WO2020202940A1 - 流通式反応用の触媒混合物 - Google Patents

流通式反応用の触媒混合物 Download PDF

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WO2020202940A1
WO2020202940A1 PCT/JP2020/008248 JP2020008248W WO2020202940A1 WO 2020202940 A1 WO2020202940 A1 WO 2020202940A1 JP 2020008248 W JP2020008248 W JP 2020008248W WO 2020202940 A1 WO2020202940 A1 WO 2020202940A1
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reaction
group
catalyst mixture
catalyst
mixture according
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French (fr)
Japanese (ja)
Inventor
卓也 井門
雄太 齋藤
真樹 谷
小林　修
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Kumiai Chemical Industry Co Ltd
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Kumiai Chemical Industry Co Ltd
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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
    • B01J23/38—Catalysts comprising metals or metal oxides or hydroxides, not provided for in group B01J21/00 of noble metals
    • B01J23/40—Catalysts comprising metals or metal oxides or hydroxides, not provided for in group B01J21/00 of noble metals of the platinum group metals
    • B01J23/42—Platinum
    • 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
    • B01J23/38—Catalysts comprising metals or metal oxides or hydroxides, not provided for in group B01J21/00 of noble metals
    • B01J23/40—Catalysts comprising metals or metal oxides or hydroxides, not provided for in group B01J21/00 of noble metals of the platinum group metals
    • B01J23/44—Palladium
    • 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
    • B01J8/00—Chemical or physical processes in general, conducted in the presence of fluids and solid particles; Apparatus for such processes
    • B01J8/02—Chemical or physical processes in general, conducted in the presence of fluids and solid particles; Apparatus for such processes with stationary particles, e.g. in fixed beds
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
    • C07B61/00—Other general methods
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C1/00—Preparation of hydrocarbons from one or more compounds, none of them being a hydrocarbon
    • C07C1/20—Preparation of hydrocarbons from one or more compounds, none of them being a hydrocarbon starting from organic compounds containing only oxygen atoms as heteroatoms
    • C07C1/22—Preparation of hydrocarbons from one or more compounds, none of them being a hydrocarbon starting from organic compounds containing only oxygen atoms as heteroatoms by reduction
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C15/00—Cyclic hydrocarbons containing only six-membered aromatic rings as cyclic parts
    • C07C15/02—Monocyclic hydrocarbons
    • C07C15/067—C8H10 hydrocarbons
    • C07C15/073—Ethylbenzene
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C213/00—Preparation of compounds containing amino and hydroxy, amino and etherified hydroxy or amino and esterified hydroxy groups bound to the same carbon skeleton
    • C07C213/02—Preparation of compounds containing amino and hydroxy, amino and etherified hydroxy or amino and esterified hydroxy groups bound to the same carbon skeleton by reactions involving the formation of amino groups from compounds containing hydroxy groups or etherified or esterified hydroxy groups
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C213/00—Preparation of compounds containing amino and hydroxy, amino and etherified hydroxy or amino and esterified hydroxy groups bound to the same carbon skeleton
    • C07C213/08—Preparation of compounds containing amino and hydroxy, amino and etherified hydroxy or amino and esterified hydroxy groups bound to the same carbon skeleton by reactions not involving the formation of amino groups, hydroxy groups or etherified or esterified hydroxy groups
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C217/00—Compounds containing amino and etherified hydroxy groups bound to the same carbon skeleton
    • C07C217/78—Compounds containing amino and etherified hydroxy groups bound to the same carbon skeleton having amino groups and etherified hydroxy groups bound to carbon atoms of six-membered aromatic rings of the same carbon skeleton
    • C07C217/80—Compounds containing amino and etherified hydroxy groups bound to the same carbon skeleton having amino groups and etherified hydroxy groups bound to carbon atoms of six-membered aromatic rings of the same carbon skeleton having amino groups and etherified hydroxy groups bound to carbon atoms of non-condensed six-membered aromatic rings
    • C07C217/82—Compounds containing amino and etherified hydroxy groups bound to the same carbon skeleton having amino groups and etherified hydroxy groups bound to carbon atoms of six-membered aromatic rings of the same carbon skeleton having amino groups and etherified hydroxy groups bound to carbon atoms of non-condensed six-membered aromatic rings of the same non-condensed six-membered aromatic ring
    • C07C217/92—Compounds containing amino and etherified hydroxy groups bound to the same carbon skeleton having amino groups and etherified hydroxy groups bound to carbon atoms of six-membered aromatic rings of the same carbon skeleton having amino groups and etherified hydroxy groups bound to carbon atoms of non-condensed six-membered aromatic rings of the same non-condensed six-membered aromatic ring the nitrogen atom of at least one of the amino groups being further bound to a carbon atom of a six-membered aromatic ring
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C249/00—Preparation of compounds containing nitrogen atoms doubly-bound to a carbon skeleton
    • C07C249/04—Preparation of compounds containing nitrogen atoms doubly-bound to a carbon skeleton of oximes
    • C07C249/12—Preparation of compounds containing nitrogen atoms doubly-bound to a carbon skeleton of oximes by reactions not involving the formation of oxyimino groups
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C251/00—Compounds containing nitrogen atoms doubly-bound to a carbon skeleton
    • C07C251/32—Oximes
    • C07C251/34—Oximes with oxygen atoms of oxyimino groups bound to hydrogen atoms or to carbon atoms of unsubstituted hydrocarbon radicals
    • C07C251/36—Oximes with oxygen atoms of oxyimino groups bound to hydrogen atoms or to carbon atoms of unsubstituted hydrocarbon radicals with the carbon atoms of the oxyimino groups bound to hydrogen atoms or to acyclic carbon atoms
    • C07C251/40—Oximes with oxygen atoms of oxyimino groups bound to hydrogen atoms or to carbon atoms of unsubstituted hydrocarbon radicals with the carbon atoms of the oxyimino groups bound to hydrogen atoms or to acyclic carbon atoms to carbon atoms of an unsaturated carbon skeleton
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C251/00—Compounds containing nitrogen atoms doubly-bound to a carbon skeleton
    • C07C251/32—Oximes
    • C07C251/34—Oximes with oxygen atoms of oxyimino groups bound to hydrogen atoms or to carbon atoms of unsubstituted hydrocarbon radicals
    • C07C251/48—Oximes with oxygen atoms of oxyimino groups bound to hydrogen atoms or to carbon atoms of unsubstituted hydrocarbon radicals with the carbon atom of at least one of the oxyimino groups bound to a carbon atom of a six-membered aromatic ring
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C29/00—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom not belonging to a six-membered aromatic ring
    • C07C29/132—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom not belonging to a six-membered aromatic ring by reduction of an oxygen containing functional group
    • C07C29/136—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom not belonging to a six-membered aromatic ring by reduction of an oxygen containing functional group of >C=O containing groups, e.g. —COOH
    • C07C29/14—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom not belonging to a six-membered aromatic ring by reduction of an oxygen containing functional group of >C=O containing groups, e.g. —COOH of a —CHO group
    • C07C29/141—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom not belonging to a six-membered aromatic ring by reduction of an oxygen containing functional group of >C=O containing groups, e.g. —COOH of a —CHO group with hydrogen or hydrogen-containing gases
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C33/00—Unsaturated compounds having hydroxy or O-metal groups bound to acyclic carbon atoms
    • C07C33/18—Monohydroxylic alcohols containing only six-membered aromatic rings as cyclic part
    • C07C33/20—Monohydroxylic alcohols containing only six-membered aromatic rings as cyclic part monocyclic
    • C07C33/22—Benzylalcohol; phenethyl alcohol
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C5/00—Preparation of hydrocarbons from hydrocarbons containing the same number of carbon atoms
    • C07C5/02—Preparation of hydrocarbons from hydrocarbons containing the same number of carbon atoms by hydrogenation
    • C07C5/03—Preparation of hydrocarbons from hydrocarbons containing the same number of carbon atoms by hydrogenation of non-aromatic carbon-to-carbon double bonds
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
    • C07D239/02—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings
    • C07D239/24—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members
    • C07D239/28—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to ring carbon atoms
    • C07D239/46—Two or more oxygen, sulphur or nitrogen atoms
    • C07D239/52—Two oxygen atoms

Definitions

  • the present invention relates to a catalyst mixture for use in a distribution type reaction and a reaction using the same.
  • the organic synthesis reaction for producing organic compounds such as pharmaceuticals, food additives, pesticides, and plastic materials is industrially a batch-type production in which a chemical reaction proceeds while stirring a solution containing raw materials in a reaction vessel.
  • the method is mainstream.
  • Synthesis by a flow-type reaction in which a chemical reaction is carried out while continuously flowing a solution containing a raw material or the like has also been attempted.
  • Synthesis by a distribution-type reaction is excellent in environmental compatibility, reaction efficiency and safety, and the target product can be continuously and efficiently synthesized.
  • the distribution type reaction can also be applied to a reaction using a heterogeneous catalyst such as metal particles.
  • One of the methods is to fill a column arranged in the flow path with a heterogeneous catalyst and pass a reaction solution through the catalyst to carry out the reaction.
  • the disadvantage of this method is that the reaction efficiency is lowered due to the outflow or deterioration of the catalyst while the distribution reaction is continued for a long time.
  • the filled catalyst hinders the flow of the reaction solution and causes pressure loss. If the pressure loss is large, the reaction efficiency is lowered, the load on the pump and the reactor is large, and expensive pressure-resistant equipment is required, which is not industrially preferable.
  • Patent Document 1 discloses a flow synthesis system in which a column is packed with a catalyst supported and immobilized on a carrier.
  • Non-Patent Document 1 discloses a flow-type reaction in which a column is filled with DMPSi-Pd / carrier obtained by diluting a polydimethylsilane-supported palladium catalyst (DMPSi-Pd) with Al 2 O 3 or SiO 2 .
  • DMPSi-Pd polydimethylsilane-supported palladium catalyst
  • an object of the present disclosure is a catalyst mixture having sufficient catalytic efficiency, a small pressure loss when the reaction solution is circulated by filling in a flow reactor, and even after a long-time flow reaction. It is to provide a catalytic mixture that can maintain catalytic efficiency and low pressure loss.
  • the present invention is as follows.
  • a catalyst mixture that is used by filling a flow reactor (A) A transition metal catalyst supported on a carrier and catalyzing a chemical reaction (B) A catalyst mixture containing a filler that does not interfere with the chemical reaction and in which the filler is a polysaccharide. [2] The catalyst mixture according to [1], wherein the polysaccharide is cellulose or starch. [3] The catalyst mixture according to [1] or [2], wherein the polysaccharide is cellulose. [4] The catalyst mixture according to [1] to [3], wherein the weight% of the component (B) is 20 to 200% by weight with respect to the weight of the component (A).
  • [22] A method for carrying out a hydrogenation reaction or a hydrocracking reaction using a flow reactor filled with the catalyst mixture according to [1] to [10].
  • [23] A method for converting a nitro group into an amino group by passing a compound having a nitro group and hydrogen through a flow reactor having the catalyst mixture according to [1] to [10].
  • [24] A method for hydrolyzing and decomposing the benzyloxy group into a hydroxy group by passing a compound having a benzyloxy group and hydrogen through a flow reactor having the catalyst mixture according to [1] to [10].
  • [25] A method for converting a carbonyl group into a hydroxy group or an alkyl group by passing a compound having a carbonyl group and hydrogen through a flow reactor having the catalyst mixture according to [1] to [10].
  • [26] [1] A method for converting a formyl group into a hydroxy group or a methyl group by passing a compound having a formyl group and hydrogen through a flow-type reactor having the catalyst mixture according to [1] to [10].
  • [27] A method for converting an acetyl group into an ethyl group by passing a compound having an acetyl group and hydrogen through a flow reactor having the catalyst mixture according to [1] to [10].
  • [28] A method for converting a triple bond into a double bond or a single bond by passing a compound having a triple bond and hydrogen through a flow reactor having the catalyst mixture according to [1] to [10].
  • [29] A method for converting a double bond into a single bond by passing a compound having a double bond and hydrogen through a flow reactor having the catalyst mixture according to [1] to [10].
  • [30] A method for converting a vinyl group into an ethyl group by passing a compound having a vinyl group and hydrogen through a flow reactor having the catalyst mixture according to [1] to [10].
  • [31] A method for converting a cyano group into an aminomethyl group by passing a compound having a cyano group and hydrogen through a flow reactor having the catalyst mixture according to [1] to [10].
  • [32] The method according to [23], wherein the compound having a nitro group is a compound of the following formula (1), and the compound in which the nitro group is converted into an amino group is a compound of the following formula (2).
  • R is a hydrogen atom or a chlorine atom, preferably a chlorine atom.
  • the method according to [38], wherein the set temperature of the temperature control unit provided in the flow reactor is 25 ° C to 80 ° C.
  • the solvents for aromatic hydrocarbon derivatives, nitriles, and alcohols are toluene, acetonitrile, methanol, ethanol, and 2-.
  • the present disclosure provides a novel catalyst mixture. Further, according to the present disclosure, a flow-type reaction using the above-mentioned catalyst mixture can be carried out. In the catalyst mixture of the present disclosure, since the filler is flammable, the metal catalyst can be easily recovered after the reaction is completed. The flow-type reaction using the catalyst mixture of the present disclosure is industrially advantageous because it has a long catalyst life and a small pressure loss.
  • FIG. 1 schematically shows an outline of the reactor of the present invention.
  • the hydrogen gas supplied from the supply port 1 and the substrate solution supplied from the supply port 2 are mixed in the mixer 11.
  • the mixture is introduced into a tubular reaction vessel 12 heated by a temperature control unit 13 (for example, a bath, a jacket, etc.) and reacts.
  • the reaction mixture is accumulated in the container 3, and the unreacted hydrogen gas is discharged from the discharge port 4.
  • 14 is a mass flow controller
  • 15 is a pump
  • 16 is a back pressure valve
  • 17 and 18 are pressure gauges.
  • FIG. 2 is a graph showing the time course of pressure on the inlet side and the outlet side of the tubular reaction vessel in Comparative Example 1. The difference between the pressure on the inlet side and the pressure on the outlet side is the pressure loss.
  • the transition metal of the transition metal catalyst of the present invention may be any one as long as it catalyzes a desired chemical reaction, and a known transition metal used as a catalyst can be appropriately adopted.
  • the transition metal include those of the platinum group. Metals (eg platinum (Pt), palladium (Pd), ruthenium (Ru), rhodium (Rh) and iridium (Ir), etc.), manganese group metals (eg, manganese (Mn), renium (Re), etc.) , Copper group metals (eg, copper (Cu), silver (Ag) and gold (Au), etc.), iron group metals (eg, iron (Fe), cobalt (Co), nickel (Ni), etc.). Be done.
  • the transition metal may be an alloy alone or a combination of two or more.
  • the transition metal is preferably a platinum group metal, more preferably platinum or palladium.
  • the carrier of the transition metal catalyst supported on the carrier may be any carrier as long as it can support the transition metal and the catalytic reaction proceeds and the catalytic metal does not significantly flow out during the reaction, and a known material used as the catalytic carrier can be used.
  • a known material used as the catalytic carrier can be used.
  • carbon carriers eg, activated carbon, carbon black, graphite, etc.
  • polysilanes eg, polydimethylsilane, polymethylphenylsilane, etc.
  • metal oxides eg, silicon oxide, aluminum oxide, silica alumina, oxidation, etc.
  • Titanium chromium oxide, etc.
  • transition metal catalyst supported on the carrier include carbon-supported palladium (Pd / C), carbon-supported platinum (Pt / C), and polydimethylsilane-supported palladium (DMPSi-Pd), and more preferably carbon.
  • Examples thereof include supported palladium (Pd / C) and carbon-supported platinum (Pt / C).
  • the filler of the present invention is a polysaccharide.
  • the polysaccharide By using the polysaccharide as a filler (diluent), the polysaccharide itself burns, so that the metal catalyst can be easily recovered.
  • polysaccharide means starch (amylose or amylopectin and a mixture thereof), cellulose, chitin, agaralose, carrageenan, pectin and derivatives thereof, and mixtures thereof.
  • the polysaccharide is not particularly limited as long as it does not interfere with the catalytic reaction and does not dissolve in the reaction solution, and known polysaccharides can be appropriately adopted.
  • Examples of polysaccharides are starch (amylose or amylopectin), cellulose, chitin, agaralose, carrageenan, pectin and derivatives thereof, preferably starch and cellulose, more preferably cellulose.
  • starch is a compound in which an ⁇ -glucose molecule is polymerized by a glycosidic bond.
  • the botanical origin of starch is not limited. Suitable sources of starch are corn, pea, potatoes, sweet potatoes, morokoshi, bananas, barley, wheat, rice, sago, amaranth, tapioca, kuzukon, canna, and their low amylose (about 10% by weight or less amylose, preferably). Is an amylose (containing 5% by weight or less) or high amylose (containing at least about 40% by weight) species.
  • cellulose is a compound in which a ⁇ -glucose molecule is polymerized by a glucoside bond.
  • Examples of the above derivatives include cellulose derivatives and amylose derivatives.
  • Examples of cellulose derivatives include alkyl cellulose, hydroxyalkyl cellulose, alkyl (hydroxyalkyl) cellulose, carboxyalkyl cellulose, acetyl cellulose and the like.
  • Specific examples of the cellulose derivative include methyl cellulose, ethyl cellulose, ethyl methyl cellulose, hydroxyethyl cellulose, hydroxypropyl cellulose, hydroxyethyl methyl cellulose, hypromellose, carmellose, carboxymethyl ethyl cellulose, acetyl cellulose and the like.
  • powdered cellulose is also referred to as cellulose powder.
  • the terms "Powdered cellulose" and “Cellulose powder” mean cellulose processed into powder, and there are no particular restrictions on the raw material, manufacturing method, degree of purification, etc., and known powdered cellulose can be appropriately used. Can be adopted.
  • the shape of the polysaccharide is not particularly limited as long as it can be filled in the reaction vessel, but in one embodiment, the polysaccharide is a powdered polysaccharide.
  • the particle size of the powdered polysaccharide is preferably larger than the particle size of the transition metal catalyst supported on the carrier. Examples of the average particle size of the polysaccharide powder include 1 to 100 ⁇ m, 1 to 80 ⁇ m, 1 to 50 ⁇ m, 1 to 30 ⁇ m, preferably 2 to 100 ⁇ m, 5 to 50 ⁇ m, and 10 to 50 ⁇ m.
  • Examples of the apparent specific gravity (bulk density) of powdered polysaccharides are 0.1 to 1.0 g / cm 3 , 0.1 to 0.8 g / cm 3 , 0.1 to 0.6 g / cm 3 , and so on. Examples include, but are not limited to, 0.1 to 0.5 g / cm 3 , preferably 0.2 to 0.6 g / cm 3 , and 0.3 to 0.5 g / cm 3. ..
  • the ratio of the polysaccharide as a filler in the catalyst mixture 5 to 500% by weight, 5 to 500% by weight, as the weight% of the polysaccharide when the weight of the transition metal catalyst supported on the carrier is 100% by weight.
  • the range is 300% by weight, 5 to 200% by weight, 5 to 150% by weight, 20 to 100% by weight, preferably 10 to 300% by weight, 20 to 200% by weight, 25 to 200% by weight, 50 to 150% by weight. Can be mentioned.
  • the chemical reaction catalyzed by the transition metal catalyst can be any reaction as long as it can be catalyzed by the transition metal catalyst, but in one embodiment, hydrogenation, dehydrogenation, isomerization, reduction, Oxidation, hydration, and coupling reactions.
  • hydrogenation is a hydrogenation reaction or hydrogenolysis, a reaction in which a nitro group is converted to an amino group by a hydrogenation reaction, and a carbonyl group is hydrogenated.
  • Method of converting aldehyde group to hydroxy group or alkyl group by hydrogenation reaction reaction of converting aldehyde group to hydroxy group or alkyl group by hydrogenation reaction, reaction of converting acetyl group to hydroxy group or alkyl group by hydrogenation reaction, double bond
  • a reaction that converts the double bond of a group having a hydrogenation into a single bond by a hydrogenation reaction a reaction that converts the triple bond of a group having a triple bond into a double bond or a single bond by a hydrogenation reaction, and a hydrogenation of a cyano group.
  • a reaction that converts an aromatic ring into an aminomethylene group by a reaction a reaction that reduces an aromatic ring by a hydrogenation reaction, a reaction that converts a benzyloxy group into a hydroxy group by a hydrogenation reaction, and a halogen group that is converted into a hydrogen atom by a hydrogenation reaction. It is a reaction to convert and a reaction to convert a sulfonyloxy group into a hydroxy group by a hydrogenation decomposition reaction.
  • the benzyloxy group, (phenyl) is -CH 2 -O-, may have a substituent on the phenyl.
  • the reaction of converting the double bond of a group having a double bond into a single bond by a hydrogenation reaction is such that the double bond of a group having a carbon-carbon double bond is carbonated by a hydrogenation reaction.
  • the reaction of converting the triple bond of a group having a triple bond into a double bond or a single bond by a hydrogenation reaction is such that the triple bond of a group having a carbon-carbon triple bond is carbonized by a hydrogenation reaction.
  • the reaction for reducing an aromatic ring by a hydrogenation reaction is a reaction for reducing a phenyl group to a cyclohexyl group, a reaction for reducing a frill group to a tetrahydrofuryl group, or a reaction for reducing a pyrrolyl group to a pyrrolidyl group.
  • the coupling reaction is Suzuki-Miyaura coupling reaction, Negishi coupling reaction, Ulmann reaction, Glaser reaction, Mizorogi-Heck reaction, Still coupling reaction, Sonogashira coupling reaction, Kumada-Tamao cup.
  • the distribution type reaction is a reaction in which raw materials are continuously supplied, the reaction is continuously carried out, and the reaction mixture is continuously recovered.
  • the flow-type reaction is a reaction using a tube-type flow-type reactor, and the catalyst mixture is filled in the tube-type reactor.
  • the flow reactor may be provided with a temperature control means for controlling the temperature of the flow reactor, for example, a temperature control unit for heating and / or cooling. Good.
  • the temperature control unit may be any suitable, and examples of the temperature control unit include a bath, a jacket, and the like.
  • Examples of the set temperature of the temperature control unit are 15 ° C to 100 ° C, 20 ° C to 80 ° C, 25 ° C to 60 ° C, 25 ° C to 50 ° C, 25 ° C to 40 ° C, 30 ° C to 60 ° C, 30 ° C to 30 ° C. Examples thereof include a range of 50 ° C., 40 ° C. to 60 ° C., preferably 25 ° C. to 80 ° C.
  • examples of the material of the flow reactor are not particularly limited as long as it is not affected by the raw material and the solvent, and for example, a metal (for example, various alloys such as titanium, nickel, stainless steel, Hastelloy C, etc.), Examples thereof include resins (for example, fluororesin, etc.), glass (for example, silicon, quartz, etc.), porcelain (for example, cordierite, ceramics, etc.) and the like.
  • a metal for example, various alloys such as titanium, nickel, stainless steel, Hastelloy C, etc.
  • resins for example, fluororesin, etc.
  • glass for example, silicon, quartz, etc.
  • porcelain for example, cordierite, ceramics, etc.
  • the tubular flow reactor may be any one capable of continuously circulating a liquid or air-liquid mixture, and the cross-sectional shape of the tube may be circular, square or polygonal. It may be any of elliptical tubulars and the like, and it may be a combination of these shapes, but it is preferably a column (circular tube) shape.
  • the route for supplying the raw material to the tube or recovering the reaction mixture is not particularly limited, and can be connected by a polytetrafluoroethylene (PTFE) tube, a metal tube, or the like.
  • the shape of the tube in the tubular flow reactor is not particularly limited, and may be, for example, linear, curved, or coiled. Preferred shapes include, for example, a linear tubular reactor.
  • the number of pipes may be one, but two or more pipes may be bundled regularly or irregularly at appropriate intervals.
  • tubular reactors may be connected in series for use. Hydrogen gas may be introduced from the beginning of the pipe or may be introduced from the middle of the pipe.
  • the flow reactor may be provided with back pressure control means for controlling back pressure.
  • the back pressure can be controlled by providing a back pressure valve in the flow path on the outlet side of the pipe filled with the catalyst.
  • the flow reactor may be provided with a pressure measuring means for measuring the pressure of the flow reactor, for example, pressure gauges on both the inlet side and the outlet side of the catalyst-filled tube. It may be provided.
  • the flow reactor may have a mixer, if desired.
  • the mixer is not particularly limited as long as it has a function of continuously mixing two or more kinds of fluids such as gas and liquid or liquid and liquid. For example, a Y-shaped mixer, a T-shaped mixer, and a cross.
  • Examples include a type mixer and a pipeline type mixer (a line mixer including a static mixer and the like).
  • An example of the equivalent diameter of a tube in a tubular reactor is not particularly limited as long as it can continuously flow a liquid or air-liquid mixture, but for high reaction efficiency and reduction of pressure loss. In addition, it is preferably 5 mm or more for one tube. Examples of preferable equivalent diameters include 5 mm to 150 mm, 5 mm to 100 mm, 5 mm to 50 mm, more preferably 10 mm to 150 mm, 10 mm to 100 mm, 10 mm to 50 mm, and 10 mm to 30 mm for one tube.
  • the "equivalent diameter (De)" is a value defined by the following equation.
  • De 4.Af / Wp (In the formula, Af indicates the flow path cross-sectional area, and Wp indicates the wet edge length.)
  • the length of the tube in the tubular reactor can be appropriately set in consideration of the equivalent diameter of the tube, the flow rate and the time required for the reaction.
  • pressure loss means a value obtained by subtracting the pressure on the outlet side from the pressure on the inlet side of a pipe filled with a catalyst mixture of a flow reactor in a steady state (a state in which the reaction is stable).
  • the inlet side pressure means the pressure before the first pipe
  • the outlet side pressure means the pressure after the last pipe.
  • the pressure on the inlet side may be a desired pressure as long as it is less than the pressure resistance limit of the reactor, but in one embodiment, examples of the pressure at the inlet include 0.1 MPa to 10 MPa, 0.2 to 5 MPa, and 0. The range of 2 to 1 MPa, preferably 0.4 to 1.0 MPa can be mentioned.
  • the pressure loss is preferably small, less than 0.3 MPa, less than 0.2 MPa, less than 0.1 MPa, preferably less than 0.05 MPa. Further, in terms of the ratio with the pressure on the inlet side, the pressure loss is preferably less than 20%, less than 15%, less than 10%, and preferably less than 5%.
  • the catalytic mixture is used for a hydrogenation reaction.
  • a reactor having a tubular flow reactor for hydrogenation is illustrated in FIG. 1, but the reactor of the present invention is not limited thereto.
  • the hydrogen gas supplied from the supply port 1 and the substrate solution supplied from the supply port 2 are mixed by the mixer 11.
  • three or more raw materials and solvents may be supplied to the mixer, if desired.
  • the mixture is introduced into a tubular reaction vessel 12 filled with a catalyst mixture and reacts.
  • the reaction mixture is collected in the container 3, and the unreacted hydrogen gas is discharged from the discharge port 4.
  • the diameter of the tube of the tubular reaction vessel 12 is 5 mm or more for one tube.
  • Preferred equivalent diameters include 5 mm to 150 mm, 5 mm to 100 mm, 5 mm to 50 mm, more preferably 10 mm to 150 mm, 10 mm to 100 mm, 10 mm to 50 mm, and 10 mm to 30 mm for one tube.
  • Examples of the tube length of the tubular reaction vessel 12 include the range of 50 mm to 1000 mm, 50 mm to 500 mm, 50 mm to 300 mm, preferably 100 mm to 200 mm.
  • the reaction is preferably carried out in the presence of a solvent.
  • solvents include, but are not limited to: Aromatic hydrocarbon derivatives (eg, benzene, toluene, xylene, chlorobenzene, dichlorobenzene, etc.), Halogenated aliphatic hydrocarbons (eg, dichloromethane, 1,2-dichloroethane, etc.), ethers (eg, diethyl ether, diisopropyl ether, cyclopentyl methyl ether (CPME), tetrahydrofuran (THF), 1,4-dioxane, monoglime , Jiglime, etc.), Alcohols (eg, methanol, ethanol, 1-propanol, 2-propanol, 1-butanol, t-butanol, etc.), Amides (eg, N, N-dimethylformamide (DMF), N, N-dimethylacetamide (DMF), N, N-di
  • Preferred examples are toluene, acetonitrile, methanol, ethanol, 2-propanol and any combination thereof in any proportion, and more preferred examples are toluene, acetonitrile, methanol and any combination thereof in any proportion. including.
  • Additives can be used to suppress pressure rise during the reaction. However, as can be seen from the examples in the present specification, essentially, the effect of the present invention can be obtained by using a polysaccharide as a filler. Whether or not to use an additive can be appropriately determined by those skilled in the art. Examples of additives include water, formic acid, acetic acid and the like. As an example of the amount of the additive used, the equivalent (eq.) With respect to the number of moles of the substrate is in the range of 0 (zero) to 10, 0 to 5.0, 0 to 3.0, preferably 0.05 to 10. , 0.1 to 5.0, 0.1 to 3.0, and more preferably 0.1 to 1.0 equivalent.
  • Examples of the substrate concentration to be fed are 0.1 to 5.0 mol / L, 0.1 to 3.0 mol / L, 0.1 to 2.0 mol / L, and 0.1 to 1.5 mol / L. Although the range is mentioned, the substrate concentration can be appropriately adjusted by those skilled in the art.
  • the flow rate of hydrogen gas is controlled by the mass flow controller 14, and the flow rate of the substrate solution is controlled by the pump 15.
  • the total equivalent (eq.) With respect to the number of moles of the substrate of hydrogen gas is preferably 1 or more, 1.0 to 10, 1.0 to 7, 1.0 to 5, 1.0 to 3.0, The range of 1.1 to 6.0 is preferable.
  • Formic acids may be used as an equivalent (equivalent) of hydrogen.
  • Preferred examples of formic acids include, but are not limited to, formic acid, formate (eg, sodium formate, potassium formate, ammonium formate, etc.), formic acid esters (eg, methyl formate, ethyl formate, etc.) and the like.
  • the tubular reaction vessel 12 can be heated by the temperature control unit 13 (for example, a bath, a jacket, etc.).
  • the set temperature of the temperature control unit for example, bath, jacket, etc.
  • the range of ° C. to 60 ° C., 30 ° C. to 50 ° C., 40 ° C. to 60 ° C., preferably 25 ° C. to 80 ° C. can be mentioned.
  • the pressure on the inlet side can be measured by the pressure gauge 17, and the pressure on the outlet side can be measured by the pressure gauge 18, and the back pressure can be controlled by the back pressure valve 16.
  • Examples of the pressure on the inlet side include a range of 0.1 MPa to 10 MPa, 0.2 to 5 MPa, 0.2 to 1 MPa, preferably 0.4 to 1.0 MPa.
  • the numbers used herein that represent features such as quantity, size, concentration, reaction conditions, etc. are understood to be modified by the term "about".
  • the disclosed numbers are interpreted by applying the number of significant digits reported and conventional rounding techniques.
  • the disclosed numbers are interpreted to include errors that inevitably arise from the standard deviation found in each test measurement method.
  • the room temperature is 15 ° C to 30 ° C.
  • the reaction was carried out using a flow-type reaction vessel (KeyChem-H (registered trademark) manufactured by YMC Co., Ltd.) shown in FIG.
  • the substrate solution is sent from the supply port 2 by the single plunger pump 15, and the hydrogen gas whose hydrogen source is a hydrogen storage alloy canister (YMH-500LF, manufactured by YMC Co., Ltd.) or a hydrogen cylinder is sent from the supply port 1 by the mass flow controller 14.
  • the flow rate was adjusted and supplied.
  • the substrate solution and hydrogen gas are mixed in the mixer 11 and introduced into the column-type reaction vessel 12 heated by the temperature control unit 13.
  • the column type reaction vessel 12 was previously filled with a catalyst mixture.
  • the pressure on the column inlet side was adjusted by the back pressure valve 16.
  • the reaction mixture was accumulated in a container 3 capable of discharging unreacted hydrogen gas, and the reaction mixture was analyzed by high performance liquid chromatography.
  • a PTFE tube having a diameter of 1.0 mm and a length of 10 mm to 1000 mm was used for the line connecting the respective flow paths.
  • 1% Pt / C moisture content 57%, 2.56 g, Pt 0.056 mmol, manufactured by N.E. Chemcat Co., Ltd., trade name: STAF-1M
  • cellulose powder (2.56 g, 1% Pt / C) 100 wt%, manufactured by Nippon Paper Industries, Ltd., trade name: KC Flock, W-400G) is mixed in advance and then packed in a column-type reaction vessel (manufactured by YMC Co., Ltd.) with a diameter of 10 mm and a length of 100 mm for column-type reaction.
  • the containers were connected with a PTFE tube and placed in a bath adjusted to 80 ° C.
  • CMNA 27.9 g, 0.1 mol + toluene 65.0 g, 0.75 L / mol was sent at room temperature at a set value of 0.2 ml / min.
  • hydrogen gas was introduced at a set value of 16 ml / min (3.5 eq.), Adjusted with a back pressure valve so that the pressure on the column inlet side became 0.4 MPa to 1.0 MPa, and the column was mixed with gas and liquid. Introduced into a mold reaction vessel. The discharged reaction mixture was analyzed by high performance liquid chromatography. As a result, the conversion rate was maintained at 97% or more for 36 hours. At this time, the pressure loss on the inlet side and the outlet side of the column type reaction vessel was 0.05 MPa or less.
  • Comparative Example 1 1% Pt / C (moisture content 57%, 2.56 g, Pt 0.056 mmol, manufactured by N.E. Chemcat Co., Ltd., trade name: STAF-1M) in a column type reaction vessel with a diameter of 10 mm and a length of 50 mm (stock) It was packed in (manufactured by YMC Co., Ltd.), and as described above, the column type reaction vessel was connected with a PTFE tube and placed in a bath adjusted to 80 ° C.
  • CMNA 27.9 g, 0.1 mol + toluene 65.0 g, 0.75 L / mol was sent at room temperature at a set value of 0.2 ml / min.
  • hydrogen gas was introduced at a set value of 14 ml / min (3.1 eq.), Adjusted with a back pressure valve so that the pressure on the column inlet side became 0.4 MPa to 1.0 MPa, and the column was mixed with gas and liquid. Introduced into a mold reaction vessel.
  • the discharged reaction mixture was analyzed by high performance liquid chromatography. As a result, the conversion rate was 97% or more up to 0.5 hours. However, since then, the conversion rate has dropped to less than 97%.
  • the change in pressure between the inlet side and the outlet side of the column type reaction vessel is shown in FIG. A pressure loss of 0.3 MPa to 0.4 MPa was confirmed.
  • Comparative Example 2 1% Pt / C (moisture content 57%, 2.65 g, Pt 0.058 mmol, manufactured by N.E.Chemcat Co., Ltd., trade name: STAF-1M) and activated clay (2.65 g, 1% Pt / C) 100 wt%) was mixed in advance, and then filled in a column-type reaction vessel (manufactured by YMC Co., Ltd.) having a diameter of 10 mm and a length of 150 mm, and the reaction was carried out under the same conditions as in Example 1 except for the above.
  • a column-type reaction vessel manufactured by YMC Co., Ltd.
  • the conversion rate was 97% or more at the start of the reaction, and the pressure loss on the inlet side and the outlet side of the column type reaction vessel was 0.05 MPa or less. However, it was confirmed that the conversion rate decreased with time, and the reaction was not stable.
  • Comparative Example 3 1% Pt / C (moisture content 55.5%, 2.54 g, Pt 0.058 mmol, manufactured by N.E. Chemcat Co., Ltd., trade name: STAF-1M) and silica gel (2.54 g, 1% Pt / C) 100 wt%, Kanto Chemical Co., Inc., trade name: silica gel 60N) was mixed in advance, and then filled in a column-type reaction vessel (manufactured by YMC Co., Ltd.) having a diameter of 10 mm and a length of 100 mm. The reaction was carried out under the same conditions as above. As a result, the conversion rate was maintained at 97% or more for up to 4 hours. However, the pressure loss increased with time and the inlet pressure exceeded 1 MPa, so the operation was stopped.
  • Comparative Example 4 1% Pt / C (moisture content 57%, 1.51 g, 0.033 mmol as Pt, manufactured by N.E. Chemcat Co., Ltd., trade name: STAF-1M) and alumina (1.51 g, with respect to 1% Pt / C) 100 wt%) in advance, then packed in a column-type reaction vessel (manufactured by YMC Co., Ltd.) with a diameter of 10 mm and a length of 50 mm, the column-type reaction vessel is connected with a PTFE tube, and placed in a bath adjusted to 60 ° C. It was.
  • a column-type reaction vessel manufactured by YMC Co., Ltd.
  • CMNA 27.9 g, 0.1 mol + toluene 65.0 g, 0.75 L / mol was sent at room temperature at a set value of 0.2 ml / min.
  • hydrogen gas was introduced at a set value of 16 ml / min (3.5 eq.), Adjusted with a back pressure valve so that the pressure on the column inlet side became 0.4 MPa to 1.0 MPa, and the column was mixed with gas and liquid. Introduced into a mold reaction vessel. The discharged reaction mixture was analyzed by high performance liquid chromatography.
  • the conversion rate was 97% or more at the start of the reaction, and the pressure loss on the inlet side and the outlet side of the column type reaction vessel was 0.05 MPa or less.
  • the conversion rate decreased with the passage of time, the conversion rate after 9 hours was 54.6%, and the conversion rate decreased to 5.1% after 11 hours.
  • Example 2 1% Pt / C (moisture content 55.5%, 1.85 g, 0.042 mmol as Pt, manufactured by N.E. Chemcat Co., Ltd., trade name: STAF-1M) and cellulose powder (0.46 g, 1% Pt / 24.9 wt% of C, manufactured by Nippon Paper Industries, Ltd., trade name: KC Flock, W-400Y) is mixed in advance and then packed in a column-type reaction vessel (manufactured by YMC Co., Ltd.) with a diameter of 10 mm and a length of 50 mm. Other than that, the reaction was carried out under the same conditions as in Example 1. As a result, the conversion rate was maintained at 98% or more for 12 hours or more.
  • Example 3 1% Pt / C (moisture content 55.5%, 2.47 g, 0.056 mmol as Pt, manufactured by N.E. Chemcat Co., Ltd., trade name: STAF-1M) and cellulose powder (0.13 g, 1% Pt / 5.3 wt% of C, manufactured by Nippon Paper Industries, Ltd., trade name: KC Flock, W-400Y) is mixed in advance and then packed in a column-type reaction vessel (manufactured by YMC Co., Ltd.) with a diameter of 10 mm and a length of 50 mm. Other than that, the reaction was carried out under the same conditions as in Example 1. As a result, the inlet pressure exceeded 1 MPa after 50 minutes, so the operation was stopped. The conversion rate up to 50 minutes was 82.4%.
  • 1% Pt / C moisture content 55.5%, 1.00 g, 0.023 mmol as Pt, manufactured by NE Chemcat Co., Ltd., trade name: STAF-1M
  • cellulose powder (1.00 g, 1% Pt / 100 wt% of C, manufactured by Nippon Paper Industries, Ltd., trade name: KC Flock, W-400Y) is mixed in advance, and then packed in a column-type reaction vessel (manufactured by YMC Co., Ltd.) having a diameter of 10 mm and a length of 50 mm.
  • the column type reaction vessel was connected with a PTFE tube and placed in a bath adjusted to 50 ° C.
  • CMNA 27.9 g, 0.1 mol + acetonitrile 131.3 g, 1.51 L / mol was sent at room temperature at a set value of 0.4 ml / min.
  • hydrogen gas was introduced at a set value of 27 ml / min (6 eq.), Adjusted with a back pressure valve so that the pressure on the column inlet side became 0.4 MPa to 1.0 MPa, and the column type reaction was performed while mixing gas and liquid. Introduced into a container. The discharged reaction mixture was analyzed by high performance liquid chromatography. As a result, the conversion rate was maintained at 98% or more at 3 hours.
  • Example 5-7 was carried out under the same conditions as in Example 4 except that the scale was changed as shown in Table 1. The results are shown in Table 1. In each of the examples, the average conversion rate of 98% or more was maintained during the total operation time shown in Table 1.
  • Example 8 1% Pt / C (moisture content 55.5%, 8.51 g, Pt 0.194 mmol, manufactured by N.E.Chemcat Co., Ltd., trade name: STAF-1M) and cellulose powder (crystalline cellulose, 8.51 g, 1) 100 wt% with respect to% Pt / C, manufactured by Serva, sold by Fujifilm Wako Pure Chemical Industries, Ltd., manufacturer code 14205.02), and then a column-type reaction vessel with a diameter of 20 mm and a length of 100 mm (stock) The reaction was carried out under the same conditions as in Example 6 except that the mixture was packed in (manufactured by YMC Co., Ltd.). As a result, the conversion rate was maintained at 98% or more for 5 hours or more.
  • CMNA 27.9 g, 0.1 mol + acetonitrile 131.3 g, 1.51 L / mol was sent at room temperature at a set value of 0.4 ml / min.
  • hydrogen gas was introduced at a set value of 27 ml / min (6 eq.), Adjusted with a back pressure valve so that the pressure on the column inlet side became 0.4 MPa to 1.0 MPa, and the column type reaction was performed while mixing gas and liquid. Introduced into a container.
  • the discharged reaction mixture was analyzed by high performance liquid chromatography. As a result, the conversion rate was maintained at 98% or more at 4 hours. At this time, the pressure loss on the inlet side and the outlet side of the column type reaction vessel was 0.07 MPa or less.
  • 10% Pd / C (water content 55%, 1.80 g, 0.761 mmol as Pd, manufactured by Tokyo Chemical Industry Co., Ltd.) and cellulose powder (0.75 g, 41.7% with respect to 10% Pd / C, Japan Paper Industries, Ltd., trade name: KC Flock, W-400G) was mixed in advance and then packed in a column-type reaction vessel (manufactured by YMC Co., Ltd.) having a diameter of 10 mm and a length of 50 mm.
  • the column type reaction vessel was connected to a hydrogenation reactor (manufactured by YMC Co., Ltd.) with a PTFE tube and placed in a water bath adjusted to 30 ° C.
  • ISAMe-Bn solution adjusted to 0.15 mol / l (50 wt% ISAMe-Bn toluene solution 31.3 g, 0.05 mol + methanol 233.7 g, 5.90 L / mol + formic acid 0.46 g, 0.2 eq.)
  • the solution was sent at a set value of 1.5 ml / min.
  • hydrogen gas was introduced at a set value of 6 ml / min (1.1 eq.), Adjusted with a back pressure valve so that the pressure on the column inlet side became 0.4 MPa to 1.0 MPa, and the column was mixed with gas and liquid. Introduced into a mold reaction vessel.
  • the discharged reaction mixture was analyzed by high performance liquid chromatography. As a result, the conversion rate after 3 hours was 92.5%.
  • the pressure loss on the inlet side and the outlet side of the column type reaction vessel was 0.05 MPa or less.
  • Comparative Example 5 A column-type reaction vessel (manufactured by YMC Co., Ltd.) having a diameter of 10 mm and a length of 50 mm was filled with 10% Pd / C (moisture content 55%, 3.39 g, Pd 1.433 mmol, manufactured by Tokyo Chemical Industry Co., Ltd.). Other than that, the reaction was carried out under the same conditions as in Example 10. As a result, the conversion rate after 3 hours was 70.5%. At this time, the pressure loss on the inlet side and the outlet side of the column type reaction vessel was 0.10 MPa.
  • Example 11 10% Pd / C (moisture content 55%, 1.59 g, Pd 0.672 mmol, manufactured by Tokyo Chemical Industry Co., Ltd.) and cellulose powder (0.66 g, 41.5% with respect to 10% Pd / C, Japan Paper Industries, trade name: KC Flock, W-400G) was mixed in advance and then filled in a column-type reaction vessel (manufactured by YMC Co., Ltd.) having a diameter of 10 mm and a length of 50 mm.
  • a column-type reaction vessel manufactured by YMC Co., Ltd.
  • 10% Pd / C (water content 55%, 1.74 g, 0.736 mmol as Pd, manufactured by Tokyo Chemical Industry Co., Ltd.) and cellulose powder (0.73 g, 42.0% with respect to 10% Pd / C, Japan Paper Industries, Ltd., trade name: KC Flock, W-400Y) was mixed in advance and then packed in a column-type reaction vessel (manufactured by YMC Co., Ltd.) having a diameter of 10 mm and a length of 50 mm.
  • the column type reaction vessel was connected to a hydrogenation reactor (manufactured by YMC Co., Ltd.) with a PTFE tube and placed in a water bath adjusted to 60 ° C.
  • NPA solution adjusted to 0.18 mol / l (NPA 33.53 g, 0.1 mol + acetonitrile 416.02 g, 5.29 L / mol) was sent at room temperature at a set value of 0.8 ml / min.
  • hydrogen gas was introduced at a set value of 11 ml / min (3.5 eq.), Adjusted with a back pressure valve so that the pressure on the column inlet side became 0.4 MPa to 1.0 MPa, and the column was mixed with gas and liquid. Introduced into a mold reaction vessel.
  • the discharged reaction mixture was analyzed by high performance liquid chromatography. As a result, the conversion rate after 4 hours was 90.6%.
  • the pressure loss on the inlet side and the outlet side of the column type reaction vessel was 0.05 MPa or less.
  • Comparative Example 6 10% Pd / C (moisture content 55%, 2.05 g, Pd 0.867 mmol, manufactured by Tokyo Chemical Industry Co., Ltd.) and silica gel (0.86 g, 42.0 wt% with respect to 1% Pt / C, Kanto Chemical Co., Inc. Co., Ltd., trade name: silica gel 60N) was mixed in advance and then filled in a column-type reaction vessel (manufactured by YMC Co., Ltd.) having a diameter of 10 mm and a length of 50 mm. As a result of carrying out the reaction under the same conditions as in Example 12 except for the above, the conversion rate after 4 hours was 71.5%. At this time, the pressure loss on the inlet side and the outlet side of the column type reaction vessel was 0.05 MPa or less.
  • a benzaldehyde solution adjusted to 0.5 mol / l (benzaldehyde 10.6 g, 0.1 mol + methanol 149.6 g, 1.89 L / mol) was sent at room temperature at a set value of 0.7 ml / min.
  • hydrogen gas was introduced at a set value of 8 ml / min (1.0 eq.), Adjusted with a back pressure valve so that the pressure on the column inlet side became 0.1 MPa to 1.0 MPa, and the column was mixed with gas and liquid. Introduced into a mold reaction vessel. The discharged reaction mixture was analyzed by gas chromatography. As a result, the conversion rate after 4 hours was 98.7%. After 4 hours, the pressure loss on the inlet side and the outlet side of the column type reaction vessel was 0.02 MPa.
  • 10% Pd / C (water content 55%, 1.76 g, 0.744 mmol as Pd, manufactured by Tokyo Chemical Industry Co., Ltd.) and cellulose powder (0.73 g, 41.7 wt% with respect to 10% Pd / C, Japan Paper Industries, Ltd., trade name: KC Flock, W-400Y) was mixed in advance and then packed in a column-type reaction vessel (manufactured by YMC Co., Ltd.) having a diameter of 10 mm and a length of 50 mm.
  • the column type reaction vessel was connected to a hydrogenation reactor (manufactured by YMC Co., Ltd.) with a Teflon tube and placed in a water bath adjusted to 40 ° C.
  • a styrene solution adjusted to 0.5 mol / l (styrene 10.4 g, 0.1 mol + methanol 148.6 g, 1.88 L / mol) was sent at room temperature at a set value of 0.4 ml / min.
  • hydrogen gas was introduced at a set value of 9 ml / min (2.0 eq.), Adjusted with a back pressure valve so that the pressure on the column inlet side became 0.1 MPa to 1.0 MPa, and the column was mixed with gas and liquid. Introduced into a mold reaction vessel.
  • the discharged reaction mixture was analyzed by gas chromatography. As a result, the conversion rate after 4 hours was 100%. After 4 hours, the pressure loss on the inlet side and the outlet side of the column type reaction vessel was 0.09 MPa.
  • Example 1 is an example in which powdered cellulose is used as a filler. A high conversion rate was maintained for a long time, and the pressure loss was small. Comparative Example 1 is an example in which the reaction was attempted under almost the same conditions as in Example 1 without using a polysaccharide as a filler. The pressure loss was large and the conversion rate decreased over time. Comparative Example 2-4 is an example in which activated clay, silica gel, and alumina are mixed as a filler instead of polysaccharides. At the beginning of the reaction, a high conversion rate and a small pressure loss were obtained, but with the passage of time, the conversion rate decreased or the pressure loss increased. Examples 2 and 3 are examples in which the weight ratio of the filler in the catalyst mixture is changed.
  • Example 4 is an example in which the solvent is changed from toluene to acetonitrile. It can be seen that a high conversion rate is maintained.
  • Example 5-7 is an example in which the column diameter and the flow velocity are changed from Example 4. In all cases, a high conversion rate was maintained during the operating hours.
  • Example 8 is an example in which crystalline cellulose is used as a filler. In this example as well, a high conversion rate was maintained for a long time.
  • Example 10 and Comparative Example 5 are examples in which the catalyst mixture of the present invention is applied to the hydrocracking reaction. From these comparisons, it was found that the pressure loss can be suppressed and a high conversion rate can be obtained for a long time by using the catalyst mixture of the present invention.
  • Example 11 is an example in which the scale is changed from Example 10. A high conversion rate was maintained for a long time.
  • Example 12 and Comparative Example 6 are examples in which the catalyst mixture of the present invention is applied to a reaction different from that of Example 1. From these comparisons, it was found that the pressure loss can be suppressed and a high conversion rate can be obtained for a long time by using the catalyst mixture of the present invention.
  • the present disclosure provides a catalyst mixture for performing an efficient flow-type reaction.
  • the flow-type reaction using the catalyst mixture of the present disclosure is industrially advantageous because the pressure loss is small and the life of the catalyst is long. Therefore, the present invention has high industrial applicability.

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CN114591190A (zh) * 2022-03-29 2022-06-07 浙江辰阳化工有限公司 一种催化加氢合成普鲁卡因的方法

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JPS505675B1 (https=) * 1969-12-19 1975-03-06
JPS55116442A (en) * 1979-02-28 1980-09-08 Yardney Electric Corp Preparation of catalyst for hydrogenation
JPH02144149A (ja) * 1988-11-22 1990-06-01 Ube Ind Ltd 白金族金属担持触媒の再活性化方法
JPH0525101A (ja) * 1990-12-07 1993-02-02 Bayer Ag アニリンの製造方法
JPH05305218A (ja) * 1992-04-28 1993-11-19 Kooken:Kk 消臭方法及び消臭材・消臭素材
WO2005035122A1 (ja) * 2003-10-08 2005-04-21 Kao Corporation ３級アミン製造用フィルム型触媒及びそれを用いた３級アミンの製造方法

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JPS505675B1 (https=) * 1969-12-19 1975-03-06
JPS55116442A (en) * 1979-02-28 1980-09-08 Yardney Electric Corp Preparation of catalyst for hydrogenation
JPH02144149A (ja) * 1988-11-22 1990-06-01 Ube Ind Ltd 白金族金属担持触媒の再活性化方法
JPH0525101A (ja) * 1990-12-07 1993-02-02 Bayer Ag アニリンの製造方法
JPH05305218A (ja) * 1992-04-28 1993-11-19 Kooken:Kk 消臭方法及び消臭材・消臭素材
WO2005035122A1 (ja) * 2003-10-08 2005-04-21 Kao Corporation ３級アミン製造用フィルム型触媒及びそれを用いた３級アミンの製造方法

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* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN114591190A (zh) * 2022-03-29 2022-06-07 浙江辰阳化工有限公司 一种催化加氢合成普鲁卡因的方法
CN114591190B (zh) * 2022-03-29 2024-04-09 浙江辰阳化工有限公司 一种催化加氢合成普鲁卡因的方法

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