CN110026212B - Cracking catalyst and method for preparing sitafloxacin intermediate by using same - Google Patents
Cracking catalyst and method for preparing sitafloxacin intermediate by using same Download PDFInfo
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- CN110026212B CN110026212B CN201910433212.1A CN201910433212A CN110026212B CN 110026212 B CN110026212 B CN 110026212B CN 201910433212 A CN201910433212 A CN 201910433212A CN 110026212 B CN110026212 B CN 110026212B
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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
- B01J27/00—Catalysts comprising the elements or compounds of halogens, sulfur, selenium, tellurium, phosphorus or nitrogen; Catalysts comprising carbon compounds
- B01J27/02—Sulfur, selenium or tellurium; Compounds thereof
- B01J27/053—Sulfates
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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
- B01J27/00—Catalysts comprising the elements or compounds of halogens, sulfur, selenium, tellurium, phosphorus or nitrogen; Catalysts comprising carbon compounds
- B01J27/06—Halogens; Compounds thereof
- B01J27/138—Halogens; Compounds thereof with alkaline earth metals, magnesium, beryllium, zinc, cadmium or mercury
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C41/00—Preparation of ethers; Preparation of compounds having groups, groups or groups
- C07C41/01—Preparation of ethers
- C07C41/18—Preparation of ethers by reactions not forming ether-oxygen bonds
- C07C41/30—Preparation of ethers by reactions not forming ether-oxygen bonds by increasing the number of carbon atoms, e.g. by oligomerisation
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2601/00—Systems containing only non-condensed rings
- C07C2601/02—Systems containing only non-condensed rings with a three-membered ring
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Abstract
The invention discloses a cracking catalyst, which is prepared from the following components in parts by weight of 1: 1-3, and mixing the active ingredients with a carrier, wherein the active ingredients are more than two of sulfates, nitrates, halides or oxides of metal lithium, magnesium, chromium, iron, nickel, zinc, copper, aluminum, silver or palladium; the carrier is one or more than two of active carbon, graphite powder or gypsum powder. Also discloses a method for preparing the sitafloxacin intermediate 2-chloro-2-fluoro-1-benzyloxymethylcyclopropane, which comprises the steps of (1) filling a catalyst subjected to full mixing treatment into a tubular reactor provided with a copper wire mesh, and performing nitrogen replacement treatment at the temperature of 300-500 ℃; (2) and (2) introducing dichloromonofluoromethane and allyl benzyl ether in a gas holder into the tubular reactor in the step (1) in a gas-phase contact manner, reacting at the temperature of 500-700 ℃, and carrying out continuous reaction to obtain a sitafloxacin intermediate 2-chloro-2-fluoro-1-benzyloxymethyl cyclopropane. The reaction may be carried out continuously.
Description
Technical Field
The invention relates to a cracking catalyst and a method for preparing a sitafloxacin intermediate 2-chloro-2-fluoro-1-benzyloxymethylcyclopropane by using the cracking catalyst.
Background
Sitafloxacin (Sitafloxacin) is a broad-spectrum quinolone antibacterial drug developed by the first three pharmaceutical co-located companies in Japan, is firstly marketed in Japan in 2008, is clinically used for treating serious refractory bacterial infection, recurrent infection and some drug-resistant bacterial infection, has good pharmacokinetic characteristics, has few adverse reactions, and is obviously enhanced by most similar drugs with large in-vitro antibacterial activity. Has wide antibacterial spectrum and especially strong antibacterial activity to respiratory tract bacteria. The product has good oral absorption, high bioavailability and small individual difference, is mostly discharged with urine in an original shape after being taken, has little influence on pharmacokinetics due to repeated administration, can not cause accumulation, has wide tissue distribution, and has higher drug concentration in various tissues outside a central nervous system than blood drug concentration, so the product is expected to become an important drug for treating single or mixed bacterial infection of respiratory tract, urogenital system, postoperative and the like.
In the synthesis of sitafloxacin, 2-chloro-2-fluoro-1-benzyloxymethylcyclopropane is a key intermediate. The synthesis research is mainly carried out at home and abroad by obtaining the fluorocarbine by using diethyl zinc and diiodofluoromethane and then carrying out a series of reactions with olefin to finally obtain the target product. In addition, carbene is generated by using ethyl diazoacetate under the action of a catalyst to react with fluoroolefin, the reaction condition is harsh, the ethyl diazoacetate is easy to explode in the using process, and the large-scale production is also limited.
Disclosure of Invention
The technical problem to be solved by the invention is to provide a cracking catalyst, and the catalyst is used for preparing a sitafloxacin intermediate 2-chloro-2-fluoro-1-benzyloxymethyl cyclopropane, so that a new idea for preparing the sitafloxacin intermediate 2-chloro-2-fluoro-1-benzyloxymethyl cyclopropane through a continuous reaction is realized.
In order to solve the technical problems, the invention firstly discloses a cracking catalyst, which is prepared from the following components in percentage by weight of 1: 1-3, wherein the active ingredient is prepared by mixing more than two of metal lithium, magnesium, chromium, iron, nickel, zinc, copper, aluminum, silver or palladium sulfate, nitrate, halide or oxide in any proportion, namely at least two of metal lithium, magnesium, chromium, iron, nickel, zinc, copper, aluminum, silver or palladium sulfate, nitrate, halide or oxide; the carrier is one or more than two of active carbon, graphite powder or gypsum powder which are mixed in any proportion.
Furthermore, the catalyst is filled into a reaction container before use, and is subjected to nitrogen replacement treatment at the temperature of 300-500 ℃.
The invention also discloses a method for preparing sitafloxacin intermediate 2-chloro-2-fluoro-1-benzyloxymethylcyclopropane by using the cracking catalyst, which comprises the following steps
(1) Filling the catalyst subjected to the full mixing treatment into a tubular reactor filled with a copper wire mesh, and performing nitrogen replacement treatment at the temperature of 300-500 ℃;
(2) and (2) introducing dichloromonofluoromethane and allyl benzyl ether in a gas holder into the tubular reactor in the step (1) in a gas-phase contact manner, reacting at the temperature of 500-700 ℃, and carrying out continuous reaction to obtain a sitafloxacin intermediate 2-chloro-2-fluoro-1-benzyloxymethyl cyclopropane.
Further, the molar ratio of the allyl benzyl ether to the dichlorofluoromethane is 1: 1 to 3.
Enterprises generally engaged in the production process of fluoroalkanes carry out substitution reaction on trichloromethane and hydrogen fluoride to prepare dichlorofluoromethane (commonly called R21 or HFC-21), and for the enterprises, the significance of expanding downstream products of the dichlorofluoromethane is great, the utilization rate of the dichlorofluoromethane is improved, and the income is greatly increased. The invention develops a new cracking catalyst, the application range of dichlorofluoromethane products of related enterprises of fluorinated alkanes is expanded by using the catalyst, the gas phase reaction can be continuously produced, the conversion rate is high, the operation is convenient, the production cost is low, and the catalyst is not decomposed and is non-combustible and can be continuously used in a dry environment. Is suitable for industrial production.
Detailed Description
The present invention will be described more specifically with reference to examples. The practice of the present invention is not limited to the following examples, and any modification or variation of the present invention is within the scope of the present invention.
Example 1 preparation of catalyst 1
60kg of magnesium sulfate, 60kg of zinc sulfate, 120kg of activated carbon, 50kg of graphite powder and 50kg of gypsum powder are fully mixed, filled into a tubular reactor provided with a copper wire mesh and subjected to nitrogen replacement at 300 ℃ to prepare the catalyst 1.
Example 2 preparation of catalyst 2
20kg of copper sulfate, 20kg of zinc oxide, 40kg of chromium oxide, 40kg of aluminum chloride, 10kg of palladium chloride and 130kg of activated carbon are fully mixed, filled into a tubular reactor provided with a copper wire mesh and replaced by nitrogen at 350 ℃ to prepare the catalyst 2.
Example 3 preparation of catalyst 3
50kg of copper nitrate, 20kg of zinc oxide, 10kg of ferric oxide, 20kg of nickel chloride, 10kg of palladium chloride and 330kg of activated carbon are fully mixed, filled into a tubular reactor with a copper wire mesh and replaced by nitrogen at 350 ℃ to prepare the catalyst 3.
Example 4 preparation of catalyst 4
20kg of copper sulfate, 20kg of zinc oxide, 20kg of chromium oxide, 10kg of silver chloride, 10kg of palladium chloride and 120kg of graphite powder are fully mixed and filled into a tubular reactor provided with a copper wire mesh, and 120kg of gypsum powder is replaced by nitrogen at 500 ℃ to prepare the catalyst 4.
Example 5 preparation of catalyst 5
20kg of copper oxide, 20kg of zinc oxide, 20kg of chromium oxide, 50kg of aluminum chloride, 20kg of magnesium chloride and 130kg of graphite powder are fully mixed, filled into a tubular reactor filled with a copper wire mesh and replaced by nitrogen at 500 ℃ to prepare the catalyst 5.
Example 6 preparation of catalyst 6
20kg of lithium oxide, 20kg of zinc chloride, 20kg of chromium oxide, 50kg of aluminum chloride, 20kg of copper sulfate and 130kg of graphite powder are fully mixed, filled into a tubular reactor provided with a copper wire mesh and replaced by nitrogen at 500 ℃ to prepare the catalyst 6.
EXAMPLE 72 preparation of chloro-2-fluoro-1-benzyloxymethylcyclopropane
In a tubular reactor filled with prepared cracking catalyst 1 and equipped with copper wire mesh, 148kg/h (1 mol/h) of allyl benzyl ether and 103kg/h (1 mol/h) of dichlorofluoromethane in a gas holder were introduced into the tubular reactor in a gas phase contact manner, the reaction temperature was controlled at 500 ℃, and the reaction pressure was controlled at 1kg/cm2The reaction is carried out under absolute pressure, after the reaction is finished, the materials are distilled into a condensation separation tower for separation, 214kg/h of 2-chloro-2-fluoro-1-benzyloxymethylcyclopropane is prepared, the conversion rate is 99 percent, and the purity is 99 percent.
EXAMPLE 82 preparation of chloro-2-fluoro-1-benzyloxymethylcyclopropane
In a tubular reactor filled with prepared cracking catalyst 2 and equipped with copper wire mesh, 148kg/h allyl benzyl ether and 115kg/h dichlorofluoromethane in a gas holder were contacted with each other and introduced into the tubular reactor, the reaction temperature was controlled at 500 deg.C, and the reaction pressure was controlled at 1kg/cm2The reaction is carried out under absolute pressure, after the reaction is finished, the materials are distilled into a condensation separation tower for separation, 214kg/h of 2-chloro-2-fluoro-1-benzyloxymethylcyclopropane is prepared, the conversion rate is 99 percent, and the purity is 99 percent.
EXAMPLE preparation of 92-chloro-2-fluoro-1-benzyloxymethylcyclopropane
In the presence of prepared cracking catalystIn a tubular reactor filled with a copper wire mesh and filled with the agent 3, 148kg/h of allyl benzyl ether in a gas holder and 120kg/h of dichlorofluoromethane are contacted and introduced into the tubular reactor, the reaction temperature is controlled at 500 ℃, and the reaction pressure is controlled at 1kg/cm2The reaction is carried out under absolute pressure, after the reaction is finished, the materials are distilled into a condensation separation tower for separation, 214kg/h of 2-chloro-2-fluoro-1-benzyloxymethylcyclopropane is prepared, the conversion rate is 99 percent, and the purity is 99 percent.
EXAMPLE 102 preparation of chloro-2-fluoro-1-benzyloxymethylcyclopropane
In a tubular reactor filled with prepared cracking catalyst 4 and equipped with copper wire mesh, 148kg/h allyl benzyl ether and 155kg/h dichlorofluoromethane in a gas holder were contacted with each other and introduced into the tubular reactor, the reaction temperature was controlled at 500 ℃ and the reaction pressure was controlled at 1kg/cm2The reaction is carried out under absolute pressure, after the reaction is finished, the materials are distilled into a condensation separation tower for separation, 214kg/h of 2-chloro-2-fluoro-1-benzyloxymethylcyclopropane is prepared, the conversion rate is 99 percent, and the purity is 99 percent.
EXAMPLE 112 preparation of chloro-2-fluoro-1-benzyloxymethylcyclopropane
In a tubular reactor filled with prepared cracking catalyst 5 and equipped with copper wire mesh, 148kg/h allyl benzyl ether and 206kg/h dichlorofluoromethane in a gas holder were contacted with each other and introduced into the tubular reactor, the reaction temperature was controlled at 500 deg.C, and the reaction pressure was controlled at 1kg/cm2The reaction is carried out under absolute pressure, after the reaction is finished, the materials are distilled into a condensation separation tower for separation, 214kg/h of 2-chloro-2-fluoro-1-benzyloxymethylcyclopropane is prepared, the conversion rate is 99 percent, and the purity is 99 percent.
EXAMPLE 122 preparation of chloro-2-fluoro-1-benzyloxymethylcyclopropane
In a tubular reactor filled with prepared cracking catalyst 6 and equipped with copper wire mesh, 148kg/h allyl benzyl ether and 309kg/h dichlorofluoromethane in a gas holder were contacted with each other and introduced into the tubular reactor, the reaction temperature was controlled at 500 deg.C, and the reaction pressure was controlled at 1kg/cm2The reaction is carried out under absolute pressure, after the reaction is finished, the materials are distilled into a condensation separation tower for separation, 214kg/h of 2-chloro-2-fluoro-1-benzyloxymethylcyclopropane is prepared, the conversion rate is 99 percent, and the purity is 99 percent.
Claims (2)
1. A method for preparing a sitafloxacin intermediate 2-chloro-2-fluoro-1-benzyloxymethylcyclopropane is characterized by comprising the following steps: the method comprises
(1) Filling the catalyst into a tubular reactor filled with a copper wire mesh, and performing nitrogen replacement treatment at the temperature of 300-500 ℃;
(2) introducing dichloromonofluoromethane and allyl benzyl ether in a gas holder into the tubular reactor in the step (1) in a gas-phase contact manner, reacting at the temperature of 500-700 ℃, and carrying out continuous reaction to obtain a sitafloxacin intermediate 2-chloro-2-fluoro-1-benzyloxymethyl cyclopropane,
the catalyst is prepared from the following components in a weight ratio of 1: 1-3, and fully mixing an active ingredient and a carrier, wherein the active ingredient is more than two of sulfate, nitrate, halide or oxide of metal lithium, magnesium, chromium, iron, nickel, zinc, copper, aluminum, silver or palladium; the carrier is one or more than two of active carbon, graphite powder or gypsum powder.
2. The method of claim 1, further comprising: the molar ratio of the allyl benzyl ether to the dichlorofluoromethane is 1: 1 to 3.
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Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| AU1768383A (en) * | 1982-08-09 | 1984-02-16 | Syntex (U.S.A.) Inc. | Substituted 9-propoxymethylpurines |
| JPS59172432A (en) * | 1983-03-22 | 1984-09-29 | Ube Ind Ltd | Preparation of 1-phenyl-2-alkoxyalkanes |
Family Cites Families (11)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1142124C (en) * | 2001-03-22 | 2004-03-17 | 中国科学院大连化学物理研究所 | Carried copper-base catalyst for cyclopropanizing reaction of olefine and its application |
| CN1180884C (en) * | 2001-07-13 | 2004-12-22 | 中国科学院大连化学物理研究所 | Catalyst for cyclopropanizing reaction of olefine and its preparing process |
| GB0428294D0 (en) * | 2004-12-24 | 2005-01-26 | Givaudan Sa | Process |
| CN100388976C (en) * | 2006-07-07 | 2008-05-21 | 宁夏大学 | Catalyst for dehydrochlorination of chloralkane to produce chloroalkene and its preparation method |
| CN100571867C (en) * | 2007-02-12 | 2009-12-23 | 浙江大学 | The Catalysts and its preparation method of cracking isobutene by methyl-tert-butyl ether |
| CN102936185B (en) * | 2012-11-21 | 2015-01-28 | 临海市利民化工有限公司 | Method for preparing 1,1-difluoroethylene by cracking of 1,1,1-difluoro-1-chloroethane |
| CN103524487B (en) * | 2013-09-29 | 2015-12-02 | 南京优科生物医药研究有限公司 | A kind of preparation method of Sitafloxacin |
| CN104785306B (en) * | 2015-03-18 | 2017-12-22 | 巨化集团技术中心 | A kind of vapor-phase thermal cracking trichloroethanes prepares the in-situ activation and evaluation method of the magnesium-base catalyst of cis dichloroethylene |
| CN106854220B (en) * | 2015-12-09 | 2019-06-18 | 中国科学院大连化学物理研究所 | The preparation and application of two kinds of chiral ligands, chiral porous organic polymer |
| CN107626291B (en) * | 2017-09-29 | 2020-07-07 | 中国科学院上海有机化学研究所 | Application of supported catalyst in trifluoromethane cracking |
| CN109293513B (en) * | 2018-10-09 | 2021-10-08 | 江西富祥药业股份有限公司 | Preparation method of sitafloxacin intermediate |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| AU1768383A (en) * | 1982-08-09 | 1984-02-16 | Syntex (U.S.A.) Inc. | Substituted 9-propoxymethylpurines |
| JPS59172432A (en) * | 1983-03-22 | 1984-09-29 | Ube Ind Ltd | Preparation of 1-phenyl-2-alkoxyalkanes |
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