WO2005073155A1 - マイクロリアクターを用いてアルデヒド化合物又はケトン化合物を製造する方法 - Google Patents
マイクロリアクターを用いてアルデヒド化合物又はケトン化合物を製造する方法 Download PDFInfo
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- WO2005073155A1 WO2005073155A1 PCT/JP2004/017666 JP2004017666W WO2005073155A1 WO 2005073155 A1 WO2005073155 A1 WO 2005073155A1 JP 2004017666 W JP2004017666 W JP 2004017666W WO 2005073155 A1 WO2005073155 A1 WO 2005073155A1
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C45/00—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds
- C07C45/27—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by oxidation
- C07C45/29—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by oxidation of hydroxy groups
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C45/00—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds
- C07C45/51—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by pyrolysis, rearrangement or decomposition
- C07C45/511—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by pyrolysis, rearrangement or decomposition involving transformation of singly bound oxygen functional groups to >C = O groups
- C07C45/513—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by pyrolysis, rearrangement or decomposition involving transformation of singly bound oxygen functional groups to >C = O groups the singly bound functional group being an etherified hydroxyl group
Definitions
- the present invention relates to an aldehyde compound or ketone using a microreactor.
- the present invention relates to a method for producing a compound. More specifically, the present invention provides a primary or secondary alcohol by Swern oxidation reaction.
- the present invention relates to a method for producing an aldehyde compound or a ketone compound from a microorganism using a microreactor.
- Patent Document 1 discloses that aldehydes and / or ketones are used to convert aldols by a catalytic reaction at a temperature of 110 to 250 ° C. It is disclosed that a microstructured reaction system is used for production, and Japanese Patent Application Laid-Open No. 2003-113185 discloses a microreactor using a microreactor. A method for producing an aryl boron compound and an alkyl boron compound by reacting a lithium aromatic compound and an aliphatic compound with a boron compound at a temperature of 60 ° C. to + 30 ° C. is disclosed.
- JP-A-2003-503630 discloses that an acylating agent and a strong acid are combined with an organic compound (preferably an aromatic or heteroaromatic compound). A method is disclosed in which a free delta rajanylation reaction is carried out at a temperature of 10 to 90 ° C. in a microreactor.
- Patent Document 4 discloses that a halide of arylmagne, ammonium and alkylmagnesium and a boron compound are mixed in a microreactor. A method for producing aryl boron and alkylboron at a temperature of 60 ° C. to + 80 ° C. is disclosed.
- Patent Document 1 Japanese Patent Application Laid-Open No. 2000-150550
- Patent Document 2 Japanese Patent Application Laid-Open No. 2000-113-185
- Patent Document 3 Japanese Patent Application Laid-Open No. 2003-50063 / 39 No.
- Patent Document 4 Japanese Patent Application Laid-Open No. 2003-128680 Disclosure of the invention
- An object of the present invention is to obtain a high yield of an aldehyde compound or ketone compound from a primary or secondary alcohol using a microphone-mouth reactor at a relatively higher temperature than the conventional method in a short time.
- the purpose is to provide a method of manufacturing by using the method.
- a method for producing an aldehyde compound or a ketone compound using the microreactor of the present invention comprises the steps of: mixing a liquid containing a sulfoxide compound with a liquid containing an activator for a sulfoxide compound; Mixing the liquid containing the activated form of the sulfoxide compound with the liquid containing at least one selected from the primary and secondary alcohols in the step (1) of producing an activated form of the compound; (2) preparing a liquid containing an alkoxysulfonium salt, and mixing and reacting the obtained liquid containing an alkoxysulfonium salt with a liquid containing a basic compound. (3) preparing a liquid containing an aldehyde or a ketonized food corresponding to the alcohol, wherein at least one of the steps (1), (2) and (3) is performed. Mel 1 step, which is characterized in that performed using the micro-reactor.
- the microreactor is connected to two liquid introduction channels having a fine cross-sectional shape for introducing two kinds of liquids and connected to the liquid introduction channel.
- a micro-mixer section with a fine cross-section for mixing and reacting the two liquids with each other, and a fine cross-section for deriving the reaction product liquid from this micro-mixer section It is preferable to have one liquid outlet channel having a shape.
- two steps that are continuously performed It is performed by using a chlorine reactor, and it is preferable that the liquid outlet channel of the upstream reactor and the liquid inlet channel of the downstream downstream reactor are connected to each other by a capillary connecting tube.
- the steps (1) and (2) are preferably performed in a microreactor.
- the temperature of the liquid therein is adjusted to a desired value.
- the liquid temperature in the capillary continuous tube is adjusted to a desired value.
- a ratio of a major axis / minor axis of a cross section of the liquid introduction channel, a part of the liquid micromixer, and the liquid outlet channel of the microreactor is 1 or more; But 1 ⁇ ! It is preferably in the range of ⁇ 1 mm.
- the flow rate of the liquid derived from the liquid micromixer may be adjusted so that two liquids mixed in the microreactor have a desired mixing efficiency and a desired mixing efficiency. It is preferable to specify that the reaction can be carried out with a residence time of not more than one. -In the production method of the present invention, the residence time of the liquid in the microreactor is preferably set to 0.001 to 60 seconds.
- the step (1) is performed using a microreactor, and the micromixer of the mixed reaction liquid of the liquid containing the sulfoxide compound and the liquid containing the activator is used.
- the residence time from the partial inlet to the inlet of the reactor for the step (2) is preferably 0.0001 to 60 seconds.
- the step (1) is preferably performed in a microreactor, and the mixing reaction temperature is preferably adjusted in a range of ⁇ 80 to 50 ° C. More preferably, it is ⁇ 40 ° C.
- the step (2) is carried out in a microreactor, and the mixing reaction temperature is preferably adjusted in the range of 180 to 50 ° C, More preferably at 40 ° C.
- the sulfoxide compound is selected from dialkyl sulfoxide.
- dimethinoresulfoxide is used as the dialkyl sulfoxide.
- the activator for a sulfoxide compound may be acetic anhydride, oxalyl chloride, trifluoroacetic anhydride, trifluoromethansulfonic anhydride, diphosphorus pentoxide, chlorine, benzoyl chloride, Acetinolechloride, methansolephoninolechloride, p-toluenesulfuricide mouth, sulfur trioxide-pyridine complex, and 2,4,6—tricyclomouth 1,3,5 ⁇ ⁇ It is preferably selected from triazine.
- the primary and secondary alcohols are C! One C 2.
- Saturated and unsaturated aliphatic primary and secondary alcohols or alicyclic It is preferably selected from saturated and unsaturated aliphatic primary and secondary alcohols having the formula aromatic hydrocarbon group, and saturated and unsaturated primary and secondary alcohols having the heterocyclic group.
- the basic compound is selected from an organic amine compound.
- the organic amine compound is selected from trialkylamine.
- the molar ratio of the sulfoxide compound supplied to the first step to the primary or secondary alcohol supplied to the second step is 1: 1 to 20: 1. It is preferable to be within the range.
- the molar ratio of the activator for a sulfoxide compound supplied to the first step to the primary or secondary alcohol supplied to the second step is 1: 1 to 2: 1. It is preferably within the range.
- the molar amount of the basic compound supplied to the third step is 2 to 20 times the molar amount of the primary or secondary alcohol supplied to the second step. Is preferred.
- the production method of the present invention may further include isolating the target aldehyde or ketone compound from the aldehyde or ketone compound-containing liquid prepared in the step (3).
- the method in producing an aldehyde compound or a ketone compound from a primary or secondary alcohol, the method is used in a conventional method by using a microreactor in at least one step.
- a relatively high temperature for example, around 20 ° C, can be used instead of the low temperature of 150 ° C, and the target compound can be produced in a high yield in a short time.
- a method for producing a corresponding aldehyde compound or ketone compound from a primary or secondary alcohol using the microreactor of the present invention comprises the steps of:
- a liquid containing an activated form of the sulfoxide compound and a liquid containing at least one selected from primary and secondary alcohols are mixed and reacted to have an alkoxysulfonium salt.
- the microreactor is more preferably used in at least two of the above steps (1), (2) and (3), more preferably in at least the steps (1) and (2).
- the steps (1), (2) and (3) of the production method of the present invention used in the three steps (1), (2) and (3) are carried out according to the following reaction formula (1). . Process (1
- R 1 and R 2 each independently represent a hydrocarbon group or a heterocyclic organic group, and R 1 and R 2 may be linked to each other to form a cyclic group, or Is one of R 1 and R 2 represents a hydrocarbon group or a heterocyclic organic group, and the other represents a hydrogen atom.
- two liquid introduction channels having a fine sectional shape for introducing two kinds of liquids, and this liquid It is connected to the introduction channel and is used to mix and react the two introduced liquids with each other.
- the two kinds of liquids are uniformly mixed, and the temperature is adjusted to a desired temperature in the micromixer section and the liquid outlet channel.
- the liquid discharge channel of the reactor in the upstream step and the downstream X reactors that are continuous with the liquid outlet channel are used. It is preferable that the liquid introduction channel and the liquid introduction channel are connected to each other by a capillary connection tube.
- the liquid mixtures uniformly mixed with each other in the micromixer are mixed with the micromixer.
- the temperature is adjusted to a desired temperature in the liquid outlet channel, and the desired reaction can be advanced and completed in the micromixer, the liquid outlet channel, and the capillary tube.
- the capillary connecting tube is preferably provided with a means for adjusting the temperature of the liquid flowing therethrough to a desired value, for example, a constant temperature bath, a temperature control jacket, or the like.
- a microreactor is used in at least the two steps (1) and (2).
- the main reaction of the production method of the present invention is performed. Steps (1) and (2) are precisely controlled, and each reaction can be completed with high efficiency within a reduced time.
- the cross-sectional areas of the liquid introduction channel, a part of the liquid micromixer, and the liquid outlet channel are preferably 0.7 ⁇ 1 respectively.
- 2 ⁇ l mm 2 (more preferably 0. 0 0 7 mm 2 ⁇ 0 7 mm 2.), 0 7 ⁇ ⁇ 2 ⁇ :.
- L mm 2 ( good Ri preferably 0. 0 0 7 mm 2 ⁇ 0. 7 mm 2), and 0 ⁇ 7 / zm 2 ⁇ 1 mm 2 ( yo Ri preferably 0. 0 0 7 mm 2 ⁇ 0.
- each minor axis is 1 ⁇ ! It is preferably in the range of ⁇ l mm, more preferably 25 ⁇ ! ⁇ 500 ⁇ .
- the flow rate of the liquid derived from the liquid micromixer is such that two kinds of liquids mixed in the microphone mouth reactor have a desired mixing efficiency and It is preferable to define the reaction so that the reaction can be performed with a desired residence time.
- the reaction time of each of the reactions (1), (2), and (3) can be appropriately set.
- the residence time of the liquid in the microreactor Is preferably set to 0.001 to 60 seconds.
- the step (1) is performed in a microreactor, and the mixing reaction temperature is preferably from 130 to 50 ° C.
- the step (2 ′) is performed in a micro-reactor.
- the reaction is carried out in a reactor, and the mixing reaction temperature is preferably from 180 to 5.0 ° C, more preferably from 130 to 40 ° C.
- the step without using a microreactor uses a reactor having two liquid supply means and one generated liquid discharge means, for example, a T-joint type reactor. Can be.
- the reactor is provided with a temperature adjusting means, a liquid flow rate adjusting means, and the like.
- the sulfoxide and compound supplied to step (1) of the production method of the present invention are preferably selected from dialkyl sulfoxides, and more preferably dimethyl sulfoxide.
- Sulfoxide compound As the liquid containing, a solution of a sulfoxide compound in an organic solvent is usually used, but when the sulfoxide compound is a liquid, it can be used as it is. '
- the organic solvent is not particularly limited as long as it is a solvent conventionally used in the Swern oxidation reaction, and examples thereof include methylene chloride, 1,2-dichloromethane, 1,2-dichlorobenzene, and 1,2-dichloromethane.
- Chlorinated hydrocarbons such as benzene, aromatic hydrocarbons such as benzene, toluene, xylene, ethenole ethers such as ethynoleether, diisopropyl ether, dibutyl ether, dimethoxetane, tetrahydrofuran, and dioxane; Saturated hydrocarbons such as pentane, hexane, heptane, octane, and hexahedral hexane; acetonitrile, propionitol, hexamethylphosphoramide (HMPA); and the like.
- methylene chloride, toluene and chlorobenzene are used.
- the concentration of the sulfoxide compound in the liquid containing the sulfoxide compound is preferably from 0.1 to 20 mol Z liter.
- the activator for a sulfoxide compound used in the step (1) of the production method of the present invention may be acetic anhydride, oxalyl chloride, trifluoroacetic anhydride, trifluoromethanesulfonic anhydride, or dipentoxide.
- the activator-containing liquid is prepared by dissolving the activator in an organic solvent.
- This organic solvent is preferably the same as the organic solvent for the sulfoxide compound.
- the activator concentration in the activator-containing liquid is 0.1 to 15 Preferably, it is mol / liter.
- step (1) of the production method of the present invention the step (1) of the reaction formula (1)
- step (1) E.g., trifluoroacetic anhydride
- the process (1) is mixed violently using a microreactor, and the predetermined temperature control is performed precisely, and the process is completed within a short time.
- the activator-containing liquid can be sent to the step (2) by preventing or reducing the erer rearrangement, and introduced from the step (1).
- Activator-containing liquid And a liquid containing at least one kind of secondary alcohol, and the mixture is reacted.
- the liquid containing the alkoxysulfonium salt shown in 2) is prepared.
- the primary and secondary alcohols used in step (2) of the production method of the present invention are the primary alcohol and the secondary alcohol.
- An OH group is bonded to a carbon atom of an aliphatic hydrocarbon group and does not include a carbon atom that forms an aromatic ring (phenolic OH group). But, for example, the following alcohols.
- C: - C 12 cycloaliphatic alicyclic primary alcohols are primary OH group via the above linear hydrocarbon group to a carbon atom is bonded to a hydrocarbon ring.
- Aromatic primary alcohols in which a mono-OH group is bonded to a carbon atom of an aromatic hydrocarbon ring via the above-mentioned linear hydrocarbon group.
- Penzino Leano Reconore Fénetino Reno Reno, Ninamil alcohol, Salicino Leno Reno, and 2-Fenino Leno Reno.
- Heterocyclic primary alcohols in which a monoOH group is bonded to the carbon atom of the heterocyclic group via a linear hydrocarbon group of Cr or more.
- cyclohexanol 2-methylcyclohexanolone, 3—methylcyclohexanol, 4-methylcyclohexanolone, 2—ethylcyclohexanol, 3
- step (2) of the production method of the present invention those in which the primary alcohol or the secondary alcohol forms a solid at the reaction temperature of the step (2) are the same organic solvents as the organic solvent for the step (1). Used after dissolution.
- the alcohol concentration at this time is preferably from 0.1 to 15 mol / liter.
- step (2) of the production method of the present invention is carried out in a microreactor, the rearrangement of the alkoxysulfonium salt described in the chemical formula (1) is prevented or reduced, and the obtained alkoxy is obtained.
- the sulfonium salt-containing liquid can be sent to step (3).
- the liquid containing an alkoxysulfonium salt is mixed with a liquid containing a basic compound, and reacts with each other to react with each other to form an aldehyde compound or ketone corresponding to the primary or secondary alcohol.
- a liquid containing a ton compound is prepared. .
- the basic compound is an organic amine compound, for example, an alkylamine compound, triethylamine, tripropylamine, tributylamine, getinolemethinoreamin, or acetylenecyclohexenorea. And triisopropylamine, more preferably trialkylamine, and more preferably triethylamine.
- the basic compound used cannot maintain a liquid form at the reaction temperature of the step (3), it is used by dissolving it in the same solvent as the organic solvent used in the step (1). At this time, the concentration of the basic compound is 0.1 to 20 mol / liter. Preferably.
- the mixing reaction temperature in the step (3) is preferably from 130 to 40 ° C, more preferably from 0 to 40 ° C, and the residence time is preferably from 1 second to 5 hours. It is more preferably 10 minutes to 1 hour. .
- the liquid containing the aldehyde or ketone compound prepared in step (3) is derived from step (3), and if necessary, this liquid may be used as a means for isolating the target compound, for example, extraction, distillation, crystallization, silica gel. It is used in processes such as power column chromatography.
- the molar ratio of the sulfol compound in the step (1) to the primary or secondary alcohol in the step (2) is 1: 1 to 20: 1. It is preferably in the range of 1.1: 1 to 3: 1, more preferably in the range of 1.1: 1 to 3: 1. If the molar ratio is less than 1: 1, unreacted primary or secondary alcohol may remain, and if it is higher than 20: 1, an excess may result.
- the separation operation of the sulfonyl compound of the above becomes complicated, which may cause inconvenience in industrial and economical aspects.
- step (1) When step (1) is performed using a microreactor, a mixed reaction solution of the sulfoxide compound-containing liquid and the activator-containing liquid is supplied from the inlet of the micromixer section to the reactor for step (2).
- the time for staying at the entrance of the water is preferably 0.01 to 60 seconds, more preferably 0.01 to 3 seconds.
- the molar ratio of the sulfonyl compound activator provided in step (1) to the primary or secondary alcohol provided in step (2) is 1: 1 to 2: It is preferably in the range of 1, and more preferably in the range of 1.1: 1 to 1.5: 1. If this mole ratio is less than 1: 1, unreacted primary or secondary alcohol remains.
- the molar amount of the basic compound supplied to step (3) of the production method of the present invention is preferably 2 to 20 times, preferably 2.5 to 6 times the molar amount of the primary or secondary alcohol. Is more preferable.
- the reaction efficiency from the alkoxysulfonium salt to the aldehyde or ketone becomes insufficient. If it exceeds 20 times, it may be unfavorable in industrial and economic aspects.
- the aldehyde compound or ketone compound obtained by the production method of the present invention corresponds to the starting material primary alcohol or secondary alcohol, respectively.
- the following compounds can be produced.
- saturated aliphatic aldehydes eg, formaldehyde, acetate aldehyde, propionaldehyde, butyl aldehyde, hexanal, higher aldehydes (octaaldehyde, nonaaldehyde, etc.)
- unsaturated aliphatics Aldehydes eg, acrolein etc.
- glyoxal methyldali oxal
- aliphatic poly aldehydes eg, malonaldehyde, succinaldehyde, glutaraldehyde, adipine aldehyde, pimmelaldehyde
- aliphatic aldehydes such as aminoaceto aldehyde; benzaldehyde, oxybenz aldehyde, nitrovenz aldehyde, amino benzo aldehyde
- Aliphatic ketones such as acetone, methylethylketone, getylketone, dipropylketone, methinolepropylketone, methylbutylketone, and pinacolone; cyclopentanone, cyclohexanone, cyclohexanone, and 2 -Methylcyclohexanone, 2-ethylsilicone hexanone, 2,6-dimethinoresic hexanone, 4-cyclochlorohexanone, 4-methoxycyclohexanone, tontone, camphor, etc.
- Aromatic ketones (cyclic ketones); aromatic ketones such as acetate phenone, propiophenone, benzophenone, deoxybenzoin, and 1_naphthalenone; indene 1-one, 1,. Heterocyclic ketones such as 2,3_indrion, fluorene-91-one, and 4-vinylanone.
- the aldehyde compound and the ketone compound are useful in fields such as organic compound drugs and agricultural chemicals.
- Example 1 The aldehyde compound and the ketone compound are useful in fields such as organic compound drugs and agricultural chemicals.
- a SUS tube (inner diameter: 1.0 mm, length: 20 cm) was connected to each of the two sulfoxide-containing liquids and the liquid channel containing the activator for the sulfoxide compound, and each was connected to a liquid supply source.
- a microreactor (same as for process (1)) was used.
- a SUS tube (0.1 mm inner diameter, length 3.mm) for connecting the reaction product liquid derivation channel of the microreactor in step (1) and the reaction product liquid introduction channel of the microreactor in step (2).
- SUS tube (inner diameter 1.0 mm, length 20 cm) connecting the alcohol supply source and the microphone outlet reactor for the process (2) Connected.
- Microreactor (same as microreactor for process (1))
- the reaction product liquid outlet channel of the microphone mouth reactor in step (2) and the reaction product liquid introduction channel for step (3) are connected by a SUS tube (1.0 mm in diameter, 10 cm in length) for connection. Connected.
- the basic compound introduction channel of the microreactor for the process (3) and the basic compound supply source were connected by a SUS tube (inner diameter 1.0 mm, length 20 cm), and the reaction was performed.
- a SUS tube (1.0 mm ID, 20 cm length) for deriving the reaction product solution was connected to the product solution derivation channel.
- the microreactor for the above steps (1), (2) and (3) and the SUS tube connected to the microreactor are kept at a low temperature of 20 ° C. It was immersed in a warm bath.
- a PTFE tube polyethylene tetrafluoroethylene
- inner diameter l mm, length 50 cm is connected to the end of the SUS tube for deriving the reaction product of the microreactor for step (3).
- inner diameter: 1.0 mm, length: 100 cm was immersed in a water bath at a temperature of 30 ° C.
- the solution is sent to the chlorreactor, and at the same time, the oxanol / methylene chloride solution with a concentration of 1.0 mol liter is fed to the microreactor for the process (2) at a flow rate of 2.OmlZ.
- the reaction product was sent to the microreactor for step (3), and at the same time, a 1.4 mol / liter triethylamine Z methylene chloride solution was flowed. 4.
- the step (3) for people Ik necked reaction product solution derived from Li A Kuta one was collected for 1 minute in a sample bottle containing an internal standard.
- the amount of TFAA used in the above step (1) was 1.5 equivalents, the reaction temperature in the step (1) was ⁇ 20 ° C., and the reaction time was 0.01 second. 'The content of the compound in the collected reaction product solution was determined by gas chromatography internal standard method. The results are shown below.
- a SUS tube (inner diameter: 1.0 mm, length: 20 cm) was connected to each of the two sulfoxide-containing liquid and the liquid channel containing the activator for the sulfoxide compound, and each was connected to a liquid supply source.
- a microreactor (same as for process (1)) was used.
- Micro reactor (same as micro reactor for process (1))
- the reaction product outlet channel of the microreactor in step (2) and the reaction product inlet channel for step (3) are connected to the SU
- the connection was made with an S tube (inner diameter: 1.0, length: 10 cm).
- the basic compound introduction channel of the microreactor for the process (3) and the basic compound supply source were connected by a SUS tube (inner diameter 1.0 mm, length 2 Ocm), A SUS tube (1.0 mm inner diameter, 20 cm length) for deriving the reaction product solution was connected to the reaction product solution derivation channel.
- the microreactor for the steps (1), (2) and (3) and the SUS tube connected to the microreactor were immersed in a low-temperature constant temperature bath set at a temperature of ⁇ 20 ° C.
- PTFE Pulrite Torafuruo port ethylene tubing
- inner diameter l mm, length 5 0 cm An inner diameter of 1.0 mm and a length of 100 era
- SUS tube An inner diameter of 1.0 mm and a length of 100 era
- the microreactor for the process (1) was added to a dimethylsulfoxide / methylene chloride solution having a concentration of 4.0 mol / liter and a solution having a concentration of 3.0 mol / liter.
- a solution of acetic anhydride (TFAA) in methylene chloride / methylene chloride was fed at a flow rate of 1. OmlZ each, and after a reaction mixture residence time of 0.05 seconds, the reaction product was immediately added to the step (2).
- TFAA acetic anhydride
- reaction product was immediately sent to the microreactor for step (3), and at the same time, a triethylamine with a concentration of 1.4 mol / litre concentration was added. / Methylene chloride solution at a flow rate of 4. OnilZ After working for 4 minutes, the reaction product derived from the microreactor for step (3) was collected in a sample bottle containing an internal standard substance for 1 minute. The amount of TFAA used in the above step (1) was 1.5 equivalents, the reaction temperature in the step (1) was ⁇ 20 ° C., and the reaction time was 0.05 seconds.
- the content of the compound in the collected reaction product solution was quantified by gas chromatography internal standard method. The results are shown below.
- inlay Ag plating, fine liquid introduction channel width: 40 ⁇ m) were used. .
- a SUS tube (inner diameter: 1.0 mm, length: 20 cm) was connected to each of the two sulfoxide-containing liquids and the liquid channel containing the activator for the sulfoxide compound, and each was connected to a liquid supply source.
- a microreactor (same as for process (1)) was used.
- a SUS tube for connection (1.0 mm ID, length) is connected between the reaction product liquid derivation channel of the microreactor in step (1) and the reaction product liquid introduction channel of the microreactor in step (2).
- Microreactor (same as microreactor for process (1))
- reaction product solution outlet channel of the microreactor in step (2) and the reaction product solution introduction channel for step (3) were connected by a connecting SUS tube (1.0 mm in diameter, 10 cm in length).
- the channel for introducing the base compound of the microreactor for the process (3) and the supply source of the basic compound are connected by a SUS tube (inner diameter 1.0 mm, length 20 cm).
- a SUS tube (1.0 mm ID, 20 cm length) for deriving the reaction product solution was connected to the reaction product solution derivation channel.
- the microreactor for the above steps (1), (2) and (3) and the SUS tube connected to the microreactor were immersed in a low-temperature constant temperature bath set at a temperature of 20 ° C.
- PTFE Polytetrafluoroethylene
- inner diameter l mm, length 50 cm is connected to the end of the SUS tube for reaction of the micro-reactor for the process (3), which is used to derive the product solution.
- a tube (inner diameter: 1.0 mm, length: 100 cm) was connected, and only this connection tube was immersed in a water bath at a temperature of 30 ° C.
- the dimethylsulfoxide Z-methylene chloride solution with a concentration of 4.0 mol / liter and the trifluoride with a concentration of 3.0 mol / liter were introduced into the microreactor for the process (1).
- the acetic anhydride (TFAA) / methylene chloride solution was sent at a flow rate of 1. OmlZ, respectively.
- the reaction product was immediately added to the microreactor for step (2). Transfer to the actor and at the same time
- the hexanol / methylene chloride solution at the mouth of the litol was sent to the microreactor for the process (2) at a flow rate of 2.
- the amount of TFAA used in the above step (1) was 1.5 equivalents, the reaction temperature in the step (1) was 120 ° C., and the reaction time was 2.4 seconds.
- the content of the compound in the collected reaction product solution was determined by gas chromatography using an internal standard method. The results are shown below. .
- a microreactor (same as for step (1)) was used.
- a SUS tube (inner diameter: 1.0 mm, length: 1 mm) is used to connect the reaction product liquid derivation channel of the microreactor in step (1) and the reaction product liquid introduction channel of the microreactor in step (2). 0 cm), and the alcohol supply source and the alcohol inlet channel of the reactor for the process (2) are connected by a SUS tube (1.0 mm ID, 20 cm length). Connected.
- Micro-reactor (same as micro-reactor for process (1))
- the reaction product solution outlet channel of the microreactor in step (2) and the anti-product solution introduction channel for step (3) are connected by a SUS tube (1.0 mm ID, 10 cm length) for connection. Connected.
- the basic compound introduction channel of the microreactor for the process (3) and the basic compound supply source were connected by a SUS tube (inner diameter 1.0 mm, length 2.0 cm).
- a SUS tube (1.0 mm ID, 20 cm length) for deriving the reaction product was connected to the reaction product channel.
- the microreactor for the above steps (1), (2), and (3) and the SUS tube connected to the microreactor were immersed in a low-temperature oven set at a temperature of 120 ° C.
- a PTFE (polytetrafluoroethylene) tube (inner diameter 1 ⁇ , length 50 cm) is connected to the end of the SUS tube for deriving the reaction product solution of the micro reactor for step (3).
- SUS A tube (1.0 mm inner diameter, 100 cm length) was connected, and only this connection tube was immersed in a water bath at a temperature of 30 ° C.
- a microreactor for the process (1) was added to a dimethylsulfoxide Z-methylene chloride solution with a concentration of 4.0 mol / liter and trifluoride with a concentration of 3.0 mol / liter.
- Acetic anhydride (TFAA) / methylene chloride solution at a flow rate of 1. OmlZ each, and after 24 seconds of residence time of the reaction mixture, the reaction product was immediately added to the microfluidic solution for step (2).
- the amount of TFAA used in the above step (1) was 1.5 equivalents, the reaction temperature in the step (1) was 120 ° C., and the reaction time was 24 seconds.
- the content of the compound in the collected reaction product solution was determined by gas chromatography internal standard method. The results are shown below.
- cyclohexanol is converted to cyclohexane.
- the steps (1), (2) and (3) were performed using the following reactor.
- a SUS tube (inner diameter: 1.0 mm, length: 2 Ocm) was connected to each of the two sulfoxide-containing liquids and the liquid channel containing the activator for the sulfoxide compound, and this was connected to the liquid supply source. .
- a microreactor (same as for step (1)) was used.
- reaction product liquid introduction channel of the microreactor in step (1) and the reaction product liquid introduction channel of the microreactor in step (2) are connected to a connecting SUS tube (1.0 mm in diameter, 10 mm in length). cm), and the alcohol supply source was connected to the alcohol introduction channel of the reactor with the microphone opening for step (2) using a SUS chip (inner diameter 1.0 mm, length 20 cm).
- Microreactor (Same as microreactor for process (1)
- the reaction product solution outlet channel of the microreactor in step (2) and the reaction product solution introduction channel for step (3) are connected to a SUS tube (1.0 mm in inner diameter, 100 cm in length) for connection. More connected.
- the basic compound introduction channel of the microreactor for the process (3) and the basic compound supply source were connected to a SUS tube (inner diameter).
- a SUS tube (1.0 mm inside diameter, 20 cm long) for connecting the reaction product solution was connected to the reaction product solution channel. .
- microreactors for the above steps (1), (2) and (3) and the SUS tubes connected to the microreactors were immersed in a low-temperature constant-temperature bath set at a temperature of 20 ° C.
- the microreactor for the process (1) was placed in a 4.0 mol / liter concentration of dimethylsulfoxydono methylene chloride solution, and a 3.0 mol concentration of Z-liter was prepared.
- Acetonitrile anhydride (TF AA) and methylene chloride solution were each sent at a flow rate of 1.0 ml, and after a reaction mixture residence time of 2.4 seconds, the reaction product was immediately used for the step (2).
- the solution is sent to the microreactor, and at the same time, a cyclohexanol / methylene chloride solution with a concentration of 1.0 mol / liter is sent to the microreactor for step (2) at a flow rate of 2.OmlZ.
- the reaction product was sent to the microreactor for the process (3), and at the same time, triethylamine / chloride with a concentration of 1.4 mol / liter was added.
- the methylene solution was sent at a flow rate of 4.
- the step (3) the reaction product solution derived from the micro re actor one for and collected for one minute in a sample bottle containing an internal standard.
- the amount of TFAA used in the above step (1) was 1.5 equivalents, the reaction temperature in the step (1) was 120 ° C., and the reaction time was 2.4 seconds.
- the content of the compound in the collected reaction product solution was quantified by gas chromatography internal standard method. The results are shown below.
- T-shaped joint type reactor cross-sectional inside diameter: 0.8 mm
- a SUS tube (inner diameter: 1. Oram, length 20 cm) is connected to each of the two liquid introduction channels containing the sulfoxide-containing liquid and the activator for the sulfoxide and compound, and this is connected to the liquid supply source. did.
- a SUS tube (1.0 mm ID, length 1 mm) for connecting the reaction product liquid introduction channel of the L-shaped joint type reactor in step (1) and the reaction product liquid introduction channel of the microreactor in step (2). 0 cm), and the alcohol supply source and the alcohol inlet channel of the reactor for the process (-2) are connected by a SUS tube (inner diameter 1.0 mm, length 20 cm). Connected.
- Micro reactor (same as micro reactor for process (2))
- reaction product solution outlet channel of the microreactor in step (2) and the reaction product solution introduction channel for step (3) are connected by a SUS tube (1.0 mm ID, 10 cm length) for connection. did.
- the basic compound introduction channel of the microreactor for step (3) and the basic compound supply source are connected by a SUS tube (1.0 mm in inner diameter, 20 cm in length), and the reaction product liquid is derived.
- a SUS tube (1.0 mm in inner diameter, 20 cm in length) for deriving the reaction product solution was connected to the channel.
- the reactor for the step (1), the microreactor for the steps (2) and (3), and the SUS tube connected to the reactor were immersed in a low-temperature constant temperature bath set at a temperature of 120 ° C.
- a PTFE (polytetrafluoroethylene) .tube (inner diameter l mm, length 50 cm) is connected to the end of the SUS tube for deriving the reaction product liquid of the microreactor for step (3).
- the tube (inner diameter 1.0 mm, length 100 cm) was connected, and only this connecting tube was immersed in a water bath at a temperature of 30 ° C.
- the microreactor for the process (1) was placed in a dimethylsulfoxide / methylene chloride solution with a concentration of 4.0 mol / liter and a solution with a concentration of 3.0 mol / liter.
- the acetic anhydride (TF AA) / methylene chloride solution was fed at a flow rate of 1. OmlZ, respectively, and the reaction mixture was retained for 2.4 seconds.
- reaction product solution is transferred to the process (3) Liquid was sent to the reactor, and at the same time, a 1.4 mol / liter solution of triethylamine Z methylene chloride was sent at a flow rate of 4.Oml / min.
- the reaction product derived from the microreactor for the step ('3) was collected in a sample bottle containing an internal standard substance for 1 minute.
- the amount of TFAA used in the above step (1) was 1.5 equivalents, the reaction temperature in the step (1) was 120 ° C., and the reaction time was 2.4 seconds.
- the content of the compound in the collected reaction product solution was quantified by a gas chromatograph internal standard method. The results are shown below.
- the steps (1), (2) and (3) were carried out using the following reactor. .
- a SUS tube In each of the two sulfoxide-containing liquids and the liquid channel containing the activator for the sulfoxide compound, a SUS tube.
- a T-shaped joint type reactor (0.8 mm cross-sectional inside diameter) was used.
- a SUS tube (1.0 mm ID, 10 mm length) for connecting the reaction product liquid introduction channel of the microreactor in step (1) and the reaction product liquid introduction channel of the reactor in step (2). cm), and the alcohol supply source and the alcohol introduction channel of the reactor for the process (2) were connected by a SUS tube (inner diameter 1.0 mm , length 20 cm).
- Microreactor (same as microreactor for process (1))
- reaction product liquid outlet channel of the reactor in step (2) and the reaction product liquid introduction channel for step (3) were connected by a connecting SUS tube (inner diameter 1.0 mm, length 10 cm).
- basic compound introduction channel of the microreactor for step (3) and the basic compound supply source were connected by a SUS tube (diameter 1.0 nun, length 20 cm), A SUS tube (1.0 in inside diameter, 20 cm in length) for deriving the reaction product solution was connected to the reaction product solution outlet channel.
- the microreactor for the steps (1) and (3) and the SS tube connected to the microreactor for the step (2) were immersed in a low-temperature constant-temperature bath set at a temperature of 120 ° C.
- a PTFE (polytetrafluoroethylene) tube (inner diameter l mm, length 50 cm) is connected to the end of the SUS tube for deriving the reaction product liquid of the micro reactor for the process (3).
- a tube (inside diameter 1.0 mm, length 100 cm) was connected, and only this connection tube was immersed in a water bath at a temperature of 30 ° C.
- a microreactor for the process (1) Using a gas tight syringe, a microreactor for the process (1) Then, a 4.0 mol-liter concentration of dimethylsulfoxide methylene chloride solution and a 3.0-mol-liter concentration of trifluoracetic acid acetic anhydride (TFAA) / methylene chloride solution were each supplied at a flow rate of 1.0 mol. After the reaction mixture was retained for 2.4 seconds, the reaction product was immediately sent to the microreactor for the process (2), and simultaneously the cyclodextrin with a concentration of 1.0 mol / liter was added. Hexanol The methylene chloride solution is fed into the reactor for step (2) at a flow rate of 2.0 ml / min.
- TFAA trifluoracetic acid acetic anhydride
- reaction product is immediately used for step (3).
- the solution was sent to the microreactor, and at the same time, a 1.4 mol Z liter solution of triethylamine / methylene chloride was sent at a flow rate of 4.OmlZ minutes.
- the reaction product derived from the microreactor for step (3) is The sample was collected in a sample bottle containing the internal standard for 1 minute. .
- the amount of TFAA used in the above step (1) was 1.5 equivalents, the reaction temperature in the step (1) was 120 ° C., and the reaction time was 2.4 seconds.
- the content of the compound in the collected reaction product solution was quantified by a gas chromatograph internal standard method. The results are shown below.
- a microreactor (same as for step (1)) was used.
- a SUS tube for connection (1.0 mm in diameter, 10 mm in length) was used to connect the reaction product liquid derivation channel of the microreactor in step (1) and the reaction product liquid introduction channel of the microreactor in step (2).
- the alcohol supply source and the alcohol introduction channel of the microphone mouth reactor for step (2) are connected by a SUS tube (inner diameter 1.0 mm, length 20 cm). Connected.
- a T-shaped joint type reactor (cross-sectional inside diameter 0.8 mm) was used.
- reaction product solution outlet channel of the microphone-mouth reactor in step (2) and the reaction product solution introduction channel for step (3) are connected with a SUS tube (1.0 mm in diameter, 10 cm in length) for connection. did.
- the basic compound introduction channel of the microreactor for the process (3) and the basic compound supply source were connected by a SUS tube (inner diameter 1.0 mm, length 20 cm) to generate the reaction.
- a SUS tube (1.0 mm ID, 20 cm length) for deriving the reaction product liquid was connected to the liquid derivation channel. .
- the reactor for the above steps (1) and (2) and the SUS tube connected to the reactor for the step (3) were set to a temperature of ⁇ 20 ° C. It was immersed in the kept low-temperature constant temperature bath.
- a PTFE (polytetrafluoroethylene) tube (inner diameter l mm, length 5 Ocm) was connected to the end of the SUS tube for deriving the reaction product liquid of the micro reactor for step (3).
- a SUS tube (1.0 mm inside diameter, 100 cm length) was connected, and only this connection tube was immersed in a water bath at a temperature of 30 ° C.
- a dimer sulfoxide / methylene chloride solution with a concentration of 4.0 moles Z liter and a trimol with a concentration of 3.0 moles Z liter were added to the microreactor for the process (1).
- Fluoroacetic anhydride (TF AA) / methylene chloride solution was sent at a flow rate of 1. OmlZ min, respectively. After a reaction mixture residence time of 2.4 seconds, the reaction product was immediately used for step (2).
- the solution was sent to the microreactor, and at the same time, a xanol Z methylene chloride solution was sent at a flow rate of 2.Oml / min to the mouth of the solution with a concentration of 1.0 mole Z liter, and the reaction mixture residence time was 1.2 seconds.
- the reaction product solution is sent to the microreactor for step (3), and at the same time, a solution of triethylamine / methylene chloride having a concentration of 1.4 mol / liter and a flow rate of 4.OmlZ
- the solution for step (3) The black reaction product solution derived from the reactor and collected for one minute in a sample bottle containing an internal standard.
- the amount of TFAA used in the above step (1) was 1.5 equivalents, the reaction temperature in the step (1) was 120 ° C., and the reaction time was 2.4 seconds.
- the content of the compound in the collected reaction product solution was quantified by gas chromatography internal standard method. The results are shown below.
- a T-joint type reactor (cross-sectional inside diameter: 0.8 mm) was used.
- the reaction product liquid derivation channel of the microreactor in step (1) and the reaction product liquid introduction channel of the reactor in step (2) are connected by a SUS tube (inner diameter 10 mm, length 10 cm) for connection.
- the connection was made, and the alcohol supply source and the alcohol introduction channel of the microreactor for the step (2) were connected with a SUS tube (inner diameter 1.0 mm, length 20 cm).
- a microreactor (same as the microreactor for step (1)) was used.
- reaction product liquid outlet channel of the reactor in step (2) and the reaction product liquid introduction channel of the microreactor for step (3) are connected to a SUS tube (1.0 mm in diameter, 10 cm in length) for connection. Better connection did.
- the basic compound introduction channel of the microreactor for the process (3) and the basic compound supply source are connected by a SUS tube (inner diameter 1.0 mm, length 2 Ocm), and the reaction product solution outlet channel A SUS tube (inner diameter: 1.0 mm, length: 20 cm) for deriving the reaction product solution was connected.
- the microreactor for the steps (1) and (3) and the SUS tube connected to the microreactor for the step (2) were immersed in a low-temperature constant temperature bath set at a temperature of -20 ° C.
- a PTFE tube polytetrafluoroethylene
- inner diameter l mm, length 50 cm is connected to the end of the SUS tube for deriving the reaction product liquid in the microreactor for step (3).
- a 4.0-monoliter Z-liter dimethylsulfoxide / methylene chloride solution and a 2.4-mol / liter concentration were added to the microreactor for the process (1).
- Trifluoroacetic anhydride (TF AA) methyl chloride solution was fed at a flow rate of 1.OmlZ min, and the reaction mixture was retained for 2.4 seconds.
- the solution was fed to the reactor for step (2), and simultaneously, a solution of cyclohexanol in methylene chloride having a concentration of 1.0 mol / liter was sent into the reactor for step (2) at a flow rate of 2. OmlZ.
- the reaction product was sent to the microreactor for the step (3), and at the same time, the concentration of 1.4 mol / liter of triethylamine / methylene chloride.
- the solution was sent at a flow rate of 4.Oml / min, and after the above reaction operation was performed for 4 minutes, (3) the for micro reaction product solution derived from the re actor, was collected for 1 minute in a sample bottle containing an internal standard.
- the amount of TFAA used in the above step (1) was 1.2 equivalents, the reaction temperature in the step (1) was 120 ° C, and the reaction time was 2.4 seconds. I got it.
- the content of the compound in the collected reaction product solution was quantified by a gas chromatograph standard method. The results are shown below.
- a SUS tube (inner diameter: 1.0 mm, length: 20 cm) was connected to each of the two sulfoxide-containing liquids and the liquid introduction channel containing the activator for the sulfoxide compound, and this was connected to the liquid supply source.
- a microreactor (same as for step (1)) was used.
- '' A SUS tube (1.0 mm ID, 10 cm length) for connecting the reaction product liquid derivation channel of the microreactor in step (1) and the reaction product liquid introduction channel of the microreactor in step (2) )
- Internal diameter 1.0 mm, length 20 cm).
- a microreactor (same as the miter port reactor for step (1)) was used.
- reaction product liquid outlet channel of the microreactor in the step (2) and the reaction product liquid introduction channel for the step (3) were connected by a connecting SUS tube (inner diameter 1.0 Omm, length 10 cm).
- the basic compound introduction channel of the microreactor for the process (3) and the basic compound supply source are connected by a SUS tube '(inner diameter: 1.0 mm, length: 20 cm) to generate anti- ⁇ A SUS tube (1.0 mm ID, 20 cm length) for deriving the reaction product liquid was connected to the liquid derivation channel.
- micro-reactors and actors for the above steps (1), (2) and (3) and the SUS tube connected to the micro-reactors were immersed in a low-temperature constant temperature bath set at a temperature of 20 ° C.
- a PTFE (polytetrafluoroethylene) tube (inner diameter ⁇ !, length 50 cm) is connected to the end of the SUS tube for deriving the reaction product solution of the microreactor for the process (3).
- a SUS tube (1.0 mm inside diameter, 100 cm length) was connected, and only this connection tube was immersed in a water bath at a temperature of 30 ° C.
- a hexanol / methylene chloride solution with a concentration of 1.0 mol / liter at the mouth of the liquid was sent at a flow rate of 2.0 mL / min to the micromixer for step (2), and the reaction mixture Immediately after the residence time of 1.2 seconds, the reaction product solution was sent to the microreactor for step (3), and at the same time, a 1.5 mol / L solution of triethylamine / methylene chloride was added.
- Flow rate 4. After sending the solution at OmlZ minutes and performing the above-mentioned reaction operation for 4 minutes, the reaction product solution derived from the microreactor for step (3) was placed in a sample bottle containing an internal standard substance for 1 minute. Collected.
- the amount of TFAA used in the above step (1) was 1.0 equivalent, the reaction temperature in the step (1) was 120 ° C., and the reaction time was 2.4 seconds.
- the content of the compound in the collected reaction product solution was determined by gas chromatography internal standard method. The results are shown below.
- a SUS tube (inner diameter: 1.0 mm , length: 20 cm) is connected to each of the two liquid introduction channels containing the sulfoxide-containing liquid and the activator for the sulfoxide compound, and this is connected to the liquid supply source. I It was.
- a microreactor (same as for step (1)) was used.
- a SUS tube (1.0 mm in diameter, 10 cm in length) was used to connect the reaction product liquid derivation channel of the microreactor in step (1) and the reaction product liquid introduction channel of the microreactor in step (2). ), And the alcohol supply source was connected to the alcohol introduction channel of the microphone port reactor for the process (2) by a SUS tube (inner diameter 1.0 mm, length 20 cm).
- Micro reactor (same as micro reactor for process (1))
- reaction product liquid outlet channel of the microreactor in step (2) and the reaction product liquid introduction channel for step (3) are connected by a SUS tube (1.0 mm in diameter, 10 cm in length) for connection. Connected.
- basic compound introduction channel of the micro reactor for step (3) and the basic compound supply source are connected by a SUS tube (diameter: 1.0 mm, length: 20 cm). Then, a SUS tube (1.0 min ID, 20 cm length) for deriving the reaction product solution was connected to the reaction product solution derivation channel.
- microreactors for the above steps (1), (2) and (3) and the SUS tubes connected to the microreactors were immersed in a low-temperature constant temperature bath set at a temperature of ⁇ 20 ° C.
- a PTFE tube Polytetrafluoroethylene
- SUS tube Diameter: 50 cm
- DMSO dimethyl sulfoxide
- TFAA Fluoroacetic acetic anhydride
- the reaction product liquid was sent to the microreactor for step (3), and at the same time, the concentration of 1. 5 mol / liter trietinoreamine Pump the Z-methylene chloride solution at a flow rate of 4.0 mlZ. After the above-mentioned reaction operation was performed for 4 minutes, the reaction product derived from the reactor for the step (3) was collected in a sample bottle containing an internal standard substance for 1 minute.
- the amounts of DMS O and TFAA used in the above step (1) were 1.0 equivalent, the reaction temperature in the step (1) was ⁇ 20 ° C., and the reaction time was 2.4 seconds.
- the content of the compound in the collected reaction product solution was quantified by gas chromatography internal standard method. The results are shown below.
- a SUS tube (inner diameter: 1.0 mm, length: 20 cm) was connected to each of the two sulfoxide-containing liquids and the liquid channel containing the activator for the sulfoxide compound, and this was connected to the liquid supply source. .
- a microreactor (same as for process (1)) was used.
- Microactor (same as microactor for process (1))
- reaction product solution outlet channel of the microreactor in step (2) and the reaction product solution introduction channel for step (3) are connected by a connecting SUS tube (inner diameter: 1.0 mm, length: 10 cm). Connected.
- the basic compound introduction channel of the microreactor for the step (3) and the basic compound supply source were connected by a SUS tube (inner diameter: 1.0 mm, length: 20 cm) to generate a reaction.
- a SUS tube (1.0 mm ID, length 20 cm).
- the microreactor for the above steps (1), (2) and (3) and the SUS tube connected to the microreactor were immersed in a low-temperature constant temperature bath set at a temperature of 120 ° C.
- a PTFE (Polytetrafluoroethylene) tube (inner diameter l mm, length 50 cm) is connected to the end of the SUS tube for deriving the reaction product solution of the microreactor for step (3).
- a SUS tube inner diameter 1.0mni, length 100 era was connected, and only this connection tube was immersed in a water bath at a temperature of 30 ° C.
- the microreactor for the process (1) was added to a dimethylsulfoxide / methylene chloride solution with a concentration of 4.0 mol / liter and a trifluorine solution with a concentration of 2.4 mol / liter.
- Acetic anhydride (TF AA) Z methylene chloride solution was sent at a flow rate of 1. OmlZ min, and the reaction mixture was retained for 2.4 seconds.
- a hexanol / methylene chloride solution with a concentration of 1.0 mol Z liter was sent at a flow rate of 2.Onil / min, and the reaction mixture was retained.
- the reaction product is sent to the microreactor for step (3), and at the same time, a 3.0 mol / liter concentration of triethylamine Z-methylene chloride solution At a flow rate of 4.0 ml / min, and after performing the above-mentioned reaction operation for 4 minutes, the step (3)
- the amount of TFAA used in the above step (1) was 1.2 equivalents, the reaction temperature in the step (1) was 120 ° C., and the reaction time was 2.4 seconds.
- the content of the compound in the collected reaction product solution was quantified by gas chromatography internal standard method. The results are shown below.
- Each of the two sulfoxide-containing liquids and the sulfoxide-containing activator-containing liquid introduction channel has a s SS tube (inner diameter:
- a microreactor (same as for step (1)) was used.
- reaction product liquid derivation channel of the microreactor in the step (1) and the reaction product liquid introduction channel of the microreactor in the step (2) are connected with a SUS tube for connection (1.0 mm in diameter, length of 1 mm). 0 cm), and the alcohol supply source and the alcohol introduction channel of the microphone mouth reactor for the process (2) are connected by SUS tubing (1.0 mm ID, 20 cm length). Connected.
- Microreactor (Same as microreactor for process (1)
- the reaction product solution outlet channel of the microreactor in the step (2) and the reaction product solution introduction channel for the step (3) were connected by a SUS tube for connection (1.0 in inner diameter, 10 cm in length).
- the basic compound introduction channel of the microreactor for step (3) and the basic compound supply source were connected by a SUS tube (inner diameter 1.0 mm, length 20 cm), and the reaction product A SUS tube (1.0 mm inner diameter, 20 cm length) for deriving the reaction product liquid was connected to the outlet channel.
- microreactor for the above steps (1), (2) and (3) and the SUS tube connected to the microreactor were immersed in a low-temperature constant temperature bath set at a temperature of 120 ° C.
- PTFE Pulrite Torafuruo port ethylene
- inner diameter l mm, length 5 0 cni SUS tube through the (inner diameter 1. Oram, length 100 cm) was connected, and only this connection tube was immersed in a water bath at a temperature of 30 ° C.
- reaction product was sent to the reactor for the process (3), and at the same time, the concentration of 0.3 mol / liter of triethylamine / liter was added.
- the methylene chloride solution is sent at a flow rate of 4.
- microphone for step (3) B Li Aku The reaction product derived from the sampler was collected for 1 minute in a sample bottle containing an internal standard.
- the amount of TFAA used in the above step (1) was 1.2 equivalents, the reaction temperature in the step (1) was 120 ° C., and the reaction time was 2.4 seconds.
- the content of the compound in the collected reaction product solution was quantified by gas chromatography internal standard method. The results are shown below.
- a microreactor (same as for step (1)) was used.
- Microreactor (Same as microreactor for process (1)
- reaction product liquid outlet channel of the microreactor in step (2) and the reaction product liquid introduction channel for step (3) were connected by a SUS tube (inner diameter 1.0 mm, length 10 cm) for connection.
- the basic compound introduction channel of the microreactor for the step (3) and the basic compound supply source are connected by SUS, a tube (1.0 mm in inner diameter, 20 cm in length), and the reaction product A SUS tube (1.0 mm ID, 20 cm length) for deriving the reaction product liquid was connected to the outlet channel.
- the microreactor for the above steps (1), (2), and (3) and the SUS tube connected to the microreactor were immersed in a low-temperature constant temperature bath set at a temperature of 0 ° C.
- a PTFE (polytetrafluoroethylene) tube (inner diameter l mm, length 50 cm) is used to connect the SUS tube (inner diameter) to the end of the SUS tube for deriving the reaction product solution of the microreactor for step (3). (1.0 mm, length: 100 cm), and only this connection tube was immersed in a water bath at a temperature of 30 ° C.
- the microreactor for the process (1) was placed in a 4.0 mol / liter dimethyl sulfoxide / methylene chloride solution and a 3.0 mol / liter trifluoracetic anhydride ( TF AA) / methylene chloride solution at a flow rate of 1.0 ml / min. After the reaction mixture dwell time of 2.4 seconds, the reaction product is immediately sent to the microreactor for the process (2), and at the same time, the concentration of the solution is 1.0 mol / liter.
- TF AA trifluoracetic anhydride
- the hexanol / methylene chloride solution was sent at a flow rate of 2.0 ml / min to the microreactor for step (2), and after a reaction mixture liquid residence time of 1.2 seconds, the reaction product was immediately added to the step (2).
- the amount of TFAA used in the above step (1) was 1.5 equivalents, the reaction temperature in step (1) was 0 ° C, and the reaction time was 2.4 seconds.
- Compounds in the collected reaction product liquid Content was determined by gas chromatography internal standard method. The results are shown below.
- a microreactor (same as for step (1)) was used.
- a SUS tube (1.0 mm in inner length, 10 mm in length) for connecting the reaction product liquid introduction channel of the microreactor in step (1) and the reaction product liquid introduction channel of the microreactor in step (2) is used. cm), and the alcohol supply source and the alcohol inlet channel of the microphone mouth reactor for the process (2) were connected by a SUS tube (1.0 dragon inside diameter, 20 cm length).
- Micro reactor (same as micro reactor for process (1))
- reaction product solution outlet channel of the microreactor in step (2) and the reaction product solution introduction channel for step (3) were connected by a connecting SUS tube (inner diameter 1.0 mm, length 10 cm).
- the basic compound introduction channel of the microreactor for the process (3) and the basic compound supply source were connected by a SUS tube (inner diameter 1.0 mm, length 20 cm), and the reaction was performed.
- a SUS tube (1.0 mm ID, 20 cm length) for deriving the reaction product liquid was connected to the product solution derivation channel.
- the microreactor for the above steps (1), (2) and (3) and the SUS tube connected to the microreactor were immersed in a low-temperature constant-temperature bath set at a temperature of 20 ° C.
- the reaction product of the micro reactor for process (3) Connect the SUS tube (inner diameter 1.. . ⁇ length 100 cm) to the end of the SUS tube for deriving the solution via a PTFE (polytetrafluoroethylene) tube (inner diameter l mm, length 50 cm) Then, only this connection tube was immersed in a water bath at a temperature of 30 ° C.
- reaction product solution was sent to the microreactor for step 3), and at the same time, a 1.5 mol / liter solution of triethylamine Z methylene chloride solution was added. At a flow rate of 4.0 ml / min. After 4 minutes, the reaction product derived from the microreactor for step (3) was collected in a sample bottle containing an internal standard for 1 minute.
- the amount of TFAA used in the above step (1) was 1.2 equivalents, the reaction temperature in the step (1) was ⁇ 20 ° C., and the reaction time was 2.4 seconds.
- the content of the compound in the collected reaction product solution was quantified by gas chromatography 'graph internal standard method. The results are shown below.
- the steps (1), (2) and (3) were carried out using the following reactor.
- a SUS tube (inner diameter: 1.0 mm, length: 2 Ocm) was connected to each of the two sulfoxide-containing liquids and the liquid channel containing the activator for the sulfoxide compound, and this was connected to the liquid supply source. .
- a microreactor (same as for step (1)) was used.
- a SUS tube (1.0 mm ID, length 1 mm) for connecting the reaction product liquid introduction channel of the microreactor in step (1) and the reaction product liquid introduction channel of the microreactor in step (2). 0 cm), and the alcohol supply source and the alcohol introduction channel of the microphone mouth reactor for the process (2) were connected by a SUS tube (inner diameter 1.0 mm, length 20 cm). .
- Microreactor (Same as microreactor for process (1)
- reaction product solution outlet channel of the microreactor in step (2) and the reaction product solution introduction channel for step (3) are connected by a connecting SUS tube (inner diameter 1.0 mm, length 10 cm). did. Ma
- the basic compound introduction channel of the microreactor for the process (3) and the basic compound supply source were connected by a SUS tube (inner diameter: 1.0 ⁇ , length: 20 cm), and the reaction product liquid was derived.
- a SUS tube (1.0 mm ID, 20 cm length) for deriving the reaction product was connected to the channel.
- microreactors for the above steps (1), (2), and (3) and the SUS tubes connected to the microreactors were immersed in a low-temperature constant temperature bath set at a temperature of 120 ° C.
- a PTFE tube polyethylene tetrafluoroethylene
- ner diameter l mra outer diameter
- length 5 Ocm outer diameter
- this connection tube alone was immersed in a water bath at a temperature of 30 ° C.
- the microreactor for the process (1) was added to a 4.0 molar concentration of dimethylsulfoxide in methylene chloride and a 2.4 molar concentration of trifluoroacetic acid.
- Anhydrous anhydride (TF AA) and methylene chloride solution were each sent at a flow rate of 1.0 ml / min, and after 2.4 seconds of residence time of the reaction mixture, the reaction product was immediately added to the microphone for step (2).
- reaction product was sent to the microreactor for step (3), and at the same time, triethylamine methylene chloride having a concentration of 1.5 mol liter was used. The solution was sent at a flow rate of 4.Oml / min, and the above reaction procedure was performed. After 4 minutes, the reaction product derived from the microreactor for step (3) was collected in a sample bottle containing an internal standard for 1 minute.
- the amount of TFAA used in the above step (1) was 1.2 equivalents
- the reaction temperature in step (1) was 120 ° C and the reaction time was 2.4 seconds.
- the content of the compound in the collected reaction product solution was determined by gas chromatography internal standard method. The results are shown below.
- a SUS tube (inner diameter: 1.0 mm, length: 20 cm) was connected to each of the two sulfoxide-containing liquids and the liquid channel containing the activator for the sulfoxide compound, and this was connected to the liquid supply source. .
- a microreactor (same as for step (1)) was used.
- a SUS tube for connection (1.0 mm ID, length) is connected between the reaction product liquid derivation channel of the microreactor in step (1) and the reaction product liquid introduction channel of the microreactor in step (2). 10 cm), connect the alcohol supply source and the process (2) microphone
- the mouth reactor was connected to the anorecol introduction channel using a SUS tube (inner diameter 1.0 mm, length 20 cm).
- Micro reactor (same as micro reactor for process (1))
- the reaction product liquid outlet channel of the microreactor in step (2) was connected to the reaction product liquid introduction channel for step (3) by a connecting SUS tube (1.0 ⁇ in inside diameter, 10 cm in length).
- the basic compound introduction channel of the microreactor for the process (3) and the basic compound supply source are connected by a SUS tube (1.0 mm in inner diameter, 2 O cm in length), and the reaction product liquid is derived.
- a SUS tube (1.0 nm inside diameter, 20 cm length) for deriving the reaction solution was connected to the channel.
- the microreactor for the above steps (1), (2) and (3) and the SUS tube connected to the microreactor were immersed in a low-temperature constant temperature bath set at a temperature of 120 ° C.
- the SUS tube inside diameter l mm, length 50 cm
- the SUS tube inside diameter l mm, length 50 cm
- the reaction product solution of the microreactor for step (3) is connected to the end of the SUS tube for deriving the reaction product solution of the microreactor for step (3). (1.0 mm, length: 100 cm), and only this connection tube was immersed in a water bath at a temperature of 30 ° C.
- the microreactor for the process (1) was added to a dimethylsulfoxydonomethylene chloride solution with a concentration of 4.0 moles and a toluene solution with a concentration of 2.4 moles / liter.
- Fluoroacetic anhydride (TF AA) and methylene chloride solution were each sent at a flow rate of 1. Oiul / min, and after a reaction mixture residence time of 2.4 seconds, the reaction product was immediately used for step (2).
- the solution is sent to the microreactor, and at the same time, a hexane / methylene chloride solution with a concentration of 1.0 M
- the OmlZ fraction is sent to the microreactor for step (2), and immediately after the reaction mixture liquid residence time of 1.2 seconds, the reaction product liquid is sent to the microreactor for step (3).
- a solution of triethylamine / methylene chloride at a concentration of 1.'4 mol / liter was sent at a flow rate of 4. Oml / min, and after the above reaction operation was performed for 4 minutes, the microfluidic solution for step (3) was used.
- the reaction product derived from the reactor was collected in a sample bottle containing a part of the standard substance for 1 minute.
- the amount of TFAA used in the above step (1) was 1.2 equivalents, the reaction temperature in the step (1) was 120 ° C., and the reaction time was 2.4 seconds.
- the content of the compound in the collected reaction product solution was quantified by a gas chromatograph internal standard method. The results are shown below.
- a microreactor (same as for step (1)) was used.
- a SUS tube for connection (1.0 mm ID, length) is connected to the reaction product liquid introduction channel of the microreactor in step (1) and the reaction product liquid introduction channel of the microreactor in step (2). 10 cm), and the alcohol supply source and the alcohol introduction channel of the microphone opening reactor for the process (2) were connected by a SUS tube (1.0 mm in diameter, 20 cm in length).
- Micro reactor (same as micro reactor for process (1))
- reaction product solution outlet channel of the microreactor in step (2) and the reaction product solution introduction channel for step (3) are connected by a SUS tube (1.0 mm in diameter, 10 cm in length) for connection.
- SUS tube 1.0 mm in diameter, 10 cm in length
- basic compound introduction channel of the microreactor for the process (3) and the basic compound supply source were connected by a SUS tube (inner diameter 1.0 mm, length 20 cm)
- a SUS tube 1.0 ⁇ inner diameter, 20 cm length
- the microreactor for the above steps (1), (2) and (3) and the SUS tube connected to the microreactor were immersed in a low-temperature constant temperature bath set at a temperature of ⁇ 20 ° C.
- PTFE Pulrite Torafuruo port ethylene tubing (inner diameter l mm, length 5 0 cm) through a SUS tube ( (Inner diameter 1.0 mm, length 100 cm). Only the probe was immersed in a water bath at a temperature of 30 ° C.
- step (3) a reaction product solution derived from the micro reactance coater for., was collected for 1 minute in a sample bottle containing an internal standard.
- the amount of TFAA used in the above step (1) was 1.2 equivalents, the reaction temperature in the step (1) was ⁇ 20 ° C., and the reaction time was 2.′4 seconds.
- the content of the compound in the collected reaction product solution was quantified by gas chromatography internal standard method. The results are shown below.
- a SUS tube (inner diameter: 1.0 mm, length: 20 cm) was connected to each of the two sulfoxide-containing liquids and the liquid channel containing the activator for the sulfoxide compound, and this was connected to the liquid supply source. .
- a microreactor (same as for step (1)) was used.
- a SUS tube (0.1 mm in inner diameter, length 3 .1 mm) for connecting the reaction product liquid introduction channel of the microreactor of step (1) and the reaction product introduction channel of the microreactor of step (2). 2 cm), and the alcohol supply source and the alcohol introduction channel of the microreactor for the process (2) were connected by a SUS tube (inner diameter 1.0 mm, length 20 cm).
- Microreactor (Same as microreactor for process (1)
- reaction product solution outlet channel of the microreactor in the step (2) and the reaction product solution introduction channel for the step (3) were connected by a connecting SUS tube (inner diameter: 1.0 mm, length: 10 cm).
- the basic compound introduction channel of the microreactor for step (3) and the basic compound supply source were connected by a SUS tube (inner diameter 1.0 mm, length 20 cm), and the reaction was performed.
- a SUS tube (1.0 mm ID, length 20 cm).
- microreactor for the above steps (1), (2) and (3) and the SUS tube connected to the microreactor were immersed in a low-temperature constant temperature bath set at a temperature of 20 ° C.
- end of the reaction raw Narueki derivation SUS tube of step (3) microreactor for, PTFE (Porite Torafuruo port ethylene) tubing (inner diameter l mm, length 5 0 cm) through a SUS tube (inner diameter (1.0 mm, length: 100 cm), and only this connection tube was immersed in a water bath at a temperature of 30 ° C.
- the solution is fed to the reactor, and at the same time, a oxanol / methylene chloride solution is fed into the mouth of the solution at a concentration of 1.0 mol / liter at a flow rate of 2.OmlZ, and the reaction mixture is retained for 1.2 seconds.
- the reaction product solution is sent to the microreactor for step (3), and at the same time, a 1.5 mol / liter triethylamine / methylene chloride solution is supplied at a flow rate of 4.O ml / min.
- the process (3) The reaction product solution derived from the micro-reactor was collected 1 minute in a sample bottle containing an internal standard.
- the amount of TFAA used in the above step (1) was 1.2 equivalents, the reaction temperature in the step (1) was 120 ° C, and the reaction time was 0.01 seconds.
- the content of the compound in the collected reaction product solution was determined by gas chromatography internal standard method. The results are shown below.
- sucrose hexanone from sucrose hexanol by the production method of the present invention, the steps (1), (2), and (3) were performed using the following reactor.
- a SUS tube (inner diameter: 1.0 mm, length: 20 cm) was connected to each of the two liquid introduction channels containing the sulfoxide, and the liquid containing the activator for the compound. Connected to.
- a microreactor (same as for process (1)) was used.
- a SUS tube (0.1 mm in inner diameter, length of 3.1 mm) for connecting the reaction product liquid introduction channel of the microreactor in step (1) and the reaction product liquid introduction channel of the microreactor in step (2). 2 cm), connect the alcohol supply source and the alcohol introduction channel of the process (2) ⁇ reactor mouth to the SUS tube (inner diameter 1.0 min, length 20 cm). More connected.
- Microreactor (Same as microreactor for process (1)
- the reaction product liquid derivation channel of the microreactor in step (2) and the reaction product liquid introduction channel for step (3) are connected to a SUS tube for connection (1.0 mm ID, 10 cm length).
- the basic compound introduction channel of the microreactor for the step (3) and the basic compound supply source were connected by a SUS tube (inner diameter 1.0 mm, length 20 cm).
- a SUS tube (1.0 mm inner diameter, 20 cm length) for deriving the reaction product solution was connected to the reaction product solution derivation channel.
- the microreactor for the above steps (1), (2), and (3) and the SUS tube connected to the microreactor were immersed in a low-temperature constant temperature bath at a temperature of 0 ° C.
- a PTFE (polytetrafluoroethylene) tube (inner diameter l mm, length 50 cm) is connected to the end of the SUS tube for deriving the reaction product solution of the micro reactor for the process (3). (With an inner diameter of 1.0 mm and a length of 100 cm), and this connection tube alone was immersed in a water bath at a temperature of 30 ° C.
- a microreactor for the process (1) was added to a dimethylsulfoxide chloride / methylene chloride solution with a concentration of 4.0 moles Z and a trifluoacetic acid with a concentration of 2.4 moles / liter.
- Anhydrous anhydride (TF AA) and methylene chloride solution were each sent at a flow rate of 1.0 ml / min. After the reaction mixture had a residence time of 0.01 second, the reaction product was immediately added to the microreactor for step (2).
- the solution is sent to the actor, and at the same time, a solution of 1.0 mol Z liter of the hexanol Z methylene chloride solution is sent to the micro reactor for the process (2) at a flow rate of 2.Oml / min.
- the reaction product was sent to the microreactor for step (3), and at the same time, triethylamine / chloride with a concentration of 1.5 mol / liter was added.
- the microcleaner for process (3) The reaction product derived from the reactor was collected in a sample bottle containing an internal standard for 1 minute.
- the amount of TFAA used in the above step (1) was 1.2 equivalents, the reaction temperature in the step (1) was 0 ° C., and the reaction time was 0.01 seconds.
- the content of the compound in the collected reaction product solution was determined by gas chromatography internal standard method. The results are shown below.
- a SUS tube (inner diameter: 1.0 mm, length: 20 cm) was connected to each of the two liquid channels containing the sulfoxide-containing liquid and the activator for the sulfoxide compound, and this was connected to the liquid supply source.
- reaction product liquid introduction channel of the microreactor in step (2) are connected with a SUS tube (inner diameter 0.1 mm, length 3.2 cm) for connection.
- the alcohol introduction channel of the microreactor for (2) was connected with a SUS tube (1.0 mm inside diameter, 20 cm length).
- reaction product solution outlet channel of the microreactor in step (2) and the reaction product solution introduction channel for step (3) were connected by a connecting SUS tube (inner diameter 1.0 mm, length 10 cm).
- basic compound introduction channel of the microreactor for the step (3) and the basic compound supply source were connected by a SU S. tube (inner diameter 1.0 mm, length 20 cm), A SUS tube (1.0 mm ID, 20 cm length) for deriving the reaction product solution was connected to the reaction product solution channel. .
- the microreactor for the above steps (1), (2) and (3) and the SUS tube connected to the microreactor were immersed in a low-temperature constant temperature bath set at a temperature of 20 ° C.
- the SUS tube (inside diameter l mm, length 50 cm) is passed through the PTFE tube (inside diameter lmm, length 50 cm) to the end of the SUS tube for deriving the reaction product liquid of the microreactor for step (3).
- 1.0 mm, length lOO cni was connected, and only this connection tube was immersed in a water bath at a temperature of 30 ° C.
- a microreactor for the process (1) was added to a 4.0 mol / liter concentration of dimethyl sulfoxide / methylene chloride solution and a 2.4 mol / liter concentration of trifluoroacetic acid.
- the reaction mixture is immediately sent to the microreactor for the process (2) after the reaction mixture dwell time is 0.01 seconds, and at the same time, the concentration of the solution is adjusted to 1.0 mol Z liter.
- the hexanol / methylene chloride solution was sent to the microreactor for the process (2) at a flow rate of 2.0 ml / min, and immediately after the reaction mixture liquid residence time of 1.2 seconds, the reaction product was The solution was sent to the microreactor for step (3), and at the same time, a solution of triethylamine Z methylene chloride having a concentration of 1.4 mol liter was sent at a flow rate of 4.OmlZ, and the above-described reaction operation was performed for 4 minutes. Thereafter, the reaction product derived from the microreactor for step (3) was collected in a sample bottle containing an internal standard substance for 1 minute.
- the amount of TFAA used in the above step (1) was 1.2 equivalents, the reaction temperature in the step (1) was 20 ° C., and the reaction time was 0.01 second. .
- the content of the compound in the collected reaction product solution was determined by gas chromatography internal standard method. The results are shown below.
- a microreactor (same as for process ()) was used.
- a SUS tube for connection (1.0 mm in inner length, 10 mm in length) is used to connect the reaction product liquid derivation channel of the microreactor in step (1) and the reaction product liquid introduction channel of the microreactor in step (2). ), and the alcohol supply source was connected to the alcohol introduction channel of the microphone mouth reactor for the process (2) using a SUS tube (inner diameter 1.0 mm, length 20 cm). .
- Micro reactor (same as micro reactor for process (1))
- the reaction product outlet channel of the microreactor in step (2) and the reaction product inlet channel for step (3) were connected by a connecting SUS tube (inner diameter 1.0 mm, length 10 cm).
- the basic compound introduction channel of the microreactor for the process (3) and the basic compound supply source were connected by a SUS tube (inner diameter 1.0 mm, length 20 cm), and the reaction was performed.
- a SUS tube (1.0 ⁇ in inside diameter, 20 cm in length) for deriving the reaction product liquid was connected to the product liquid derivation channel.
- the microreactor for the above steps (1), (2) and (3) and the SUS tube connected to the microreactor were immersed in a low-temperature constant temperature bath set at a temperature of 0 ° C.
- the reaction product liquid of the microreactor for process (3) Connect a SUS tube (1.0 mm in diameter, 100 cm in length) to the end of the SUS tube for derivation via a PTFE (polytetrafluoroethylene) tube (inner diameter l mm, length 50 cm). Only this connection tube was immersed in a water bath at a temperature of 30 ° C.
- a dimethylsulfoxide / methylene chloride solution with a concentration of 4.0 mol / liter and a trifluoride solution with a concentration of 2.4 mol / liter were added to the microreactor for the process (1) using a gas tight syringe.
- the acetic anhydride (TFAA) / methylene chloride solution was sent at a flow rate of 1.0 ml / min, respectively. After a residence time of the reaction mixture of 2.3 seconds, the reaction product was immediately used for the step (2). The solution is sent to the microreactor.
- the solution of hexanol Z methylene chloride at a flow rate of 1.0 mol Z liter is sent to the microreactor for the process (2) at a flow rate of 2.0 ml / min.
- the reaction product solution was sent to the reactor for the process (3), and at the same time, triethylamine / concentration of 1.5 mol Z liter was added.
- the methylene chloride solution was sent at a flow rate of 4. After 4 minutes, the reaction product derived from the microreactor for step (3) was collected in a sample bottle containing an internal standard for 1 minute.
- the amount of TFAA used in the above step (1) was 1.2 equivalents, the reaction temperature in the step (1) was 0 ° C., and the reaction time was 2.4 seconds.
- the results are shown below.
- Cyclohexanone 32 2% Cyclohexanolate Trifolenoacetate.7% Cyclic hexinolemethinolethiomethinoleate 3% Cyclohexanolone 50%
- Cyclohexanone 32 2% Cyclohexanolate Trifolenoacetate.7% Cyclic hexinolemethinolethiomethinoleate 3% Cyclohexanolone 50%
- a SUS tube (inner diameter: 1.0 mm, length: 2 Ocm) was connected to each of the two sulfoxide-containing liquids and the liquid channel containing the activator for the sulfoxide compound, and this was connected to the liquid supply source. .
- a microreactor (same as for step (1)) was used.
- reaction product liquid derivation channel of the microreactor in step (1) and the reaction product liquid introduction channel of the microreactor in step (2) are connected to a SUS tube for connection (0.25 mm in inner diameter, 3 mm in length). 2 cm) to connect the alcohol supply source and the alcohol inlet channel of the reactor for the process (2) with a SUS tube (inner diameter 1.0 mm, length 20 cm) Connected by
- Microreactor (same as microreactor for process (1))
- reaction product solution outlet channel of the microreactor in step (2) and the reaction product solution introduction channel for step (3) were connected by a connecting SUS tube (inner diameter 1.0 mm, length 10 cm). .
- SUS tube inner diameter 1.0 mm, length 10 cm.
- the basic compound introduction channel of the microreactor for step (3) and the basic compound supply source were connected by a SUS tube (inner diameter: 1. Oram, length: 20 cm), and the reaction product A SUS tube (1.0 mm inner diameter, 20 cm length) for deriving the reaction product solution was connected to the outlet channel.
- microreactor for the above steps (1), (2), and (3) and the SUS tube connected to the microreactor were immersed in a low-temperature constant temperature bath set at a temperature of 120 ° C.
- a dimethylsulfoxide / methylene chloride solution with a concentration of 2.0 mol / liter was flowed into the microreactor for the process (1) at a flow rate of 4.0 ml / min.
- a solution of trifluoroacetic anhydride (TF AA) Z in methylene chloride was supplied at a flow rate of 2.0 ml / min, and the reaction mixture was immediately discharged after 2 seconds of residence time of the reaction mixture.
- the solution is sent to the microreactor for (2), and at the same time, a cyclohexanol / methylene chloride solution having a concentration of 2.0 mol / liter is supplied to the microreactor for process (2) at a flow rate of 2.
- reaction product solution derived from the B reactor and collected for one minute in a sample bottle containing an internal standard.
- a SUS tube (inner diameter: 1.0 mm, length: 20 cm) was connected to each of the two sulfoxide-containing liquids and the liquid channel containing the activator for the sulfoxide compound, and this was connected to the liquid supply source. .
- a microreactor (same as for step (1)) was used.
- a SUS tube for connection (inner diameter 1.0 ⁇ , length 10 cm) is used to connect the reaction product liquid derivation channel of the microreactor in step (1) and the reaction product liquid introduction channel of the microreactor in step (2).
- the alcohol supply source was connected to the alcohol introduction channel of the reactor with the microphone opening for the process (2) using a SUS tube (inner diameter 1.0, length 20 cm).
- Microreactor (Same as microreactor for process (1)
- reaction product liquid outlet channel of the microreactor in step (2) and the reaction product liquid introduction channel for step (3) are connected by a SUS tube (1.0 mm ID, 10 cm length) for connection. did. Ma
- the basic compound introduction channel of the microreactor for the process (3) and the basic compound supply source were connected by a SUS tube (inner diameter 1.0 mm, length 20 cm), and the reaction was generated.
- a SUS tube (1.0 in inside diameter, 20 cm in length) for connecting the reaction product solution was connected to the solution delivery channel.
- microreactor for the above steps (1), (2), and (3) and the SUS tube connected to the microreactor were immersed in a low-temperature constant temperature bath set at a temperature of 120 ° C.
- a dimethylsulfoxide / methylene chloride solution with a concentration of 2.0 mol / liter was flowed into the microreactor for the process (1) at a flow rate of 4.OmlZ and a concentration of 3.0 mol / liter.
- Toluene trifluoroacetic anhydride (TF AA) Z methylene chloride solution was sent at a flow rate of 2.Oml / min, and the reaction mixture was immediately discharged after 0.8 seconds of residence time of the reaction mixture.
- the solution is sent to the microreactor for (2), and simultaneously, a methylene chloride solution of cyclohexanol at a concentration of 2.0 mol / liter is supplied at a flow rate of 2. Oml / min.
- the reaction product is immediately sent to the microreactor for step (3), and at the same time, triethylamine is supplied at a flow rate of 1.
- the for micro reaction product solution derived from the re actor was collected for 1 minute in a sample bottle containing an internal standard. The content of the compound in the collected reaction product solution was quantified by gas chromatography internal standard method. The results are shown below.
- a SUS tube (inner diameter: 1.0 mm, length: 2 Ocm) was connected to each of the two sulfoxide-containing liquids and the liquid channel containing the activator for the sulfoxide compound, and this was connected to the liquid supply source. .
- a SUS tube (1.0 mm in inner diameter, 10 mm in length) was used to connect the reaction product liquid derivation channel of the microreactor in step (1) and the reaction product liquid introduction channel of the microreactor in step (2). cm), and the alcohol supply source was connected to the alcohol introduction channel of the reactor with the microphone opening for the step (2) using a SUS tube (inner diameter 1.0 mm, length 20 cm).
- Micro reactor (same as micro reactor for process (1))
- reaction product solution outlet channel of the microreactor in step (2) and the reaction product solution introduction channel for step (3) are connected by a connecting SUS tube (inner diameter: 1.0 mm, length: 10 cm). Connected. Ma
- the basic compound introduction channel of the microreactor for step (3) and the basic compound supply source were connected by a SUS tube (1.0 mm in inner diameter, 20 cm in length), and the reaction product A SUS tube (1.0 mm inner diameter, 20 cm length) for deriving the reaction product liquid was connected to the outlet channel.
- microreactor for the above steps (1), (2), (3) and the SUS tube connected to the microreactor were immersed in a low-temperature constant temperature bath set at a temperature of 30 ° C.
- a dimethylsulfoxide / methylene chloride solution with a concentration of 2.0 mol / liter was added to the microreactor for the process (1) at a flow rate of 4.OmlZ and a concentration of 3.
- a solution of 0 mol / liter of trifluoroacetic anhydride (TFAA) / methylene chloride was sent at a flow rate of 2.
- reaction product is sent to the microreactor for step (2), and at the same time, a cyclohexanol Z methylene chloride solution having a concentration of 2.0 mol / liter is flowed at a flow rate of 2.Oml / min.
- the solution is sent to the microreactor for (2), and after 0.6 seconds of residence time of the reaction mixture, the reaction product is immediately sent to the microreactor for step (3), and at the same time, triethylamine is sent.
- the solution was sent at a flow rate of 1.6 mlZ, and after performing the above-mentioned reaction operation for 4 minutes, The microphone b reaction product solution derived from the re actor, was collected for 1 minute in a sample bottle containing an internal standard.
- the content of the compound in the collected reaction product solution was quantified by gas chromatography internal standard method. The results are shown below.
- a SUS tube (inner diameter: 1. ⁇ , length 20 cm) was connected to each of the two sulfoxide-containing liquids and the liquid channel containing the activator for the sulfoxide compound, and this was connected to the liquid supply source. .
- a microreactor (same as for step (1)) was used.
- a SUS tube (1.0 mm ID, length 1 mm) for connecting the reaction product liquid introduction channel of the microreactor in step (1) and the reaction product liquid introduction channel of the microreactor in step (2). 0 cm), and the alcohol supply source was connected to the alcohol inlet channel of the reactor with the microphone opening for the process (2) using a SUS tube (1.0 mm in diameter, 20 cm in length).
- Microreactor (Same as microreactor for process (1)
- a SUS tube (inner diameter 0.25 mm, length 3.2 cm) was used to connect the reaction product solution outlet channel of the micro reactor in step (2) and the reaction product solution introduction channel for step (3). ) .
- the basic compound introduction channel of the microreactor for the step (3) and the basic compound supply source were connected by a SUS tube (inner diameter 1. ⁇ , length 20 cm), and the reaction was generated.
- a SUS tube (1.0 mm ID, 20 cm length) for deriving the reaction product liquid was connected to the liquid derivation channel.
- microreactors for the above steps (1), (2) and (3) and the SUS tube connected to the microreactors were immersed in a low-temperature constant temperature bath set at a temperature of 120 ° C.
- a dimethylsulfoxide / methylene chloride solution with a concentration of 2.0 mol / liter at a flow rate of 4.0 ml / min was added to the microreactor for the process (1) at a flow rate of 4.0 ml / min.
- a solution of 0 mol / liter of trifluoroacetic anhydride (TF AA) Z methylene chloride was fed at a flow rate of 2.0 ffl lZ, and immediately after the reaction mixture residence time of 0,8 seconds, Then, the reaction product solution is sent to the microreactor for step (2), and at the same time, a solution of hexanol / methylene chloride having a concentration of 2.0 mol / liter at the mouth of the cycle is fed at a flow rate of 2.0 ml / min.
- reaction mixture is sent to the microreactor for step (3) and immediately after the residence time of the reaction mixture for 0.01 seconds, the reaction product is sent to the microreactor for step (3), and After feeding tilamine at a flow rate of 1.6 ml / min and performing the above reaction for 4 minutes, The reaction raw Narueki derived from microreactor for 3), were collected 1 minute in a sample bottle containing an internal standard.
- the content of the compound in the collected reaction product solution was determined by gas chromatography internal standard method. The results are shown below.
- a SUS tube (inner diameter: 1.0 mm, length: 20 cm) was connected to each of the two sulfoxide-containing liquids and the liquid channel containing the activator for the sulfoxide compound, and this was connected to the liquid supply source. .
- a microreactor (same as for step (1)) was used.
- a SUS tube (1.0 mm inner diameter, 10 mm length) for connecting the reaction product liquid introduction channel of the microreactor of step (1) and the reaction product liquid introduction channel of the microreactor of step (2) was used. cm), and the alcohol supply source was connected to the alcohol introduction channel of the reactor with the microphone port for the step (2) using a SUS tube (inner diameter 1.0 mm, length 20 cm).
- Microreactor (Same as microreactor for process (1)
- reaction product solution outlet channel of the microreactor in step (2) and the reaction product solution introduction channel for step (3) are connected by a SUS tube (1.0 mm in diameter, 30 cm in length) for connection. Connected. Ma
- the basic compound introduction channel of the microreactor for the process (3) and the basic compound supply source are connected by a SUS tube (1.0 mm ID, 20 cm length), and the reaction product liquid output channel A SUS tube (1.0 mm inside diameter, 20 cm length) for deriving the reaction product solution was connected to this.
- microreactor for the above steps (1), (2) and (3) and the SUS tube connected to the microreactor were immersed in a low-temperature constant temperature bath set at a temperature of ⁇ 20 ° C.
- dimethylsnorreoxide / methylene chloride solution with a concentration of 2.0 mol Z liter was added to the microreactor for the process (1) at a flow rate of 4.OmlZ and a concentration of 3.0 mol.
- a mole / liter of trifluoroacetic anhydride (TFAA) / methylene chloride solution was fed at a flow rate of 2.OmlZ, and the reaction was immediately generated after 0.8 seconds of residence time of the reaction mixture.
- the solution is sent to the microreactor for step (2), and simultaneously, a 2.0-mole-liter concentration of hexanol methylene chloride solution at the mouth is flowed at a flow rate of 2. OmlZ.
- reaction mixture After 1.8 seconds, the reaction mixture is immediately sent to the microreactor for step (3), and at the same time, triethylamine is supplied at a flow rate of 1.6 mlZ min. After performing the above-mentioned reaction operation for 4 minutes, use the microphone for process (3).
- the reaction product derived from the reactor was collected in a sample bottle containing an internal standard for 1 minute.
- the content of the compound in the collected reaction product solution was quantified by gas chromatography 'graph internal standard method. The results are shown below.
- a SUS tube (inner diameter: 1.0 mm, length: 2 Ocm) was connected to each of the two sulfoxide-containing liquids and the liquid channel containing the activator for the sulfoxide compound, and this was connected to the liquid supply source. . .
- a microreactor (same as for step (1)) was used.
- a SUS tube for connection (1.0 mm ID, 10 mm in length) is used to connect the reaction product liquid derivation channel of the microreactor in step (1) and the reaction product liquid introduction channel of the microreactor in step (2). ), and the alcohol supply source was connected to the alcohol introduction channel of the microphone mouth reactor for the process (2) using a SUS tube (inner diameter 1.0 mm, length 20 cm). .
- Micro reactor (same as micro reactor for process (1))
- reaction product solution outlet channel of the microreactor in step (2) and the reaction product solution introduction channel for step (3) were connected by a connecting SUS tube (inner diameter 1.0 mm, length 10 cm). .
- SUS tube inner diameter 1.0 mm, length 10 cm.
- the basic compound introduction channel of the microreactor for step (3) and the basic compound supply source were connected by a SUS tube (1.0 mm in inside diameter, 20 cm in length), and the reaction product A SUS tube (1.0 mm ID, 20 cm length) for deriving the reaction product liquid was connected to the outlet channel.
- microreactor for the above steps (1), (2) and (3) and the SUS tube connected to the microreactor were immersed in a low-temperature constant temperature bath set at a temperature of 120 ° C. '
- a 2.2 mol / liter concentration of dimethylsulfoxide Z-methylene chloride solution was added to the microreactor for the process (1) at a flow rate of 1.0 mlZ and a concentration of 2.1 ml / liter.
- a mole / liter of trifluoroacetic anhydride (TFAA) Z methylene chloride solution was sent at a flow rate of 1. OmlZ, and the reaction was immediately continued after a reaction mixture residence time of 2.4 seconds.
- TFAA trifluoroacetic anhydride
- the product solution is sent to the microreactor for the step (2), and at the same time, a solution of oxanol Z methylene chloride having a concentration of 1.0 mol / liter in the mouth of the mouth is supplied at a flow rate of 2. OmlZ min.
- the reaction mixture is sent to the microreactor for step (3) immediately after the residence time of the reaction mixture is 1.2 seconds, and the triethylamine is simultaneously sent to the microreactor for step (3).
- the solution was sent at a flow rate of 0.8 mlZ, and the above reaction was performed for 4 minutes. 3)
- the reaction product derived from the microreactor was collected in a sample bottle containing an internal standard for 1 minute.
- the content of the compound in the collected reaction product solution was quantified by gas chromatography 'graph internal standard method. The results are shown below.
- a SUS tube (inner diameter: 1.0 mm, length 20 cm) is connected to each of the two sulfoxide-containing liquids and the liquid introduction channel containing the activator for the sulfoxide compound, and this is connected to the liquid supply source. did.
- a microreactor (same as for step (1)) was used.
- a SUS tube for connection (1.0 mm ID, 1.0 mm in length) is used to connect the reaction product liquid derivation channel of the microreactor in step (1) and the reaction product liquid introduction channel of the microreactor in step (2). ), and the alcohol supply source and the alcohol introduction channel of the reactor for the process (2) are connected with a SUS tube (inner diameter 1.0 mm, length 20 cm). did.
- Microreactor (Same as microreactor for process (1)
- reaction product liquid outlet channel of the microreactor in the step (2) and the reaction product liquid introduction channel for the step (3) were connected by a connecting SUS tube (inner diameter: 1.0 mm, length: 10 cm).
- the basic compound introduction channel of the microreactor for the process (3) and the basic compound supply source are connected by a SUS tube (inner diameter: 1.0 mm, length: 20 cm), and the reaction product liquid outlet channel is connected.
- a SUS tube (1.0 mm inside diameter, 20 cm length) for connecting the reaction product solution was connected to the tube.
- microreactors for the above steps (1), (2), and (3) and the SUS tube connected to the microreactors were immersed in a low-temperature constant temperature bath set at a temperature of 120 ° C.
- a PTFE (polytetrafluoroethylene) tube (inner diameter l mm, length 50 cm) is used to connect the SUS tube (end) to the end of the SUS tube for deriving the reaction product solution of the microreactor for step (3). (Diameter: 1.0 mm, length: 100 cm), and only this connection tube was immersed in a water bath at a temperature of 30 ° C.
- a 2.2 mol / liter dimethylsulfoxide / methylene chloride solution at a flow rate of 1.0 mlZ was added to the microreactor for the process (1) at a flow rate of 1.0 mlZ, and a concentration of 2.1 mol / liter.
- a solution of trifluoroacetic anhydride (TFAA) / methylene chloride in a little amount was fed at a flow rate of 1.0 ml / min, and the reaction was immediately generated after a residence time of 2.4 seconds of the reaction mixture.
- TFAA trifluoroacetic anhydride
- the solution was sent to the microreactor for step (2), and at the same time, a hexanol / methylene chloride solution having a concentration of 1.0 mol Z liter was added to the step (2) at a flow rate of 2.0 ml / min. ) And immediately after the reaction mixture dwell time of 1.2 seconds, the reaction product is sent to the microreactor for step (3), and at the same time, triethylamine. The solution was sent at a flow rate of 0.8 ml / min. The reaction product derived from the microactor was collected in a sample bottle containing an internal standard for 1 minute. .
- a SUS tube (inner diameter: 1.0 mm, length: 20 cm) is connected to each of the two liquid channels containing the sulfoxide-containing liquid and the activator for the sulfoxide compound, and this is connected to the liquid supply source. did.
- a microreactor (same as for step (1)) was used.
- a SUS tube (1.0 mm inner diameter, inner diameter: 1.0 mm) for connecting the reaction product liquid introduction channel of the micro reactor in step (1) and the reaction product liquid introduction channel of the micro reactor in step (2). (Length: 10 cm), connect the alcohol supply source and the alcohol inlet channel of the reactor for the process (2) with a SUS tube (internal diameter: 1.0 min, length: 20 cm) More connected.
- Microactor (same as microactor for process (1)) ) was used.
- reaction product solution outlet channel of the microreactor in step (2) and the reaction product solution introduction channel for step (3) were connected with a SUS tube (1.0 mm in diameter, 10 cm in length) for connection.
- the basic compound introduction channel of the microreactor for the process (3) and the basic compound supply source were connected by a SUS tube (inner diameter 1.0 mm, length 20 cm), and the reaction was performed.
- a SUS tube (1.0 mm ID, 20 cm length) for deriving the reaction product solution was connected to the product solution channel.
- the microreactor for the above steps (1), (2), and (3) and the SUS tube connected to the microreactor were immersed in a low-temperature constant temperature bath set at a temperature of 120 ° C.
- a PTFE tube Polytetrafluoroethylene
- SUS tube (diameter: 50 cm) to the end of the SUS tube for deriving the reaction product solution of the microreactor for step (3).
- 1.0 mm, length: 100 cm was immersed in a water bath at a temperature of 30 ° C.
- the content of the compound in the collected reaction product solution was quantified by gas chromatography internal standard method. The results are shown below.
- the temperature of the obtained mixture is returned to room temperature, an internal standard is added thereto, and the content of the compound contained in the mixture is determined by gas chromatograph internal standard method. Was measured. The measurement results are shown below.
- the temperature of the obtained mixture is returned to room temperature, an internal standard is added thereto, and the content of the compound contained in the mixture is determined by gas chromatography internal standard method. Was measured. The measurement results are shown below.
- the mixture was stirred at the above temperature for 10 minutes after the dropwise mixing.
- the resulting mixture is mixed with 1.5 mol liter of triethylamine / chloride. 4 ml of the methylene solution was mixed dropwise at an addition rate of 0.4 mlZ.
- the temperature of the obtained mixed solution is returned to room temperature, an internal standard is added thereto, and the content of the compound contained in the mixed solution is measured by a gas chromatograph internal standard method. did. The measurement results are shown below.
- Step 2 From the other inlet of the second group (Step 2), and then immediately The reaction product solution is sent from the second reaction solution outlet to one of the third two inlets, and 1.4 mo1 / L triethylamine methylene chloride from the third other inlet. The solution was sent at 4.0 mL / min. (Step 3). After sending the solution for 4 minutes, the reaction solution generated in the third unit was sampled from the outlet of the third unit into a sample bottle containing an internal standard substance for 1 minute. The product yield was determined by the GC internal standard method. '
- reaction substrate (starting compound) sent to the second group and the target reaction product obtained from the third group are as follows.
- Reaction substrate Decanol
- Target reaction product decanal ⁇ Examples 3 4 to 36
- Example 40 and 41 three single mixers Ver. 2 (inlay: Ag plating, fine liquid introduction channel width: 40 m) manufactured by IMM (Germany) were used.
- the tubes were connected to form a reactor.
- the above part of the apparatus was immersed in a low-temperature constant-temperature water bath at the predetermined temperature shown in Table 2.
- Step 1 Using a gas tight syringe manufactured by Hamilton Co., Ltd., 4.0 mo 1 ZL of dimethyl sulfoxide Z methylene chloride solution and 2.4 mol / L of trifluoroacetic anhydride Z methylene chloride solution through two inlets of the first group At a flow rate of 1.0 mL / min. (Step 1), and then immediately the reaction product is discharged from the outlet of the first unit to one of the two inlets of the second unit. To the other inlet of the second unit, 1. O mo 1 / L The hexanol / methylene chloride solution was sent at a rate of 2.O mL / min.
- Step 2 the reaction product was immediately transferred from the second outlet to one of the third inlets. Then, a 1.5 mol / L solution of triethylamine / methylene chloride was fed at 4.0 mL / min. From another inlet (step 3). After sending the solution for 4 minutes, the reaction product was sampled from the outlet of the third unit into a sample bottle containing an internal standard for 1 minute. The product yield was determined by the GC internal standard method. Table 2 shows the reaction results.
- a SUS tube was connected to three IMM (Germany) single mixers Ver. 2 (inlay: Ag-mec, fine liquid introduction channel width: 40 ⁇ m) to construct a reactor. .
- the above part of the apparatus was immersed in a low-temperature constant temperature water bath at 0 ° C.
- Step 1 Using a gas tight syringe manufactured by Hamilton, a 4.0 mo 1 ZL dimethyl sulfoxide / methylene chloride solution and a 2.4 mol / L trifluor
- the acetic anhydride Z methylene chloride solutions were each sent at 1.0 OmL Zmin. (Step 1), and then the reaction product of the first group was immediately poured into the two inlets of the second group. And then feed 1.0 Omo 1 ZL of cyclohexanol Z methylene chloride solution through the other inlet of the second unit into the second unit at 2.0 mL Zmin.
- reaction product liquid is sent from one of the second outlets to one of the third two inlets, and 1.5 m 0 from the other third inlet.
- a 1 / L solution of triethylamine / methylene chloride was fed into the third system at 4.0 mL / min. (Step 3). After sending the solution for 4 minutes, the reaction solution generated in the third group was sampled from the outlet of the second group into a sample bottle containing an internal standard substance for 1 minute. Product yield is GC ⁇ Determined by the standard method. Table 3 shows the reaction results.
- the above part of this apparatus was immersed in a low-temperature constant-temperature water bath at the prescribed temperature shown in Table 4.
- Step 1 Omol / L dimethinoresnorreoxide / methylene chloride solution, and 2.4 mo1 / L Trifluoroacetic anhydride / methylene chloride solution was sent at 1.0 mL / min. (Step 1), and the first reaction product solution was immediately discharged from the first outlet. Feed into one of the two inlets of the second group, and feed 1.0 Omol ZL of cyclohexanol / methylene chloride solution at 2.0 mL / min. From the other inlet (Step 2) did.
- the second reaction product liquid is immediately sent from the second outlet to one of the third two inlets, and 1.5 mo 1 ZL of triethylamid chloride is supplied from the other third inlet.
- the methylene solution was sent at 4.0 mL / min. (Step 3). After sending the solution for 4 minutes, the reaction solution generated in the third unit was sampled from the outlet into a sample bottle containing an internal standard substance for 1 minute. Product yield was determined by GC internal standard method. Table 4 shows the reaction results.
- a $ US tube was connected to three IMM (Germany) single mixers Ver. 2 (inlay: Ag plating, fine liquid introduction channel width: 40 ⁇ m) to construct a reactor. .
- the above part of this device was immersed in a low-temperature constant temperature water bath at 0 ° C.
- Step 1 Using a Hamilton gas tight syringe, 4.0 m 0 1 ZL of dimethylsulfoxide in methylene chloride and 2.4 m 0 1 ZL of trifluoroacetic anhydride Z chloride through the two inlets of the first group Each methylene solution was sent at 1.0 Om LZm in. (Step 1), and then the reaction product was immediately sent from the first outlet to one of the second two inlets. From the other inlet of the second group, 1. Send Omo 1 ZL of cyclohexanol Z methylene chloride solution at 2. Oml / min.
- Step 2 The reaction product is fed into one of the two inlets of the third group from the outlet of the third group, and 1.5 mol ZL of triethylamine / methylene chloride solution is added to 4.0 ml of the other inlet of the third group. / min. (Step 3). After sending the solution for 4 minutes, the third reaction solution was sampled from the outlet into the sample bottle containing the internal standard for 1 minute. The product yield was determined by the GC internal standard method. Table 5 shows the reaction results.
- a SUS tube was connected to three single mixers Ver. 2 (inlay: Ag-mechanical, fine liquid introduction channel width: 40 ⁇ m) manufactured by IMM (Germany) to construct a reactor.
- Step 1 Using a Hamilton gas tight syringe, 4.0 m 0 1 / L dimethyl sulfoxide / methylene chloride solution and 2.4 mo 1 / L trifluoro ⁇ anhydride at the two inlets of the first unit / Methylene chloride solution at 1.0 mL / min. (Step 1), and then immediately transfer the reaction product from one outlet to one of the two inlets of the second. To the other inlet, and send 1.0 mol 1 ZL of cyclohexanone methylene chloride solution at 2.0 mL / min.
- Step 2 the reaction product was sent to one of the two inlets of the third group, and 1.5 mol 1 ZL of triethylamine Z methylene chloride solution was added to the other inlet of the third group.
- the solution was fed at a flow rate of mL / min (Step 3). After sending the solution for 4 minutes, the reaction product was sampled from the third outlet into a sample bottle containing the internal standard for 1 minute. The product yield was determined by the GC internal standard method. Table 6 shows the reaction results.
- a SUS tube was connected to three single mixers Ver.2 (inlay: Ag-mechanical, fine liquid introduction channel width: 40 ⁇ m) manufactured by IMM (Germany) to construct a reactor. .
- the second reaction product liquid was sent from the second outlet to one of the third two inlets, and to the other inlet of the third, 1.5 mo 1 / L of triethylamine Z methylene chloride solution was sent at 4.0 mL_min. (Step 3). After sending the solution for 4 minutes, the reaction product solution was sampled from the third outlet into the sample bottle containing the internal standard for 1 minute. The product yield was determined by GC internal standard method. Table 7 shows the reaction results.
- three IMM companies Germany
- a stainless steel tube was connected to a Syndall mixer Ver. 2 (inlay: Ag-mesh, fine liquid introduction channel width: 40 ⁇ ) to construct a reactor.
- Step 3 Of triethylamine / methylene chloride was sent at 4.0 mL / mi ⁇ .
- Step 3 After sending the solution for 4 minutes, the reaction solution was sampled from the third outlet into the sample bottle containing the internal standard for 1 minute. The product yield was determined by the GC internal standard method. Table 8 shows the reaction results.
- Example 53 In each of Examples 53 and 54, three single mixers Ver. 2 manufactured by IMM (Germany) (inlay: manufactured by Ag-Mec, 'fine liquid introduction channel width: 40 ⁇ m) ⁇ ) was connected to a SUS tube to construct a reactor.
- Step 1 Using Hamilton's gas tight syringe, 2.0 m 0 1 ZL of dimethylsulfoxide methylene chloride solution from the first two inlets, and 2. Omol / L of trifluoroacetic anhydride The methylene chloride solution was sent at a rate of 1.0 mL / min. (Step 1), and the reaction product was immediately transferred from one outlet to one of the two inlets of the second. To the cyclone of 1.0 O 1 / L from the other inlet of the second unit, and then send the xanol Z methylene chloride solution at 2. Om L Zm. In. (Step 2).
- the reaction product is sent to one of the third two inlets, and 1.5 mo 1 / L triethyla from the other third inlet.
- the mine / methylene chloride solution was sent at 4.0 mL / min (Step 3) .
- the third reaction solution was charged with the internal standard substance from the third outlet.
- the yield of the product was determined Ri by the GC internal standard method. Shows the reaction results in Table 9.
- the above part of the apparatus was immersed in a low-temperature constant-temperature water bath having a predetermined temperature shown in Table 10.
- Step 2 the reaction product solution was sent to one of the two inlets of the third group, and a 1.5 mol ZL solution of trietinoreamin / methylene chloride was added at 4.0 mL / min from the other inlet of the third group.
- the solution was sent (step 3). After sending the solution for 4 minutes, the third reaction solution was sampled for 1 minute into the sample bottle containing the internal standard substance from the third outlet. The product yield was determined by the GC internal standard method. The reaction results are shown in Table 10.
- the production method of the present invention is capable of producing a corresponding aldehyde compound or ketone compound from a primary alcohol or a secondary alcohol at a temperature relatively lower than the required temperature of the conventional method such as ⁇ 30 ° C. or lower. It enables production at a very high temperature in a short time and with a high yield, and is extremely useful in practical use.
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- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
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Abstract
Description
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Priority Applications (4)
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CA2554539A CA2554539C (en) | 2004-01-28 | 2004-11-22 | Method for producing aldehyde compound or ketone compound by using microreactor |
US10/587,369 US7332632B2 (en) | 2004-01-28 | 2004-11-22 | Method for producing aldehyde compound or ketone compound by using microreactor |
EP04799868A EP1710223B1 (en) | 2004-01-28 | 2004-11-22 | Process for producing aldehyde compound or ketone compound with use of microreactor |
JP2005517381A JP4661597B2 (ja) | 2004-01-28 | 2004-11-22 | マイクロリアクターを用いてアルデヒド化合物又はケトン化合物を製造する方法 |
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US (1) | US7332632B2 (ja) |
EP (1) | EP1710223B1 (ja) |
JP (1) | JP4661597B2 (ja) |
CA (1) | CA2554539C (ja) |
WO (1) | WO2005073155A1 (ja) |
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WO2017057461A1 (ja) * | 2015-09-30 | 2017-04-06 | 富士フイルムファインケミカルズ株式会社 | アルデヒド化合物またはケトン化合物の製造方法 |
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HUE049360T2 (hu) * | 2006-05-23 | 2020-09-28 | Dpx Holdings Bv | Eljárás vegyületek elõállítására veszélyes intermediereken keresztül, sorba kötött mikroreaktorokban |
US20100179352A1 (en) * | 2007-06-04 | 2010-07-15 | Basf Se Patents, Trademarks And Licences | Process for the preparation of cyclopentanone |
ES2537157B8 (es) * | 2013-12-02 | 2018-05-28 | Universidad De Burgos | Procedimiento para la ruptura oxidante de 1,2-dioles empleando dimetil sulfoxido como agente oxidante |
CN111471034A (zh) * | 2020-03-18 | 2020-07-31 | 南京欧信医药技术有限公司 | 连续流微通道反应器中氧化制备瑞舒伐他汀侧链的方法 |
Citations (2)
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JPS57175138A (en) * | 1981-04-23 | 1982-10-28 | Mitsui Toatsu Chem Inc | Preparation of alkoxyaldehyde |
WO2003064363A1 (fr) * | 2002-01-31 | 2003-08-07 | Rhodia Chimie | Procede de preparation d'un aldehyde aromatique. |
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US4585622A (en) * | 1983-02-02 | 1986-04-29 | Ae/Cds, Autoclave, Inc. | Chemical microreactor having close temperature control |
DE19935691A1 (de) * | 1999-07-29 | 2001-02-01 | Merck Patent Gmbh | Friedel-Crafts-Acylierung im statischen Mikromischer |
EP1193214B1 (en) * | 2000-09-27 | 2007-01-03 | STMicroelectronics S.r.l. | Integrated chemical microreactor, thermally insulated from detection electrodes, and manufacturing method therefor |
DE10055758A1 (de) * | 2000-11-07 | 2002-05-16 | Siemens Axiva Gmbh & Co Kg | Verfahren zur Herstellung von Aldolen unter Verwendung eines mikrostrukturierten Reaktionssystems |
DE10139664A1 (de) | 2001-08-11 | 2003-02-20 | Clariant Gmbh | Verfahren zur Herstellung von Aryl- und Alkyl-Bor-Verbindungen in Mikroreaktoren |
DE10140857A1 (de) | 2001-08-21 | 2003-03-06 | Clariant Gmbh | Verfahren zur Herstellung von Aryl- und Alkyl-Bor-Verbindungen in Mikroreaktoren |
US6960235B2 (en) * | 2001-12-05 | 2005-11-01 | The Regents Of The University Of California | Chemical microreactor and method thereof |
-
2004
- 2004-11-22 WO PCT/JP2004/017666 patent/WO2005073155A1/ja not_active Application Discontinuation
- 2004-11-22 JP JP2005517381A patent/JP4661597B2/ja not_active Expired - Fee Related
- 2004-11-22 EP EP04799868A patent/EP1710223B1/en not_active Not-in-force
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Patent Citations (2)
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---|---|---|---|---|
JPS57175138A (en) * | 1981-04-23 | 1982-10-28 | Mitsui Toatsu Chem Inc | Preparation of alkoxyaldehyde |
WO2003064363A1 (fr) * | 2002-01-31 | 2003-08-07 | Rhodia Chimie | Procede de preparation d'un aldehyde aromatique. |
Non-Patent Citations (3)
Title |
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APPENDINO G. ET AL: "Reaction of 4-hydroxycoumarin derivatives with activated dimethyl sulfoxide", JOURNAL OF THE CHEMICAL SOCIETY, PERKIN TRANSACTIONS 1: ORGANIC AND BIO-ORGANIC CHEMISTRY, vol. 1989, no. 12, 1972 - 1999, pages 2305 - 2309, XP002986307 * |
OMURA K. ET AL: "Dimethyl sulfoxide-trifluoroacetic anhydride. New reagent for oxidation of alcohols to carbonyls", JOURNAL OF ORGANIC CHEMISTRY, vol. 41, no. 6, 1976, pages 957 - 962, XP002986306 * |
See also references of EP1710223A4 * |
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WO2017057461A1 (ja) * | 2015-09-30 | 2017-04-06 | 富士フイルムファインケミカルズ株式会社 | アルデヒド化合物またはケトン化合物の製造方法 |
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EP1710223B1 (en) | 2012-10-31 |
JPWO2005073155A1 (ja) | 2008-01-10 |
CA2554539C (en) | 2012-10-23 |
US20070149823A1 (en) | 2007-06-28 |
CA2554539A1 (en) | 2005-08-11 |
EP1710223A1 (en) | 2006-10-11 |
JP4661597B2 (ja) | 2011-03-30 |
EP1710223A4 (en) | 2007-12-19 |
US7332632B2 (en) | 2008-02-19 |
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