Method for preparing habanolide and intermediate thereof

Abstract

Disclosed is a method for preparing habanolide and an intermediate thereof. At least one process in the preparation steps for habanolide is carried out in the presence of a catalyst system comprising a novel metal oxide-supported catalyst. The method causes the habanolide preparation process to be relatively simple, reaction conditions can be relatively mild, and the catalyst is easy to separate and recover, avoiding problems associated with catalysts used in the prior art, such as high risk, generation of large amounts of waste after the reaction, and difficulty in separating the catalyst from the product, which result in lower product quality.

Description

Preparation method of halbanol and intermediates thereof TECHNICAL FIELD

[0001] The present application relates to the technical field of organic synthesis, in particular to a preparation method of halbanol and intermediates thereof. BACKGROUND

[0002] Halbanol is a representative material of macrocyclic musk in synthetic musk, and has the advantages of degradability. Halbanol can be synthesized by taking cyclododecanone and allyl alcohol as starting materials, but there are certain problems in each step. For example, in the patent US3856815A, cyclododecanone and allyl alcohol are used as raw materials, and t-butyl peroxide is used as a catalyst to synthesize 2-(3-hydroxypropyl)cyclododecanone, and 2-(3-hydroxypropyl)cyclododecanone is dehydrated to generate dodecahydropyran (DDP) under the action of a phosphoric acid catalyst; this process requires a large amount of t-butyl peroxide, and t-butyl peroxide is unstable, which causes the reaction process to be unstable and dangerous, and the use of phosphoric acid as a catalyst requires subsequent neutralization with lye and water washing, which complicates the operation and increases the amount of three wastes. For another example, in the patent CN1867556A, dodecahydropyran (DDP) is oxidized in propionic acid solution by using trifluoroacetic acid as a catalyst and a 50% hydrogen peroxide aqueous solution as an oxidizing agent to obtain DDP-OOH, and DDP-OOH is decomposed in a polyethylene glycol solvent under the catalysis of copper acetate to obtain halbanol; this method uses trifluoroacetic acid as a catalyst, which has a large environmental hidden danger and requires high equipment; copper acetate is used as a catalyst for the decomposition of DDP-OOH, and copper acetate can be partially dissolved in the product halbanol, which requires a large pressure for subsequent separation. In particular, referring to the above two patent documents, in the process of synthesizing halbanol, basically each step requires a catalyst, and multiple steps require multiple corresponding catalysts, and some catalysts are unstable or difficult to separate, and even need to be converted into other substances for post-treatment and discharge, which brings great difficulty to industrial application. SUMMARY

[0003] The present application aims to overcome one or more of the problems in the prior art and provide an improved preparation method of halbanol and intermediates thereof.

[0004] At least one process in each preparation step of the preparation of halbanol and intermediates thereof in the present application is carried out in the presence of a novel metal oxide supported catalyst, which can solve at least one problem in the prior art.

[0005] Based on this, one technical solution adopted by the present application is a preparation method of halbanol, which comprises:

[0006] Reaction (1): cyclododecanone and allyl alcohol are reacted in the presence of a catalyst to generate a compound represented by formula (I);

[0007] Reaction (2): reacting the compound represented by the formula (I) to produce a compound represented by the formula (II) in the presence of a catalyst;

[0008] Reaction (3): reacting the compound represented by the formula (II) with hydrogen peroxide in the presence of a catalyst to produce a compound represented by the formula (III);

[0009] Reaction (4): reacting the compound represented by the formula (III) to produce halbanol in the presence of a catalyst;

[0010] The catalyst used in one, two, three or four of the reactions (1), (2), (3) and (4) includes a metal oxide supported catalyst selected from a metal oxide supported heteropoly acid and a metal oxide supported composite catalyst, wherein:

[0011] The metal oxide supported heteropoly acid includes a metal oxide support having a three-dimensional porous structure and a heteropoly acid dispersed in a monomolecular state and connected to the metal oxide support, the heteropoly acid being a proton type heteropoly acid capable of providing hydrogen ions;

[0012] The metal oxide supported composite catalyst includes a metal oxide support having a three-dimensional porous structure, a heteropoly acid dispersed in a monomolecular state and connected to the metal oxide support, and an active metal component dispersed in a monatomic state and connected to one or both of the heteropoly acid and the metal oxide support, the heteropoly acid being a proton type heteropoly acid capable of providing hydrogen ions.

[0013] In some embodiments of the present application, the catalyst used in the reactions (2) and (3) each includes the metal oxide supported composite catalyst, or the catalyst used in the reactions (2) and (3) each includes the metal oxide supported heteropoly acid.

[0014] According to some preferred aspects of the present application, the catalyst used in the reaction (1) and / or the reaction (4) includes the metal oxide supported composite catalyst.

[0015] According to some preferred aspects of the present application, the catalyst used in the reactions (1) to (4) each includes the metal oxide supported composite catalyst.

[0016] In some embodiments of the present application, in the reaction (1), the amount of the catalyst used is 0.01wt.% to 2wt.% of the cyclododecanone; and / or, in the reaction (1), the reaction temperature is 80 to 160°C.

[0017] According to some preferred aspects of the present application, in the reaction (1), the amount of the catalyst used is 0.01wt.% to 1wt.% of the cyclododecanone; and / or, in the reaction (1), the reaction temperature is 80 to 120°C.

[0018] In some embodiments of the present application, in the reaction (2), the amount of the catalyst used is 0.01wt.% to 2wt.% of the compound of formula (I); and / or, in the reaction (2), the reaction temperature is 80 to 160°C, and the reaction pressure is -0.01 to 0.1 MPa.

[0019] According to some preferred aspects of the present application, in the reaction (2), the amount of the catalyst used is 0.01wt.% to 1wt.% of the compound of formula (I); and / or, in the reaction (2), the reaction temperature is 80 to 95°C, and the reaction pressure is -0.001 to 0.07 MPa.

[0020] In some embodiments of the present application, in the reaction (3), the amount of the catalyst used is 0.01wt.% to 2wt.% of the compound of formula (II); and / or, in the reaction (3), the reaction temperature is -10 to 50°C.

[0021] According to some preferred aspects of the present application, in the reaction (3), the amount of the catalyst used is 0.01wt.% to 1wt.% of the compound of formula (II); and / or, in the reaction (3), the reaction temperature is -10 to 10°C.

[0022] In some embodiments of the present application, in the reaction (4), the amount of the catalyst used is 0.01wt.% to 2wt.% of the compound of formula (III); and / or, in the reaction (4), the reaction temperature is 20 to 120°C.

[0023] According to some preferred aspects of the present application, in the reaction (4), the amount of the catalyst used is 0.01wt.% to 0.8wt.% of the compound of formula (III); and / or, in the reaction (4), the reaction temperature is 20 to 80°C.

[0024] In some embodiments of the present application, in the reaction (1), the molar ratio of the cyclododecanone to the allyl alcohol is 1-10:1.

[0025] In some embodiments of the present application, in the reaction (3), the solvent used in the reaction is a combination of one or more selected from formic acid, acetic acid, propionic acid, butyric acid, valeric acid, hexanoic acid, heptanoic acid and octanoic acid, and the mass ratio of the solvent to the compound of formula (II) is 0.5-10:1.

[0026] In some embodiments of the present application, in the reaction (3), the mass concentration of the hydrogen peroxide is 27.5%-50%, and the molar ratio of the compound of formula (II) to the hydrogen peroxide in the hydrogen peroxide is 1:0.6-3.

[0027] In some embodiments of the present application, in the reaction (4), the solvent used in the reaction is a combination of one or more selected from methanol, ethanol, isopropanol, butanol, pentanol, hexanol, heptanol, octanol, nonanol, decanol, ethylene glycol and polyethylene glycol, and the mass ratio of the solvent to the compound of formula (III) is 0.5-10:1.

[0028] According to some specific aspects of the present application, in the protonic heteropoly acid, heteroatoms and polyatoms are bridged by oxygen atoms, the heteroatoms include at least one selected from P, Si, Fe and Co, and the polyatoms include at least one selected from Mo, W, V, Nb and Ta.

[0029] In some preferred embodiments of the present application, in the metal oxide supported heteropoly acid and the metal oxide supported composite catalyst, the protonic heteropoly acid is connected to the metal oxide carrier by at least a covalent bond. Further, a covalent bond is formed between the polyatom in the protonic heteropoly acid, the terminal oxygen in the protonic heteropoly acid and the metal atom in the metal oxide carrier.

[0030] Further, in the metal oxide supported heteropoly acid and the metal oxide supported composite catalyst, the protonic heteropoly acid is uniformly dispersed in the framework, inside the pores and on the surface of the metal oxide carrier.

[0031] In some preferred embodiments of the present application, the active metal component is connected to the protonic heteropoly acid by a chemical bond, the chemical bond includes a coordination bond, and the active metal component is selectively adsorbed on the metal oxide carrier.

[0032] In some preferred embodiments of the present application, the active metal component is a combination of one or more selected from transition metals.

[0033] Further, the active metal component is a combination of one or more selected from groups IB-ⅡB and groups VB-ⅧB.

[0034] Further, the active metal component is a combination of one or more selected from Pd, Pt, Ru, Au, Ag, Rh, Ni, Cu, Fe and Co.

[0035] In some preferred embodiments of the present application, the mass content of the active metal component in the metal oxide supported composite catalyst is 0.01%-15% by mass percentage.

[0036] Further, the mass content of the active metal component in the metal oxide supported composite catalyst is 0.04%-15% by mass percentage.

[0037] According to some specific aspects of the present application, the protonic heteropoly acid comprises a combination of one or more selected from phosphomolybdic acid, phosphotungstic acid, silicotungstic acid, silicomolybdic acid, phosphovanadic heteropoly acid, phosphoniobic heteropoly acid, phosphotantalum heteropoly acid, ferric molybdenum heteropoly acid, ferric tungsten heteropoly acid, ferric vanadic heteropoly acid, cobalt molybdenum heteropoly acid, cobalt tungsten heteropoly acid, cobalt vanadic heteropoly acid.

[0038] In some preferred embodiments of the present application, the mass content of the protonic heteropoly acid in the metal oxide supported heteropoly acid, the metal oxide supported composite catalyst is 1%-68% by mass percentage, respectively.

[0039] Further, the mass content of the protonic heteropoly acid in the metal oxide supported heteropoly acid, the metal oxide supported composite catalyst is 7%-45% by mass percentage, respectively.

[0040] Further, the mass content of the protonic heteropoly acid in the metal oxide supported heteropoly acid, the metal oxide supported composite catalyst is 7%-45% by mass percentage, respectively.

[0041] In some preferred embodiments of the present application, the specific surface area of the metal oxide supported heteropoly acid, the metal oxide supported composite catalyst is greater than or equal to 200 m 2 / g, as determined by BET method.

[0042] Further, the specific surface area of the metal oxide supported heteropoly acid, the metal oxide supported composite catalyst is less than or equal to 1000 m 2 / g, as determined by BET method.

[0043] According to some preferred aspects of the present application, the specific surface area of the metal oxide supported heteropoly acid, the metal oxide supported composite catalyst is 200-800 m 2 / g, as determined by BET method.

[0044] In some embodiments of the present application, the average pore size of the metal oxide supported heteropoly acid and the average pore size of the metal oxide supported composite catalyst are independently in the range of 2-30 nm, and the average pore volume of the metal oxide supported heteropoly acid and the average pore volume of the metal oxide supported composite catalyst are independently in the range of 0.4-1.5 cc / g.

[0045] In some preferred embodiments of the present application, the average density of the metal oxide supported heteropoly acid and the average density of the metal oxide supported composite catalyst are independently in the range of 0.5-4 g / cm 3 .

[0046] In some preferred embodiments of the present application, the average particle size of the metal oxide supported heteropoly acid and the average particle size of the metal oxide supported composite catalyst are independently in the range of 10-350 nm. Further, the average particle size of the metal oxide supported composite catalyst is in the range of 80-250 nm.

[0047] In some preferred embodiments of the present application, each pore in the three-dimensional porous structure is randomly distributed in the three-dimensional direction.

[0048] Further, in some embodiments of the present application, the metal oxide support has a three-dimensional hollow porous structure. Preferably, the three-dimensional hollow porous structure has a single hollow chamber or a hollow cavity combination formed by a plurality of hollow chambers in a connected state or a partially connected state. In some embodiments, the diameter of the hollow chamber or the hollow cavity combination is in the range of 1-90 nm; or the ratio of the diameter of the hollow chamber or the hollow cavity combination to the particle size of the metal oxide supported composite catalyst is in the range of 0.3-0.9:1.

[0049] In some embodiments, the metal oxide supported heteropoly acid and the metal oxide supported composite catalyst can independently be in a spherical structure. The "spherical structure" refers to a standard spherical structure or a structure close to a spherical structure, i.e., including a substantially spherical manner.

[0050] In some embodiments, the metal oxide support includes a zinc oxide support, a magnesium oxide support, a copper oxide support, an aluminum oxide support, or a titanium oxide support.

[0051] According to some preferred aspects of the present application, the metal oxide supported heteropoly acid is prepared by a preparation method satisfying the following conditions:

[0052] (a) using a precursor of metal oxide as raw material, wherein the precursor of metal oxide refers to a substance that can be converted into a metal oxide through one or more conversion processes, and the conversion process at least includes a process that generates a chemical reaction;

[0053] (b) performing the one or more conversion processes in the presence of the protic heteropoly acid and water;

[0054] The metal oxide supported composite catalyst is prepared by a preparation method satisfying the following conditions:

[0055] (a) using a precursor of metal oxide and a precursor of active metal as raw materials, respectively, wherein the precursor of metal oxide and the precursor of active metal are substances that can be converted into metal oxide or active metal components through one or more conversion processes, and the conversion processes at least include a process of generating chemical reactions;

[0056] (b) the one or more conversion processes are carried out in the presence of the protic heteropoly acid and water.

[0057] During the preparation process, the protic heteropoly acid can participate in the conversion process of the precursor of metal oxide, and the two work together to not only facilitate the formation of the conversion of the three-dimensional porous metal oxide carrier, but also facilitate the dispersion of the protic heteropoly acid in a monomolecular state, and further facilitate the connection between the protic heteropoly acid and the metal oxide carrier to be more stable, for example, facilitate the formation of covalent bonds between the polyatomic atoms in the protic heteropoly acid, the terminal oxygen in the protic heteropoly acid and the metal atoms in the metal oxide carrier, and further possible hydrogen bonding forces, etc.

[0058] In some preferred embodiments of the present application, in the preparation method of the metal oxide supported heteropoly acid and the metal oxide supported composite catalyst, the precursor of metal oxide is selected from acidic, basic or neutral compounds containing metal and organic groups, and further, the compound containing metal and organic groups is selected from C1-C12 metal alkoxide, C1-C12 hydrocarbon metal, metal organic complex or complex.

[0059] In some preferred embodiments of the present application, in the preparation method of the metal oxide supported heteropoly acid and the metal oxide supported composite catalyst, the precursor of metal oxide is a substance that can be converted into the metal oxide through a gelation process and a calcination process performed in sequence.

[0060] Further, the preparation method of the metal oxide supported heteropoly acid and the metal oxide supported composite catalyst respectively further satisfies the following conditions:

[0061] (c) the conversion process includes a gelation process, and the gelation process is carried out in the presence of water, an organic solvent and a surfactant at the same time.

[0062] In some preferred embodiments of the present application, the preparation method of the metal oxide supported heteropoly acid comprises gelation treatment and calcination treatment in sequence; the gelation treatment comprises: mixing and reacting the proton-type heteropoly acid and a precursor of metal oxide in the presence of water, an organic solvent and a surfactant, and inducing by solvent evaporation to form a gel; the calcination treatment comprises: drying the gel and then calcining to obtain the metal oxide supported heteropoly acid;

[0063] The preparation method of the metal oxide supported composite catalyst comprises gelation treatment, calcination treatment and reduction treatment in sequence; the gelation treatment comprises: mixing and reacting the proton-type heteropoly acid and a precursor of metal oxide in the presence of water, an organic solvent and a surfactant, and inducing by solvent evaporation to form a gel; the calcination treatment comprises: drying the gel and then calcining; the reduction treatment is performed in the presence of a reducing agent, and the metal oxide supported composite catalyst is obtained after reduction; wherein, the preparation method of the metal oxide supported composite catalyst further comprises a step of adding a precursor of active metal before the mixing and reacting, or a step of coating with a solution containing the precursor of active metal after the calcination treatment and before the reduction treatment, the coating comprising spraying, brushing, rolling, dipping or scraping.

[0064] In some embodiments of the present application, in the preparation method of the metal oxide supported heteropoly acid and the metal oxide supported composite catalyst, the precursor of metal oxide is selected from alcohol aluminum compounds, alcohol magnesium compounds, alcohol copper compounds, alcohol zinc compounds, alcohol titanium compounds, hydrocarbyl aluminum compounds, hydrocarbyl titanium compounds, hydrocarbyl zinc compounds, organic aluminum salts, organic titanium salts and organic zinc salts.

[0065] Further, in the preparation method of the metal oxide supported heteropoly acid and the metal oxide supported composite catalyst, the precursor of metal oxide is selected from trimethylaluminum, triethylaluminum, triisobutylaluminum, diethylaluminum chloride, aluminum isopropoxide, aluminum n-butoxide, aluminum acetate, aluminum propionate, titanium acetylacetonate, tetraethyl titanate, tetraisopropyl titanate, tetrabutyl titanate or zinc acetylacetonate.

[0066] In some embodiments of the present application, in the preparation method of the metal oxide supported heteropoly acid and the metal oxide supported composite catalyst, the precursor of active metal is a salt of active metal component and / or an acid of active metal component, the salt of active metal component comprises a combination of one or more selected from metal nitrate, metal sulfate, metal halide, metal acetylacetonate complex and metal sulfide, and the acid of active metal component comprises a halogenated metal acid.

[0067] Further, in the preparation method of the metal oxide supported heteropoly acid, the metal oxide supported composite catalyst, the active metal precursor is a combination of one or more selected from the group consisting of palladium chloride, palladium nitrate, platinum acetylacetone, gold chloride, silver nitrate, ruthenium chloride, ruthenium nitrate, rhodium chloride, rhodium nitrate, cobalt nitrate, nickel nitrate, iron chloride, iron sulfate, copper nitrate, copper sulfate, chloroplatinic acid, chloropalladic acid, chloroauric acid, and rhodium acetylacetone.

[0068] According to some preferred aspects of the present application, in the preparation method of the metal oxide supported heteropoly acid, the metal oxide supported composite catalyst, the mass ratio of the water to the precursor of the metal oxide is 0.001-15:1; further, the mass ratio of the water to the precursor of the metal oxide is 0.01-10:1; in some embodiments of the present application, the mass ratio of the water to the precursor of the metal oxide is 0.01-6:1, for example, it can also be 0.01-3:1, or 0.02-3:1, or 0.04-1:1.

[0069] In some embodiments of the present application, the mass ratio of the water to the precursor of the metal oxide is 0.1-5:1.

[0070] According to some preferred aspects of the present application, in the preparation method of the metal oxide supported heteropoly acid, the metal oxide supported composite catalyst, the volume ratio of the water to the organic solvent is 0.001-5:1. Further, the volume ratio of the water to the organic solvent is 0.001-2:1. In some embodiments of the present application, the volume ratio of the water to the organic solvent is 0.001-1:1, for example, it can also be 0.001-0.5:1, or 0.001-0.2:1.

[0071] In some embodiments of the present application, in the preparation method of the metal oxide supported heteropoly acid, the metal oxide supported composite catalyst, the volume ratio of the water to the organic solvent is 0.005-1:1.

[0072] In some preferred embodiments of the present application, in the preparation method of the metal oxide supported heteropoly acid, the metal oxide supported composite catalyst, the organic solvent is a polar organic solvent.

[0073] Further, the mass ratio of the proton type heteropoly acid to the organic solvent is 1:80-1000.

[0074] Further, the organic solvent is a combination of one or more selected from the group consisting of methanol, ethanol, isopropanol, acetone, tetrahydrofuran, and N,N-dimethylformamide. In some embodiments of the present application, the organic solvent does not contain water.

[0075] In some preferred embodiments of the present application, in the preparation method of the metal oxide supported heteropoly acid, the metal oxide supported composite catalyst, the surfactant is a block copolymer non-ionic surfactant and / or an ionic surfactant.

[0076] Further, the block copolymer non-ionic surfactant comprises a combination of one or more selected from non-ionic surfactant P123, non-ionic surfactant F127, and non-ionic surfactant F108.

[0077] Further, the ionic surfactant comprises a combination of one or more selected from cetyltrimethylammonium bromide (CTAB), sodium oleate, sodium dodecylbenzenesulfonate, and sodium stearate.

[0078] In some preferred embodiments of the present application, the mass ratio of the surfactant to the proton-type heteropoly acid is 3-30:1.

[0079] According to some preferred aspects of the present application, in the preparation method of the metal oxide supported heteropoly acid, the metal oxide supported composite catalyst, the temperature of the mixing reaction is controlled to be 20-50°C and the reaction time is controlled to be no less than 12h.

[0080] In some preferred embodiments of the present application, the temperature of the mixing reaction is controlled to be 20-40°C.

[0081] In some preferred embodiments of the present application, the time of the mixing reaction is controlled to be 12-48h.

[0082] Further, the time of the mixing reaction is controlled to be 12-15h, 15-18h, 18-21h, 21-24h, 24-27h, 27-30h, or 30-48h.

[0083] In some preferred embodiments of the present application, in the preparation method of the metal oxide supported heteropoly acid, the metal oxide supported composite catalyst, the solvent evaporation induction is controlled to be performed at a temperature of 40-120°C for a time of 1-72h.

[0084] Further, the solvent evaporation induction is controlled to be performed at a temperature of 60-75°C for a time of 10-60h.

[0085] In some preferred embodiments of the present application, in the preparation method of the metal oxide supported heteropoly acid, the metal oxide supported composite catalyst, the calcination is performed at a temperature of 200-700°C.

[0086] Further, the calcination is performed in a muffle furnace.

[0087] Further, the calcination time is controlled to be 1-6h.

[0088] Further, the heating rate of the calcination is controlled to be 1-30℃ / min.

[0089] In some preferred embodiments of the present application, the calcination is performed in an oxygen-containing environment, which includes an air atmosphere or a pure oxygen atmosphere formed by introducing pure oxygen gas with a purity of more than 99%.

[0090] In some preferred embodiments of the present application, when the preparation method of the metal oxide supported composite catalyst uses impregnation (dip coating) or spraying with a solution containing the active metal precursor after the calcination treatment and before the reduction treatment, the active metal precursor and the solid obtained by the calcination are dispersed in a solvent respectively, mixed and stirred, separated, to obtain a solid loaded with the active metal precursor, and then the reduction treatment is performed.

[0091] Further, the solvent can be a ketone solvent, for example, acetone, etc.

[0092] According to some specific aspects of the present application, when the preparation method of the metal oxide supported composite catalyst uses impregnation or spraying with a solution containing the active metal precursor after the calcination treatment and before the reduction treatment, a solid loaded with the active metal precursor can be obtained; further, in some specific cases, the active metal precursor can be dispersed in a ketone solvent, fully stirred, and then the solid obtained by the calcination is ultrasonically dispersed in the aforementioned solution, continuously stirred, heated, until the ketone solvent is completely evaporated, to obtain a solid loaded with the active metal precursor.

[0093] In some preferred embodiments of the present application, the reduction treatment includes: performing a first calcination in an oxygen-containing environment, and then performing a second calcination in a reducing atmosphere.

[0094] Further, the calcination temperature of the first calcination is controlled to be 200-400℃.

[0095] Further, the calcination temperature of the second calcination is controlled to be 150-300℃.

[0096] In some preferred embodiments of the present application, the calcination temperature of the second calcination is lower than the calcination temperature of the first calcination.

[0097] In some preferred embodiments of the present application, in the reduction process, the aerobic environment comprises an air atmosphere or a pure oxygen atmosphere formed by introducing a pure oxygen gas with a purity greater than 99%, and the reducing atmosphere comprises a hydrogen atmosphere.

[0098] According to some specific aspects of the present application, when the preparation method of the metal oxide supported composite catalyst employs the addition of an active metal precursor before the mixing reaction, the implementation of the gelation process comprises:

[0099] The protonic heteropoly acid, water and organic solvent are mixed and uniformly dispersed to obtain a first solution; then the surfactant, the precursor of the metal oxide and the active metal precursor are added into the first solution for mixing and dispersion, the reaction is carried out at room temperature, and a gel is prepared through solvent evaporation induction.

[0100] In some embodiments of the present application, the catalyst employed in one, two, three or four of the reactions (1), (2), (3) and (4) comprises a metal oxide supported catalyst and at least one other catalyst different from the metal oxide supported catalyst, wherein the mass content of the metal oxide supported catalyst is more than 50%.

[0101] In some embodiments of the present application, in the catalyst in the reactions (1), (2), (3) and (4), the mass content of the metal oxide supported catalyst is more than 55%, or more than 60%, or more than 65%, or more than 70%, or more than 75%, or more than 80%, or more than 85%, or more than 90%, or more than 95%, or more than 96%, or more than 97%, or more than 98%, or more than 99%.

[0102] Yet another technical solution provided by the present application is a preparation method of halbanol, which comprises: allowing 1-hydroperoxy-16-oxabicyclo(10.4.0)hexadecane shown in formula (III) to react in the presence of the metal oxide supported composite catalyst as described above to generate the halbanol.

[0103] Yet another technical solution provided by the present application is a preparation method of a halbanol intermediate, which is 2-(3-hydroxypropyl)cyclododecanone shown in formula (I), the preparation method comprising: allowing cyclododecanone and allyl alcohol to react in the presence of the metal oxide supported composite catalyst as described above to generate the 2-(3-hydroxypropyl)cyclododecanone.

[0104] The application provides another technical scheme: a preparation method of a halbanol intermediate, the halbanol intermediate is 13-oxabicyclo(10.4.0)-1(12)hexadecene shown in formula (II), and the preparation method comprises: allowing a compound shown in formula (I) to react in the presence of the metal oxide supported heteropoly acid and / or the metal oxide supported composite catalyst to generate the 13-oxabicyclo(10.4.0)-1(12)hexadecene;

[0105] The application provides another technical scheme: a preparation method of a halbanol intermediate, the halbanol intermediate is 1-hydroperoxy-16-oxabicyclo(10.4.0)hexadecane shown in formula (III), and the preparation method comprises: allowing a compound shown in formula (II) to react with hydrogen peroxide in the presence of the metal oxide supported heteropoly acid and / or the metal oxide supported composite catalyst to generate the 1-hydroperoxy-16-oxabicyclo(10.4.0)hexadecane;

[0106] Compared with the prior art, the application has the following advantages due to the use of the above technical scheme:

[0107] The application provides an improved preparation method of halbanol and an intermediate thereof, at least one process in each preparation step of the halbanol is carried out in the presence of a catalyst system containing a novel metal oxide supported catalyst, the method makes the preparation process of the halbanol relatively simple, the reaction conditions can be relatively milder, the catalyst is easy to separate and recycle, and the problems of great danger, much waste after reaction, poor product quality caused by the difficulty in separation of the catalyst dispersed in the product and the like in the catalyst used in the prior art are avoided.

[0108] Further, the preparation process of the halbanol has four steps, and the four reaction steps can all be carried out in the presence of the catalyst system containing the novel metal oxide supported catalyst, that is, the types of catalysts in each step are relatively reduced, the difficulty in selection of the catalyst is reduced, meanwhile, the reduction of the types of catalysts is also beneficial to the promotion of industrialized mass production, and the novel metal oxide supported catalyst in the application exists in a solid form, is easy to separate and recycle, and can also have high activity, which is beneficial to the preparation of the halbanol with high yield and the reduction of production cost. BRIEF DESCRIPTION OF DRAWINGS

[0109] Fig. 1 is an XRD spectrum of the catalyst Pd-H3PMo / AS-20H prepared in application example 1;

[0110] Fig. 2 is a scanning electron microscope image of the catalyst Pd-H3PMo / AS-20H prepared in application example 1;

[0111] Figure 3 is a transmission electron microscope image of the catalyst Pd-H3PMo / AS-20H prepared in Application Example 1;

[0112] Figure 4 is a spherical aberration electron microscope image of the catalyst Pd-H3PMo / AS-20H prepared in Application Example 1;

[0113] Figure 5 is a histogram of the particle size distribution of the corresponding heteropoly acid of the catalyst Pd-H3PMo / AS-20H prepared in Application Example 1;

[0114] Figure 6 is a nitrogen adsorption-desorption graph of the catalyst Pd-H3PMo / AS-20H prepared in Application Example 1;

[0115] Figure 7 is a gas chromatography analysis spectrum of 2-(3-hydroxypropyl)cyclododecanone prepared in Application Example 3;

[0116] Figure 8 is an XRD spectrum of the catalyst prepared in Application Example 22;

[0117] Figure 9 is a transmission electron microscope image of the catalyst prepared in Application Example 22;

[0118] Figure 10 is a gas chromatography analysis spectrum of 13-oxabicyclo(10.4.0)-1(12)hexadecene prepared in Application Example 22;

[0119] Figure 11 is a gas chromatography analysis spectrum of halbanolide prepared in Application Example 47. DETAILED DESCRIPTION

[0120] The present application is directed to the problems of great risk, much three wastes after reaction, difficult to separate from product, and low product quality caused by the catalyst used in the existing process for preparing halbanol. The inventors accidentally found that the one-step, two-step or more steps of the four-step reaction of halbanol catalyzed by the catalyst system containing at least metal oxide supported catalyst, in some specific embodiments, specifically the catalyst system containing at least metal oxide supported heteropoly acid and / or metal oxide supported composite catalyst, obtained satisfactory technical effect. Further analysis shows that the excellent technical effect should be due to the new structure of the metal oxide supported catalyst first proposed in the present application. The new catalyst structure includes a three-dimensional porous metal oxide carrier, a proton-type heteropoly acid dispersed in a monomolecular state and connected to the metal oxide carrier, forming a metal oxide supported heteropoly acid, and when further including an active metal component dispersed in a monatomic state and connected to one or both of the heteropoly acid and the metal oxide carrier, forming a metal oxide supported composite catalyst, which is a catalyst form of double monodisperse and three-dimensional porous metal oxide. In which: the proton-type heteropoly acid is uniformly distributed in a monomolecular state, so that the active sites of the proton-type heteropoly acid are fully exposed; at the same time, the monomolecular state in the metal oxide supported composite catalyst promotes the active metal component to be dispersed in a monatomic form and always maintain a uniform dispersion state; the metal oxide carrier, the proton-type heteropoly acid and / or the proton-type heteropoly acid and the active metal component form a stable strong interaction and improve the microstructure, and construct a stable loading state, and at the same time can form a catalyst with a three-dimensional porous structure, which significantly improves the catalytic performance.

[0121] The above scheme will be further described in combination with specific examples; it should be understood that these examples are used to illustrate the basic principles, main features and advantages of the present application, and the present application is not limited in scope by the following examples; the implementation conditions used in the examples can be further adjusted according to specific requirements, and the implementation conditions not specified are usually the conditions in conventional experiments.

[0122] In the following examples, all raw materials are obtained from commercial sources or prepared by conventional methods in the art, unless otherwise specified.

[0123] Surfactant: P123 was purchased from Sigma-Aldrich.

[0124] Application Example 1:

[0125] This example provides a method for preparing 2-(3-hydroxypropyl)cyclododecanone (i.e., the compound shown in formula (I)), and the reaction route is as follows:

[0126] In a 2L reaction kettle, 6g of catalyst, 1200g of cyclododecanone, and 116g of allyl alcohol were sequentially added, and the temperature was raised to 110℃. The allyl alcohol was added dropwise over a period of 6h, and the reaction was maintained at a constant temperature for 2h. The product was separated and analyzed using an Agilent 7890 gas chromatograph, with an HP-INNOWax column and an FID detector.

[0127] The catalyst is a metal oxide supported composite catalyst, which comprises a metal oxide support having a three-dimensional porous structure, a heteropoly acid dispersed in a monomolecular state and connected to the metal oxide support, and an active metal component dispersed in a monatomic state and connected to one or both of the heteropoly acid and the metal oxide support, the heteropoly acid being a proton type heteropoly acid capable of providing hydrogen ions.

[0128] The preparation method of the catalyst comprises the following steps: 2.9g of phosphomolybdic acid is mixed with 500mL of anhydrous ethanol and 20mL of deionized water, and is fully stirred and uniformly dispersed. Then, 20g of P123 and 50g of aluminum isopropoxide are sequentially added, and are fully reacted at room temperature for 24h. Subsequently, solvent evaporation induction is performed at 70℃ for 48h to obtain a gel, which is then placed in an oven for drying overnight. The obtained solid after drying is calcined in a muffle furnace at 350℃ under an air atmosphere for 3h at a heating rate of 5℃ / min to obtain a metal oxide supported heteropoly acid. 31.2mL of a palladium nitrate solution (100mg of palladium nitrate dissolved in 100mL of acetone) is added to 150mL of acetone and fully stirred. Then, 3g of the metal oxide supported heteropoly acid is ultrasonically dispersed in the above solution, and after continuous stirring for 6h, the mixture is heated to 40℃ until the acetone is completely evaporated. Then, the obtained solid is placed in a muffle furnace and calcined at 300℃ under an air atmosphere at a heating rate of 5℃ / min for 2h. Next, the obtained sample is reduced in a muffle furnace under a pure H2 atmosphere at 250℃ for 2h, and after natural cooling, a metal oxide supported composite catalyst is obtained, which is denoted as Pd-H3PMo / AS-20H.

[0129] The obtained metal oxide supported composite catalyst is structurally characterized. The actual loading of phosphomolybdic acid in the catalyst is about 22%, and the actual loading of palladium is about 0.6%.

[0130] FIG. 1 is an XRD pattern of Pd-H3PMo / AS-20H. It is observed that there are no characteristic diffraction peaks of the heteropoly acid molecules or palladium, indicating that the heteropoly acid and palladium are uniformly dispersed on the catalyst.

[0131] FIG. 2 is an SEM (scanning electron microscope) pattern of Pd-H3PMo / AS-20H. It is observed that the catalyst is a three-dimensional porous structure assembled from two-dimensional sheets.

[0132] Figure 3 is a TEM image of Pd-H3PMo / AS-20H. It is observed that the catalyst is a three-dimensional hollow porous structure assembled by two-dimensional sheets, the diameter of the catalyst is about 181 nm, and the diameter of the hollow part is about 80 nm. No palladium particles are observed, indicating that palladium is highly dispersed.

[0133] Figure 4 is a STEM-HAADF image of Pd-H3PMo / AS-20H, and Figure 5 is a corresponding particle size distribution histogram. It is observed that there are single clusters of phosphomolybdate with a size of about 0.71 nm on the catalyst, indicating that phosphomolybdate is monomolecularly dispersed on the catalyst Pd-H3PMo / AS-20H.

[0134] Figure 6 is a nitrogen adsorption-desorption graph of Pd-H3PMo / AS-20H. It is observed that the nitrogen adsorption-desorption graph of the catalyst exhibits a typical type IV adsorption-desorption curve with a type I hysteresis loop, indicating that there is a large amount of mesoporous structure in the catalyst.

[0135] The catalyst is spherical with a diameter of about 181 nm, a specific surface area of about 697 m 2 / g, an average pore size of about 6.6 nm, an average pore volume of about 1.3 cc / g, and an average density of about 2.6 g / cm 3 .

[0136] Application Example 2-4:

[0137] The basic procedure is the same as that of Application Example 1, except that some conditions are different. The specific conditions and the results of the catalytic reaction are shown in Table 1.

[0138] Table 1

[0139] Figure 7 is a gas chromatography analysis spectrum of 2-(3-hydroxypropyl)cyclododecanone prepared in Application Example 3.

[0140] Application Examples 5-21:

[0141] The basic procedure is the same as that of Application Example 1, except that the catalyst and its preparation conditions are different from those of Application Example 1. The specific preparation conditions of the catalyst and the results of the catalytic reaction are shown in Table 2.

[0142] Table 2

[0143] Application Example 22:

[0144] This example provides a method for preparing 13-oxabicyclo(10.4.0)-1(12)hexadecene (i.e., the compound shown in formula (II)), and the reaction scheme is as follows:

[0145] In a 2L reactor, 6g of catalyst was added, 1200g of 2-(3-hydroxypropyl)cyclododecanone (compound shown in formula (I)) was added, and the system was heated to 90°C, and the vacuum degree was controlled at about 350mmHg, and the reaction was carried out for 12h. After the product was separated, Agilent 7890 gas chromatograph was used for analysis, wherein the chromatographic column was HP-INNOWax, and the detector was FID detector;

[0146] The catalyst is a metal oxide supported heteropoly acid, which comprises a metal oxide carrier having a three-dimensional porous structure and a heteropoly acid dispersed in a monomolecular state and connected to the metal oxide carrier, the heteropoly acid being a proton type heteropoly acid capable of providing hydrogen ions;

[0147] Specifically, the preparation method of the catalyst comprises: weighing 2.9g of phosphomolybdic acid, mixing with 500mL of anhydrous ethanol and 20mL of deionized water, fully stirring, uniformly dispersing, then sequentially adding 20g of P123 and 50g of aluminum isopropoxide, fully reacting at room temperature for 24h, then performing solvent evaporation induction at 70°C, and after 48h, a gel is obtained, which is then placed in an oven for drying overnight. The solid obtained after drying is placed in a muffle furnace and calcined at 350°C under an air atmosphere for 3h, with a heating rate of 5°C / min, to obtain a metal oxide supported heteropoly acid, which is denoted as H3PMo / AS-20H.

[0148] The obtained metal oxide supported heteropoly acid is subjected to structural characterization. The actual loading amount of phosphomolybdic acid in the catalyst is about 21.8%.

[0149] FIG. 8 is an XRD pattern of H3PMo / AS-20H. It is observed that no characteristic diffraction peak of the heteropoly acid molecule appears on the XRD pattern, indicating that the heteropoly acid is uniformly dispersed on the catalyst.

[0150] FIG. 9 is a TEM pattern of H3PMo / AS-20H. The catalyst has a three-dimensional hollow porous structure assembled by two-dimensional sheets, the diameter of the catalyst is about 180nm, and the diameter of the hollow part is about 80nm.

[0151] The H3PMo / AS-20H catalyst is spherical, with a diameter of about 180nm, a specific surface area of about 701m 2 / g, an average pore size of about 6.5nm, an average pore volume of about 1.4cc / g, and an average density of about 3.0g / cm 3 .

[0152] Application Examples 23-25:

[0153] The application examples 23-25 are basically the same as the application example 22, except that some conditions are different. The specific conditions and the results of the catalytic reaction are shown in Table 3.

[0154] Table 3

[0155] Figure 10 is a gas chromatogram of 13-oxabicyclo(10.4.0)-1(12)hexadecene prepared in Example 22.

[0156] Examples 26-33:

[0157] The example is basically the same as Example 22, except that the catalyst and its preparation conditions are different from those of Example 22. The preparation conditions of the specific catalyst and the results of the catalytic reaction are shown in Table 4.

[0158] Table 4

[0159] Example 34:

[0160] This example provides a method for preparing 1-hydroperoxy-16-oxabicyclo(10.4.0)hexadecane (i.e., the compound shown in formula (III)), and the reaction scheme is as follows:

[0161] In a 2L reaction kettle, 2g of catalyst, 353g of 13-oxabicyclo(10.4.0)-1(12)hexadecene (the compound shown in formula (II)), and 400g of acetic acid were sequentially added, and the temperature was kept at 0°C. Then 195g of hydrogen peroxide (mass concentration of 27.5%) was added dropwise, and the dropwise addition took 1 hour. The reaction was kept at constant temperature for 3h. After the product was separated, it was analyzed using an Agilent 7890 gas chromatograph, wherein the chromatographic column was HP-INNOWax, and the detector was an FID detector.

[0162] The catalyst of this example uses the catalyst of Example 22.

[0163] Examples 35-38:

[0164] The example is basically the same as Example 34, except that some conditions are different. The specific conditions and the results of the catalytic reaction are shown in Table 5.

[0165] Table 5

[0166] Examples 39-46:

[0167] The example is basically the same as Example 34, except that the catalyst is different from that of Example 34. The specific catalyst and the results of the catalytic reaction are shown in Table 6.

[0168] Table 6

[0169] Example 47:

[0170] This example provides a method for preparing halbanol, and the reaction scheme is as follows:

[0171] In a 2L reactor, 3g catalyst, 600g DDP-OOH (1-hydroperoxy-16-oxabicyclo(10.4.0)hexadecane, compound shown in formula (III)), 600g methanol were added in sequence, and the temperature was raised to 60°C and kept for 8h. The product was separated and analyzed by Agilent 7890 gas chromatograph, wherein the chromatographic column was HP-INNOWax and the detector was FID detector;

[0172] The catalyst of this example was the catalyst of application example 1.

[0173] Application examples 48-50:

[0174] The basic procedure was the same as that of application example 47, except that the conditions were different. The specific conditions and catalytic reaction results are shown in Table 7.

[0175] Table 7

[0176] Figure 11 is a gas chromatogram of habanolide prepared in application example 47.

[0177] Application examples 51-67:

[0178] The basic procedure was the same as that of application example 47, except that the catalyst was different from that of application example 47. The specific catalyst and catalytic reaction results are shown in Table 8.

[0179] Table 8

[0180] Application example 68:

[0181] This example provides a method for preparing 13-oxabicyclo(10.4.0)-1(12)hexadecene (i.e. compound shown in formula (II)), which is basically the same as application example 22, except that the catalyst is the metal oxide supported composite catalyst of application example 1. The conversion rate is 95.2% and the selectivity is 94.5%.

[0182] Application example 69:

[0183] This example provides a method for preparing 1-hydroperoxy-16-oxabicyclo(10.4.0)hexadecane (i.e. compound shown in formula (III)), which is basically the same as application example 22, except that the catalyst is the metal oxide supported composite catalyst of application example 1. The conversion rate is 98.7% and the selectivity is 99.4%.

[0184] The above examples are only for illustrating the technical concept and characteristics of the present application, and the purpose is to enable those skilled in the art to understand the content of the present application and to implement it, and cannot limit the protection scope of the present application. Any equivalent changes or modifications made according to the spirit and essence of the present application should be covered within the protection scope of the present application.

[0185] The endpoints of the ranges and any values described herein are not limited to the precise values recited as exactly that endpoint point, but rather to be understood as being approximate thereof. For ranges, the endpoints are to be understood to be the starting and ending values, and the endpoint values are to be understood to be independently combinable with each other to generate new ranges not specifically listed.

Claims

1. A process for the preparation of habanolide, characterized in that, The preparation method comprises: Reaction (1): reacting cyclododecanone with allyl alcohol in the presence of a catalyst to form a compound represented by formula (I); Reaction (2): the compound of formula (I) is used as a substrate to prepare the compound of formula (II) in the presence of a catalyst; Reaction (3): reacting the compound of formula (II) with hydrogen peroxide in the presence of a catalyst to form a compound of formula (III); Reaction (4): the compound of formula (III) as substrate, in the presence of a catalyst to prepare habanenol; The catalyst used in one, two, three or four of the reaction (1), reaction (2), reaction (3), reaction (4) comprises a metal oxide supported catalyst selected from a metal oxide supported heteropoly acid, a metal oxide supported composite catalyst, wherein: The metal oxide supported heteropoly acid comprises a metal oxide carrier with a three-dimensional porous structure and a heteropoly acid dispersed in a monomolecular state and connected to the metal oxide carrier, the heteropoly acid being a proton type heteropoly acid capable of providing hydrogen ions; The metal oxide supported composite catalyst comprises a metal oxide carrier with a three-dimensional porous structure, a heteropoly acid dispersed in a monomolecular state and connected to the metal oxide carrier, and an active metal component dispersed in a monatomic state and connected to one or both of the heteropoly acid and the metal oxide carrier, the heteropoly acid being a proton type heteropoly acid capable of providing hydrogen ions.

2. The process for the preparation of halbanol according to claim 1, characterized in that, The catalyst used in the reaction (2) and the reaction (3) both comprises the metal oxide supported composite catalyst, or the catalyst used in the reaction (2) and the reaction (3) both comprises the metal oxide supported heteropoly acid.

3. The process for the preparation of halbanol according to claim 1, characterized in that, The catalyst used in the reaction (1) and / or the reaction (4) comprises the metal oxide supported composite catalyst.

4. The process for the preparation of halbanol according to claim 1, characterized in that, The catalyst used in the reaction (1) to (4) all comprises the metal oxide supported composite catalyst.

5. The process for the preparation of halbanol according to claim 1, characterized in that, In the reaction (1), the feeding amount of the catalyst is 0.01wt.%-2wt.% of the cyclododecanone; and / or, in the reaction (1), the reaction temperature is 80-160℃.

6. The process for the preparation of halbanol according to claim 5, characterized in that, In the reaction (1), the feeding amount of the catalyst is 0.01wt.%-1wt.% of the cyclododecanone; and / or, in the reaction (1), the reaction temperature is 80-120℃.

7. The process for the preparation of halbanol according to claim 1, characterized in that, In the reaction (2), the feeding amount of the catalyst is 0.01wt.%-2wt.% of the compound represented by the formula (I); and / or, in the reaction (2), the reaction temperature is 80-160℃, and the reaction pressure is-0.01-0.1MPa.

8. The process for the preparation of halbanol according to claim 7, characterized in that, In the reaction (2), the feeding amount of the catalyst is 0.01wt.%-1wt.% of the compound represented by the formula (I); and / or, in the reaction (2), the reaction temperature is 80-95℃, and the reaction pressure is-0.001-0.07MPa.

9. The process for the preparation of halbanol according to claim 1, characterized in that, In the reaction (3), the feeding amount of the catalyst is 0.01wt.%-2wt.% of the compound represented by the formula (II); and / or, in the reaction (3), the reaction temperature is-10-50℃.

10. The process for the preparation of halbanol according to claim 9, characterized in that, In the reaction (3), the feeding amount of the catalyst is 0.01wt.%-1wt.% of the compound represented by the formula (II); and / or, in the reaction (3), the reaction temperature is-10-10℃.

11. The process for the preparation of halbanol according to claim 1, characterized in that, The feeding amount of the catalyst in the reaction (4) is 0.01wt.%-2wt.% of the compound of formula (III); and / or, the temperature of the reaction in the reaction (4) is 20-120℃.

12. The process for the preparation of halbanol according to claim 11, characterized in that, The feeding amount of the catalyst in the reaction (4) is 0.01wt.%-0.8wt.% of the compound of formula (III); and / or, the temperature of the reaction in the reaction (4) is 20-80℃, preferably, the temperature of the reaction in the reaction (4) is 30-80℃.

13. The process for the preparation of halbanol according to claim 1, characterized in that, The molar ratio of the cyclododecanone to the allyl alcohol in the reaction (1) is 1-10:1; and / or, the solvent used in the reaction (3) is a combination of one or more selected from formic acid, acetic acid, propionic acid, butyric acid, valeric acid, hexanoic acid, heptanoic acid and octanoic acid, preferably, the mass ratio of the solvent to the compound of formula (II) is 0.5-10:1, the mass concentration of the hydrogen peroxide is 27.5%-50%, further preferably, the molar ratio of the compound of formula (II) to the hydrogen peroxide in the hydrogen peroxide is 1:0.6-3; and / or, the solvent used in the reaction (4) is a combination of one or more selected from methanol, ethanol, isopropanol, butanol, pentanol, hexanol, heptanol, octanol, nonanol, decanol, ethylene glycol and polyethylene glycol, preferably, the mass ratio of the solvent to the compound of formula (III) is 0.5-10:1; and / or, in the metal oxide supported heteropoly acid and the metal oxide supported composite catalyst, the protonic heteropoly acid is connected to the metal oxide carrier by at least a covalent bond.

14. The process for the preparation of halbanol according to any one of claims 1 to 13, characterized in that, In the protonic heteropoly acid, heteroatoms and polyatoms are bridged by oxygen atoms, the heteroatoms include at least one selected from P, Si, Fe and Co, the polyatoms include at least one selected from Mo, W, V, Nb and Ta; a covalent bond is formed between the polyatoms in the protonic heteropoly acid, the terminal oxygen in the protonic heteropoly acid and the metal atoms in the metal oxide carrier; and / or, the protonic heteropoly acid is uniformly dispersed in the skeleton, inside the pores and on the surface of the metal oxide carrier; and / or, the active metal component is connected to the protonic heteropoly acid by a chemical bond, the chemical bond includes a coordination bond, the active metal component is also selectively adsorbed on the metal oxide carrier; and / or, the active metal component is a combination of one or more selected from transition metals, preferably, the active metal component is a combination of one or more selected from groups IB-ⅡB and groups VB-ⅧB, further preferably, the active metal component is a combination of one or more selected from Pd, Pt, Ru, Au, Ag, Rh, Ni, Cu, Fe and Co; and / or, in the metal oxide supported composite catalyst, the mass content of the active metal component is 0.01%-15%, preferably 0.04%-15% in terms of mass percentage.

15. The process for the preparation of halbanol according to any one of claims 1 to 13, characterized in that, The protonic heteropoly acid comprises one or more combinations selected from phosphomolybdic acid, phosphotungstic acid, silicotungstic acid, silicomolybdic acid, phosphovanadic heteropoly acid, phosphoniobic heteropoly acid, phosphotantalum heteropoly acid, iron molybdenum heteropoly acid, iron tungsten heteropoly acid, iron vanadium heteropoly acid, cobalt molybdenum heteropoly acid, cobalt tungsten heteropoly acid, cobalt vanadium heteropoly acid; and / or the mass content of the protonic heteropoly acid in the metal oxide supported heteropoly acid and the metal oxide supported composite catalyst is 1%-68%, preferably 7%-45%, and further preferably 7%-25% by mass percentage; and / or the specific surface area of the metal oxide supported heteropoly acid and the metal oxide supported composite catalyst is greater than or equal to 200 m 2 / g, preferably less than or equal to 1000 m 2 / g, and further preferably 200-800 m 2 / g, measured by the BET method; and / or the metal oxide carrier comprises a zinc oxide carrier, a magnesium oxide carrier, a copper oxide carrier, an aluminum oxide carrier, or a titanium oxide carrier; and / or the average pore size of the metal oxide supported heteropoly acid and the metal oxide supported composite catalyst is 2-30 nm, and the average pore volume is 0.4-1.5 cc / g; and / or the average density of the metal oxide supported heteropoly acid and the metal oxide supported composite catalyst is 0.5-4.0 g / cm 3 ; and / or the average particle size of the metal oxide supported heteropoly acid and the metal oxide supported composite catalyst is 10-350 nm, and preferably 80-250 nm.

16. The process for the preparation of halbanol according to any one of claims 1 to 13, characterized in that, Each of the pores in the three-dimensional porous structure is randomly distributed in three-dimensional direction; and / or, the metal oxide carrier has a three-dimensional hollow porous structure; preferably, the hollow structure has a single hollow chamber or a hollow combination formed by a plurality of hollow chambers which are all or partially communicated; further preferably, the diameter of the hollow chamber or the hollow combination is 1-90 nm; or, the ratio of the diameter of the hollow chamber or the hollow combination to the particle size of the metal oxide loaded composite catalyst is 0.3-0.9:1; and / or, the metal oxide loaded heteropoly acid, the metal oxide loaded composite catalyst can independently be a spherical structure.

17. The process for the preparation of halbanol according to any one of claims 1 to 13, characterized in that, The metal oxide loaded heteropoly acid is prepared by a preparation method satisfying the following conditions: (a) using a precursor of metal oxide as raw material, the precursor of metal oxide refers to a substance which can be converted into metal oxide through one or more steps of conversion treatment, the conversion treatment at least includes a treatment of generating chemical reaction; (b) the one or more steps of conversion treatment is carried out in the presence of the protic heteropoly acid and water; The metal oxide loaded composite catalyst is prepared by a preparation method satisfying the following conditions: (a) using a precursor of metal oxide and a precursor of active metal as raw material respectively, the precursor of metal oxide and the precursor of active metal respectively refers to a substance which can be converted into metal oxide or active metal component through one or more steps of conversion treatment, the conversion treatment at least includes a treatment of generating chemical reaction; (b) the one or more steps of conversion treatment is carried out in the presence of the protic heteropoly acid and water.

18. The process for the preparation of halbanol according to claim 17, characterized in that, The precursor of metal oxide is a substance which can be converted into the metal oxide carrier with three-dimensional porous structure through gelation treatment and calcination treatment in sequence; and / or, the preparation method of the metal oxide loaded heteropoly acid or the metal oxide loaded composite catalyst further satisfies the condition: (c) the conversion treatment includes gelation treatment, and the gelation treatment is carried out in the presence of water, organic solvent and surfactant simultaneously.

19. The process for the preparation of halbanol according to any one of claims 1 to 13, characterized in that, The preparation method of the metal oxide loaded heteropoly acid includes gelation treatment and calcination treatment in sequence; the gelation treatment includes: mixing reaction of the protic heteropoly acid and the precursor of metal oxide in the presence of water, organic solvent and surfactant, and inducing by solvent evaporation to prepare gel; the calcination treatment includes: drying the gel and then calcining to obtain the metal oxide loaded heteropoly acid; The preparation method of the metal oxide supported composite catalyst comprises gelation treatment, calcination treatment and reduction treatment in sequence; the gelation treatment comprises: mixing and reacting the protonic heteropoly acid and a precursor of metal oxide in the presence of water, an organic solvent and a surfactant, and inducing solvent evaporation to prepare a gel; the calcination treatment comprises: drying the gel and then calcining, and the reduction treatment is performed in the presence of a reducing agent, and the metal oxide supported composite catalyst is obtained after reduction; wherein, the preparation method of the metal oxide supported composite catalyst further comprises a step of adding an active metal precursor before the mixing reaction, or a step of coating with a solution containing the active metal precursor after the calcination treatment and before the reduction treatment.

20. The process for the preparation of halbanol according to claim 19, characterized in that, The precursor of the metal oxide is selected from acidic, basic or neutral compounds containing metal and organic groups, preferably, the compound containing metal and organic groups is selected from C1-C12 metal alkoxide, C1-C12 hydrocarbon metal, metal organic complex or complex, further preferably, the precursor of the metal oxide is selected from aluminum alcohol compound, magnesium alcohol compound, copper alcohol compound, zinc alcohol compound, titanium alcohol compound, hydrocarbyl aluminum compound, hydrocarbyl titanium compound, hydrocarbyl zinc compound, organic aluminum salt, organic titanium salt and organic zinc salt, and further preferably, the precursor of the metal oxide is a combination of one or more selected from trimethylaluminum, triethylaluminum, triisobutylaluminum, diethylaluminum chloride, aluminum isopropyl alcohol, aluminum n-butyl alcohol, aluminum acetate, aluminum propionate, titanium acetylacetate, titanium tetraethyl titanate, titanium tetraisopropyl titanate, titanium tetrabutyl titanate and zinc acetylacetate; and / or, the active metal precursor is a salt of active metal component and / or an acid of active metal component, the salt of active metal component includes a combination of one or more selected from metal nitrate, metal sulfate, metal halide, metal acetylacetone complex, metal sulfide, and the acid of active metal component includes halogenated metal acid; preferably, the active metal precursor is a combination of one or more selected from palladium chloride, palladium nitrate, platinum acetylacetone, gold chloride, silver nitrate, ruthenium chloride, ruthenium nitrate, rhodium chloride, rhodium nitrate, cobalt nitrate, nickel nitrate, iron chloride, iron sulfate, copper nitrate, copper sulfate, chloroplatinic acid, chloropalladic acid, chloroauric acid and rhodium acetylacetone.

21. The process for the preparation of halbanol according to claim 19, characterized in that, The organic solvent is a polar organic solvent, preferably, the organic solvent is a combination of one or more selected from methanol, ethanol, isopropyl alcohol, acetone, tetrahydrofuran and N,N-dimethylformamide; and / or, the surfactant is a block copolymer non-ionic surfactant and / or an ionic surfactant; preferably, the block copolymer non-ionic surfactant includes a combination of one or more selected from non-ionic surfactant P123, non-ionic surfactant F127 and non-ionic surfactant F108, and the ionic surfactant includes a combination of one or more selected from cetyltrimethylammonium bromide (CTAB), sodium oleate, sodium dodecylbenzenesulfonate and sodium stearate; and / or, In the preparation method of the metal oxide supported heteropoly acid, the metal oxide supported composite catalyst: The temperature of the mixing reaction is controlled to be 20-50 DEG C, and the reaction time is controlled to be no less than 12 hours; and / or, the solvent evaporation induction is controlled to be carried out at a temperature of 40-120 DEG C for 1-72 hours; and / or, the calcination is carried out at 200-700 DEG C; and / or, the calcination is carried out in an oxygen-containing environment, which includes an air atmosphere or a pure oxygen atmosphere formed by introducing a pure oxygen gas with a purity of more than 99%; And / or, the reduction treatment includes: firstly carrying out calcination in an oxygen-containing environment, and then carrying out second calcination in a reducing atmosphere; preferably, the calcination temperature of the first calcination is 200-400 DEG C, and the calcination temperature of the second calcination is 150-300 DEG C.

22. A process for the preparation of habanolide, characterized by, The preparation method comprises: allowing 1-hydroperoxy-16-oxabicyclo(10.4.0)hexadecane shown in formula (III) to react in the presence of a metal oxide supported composite catalyst to generate the halenolide, wherein the metal oxide supported composite catalyst is the same as the metal oxide supported composite catalyst in any one of claims 1-21.

23. A method for preparing a halbanol intermediate, the halbanol intermediate being 2-(3-hydroxypropyl)cyclododecanone as shown in formula (I), characterized in that, The production method comprises: reacting cyclododecanone and allyl alcohol in the presence of a metal oxide-supported composite catalyst to produce the 2-(3-hydroxypropyl)cyclododecanone, the metal oxide-supported composite catalyst being the same as the metal oxide-supported composite catalyst according to any one of claims 1-21; 24. A process for the preparation of a halbanyl intermediate, said halbanyl intermediate being 13-oxabicyclo(10.4.0)-l(12)hexadecene of formula (II), characterized in that, The preparation method comprises: allowing a compound shown in formula (I) to react in the presence of a metal oxide supported heteropoly acid and / or a metal oxide supported composite catalyst to generate the 13-oxabicyclo(10.4.0)-1(12)hexadecene, wherein the metal oxide supported heteropoly acid and the metal oxide supported composite catalyst are respectively the metal oxide supported heteropoly acid and the metal oxide supported composite catalyst according to any one of claims 1-21.

25. A process for the preparation of a halbanol intermediate, said halbanol intermediate being l-hydroperoxy-16-oxabicyclo(10.4.0)hexadecane of formula (III), characterized in that, The preparation method comprises: reacting a compound shown in formula (II) with hydrogen peroxide in the presence of a metal oxide supported heteropoly acid and / or a metal oxide supported composite catalyst to generate the 1-hydroperoxy-16-oxabicyclo(10.4.0)hexadecane, wherein the metal oxide supported heteropoly acid and / or the metal oxide supported composite catalyst are respectively the metal oxide supported heteropoly acid and / or the metal oxide supported composite catalyst according to any one of claims 1-21.

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