (t, J=7.1Hz, 3H)；13C NMR(101MHz,CDCl3)δ 172.65,166.94,163.25,132.78,130.61,128.94,128.85,128.18,127.78,126.00,125.04, 124.23,122.97,122.78,101.31,77.38,77.07,76.75,62.32,61.06,14.48,14.18.
Embodiment 11:ethyl 10-hydroxy-6,8-dimethylphenanthrene-9-carboxylate (8a) Synthesis
The method of synthesis formula (1) compound includes the following steps:
By the phenyl boric acid (3.6mmol, 435mg) in embodiment 1 replace with 3,5- dimethylphenyl boronic acid (3.6mmol, 540mg), with embodiment 1, that finally obtain is formula (1) compound ethyl3- (3', 5'- for other methods and condition dimethyl-[1,1'-biphenyl]-2-yl)-3-oxopropanoate。
The method of synthesis formula (2) compound includes the following steps:
Formula (1) compound ethyl 3- (3', 5'-dimethyl- [1,1'-biphenyl] -2- is added in the reactor Yl) -3-oxopropanoate (0.25mmol, 75.0mg), N- bromo-succinimide (0.1mmol, 17.8mg), tert-butyl Hydrogen peroxide (0.875mmol, 78.86mg), sodium dihydrogen phosphate dihydrate (0.25mmol, 39mg), tetrahydrofuran 2mL, envelope Mouthful, it is stirred to react at 80 DEG C 15 hours.It is cooled to room temperature, after solvent is removed under reduced pressure, passes through column chromatographic isolation and purification (eluant, eluent It is petroleum ether than ethyl acetate 200:1) obtain formula (2) compound ethyl 10-hydroxy-6,8- Dimethylphenanthrene-9-carboxylate (8a) 41.4mg, yield 56%.
1H NMR (400MHz, Chloroform-d) δ 10.82 (s, 1H), 8.54 (d, J=8.1Hz, 1H), 8.42 (d, J =7.8Hz, 1H), 8.19 (s, 1H), 7.70 (t, J=7.3Hz, 1H), 7.59 (t, J=7.1Hz, 1H), 7.23 (s, 1H), 4.42 (q, J=7.4Hz, 2H), 2.51 (s, 3H), 2.47 (s, 3H), 1.34 (t, J=6.9Hz, 3H)；13C NMR(101MHz, CDCl3)δ171.80,157.68,133.98,133.55,132.09,129.88,127.31,126.76,126.53,124.66, 124.52,122.77,120.36,103.62,77.41,77.09,76.77,61.77,22.86,21.52,14.19.
The conjunction of embodiment 12:ethyl 5-fluoro-10-hydroxyphenanthrene-9-carboxylate (9a) At
The method of synthesis formula (1) compound includes the following steps:
Phenyl boric acid (3.6mmol, 435mg) in embodiment 1 is replaced with into 2- fluorobenzoic boric acid (3.6mmol, 504mg), With embodiment 1, that finally obtain is formula (1) compound ethyl 3- (2'-fluoro- [1,1'- for his method and condition biphenyl]-2-yl)-3-oxopropanoate。
The method of synthesis formula (2) compound includes the following steps:
Formula (1) compound ethyl 3- (2'-fluoro- [1,1'-biphenyl] -2-yl) -3- is added in the reactor Oxopropanoate (0.25mmol, 71.0mg), N- bromo-succinimide (0.1mmol, 17.8mg), tert-butyl hydroperoxide Hydrogen (0.875mmol, 78.86mg), sodium dihydrogen phosphate dihydrate (0.25mmol, 39mg), tetrahydrofuran 2mL, sealing, 80 It is stirred to react at DEG C 15 hours.It is cooled to room temperature, after solvent is removed under reduced pressure, by column chromatographic isolation and purification, (eluant, eluent is petroleum Ether) obtain formula (2) compound ethyl 5-fluoro-10-hydroxyphenanthrene-9-carboxylate (9a) 64.0mg, yield 91%.
1H NMR (400MHz, Chloroform-d) δ 13.21 (s, 1H), 9.02 (d, J=5.5Hz, 1H), 8.57 (t, J =8.6Hz, 2H), 7.77 (t, J=7.4Hz, 1H), 7.66 (t, J=7.4Hz, 1H), 7.46 (q, J=7.8Hz, 1H), 7.19 (dd, J=14.2,7.9Hz, 1H), 4.59 (q, J=6.9Hz, 2H), 1.53 (t, J=7.0Hz, 3H)；13C NMR(101MHz, CDCl3)δ172.52,162.82,160.29,132.01,131.97,131.37,131.33,130.78,130.76,127.62, 127.42,127.34,127.31,127.07,127.05,125.66,124.63,101.52,77.35,77.03,76.71, 62.25,14.33.
The conjunction of embodiment 13:ethyl 2-fluoro-10-hydroxyphenanthrene-9-carboxylate (10a) At
The method of synthesis formula (1) compound includes the following steps:
By the 2 '-bromoacetophenones (3mmol, 405 μ L) in embodiment 1 replace with 5 '-fluoro- 2 '-bromoacetophenones (3mmol, 648mg), other methods and condition be with embodiment 1, finally obtain be formula (1) compound ethyl3- (4-fluoro- [1, 1'-biphenyl]-2-yl)-3-oxopropanoate。
The method of synthesis formula (2) compound includes the following steps:
Formula (1) compound ethyl 3- (4-fluoro- [1,1'-biphenyl] -2-yl) -3- is added in the reactor Oxopropanoate (0.25mmol, 74.0mg), N- bromo-succinimide (0.1mmol, 17.8mg), tert-butyl hydroperoxide Hydrogen (0.875mmol, 78.86mg), sodium dihydrogen phosphate dihydrate (0.25mmol, 39mg), tetrahydrofuran 2mL, sealing, 80 It is stirred to react at DEG C 15 hours.It is cooled to room temperature, after solvent is removed under reduced pressure, by column chromatographic isolation and purification, (eluant, eluent is petroleum Ether) obtain formula (2) compound ethyl 5-fluoro-10-hydroxyphenanthrene-9-carboxylate (10a) 68.3mg, yield 93%.
1H NMR (400MHz, Chloroform-d) δ 13.18 (s, 1H), 8.75 (d, J=8.4Hz, 1H), 8.56-8.35 (m, 2H), 8.11 (d, J=9.8Hz, 1H), 7.50 (dt, J=28.2,6.7Hz, 3H), 4.60 (q, J=7.1Hz, 2H), 1.54 (t, J=7.1Hz, 3H)；13C NMR(101MHz,CDCl3)δ172.69,162.78,161.51,161.47,160.32, 130.14,130.12,128.89,127.38,126.04,125.70,124.92,124.84,124.48,122.62,119.24, 119.00,109.83,109.61,102.45,77.36,77.04,76.72,62.22,14.34.
Embodiment 14:ethyl 10-hydroxy-2-methoxyphenanthrene-9-carboxylate's (11a) Synthesis
The method of synthesis formula (1) compound includes the following steps:
2 '-bromoacetophenones (3mmol, 405 μ L) in embodiment 1 are replaced with into 5 '-methoxyl groups -2 '-bromoacetophenone With embodiment 1, that finally obtain is formula (1) compound ethyl3- (4- for (3mmol, 684mg), other methods and condition methoxy-[1,1'-biphenyl]-2-yl)-3-oxopropanoate。
The method of synthesis formula (2) compound includes the following steps:
Formula (1) compound ethyl 3- (4-methoxy- [1,1'-biphenyl] -2-yl) -3- is added in the reactor Oxopropanoate (0.25mmol, 77.5mg), N- bromo-succinimide (0.1mmol, 17.8mg), tert-butyl hydroperoxide Hydrogen (0.875mmol, 78.86mg), sodium dihydrogen phosphate dihydrate (0.25mmol, 39mg), tetrahydrofuran 2mL, sealing, 80 It is stirred to react at DEG C 15 hours.It is cooled to room temperature, after solvent is removed under reduced pressure, by column chromatographic isolation and purification, (eluant, eluent is petroleum Ether) obtain formula (2) compound ethyl 10-hydroxy-2-methoxyphenanthrene-9-carboxylate (11a) 68.7mg, yield 89%.
1H NMR (400MHz, Chloroform-d) δ 13.31 (s, 1H), 8.70 (d, J=8.5Hz, 1H), 8.35 (d, J =9.1Hz, 2H), 7.79 (s, 1H), 7.45 (t, J=7.7Hz, 1H), 7.35 (t, J=7.5Hz, 1H), 7.18-7.09 (m, 1H), 4.49 (q, J=7.1Hz, 2H), 3.91 (s, 3H), 1.44 (t, J=7.1Hz, 3H)；13C NMR(101MHz,CDCl3)δ 173.03,163.13,161.54,135.73,130.18,127.73,126.96,126.08,125.53,123.83,122.85, 119.47,116.31,104.18,99.72,77.36,77.04,76.73,61.85,55.47,14.40.
The conjunction of embodiment 15:ethyl 2-chloro-10-hydroxyphenanthrene-9-carboxylate (12a) At
The method of synthesis formula (1) compound includes the following steps:
By the 2 '-bromoacetophenones (3mmol, 405 μ L) in embodiment 1 replace with 5 '-chloro- 2 '-bromoacetophenones (3mmol, 696mg), other methods and condition be with embodiment 1, finally obtain be formula (1) compound ethyl3- (4-chloro- [1, 1'-biphenyl]-2-yl)-3-oxopropanoate。
The method of synthesis formula (2) compound includes the following steps:
Formula (1) compound ethyl 3- (4-chloro- [1,1'-biphenyl] -2-yl) -3- is added in the reactor Oxopropanoate (0.25mmol, 78.0mg), N- bromo-succinimide (0.1mmol, 17.8mg), tert-butyl hydroperoxide Hydrogen (0.875mmol, 78.86mg), sodium dihydrogen phosphate dihydrate (0.25mmol, 39mg), tetrahydrofuran 2mL, sealing, 80 It is stirred to react at DEG C 15 hours.It is cooled to room temperature, after solvent is removed under reduced pressure, by column chromatographic isolation and purification, (eluant, eluent is petroleum Ether) obtain formula (2) compound ethyl 10-hydroxy-2-methoxyphenanthrene-9-carboxylate (11a) 73mg, yield 94%.
1H NMR (400MHz, Chloroform-d) δ 13.28 (s, 1H), 8.75 (d, J=8.4Hz, 1H), 8.41 (dd, J =16.1,8.3Hz, 3H), 7.64-7.37 (m, 3H), 4.61 (q, J=6.8Hz, 2H), 1.56 (t, J=6.9Hz, 3H)；13C NMR(101MHz,CDCl3)δ172.70,162.10,136.88,134.76,129.89,128.17,127.27,126.63, 126.01,124.92,124.38,123.52,122.86,122.15,101.69,77.36,77.04,76.72,62.17, 14.35.
Embodiment 16:ethyl 5-hydroxypyrrolo [1,2-a] quinoline-4-carboxylate's (13a) Synthesis
The method of synthesis formula (1) compound includes the following steps:
Step 1: in three-neck flask be added cuprous iodide (0.25mmol 49mg), anhydrous phosphoric acid potassium (10.5mmol, 2.3g), vacuumize nitrogen protection after 2- acetyl pyrrole, after repetitive operation is primary, be subsequently added into reactant iodobenzene (6mmol, 1.3mL), ligand N, N '-dimethyl ethylenediamine, solvent toluene 5mL.Reaction mixture back flow reaction 24 under the conditions of 110 DEG C is small When, intermediate product N- phenyl -2- acetyl pyrrole can be obtained.Almost convert.Pass through silica gel column separating purification.
Step 2: 10mL anhydrous tetrahydro furan is added in three-neck flask, adds sodium hydride and (be scattered in kerosene, contain Amount is 60%, 8.4mmol, 0.336g), diethyl carbonate (8.4mmol, 0.72mL).Sealing is placed on oil bath pan and returns for 80 DEG C Stream heating.N- phenyl -2- acetyl pyrrole (3mmol, 556mg) is dissolved in 10mL anhydrous tetrahydro furan, under reflux conditions It is added drop-wise in reaction mixture dropwise.Until N- phenyl -2- acetyl pyrrole is totally consumed, stopping reaction almost turning Change.By the way that formula (1) compound ethyl 3-oxo-3- (1-phenyl-1H-pyrrol-2- can be obtained after silica gel column separating purification yl)propanoate。
The method of synthesis formula (2) compound includes the following steps:
Formula (1) compound ethyl 3-oxo-3- (1-phenyl-1H-pyrrol-2-yl) is added in the reactor Propanoate (0.25mmol, 63mg), N- bromo-succinimide (0.1mmol, 17.8mg), tert-butyl hydroperoxide (0.875mmol, 78.86mg), sodium dihydrogen phosphate dihydrate (0.25mmol, 39mg), tetrahydrofuran 2mL, sealing, at 90 DEG C Under be stirred to react 15 hours.It is cooled to room temperature, after solvent is removed under reduced pressure, passes through column chromatographic isolation and purification (eluant, eluent is petroleum ether) Obtain formula (2) compound ethyl 5-hydroxypyrrolo [1,2-a] quinoline-4-carboxylate (13a) 42.2mg, yield 72%.
1H NMR (400MHz, Chloroform-d) δ 13.44 (s, 1H), 8.62 (d, J=7.9Hz, 1H), 7.85 (s, 1H), 7.76 (d, J=8.0Hz, 1H), 7.38-7.26 (m, 2H), 7.08 (d, J=3.6Hz, 1H), 6.89-6.66 (m, 1H), 4.52 (q, J=7.1Hz, 2H), 1.51 (t, J=7.1Hz, 3H)13C NMR(101MHz,CDCl3)δ172.37,159.64, 129.26,126.82,125.11,124.62,124.46,121.32,116.16,114.26,113.62,107.48,94.22, 77.40,77.08,76.76,61.74,14.41.
The foregoing is merely illustrative of the preferred embodiments of the present invention, is not intended to limit the invention, all in essence of the invention Within mind and principle, made any modification equivalent replacement is improved etc., it should all be included in the protection scope of the present invention.

Claims (10)

1. the synthetic method of a kind of polysubstituted 10- hydroxyl phenanthrene and its derivative, it is characterised in that: this method comprises: formula (1) is changed It closes object and formula (2) compound is made under the action of bromine catalyst, additive, peroxide and organic solvent, reaction formula is such as Under:
Wherein, R1For hydrogen, halogen, aryl, alkyl or alkoxy, binding site is 3 or 4 or 5 or 6；R2For hydrogen, Halogen, aryl, alkyl, alkoxy or ester group, 2 ' position of binding site or 3 ' positions or 4 ' positions or 5 ' positions or 6 ' positions；EWG is cyanogen Base, methoxy are for formoxyl, ethoxy for formoxyl or N- phenyl formamide base.
2. the synthetic method of a kind of polysubstituted 10- hydroxyl phenanthrene according to claim 1 and its derivative, it is characterised in that: Formula (1) compound, the molar ratio containing bromine catalyst, peroxide and additive are 1:(0.05~0.8): (1~5): (0.4~3).
3. the synthetic method of a kind of polysubstituted 10- hydroxyl phenanthrene according to claim 1 or 2 and its derivative, feature exist In: the bromine catalyst that contains is N- bromo-succinimide, N- bromine phthalimide, tetrabutylammonium bromide, lithium bromide, sodium bromide, bromine Change potassium, hydrobromic acid, triphenyl phosphorus hydrobromate, bromine ethylamine hydrobromide, bromobenzene, bromodiphenyl methane, benzyl bromine, dibromo isocyanide urine The mixture of one or more of amine in acid, N- bromo acetamide or N- bromo hexamethylene；Preferably, the brominated catalysis Agent is N- bromo-succinimide, N- bromine phthalimide, in N- bromo hexamethylene in amine, dibromo isocyanurate or bromine ethylamine hydrobromide One or more kinds of mixtures；It is furthermore preferred that the bromine catalyst that contains is N- bromo-succinimide.
4. the synthetic method of a kind of polysubstituted 10- hydroxyl phenanthrene according to claim 1 or 2 and its derivative, feature exist In: the peroxide be tert-butyl hydroperoxide, hydrogen peroxide, di-tert-butyl peroxide, cumyl hydroperoxide, One of chloroperoxybenzoic acid, peroxidized t-butyl perbenzoate, ammonium persulfate-sodium bisulfate, potassium peroxydisulfate or iodobenzene acetate or Two or more mixtures；Preferably, the peroxide is tert-butyl hydroperoxide.
5. the synthetic method of a kind of polysubstituted 10- hydroxyl phenanthrene according to claim 1 or 2 and its derivative, feature exist In: the additive is in sodium dihydrogen phosphate and its hydrate, acetic acid, triphenyl phosphorus, citric acid, pyridine, sodium acetate or DBU One or more kinds of mixtures；Preferably, the additive is one of sodium dihydrogen phosphate, acetic acid or citric acid or two Kind or more mixture.
6. the synthetic method of a kind of polysubstituted 10- hydroxyl phenanthrene according to claim 1 or 2 and its derivative, feature exist In: the additional amount of the organic solvent is 4~100 times of formula (1) compound by weight.
7. the synthetic method of a kind of polysubstituted 10- hydroxyl phenanthrene according to claim 1 or 2 and its derivative, feature exist In: the reaction temperature of this method is 60~100 DEG C, and the reaction time is 0.5~15 hour.
8. the synthetic method of a kind of polysubstituted 10- hydroxyl phenanthrene according to claim 1 or 2 and its derivative, feature exist In: when EWG is cyano, the synthetic method of formula (1) compound is as follows:
When EWG be methoxy for formoxyl or ethoxy for formoxyl when, the synthetic method of formula (1) compound is as follows:
When EWG is N- phenyl formamide base, the synthetic method of formula (1) compound is as follows:
9. the synthetic method of a kind of polysubstituted 10- hydroxyl phenanthrene according to claim 8 and its derivative, it is characterised in that: Organic solvent in formula (1) compound synthesis method is toluene, 1,4- dioxane, N, N '-dimethyl formamide, ethyl alcohol or first The mixture of one or more of alcohol；
By the organic solvent in the method for formula (1) compound synthesis formula (2) compound be ethyl alcohol, methanol, glycol dimethyl ether, 1, 4- dioxane, tetrahydrofuran, 1,2- methylene chloride, carbon tetrachloride or N, one or both of N '-dimethyl formamide with On mixture；Preferably, organic solvent is tetrahydrofuran.
10. a kind of polysubstituted 10- hydroxyl phenanthrene and its derivative, it is characterised in that: the compound has the knot of chemistry shown in formula (2) Structure:
Wherein, R1For hydrogen, halogen, aryl, alkyl or alkoxy, binding site is 3 or 4 or 5 or 6；R2For hydrogen, Halogen, aryl, alkyl, alkoxy or ester group, 2 ' position of binding site or 3 ' positions or 4 ' positions or 5 ' positions or 6 ' positions；EWG is cyanogen Base, methoxy are for formoxyl, ethoxy for formoxyl or N- phenyl formamide base.
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