WO2022198478A1 - 负载型催化剂以及蔗糖-6-酯的合成方法 - Google Patents

负载型催化剂以及蔗糖-6-酯的合成方法 Download PDF

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WO2022198478A1
WO2022198478A1 PCT/CN2021/082598 CN2021082598W WO2022198478A1 WO 2022198478 A1 WO2022198478 A1 WO 2022198478A1 CN 2021082598 W CN2021082598 W CN 2021082598W WO 2022198478 A1 WO2022198478 A1 WO 2022198478A1
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sucrose
ester
supported catalyst
group
reaction
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French (fr)
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张正颂
杨志健
赵金刚
李正华
陈朝晖
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Anhui Jinhe Industrial Co Ltd
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Anhui Jinhe Industrial Co Ltd
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Priority to US18/036,623 priority Critical patent/US20230415126A1/en
Priority to MX2023005915A priority patent/MX2023005915A/es
Priority to CN202180000705.1A priority patent/CN113195099B/zh
Priority to EP21932106.4A priority patent/EP4205845B1/en
Priority to PCT/CN2021/082598 priority patent/WO2022198478A1/zh
Publication of WO2022198478A1 publication Critical patent/WO2022198478A1/zh
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    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J23/00—Catalysts comprising metals or metal oxides or hydroxides, not provided for in group B01J21/00
    • B01J23/14—Catalysts comprising metals or metal oxides or hydroxides, not provided for in group B01J21/00 of germanium, tin or lead
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J31/00—Catalysts comprising hydrides, coordination complexes or organic compounds
    • B01J31/02—Catalysts comprising hydrides, coordination complexes or organic compounds containing organic compounds or metal hydrides
    • B01J31/12—Catalysts comprising hydrides, coordination complexes or organic compounds containing organic compounds or metal hydrides containing organo-metallic compounds or metal hydrides
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
    • C07F7/00—Compounds containing elements of Groups 4 or 14 of the Periodic Table
    • C07F7/22—Tin compounds
    • C07F7/2224—Compounds having one or more tin-oxygen linkages
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J31/00—Catalysts comprising hydrides, coordination complexes or organic compounds
    • B01J31/02—Catalysts comprising hydrides, coordination complexes or organic compounds containing organic compounds or metal hydrides
    • B01J31/12—Catalysts comprising hydrides, coordination complexes or organic compounds containing organic compounds or metal hydrides containing organo-metallic compounds or metal hydrides
    • B01J31/123—Organometallic polymers, e.g. comprising C-Si bonds in the main chain or in subunits grafted to the main chain
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J31/00—Catalysts comprising hydrides, coordination complexes or organic compounds
    • B01J31/02—Catalysts comprising hydrides, coordination complexes or organic compounds containing organic compounds or metal hydrides
    • B01J31/12—Catalysts comprising hydrides, coordination complexes or organic compounds containing organic compounds or metal hydrides containing organo-metallic compounds or metal hydrides
    • B01J31/123—Organometallic polymers, e.g. comprising C-Si bonds in the main chain or in subunits grafted to the main chain
    • B01J31/124—Silicones or siloxanes or comprising such units
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J35/00—Catalysts, in general, characterised by their form or physical properties
    • B01J35/60—Catalysts, in general, characterised by their form or physical properties characterised by their surface properties or porosity
    • B01J35/61—Surface area
    • B01J35/615—100-500 m2/g
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D407/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having oxygen atoms as the only ring hetero atoms, not provided for by group C07D405/00
    • C07D407/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having oxygen atoms as the only ring hetero atoms, not provided for by group C07D405/00 containing two hetero rings
    • C07D407/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having oxygen atoms as the only ring hetero atoms, not provided for by group C07D405/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
    • C07H1/00—Processes for the preparation of sugar derivatives
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
    • C07H13/00—Compounds containing saccharide radicals esterified by carbonic acid or derivatives thereof, or by organic acids, e.g. phosphonic acids
    • C07H13/02—Compounds containing saccharide radicals esterified by carbonic acid or derivatives thereof, or by organic acids, e.g. phosphonic acids by carboxylic acids
    • C07H13/04—Compounds containing saccharide radicals esterified by carbonic acid or derivatives thereof, or by organic acids, e.g. phosphonic acids by carboxylic acids having the esterifying carboxyl radicals attached to acyclic carbon atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
    • C07H13/00—Compounds containing saccharide radicals esterified by carbonic acid or derivatives thereof, or by organic acids, e.g. phosphonic acids
    • C07H13/02—Compounds containing saccharide radicals esterified by carbonic acid or derivatives thereof, or by organic acids, e.g. phosphonic acids by carboxylic acids
    • C07H13/04—Compounds containing saccharide radicals esterified by carbonic acid or derivatives thereof, or by organic acids, e.g. phosphonic acids by carboxylic acids having the esterifying carboxyl radicals attached to acyclic carbon atoms
    • C07H13/06—Fatty acids
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J21/00—Catalysts comprising the elements, oxides, or hydroxides of magnesium, boron, aluminium, carbon, silicon, titanium, zirconium, or hafnium
    • B01J21/06—Silicon, titanium, zirconium or hafnium; Oxides or hydroxides thereof
    • B01J21/08—Silica
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J2231/00—Catalytic reactions performed with catalysts classified in B01J31/00
    • B01J2231/40—Substitution reactions at carbon centres, e.g. C-C or C-X, i.e. carbon-hetero atom, cross-coupling, C-H activation or ring-opening reactions
    • B01J2231/49—Esterification or transesterification
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J2531/00—Additional information regarding catalytic systems classified in B01J31/00
    • B01J2531/40—Complexes comprising metals of Group IV (IVA or IVB) as the central metal
    • B01J2531/42—Tin
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J31/00—Catalysts comprising hydrides, coordination complexes or organic compounds
    • B01J31/02—Catalysts comprising hydrides, coordination complexes or organic compounds containing organic compounds or metal hydrides
    • B01J31/12—Catalysts comprising hydrides, coordination complexes or organic compounds containing organic compounds or metal hydrides containing organo-metallic compounds or metal hydrides
    • B01J31/122—Metal aryl or alkyl compounds

Definitions

  • the invention belongs to the technical field of fine chemicals, and particularly relates to a supported catalyst and a method for synthesizing sucrose-6-ester.
  • sucrose-6-carboxylate namely sucrose-6-ester
  • sucrose-6-fatty acid ester is a kind of polyol type non-ionic surfactant with excellent emulsifying properties, widely used in food, medicine, cosmetics and other industries; for example, sucrose rosin ester is also an excellent emulsifier; sucrose-6-acetate is not only a raw material for the synthesis of sucrose-6-fatty acid ester and sucrose acetate isobutyrate, but also a raw material for the synthesis of sucralose.
  • sucrose-6-ester is the single-group protection method: organotin compound and sucrose are dehydrated in polar solvent to form sucrose organotin ester solution, followed by sucrose organotin ester solution and acylating agent Carboxylic acid anhydrides react with high selectivity to yield sucrose-6-carboxylates.
  • the single-group protection method has mild process conditions, high selectivity, high yield, catalyst recycling, and less three wastes, so it has become the main process for producing sucrose-6-ester. But the single-group protection method still has many shortcomings. For example, this method needs to be divided into two-step reaction process. The first step is to form sucrose organotin ester, and the second step is to react with carboxylic acid anhydride to generate sucrose-6-carboxylate after cooling down. In the follow-up, it is necessary to add water to quench the remaining carboxylic acid anhydride, recover the organotin through solvent extraction, and then concentrate it to a certain volume before the next reaction or application can be carried out.
  • the present application is proposed to provide a supported catalyst and a method for synthesizing sucrose-6-esters that overcome the above problems or at least partially solve the above problems.
  • a supported catalyst for catalyzing the transesterification reaction of sucrose and carboxylate comprising an active functional component and an inorganic carrier; wherein the active functional component is of formula (1)
  • the active functional component is of formula (1)
  • n is a natural number greater than or equal to 2;
  • R is an atom connected to the surface of the inorganic carrier; one or both of R 1 , R 2 and R 3 are hydrocarbon groups, and the rest are independently selected from oxygen atoms, hydroxyl groups, hydrocarbon groups Either oxy or acetoxy.
  • R is selected from any one of silicon, oxygen, nitrogen, sulfur and phosphorus atoms.
  • the hydrocarbon group is an alkyl group, a cycloalkyl group, an aryl group or an aralkyl group, preferably an alkyl group, and in some embodiments, n-butyl group.
  • the alkoxy group is selected from alkoxy group or phenoxy group, and in some embodiments, is methoxy group, ethoxy group, n-propoxy group, n-butoxy group, n-pentoxy or n-hexyloxy, in other embodiments, is methoxy.
  • the inorganic carrier is selected from a mixture of one or more of silica, titania, activated carbon and alumina, and in some embodiments, is silica.
  • the specific surface area of the inorganic carrier is greater than 10 m 2 /g, in some embodiments, greater than 30 m 2 /g, and in other embodiments, greater than 100 m 2 /g.
  • the active functional component accounts for 1 ppm to 40% of the weight of the inorganic carrier, preferably 1000 ppm to 10%.
  • sucrose-6-ester which adopts any of the above supported catalysts to catalyze transesterification of sucrose and carboxylic acid lower alcohol ester to obtain sucrose-6-ester. ester.
  • the synthetic method of above-mentioned sucrose-6-ester comprises:
  • Sucrose dissolving step heating and dissolving sucrose in a polar aprotic solvent to form a sucrose solution;
  • Catalyst adding step adding any of the above-mentioned supported catalysts to the sucrose solution to form a reaction suspension;
  • Transesterification reaction step adding the carboxylic acid lower alcohol ester into the reaction suspension, and performing dehydration and dealcoholization treatment to promote the transesterification reaction to obtain a reaction mixture solution with sucrose-6-ester as the main product.
  • the synthetic method of above-mentioned sucrose-6-ester also includes:
  • Post-processing step filter the reaction mixed solution to separate the supported catalyst therein to obtain a sucrose-6-ester mother liquor.
  • carboxylic acid lower alcohol ester is selected from stearic acid, benzoic acid, acetic acid, butyric acid, lauric acid methyl ester, ethyl ester, propyl ester , one or more of isopropyl ester, n-butyl ester, isobutyl ester, tert-butyl ester and benzyl ester, in some embodiments, selected from methyl stearate, ethyl acetate One or more of ester and methyl benzoate.
  • the polar aprotic solvent is selected from dimethyl sulfoxide, acetonitrile, 1,4-dioxane, methyl ethyl ketone, methyl isobutyl ketone, nitro In methylmethane, nitroethane, cyclohexanone, N-methylpyrrolidone, N-methylpyrrolidone, N,N-dimethylacetamide, hexamethylphosphoramide and N,N-dimethylformamide One or more of, in some embodiments, selected from acetonitrile and/or N,N-dimethylformamide.
  • the ratio of polar aprotic solvent volume consumption to the sucrose mass consumption is 2 ⁇ 50mg/L, in some embodiments 4 ⁇ 20mg/L , and in other embodiments, it is 6 to 10 mg/L;
  • the ratio of the molar dosage of the supported catalyst to the molar dosage of sucrose is 0.01-2, and in some embodiments, 0.05-0.5;
  • the volume usage of the carboxylic acid lower alcohol ester is less than 30% of the volume usage of the polar aprotic solvent, in some embodiments, less than 20%, and in other embodiments, less than 15%.
  • the dehydration and dealcoholization treatment is realized by distilling off the polar aprotic solvent or carboxylic acid lower alcohol ester additionally added to the reaction suspension.
  • the distillation conditions are: the distillation temperature is 40-100°C, in some embodiments, 60-80°C; the distillation pressure is 0.01kPa-100kPa, in some In embodiments, it is 0.5 kPa to 90 kPa; the distillation time is 1 minute to 12 hours, and in some embodiments, 30 minutes to 4 hours.
  • the transesterification reaction step is realized by a kettle-type reactor or a continuous countercurrent reactive distillation column.
  • the present application provides a supported catalyst.
  • the obtained supported catalyst can catalyze sucrose and carboxyl with high selectivity.
  • the acid lower alcohol ester undergoes a transesterification reaction to obtain sucrose-6-ester.
  • the catalyst can be recovered by filtration, and the catalyst has almost no loss and can be recovered basically. In this way, not only does it not need to supplement new catalyst for each production, but also there is no catalyst entrained in the product, which will not affect the subsequent production.
  • reaction steps have adverse effects; and the use of carboxylic acid lower alcohol esters as reaction raw materials can avoid the control restrictions of using carboxylic acid anhydrides in the prior art, and can also avoid the need for the remaining acylating agent to be quenched with water, and the recovery of catalysts and subsequent dehydration process are complicated. and other problems, the overall process is simpler and easier to implement, and the economic benefits are significant in terms of manpower, equipment, and energy consumption.
  • the concept of the present application is that, in the prior art, there is a process load for the production of sucrose-6-ester by the single-group protection method in the prior art, and the recovery of the liquid organotin catalyst is difficult, which has adverse effects on the subsequent generation steps, And the current situation of strict control of raw material carboxylic acid anhydride, a solid-state supported catalyst is proposed.
  • the obtained catalyst can efficiently catalyze the esterification of sucrose and carboxylic acid lower alcohol ester.
  • the exchange reaction to obtain sucrose-6-ester not only facilitates catalyst recovery, but also bypasses the need to use carboxylic acid anhydride.
  • a supported catalyst for catalyzing the transesterification reaction of sucrose and carboxylate, the catalyst comprising an active functional component and an inorganic carrier; wherein the active functional component is of formula ( 1) Compounds represented by:
  • n is a natural number greater than or equal to 2;
  • R is an atom connected to the surface of the inorganic carrier; one or both of R 1 , R 2 and R 3 are hydrocarbon groups, and the rest are independently selected from oxygen atoms, hydroxyl groups, hydrocarbon groups Either oxy or acetoxy.
  • R is an atom connected to the surface of the inorganic carrier, which can be, but is not limited to, any atom selected from silicon, oxygen, nitrogen, sulfur and phosphorus atoms.
  • the inorganic carrier can be, but is not limited to, any atom selected from silicon, oxygen, nitrogen, sulfur and phosphorus atoms.
  • the inorganic carrier may be, but is not limited to, a mixture of one or more selected from the group consisting of silica, titania, activated carbon, and alumina, and in some embodiments, is silica.
  • the inorganic carrier On the surface of the inorganic carrier, there are usually atoms or groups that can form covalent bonds, such as the hydroxyl group on the surface of silica or the oxygen atom left after the hydrogen atom in the hydroxyl group is broken. These atoms or groups can interact with R The represented atoms form covalent bonds, so that the active functional components are supported on the surface of the inorganic carrier, or in the pores of the inorganic carrier. It should be noted that the combination of the organic tin active functional component and the inorganic carrier is not limited to the above-mentioned covalent bond form, and the above is only an illustrative example, so that those skilled in the art can more easily understand the present application.
  • any of the above supported catalysts can be prepared by fixing the organotin active functional component represented by formula (1) on the surface of the inorganic carrier by forming a chemical bond, and the preparation method of the supported catalyst is not limited in this application. , those skilled in the art can refer to the prior art.
  • an organotin catalyst that forms silicon-coupled atoms on the surface of silicon oxide is to use a solvent with a carrier with a silicon oxide surface (which can be silicon oxide or other carriers coated with silicon oxide) to form a suspension, and then the organic
  • the organotin active functional component of the siloxane or chlorosilane structure is added to the suspension, and the reaction is kept warm, so that the organosiloxane or chlorosilane structure forms a covalent link with the surface of the silicon oxide, and the loaded organic tin is obtained.
  • a catalyst for the active energy component of tin is to use a solvent with a carrier with a silicon oxide surface (which can be silicon oxide or other carriers coated with silicon oxide) to form a suspension, and then the organic
  • the organotin active functional component of the siloxane or chlorosilane structure is added to the suspension, and the reaction is kept warm, so that the organosiloxane or chlorosilane structure forms a covalent link with the surface of
  • the supported catalyst that forms nitrogen-coupling atoms on the aminated surface is to suspend the carrier with the aminated surface in a solvent, and then add the halogen-substituted organotin active energy component into the suspension, and the reaction is kept warm. , so that the amino group reacts with the halogenated hydrocarbon structure to form a covalent link, and a catalyst loaded with an organotin active component is obtained.
  • the hydrocarbon group in the above-mentioned supported catalyst, may be, but not limited to, an alkyl group, a cycloalkyl group, an aryl group or an aralkyl group, in some embodiments an alkyl group, and in In other embodiments, it is n-butyl.
  • the alkyl group can be but not limited to methyl, ethyl, propyl, isopropyl, butyl, isobutyl, tert-butyl, pentyl, isopentyl, neopentyl, n-hexyl, branched Hexyl, n-heptane, branched heptane, n-octane, branched octane.
  • Cycloalkyl can be, but is not limited to, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, monosubstituted cyclopropyl, such as methylcyclopropyl, ethylcyclopropyl, etc.; disubstituted cyclopropyl base, such as dimethylcyclopropyl, methylethylcyclopropyl, etc.; monosubstituted cyclobutyl, disubstituted cyclobutyl, trisubstituted cyclobutyl, such as trimethylcyclobutyl; monosubstituted cyclobutyl cyclopentyl, disubstituted cyclopentyl, trisubstituted cyclopentyl, such as methylethylcyclopentyl; monosubstituted cyclohexyl, disubstituted cyclohexyl
  • Cycloalkyl can also be, but is not limited to, cyclopropenyl, cyclobutenyl, cyclopentenyl, cyclohexenyl, cyclopropynyl, cyclobutynyl, cyclopentynyl, cyclohexynyl, monosubstituted Cyclopropenyl, disubstituted cyclopropenyl, such as methylcyclopropenyl; monosubstituted cyclobutenyl, disubstituted cyclobutenyl, trisubstituted cyclobutenyl, such as dimethylcyclobutenyl; one Substituted cyclopentenyl, disubstituted cyclopentenyl, trisubstituted cyclopentenyl, such as methylethylcyclopentenyl; monosubstituted cyclohexenyl, disubstituted cyclohex
  • Aryl can be but not limited to phenyl, mono-substituted phenyl, di-substituted phenyl, tri-substituted phenyl, tetra-substituted phenyl, penta-substituted phenyl, hexa-substituted phenyl, such as methyl ethyl phenyl, benzo Cyclobutyl, benzocyclopentyl, etc.
  • Aralkyl can be but not limited to mono-substituted phenyl, di-substituted phenyl, tri-substituted phenyl, tetra-substituted phenyl, penta-substituted phenyl, hexa-substituted phenyl, such as methylethylphenyl, benzocyclobutane base, benzocyclopentyl, etc.
  • the alkoxy group in the above-mentioned supported catalyst, can be selected from, but not limited to, alkoxy group or phenoxy group, wherein the alkoxy group can be, but not limited to, methoxy group , ethoxy, n-propoxy, n-butoxy, n-pentoxy or n-hexyloxy, and in other embodiments, methoxy.
  • the specific surface area of the inorganic carrier is greater than 10 m 2 /g, in some embodiments, greater than 30 m 2 /g, and in other embodiments, greater than 100 m 2 /g.
  • the specific surface area refers to the total area possessed by a unit mass of material.
  • the specific surface area of the inorganic carrier can be measured by any one of the prior art methods, such as continuous flow method (ie dynamic method) and static capacity method.
  • continuous flow method ie dynamic method
  • static capacity method ie dynamic method
  • an inorganic carrier is used as a catalyst, generally a larger specific surface area can achieve better technical effects, because it can provide more sites that can be connected with R atoms.
  • the specific surface area of the inorganic carrier can be, but not limited to, greater than 10 m 2 /g, in some embodiments, greater than 30 m 2 /g, and in other embodiments, greater than 100 m 2 /g.
  • the active functional component accounts for 1 ppm to 40% by weight of the inorganic carrier, and in other embodiments, it is 1000 ppm to 10%.
  • the present application has obtained a preferred ratio of active functional components to inorganic carriers.
  • the active functional components account for 1 ppm to 40% of the weight of the inorganic carrier, and in other embodiments, it is 1000 ppm to 1000 ppm. 10%. If the active functional component accounts for less than 1 ppm of the weight of the inorganic carrier, the content of the active functional component is too small to effectively catalyze the transesterification reaction between sucrose and carboxylic acid lower alcohol ester.
  • Esters other than the 6-position substitution product make the reaction yield low; if the active functional component accounts for less than 40% of the weight of the inorganic carrier, the content of the active functional component is too much, and the inorganic carrier cannot provide enough active sites
  • the active functional components are loaded on the spot, so that in the process of catalyst preparation, a large number of active functional components cannot be effectively supported on the surface of the catalyst, resulting in waste of active functional components and no other beneficial effects.
  • the present application also provides a method for synthesizing sucrose-6-ester, which adopts any of the above supported catalysts to catalyze transesterification of sucrose and carboxylic acid lower alcohol esters to obtain sucrose -6-ester.
  • bis-tin or multi-tin organic oxides such as bis(hydrocarbyl)tin oxide, 1,3-bis(hydrocarbyl)-1,1,3,3-tetra-(hydrocarbyl)bis
  • stannoxane 1,3-diacyloxy-1,1,3,3-tetra-(hydrocarbyl)distannoxane, 1-acyloxy-1,1,3,3-tetra-(hydrocarbyl) Distannoxane and diacyloxydihydrocarbyl tin, etc.
  • sucrose to generate organotin ester solution
  • acid anhydride to generate sucrose-6-ester.
  • the phases are distributed, and it is difficult to completely recover, resulting in the loss of 1-5% of the catalyst each time with the material entrainment and other reasons during the reaction process. Catalysts can also adversely affect subsequent chlorination reactions.
  • the obtained supported catalyst can catalyze the transesterification reaction of sucrose and carboxylic acid lower alcohol ester with high selectivity, and obtain sucrose-6 -ester.
  • the catalyst can be recovered by filtration, and the catalyst has almost no loss and can be recovered basically. In this way, not only does it not need to supplement new catalyst for each production, but also there is no catalyst entrained in the product, which will not affect the subsequent production.
  • reaction steps have adverse effects; and the use of carboxylic acid lower alcohol esters as reaction raw materials can avoid the control restrictions of using carboxylic acid anhydrides in the prior art, and can also avoid the need for the remaining acylating agent to be quenched with water, and the recovery of catalysts and subsequent dehydration process are complicated. and other problems, the overall process is simpler and easier to implement, and the economic benefits are significant in terms of manpower, equipment, and energy consumption; therefore, the method provided by this application can greatly improve production efficiency, realize large-scale operation, and increase the operability of the process; simplify production process, to achieve higher automatic operation; reduce energy consumption, reduce operating costs, and achieve the purpose of large-scale industrial production.
  • the above-mentioned synthetic method of sucrose-6-ester at least comprises the following steps:
  • sucrose is heated and dissolved in a polar aprotic solvent to form a sucrose solution.
  • the application does not limit the dissolving temperature and dissolving method of sucrose, as long as the sucrose can be completely dissolved, for example, the dissolving temperature can be from room temperature to 80° C., and auxiliary stirring means can also be used to accelerate the dissolving of sucrose to obtain a sucrose solution.
  • Catalyst adding step adding any of the above supported catalysts to the sucrose solution to form a reaction suspension.
  • the supported catalyst is solid, it may be but not limited to granular. Therefore, after the catalyst is added to the sucrose solution, a suspension will be formed. Therefore, in the present application, the transesterification of sucrose with lower alcohol esters of carboxylic acids is carried out in a biphasic solution.
  • the transesterification reaction step adding the carboxylic acid lower alcohol ester into the reaction suspension, and performing dehydration and dealcoholization treatment to promote the transesterification reaction to obtain a reaction mixture solution with sucrose-6-ester as the main product.
  • the mixture obtained by the reaction of sucrose and carboxylic acid lower alcohol ester has the main product sucrose-6-ester, by-product water and lower alcohol, as well as a very small amount of sucrose and carboxylic acid lower alcohol ester that have not been completely reacted, so dehydration and dealcoholization can Significantly promotes the transesterification reaction to proceed in the forward direction, improves the conversion rate of sucrose, and improves the yield of sucrose-6-ester.
  • the above-mentioned method for synthesizing sucrose-6-ester further includes: a post-processing step: filtering the reaction mixture to separate the supported catalyst therein to obtain a sucrose-6-ester mother liquor.
  • the supported catalyst since the supported catalyst is solid, after the transesterification reaction is completed, the catalyst can be basically completely separated by simple filtration, and the sucrose- 6-ester mother liquor, further, in order to obtain higher purity sucrose-6-ester solution, the mode of distillation can be taken to steam out the solvent in the sucrose-6-ester mother liquor and the carboxylic acid lower alcohol ester that did not participate in the reaction, namely Sucrose-6-ester can be obtained with higher selectivity.
  • the transesterification reaction step is realized by a kettle-type reactor or a continuous countercurrent reactive distillation column.
  • the transesterification reaction of the present application can be carried out in a conventional kettle-type reactor, or in a continuous countercurrent reactive distillation tower, such as a packed tower, a tray tower, or a thermal spray reactor, etc.
  • a continuous countercurrent reactive distillation tower such as a packed tower, a tray tower, or a thermal spray reactor, etc.
  • the type of polar aprotic solvent is not limited, and can be selected from, but not limited to, dimethyl sulfoxide, acetonitrile, 1,4-dioxane, methyl ethyl ketone, methyl isobutyl Ketones, Nitromethane, Nitroethane, Cyclohexanone, N-Methylpyrrolidone, N-Methylpyrrolidone, N,N-Dimethylacetamide, Hexamethylphosphoramide and N,N-Dimethyl
  • One or more mixtures of formamides are selected from acetonitrile and/or N,N-dimethylformamide.
  • the amount of polar aprotic solvent is not limited, and the volume amount of polar aprotic solvent may be, but not limited to, the ratio of the amount of sucrose to the mass amount of 2 to 50 mg/L. In some embodiments It is 4-20 mg/L, and in other embodiments, it is 6-10 mg/L.
  • the volume dosage of the polar aprotic solvent is less than 2 times the mass dosage of sucrose, the dosage is too small to completely dissolve the sucrose, resulting in a waste of part of the sucrose raw material, and because the sucrose exists in a solid form, it will affect the subsequent reaction process heat transfer and mass transfer in the process; if the mass dosage of the mixed solvent is more than 50 times the mass dosage of sucrose, the dosage will be too much, resulting in waste of raw materials, and at the same time, it will bring great trouble to the subsequent processing of the solvent, and even cause It results in excessive energy consumption, increased production costs, reduced efficiency and environmental pollution.
  • the amount of the catalyst is not limited.
  • the molar amount of the supported catalyst can be but not limited to a ratio of 0.01 to 2 to the molar amount of sucrose.
  • Medium is 0.05 to 0.5.
  • the molar dosage of the supported catalyst is less than 1% of the molar dosage of sucrose in terms of active functional components, the dosage is too small, resulting in a large amount of sucrose remaining in the reactant that cannot participate in the reaction, which is not conducive to the forward progress of the reaction; If the molar amount of the supported catalyst is more than 200% of the molar amount of sucrose, the amount is too much, which may cause diester or polyesterification reaction and produce a large amount of by-products.
  • the type of carboxylic acid lower alcohol ester is not limited, but can be selected from stearic acid, benzoic acid, acetic acid, butyric acid, but not limited to One or more of the methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, tert-butyl and benzyl esters of lauric acid, in In other embodiments, it can be selected from one or more of methyl stearate, ethyl acetate and methyl benzoate.
  • the amount of carboxylic acid lower alcohol ester is not limited, and the volume consumption of carboxylic acid lower alcohol ester is less than 30% of the volume consumption of polar aprotic solvent, in some embodiments, less than 20% %, in other embodiments, less than 15%. If the volume dosage of the carboxylic acid lower alcohol ester is greater than 30% of the volume dosage of the polar aprotic solvent, it will cause unnecessary waste and cannot bring about other beneficial effects.
  • the treatment of dehydration and dealcoholization can adopt the existing technology, such as distillation under reduced pressure, etc., or adopt the method recommended in this example.
  • Polar aprotic solvents or carboxylic acid lower alcohol esters and then dehydration and dealcoholization is achieved by distilling off these additional polar aprotic solvents or carboxylic acid lower alcohol esters, because water or by-product lower alcohols will dissolve in or In the process of evaporating the two in polar aprotic solvent or carboxylic acid lower alcohol ester, water or lower alcohol will be taken out of the reaction system to achieve the purpose of separating water and lower alcohol.
  • the conditions of the dehydration and dealcoholization process are not limited.
  • the distillation conditions may be, but are not limited to, the distillation temperature of 40°C to 100°C, and the distillation pressure of 0.01kPa ⁇ 100 kPa, the distillation time is 1 minute to 12 hours; in other embodiments, the distillation temperature is 60 to 80° C.; the distillation pressure is 0.5 kPa to 90 kPa; and the distillation time is 30 minutes to 4 hours.
  • distillation temperature is less than 40°C, the distillation pressure is greater than 100kPa, and the distillation time is less than 1 minute, the water and lower alcohols generated by the transesterification cannot be completely separated, the distillation speed is too slow, the degree of distillation is not thorough enough, and the separation effect is not good; If the distillation temperature is greater than 100 ° C, the distillation pressure is less than 0.01kPa, and the distillation time is longer than 12 hours, the distillation speed is too fast, the reaction process is not easy to control, and the target product is easily evaporated with the evaporative material, resulting in a drop in yield.
  • sucrose-6-ester synthesized in this application varies according to the type of carboxylic acid lower alcohol ester, and can be used as food additives, chemical products or synthetic intermediates of other reactions, such as sucrose-6-acetate and sucrose-6-acetate. Both 6-benzoates can be used as intermediates in the synthesis of the sweetener sucralose.
  • normalization means that when the mixture of substances is separated and measured by high performance liquid chromatography, the amount of all substances is artificially specified as 100%, and the percentage of each substance in all substances is determined according to the peak area.
  • the determination of the water content uses the Karl Fischer method or the water content measuring instrument, please refer to the prior art, which will not be repeated in each embodiment.
  • the surface of ⁇ -trimethoxysilyldodecylbutyltin oxide with a comparative surface area of 200-450 m 2 /g white carbon black is used for coupling treatment to form a supported catalyst C1.
  • a suspension reaction solution was prepared, heated to 80°C to dissolve into a solution, and then 2m3 of methyl acetate was added to form a suspension solution.
  • the adopted bubble column reactor is used for transesterification, wherein the diameter of the bubble column is 50 cm, the size of the bubble cap is 30 ⁇ 8 mm, the number of plates is 20, the residence time is about 30 minutes, and the reaction temperature is 60 ° C. After the reaction is completed, sucrose-6 -Acetate-based suspension.
  • sucrose-6-acetate-based mixture is directly filtered to recover the supported catalyst to obtain a sucrose-6-acetate mother liquor, and the obtained supported catalyst is washed with a small amount of solvent before reuse.
  • sucrose-6-acetate mother liquor is about 11 m 3 , and it is calculated to contain about 10% of sugar compounds.
  • HPLC analysis the product is as follows:
  • the surface of the white carbon black with a specific surface area of 200-450 m 2 /g is activated with ⁇ -aminotrimethoxysilane, and then the surface of the white carbon black is subjected to coupling treatment with ⁇ -chlorohexyldibutyltin oxide to obtain Supported catalyst C2.
  • the prepared supported catalyst C2 was used as a catalyst, and 70 g of sucrose and 300 mL of DMF were added to the sucrose solvent formed by heating to 80°C.
  • the transesterification reaction was carried out by continuously adding ethyl acetate negative pressure distillation method, and the reaction conditions were: negative pressure 95kPa, reaction temperature 70 °C, continuously replenishing ethyl acetate, until the alcohol content in the ethyl acetate that was distilled out reached 100ppm or less, the ester
  • the exchange reaction takes about 2 hours to obtain a sucrose-6-acetate-based suspension.
  • the obtained suspension is filtered, and the catalyst is recovered to obtain a sucrose-6-acetate mother liquor, and the obtained catalyst is washed with a small amount of solvent before reuse.
  • sucrose-6-acetate mother liquor is calculated to contain about 20% of sugar compounds, and analyzed by HPLC, the product is as follows:
  • Coupling treatment is performed on the surface of alumina with a specific surface area of ⁇ -hexyldibutyltin oxide phosphate of 100-250 m 2 /g to obtain a supported catalyst C3.
  • the prepared supported catalyst C3 was used as a catalyst, and 70 g of sucrose and 300 mL of DMF were added to the sucrose solution formed by heating to 80°C.
  • the reaction conditions are: negative pressure 95kPa, reaction temperature 65 °C, continuously supplement anhydrous DMF, until the alcohol content in the DMF solvent is evaporated below 100ppm to stop the reaction, transesterification The reaction took about 4 hours to obtain a sucrose-6-acetate-based suspension.
  • the above suspension is directly filtered to recover the catalyst to obtain a sucrose-6-acetate mother liquor, and the obtained catalyst is washed with a small amount of solvent before reuse.
  • sucrose-6-acetate mother liquor is calculated to contain about 20% of sugar compounds, and analyzed by HPLC, the product is as follows:
  • the surface of silica with a comparative surface area of 200-450 m 2 /g of ⁇ -mercaptotrimethoxysilane was used for activation treatment, and then coupled with ⁇ -chlorohexyldibutyltin oxide to obtain a supported catalyst C4.
  • the macroporous activated carbon Take the macroporous activated carbon with a specific surface of about 1000m 2 /g, use hydrogen peroxide to activate its surface, modify it into a hydrophilic surface, and use the tetrabutyl titanate method to coat the surface of the activated carbon with a layer of about 10nm.
  • the titanium dioxide was centrifuged, washed and dried for later use.
  • ⁇ -hydroxytrimethoxysilane was used to modify the surface of activated carbon coated with titanium dioxide with hydroxyl groups, and the surface hydroxyl modified macroporous activated carbon was coupled with ⁇ -chlorohexyldibutyltin oxide to obtain a supported catalyst C5.
  • the supported catalyst C5 was used as a catalyst, and 70 g of sucrose and 300 mL of DMF were added to the sucrose solution obtained by heating to 80°C.
  • a negative pressure is used to carry out the transesterification reaction, and the reaction conditions are: negative pressure 95kPa, temperature 75 °C, constantly replenishing anhydrous DMF, until the water content in the DMF solvent is evaporated below 100ppm, and it takes about 4 hours to obtain Suspension with sucrose-6-acetate as the main product.
  • the obtained suspension is calculated to contain about 20% of sugar compounds, add 1:2 cyclohexane, and dropwise add acetic anhydride in a ratio of 1.1:1 at a temperature of ⁇ 10 ° C to carry out acylation reaction, at ⁇ 10 After continuing the reaction for 2 hours at a temperature of °C, the reaction was quenched with 0.05:1 water. Centrifugal separation, washing and recovery of the supported catalyst. Obtain sucrose-6-acetate mother liquor (water content is about 5%, subsequent application must be dehydrated first), through HPLC analysis, the product is as follows:
  • the dehydration is carried out by the method of falling liquid in the packed tower.
  • the diameter of the packed tower is 40 mm, 3 ⁇ 8 glass spring packing, and the packing height is 1 meter, which is equivalent to a 10-stage tray.
  • reaction mixture solution prepared above was placed at the inlet of the top of the packed column, and the negative pressure was kept at 0.5 kPa, and at the same time, cyclohexane vapor (100° C., 4 atm) was fed to the gas inlet of the flask at the bottom of the packed column.
  • the reaction mixture solution is reacted with cyclohexane vapor in countercurrent contact, and the vapor containing cyclohexane, water and DMF in the top distillate of the packed column is condensed and collected, and can be recycled after being dried and anhydrous.
  • a liquid sample was collected in the bottom flask of the packed column and the resulting product was clear, light amber in color.
  • the residence time of the reaction liquid in the gas-liquid exchange reactor is about 1 min.
  • the obtained solution is calculated to contain 10% sucrose, and the obtained solution is pressed into another reaction kettle, and acetic anhydride is added dropwise at a temperature lower than 10 ° C according to the mass ratio of sucrose and acetic anhydride to be 1:1.1.
  • the acylation reaction was quenched with 0.25:1 water after continuing the reaction for 2 hours at a temperature below 10°C.
  • the organotin compound was extracted with 1:1 cyclohexane, the obtained sucrose-6-ethyl ester solution was analyzed by high performance liquid chromatography, and the product was as follows:
  • Examples 1 to 4 and Comparative Example 1 that the use of the catalysts provided in the present application to catalyze the conversion of sucrose and carboxylic acid lower alcohol esters can significantly improve the selectivity of sucrose-6-esters.
  • the highest yield of sucrose-6-acid was 17.93% (90.6% normalized); while the comparative example 1 was only 16.264% (85.6% normalized).
  • sucrose-6-carboxylate prepared by the present application has higher yield, lower probability of side reactions, and higher sucrose-6-carboxylate. The reaction is complete.
  • sucrose-6-ethyl ester it can be seen from the yield of sucrose-6-ethyl ester that some examples in this application can reach 17.93% (90.6% normalized), while the yield of sucrose-6-acetate in Comparative Example 1 is only sucrose-6 -Acetate 7.56% (72.05% normalized), that is to say, the yield of sucrose-6-carboxylate in the present application is significantly higher than that of the prior art; for the same reason, from the content of diacetate and sucrose in the reaction product It can be seen that the probability of occurrence of side reactions in the present application is significantly reduced, and the conversion of sucrose is more complete.
  • the present application provides a supported catalyst.
  • the obtained supported catalyst can catalyze sucrose and carboxyl with high selectivity.
  • the acid lower alcohol ester undergoes a transesterification reaction to obtain sucrose-6-ester.
  • the catalyst can be recovered by filtration, and the catalyst has almost no loss and can be recovered basically. In this way, not only does it not need to supplement new catalyst for each production, but also there is no catalyst entrained in the product, which will not affect the subsequent production.
  • reaction steps have adverse effects; and the use of carboxylic acid lower alcohol esters as reaction raw materials can avoid the control restrictions of using carboxylic acid anhydrides in the prior art, and can also avoid the need for the remaining acylating agent to be quenched with water, and the recovery of catalysts and subsequent dehydration process are complicated. and other problems, the overall process is simpler and easier to implement, and the economic benefits are significant in terms of manpower, equipment, and energy consumption.

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Abstract

本申请提供了负载型催化剂以及蔗糖-6-酯的合成方法，其中，负载型催化剂用于催化蔗糖与羧酸酯的酯交换反应，该催化剂包括活性功能组分和无机载体；其中，活性功能组分为式(1)表示的化合物，其中，n为大于等于2的自然数；R为与所述无机载体的表面连接的原子；R1、R2和R3中的一个或两个为烃基，其余分别独立地选自氧原子、羟基、烃氧基和乙酰氧基中的任意一个。本申请的催化剂能够高选择性地催化蔗糖与羧酸低级醇酯进行酯交换反应，获得蔗糖-6-酯，反应完后通过过滤即可回收催化剂，催化剂几乎没有损失，且避免了使用管制物品羧酸酐。

Description

负载型催化剂以及蔗糖-6-酯的合成方法 技术领域
本发明属于精细化工技术领域，具体涉及负载型催化剂以及蔗糖-6-酯的合成方法。
发明背景
蔗糖-6-羧酸酯，即蔗糖-6-酯是重要的化工产品和中间体(章朝晖，广西南宁木薯技术开发中心，蔗糖化学衍生物[J].精细石油化工进展，2000，1(6):8-13.)，在工业上应用广泛，比如蔗糖-6-脂肪酸酯，是一类多元醇型非离子表面活性剂，具有优良的乳化性能，广泛用于食品、医药、化妆品等工业；又比如蔗糖松香酸酯也是一种优良的乳化剂；蔗糖-6-乙酸酯不仅是合成蔗糖-6-脂肪酸酯和蔗糖乙酸异丁酸酯的原料，也是合成三氯蔗糖的重要中间体(吴红英,浙江大学化学工程与生物工程学院,吴红英,等.甜味剂三氯蔗糖合成法的最新进展[J].化工进展,2016,35(1):227-238.)。因此，蔗糖-6-酯的合成具有重要的现实价值。
目前应用最广泛的蔗糖-6-酯的合成技术为单基团保护法：有机锡化合物与蔗糖在极性溶剂中，脱水后形成蔗糖有机锡酯溶液，随后蔗糖有机锡酯溶液与酰化剂羧酸酐发生高选择性的反应得到蔗糖-6-羧酸酯。
单基团保护法工艺条件温和、高选择性、收率高、催化剂循环、三废少，因而成为当前生产蔗糖-6-酯主要的工艺。但单基团保护法仍然有很多不足之处，如该方法需要分成两步反应工艺，第一步形成蔗糖有机锡酯，第二步降温后与羧酸酐反应生成蔗糖-6-羧酸酯，后续需要加水淬灭剩余的羧酸酐，通过溶剂萃取回收有机锡后再浓缩定容才能进行下一步反应或应用，在这个过程中，有机锡催化剂分离困难，需要加水淬灭、萃取、回收套用，并且由于有机锡化合物萃取回收时在轻相有分布，很难完全回收，导致反应过程中每次会有1～5％的催化剂随着物料夹带等原因损失掉，不仅每次生产必须补充新的有机锡催化剂，而被夹带走的催化剂还会对后续的氯代反应产生不好的影响；整体工艺操作、人工能耗和生产成本是比较大的问题；再者由于羧酸酐，尤其是乙酸酐是属于管制品，因而采用此法制备蔗糖-6-乙酸酯会受到诸多管制。
需要说明的是，这里的陈述仅提供与本申请有关的背景信息，而不必然地构成 现有技术。
发明内容
鉴于上述问题，提出了本申请以便提供一种克服上述问题或者至少部分地解决上述问题的负载型催化剂以及蔗糖-6-酯的合成方法。
根据本申请的一方面，提供了一种负载型催化剂，用于催化蔗糖与羧酸酯的酯交换反应，该催化剂包括活性功能组分和无机载体；其中，活性功能组分为式(1)表示的化合物：
式(1)：
Figure PCTCN2021082598-appb-000001
其中，n为大于等于2的自然数；R为与无机载体的表面连接的原子；R 1、R 2和R 3中的一个或两个为烃基，其余分别独立地选自氧原子、羟基、烃氧基和乙酰氧基中的任意一个。
可选的，在上述的负载型催化剂中，R选自硅、氧、氮、硫和磷原子中的任意一个。
可选的，在上述的负载型催化剂中，烃基为烷基、环烷基、芳基或芳烷基，优选为烷基，在一些实施例中，为正丁基。
可选的，在上述的负载型催化剂中，烃氧基选自烷氧基或苯氧基，在一些实施例中，为甲氧基、乙氧基、正丙氧基、正丁氧基、正戊氧基或正己氧基，在另一些实施例中，为甲氧基。
可选的，在上述的负载型催化剂中，无机载体选自二氧化硅、二氧化钛、活性炭和氧化铝中的一种或多种组成的混合物，在一些实施例中，为二氧化硅。
可选的，在上述的负载型催化剂中，无机载体的比表面积大于10m 2/g，在一些实施例中，大于30m 2/g，在另一些实施例中，大于100m 2/g。
可选的，在上述的负载型催化剂中活性功能组分占无机载体重量的1ppm～40％，优选为1000ppm～10％。
根据本申请的另一方面，提供了一种蔗糖-6-酯的合成方法，该方法采用上述 任一的负载型催化剂催化蔗糖与羧酸低级醇酯进行酯交换反应，以获得蔗糖-6-酯。
可选的，上述的蔗糖-6-酯的合成方法包括：
蔗糖溶解步骤：将蔗糖加热溶解于极性非质子溶剂中，形成蔗糖溶液；
催化剂加入步骤：将上述任一的负载型催化剂加入蔗糖溶液，形成反应悬浮液；以及
酯交换反应步骤：将羧酸低级醇酯加入反应悬浮液中，并进行脱水脱醇处理，以促进酯交换反应，得到以蔗糖-6-酯为主产物的反应混合溶液。
可选的，上述的蔗糖-6-酯的合成方法还包括：
后处理步骤：将反应混合溶液进行过滤，以分离其中的负载型催化剂，得到蔗糖-6-酯母液。
可选的，在上述的蔗糖-6-酯的合成方法中，羧酸低级醇酯选自硬脂酸、苯甲酸、乙酸、丁酸、月桂酸的甲基酯、乙基酯、丙基酯、异丙基酯、正丁基酯、异丁基酯、叔丁基酯和苯甲基酯中的一种或几种，在一些实施例中，选自硬脂酸甲基酯、乙酸乙酯和苯甲酸甲酯的一种或几种。
可选的，在上述的蔗糖-6-酯的合成方法中，极性非质子溶剂选自二甲亚砜、乙腈、1,4-二氧六环、甲乙酮、甲基异丁基酮、硝基甲烷、硝基乙烷、环己酮、N-甲基吡咯烷酮、N-甲基吡咯烷酮、N,N-二甲基乙酰胺、六甲基磷酰胺和N,N-二甲基甲酰胺中的一种或几种，在一些实施例中，选自乙腈和/或N,N-二甲基甲酰胺。
可选的，在上述的蔗糖-6-酯的合成方法中，极性非质子溶剂体积用量与所述蔗糖质量用量的比为2～50mg/L，在一些实施例中为4～20mg/L，在另一些实施例中为6～10mg/L；
以活性功能组分计，负载型催化剂的摩尔用量与蔗糖的摩尔用量的比为0.01～2，在一些实施例中为0.05～0.5；
羧酸低级醇酯的体积用量小于极性非质子溶剂的体积用量的30％，在一些实施例中，小于20％，在另一些实施例中，小于15％。
可选的，在上述的蔗糖-6-酯的合成方法中，脱水脱醇处理是通过蒸馏出向所述反应悬浮液中额外添加的极性非质子溶剂或羧酸低级醇酯实现的。
可选的，在上述的蔗糖-6-酯的合成方法中，蒸馏的条件为：蒸馏温度为40～100℃，在一些实施例中为60～80℃；蒸馏压力0.01kPa～100kPa，在一些实施例中为0.5kPa～90kPa；蒸馏时间为1分钟～12小时，在一些实施例中为30分钟～4 小时。
可选的，在上述的蔗糖-6-酯的合成方法中，酯交换反应步骤通过釜式反应釜或连续逆流反应蒸馏塔实现。
综上所述，本申请提供了一种负载型催化剂，通过将式(1)表示的有机单锡活性组分化合物负载在无机载体上，得到的负载型催化剂能够高选择性的催化蔗糖与羧酸低级醇酯进行酯交换反应，获得蔗糖-6-酯。反应完后通过过滤即可回收催化剂，催化剂几乎没有损失，基本能够完全回收，这样，不仅每次生产不须额外补充新的催化剂，而且在产物中没有夹带走的催化剂，不会对后续的反应步骤产生不良影响；而使用羧酸低级醇酯作为反应原料，可以避开现有技术中使用羧酸酐的管控限制，也能避免剩余酰化剂需要加水淬灭后回收催化剂和后续脱水过程复杂等问题，整体工艺更加简单、易实现，在人力、设备、耗能方面经济效益显著。
上述说明仅是本申请技术方案的概述，为了能够更清楚了解本申请的技术手段，而可依照说明书的内容予以实施，并且为了让本申请的上述和其它目的、特征和优点能够更明显易懂，以下特举本申请的具体实施方式。
实施本发明的方式
下面将参照附图更详细地描述本申请的示例性实施例。虽然附图中显示了本申请的示例性实施例，然而应当理解，可以以各种形式实现本申请而不应被这里阐述的实施例所限制。相反，提供这些实施例是为了能够更透彻地理解本申请，并且能够将本申请的范围完整的传达给本领域的技术人员。
本申请的构思在于，现有技术中，针对现有技术中采用单基团保护法生产蔗糖-6-酯存在着工艺负载，液态的有机锡催化剂回收困难，对后续的生成步骤造成不良影响，且原材料羧酸酐管控严格的现状，提出了一种固态的负载型催化剂，通过将单锡有机活性组分负载在无机载体上，使得获得的催化剂能够高效地催化蔗糖与羧酸低级醇酯进行酯交换反应，获得蔗糖-6-酯，不仅催化剂回收容易，且绕过了必须使用羧酸酐的环节。
在本申请的一些实施例中，提供了一种负载型催化剂，用于催化蔗糖与羧酸酯的酯交换反应，该催化剂包括活性功能组分和无机载体；其中，活性功能组分为式(1)表示的化合物：
式(1)：
Figure PCTCN2021082598-appb-000002
其中，n为大于等于2的自然数；R为与无机载体的表面连接的原子；R 1、R 2和R 3中的一个或两个为烃基，其余分别独立地选自氧原子、羟基、烃氧基和乙酰氧基中的任意一个。
具体的，在本申请的一些实施例中，在上述的负载型催化剂中，R是与无机载体的表面连接的原子，可以但不限于选自硅、氧、氮、硫和磷原子中的任意一个。
在本申请的一些实施例中，无机载体可以但不限于选自二氧化硅、二氧化钛、活性炭和氧化铝中的一种或多种组成的混合物，在一些实施例中，为二氧化硅。
在无机载体的表面通常存在着可以形成共价键的原子或基团，如二氧化硅表面的羟基基团或者羟基中的氢原子断裂后留下的氧原子，这些原子或基团能够与R表示的原子形成共价键，从而使活性功能组分负载在无机载体的表面，或者无机载体的孔道内。需要说明的是，有机锡活性功能组分与无机载体的结合方式并不局限于上述的共价键形式，上述仅作为说明示例，以便本领域技术人员更容易理解本申请。
因此，凡是通过形成化学键的方式将式(1)表示的有机锡活性功能组分固定在无机载体表面即可制备上述任一的负载型催化剂，本申请对该负载型催化剂的制备方法不做限定，本领域技术人员参照现有技术即可。例如，在氧化硅表面形成硅偶联原子的有机锡催化剂，就是将具有氧化硅表面的载体(可以是氧化硅，也可以是氧化硅包覆的其他载体)使用溶剂形成悬浮液，然后将有机硅氧烷或氯代硅烷结构的有机锡活性功能组分加入到悬浮液中，保温反应，使得有机硅氧烷或氯代硅烷结构与氧化硅表面形成共价的链接，就得到了负载了有机锡活性能够组分的催化剂。再例如，在氨基化表面形成氮偶联原子的负载型催化剂，就是将具有氨基化表面的载体悬浮在溶剂中，然后将卤原子取代的有机锡活性能够组分加入到悬浮液中，保温反应，使得氨基和卤代烃结构反应形成共价的链接，就得到了负载了有机锡活性能够组分的催化剂。
具体的，在本申请的一些实施例中，在上述的负载型催化剂中，烃基可以为但不限于烷基、环烷基、芳基或芳烷基，在一些实施例中为烷基，在另一些实施例中，为正丁基。
其中，烷基可以为但不限于甲基、乙基、丙基、异丙基、丁基、异丁基、叔丁基、戊基、异戊基、新戊基、正已基、支链已基、正庚烷、支链庚烷、正辛烷、支链辛烷。
环烷基可以为但不限于环丙基、环丁基、环戊基、环已基、一取代的环丙基，如甲基环丙基、乙基环丙基等；二取代的环丙基，如二甲基环丙基、甲基乙基环丙基等；一取代的环丁基、二取代的环丁基、三取代的环丁基，如三甲基环丁基；一取代的环戊基、二取代的环戊基、三取代的环戊基，如甲基乙基环戊基；一取代的环已基、二取代的环已基，如甲基环已基。环烷基还可以为但不限于环丙烯基、环丁烯基、环戊烯基、环已烯基、环丙炔基、环丁炔基、环戊炔基、环已炔基、一取代环丙烯基、二取代环丙烯基，如甲基环丙烯基；一取代环丁烯基、二取代的环丁烯基、三取代的环丁烯基，如二甲基环丁烯基；一取代的环戊烯基、二取代的环戊烯基、三取代的环戊烯基，如甲基乙基环戊烯基；一取代的环已烯基、二取代的环已烯基，如甲基环已烯基；一取代环丙炔基、二取代环丙炔基，如二甲基环丙炔基；一取代环丁炔基、二取代的环丁炔基、三取代的环丁炔基，如乙基环丁炔基；一取代的环戊炔基、二取代的环戊炔基、三取代的环戊炔基，如甲基乙基环戊炔基；一取代的环已炔基、二取代的环已炔基，如甲基环已炔基。
芳基可以为但不限于苯基、一取代苯基、二取代苯基、三取代苯基、四取代苯基、五取代苯基、六取代苯基，如甲基乙基苯基、苯并环丁基、苯并环戊基等。
芳烷基可以为但不限于一取代苯基、二取代苯基、三取代苯基、四取代苯基、五取代苯基、六取代苯基，如甲基乙基苯基、苯并环丁基、苯并环戊基等。
具体的，在本申请的一些实施例中，在上述的负载型催化剂中，烃氧基可以但不限于选自烷氧基或苯氧基，其中，烷氧基可以为但不限于甲氧基、乙氧基、正丙氧基、正丁氧基、正戊氧基或正己氧基，在另一些实施例中，为甲氧基。
在本申请的一些实施例中，在上述的负载型催化剂中，无机载体的比表面积大于10m 2/g，在一些实施例中，大于30m 2/g，在另一些实施例中，大于100m 2/g。
比表面积是指单位质量物料所具有的总面积，在本申请中，无机载体的比表面积可采用现有技术中的任意一种测量，如连续流动法(即动态法)和静态容量法。在无机载体在作为催化剂使用时，通常比表面积大能够获得比较好的技术效果，因为能够提供更多可以与R原子连接的位点，在本申请中，无机载体的比表面积可以但不限于大于10m 2/g，在一些实施例中，大于30m 2/g，在另一些实施例中，大于100m 2/g。
在本申请的一些实施例中，在上述的负载型催化剂中，活性功能组分占无机载体重量的1ppm～40％，在另一些实施例中为1000ppm～10％。
通过大量实验，本申请获得了活性功能组分与无机载体的较佳占比，在一些实施例中，活性功能组分占无机载体重量的1ppm～40％，在另一些实施例中为1000ppm～10％。若活性功能组分占无机载体重量的小于1ppm，则活性功能组分的含量过少，不能够有效催化蔗糖与羧酸低级醇酯进行酯交换反应，一方面使得反应选择性低，生成大量除6位取代产物以外的酯类，另一方面使得反应产率低下；若活性功能组分占无机载体重量的小于40％，则活性功能组分的含量过多，无机载体不能提供足够的活性位点供活性功能组分负载，使得在催化剂制备的过程中，大量的活性功能组分不能有效负载在催化剂表面，造成活性功能组分的浪费，且不能带来其他有益效果。
根据本申请的一些实施例，本申请还提供了一种蔗糖-6-酯的合成方法，该方法采用上述任一的负载型催化剂催化蔗糖与羧酸低级醇酯进行酯交换反应，以获得蔗糖-6-酯。
在现有技术中，通常采用双锡或多锡有机氧化物，如氧化二(烃基)锡、1,3-二(烃氧基)-1,1,3,3-四-(烃基)二锡氧烷、1,3-二酰氧基-1,1,3,3-四-(烃基)二锡氧烷、1-酰氧基-1,1,3,3-四-(烃基)二锡氧烷和二酰氧基二烃基锡等，与蔗糖生成有机锡酯溶液，再进一步与酸酐反应生成蔗糖-6-酯，由于二锡的结构，有机锡化物在萃取回收时，在轻相有分布，很难完全回收，导致反应过程中每次会有1～5％的催化剂随着物料夹带等原因损失掉，不仅每次生产必须补充新的有机锡化物，而且被夹带走的催化剂还会对后续的氯代反应产生不好的影响。
本申请通过将式(1)表示的有机单锡活性组分化合物负载在无机载体上，得到的负载型催化剂能够高选择性地催化蔗糖与羧酸低级醇酯进行酯交换反应，获得蔗糖-6-酯。反应完后通过过滤即可回收催化剂，催化剂几乎没有损失，基本能够完全回收，这样，不仅每次生产不须额外补充新的催化剂，而且在产物中没有夹带走的催化剂，不会对后续的反应步骤产生不良影响；而使用羧酸低级醇酯作为反应原料，可以避开现有技术中使用羧酸酐的管控限制，也能避免剩余酰化剂需要加水淬灭后回收催化剂和后续脱水过程复杂等问题，整体工艺更加简单、易实现，在人力、设备、耗能方面经济效益显著；因此，本申请提供的方法可以大大提高生产效率，实现规模化运行，增加工艺的可操作性；简化生产工艺，实现更高的自动化操作；降低能耗，降低运行成本，实现了大规模的工业化生产的目的。
根据本申请的一些实施例，上述的蔗糖-6-酯的合成方法至少包括以下步骤：
蔗糖溶解步骤：将蔗糖加热溶解于极性非质子溶剂中，形成蔗糖溶液。
本申请对于蔗糖的溶解温度和溶解方法不做限制，凡是能够使蔗糖完全溶解即可，如溶解温度可以为室温～80℃，还可以辅助搅拌手段加速蔗糖的溶解，得到蔗糖溶液。
催化剂加入步骤：将上述任一的负载型催化剂加入蔗糖溶液，形成反应悬浮液。
将上述任一的负载型催化剂加入蔗糖溶液中，由于负载型催化剂为固体，具体可以但不限于颗粒状，因此催化剂加入蔗糖溶液后，会形成悬浮液。因此，在本申请中，蔗糖与羧酸低级醇酯的酯交换反应是在两相溶液中进行。
以及酯交换反应步骤：将羧酸低级醇酯加入反应悬浮液中，并进行脱水脱醇处理，以促进酯交换反应，得到以蔗糖-6-酯为主产物的反应混合溶液。
蔗糖与羧酸低级醇酯反应得到的混合物有主产物蔗糖-6-酯、副产物水和低级醇，还有未能彻底反应的极少量的蔗糖和羧酸低级醇酯，因此脱水脱醇能够显著促进酯交换反应向正向进行，提高蔗糖的转化率，提高蔗糖-6-酯的收率。
在本申请的一些实施例中，上述的蔗糖-6-酯的合成方法还包括：后处理步骤：将反应混合溶液进行过滤，以分离其中的负载型催化剂，得到蔗糖-6-酯母液。
也就是说在本申请中，由于负载型催化剂为固体，当酯交换反应进行完毕后，可以通过简单的过滤即可基本完全过滤分离出催化剂，即可得到能够直接用于下一步反应的蔗糖-6-酯母液，进一步的，为了得到更高纯度的蔗糖-6-酯溶液，可以采取蒸馏的方式，蒸出蔗糖-6-酯母液中的溶剂和未参加反应的羧酸低级醇酯，即可更高选择性地得到蔗糖-6-酯。
在本申请的一些实施例中，在上述的蔗糖-6-酯的合成方法中，酯交换反应步骤通过釜式反应釜或连续逆流反应蒸馏塔实现。
本申请的酯交换反应可以在常规的釜式反应釜，也可以在连续逆流反应蒸馏塔，如填料塔、板式塔，再比如热喷雾反应器等，上述仪器设备及其操作均可参考现有技术，不再赘述。
极性非质子溶剂的种类和用量
在本申请的一些实施例中，对极性非质子溶剂的种类不做限制，可以但不限于选自二甲亚砜、乙腈、1,4-二氧六环、甲乙酮、甲基异丁基酮、硝基甲烷、硝基乙烷、环己酮、N-甲基吡咯烷酮、N-甲基吡咯烷酮、N,N-二甲基乙酰胺、六甲基磷酰胺和N,N-二甲基甲酰胺中的一种或几种的混合物，在另一些实施例中，选自乙 腈和/或N,N-二甲基甲酰胺。
在本申请的一些实施例中，对极性非质子溶剂的用量不做限制，极性非质子溶剂体积用量可以但不限于与蔗糖质量用量的比为2～50mg/L，在一些实施例中为4～20mg/L，在另一些实施例中为6～10mg/L。
如果极性非质子溶剂的体积用量少于蔗糖的质量用量的2倍，则用量过少，不能完全溶解蔗糖，造成一部分蔗糖原料的浪费，且由于蔗糖以固体形式存在，会影响后续反应过程中的传热和传质；如果混合溶剂的质量用量多于蔗糖的质量用量的50倍，则用量过多，造成原料浪费的同时，对后续的溶剂的处理带来很大的麻烦，甚至会造成能耗过大、生产成本提高、效率降低和环境的污染。
催化剂的用量
在本申请的一些实施例中，对催化剂的用量不做限制，以活性功能组分计，负载型催化剂的摩尔用量可以但不限于与蔗糖的摩尔用量的比为0.01～2，在一些实施例中为0.05～0.5。
如果以活性功能组分计，负载型催化剂的摩尔用量少于蔗糖的摩尔用量的1％，则用量过少，造成反应物中剩余大量的蔗糖不能参加反应，不利于反应的正向进行；如果负载型催化剂的摩尔用量多于蔗糖的摩尔用量的200％，则用量过多，可能造成发生双酯或多酯化反应，产生大量的副产物。
羧酸低级醇酯的种类和用量
在本申请的一些实施例中，在上述的蔗糖-6-酯的合成方法中，对羧酸低级醇酯的种类不做限制，可以但不限于选自硬脂酸、苯甲酸、乙酸、丁酸、月桂酸的甲基酯、乙基酯、丙基酯、异丙基酯、正丁基酯、异丁基酯、叔丁基酯和苯甲基酯中的一种或几种，在另一些实施例中，可选自硬脂酸甲基酯、乙酸乙酯和苯甲酸甲酯的一种或几种。
在本申请的一些实施例中，对羧酸低级醇酯的用量不做限制，羧酸低级醇酯的体积用量小于极性非质子溶剂的体积用量的30％，在一些实施例中，小于20％，在另一些实施例中，小于15％。如果羧酸低级醇酯的体积用量大于极性非质子溶剂的体积用量的30％，会造成不必要的浪费，并不能带来其他有益效果。
脱水脱醇的处理
在本申请中，脱水脱醇的处理可以采用现有技术，如减压蒸馏等，也可采用本实施例推荐的方法，在本申请的酯交换反应过程中，向反应混合物中额外增加过量的极性非质子溶剂或羧酸低级醇酯，然后通过蒸馏出这些额外添加的极性非质子溶 剂或羧酸低级醇酯来实现脱水脱醇的目的，因为水或者副产物低级醇会溶于或者裹挟于极性非质子溶剂或羧酸低级醇酯中，将这二者蒸发出的过程中，就会将水或者低级醇带离反应体系，以达到分离水和低级醇的目的。
在本申请的一些实施例中，对脱水脱醇过程的条件不做限制，在另一些实施例中，蒸馏的条件可以但不限于为：蒸馏温度为40℃～100℃，蒸馏压力0.01kPa～100kPa，蒸馏时间为1分钟～12小时；在另一些实施例中，蒸馏温度为60～80℃；蒸馏压力为0.5kPa～90kPa；蒸馏时间为30分钟～4小时。
若蒸馏温度小于40℃，蒸馏压力大于100kPa，蒸馏时间短于1分钟，不能够将酯交换反应生成的水和低级醇彻底地分离，蒸馏速度过慢，蒸馏程度不够彻底，分离效果不好；若蒸馏温度大于100℃，蒸馏压力小于0.01kPa，蒸馏时间为长于12小时，则蒸馏速度过快，反应过程不好控制，并且目标产物容易随着蒸发物被蒸出，导致产率下降。
本申请合成得到的蔗糖-6-酯根据羧酸低级醇酯的种类不同而不同，均可以用作食品添加剂、化工产品或其他反应的合成中间体，如蔗糖-6-乙酸酯和蔗糖-6-苯甲酸酯均可以用作合成甜味剂三氯蔗糖的中间体。
本申请中涉及的测试方法
本申请中各实施例和对比例中各物质的含量或纯度，包括蔗糖、蔗糖-6-酯等采用高效液相色谱(High Performance Liquid Chromatography，HPLC)方法在下述条件下测得，在各个实施例中不再赘述。
高效液相色谱的分析测定条件：日本岛津高效液相色谱仪，配RID-10A示差折光检测，LC-10ADVP高压泵，CTO-10ASVP恒温箱；色谱柱：Agilent XDB C18柱(250mm×4.6mm，5μm)；流动相：甲醇-0.125％磷酸氢二钾水溶液(4：6)；柱温：30℃；流量：1.0mL/min。其中，需要甲醇(色谱纯)、磷酸氢二钾(分析纯)、超纯水、各标准物质，外标法测量含量。
其中，“归一化”是指在采用高效液相色谱法的混合物质进行分离测定时，人为规定所有物质的量为100％，按照谱峰面积确定各物质占所有物质的百分比。
水分的测试方法
水含量的测定使用卡尔费休法或者采用水含量测定仪，请参考现有技术，在各个实施例中不再赘述。
实施例1
用γ-三甲氧硅基十二烷基丁基氧化锡对比表面积为200～450m 2/g白炭黑的表面进行偶联处理，形成负载型催化剂C1。
按照蔗糖1000Kg，负载型催化剂C1 2000Kg和DMF10m 3的比例配置成悬浮反应液，加热至80℃溶解成溶液，再添加乙酸甲酯2m 3形成悬浮溶液。
采用的泡罩塔反应器进行酯交换反应，其中泡罩塔直径50厘米，泡罩尺寸30×8mm，板数20，停留时间约30分钟，反应温度为60℃，反应完毕得到以蔗糖-6-乙酸酯为主的悬浊液。
将上述的蔗糖-6-乙酸酯为主的混合物直接过滤回收负载型催化剂，得到蔗糖-6-乙酸酯母液，得到的负载型催化剂采用少量溶剂洗涤后待复用。
获得的蔗糖-6-乙酸酯母液约为11m 3，经计算约含有10％的糖化合物，通过HPLC分析，产物如下：
a.蔗糖-6-乙酸酯10.33％(89.9％归一化)；
b.二乙酸酯0.99％(8.7％归一化)；
c.蔗糖0.04％(0.23％归一化)。
实施例2
用γ-氨基三甲氧基硅烷将比表面积为200～450m 2/g的白炭黑的表面进行活化处理，再用γ-氯己基二丁基氧化锡对白炭黑的表面进行偶联处理，得到负载型催化剂C2。
将制备的负载型催化剂C2作为催化剂，加入蔗糖70g和DMF300mL，加热至80℃形成的蔗糖溶剂中。
采用连续添加乙酸乙酯负压蒸馏法进行酯交换反应，反应条件为：负压95kPa，反应温度70℃，不断补充乙酸乙酯，至蒸出乙酸乙酯中含醇含量达到100ppm以下停止，酯交换反应约需要2小时，得到以蔗糖-6-乙酸酯为主的悬浊液。
过滤得到的悬浊液，并回收催化剂，得到蔗糖-6-乙酸酯母液，将得到的催化剂使用少量溶剂洗涤后待复用。
得到的蔗糖-6-乙酸酯母液内经计算约含有20％的糖化合物，通过HPLC分析，产物如下：
a.蔗糖-6-乙酸酯17.5％(89.6％归一化)；
b.二乙酸酯1.68％(8.3％归一化)；
c.蔗糖0.05％(0.25％归一化)。
实施例3
用γ-磷酸己基二丁基氧化锡对比表面积为100～250m 2/g的氧化铝的表面进行偶联处理，得到负载型催化剂C3。
将制备的负载型催化剂C3作为催化剂，加入蔗糖70g和DMF300mL，加热至80℃形成的蔗糖溶液中。
采用连续添加硬脂酸乙酯负压进行酯交换反应，反应条件为：负压95kPa，反应温度65℃，不断补充无水DMF，至蒸出DMF溶剂中含醇量100ppm以下停止反应，酯交换反应大约需要4小时，得到以蔗糖-6-乙酸酯为主的悬浊液。
将上述悬浮液直接过滤回收催化剂并得到蔗糖-6-乙酸酯母液，将得到的催化剂使用少量溶剂洗涤后待复用。
得到的蔗糖-6-乙酸酯母液内经计算约含有20％的糖化合物，通过HPLC分析，产物如下：
a.蔗糖-6-硬脂酸17.93％(90.6％归一化)；
b.二硬脂酸酯1.52％(7.7％归一化)；
c.蔗糖0.04％(0.23％归一化)。
实施例4
先取γ-巯基三甲氧基硅烷对比表面积200～450m 2/g的白炭黑的表面进行活化处理，再用γ-氯己基二丁基氧化锡进行偶联，得到负载型催化剂C4。
在一个1000mL的四口圆底烧瓶中，装有机械搅拌，温度计和带有分水器的冷凝管中，加入150g蔗糖和600mL的DMF，加热至90℃以使蔗糖完全溶解，冷至60℃加入120g负载型催化剂C4和150mL月桂酸甲酯，加热至90℃，负压蒸馏，以促进酯交换反应，约5个小时反应结束，冷至室温过滤回收催化剂，得到为蔗糖-6-月桂酸酯母液，通过HPLC分析，产物如下：
a.蔗糖-6-月桂酸酯19.05％(86.5％归一化)；
b.二月桂酸酯2.43％(11.0％归一化)；
c.蔗糖0.09％(0.36％归一化)。
对比例1
取比表面在1000m 2/g左右的大孔活性炭，采用双氧水对其表面进行活化处理， 将其改性为亲水性表面，使用钛酸四丁酯法在活性炭表面包覆一层约10nm后的二氧化钛，离心洗涤干燥后备用。取γ-羟基三甲氧基硅烷在包覆二氧化钛的活性炭表面进行羟基修饰，表面羟基修饰后的大孔活性炭用γ-氯己基二丁基氧化锡偶联处理，得到负载型催化剂C5。
将负载型催化剂C5作为催化剂，加入蔗糖70g和DMF300mL，加热至80℃得到的蔗糖溶液中。
在常规反应釜中，采用负压进行酯交换反应，反应条件为：负压95kPa，温度75℃，不断补充无水DMF，至蒸出DMF溶剂中含水量100ppm以下停止，约需要4小时，得到以蔗糖-6-乙酸酯为主要产物的悬浊液。
得到的悬浊液经计算约含有20％的糖化合物，加入1：2的环己烷，在<10℃的温度条件下按照1.1：1的比例滴加乙酸酐进行酰化反应，在<10℃的温度下继续反应2小时之后，用0.05：1的水进行淬灭反应。离心分离，洗涤回收负载催化剂。得到蔗糖-6-乙酸酯母液(含水量约5％，后续应用必须先脱水)，通过HPLC分析，产物如下：
a.蔗糖-6-乙酸酯16.264％(85.6％归一化)；
b.二乙酸酯2.337％(12.3％归一化)；
c.蔗糖0.06％(0.31％归一化)。
对比例2
按照蔗糖、有机锡酯促进剂(1,1,3-二乙酰氧基-1,1,3,3-四丁基二锡氧烷)、非质子极性溶剂(DMF)的质量比例为1：2：10配置成300公斤反应液，加热90℃溶解成反应混合溶液。
采用填料塔降液的方式进行脱水，填料塔直径40毫米，3×8玻璃弹簧填料，填料高度1米，相当于10级塔板。
将上述制备的反应混合溶液在填料塔的顶部的入口，保持负压在0.5kPa，同时，将环己烷蒸气(100℃，4atm)进料至填料塔底部烧瓶气体入口。反应混合溶液与环己烷蒸气逆流接触反应，填料塔的顶部馏出物含有环己烷、水和DMF的蒸气经冷凝并且收集，经过干燥无水处理后方可循环使用。
填料塔底部烧瓶收集液体样品，所得产物为透明、浅琥珀色。反应液在气液交换反应器内停留时间约1min。
得到的溶液经计算含有10％的蔗糖，将得到的溶液压到另一个反应釜，在低于 10℃的温度条件下按照蔗糖与乙酸酐的质量比为1：1.1的比例滴加乙酸酐进行酰化反应，在低于10℃的温度下继续反应2小时之后，用0.25：1的水进行淬灭反应。用1：1的环己烷萃取有机锡化合物，得到的蔗糖-6-乙酯溶液通过高效液相色谱法分析，产物如下：
a.蔗糖-6-乙酸酯7.56％(72.05％归一化)；
b.二乙酸酯0.46％(4.36％归一化)；
c.蔗糖2.39％(22.76％归一化)。
从实施例1～4和对比例1中可以看出，采用本申请提供的催化剂催化蔗糖与羧酸低级醇酯的能够显著提升蔗糖-6-酯的选择性，在实施例1～4中，蔗糖-6-酸的最高收益可达17.93％(90.6％归一化)；而对比例1仅为16.264％(85.6％归一化)。
从实施例1～4和对比例2中可以看出，与对比例2采用的单基团保护法相比，本申请制备的蔗糖-6-羧酸酯的产量高、副反应发生概率低、蔗糖反应完全。以蔗糖-6-乙酯产量可以看出，本申请中一些实施例可达到17.93％(90.6％归一化)，而对比例1中蔗糖-6-乙酸酯中的产量仅为蔗糖-6-乙酸酯7.56％(72.05％归一化)，也就是说本申请蔗糖-6-羧酸酯的产量显著高于现有技术；同理，由反应产物中的二乙酸酯、蔗糖含量可以看出，本申请中副反应发生概率显著降低，蔗糖转化得更加彻底。
综上所述，本申请提供了一种负载型催化剂，通过将式(1)表示的有机单锡活性组分化合物负载在无机载体上，得到的负载型催化剂能够高选择性的催化蔗糖与羧酸低级醇酯进行酯交换反应，获得蔗糖-6-酯。反应完后通过过滤即可回收催化剂，催化剂几乎没有损失，基本能够完全回收，这样，不仅每次生产不须额外补充新的催化剂，而且在产物中没有夹带走的催化剂，不会对后续的反应步骤产生不良影响；而使用羧酸低级醇酯作为反应原料，可以避开现有技术中使用羧酸酐的管控限制，也能避免剩余酰化剂需要加水淬灭后回收催化剂和后续脱水过程复杂等问题，整体工艺更加简单、易实现，在人力、设备、耗能方面经济效益显著。
以上所述，仅为本申请的具体实施方式，在本申请的上述教导下，本领域技术人员可以在上述实施例的基础上进行其他的改进或变形。本领域技术人员应该明白，上述的具体描述只是更好的解释本申请的目的，本申请的保护范围应以权利要求的保护范围为准。
此外，本领域的技术人员能够理解，尽管在此所述的一些实施例包括其它实施例中所包括的某些特征而不是其它特征，但是不同实施例的特征的组合意味着处于本申请的范围之内并且形成不同的实施例。例如，在下面的权利要求书中，所要求保护的实施例的任意之一都可以以任意的组合方式来使用。

Claims (16)

  1. 一种负载型催化剂，用于催化蔗糖与羧酸酯的酯交换反应，其特征在于，所述催化剂包括活性功能组分和无机载体；其中，所述活性功能组分为式(1)表示的化合物：
    式(1)：
    Figure PCTCN2021082598-appb-100001
    其中，n为大于等于2的自然数；R为与所述无机载体的表面连接的原子；R 1、R 2和R 3中的一个或两个为烃基，其余分别独立地选自氧原子、羟基、烃氧基和乙酰氧基中的任意一个。
  2. 根据权利要求1所述的负载型催化剂，其特征在于，所述R选自硅、氧、氮、硫和磷原子中的任意一个。
  3. 根据权利要求1所述的负载型催化剂，其特征在于，所述烃基为烷基、环烷基、芳基或芳烷基，优选为烷基，更优选为正丁基。
  4. 根据权利要求1所述的负载型催化剂，其特征在于，所述烃氧基选自烷氧基或苯氧基，优选为甲氧基、乙氧基、正丙氧基、正丁氧基、正戊氧基或正己氧基，更优选甲氧基。
  5. 根据权利要求1所述的负载型催化剂，其特征在于，所述无机载体选自二氧化硅、二氧化钛、活性炭和氧化铝中的一种或多种组成的混合物，优选为二氧化硅。
  6. 根据权利要求1所述的负载型催化剂，其特征在于，所述无机载体的比表面积大于10m 2/g，优选大于30m 2/g，更优选大于100m 2/g。
  7. 根据权利要求1～6中任一项所述的负载型催化剂，其特征在于，所述活性功能组分占所述无机载体的重量的1ppm～40％，优选为1000ppm～10％。
  8. 一种蔗糖-6-酯的合成方法，其特征在于，采用权利要求1～7中任一项所述的负载型催化剂催化蔗糖与羧酸低级醇酯进行酯交换反应，以获得蔗糖-6-酯。
  9. 根据权利要求8所述的合成方法，其特征在于，所述合成方法包括：
    蔗糖溶解步骤：将蔗糖加热溶解于极性非质子溶剂中，形成蔗糖溶液；
    催化剂加入步骤：将权利要求1～7中任一项所述的负载型催化剂加入所述蔗糖溶液，形成反应悬浮液；以及
    酯交换反应步骤：将羧酸低级醇酯加入所述反应悬浮液中，并进行脱水脱醇处理，以促进酯交换反应，得到以蔗糖-6-酯为主产物的反应混合溶液。
  10. 根据权利要求9所述的合成方法，其特征在于，还包括：
    后处理步骤：将所述反应混合溶液进行过滤，以分离其中的负载型催化剂，得到蔗糖-6-酯母液。
  11. 根据权利要求9所述的合成方法，其特征在于，所述羧酸低级醇酯选自硬脂酸、苯甲酸、乙酸、丁酸、月桂酸的甲基酯、乙基酯、丙基酯、异丙基酯、正丁基酯、异丁基酯、叔丁基酯和苯甲基酯中的一种或几种，优选硬脂酸甲基酯、乙酸乙酯和苯甲酸甲酯的一种或几种。
  12. 根据权利要求9所述的合成方法，其特征在于，所述极性非质子溶剂选自二甲亚砜、乙腈、1,4-二氧六环、甲乙酮、甲基异丁基酮、硝基甲烷、硝基乙烷、环己酮、N-甲基吡咯烷酮、N-甲基吡咯烷酮、N,N-二甲基乙酰胺、六甲基磷酰胺和N,N-二甲基甲酰胺中的一种或几种，优选乙腈和/或N,N-二甲基甲酰胺。
  13. 根据权利要求9所述的合成方法，其特征在于，所述极性非质子溶剂体积用量与所述蔗糖的质量用量的比为2～50mg/L，优选4～20mg/L，更优选6～10mg/L；
    以活性功能组分计，所述负载型催化剂的摩尔用量与所述蔗糖的摩尔用量的比为0.01～2，优选为0.05～0.5；
    所述羧酸低级醇酯的体积用量小于所述极性非质子溶剂的体积用量的30％，优选小于20％，更优选小于15％。
  14. 根据权利要求9～13任一项所述的合成方法，其特征在于，所述脱水脱醇处理是通过蒸馏出向所述反应悬浮液中额外添加的极性非质子溶剂或羧酸低级醇酯实现的。
  15. 根据权利要求14所述的合成方法，其特征在于，所述蒸馏的条件为：蒸馏温度为40～100℃，优选60～80℃；蒸馏压力0.01kPa～100kPa，优选0.5kPa～90kPa；蒸馏时间为1分钟～12小时，优选30分钟～4小时。
  16. 根据权利要求9～13任一项所述的合成方法，所述酯交换反应步骤通过釜式反应釜或连续逆流反应蒸馏塔实现。
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