WO2021103798A1 - Method for preparing lactone compound - Google Patents

Abstract

Disclosed is a method for preparing a lactone compound, the method comprising performing an oxidation reaction on a cyclic ketone using molecular oxygen in the presence of an organic nitrogen-oxygen radical precursor, a free radical initiator, an alcohol and a Sn-based catalyst, or performing an oxidation reaction on a cyclic alcohol using molecular oxygen in the presence of an organic nitrogen-oxygen radical precursor, a Sn-based catalyst and a free radical initiator.

Description

Preparation method of lactone compound

Related application

This application claims the priority of the Chinese patent application filed on November 28, 2019, the application number is 201911190807.5, and the invention title is "Method for Preparation of Lactone Compounds", the entire content of which is incorporated in this application by reference.

Technical field

This application relates to the technical field of organic chemistry synthesis, in particular to a method for preparing lactone compounds.

Background technique

Lactone compounds refer to oxidation of substituted or unsubstituted cyclic ketone compounds to generate corresponding compounds, of which ε-caprolactone is the most widely used. ε-caprolactone is an important chemical intermediate, mainly used in the production of polycaprolactone, and can also be copolymerized or blended with other esters to synthesize high molecular polymers. Polycaprolactone has a wide range of applications in the field of medical materials due to its excellent biocompatibility and degradability, as well as good drug penetration. Polycaprolactone has good thermoplasticity, molding processability and environmental protection. With the improvement of environmental protection requirements, polycaprolactone is also expected to replace existing ordinary plastics and has huge market potential in the field of disposable packaging materials and mulching films.

At present, organic peroxyacids (such as peroxyacetic acid, trifluoroperoxyacetic acid, peroxybenzoic acid and m-chloroperoxybenzoic acid, etc.) and cyclohexanone undergo the Beeyer-Villiger oxidation reaction to synthesize ε-caprolactone. The main method, but the peroxyacid used in this traditional process is unstable, and the safety control is difficult. The utilization of peroxyacid atoms is not high, and organic waste acids of the same amount will be produced, which seriously pollutes the environment. In recent years, the method of oxidizing cyclohexanone to synthesize ε-caprolactone with oxygen or hydrogen peroxide as oxidant has become a research hotspot at home and abroad.

Oxygen as the oxidant in the Baeyer-Villiger reaction of cyclohexanone has the advantages of safety, few by-products, low cost and easy availability, and low environmental pollution. However, the oxygen oxidizing ability is weak, and aldehydes must be added as a co-oxidant during the reaction. Oxygen oxidizes aldehydes. Peroxyacid, peroxyacid and ketone are then oxidized to synthesize ester. The most commonly used co-oxidant is benzaldehyde, but the use efficiency of benzaldehyde is limited (the molar amount of benzaldehyde is generally 2-3 times the molar amount of oxygen), and the price of benzaldehyde is relatively high, and it turns into a cheap one during the reaction. Benzoic acid has reduced economic value, leading to high economic costs. In addition, the boiling points of benzoic acid and ε-caprolactone are close, making separation difficult.

Fukuda (Tetrahedron Letters, 2001, 42, 3479-3481) et al. reported that the mixture of cyclohexanol and cyclohexanone (KA oil) was used as a raw material to synthesize ε-caprolactone. First, molecular oxygen was used as an oxidant and N-hydroxyl Phthalimide (NHPI) and azobisisobutyronitrile (AIBN) are used as catalysts to oxidize cyclohexanol to generate cyclohexanone and 1-hydroxy-1-peroxycyclohexane, and then InCl ₃ is used as catalyst Catalytic oxidation of cyclohexanone to ε-caprolactone, the conversion rate of cyclohexanol is 80%, the selectivity of ε-caprolactone (based on the conversion amount of cyclohexanol) is 33.3%, and the selectivity of cyclohexanone ( Based on the conversion amount of cyclohexanol) was 41.7%. KA oil comes from cyclohexane air oxidation, the raw material cost is low, but the selectivity of ε-caprolactone is low. During the reaction, cyclohexanone and hydrogen peroxide produce more dicyclohexyl peroxide, such as 1-hydroxy- 1'-hydroperoxydicyclohexyl peroxide, 1,1'-dihydroxydicyclohexyl peroxide, 7,8,15,16-tetraoxadispiro[5.2.5.2]hexadecane, etc. Although these dicyclohexyl peroxides can be _{converted into cyclohexanol and cyclohexanone by PPh 3} treatment, they will increase production costs. In addition, InCl ₃ is expensive and cannot be recycled.

Kamae (Bull.Chem.Soc.Jpn.2009,82,7:891-895) et al. reported that 1,1,1,3,3,3-hexafluoroisopropanol (HFIP) and/or p-toluene In sulfonic acid (p-TsOH), dicyclohexyl peroxide can be converted to caprolactone. Patent WO2008108072 publicly reported that in the presence of NHPI, molecular oxygen was used to oxidize cyclohexanol, and then treated with HFIP to obtain ε-caprolactone. Stir a mixture of 60mmol cyclohexanol, 120mmol cyclohexanone, 6mmol NHPI, 3mmol AIBN and 30mL HFIP in an oxygen atmosphere for 20h, the reaction temperature is 348K, the conversion rate of cyclohexanol is 8.3%, and the conversion rate of cyclohexanone is 33.6 %, the selectivity of caprolactone (based on the conversion amount of cyclohexanone) is 71.4%. Du (Molecular Catalysis 2019,467,24-2) et al. reported that using HFIP as a solvent, NHPI and cerium ammonium nitrate catalyze the oxidation of KA oil by oxygen to generate caprolactone. HFIP is beneficial to the synthesis of ε-caprolactone, but cyclohexanol The conversion rate of HFIP is low, the amount of HFIP is large (the amount of HFIP is 30 times that of cyclohexanone), the price is expensive, and the process cost is high, which is not conducive to industrial production.

As a green oxidant, hydrogen peroxide has only water as a by-product after the reaction, which is environmentally friendly, so it has attracted more and more attention. Patent US 6,531,615 publicly reported that HMS-C-SbF ₃ was used as a catalyst and 70wt% H ₂ O _{2 was used} as an oxidant to catalyze the synthesis of ε-caprolactone from cyclohexanone. The reaction temperature was 343K and the yield of ε-caprolactone was 40.3%. However, the use of high-concentration hydrogen peroxide has potential safety hazards of corrosion and explosion. From the perspective of industrial safety production, using low-concentration hydrogen peroxide as an oxidant is an ideal choice, but low-concentration hydrogen peroxide has a weak ability to oxidize it. Need to rely on efficient catalysts.

Corma (Nature, 2001, 412, 423-425) et al. reported that Sn-beta molecular sieves were hydrothermally synthesized in a fluorine-containing system and used to catalyze the _{Baeyer-Villiger reaction of H 2} O ₂ and cyclohexanone to synthesize ε-caprolactone , At a reaction temperature of 90°C, reacting for 3 hours, 35wt% H ₂ O ₂ ( _{the molar amount of H 2} O ₂ is 1.5 times the molar amount of cyclohexanone), the conversion rate of cyclohexanone reaches 52%, ε-hexanone The selectivity of lactones is greater than 98%. The four-coordinated Sn atom in the framework of the Sn-beta molecular sieve can accept electron pairs to form a Lewis acid center, which can combine with the lone pair of electrons in the carbonyl group, thus exhibiting excellent catalytic activity. However, due to the water brought in by the aqueous hydrogen peroxide solution and the water produced by the reaction, the reaction system contains more water, which is easy to hydrolyze the unstable ε-caprolactone, especially in the presence of high concentrations of hydrogen peroxide. This hydrolysis reaction will be promoted, resulting in a lower yield of ε-caprolactone. In addition, the amount of hydrogen peroxide solution is large, the utilization rate of hydrogen peroxide is low, and the production cost is increased. Therefore, how to reduce the water content in the reaction system, improve the utilization rate of hydrogen peroxide and the selectivity and yield of ε-caprolactone is of great significance for the development of safe, green and efficient ε-caprolactone synthesis technology.

Summary of the invention

According to various embodiments of the present application, a method for preparing lactone compounds is provided. In the presence of organic nitroxide radical precursors, radical initiators, alcohols and Sn-based catalysts, molecular oxygen is used for the following formula The ketone represented by (1) undergoes an oxidation reaction to obtain a lactone compound represented by the following formula (2), wherein the organic nitroxide radical precursor is a nitrogen-containing ring having a skeleton represented by the following formula (3) Like compound;

In formula (1) and formula (2), R ^a and R ^{b are the} same or different, and represent an organic group having a carbon atom at the bonding site of the adjacent carbonyl carbon atom, and R ^a and R ^{b are} independently selected from alkane group, an alkenyl group, an alkynyl group, an alicyclic hydrocarbon group, aromatic hydrocarbon group or heterocyclic group, R ^a and R ^b are bonded to each other with the adjacent carbonyl carbon atom to form a ring together;

In the formula (3), R represents a protective group of a hydroxyl group or a hydrogen atom.

In the above preparation method, under the oxidation of molecular oxygen, the organic nitroxide radical precursor, the free radical initiator and the alcohol can interact to generate H ₂ O ₂ in situ, and then, the H _{2 generated in situ by the cyclic ketone} O ₂ and Sn-based catalysts are oxidized to generate corresponding lactones, which realizes the combination of in-situ synthesis of hydrogen peroxide and Baeyer-Villiger oxidation of cyclic ketones.

Therefore, the above preparation method can catalyze the oxidation of cyclic ketones by hydrogen peroxide generated in situ, reduce the water content in the reaction system, reduce the hydrolysis of lactone compounds, and further improve the selectivity and yield of lactone compounds.

In one of the embodiments, the alcohol is a secondary alcohol represented by the following formula (4),

In formula (4), R ^c and R ^{d are the} same or different and represent an organic group having a carbon atom at the bonding site of the adjacent hydroxyl carbon atom. R ^c and R ^{d are} independently selected from alkyl groups and alkenyl groups. , Alkynyl group, alicyclic hydrocarbon group, aromatic hydrocarbon group or heterocyclic group, or R ^c and ^Rd are bonded to each other and form a ring with adjacent hydroxyl carbon atoms.

In one of the embodiments, the alcohol is at least one of benzhydrol, 2-adamantanol, cyclohexanol, 2-methylcyclohexanol, and 1-phenylethanol.

In one of the embodiments, the ketone is at least one of 2-adamantanone, cyclohexanone, cyclopentanone, 3-methylcyclohexanone, and 2-norbornone.

In one of the embodiments, the molar ratio of the ketone to the alcohol is 0.5:1 to 4:1.

In one of the embodiments, the organic nitroxide radical precursor is selected from the nitrogen-containing ring represented by the following formula (3-1), (3-2), (3-3) or (3-4) Compound,

In formulas (3-1), (3-2), (3-3) or (3-4), R ₁ , R ₂ , and R _{3 are} independently selected from a hydrogen atom, an alkyl group, a cycloalkyl group, and an aryl group , Heterocycle, hydroxyl, nitro or halogen, or at least two of _{R 1} , R ₂ , and R _{3 form a ring.}

In one of the embodiments, the organic nitroxide radical precursor is selected from at least one of the nitrogen-containing cyclic compounds represented by the following formulas (3-5)-(3-16),

In one of the embodiments, the organic nitroxide radical precursor is selected from N-hydroxysuccinimide represented by formula (3-5) and N-hydroxyphthalimide represented by formula (3-8) Dicarboximide, 2-hydroxyisoquinoline-1,3(2H,4H)-dione represented by formula (3-13), N-hydroxy-1,8 represented by formula (3-15) -At least one of naphthalimide and N-hydroxy 5-norbornene-2,3-dicarboximide represented by formula (3-16).

In one of the embodiments, the free radical initiator includes at least one of azobisisobutyronitrile, azobisisovaleronitrile, azobisisoheptonitrile, and dimethyl azobisisobutyrate.

In one of the embodiments, the molar ratio of the radical initiator to the organic nitroxide radical precursor is 0.2:1 to 1:1.

In one of the embodiments, the Sn-based catalyst includes Sn-based fluorine-containing two-phase system catalyst, Sn-based molecular sieve, Sn-based mesoporous composite, Sn-based clay, Sn-based metal oxide, or Sn-based polymer catalyst. At least one.

In one of the embodiments, the Sn-based catalyst is Sn-beta molecular sieve.

In one of the embodiments, the molar ratio of the organic nitroxide radical precursor to the alcohol is 0.05:1 to 0.3:1.

In one of the embodiments, the molar ratio of the Sn-based catalyst to the alcohol is 0.002:1-0.01:1, wherein the molar amount of the Sn-based catalyst is calculated based on the molar amount of Sn.

In one of the embodiments, the oxidation reaction is carried out in a reaction system in which an organic solvent is used as the solvent. The organic solvent includes 1,4-dioxane, methyl tert-butyl ether, ethyl acetate, and butyl acetate. , At least one of isopropyl acetate, chlorobenzene, and methyl benzoate.

In one of the embodiments, based on 1 mmol of the alcohol, the mass of the organic solvent is 1 g-4 g.

In one of the embodiments, the temperature of the oxidation reaction is 60°C-85°C, and the reaction time is 4h-24h.

A preparation method of lactone compound, in the presence of the above-defined organic nitroxide radical precursor, Sn-based catalyst and free radical initiator, molecular oxygen is used to react the cyclic alcohol represented by the following formula (5) Perform oxidation to obtain a lactone compound represented by the following formula (6);

In formula (5) and formula (6), R ^e and R ^{f are the} same or different, representing an organic group having a carbon atom at the bonding site of the adjacent hydroxyl carbon atom, and R ^e and R ^{f are} independently selected from alkane Group, alkenyl group, alkynyl group, alicyclic hydrocarbon group, aromatic hydrocarbon group or heterocyclic group, R ^e and R ^f are bonded to each other and form a ring with adjacent hydroxyl carbon atoms.

In the above preparation method, the cyclic alcohol synthesizes hydrogen peroxide in situ while also generating corresponding cyclic ketones, and the cyclic ketones generated in situ produce lactones under the action of hydrogen peroxide generated in situ and Sn-based catalysts. Compound. Thus, the combination of in-situ synthesis of hydrogen peroxide and Baeyer-Villiger oxidation reaction of cyclic ketones is also realized, which can also reduce the water content in the reaction system, reduce the hydrolysis of lactone compounds, and increase the selection of lactone compounds. Sex and yield.

In one embodiment, the cyclic alcohol represented by formula (5) is oxidized in the presence of a ketone. This ketone can correspond to the cyclic ketone represented by the above formula (1). In one or more embodiments, the ketone uses a cyclic ketone corresponding to the cyclic alcohol represented by formula (5). For example, when cyclohexanol is used for oxidation, cyclohexanone is used.

The molar ratio of the above ketone to the above cyclic alcohol is 0.5:1 to 4:1.

Detailed ways

In order to make the purpose, technical solutions, and advantages of the present application clearer, the following examples are used to further describe the present application in detail. It should be understood that the specific embodiments described here are only used to explain the application, and are not used to limit the application.

In the preparation method of the first lactone compound provided by the embodiment of the application, in the presence of an organic nitroxide radical precursor, a free radical initiator, an alcohol and a Sn-based catalyst, molecular oxygen is used for the following formula (1 The ketone represented by) is oxidized to obtain a lactone compound represented by the following formula (2), wherein the organic nitroxide radical precursor is a nitrogen-containing cyclic compound having a skeleton represented by the following formula (3);

In formula (1) and formula (2), R ^a and R ^{b are the} same or different, and represent an organic group having a carbon atom at the bonding site of the adjacent carbonyl carbon atom, and R ^a and R ^{b are} independently selected from alkane group, an alkenyl group, an alkynyl group, an alicyclic hydrocarbon group, aromatic hydrocarbon group or heterocyclic group, R ^a and R ^b are bonded to each other with the adjacent carbonyl carbon atom to form a ring together;

In the formula (3), R represents a protective group of a hydroxyl group or a hydrogen atom.

The first preparation method of this application uses a one-pot method to mix organic nitroxide radical precursors, free radical initiators, alcohols, Sn-based catalysts and cyclic ketones. Under the oxidation of molecular oxygen, the organic nitroxides are free The base precursor, free radical initiator and alcohol interact to generate H ₂ O ₂ in situ, and the cyclic ketone is oxidized to the corresponding lactone under the action of _{the H 2} O _{2 and Sn-based catalyst generated in situ, thereby realizing hydrogen peroxide} Combination of in-situ synthesis and Baeyer-Villiger oxidation of cyclic ketones. Therefore, the cyclic ketone can be catalyzed and oxidized by the hydrogen peroxide generated in situ, the water content in the reaction system can be reduced, the hydrolysis of lactone compounds can be reduced, and the selectivity and yield of lactone compounds can be improved.

In the ketone represented by formula (1) in the present application, ^{the ring formed by Ra} and ^Rb bonded to each other and formed with adjacent carbonyl carbon atoms includes: 3-membered-20-membered alicyclic hydrocarbon ring (cycloalkane ring or cycloalkene Ring), preferably a 3- to 15-membered alicyclic hydrocarbon ring, more preferably a 3- to 12-membered alicyclic hydrocarbon ring, such as cyclopropane, cyclobutane, cyclopentane, cyclopentene, cyclohexene Alkenes, cyclooctane, cyclododecane, etc.; or, 2-membered to 4-membered bridged cyclic hydrocarbon ring or bridged cyclic heterocyclic ring, such as norbornene ring, norbornene ring, adamantane, etc.; or, 5 8-membered non-aromatic heterocyclic ring, such as tetrahydrofuran, pyrrolidine, piperidine, etc.

The ring formed by R ^a and R ^b bonded with each other and the adjacent carbonyl carbon atoms also has optional substituents, such as halogen atoms, alkyl groups, alkenyl groups, alkynyl groups, hydroxyl groups, alkoxy groups, and acyloxy groups. , Carboxyl group, substituted or unsubstituted amino group, alicyclic hydrocarbon group, aromatic hydrocarbon group, heterocyclic group, etc. In addition, an aromatic or non-aromatic ring (hydrocarbon ring or heterocyclic ring) may be condensed on the ring formed by ^Ra and R ^{b bonded to each other and formed together with adjacent carbonyl carbon atoms.} The substitution on the ring is preferably substitution at the 2, 3, and 4 positions.

In one or more embodiments, the ketone in this application is 2-adamantanone, cyclohexanone, cyclopentanone, 2-methylcyclohexanone, 3-methylcyclohexanone, 2-norbornone At least one of.

In one or more embodiments, the alcohol may be a secondary alcohol represented by formula (4),

In formula (4), R ^c and R ^{d are the} same or different, and represent an organic group having a carbon atom at the bonding site of the adjacent hydroxyl carbon atom, including a hydrocarbon group or a heterocyclic group, or R ^c and R ^d are mutually Bonding and forming a ring with adjacent hydroxyl carbon atoms.

In one or more embodiments, the hydrocarbyl group may be a linear or branched substituted hydrocarbyl group with various carbon chain lengths, including: aliphatic hydrocarbon groups with 1-20 carbon atoms such as alkyl, alkenyl, or alkynyl. , Preferably 1-15 aliphatic hydrocarbon groups, more preferably 1-10 aliphatic hydrocarbon groups; or, cyclopropyl, cyclobutyl, cyclopentyl, cyclopentenyl, cyclohexyl, cyclohexenyl, cyclo 3-20 membered alicyclic hydrocarbon groups (cycloalkyl or cycloalkenyl) such as octyl and cyclododecyl; or, phenyl, naphthyl, anthracenyl, phenanthryl, fluorenyl and other carbon atoms with 6 -18 aromatic hydrocarbon groups and so on.

In one or more embodiments, the heterocyclic group may include at least one of an oxygen-containing heterocycle, a sulfur-containing heterocycle, and a nitrogen-containing heterocycle, such as tetrahydrofuran, thiophene, thiazole, pyrrole, pyrrolidine, piperidine, Pyrazole, quinazoline, piperidine, oxazole, etc.

The ring formed by R ^c and R ^d together with adjacent hydroxyl carbon atoms includes: 3-membered-20-membered alicyclic hydrocarbon ring (cycloalkane ring or cycloalkene ring), preferably 3-membered-15-membered ring An alicyclic hydrocarbon ring, more preferably a 3- to 12-membered alicyclic hydrocarbon ring, such as cyclopropane, cyclobutane, cyclopentane, cyclopentene, cyclohexene, cyclooctane, cyclododecane, etc. ; Or, 2-membered 4-membered bridged cyclic hydrocarbon ring or bridged cyclic heterocyclic ring, such as norbornane ring, norbornene ring, adamantane, etc.; or, 5-membered 8-membered non-aromatic heterocyclic ring, For example, tetrahydrofuran, pyrrolidine, piperidine, etc.

The above-mentioned organic groups and R ^c and R ^d bond to each other and form a ring together with the adjacent hydroxyl carbon atoms, which also have optional substituents, such as halogen atoms, alkyl groups, alkenyl groups, alkynyl groups, hydroxyl groups, and alkoxy groups. Group, acyloxy group, carboxyl group, substituted or unsubstituted amino group, alicyclic hydrocarbon group, aromatic hydrocarbon group, heterocyclic group, etc. In addition, an aromatic or non-aromatic ring (hydrocarbon ring or heterocyclic ring) may be condensed on the aforementioned ring. The substitution on the ring is preferably substitution at the 2, 3, and 4 positions.

In one or more embodiments, the alcohol may also be at least one of benzhydrol, 2-adamantanol, cyclohexanol, 2-methylcyclohexanol, and 1-phenylethanol.

The molar ratio of the ketone to the alcohol is 0.5:1 to 4:1.

In the present application, the organic nitroxide radical precursor uses a nitrogen-containing cyclic compound containing a skeleton represented by formula (3), which serves as a catalyst for in-situ generation of hydrogen peroxide from the oxidation of alcohol in the preparation reaction system of the lactone compound. Reagents,

In the formula (3), R represents a protective group of a hydroxyl group or a hydrogen atom, and is preferably a hydrogen atom.

As the protective group for the hydroxyl group, R can use the protective group for the hydroxyl group generally used in the field of organic synthesis, preferably a group capable of forming an acetal or hemiacetal with the hydroxyl group, or from carboxylic acid, sulfonic acid, carbonic acid Hydrolyzable protective groups such as acyl, sulfonyl, alkoxycarbonyl, carbamoyl, etc., which can be removed by hydrolysis, obtained by removing hydroxyl groups from acids such as carbamic acid, sulfuric acid, phosphoric acid, and boric acid.

In one or more embodiments, the organic nitroxide radical precursor is selected from the nitrogen-containing cyclic ring represented by the following formula (3-1), (3-2), (3-3) or (3-4) Compound,

In formulas (3-1), (3-2), (3-3) or (3-4), R ₁ , R ₂ , and R _{3 are} independently selected from a hydrogen atom, an alkyl group, a cycloalkyl group, and an aryl group , Heterocycle, hydroxyl, nitro or halogen, or at least two of _{R 1} , R ₂ , and R _{3 form a ring.}

The above-mentioned alkyl group can be selected from alkyl groups with 1-8 carbon atoms, cycloalkyl groups can be selected from alkyl groups with 3-7 carbon atoms, and aromatic groups can be selected from benzene ring, pyridine, anthracene, pyrrole ring, etc., heterocycle It can be selected from a five-membered ring or a six-membered ring containing N and S.

When the organic nitroxide radical precursor is the formula (3-1) or (3-2), the substituents R ₁ and R _{2 may} be substituted independently or form a ring. This ring can be a saturated ring or an unsaturated ring; this ring can be a carbocyclic ring or a carbocyclic heterocyclic ring.

When the organic nitroxide radical precursor is of formula (3-3) or (3-4), R ₁ , R ₂ , and R ₃ may be substituted independently, or may form a ring. This ring may be a saturated ring or an unsaturated ring.

The above-mentioned substituents R ₁ , R ₂ , and R ₃ may still be further substituted with other functional groups, and may be alkyl, cycloalkyl, aromatic, heterocyclic, hydroxyl, nitro, halogen, or hydrogen atoms.

In one or more embodiments, the organic nitroxide radical precursor is selected from at least one of the nitrogen-containing cyclic compounds represented by the following formulas (3-5)-(3-16),

In one or more embodiments, the organic nitroxide radical precursor is selected from the group consisting of N-hydroxysuccinimide (NHS) represented by formula (3-5) and formula (3-8) N-hydroxyphthalimide (NHPI), 2-hydroxyisoquinoline-1,3(2H,4H)-dione (HQD) represented by formula (3-13), formula (3-15) ) Shown in N-hydroxy-1,8-naphthalimide, formula (3-16) shown in N-hydroxy 5-norbornene-2,3-dicarboximide (HONB) At least one of.

The molar ratio of the organic nitroxide radical precursor to the alcohol is 0.05:1-0.3:1.

In this application, the free radical initiator is beneficial to increase the generation of free radicals from the organic nitroxide free radical precursor, thereby increasing the conversion rate of alcohol. Free radical initiators include at least one of azobisisobutyronitrile (AIBN), azobisisovaleronitrile (AMBN), azobisisoheptonitrile (ABVN), and dimethyl azobisisobutyrate (AIBME) One kind.

The molar ratio of the radical initiator to the organic nitroxide radical precursor is 0.2:1 to 1:1.

In this application, Sn-based catalysts can be homogeneous catalyst materials or Sn-based heterogeneous catalyst materials, including Sn-based fluorine-containing two-phase system catalysts, Sn-based molecular sieves, Sn-based mesoporous composites, Sn-based clays, and Sn-based metal oxidation At least one of the Sn-based polymer catalyst.

In one or more embodiments, the Sn-based catalyst is a Sn-beta molecular sieve. The content of Sn in the Sn-beta molecular sieve can be changed appropriately. When the content of Sn changes, the amount of Sn-beta molecular sieve can also be changed accordingly.

The molar ratio of the above-mentioned Sn-based catalyst to the above-mentioned alcohol is 0.002:1-0.01:1, wherein the molar amount of the Sn-based catalyst is calculated based on the molar amount of Sn.

In one or more embodiments, an organic solvent is also added to the preparation method, specifically the organic nitroxide radical precursor, radical initiator, alcohol, Sn-based catalyst, and ketone are mixed with the organic solvent, and then in an oxygen-containing atmosphere Under the oxidation reaction.

The above-mentioned organic solvent includes at least one of 1,4-dioxane, methyl tert-butyl ether, ethyl acetate, butyl acetate, isopropyl acetate, chlorobenzene, and methyl benzoate. It is preferably 1,4-dioxane, isopropyl acetate or methyl benzoate, and more preferably 1,4-dioxane.

Based on 1 mmol of the alcohol, the mass of the organic solvent is 1 g-4 g.

In this application, there is no obvious limitation on molecular oxygen, which can be pure oxygen, oxygen-enriched air, air, or one or more diluted oxygen from inert gases such as nitrogen, helium, and argon. In one or more embodiments, the molecular oxygen is a mixed gas of pure oxygen, 5% oxygen and 95% nitrogen.

The pressure of the above oxidation reaction can be any pressure from normal pressure to high pressure, but the higher the pressure, the more by-products and the more the lactone compound will decompose. Therefore, in one or more embodiments, the reaction pressure is 0.1 MPa -0.5MPa, preferably normal pressure.

The reaction temperature also has a great influence on the oxidation reaction. The higher the temperature, the higher the conversion rate. However, a higher temperature will also increase the generation of side reactions and reduce the selectivity of lactone compounds, and high temperature may cause the loss of Sn-based catalysts. live. In one or more embodiments, the temperature of the oxidation reaction is 60°C-85°C, and the time of the oxidation reaction is 4h-24h.

The above-mentioned oxidation reaction can be carried out in the presence of oxygen or in the flow of oxygen, and can be carried out by commonly used methods such as batch, semi-batch, and continuous. Reactors such as circulating reactors and bubbling reactors can be used.

After the above oxidation reaction is completed, the product post-treatment step may include separation and purification of lactone compounds, by-product ketones, and recovery of Sn-based catalysts. The specific post-treatment process includes: cooling the completely reacted mixed solution to room temperature, distilling off the solvent, and then rectifying the remaining reaction liquid to separate the lactone compound and the by-product ketone, and recovering the Sn-based catalyst, and the Sn-based catalyst is washed , It can be used repeatedly after drying.

In the preparation method of the second lactone compound provided in the examples of the application, in the presence of the above-defined organic nitroxide radical precursor, Sn-based catalyst and free radical initiator, molecular oxygen is used for the following The cyclic alcohol represented by the formula (5) is oxidized to obtain a lactone compound represented by the following formula (6);

In formula (5) and formula (6), R ^e and R ^{f are the} same or different, representing an organic group having a carbon atom at the bonding site of the adjacent hydroxyl carbon atom, and R ^e and R ^{f are} independently selected from alkane Group, alkenyl group, alkynyl group, alicyclic hydrocarbon group, aromatic hydrocarbon group or heterocyclic group, R ^e and R ^f are bonded to each other and form a ring with adjacent hydroxyl carbon atoms.

In the second preparation method of lactone compounds, the cyclic alcohol synthesizes hydrogen peroxide in situ while also generating the corresponding cyclic ketone. The cyclic ketone generated in situ generates hydrogen peroxide and Sn-based catalyst in situ. Under the action of the production of lactone compounds.

In the second method for preparing lactone compounds, in the cyclic alcohol represented by formula (4), the ring formed by R ^e and R ^f bonded to each other and formed with adjacent hydroxyl carbon atoms includes: 3-membered-20-membered lipid Cyclic hydrocarbon ring (cycloalkane ring or cycloalkene ring), preferably 3- to 15-membered alicyclic hydrocarbon ring, more preferably 3- to 12-membered alicyclic hydrocarbon ring, such as cyclopropane, cyclobutane , Cyclopentane, cyclopentene, cyclohexene, cyclooctane, cyclododecane, etc.; or, 2 to 4 member bridged cyclic hydrocarbon ring or bridged cyclic heterocyclic ring, such as norbornane ring, norbornane ring, or Borene ring, adamantane, etc.; or, 5-membered-8-membered non-aromatic heterocyclic ring, such as tetrahydrofuran, pyrrolidine, piperidine, etc.

The ring formed by R ^e and R ^f bonded to each other and formed with adjacent hydroxyl carbon atoms also has optional substituents, such as halogen atoms, alkyl groups, alkenyl groups, alkynyl groups, hydroxyl groups, alkoxy groups, and acyloxy groups. , Carboxyl, substituted or unsubstituted amino, alicyclic hydrocarbon group, aromatic hydrocarbon group, heterocyclic group, etc. In addition, an aromatic or non-aromatic ring (hydrocarbon ring or heterocyclic ring) may be condensed on the aforementioned ring. The substitution on the ring is preferably substitution at the 2, 3, and 4 positions.

In one or more embodiments, the cyclic alcohol in the second lactone compound is at least one of 2-adamantanol, cyclohexanol, and 2-methylcyclohexanol.

In the second method for preparing a lactone compound, it is preferable to oxidize the cyclic alcohol represented by formula (5) in the presence of a ketone. This ketone can correspond to the cyclic ketone represented by the above formula (1). In one or more embodiments, the ketone uses a cyclic ketone corresponding to the cyclic alcohol represented by formula (5). For example, when cyclohexanol is used for oxidation, cyclohexanone is used.

The molar ratio of the above ketone to the above cyclic alcohol is 0.5:1 to 4:1.

The preparation methods of the two lactone compounds provided in the examples of this application can both generate hydrogen peroxide in situ and be used in conjunction with a Sn-based catalyst to catalyze the oxidation of cyclic ketones to synthesize lactones, thereby realizing the in-situ synthesis of hydrogen peroxide and the synthesis of cyclic ketones. The combination of Baeyer-Villiger oxidation reaction has simple process and strong operability. At the same time, the in-situ synthesis of hydrogen peroxide can not only reduce the water content in the reaction system, reduce lactone hydrolysis, and improve the selectivity and yield of lactones, but also avoid the storage and transportation of hydrogen peroxide, making it safer, more reliable, and better. Industrial application prospects.

In addition, the raw materials in this application are readily available and low in cost, and the by-products are ketones with industrial application value, which improves the economic feasibility of the preparation process.

The application will be further described below in conjunction with specific embodiments, but the scope of protection of the application is not limited to those described in the embodiments.

In the following examples, the conversion rate of alcohol, the selectivity of ketones, and the selectivity of lactones were measured by gas chromatography. The gas chromatograph is Agilent 7820A (Agilent DB-35ms column, 30m×0.32mm×0.25μm; FID detector), the detection method adopts the internal standard method, with naphthalene as the internal standard substance.

For the first method for preparing lactones, the conversion rate of ketone (Cketone), the selectivity of ester (Slactone), and the yield of ester (Y _lactone ) are calculated on the basis of ketone. The calculation method is as follows:

When there is a conversion relationship between alcohol and ketone in the system (for example, cyclohexanol and cyclohexanone), the selectivity of the ester and the yield of the ester are calculated as follows:

For the second method of preparing lactones, calculate the conversion rate of alcohol (C), the selectivity of ketones (S _ketone ), the selectivity of esters (S1 _lactone ), and the yield of esters (Y _lactone ) based on alcohol. , Using the following calculation method:

When there is a conversion relationship between the alcohol and ketone before the reaction in the system, the calculation of the selectivity of the ester and the yield of the ester is consistent with the calculation method of the same situation in the first preparation method:

The preparation method of Sn-beta molecular sieve is: the preparation of Sn-beta molecular sieve by the method of dealumination and doping, reference (ACS Catalysis, 2014, 4, 8, 2801-2810). Weigh 2g of Al-Beta molecular sieve (the manufacturer is Nankai University Catalyst Factory, the _{molar ratio of SiO 2} to Al ₂ O ₃ is 25) and add it to a round bottom flask containing 54g of nitric acid solution (the concentration of nitric acid solution is 13 mol/L), 100 Heat at reflux for 20h. Filter and wash with distilled water to neutrality, and then dry in a blast oven at 110°C for 12 hours to obtain dealuminated Beta molecular sieve. Then weigh an appropriate amount of 0.05g dimethyltin dichloride and add it to 1.0g dealuminated Beta molecular sieve (the Sn mass percentage in the Sn-beta molecular sieve prepared by ICP-AES detection is 2.2wt%), and grind in an agate mortar 20 minutes, and finally calcined in a muffle furnace at 550°C for 4 hours to obtain Sn-beta molecular sieves. The mass percentage of Sn in the Sn-beta molecular sieve can be changed as needed. When the content of Sn changes, the amount of Sn-beta molecular sieve in the following examples will also be changed accordingly. The amount of Sn-beta molecular sieve is based on the mass percentage of Sn.

The preparation method of Sn-Y, Sn-MCM-41 and Sn-USY molecular sieve is the same as that of Sn-beta molecular sieve. The raw material HY molecular sieve (the _{molar ratio of SiO 2} and Al ₂ O ₃ is 5.1), MCM-41 (SiO ₂ and The manufacturers of Al ₂ O ₃ molar ratio of 25) and H-USY (SiO ₂ to Al ₂ O ₃ molar ratio of 5.4) are both Nankai University Catalyst Factory.

Example 1

In a 25 mL three-necked flask connected with an O ₂ balloon, add 2 mmol of cyclohexanol, 4 g of 1,4-dioxane, 0.4 mmol of NHPI, 0.2 mmol of AIBN, 4 mmol of cyclohexanone, and the mass percentage of Sn 68 mg of 2.2wt% Sn-beta molecular sieve (the molar amount of Sn is about 0.63 mol% of cyclohexanol), the reaction is stirred for 12h, and the reaction temperature is controlled to 75°C. After the completion of the reaction, the reaction solution was cooled to room temperature, and samples were taken for detection by GC. The results are shown in Table 1.

Example 2

In a 25mL three-necked flask connected with an O ₂ balloon, add 2 mmol of cyclohexanol, 4 g of 1,4-dioxane, 0.4 mmol of NHS, 0.2 mmol of AIBN, 4 mmol of cyclohexanone, and the mass percentage of Sn. 68 mg of 2.2wt% Sn-beta molecular sieve (the molar amount of Sn is about 0.63 mol% of cyclohexanol), the reaction is stirred for 12h, and the reaction temperature is controlled to 75°C. After the completion of the reaction, the reaction solution was cooled to room temperature, and samples were taken for detection by GC.

Example 3

In a 25mL three-necked flask connected with an O ₂ balloon, add 2 mmol of cyclohexanol, 4 g of 1,4-dioxane, 0.4 mmol of HONB, 0.2 mmol of AIBN, 4 mmol of cyclohexanone, and the mass percentage of Sn 68 mg of 2.2wt% Sn-beta molecular sieve (the molar amount of Sn is about 0.63 mol% of cyclohexanol), the reaction is stirred for 12h, and the reaction temperature is controlled to 75°C. After the completion of the reaction, the reaction solution was cooled to room temperature, and samples were taken for detection by GC.

Example 4

In a 25 mL three-necked flask connected with an O ₂ balloon, add 2 mmol of cyclohexanol, 4 g of 1,4-dioxane, 0.4 mmol of NHNI, 0.2 mmol of AIBN, 4 mmol of cyclohexanone, and the mass percentage of Sn 68 mg of 2.2wt% Sn-beta molecular sieve (the molar amount of Sn is about 0.63 mol% of cyclohexanol), the reaction was stirred for 12h, and the reaction temperature was controlled to 75°C. After the completion of the reaction, the reaction solution was cooled to room temperature, and samples were taken for detection by GC.

Comparing Examples 1, 2, 3, and 4, the results are shown in Table 1 below, indicating that NHPI has a better catalytic oxidation effect.

Table 1

Example 5

In a 25 mL three-necked flask connected with an O ₂ balloon, add 2 mmol of cyclohexanol, 4 g of 1,4-dioxane, 0.4 mmol of NHPI, 0.2 mmol of AMBN, 4 mmol of cyclohexanone, and the mass percentage of Sn. 68 mg of 2.2wt% Sn-beta molecular sieve (the molar amount of Sn is about 0.63 mol% of cyclohexanol), the reaction was stirred for 12h, and the reaction temperature was controlled to 75°C. After the completion of the reaction, the reaction solution was cooled to room temperature, and samples were taken for detection by GC.

Example 6

In a 25mL three-necked flask connected with an O ₂ balloon, add 2 mmol of cyclohexanol, 4 g of 1,4-dioxane, 0.4 mmol of NHPI, 0.2 mmol of ABVN, 4 mmol of cyclohexanone, and the mass percentage of Sn 68 mg of 2.2wt% Sn-beta molecular sieve (the molar amount of Sn is about 0.63 mol% of cyclohexanol), the reaction was stirred for 12h, and the reaction temperature was controlled to 75°C. After the reaction, the reaction solution was cooled to room temperature, and samples were taken for detection by GC.

Example 7

In a 25mL three-neck flask connected with an O ₂ balloon, add 2mmol of cyclohexanol, 4g of 1,4-dioxane, 0.4mmol for NHPI, 0.2mmol for AIBME, 4mmol for cyclohexanone, and the mass percentage of Sn 68 mg of 2.2wt% Sn-beta molecular sieve (the molar amount of Sn is about 0.63 mol% of cyclohexanol), the reaction was stirred for 12h, and the reaction temperature was controlled to 75°C. After the completion of the reaction, the reaction solution was cooled to room temperature, and samples were taken for detection by GC.

Comparing Examples 1, 5, 6, and 7, the results are shown in Table 2 below, indicating that AIBN has a better catalytic oxidation effect.

Table 2

Examples 8-12

The feed moles of cycloethanol, solvent, cyclohexanone and Sn-beta molecular sieve remain unchanged, and different amounts of organic nitroxide radical precursor and radical initiator are used respectively. Example 1 is repeated. The results are shown in Table 3 below. The amount of organic nitroxide radical precursor and radical initiator in 3 is based on the amount of cycloethanol.

Comparative example 1

Without adding the organic nitroxide free radical precursor and free radical initiator, Example 1 was repeated. After detection and analysis, the cyclohexanol conversion rate was <1%, and no target product was generated.

Comparative example 2

Only the organic nitroxide radical precursor is added, and the free radical initiator is not added, and Example 1 is repeated. After detection and analysis, the alcohol conversion rate and the selectivity of caprolactone are very low.

table 3

It can be seen from Example 1, Example 8 and Example 9 that when the amount of the organic nitroxide radical precursor remains unchanged, as the amount of the radical initiator increases, the alcohol conversion rate increases, indicating that free radical initiation The increase in the amount of the agent is beneficial to the oxidation of cyclohexanol, but when the amount of free radical initiator increases to 20% of cyclohexanol and the AIBN/NHPI reaches 1:1, the conversion rate of cyclohexanol increases significantly, but the internal The selectivity of esters is significantly reduced, and the total selection of cyclohexanone and caprolactone is also less than 90%. Therefore, the premise of ensuring that the total selectivity of cyclohexanone and caprolactone is high and the selectivity of caprolactone is as high as possible When the dosage ratio of AIBNI and NHPI is 0.5:1, it has a better effect.

It can be seen from Example 1 and Examples 10-12 that when the dosage ratio of AIBNI and NHPI is 0.5:1, as the dosage of NHPI and AIBN increases, the alcohol conversion rate increases, indicating that increasing the dosage of NHPI and AIBN is beneficial The oxidation of cyclohexanol, but when the dosages of NHPI and AIBN are 30% and 15% of cyclohexanol, the selectivity of caprolactone is significantly reduced. The total selection of both cyclohexanone and caprolactone is less than 90%, so Under the premise of ensuring that the total selectivity of cyclohexanone and caprolactone is high and the selectivity of caprolactone is as high as possible, NHPI and AIBN have the best effect when the amounts of NHPI and AIBN are respectively 20% and 10% of cyclohexanol.

Example 13-Example 18

The feeding moles of cyclohexanol, organic nitroxide radical precursor NHPI, radical initiator AIBN, solvent and cyclohexanone remained unchanged, and Example 1 was repeated with different types and amounts of Sn-based catalysts. The results are shown in the table below. 4.

Comparative example 3

Example 1 was repeated without adding Sn-based catalyst. After detection and analysis, the conversion rate of cyclohexanol was 41%, of which 93% was converted into cyclohexanone, and only 6% was converted into caprolactone, indicating that the Sn-based catalyst mainly participates in ketones. The catalytic oxidation process of oxidation to ester, and the Sn-based catalyst is very important in the reaction system of this application.

Table 4

It can be seen from Examples 1 and 13-15 that the increase in the amount of Sn-beta molecular sieve is beneficial to the increase in the selectivity of caprolactone, and has no obvious effect on the conversion of cyclohexanol. When the amount of Sn-beta molecular sieve exceeds 68mg, that is, when Sn:cyclohexanol exceeds 0.63mol%, the selectivity of caprolactone is not significantly improved. When the amount of Sn-beta is 68mg, that is, when Sn:cyclohexanol exceeds 0.63mol%, Caprolactone has better selectivity. It can be seen from Examples 16-18 that among the Sn-based catalysts Sn-Y, Sn-MCM-41, Sn-USY and Sn-beta molecular sieves, Sn-beta molecular sieves have better catalytic effects.

Example 19-Example 22

Cyclohexanol, organic nitroxide radical precursor NHPI, free radical initiator AIBN, solvent and Sn-beta molecular sieve catalyst have the same number of moles. Repeat Example 1 with different amounts of cyclohexanone. The results are shown in the table below. 5.

table 5

It can be seen from Examples 1 and 19-22 that during the oxidation process, adding an appropriate amount of cyclohexanone can increase the conversion rate of cyclohexanol and increase the selectivity of caprolactone, but when the amount of cyclohexanone is used Too much will cause the selectivity of cyclohexanone and caprolactone to decrease.

Example 23-Example 24

The 1,4-dioxane was replaced with acetonitrile, isopropyl acetate, and methyl benzoate respectively, and Example 1 was repeated. The results are shown in Table 6 below.

Comparative example 4

The 1,4-dioxane was replaced with acetonitrile, and Example 1 was repeated. After detection and analysis, the conversion rate of cyclohexanol was 51%, of which 16% was converted into cyclohexanone, and only 31% was converted into caprolactone.

Table 6

It can be seen from Examples 1 and 23-24 that the reaction solvent has a greater influence on the selectivity of caprolactone and cyclohexanone, compared with isopropyl acetate, methyl benzoate, and 1,4-dioxane. As a solvent, hexacyclic ring has higher selectivity for cyclohexanone and caprolactone.

Example 25-Example 27

Example 1 was repeated by adjusting different reaction temperatures, and the results are shown in Table 7 below.

Table 7

It can be seen from Examples 1 and 25-27 that the reaction temperature has a certain influence on the reaction. The increase of the reaction temperature is beneficial to increase the conversion rate of cyclohexanol, but when the temperature reaches 85°C, cyclohexanone and caprolactone The selectivity is greatly reduced. Therefore, under the premise of ensuring high selectivity of cyclohexanone and caprolactone (total selectivity greater than 90%), the reaction temperature is preferably 75°C.

Example 28-Example 29

Example 1 was repeated by adjusting different reaction times, and the results are shown in Table 8 below.

Table 8

It can be seen from Examples 1 and 28-29 that the reaction time also has a certain influence on the reaction. Increasing the reaction time is beneficial to increase the conversion rate of cyclohexanol, but it will lead to a decrease in the selectivity of cyclohexanone and caprolactone.

Example 30-Example 31

The other experimental conditions were the same, and Example 1 was repeated by adjusting the different dosages of 1,4-dioxane as the solvent. The results are shown in Table 9 below.

Table 9

It can be seen from Examples 1 and 30-31 that the amount of solvent 1,4-dioxane also has a certain effect on the reaction. Reducing the amount of solvent is beneficial to increase the conversion rate of cyclohexanol, but it will lead to cyclohexanone. The selectivity to caprolactone decreases, and the amount of solvent increases, and the yield of caprolactone decreases.

The following are comparative _{examples 5-9 using external H 2} O ₂ (mass fraction of 30wt% H ₂ O ₂ aqueous solution) for the oxidation reaction, which is compared with _{the oxidation effect of in-situ H 2} O ₂ generated in Example 1, and the results are shown below Table 10 shows. According to the experimental results of Example 1, when the conversion rate of cyclohexanol is 50%, about 1 mmol of cyclohexanone and 1 mmol of in-situ H ₂ O _{2 are} generated after the oxidation reaction of 2 mmol of cyclohexanol.

Comparative example 5

The difference from Example 1 is that instead of generating H ₂ O ₂ in situ, the catalytic oxidation reaction is carried out by adding H ₂ O _2. Specifically, in a 25 mL three-necked flask connected with an O ₂ balloon, add 5 mmol of cyclohexanone, 4 g of 1,4-dioxane, 68 mg of Sn-beta molecular sieve, a _{dosage of 1 mmol of H 2} O ₂ and a reaction temperature of 75°C. , Stir the reaction for 12h. After the completion of the reaction, the reaction solution was cooled to room temperature, and samples were taken for detection by GC.

Comparative example 6

0.4 mmol NHPI was added to the reaction system of Comparative Example 5, and Comparative Example 5 was repeated.

Comparative example 7

0.2 mmol AIBN was added to the reaction system of Comparative Example 5, and Comparative Example 5 was repeated.

Comparative example 8

In the reaction system of Comparative Example 5, 0.4 mmol of NHPI and 0.2 mmol of AIBN were added to the reaction system of Comparative Example 5, and Comparative Example 5 was repeated.

Comparative example 9

In the reaction system of Comparative Example 5, 0.4 mmol of NHPI, 0.2 mmol of AIBN, and 2 mmol of cyclohexanol were added to the reaction system of Comparative Example 5, and Comparative Example 5 was repeated.

Table 10

H ₂ O ₂ utilization efficiency calculation formula:

It can be seen from Example 1 and Comparative Examples 5-9 that in the _{reaction system of Sn-beta molecular sieve catalyzed by H 2} O _{2 to} oxidize cyclohexanone to synthesize caprolactone, the conversion rate of cyclohexanone is similar and low, mainly due to The amount of H ₂ O _{2 added} is low (the _{molar amount of H 2} O ₂ is 20% of the molar amount of cyclohexanone), and the addition of NHPI is beneficial to improve the selectivity of caprolactone and the _{utilization of H 2} O _{2. The} addition of AIBN has It is beneficial to improve the selectivity of caprolactone, but the _{utilization rate of H 2} O ₂ is not significantly improved. In addition, the addition of cyclohexanol is beneficial to increase the selectivity of caprolactone.

More importantly, in the synthesis of caprolactone from cyclohexanone catalyzed by Sn-beta molecular sieve, in-situ H ₂ O ₂ has a better oxidation effect than external H ₂ O _{2 (30wt%).}

Example 32-Example 37

Using different alcohols and ketones as reactants, respectively, Example 1 was repeated, and the results are shown in Table 11.

Table 11

The various technical features of the above-mentioned embodiments can be combined arbitrarily. In order to make the description concise, all possible combinations of the various technical features in the above-mentioned embodiments are not described. However, as long as there is no contradiction in the combination of these technical features, All should be considered as the scope of this specification.

The above-mentioned embodiments only express several implementation manners of the present application, and their description is relatively specific and detailed, but they should not be interpreted as a limitation on the scope of the patent application. It should be pointed out that for those of ordinary skill in the art, without departing from the concept of this application, several modifications and improvements can be made, and these all fall within the protection scope of this application. Therefore, the scope of protection of the patent of this application shall be subject to the appended claims.

Claims (19)

1. A method for preparing a lactone compound, characterized in that, in the presence of an organic nitroxide radical precursor, a radical initiator, an alcohol and a Sn-based catalyst, molecular oxygen is used to treat the ketone represented by the following formula (1) The oxidation reaction is performed to obtain a lactone compound represented by the following formula (2), wherein the organic nitroxide radical precursor is a nitrogen-containing cyclic compound having a skeleton represented by the following formula (3);

   

   In formula (1) and formula (2), R ^a and R ^{b are the} same or different, and represent an organic group having a carbon atom at the bonding site of the adjacent carbonyl carbon atom, and R ^a and R ^{b are} independently selected from alkane group, an alkenyl group, an alkynyl group, an alicyclic hydrocarbon group, aromatic hydrocarbon group or heterocyclic group, R ^a and R ^b are bonded to each other with the adjacent carbonyl carbon atom to form a ring together;

   

   In the formula (3), R represents a protective group of a hydroxyl group or a hydrogen atom.
2. The method for preparing a lactone compound according to claim 1, wherein the alcohol is a secondary alcohol represented by the following formula (4),

   

   In formula (4), R ^c and R ^{d are the} same or different and represent an organic group having a carbon atom at the bonding site of the adjacent hydroxyl carbon atom. R ^c and R ^{d are} independently selected from alkyl groups and alkenyl groups. , Alkynyl group, alicyclic hydrocarbon group, aromatic hydrocarbon group or heterocyclic group, or R ^c and ^Rd are bonded to each other and form a ring with adjacent hydroxyl carbon atoms.
3. The method for preparing lactone compounds according to claim 1, wherein the alcohol is benzhydrol, 2-adamantanol, cyclohexanol, 2-methylcyclohexanol, 1-phenylethanol At least one of.
4. The method for preparing lactone compounds according to claim 1, wherein the ketone is 2-adamantanone, cyclohexanone, cyclopentanone, 3-methylcyclohexanone, 2-norbornone At least one of them.
5. The method for preparing lactone compounds according to claim 1, wherein the molar ratio of the ketone to the alcohol is 0.5:1 to 4:1.
6. The method for preparing lactone compounds according to claim 1, wherein the organic nitroxide radical precursor is selected from the following formulas (3-1), (3-2), (3-3) or The nitrogen-containing cyclic compound shown in (3-4),

   

   In formulas (3-1), (3-2), (3-3) or (3-4), R ₁ , R ₂ , and R _{3 are} independently selected from a hydrogen atom, an alkyl group, a cycloalkyl group, and an aryl group , Heterocycle, hydroxyl, nitro or halogen, or at least two of _{R 1} , R ₂ , and R _{3 form a ring.}
7. The method for preparing lactone compounds according to claim 1, wherein the organic nitroxide radical precursor is selected from the nitrogen-containing cyclic compounds represented by the following formulas (3-5)-(3-16) At least one of the compounds,

   
8. The method for preparing lactone compounds according to claim 7, wherein the organic nitroxide radical precursor is selected from the group consisting of N-hydroxysuccinimide represented by formula (3-5), formula ( 3-8) N-hydroxyphthalimide represented by formula (3-13), 2-hydroxyisoquinoline-1,3(2H,4H)-dione represented by formula (3-13), formula (3- 15) At least one of the N-hydroxy-1,8-naphthalimide represented by the formula (3-16) and the N-hydroxy-5-norbornene-2,3-dimethylimide represented by the formula (3-16) One kind.
9. The method for preparing lactone compounds according to claim 1, wherein the free radical initiator comprises azobisisobutyronitrile, azobisisovaleronitrile, azobisisoheptonitrile, azobis At least one of dimethyl isobutyrate.
10. The method for preparing lactone compounds according to claim 9, wherein the molar ratio of the radical initiator to the organic nitroxide radical precursor is 0.2:1 to 1:1.
11. The method for preparing lactone compounds according to claim 1, wherein the Sn-based catalyst comprises Sn-based fluorine-containing two-phase system catalyst, Sn-based molecular sieve, Sn-based mesoporous composite, Sn-based clay, Sn At least one of metal oxide-based or Sn-based polymer catalysts.
12. The method for preparing lactone compounds according to claim 11, wherein the Sn-based catalyst is Sn-beta molecular sieve.
13. The method for preparing lactone compounds according to claim 1, wherein the molar ratio of the organic nitroxide radical precursor to the alcohol is 0.05:1-0.3:1.
14. The method for preparing lactone compounds according to claim 1, wherein the molar ratio of the Sn-based catalyst to the alcohol is 0.002:1-0.01:1, wherein the molar amount of the Sn-based catalyst Calculated based on the molar amount of Sn.
15. The method for preparing lactone compounds according to any one of claims 1-14, wherein the oxidation reaction is carried out in a reaction system in which an organic solvent is used as a solvent, and the organic solvent includes 1,4-dioxide. At least one of six rings, methyl tert-butyl ether, ethyl acetate, butyl acetate, isopropyl acetate, chlorobenzene, and methyl benzoate.
16. The method for preparing lactone compounds according to claim 15, characterized in that, based on 1 mmol of the alcohol, the mass of the organic solvent is 1 g-4 g.
17. The method for preparing lactone compounds according to claim 15, wherein the temperature of the oxidation reaction is 60°C-85°C, and the reaction time is 4h-24h.
18. A method for preparing lactone compounds, characterized in that, in the presence of the organic nitroxide radical precursor, Sn-based catalyst and free radical initiator as defined in any one of claims 1-17, the molecular state is used Oxygen oxidizes the cyclic alcohol represented by the following formula (5) to obtain a lactone compound represented by the following formula (6);

    

    In formula (5) and formula (6), R ^e and R ^{f are the} same or different, representing an organic group having a carbon atom at the bonding site of the adjacent hydroxyl carbon atom, and R ^e and R ^{f are} independently selected from alkane Group, alkenyl group, alkynyl group, alicyclic hydrocarbon group, aromatic hydrocarbon group or heterocyclic group, R ^e and R ^f are bonded to each other and form a ring with adjacent hydroxyl carbon atoms.
19. The method for preparing a lactone compound according to claim 18, wherein the cyclic alcohol represented by the formula (5) is oxidized in the presence of a ketone.