Preparation method of aromatic ketone derivative

Abstract

The invention belongs to the field of preparation of material intermediates, and particularly relates to a preparation method of an aromatic ketone derivative. The aromatic ketone derivative is prepared from raw materials through a ring-closing reaction, a ring-opening reaction, a ring-closing reaction and a halogen substitution reaction in sequence. According to the method, reaction conditions and catalyst selection in each step are low in cost and safe, side reactions are inhibited, and meanwhile it is ensured that the most effective catalyst can be utilized in the synthesis process so as to improve the reaction efficiency and the product yield. The reaction temperature, time and solvent selection in each step are easy to realize, and the stability and safety of the reaction process are ensured.

Description

Technical Field

[0001] The invention belongs to the field of material intermediate preparation, and specifically relates to a method for preparing an aromatic ketone derivative. Background Art

[0002] Iridoid compounds and their analogs may be used to prepare organic optoelectronic materials due to their unique spectral properties (such as absorption and fluorescence characteristics), such as donor or acceptor materials in organic solar cells, light-emitting layer materials in organic electroluminescent devices (OLEDs), optical switches or optical limiting materials, etc. The introduction of halogen atoms into the molecular structure may also increase the stability, oxidation resistance or weather resistance of the material, and can be applied to organic photovoltaic materials, nonlinear optical materials, magnetic materials, etc.

[0003] By modifying or embedding the cycloolefin skeleton into various material systems through Michael addition, Diels-Alder and other reactions, a variety of specific functions can be achieved. For example, the cycloolefin skeleton containing cycloolefin ether terpene compounds in 2-iodo-4-methyl-10,11-dihydro-5H-dibenzo[a,d][7]cycloolefin-5-one has good morphological stability and hole-electron transport properties, and has a triplet energy of up to 3.0eV. Its high triplet energy is very suitable for preparing the main material of blue, green and red phosphorescent OLEDs, and the corresponding maximum EQE is 17.8%, 27.0% and 28.1%, respectively, showing a low efficiency roll-off at high brightness. The good activity and reactivity of cycloolefin ether terpene compounds in electrochemistry make them play an important role in optoelectronic materials, sensor materials, organic semiconductors, photochromic materials, etc., but at present, the combination of binding active sites with cycloolefin skeletons has always been one of the difficult technical problems to solve. The present invention provides a practical method for preparing cycloolefin ether terpene derivatives. Summary of the invention

[0004] In order to solve the deficiencies of the prior art, the present invention provides a method for preparing an aromatic ketone derivative.

[0005] The technical solution provided by the present invention is as follows:

[0006] A method for preparing an aromatic ketone derivative, wherein the aromatic ketone derivative has a structural formula shown in Formula 1: wherein Ar1 and Ar2 are the same or different, and Ar1 and Ar2 are independently selected from C 6-30 The aromatic group; its preparation steps are as follows:

[0007]

[0008] Ar3 and Ar4 are the same or different, and Ar3 and Ar4 are independently selected from C substituted by one or more R 6-30 The aromatic group, wherein the R is independently selected from H, hydroxyl, amino, acyloxy, C 1-5 Alkoxy, substituted or unsubstituted C 1-10 Alkyl or substituted or unsubstituted C 6-30 Aryl, R is bonded or fused to Ar3 and Ar4;

[0009] Step 1: using raw material I and raw material II and a metal ion-containing organic catalyst to perform a ring-closing reaction to obtain intermediate I;

[0010] Step 2: Intermediate I, halogen acid and inorganic phosphorus undergo a ring-opening reaction to obtain intermediate II;

[0011] Step 3: Intermediate II, a dehydrating agent, and a metal ion catalyst undergo a ring-closing reaction to obtain intermediate III;

[0012] Step 4: One or more H on Ar3 or Ar4 of intermediate III is replaced by halogen to obtain intermediate IV.

[0013] The Ar1 and Ar2 are the same or different and are selected from the structural formula shown in Formula 2 or Formula 3: Wherein, * is the condensation site with cycloheptanone in Formula 1, and any two sites * in Formula 3 are condensed with cycloheptanone in Formula 1; m is a natural integer of 0-3, such as 0, 1, 2, 3, a+m≤4; n is a natural integer of 0-5, such as 0, 1, 2, 3, 4, 5, a+n≤6; X is a halogen. X is preferably I or Br.

[0014] Furthermore, a=1, and the aromatic ketone derivative has the structural formula shown in Formula 4, Formula 5, and Formula 6:

[0015] m1, m2, m3, m4 are all natural integers of 0-3, such as 0, 1, 2, 3, n1, n2 are all natural integers of 0-5, such as 0, 1, 2, 3, 4, 5, R1, R2, R3, R4, R5, R6 are the same or different, R1, R2, R3, R4, R5, R6 are independently selected from H, hydroxyl, acyloxy, amino substituted or unsubstituted by alkyl, C 1-5 Alkoxy, substituted or unsubstituted C 1-10 Alkyl or substituted or unsubstituted C 6-30 The aromatic group.

[0016] Furthermore, the C 1-5 The alkoxy group is selected from methoxy; the substituted or unsubstituted C 1-10 The alkyl group is selected from methyl, ethyl and n-propyl.

[0017] Preferably, when the aromatic ketone derivative has the structural formula shown in Formula 4, m1 is 1, and m2 is a natural integer of 0-3, the preparation method thereof is as follows:

[0018]

[0019] Wherein, when m2 is 1, R2 is selected from hydroxyl, methoxy, and phenyl, and when R2 is phenyl, it is fused with phenylacetylene.

[0020] Specifically, in the technical solution of the present application, the ring-closing reaction in step 1 is as follows: after uniformly mixing raw material I, raw material II and a metal ion-containing organic catalyst, the reaction is maintained at 90-100° C. for 2-5 hours to obtain intermediate I.

[0021] Wherein, the metal ion-containing organic catalyst is selected from any one or more combinations of platinum group metal ion catalysts. Platinum group metal ion catalysts include, but are not limited to, platinum metal ion catalysts, palladium metal ion catalysts, and rhodium metal ion catalysts. Examples include, but are not limited to, palladium acetate, tetrakistriphenylphosphine palladium, and ditriphenylphosphine palladium dichloride.

[0022] The ring-opening reaction in step 2 is specifically as follows: intermediate I, halogen-containing acid and inorganic phosphorus are mixed, the temperature is controlled at 150-180°C, and the reaction is carried out for 8-10 hours to obtain intermediate II. The halogen-containing acid is selected from any one of perhalogen acid, hydrogen halide or halogen acid, preferably, the halogen-containing acid is selected from hydrogen halide, including but not limited to hydrochloric acid and hydroiodic acid.

[0023] The ring-closing reaction in step 3 is specifically as follows: adding intermediate II to benzene solvent, adding a dehydrating agent and a metal ion catalyst, controlling the temperature at 25-40°C, and reacting for 2-3 hours to obtain intermediate III. Among them, the dehydrating agent is preferably thionyl chloride. Preferably, the dehydrating agent is selected from thionyl chloride; the metal ion catalyst is selected from one or more combinations of ferric chloride and aluminum chloride.

[0024] Step 4 specifically includes the following reactions:

[0025] S4-1: adding intermediate III and a metal ion catalyst to a nitric acid solution to react and prepare intermediate IV in which at least one H on the aromatic group fused with cycloheptanone is replaced by a nitro group;

[0026] S4-2: adding intermediate IV to an alcohol-water solvent, adding an acid solution and a metal catalyst to react to prepare intermediate V in which the nitro group is aminated;

[0027] S4-3: The intermediate V, an acid reagent, a nitrate and a halide are reacted to prepare a product in which the amino group is substituted by a halogen.

[0028] The S4-1 nitration reaction is specifically as follows: adding intermediate III and metal ion catalyst into nitric acid solution, controlling the temperature at 100-110° C., and reacting for 2-3 hours to obtain intermediate IV. The metal ion catalyst is selected from one or more combinations of ferric chloride and aluminum chloride.

[0029] The S4-2 reduction reaction is specifically as follows: adding intermediate IV to an alcohol-water solvent, adding ammonium chloride and a metal ion catalyst, controlling the temperature at 80-90° C., and reacting for 0.5-1 h to obtain intermediate V. Conventional alcohol reagents can be selected for use, including but not limited to methanol-water solvent, ethanol-water solvent, and 1,2-propylene glycol-water solvent. The metal catalyst is selected from any one or more combinations of copper catalysts, iron catalysts, and aluminum catalysts.

[0030] The S4-3 is specifically as follows: adding the intermediate V to a solvent, adding an inorganic acid, a halide and a nitrite, controlling the temperature at 0-25° C., and reacting for 1-2 hours to obtain a compound of formula 1. The inorganic acid, the halide and the nitrite are specifically selected from hydrochloric acid, potassium iodide and sodium nitrite.

[0031] The compound shown in formula 1 can be used to prepare optoelectronic materials, sensor materials, organic semiconductors, and photochromic materials.

[0032] Compared with existing technologies:

[0033] The present invention realizes the precise construction of complex molecular structures through designed chemical reaction steps and specific reagent selection, ensuring high yield and high purity of the target product. The selection of the application scheme takes into account environmental factors and cost-effectiveness, reduces the use of expensive or difficult-to-handle reagents, and is safe and environmentally friendly. The reaction conditions and catalyst selection of each step are low-cost, safe, and inhibit side reactions, while ensuring that the synthesis process can use the most effective catalyst to improve reaction efficiency and product yield, and the product purity can reach more than 99.95%. The reaction temperature, time and solvent selection in each step are easy to implement, ensuring the stability and safety of the reaction process. The synthesis route of a dibenzocycloketone derivative provided by the present invention has the advantages of economical raw materials, environmental friendliness, simple steps, high efficiency and good safety, and is practical. BRIEF DESCRIPTION OF THE DRAWINGS

[0034] Figure 1 This is the H-NMR characterization spectrum of compound D-1 prepared in Example 1. DETAILED DESCRIPTION

[0035] The principles and features of the present invention are described below. The examples given are only used to explain the present invention and are not used to limit the scope of the present invention.

[0036] If the specific conditions are not specified in the examples, the experiments were carried out under conventional conditions or conditions recommended by the manufacturer. If the manufacturers of reagents or instruments are not specified, they are all conventional products that can be purchased commercially.

[0037] Embodiment 1:

[0038]

[0039] Step 1: In a 500mL reaction bottle, compound A1-1 (20.43g, 0.2mol), compound A1-2 (27.23g, 0.2mol), and 1g of palladium acetate were added to 200ml of N,N-dimethylformamide at room temperature, the temperature was set at 95°C, N2 was introduced, the reaction was continued for 3h, and after the reaction was completed after TLC monitoring, it was spin-dried, 200ml of tetrahydrofuran solution was added, and the solution was heated to 60°C. After dissolution and clarification, 250ml of ethanol was slowly added dropwise to the solution. After stirring at a constant temperature for 1h, the temperature was lowered to room temperature and stirred for 1h. Filtered with suction, the filter cake was dried to obtain 42.06g of compound S1-2 with a yield of 89%.

[0040] Step 2: In a 500mL reaction bottle, compound S1-2 (40g, 0.17mol) and 1g of phosphorus were dissolved in 200ml of acetic acid solution, and hydrochloric acid was slowly added dropwise, and the pH was adjusted to between 1-2. The reaction was carried out at 170°C for 10h. After the reaction was completed by TLC monitoring, saturated sodium bicarbonate was slowly added dropwise to the reaction solution, and the pH was adjusted to 7-8. 100ml of dichloromethane was added to the reaction solution, and the mixture was shaken and stirred. The organic phase was separated and collected and dried to obtain 36.61g of compound S1-3 with a yield of 90%.

[0041] Step 3: In a 500mL reaction bottle, compound S1-3 (30g, 0.12mol) and 2g of carbon disulfide were dissolved in 200ml of benzene and stirred evenly, then 75g of dichlorothionyl and 2g of aluminum chloride were added thereto, and the mixture was reacted at 30°C for 3h. After the reaction was completed by TLC monitoring, the reaction liquid was filtered, the filtrate was taken, heated and spin-dried to obtain 21.65g of compound S1-4, with a yield of 78%.

[0042] Step 4: In a 500mL reaction bottle, add compound S1-4 (15g, 0.07mol) and 1g aluminum chloride to 200ml nitric acid, set the temperature at 110℃ for reaction for 2h, monitor the reaction by TLC, spin dry, add to 200ml ethyl acetate solution, heat to 70℃, and after dissolution and clarification, slowly add 50ml of methanol to the solution, stir at constant temperature for 1h, then cool to room temperature and stir for 1h, filter with suction, and dry the filter cake to obtain 14.79g compound S1-5 with a yield of 82%.

[0043] Step 5: In a 500mL reaction bottle, compound S1-5 (10g, 0.04mol), 3g ammonium chloride and 1g iron powder were added to 200ml 70% ethanol aqueous solution, the temperature was set at 80°C for reaction for 1h, and after the reaction was completed by TLC monitoring, the reaction liquid was filtered, the filtrate was taken, heated and spin-dried, 200ml of ethyl acetate solution was added, heated to 50°C, and after dissolution and clarification, 50ml of petroleum ether was slowly added dropwise to the solution, and the temperature was stirred for 1h, then cooled to room temperature and stirred for 1h, filtered, and the filter cake was dried to obtain 7.99g of compound S1-6 with a yield of 90%.

[0044] Step 6: In a 500mL reaction bottle, compound S1-6 (4g, 0.02mol), 1g potassium iodide and 1g sodium nitrite were added to 200ml water, hydrochloric acid was slowly added to the reaction solution, the temperature was set at 10°C for 2h, after TLC monitoring, saturated sodium bicarbonate was slowly added to the reaction solution, the pH was adjusted to 7-8, 50ml of dichloromethane was added to the reaction solution, shaken and stirred, separated, the organic phase was collected, and dried to obtain 4.99g of compound D1, with a yield of 85%. The molecular weight was determined by mass spectrometry (MALDI-TOF-MS) to be 348.08, which was determined to be the target compound D1. Figure 1 Shown is the H-NMR characterization spectrum of compound D-1.

[0045] Embodiment 2:

[0046]

[0047] Step 1: In a 500mL reaction bottle, compound A2-1 (23.63g, 0.2mol), compound A2-2 (24.42g, 0.2mol) and 1g palladium acetate were added to 200mlN,N-dimethylformamide at room temperature, the temperature was set at 95°C, N2 was introduced, the reaction was continued for 3h, and after completion of the reaction monitored by TLC, the solution was spin-dried, 200ml of tetrahydrofuran solution was added, and the solution was heated to 60°C. After dissolution and clarification, 250ml of ethanol was slowly added dropwise to the solution. The solution was stirred at a constant temperature for 1h, then cooled to room temperature and stirred for 1h. The solution was filtered and the filter cake was dried to obtain 43.36g of compound S2-2 with a yield of 91%.

[0048] Step 2: In a 500mL reaction bottle, compound S2-2 (35g, 0.15mol) and 0.5g of phosphorus were dissolved in 200ml of acetic acid solution, and hydrochloric acid was slowly added dropwise, and the pH was adjusted to between 1-2. The reaction was carried out at 170°C for 10h. After the reaction was completed by TLC monitoring, saturated sodium bicarbonate was slowly added dropwise to the reaction solution, and the pH was adjusted to 7-8. 100ml of dichloromethane was added to the reaction solution, and the mixture was shaken and stirred. The organic phase was separated and collected and dried to obtain 30.25g of compound S2-3 with a yield of 85%.

[0049] Step 3: In a 500mL reaction bottle, compound S2-3 (30g, 0.12mol) and 2g of carbon disulfide were dissolved in 200ml of benzene and stirred evenly, then 75g of dichlorothionyl and 2g of aluminum chloride were added thereto, and the mixture was reacted at 30°C for 3h. After the reaction was completed by TLC monitoring, the reaction liquid was filtered, the filtrate was taken, heated and spin-dried to obtain 22.49g of compound S2-4, with a yield of 81%.

[0050] Step 4: In a 500mL reaction bottle, add compound S2-4 (20g, 0.09mol) and 1g aluminum chloride to 200ml nitric acid, set the temperature at 110℃ for reaction for 2h, monitor the reaction by TLC, spin dry, add to 200ml ethyl acetate solution, heat to 70℃, and after dissolution and clarification, slowly add 50ml of methanol to the solution, stir at constant temperature for 1h, then cool to room temperature and stir for 1h, filter, and dry the filter cake to obtain 18.01g of compound S2-5 with a yield of 75%.

[0051] Step 5: In a 500mL reaction bottle, compound S2-5 (15g, 0.06mol), 50ml hydrochloric acid and 1g of iron powder were added to 200ml of 70% ethanol aqueous solution, and the temperature was set at 80°C for reaction for 1h. After the reaction was completed by TLC monitoring, the reaction liquid was filtered, the filtrate was taken, heated and spin-dried, 200ml of ethyl acetate solution was added, and heated to 50°C. After dissolution and clarification, 50ml of petroleum ether was slowly added dropwise to the solution. After stirring at a constant temperature for 1h, the temperature was lowered to room temperature and stirred for 1h, filtered, and the filter cake was dried to obtain 10.8g of compound S2-6 with a yield of 81%.

[0052] Step 6: In a 500mL reaction bottle, compound S2-6 (10g, 0.04mol), 1g potassium iodide and 1g sodium nitrite were added to 200ml water, hydrochloric acid was slowly added to the reaction solution, the temperature was set at 10°C for 2h, after TLC monitoring, saturated sodium bicarbonate was slowly added to the reaction solution, the pH was adjusted to 7-8, 50ml volume of dichloromethane was added to the reaction solution, shaken and stirred, separated, the organic phase was collected, and dried to obtain 11.71g of compound D2, with a yield of 80%. The molecular weight was determined by mass spectrometer (MALDI-TOF-MS) to be 350.03, which was determined to be the target compound D2.

[0053] Embodiment 3:

[0054]

[0055] Step 1: In a 500mL reaction bottle, compound A3-1 (26.43g, 0.2mol), compound A3-2 (27.23g, 0.2mol) and 1g palladium acetate were added to 200mlN,N-dimethylformamide at room temperature, the temperature was set at 95°C, N2 was introduced, the reaction was continued for 3h, and after completion of the reaction monitored by TLC, the solution was spin-dried, 200ml of tetrahydrofuran solution was added, and the solution was heated to 60°C. After dissolution and clarification, 250ml of ethanol was slowly added dropwise to the solution. The solution was stirred at a constant temperature for 1h, then cooled to room temperature and stirred for 1h. The solution was filtered and the filter cake was dried to obtain 49.53g of compound S3-2 with a yield of 93%.

[0056] Step 2: In a 500mL reaction bottle, compound S3-2 (45g, 0.17mol) and 0.5g of phosphorus were dissolved in 200ml of acetic acid solution, and hydrochloric acid was slowly added dropwise, and the pH was adjusted to between 1-2. The reaction was carried out at 170°C for 10h. After the reaction was completed by TLC monitoring, saturated sodium bicarbonate was slowly added dropwise to the reaction solution, and the pH was adjusted to 7-8. 100ml of dichloromethane was added to the reaction solution, and the mixture was shaken and stirred. The organic phase was separated and collected and dried to obtain 40.20g of compound S3-3 with a yield of 88%.

[0057] Step 3: In a 500mL reaction bottle, compound S3-3 (35g, 0.13mol) and 2g of carbon disulfide were dissolved in 200ml of benzene and stirred evenly, then 75g of dichlorothionyl and 2g of aluminum chloride were added thereto, and the mixture was reacted at 30°C for 3h. After the reaction was completed by TLC monitoring, the reaction liquid was filtered, the filtrate was taken, heated and spin-dried to obtain 24.5g of compound S3-4, with a yield of 75%.

[0058] Step 4: In a 500mL reaction bottle, add compound S3-4 (20g, 0.08mol) and 1g aluminum chloride to 200ml nitric acid, set the temperature at 110℃ for reaction for 2h, monitor the reaction by TLC, spin dry, add to 200ml ethyl acetate solution, heat to 70℃, and after dissolution and clarification, slowly add 50ml of methanol to the solution, stir at constant temperature for 1h, then cool to room temperature and stir for 1h, filter, and dry the filter cake to obtain 18.38g of compound S3-5 with a yield of 78%.

[0059] Step 5: In a 500mL reaction bottle, compound S3-5 (15g, 0.05mol), 3g ammonium chloride and 1g copper powder were added to 200ml 70% ethanol aqueous solution, and the temperature was set at 80°C for reaction for 1h. After the reaction was completed by TLC monitoring, the reaction liquid was filtered, the filtrate was taken, heated and spin-dried, 200ml of ethyl acetate solution was added, heated to 50°C, and after dissolution and clarification, 50ml of petroleum ether was slowly added dropwise to the solution. After stirring at a constant temperature for 1h, the temperature was lowered to room temperature and stirred for 1h, filtered, and the filter cake was dried to obtain 11.60g of compound S3-6 with a yield of 86%.

[0060] Step 6: In a 500mL reaction bottle, compound S3-6 (10g, 0.04mol), 1g cuprous bromide and 1g sodium nitrite were added to 200ml water, hydrochloric acid was slowly added to the reaction solution, the temperature was set at 10°C for 2h, after TLC monitoring, saturated sodium bicarbonate was slowly added to the reaction solution, the pH was adjusted to 7-8, 50ml volume of dichloromethane was added to the reaction solution, shaken and stirred, separated, the organic phase was collected, and dried to obtain 10.90g of compound D3, with a yield of 88%. The molecular weight was determined by mass spectrometry (MALDI-TOF-MS) to be 330.95, which was determined to be the target compound D3.

[0061] Example 4

[0062]

[0063] Step 1: In a 500mL reaction bottle, compound A4-1 (30.44g, 0.2mol), compound A4-2 (27.23g, 0.2mol) and 1g palladium acetate were added to 200mlN,N-dimethylformamide at room temperature, the temperature was set at 95°C, N2 was introduced, the reaction was continued for 3h, and after completion of the reaction monitored by TLC, the solution was spin-dried, 200ml of tetrahydrofuran solution was added, and the solution was heated to 60°C. After dissolution and clarification, 250ml of ethanol was slowly added dropwise to the solution. The solution was stirred at a constant temperature for 1h, then cooled to room temperature and stirred for 1h. The solution was filtered and the filter cake was dried to obtain 49.82g of compound S4-2 with a yield of 87%.

[0064] Step 2: In a 500mL reaction bottle, compound S4-2 (45g, 0.16mol) and 0.5g of phosphorus were dissolved in 200ml of acetic acid solution, and hydrochloric acid was slowly added dropwise, and the pH was adjusted to between 1-2. The reaction was carried out at 170°C for 10h. After the reaction was completed by TLC monitoring, saturated sodium bicarbonate was slowly added dropwise to the reaction solution, and the pH was adjusted to 7-8. 100ml of dichloromethane was added to the reaction solution, and the mixture was shaken and stirred. The organic phase was separated and collected and dried to obtain 39.70g of compound S4-3 with a yield of 87%.

[0065] Step 3: In a 500mL reaction bottle, compound S4-3 (35g, 0.12mol) and 2g of carbon disulfide were dissolved in 200ml of benzene and stirred evenly, then 75g of dichlorothionyl and 2g of aluminum chloride were added thereto, and the mixture was reacted at 30°C for 3h. After the reaction was completed by TLC monitoring, the reaction liquid was filtered, the filtrate was taken, heated and spin-dried to obtain 26.26g of compound S4-4, with a yield of 80%.

[0066] Step 4: In a 500mL reaction bottle, add compound S4-4 (25g, 0.09mol) and 1g aluminum chloride to 200ml nitric acid, set the temperature at 110℃ for reaction for 2h, monitor the reaction by TLC, spin dry, add to 200ml ethyl acetate solution, heat to 70℃, and after dissolution and clarification, slowly add 50ml of methanol to the solution, stir at constant temperature for 1h, then cool to room temperature and stir for 1h, filter, and dry the filter cake to obtain 23.30g of compound S4-5 with a yield of 80%.

[0067] Step 5: In a 500mL reaction bottle, compound S4-5 (20g, 0.06mol), 3g ammonium chloride and 1g copper powder were added to 200ml 70% ethanol aqueous solution, the temperature was set at 80°C for reaction for 1h, and after the reaction was completed by TLC monitoring, the reaction liquid was filtered, the filtrate was taken, heated and spin-dried, 200ml of ethyl acetate solution was added, heated to 50°C, and after dissolution and clarification, 50ml of petroleum ether was slowly added dropwise to the solution, and the temperature was stirred for 1h, then cooled to room temperature and stirred for 1h, filtered, and the filter cake was dried to obtain 15.21g of compound S4-6 with a yield of 84%.

[0068] Step 6: In a 500mL reaction bottle, compound S4-6 (15g, 0.05mol), 1g cuprous bromide and 1g sodium nitrite were added to 200ml water, hydrochloric acid was slowly added to the reaction solution, the temperature was set at 10°C for 2h, after TLC monitoring, saturated sodium bicarbonate was slowly added to the reaction solution, the pH was adjusted to 7-8, 50ml volume of dichloromethane was added to the reaction solution, shaken and stirred, separated, the organic phase was collected, and dried to obtain 15.22g of compound D4, with a yield of 83%. The molecular weight was determined by mass spectrometry (MALDI-TOF-MS) to be 350.51, which was determined to be the target compound D4.

[0069] Comparative Example 1:

[0070]

[0071] Step 1: In a 500mL reaction bottle, compound A5-1 (51.07g, 0.5mol), compound A5-2 (124.01g, 0.5mol), 89.7gTEA, 1gCuI, 1gPd(PPh3)2Cl2 were added to 200ml toluene at room temperature, the temperature was set at 75°C, N2 was introduced, and the reaction was continued for 15h. After the reaction was completed as monitored by TLC, dilute hydrochloric acid was added to quench the reaction, and the reaction was extracted with ethyl acetate. The organic phase was taken, washed with water and saturated sodium chloride, and dried to obtain 68.90g of compound S5-2 with a yield of 62%.

[0072] Step 2: In a 500 mL reaction bottle, compound S5-2 (60 g, 0.27 mol) and 1 g of Pd / C were dissolved in 200 ml of methanol solution, the reaction liquid was filtered, the filtrate was taken, heated and spin-dried to obtain 31.16 g of compound S5-3 with a yield of 51%.

[0073] Step 3: In a 300mL reaction bottle, compound S5-3 (30g, 0.13mol) was dissolved in 100ml methanol solution, and 20ml sodium hydroxide solution was added. The temperature was set at 80°C and the reaction was carried out for 20h. After the reaction was completed by TLC monitoring, hydrochloric acid was slowly added dropwise, and the pH was adjusted to between 1-2. The mixture was extracted with dichloromethane, and the organic phase was taken, washed with water and saturated sodium chloride, and dried to obtain 11.87g of compound S5-4 with a yield of 43%.

[0074] Step 4: In a 500mL reaction bottle, add compound S5-4 (10g, 0.05mol) and 1g aluminum chloride to 200ml nitric acid, set the temperature at 110℃ for reaction for 2h. After the reaction is completed, spin dry, add to 200ml of ethyl acetate solution, heat to 70℃, and after dissolution and clarification, slowly add 50ml of methanol to the solution, stir at a constant temperature for 1h, then cool to room temperature and stir for 1h, filter, and dry the filter cake to obtain 8.51g of compound S5-5 with a yield of 70%.

[0075] Step 5: In a 500mL reaction bottle, add compound S5-5 (8g, 0.03mol), 3g ammonium chloride and 1g iron powder to 200ml 70% ethanol aqueous solution, set the temperature to 80°C for reaction for 1h. After the reaction is completed, filter the reaction liquid, take the filtrate, heat and spin dry, add 200ml of ethyl acetate solution, heat to 50°C, and after dissolution and clarification, slowly add 50ml of petroleum ether to the solution, stir at a constant temperature for 1h, then cool to room temperature and stir for 1h, filter, and dry the filter cake to obtain 5.22g of compound S5-6 with a yield of 74%.

[0076] Step 6: In a 500mL reaction bottle, compound S5-6 (5g, 0.02mol), 1g potassium iodide and 1g sodium nitrite were added to 200ml water, hydrochloric acid was slowly added to the reaction solution, the temperature was set at 10°C for 2h, after the reaction, saturated sodium bicarbonate was slowly added to the reaction solution, the pH was adjusted to 7-8, 50ml of dichloromethane was added to the reaction solution, shaken and stirred, separated, the organic phase was collected, and dried to obtain 5.91g of compound D5, with a yield of 79%. The molecular weight was determined by mass spectrometry (MALDI-TOF-MS) to be 334.05, which was determined to be the target compound D5.

[0077] The above description is only a preferred embodiment of the present invention and is not intended to limit the present invention. Any modifications, equivalent substitutions, improvements, etc. made within the spirit and principle of the present invention should be included in the protection scope of the present invention.

Claims

1. A method for preparing an aromatic ketone derivative, characterized in that: The aromatic ketone derivative has a structural formula shown in Formula 1: wherein Ar1 and Ar2 are the same or different, and Ar1 and Ar2 are independently selected from C 6-30 The aromatic group; its preparation steps are as follows: Ar3 and Ar4 are the same or different, and Ar3 and Ar4 are independently selected from C substituted by one or more R 6-30 The aromatic group, wherein the R is independently selected from H, hydroxyl, amino, acyloxy, C 1-5 Alkoxy, substituted or unsubstituted C 1-10 Alkyl or substituted or unsubstituted C 6-30 Aryl, R is bonded or fused to Ar3 and Ar4; Step 1: using raw material Ⅰ, raw material Ⅱ, and metal ion-containing organic catalyst to perform ring-closing reaction to obtain intermediate Ⅰ; Step 2: Intermediate I, halogen acid and inorganic phosphorus undergo a ring-opening reaction to obtain intermediate II; Step 3: Intermediate II, a dehydrating agent, and a metal ion catalyst undergo a ring-closing reaction to obtain intermediate III; Step 4: One or more H on Ar3 or Ar4 of intermediate III is replaced by halogen to obtain intermediate IV.

2. The method for preparing an aromatic ketone derivative according to claim 1, characterized in that: The Ar1 and Ar2 are independently selected from the structural formula shown in Formula 2 or Formula 3: Wherein, * is the fusion site with cycloheptanone in formula 1, and any two sites * in formula 3 are fused with cycloheptanone in formula 1; m is a natural integer of 0-3, a+m≤4; n is a natural integer of 0-5, a+n≤6; X is a halogen; and a is a natural integer of 1-3.

3. The method for preparing an aromatic ketone derivative according to claim 2, characterized in that: a=1, the aromatic ketone derivative has the structural formula shown in Formula 4, Formula 5, and Formula 6: m1, m2, m3, m4 are natural integers of 0-3, n1, n2 are natural integers of 0-5, R1, R2, R3, R4, R5, R6 are the same or different, R1, R2, R3, R4, R5, R6 are independently selected from H, hydroxyl, acyloxy, amino substituted or unsubstituted by alkyl, C 1-5 Alkoxy, substituted or unsubstituted C 1-10 Alkyl or substituted or unsubstituted C 6-30 The aromatic group.

4. The method for preparing an aromatic ketone derivative according to claim 3, characterized in that: The C 1-5 The alkoxy group is selected from methoxy; the substituted or unsubstituted C 1-10 The alkyl group is selected from methyl, ethyl and n-propyl.

5. The method for preparing an aromatic ketone derivative according to claim 3, characterized in that: When the aromatic ketone derivative has the structural formula shown in Formula 4, m1 is 1, and m2 is a natural integer of 0-3, the preparation method thereof is as follows:

6. The method for preparing an aromatic ketone derivative according to claim 5, characterized in that: When m2 is 1, the R2 is selected from hydroxyl, methoxy, and phenyl. When R2 is phenyl, it is fused with phenylacetylene.

7. The method for preparing an aromatic ketone derivative according to claim 1, characterized in that: The halogen-containing acid in step 2 is selected from hydrogen halide.

8. The method for preparing an aromatic ketone derivative according to claim 1, characterized in that: The metal ion-containing organic catalyst in step 1 is selected from any one or more combinations of platinum group metal ion catalysts.

9. The method for preparing an aromatic ketone derivative according to claim 1, characterized in that: The step 4 specifically includes the following reactions: S4-1: adding intermediate III and a metal ion catalyst to a nitric acid solution to react to prepare intermediate IV in which at least one H on the aromatic group fused with cycloheptanone is replaced by a nitro group; S4-2: adding intermediate IV to an alcohol-water solvent, adding an acid solution and a metal catalyst to react to prepare intermediate V in which the nitro group is aminated; S4-3: reacting the intermediate V, an acid reagent, a nitrate, and a halide to prepare a product in which the amino group is substituted with a halogen; The product structure is shown in Formula 1.

10. The method for preparing an aromatic ketone derivative according to claim 9, characterized in that: In step S4-2, the acid solution is selected from any one or more combinations of ammonium chloride, hydrochloric acid, acetic acid, and nitric acid; the metal catalyst is selected from any one or more combinations of copper catalyst, iron catalyst, and aluminum catalyst.

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