CN104529895B - Synthetic method of replacing nitrogen-containing heterocyclic compound - Google Patents

Abstract

The invention relates to a synthetic method of a nitrogen-containing heterocyclic compound. The method comprises the following step: in a solvent, reacting an aryl carbonyl compound with aryl trifluoroborate in the presence of a palladium catalyst, a nitrogen-containing ligand and an accelerator to further prepare the nitrogen-containing heterocyclic compound. The method is simple in reaction, simple and convenient to operate and high in yield, is a totally new synthetic method of a nitrogen-containing heterocyclic compound, provides a new synthetic route for preparation of the type of compound and has good scientific research value and industrialization potency.

Description

A kind of synthetic method of substituting nitrogen-containing heterocyclic compound

technical field

The invention relates to a synthesis method of a heteroatom-containing condensed ring compound, in particular to a synthesis method of a nitrogen-containing heterocyclic compound with an isoquinoline skeleton, and belongs to the field of organic chemical synthesis.

Background technique

In many specific application areas involving organic chemistry, especially in the field of medicinal chemistry, nitrogen-containing heterocyclic compounds are widely used as pharmaceutical intermediates, or the final active pharmaceutical compounds often contain nitrogen-containing heterocyclic rings, which are Because nitrogen-containing heterocyclic compounds have potential biological activity and medicinal value, they have attracted extensive attention.

In a wide variety of nitrogen-containing heterocyclic compounds, the isoquinoline skeleton plays an important role and status, and is an important precursor, fragment and/or intermediate for the synthesis of various drugs, for example, it is an important component of antibacterial drugs, By introducing an isoquinoline skeleton, the resulting drug usually has many advantages such as antibacterial, antiviral, antitumor, and antidepressant.

For isoquinoline compounds and their synthesis, scientific researchers have synthesized a variety of new isoquinoline compounds and their preparation methods, thus providing basic raw materials for the synthesis of final pharmaceutical compounds. For example, the following isoquinoline compounds in the prior art Quinoline compound and/or its synthetic method:

A kind of synthetic method of 7-bromoisoquinoline is disclosed in CN102875465A, and 7-bromoisoquinoline is obtained through a multi-step reaction in a non-aqueous solvent through the diazotization bromine method, and the specific reaction process is as follows:

CN102627604A discloses two types of isoquinoline derivatives and their application as anticancer drugs. After research, it is found that they have significant inhibitory and killing activities on human cancer cells. The structural formulas of the two types of isoquinoline compounds are as follows:

WO2012086727A discloses an isoquinoline-6-sulfonamide derivative, which can be used to treat glaucoma, ocular hypertension and circulatory system diseases. The structure of the derivative is as follows:

The derivative can be obtained through multiple synthetic routes and up to at least 4 steps of reaction.

WO2012026529A discloses a new synthesis method of isoquinoline derivatives, comprising reacting a compound of formula III with a compound of formula II in the presence of at least one of a nitrile solvent, an amide solvent, a sulfoxide solvent and a urea solvent and a base The compound of formula I is obtained:

WO2011162274A discloses an isoquinoline derivative, which can be used as a CRTH2 inhibitor, with the following structural formula:

The compound is obtained through at least five steps of reaction, and the reaction process is cumbersome and the reagents are expensive.

WO2010027889A discloses a method for substituting isoquinoline compounds of formula I, the method comprising:

In the presence of methanol and hypervalent iodine oxidant, the compound of formula A is treated with anhydrous acid, and then the resulting product is treated with a chlorinating agent to obtain the compound of formula I, wherein the structural formula of the compound of formula I and A is as follows:

CN101544636A discloses a pharmaceutically active polyhalogenated isoquinoline derivative of formula I and its synthesis method. The derivative is obtained by grinding and heating II and III under solvent-free conditions, and then adding a catalyst to continue the reaction:

As mentioned above, although various methods for preparing isoquinoline compounds have been disclosed in the prior art, these methods either have a large number of reaction steps, or have low product yields, or use expensive reagents, which still cannot meet the current requirements for isoquinoline compounds. The large-scale and simple requirements of the preparation method of nitrogen-containing heterocyclic compounds with morphine skeleton. Therefore, the exploration of the preparation method of nitrogen-containing heterocyclic compounds containing isoquinoline skeleton is still an important development direction and focus of attention in this field.

Contents of the invention

In view of this, in order to solve many defects in the above-mentioned prior art, such as low yield, cumbersome process, expensive and rare reagents, etc., the inventors have carried out a chemical synthesis method for nitrogen-containing heterocyclic compounds containing isoquinoline skeletons. In-depth research, after paying a lot of creative work, thus completed the present invention.

Here, the applicant intends to explain that the technical solution of the present invention was completed under the support of the Zhejiang Provincial Natural Science Foundation (No.: LY14B020009), for which he would like to express his gratitude.

The invention relates to a synthesis method of a nitrogen-containing heterocyclic compound, the method comprising, in a solvent, in the presence of a palladium catalyst, a nitrogen-containing ligand and a promoter, making an aryl carbonyl compound react with an aryl trifluoroborate One-step reaction to obtain isoquinoline compounds.

Specifically, the present invention provides a kind of synthetic method of nitrogen-containing heterocyclic compound shown in formula (I),

The methods include:

In the presence of palladium catalyst, nitrogen-containing ligand and promotor, formula (II) compound reacts with formula (III) compound in reaction solvent, generates the nitrogen-containing heterocyclic compound of formula (I),

Wherein: R ₁ is selected from H, halogen, nitro, C ₁ -C ₆ alkyl, C ₁ -C ₆ alkoxy, halogenated C ₁ -C ₆ alkyl, halogenated C ₁ -C ₆ alkoxy or phenyl;

R ₂ is selected from H, halogen or C ₁ -C ₆ alkyl;

M is an alkali metal element;

Ar ₁ and Ar ₂ are each independently phenyl, phenyl with 1-5 substituents, naphthyl or naphthyl with 1-5 substituents;

The substituent is halogen, C ₁ -C ₆ alkyl, C ₁ -C ₆ alkoxy, halogenated C ₁ -C ₆ alkyl, halogenated C ₁ -C ₆ alkoxy or phenyl.

In the synthesis method of the present invention, the palladium catalyst is an organic palladium or an inorganic palladium compound. For example, palladium acetylacetonate (Pd(acac) ₂ ), palladium acetate, palladium trifluoroacetate, palladium chloride, Na ₂ PdCl ₄ , Pd(NH ₃ ) ₄ Cl ₂ , Pd(PPh ₃ ) ₄ , PdCl ₂ ( dppf), dppePdCl ₂ , Na ₂ PdCl ₂ , PdCl ₂ (CH ₃ CN) ₂ , PdCl ₂ (PPh ₃ ) ₂ , Pd(NH ₃ ) ₄ Cl ₂ , PdCl ₂ (cod) mixture of species.

Preferably, the palladium catalyst is selected from any one or a mixture of palladium acetylacetonate (Pd(acac) ₂ ), palladium acetate, palladium trifluoroacetate, palladium chloride, most preferably palladium acetylacetonate (Pd (acac) ₂ ).

In the synthesis method of the present invention, the nitrogen-containing ligand is L1 or L2:

Wherein, X ₁ -X ₈ are each independently selected from H or C ₁ -C ₆ alkyl, and Y ₁ -Y ₄ are each independently selected from H, C ₁ -C ₆ alkyl or phenyl.

The nitrogen-containing ligand is preferably any one of the following formulas L-1 to L-4:

The nitrogen-containing ligand is most preferably L-1, that is, 2,2'-bipyridine (hereinafter sometimes abbreviated as "bpy").

In the method of the present invention, the meaning of C ₁ -C ₆ alkyl refers to a straight chain or branched chain alkyl group with 1-6 carbon atoms, non-limiting examples may be methyl, ethyl, n- Propyl, isopropyl, n-butyl, sec-butyl, isobutyl, tert-butyl, n-pentyl, isopentyl or n-hexyl, etc.

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

In the method of the present invention, unless otherwise specified, the halogen or the halogen in the halogeno group can be, for example, F, Cl, Br or I.

In the synthesis method of the present invention, M is an alkali metal element, such as Li, Na or K.

In the method of the present invention, Ar ₁ or Ar ₂ are each independently phenyl, phenyl with 1-5 substituents, naphthyl or naphthyl with 1-5 substituents, wherein The phenyl or naphthyl group may be substituted by 1-5 substituents (the substituents are as defined above), for example, 1, 2, 3, 4 or 5 substituents.

In the synthetic method of the present invention, the accelerator is trifluoroacetic acid (TFA), the compound of the following formula (IV) or the monohydrate of the compound of formula (IV):

Wherein R is H, nitro or C ₁ -C ₆ alkyl.

The accelerator is preferably a compound of formula (IV) or a monohydrate of a compound of formula (IV), more preferably a monohydrate of a compound of formula (IV), more preferably p-toluenesulfonic acid or p-toluenesulfonic acid monohydrate compounds, most preferably p-toluenesulfonic acid monohydrate.

In the synthesis method of the present invention, the reaction solvent is water, benzene, toluene, xylene, chlorobenzene, 1,4-dioxane, 1,6-dioxane, tetrahydrofuran (THF), 2-methyltetrahydrofuran, N,N-dimethylformamide (DMF), dimethylsulfoxide (DMSO), dichloromethane, chloroform, carbon tetrachloride, dichloroethane, n-hexane, ether , methanol, ethanol, n-propanol, isopropanol, butanol, pentanol, hexanol, etc., most preferably water. The amount of reaction solvent used is not particularly limited, and can be selected according to common knowledge in the field of organic synthesis, such as selecting an amount that allows the reaction to proceed smoothly and is easy to control, or an amount that is convenient for post-treatment.

In the synthesis method of the present invention, the molar ratio of the compound of formula (II) to the compound of (III) is 1:1-3, and this range includes any subrange range therein, and also includes any specific Point value, for example, can be 1:1, 1:1.2, 1:1.4, 1:1.6, 1:1.8, 1:2, 1:2.2, 1:2.4, 1:2.6, 1:2.8 or 1 :3.

In the synthesis method of the present invention, the molar dosage of the palladium catalyst is 2-10% of the molar dosage of the compound of formula (II), such as 2%, 3%, 4%, 5%, 6%, 7% %, 8%, 9% or 10%.

In the synthesis method of the present invention, the molar ratio of the palladium catalyst to the nitrogen-containing ligand is 1:2-3, such as 1:1.2, 1:1.5, 1:1.7, 1:1.9, 1:2, 1:2.2, 1:2.4, 1:2.6, 1:2.8, or 1:3.

In the synthesis method of the present invention, the molar ratio of the formula (II) to the accelerator is 1:5-15, such as 1:5, 1:7, 1:9, 1:10, 1:12, 1:14, or 1:15.

In the synthesis method of the present invention, the reaction temperature is 60-140°C, non-limitingly, for example, 60°C, 70°C, 80°C, 90°C, 100°C, 110°C, 120°C, 130°C or 140°C ℃.

In the synthetic method of the present invention, the reaction time is not particularly limited, for example, the residual percentage of the target product or raw material can be detected by liquid chromatography to determine the appropriate reaction time, which is usually 15-30 hours, non-limiting For example, 15 hours, 17 hours, 19 hours, 21 hours, 23 hours, 25 hours, 27 hours, 29 hours or 30 hours.

In the synthesis method of the present invention, the post-treatment after the reaction can be as follows: after the reaction, the mixture is poured into ethyl acetate, washed with saturated _NaHCO3 aqueous solution and brine in sequence, and washed with acetic acid in the water layer. After extraction with ethyl ester, the organic layers were combined (i.e., the washed organic layer and the extracted organic layer _were combined), dried with anhydrous _Na2SO4 , the solvent was evaporated under negative pressure, and the residue was passed through flash column chromatography (n-hexane/acetic acid ethyl ester, the volume ratio of the two is 1:1-3) to obtain the target product.

In the synthesis method of the present invention, as an exemplary example, Ar ₁ is phenyl, 3-tolyl, p-chlorophenyl or naphthalene-2-yl.

In the synthesis method of the present invention, as an exemplary example, Ar ₂ is phenyl, 3-tolyl, p-chlorophenyl or naphthalene-2-yl.

In the synthesis method of the present invention, as an exemplary example, R ₂ is H or ethyl.

Compared with the prior art, the present invention selects compounds of formula (II) and (III) as reaction substrates, uses a palladium compound as a catalyst, and obtains a nitrogen-containing heterocycle through the synergistic effect of a specific nitrogen-containing ligand accelerator. compound. The method has the advantages of simple reaction, convenient operation and high yield, is a brand-new synthesis method of nitrogen-containing heterocyclic compounds, and provides a new synthetic route for the preparation of nitrogen-containing heterocyclic compounds.

detailed description

The present invention will be described in detail below through specific examples, but the use and purpose of these exemplary embodiments are only used to exemplify the present invention, and do not constitute any form of any limitation to the actual protection scope of the present invention, nor will the present invention The scope of protection is limited to this.

Wherein the following groups refer to the following meanings:

Me: methyl; Ph: phenyl.

Embodiment 1: the synthesis of 1,3-two m-tolylisoquinolines

Add 100ml of water, 20mmol of formula (II) compound (wherein Ar ₁ is 3-tolyl), 20mmol of formula (III) compound, 0.4mmol of palladium acetylacetonate, 0.8mmol of nitrogen-containing ligand L-1 and 100mmol of para Toluenesulfonic acid monohydrate was reacted at 60°C for 25 hours with stirring. After the reaction was finished, the mixture was poured into ethyl acetate, washed with saturated _NaHCO3 aqueous solution and brine successively, and after the aqueous layer was extracted with ethyl acetate, the organic layer was combined (that is, the organic layer after washing and the organic layer obtained by extraction were combined). layer), dried over anhydrous Na ₂ SO ₄ , evaporated under negative pressure to remove the solvent, and the residue was purified by flash column chromatography (n-hexane/ethyl acetate, the volume ratio of the two was 1:1) to obtain the target product as a liquid. Yield 71.9%, purity 98.7% (HPLC).

NMR: ¹ HNMR (500MHz, CDCl ₃ ) δ8.11(d, J=10Hz, 1H), 8.05(d, J=10Hz, 2H), 7.98(d, J=10Hz, 1H), 7.93(d, J=5Hz,1H),7.68(dd,J=10Hz,1H),7.62(s,1H),7.58(d,J=10Hz,1H),7.43-7.52(m,2H)7.39(dd,J= 5Hz, 1H), 7.33(d, J=10Hz, 1H), 7.22(d, J=10Hz, 1H), 2.49(s, 3H), 2.46(s, 3H).

Embodiment 2: the synthesis of 1,3-two p-chlorophenylisoquinolines

Add 100ml of water, 20mmol of formula (II) compound (wherein Ar ₁ is p-chlorophenyl), 40mmol of formula (III) compound, 1mmol of palladium acetylacetonate, 2.5mmol of nitrogen-containing ligand L-1 and 300mmol of p-toluene in the reaction vessel Sulfonic acid monohydrate was reacted at 80°C for 15 hours with stirring. After the reaction was finished, the mixture was poured into ethyl acetate, washed with saturated _NaHCO3 aqueous solution and brine successively, and after the aqueous layer was extracted with ethyl acetate, the organic layer was combined (that is, the organic layer after washing and the organic layer obtained by extraction were combined). layer), dried over anhydrous Na ₂ SO ₄ , evaporated to remove the solvent under negative pressure, and the residue was purified by flash column chromatography (n-hexane/ethyl acetate, the volume ratio of the two was 1:2) to obtain the target product as a solid. Yield 92.4%, purity 98.7% (HPLC).

Melting point: 150-151°C;

NMR: ¹ HNMR (500MHz, CDCl ₃ ) δ8.06-8.15 (m, 4H), 7.94 (d, J = 10Hz, 1H), 7.69-7.75 (m, 3H), 7.53-7.56 (m, 3H) , 7.46 (d, J=10Hz, 2H).

Embodiment 3: Synthesis of 1,3-binaphth-2-ylisoquinoline

Add 100ml water, 20mmol formula (II) compound (wherein Ar ₁ is naphthalene-2-yl), 30mmol formula (III) compound, 1.5mmol palladium acetylacetonate, 3.5mmol nitrogen-containing ligand L-1 and 150mmol P-toluenesulfonic acid monohydrate was reacted at 120°C for 20 hours while stirring. After the reaction was finished, the mixture was poured into ethyl acetate, washed with saturated _NaHCO3 aqueous solution and brine successively, and after the aqueous layer was extracted with ethyl acetate, the organic layer was combined (that is, the organic layer after washing and the organic layer obtained by extraction were combined). layer), dried over anhydrous Na ₂ SO ₄ , evaporated to remove the solvent under negative pressure, and the residue was purified by flash column chromatography (n-hexane/ethyl acetate, the volume ratio of the two was 1:1) to obtain the target product as a solid. Yield 62.7%, purity 98.2% (HPLC).

Melting point: 119-121°C;

NMR: ¹ HNMR (500MHz, CDCl ₃ ) δ8.76 (s, 1H), 8.19-8.38 (m, 4H), 7.87-8.07 (m, 8H), 7.69-7.72 (m, 1H), 7.49-7.59 (m,5H).

Embodiment 4: Synthesis of 7-bromo-1,3-diphenylisoquinoline

Add 100ml of water, 20mmol of formula (II) compound (wherein Ar is phenyl), 40mmol _of formula (III) compound, 0.8mmol of palladium acetylacetonate, 1.8mmol of nitrogen-containing ligand L-1 and 200mmol of p-toluenesulfonate in the reaction vessel Acid monohydrate, reacted at 90°C for 20 hours with stirring. After the reaction was finished, the mixture was poured into ethyl acetate, washed with saturated _NaHCO3 aqueous solution and brine successively, and after the aqueous layer was extracted with ethyl acetate, the organic layer was combined (that is, the organic layer after washing and the organic layer obtained by extraction were combined). layer), dried over anhydrous Na ₂ SO ₄ , evaporated to remove the solvent under negative pressure, and the residue was purified by flash column chromatography (n-hexane/ethyl acetate, the volume ratio of the two was 1:2) to obtain the target product as a solid. Yield 65.2%, purity 98.6% (HPLC).

Melting point: 136-137°C;

Nuclear Magnetic Resonance: ¹ HNMR (500MHz, CDCl ₃ ) δ8.18-8.26 (m, 3H), 8.01 (s, 1H), 7.71-7.79 (m, 4H), 7.47-7.58 (m, 5H), 7.39-7.42 (m,1H).

Embodiment 5: the synthesis of 4-ethyl-1,3-diphenylisoquinoline

Add 100ml of water, 20mmol of formula (II) compound (wherein Ar is phenyl), 45mmol _of formula (III) compound, 1mmol of palladium acetylacetonate, 2.5mmol of nitrogen-containing ligand L-1 and 150mmol of p-toluenesulfonic acid in the reaction vessel Monohydrate, reacted at 100°C for 20 hours with stirring. After the reaction was finished, the mixture was poured into ethyl acetate, washed with saturated _NaHCO3 aqueous solution and brine successively, and after the aqueous layer was extracted with ethyl acetate, the organic layer was combined (that is, the organic layer after washing and the organic layer obtained by extraction were combined). layer), dried over anhydrous Na ₂ SO ₄ , evaporated under negative pressure to remove the solvent, and the residue was purified by flash column chromatography (n-hexane/ethyl acetate, the volume ratio of the two was 1:3) to obtain the target product as a solid. Yield 67.9%, purity 98.9% (HPLC).

Melting point: 121-123°C;

NMR: ¹ HNMR (500MHz, CDCl ₃ ) δ8.12-8.16 (m, 2H), 7.70-7.76 (m, 3H), 7.58-7.59 (m, 2H), 7.43-7.54 (m, 6H), 7.37 -7.40 (m, 1H), 3.10 (q, J=5.0Hz, 2H), 1.35 (t, J=5.0Hz, 3H).

As can be seen from the above-mentioned Examples 1-5, when using the complex system constructed by the reaction substrate, catalyst, ligand and promoter of the present invention, various types of arylcarbonyl can be produced with higher yield and high purity Compound and phenyl borate to obtain the corresponding nitrogen-containing heterocyclic compound with isoquinoline skeleton.

Example 6-11

Except that the catalyst palladium acetylacetonate is all replaced by the following palladium compounds, in the same manner as in Examples 1-5, Embodiments 6-11 are respectively implemented, and the corresponding relationship of its embodiments and the production of corresponding nitrogen-containing heterocyclic compounds The rates are shown in the table below.

As can be seen from the table above, when palladium acetate, palladium trifluoroacetate and palladium chloride are used, the yields of corresponding products are significantly reduced, which proves that palladium acetylacetonate has the best catalytic properties and unique catalytic properties oneness.

Examples 12-21

Except that the catalyst palladium acetylacetonate is all replaced by the following palladium compound, in the same manner as in Example 1-5, Examples 12-21 are respectively implemented, the corresponding relationship of its examples and the corresponding diarylisoquinoline compound The yields are shown in the table below.

Note: "--" means no reaction.

As can be seen from the above table, when other palladium compounds are used, almost no reaction occurs.

Examples 22-33

Except that the solvent water therein is replaced by the solvent in the following table, in the same manner as in Example 1-5, Examples 22-33 are respectively implemented, and the corresponding relationship of the examples and the corresponding diarylisoquinoline compound The yields are shown in the table below.

As can be seen from the above table, when other organic solvents are used, the reaction can also be carried out, but the yield is significantly reduced, thus proving that in this organic reaction, with respect to the organic solvent, the water that is the non-organic solvent is instead Has the best solvent effect.

Examples 34-44

In addition to replacing the ligand L-1 with the following ligands, in the same manner as in Examples 1-5, Examples 34-44 were respectively implemented, and the corresponding relationship of the examples and the corresponding diarylisoquinoline compound The yields are shown in the table below.

Except that when the ligand was changed to the following ligand, the embodiments 40-44 were respectively implemented in the same manner as in Examples 1-5:

The yields of the corresponding nitrogen-containing heterocyclic compounds were found to be 24.9-37.5%.

It can be seen that the ligands of the present invention have a significant impact on the smooth progress of the reaction and the high yield of the product. Among them, 2,2'-bipyridine has the best synergistic effect, even if it has the same parent structure as 4 , neither 4'-dimethylbipyridine nor 5,5'-dimethylbipyridine can achieve the same reaction effect.

Examples 45-49

Except that the p-toluenesulfonic acid monohydrate wherein is replaced by the following promoters, in the same manner as in Examples 1-5, Examples 45-49 were respectively implemented, and the corresponding relationship of the examples and the corresponding nitrogen-containing heterocyclic compound The yields are shown in the table below.

Examples 50-54

Except that no accelerator was used, Examples 50-54 were respectively implemented in the same manner as Examples 1-5, and the corresponding relations of the examples and the yields of the corresponding nitrogen-containing heterocyclic compounds are shown in the following table.

Note: "--" means not included.

As can be seen from Examples 45-54, the promotor has a significant impact on the productive rate of the product, wherein p-toluenesulfonic acid monohydrate has the best promoting system effect, even if p-toluenesulfonic acid is adopted, its productive rate is also significantly lower than p-Toluenesulfonic acid monohydrate. And when no accelerator is used, the product yield is greatly reduced, and even the necessity of research is no longer necessary and the potential of industrialization is lost

In summary, it can be clearly seen from all the above examples that when the method of the present invention is adopted, a palladium catalyst selected from palladium (especially palladium acetylacetonate), a nitrogen-containing ligand selected from L-1 to L-4 body (especially L-1), and a suitable solvent (especially water) and a suitable promoter (especially p-toluenesulfonic acid monohydrate) composite reaction system, can be obtained with high yield and high purity The nitrogen-containing heterocyclic compound with quinoline skeleton is a new synthetic method with great industrial application prospects, and provides a new synthetic route for the efficient and rapid synthesis of nitrogen-containing heterocyclic compounds.

It should be understood that these examples are only used to illustrate the present invention and are not intended to limit the protection scope of the present invention. In addition, it should also be understood that after reading the technical content of the present invention, those skilled in the art can make various changes, modifications and/or variations to the present invention, and all these equivalent forms also fall within the appended claims of the present application. within the defined scope of protection.

Claims (7)

1. a synthetic method of nitrogen-containing heterocyclic compound shown in formula (I), The methods include: In the presence of palladium catalyst, nitrogen-containing ligand and promotor, formula (II) compound reacts with formula (III) compound in reaction solvent, generates the nitrogen-containing heterocyclic compound of formula (I), Wherein: R ₁ is selected from H, halogen, nitro, C ₁ -C ₆ alkyl, C ₁ -C ₆ alkoxy, halogenated C ₁ -C ₆ alkyl, halogenated C ₁ -C ₆ alkoxy or phenyl; R ₂ is selected from H, halogen or C ₁ -C ₆ alkyl; M is an alkali metal element; Ar ₁ and Ar ₂ are each independently phenyl, phenyl with 1-5 substituents, naphthyl or naphthyl with 1-5 substituents; The substituent is halogen, C ₁ -C ₆ alkyl, C ₁ -C ₆ alkoxy, halogenated C ₁ -C ₆ alkyl, halogenated C ₁ -C ₆ alkoxy or phenyl; The palladium catalyst is palladium acetylacetonate; The nitrogen-containing ligand is the following formula L-1: The accelerator is p-toluenesulfonic acid or p-toluenesulfonic acid monohydrate; The reaction solvent is water. 2. synthetic method as claimed in claim 1, is characterized in that: described promotor is p-toluenesulfonic acid monohydrate. 3. the synthetic method as claimed in claim 1, is characterized in that: the mol ratio of described formula (II) compound and formula (III) compound is 1:1-3. 4. The synthetic method according to claim 1, characterized in that: the molar amount of the palladium catalyst is 2-10% of the molar amount of the compound of formula (II). 5. The synthetic method according to claim 1, characterized in that: the mol ratio of the palladium catalyst to the nitrogen-containing ligand is 1:2-3. 6. The synthetic method according to any one of claims 1-5, characterized in that: the mol ratio of the formula (II) to the accelerator is 1:5-15. 7. The synthesis method according to claim 6, characterized in that: the reaction temperature is 60-140° C.; the reaction time is 15-30 hours.