CN114394913A

CN114394913A - Synthetic method of oxime ether derivative

Info

Publication number: CN114394913A
Application number: CN202111642798.6A
Authority: CN
Inventors: 苗成霞; 庄宏凤; 韩峰; 吕皓天; 刘巧文
Original assignee: Shandong Agricultural University
Current assignee: Shandong Agricultural University
Priority date: 2021-12-30
Filing date: 2021-12-30
Publication date: 2022-04-26
Anticipated expiration: 2041-12-30
Also published as: CN114394913B

Abstract

The invention relates to a synthetic method of oxime ether derivatives, belonging to the field of organic compound synthesis; dissolving an initial substrate alcohol compound and an oxime compound in a solvent, adding a heteropoly acid catalyst and an additive, and generating oxime in an air atmosphere at 25-100 DEG COPerforming alkylation reaction for 0.5-12 hours to synthesize oxime ether derivatives; the method adopts green catalyst heteropolyacid as a catalyst and green solvents such as dimethyl carbonate and the like, and has the advantages of simple reaction conditions, no metal, low catalyst consumption, mild reaction conditions and wide substrate applicability; in addition, the method is simple and easy to operate, high in yield, capable of realizing direct conversion of alcohol, green and environment-friendly, and high in atom economy, and the only byproduct is non-toxic and harmless water.

Description

Synthetic method of oxime ether derivative

Technical Field

The invention belongs to the technical field of organic compound synthesis, and particularly relates to a synthesis method of an oxime ether derivative.

Background

As an important and widely-used structural group, oxime ether not only widely exists in pharmaceutical chemistry due to biological characteristics, but also can be used for constructing heterocyclic compounds such as isoxazole and the like in organic synthesis. For example, the etieresin containing an oxime ether structure has the efficacy of treating insomnia. In conventional processes, the reaction of carbonyl compounds with catalysts is carried out by adding additional additives or catalystsOThe condensation of alkylhydroxylamine hydrochloride to form the oxime ether (Angew. chem. int. Ed. 2017, 56, 2454-2458.). Currently, oximes are used as substrates, and compounds such as halides, acetates, phosphates, epoxides, alkenes, arylboron and diaryliodonium salts participate in oximesOAlkylation has been widely studied for the synthesis of oxime ethers (RSC adv. 2016, 6, 17740-.

However, such cross-coupling and substitution reactions are typically accomplished in a chlorine-containing solvent using transition metal catalysis in the presence of stoichiometric bases or oxidants, generate large amounts of waste, and are low in atom economy. The ligands triphenylphosphine or the more toxic carbon tetrachloride were necessary in the reported reactions for the construction of oxime ethers by the alcohol and oxime reactions (J. chem. Soc., Perkin Trans. 1, 1976, 1708-. For example, in a stoichiometric amount of a strong base CsCO₃And Lewis acids Sc (OTf)₃In the presence of dichloroethane as a solvent, the intramolecular reaction of oxime and hydroxyl is realized by Ir catalysisOAllylation to give a wide variety of cyclic five-, six-, and seven-membered ring oxime ethers (org. Lett. 2021, 23, 2643-2647).

For example, CN108314630A discloses an oxime ether derivative, a preparation method and an application thereof, wherein the oxime ether derivative is any of 1) -6): 1) 5-bromo 1-naphthalenemethyloxime ether; 2) 5-methoxy-1-naphthalimide ether: 3) 5-benzene1-naphthalimide ether; 4) 5-p-methoxyphenyl-1-naphthoximino ether: 5) 5-p-ethoxyphenyl-1-naphthalimide ether; 6) 3-5-Ethyl group (E) -1-naphthalimide ether. The oxime ether derivative is synthesized by taking 1-naphthoic acid as a raw material through coupling reaction such as methoxylation, Suzuki reaction, Heck reaction and the like, acylation reaction and oximation reaction.

In the above reaction, a precursor of oxime and alcohol has a complicated reaction catalyst system, a large number of by-products are produced, and the reaction is generally carried out in a chlorine-containing solvent and an excess amount of alkali, which results in a disadvantage of low yield and atom economy.

At present, the requirements for the quality of fine organic chemicals such as medicines, pesticides and the like are high, the production process is complex, the dosage of solvents and auxiliaries is large, the discharge amount of three wastes is large, the environmental pollution and the resource waste are serious, the requirements for the catalyst of the drug intermediate are higher, and the synthesis of the related drug intermediate is limited by the etherification reaction which takes a large amount of transition metals as the catalyst at present.

Therefore, the development of a catalytic system which takes alcohol as a substrate and water as a unique byproduct, has high atom economy, is environment-friendly, simple, efficient and cheap is very important for realizing the etherification reaction of oxime and alcohol.

Disclosure of Invention

Aiming at the problems of the existing system, the invention aims to provide a simple, efficient, environment-friendly and high atom economy path for realizing the oxime etherification reaction of alcohol and oxime by using a green catalyst heteropoly acid and a green solvent under mild conditions.

The heteropoly acid is used as a green solid acid, and has the characteristics of stability, no toxicity, high efficiency and cleanness under homogeneous or heterogeneous catalysis; dimethyl carbonate (DMC) is receiving increasing attention as a green solvent for organic reactions due to its low toxicity, low viscosity and high biodegradability.

The technical scheme of the invention is as follows:

dissolving starting substrate alcohols and oxime compounds in a solvent, adding a catalyst heteropoly acid and an additive, and generating oxime at 25-100 DEG COAlkylation reaction for 0.5-12 h to synthesize oxime ether derivativeThe reaction formula is as follows:

wherein: r¹Is phenyl, 4-CH₃Phenyl, 4-OCH₃Phenyl, 4-Ph phenyl, 4-F phenyl, 4-Cl phenyl, 4-Br phenyl, 4-CF₃Phenyl, 4-NO₂Phenyl, 2-CH₃Phenyl, 3-CH₃Phenyl, 2-chlorophenyl, 3-chlorophenyl, 2-fluorophenyl, 3-fluorophenyl, 1-tetrahydronaphthyl, 9H-fluorenyl, benzyl, 3-pyridyl, 2-furyl, methyl, 1-propenylbenzene, tetrahydro-2H-pyranyl, cyclohexyl; r²Is phenyl, 4-CH₃Phenyl, 4-fluorophenyl, 4-chlorophenyl, methyl, benzyl; r³Is hydrogen, phenyl, 4-CH₃Phenyl, 4-CH₃Phenyl, 4-Ph phenyl, 4-F phenyl, 4-Cl phenyl, 4-Br phenyl, 4-CF₃Phenyl, 2-CH₃Phenyl, 3-CH₃Phenyl, methyl, cyclohexyl, ethyl, propylbenzene, adamantyl, 1-propenylbenzene; r⁴Is phenyl, 4-CH₃Phenyl, 4-chlorophenyl, methyl; r⁵Is phenyl, methyl, hydrogen.

Wherein, the oxime compound comprises but is not limited to one of benzophenone oximes, acetophenone oximes, aliphatic ketoxime and ketoxime compounds containing hetero atoms; the alcohol compound includes but is not limited to one of triphenylmethanol, diphenylmethanol, allyl alcohol and tertiary aliphatic alcohol.

Preferably, the molar ratio of the alcohol to the oxime compound is 0.2: 1-3: 1;

preferably, the catalyst is one of phosphotungstic acid, phosphomolybdic acid and tungstosilicic acid;

preferably, the additive is selected from one of 4A molecular sieve, anhydrous sodium sulfate, anhydrous magnesium sulfate and silica gel;

the solvent includes but is not limited to dimethyl carbonate, 1, 2-dichloroethane, dichloromethane, diethyl ether, acetonitrile, 1, 4-dioxane, cyclopentyl methyl ether, tetrahydrofuran, 2-methyl tetrahydrofuran, acetone, ethyl acetate, ethyl lactateEster, dimethyl sulfoxide,N,N-one of dimethylformamide, ethanol, methanol, toluene, cyclohexane and n-hexane;

preferably, the molar ratio of the heteropolyacid catalyst amount to the oxime compound is 0.001: 1-0.1: 1;

preferably, the molar ratio of the additive to the oxime compound is 0.2: 1-4: 1;

preferably, of said oximesOAnd (3) carrying out alkylation reaction in an air atmosphere, wherein the reaction temperature is 25-100 ℃, and the reaction time is 0.5-12 h.

The invention has the beneficial effects that:

1. the catalyst is a green heteropoly acid catalyst, so that the use of corrosive strong acid is avoided, the catalyst is low in dosage and high in efficiency, and the reaction can still occur when the catalyst is 0.2 mol%, so that a good effect is obtained;

2. the catalytic system belongs to a metal-free system, the post-treatment is simple, and the problems of metal residue and environmental pollution are avoided;

3. the solvent adopted in the reaction is a green solvent, such as dimethyl carbonate, so that the use of the traditional solvent is avoided, and the method is environment-friendly;

4. the reaction condition is simple and mild, and the reaction can be smoothly carried out without the harsh conditions of no water and no oxygen;

5. the direct conversion of alcohol is realized by the reaction, which is different from most methods that alcohol derivatives are used to participate in the reaction, and the byproduct is water, so that the atom economy is high, and the method is environment-friendly;

6. the raw materials of the biological reaction system are easy to obtain, the applicability of the substrate is good, the aromatic, aliphatic and oxime or alcohol compounds containing hetero atoms can be used for constructing oxime ether, and the yield is high and is usually more than 90%.

Detailed Description

The present invention will be better understood by those skilled in the art and will now be further described with reference to specific embodiments.

The oxime etherification reaction of alcohol and oxime is carried out as follows:

1. adding oximes, alcohols, a catalyst, an additive and a solvent into a 25 mL reaction tube in sequence, wherein the molar ratio of the oximes to the alcohols is 0.2: 1-3: 1, the catalyst is used in an amount of 0.1-10 mol%, and the reaction is carried out at 25-100 ℃ for 0.5-12 h.

2. The progress of the reaction was monitored by TLC (thin layer chromatography), after the reaction was completed, an appropriate amount of triethylamine was added to neutralize the acidic catalyst, the mixture was filtered, washed with ethyl acetate (3 × 10 mL), evaporated under reduced pressure, the solvent was removed, and the product was purified by column chromatography (eluent petroleum ether).

Example 1

Benzophenone oxime and triphenyl carbinol synthesize benzophenone O-trityl oxime, the steps are as follows:

(1) into a 25 mL reaction tube, benzophenone oxime (0.3 mmol, 0.0592 g), trityl alcohol (0.9 mmol, 0.2343 g), phosphotungstic acid (1 mol%, 0.0087 g), anhydrous magnesium sulfate (1.2 eq., 0.0433 g) and 2 mL dimethyl carbonate were added, and stirred at room temperature for 2 hours;

(2) after the reaction is finished, adding a proper amount of triethylamine to neutralize the acid catalyst, filtering the mixture, washing the mixture by ethyl acetate (3X 10 mL), decompressing and rotary-evaporating the mixture, removing the solvent, and purifying the product by column chromatography (silica gel column is adopted, and the eluent is petroleum ether) to obtain the target product benzophenone O-trityl oxime with the yield of 98%.

And (3) nuclear magnetic resonance characterization of a product:¹H NMR (400 MHz, CDCl₃) δ 7.49-7.38 (m, 5H), 7.33-7.17 (m, 20H). ¹³C NMR (101 MHz, CDCl₃) δ 156.8, 144.8, 136.8, 134.0, 129.4, 129.3, 129.2, 128.8, 128.17, 128.16, 128.1, 127.6, 127.1, 91.5. HRMS m/z: [M+Na]⁺ calcd. for C₃₂H₂₅NONa 462.1828, found 462. 1837.

example 2

The experimental procedure is the same as that of example 1, except that catalyst phosphomolybdic acid (1 mol%, 0.0055 g) is added to the system to replace phosphotungstic acid, and the reaction is carried out at room temperature for 0.5 h to obtain the target product benzophenone O-trityl oxime with a yield of 95%.

Example 3

The experimental procedure is the same as example 1, catalyst tungstosilicic acid (1 mol%, 0.0086 g) is added to the system to replace phosphotungstic acid, and the reaction is carried out at room temperature for 0.5 h to obtain the target product benzophenone O-trityl oxime with a yield of 72%.

Example 4

The experimental procedure is the same as example 1, catalyst phosphotungstic acid (0.1 mol%, 0.0009 g) is added to the system to replace phosphotungstic acid, and the reaction is carried out at room temperature for 0.5 h to obtain the target product benzophenone O-trityl oxime with a yield of 82%.

Example 5

The experimental procedure is the same as example 1, catalyst phosphomolybdic acid (0.1 mol%, 0.0006 g) is added to the system to replace phosphotungstic acid, and the reaction is carried out at room temperature for 0.5 h to obtain the target product benzophenone O-trityl oxime with a yield of 71%.

Example 6

4,4 '-dimethyl benzophenone oxime and triphenyl carbinol synthesize 4, 4' -dimethyl benzophenone O-trityl oxime, which comprises the following steps:

(1) 4, 4' -dimethylbenzophenone oxime (0.3 mmol, 0.0676 g), trityl alcohol (0.9 mmol, 0.2343 g), phosphotungstic acid (1 mol%, 0.0087 g), anhydrous magnesium sulfate (1.2 eq., 0.0433 g), and 2 mL dimethyl carbonate were added to a 25 mL reaction tube and stirred at room temperature for 2 hours;

(2) after the reaction is finished, adding a proper amount of triethylamine to neutralize the acid catalyst, filtering the mixture, washing the mixture with ethyl acetate (3X 10 mL), decompressing and rotary-steaming the mixture, removing the solvent, and purifying the product by column chromatography (silica gel column is adopted, and the eluent is petroleum ether) to obtain the target product 4, 4' -dimethyl benzophenone O-trityl oxime with the yield of 92 percent.

And (3) nuclear magnetic resonance characterization of a product:¹H NMR (400 MHz, CDCl₃) δ 7.34-7.20 (m, 19H), 7.15 (d, J = 7.0 Hz, 2H), 7.01 (d, J = 7.8 Hz, 2H), 2.43 (s, 3H), 2.28 (s, 3H). ¹³C NMR (101 MHz, CDCl₃) δ 156.6, 144.9, 139.1, 138.6, 134.4, 131.0, 129.5, 129.4, 128.8, 128.7, 128.2, 127.6, 127.0, 91.3, 21.6, 21.4. HRMS m/z: [M+H]⁺calcd. for C₃₄H₃₀NO 468.2322, found 468.2316.

example 7

4,4 '-dichlorobenzophenone O-trityl oxime is synthesized by 4, 4' -dichlorobenzophenone oxime and triphenyl methanol, and the steps are as follows:

(1) 4, 4' -dichlorobenzophenone oxime (0.3 mmol, 0.0798 g), trityl alcohol (0.9 mmol, 0.2343 g), phosphotungstic acid (1 mol%, 0.0087 g), anhydrous magnesium sulfate (1.2 eq., 0.0433 g) and 2 mL dimethyl carbonate were added to a 25 mL reaction tube and stirred at room temperature for 2 hours;

(2) after the reaction is finished, adding a proper amount of triethylamine to neutralize the acid catalyst, filtering the mixture, washing the mixture with ethyl acetate (3X 10 mL), decompressing and rotary-steaming the mixture, removing the solvent, and purifying the product by column chromatography (silica gel column is adopted, and the eluent is petroleum ether) to obtain the target product 4, 4' -dichlorobenzophenone O-trityl oxime with the yield of 90%.

And (3) nuclear magnetic resonance characterization of a product:¹H NMR (400 MHz, CDCl₃) δ 7.45 (d, J = 7.3 Hz, 2H), 7.36-7.23 (m, 17H), 7.16 (d, J = 10.6 Hz, 4H). ¹³C NMR (101 MHz, CDCl₃) δ 154.7, 144.4, 135.5, 135.1, 134.9, 131.7, 130.9, 129.3, 129.2, 128.6, 128.5, 127.7, 127.3, 92.0. HRMS m/z: [M+H]⁺ calcd. for C₃₂H₂₄Cl₂NO 508.1229, found 508.1218.

example 8

4-methylbenzophenone O-trityl oxime is synthesized from 4-methylbenzophenone oxime and triphenylmethanol by the following steps:

(1) 4-Methylbenzophenone oxime (0.3 mmol, 0.0634 g), trityl alcohol (0.9 mmol, 0.2343 g), phosphotungstic acid (1 mol%, 0.0087 g), anhydrous magnesium sulfate (1.2 eq., 0.0433 g), and 2 mL dimethyl carbonate were charged into a 25 mL reaction tube, and stirred at room temperature for 2 hours;

(2) after the reaction is finished, adding a proper amount of triethylamine to neutralize the acid catalyst, filtering the mixture, washing the mixture with ethyl acetate (3X 10 mL), decompressing and rotary-steaming the mixture, removing the solvent, and purifying the product by column chromatography (silica gel column is adopted, and the eluent is petroleum ether) to obtain the target product 4-methylbenzophenone O-trityl oxime with the yield of 94%.

And (3) nuclear magnetic resonance characterization of a product:¹H NMR (400 MHz, CDCl₃) δ 7.32 (d, J = 7.0 Hz, 8H), 7.28-7.12 (m, 16H), 2.36 (d, J = 56.7 Hz, 3H).¹³C NMR (101 MHz, CDCl₃) δ 156.7, 144.8, 138.7, 137.2, 130.8, 129.6, 129.4, 129.3, 129.1, 128.8, 128.3, 128.1, 127.6, 127.1, 91.5, 21.7. HRMS m/z: [M+Na]⁺ calcd. for C₃₃H₂₇NO Na 476.1985, found 476.1976.

example 9

4-trifluoromethyl benzophenone oxime and triphenyl carbinol to synthesize the 4-trifluoromethyl benzophenone O-trityl oxime by the following steps:

(1) 4-trifluoromethyl benzophenone oxime (0.3 mmol, 0.0796 g), trityl alcohol (0.9 mmol, 0.2343 g), phosphotungstic acid (1 mol%, 0.0087 g), anhydrous magnesium sulfate (1.2 eq., 0.0433 g) and 2 mL of dimethyl carbonate were added to a 25 mL reaction tube, and stirred at room temperature for 2 hours;

(2) after the reaction is finished, adding a proper amount of triethylamine to neutralize the acid catalyst, filtering the mixture, washing the mixture with ethyl acetate (3X 10 mL), decompressing and rotary-steaming the mixture, removing the solvent, and purifying the product by column chromatography (silica gel column is adopted, and the eluent is petroleum ether) to obtain the target product 4-trifluoromethyl benzophenone O-trityl oxime with the yield of 93 percent.

And (3) nuclear magnetic resonance characterization of a product:¹H NMR (400 MHz, CDCl₃) δ 7.74 (d, J = 8.0 Hz, 2H), 7.51 (d, J = 7.9 Hz, 2H), 7.24 (q, J = 7.6, 5.9 Hz, 20H). ¹³C NMR (101 MHz, CDCl₃) δ155.7, 144.4, 137.7, 135.9, 131.0, 130.6, 129.7, 129.6, 129.2, 128.4, 127.8, 127.7, 127.3, 125.30, 125.26, 125.2, 91.9. HRMS m/z: [M+H]⁺ calcd. for C₃₃H₂₅F₃NO 508.1883, found 508.1893.

example 10

2-methylbenzophenone O-trityl oxime is synthesized from 2-methylbenzophenone oxime and triphenylmethanol by the following steps:

(1) 2-Methylbenzophenone oxime (0.3 mmol, 0.0634 g), trityl alcohol (0.9 mmol, 0.2343 g), phosphotungstic acid (1 mol%, 0.0087 g), anhydrous magnesium sulfate (1.2 eq., 0.0433 g), and 2 mL dimethyl carbonate were charged into a 25 mL reaction tube, and stirred at room temperature for 2 hours;

(2) after the reaction is finished, adding a proper amount of triethylamine to neutralize the acid catalyst, filtering the mixture, washing the mixture with ethyl acetate (3X 10 mL), decompressing and rotary-steaming the mixture, removing the solvent, and purifying the product by column chromatography (silica gel column is adopted, and the eluent is petroleum ether) to obtain the target product 2-methylbenzophenone O-trityl oxime with the yield of 96%.

And (3) nuclear magnetic resonance characterization of a product:¹H NMR (400 MHz, CDCl₃) δ 7.37-7.18 (m, 23H), 7.14 (d, J = 7.6 Hz, 1H), 1.95 (s, 3H). ¹³C NMR (101 MHz, CDCl₃) δ 157.1, 144.7, 136.0, 135.9, 134.4, 130.0, 129.24, 129.20, 128.4, 128.3, 127.9, 127.6, 127.1, 127.0, 125.8, 91.0, 19.5. HRMS m/z: [M+Na]⁺ calcd. for C₃₃H₂₇NONa 476.1985, found 476.1988.

example 11

The acetophenone O-trityl oxime is synthesized by acetophenone oxime and triphenyl methanol, and the steps are as follows:

(1) in a 25 mL reaction tube, acetophenone oxime (0.3 mmol, 0.0405 g), trityl alcohol (0.9 mmol, 0.2343 g), phosphotungstic acid (1 mol%, 0.0087 g), anhydrous magnesium sulfate (1.2 eq., 0.0433 g) and 2 mL dimethyl carbonate were added, and stirred at room temperature for 2 h;

(2) after the reaction is finished, adding a proper amount of triethylamine to neutralize the acid catalyst, filtering the mixture, washing the mixture by ethyl acetate (3X 10 mL), decompressing and rotary-steaming the mixture, removing the solvent, and purifying the product by column chromatography (silica gel column is adopted, and the eluent is petroleum ether) to obtain the target product acetophenone O-trityl oxime with the yield of 91 percent.

And (3) nuclear magnetic resonance characterization of a product:¹H NMR (400 MHz, CDCl₃) δ 7.47-7.36 (m, 8H), 7.32-7.23 (m, 12H), 2.40 (s, 3H). ¹³C NMR (101 MHz, CDCl₃) δ 154.1, 144.9, 137.0, 129.4, 128.9, 128.3, 127.6, 127.1, 126.3, 91.0, 13.2. HRMS m/z: [M+H]⁺ calcd. for C₂₇H₂₄NO 378.1852,, found 378.1849.

example 12

4-methoxy acetophenone O-trityl oxime is synthesized by 4-methoxy acetophenone oxime and triphenyl methanol, and the steps are as follows:

(1) 4-Methoxybenzylketoxime (0.3 mmol, 0.0496 g), trityl alcohol (0.9 mmol, 0.2343 g), phosphotungstic acid (1 mol%, 0.0087 g), anhydrous magnesium sulfate (1.2 eq., 0.0433 g), and 2 mL of dimethyl carbonate were added to a 25 mL reaction tube, and stirred at room temperature for 2 hours;

(2) after the reaction is finished, adding a proper amount of triethylamine to neutralize the acid catalyst, filtering the mixture, washing the mixture with ethyl acetate (3X 10 mL), decompressing and rotary evaporating the mixture, removing the solvent, and purifying the product by column chromatography (silica gel column is adopted, and the eluent is petroleum ether) to obtain the target product 4-methoxyacetophenone O-trityl oxime with the yield of 83 percent.

And (3) nuclear magnetic resonance characterization of a product:¹H NMR (400 MHz, CDCl₃) δ 7.39 (d, J = 7.7 Hz, 8H), 7.31-7.23 (m, 9H), 6.77 (d, J = 6.9 Hz, 2H), 3.76 (s, 3H), 2.37 (s, 3H). ¹³C NMR (101 MHz, CDCl₃) δ 160.3, 153.6, 145.0, 129.7, 129.4, 127.58, 127.55, 127.1, 113.7, 90.8, 55.4, 13.1. HRMS m/z: [M+H]⁺ calcd. for C₂₈H₂₆NO₂408.1958, found 408.1950.

example 13

4-fluorobenzophenone O-trityl oxime is synthesized from 4-fluorobenzophenone oxime and triphenylmethanol by the following steps:

(1) 4-Fluorophenylacetylketoxime (0.3 mmol, 0.0459 g), trityl alcohol (0.9 mmol, 0.2343 g), phosphotungstic acid (1 mol%, 0.0087 g), anhydrous magnesium sulfate (1.2 eq., 0.0433 g), and 2 mL dimethyl carbonate were added to a 25 mL reaction tube and stirred at room temperature for 2 hours;

(2) after the reaction is finished, adding a proper amount of triethylamine to neutralize the acid catalyst, filtering the mixture, washing the mixture with ethyl acetate (3X 10 mL), decompressing and rotary-steaming the mixture, removing the solvent, and purifying the product by column chromatography (silica gel column is adopted, and the eluent is petroleum ether) to obtain the target product 4-fluoro acetophenone O-trityl oxime with the yield of 98%.

And (3) nuclear magnetic resonance characterization of a product:¹H NMR (400 MHz, CDCl₃) δ 7.51-7.24 (m, 17H), 6.92 (t, J = 8.5 Hz, 2H), 2.38 (s, 3H). ¹³C NMR (101 MHz, CDCl₃) δ 164.6, 162.1, 153.2, 144.9, 133.2, 133.1, 129.3, 127.6, 127.2, 115.3, 115.1, 91.1, 13.2. HRMS m/z: [M+H]⁺ calcd. for C₂₇H₂₃FNO 396.1758, found 396.1766.

example 14

1-tetrahydronaphthyl ketone O-trityl oxime is synthesized by 1-tetrahydronaphthyl ketoxime and triphenyl methanol, and the steps are as follows:

(1) 1-tetrahydronaphthalenone oxime (0.3 mmol, 0.0484 g), trityl alcohol (0.9 mmol, 0.2343 g), phosphotungstic acid (1 mol%, 0.0087 g), anhydrous magnesium sulfate (1.2 eq., 0.0433 g) and 2 mL dimethyl carbonate were added to a 25 mL reaction tube and stirred at room temperature for 2 h;

(2) after the reaction is finished, adding a proper amount of triethylamine to neutralize the acid catalyst, filtering the mixture, washing the mixture with ethyl acetate (3X 10 mL), decompressing and rotary-steaming the mixture, removing the solvent, and purifying the product by column chromatography (silica gel column is adopted, and the eluent is petroleum ether) to obtain the target product 1-tetralone O-trityl oxime with the yield of 92 percent.

And (3) nuclear magnetic resonance characterization of a product:¹H NMR (400 MHz, CDCl₃) δ 7.62 (d, J = 7.9 Hz, 1H), 7.39 (d, J = 7.6 Hz, 6H), 7.27 (dt, J = 13.8, 7.9 Hz, 9H), 7.16 (t, J = 7.5 Hz, 1H), 7.09-7.00 (m, 2H), 2.97 (t, J = 6.7 Hz, 2H), 2.73 (t, J = 6.1 Hz, 2H), 1.87 (p, J = 6.4 Hz, 2H).¹³C NMR (101 MHz, CDCl₃) δ 153.6, 145.0, 139.4, 131.4, 129.4, 128.8, 128.5, 127.6, 127.1, 126.3, 124.8, 90.9, 29.9, 25.1, 21.6. HRMS m/z: [M+Na]⁺ calcd. for C₂₉H₂₅NONa 426.1828, found 426.1829.

example 15

Synthesizing 9H-fluorenone O-trityl oxime by using 9H-fluorenone oxime and triphenyl carbinol, and comprising the following steps:

(1) into a 25 mL reaction tube were added 9H-fluorenone oxime (0.3 mmol, 0.0586 g), trityl alcohol (0.9 mmol, 0.2343 g), phosphotungstic acid (1 mol%, 0.0087 g), anhydrous magnesium sulfate (1.2 eq., 0.0433 g), and 2 mL dimethyl carbonate, and the mixture was stirred at room temperature for 2 hours;

(2) after the reaction is finished, adding a proper amount of triethylamine to neutralize the acid catalyst, filtering the mixture, washing the mixture with ethyl acetate (3X 10 mL), decompressing and rotary-steaming the mixture, removing the solvent, and purifying the product by column chromatography (silica gel column is adopted, and the eluent is petroleum ether) to obtain the target product 9H-fluorenone O-trityl oxime with the yield of 91 percent.

And (3) nuclear magnetic resonance characterization of a product:¹H NMR (400 MHz, CDCl₃) δ 8.52 (d, J = 7.5 Hz, 1H), 7.64 (d, J = 7.5 Hz, 1H), 7.57 (d, J = 7.6 Hz, 1H), 7.52-7.21 (m, 20H), 7.15 (t, J = 7.6 Hz, 1H). ¹³C NMR (101 MHz, CDCl₃) δ 152.0, 144.3, 141.8, 140.0, 136.2, 131.0, 130.5, 129.8, 129.6, 129.0, 128.4, 127.84, 127.76, 127.5, 122.0, 120.0, 119.8, 93.4. HRMS m/z: [M+H]⁺ calcd. for C₃₂H₂₄NO 438.1852, found 438.1858.

example 16

Chalcone oxime and triphenylmethanol to synthesize chalcone O-trityl oxime, the steps are as follows:

(1) in a 25 mL reaction tube, chalcone oxime (0.3 mmol, 0.0670 g), trityl alcohol (0.9 mmol, 0.2343 g), phosphotungstic acid (1 mol%, 0.0087 g), anhydrous magnesium sulfate (1.2 eq., 0.0433 g), and 2 mL dimethyl carbonate were added, and stirred at room temperature for 2 h;

(2) after the reaction is finished, adding a proper amount of triethylamine to neutralize the acid catalyst, filtering the mixture, washing the mixture by ethyl acetate (3X 10 mL), decompressing and rotary-steaming the mixture, removing the solvent, and purifying the product by column chromatography (silica gel column is adopted, and the eluent is petroleum ether) to obtain the target product chalcone O-trityl oxime with the yield of 87%.

And (3) nuclear magnetic resonance characterization of a product:¹H NMR (400 MHz, CDCl₃) δ 7.78 (d, J = 16.8 Hz, 1H), 7.50 (d, J = 7.5 Hz, 2H), 7.43-7.24 (m, 23H), 6.83 (d, J = 16.6 Hz, 1H). ¹³C NMR (101 MHz, CDCl₃) δ 156.5, 144.8, 139.0, 136.5, 135.5, 129.5, 129.4, 129.20, 129.18, 128.97, 128.95, 128.3, 127.7, 127.6, 127.5, 127.2, 118.4, 91.5. HRMS m/z: [M+Na]⁺ calcd. for C₃₄H₂₇NONa 488.1985, found 488.1983.

example 17

1- (pyridine-3-yl) ethane-1-ketoxime and triphenyl methanol are synthesized into 1- (pyridine-3-yl) ethane-1-keton O-trityl oxime by the following steps:

(1) 1- (pyridin-3-yl) ethane-1-ketoxime (0.3 mmol, 0.0408 g), trityl alcohol (0.9 mmol, 0.2343 g), phosphotungstic acid (1 mol%, 0.0087 g), anhydrous magnesium sulfate (1.2 eq., 0.0433 g), and 2 mL dimethyl carbonate were added to a 25 mL reaction tube and stirred at 100 ℃ for 12 h;

(2) after the reaction is completed, an appropriate amount of triethylamine is added to neutralize the acidic catalyst, the mixture is filtered, washed with ethyl acetate (3 × 10 mL), rotary-evaporated under reduced pressure, the solvent is removed, and the product is purified by column chromatography (silica gel column is used, eluent is petroleum ether: ethyl acetate = 10: 3) to obtain the target product 1- (pyridin-3-yl) ethane-1-one O-trityl oxime with a yield of 24%.

And (3) nuclear magnetic resonance characterization of a product:¹H NMR (400 MHz, CDCl₃) δ 8.68 (s, 1H), 8.50 (s, 1H), 7.71 (d, J = 8.0 Hz, 1H), 7.38 (d, J = 7.6 Hz, 6H), 7.28 (dt, J = 13.2, 6.1 Hz, 9H), 7.18 (t, J = 6.4 Hz, 1H), 2.41 (s, 3H). ¹³C NMR (101 MHz, CDCl₃) δ 151.9, 149.7, 147.5, 144.6, 133.6, 132.7, 129.3, 127.7, 127.3, 123.3, 91.5, 12.9. HRMS m/z: [M+H]⁺ calcd. for C₂₆H₂₃N₂O 379.1805, found 379.1806.

example 18

1- (furan-2-yl) ethane-1-ketoxime and triphenyl methanol are used for synthesizing 1- (furan-2-yl) ethane-1-keton O-trityl oxime, and the steps are as follows:

(1) 1- (furan-2-yl) ethane-1-ketoxime (0.3 mmol, 0.0375 g), trityl alcohol (0.9 mmol, 0.2343 g), phosphotungstic acid (1 mol%, 0.0087 g), anhydrous magnesium sulfate (1.2 eq., 0.0433 g), and 2 mL dimethyl carbonate were added to a 25 mL reaction tube, and stirred at room temperature for 2 h;

(2) after the reaction is finished, adding a proper amount of triethylamine to neutralize the acid catalyst, filtering the mixture, washing the mixture by ethyl acetate (3X 10 mL), decompressing and rotary-evaporating the mixture, removing the solvent, and purifying the product by column chromatography (silica gel column is adopted, and the eluent is petroleum ether) to obtain the target product 1- (furan-2-yl) ethane-1-ketone O-trityl oxime with the yield of 80 percent.

And (3) nuclear magnetic resonance characterization of a product:¹H NMR (400 MHz, CDCl₃) δ 7.48-7.18 (m, 16H), 6.46 (t, J = 2.7 Hz, 1H), 6.32 (d, J = 3.1 Hz, 1H), 2.33 (s, 3H). ¹³C NMR (101 MHz, CDCl₃) δ 150.9, 147.4, 144.8, 143.1, 129.4, 127.6, 127.2, 111.3, 108.9, 91.0, 12.5. HRMS m/z: [M+Na]⁺ calcd. for C₂₅H₂₁NO₂Na 390.1465, found 390.1463.

example 19

tetrahydro-4H-pyran-4-ketoxime and triphenylmethanol are synthesized into tetrahydro-4H-pyran-4-ketonic O-trityl oxime by the following steps:

(1) in a 25 mL reaction tube, tetrahydro-4H-pyran-4-one oxime (0.3 mmol, 0.0345 g), trityl alcohol (0.9 mmol, 0.2343 g), phosphotungstic acid (1 mol%, 0.0087 g), anhydrous magnesium sulfate (1.2 eq., 0.0433 g), and 2 mL dimethyl carbonate were added, and stirred at 80 ℃ for 2H;

(2) after the reaction is finished, adding a proper amount of triethylamine to neutralize the acid catalyst, filtering the mixture, washing the mixture with ethyl acetate (3X 10 mL), decompressing and rotary-steaming the mixture, removing the solvent, and purifying the product by column chromatography (silica gel column is adopted, and the eluent is petroleum ether) to obtain the target product tetrahydro-4H-pyran-4-one O-trityl oxime with the yield of 59 percent.

And (3) nuclear magnetic resonance characterization of a product:¹H NMR (400 MHz, CDCl₃) δ 7.29 (dt, J = 22.8, 7.4 Hz, 15H), 3.68 (q, J = 5.7 Hz, 4H), 2.79 (t, J = 4.9 Hz, 2H), 2.25 (t, J = 4.8 Hz, 2H). ¹³C NMR (101 MHz, CDCl₃) δ 156.0, 144.8, 129.2, 127.6, 127.1, 90.1, 68.7, 67.0, 32.7, 27.7. HRMS m/z: [M+H]⁺ calcd. for C₂₄H₂₄NO₂ 358.1802, found 358.1796.

example 20

Dibenzyl ketone O-trityl oxime is synthesized by dibenzyl ketoxime and triphenyl methanol, and the steps are as follows:

(1) dibenzylketoxime (0.3 mmol, 0.0676 g), trityl alcohol (0.9 mmol, 0.2343 g), phosphotungstic acid (1 mol%, 0.0087 g), anhydrous magnesium sulfate (1.2 eq., 0.0433 g) and 2 mL of dimethyl carbonate were added to a 25 mL reaction tube, and stirred at room temperature for 2 hours;

(2) after the reaction is finished, adding a proper amount of triethylamine to neutralize the acid catalyst, filtering the mixture, washing the mixture by ethyl acetate (3X 10 mL), decompressing and rotary-evaporating the mixture, removing the solvent, and purifying the product by column chromatography (silica gel column is adopted, and the eluent is petroleum ether) to obtain the target product dibenzyl ketone O-trityl oxime with the yield of 93 percent.

And (3) nuclear magnetic resonance characterization of a product:¹H NMR (400 MHz, CDCl₃) δ 7.49-7.09 (m, 23H), 6.85 (d, J = 6.7 Hz, 2H), 3.68 (s, 2H), 3.28 (s, 2H). ¹³C NMR (101 MHz, CDCl₃) δ 158.2, 144.9, 137.1, 136.9, 129.34, 129.30, 129.26, 128.7, 128.4, 127.7, 127.1, 126.6, 126.5, 90.7, 39.8, 33.8. HRMS m/z: [M+H]⁺ calcd. for C₃₄H₃₀NO 468.2322, found 468.2317.

example 21

Synthesizing cyclohexanone oxime and triphenyl methanol into cyclohexanone O-trityl oxime by the following steps:

(1) in a 25 mL reaction tube, cyclohexanone oxime (0.3 mmol, 0.0339 g), trityl alcohol (0.9 mmol, 0.2343 g), phosphotungstic acid (1 mol%, 0.0087 g), anhydrous magnesium sulfate (1.2 eq., 0.0433 g), and 2 mL dimethyl carbonate were added, and stirred at 80 ℃ for 2 h;

(2) after the reaction is finished, adding a proper amount of triethylamine to neutralize the acid catalyst, filtering the mixture, washing the mixture with ethyl acetate (3X 10 mL), decompressing and rotary-steaming the mixture, removing the solvent, and purifying the product by column chromatography (silica gel column is adopted, and the eluent is petroleum ether) to obtain the target product cyclohexanone O-trityl oxime with the yield of 65%.

And (3) nuclear magnetic resonance characterization of a product:¹H NMR (400 MHz, CDCl₃) δ 7.38-7.20 (m, 15H), 2.62 (t, J = 5.8 Hz, 2H), 2.08 (d, J = 6.1 Hz, 2H), 1.54 (t, J = 7.5 Hz, 6H). ¹³C NMR (101 MHz, CDCl₃) δ 160.9, 145.1, 129.3, 127.5, 126.9, 89.6, 32. 5, 27.3, 26.2, 26.1, 26.0. HRMS m/z: [M+H]⁺ calcd. for C₂₅H₂₆NO 356.2009, found 356.2008.

example 22

Acetone oxime and triphenyl carbinol to synthesize acetone O-trityl oxime, which comprises the following steps:

(1) acetone oxime (0.3 mmol, 0.0219 g), trityl alcohol (0.9 mmol, 0.2343 g), phosphotungstic acid (1 mol%, 0.0087 g), anhydrous magnesium sulfate (1.2 eq., 0.0433 g) and 2 mL dimethyl carbonate were added to a 25 mL reaction tube, and stirred at 80 ℃ for 2 hours;

(2) after the reaction is finished, adding a proper amount of triethylamine to neutralize the acid catalyst, filtering the mixture, washing the mixture by ethyl acetate (3X 10 mL), decompressing and rotary-steaming the mixture, removing the solvent, and purifying the product by column chromatography (silica gel column is adopted, and the eluent is petroleum ether) to obtain the target product acetone O-trityl oxime with the yield of 65%.

And (3) nuclear magnetic resonance characterization of a product:¹H NMR (400 MHz, CDCl₃) δ 7.54-7.16 (m, 15H), 2.03 (d, J = 17.5 Hz, 3H), 1.79 (d, J = 16.5 Hz, 3H). ¹³C NMR (101 MHz, CDCl₃) δ 154.8, 145.2, 129.3, 127.6 127.0, 89.7, 22.2, 16.5. HRMS m/z: [M+H]⁺ calcd. for C₂₂H₂₂NO 316.1696, found 316.1688.s

example 23

Benzophenone oxime and 4-phenyl trityl alcohol are synthesized into benzophenone O- ([1,1' -biphenyl ] -4-yl benzhydryl) oxime by the following steps:

(1) into a 25 mL reaction tube, benzophenone oxime (0.3 mmol, 0.0592 g), 4-phenyltrityl alcohol (0.9 mmol, 0.3028 g), phosphotungstic acid (1 mol%, 0.0087 g), anhydrous magnesium sulfate (1.2 eq., 0.0433 g), and 2 mL dimethyl carbonate were added, and stirred at room temperature for 2 hours;

(2) after the reaction is finished, adding a proper amount of triethylamine to neutralize the acid catalyst, filtering the mixture, washing the mixture by ethyl acetate (3X 10 mL), decompressing and rotary-evaporating the mixture, removing the solvent, and purifying the product by column chromatography (silica gel column is adopted, and the eluent is petroleum ether) to obtain the target product benzophenone O- ([1,1' -biphenyl ] -4-yl-benzhydryl) oxime with the yield of 93 percent.

And (3) nuclear magnetic resonance characterization of a product:¹H NMR (400 MHz, CDCl₃) δ 7.58 (d, J = 7.6 Hz, 2H), 7.52-7.18 (m, 27H). ¹³C NMR (101 MHz, CDCl₃) δ 156.9, 144.7, 143.8, 140.9, 139.7, 136.8, 133.9, 129.7, 129.4, 129.3, 129.2, 128.84, 128.82, 128.19, 128.17, 128.14, 128.09, 128.05, 127.7, 127.3, 127.19, 127.15, 126.3, 91.3. HRMS m/z: [M+Na]⁺ calcd. for C₃₈H₂₉NONa 538.2141, found 538.2151.

example 24

Benzophenone O- ((4-chlorphenyl) benzhydryl) oxime is synthesized by benzophenone oxime and 4-chloro triphenyl carbinol, and the steps are as follows:

(1) into a 25 mL reaction tube, benzophenone oxime (0.3 mmol, 0.0592 g), 4-chlorotrityl alcohol (0.9 mmol, 0.2653 g), phosphotungstic acid (1 mol%, 0.0087 g), anhydrous magnesium sulfate (1.2 eq., 0.0433 g), and 2 mL dimethyl carbonate were added, and stirred at room temperature for 2 hours;

(2) after the reaction is finished, adding a proper amount of triethylamine to neutralize the acid catalyst, filtering the mixture, washing the mixture with ethyl acetate (3X 10 mL), carrying out reduced pressure rotary evaporation, removing the solvent, and purifying the product by adopting column chromatography (a silica gel column is adopted, and an eluent is petroleum ether) to obtain the target product benzophenone O- ((4-chlorophenyl) benzhydryl) oxime with the yield of 98%.

And (3) nuclear magnetic resonance characterization of a product:¹H NMR (400 MHz, CDCl₃) δ 7.46 (d, J = 7.7 Hz, 3H), 7.38 (d, J = 7.1 Hz, 2H), 7.31-7.19 (m, 19H). ¹³C NMR (101 MHz, CDCl₃) δ 157.2, 144.3, 143.3, 136.6, 133.8, 133.1, 130.9, 129.3, 129.3, 129.1, 128.9, 128.2, 127.8, 127.7, 127.3, 91.0. HRMS m/z: [M+Na]⁺ calcd. for C₃₂H₂₄ClNONa 496.1439, found 496.1442.

example 25

Benzophenone O- (bis (4-chlorophenyl) (phenyl) methyl) oxime is synthesized by benzophenone oxime and 4, 4' -dichlorotrityl alcohol by the following steps:

(1) into a 25 mL reaction tube, benzophenone oxime (0.3 mmol, 0.0592 g), 4' -dichlorotrityl alcohol (0.9 mmol, 0.2963 g), phosphotungstic acid (1 mol%, 0.0087 g), anhydrous magnesium sulfate (1.2 eq., 0.0433 g), and 2 mL dimethyl carbonate were added, and stirred at room temperature for 2 hours;

(2) after the reaction is finished, adding a proper amount of triethylamine to neutralize the acid catalyst, filtering the mixture, washing the mixture with ethyl acetate (3X 10 mL), carrying out reduced pressure rotary evaporation, removing the solvent, and carrying out product purification by column chromatography (silica gel column is adopted, and the eluent is petroleum ether) to obtain the target product benzophenone O- (bis (4-chlorophenyl) (phenyl) methyl) oxime with the yield of 95%.

And (3) nuclear magnetic resonance characterization of a product:¹H NMR (400 MHz, CDCl₃) δ 7.47 (d, J = 6.4 Hz, 3H), 7.36 (d, J = 7.0 Hz, 2H), 7.24 (h, J = 7.1 Hz, 18H). ¹³C NMR (101 MHz, CDCl₃) δ157.6, 143.9, 142.6, 136.4, 133.7, 133.3, 130.7, 129.5, 129.2, 129.0, 128.9, 128.3, 127.91, 127.89, 127.5, 90.5. HRMS m/z: [M+H]⁺ calcd. for C₃₂H₂₄Cl₂NO 508.1229, found 508.1228.

example 26

Benzophenone O- (1, 1-diphenyl ethyl) oxime is synthesized by benzophenone oxime and 1, 1-diphenyl ethanol, and the steps are as follows:

(1) in a 25 mL reaction tube, benzophenone oxime (0.3 mmol, 0.0592 g), 1-diphenylethanol (0.9 mmol, 0.1784 g), phosphotungstic acid (1 mol%, 0.0087 g), anhydrous magnesium sulfate (1.2 eq., 0.0433 g) and 2 mL dimethyl carbonate were added, and stirred at room temperature for 2 hours;

(2) after the reaction is finished, adding a proper amount of triethylamine to neutralize the acid catalyst, filtering the mixture, washing the mixture by ethyl acetate (3X 10 mL), decompressing and rotary-evaporating the mixture, removing the solvent, and purifying the product by column chromatography (silica gel column is adopted, and the eluent is petroleum ether) to obtain the target product benzophenone O- (1, 1-diphenyl ethyl) oxime with the yield of 65 percent.

And (3) nuclear magnetic resonance characterization of a product:¹H NMR (400 MHz, CDCl₃) δ 7.46 (q, J = 6.6 Hz, 5H), 7.36-7.18 (m, 15H), 2.14 (s, 3H). ¹³C NMR (101 MHz, CDCl₃) δ 156.8, 146.5, 136.9, 134.1, 129.4, 129.2, 128.7, 128.2, 127.99, 127.95, 126.80, 126.77, 85.9, 27.4. HRMS m/z: [M+H]⁺ calcd. for C₂₇H₂₄NO 378.1852, found 378.1858.

example 27

Benzophenone O- (2-phenylpropane-2-yl) oxime is synthesized by benzophenone oxime and 2-phenyl-2-propanol by the following steps:

(1) in a 25 mL reaction tube, benzophenone oxime (0.3 mmol, 0.0592 g), 2-phenyl-2-propanol (0.9 mmol, 0.1226 g), phosphotungstic acid (1 mol%, 0.0087 g), anhydrous magnesium sulfate (1.2 eq., 0.0433 g) and 2 mL dimethyl carbonate were added and stirred at room temperature for 2 h;

(2) after the reaction is finished, adding a proper amount of triethylamine to neutralize the acid catalyst, filtering the mixture, washing the mixture with ethyl acetate (3X 10 mL), decompressing and rotary-evaporating the mixture, removing the solvent, and purifying the product by column chromatography (silica gel column is adopted, and the eluent is petroleum ether) to obtain the target product benzophenone O- (2-phenylpropan-2-yl) oxime with the yield of 28 percent.

And (3) nuclear magnetic resonance characterization of a product:¹H NMR (400 MHz, CDCl₃) δ 7.41 (d, J = 8.3 Hz, 7H), 7.35-7.18 (m, 8H), 1.69 (s, 6H). ¹³C NMR (101 MHz, CDCl₃) δ 155.8, 147.5, 137.3, 134.0, 129.6, 129.0, 128.6, 128.2, 128.1, 128.0, 126.6, 125.5, 82.4, 28.4.HRMS m/z: [M+Na]⁺ calcd. for C₂₂H₂₁NONa 338.1515, found 338.1516.

example 28

Benzophenone oxime and 2-methyl-4-phenylbutan-2-ol are synthesized into benzophenone O- (2-methyl-4-phenylbutan-2-yl) oxime by the following steps:

(1) into a 25 mL reaction tube was added benzophenone oxime (0.3 mmol, 0.0592 g), 2-methyl-4-phenylbutan-2-ol (0.9 mmol, 0.1478 g), phosphotungstic acid (1 mol%, 0.0087 g), anhydrous magnesium sulfate (1.2 eq., 0.0433 g), and 2 mL dimethyl carbonate, and stirred at 100 ℃ for 12 h.

(2) After the reaction is finished, adding a proper amount of triethylamine to neutralize the acid catalyst, filtering the mixture, washing the mixture with ethyl acetate (3X 10 mL), decompressing and rotary-evaporating the mixture, removing the solvent, and purifying the product by column chromatography (silica gel column is adopted, and the eluent is petroleum ether) to obtain the target product benzophenone O- (2-methyl-4-phenylbutan-2-yl) oxime with the yield of 17 percent.

And (3) nuclear magnetic resonance characterization of a product:¹H NMR (400 MHz, CDCl₃) δ 7.52 (d, J = 7.1 Hz, 2H), 7.45-7.23 (m, 10H), 7.15 (t, J = 8.9 Hz, 3H), 2.65-2.54 (m, 2H), 1.95 (d, J = 16.5 Hz, 2H), 1.37 (s, 6H). ¹³C NMR (101 MHz, CDCl₃) δ 155.2, 143.2, 137.5, 133.9, 129.7, 129.0, 128.53, 128.49, 128.4, 128.2, 127.9, 125.7, 80.9, 42.8, 30.6, 25.9. HRMS m/z: [M+H]⁺ calcd. for C₂₄H₂₆NO 344.2009, found 344.2009.

example 29

Benzophenone O- (tert-butyl) oxime is synthesized by benzophenone oxime and tert-butanol by the following steps:

(1) in a 25 mL reaction tube, benzophenone oxime (0.3 mmol, 0.0592 g), tert-butanol (0.9 mmol, 0.0667 g), phosphotungstic acid (1 mol%, 0.0087 g), anhydrous magnesium sulfate (1.2 eq., 0.0433 g) and 2 mL dimethyl carbonate were added, and stirred at 100 ℃ for 12 hours;

(2) after the reaction is finished, adding a proper amount of triethylamine to neutralize the acid catalyst, filtering the mixture, washing the mixture by ethyl acetate (3X 10 mL), decompressing and rotary-evaporating the mixture, removing the solvent, and purifying the product by column chromatography (silica gel column is adopted, and the eluent is petroleum ether) to obtain the target product benzophenone O- (tert-butyl) oxime with the yield of 47 percent.

And (3) nuclear magnetic resonance characterization of a product:¹H NMR (400 MHz, CDCl₃) δ 7.50 (d, J = 7.4 Hz, 2H), 7.43-7.21 (m, 8H), 1.34 (s, 9H). ¹³C NMR (101 MHz, CDCl₃) δ 154.7, 137.7, 133.8, 129.9, 128.9, 128.5, 128.2, 128.0, 127.9, 79.4, 27.8. HRMS m/z: [M+H]⁺calcd. for C₁₇H₂₀NO 254.1539, found 254.1546.

example 30

Benzophenone O- (tertiary amyl) oxime is synthesized by benzophenone oxime and tertiary amyl alcohol by the following steps:

(1) in a 25 mL reaction tube, benzophenone oxime (0.3 mmol, 0.0592 g), tert-amyl alcohol (0.9 mmol, 0.0793 g), phosphotungstic acid (1 mol%, 0.0087 g), anhydrous magnesium sulfate (1.2 eq., 0.0433 g) and 2 mL dimethyl carbonate were added and stirred at 100 ℃ for 12 h;

(2) after the reaction is finished, adding a proper amount of triethylamine to neutralize the acid catalyst, filtering the mixture, washing the mixture by ethyl acetate (3X 10 mL), decompressing and rotary-evaporating the mixture, removing the solvent, and purifying the product by column chromatography (silica gel column is adopted, and the eluent is petroleum ether) to obtain the target product benzophenone O- (tertiary amyl) oxime with the yield of 13 percent.

And (3) nuclear magnetic resonance characterization of a product:¹H NMR (400 MHz, CDCl₃) δ 7.52 (dd, J = 7.4, 2.3 Hz, 2H), 7.45-7.29 (m, 8H), 1.70 (q, J = 7.5 Hz, 2H), 1.32 (s, 6H), 0.87 (t, J = 7.5 Hz, 3H).¹³C NMR (101 MHz, CDCl₃) δ 154.8, 137.8, 134.0, 129.7, 128.8, 128.4, 128.2, 128.0, 127.9, 81.56, 33.1, 25.4, 8.5. HRMS m/z: [M+H]⁺ calcd. for C₁₈H₂₂NO 268.1696, found 268.1698.

example 31

Benzophenone O- (1-methylcyclohexyl) oxime is synthesized from benzophenone oxime and 1-methylcyclohexanol by the following steps:

(1) into a 25 mL reaction tube, benzophenone oxime (0.3 mmol, 0.0592 g), 1-methylcyclohexanol (0.9 mmol, 0.1028 g), phosphotungstic acid (1 mol%, 0.0087 g), anhydrous magnesium sulfate (1.2 eq., 0.0433 g), and 2 mL dimethyl carbonate were added, and stirred at 100 ℃ for 12 hours;

(2) after the reaction is finished, adding a proper amount of triethylamine to neutralize the acid catalyst, filtering the mixture, washing the mixture by using ethyl acetate (3X 10 mL), decompressing and rotary-steaming the mixture, removing the solvent, and purifying the product by using column chromatography (using a silica gel column and using petroleum ether as an eluent) to obtain the target product benzophenone O- (1-methylcyclohexyl) oxime with the yield of 10 percent.

And (3) nuclear magnetic resonance characterization of a product:¹H NMR (400 MHz, CDCl₃) δ 7.55-7.48 (m, 2H), 7.45-7.29 (m, 8H), 2.01-1.87 (m, 2H), 1.56-1.34 (m, 10H), 1.30-1.19 (m, 1H).¹³C NMR (101 MHz, CDCl₃) δ 154.9, 137.7, 134.1, 129.7, 128.8, 128.4, 128.2, 127.9, 80.0, 36.3, 26.3, 25.8, 22.3. HRMS m/z: [M+H]⁺ calcd. for C₂₀H₂₄NO 294.1852, found 294.1851.

example 32

Synthesizing benzophenone O-adamantane-1-yl oxime from benzophenone oxime and 1-adamantanol by the following steps:

(1) into a 25 mL reaction tube, benzophenone oxime (0.3 mmol, 0.0592 g), 1-adamantanol (0.9 mmol, 0.1370 g), phosphotungstic acid (1 mol%, 0.0087 g), anhydrous magnesium sulfate (1.2 eq., 0.0433 g), and 2 mL dimethyl carbonate were added, and stirred at 100 ℃ for 12 hours;

(2) after the reaction is finished, adding a proper amount of triethylamine to neutralize the acid catalyst, filtering the mixture, washing the mixture by using ethyl acetate (3X 10 mL), decompressing and rotary-evaporating the mixture, removing the solvent, and purifying the product by adopting column chromatography (adopting a silica gel column and using petroleum ether as an eluent) to obtain the target product benzophenone O-adamantane-1-yl oxime with the yield of 92 percent.

And (3) nuclear magnetic resonance characterization of a product:¹H NMR (400 MHz, CDCl₃) δ 7.51 (dd, J = 7.5, 2.2 Hz, 2H), 7.43-7.28 (m, 8H), 2.27-2.14 (m, 3H), 1.95 (d, J = 3.0 Hz, 6H), 1.68 (t, J = 3.1 Hz, 6H). ¹³C NMR (101 MHz, CDCl₃) δ 155.0, 137.8, 133.9, 129.9, 128.8, 128.5, 128.2, 128.0, 127.9, 78.4, 41.8, 36.7, 30.8. HRMS m/z: [M+H]⁺ calcd. for C₂₃H₂₆NO 332.2009, found 332.2004.

example 33

The benzophenone O-benzhydryl oxime is synthesized by benzophenone oxime and benzhydryl alcohol, and the steps are as follows:

(1) into a 25 mL reaction tube, benzophenone oxime (0.3 mmol, 0.0592 g), benzhydrol (0.9 mmol, 0.1658 g), phosphotungstic acid (1 mol%, 0.0087 g), anhydrous magnesium sulfate (1.2 eq., 0.0433 g) and 2 mL dimethyl carbonate were added, and stirred at 100 ℃ for 12 hours;

(2) after the reaction is finished, adding a proper amount of triethylamine to neutralize the acid catalyst, filtering the mixture, washing the mixture by ethyl acetate (3X 10 mL), decompressing and rotary-evaporating the mixture, removing the solvent, and purifying the product by column chromatography (silica gel column is adopted, and the eluent is petroleum ether) to obtain the target product benzophenone O-benzhydryloxime with the yield of 97 percent.

And (3) nuclear magnetic resonance characterization of a product:¹H NMR (400 MHz, CDCl₃) δ 7.47-7.38 (m, 7H), 7.31-7.22 (m, 13H), 6.38 (s, 1H). ¹³C NMR (101 MHz, CDCl₃) δ 157.5, 141.9, 136.6, 133.6, 129.5, 129.4, 128.9, 128.4, 128.3, 128.2, 128.1, 127.5, 127.4, 87.4. HRMS m/z: [M+H]⁺ calcd. for C₂₆H₂₂NO 364.1696, found 364.1690.

example 34

Synthesizing benzophenone O- (1-phenethyl) oxime from benzophenone oxime and 1-phenethyl alcohol by the following steps:

(1) in a 25 mL reaction tube, benzophenone oxime (0.3 mmol, 0.0592 g), 1-phenylethyl alcohol (0.9 mmol, 0.1099 g), phosphotungstic acid (1 mol%, 0.0087 g), anhydrous magnesium sulfate (1.2 eq., 0.0433 g) and 2 mL dimethyl carbonate were added, and stirred at 80 ℃ for 12 hours;

(2) after the reaction is finished, adding a proper amount of triethylamine to neutralize the acid catalyst, filtering the mixture, washing the mixture by using ethyl acetate (3X 10 mL), decompressing and rotary-evaporating the mixture, removing the solvent, and purifying the product by using column chromatography (using a silica gel column and using petroleum ether as an eluent) to obtain the target product benzophenone O- (1-phenethyl) oxime with the yield of 78 percent.

And (3) nuclear magnetic resonance characterization of a product:¹H NMR (400 MHz, CDCl₃) δ 7.49-7.41 (m, 7H), 7.38-7.29 (m, 8H), 5.45 (q, J = 6.6 Hz, 1H), 1.59 (d, J = 6.7 Hz, 3H).¹³C NMR (101 MHz, CDCl₃) δ 156.6, 143.7, 136.9, 133.7, 129.6, 129.2, 128.8, 128.3, 128.2, 128.10, 128.05, 127.3, 126.4, 81.8, 22.4. HRMS m/z: [M+H]⁺ calcd. for C₂₁H₂₀NO 302.1539, found 302.1545.

example 35

Synthesis of diphenyl ketone O- (1, 3-diphenyl allyl) oxime from benzophenone oxime and chalcone comprises the following steps:

(1) into a 25 mL reaction tube, benzophenone oxime (0.3 mmol, 0.0592 g), chalcone (0.9 mmol, 0.1893 g), phosphotungstic acid (1 mol%, 0.0087 g), anhydrous magnesium sulfate (1.2 eq., 0.0433 g), and 2 mL dimethyl carbonate were added, and stirred at room temperature for 2 hours;

(2) after the reaction is finished, adding a proper amount of triethylamine to neutralize the acid catalyst, filtering the mixture, washing the mixture with ethyl acetate (3X 10 mL), decompressing and rotary-evaporating the mixture, removing the solvent, and purifying the product by column chromatography (silica gel column is adopted, and the eluent is petroleum ether) to obtain the target product diphenyl ketone O- (1, 3-diphenyl allyl) oxime with the yield of 94%.

And (3) nuclear magnetic resonance characterization of a product:¹H NMR (400 MHz, CDCl₃) δ 7.50-7.20 (m, 20H), 6.60 (d, J = 15.9 Hz, 1H), 6.43 (dd, J = 16.0, 6.6 Hz, 1H), 5.94 (d, J = 6.8 Hz, 1H).¹³C NMR (101 MHz, CDCl₃) δ 157.3, 140.9, 136.9, 136.7, 133.6, 132.0, 129.6, 129.4, 128. 9, 128.6, 128.5, 128.3, 128.2, 128.1, 127.8, 127.7, 127.3, 126.8, 86.3. HRMS m/z: [M+Na]⁺ calcd. for C₂₈H₂₃NONa 412.1672, found 412.1678。

Claims

1. the synthesis method of oxime ether derivatives is characterized in that starting substrate alcohol compounds and oxime compounds are dissolved in a solvent, heteropoly acid catalysts and additives are added, and oxime generation is carried out at 25-100 DEG COPerforming alkylation reaction for 0.5-12 hours to synthesize the oxime ether derivative, wherein the reaction formula is as follows:

2. The method of synthesizing an oxime ether derivative as claimed in claim 1 wherein the alcohol compound comprises any one of triphenylcarbinol, diphenylcarbinol, allyl alcohol and tertiary aliphatic alcohol.

3. The process for synthesizing an oxime ether derivative according to claim 1 wherein the oxime compound comprises any one of benzophenone oximes, acetophenone oximes, aliphatic ketoximes and ketoximes containing hetero atoms.

4. The process for synthesizing oxime ether derivatives according to claim 1 wherein the molar ratio of the alcohol compound to the oxime compound is 0.2: 1-3: 1.

5. the process for synthesizing an oxime ether derivative as claimed in claim 1, wherein the heteropoly acid catalyst comprises any one of phosphotungstic acid, silicotungstic acid and phosphomolybdic acid.

6. The method for synthesizing an oxime ether derivative as claimed in claim 1, wherein the additive is selected from any one of 4A molecular sieve, anhydrous sodium sulfate, anhydrous magnesium sulfate and silica gel.

7. The method of claim 1, wherein the solvent is selected from the group consisting of dimethyl carbonate, 1, 2-dichloroethane, dichloromethane, diethyl ether, acetonitrile, 1, 4-dioxane, cyclopentyl methyl ether, tetrahydrofuran, 2-methyltetrahydrofuran, acetone, ethyl acetate, ethyl lactate, dimethyl sulfoxide, methyl ether, ethyl acetate, methyl ether, ethyl acetate, methyl sulfoxide, ethyl acetate, ethyl sulfoxide, dimethyl sulfoxide, and ethyl acetate,N,N-any one of dimethylformamide, ethanol, methanol, toluene, cyclohexane and n-hexane.

8. The process for synthesizing an oxime ether derivative according to claim 1 wherein the molar ratio of the heteropolyacid catalyst to the oxime compound is 0.001: 1-0.1: 1.

9. the process for the synthesis of oxime ether derivatives of claim 1 wherein the molar ratio of additive to oxime compound is 0.2: 1-4: 1.

10. the method for synthesizing an oxime ether derivative according to any one of claims 1 to 9 wherein the reaction is carried out in an air atmosphere.