阅读说明：本技术 一种制备三氯蔗糖-6-乙酯的方法 (Method for preparing sucralose-6-ethyl ester ) 是由 刘杰 朱梦瑶 张静 任一臻 陈来中 张永振 于 2020-05-27 设计创作，主要内容包括：本发明公开了一种三氯蔗糖-6-乙酯的制备方法,在负载型Pd催化剂的作用下,蔗糖-6-乙酯与氯化四唑蓝(CAS:1871-22-3)发生反应,经结晶分离出产品,所使用的负载型Pd催化剂,由Pd前体、配体、添加剂和载体制备得到。本发明主要优点在于由蔗糖-6-乙酯与氯化四唑蓝反应制得三氯蔗糖-6-乙酯,添加剂的加入,有效的抑制了多氯化副反应的发生,负载型Pd催化剂活性高,副反应杂质少,选择性高,不易流失,操作简单,经济效益好。(The invention discloses a preparation method of sucralose-6-ethyl ester, under the action of a supported Pd catalyst, reacting sucrose-6-ethyl ester with tetrazolium chloride blue (CAS:1871-22-3), and crystallizing to separate out a product, wherein the used supported Pd catalyst is prepared from a Pd precursor, a ligand, an additive and a carrier. The invention has the main advantages that the sucralose-6-ethyl ester is prepared by the reaction of the sucrose-6-ethyl ester and the tetrazolium chloride blue, the addition of the additive effectively inhibits the occurrence of polychlorinated side reactions, and the supported Pd catalyst has high activity, less side reaction impurities, high selectivity, difficult loss, simple operation and good economic benefit.)

1. a method for preparing sucralose-6-ethyl ester comprises the following steps: under the action of a supported Pd catalyst, sucrose-6-ethyl ester and chlorinated tetrazolium blue are subjected to selective chlorination reaction in a solvent to generate sucralose-6-ethyl ester, and a product is separated.

2. The process according to claim 1, characterized in that the supported Pd catalyst, expressed as Pd-X-Y/Z,

wherein X is a ligand selected from one or more of 1, 2-bis (diphenylphosphino) benzene, triphenylphosphine, tributylphosphine, tricyclohexylphosphine, bis (diphenylphosphino) butane, 1, 3-bisdiphenylphosphinopropane, 1-binaphthyl-2, 2 '-bisdiphenylphosphine, 4, 5-bisdiphenylphosphine-9, 9-dimethoxyxanthene, preferably 1, 1-binaphthyl-2, 2' -bisdiphenylphosphine and/or 1, 3-bisdiphenylphosphinopropane;

y is an additive selected from one or more of bipyridyl, quinoline, diphenyl disulfide, pyridine, triazine and substituted pyridine, quinoline and triazine, wherein the substituent is selected from halogen, methyl and tert-butyl, and the additive is preferably one or more of 2, 2-bipyridyl, quinoline, diphenyl disulfide and pyridine;

z is a carrier and is selected from one or more of diatomite, kaolin, molecular sieve, neutral alumina and silica, preferably one or more of kaolin, 4A molecular sieve and silica.

3. The method of claim 2, wherein the mass fraction of Pd in the catalyst is 8-20%, the mass fraction of X is 16-40%, the mass fraction of Y is 20-35%, and the mass fraction of Z is 20-55%, based on the total weight of the catalyst; preferably, the mass fraction of Pd is 10-15%, the mass fraction of X is 20-35%, the mass fraction of Y is 25-35%, and the mass fraction of Z is 25-45%.

4. A process according to any one of claims 1 to 3, characterized in that the supported Pd catalyst is used in an amount of 15 to 20 wt.%, relative to sucrose-6-acetate.

5. The method according to any one of claims 1 to 4, wherein the molar ratio of sucrose-6-ethyl ester to tetrazolium chloride blue is from 1:3 to 1: 4.

6. The method as claimed in any one of claims 1 to 5, wherein the reaction temperature is raised by three-stage temperature programming, the first stage is raising the temperature to 45-75 ℃ within 0.5-1 hour and maintaining the temperature for 1-2 hours, the second stage is raising the temperature to 8-100 ℃ within 0.5-1 hour and maintaining the temperature for 1-2 hours, and the third stage is raising the temperature to 110-125 ℃ within 0.5-1 hour and maintaining the temperature for 1-3 hours.

7. A process according to any one of claims 1 to 6, characterized in that the solvent is DMF and/or DMAC in an amount of 5 to 10 times the mass of sucrose-6-ethyl ester.

8. The process according to any one of claims 1 to 7, wherein the product is isolated by thermal crystallization in ethyl acetate.

9. The process according to any one of claims 1 to 8, wherein the supported Pd catalyst is prepared by a process comprising the steps of:

(1) mixing a Pd-containing compound, a ligand X and an additive Y in water, stirring and fully mixing at 50-80 ℃, and then dispersing a carrier Z in the aqueous solution to obtain a suspension;

(2) adding an alkaline precipitator into the suspension until the pH value is 9-12, and aging to obtain slurry;

(3) and carrying out aftertreatment on the slurry to obtain the supported Pd catalyst.

10. The method according to claim 9, wherein in step (1), the Pd-containing compound is selected from Pd (OAc)₂、Pd(dppf)Cl₂、Pd(dba)₂One or more of tetratriphenylphosphine palladium and bis (tri-tert-butylphosphine) palladium, preferably Pd (dba)₂And/or bis (tri-tert-butylphosphine) palladium; and/or

In the step (2), the alkaline precipitator is selected from one or more of sodium hydroxide, sodium carbonate, ammonium carbonate and ammonia water; the aging time is 3-6h, and the aging temperature is 55-85 ℃; and/or

In the step (3), the post-treatment specifically comprises: filtering and washing the slurry to obtain a filter cake, drying the filter cake, and roasting, crushing and tabletting the filter cake; wherein the drying temperature is 115-135 ℃, and the drying time is 9-18 h; the roasting temperature is 350-550 ℃, and the roasting time is 7-23 h.

Technical Field

The invention relates to a method for preparing sucralose-6-ethyl ester, belonging to the technical field of chemical industry.

Technical Field

Sucralose is a sweetener which is developed by the company of England Teley and university of London and applied for patent in 1976, is a functional sweetener which only takes sucrose as a raw material, has the original trade name of Splenda, and has the sweetness which can be 600 times that of the sucrose. The sweetener has the characteristics of no energy, high sweetness, pure sweetness, high safety and the like, and is one of the most excellent functional sweeteners at present.

Sucralose-6-ethyl ester is an important intermediate for synthesizing sucralose, and two methods, namely a phosgene chlorination method and a thionyl chloride chlorination method, are currently industrialized. The phosgene chlorination method has the disadvantages of potential safety hazards due to the use of a highly toxic substance phosgene, and the thionyl chloride chlorination method can decompose sulfur dioxide waste gas generated to influence the product quality and has low yield.

Patent US4980463 refers to a method for preparing sucralose-6-ethyl ester by chlorinating sucrose-6-ethyl ester with phosgene, which has the disadvantages of more waste solvent, troublesome solvent recovery and high energy consumption, and also has the disadvantages of troublesome post-treatment and high toxicity by using phosgene tail gas.

Patents CN1962675A, CN101029062A, and CN103145772A mention methods for preparing sucralose-6-ethyl ester by using thionyl chloride to chlorinate sucrose-6-ethyl ester, which also have the disadvantages of more generated waste solvents, troublesome solvent recovery, and high energy consumption, and the use of thionyl chloride can generate sulfur dioxide waste gas, which affects the product quality, and the methods have low yield and high cost.

Aiming at the defects in the process, a new method for synthesizing sucralose-6-ethyl ester is urgently needed to be developed, and the problems of high production energy consumption, low product yield, low selectivity, low safety and the like in the existing production are solved.

Disclosure of Invention

One of the purposes of the invention is to provide a novel method for preparing sucralose-6-ethyl ester.

It is another object of the present invention to provide a method for preparing the catalyst used in the above method.

In order to realize the first invention purpose, the invention provides a preparation method of sucralose-6-ethyl ester, and particularly relates to a method for producing sucralose-6-ethyl ester by carrying out selective chlorination reaction on sucrose-6-ethyl ester and tetrazolium chloride blue (CAS:1871-22-3) by using a supported Pd catalyst. By the method, phosgene and thionyl chloride are avoided, and potential safety hazards are reduced; the used supported catalyst is easy to separate, the problem of difficult solvent recovery is avoided, the operation steps of post-reaction treatment can be effectively reduced, the energy consumption is reduced, and the catalyst is environment-friendly and avoids the problem of environmental pollution. The adopted scheme comprises the following steps:

a method for preparing sucralose-6-ethyl ester comprises the following steps: under the action of a supported Pd catalyst, sucrose-6-ethyl ester and tetrazolium chloride blue are subjected to selective chlorination reaction in a solvent to generate sucralose-6-ethyl ester, the solvent is removed, and the product is separated by crystallization.

The reaction route of the invention is as follows:

in the preparation method, the dosage of the supported Pd catalyst is 15-20 wt% relative to the sucrose-6-ethyl ester.

In the preparation method, the molar ratio of the sucrose-6-ethyl ester to the tetrazolium chloride blue is 1:3-1: 4.

In the preparation method, three-level temperature programming is adopted: the first stage is heating to 45-75 deg.C within 0.5-1 hr and maintaining for 1-2 hr, the second stage is heating to 8-100 deg.C within 0.5-1 hr and maintaining for 1-2 hr, and the third stage is heating to 110-125 deg.C within 0.5-1 hr and maintaining for 1-3 hr.

In the preparation method, the solvent can be DMF and/or DMAC, and the dosage of the solvent is 5-10 times of the mass of the sucrose-6-ethyl ester.

In the preparation method, the product can be crystallized by a known method, for example, by a thermal crystallization method in ethyl acetate.

In the preparation method, the supported Pd catalyst is expressed as Pd-X-Y/Z,

wherein X is a ligand selected from one or more of 1, 2-bis (diphenylphosphino) benzene, triphenylphosphine, tributylphosphine, tricyclohexylphosphine, bis (diphenylphosphino) butane (dppb), 1, 3-bis-diphenylphosphinopropane (dppp), 1-binaphthyl-2, 2' -bis-diphenylphosphine (BINAP), 4, 5-bis-diphenylphosphino-9, 9-dimethoxyxanthene (XantPhos), preferably BINAP and/or dppp;

y is an additive selected from one or more of bipyridyl, quinoline, diphenyl disulfide, pyridine, triazine and substituted pyridine, quinoline and triazine, the substituent can be halogen, methyl and tert-butyl, and the additive is preferably one or more of 2, 2-bipyridyl, quinoline, diphenyl disulfide and pyridine;

z is a carrier and is selected from one or more of diatomite, kaolin, molecular sieve, neutral alumina and silica, preferably one or more of kaolin, 4A molecular sieve and silica.

In the catalyst of the invention, Pd in the supported Pd catalyst exists in a valence state of 0. Based on the total weight of the catalyst, wherein the mass fraction of Pd is 8-20%, the mass fraction of X is 16-40%, the mass fraction of Y is 20-35%, and the mass fraction of Z is 20-55%; preferably, the mass fraction of Pd is 10-15%, the mass fraction of X is 20-35%, the mass fraction of Y is 25-35%, and the mass fraction of Z is 25-45%.

In the catalyst structure, Pd is a metal element and exists in the catalyst in a complexing mode, X is an organic matter containing a P element, and a chemical bond and a coordination bond are formed with Pd through lone-pair electrons on P in the catalyst; y is an organic substance containing N, S element, and generation of polychlorinated side reaction can be inhibited through forming a coordination bond between lone pair electrons on N, S and Pd; pd and X, Y form a metal-organic framework material together; the carrier Z plays a role in dispersing metal organic framework materials, so that the atoms of the active center of the catalyst are distributed more uniformly, and the aggregation of the active center is avoided.

In the invention, the preparation method of the supported Pd catalyst comprises the following steps:

(1) mixing a Pd-containing compound, a ligand X and an additive Y in water, stirring for 4-7h at 50-80 ℃, and fully mixing, and then dispersing a carrier Z in the aqueous solution to obtain a suspension;

(2) dropwise adding an alkaline precipitator into the suspension until the pH value is 9-12, and aging to obtain slurry; the temperature is controlled to be 25-45 ℃ in the dropping process;

(3) and carrying out aftertreatment on the slurry to obtain the supported Pd catalyst.

In the preparation method of the catalyst, in the step (1), the amount of water is not particularly limited, and the Pd-containing compound, the ligand X, and the additive Y to be added may be completely dissolved.

In the preparation method of the catalyst, in the step (1), the Pd-containing compound is selected from Pd (OAc)₂、 Pd(dppf)Cl₂、Pd(dba)₂One or more of tetratriphenylphosphine palladium and bis (tri-tert-butylphosphine) palladium, preferably Pd (dba)₂And/or bis (tri-tert-butylphosphine) palladium.

In the preparation method of the catalyst, in the step (2), the alkaline precipitator is selected from one or more of sodium hydroxide, sodium carbonate, ammonium carbonate and ammonia water, and can be an aqueous solution with the concentration of 15-35 wt%; the aging time is 3-6h, and the aging temperature is 55-85 ℃.

In the preparation method of the catalyst, in the step (3), the post-treatment specifically comprises the following steps: and filtering and washing the slurry to obtain a filter cake, drying the filter cake, and then roasting, crushing, tabletting and forming the filter cake. Wherein the drying temperature is 115-135 ℃, and the drying time is 9-18 h; the roasting temperature is 350-550 ℃, and the roasting time is 7-23 h.

The invention has the advantages that:

1. the method has the advantages of simple process route, simple operation and low raw material cost.

2. The prepared load type Pd catalyst has the advantages that the introduction of the carrier and the organic ligand greatly improves the dispersion degree of the metal atoms of the active center of the catalyst; lone-pair electrons on P in the catalyst skeleton and the lone-pair electrons on N, S in the additive form coordination bonds with Pd, and the concentration of reactants on the surface of the catalyst is increased in the process of catalytic reaction of the catalyst; the active component of the catalyst is matched with the additive for use, so that the generation of polychlorinated byproducts can be effectively inhibited.

3. The invention can produce the sucralose-6-ethyl ester by chlorination at lower operation temperature, the conversion rate of the raw materials is more than 90 percent, and the selectivity of the product is more than 90 percent.

Detailed Description

The present invention is further illustrated in detail by the following examples, but the scope of the present invention is not limited to these examples.

Liquid chromatography analysis conditions of the product: waters liquid chromatograph, Waters Xbridge amide column, ELSD detector, mobile phase acetonitrile/water 70/30, column temperature 40 ℃.

The sources of the apparatus and reagents in the following examples are shown in table 1 below:

TABLE 1

Instrument and reagent	Origin of origin	Specification of
			Liquid chromatograph	Waters
ICP spectrometer	Agilent	ICP-OES 720 model
			Sucrose-6-ethyl ester	Is commercially available	>99％
Blue tetrazolium chloride	Is commercially available	>99％

The inorganic salts used in the following examples are all commercially available unless otherwise specified.