WO2020050368A1 - Procédé de préparation d'un réactif de vilsmeier - Google Patents

Procédé de préparation d'un réactif de vilsmeier Download PDF

Info

Publication number
WO2020050368A1
WO2020050368A1 PCT/JP2019/035031 JP2019035031W WO2020050368A1 WO 2020050368 A1 WO2020050368 A1 WO 2020050368A1 JP 2019035031 W JP2019035031 W JP 2019035031W WO 2020050368 A1 WO2020050368 A1 WO 2020050368A1
Authority
WO
WIPO (PCT)
Prior art keywords
reaction
group
vilsmeier reagent
mmol
halogenated hydrocarbon
Prior art date
Application number
PCT/JP2019/035031
Other languages
English (en)
Japanese (ja)
Inventor
明彦 津田
岡添　隆
和田　明宏
森　信明
小西　克彦
Original Assignee
国立大学法人神戸大学
Ａｇｃ株式会社
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by 国立大学法人神戸大学, Ａｇｃ株式会社 filed Critical 国立大学法人神戸大学
Priority to JP2020541302A priority Critical patent/JP7344518B2/ja
Publication of WO2020050368A1 publication Critical patent/WO2020050368A1/fr

Links

Images

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
    • C07B41/00—Formation or introduction of functional groups containing oxygen
    • C07B41/06—Formation or introduction of functional groups containing oxygen of carbonyl groups
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
    • C07B41/00—Formation or introduction of functional groups containing oxygen
    • C07B41/08—Formation or introduction of functional groups containing oxygen of carboxyl groups or salts, halides or anhydrides thereof
    • C07B41/10—Salts, halides or anhydrides of carboxyl groups
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
    • C07B41/00—Formation or introduction of functional groups containing oxygen
    • C07B41/12—Formation or introduction of functional groups containing oxygen of carboxylic acid ester groups
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
    • C07B61/00—Other general methods
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C249/00—Preparation of compounds containing nitrogen atoms doubly-bound to a carbon skeleton
    • C07C249/02—Preparation of compounds containing nitrogen atoms doubly-bound to a carbon skeleton of compounds containing imino groups
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C251/00—Compounds containing nitrogen atoms doubly-bound to a carbon skeleton
    • C07C251/02—Compounds containing nitrogen atoms doubly-bound to a carbon skeleton containing imino groups
    • C07C251/30—Compounds containing nitrogen atoms doubly-bound to a carbon skeleton containing imino groups having nitrogen atoms of imino groups quaternised
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C205/00—Compounds containing nitro groups bound to a carbon skeleton
    • C07C205/49—Compounds containing nitro groups bound to a carbon skeleton the carbon skeleton being further substituted by carboxyl groups
    • C07C205/57—Compounds containing nitro groups bound to a carbon skeleton the carbon skeleton being further substituted by carboxyl groups having nitro groups and carboxyl groups bound to carbon atoms of six-membered aromatic rings of the carbon skeleton
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C51/00—Preparation of carboxylic acids or their salts, halides or anhydrides
    • C07C51/58—Preparation of carboxylic acid halides
    • C07C51/60—Preparation of carboxylic acid halides by conversion of carboxylic acids or their anhydrides or esters, lactones, salts into halides with the same carboxylic acid part
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C53/00—Saturated compounds having only one carboxyl group bound to an acyclic carbon atom or hydrogen
    • C07C53/38—Acyl halides
    • C07C53/40—Acetyl halides
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C53/00—Saturated compounds having only one carboxyl group bound to an acyclic carbon atom or hydrogen
    • C07C53/38—Acyl halides
    • C07C53/42—Acyl halides of acids containing three or more carbon atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C53/00—Saturated compounds having only one carboxyl group bound to an acyclic carbon atom or hydrogen
    • C07C53/38—Acyl halides
    • C07C53/46—Acyl halides containing halogen outside the carbonyl halide group
    • C07C53/48—Halogenated acetyl halides
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C55/00—Saturated compounds having more than one carboxyl group bound to acyclic carbon atoms
    • C07C55/36—Acyl halides
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C57/00—Unsaturated compounds having carboxyl groups bound to acyclic carbon atoms
    • C07C57/64—Acyl halides
    • C07C57/66—Acyl halides with only carbon-to-carbon double bonds as unsaturation
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C63/00—Compounds having carboxyl groups bound to a carbon atoms of six-membered aromatic rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C63/00—Compounds having carboxyl groups bound to a carbon atoms of six-membered aromatic rings
    • C07C63/68—Compounds having carboxyl groups bound to a carbon atoms of six-membered aromatic rings containing halogen
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C65/00—Compounds having carboxyl groups bound to carbon atoms of six—membered aromatic rings and containing any of the groups OH, O—metal, —CHO, keto, ether, groups, groups, or groups
    • C07C65/21—Compounds having carboxyl groups bound to carbon atoms of six—membered aromatic rings and containing any of the groups OH, O—metal, —CHO, keto, ether, groups, groups, or groups containing ether groups, groups, groups, or groups
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C67/00—Preparation of carboxylic acid esters
    • C07C67/18—Preparation of carboxylic acid esters by conversion of a group containing nitrogen into an ester group
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C69/00—Esters of carboxylic acids; Esters of carbonic or haloformic acids
    • C07C69/02—Esters of acyclic saturated monocarboxylic acids having the carboxyl group bound to an acyclic carbon atom or to hydrogen
    • C07C69/04—Formic acid esters
    • C07C69/06—Formic acid esters of monohydroxylic compounds
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C69/00—Esters of carboxylic acids; Esters of carbonic or haloformic acids
    • C07C69/02—Esters of acyclic saturated monocarboxylic acids having the carboxyl group bound to an acyclic carbon atom or to hydrogen
    • C07C69/04—Formic acid esters
    • C07C69/08—Formic acid esters of dihydroxylic compounds
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
    • C07D207/02—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D207/30—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having two double bonds between ring members or between ring members and non-ring members
    • C07D207/32—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having two double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
    • C07D207/33—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having two double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms with substituted hydrocarbon radicals, directly attached to ring carbon atoms
    • C07D207/333—Radicals substituted by oxygen or sulfur atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
    • C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
    • C07D209/04—Indoles; Hydrogenated indoles
    • C07D209/10—Indoles; Hydrogenated indoles with substituted hydrocarbon radicals attached to carbon atoms of the hetero ring
    • C07D209/12—Radicals substituted by oxygen atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D307/00—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom
    • C07D307/02—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings
    • C07D307/34—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
    • C07D307/38—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with substituted hydrocarbon radicals attached to ring carbon atoms
    • C07D307/40—Radicals substituted by oxygen atoms
    • C07D307/46—Doubly bound oxygen atoms, or two oxygen atoms singly bound to the same carbon atom
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D307/00—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom
    • C07D307/02—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings
    • C07D307/34—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
    • C07D307/38—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with substituted hydrocarbon radicals attached to ring carbon atoms
    • C07D307/40—Radicals substituted by oxygen atoms
    • C07D307/46—Doubly bound oxygen atoms, or two oxygen atoms singly bound to the same carbon atom
    • C07D307/48—Furfural
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D307/00—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom
    • C07D307/77—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom ortho- or peri-condensed with carbocyclic rings or ring systems
    • C07D307/78—Benzo [b] furans; Hydrogenated benzo [b] furans
    • C07D307/79—Benzo [b] furans; Hydrogenated benzo [b] furans with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to carbon atoms of the hetero ring
    • C07D307/80—Radicals substituted by oxygen atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D333/00—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom
    • C07D333/02—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings
    • C07D333/04—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom
    • C07D333/06—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to the ring carbon atoms
    • C07D333/22—Radicals substituted by doubly bound hetero atoms, or by two hetero atoms other than halogen singly bound to the same carbon atom
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D333/00—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom
    • C07D333/02—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings
    • C07D333/04—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom
    • C07D333/26—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D333/38—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals

Definitions

  • the present invention provides a method for producing a Vilsmeier reagent that can be carried out safely and simply at low cost, and the production of an aromatic aldehyde or an aromatic ketone, a carboxylic acid halide, and a formate using the Vilsmeier reagent. How to do it.
  • the Vilsmeier reagents are electrophiles that cause addition reactions to electron-rich alkenes and aromatic rings, for example, for the formylation of aromatic compounds with active groups and the conversion of carboxy groups to haloformyl groups. Is done.
  • the Vilsmeier reagent is generally formed from a chlorinating agent such as phosgene, oxalyl chloride, phosphorus trichloride, phosphorus pentachloride, thionyl chloride, and an amide compound (Patent Document 1).
  • chlorinating agents are very toxic, and some produce toxic and corrosive gases on contact with water, making them difficult to store and dangerous to handle.
  • phosgene has a history of being used as a suffocating poisonous gas, and has a risk of death or the like due to inhalation during use.
  • Chlorinating agents other than phosgene are also corrosive, such as thionyl chloride, which produces sulfur dioxide and hydrogen chloride as by-products, and is expensive to treat.
  • Patent Document 2 discloses a method for producing a Vilsmeier reagent using phthalic acid dichloride which is safer as a chlorinating agent.
  • phthalic dichloride increases costs.
  • this method since phthalic anhydride is by-produced, a high cost is required for the purification process of the target compound.
  • Patent Document 3 a method for producing a urea derivative or a carbonate derivative by blowing a decomposition product generated by light irradiation on chloroform or the like in the presence of oxygen into an amine solution or a phenol solution has been developed.
  • Patent Document 4 discloses a method for producing a chloroformate by irradiating a mixture containing a halogenated hydrocarbon and an alcohol with light in the presence of oxygen.
  • the present invention provides a method for producing a Vilsmeier reagent that is safe and simple and can be carried out at low cost, and an aromatic aldehyde or aromatic ketone, a carboxylic acid halide, and a formate ester using the Vilsmeier reagent. It is intended to provide a method of manufacturing.
  • the present inventors have intensively studied to solve the above problems. As a result, they have found that a Vilsmeier reagent can be produced by irradiating a composition containing a halogenated hydrocarbon and an amide compound with light in the presence of oxygen, thereby completing the present invention.
  • a Vilsmeier reagent can be produced by irradiating a composition containing a halogenated hydrocarbon and an amide compound with light in the presence of oxygen, thereby completing the present invention.
  • the present invention will be described.
  • the Vilsmeier reagent is a salt represented by the following formula (I): [Where, R 1 represents a hydrogen atom, a C 1-6 alkyl group, or a C 6-12 aromatic hydrocarbon group which may have a substituent, R 2 and R 3 independently represent a C 1-6 alkyl group or a C 6-12 aromatic hydrocarbon group which may have a substituent, and R 2 and R 3 together And may form a ring structure of 4 to 7 members, X represents a halogeno group selected from the group consisting of chloro, bromo and iodo, Y - represents a counter anion.
  • [7] A method for producing an aromatic aldehyde or an aromatic ketone, A step of producing a Vilsmeier reagent by the method according to any one of the above [1] to [6], and Reacting the Vilsmeier reagent with an aromatic compound having an active group.
  • a method for producing a carboxylic acid halide A step of producing a Vilsmeier reagent by the method according to any one of the above [1] to [6], and A method comprising reacting the Vilsmeier reagent with a carboxylic acid compound represented by the following formula (III) to convert a carboxy group of the carboxylic acid compound into a haloformyl group.
  • R 4 - (CO 2 H) n (III) [Wherein, R 4 represents an n-valent organic group, and n represents an integer of 1 or more and 4 or less. ]
  • a method for producing a formate ester A step of producing a Vilsmeier reagent by the method according to any one of the above [1] to [6], and Reacting the Vilsmeier reagent with a hydroxyl group-containing compound.
  • a highly reactive and useful Vilsmeier reagent is used in place of a dangerous compound such as phosgene, and a halogenated hydrocarbon which is also used as a general-purpose solvent. Can be manufactured. At this time, only carbon dioxide and hydrogen chloride are by-produced, and since they can be discharged out of the system as gas, purification is not required in principle. It is also possible to produce an aromatic aldehyde or aromatic ketone, a carboxylic acid halide, and a formate in the same system using the produced Vilsmeier reagent. Therefore, the present invention is industrially extremely useful as an industrial production technique for aromatic aldehydes or ketones, carboxylic acid halides, and formate.
  • FIG. 1 is a schematic diagram illustrating an example of a configuration of a reaction device used in the present invention.
  • the C 1-4 halogenated hydrocarbon used in the present invention is a hydrocarbon having 1 to 4 carbon atoms and having at least one halogeno group selected from a group consisting essentially of chloro, bromo and iodo. .
  • Such C 1-4 halogenated hydrocarbons are probably decomposed by irradiation light and oxygen, converted to carbonyl halides or carbonyl halide-like compounds, reacted with amide compounds, and further attacked by halide ions. It is believed that a Vilsmeier reagent is formed. Even if a harmful carbonyl halide is formed, the carbonyl halide reacts immediately with the amide compound due to its extremely high reactivity, and does not leak out of the reaction solution. It is believed that there is.
  • the present invention is a technique for producing a useful compound by photodecomposing a C 1-4 halogenated hydrocarbon, and greatly contributes industrially and environmentally.
  • the C1-4 halogenated hydrocarbon is an alkane, alkene or alkyne having 1 or more and 4 or less carbon atoms substituted with one or more halogeno groups selected from the group consisting essentially of chloro, bromo and iodo. .
  • the C 1-4 halogenated hydrocarbon is considered to be decomposed by the irradiation light and oxygen and to perform the same function as the carbonyl halide.
  • C 1-2 halogenated hydrocarbons are preferred, and halogenomethane is more preferred.
  • alkene or alkyne having one or more unsaturated bonds is preferable so that the decomposition proceeds more easily.
  • a C 1-4 polyhalogenated hydrocarbon having two or more halogeno groups is preferable, and a C 1-2 polyhalogenated hydrocarbon is more preferable.
  • the halogeno group may be transferred with the decomposition, a C 1-4 halogenated hydrocarbon having two or more halogeno groups on the same carbon is preferable.
  • Specific C 1-4 halogenated hydrocarbons include, for example, halomethanes such as dichloromethane, chloroform, dibromomethane, bromoform, iodomethane, diiodomethane; 1,1,2-trichloroethane, 1,1,1-trichloroethane, Haloethanes such as 1,2,2-tetrachloroethane and 1,1,1,2-tetrachloroethane; halopropanes such as 1,1,1,3-tetrachloropropane; tetrachloromethane, tetrabromomethane, tetraiodomethane, Perhaloalkanes such as hexachloroethane and hexabromoethane; and perhaloethenes such as 1,1,2,2-tetrachloroethene and 1,1,2,2-tetrabromoethene.
  • halomethanes such as dich
  • the C1-4 halogenated hydrocarbon may be appropriately selected according to the intended chemical reaction or the desired product, and may be used alone or in combination of two or more. May be. Preferably, only one C 1-4 halogenated hydrocarbon is used depending on the production target compound. Any C 1-4 halogenated hydrocarbon that is liquid at normal pressure or normal temperature or at the reaction temperature can also serve as a solvent. Among the C 1-4 halogenated hydrocarbons, compounds having a chloro group are preferred.
  • the C 1-4 halogenated hydrocarbon used in the method of the present invention inexpensive chloroform which is also used as a general-purpose solvent is most preferable.
  • a C 1-4 halogenated hydrocarbon once used as a solvent may be recovered and reused.
  • the reaction may be inhibited, so that it is preferable to purify to some extent.
  • the reaction is considered to proceed even if about 1% by volume of water is contained, it is not necessary to perform excessive purification that lowers the productivity.
  • the water content is more preferably 0.5% by volume or less, still more preferably 0.2% by volume or less, and even more preferably 0.1% by volume or less.
  • the recycled C 1-4 halogenated hydrocarbon may include a decomposition product of the C 1-4 halogenated hydrocarbon.
  • the amount of the C 1-4 halogenated hydrocarbon to be used may be appropriately determined within a range in which the amide compound can be sufficiently converted into the Vilsmeier reagent.
  • the upper limit of the use amount of the C 1-4 halogenated hydrocarbon is not particularly limited, but may be, for example, 200 times or less the molar amount of the amide compound.
  • the amount used is preferably 1-fold or more, 5-fold or more, or 10-fold or more, more preferably 20-fold or more, and even more preferably 25-fold or more. According to the experimental findings by the present inventors, it is observed that the smaller the amount of the amide compound relative to the C 1-4 halogenated hydrocarbon, the higher the production efficiency of the Vilsmeier reagent.
  • a C 1-4 halogenated hydrocarbon When a C 1-4 halogenated hydrocarbon can be used as a solvent, it can be used in an amount of 50 times or more. The amount used is preferably 150 times or less or 100 times or less. The specific amount of the C 1-4 halogenated hydrocarbon to be used may be determined by a preliminary experiment or the like.
  • the oxygen source may be any gas containing oxygen, and for example, air or purified oxygen can be used.
  • the purified oxygen may be used by mixing with an inert gas such as nitrogen or argon. Air can be used in terms of cost and ease.
  • the oxygen content in the gas used as the oxygen source is preferably about 15% by volume or more and 100% by volume or less. It is also preferable to use substantially only oxygen other than the inevitable impurities.
  • the oxygen content may be appropriately determined depending on the type of the above-mentioned C 1-4 halogenated hydrocarbon or the like.
  • the oxygen content is preferably 15% by volume or more and 100% by volume or less
  • the oxygen content is preferably 90% by volume or more and 100% by volume or less. Note that even when oxygen (oxygen content 100 vol%) is used, the oxygen content can be controlled within the above range by adjusting the flow rate of oxygen into the reaction system.
  • the method for supplying the gas containing oxygen is not particularly limited, and the gas may be supplied into the reaction system from an oxygen cylinder equipped with a flow controller, or may be supplied from the oxygen generator into the reaction system.
  • the reaction according to the present invention may be performed under a gas stream of a gas containing oxygen, but from the viewpoint of increasing the yield of a product, the gas containing oxygen may be supplied into the composition by bubbling. preferable.
  • the amount of the gas containing oxygen may be appropriately determined according to the amount of the C 1-4 halogenated hydrocarbon, the shape of the reaction vessel, and the like.
  • the amount of gas per minute supplied to the reaction vessel with respect to the C 1-4 halogenated hydrocarbon present in the reaction vessel is preferably 5 times or more.
  • the ratio is more preferably 25 times or more, and even more preferably 50 times or more.
  • the upper limit of the ratio is not particularly limited, it is preferably 500 times or less, more preferably 250 times or less, and even more preferably 150 times or less.
  • the amount of oxygen per minute supplied to the reaction vessel with respect to the C 1-4 halogenated hydrocarbon present in the reaction vessel can be 5 times or more and 25 times or less. If the flow rate of the gas is too large, the C 1-4 halogenated hydrocarbon may be volatilized, while if it is too small, the reaction may not easily proceed.
  • a solvent may be added to the composition containing a C 1-4 halogenated hydrocarbon.
  • C 1-4 halogenated hydrocarbon is not liquid at room temperature and atmospheric pressure, C 1-4 can appropriately dissolve the halogenated hydrocarbon, solvent is that and does not inhibit the decomposition of the C 1-4 halogenated hydrocarbons preferable.
  • a solvent examples include ketone solvents such as acetone, methyl ethyl ketone, methyl isobutyl ketone, and cyclohexanone; ester solvents such as ethyl acetate; aliphatic hydrocarbon solvents such as n-hexane; ethers such as diethyl ether, tetrahydrofuran, and dioxane.
  • ketone solvents such as acetone, methyl ethyl ketone, methyl isobutyl ketone, and cyclohexanone
  • ester solvents such as ethyl acetate
  • aliphatic hydrocarbon solvents such as n-hexane
  • ethers such as diethyl ether, tetrahydrofuran, and dioxane.
  • System solvent Nitrile solvents such as acetonitrile can be mentioned.
  • the light irradiated to the mixture is preferably light containing short-wavelength light, more preferably light containing ultraviolet light, more specifically light containing light having a wavelength of 180 nm or more and 500 nm or less, and has a peak wavelength of 180 nm or more and 500 nm.
  • Light included in the following range is more preferable.
  • the wavelength of the light may be appropriately determined according to the type of the C 1-4 halogenated hydrocarbon, but is preferably 400 nm or less, more preferably 300 nm or less. When the irradiation light contains light in the above wavelength range, the C 1-4 halogenated hydrocarbon can be efficiently oxidatively photodecomposed.
  • high-energy light including UV-B having a wavelength of 280 to 315 nm and / or UV-C having a wavelength of 180 to 280 nm can be used, and high-energy light including UV-C having a wavelength of 180 to 280 nm can be used. Is preferred. Further, light having a peak wavelength in the range of 280 nm to 315 nm and / or 180 nm to 280 nm is preferable, and light having a peak wavelength in the range of 180 nm to 280 nm is more preferable.
  • the light irradiation means is not particularly limited as long as it can irradiate the light of the above-mentioned wavelength.
  • Examples of the light source including light of such a wavelength range in a wavelength range include, for example, sunlight, a low-pressure mercury lamp, and a medium-pressure mercury. Lamps, high-pressure mercury lamps, ultra-high-pressure mercury lamps, chemical lamps, black light lamps, metal halide lamps, halogen lamps, incandescent lamps and the like. From the viewpoint of reaction efficiency and cost, a low-pressure mercury lamp is preferably used.
  • Conditions such as the intensity of irradiation light and irradiation time may be appropriately set depending on the type and amount of starting material used.
  • a desired light intensity at the shortest distance position of the composition from a light source is 10 mW / cm 2. It is preferably at least 500 mW / cm 2 .
  • the shortest distance between the light source and the halogenated methane is preferably 1 m or less, more preferably 50 cm or less, even more preferably 10 cm or less or 5 cm or less.
  • the lower limit of the shortest distance is not particularly limited, but may be 0 cm, that is, the light source may be immersed in halogenated methane.
  • the shortest distance When light is irradiated from the side of the reaction vessel, the shortest distance may be 1 cm or more or 2 cm or more.
  • the light irradiation time is preferably from 0.5 to 10 hours, more preferably from 1 to 6 hours, even more preferably from 2 to 4 hours.
  • the mode of light irradiation is also not particularly limited, such as a mode in which light is continuously irradiated from the start to the end of the reaction, a mode in which light irradiation and non-irradiation are alternately repeated, and a mode in which light is irradiated only for a predetermined time from the start of the reaction. Either mode can be adopted, but a mode in which light is continuously irradiated from the start to the end of the reaction is preferable.
  • the temperature at which the C 1-4 halogenated hydrocarbon is decomposed is not particularly limited, and may be appropriately adjusted.
  • the temperature may be set to ⁇ 20 ° C. or more and 60 ° C. or less.
  • the temperature is more preferably ⁇ 10 ° C. or higher, still more preferably 0 ° C. or higher or 10 ° C. or higher, and is more preferably 50 ° C. or lower or 40 ° C. or lower, even more preferably 30 ° C. or lower.
  • the reaction may be performed at room temperature without controlling the temperature.
  • the reaction temperature is preferably 10 ° C or lower, more preferably 5 ° C or lower.
  • the reaction may be continued at 10 ° C. or higher and 60 ° C. or lower for 1 minute to 5 hours under general light such as a fluorescent lamp without irradiation of high energy light.
  • the decomposition product of the C 1-4 halogenated hydrocarbon is reacted with the amide compound represented by the formula (II).
  • Step of the reaction with the amide compound may be carried out simultaneously with the decomposition process of the C 1-4 halogenated hydrocarbons, may be performed after the decomposition step of C 1-4 halogenated hydrocarbons.
  • the amide compound may be added to the composition containing the C 1-4 halogenated hydrocarbon.
  • the composition containing a C 1-4 halogenated hydrocarbon may be irradiated with light, and the amide compound may be added while the light irradiation is continued. In these cases, the decomposition product of the C 1-4 halogenated hydrocarbon can quickly react with the amide compound, and leakage of the decomposition product can be suppressed.
  • the C 1-4 halogenated hydrocarbon is decomposed by light irradiation, and then light irradiation, particularly of high energy light Irradiation may be stopped and an amide compound may be added.
  • this embodiment allows the decomposition of the C 1-4 halogenated hydrocarbon and the reaction with the amide compound to be performed efficiently.
  • this embodiment is particularly suitable for implementing the present invention with a large capacity.
  • amide compound (II) an amide compound represented by the following formula (II) is preferable.
  • the compound represented by the formula (II) may be abbreviated as “amide compound (II)”.
  • R 1 represents a hydrogen atom (—H), a C 1-6 alkyl group, or a C 6-12 aromatic hydrocarbon group which may have a substituent
  • R 2 and R 3 represent Independently represents a C 1-6 alkyl group or a C 6-12 aromatic hydrocarbon group which may have a substituent
  • R 2 and R 3 together form a 4-membered or more It may form a ring structure of less than or equal to member.
  • C 1-6 alkyl group refers to a linear or branched monovalent saturated aliphatic hydrocarbon group having 1 to 6 carbon atoms.
  • it is a C 1-4 alkyl group, more preferably a C 1-2 alkyl group, and most preferably methyl.
  • the “C 6-12 aromatic hydrocarbon group” refers to a monovalent aromatic hydrocarbon group having 6 to 12 carbon atoms.
  • phenyl, naphthyl, indenyl and biphenyl groups preferably phenyl.
  • the C 6-12 aromatic hydrocarbon group may have a substituent.
  • the substituent is not particularly limited as long as it does not inhibit the reaction according to the present invention, and examples thereof include a C 1-6 alkyl group, a C 1-6 alkoxy group, a halogeno group, a nitro group, and a cyano group.
  • One or more substituents selected may be mentioned.
  • the number of substituents is not particularly limited as long as it can be substituted, but may be, for example, from 1 to 5, preferably 3 or less, more preferably 2 or less, and still more preferably 1. When the number of substituents is 2 or more, the substituents may be the same or different.
  • C 1-6 alkoxy group refers to a linear or branched aliphatic hydrocarbonoxy group having 1 to 6 carbon atoms.
  • methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, isobutoxy, t-butoxy, n-pentoxy, n-hexoxy, etc. preferably C 1-4 alkoxy group, more preferably C 1 alkoxy group -2 alkoxy group, more preferably methoxy.
  • halogeno group as the substituent for the C 6-12 aromatic hydrocarbon group may be chloro, bromo, iodo or fluoro.
  • Examples of the 4- to 7-membered ring structure formed by R 2 and R 3 together with a nitrogen atom include a pyrrolidyl group, a piperidyl group, and a morpholino group.
  • amide compound (II) examples include N, N-dimethylformamide (DMF), N, N-dimethylacetamide (DMA), N-methyl-N-phenylformamide, N-methylpyrrolidone (NMP), Examples thereof include 1,3-dimethylimidazolidinone (DMI), tetramethyl urea, tetraethyl urea, and tetrabutyl urea, and DMF is preferred from the viewpoint of versatility and cost.
  • the composition containing the C 1-4 halogenated hydrocarbon and the amide compound is irradiated with light in the presence of oxygen.
  • chloroform which is available at a low cost is most preferable.
  • the manner of mixing the C 1-4 halogenated hydrocarbon and the amide compound is not particularly limited.
  • the entire amount of each compound may be mixed in advance, added in several portions, or added continuously at an arbitrary rate.
  • a solvent that can appropriately dissolve these starting compounds and does not inhibit the reaction of the present invention may be used.
  • examples of such a solvent include aliphatic hydrocarbon solvents such as n-hexane; ether solvents such as diethyl ether, tetrahydrofuran and dioxane; and nitrile solvents such as acetonitrile.
  • the temperature during the reaction is not particularly limited, and may be appropriately adjusted.
  • the temperature may be -20 ° C or higher and 60 ° C or lower.
  • the temperature is more preferably ⁇ 10 ° C. or more, still more preferably 0 ° C. or more, more preferably 50 ° C. or less or 40 ° C. or less, and even more preferably 30 ° C. or less.
  • the reaction may be performed at room temperature without controlling the temperature.
  • the reaction temperature is preferably 10 ° C or lower, more preferably 5 ° C or lower.
  • FIG. 1 shows one embodiment of a reactor that can be used in the production method of the present invention.
  • the reaction apparatus shown in FIG. 1 has a light irradiation means 1 in a tubular reaction vessel 6.
  • the above-mentioned each raw material compound is added into the cylindrical reaction vessel 6, and light is irradiated while supplying a gas containing oxygen into the reaction vessel 6 or bubbling the gas containing oxygen into the mixture (not shown).
  • the reaction is performed by irradiating light from the means 1.
  • the jacket is preferably made of a material that transmits the short-wavelength light.
  • Light irradiation may be performed from the outside of the reaction vessel.
  • the reaction vessel is preferably made of a material that transmits the short-wavelength light.
  • the material that transmits the short-wavelength light is not particularly limited as long as the effect of the present invention is not impaired, but quartz glass is preferably exemplified.
  • the resulting Vilsmeier reagent is a salt represented by the following formula (I).
  • R 1 to R 3 have the same meanings as described above, X represents a halogeno group selected from the group consisting of chloro, bromo and iodo, and Y ⁇ represents a counter anion. ]
  • Examples of Y ⁇ in formula (I) include, but are not particularly limited to, chloride ions, bromide ions, and iodide ions derived from C 1-4 halogenated hydrocarbons.
  • a compound in which X is chloro and Y - is a chloride ion is preferable from the viewpoint of availability.
  • a compound capable of reacting with the Vilsmeier reagent By further adding a compound capable of reacting with the Vilsmeier reagent to the reaction solution containing the Vilsmeier reagent, it is possible to cause a further reaction to proceed in the same system.
  • a compound capable of reacting with the Vilsmeier reagent can be converted into an aldehyde or a ketone using a Vilsmeier reagent.
  • Such a reaction is known as the Vilsmeier-Haack reaction.
  • the Vilsmeier reagent converts a carboxy group of a carboxylic acid compound into a haloformyl group.
  • a formic ester is obtained by reacting a hydroxyl group-containing compound with a Vilsmeier reagent.
  • An aromatic compound having an active group is an aromatic compound activated by a substituent or the like.
  • an amino group containing an alkylamino group substituted with an alkyl group or a hydroxyl group strongly activates an aromatic compound.
  • these substituents are referred to as activating groups.
  • compounds such as anthracene in which an aromatic ring is condensed and a conjugated system is expanded, are also activated, and are subjected to aldehyde or ketone formation by a Vilsmeier reagent. It is considered that the ⁇ electron at the activated site is electrophilically reacted with the Vilsmeier reagent, and is converted into an aldehyde or a ketone.
  • the active aromatic compound is not particularly limited as long as it is activated and can be aldehyde or ketonized by the Vilsmeier reagent.
  • C 1-10 such as benzene or naphthalene substituted by the activating group can be used.
  • the amount of the active aromatic compound to be used may be appropriately adjusted, and may be, for example, 0.1 to 1.0 times the mol of the amide compound.
  • the reaction conditions for aldehyde conversion or ketonization may be determined appropriately.
  • the active aromatic compound may be added to the reaction solution after confirming consumption of the amide compound and formation of the Vilsmeier reagent by thin layer chromatography, NMR, or the like.
  • the active aromatic compound may be added as it is, or a solution of the active aromatic compound may be added.
  • the solvent for the active aromatic compound solution is not particularly limited as long as it can appropriately dissolve the active aromatic compound and does not inhibit the reaction.
  • dichloromethane, chloroform, carbon tetrachloride, chloropropane, chlorobutane, chloropentane Halogenated hydrocarbon solvents such as chlorohexane; ketone solvents such as acetone and methyl ethyl ketone; nitrile solvents such as acetonitrile; aromatic hydrocarbon solvents such as benzene, toluene and chlorobenzene; ether solvents such as diethyl ether, tetrahydrofuran and dioxane Can be mentioned.
  • reaction conditions for the aldehyde or ketonization may be appropriately adjusted.
  • the reaction temperature may be -10 ° C. or higher, including the temperature at the time of addition of the active aromatic compound, and the heating and reflux conditions may be employed.
  • the heating and reflux conditions may be employed.
  • R 1 is a hydrogen atom
  • an aromatic aldehyde is obtained
  • R 1 is an alkyl group or an aromatic hydrocarbon group
  • an aromatic ketone is obtained.
  • a saturated sodium carbonate aqueous solution or a saturated sodium bicarbonate aqueous solution is added to the reaction solution after the reaction to stop the reaction, liquid separation is performed, the aqueous layer is extracted with an organic solvent, and the organic layer and the extract are combined to obtain anhydrous sodium sulfate.
  • the target compound, an aromatic aldehyde or aromatic ketone may be purified by a conventional method such as recrystallization, silica gel column chromatography, or distillation.
  • the carboxylic acid compound When the carboxy group of the carboxylic acid compound is converted to a haloformyl group by the Vilsmeier reagent, the carboxylic acid compound may be added to the composition containing the C 1-4 halogenated hydrocarbon and the amide compound before light irradiation. Then, the carboxylic acid compound may be added intermittently or continuously at appropriate times before the light irradiation, during the light irradiation, and after the light irradiation, or the carboxylic acid compound may be added after the light irradiation. That is, a step of adding a carboxylic acid compound to convert a carboxy group to a haloformyl group after the step of producing the Vilsmeier reagent may be performed, or both steps may be performed simultaneously.
  • Examples of the carboxylic acid compound converting a carboxy group to a haloformyl group include a compound represented by the following formula (III).
  • R 4 - (CO 2 H) n (III) [Wherein, R 4 represents an n-valent organic group, and n represents an integer of 1 or more and 4 or less. ]
  • the organic group is not particularly limited as long as it does not inhibit the reaction.
  • Examples thereof include a C 1-18 hydrocarbon group which may have a substituent and the above-mentioned heteroaryl group which may have a substituent. it can.
  • the substituent include one or more substituents selected from the group consisting of a C 1-6 alkyl group, a C 1-6 alkoxy group, a halogeno group, a nitro group, and a cyano group.
  • Examples of the C 1-18 hydrocarbon group include a monovalent C 1-18 alkyl group, a C 2-18 alkenyl group, a C 2-18 alkynyl group, a C 6-18 aromatic hydrocarbon group, and a C 2-18 hydrocarbon group.
  • Hydrocarbon groups corresponding to those having a valence of 4 or more and 4 or less can be mentioned.
  • one or more carbon atoms are —O—, —S—, —NR 5 — (R 5 is a hydrogen atom or And a hetero atom such as a C 1-6 alkyl group).
  • the carboxylic acid compound may be added as it is, or a solution of the carboxylic acid compound may be added.
  • the solvent for the carboxylic acid compound solvent is not particularly limited as long as it can appropriately dissolve the carboxylic acid compound and does not inhibit the reaction. Examples thereof include dichloromethane, chloroform, carbon tetrachloride, chloropropane, chlorobutane, chloropentane, and chlorohexane.
  • Halogenated hydrocarbon solvents such as benzene, toluene, chlorobenzene and the like; and ether solvents such as diethyl ether, tetrahydrofuran and dioxane.
  • the amount of the carboxylic acid compound to be used may be appropriately adjusted, and may be, for example, 0.1 to 3.0 times the mol of the amide compound.
  • the conditions for the reaction for converting a carboxy group to a haloformyl group may be determined as appropriate.
  • the reaction temperature can be from 0 ° C. to 50 ° C.
  • the reaction time can be from 10 minutes to 20 hours.
  • Carboxylic acid halides are often highly reactive and unstable, so isolation may be difficult. Therefore, after the reaction of the Vilsmeier reagent with the carboxylic acid compound, it is preferable to add a compound to be reacted with the carboxylic acid halide, such as an alcohol compound or an amine compound, to the reaction solution. After the reaction, a usual post-treatment may be performed, or the target compound may be purified by a conventional method.
  • a compound to be reacted with the carboxylic acid halide such as an alcohol compound or an amine compound
  • the hydroxyl group-containing compound When a formic ester is obtained by reacting a Vilsmeier reagent with a hydroxyl group-containing compound, the hydroxyl group-containing compound may be added to the composition containing the C 1-4 halogenated hydrocarbon and the amide compound before light irradiation.
  • the hydroxyl group-containing compound may be added intermittently or continuously as appropriate before or after the light irradiation, after the light irradiation, and after the light irradiation, or the hydroxyl group-containing compound may be added after the light irradiation. That is, the step of adding the hydroxyl group-containing compound may be performed after the step of producing the Vilsmeier reagent, or both steps may be performed simultaneously.
  • the hydroxyl group-containing compound may be added as it is, or a solution of the hydroxyl group-containing compound may be added.
  • the solvent for the hydroxyl group-containing compound solution is not particularly limited as long as it can appropriately dissolve the hydroxyl group-containing compound and does not inhibit the reaction. Examples thereof include dichloromethane, chloroform, carbon tetrachloride, chloropropane, chlorobutane, chloropentane, and chlorohexane.
  • Halogenated hydrocarbon solvents such as acetonitrile; ether solvents such as diethyl ether, tetrahydrofuran and dioxane.
  • the hydroxyl group-containing compound is not particularly limited as long as it has at least one reactive hydroxyl group, and examples thereof include an alcohol compound and a phenol compound.
  • Examples of the alcohol compound include C 1-20 alcohols such as methanol, ethanol, n-propanol, isopropanol, n-butanol, isobutanol, s-butanol, t-butanol, n-pentanol and isopentanol; C 1-20 halogeno alcohols such as methanol, 2-fluoroethanol, 2-chloroethanol, 2-bromoethanol, 2-iodoethanol, 2,2,2-fluoroethanol; ethylene glycol, propylene glycol, 1,4-butane Examples thereof include diol compounds such as diol and 1,6-hexanediol; triol compounds such as glycerin; and tetraol compounds such as pentaerythritol.
  • C 1-20 alcohols such as methanol, ethanol, n-propanol, isopropanol, n-butanol, isobutanol, s-butan
  • phenol compound examples include monohydric phenol compounds such as phenol, naphthol, cresol, butylphenol, amylphenol, chlorophenol, and bromophenol; catechol, bisphenol AG, bisphenol M, bisphenol S, bisphenol P, bisphenol Z, and the like. Dihydric phenol compounds; trihydric phenol compounds such as trihydroxybenzene can be exemplified.
  • the amount of the hydroxyl group-containing compound used may be appropriately adjusted.
  • the amount of the hydroxyl group-containing compound having one hydroxyl group may be 0.1 to 3.0 times the amide compound. it can.
  • the amount of the hydroxyl group-containing compound having m hydroxyl groups may be adjusted using 1 / m of the amount of the hydroxyl group-containing compound having one hydroxyl group as a guide.
  • the reaction conditions of the Vilsmeier reagent and the hydroxyl group-containing compound may be determined as appropriate.
  • the reaction temperature can be from -10 ° C to 50 ° C, and the reaction time can be from 10 minutes to 20 hours.
  • a saturated sodium carbonate aqueous solution or a saturated sodium bicarbonate aqueous solution is added to the reaction solution after the reaction to stop the reaction, liquid separation is performed, the aqueous layer is extracted with an organic solvent, and the organic layer and the extract are combined to obtain anhydrous sodium sulfate.
  • the formic ester as the target compound may be purified by a conventional method such as recrystallization, silica gel column chromatography, or distillation.
  • Example 1 Production of Vilsmeier Reagent
  • a tubular reaction vessel (diameter 42 mm) equipped with a quartz glass jacket having a diameter of 30 mm in the center was prepared, and a low-pressure mercury lamp (manufactured by SEN Light, UVL20PH-6, 20 W) was provided in the quartz glass jacket. , ⁇ 24 ⁇ 120 mm), and purified chloroform (20 mL, 248 mmol) and DMF (1.55 mL, 20 mmol) were added into the reaction vessel.
  • the reaction was carried out at a temperature of 30 ° C. for 2 hours while irradiating light with the low-pressure mercury lamp while bubbling oxygen gas at 0.5 L / min while stirring the mixed solution.
  • the ratio of residual DMF to the Vilsmeier reagent in the upper layer was about 1: 4 from the peak intensity, and it was estimated that a maximum of 16 mmol of the Vilsmeier reagent was generated.
  • Example 2 Production of pyrrole-2-carboxaldehyde Purified chloroform (20 mL, 248 mmol) and DMF (1.56 mL, 20 mmol) were added to the reaction vessel of Example 1. The reaction was carried out at 30 ° C. for 2 hours while irradiating light with the low-pressure mercury lamp while bubbling oxygen gas at 0.5 L / min while stirring the mixed solution. Subsequently, the reaction temperature was raised to 50 ° C., and the mixture was stirred until no bubbles were generated. Thereafter, the reaction vessel was immersed in an ice bath, pyrrole (0.74 mL, 10 mmol) was added, and the mixture was heated under reflux for 30 minutes.
  • Example 3 Production of 1-methyl-2-pyrrolecarboxaldehyde
  • a chloroform solution (5 mL) of 1-methylpyrrole (0.74 mL, 10 mmol) was used instead of pyrrole, and the aqueous layer was extracted with dichloromethane.
  • a concentrate was obtained in the same manner except that the above procedure was performed.
  • the concentrate was analyzed by 1 H-NMR, it was possible to confirm the formation of 1-methyl-2-pyrrolecarboxaldehyde as a target compound (yield> 99%).
  • Example 4 Production of 2-formylfuran
  • furan (0.73 mL, 10 mmol) was used instead of pyrrole, and after adding furan, the reaction was allowed to proceed at 0 ° C for 30 minutes, and then at room temperature for 2 hours. Then, a concentrate was obtained in the same manner except that the aqueous layer was extracted with dichloromethane. When the concentrate was analyzed by 1 H-NMR, formation of 2-formylfuran as a target compound could be confirmed (yield: 60%). As described above, no formylation of unsubstituted furan with the Vilsmeier reagent has been reported, but it has been demonstrated that the present invention allows formylation of unsubstituted furan.
  • Example 5 Production of 5-methylfurfural A cylindrical reaction vessel (diameter 42 mm) equipped with a quartz glass jacket having a diameter of 30 mm in the center was prepared, and a low-pressure mercury lamp (manufactured by SEN Light, UVL20PH-6, 20 W, ⁇ 24 ⁇ 120 mm), and purified chloroform (20 mL, 248 mmol) and DMF (3.5 mL, 45 mmol) were added into the reaction vessel. The reaction was carried out at 30 ° C. for 3 hours while irradiating the low pressure mercury lamp with light while bubbling oxygen gas at 0.5 L / min while stirring the mixed solution.
  • a low-pressure mercury lamp manufactured by SEN Light, UVL20PH-6, 20 W, ⁇ 24 ⁇ 120 mm
  • purified chloroform 20 mL, 248 mmol
  • DMF 3.5 mL, 45 mmol
  • the reaction temperature was raised to 50 ° C., and the mixture was stirred until no bubbles were generated. Thereafter, the reaction vessel was immersed in an ice bath, 2-methylfuran (0.9 mL, 10 mmol) was added, and the mixture was stirred at 0 ° C. for 1 hour. Then, a saturated aqueous solution of sodium carbonate (30 mL) was added, and the mixture was stirred for 15 minutes. The reaction solution separated into two layers was separated, and the aqueous layer was extracted with ethyl acetate. The organic layer and the extract were combined, dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated under reduced pressure. When the concentrate was analyzed by 1 H-NMR, the formation of 5-methylfurfural, which was the target compound, could be confirmed (yield: 80%).
  • Example 6 Production of 2-formylthiophene Purified chloroform (20 mL, 248 mmol) and DMF (1.2 mL, 15 mmol) were added into the reaction vessel of Example 1. The reaction was carried out at 30 ° C. for 2 hours while irradiating light with the low-pressure mercury lamp while bubbling oxygen gas at 0.5 L / min while stirring the mixed solution. Subsequently, the light irradiation was stopped, the reaction temperature was raised to 50 ° C., and the mixture was stirred for 30 minutes. Thereafter, thiophene (0.74 mL, 10 mmol) was added dropwise at room temperature, and the mixture was refluxed for 6 hours.
  • reaction solution was added to a saturated aqueous sodium carbonate solution (30 mL) at 0 ° C., and the mixture was stirred for 30 minutes. Chloroform was added to the reaction solution, the reaction solution separated into two layers was separated, and the aqueous layer was extracted with chloroform. The organic layer and the extract were combined, dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated under reduced pressure. When the concentrate was analyzed by 1 H-NMR, formation of 2-formylthiophene as a target compound could be confirmed (yield: 61%). As described above, formylation of unsubstituted thiophene with the Vilsmeier reagent has not been reported, but it has been demonstrated that formalization of unsubstituted thiophene is possible according to the present invention.
  • Example 7 Production of 5-methyl-2-formylthiophene A concentrate was obtained in the same manner as in Example 2 except that 2-methylthiophene (0.97 mL, 10 mmol) was used instead of pyrrole. When the concentrate was analyzed by 1 H-NMR, the formation of 5-methyl-2-formylthiophene as the target compound could be confirmed (yield: 56%).
  • Example 8 Preparation of 2-formyl-3-methylthiophene or 2-formyl-4-methylthiophene
  • 3-methylthiophene (0.97 mL, 10 mmol) was used instead of pyrrole to obtain 3-methylthiophene.
  • the heating and refluxing time after the dropwise addition was changed to 2 hours.
  • the yield of 2-formyl-3-methylthiophene was 74%
  • the yield of 2-formyl-4-methylthiophene was 16%.
  • Example 9 Preparation of 2-formyl-3-methylthiophene or 2-formyl-4-methylthiophene Same as Example 8 except that 1-pyrrolidinecarboxaldehyde (1.98 mL, 20 mmol) was used instead of DMF. To give a concentrate. When the concentrate was analyzed by 1 H-NMR, the yield of 2-formyl-3-methylthiophene was 11%, and the yield of 2-formyl-4-methylthiophene was 4%.
  • Example 10 Production of 3-formylindole
  • a reaction solution containing a Vilsmeier reagent was prepared.
  • a solution of indole (1.17 g, 10 mmol) in DMF (10 mL) was added to the reaction solution, and the mixture was stirred at room temperature for 2 hours. Further, a 7.5 mol / L aqueous sodium hydroxide solution (20 mL) was added, and the mixture was stirred at 0 ° C. for 15 minutes.
  • the reaction solution separated into two layers was separated, and the aqueous layer was extracted with diethyl ether.
  • the organic layer and the extract were combined, dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated under reduced pressure.
  • Example 11 Photoformylation reaction of bipyrrole derivative Purified chloroform (20 mL, 248 mmol) and DMF (0.56 mL, 7.23 mmol) were added into the reaction vessel of Example 1. The reaction was carried out at 30 ° C. for 2 hours while irradiating light with the low-pressure mercury lamp while bubbling oxygen gas at 0.5 L / min while stirring the mixed solution. Subsequently, the light irradiation was stopped, the reaction temperature was raised to 50 ° C., and the mixture was stirred for 30 minutes.
  • Example 12 Production of bis (pyrrole-2-carboxaldehyde) Into the reaction vessel of Example 1, purified chloroform (20 mL, 248 mmol) and DMF (1.15 mL, 14.9 mmol) were added. The reaction was carried out at 10 ° C. for 6 hours while irradiating light with the low-pressure mercury lamp while bubbling oxygen gas at 0.5 L / min while stirring the mixed solution. Subsequently, the reaction temperature was raised to 50 ° C., and the mixture was stirred for 30 minutes. Thereafter, the reaction vessel was immersed in an ice bath, bipyrrole (420 mg, 3.18 mmol) was added, and the mixture was heated under reflux for 30 minutes.
  • bipyrrole 420 mg, 3.18 mmol
  • Example 13 Formylation reaction of benzofuran Purified chloroform (20 mL, 248 mmol) and DMF (1.56 mL, 20 mmol) were added to the reaction vessel of Example 1. The reaction was carried out at 0 ° C. for 5 hours while irradiating the low pressure mercury lamp with light while bubbling oxygen gas at 0.5 L / min while stirring the mixed solution. Subsequently, the reaction temperature was raised to room temperature, benzofuran (1.0 mL, 9 mmol) was added, and the mixture was stirred at 70 ° C. for 30 minutes, and further heated under reflux for 20 hours. Then, a saturated aqueous sodium carbonate solution (20 mL) was added, and the mixture was stirred for 15 minutes.
  • benzofuran 1.0 mL, 9 mmol
  • Example 14 Production of phenylpyrrolyl ketone Purified chloroform (20 mL, 248 mmol) and N, N-dimethylbenzamide (3 g, 20 mmol) were added to the reaction vessel of Example 1. The reaction was carried out at 30 ° C. for 3 hours while irradiating the low pressure mercury lamp with light while bubbling oxygen gas at 0.5 L / min while stirring the mixed solution. Subsequently, the light irradiation was stopped, the reaction temperature was raised to 50 ° C., and the mixture was stirred for 30 minutes. Thereafter, pyrrole (0.7 mL, 10 mmol) was added, and the mixture was heated under reflux for 30 minutes.
  • Example 15 Production of 2-acetylpyrrole Purified chloroform (20 mL, 248 mmol) and N, N-dimethylacetamide (1.7 g, 20 mmol) were added to the reaction vessel of Example 1. The reaction was carried out at 30 ° C. for 3 hours while irradiating the low pressure mercury lamp with light while bubbling oxygen gas at 0.5 L / min while stirring the mixed solution. Subsequently, the light irradiation was stopped, and the mixture was stirred at 30 ° C. for 30 minutes. Thereafter, pyrrole (0.7 mL, 10 mmol) was added, and the mixture was stirred overnight. Next, the resulting insoluble salts were removed by suction filtration, and the filtrate was concentrated under reduced pressure to obtain the desired compound (yield: 0.39 g, yield: 36.0%).
  • Comparative Example 1 Purified chloroform (30 mL, 372 mmol) and benzoic acid (1.22 g, 10 mmol) were added into the reaction vessel of Example 1. The reaction was carried out at 10 ° C. for 3 hours while bubbling oxygen gas at 0.5 L / min and irradiating light with the low-pressure mercury lamp while stirring the mixed solution. The reaction solution was analyzed by 1 H-NMR, but the reaction did not proceed at all. The reason why the reaction did not proceed is probably due to the fact that the Vilsmeier reagent was not generated because no amide compound was used.
  • Example 16 Production of benzoyl chloride and amidation thereof Into the reaction vessel of Example 1, purified chloroform (30 mL, 372 mmol), DMF (0.4 mL, 5 mmol) and benzoic acid (1.22 g, 10 mmol) were added. The reaction was carried out at 10 ° C. for 3 hours while bubbling oxygen gas at 0.5 L / min and irradiating light with the low-pressure mercury lamp while stirring the mixed solution. When the reaction solution was analyzed by 1 H-NMR, benzoyl chloride was produced in a yield of 95%.
  • Example 17 Production of benzoyl chloride Into the reaction vessel of Example 1, purified chloroform (30 mL, 372 mmol), DMF (0.4 mL, 5 mmol) and benzoic acid (1.22 g, 10 mmol) were added. The reaction was carried out at 30 ° C. for 2 hours while irradiating light with the low-pressure mercury lamp while bubbling oxygen gas at 0.5 L / min while stirring the mixed solution. When the reaction solution was analyzed by 1 H-NMR, benzoyl chloride was quantitatively formed.
  • Example 18 Production of benzoyl chloride Tetrachloroethylene (30 mL, 293 mmol), DMF (0.4 mL, 5 mmol) and benzoic acid (1.22 g, 10 mmol) were added to the reaction vessel of Example 1. The reaction was carried out at 30 ° C. for 2 hours while irradiating light with the low-pressure mercury lamp while bubbling oxygen gas at 0.5 L / min while stirring the mixed solution. When the reaction solution was analyzed by 1 H-NMR, benzoyl chloride was produced in a yield of 8.5%.
  • Example 19 Production of acetyl chloride Into the reaction vessel of Example 1, purified chloroform (20 mL, 248 mmol), DMF (0.4 mL, 5 mmol) and acetic acid (0.57 mL, 10 mmol) were added. The reaction was carried out at 30 ° C. for 3 hours while irradiating the low pressure mercury lamp with light while bubbling oxygen gas at 0.5 L / min while stirring the mixed solution. When the reaction solution was analyzed by 1 H-NMR, acetyl chloride was produced in a yield of 90%.
  • Example 20 Production of propionyl chloride The reaction was carried out in the same manner as in Example 19 except that propionic acid (0.67 mL, 10 mmol) was used instead of acetic acid. When the reaction solution was analyzed by 1 H-NMR, formation of propionyl chloride was confirmed (yield: 90%).
  • Example 21 Production of dichloroacetyl chloride The reaction was carried out in the same manner as in Example 19, except that dichloroacetic acid (0.82 mL, 10 mmol) was used instead of acetic acid, and the reaction time was changed to 2 hours. When the reaction solution was analyzed by 1 H-NMR, it was confirmed that dichloroacetyl chloride was generated quantitatively.
  • Example 22 Production of acryloyl chloride The reaction was carried out in the same manner as in Example 19, except that acrylacetic acid (0.69 mL, 10 mmol) was used instead of acetic acid, and the reaction time was changed to 2 hours. When the reaction solution was analyzed by 1 H-NMR, formation of acryloyl chloride was confirmed (yield: 14%).
  • Example 23 Production of maloyl chloride The reaction was carried out in the same manner as in Example 19, except that malonic acid (1.04 g, 10 mmol) was used instead of acetic acid, and 2 mL (25 mmol) of DMF was used. When the reaction solution was analyzed by 1 H-NMR, formation of maloyl chloride was confirmed (yield: 82%).
  • Example 24 Production of 4-nitrobenzoyl chloride The reaction was carried out in the same manner as in Example 19 except that 4-nitrobenzoic acid (1.04 mL, 10 mmol) was used instead of acetic acid. When the reaction solution was analyzed by 1 H-NMR, formation of 4-nitrobenzoyl chloride was confirmed (yield: 83%).
  • Example 25 Preparation of 4-methoxybenzoyl chloride
  • 4-methoxybenzoic acid (1.52 g, 10 mmol) was used in place of acetic acid, and 3.2 mL (46 mmol) of DMF was used. The reaction was performed. When the reaction solution was analyzed by 1 H-NMR, formation of 4-methoxybenzoyl chloride was confirmed (yield: 89%).
  • Example 26 Production of 2-thiophenecarbonyl chloride
  • 2-thiophenecarboxylic acid (1.28 g, 10 mmol) was used instead of acetic acid, and 2 mL (25 mmol) of DMF was used, and the reaction time was set to 2 hours.
  • the reaction was carried out in the same manner except for the above.
  • the reaction solution was analyzed by 1 H-NMR, formation of 2-thiophenecarbonyl chloride could be confirmed (yield: 93%).
  • Example 27 Production of 2-furancarbonyl chloride The reaction was carried out in the same manner as in Example 19, except that 2-furancarboxylicacetic acid (1.12 g, 10 mmol) was used instead of acetic acid, and the reaction time was changed to 2 hours. Was. When the reaction solution was analyzed by 1 H-NMR, it was confirmed that 2-furancarbonyl chloride was generated quantitatively.
  • Example 28 Production of terephthalic acid dianilide Into the reaction vessel of Example 1, purified chloroform (20 mL, 248 mmol), DMF (2.4 mL, 30 mmol) and terephthalic acid (0.41 g, 2.5 mmol) were added. The reaction was carried out at 30 ° C. for 2 hours while irradiating light with the low-pressure mercury lamp while bubbling oxygen gas at 0.5 L / min while stirring the mixed solution. Subsequently, the reaction temperature was raised to 50 ° C., and the mixture was stirred until no bubbles were generated. The reaction solution was analyzed by 1 H-NMR to confirm the formation of terephthalic acid dichloride.
  • Example 29 Production of phthalic anhydride
  • Purified chloroform (20 mL, 248 mmol), DMF (0.8 mL, 10 mmol) and phthalic acid (1.66 g, 10 mmol) were added to the reaction vessel of Example 1.
  • the reaction was carried out at 30 ° C. for 2 hours while irradiating light with the low-pressure mercury lamp while bubbling oxygen gas at 0.5 L / min while stirring the mixed solution.
  • the reaction solution was analyzed by 1 H-NMR, and the formation of phthalic anhydride was confirmed.
  • phthalic acid dichloride was once generated from phthalic acid, and phthalic acid dichloride was further reacted with DMF to generate phthalic anhydride.
  • Example 30 Production of 2,2,2-trifluoropropionic acid chloride
  • 2,2,2-trifluoropropionic acid (0.87 mL, 10 mmol) was used in place of acetic acid, and DMF was added at 0.
  • the reaction was carried out in the same manner except that 3 mL (4 mmol) was used, the reaction temperature was 20 ° C., and the reaction time was 2 hours.
  • the reaction solution was analyzed by 1 H-NMR, it was confirmed that 2,2,2-trifluoropropionic acid chloride was generated quantitatively.
  • Example 31 Preparation of 4-fluorobenzoic acid chloride
  • 4-fluorobenzoic acid 715 mg, 5 mmol
  • acetic acid 0.9 mL (11.6 mmol)
  • DMF dimethyl sulfoxide
  • the reaction was carried out in the same manner except that the reaction time was 2 hours.
  • the reaction solution was analyzed by 1 H-NMR, it was confirmed that 4-fluorobenzoic acid chloride was generated quantitatively.
  • Example 32 Production of pentafluorobenzoic acid anilide Purified chloroform (20 mL, 248 mmol), DMF (0.4 mL, 5 mmol) and pentafluorobenzoic acid (1.06 g, 5 mmol) were added into the reaction vessel of Example 1. . The reaction was carried out at 30 ° C. for 2 hours while irradiating light with the low-pressure mercury lamp while bubbling oxygen gas at 0.5 L / min while stirring the mixed solution. Subsequently, the reaction temperature was raised to 50 ° C., and the mixture was stirred until no bubbles were generated. Aniline (0.46 mL, 5 mmol) was added to the above reaction solution, and the mixture was stirred at room temperature for 3 hours.
  • Example 33 Production of methyl formate Into the reaction vessel of Example 1, purified chloroform (20 mL, 248 mmol) and DMF (1.56 mL, 20 mmol) were added. The reaction was carried out at 30 ° C. for 2 hours while irradiating light with the low-pressure mercury lamp while bubbling oxygen gas at 0.5 L / min while stirring the mixed solution. Subsequently, the light irradiation was stopped, the reaction temperature was raised to 50 ° C., and the mixture was stirred for 30 minutes. The reaction solution was cooled to 0 ° C., methanol (0.81 mL, 10 mmol) was added, and the mixture was stirred at room temperature for 30 minutes.
  • reaction solution was added to an ice-cooled saturated aqueous sodium hydrogen carbonate solution, and the mixture was separated.
  • the aqueous layer was extracted with chloroform, the organic layer and the extract were combined, dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated under reduced pressure.
  • the concentrate was analyzed by 1 H-NMR, formation of methyl formate could be confirmed (yield: 53%).
  • Example 34 Production of ethyl formate Ethyl formate was obtained in the same manner as in Example 33 except that ethanol (0.79 mL, 10 mmol) was used instead of methanol (yield: 88%).
  • Example 35 Production of isopropyl formate Into the reaction vessel of Example 1, purified chloroform (20 mL, 248 mmol) and DMF (1.56 mL, 20 mmol) were added. The reaction was carried out at 30 ° C. for 2 hours while irradiating light with the low-pressure mercury lamp while bubbling oxygen gas at 0.5 L / min while stirring the mixed solution. Subsequently, the light irradiation was stopped, the reaction temperature was raised to 50 ° C., and the mixture was stirred for 15 minutes. The reaction solution was cooled to 0 ° C., and isopropanol (0.77 mL, 10 mmol) was added, followed by stirring at room temperature for 12 hours.
  • reaction solution was added to an ice-cooled saturated aqueous solution of sodium hydrogen carbonate, and the mixture was stirred for 30 minutes.
  • the reaction solution was separated, the aqueous layer was extracted with chloroform, the organic layer and the extract were combined, dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated under reduced pressure.
  • the concentrate was analyzed by 1 H-NMR, formation of isopropyl formate could be confirmed (yield: 28%).
  • Example 36 Production of isopropyl formate Isopropyl formate was obtained in the same manner as in Example 35 except that pyridine (1.6 mL, 20 mmol) was added dropwise at 0 ° C in addition to isopropanol (yield: 51%).
  • Example 37 Production of phenyl formate Into the reaction vessel of Example 1, purified chloroform (20 mL, 248 mmol) and DMF (1.56 mL, 20 mmol) were added. The reaction was carried out at 30 ° C. for 2 hours while irradiating light with the low-pressure mercury lamp while bubbling oxygen gas at 0.5 L / min while stirring the mixed solution. Subsequently, the light irradiation was stopped, the reaction temperature was raised to 50 ° C., and the mixture was stirred for 15 minutes. The reaction solution was cooled to 0 ° C., phenol (0.94 g, 10 mmol) was added dropwise, and the mixture was stirred at room temperature for 6 hours.
  • reaction solution was added to an ice-cooled saturated aqueous solution of sodium hydrogen carbonate, and the mixture was stirred for 30 minutes.
  • the reaction solution was separated, the aqueous layer was extracted with chloroform, the organic layer and the extract were combined, dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated under reduced pressure.
  • the concentrate was analyzed by 1 H-NMR, formation of phenyl formate could be confirmed (yield: 82%).
  • Example 38 Production of 2,2,2-trifluoroethanol formate Purified chloroform (20 mL, 248 mmol) and DMF (1.56 mL, 20 mmol) were added to the reaction vessel of Example 1. The reaction was carried out at 30 ° C. for 2 hours while irradiating light with the low-pressure mercury lamp while bubbling oxygen gas at 0.5 L / min while stirring the mixed solution. Subsequently, the light irradiation was stopped, the reaction temperature was raised to 50 ° C., and the mixture was stirred for 30 minutes. The reaction solution was cooled to 0 ° C., 2,2,2-trifluoroethanol (0.94 g, 10 mmol) was added dropwise, and the mixture was stirred at room temperature for 12 hours.
  • reaction solution was added to an ice-cooled saturated aqueous solution of sodium hydrogen carbonate, and the mixture was stirred for 30 minutes.
  • the reaction solution was separated, the aqueous layer was extracted with chloroform, the organic layer and the extract were combined, dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated under reduced pressure.
  • the concentrate was analyzed by 1 H-NMR, formation of 2,2,2-trifluoroethanol formate could be confirmed (yield: 67%).
  • Example 39 Production of 1,6-hexanediol diformate Purified chloroform (20 mL, 248 mmol) and DMF (1.56 mL, 20 mmol) were added to the reaction vessel of Example 1. The reaction was carried out at 30 ° C. for 2 hours while irradiating light with the low-pressure mercury lamp while bubbling oxygen gas at 0.5 L / min while stirring the mixed solution. Subsequently, the light irradiation was stopped, the reaction temperature was raised to 50 ° C., and the mixture was stirred for 15 minutes.
  • the reaction solution was cooled to 0 ° C., 1,6-hexanediol (0.59 g, 5 mmol) was added dropwise, and the mixture was stirred at room temperature for 1 hour. Then, the reaction solution was added to an ice-cooled saturated aqueous solution of sodium hydrogen carbonate, and the mixture was stirred for 30 minutes. The reaction solution was separated, the aqueous layer was extracted with chloroform, the organic layer and the extract were combined, dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated under reduced pressure. When the concentrate was analyzed by 1 H-NMR, formation of 1,6-hexanediol diformate could be confirmed (yield: 52%).
  • Example 40 Examination of reaction temperature The reaction temperature at the time of preparing the Vilsmeier reagent was examined. Specifically, purified chloroform (20 mL, 248 mmol) and DMF (1.56 mL, 20 mmol) were added into the reaction vessel of Example 1. The reaction was carried out for 6 hours while bubbling oxygen gas at 0.5 L / min and irradiating light with the low-pressure mercury lamp while adjusting the temperature in the range of 0 to 30 ° C. while stirring the mixed solution. Thereafter, when the stirring was stopped, the reaction solution was separated into two layers. The upper layer was analyzed by 1 H-NMR, and the conversion from DMF to Vilsmeier reagent was determined from the peak intensity. Table 1 shows the results.
  • Example 41 Examination of the amount of the amide compound The optimal amount of the amide compound at the time of preparing the Vilsmeier reagent was examined. Specifically, purified chloroform (20 mL, 248 mmol) and DMF in the range of 0.78 to 4.68 mL (10 to 60 mmol) were added into the reaction vessel of Example 1. The reaction was carried out for 5 to 27 hours while controlling the temperature in the range of 0 to 30 ° C. while bubbling oxygen gas at 0.5 L / min and irradiating light with the low-pressure mercury lamp while stirring the mixed solution. . Thereafter, when the stirring was stopped, the reaction solution was separated into two layers. The upper layer was analyzed by 1 H-NMR, and the conversion from DMF to Vilsmeier reagent was determined from the peak intensity. Table 2 shows the results.
  • Example 42 Production of 2-formylfuran Purified chloroform (20 mL, 248 mmol) and DMF (0.78 mL, 10 mmol) were added to the reaction vessel of Example 1. The reaction was carried out at 0 ° C. for 6 hours while irradiating light with the low-pressure mercury lamp while bubbling oxygen gas at 0.5 L / min while stirring the mixed solution. Subsequently, the reaction temperature was raised to 50 ° C., and the mixture was stirred for 1 hour. Thereafter, the reaction vessel was immersed in an ice bath, and furan (0.73 mL, 10 mmol) dissolved in acetone (3 mL) was added dropwise, followed by stirring at 20 ° C for 2 hours.
  • Example 43 Production of 2-formylfuran Purified chloroform (20 mL, 248 mmol) and DMF (0.78 mL, 10 mmol) were added to the reaction vessel of Example 1. The reaction was carried out at 0 ° C. for 6 hours while irradiating light with the low-pressure mercury lamp while bubbling oxygen gas at 0.5 L / min while stirring the mixed solution. Subsequently, the reaction temperature was raised to 50 ° C., and the mixture was stirred for 1 hour. Thereafter, the reaction vessel was immersed in an ice bath, and furan (0.73 mL, 10 mmol) dissolved in acetonitrile (3 mL) was added dropwise, followed by stirring at 20 ° C. for 2 hours.

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)

Abstract

Le but de la présente invention est de fournir : un procédé de préparation d'un réactif de Vilsmeier, qui peut être mis en œuvre en toute sécurité, de manière facile, et à un faible coût ; ainsi qu'un procédé de production d'un aldéhyde aromatique ou d'une cétone aromatique, d'un halogénure carboxylique et d'un ester formique. L'invention concerne un procédé de préparation d'un réactif de Vilsmeier caractérisé en ce qu'il comprend : une étape consistant à dégrader un hydrocarbure halogéné en C1-4 par irradiation avec de la lumière, en présence d'une enzyme, d'une composition comprenant un hydrocarbure halogéné en C1-4 ayant au moins un groupe halogène choisi dans le groupe constitué par le chlore, le brome et l'iode ; et une étape consistant à faire réagir un produit dégradé de l'hydrocarbure halogéné en C1-4 avec un composé amide spécifique.
PCT/JP2019/035031 2018-09-06 2019-09-05 Procédé de préparation d'un réactif de vilsmeier WO2020050368A1 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
JP2020541302A JP7344518B2 (ja) 2018-09-06 2019-09-05 ビルスマイヤー試薬の製造方法

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
JP2018167032 2018-09-06
JP2018-167032 2018-09-06

Publications (1)

Publication Number Publication Date
WO2020050368A1 true WO2020050368A1 (fr) 2020-03-12

Family

ID=69721924

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/JP2019/035031 WO2020050368A1 (fr) 2018-09-06 2019-09-05 Procédé de préparation d'un réactif de vilsmeier

Country Status (2)

Country Link
JP (1) JP7344518B2 (fr)
WO (1) WO2020050368A1 (fr)

Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2022172745A1 (fr) * 2021-02-12 2022-08-18 国立大学法人神戸大学 Procédé de production de carbonyle halogéné
JPWO2022172744A1 (fr) * 2021-02-12 2022-08-18
CN117964512A (zh) * 2024-04-01 2024-05-03 山东惟普控股有限公司 一种n,n-二甲基-3-甲氧基丙酰胺的合成方法
CN117964512B (zh) * 2024-04-01 2024-06-04 山东惟普控股有限公司 一种n,n-二甲基-3-甲氧基丙酰胺的合成方法

Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2008105464A1 (fr) * 2007-03-01 2008-09-04 Mitsui Chemicals, Inc. Procédé de fabrication d'un chlorure d'acide carboxylique
JP2012136502A (ja) * 2010-12-10 2012-07-19 Ihara Nikkei Kagaku Kogyo Kk イミドイルクロリド化合物の製造方法及びそれを用いた各種化合物の製造方法
JP2013181028A (ja) * 2012-03-05 2013-09-12 Kobe Univ ハロゲン化炭化水素に光照射して得られる混合物の使用
JP2013541533A (ja) * 2010-09-30 2013-11-14 アーウーテー グループ 連続ホスゲン化のための装置及び方法

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2008105464A1 (fr) * 2007-03-01 2008-09-04 Mitsui Chemicals, Inc. Procédé de fabrication d'un chlorure d'acide carboxylique
JP2013541533A (ja) * 2010-09-30 2013-11-14 アーウーテー グループ 連続ホスゲン化のための装置及び方法
JP2012136502A (ja) * 2010-12-10 2012-07-19 Ihara Nikkei Kagaku Kogyo Kk イミドイルクロリド化合物の製造方法及びそれを用いた各種化合物の製造方法
JP2013181028A (ja) * 2012-03-05 2013-09-12 Kobe Univ ハロゲン化炭化水素に光照射して得られる混合物の使用

Non-Patent Citations (3)

* Cited by examiner, † Cited by third party
Title
BARRETT, ANTHONY G. M. ET AL.: "Nucleophilic Substitution Reaction of (Alkoxymethylene)dimethylammonium Chloride", THE JOURNAL OF ORGANIC CHEMISTRY, vol. 63, no. 18, 1998, pages 6273 - 6280, XP055205955, ISSN: 1520-6904, DOI: 10.1021/jo980583j *
CHEN, YUESU ET AL.: "Visible Light-Promoted Beckmann Rearrangements: Separating Sequential Photochemical and Thermal Phenomena in a Contituous Flow Reactor", EUROPEAN JOURNAL OF ORGANIC CHEMISTRY, vol. 2019, no. 11, 15 February 2019 (2019-02-15), pages 2163 - 2171, XP055690921, ISSN: 1434-193X *
ZHAO, YUBAO ET AL.: "Visible-Light-Driven Conversion of Alcohols into Iodide Derivatives with Iodoform", CHEMPHOTOCHEM, vol. 2, no. 8, 2018, pages 720 - 724, XP055690926, ISSN: 2367-0932, [retrieved on 20180503] *

Cited By (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2022172745A1 (fr) * 2021-02-12 2022-08-18 国立大学法人神戸大学 Procédé de production de carbonyle halogéné
JPWO2022172744A1 (fr) * 2021-02-12 2022-08-18
WO2022172744A1 (fr) * 2021-02-12 2022-08-18 国立大学法人神戸大学 Procédé de production d'halogénure de carbonyle
JP7239953B2 (ja) 2021-02-12 2023-03-15 国立大学法人神戸大学 ハロゲン化カルボニルの製造方法
CN117964512A (zh) * 2024-04-01 2024-05-03 山东惟普控股有限公司 一种n,n-二甲基-3-甲氧基丙酰胺的合成方法
CN117964512B (zh) * 2024-04-01 2024-06-04 山东惟普控股有限公司 一种n,n-二甲基-3-甲氧基丙酰胺的合成方法

Also Published As

Publication number Publication date
JP7344518B2 (ja) 2023-09-14
JPWO2020050368A1 (ja) 2021-08-30

Similar Documents

Publication Publication Date Title
CN107141248B (zh) 一种可见光催化合成3-砜基螺环三烯酮化合物的方法
JP6057449B2 (ja) ハロゲン化蟻酸エステルの製造方法
WO2020050368A1 (fr) Procédé de préparation d'un réactif de vilsmeier
Jaiswal et al. The palladium (ii)-catalyzed regioselective ortho-C–H bromination/iodination of arylacetamides with in situ generated imidic acid as the directing group: mechanistic exploration
JP5574509B2 (ja) 芳香族アルデヒドの芳香族アシルハライドへの変換方法
JP7356707B2 (ja) アミノ酸－ｎ－カルボン酸無水物の製造方法
Kim et al. A new convenient method for the generation of alkoxy radicals from N-alkoxydithiocarbamates
CN107337663B (zh) 一种可见光诱导3-硫代螺环三烯酮化合物的制备方法
JP3918883B2 (ja) ベンゾイルクロライド類の製造方法
JPH03123762A (ja) ２，４‐または２，６‐ジハロゲノアニリンの製法
KR101109942B1 (ko) 방향족 불포화 화합물의 제조 방법
JP3814839B2 (ja) 芳香族ジアルデヒドの製造方法
Bellesia et al. 2, 2-Dichlorination of Aldehydes with the 2, 6-Lutidine· HCl/Cl2/CH2Cl2 System: an Environmentally Benign Process Suitable for Scale Up
Wu et al. CuLi2Cl4 catalysed cross-coupling strategy for the formal synthesis of the diterpenoid (+)-subersic acid from (–)-sclareol
JP2004026778A (ja) １−アダマンタノール類の製造方法
KR20060136357A (ko) 방향족 불포화 화합물의 제조 방법
JP2012144508A (ja) トリフェニレン誘導体の製造法
JP5360668B2 (ja) カルボニル化合物の製造方法
JPH09124538A (ja) 芳香族ジアルデヒド類の製造方法
JP4956760B2 (ja) ３−ブロモ安息香酸またはそのアルキルエステルの製造方法
Xu et al. Visible-Light-Driven Oxidative Chlorination of Alkyl sp3 C–H Bonds with HCl/Air at Room Temperature
Tariq Chiral Hypervalent Iodine Mediated Enantioselective Phenol and Naphthol Dearomatisation: A Rapid Access to Oxazoline Based Spirocycles
KR20230128318A (ko) 할로겐화 카르보닐의 제조 방법
CN116947613A (zh) 一种环保高效的全氟己酮的合成方法
JP2004083550A (ja) 含フッ素アルキルハロゲン化物の製造方法

Legal Events

Date Code Title Description
121 Ep: the epo has been informed by wipo that ep was designated in this application

Ref document number: 19858393

Country of ref document: EP

Kind code of ref document: A1

ENP Entry into the national phase

Ref document number: 2020541302

Country of ref document: JP

Kind code of ref document: A

NENP Non-entry into the national phase

Ref country code: DE

122 Ep: pct application non-entry in european phase

Ref document number: 19858393

Country of ref document: EP

Kind code of ref document: A1