1. A biaryl compound is characterized in that the chemical structural formula of the compound is shown as the following formula (I):

in the formula (I), R¹Is any one of methoxyl, methyl, trifluoromethyl, dimethylamino, trifluoromethoxy, cyano, ester group, halogen, 1, 3-dioxolan-2-yl and dimethyl tert-butyl siloxy;

R²is methyl or methoxyAny one of a group, benzyloxy group, methylthio group, cyano group, ester group, dimethylamino group, halogen, dimethyl tert-butylsiloxy group, 2-methyl-1, 3-dioxolan-2-yl group, and heterocycle;

x is nitrogen atom or hydrocarbon.

2. The biaryl compound of claim 1 wherein said halogen is fluorine or chlorine; the heterocyclic ring is not furan or benzofuran.

3. A preparation method of biaryl compounds is characterized by comprising the following steps:

(1) adding a mixture consisting of magnesium chips and lithium chloride into a schlenk sealed tube, reacting for 2-4 min under the conditions of reduced pressure and 310-330 ℃, and cooling to room temperature to obtain a reactant 1; wherein the molar ratio of the magnesium chips to the lithium chloride is 3 mmol: 1.8-2.2 mmol;

(2) adding ultra-dry tetrahydrofuran into the sealed tube, pumping nitrogen out of the sealed tube for three times, respectively adding aryl quaternary ammonium salt, 5 mol% of catalyst, aryl bromide and N, N, N ', N' -tetramethyl ethylenediamine into the sealed tube, stirring and reacting for 6-12 hours at 25-60 ℃, and quenching by using a saturated ammonium chloride solution to obtain a reactant 2; wherein the molar volume ratio of the ultra-dry tetrahydrofuran, the aryl quaternary ammonium salt, the catalyst, the aryl bromide and the N, N, N ', N' -tetramethyl ethylenediamine is 2-4 mL: 1 mmol: 0.05 mmol: 1-3 mmol: 2mmol of the active carbon;

(3) and (3) sequentially extracting, washing, drying, removing extract liquor and purifying the reactant 2 to obtain the biaryl compound.

4. The method for producing a biaryl compound according to claim 3, wherein in step (2), the aryl quaternary ammonium salt is phenyltrimethyl quaternary ammonium iodide, 4-methylphenyltrimethyl quaternary ammonium iodide, 3-methylphenyltrimethyl quaternary ammonium iodide, 2-methylphenyltrimethyl quaternary ammonium iodide, 4-trifluoromethylphenyltrimethyl quaternary ammonium iodide, 4-trifluoromethoxyphenyltrimethyl quaternary ammonium iodide, 4-cyanophenyltrimethyl quaternary ammonium iodide, 4-ethoxycarbonylphenyltrimethyl quaternary ammonium iodide, 4-fluorophenyltrimethyl quaternary ammonium iodide, 4-chlorophenyltrimethyl quaternary ammonium iodide, 4-methoxyphenyltrimethyl quaternary ammonium iodide, 4-dimethylaminophenyltrimethyl quaternary ammonium iodide, 4-chlorophenyltrimethyl quaternary ammonium iodide, or the like, 4- (1, 3-dioxolan-2-yl) phenyl trimethyl quaternary ammonium salt iodide, 4-dimethyl tert-butyl siloxy phenyl trimethyl quaternary ammonium salt iodide and 3-pyridyl trimethyl quaternary ammonium salt iodide.

5. The method for preparing biaryl according to claim 3, wherein in step (2), the aryl bromide is any one or more of bromobenzene, 4-methylbromobenzene, 4-methoxybromobenzene, 3-methoxybromobenzene, 2-methoxybromobenzene, 4-benzyloxybromobenzene, 4-methylthiobromobenzene, 4-cyanoborobenzene, 4-ethoxycarbonylbromobenzene, 4-dimethylaminobromobenzene, 4-fluorobromobenzene, 4-chlorobromobenzene, 4-dimethyl-tert-butylsiloxy bromobenzene, 4- (2-methyl-1, 3-dioxacyclopent-2-yl) bromobenzene, 2-bromodibenzofuran, and 5-bromobenzofuran.

6. The method of producing a biaryl compound according to claim 3, wherein in the step (2), the catalyst is any one of bis (triphenylphosphine) palladium dichloride, iron trichloride, bis (triphenylphosphine) cobalt dichloride, and bis (triphenylphosphine) nickel dichloride.

7. The method of producing a biaryl compound according to claim 6, wherein in the step (2), the catalyst is bis triphenylphosphine palladium dichloride.

8. The method for producing a biaryl compound according to claim 3, wherein in the step (2), the reaction is carried out at 25 ℃ for 12 hours with stirring; the molar ratio of the aryl quaternary ammonium salt to the aryl bromide is 1: 2.

9. The process for producing a biaryl compound according to claim 3, wherein in the step (3), the reaction product 2 is extracted with ethyl acetate, the extract is washed with saturated brine and dried over anhydrous sodium sulfate, the extract is removed by rotary evaporation, and the crude product is purified by silica gel column chromatography to obtain the biaryl compound.

10. Use of the biaryl compound of claim 1 or 2 in the preparation of a compound containing a biaryl structure.

Background

Biaryl compounds are one of the most important parts of chemicals and have specific roles in the chemical and pharmaceutical industries. Recently, molecules containing biaryl-based structures have been increasingly used in the fields of pharmaceuticals, agrochemicals, polymers and materials. Therefore, it is necessary to develop a more economical and efficient preparation method for constructing biaryl compounds.

The preparation of quaternary ammonium salts is simple and requires only the extensive presence of amines with alkyl electrophiles, such as: and (3) methyl iodide or methyl trifluoromethanesulfonate. In recent years, quaternary ammonium salt as a multifunctional reagent is proved to be capable of effectively participating in various organic conversion processes, and preparation of various important organic molecules and organic building blocks is realized. The cross-coupling of electrophilic quaternary aryl ammonium salts with nucleophilic coupling substrates, including aryl magnesium, aryl lithium, aryl aluminum, aryl zinc, aryl tin, and aryl boronic acid reagents, under transition metal catalysis has been well studied.

However, the nucleophilic organometallic reagent used in the synthesis of diaryl compounds using aryl quaternary ammonium salts is prepared in advance, and most of them are sensitive to air or water vapor. Therefore, the direct cross coupling of the aryl quaternary ammonium salt and the aryl halide is realized, a brand-new method for preparing the biaryl compound is developed, and the improvement of the harsh synthesis conditions is one of the research hotspots of the current synthesis.

Disclosure of Invention

The invention aims to provide a preparation method of a biaryl compound, and aims to overcome various defects in the existing preparation process of the biaryl compound.

Still another object of the present invention is to provide a biaryl compound obtained by the above production method.

Another object of the present invention is to provide the use of the biaryl compound.

The invention is realized by the following steps that the chemical structural formula of the biaryl compound is shown as the following formula (I):

in the formula (I), R¹Is methoxy or methylAny one of trifluoromethyl, dimethylamino, trifluoromethoxy, cyano, ester group, halogen, 1, 3-dioxolan-2-yl, and dimethyl tert-butylsiloxy;

R²is any one of methyl, methoxy, benzyloxy, methylthio, cyano, ester group, dimethylamino, halogen, dimethyl tert-butylsiloxy, 2-methyl-1, 3-dioxolan-2-yl and heterocycle;

x is nitrogen atom or hydrocarbon.

Preferably, the halogen is not fluorine or chlorine; the heterocyclic ring is furan or benzofuran.

The invention further discloses a preparation method of the biaryl compound, which comprises the following steps:

(1) adding a mixture consisting of magnesium chips and lithium chloride into a schlenk sealed tube, reacting for 2-4 min under the conditions of reduced pressure and 310-330 ℃, and cooling to room temperature to obtain a reactant 1; wherein the molar ratio of the magnesium chips to the lithium chloride is 3 mmol: 1.8-2.2 mmol;

(2) adding ultra-dry tetrahydrofuran into the sealed tube, pumping nitrogen out of the sealed tube for three times, respectively adding aryl quaternary ammonium salt, 5 mol% of catalyst, aryl bromide and N, N, N ', N' -tetramethyl ethylenediamine into the sealed tube, stirring and reacting for 6-12 hours at 25-60 ℃, and quenching by using a saturated ammonium chloride solution to obtain a reactant 2; wherein the molar volume ratio of the ultra-dry tetrahydrofuran, the aryl quaternary ammonium salt, the catalyst, the aryl bromide and the N, N, N ', N' -tetramethyl ethylenediamine is 2-4 mL: 1 mmol: 0.05 mmol: 1-3 mmol: 2mmol of the active carbon;

(3) and (3) sequentially extracting, washing, drying, removing extract liquor and purifying the reactant 2 to obtain the biaryl compound.

Preferably, in step (2), the aryl quaternary ammonium salt is phenyl trimethyl quaternary ammonium salt iodide, 4-methylphenyl trimethyl quaternary ammonium salt iodide, 3-methylphenyl trimethyl quaternary ammonium salt iodide, 2-methylphenyl trimethyl quaternary ammonium salt iodide, 4-trifluoromethylphenyl trimethyl quaternary ammonium salt iodide, 4-trifluoromethoxyphenyl trimethyl quaternary ammonium salt iodide, 4-cyanophenyl trimethyl quaternary ammonium salt iodide, 4-ethoxycarbonylphenyl trimethyl quaternary ammonium salt iodide, 4-fluorophenyl trimethyl quaternary ammonium salt iodide, 4-chlorophenyl trimethyl quaternary ammonium salt iodide, 4-methoxyphenyl trimethyl quaternary ammonium salt iodide, 4-dimethylaminophenyl trimethyl quaternary ammonium salt iodide, 4- (1, 3-dioxolan-2-yl) phenyl trimethyl quaternary ammonium salt iodide, or a mixture thereof, 4-dimethyl tert-butyl siloxy phenyl trimethyl quaternary ammonium salt iodide and 3-pyridyl trimethyl quaternary ammonium salt iodide.

Preferably, in step (2), the aryl bromide is any one or more of bromobenzene, 4-methylbromobenzene, 4-methoxybromobenzene, 3-methoxybromobenzene, 2-methoxybromobenzene, 4-benzyloxybromobenzene, 4-methylthiobromobenzene, 4-cyanoborobenzene, 4-ethoxycarbonylbromobenzene, 4-dimethylaminobromobenzene, 4-fluorobromobenzene, 4-chlorobromobenzene, 4-dimethyl-tert-butylsiloxy-bromobenzene, 4- (2-methyl-1, 3-dioxolan-2-yl) bromobenzene, 2-bromodibenzofuran, 5-bromobenzofuran.

Preferably, in the step (2), the catalyst is any one of bis (triphenylphosphine) palladium dichloride, ferric trichloride, bis (triphenylphosphine) cobalt dichloride and bis (triphenylphosphine) nickel dichloride.

Preferably, in step (2), the catalyst is bis triphenylphosphine palladium dichloride.

Preferably, in step (2), the reaction is stirred at 25 ℃ for 12 hours; the molar ratio of the aryl quaternary ammonium salt to the aryl bromide is 1: 2.

Preferably, in step (3), the reaction product 2 is extracted with ethyl acetate, the extract is washed with saturated brine and dried over anhydrous sodium sulfate, the extract is removed by rotary evaporation, and the crude product is purified by silica gel column chromatography to obtain the biaryl compound.

The invention further discloses an application of the biaryl compound in preparing a compound containing a biaryl structure.

The invention overcomes the defects of the prior art and provides a biaryl compound and a preparation method and application thereof. The invention adopts a method for direct reduction cross-coupling reaction of aryl quaternary ammonium salt and aryl halide, a reaction system uses reagents such as palladium catalyst, magnesium chips, lithium chloride, TMEDA and the like, the reaction can be efficiently carried out in a one-pot method mode in tetrahydrofuran solution at room temperature, corresponding target products can be obtained with moderate to good yield, the reaction also has better functional group tolerance, and the chemical equation of the reaction is shown as follows:

in the preparation of the compound, a series of biaryl compounds can be efficiently synthesized by regulating and controlling a series of conditions such as the type of the selected catalyst, the proportion of reactants, a solvent for reaction, reaction temperature and the like. Among these, for different catalysts, such as: the method is characterized in that the optimization is carried out on the palladium bis (triphenylphosphine) dichloride, the ferric trichloride, the cobalt bis (triphenylphosphine) dichloride and the nickel bis (triphenylphosphine) dichloride, the effect of the palladium bis (triphenylphosphine) dichloride is optimal, and the yield is highest; different ratios between aryl quaternary ammonium salts and aryl bromides 1: (1-3), adding 1:2, optimizing; for different solvents, such as: n, N-dimethylformamide, dimethyl sulfoxide, N-dimethylacetamide, acetonitrile, 1, 4-dioxane and tetrahydrofuran are optimized, and the tetrahydrofuran effect is optimal and the yield is highest; the target product can be obtained at different temperatures within the range of 25-60 ℃, the temperature is optimal at 25 ℃, and the yield is highest; the corresponding product can be obtained after the reaction is carried out for 6-24 hours, the reaction time is optimal within 12 hours, and the yield is highest.

Compared with the defects and shortcomings of the prior art, the invention has the following beneficial effects:

(1) the invention provides a novel method for synthesizing biaryl compounds from simple and easily-obtained aryl quaternary ammonium salt and aryl bromide raw materials, and expands the substrate preparation range of the compounds;

(2) in the preparation method, cheap and easily available aryl halide is used as a coupling substrate, so that the reaction has the advantages of convenient operation and economic steps, and organic metal compounds which are prepared in advance and are sensitive to water and air are avoided;

(3) the preparation method has mild reaction conditions, and has the characteristics of simple post-treatment, green steps, low pollution, high economic benefit and the like;

(4) the biaryl compound prepared by the invention has good functional group tolerance and substrate universality.

Drawings

FIG. 1 is a hydrogen spectrum of 4-methoxybiphenyl 1;

FIG. 2 is a carbon spectrum of 4-methoxybiphenyl 1;

FIG. 3 is a hydrogen spectrum of 4-benzyloxybiphenyl 4;

FIG. 4 is a carbon spectrum of 4-benzyloxybiphenyl 4;

FIG. 5 is a hydrogen spectrum of 3-methoxybiphenyl 6;

FIG. 6 is a carbon spectrum of 3-methoxybiphenyl 6;

FIG. 7 is a hydrogen spectrum of 4-dimethylaminobiphenyl 10;

FIG. 8 is a carbon spectrum of 4-dimethylaminobiphenyl 10;

FIG. 9 is a hydrogen spectrum of 4-fluoro-4 '-methoxy-1, 1' -biphenyl 26;

FIG. 10 is the fluorine spectrum of 4-fluoro-4 '-methoxy-1, 1' -biphenyl 26;

FIG. 11 is a carbon spectrum of 4-fluoro-4 '-methoxy-1, 1' -biphenyl 26;

FIG. 12 is a hydrogen spectrum of 2- (4 '-methoxy- [1,1' -biphenyl ] -4-yl) -1, 3-dioxolane 30;

FIG. 13 is a carbon spectrum of 2- (4 '-methoxy- [1,1' -biphenyl ] -4-yl) -1, 3-dioxolane 30.

Detailed Description

In order to make the objects, technical solutions and advantages of the present invention more apparent, the present invention is described in further detail below with reference to the accompanying drawings and embodiments. It should be understood that the specific embodiments described herein are merely illustrative of the invention and are not intended to limit the invention.

Example 1

(1) Magnesium turnings (72.9mg, 3mmol, 3equiv.) and lithium chloride (84.8mg, 2mmol, 2equiv.) were weighed and added to a schlenk lock tube. The mixture of magnesium turnings and lithium chloride was then heated under reduced pressure using an electric heating gun (320 ℃,3 minutes).

(2) After the mixture was cooled to room temperature, 3mL of ultra-dry tetrahydrofuran was added thereto, followed by purging the tube with nitrogen three times. Subsequently, phenyltrimethyl quaternary ammonium iodide (263.1mg, 1mmol, 1equiv.) and bis-triphenylphosphine palladium dichloride (35.1mg, 0.05mmol, 5 mol%), 4-methoxybromobenzene (374.1mg, 2mmol, 2equiv.) and N, N, N ', N' -tetramethylethylenediamine (232.4mg, 2mmol, 2equiv.) were added to the block tube, respectively, and the mixture was stirred at room temperature for 12 hours.

(3) Then quenched with saturated ammonium chloride solution and extracted with ethyl acetate. Washing the extract with saturated saline solution, drying the extract with anhydrous sodium sulfate, removing the extract by rotary evaporation, purifying the crude product by silica gel column chromatography (under the conditions of column chromatography separation, the stationary phase is silica gel powder with 300-400 meshes, the mobile phase is ethyl acetate (A) and petroleum ether (B), and the mobile phase change process (A: B) is 1: 100 → 1: 20), and finally obtaining 165.4mg of the target product, namely 4-methoxybiphenyl 1.

The above 4-methoxybiphenyl 1 was characterized as shown in fig. 1 and 2, and the results were: a white solid;¹HNMR(400MHz,CDCl₃):δ7.65–7.56(m,4H),7.51–7.44(m,2H),7.39–7.34(m,1H),7.06–7.01(m,2H),3.89(s,3H)ppm.¹³C NMR(100MHz,CDCl₃):δ159.0,140.7,133.7,128.7,128.1,126.7,126.6,114.1,55.3ppm.IR(KBr):(＝2961,2836,1606,1522,1488,1288,1252,1035,834,760,688cm^-1.HRMS(m/z):calcd for C₁₃H₁₃O[M+H]⁺185.0961,found:185.0965.

according to the characterization data, the prepared reaction product 1 is 4-methoxybiphenyl (the purity is more than 98 percent); the product yield was calculated to be 90%.

Examples 2 to 32

Examples 2-32 are substantially the same as example 1 above, except that in step (1), the aryl quaternary ammonium salt and the aryl bromide are different, as shown in table 1 below:

TABLE 1 examples 2 to 32

The products in the table above were randomly selected and characterized, wherein FIG. 3 is a hydrogen spectrum of the product 4 (4-benzyloxybiphenyl), and FIG. 4 is a carbon spectrum of the product 4 (4-benzyloxybiphenyl); FIG. 5 is a hydrogen spectrum of the product 6 (3-methoxybiphenyl), and FIG. 6 is a carbon spectrum of the product 6 (3-methoxybiphenyl); FIG. 7 is a hydrogen spectrum of the product 10 (4-dimethylaminobiphenyl) and FIG. 8 is a carbon spectrum of the product 10 (4-dimethylaminobiphenyl); fig. 9 is a hydrogen spectrum of the product 26 (4-fluoro-4 '-methoxy-1, 1' -biphenyl), fig. 10 is a fluorine spectrum of the product 26 (4-fluoro-4 '-methoxy-1, 1' -biphenyl), and fig. 11 is a carbon spectrum of the product 26 (4-fluoro-4 '-methoxy-1, 1' -biphenyl); FIG. 12 is a hydrogen spectrum of the product 30(2- (4 '-methoxy- [1,1' -biphenyl ] -4-yl) -1, 3-dioxolane), and FIG. 13 is a carbon spectrum of the product 30(2- (4 '-methoxy- [1,1' -biphenyl ] -4-yl) -1, 3-dioxolane).

Examples 33 to 43

Examples 33 to 43 are substantially the same as example 1 above, except that in step (1), the catalyst, solvent, temperature (. degree. C.) and time (h) are different, as shown in Table 2 below:

TABLE 2

Example numbering	Catalyst and process for preparing same	Solvent(s)	Temperature (. degree.C.)	Time (h)	Yield (%)
						33	Bis (triphenylphosphine) palladium dichloride	N, N-dimethylformamide	25	12	0
34	Bis (triphenylphosphine) palladium dichloride	DMSO	25	12	0
						35	Bis (triphenylphosphine) palladium dichloride	N, N-dimethyl acetamide	25	12	0
36	Bis (triphenylphosphine) palladium dichloride	Acetonitrile	25	12	0
						37	Bis (triphenylphosphine) palladium dichloride	1, 4-dioxane	25	12	0
38	Ferric chloride	Tetrahydrofuran (THF)	25	12	<5
						39	Bis (triphenylphosphine) cobalt dichloride	Tetrahydrofuran (THF)	25	12	<5
40	Bis (triphenylphosphine) nickel dichloride	Tetrahydrofuran (THF)	25	12	<5
						41	Bis (triphenylphosphine) palladium dichloride	Tetrahydrofuran (THF)	60	12	29
42	Bis (triphenylphosphine) palladium dichloride	Tetrahydrofuran (THF)	25	24	89
						43	Bis (triphenylphosphine) palladium dichloride	Tetrahydrofuran (THF)	25	6	85

As can be seen from Table 2, under the same reaction conditions, the reaction was carried out using palladium bis (triphenylphosphine) dichloride as a catalyst, and under the conditions of N, N-dimethylformamide, DMSO, N-dimethylacetamide, acetonitrile and 1, 4-dioxane solvent, the target product 1 was not obtained. Catalysts are used, such as: the 4-methoxybiphenyl product 1 is synthesized by ferric trichloride, bis (triphenylphosphine) cobalt dichloride or bis (triphenylphosphine) nickel dichloride, the yield is extremely small, and the yield is different from that of the embodiment 1(90 percent) of the invention. In addition, target products can be obtained at different temperatures within the range of 25-60 ℃, and the temperature is optimal at 25 ℃; the corresponding product can be obtained after 6-24 hours of reaction, and the reaction time is optimal in 12 hours.

The above description is only for the purpose of illustrating the preferred embodiments of the present invention and is not to be construed as limiting the invention, and any modifications, equivalents and improvements made within the spirit and principle of the present invention are intended to be included within the scope of the present invention.