CN107954821A - A kind of ruthenium catalysis dibenzyl ketone prepares method and the application of more virtue substitution naphthalene derivativeses with interior alkynes cyclization - Google Patents

Abstract

Method and the application of more virtue substitution naphthalene derivativeses are prepared with interior alkynes cyclization the present invention relates to a kind of ruthenium catalysis dibenzyl ketone.The present invention uses more cheap ruthenium ([RuCl₂(p‑cymene)]₂) catalyst is used as, dibenzyl ketone β H are activated synthesis hexatomic ring generates more virtue substitution naphthalene derivativeses；Without additive and oxidant in reaction process, using only simple alkali, carry out under mild reaction conditions.Synthetic method provided by the invention is simple and practicable, scientific and reasonable, environmentally protective, economical and practical, is adapted to large-scale production.

Description

A ruthenium-catalyzed cyclization reaction of dibenzyl ketone and internal alkyne to prepare polyaromatic substituted naphthalene derivatives methods and applications

technical field

The invention relates to the fields of medical technology and photoelectric 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., and polyaromatic substitution Naphthalene derivatives also have important applications in drug synthesis. The preparation method adopted in the prior art has made a great breakthrough compared with the relatively harsh conditions of the previous cyclometallation, aryl halide, aryl acid and the like. At present, under mild conditions, polyaromatic substituted naphthalene derivatives are prepared by the cyclization reaction of the C-H bond (even double C-H bond) of the aromatic benzene ring and alkyne under mild conditions. However, there are defects in this method. These reactions require a certain amount of ligand or an equivalent metal salt as an oxidant to complete the catalytic cycle, which not only increases the production cost, but most of the metal salts are heavy metal (copper, silver, etc.) salts that pollute the environment. . Based on this, more environmentally friendly, green and economical methods are needed in this field to synthesize polyaromatic substituted naphthalene derivatives.

Contents of the invention

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

The present invention adopts the following technical scheme: derivatives of polyaromatic substituted naphthalene have a structure as shown in general formula I:

Another object of the present invention is to claim the preparation method of the derivatives of the above-mentioned polyaromatic substituted naphthalene, that is: dibenzyl ketone and internal alkyne As raw material, add [RuCl ₂ (p-cymene)] ₂ , base and non-polar organic solvent, heat to 80-100°C under nitrogen atmosphere, react for 12-24h, and separate by column chromatography to obtain derivatives of polyaromatic substituted naphthalene The described internal alkyne and dibenzyl ketone mol ratio is 1:2, [RuCl ₂ (p-cymene)] ₂ accounts for 15mol% of internal alkyne, and the mol ratio of alkali and dibenzyl ketone is 1: 1.

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 _Na2CO3 are preferred.

As a preferred embodiment of the present invention, the preparation method of the polyaromatic substituted naphthalene derivatives is: placing dibenzyl ketone and internal alkyne in a sealed tube, adding [RuCl ₂ (p-cymene)] ₂ and toluene, and simultaneously Add dry sodium carbonate and potassium acetate and heat to 100°C under nitrogen atmosphere to react for 24 hours, and separate by column chromatography to obtain derivatives of polyaromatic substituted naphthalene.

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

For example, for novel tyrosine protein kinase inhibitors or Blu-ray material preparation.

Compared with prior art, the beneficial effect of the present invention is:

The present invention uses relatively cheap ruthenium ([RuCl ₂ (p-cymene)] ₂ ) as a catalyst to activate dibenzyl ketone β-H to synthesize a six-membered ring to generate polyaromatic substituted naphthalene derivatives; no additives are needed in the reaction process And oxidizing agent, only use simple base, carry out under mild reaction condition. The synthesis method provided by the invention is simple, feasible, scientific and reasonable, environmentally friendly, economical and practical, and suitable for large-scale production.

Detailed ways

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

Example 1

Add dibenzyl ketone (42 mg, 0.2 mmol), corresponding internal alkyne (0.1 mmol), catalyst [RuCl ₂ (p-cymene)] ₂ (9 mg, 15% mol) to a 25 mL capped tube with a magnet , 0.5mL toluene, then add dry sodium carbonate (21mg, 0.2mmol), potassium acetate (19mg, 0.2mmol), replace nitrogen three times, react at 100°C for 24 hours, then separate through column chromatography (eluent: Petroleum ether) to obtain the target compound. Characterization is as follows.

3-Benzyl-1-methyl-2-phenylnaphthalene: Yield: 40%. Melting point: 76-77°C. ¹ H NMR (CDCl ₃ , 400MHz) δ8.03(d, J=8.0Hz, 1H), 7.79(d, J=8.0Hz, 1H), 7.47-7.52(m, 3H), 7.33-7.36(m, ¹³ C NMR (CDCl ₃ ,100MHz)δ141.0,140.9,140.1,137.4,132.8,132.1,129.7,129.1,128.2,128.1,128.1,126.7,126.5,125.7,125.6,125.6,124.4,40.8,16.6 HR calcd for C ₂₄ H ₂₀ (M ⁺ ):308.1565,found:308.1563.

Comparative example: add 0.1mmol of toluene acetylene, aromatic ketone to a 25mL sealed tube with a magnet (0.2mmol), catalyst [RuCl ₂ (p-cymene)] ₂ 0.01mol, then add 0.5mL organic solvent and dry base equimolar with aromatic ketone, replace nitrogen three times, react at 100°C for 24 hours, then Column chromatographic separation (eluent is: petroleum ether) to obtain the target compound Calculate the yield, and the results are shown in Table 1.

Table 1

serial number alkali Organic solvents Yield 1 KOAc PhMe 0 2 LiOAc PhMe 0 3 NaOAc PhMe rare 4 cSO PhMe 20 5 Li ₂ CO ₃ PhMe rare 6 Na ₂ CO ₃ PhMe rare 7 K ₂ CO ₃ PhMe 25 8 Cs ₂ CO ₃ PhMe twenty three 9 _KOAc , _Na2CO3 PhMe 52 10 _KOAc , _Na2CO3 DCE twenty three 11 _KOAc , _Na2CO3 PhF twenty one 12 _KOAc , _Na2CO3 CH ₃ CN 0 13 _KOAc , _Na2CO3 DMSO 0 14 _KOAc , _Na2CO3 PhMe 70%*

*The yield when the catalyst is 0.015mmol

From the data in Table 1 and the comparison of the yield of Example 1, it can be seen that when the organic solvent is selected toluene, and the alkali is sodium carbonate and potassium acetate, the catalyst consumption is 15mol%, and the yield is the highest. Therefore, the optimal reaction conditions were used in the experiment.

The above is only a preferred embodiment of the present invention, but the scope of protection of the present invention is not limited thereto, any person familiar with the technical field within the technical scope of the disclosure of the present invention, according to the present invention Any equivalent replacement or change of the created technical solution and its inventive concept shall be covered within the scope of protection of the present invention.

Claims (8)

1. a kind of more virtue substitution naphthalene derivatives, it is characterised in that there is the structure as shown in general formula I：

A kind of 2. preparation methods of virtue substitution naphthalene derivativeses more as claimed in claim 1, it is characterised in that by dibenzyl ketone with Interior alkynesAs raw material, [RuCl is added₂(p-cymene)]₂, alkali and non-polar organic solvent, in a nitrogen environment 80-100 DEG C of reaction 12-24h is heated to, more virtue substitution naphthalene derivatives are obtained through column chromatography for separation；The interior alkynes and dibenzyl Base ketone molar ratio is 1:2, [RuCl₂(p-cymene)]₂Account for the 15mol% of interior alkynes, the molar ratio of alkali and dibenzyl ketone is 1:1.

3. according to the method described in claim 2, it is characterized in that, the non-polar organic solvent is benzene, toluene, two chloroethenes It is any in alkane, chloroform, styrene, cyclohexane or hexane.

4. according to the method described in claim 3, it is characterized in that, organic solvent is toluene.

5. according to the method described in claim 2, it is characterized in that, the alkali is KOAc, Na₂CO₃、Cs₂CO₃、K₂CO₃、 Li₂CO₃, one or more in NaOAc, LiOAc.

6. according to the method described in claim 5, it is characterized in that, the alkali is KOAc and Na₂CO₃。

7. according to the method described in claim 2, it is characterized in that, the preparation method of more virtue substitution naphthalene derivativeses is：By two Benzyl ketone withIt is placed in tube sealing, adds [RuCl₂(p-cymene)]₂And toluene, while add dry carbonic acid Sodium and potassium acetate be heated in a nitrogen environment 100 DEG C of reactions 24 it is small when, obtain the derivatives of more virtue substitution naphthalenes through column chromatography for separation Thing；

DescribedIt is 1 with dibenzyl ketone molar ratio:2, [RuCl₂(p-cymene)]₂The 15mol% of interior alkynes is accounted for, The molar ratio of alkali and dibenzyl ketone is 1:1.

A kind of 8. application of more virtue substitution naphthalene derivativeses as claimed in claim 1 in medicine preparation and field of photovoltaic materials.