Preparation method of oxime ester compound

Abstract

The invention provides a preparation method of an oxime ester compound, and belongs to the technical field of photoresist. The preparation method of the oxime ester compound comprises the following steps: carrying out Friedel-Crafts reaction on a compound shown in a formula I and a compound shown in a formula II to obtain a compound shown in a formula III; performing oximation reaction on the compound in the formula III to obtain a compound in a formula IV; performing esterification reaction on the compound in formula IV to obtain a compound in formula V; therefore, 2-[(E)-acetoxyl nitrogen subunit]-1-[4-(phenyl sulfenyl) phenyl] octyl-1-ketone is prepared through the reaction of diphenyl sulfide and n-caprylic acid, the reaction of 1-[4-(phenyl sulfenyl) phenyl]-1-octanone and sodium nitrite or alkyl nitrite, and the reaction of (2E)-2-(isonitroso)-1-[4-(phenyl sulfenyl) phenyl] octane-1-ketone and an acetylation reagent. The production cost for preparing the oxime ester compound is reduced, and the yield and the purity of the oxime ester compound are improved.

Description

Technical Field

[0001] The invention relates to the technical field of photoresists, and in particular to a method for preparing an oxime ester compound. Background Art

[0002] The photosensitive composition is a material obtained by adding a photopolymerization initiator to a polymerizable compound having an ethylenically unsaturated bond. The photosensitive composition can be polymerized and cured by irradiating it with light of 405 nm or 365 nm, and can be used in photocurable inks, photosensitive printing plates, various photoresists, etc. Since a photosensitive composition having sensitivity to a light source of a short wavelength can perform fine printing, a photopolymerization initiator having excellent sensitivity to a light source of 365 nm is particularly required.

[0003] As a photopolymerization initiator having excellent sensitivity to a light source of 365 nm, 2-[(E)-acetoxynitrylidene]-1-[4-(phenylthio)phenyl]octan-1-one is a negative photosensitive resin composition.

[0004] At present, Japanese patent JP2013249269A synthesizes 2-[(E)-acetoxy nitrogen subunit]-1-[4-(phenylthio) phenyl] octan-1-one in three steps. Among them, the first step is: using diphenyl sulfide as a raw material, aluminum chloride as a Lewis acid, and dichloromethane as a solvent, reacting at 20°C to synthesize the first step intermediate. The second step is: using ethanol as a solvent, hydroxylamine hydrochloride as an oximation reagent, ethanol / water, and reacting at 70°C to synthesize the second step intermediate. The third step is: using acetyl chloride as an acylating agent, triethylamine as a base, and dichloromethane as a solvent to synthesize 2-[(E)-acetoxy nitrogen subunit]-1-[4-(phenylthio) phenyl] octan-1-one. The specific reaction route is as follows:

[0005]

[0006] However, the following multi-substituted impurities exist in the first step of the synthesis reaction, the process has poor selectivity, low yield, and is difficult to purify. The specific reaction route is as follows:

[0007] Summary of the invention

[0008] In view of this, the object of the present invention is to provide a method for preparing an oxime ester compound, aiming to reduce the cost of preparing the oxime ester compound and improve the yield and purity of the oxime ester compound.

[0009] To achieve the above object, the present invention provides a method for preparing an oxime ester compound, comprising the following steps:

[0010]

[0011] (1) The compound of formula I and the compound of formula II are subjected to Friedel-Crafts reaction to obtain a compound of formula III;

[0012] (2) reacting the compound of formula III to obtain the compound of formula IV;

[0013] (3) The compound of formula IV is subjected to esterification reaction to obtain the compound of formula V.

[0014] Optionally, the step (1) comprises:

[0015] The compound of formula I, the compound of formula II and the first catalyst are added into the first solvent for reaction to obtain the compound of formula III.

[0016] Optionally, the step (1) comprises:

[0017] Add the compound of formula I, the compound of formula II and the first catalyst into the first solvent, raise the temperature to 60-70° C. and react for 12-24 hours;

[0018] Cooling to 20-30° C., adding a first acidic solution for quenching, and then separating to obtain a first organic phase;

[0019] After concentrating the first organic phase at 50-70° C., adding the first alcohol solvent and heating to 50-70° C. to dissolve and clarify, cooling to 10-20° C. to crystallize, filter and dry to obtain the compound of formula III.

[0020] Optionally, the first catalyst is selected from one of zinc chloride, ferric chloride and boron trifluoride;

[0021] The first solvent is selected from one or more of toluene, xylene, dichloroethane, nitrobenzene and nitromethane;

[0022] The first acidic solution is selected from one of a sulfuric acid aqueous solution, a phosphoric acid aqueous solution and a hydrochloric acid aqueous solution;

[0023] The first alcohol solvent is selected from one of methanol, ethanol and isopropanol;

[0024] The molar ratio of the compound I to the compound II is 1:1.05-2.

[0025] Optionally, the step (2) includes:

[0026] Add the compound of formula III into the second solvent, dissolve and clarify, cool to 10-20°C, add sodium nitrite, and drop concentrated hydrochloric acid at 10-20°C to react for 2-3 hours;

[0027] Add the first alkaline solution to quench, adjust the pH value to 8-9, and then separate the liquids to obtain a second organic phase;

[0028] The second organic phase is concentrated to obtain the compound of formula IV.

[0029] Optionally, the second solvent is selected from one of methyl tert-ether, ethyl acetate and tetrahydrofuran;

[0030] The first alkaline solution is selected from one of sodium bicarbonate solution, sodium carbonate solution, potassium carbonate solution, potassium hydroxide solution and sodium hydroxide solution;

[0031] The molar ratio of the compound of formula III to sodium nitrite is 1:1.2-1.5.

[0032] Optionally, the step (2) includes:

[0033] The compound of formula III is subjected to oximation reaction with alkyl nitrite and trimethylsilyl chloride to obtain the compound of formula IV.

[0034] Optionally, the step of reacting the compound of formula III with alkyl nitrite and trimethylsilyl chloride to obtain the compound of formula IV comprises:

[0035] Add the compound of formula III into the third solvent, dissolve and clarify, cool to 10-20°C, add alkyl nitrite, and dropwise add trimethylsilyl chloride at 10-20°C to react for 2-4 hours;

[0036] A second alkaline solution is added to quench, and the pH value is adjusted to 8-9, followed by separation to obtain a third organic phase;

[0037] The third organic phase is concentrated to obtain the compound of formula IV.

[0038] Optionally, the third solvent is selected from one of methyl tert-ether, ethyl acetate and tetrahydrofuran;

[0039] The alkyl nitrite is isobutyl nitrite or n-butyl nitrite;

[0040] The second alkaline solution is selected from one of sodium bicarbonate solution, sodium carbonate solution, potassium carbonate solution, potassium hydroxide solution and sodium hydroxide solution;

[0041] The molar ratio of the compound of formula III to the alkyl nitrite and trimethylsilyl chloride is 1:1.2-1.5:1.2-1.5.

[0042] Optionally, the step (3) comprises:

[0043] Add the compound of formula IV to the fourth solvent, dissolve and clarify, cool to 0-10°C, add the first basic compound first, then add the acetylating agent, and react at 0-10°C for 1-2h;

[0044] Add a second acidic solution to quench, adjust the pH value to 6-8, and then separate the liquids to obtain a fifth organic phase;

[0045] The fifth organic phase is washed and concentrated, and the second alcohol solvent is added to the concentrated fifth organic phase. The temperature is raised to 50-70° C. to dissolve and clarify, and then the temperature is lowered to 0-10° C. to crystallize, filter, and dry to obtain a compound of formula V.

[0046] Optionally, the fourth solvent is selected from one of methyl tert-ether, ethyl acetate and tetrahydrofuran;

[0047] The first basic compound is selected from one of triethylamine, pyridine, piperidine, DIEA, sodium bicarbonate and sodium carbonate;

[0048] The acetylating agent is selected from one of acetic anhydride and acetyl chloride;

[0049] The second acidic solution is selected from one of a sulfuric acid aqueous solution, a phosphoric acid aqueous solution and a hydrochloric acid aqueous solution;

[0050] The second alcohol solvent is selected from one of methanol, ethanol and isopropanol;

[0051] The molar ratio of the compound of formula IV to the first basic compound and the acetylating agent is 1:1.2-1.5:1.2-1.5.

[0052] The present invention provides a method for preparing an oxime ester compound, comprising the following steps: a compound of formula I and a compound of formula II are subjected to Friedel-Crafts reaction to obtain a compound of formula III; the compound of formula III is subjected to oximation reaction to obtain a compound of formula IV; the compound of formula IV is subjected to esterification reaction to obtain a compound of formula V. Thus, the present invention prepares 2-[(E)-acetoxy nitrogen subunit]-1-[4-(phenylthio)phenyl]octan-1-one by reacting diphenyl sulfide with n-octanoic acid, reacting 1-[4-(phenylthio)phenyl]-1-octanone with sodium nitrite or alkyl nitrite, and reacting (2E)-2-(isonitroso)-1-[4-(phenylthio)phenyl]octan-1-one with an acetylating agent, thereby reducing the production cost of preparing the oxime ester compound and improving the yield and purity of the oxime ester compound. BRIEF DESCRIPTION OF THE DRAWINGS

[0053] Figure 1 is the HPLC spectrum of the oxime ester compound of the present invention;

[0054] Figure 2 It is the H NMR spectrum of the oxime ester compound of the present invention. DETAILED DESCRIPTION

[0055] The technical solution of the present invention will be clearly and completely described below in conjunction with the embodiments of the present invention.

[0056] The present invention provides a method for preparing an oxime ester compound, comprising the following steps:

[0057]

[0058] (1) The compound of formula I and the compound of formula II are subjected to Friedel-Crafts reaction to obtain a compound of formula III;

[0059] (2) reacting the compound of formula III to obtain the compound of formula IV;

[0060] (3) The compound of formula IV is subjected to esterification reaction to obtain the compound of formula V.

[0061] Unless otherwise specified, the present invention has no special requirements on the sources of the raw materials used in the preparation, and commercially available products known to those skilled in the art can be used.

[0062] In the present invention, the step (1) may include:

[0063] The compound of formula I, the compound of formula II and the first catalyst are added into the first solvent for reaction to obtain the compound of formula III.

[0064] In the present invention, the step (1) may also include: adding the compound of formula I, the compound of formula II and the first catalyst into the first solvent, heating to 60-70° C. and reacting for 12-24 hours;

[0065] Cooling to 20-30° C., adding a first acidic solution for quenching, and then separating to obtain a first organic phase;

[0066] After concentrating the first organic phase at 50-70° C., adding the first alcohol solvent and heating to 50-70° C. to dissolve and clarify, cooling to 10-20° C. to crystallize for 1-2 hours, filtering and drying to obtain the compound of formula III.

[0067] In the present invention, the step (2) may include:

[0068] Add the compound of formula III into the second solvent, dissolve and clarify, cool to 10-20°C, add sodium nitrite, and drop concentrated hydrochloric acid at 10-20°C to react for 2-3 hours;

[0069] Add the first alkaline solution to quench, adjust the pH value to 8-9, and then separate the liquids to obtain a second organic phase;

[0070] The second organic phase is concentrated to obtain the compound of formula IV.

[0071] In the present invention, the step (2) may further include:

[0072] The compound of formula III is subjected to oximation reaction with alkyl nitrite and trimethylsilyl chloride to obtain the compound of formula IV.

[0073] Wherein, the compound of formula III is subjected to oximation reaction with alkyl nitrite and trimethylsilyl chloride to obtain the compound of formula IV as follows:

[0074]

[0075] In the present invention, the step of obtaining the compound of formula IV by oximation reaction of the compound of formula III with alkyl nitrite and trimethylsilyl chloride comprises:

[0076] Add the compound of formula III into the third solvent, dissolve and clarify, cool to 10-20°C, add alkyl nitrite, and dropwise add trimethylsilyl chloride at 10-20°C to react for 2-4 hours;

[0077] A second alkaline solution is added to quench, and the pH value is adjusted to 8-9, followed by separation to obtain a third organic phase;

[0078] The third organic phase is concentrated to obtain the compound of formula IV.

[0079] In the present invention, after obtaining the third organic phase, the third organic phase can be washed with saturated brine and then separated to obtain a fourth organic phase; then, the fourth organic phase is concentrated to obtain the compound of formula IV.

[0080] In the present invention, the step (3) comprises:

[0081] Add the compound of formula IV to the fourth solvent, dissolve and clarify, cool to 0-10°C, add the first basic compound first, then add the acetylating agent, and react at 0-10°C for 1-2h;

[0082] Add a second acidic solution to quench, adjust the pH value to 6-8, and then separate the liquids to obtain a fifth organic phase;

[0083] The fifth organic phase is washed and concentrated, and the second alcohol solvent is added to the concentrated fifth organic phase. The temperature is raised to 50-70° C. to dissolve and clarify, and the temperature is lowered to 0-10° C. to crystallize 1-2, filter, and dry to obtain a compound of formula V.

[0084] In the present invention, the first solvent is selected from one or more of toluene, xylene, dichloroethane, nitrobenzene and nitromethane;

[0085] In the present invention, the first acidic solution is selected from one of a sulfuric acid aqueous solution, a phosphoric acid aqueous solution and a hydrochloric acid aqueous solution;

[0086] In the present invention, the first alcohol solvent is selected from one of methanol, ethanol and isopropanol;

[0087] In the present invention, the molar ratio of the compound I to the compound II is 1:1.05-2.

[0088] In the present invention, the second solvent is selected from one of methyl tert-ether, ethyl acetate and tetrahydrofuran;

[0089] In the present invention, the first alkaline solution is selected from one of sodium bicarbonate solution, sodium carbonate solution, potassium carbonate solution, potassium hydroxide solution and sodium hydroxide solution;

[0090] In the present invention, the molar ratio of the compound of formula III to sodium nitrite is 1:1.2-1.5.

[0091] In the present invention, the third solvent is selected from one of methyl tert-ether, ethyl acetate and tetrahydrofuran;

[0092] In the present invention, the alkyl nitrite is isobutyl nitrite or n-butyl nitrite;

[0093] In the present invention, the second alkaline solution is selected from one of a sodium bicarbonate solution, a sodium carbonate solution, a potassium carbonate solution, a potassium hydroxide solution and a sodium hydroxide solution.

[0094] In the present invention, the molar ratio of the compound of formula III to the alkyl nitrite and trimethylsilyl chloride is 1:1.2-1.5:1.2-1.5.

[0095] In the present invention, the fourth solvent is selected from one of methyl tert-ether, ethyl acetate and tetrahydrofuran;

[0096] In the present invention, the first basic compound is selected from one of triethylamine, pyridine, piperidine, DIEA, sodium bicarbonate and sodium carbonate;

[0097] In the present invention, the acetylating agent is selected from one of acetic anhydride and acetyl chloride;

[0098] In the present invention, the second acidic solution is selected from one of a sulfuric acid aqueous solution, a phosphoric acid aqueous solution and a hydrochloric acid aqueous solution;

[0099] In the present invention, the second alcohol solvent is selected from one of methanol, ethanol and isopropanol;

[0100] In the present invention, the molar ratio of the compound of formula IV to the first basic compound and the acetylating agent is 1:1.2-1.5:1.2-1.5

[0101] The technical solution of the present invention will be clearly and completely described below in combination with the embodiments of the present invention.

[0102] Example 1

[0103] 1) Add diphenyl sulfide (10.0 g, 53.68 mmol), toluene (100 mL), zinc chloride (7.3 g, 56.37 mmol) and n-octanoic acid (8.1 g, 56.37 mmol) to a 250 mL three-necked flask, heat to 60 ° C and react for 12 hours. After the reaction is completed, cool the system to 20 ° C, add the reaction solution to a pre-prepared sulfuric acid aqueous solution (5 g concentrated sulfuric acid, 100 ml water) to quench, separate the organic phase, extract the aqueous phase once with 50 ml toluene, combine the organic phases, wash the organic phase with 100 ml purified water, concentrate the organic phase at 70 ° C, add 50 g methanol after concentration, heat to 50 ° C to completely dissolve and clarify, slowly cool to 10 ° C for crystallization for 1 h, filter, and air dry at 65 ° C to obtain 1-[4-(phenylthio)phenyl]-1-octanone as a white solid of 15.1 g, purity 95%, yield 90%.

[0104] 2) Add the compound of formula III 1-[4-(phenylthio)phenyl]-1-octanone (6.2 g, 19.84 mmol), tert-methyl ether (100 mL) and sodium nitrite (2.1 g, 29.76 mmol) to a 250 mL three-necked flask, cool to 10°C, and then slowly drop concentrated hydrochloric acid (3.3 ml, 39.68 mmol) into the system. During the dropwise addition, the reaction is exothermic and vented. The reaction temperature is controlled at 20°C for 3 h. After the reaction is complete, slowly add the reaction solution into the carbon prepared in advance. The mixture was quenched in an aqueous sodium bicarbonate solution (5 g of sodium bicarbonate, 100 ml of water). The pH of the test system was weakly alkaline. The organic phase was separated, and the aqueous phase was extracted with 100 ml of tert-methyl ether. The organic phases were combined, and the combined organic phases were washed with 100 ml of purified water. The organic phases were concentrated at 50° C. After concentration, 50 ml of tert-methyl ether was added and further concentrated to obtain (2E)-2-(isonitroso)-1-[4-(phenylthio)phenyl]octan-1-one as a yellow oil (6.1 g). The purity was 93% and the yield was 90%.

[0105] 3) Add the compound of formula IV (2E)-2-(isonitroso)-1-[4-(phenylthio)phenyl]octan-1-one (10 g, 29.29 mmol) to a 250 ml three-necked flask, stir and dissolve in ethyl acetate (50 ml), and cool to 10°C after clarification. Add triethylamine (3.9 g, 38.08 mmol) to the system without obvious heat release and gas release. Stir for 1 hour after addition, and keep the internal temperature at 10°C. Add acetic anhydride (3.6, 35.15 mmol) dropwise to the system, and the system will obviously heat up. Keep the internal temperature at 10°C for 2 hours. No solid will precipitate from the system. Slowly add 100 ml of acid water (2 g of sulfuric acid, 98 ml of water) The reaction mixture was added to the reaction solution for quenching. After quenching, the pH was adjusted to neutral and the liquids were separated. The aqueous layer was extracted once with 50 ml of ethyl acetate. The organic layers were combined and washed once with 100 ml of saturated sodium chloride aqueous solution until the pH was neutral. The ethyl acetate was concentrated at 60°C. After concentration, 50 ml of methanol was added, the temperature was raised to 60°C to dissolve and clarify, and then the temperature was slowly lowered to 10°C for crystallization for 2h. A large amount of crystalline solid was precipitated, which was filtered and dried in vacuo at 60°C to obtain 2-[(E)-acetoxynitrogen subunit]-1-[4-(phenylthio)phenyl]octan-1-one as white crystals (9.0 g, purity 99%, yield 80%).

[0106] Example 2

[0107] 1) Add diphenyl sulfide (25.0 g, 134.21 mmol), dichloroethane (250 mL), aluminum chloride (19.7 g, 147.63 mmol) and n-octanoic acid (20.3 g, 140.92 mmol) into a 500 mL three-necked flask, heat to 70 ° C and react for 24 hours. After the reaction is completed, cool the system to 28 ° C and add the reaction solution to the pre-prepared hydrochloric acid aqueous solution (15 g concentrated hydrochloric acid, 300 ml water) The organic phase was quenched in water, and the organic phase was separated. The aqueous phase was extracted with 100 ml of ethyl acetate. The organic phases were combined, washed with 200 ml of purified water, and concentrated at 50°C. After concentration, 150 g of ethanol was added, and the temperature was raised to 60°C to completely dissolve and clarify. The temperature was slowly lowered to 20°C for crystallization for 2 hours and then filtered. After air drying at 70°C, 1-[4-(phenylthio)phenyl]-1-octanone was obtained as a white solid of 31.5 g with a purity of 90% and a yield of 75%.

[0108] 2) Add the compound of formula III 1-[4-(phenylthio)phenyl]-1-octanone (15 g, 48.00 mmol), THF (250 mL) and sodium nitrite (5.0 g, 72.00 mmol) to a 500 ml three-necked flask, cool to 20°C, and then slowly drop concentrated hydrochloric acid (8 ml, 96 mmol) into the system. During the dropwise addition, the reaction is exothermic and gas is released. The internal temperature of the reaction is controlled at 10°C for 2 h. After the reaction is completed, the reaction solution is slowly added to the sodium carbonate aqueous solution (12 g sodium carbonate) prepared in advance. The reaction mixture was quenched in 200 ml of water (200 ml of sodium chloride solution) to test that the pH of the system was weakly alkaline. After quenching, the system was separated into layers to separate the organic phase. The aqueous phase was extracted with 100 ml of ethyl acetate. The organic phases were combined and washed with 150 ml of a saturated sodium chloride aqueous solution. The organic phases were concentrated at 60° C. After concentration, 100 ml of ethyl acetate was added to continue concentration to obtain (2E)-2-(isonitroso)-1-[4-(phenylthio)phenyl]octan-1-one as a yellow oil (13.1 g). The purity was 90% and the yield was 80%.

[0109] 3) Add the compound of formula IV (2E)-2-(isonitroso)-1-[4-(phenylthio)phenyl]octan-1-one (15 g, 43.93 mmol) and tert-methyl ether (100 ml) to a 250 ml three-necked flask. Stir and dissolve until clarified. Then cool to 0°C. Add sodium carbonate (6.1 g, 57.11 mmol) to the system. There is no obvious exothermic or gas release phenomenon. The sodium carbonate solid in the system does not dissolve. After the addition is completed, stir for 0.5 h. Keep the internal temperature at 0°C. Add acetic anhydride (5.4 g, 52.75 mmol) dropwise to the system. The system temperature rises significantly. Keep the internal temperature at 0°C for 1 h. Add 100 ml of hydrochloric acid water (5.8 g hydrochloric acid, 94.1 ml water) was slowly added to the reaction solution to quench. After quenching, the pH was adjusted to neutral and the liquids were separated. The aqueous layer was extracted once with 100 ml of methyl tert-ether, and the organic layers were combined. The organic layers were washed once with 200 ml of saturated sodium chloride aqueous solution until the pH was neutral. Ethyl acetate was concentrated at 50° C. After concentration, 75 ml of ethanol was added, the temperature was raised to 70° C. to dissolve and clarify, and then the temperature was slowly lowered to 0° C. for crystallization for 1 hour. A large amount of crystalline solids were precipitated, which were filtered and dried in vacuo at 50° C. to obtain 2-[(E)-acetoxynitrogen subunit]-1-[4-(phenylthio)phenyl]octan-1-one as white crystals (13.8 g). The purity was 99% and the yield was 82%.

[0110] Example 3

[0111] 1) Add diphenyl sulfide (10.0 g, 53.68 mmol), toluene (100 mL), ferric chloride (9.6 g, 59.18 mmol) and n-octanoic acid (8.1 g, 56.37 mmol) to a 250 mL three-necked flask, heat to 65 ° C for reaction for 16 hours, after the reaction is completed, cool the system by 25 ° C, add the reaction solution to a pre-prepared aqueous sulfuric acid solution (5 g concentrated sulfuric acid, 100 ml water) for quenching, separate the organic phase, extract the aqueous phase once with 50 ml toluene, combine the organic phases, wash the organic phase with 100 ml purified water, concentrate the organic phase at 60 ° C, add 50 g methanol after concentration, heat to 70 ° C to completely dissolve and clarify, slowly cool to 15 ° C for crystallization for 1.5 h, filter, and air dry at 55 ° C to obtain 1-[4-(phenylthio)phenyl]-1-octanone as a white solid of 15.1 g, with a purity of 91% and a yield of 73%.

[0112] 2) Add the compound of formula III 1-[4-(phenylthio)phenyl]-1-octanone (15 g, 48 mmol), THF (250 ml) and isobutyl nitrite (7.4 g, 72 mmol) into a 500 ml three-necked flask, and cool to 15° C. After cooling, slowly drop trimethylsilyl chloride (7.8 g, 72 mmol) into the system. During the dropwise addition, the reaction is exothermic and gas is released. The internal temperature of the reaction is controlled at 15° C. for 2.5 h. After the reaction is completed, add the prepared sodium bicarbonate aqueous solution (7.5 g sodium bicarbonate, The reaction mixture was quenched in 200 ml of water) to test the pH value of the system to be weakly alkaline. After quenching, the system was layered to separate the upper organic phase, the aqueous phase was extracted with 100 ml of ethyl acetate, the organic phases were combined, and the combined organic phases were washed with 150 ml of a saturated sodium chloride aqueous solution. The organic phases were concentrated at 65° C. After concentration, 100 ml of ethyl acetate was added to continue concentration to obtain (2E)-2-(isonitroso)-1-[4-(phenylthio)phenyl]octan-1-one as a yellow oil (13.9 g). The purity was 92.4% and the yield was 85.0%.

[0113] 3) Add the compound of formula IV (2E)-2-(isonitroso)-1-[4-(phenylthio)phenyl]octan-1-one (10 g, 29.29 mmol) to a 250 ml three-necked flask, stir and dissolve in ethyl acetate (50 ml), and cool to 5°C after clarification. Add triethylamine (3.9 g, 38.08 mmol) to the system without obvious heat release and gas release. Stir for 0.5 h after addition, and keep the internal temperature at 5°C. Add acetic anhydride (3.2 g, 40.76 mmol) dropwise to the system, and the system will obviously heat up. Keep the internal temperature at 5°C for 1.5 h, and no solid will precipitate from the system. Add 100 ml of acid water (2 g of sulfuric acid, 98 ml of Water) was slowly added to the reaction solution to quench. After quenching, the pH was adjusted to neutral and the liquids were separated. The aqueous layer was extracted once with 50 ml of ethyl acetate, the organic layers were combined, and the organic layers were washed once with 100 ml of saturated sodium chloride aqueous solution until the pH was neutral. The ethyl acetate was concentrated at 55° C. After concentration, 50 ml of methanol was added, the temperature was raised to 70° C. to dissolve and clarify, and then the temperature was slowly lowered to 5° C. for crystallization for 1.5 hours to precipitate a large amount of crystalline solids. The solids were filtered and dried in vacuo at 50° C. to obtain 2-[(E)-acetoxynitrogen subunit]-1-[4-(phenylthio)phenyl]octan-1-one as white crystals (9.0 g, purity 99%, yield 81%).

[0114] Example 4

[0115] 1) Add diphenyl sulfide (25.0 g, 134.21 mmol), dichloroethane (250 mL), aluminum chloride (19.7 g, 147.63 mmol) and n-octanoic acid (20.3 g, 140.92 mmol) to a 500 mL three-necked flask, heat to 60 ° C and react for 20 hours. After the reaction is completed, cool the system to 22 ° C and add the reaction solution to the pre-prepared hydrochloric acid aqueous solution (15 g concentrated hydrochloric acid, 300 ml water) The mixture was quenched, the organic phase was separated, the aqueous phase was extracted with 100 ml of ethyl acetate, the organic phases were combined, the organic phases were washed with 200 ml of purified water, and the organic phase was concentrated at 60°C. After concentration, 150 g of ethanol was added, the temperature was raised to 65°C to completely dissolve and clarify, the temperature was slowly lowered to 10°C to crystallize for 1.2 hours, and then filtered. After air drying at 60°C, 1-[4-(phenylthio)phenyl]-1-octanone was obtained as a white solid of 31.5 g with a purity of 90% and a yield of 76%.

[0116] 2) Add the compound of formula III 1-[4-(phenylthio)phenyl]-1-octanone (20 g, 64 mmol), methyl tert-butyl ether (300 ml) and n-butyl nitrite (9.9 g, 96 mmol) into a 500 ml three-necked flask, cool to 18°C, and then slowly drop trimethylsilyl chloride (10.5 g, 96 mmol) into the system. During the dropwise addition, the reaction is exothermic and gas is released. The internal temperature of the reaction is controlled at 13°C and the reaction is continued for 2.2 h. After the reaction is completed, an aqueous sodium hydroxide solution (8 g sodium hydroxide, 300 ml) is added into the reaction system. The reaction mixture was quenched in 100 ml of water and the pH of the test system was weakly alkaline. After quenching, the system was separated into layers to separate the organic phase. The aqueous phase was extracted with 150 ml of methyl tert-butyl ether. The organic phases were combined and washed with 200 ml of a saturated sodium chloride aqueous solution. The organic phases were concentrated at 55° C. After concentration, 100 ml of methyl tert-butyl ether was added to continue concentration to obtain (2E)-2-(isonitroso)-1-[4-(phenylthio)phenyl]octan-1-one as a yellow oil (19.3 g). The purity was 90.7% and the yield was 88.5%.

[0117] 3) Add the compound of formula IV (2E)-2-(isonitroso)-1-[4-(phenylthio)phenyl]octan-1-one (15 g, 43.93 mmol) and tert-methyl ether (100 ml) to a 250 ml three-necked flask. Stir and dissolve until clarified. Then cool to 2°C. Add sodium carbonate (6.1 g, 57.11 mmol) to the system. There is no obvious exothermic or gas release phenomenon. The sodium carbonate solid in the system does not dissolve. After the addition is complete, stir for 0.5 h, maintain the internal temperature at 3°C. Add acetyl chloride (4.3 g, 54.77 mmol) dropwise to the system. The system temperature rises significantly. Maintain the internal temperature at 8°C for 1 h. Add 100 ml of hydrochloric acid water (5.8 g hydrochloric acid, 94. 1ml water) was slowly added to the reaction solution to quench. After quenching, the pH was adjusted to neutral and the liquids were separated. The aqueous layer was extracted once with 100ml of tert-methyl ether, and the organic layers were combined. The organic layers were washed once with 200ml of saturated sodium chloride aqueous solution until the pH was neutral. Ethyl acetate was concentrated at 55°C. After concentration, 75ml of ethanol was added, the temperature was raised to 55°C to dissolve and clarify, and then the temperature was slowly lowered to 2°C for crystallization for 1h. A large amount of crystalline solid was precipitated, which was filtered and dried in vacuo at 65°C to obtain 2-[(E)-acetoxynitrogen subunit]-1-[4-(phenylthio)phenyl]octan-1-one as white crystals (13.8g, purity 99%, yield 83%).

[0118] Compared with the prior art, the preparation method of 2-[(E)-acetoxy nitrogen subunit]-1-[4-(phenylthio)phenyl]octan-1-one of the present invention uses n-octanoic acid and Lewis acid catalyst to carry out Friedel-Crafts acylation reaction, which is lower in cost and higher in yield than using n-octanoyl chloride as raw material. The intermediates in each step of the route of the present invention are easy to purify, the purity of the final product is above 99%, and the quality is easy to control. In the reaction step of diphenyl sulfide and n-octanoic acid, since n-octanoic acid is not as active as n-octanoyl chloride, the system selectivity is good, no multi-substituted impurities will appear, and the yield is 70-90%; in the reaction step of 1-[4-(phenylthio)phenyl]-1-octanone and sodium nitrite, the starting material is not easy to degrade, the operation is simpler, and the yield can reach more than 80%; the total yield of the three steps can reach 48% to 67%, and a needle-shaped crystal product can be synthesized with a purity of more than 99%. In the reaction step of (2E)-2-(isonitroso)-1-[4-(phenylthio)phenyl]octan-1-one and the acetylating agent, the alkaline compound is more widely selected as the acid-binding agent, and the alcohol solvent is used for recrystallization purification, and the yield can reach more than 80%.

[0119] Therefore, the present invention prepares 2-[(E)-acetoxy nitrogen subunit]-1-[4-(phenylthio)phenyl]octan-1-one through the reaction of diphenyl sulfide and n-octanoic acid, the reaction of 1-[4-(phenylthio)phenyl]-1-octanone and sodium nitrite or alkyl nitrite, and the reaction of (2E)-2-(isonitroso)-1-[4-(phenylthio)phenyl]octan-1-one and an acetylating agent, thereby reducing the production cost of preparing oxime ester compounds and improving the yield and purity of oxime ester compounds.

[0120] Although the above embodiment describes the present invention in detail, it is only a part of the embodiments of the present invention rather than all the embodiments. People can also obtain other embodiments based on this embodiment without creativity, and these embodiments all fall within the protection scope of the present invention.

Claims

1. A method for preparing an oxime ester compound, characterized in that: The following steps are involved: (1) The compound of formula I and the compound of formula II are subjected to Friedel-Crafts reaction to obtain a compound of formula III; (2) the compound of formula III is subjected to an oximation reaction to obtain a compound of formula IV; (3) The compound of formula IV is subjected to esterification reaction to obtain the compound of formula V.

2. The method for preparing an oxime ester compound according to claim 1, wherein The step (1) comprises: Add the compound of formula I, the compound of formula II and the first catalyst into the first solvent, raise the temperature to 60-70° C. and react for 12-24 hours; Cooling to 20-30° C., adding a first acidic solution for quenching, and then separating to obtain a first organic phase; After concentrating the first organic phase at 50-70° C., adding the first alcohol solvent and heating to 50-70° C. to dissolve and clarify, cooling to 10-20° C. to crystallize, filter and dry to obtain the compound of formula III.

3. The method for preparing an oxime ester compound according to claim 2, wherein: The first catalyst is selected from one of zinc chloride, aluminum chloride, ferric chloride and boron trifluoride; The first solvent is selected from one or more of toluene, xylene, dichloroethane, nitrobenzene and nitromethane; The first acidic solution is selected from one of a sulfuric acid aqueous solution, a phosphoric acid aqueous solution and a hydrochloric acid aqueous solution; The first alcohol solvent is selected from one of methanol, ethanol and isopropanol; The molar ratio of the compound I to the compound II is 1:1.05-2.

4. The method for preparing an oxime ester compound according to any one of claims 1 to 3, characterized in that: The step (2) comprises: Add the compound of formula III into the second solvent, dissolve and clarify, cool to 10-20°C, add sodium nitrite, and drop concentrated hydrochloric acid at 10-20°C to react for 2-3 hours; Add the first alkaline solution to quench, adjust the pH value to 8-9, and then separate the liquids to obtain a second organic phase; The second organic phase is concentrated to obtain the compound of formula IV.

5. The method for preparing an oxime ester compound according to claim 4, characterized in that: The second solvent is selected from one of tertiary methyl ether, ethyl acetate and tetrahydrofuran; The first alkaline solution is selected from one of sodium bicarbonate solution, sodium carbonate solution, potassium carbonate solution, potassium hydroxide solution and sodium hydroxide solution; The molar ratio of the compound of formula III to sodium nitrite is 1:1.2-1.

5.

6. The method for preparing an oxime ester compound according to any one of claims 1 to 3, characterized in that: The step (2) comprises: The compound of formula III is subjected to oximation reaction with alkyl nitrite and trimethylsilyl chloride to obtain the compound of formula IV.

7. The method for preparing an oxime ester compound according to claim 6, wherein: The step of subjecting the compound of formula III to oximation reaction with alkyl nitrite and trimethylsilyl chloride to obtain the compound of formula IV comprises: Add the compound of formula III into the third solvent, dissolve and clarify, cool to 10-20°C, add alkyl nitrite, and dropwise add trimethylsilyl chloride at 10-20°C to react for 2-4 hours; A second alkaline solution is added to quench, and the pH value is adjusted to 8-9, followed by separation to obtain a third organic phase; The third organic phase is concentrated to obtain the compound of formula IV.

8. The method for preparing an oxime ester compound according to claim 7, wherein: The third solvent is selected from one of methyl tert-ether, ethyl acetate and tetrahydrofuran; The alkyl nitrite is isobutyl nitrite or n-butyl nitrite; The second alkaline solution is selected from one of sodium bicarbonate solution, sodium carbonate solution, potassium carbonate solution, potassium hydroxide solution and sodium hydroxide solution; The molar ratio of the compound of formula III to the alkyl nitrite and trimethylsilyl chloride is 1:1.2-1.5:1.2-1.

5.

9. The method for preparing an oxime ester compound according to claim 1, 2, 3, 5, 7 or 8, characterized in that: The step (3) comprises: Add the compound of formula IV to the fourth solvent, dissolve and clarify, cool to 0-10°C, first add the first basic compound, then add the acetylating agent, and react at 0-10°C for 1-2h; Add a second acidic solution to quench, adjust the pH value to 6-8, and then separate the liquids to obtain a fifth organic phase; The fifth organic phase is washed and concentrated, and the second alcohol solvent is added to the concentrated fifth organic phase. The temperature is raised to 50-70° C. to dissolve and clarify, and then the temperature is lowered to 0-10° C. to crystallize, filter, and dry to obtain a compound of formula V.

10. The method for preparing an oxime ester compound according to claim 9, wherein: The fourth solvent is selected from one of methyl tert-ether, ethyl acetate and tetrahydrofuran; The first basic compound is selected from one of triethylamine, pyridine, piperidine, DIEA, sodium bicarbonate and sodium carbonate; The acetylating agent is selected from one of acetic anhydride and acetyl chloride; The second acidic solution is selected from one of a sulfuric acid aqueous solution, a phosphoric acid aqueous solution and a hydrochloric acid aqueous solution; The second alcohol solvent is selected from one of methanol, ethanol and isopropanol; The molar ratio of the compound of formula IV to the first basic compound and the acetylating agent is 1:1.2-1.5:1.2-1.5.

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