WO2016141841A1

WO2016141841A1 - Method for synthesizing pharmaceutical intermediate phenanthrene compound in potassium hydroxide environment

Info

Publication number: WO2016141841A1
Application number: PCT/CN2016/075449
Authority: WO
Inventors: 翟学研
Original assignee: 王能青
Priority date: 2015-03-06
Filing date: 2016-03-03
Publication date: 2016-09-15
Also published as: WO2016141844A1; WO2016141834A1; WO2016141827A1; CN104692986A; WO2016141839A1; WO2016141831A1; WO2016141833A1; WO2016141829A1; CN104692986B; WO2016141843A1; CN105801336A; CN105801338A; CN105801338B; WO2016141842A1; WO2016141837A1; WO2016141823A1; WO2016141826A1; WO2016141830A1; WO2016141828A1; WO2016141824A1

Abstract

The invention relates to a method for synthesizing a phenanthrene compound, as shown by formula (I) below, in a potassium hydroxide environment. The method comprises the following steps: reacting a compound as shown by formula (II) below and a compound as shown by formula (III) in a solvent under an inert atmosphere in the presence of a catalyst, an organic ligand and potassium hydroxide, and thereby obtaining the compound of formula (I), wherein R₁ and R₂ are each independently H, C₁-C₆alkyl, C₁-C₆alkoxy or halogen; and R₃ is C₆-C₁₀aryl or C₅-C₈heteroaryl, wherein the C₆-C₁₀aryl or C₅-C₈heteroaryl is optionally substituted by 1-3 substituents, and the substituents are C₁-C₆alkyl or halogen. The method achieves good effects due to the selection of a suitable catalyst, organic ligand, base and solvent, and has wide industrial application prospects.

Description

Method for synthesizing pharmaceutical intermediate phenanthrene compound in potassium hydroxide environment

Technical field

The invention relates to a method for synthesizing a fused ring compound, and more particularly to a method for synthesizing a pharmaceutical intermediate phenanthrene compound, and belongs to the field of organic synthesis and pharmaceutical intermediate synthesis.

Background technique

Fused ring compounds such as naphthalene, anthracene, phenanthrene and the like have attracted the attention and attention of pharmaceutical researchers due to their ubiquitous biological activity. Among them, phenanthrene and its derivatives are an important class of aromatic compounds, which have been widely used in drug design and synthesis, and material research and development.

It is precisely because of the excellent performance and potential of phenanthrene compounds that the research on new synthetic methods of phenanthrene and its derivatives has always been a hot issue of concern to organic chemical synthesis workers.

So far, there have been a variety of preparation processes for phenanthrene compounds in the prior art, which have studied the synthesis methods suitable for phenanthrene compounds from various angles. E.g:

Xiao Tiebo et al. ("Phenanthrene Synthesis by Eosin Y-Catalyzed, Visible Light-Induced [4+2] Benzannulation of Biaryldiazonium Salts with Alkynes", Adv. Synth. Catal., 2012, 354, 3195-3199) reported a no Metal-catalyzed, visible-induced [4+2] benzo cyclization of diaryl azo salts. The equation is as follows:

Ye Fei et al. ("Expeditious Synthesis of Phenanthrenes via CuBr2-Catalyzed Coupling of Terminal Alkynes and N-Tosylhydrazones Derived from O-Fo rmyl Biphenyls", Organic Letters, 2011, 13, 5020-5023) discloses a benzyl CuBr2 catalyzed couple The hydrazine/cyclization reaction is derived from N-p-toluenesulfonyl hydrazide of o-formylbiphenyl as a starting material, and the reaction formula is as follows:

Kwon Yongseok et al. ("Expedient Synthesis of Phenanthrenes via In (III) - Catalyzed 6-Exo-DigCycloisomerization", Organic Letters, 2013, 15, 920-923) reported an In(III) catalyzed reaction for the preparation of phenanthrene compounds, It has the advantages of high reaction efficiency and wide application range of substrate. The reaction formula is as follows:

As described above, although various methods for preparing phenanthrene compounds have been disclosed in the prior art, these methods still fail to meet the production requirements in the fields of medicine and chemical synthesis because of their inherent low production efficiency and insufficient raw materials. Use and many other issues.

In view of this, the present inventors have aimed to provide a novel catalytic synthesis method for phenanthrene compounds through a large number of experimental studies, and achieve the purpose of high yield and rapid reaction, and have a wide range of industrial application prospects.

Summary of the invention

In view of the above-mentioned many defects, the inventors have developed a synthesis method of a phenanthrene compound which can be used as a pharmaceutical intermediate after intensive research after a lot of creative labor, and completed the present invention.

Specifically, the present invention provides a method for synthesizing a phenanthrene compound represented by the following formula (I),

The method comprises: in an inert atmosphere, in the presence of a catalyst, an organic ligand and a base, in a solvent, The compound of the following formula (II) is reacted with a compound of the formula (III) to give a compound of the formula (I);

Wherein R ₁ and R ₂ are each independently H, C ₁ -C ₆ alkyl, C ₁ -C ₆ alkoxy or halogen;

R ₃ is C ₆ -C ₁₀ aryl or C ₅ -C ₈ heteroaryl, the C ₆ -C ₁₀ aryl or C ₄ -C ₈ heteroaryl optionally substituted by 1-3 substituents, for example It may be substituted by 1, 2 or 3 substituents which are C ₁ -C ₆ alkyl or halogen.

In the synthesis method of the present invention, C ₁ -C ₆ alkyl means an alkyl group having 1 to 6 carbon atoms, and may be, for example, methyl, ethyl, n-propyl, isopropyl or n-butyl. , sec-butyl, isobutyl, tert-butyl, n-pentyl, isopentyl, n-hexyl and the like.

In the synthesis method of the present invention, the C ₁ -C ₆ alkoxy group means a group in which the "C ₁ -C ₆ alkyl group" defined above is bonded to an O atom.

In the synthesis method of the present invention, the halogen may be, for example, fluorine, chlorine, bromine or iodine.

In the synthesis method of the present invention, the C ₆ -C ₁₀ aryl group means an aryl group having 6 to 10 carbon atoms, and may be, for example, a phenyl group or a naphthyl group.

In the synthesis method of the present invention, the C ₄ -C ₈ heteroaryl group means a heteroaryl group having _{4 to} ₈ carbon atoms, and may be, for example, a pyridyl group, a furthiyl group or a thienyl group.

In the synthesis method of the present invention, the catalyst is a mixture of an organic palladium compound and an organic copper compound in a molar ratio of 1:2-4, for example, 1:2, 1:3 or 1:4. .

Wherein, the organic palladium compound is exemplified by palladium acetate (Pd(OAc) ₂ ), palladium chloride (PdCl ₂ ), palladium acetylacetonate (Pd(acac) ₂ ), (1,5-cyclooctadiene). Palladium (PdCl ₂ (cod)), palladium trifluoroacetate (Pd(TFA) ₂ ), [1,1'-bis(diphenylphosphino)ferrocene]palladium dichloride (PdCl ₂ (dppf)) Any one or a mixture of any of a plurality of bis(triphenylphosphine)palladium chloride (PdCl ₂ (PPh ₃ ) ₂ ), most preferably PdCl ₂ (dppf).

Wherein, the organic copper compound is copper hexafluorophosphate ([(CH ₃ CN) ₄ Cu]PF ₆ ), copper triflate (Cu(OTf) ₂ ), copper acetylacetonate (Cu(acac)) ₂ ) Any one or more of copper acetate, most preferably copper hexafluorophosphate tetraacetonitrile ([(CH ₃ CN) ₄ Cu]PF ₆ )).

In the synthetic method of the present invention, the organic ligand is a nitrogen-containing bidentate ligand, and may be, for example, a substituted or unsubstituted bipyridine, a substituted or unsubstituted phenanthroline or the like, and for example, may be as follows L1-L4:

Most preferred is L1.

In the synthesis method of the present invention, the base is Na ₂ CO ₃ , K ₂ CO ₃ , NaOH, KOH, K ₃ PO ₄ , Na ₃ PO ₄ , NaHCO ₃ , KHCO ₃ , sodium acetate, sodium ethoxide, Any one or a mixture of any of a plurality of potassium t-butoxide, diisopropylamine, diisopropylethanolamine, etc.; most preferably diisopropylethanolamine.

In the synthesis method of the present invention, the solvent is a mixture of PEG-400 and 1-allyl-3-methylimidazolium tetrafluoroborate, and the volume ratio of the two is 1:0.1-0.3, for example, It is 1:0.1, 1:0.2 or 1:0.3.

In the synthesis method of the present invention, the inert atmosphere may be, for example, a nitrogen atmosphere or an argon atmosphere.

In the synthesis method of the present invention, the molar ratio of the compound of the formula (II) to the compound of the formula (III) is 1:2-4, and may be, for example, 1:2, 1:3 or 1:4.

In the synthesis method of the present invention, the molar ratio of the compound of the formula (II) to the catalyst is 1:0.08-0.15, that is, the molar amount of the compound of the formula (II) and the two components constituting the catalyst. The ratio of the sum of the molar amounts is from 1:0.08 to 0.15, for example, it may be 1:0.08, 1:0.1, 1:0.12, 1:0.14 or 1:0.15.

In the synthesis method of the present invention, the molar ratio of the compound of the formula (II) to the organic ligand is from 1:0.1 to 0.2, for example, it may be 1:0.1, 1:0.15 or 1:0.2.

In the synthesis method of the present invention, the molar ratio of the compound of the formula (II) to the base is 1:2-3, and may be, for example, 1:2, 1:2.5 or 1:3.

In the synthesis method of the present invention, the amount of the solvent is not strictly limited, and those skilled in the art can appropriately select the amount thereof, for example, according to making the post-treatment easy to carry out, and the reaction can be carried out smoothly.

In the synthesis method of the present invention, the reaction temperature is 60 to 80 ° C, for example, 60 ° C, 70 ° C or 80 ° C.

In the synthesis method of the present invention, the reaction time is 8 to 12 hours, for example, 8 hours, 10 hours or 12 hours.

In the synthesis method of the present invention, the post-treatment after the completion of the reaction is specifically as follows: after the reaction is completed, deionized water is added to the reaction system, thoroughly shaken, washed, and the organic layer is separated and washed again with deionized water. The organic layer was concentrated, and the organic layer was concentrated under reduced pressure. The residue obtained was purified by silica gel column chromatography eluting with a solvent mixture of n-hexanol and chloroform in a volume ratio of 1:2-4 as elution solvent. The same fractions were combined and the elution solvent was removed to give the title compound.

As described above, the present invention provides a method for synthesizing a phenanthrene compound for use as a pharmaceutical intermediate, which obtains a desired product in high yield by selection/combination/coordination of a suitable catalyst, organic compound, base and solvent. It has great benefits for the actual production of pharmaceuticals, chemicals and other intermediates, and has broad industrial application prospects.

detailed description

The invention is described in detail below with reference to the specific embodiments thereof, but the invention is not intended to limit the scope of the present invention. The scope of protection is limited to this.

In all the examples, the ligand L1 used is a ligand represented by the above formula L1 unless otherwise specified.

Example 1

A suitable solvent consisting of PEG-400 and 1-allyl-3-methylimidazolium tetrafluoroborate (1:0.1 by volume) was added to the reactor, and then replaced with nitrogen twice. The inside of the reactor was a nitrogen atmosphere; then 100 mmol of the compound of the formula (II), 2-bromo-4'-chlorobiphenyl, 200 mmol of the compound of the above formula (III), styrene, ₃ mmol of PdCl ₂ (dppf) and 6 mmol of hexafluorophosphate tetraacetonitrile were added. A composite catalyst composed of copper, 10 mmol of ligand L1 and 200 mmol of diisopropylethanolamine were heated to 60 ° C with stirring, and reacted at this temperature for 12 hours.

After the reaction is completed, deionized water is added to the reaction system, and the mixture is shaken well, washed, and the organic layer is separated, washed again with deionized water, and the organic layer is separated; the organic layer is concentrated under reduced pressure, and the residue is applied to silica gel column. Chromatography, elution with a mixed solvent of n-hexanol and chloroform in a volume ratio of 1:2 as an elution solvent, and the same components were combined by TLC to remove the eluting solvent to obtain the target compound 2-chloro-10-phenyl. Phenanthrene, the yield was 95.3%.

¹ H-NMR (300MHz, CDCl ₃ ) δ: 8.63 (d, J = 8.9 Hz, 1H), 8.49-8.44 (m, 2H), 7.84 (d, J = 2.2 Hz, 1H), 7.71 (d, J) = 8.1 Hz, 1H), 7.63 (s, 1H), 7.52 (dd, J = 8.9, 2.3 Hz, 1H), 7.51 - 7.41 (m, 6H).

Example 2

An appropriate amount of a mixed solvent consisting of PEG-400 and 1-allyl-3-methylimidazolium tetrafluoroborate (1:0.2 by volume) was added to the reactor, followed by replacement with nitrogen twice. The inside of the reactor was a nitrogen atmosphere; then 100 mmol of the compound of formula (II) 2-bromobiphenyl, 300 mmol of the compound of formula (III) 1-methyl-3-vinylbenzene, 3 mmol of PdCl ₂ (dppf) and 9 mmol of hexafluoro were added. A composite catalyst composed of copper tetraacetonitrile phosphate, 15 mmol of ligand L1 and 250 mmol of diisopropylethanolamine were heated to 70 ° C with stirring, and reacted at this temperature for 10 hours.

After the reaction is completed, deionized water is added to the reaction system, and the mixture is shaken well, washed, and the organic layer is separated, washed again with deionized water, and the organic layer is separated; the organic layer is concentrated under reduced pressure, and the residue is applied to silica gel column. Chromatography, elution with a mixed solvent of n-hexanol and chloroform in a volume ratio of 1:3 as an elution solvent, and the same components were combined by TLC to remove the elution solvent to obtain the target compound 9-m-tolylphenanthrene. The rate was 94.7%.

¹ H-NMR (300 MHz, CDCl ₃ ,) δ: 8.72 (dd, J = 8.3, 1.2 Hz, 1H), 8.51 (d, J = 1.6 Hz, 1H), 7.96 (dd, J = 8.3, 1.4 Hz, 1H), 7.83 (d, J = 8.0 Hz, 1H), 7.68-7.61 (m, 2H), 7.52 (ddd, J = 8.2, 6.9, 1.3 Hz, 1H), 7.45-7.31 (m, 4H), 7.27 -7.22 (m, 2H), 2.63 (s, 3H).

Example 3

A suitable solvent consisting of PEG-400 and 1-allyl-3-methylimidazolium tetrafluoroborate (1:0.3 by volume) was added to the reactor, and then replaced with nitrogen twice. The inside of the reactor was a nitrogen atmosphere; then 100 mmol of the compound of the above formula (II) 2-bromobiphenyl, 400 mmol of the compound of the above formula (III) 1-vinylnaphthalene, ₃ mmol of PdCl ₂ (dppf) and 12 mmol of copper hexafluorophosphate tetraacetonitrile were added. The composite catalyst, 20 mmol of ligand L1 and 300 mmol of diisopropylethanolamine were heated to 80 ° C with stirring and reacted at this temperature for 8 hours.

After the reaction is completed, deionized water is added to the reaction system, and the mixture is shaken well, washed, and the organic layer is separated, washed again with deionized water, and the organic layer is separated; the organic layer is concentrated under reduced pressure, and the residue is applied to silica gel column. Chromatography, elution with a mixed solvent of n-hexanol and chloroform in a volume ratio of 1:4 as an elution solvent, and the same component was combined by TLC to remove the eluting solvent to obtain the target compound 9-(naphthalen-1-yl) ) phenanthrene, the yield is 95.7%.

¹ H-NMR (300MHz, CDCl ₃ ) δ: 8.82 (d, J = 8.2 Hz, 2H), 8.61 (s, 1H), 8.02-7.95 (m, 2H), 7.83 (d, J = 8.0 Hz, 1H) ), 7.74 (s, 1H), 7.65-7.31 (m, 9H).

Example 4

An appropriate amount of a mixed solvent consisting of PEG-400 and 1-allyl-3-methylimidazolium tetrafluoroborate (1:0.2 by volume) was added to the reactor, followed by replacement with nitrogen twice. The inside of the reactor was a nitrogen atmosphere; then 100 mmol of the compound of the above formula (II) 2-bromobiphenyl, 300 mmol of the compound of the above formula (III) 2-vinylpyridine, ₂ mmol of PdCl ₂ (dppf) and 6 mmol of copper hexafluorophosphate tetraacetonitrile were added. The composite catalyst, 20 mmol of ligand L1 and 200 mmol of diisopropylethanolamine were heated to 70 ° C with stirring and reacted at this temperature for 12 hours.

After the reaction is completed, deionized water is added to the reaction system, and the mixture is shaken well, washed, and the organic layer is separated, washed again with deionized water, and the organic layer is separated; the organic layer is concentrated under reduced pressure, and the residue is applied to silica gel column. Chromatography, elution with a mixed solvent of n-hexanol and chloroform in a volume ratio of 1:3 as an elution solvent, and the same component was combined by TLC to remove the eluting solvent to obtain the target compound 9-(pyridin-2-yl) Filipino, the yield is 94.9%.

¹ H-NMR (300MHz, CDCl ₃ ) δ: 8.83 (d, J = 4.9 Hz, 1H), 8.76 (dd, J = 8.3, 1.3 Hz, 1H), 8.57-8.51 (m, 1H), 8.07 (dd , J=8.2, 1.4 Hz, 1H), 7.89-7.83 (m, 3H), 7.71-7.62 (m, 2H), 7.58-7.52 (m, 1H), 7.45 (dd, J = 8.1 Hz, 1.6 Hz, 1H), 7.41-7.35 (m, 2H).

Example 5-28: Investigation of Palladium Compounds of Catalysts

Example 5-8: Example 5 was carried out in the same manner as in Example 1-4 except that PdCl ₂ (dppf) was replaced with palladium acetate (Pd(OAc) 2 ), respectively. -8.

Examples 9 to 12: Examples 9 to 12 were carried out in the same manner as in Example 1-4 except that PdCl ₂ (dppf) was replaced with palladium chloride (PdCl ₂ ), respectively.

Examples 13 to 16: Examples were carried out in the same manner as in Example 1-4, except that PdCl ₂ (dppf) therein was replaced with palladium acetylacetonate (Pd(acac) ₂ ), respectively. 13-16.

Examples 17-20: except that PdCl ₂ (dppf) was replaced with (1,5-cyclooctadiene) palladium chloride (PdCl ₂ (cod)), respectively, the other operations were unchanged, and the examples were Examples 17-20 were carried out in the same manner as 1-4.

Examples 21 to 24: Other operations were carried out except that PdCl ₂ (dppf) was replaced with palladium trifluoroacetate (Pd(TFA) ₂ ), and the same was carried out in the same manner as in Example 1-4. Example 21-24.

Examples 25-28: Except that PdCl ₂ (dppf) was replaced with bis(triphenylphosphine)palladium chloride (PdCl ₂ (PPh 3 ) ₂ ), respectively, the other operations were unchanged, and Examples 1-4 Examples 25-28 were carried out in the same manner.

The yield of the obtained product is shown in Table 1 below:

Table 1: Investigation of palladium compound components

It can be seen that when PdCl ₂ (dppf) in the composite catalyst is replaced with other palladium compounds, the yield is greatly reduced, which proves that PdCl ₂ (dppf) can be the most together with copper hexafluorophosphate tetraacetonitrile. Good catalytic effect.

Example 29-40: Investigation of Catalyst Copper Compounds

Examples 29-32: The operation was the same except that copper hexafluorophosphate tetraacetonitrile was replaced with copper triflate (Cu(OTf) ₂ ), respectively, in the same manner as in Example 1-4. Examples 29-32 were implemented.

Examples 33-36: The operation was carried out except that copper hexafluorophosphate tetraacetonitrile was replaced with copper acetylacetonate (Cu(acac) ₂ ), and the same operation as in Example 1-4 was carried out. Example 33-36.

Examples 37 to 40: Examples 37 to 40 were carried out in the same manner as in Example 1-4 except that copper hexafluorophosphate tetraacetonitrile was replaced with copper acetate, respectively.

The yield of the obtained product is shown in Table 2 below:

Table 2: Investigation of copper compound components

It can be seen that when the copper hexafluorophosphate tetraacetonitrile in the composite catalyst is replaced by other copper compounds, the yield is greatly reduced, which proves that copper hexafluorophosphate tetraacetonitrile can be used together with PdCl ₂ (dppf). The best catalytic effect.

Examples 41-52: Investigation of organic ligands

Examples 41-44: Examples 41-44 were carried out in the same manner as in Examples 1-4 except that the organic ligands therein were replaced by L1 to L2, respectively.

Examples 45-48: Examples 45-48 were carried out in the same manner as in Examples 1-4 except that the organic ligands therein were replaced by L1 to L3, respectively.

Examples 49-52: Examples 49-52 were carried out in the same manner as in Examples 1-4 except that the organic ligands therein were replaced by L1 to L4, respectively.

The yield of the obtained product is shown in Table 3 below:

Table 3: Investigation of organic ligands

From this, it can be seen that among all the ligands, L1 has the best reaction effect, and even L2 which is very similar to the L1 structure has a considerable decrease in the yield.

Examples 53-64: Investigation of alkali

Examples 53-64 were carried out in the same manner as in Examples 1-4, except that the base was replaced with diisopropylethanolamine to other bases. The bases used, the corresponding relationships, and the product yields are shown. Table 4 below:

Table 4: Investigation of alkali

From this, it can be seen that when other bases are used, the yield is greatly reduced, and even the diisopropylamine which is very similar to the diisopropylethanolamine used in Examples 1-4 has a markedly lowered yield. .

Examples 65-72: Investigation of Solvents

Examples 65-68: The mixed solvents of Examples 1-4 were replaced with PEG-400, respectively, and the others were unchanged, and Examples 65-68 were obtained.

Examples 69-72: The mixed solvents of Examples 1-4 were replaced with 1-allyl-3-methylimidazolium tetrafluoroborate, respectively, and the others were unchanged, and Examples 69-72 were obtained.

The yield of the obtained product is shown in Table 5 below:

Table 5: Investigation of solvents

From this, it can be seen that when a solvent of a single component is used, the yield is considerably lowered, and the excellent effects of the present invention can be obtained only when the composition of the two is used.

Examples 73-80: Investigation of a single catalyst component

Example 73-76: Examples 1-4, respectively, of the total amount of replacement composite catalyst (dppf), i.e. the amount of PdCl ₂ (dppf) PdCl ₂ in the same amount as the original two components, the embodiment is obtained Examples 73-76.

Examples 77-80: The composite catalysts of Examples 1-4 were replaced with the same amount of copper hexafluorophosphate tetraacetonitrile, that is, the amount of copper hexafluorophosphate tetraacetonitrile was the total amount of the original two components. Examples 77-80.

The yield of the obtained product is shown in Table 6 below:

Table 6: Investigation of single catalyst components

It can be seen that when a single component catalyst is used, the yield is considerably reduced, and only when a mixture of the two is used, a unique synergistic effect is exerted on each other, thereby achieving the excellent catalytic effect of the present invention, which is not obvious. .

In summary, the present invention provides a method for synthesizing a pharmaceutical intermediate phenanthrene compound, in which a high yield is obtained by comprehensive selection and/or synergy of a catalyst, an organic ligand, a base and a solvent. The product, when changed in any one of the components or omitted, resulted in a significant decrease in product yield. It can be seen that the method of the invention has good and wide industrial application potential and can be applied to the field of synthesis of pharmaceutical intermediates.

It is to be understood that the use of these embodiments is merely illustrative of the invention and is not intended to limit the scope of the invention. In addition, it should be understood that various changes, modifications, and/or variations of the invention may be made by those skilled in the art in the appended claims. Within the limits of protection defined.

Claims

A method for synthesizing a phenanthrene compound represented by the following formula (I) in a potassium hydroxide environment,

The method comprises: reacting a compound of the following formula (II) with a compound of the formula (III) in a solvent in the presence of a catalyst, an organic ligand and a base in an inert atmosphere to obtain a compound of the formula (I);

Wherein R 1 and R 2 are each independently H, C 1 -C 6 alkyl, C 1 -C 6 alkoxy or halogen;

R3 is C 6 -C 10 aryl or C 5 -C 8 heteroaryl, the C 6 -C 10 aryl or C 4 -C 8 heteroaryl optionally substituted by 1-3 substituents, a substituent is a C 1 -C 6 alkyl group or a halogen;

The catalyst is a mixture of an organic palladium compound and an organic copper compound in a molar ratio of 1:2-4, wherein the organic palladium compound is PdCl 2 (dppf), and the organic copper compound is hexafluorophosphate Acetonitrile copper;

The organic ligand is one of the following L1-L4:

The base is potassium hydroxide;

The solvent is a mixture of PEG-400 and 1-allyl-3-methylimidazolium tetrafluoroborate in a volume ratio of 1:0.1-0.3.
The method of synthesizing the phenanthrene compound according to claim 1, wherein the organic ligand is L1.
The method of synthesizing the phenanthrene compound according to claim 1, wherein the molar ratio of the compound of the formula (II) to the compound of the formula (III) is 1:2-4.
The method of synthesizing the phenanthrene compound according to claim 1, wherein the molar ratio of the compound of the formula (II) to the catalyst is from 1:0.08 to 0.15.
The method of synthesizing the phenanthrene compound according to claim 1, wherein the molar ratio of the compound of the formula (II) to the organic ligand is from 1:0.1 to 0.2.
The method of synthesizing the phenanthrene compound according to claim 1, wherein the molar ratio of the compound of the formula (II) to the base is 1:2-3.
The method of synthesizing the phenanthrene compound according to claim 1, wherein the reaction temperature is 60 to 80 ° C; and the reaction time is 8 to 12 hours.
The method of synthesizing the phenanthrene compound according to claim 2, wherein the molar ratio of the compound of the formula (II) to the compound of the formula (III) is 1:2-4.
The method of synthesizing the phenanthrene compound according to claim 2, wherein the molar ratio of the compound of the formula (II) to the catalyst is from 1:0.08 to 0.15.
The method of synthesizing the phenanthrene compound according to claim 2, wherein the molar ratio of the compound of the formula (II) to the organic ligand is from 1:0.1 to 0.2.
The method of synthesizing the phenanthrene compound according to claim 2, wherein the molar ratio of the compound of the formula (II) to the base is 1:2-3.
The method of synthesizing the phenanthrene compound according to claim 2, wherein the reaction temperature is 60 to 80 ° C; and the reaction time is 8 to 12 hours.
A method for synthesizing a phenanthrene compound represented by the following formula (I) in a potassium hydroxide environment,

The method comprises: reacting a compound of the following formula (II) with a compound of the formula (III) in a solvent in the presence of a catalyst, an organic ligand and a base in an inert atmosphere to obtain a compound of the formula (I);

Wherein R 1 and R 2 are each independently H, C 1 -C 6 alkyl, C 1 -C 6 alkoxy or halogen;

R3 is C 6 -C 10 aryl or C 5 -C 8 heteroaryl, the C 6 -C 10 aryl or C 4 -C 8 heteroaryl optionally substituted by 1-3 substituents, a substituent is a C 1 -C 6 alkyl group or a halogen;

The catalyst is a mixture of an organic palladium compound and an organic copper compound in a molar ratio of 1:2-4, wherein the organic palladium compound is PdCl 2 (dppf), and the organic copper compound is hexafluorophosphate Acetonitrile copper;

The organic ligand is one of the following L1-L4:

The base is potassium hydroxide;

The solvent is a mixture of PEG-400 and 1-allyl-3-methylimidazolium tetrafluoroborate, the volume ratio of which is 1:0.1-0.3, the compound of the formula (II) and the formula (III) The molar ratio of the compounds is 1:2-4.
A method for synthesizing a phenanthrene compound represented by the following formula (I) in a potassium hydroxide environment,

The method comprises: reacting a compound of the following formula (II) with a compound of the formula (III) in a solvent in the presence of a catalyst, an organic ligand and a base in an inert atmosphere to obtain a compound of the formula (I);

Wherein R 1 and R 2 are each independently H, C 1 -C 6 alkyl, C 1 -C 6 alkoxy or halogen;

R3 is C 6 -C 10 aryl or C 5 -C 8 heteroaryl, the C 6 -C 10 aryl or C 4 -C 8 heteroaryl optionally substituted by 1-3 substituents, a substituent is a C 1 -C 6 alkyl group or a halogen;

The catalyst is a mixture of an organic palladium compound and an organic copper compound in a molar ratio of 1:2-4, wherein the organic palladium compound is PdCl 2 (dppf), and the organic copper compound is hexafluorophosphate Acetonitrile copper;

The organic ligand is one of the following L1-L4:

The base is potassium hydroxide;

The solvent is a mixture of PEG-400 and 1-allyl-3-methylimidazolium tetrafluoroborate in a volume ratio of 1:0.1-0.3, and the molar ratio of the compound of the formula (II) to the catalyst It is 1:0.08-0.15.