Synthesis process of cresol trozole trisilane

Abstract

The invention relates to the technical field of chemical synthesis, and particularly discloses a cresol trozole trisilane synthesis process, which comprises the following steps: by taking easily available UV-P in the market as a raw material, reacting with cheap and easily available propionyl chloride, reacting with triphenylphosphine to obtain alkene, and finally silanizing to obtain a target product. The whole reaction process has the advantages of cheap and easily available raw materials, low raw material cost, mild reaction conditions, no high-temperature 200 DEG C transposition reaction, strong reaction operability, high conversion rate, few by-products, almost equivalent reaction, no waste of raw materials, high conversion rate, total product yield of more than 80%, conventional three-step reaction, low industrialization requirement and high product yield, and is suitable for industrial production. The method has the advantages of no special requirements on production equipment, high production feasibility, less three wastes and low energy consumption, and is a synthetic route suitable for industrial production.

Description

TECHNICAL FIELD

[0001] The present application relates to the technical field of chemical synthesis, and specifically discloses a synthesis process of methylphenyltriazole trisilane. BACKGROUND

[0002] It is well known that when the skin is exposed to excessive amounts of UV light, it is permanently damaged. Among these, UV light with a wavelength of 280-320 nm (also called UV-B) can accelerate the production of pigments, causing the skin to darken; rays with a wavelength of 280 to 320 nm (called UV-B rays) can damage the natural tanning tension. For these reasons, and for aesthetic reasons, there is always a need to control this natural tanning and thus the color of the skin, so this UV-B radiation should be shielded.

[0003] UV light with a wavelength of 320-400 nm (also called UV-A) can penetrate the dermis layer of the skin, causing loss of skin elasticity and accelerated appearance of wrinkles, leading to skin aging; in abnormal cases, it can even become a pigmented skin cancer, etc. UV-A rays, in particular, cause loss of skin elasticity and appearance of wrinkles, leading to premature aging of the skin. Therefore, for aesthetic and cosmetic and health reasons, more and more people want to control the effects of UV-A rays on the skin.

[0004] The sunscreen agents used in sunscreen cosmetics are divided into physical sunscreen agents and chemical sunscreen agents, and methylphenyltriazole trisiloxane is a commonly used new type of chemical sunscreen agent, which is widely used in various high-end brands of sunscreen cream, sunscreen milk, hair conditioner and other products, with a maximum addition amount of 15%. Methylphenyltriazole trisiloxane is a new type of sunscreen agent containing a silicone structure, which has excellent formulation compatibility, and its maximum absorption wavelength is at 303 nm and 343 nm, basically covering the entire UV light wavelength band of 280-400 nm, which can more comprehensively reduce the damage of UV light to the skin; at the same time, due to the special conjugated structure and molecular hydrogen bond in its molecular structure, it has long-term light stability, thereby better improving the SPF value of the compounded system.

[0005] At present, there are few reported literatures on the synthesis of methylphenyltriazole trisiloxane.

[0006] Route one: In the patent WO2012 / 055063 and patent WO2012 / 055064, using 2-(2-hydroxy-5-methylphenyl) benzotriazole as raw material, using potassium carbonate as deprotonation agent, water / benzyl alcohol (or diphenyl ether, tetrahydro naphthalene and other high boiling point solvents) as mixed solvent, under the condition of phase transfer catalyst, and methyl allyl chloride occurs etherification reaction to synthesize intermediate I, then intermediate I occurs Claisen rearrangement reaction under the condition of more than 200 DEG C to synthesize key intermediate II, then intermediate II occurs silicon hydrogen addition under the condition of cast catalyst to synthesize target product, the synthesis route is shown as follows:

[0007] In the above process, the first step is a two-phase reaction, which needs more phase transfer catalyst and excess deprotonation agent such as potassium carbonate, not only causing waste of raw materials, but also needing a long reaction time (at least more than 20 hours), and the efficiency is very low; the second step adopts traditional Claisen rearrangement, which needs a temperature of more than 200 DEG C, at the same time, Claisen rearrangement is an exothermic reaction after reaction initiation, and once the temperature exceeds 230 DEG C, further rearrangement impurities will be generated, in the scale-up production, high temperature not only increases the difficulty and danger of industrialization, but also is exothermic reaction while heating, so it is difficult to strictly control the temperature; the third step adopts classical silicon hydrogen addition, because there are three N elements in the molecule, the lone pair electrons of N element will reduce the activity of cast catalyst, and the raw materials, reaction solvent and feeding process of this step need to be strictly controlled without water and oxygen, the anhydrous solvent is not only expensive but also difficult to reuse after recovery, and the reaction temperature needs to be strictly controlled at 65-70 DEG C, and the activity of the catalyst will be lower and the conversion rate will be reduced if the temperature is too high.

[0008] The above process can be realized in the small test stage of each step, but in the scale-up production, the raw material is wasted, the production efficiency is low, the process parameters are harsh, the danger coefficient is high, and it is also difficult to control the generation of impurities, the solvent is difficult to recover and reuse, and the three wastes are increased.

[0009] Therefore, it is necessary to provide a new synthesis process of cresol trisiloxane to solve the above existing problems. SUMMARY

[0010] In view of the problems mentioned in the prior art, the first aspect of the present application provides a cresol trisiloxane synthesis process, comprising: Compound 1, a first organic solvent, a first catalyst and propionyl chloride are mixed to obtain compound 2 by reaction; ; The compound 2 is obtained by one or more steps of reaction .

[0011] In some embodiments of the process for synthesizing the trisilane of cresol triazole, the first organic solvent is selected from the group consisting of N,N-dimethylformamide, toluene, tetrahydrofuran, methanol, ethanol, dichloromethane, and mixtures thereof.

[0012] In some embodiments of the process for synthesizing the trisilane of cresol triazole, the first catalyst is selected from the group consisting of aluminum trichloride, iron trichloride, zinc chloride, aluminum trichloride, tin tetrachloride.

[0013] In some embodiments of the process for synthesizing the trisilane of cresol triazole, the first organic solvent is selected from the group consisting of toluene, xylene, tetrahydrofuran, methanol, ethanol, and mixtures thereof.

[0014] In some embodiments of the process for synthesizing the trisilane of cresol triazole, the molar amount of the first catalyst added per 1 L of the first organic solvent is 1-3 mol.

[0015] In some embodiments of the process for synthesizing the trisilane of cresol triazole, the molar amount of compound 1 added per 1 L of the first organic solvent is 300-500 mmol.

[0016] In some embodiments of the process for synthesizing the trisilane of cresol triazole, compound 2 is subjected to one or more steps to obtain compound 5, including the steps of: mixing compound 2, boron tribromide, and a second organic solvent to obtain compound 3; ; Compound 3 is subjected to one or more steps to obtain compound 5.

[0017] In some embodiments of the process for synthesizing the trisilane of cresol triazole, the second organic solvent is selected from the group consisting of toluene, xylene, dichloromethane, tetrahydrofuran, and mixtures thereof.

[0018] In some embodiments of the process for synthesizing the trisilane of cresol triazole, the molar amount of boron tribromide added per 1 L of the second organic solvent is 700-900 mmol.

[0019] In some embodiments of the process for synthesizing the trisilane of cresol triazole, compound 3 is subjected to one or more steps to obtain compound 5, including the steps of: mixing halogenated alkane, a third organic solvent, triphenylphosphine, a first base, and compound 3 under an inert atmosphere to obtain compound 4; ; Compound 4 is subjected to one or more steps to obtain compound 5.

[0020] In some specific embodiments of the cresoltrazol trisilane synthesis process described in the first aspect, the third organic solvent is selected from any one or a mixture of acetonitrile, toluene, dichloromethane, tert-butanol, diethyl ether, tert-butylmethyl ether, and xylene.

[0021] In some specific embodiments of the cresoltrazolium trisilane synthesis process described in the first aspect, the molar amount of haloalkanes added to each 1L of the third organic solvent is 200~400mmol.

[0022] In some specific embodiments of the cresoltrazol trisilane synthesis process described in the first aspect, the haloalkane is selected from iodomethane, chloromethane, or a mixture thereof.

[0023] In some specific embodiments of the cresoltrazolium trisilane synthesis process described in the first aspect, the molar amount of triphenylphosphine added to each 1L of the third organic solvent is 300~500mmol.

[0024] In some specific embodiments of the cresoltrazolium trisilane synthesis process described in the first aspect, the first base is selected from any one or a mixture of butyllithium, sodium methoxide, sodium hydroxide, sodium tert-butoxide, potassium tert-butoxide, and LDA.

[0025] In some specific embodiments of the cresoltrazolium trisilane synthesis process described in the first aspect, the molar amount of the first alkali added to each 1L of the third organic solvent is 200~500mmol.

[0026] In some specific embodiments of the cresoltrazolium trisilane synthesis process described in the first aspect, compound 4 is obtained by a substrate reaction followed by one or more steps to yield compound 5. Compound 4, the fourth organic solvent, the second catalyst, and heptamethyltrisiloxane were mixed and reacted to give compound 5; .

[0027] In some specific embodiments of the cresoltrazolium trisilane synthesis process described in the first aspect, the fourth organic solvent is selected from any one or a mixture of toluene, xylene, dichloroethane, and diethyl ether.

[0028] In some specific embodiments of the cresoltrazolium trisilane synthesis process described in the first aspect, the second catalyst is selected from any one or a mixture of Pd / C catalysts, Speier catalysts, and Karstedt catalysts.

[0029] In some specific embodiments of the cresoltrazolium trisilane synthesis process described in the first aspect, the synthesis method of compound 1 is as follows: Compound UV-P, the second base, the fifth organic solvent, and CH3I were mixed and reacted to give compound 1. ; In some specific embodiments of the cresoltrazolium trisilane synthesis process described in the first aspect, the fifth organic solvent is selected from any one or a mixture of N,N-dimethylformamide, toluene, tetrahydrofuran, methanol, ethanol, and dichloromethane.

[0030] In some specific embodiments of the cresoltrazolium trisilane synthesis process described in the first aspect, the second base is selected from any one or a mixture of potassium carbonate, sodium carbonate, and butyllithium.

[0031] In some specific embodiments of the cresoltrazolium trisilane synthesis process described in the first aspect, the molar amount of compound UV-P added to each 1L of organic solvent is 300~400mmol.

[0032] In some specific embodiments of the cresoltrazol trisilane synthesis process described in the first aspect, the molar amount of the second alkali added to each 1L of organic solvent is 800~1200mmol.

[0033] In some specific embodiments of the cresoltrazolium trisilane synthesis process described in the first aspect, the molar amount of CH3I added to each 1L of organic solvent is 300~500mmol.

[0034] "Room temperature" refers to the indoor ambient temperature, which can be 12℃~37℃, 20℃~30℃, 25℃~30℃, or approximately 25℃.

[0035] The reagents used in this invention have not undergone further purification and are all purchased from the open and legal market, for example, from Shanghai Aladdin Biochemical Technology Co., Ltd., Xilong Scientific Co., Ltd., Sinopharm Chemical Reagent Co., Ltd., and Shanghai McLean Biochemical Technology Co., Ltd.

[0036] To address the problems existing in the prior art, the present invention provides a synthesis process for cresoltrazol trisiloxane, comprising the following steps: The above-described technical solution of the present invention has at least the following beneficial effects: This process uses readily available UV-P as a raw material, reacting it with inexpensive and readily available propionyl chloride, then reacting it with methylphosphine ylide to form an alkene, and finally silanizing it to obtain the target product. The entire reaction process utilizes inexpensive and readily available raw materials, resulting in low raw material costs.

[0037] 2: The reaction conditions are mild, with no high-temperature (200℃) transposition reaction, making the reaction highly operable, with high conversion rate and few by-products.

[0038] 3: The reactions are almost all carried out in equivalence, which does not cause waste of raw materials, has a high conversion rate, a total product yield of over 80%, and low raw material costs.

[0039] 4. All three steps are conventional reactions with low requirements for industrialization. There are no special requirements for production equipment, making production highly feasible. It produces less waste and consumes less energy, making it a suitable synthetic route for industrial production. Detailed Implementation

[0040] To make the objectives, technical solutions, and advantages of this invention clearer, the invention will be further described in detail below with reference to embodiments. The specific embodiments described herein are for illustrative purposes only and are not intended to limit the invention in any way. Furthermore, descriptions of well-known structures and technologies are omitted in the following description to avoid unnecessarily obscuring the concepts of this disclosure. The technical solutions of this invention are illustrated below, and the scope of protection claimed by this invention includes, but is not limited to, the following embodiments.

[0041] Example 1

[0042] Step 1: Compound UV-P (100 mmol, 1.0 eq) and K2CO3 (290 mmol, 2.9 eq) were added to DMF (270 mL), and CH3I (120 mmol, 1.2 eq) was added dropwise under ice bath conditions. The mixture was stirred overnight at room temperature. After the reaction was complete, water was added, and the mixture was extracted with ethyl acetate. The combined organic phases were washed with saturated brine, dried over anhydrous sodium sulfate, filtered, and subjected to rotary evaporation under reduced pressure. The resulting solution was then subjected to column chromatography to obtain compound 1.

[0043]

[0044] Step 2: Compound 1 (100 mmol, 1.0 eq), toluene (200 mL) and aluminum trichloride (0.2 mol, 2.0 eq) were added to the reaction vessel and stirred for 30 min. Then propionyl chloride (0.13 mol, 1.3 eq) was added dropwise. The mixture was heated to 80 °C and reacted for 7 h. The reaction progress was monitored by TLC. After the reaction was completed, the reaction solution was cooled to room temperature and filtered to obtain a yellow solution of compound 2.

[0045]

[0046] Step 3: Under ice bath conditions, add 70 mL of a dichloromethane solution containing 80 mmol of boron tribromide to the yellow solution of compound 2 obtained in Step 1. After the addition is complete, continue stirring for 3 h. After the reaction is complete, pour in ice water, extract with dichloromethane, wash the organic phase with saturated brine, combine the organic phases, dry the combined organic phases with anhydrous sodium sulfate, filter, evaporate the filtrate under reduced pressure, and precipitate by column chromatography to obtain compound 3.

[0047] ; Step 4: After replacing the gas in the reactor with N2 three times, add iodomethane (CH3I, 3 eq), toluene (200 ml), and triphenylphosphine (2 eq). Cool to 0°C in an ice-water bath, and add dropwise a toluene solution of butyllithium (200 ml, 2.0 eq) to obtain the reaction system. Stir for 30 min, and then add dropwise a toluene solution of compound 3 (100 ml) to the reaction system. The reaction continues until the reactants are completely reacted as monitored by HPLC. Cool to room temperature, quench the reaction with saturated NH4Cl aqueous solution, filter to remove the generated triphenylphosphine oxide, wash the filter residue with a small amount of toluene, add water to separate the layers, extract the aqueous layer three times with toluene, combine the organic phases, wash with saturated sodium chloride brine, dry with anhydrous sodium sulfate, filter and evaporate the solvent to obtain the crude product of compound 4, which can be directly used for the next reaction.

[0048]

[0049] Step 5: The crude product of compound 4 was mixed with toluene (300 mL), palladium catalyst (5% Pd / C catalyst, 45 mg palladium) was added and stirred for 30 min, the temperature was raised to 80 °C, and heptamethyltrisiloxane (24.4 g, 1.1 eq) was added dropwise. The reaction progress was monitored by TLC. After the reaction was completed, the reaction solution was cooled to room temperature, concentrated under reduced pressure to remove the solvent, 50 mL acetone was added, and the solution was heated to reflux to dissolve. Then 200 mL ethanol was added, and the temperature was lowered to 0-5 °C. A large amount of white solid precipitated. After crystallization and stirring for 3 h, the solution was filtered and dried under vacuum to obtain compound 5, 36.5 g of white solid, with a total yield of 72.9% and a purity of 99.3%.

[0050] Example 2 Step 1: Compound 1 (100 mmol, 1.0 eq), toluene (200 mL) and ferric chloride (3.0 eq) were added to the reaction vessel and stirred for 30 min. Then propionyl chloride (1.3 eq) was added dropwise, and the mixture was heated to 85 °C and reacted for 7 h. The reaction progress was monitored by TLC. After the reaction was completed, the reaction solution was cooled to room temperature and filtered to obtain a yellow solution containing compound 2.

[0051] Step 2: Under ice bath conditions, add 70 mL of a dichloromethane solution containing 80 mmol of boron tribromide to the yellow solution of compound 2 obtained in Step 1. After the addition is complete, continue stirring for 3 h. After the reaction is complete, pour in ice water, extract with dichloromethane, wash the organic phase with saturated brine, combine the organic phases, dry the combined organic phases with anhydrous sodium sulfate, filter, evaporate the filtrate under reduced pressure, and precipitate by column chromatography to obtain compound 3.

[0052] Step 3: After replacing the gas in the reactor with N2 three times, add bromomethane (CH3Br, 3.0 eq), toluene (400 mL), triphenylphosphine (1.3 eq), and sodium methoxide (2.0 eq). Heat to 60 °C and reflux. During reflux, add a toluene solution of compound 3 (90 mL) dropwise. After the addition is complete, continue reflux until the reactants are completely reacted as monitored by HPLC. Cool, filter to remove the generated triphenylphosphine oxide, wash the filter residue with a small amount of toluene, add water, separate the layers, extract the aqueous layer three times with toluene, combine the organic phases, wash with saturated sodium chloride brine, dry with anhydrous sodium sulfate, filter and evaporate the solvent to obtain the crude product of compound 4, which can be directly used for the next reaction.

[0053] Step 4: The crude product of compound 4 was mixed with toluene (300 mL), palladium catalyst (5% Pd / C catalyst, 45 mg palladium) was added and stirred for 30 min, the temperature was raised to 90 °C, and heptamethyltrisiloxane (24.4 g, 1.1 eq) was added dropwise. The reaction progress was monitored by TLC. After the reaction was completed, the reaction solution was cooled to room temperature, concentrated under reduced pressure to remove the solvent, 50 mL acetone was added, and the solution was heated to reflux to dissolve. 100 mL ethanol was added, and the temperature was lowered to 0-5 °C. A large amount of white solid precipitated. After crystallization and stirring for 3 h, the solution was filtered and dried under vacuum to obtain compound 5, 40 g of white solid. The overall yield of the four steps was 79.8%, and the purity was 99.4%.

[0054] Example 3 Step 1: Compound 1 (1.0 eq), toluene (200 mL) and zinc chloride (3.0 eq) were added to the reaction vessel and stirred for 30 min. Then propionyl chloride (1.5 eq) was added dropwise, and the mixture was heated to 78 °C and reacted for 5 h. The reaction progress was monitored by TLC. After the reaction was completed, the reaction solution was cooled to room temperature and filtered to obtain a yellow solution containing compound 2. Step 2: Under ice bath conditions, add 70 mL of a dichloromethane solution containing 80 mmol of boron tribromide to the yellow solution of compound 2 obtained in Step 1. After the addition is complete, continue stirring for 3 h. After the reaction is complete, pour in ice water, extract with dichloromethane, wash the organic phase with saturated brine, combine the organic phases, dry the combined organic phases with anhydrous sodium sulfate, filter, evaporate the filtrate under reduced pressure, and precipitate by column chromatography to obtain compound 3.

[0055] Step 3: Add 400 mL of acetonitrile solution of compound 3 to the reaction vessel, replace with N2 three times, add chloromethane (CH3Cl, 3.0 eq), triphenylphosphine (1.5 eq), and sodium hydroxide (3.0 eq), heat to 60 °C, and react until the reactants are completely reacted as monitored by HPLC. Quench with saturated NH4Cl aqueous solution, filter to remove the generated triphenylphosphine oxide, wash the filter residue with a small amount of acetonitrile, add water to separate the layers, extract the aqueous layer three times with ethyl acetate, combine the organic phases, wash with saturated sodium chloride brine, dry with anhydrous sodium sulfate, filter and evaporate the solvent to obtain the crude product of compound 4, and proceed directly to the next reaction.

[0056] Step 4: The crude product of compound 4 was mixed with toluene (300 mL), 55 mg of Speier catalyst was added and stirred for 30 min, the temperature was raised to 70 °C, and heptamethyltrisiloxane (24.4 g, 1.1 eq) was added dropwise. The reaction progress was monitored by TLC. After the reaction was completed, the reaction solution was cooled to room temperature, concentrated under reduced pressure to remove the solvent, 50 mL of acetone was added, and the solution was heated to reflux to dissolve. Then 200 mL of ethanol was added, and the solution was cooled to 8 °C. A large amount of white solid precipitated. After crystallization and stirring for 3 h, the solution was filtered and dried under vacuum to obtain compound 5, 38 g of white solid. The overall yield of the four steps was 75.9%, and the purity was 99.3%.

[0057] Example 4 Step 1: Compound 1 (100 mmol, 1.0 eq), toluene (200 mL), and a mixed catalyst of zinc chloride (1.0 eq) and aluminum trichloride (2.0 eq) were added to the reaction vessel and stirred for 30 min. Then propionyl chloride (1.3 eq) was added dropwise, and the mixture was heated to 85 °C and reacted for 7 h. The reaction progress was monitored by HPLC. After the reaction was completed, the reaction solution was cooled to room temperature and filtered to obtain a yellow solution containing compound 2. Step 2: Under ice bath conditions, add 70 mL of a dichloromethane solution containing 80 mmol of boron tribromide to the yellow solution of compound 2 obtained in Step 1. After the addition is complete, continue stirring for 3 h. After the reaction is complete, pour in ice water, extract with dichloromethane, wash the organic phase with saturated brine, combine the organic phases, dry the combined organic phases with anhydrous sodium sulfate, filter, evaporate the filtrate under reduced pressure, and precipitate by column chromatography to obtain compound 3.

[0058] Step 3: Add 400 mL of tert-butanol solution of compound 3 to the reaction vessel. After replacing the gas in the reaction vessel with N2 three times, add iodomethane (CH3I, 3.0 eq), triphenylphosphine (1.5 eq), and sodium tert-butoxide (1.2 eq). Heat to 60 °C and reflux until the reactants are completely reacted as monitored by HPLC. Cool and quench the reaction with saturated NH4Cl aqueous solution. Filter to remove the generated triphenylphosphine oxide. Wash the filter residue with a small amount of tert-butanol, add water to separate the layers, extract the aqueous layer three times with ethyl acetate, combine the organic phases, wash with saturated sodium chloride brine, dry with anhydrous sodium sulfate, filter and evaporate the solvent to obtain the crude product of compound 4, which can be directly used for the next reaction.

[0059] Step 4: The crude product of compound 4 was mixed with toluene (300 mL), 75 mg of Karstedt catalyst was added and stirred for 30 min, the temperature was raised to 120 °C, and heptamethyltrisiloxane (24.4 g, 1.1 eq) was added dropwise. The reaction progress was monitored by TLC. After the reaction was completed, the reaction solution was cooled to room temperature, concentrated under reduced pressure to remove the solvent, 50 mL of acetone was added, and the mixture was heated to reflux until dissolved. Then 200 mL of ethanol was added, and the mixture was cooled to 0-5 °C. A large amount of white solid precipitated. After crystallization and stirring for 3 h, the mixture was filtered and dried under vacuum to obtain compound 5, 41 g of white solid. The overall yield of the four steps was 81.89%, and the purity was 99.2%.

[0060] Example 5 Step 1: Compound 1 (100 mmol, 1.0 eq), toluene (200 mL) and aluminum trichloride (2.0 eq) catalyst were added to a reaction vessel and stirred for 30 min. Then propionyl chloride (1.3 eq) was added dropwise, and the mixture was heated to 85 °C and reacted for 7 h. The reaction progress was monitored by HPLC. After the reaction was completed, the reaction solution was cooled to room temperature and filtered to obtain a yellow solution containing compound 2.

[0061] Step 2: Under ice bath conditions, add 70 mL of a dichloromethane solution containing 80 mmol of boron tribromide to the yellow solution of compound 2 obtained in Step 1. After the addition is complete, continue stirring for 3 h. After the reaction is complete, pour in ice water, extract with dichloromethane, wash the organic phase with saturated brine, combine the organic phases, dry the combined organic phases with anhydrous sodium sulfate, filter, evaporate the filtrate under reduced pressure, and precipitate by column chromatography to obtain compound 3.

[0062] Step 3: Add 400 mL of the ether solution of compound 3 to the reaction vessel. After replacing the gas in the reaction vessel with N2 three times, add iodomethane (CH3I, 3.0 eq), triphenylphosphine (1.5 eq), and potassium tert-butoxide (1.2 eq). Heat to 60 °C and check the reaction is complete by HPLC. Cool and quench the reaction with saturated NH4Cl aqueous solution. Filter to remove the generated triphenylphosphine oxide. Wash the filter residue with a small amount of ether. After adding water to separate the layers, extract the aqueous layer three times with ethyl acetate. Combine the organic phases, wash with saturated sodium chloride brine, dry with anhydrous sodium sulfate, concentrate and evaporate to dryness to obtain the crude product of compound 4, which can be directly used for the next reaction.

[0063] Step 4: The crude product of compound 4 was mixed with chlorobenzene (300 mL), 100 mg of Karstedt catalyst was added and stirred for 30 min, the temperature was raised to 120 °C, and the reaction progress was monitored by TLC. After the reaction was completed, the reaction solution was cooled to room temperature, concentrated under reduced pressure to remove the solvent, 50 mL of acetone was added, and the solution was heated to reflux to dissolve. 200 mL of methanol was added, and after cooling to 0 °C, a large amount of white solid precipitated. After crystallization and stirring for 3 h, the solution was filtered and dried under vacuum to obtain compound 5, 40 g of white solid. The overall yield of the three steps was 79.8%, and the purity was 98.9%.

[0064] Example 6 Step 1: Compound 1 (100 mmol, 1.0 eq), xylene (200 mL) and aluminum trichloride (2.0 eq) were added to a reaction vessel and stirred for 30 min. Then propionyl chloride (1.3 eq) was added dropwise, and the mixture was heated to 85 °C and reacted for 7 h. The reaction progress was monitored by HPLC. After the reaction was completed, the reaction solution was cooled to room temperature and filtered to obtain a yellow solution containing compound 2.

[0065] Step 2: Under ice bath conditions, add 70 mL of a dichloromethane solution containing 80 mmol of boron tribromide to the yellow solution of compound 2 obtained in Step 1. After the addition is complete, continue stirring for 3 h. After the reaction is complete, pour in ice water, extract with dichloromethane, wash the organic phase with saturated brine, combine the organic phases, dry the combined organic phases with anhydrous sodium sulfate, filter, evaporate the filtrate under reduced pressure, and precipitate by column chromatography to obtain compound 3.

[0066] Step 3: Add 400 mL of tert-butyl methyl ether solution of compound 3 to the reaction vessel. After replacing the gas in the reaction vessel with N2 three times, add iodomethane (CH3I, 4.0 eq), triphenylphosphine (2.0 eq), and sodium tert-butoxide (2.0 eq). Heat to 60 °C and react until the reactants are completely cooled under HPLC monitoring. Quench the reaction by adding saturated NH4Cl aqueous solution. Filter to remove the generated triphenylphosphine oxide. Wash the filter residue with a small amount of tert-butyl methyl ether. After adding water to separate the layers, extract the aqueous layer three times with ethyl acetate. Combine the organic phases, wash with saturated sodium chloride brine, dry with anhydrous sodium sulfate, filter, and evaporate the solvent to obtain the crude product of compound 4, which can be directly used for the next reaction.

[0067] Step 4: The crude product of compound 4 was mixed with benzene (300 mL), 40 mg of Speier catalyst and 5 mg of Karstedt catalyst were added and stirred for 30 min, the temperature was raised to 80 °C, and heptamethyltrisiloxane (24.4 g, 1.1 eq) was added dropwise. The reaction progress was monitored by TLC. After the reaction was completed, the reaction solution was cooled to room temperature, concentrated under reduced pressure to remove the solvent, 50 mL of acetone was added, and the solution was heated to reflux to dissolve. Then 200 mL of tert-butanol was added, and after cooling to 0 °C, a large amount of white solid precipitated. After crystallization and stirring for 3 h, the solution was filtered and dried under vacuum to obtain compound 5, 42 g of white solid. The overall yield of the three steps was 83.79%, and the purity was 98.7%.

[0068] Example 7 Step 1: Compound 1 (100 mmol, 1.0 eq), toluene (200 mL) and aluminum trichloride (2.0 eq) catalyst were added to the reaction vessel and stirred for 30 min. Then propionyl chloride (1.3 eq) was added dropwise and the mixture was heated to 80 °C. The reaction process was monitored by HPLC. After the reaction was completed, the reaction solution was cooled to room temperature and filtered to obtain a yellow solution containing compound 2.

[0069] Step 2: Under ice bath conditions, add 70 mL of a dichloromethane solution containing 80 mmol of boron tribromide to the yellow solution of compound 2 obtained in Step 1. After the addition is complete, continue stirring for 3 h. After the reaction is complete, pour in ice water, extract with dichloromethane, wash the organic phase with saturated brine, combine the organic phases, dry the combined organic phases with anhydrous sodium sulfate, filter, evaporate the filtrate under reduced pressure, and precipitate by column chromatography to obtain compound 3.

[0070] Step 3: After replacing the gas in the reactor with N2 three times, add iodomethane (CH3I, 3.0 eq), toluene (400 mL), and triphenylphosphine (2.0 eq). Reflux for 3 hours. HPLC detection shows the reaction is complete. Cool to 0°C, add butyllithium (2.0 eq), and obtain the reaction system. Stir for 30 min, then add a toluene solution (100 mL) of compound 3 dropwise to the reaction system. React until the reactants are completely reacted as monitored by HPLC. Cool, add saturated NH4Cl aqueous solution to quench the reaction, filter to remove the generated triphenylphosphine oxide, wash the filter residue with a small amount of toluene, add water to separate the layers, extract the aqueous layer three times with toluene, combine the organic phases, wash with saturated sodium chloride brine, dry with anhydrous sodium sulfate, filter, and evaporate the solvent to obtain the crude product of compound 4, which is directly used for the next reaction.

[0071] Step 4: The crude product of compound 4 was mixed with chlorobenzene (300 mL), 40 mg of Speier catalyst and 5 mg of Karstedt catalyst were added and stirred for 30 min. The mixture was heated to 100 °C, and heptamethyltrisiloxane (24.4 g, 1.1 eq) was added dropwise. The reaction progress was monitored by TLC. After the reaction was completed, the reaction solution was cooled to room temperature, concentrated under reduced pressure to remove the solvent, and 100 mL of n-propanol was added. After cooling to 8 °C, a large amount of white solid precipitated. After crystallization and stirring for 3 h, the mixture was filtered and dried under vacuum to obtain compound 5, 40.2 g of white solid. The overall yield of the three steps was 80.19%, and the purity was 99.0%.

[0072] Example 8 Step 1: Compound 1 (100 mmol, 1.0 eq), toluene (200 mL) and tin tetrachloride (1.5 eq) were added to a reaction vessel and stirred for 30 min. Then propionyl chloride (1.5 eq) was added dropwise and the mixture was heated to 80 °C. The reaction process was monitored by HPLC. After the reaction was completed, the reaction solution was cooled to room temperature and filtered to obtain a yellow solution containing compound 2.

[0073] Step 2: Under ice bath conditions, add 70 mL of a dichloromethane solution containing 80 mmol of boron tribromide to the yellow solution of compound 2 obtained in Step 1. After the addition is complete, continue stirring for 3 h. After the reaction is complete, pour in ice water, extract with dichloromethane, wash the organic phase with saturated brine, combine the organic phases, dry the combined organic phases with anhydrous sodium sulfate, filter, evaporate the filtrate under reduced pressure, and precipitate by column chromatography to obtain compound 3.

[0074] Step 3: After replacing the gas in the reactor with N2 three times, add chloromethane (CH3Cl, 1.5 eq), xylene (400 mL), and triphenylphosphine (2.0 eq). Reflux for 3 hours, cool to 0°C, add LDA (1.5 eq), stir at room temperature for one hour, add 100 mL of xylene solution of compound 3 dropwise, react at 40°C until the reactants are completely reacted as monitored by HPLC, cool, quench with saturated NH4Cl aqueous solution, filter to remove the generated triphenylphosphine oxide, wash the filter residue with a small amount of xylene, add water to separate the layers, extract the aqueous layer three times with xylene, combine the organic phases, wash with saturated sodium chloride brine, dry with anhydrous sodium sulfate, filter and evaporate the solvent to obtain the crude product of compound 4, which can be directly used for the next reaction.

[0075] Step 4: The crude product of compound 4 was mixed with xylene (300 mL), 75 mg of Karstedt catalyst was added and stirred for 30 min, the temperature was raised to 80 °C, and heptamethyltrisiloxane (1.2 eq) was added dropwise. The reaction was monitored by HPLC. After the reaction was completed, the reaction solution was cooled to room temperature, concentrated under reduced pressure to remove the solvent, 50 mL of acetone was added, and the solution was heated to reflux to dissolve. Then 200 mL of ethanol was added, and the solution was cooled to 8 °C. A large amount of white solid precipitated. After crystallization and stirring for 3 h, the solution was filtered and dried under vacuum to obtain compound 5, 39 g of white solid. The overall yield of the three steps was 77.79%, and the purity was 99.1%.

[0076] The method of this invention has been described through preferred embodiments. Those skilled in the art will readily be able to modify or appropriately alter and combine the methods and applications described herein within the scope, spirit, and context of this invention to implement and apply the technology of this invention. Those skilled in the art can refer to the content herein to appropriately improve process parameters. It should be particularly noted that all similar substitutions and modifications are obvious to those skilled in the art and are considered to be included within the scope of this invention.

Claims

1. A process for synthesizing cresoltrazolium trisilane, comprising: Compound 1, a first organic solvent, a first catalyst, and propionyl chloride are mixed and reacted to give compound 2; ； Compound 2 undergoes one or more reaction steps to yield compound 5. .

2. The synthesis process of cresoltrazolium trisilane according to claim 1, characterized in that, The first organic solvent is selected from any or a mixture of N,N-dimethylformamide, toluene, tetrahydrofuran, methanol, ethanol, and dichloromethane; and / or, the first catalyst is selected from aluminum trichloride, ferric trichloride, zinc chloride, aluminum trichloride, and tin tetrachloride; and / or, the first organic solvent is selected from any or a mixture of toluene, xylene, tetrahydrofuran, methanol, and ethanol; and / or, the molar amount of the first catalyst added per 1L of the first organic solvent is 1~3mol; and / or, the molar amount of the compound added per 1L of the first organic solvent is 300~500mmol.

3. The process for synthesizing cresoltrazolium trisilane according to claim 1 or 2, characterized in that, Compound 2 is reacted in one or more steps to obtain compound 5, including the following steps: Compound 2, boron tribromide, and a second organic solvent react to yield compound 3; ； Compound 3 undergoes one or more reaction steps to yield compound 5.

4. The process for synthesizing cresoltrazolium trisilane according to claim 1, characterized in that, The second organic solvent is selected from toluene, xylene, dichloromethane, tetrahydrofuran or a mixture thereof; and / or, the molar amount of boron tribromide added to each 1L of the second organic solvent is 700~900mmol.

5. The process for synthesizing cresoltrazolium trisilane according to any one of claims 3 or 4, characterized in that, Compound 3 is reacted in one or more steps to obtain compound 5, including the following steps: Under an inert atmosphere, a mixture of haloalkanes, a third organic solvent, triphenylphosphine, a first base, and compound 3 was reacted to give compound 4; ； Compound 4 is obtained by reacting the substrate through one or more steps to yield compound 5.

6. The process for synthesizing cresoltrazolium trisilane according to claim 5, characterized in that, The third organic solvent is selected from any or a mixture of acetonitrile, toluene, dichloromethane, tert-butanol, diethyl ether, tert-butyl methyl ether, and xylene; and / or, the molar amount of haloalkanes added to each 1L of the third organic solvent is 200-400 mmol; and / or, the haloalkanes are selected from any or a mixture of iodomethane, bromomethane, and chloromethane; and / or, the molar amount of triphenylphosphine added to each 1L of the third organic solvent is 300-500 mmol; and / or, the first base is selected from any or a mixture of butyllithium, sodium methoxide, sodium hydroxide, sodium tert-butoxide, potassium tert-butoxide, and LDA; and / or, the molar amount of the first base added to each 1L of the third organic solvent is 200-500 mmol.

7. The process for synthesizing cresoltrazolium trisilane according to any one of claims 5 or 6, characterized in that, Compound 4 is obtained by a substrate reaction through one or more steps to yield compound 5. Compound 4, the fourth organic solvent, the second catalyst, and heptamethyltrisiloxane were mixed and reacted to give compound 5; 。 8. The process for synthesizing cresoltrazolium trisilane according to claim 7, characterized in that, The fourth organic solvent is selected from toluene, xylene, dichloroethane, diethyl ether or a mixture thereof; and / or, the second catalyst is selected from Pd / C catalyst, Speier catalyst, Karstedt catalyst or a mixture thereof.

9. The process for synthesizing cresoltrazolium trisilane according to any one of claims 1 to 8, characterized in that, The synthesis method of compound 1 is as follows; Compound UV-P, the second base, the fifth organic solvent, and CH3I were mixed and reacted to give compound 1. 。 10. The process for synthesizing cresoltrazolium trisilane according to claim 9, characterized in that, The fifth organic solvent is selected from any one or a mixture of N,N-dimethylformamide, toluene, tetrahydrofuran, methanol, ethanol, and dichloromethane; and / or, the second base is selected from any one or a mixture of potassium carbonate, sodium carbonate, and butyllithium; and / or, the molar amount of compound UV-P added to each 1L of organic solvent is 300~400mmol; and / or, the molar amount of the second base added to each 1L of organic solvent is 800~1200mmol; and / or, the molar amount of CH3I added to each 1L of organic solvent is 300~500mmol.

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