CN108017613B - Method for preparing polyaryl substituted naphthalene derivative by ruthenium-catalyzed reaction of heterocyclic aromatic ketone and tolane - Google Patents

Abstract

This divisional application relates to a method for preparing polyaromatic substituted naphthalene derivatives through the reaction of ruthenium-catalyzed heterocyclic aromatic ketones with diphenylacetylene. The invention uses relatively cheap ruthenium as a catalyst to activate the aromatic ketone β-H to synthesize a six-membered ring to generate a polyaromatic substituted naphthalene derivative; no additives and oxidants are required in the reaction process, only a simple base is used, and the reaction is carried out under mild reaction conditions . The synthesis method provided by the invention is simple, feasible, scientific and reasonable, environmentally friendly, economical and practical, and is suitable for large-scale production.

Description

Ruthenium-catalyzed reaction of heterocyclic aromatic ketones with diphenylacetylene to prepare polyaromatic substituted naphthalene derivatives method

This application is a division of the application number 2017113298008, the application date is December 13, 2017, and the title of the invention is "a method and application for the preparation of polyaromatic substituted naphthalene derivatives by the cyclization reaction of ruthenium-catalyzed aromatic ketones and diphenylacetylene" Application.

technical field

The invention relates to the fields of medical technology and optoelectronic materials, and mainly relates to a preparation method and application of polyaromatic substituted naphthalene derivatives.

Background technique

Due to their unique electrochemical and photochemical properties and their application in n-conjugated functional materials, polyaromatic substituted naphthalene derivatives are more and more widely used in organic fluorescent materials, semiconductor materials, etc. Naphthalene derivatives also have important applications in drug synthesis. Compared with the previous relatively harsh conditions such as cyclometallation, aryl halide, aryl acid, etc., the preparation method adopted in the prior art has made a great breakthrough. At present, polyaromatic substituted naphthalene derivatives are usually prepared by cyclization reaction of alkynes and C-H bonds (even double C-H bonds) of aromatic benzene rings catalyzed by transition metals under mild conditions. However, this method has defects. These reactions require a certain amount of ligands or equivalent metal salts as oxidants to complete the catalytic cycle, which not only increases the production cost, but also the metal salts are mostly heavy metal (copper, silver, etc.) salts that pollute the environment. . Based on this, there is a need in the art for a more environmentally friendly, green and economical method for synthesizing polyaromatic substituted naphthalene derivatives.

SUMMARY OF THE INVENTION

In order to make up for the deficiencies of the prior art, the present invention provides a kind of synthetic polyaromatic substituted naphthalene derivatives using cheap ruthenium ([RuCl ₂ (p-cymene)] ₂ ) as a catalyst under mild conditions without additives and oxidants. Methods.

The present invention adopts the following technical scheme: the derivative of polyaromatic substituted naphthalene has the structure shown in general formula I:

或-CF₃中的一种。where _R1 is One of -H or -F, R ₂ is -CH ₃ , -CH ₂ CH ₃ , -CH ₃ ,

or one of -CF ₃ .

Preferably, the derivative of the polyaromatic substituted naphthalene is:

Another object of the present invention is to claim the method for preparing the derivatives of the above-mentioned polyaromatic substituted naphthalenes, namely: using diphenylacetylene and aromatic ketone as raw materials, adding [RuCl ₂ (p-cymene)] ₂ , alkali and non-polar organic Solvent, heated to 80-100°C under nitrogen atmosphere for 12-24h, and separated by column chromatography to obtain derivatives of polyaromatic substituted naphthalene; the molar ratio of diphenylacetylene to aromatic ketone is 1:2, [RuCl ₂ (p-cymene)] ₂ accounted for 15 mol% of diphenylacetylene, and the molar ratio of base to aromatic ketone was 1:1.

其中R₁为-H或-F中的一种，R₂为

-CH₃、-CH₂CH₃、-CH₃、

或-CF₃中的一种。Preferably, the aromatic ketone is:

where _R1 is One of -H or -F, R ₂ is

-CH ₃ , -CH ₂ CH ₃ , -CH ₃ ,

or one of -CF ₃ .

中的一种。Preferably, the aromatic ketone is

one of the.

Further, the non-polar organic solvent is any one of benzene, toluene, dichloroethane, chloroform, styrene, cycloethane or hexane. Toluene is preferred.

Further, the base is one or more of KOAc, Na ₂ CO ₃ , Cs ₂ CO ₃ , K ₂ CO ₃ , Li ₂ CO ₃ , NaOAc and LiOAc. KOAc and Na ₂ CO ₃ are preferred.

As a preferred embodiment of the present invention, the preparation method of the polyaromatic substituted naphthalene derivative is as follows: placing aromatic ketone and diphenylacetylene in a sealed tube, adding [RuCl ₂ (p-cymene)] ₂ and toluene, and adding dry The sodium carbonate and potassium acetate were heated to 100 ℃ under nitrogen atmosphere for 24 hours, and the derivatives of polyaryl substituted naphthalene were obtained by column chromatography.

The third object of the present invention is to claim the application of the above-mentioned derivatives of polyaromatic substituted naphthalenes in the fields of drug preparation and optoelectronic materials.

或蓝光材料

的制备。such as novel tyrosine protein kinase inhibitors

or Blu-ray material

preparation.

Compared with the prior art, the beneficial effects of the present invention are:

In the present invention, relatively cheap ruthenium ([RuCl ₂ (p-cymene)] ₂ ) is used as a catalyst, and aromatic ketone β-H is activated to synthesize a six-membered ring to generate polyaromatic substituted naphthalene derivatives; no additives and oxidants are required in the reaction process, It is carried out under mild reaction conditions using only simple bases. The synthesis method provided by the invention is simple, feasible, scientific and reasonable, environmentally friendly, economical and practical, and is suitable for large-scale production.

Detailed ways

The present invention is described in detail below through specific embodiments, but the protection scope of the present invention is not limited. Unless otherwise specified, the experimental methods used in the present invention are all conventional methods, and the used experimental equipment, materials, reagents, etc. can be purchased from chemical companies.

Example 1

To a 25 mL sealed tube with magnetron was added diphenylacetylene (18 mg, 0.1 mmol), the corresponding aromatic ketone (0.2 mmol), catalyst [RuCl ₂ (p-cymene)] ₂ (9 mg, 15% mol), 0.5 mL of toluene, then dry sodium carbonate (21 mg, 0.2 mmol) and potassium acetate (19 mg, 0.2 mmol) were added, the nitrogen was purged three times, and the reaction was carried out at 100 ° C for 24 hours, and then separated by column chromatography (eluent: petroleum ether) ) to obtain the target compound. The characterization is as follows.

4,5-Diphenyl-6-(thiophene-2-methylene)benzo[b]thiophene: Yield: 40%. ¹ H NMR (CDCl ₃ , 400MHz) δ 7.81(s, 1H), 7.33(d, J=5.2Hz, 1H), 7.10-7.18(m, 9H), 7.00-7.02(m, 3H), 6.87( dd, J ₁ =3.6 Hz; J ₂ =5.2 Hz, 1H), 6.59-6.60 (m, 1H), 4.07 (s, 2H). ¹³ C NMR (CDCl ₃ , 100 MHz) δ 144.1, 139.7, 139.4, 135.7, 130.8,130.4,127.5,126.7,126.5,126.4,125.9,124.2,123.8,122.1,34.5.HRMS(EI-TOF)calcdfor C ₂₅ H ₁₈ S ₂ (M ⁺ ):382.0850,found:382.0847.

Example 2

To a 25 mL sealed tube with magnetron was added diphenylacetylene (18 mg, 0.1 mmol), the corresponding aromatic ketone (0.2 mmol), catalyst [RuCl ₂ (p-cymene)] ₂ (9 mg, 15% mol), 0.5 mL of toluene, then dry sodium carbonate (21 mg, 0.2 mmol) and potassium acetate (19 mg, 0.2 mmol) were added, the nitrogen was purged three times, and the reaction was carried out at 100 ° C for 24 hours, and then separated by column chromatography (eluent: petroleum ether) ) to obtain the target compound. The characterization is as follows.

3-Methyl-1,2,7-triphenylnaphthalene: Yield: 65%. Melting point: 163-165°C. ¹ H NMR (CDCl ₃ , 400 MHz) δ 7.91 (d, J=8.4 Hz, 1H), 7.79 (s, 1H), 7.69-7.73 (m, 2H), 7.52 (d, J=7.2 Hz, 2H) ,7.37(t,J=8.0Hz,2H),7.29(d,J=7.2Hz,1H),7.10-7.23(m,8H),7.02-7.05(m,2H),2.26(s,3H). ¹³ CNMR (CDCl ₃ , 100MHz) δ 141.5, 140.6, 140.4, 139.2, 139.0, 137.9, 134.7, 132.1, 131.5, 131.1, 130.1, 128.8, 127.7, 127.6, 127.5, 127.4, 127.2, 126.2, 127.2, 126.2, 12 124.9, 22.0. HRMS(EI-TOF) calcd for C ₂₉ H ₂₂ (M ⁺ ): 370.1722, found: 370.1723.

Example 3

To a 25 mL sealed tube with magnetron was added diphenylacetylene (18 mg, 0.1 mmol), the corresponding aromatic ketone (0.2 mmol), catalyst [RuCl ₂ (p-cymene)] ₂ (9 mg, 15% mol), 0.5 mL of toluene, then dry sodium carbonate (21 mg, 0.2 mmol) and potassium acetate (19 mg, 0.2 mmol) were added, nitrogen was purged three times, and the reaction was carried out at 100 ° C for 24 hours, and then separated by column chromatography (eluent: petroleum ether) ) to obtain the target compound. The characterization is as follows.

3-Ethyl-1,2-diphenylnaphthalene: Yield: 25%. Melting point: 124-125°C. ¹ H NMR (CDCl ₃ , 400MHz) δ 7.79-7.81(m, 1H), 7.72(s, 1H), 7.37-7.40(m, 2H), 7.22-7.26(m, 1H), 7.01-7.14(m , 8H), 6.96-6.98 (m, 2H), 2.51 (dd, J1 ₌ 7.6Hz _; J2=14.8Hz, 2H), 1.08 (t, J=7.6Hz, 3H). ¹³ C NMR (CDCl ₃ ,100MHz)δ140.4,140.3,139.6,139.5,138.8,133.0,131.2,131.0,130.4,127.4,127.4,126.8,126.3,126.1,125.8,125.7,125.3,27.4,15.1dcalc forC ₂₄ HRMS(EI-TOF) H ₂₀ (M ⁺ ): 308.1565, found: 308.1567.

Example 4

To a 25 mL sealed tube with magnetron was added diphenylacetylene (18 mg, 0.1 mmol), the corresponding aromatic ketone (0.2 mmol), catalyst [RuCl ₂ (p-cymene)] ₂ (9 mg, 15% mol), 0.5 mL of toluene, then dry sodium carbonate (21 mg, 0.2 mmol) and potassium acetate (19 mg, 0.2 mmol) were added, nitrogen was purged three times, and the reaction was carried out at 100 ° C for 24 hours, and then separated by column chromatography (eluent: petroleum ether) ) to obtain the target compound. The characterization is as follows.

7-Fluoro-3-methyl-1,2-diphenylnaphthalene: Yield: 30%. Melting point: 139-140℃. ¹ H NMR (CDCl ₃ , 400 MHz) δ 7.81 (dd, J ₁ =6.0 Hz; J ₂ =8.8 Hz, 1H), 7.75 (s, 1H), 7.06-7.23 (m, 10H), 7.01-7.03 ( m, 2H), 2.24 (s, 3H). ¹³ C NMR (CDCl ₃ , 100MHz) δ 161.6, 159.2, 140.8, 140.3, 138.9, 138.2 (d, J _CF =5.6Hz), 133.7 (d, J _CF =2.3 Hz), 132.3, 132.2, 130.9, 129.9 (d, J _CF = 5.6 Hz), 129.4 (d, J _CF = 8.6 Hz), 127.6 (d, J _CF = 4.9 Hz), 127.3, 126.6, 126.3, 116.2, 115.9, 110.3, 110.1, 21.8. HRMS(EI-TOF) calcd for C ₂₃ H ₁₇ F(M ⁺ ): 312.1314, found: 312.1312.

Example 5

To a 25 mL sealed tube with magnetron was added diphenylacetylene (18 mg, 0.1 mmol), the corresponding aromatic ketone (0.2 mmol), catalyst [RuCl ₂ (p-cymene)] ₂ (9 mg, 15% mol), 0.5 mL of toluene, then dry sodium carbonate (21 mg, 0.2 mmol) and potassium acetate (19 mg, 0.2 mmol) were added, nitrogen was purged three times, and the reaction was carried out at 100 ° C for 24 hours, and then separated by column chromatography (eluent: petroleum ether) ) to obtain the target compound. The characterization is as follows.

3-Isobutyl-1,2-diphenylnaphthalene: Yield: 35%. Melting point: 107-108°C. ¹ H NMR (CDCl ₃ , 400MHz) δ 7.85-7.87(m, 1H), 7.73(s, 1H), 7.43-7.47(m, 2H), 7.29-7.33(m, 1H), 7.07-7.21(m ,8H),7.01-7.03(m,2H),2.48(d,J=7.2Hz,2H),1.66-1.73(m,1H),0.76-0.78(d,J=6.4Hz,6H). ¹³ C NMR(CDCl ₃ , 100MHz)δ140.3,140.0,139.6,138.9,137.9,132.7,131.3,131.1,130.7,127.7,127.4,127.4,127.2,126.8,126.3,126.1,125.6,12,5.3,43.5. .HRMS(EI-TOF) calcd for C ₂₆ H ₂₄ (M ⁺ ): 336.1878, found: 336.1882.

Example 6

To a 25 mL sealed tube with magnetron was added diphenylacetylene (18 mg, 0.1 mmol), the corresponding aromatic ketone (0.2 mmol), catalyst [RuCl ₂ (p-cymene)] ₂ (9 mg, 15% mol), 0.5 mL of toluene, then dry sodium carbonate (21 mg, 0.2 mmol) and potassium acetate (19 mg, 0.2 mmol) were added, the nitrogen was purged three times, and the reaction was carried out at 100 ° C for 24 hours, and then separated by column chromatography (eluent: petroleum ether) ) to obtain the target compound. The characterization is as follows.

1,2-Diphenyl-3-(trifluoromethyl)naphthalene: Yield: 45%. Melting point: 118-119°C. ¹ H NMR (CDCl ₃ , 400MHz) δ 8.34(s, 1H), 8.02(d, J=8.0Hz, 1H), 7.57-7.60(m, 1H), 7.94-7.50(m, 2H), 7.18- 7.24(m, 3H), 7.13-7.16(m, 3H), 7.05-7.11(m, 4H). ¹³ C NMR (CDCl ₃ , 100MHz) δ 141.6, 138.1, 137.7, 135.9, 134.0, 131.4, 130.8(d, J _CF = 5.8Hz), 129.4, 128.9, 128.4, 128.3, 128.2, 127.6, 127.1, 126.9, 126.9, 126.8, 126.2, 126.2.HRMS(EI-TOF)calcd for C ₂₃ H ₁₅ F ₃ (M ⁺ ): 348.1126, found: 348.1124.

Comparative ratio:

计算产率，结果如表1所示。Add 0.1 mmol of diphenylacetylene, aromatic ketone to a 25 mL sealed tube with magnetron (0.2 mmol), catalyst [RuCl ₂ (p-cymene)] ₂ 0.01 mol, then add 0.5 mL of organic solvent and an equimolar dry base with aromatic ketones, purge nitrogen three times, react at 100 ° C for 24 hours, and then pass Column chromatography (eluent: petroleum ether) to obtain the target compound

The yields were calculated and the results are shown in Table 1.

Table 1

*Yield at 0.015 mmol catalyst

It can be seen from the data in Table 1 and the yield comparison of Examples 1-6 that when toluene is selected as the organic solvent, sodium carbonate and potassium acetate are selected as the base, and the catalyst dosage is 15 mol%, the yield is the highest. Therefore, this optimal reaction condition was adopted in the experiment process.

The above description is only a preferred embodiment of the present invention, but the protection scope of the present invention is not limited to this. The equivalent replacement or modification of the created technical solution and its inventive concept shall be included within the protection scope of the present invention.

Claims (1)

1. A process for preparing polyaryl substituted derivative by the reaction of heterocyclic arylketone and diphenylacetylene under catalysis of ruthenium features that the diphenylacetylene and aromatic ketone are used

As starting material, [ RuCl ] was added₂(p-cymene)]₂Heating alkali and a nonpolar organic solvent to 80-100 ℃ in a nitrogen environment for reaction for 12-24h, and performing column chromatography separation to obtain polyaryl substituted derivatives; the molar ratio of the tolane to the aromatic ketone is 1:2, [ RuCl₂(p-cymene)]₂Accounts for 15mol percent of tolane, and the molar ratio of the alkali to the aromatic ketone is 1:1

The non-polar organic solvent is toluene; the alkali is KOAc and Na₂CO₃。