[go: up one dir, main page]

WO2018105237A1 - Procédé de production d'un composé trioxopropane - Google Patents

Procédé de production d'un composé trioxopropane Download PDF

Info

Publication number
WO2018105237A1
WO2018105237A1 PCT/JP2017/037351 JP2017037351W WO2018105237A1 WO 2018105237 A1 WO2018105237 A1 WO 2018105237A1 JP 2017037351 W JP2017037351 W JP 2017037351W WO 2018105237 A1 WO2018105237 A1 WO 2018105237A1
Authority
WO
WIPO (PCT)
Prior art keywords
group
different
ion
compound
trioxopropane
Prior art date
Legal status (The legal status 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 status listed.)
Ceased
Application number
PCT/JP2017/037351
Other languages
English (en)
Japanese (ja)
Inventor
小林　修
拓 北之園
真樹 谷
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Kumiai Chemical Industry Co Ltd
Original Assignee
Kumiai Chemical Industry Co Ltd
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 Kumiai Chemical Industry Co Ltd filed Critical Kumiai Chemical Industry Co Ltd
Priority to JP2018554847A priority Critical patent/JP7030059B2/ja
Publication of WO2018105237A1 publication Critical patent/WO2018105237A1/fr
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

Links

Classifications

    • 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
    • C07C45/61—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups
    • C07C45/64—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups by introduction of functional groups containing oxygen only in singly bound form
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C49/00—Ketones; Ketenes; Dimeric ketenes; Ketonic chelates
    • C07C49/385—Saturated compounds containing a keto group being part of a ring
    • C07C49/487—Saturated compounds containing a keto group being part of a ring containing hydroxy groups
    • C07C49/497—Saturated compounds containing a keto group being part of a ring containing hydroxy groups a keto group being part of a six-membered ring
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C67/00—Preparation of carboxylic acid esters
    • C07C67/30—Preparation of carboxylic acid esters by modifying the acid moiety of the ester, such modification not being an introduction of an ester group
    • C07C67/313—Preparation of carboxylic acid esters by modifying the acid moiety of the ester, such modification not being an introduction of an ester group by introduction of doubly bound oxygen containing functional groups, e.g. carboxyl groups
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C69/00—Esters of carboxylic acids; Esters of carbonic or haloformic acids
    • C07C69/66—Esters of carboxylic acids having esterified carboxylic groups bound to acyclic carbon atoms and having any of the groups OH, O—metal, —CHO, keto, ether, acyloxy, groups, groups, or in the acid moiety
    • C07C69/67—Esters of carboxylic acids having esterified carboxylic groups bound to acyclic carbon atoms and having any of the groups OH, O—metal, —CHO, keto, ether, acyloxy, groups, groups, or in the acid moiety of saturated acids
    • C07C69/716—Esters of keto-carboxylic acids or aldehydo-carboxylic acids
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C69/00—Esters of carboxylic acids; Esters of carbonic or haloformic acids
    • C07C69/66—Esters of carboxylic acids having esterified carboxylic groups bound to acyclic carbon atoms and having any of the groups OH, O—metal, —CHO, keto, ether, acyloxy, groups, groups, or in the acid moiety
    • C07C69/73—Esters of carboxylic acids having esterified carboxylic groups bound to acyclic carbon atoms and having any of the groups OH, O—metal, —CHO, keto, ether, acyloxy, groups, groups, or in the acid moiety of unsaturated acids
    • C07C69/738—Esters of keto-carboxylic acids or aldehydo-carboxylic acids
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D319/00—Heterocyclic compounds containing six-membered rings having two oxygen atoms as the only ring hetero atoms
    • C07D319/04—1,3-Dioxanes; Hydrogenated 1,3-dioxanes
    • C07D319/06—1,3-Dioxanes; Hydrogenated 1,3-dioxanes not condensed with other rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
    • C07B61/00—Other general methods

Definitions

  • the present invention relates to a method for producing a trioxopropane compound much more efficiently than before by reacting a chlorite compound with a dioxopropane compound in the presence of a Lewis acid catalyst.
  • Trioxopropane compounds are compounds that have three keto groups in succession on the propylene chain and are important intermediates in organic synthesis.
  • a ketomalonic acid diester is a compound useful as a raw material when producing a pyrazin-2-one-3-carboxylic acid ester derivative by reacting with a diamine (Patent Documents 1-4 and Non-Patent Documents 1-2). reference). This reaction is used in the production of pharmaceuticals, agricultural chemicals and the like, particularly as a method for producing a quinoxalinone derivative from an aromatic diamine.
  • a method of producing a ketomalonic acid diester by oxidation with an oxidizing agent such as dinitrogen trioxide (for example, see Non-Patent Document 4), chromium trioxide (for example, see Non-Patent Document 6) or the like is known.
  • an oxidizing agent such as dinitrogen trioxide (for example, see Non-Patent Document 4), chromium trioxide (for example, see Non-Patent Document 6) or the like.
  • these methods have problems such as reagent toxicity, reagent safety, poor operability, low yield and / or the use of special reaction equipment.
  • Patent Document 6 Furthermore, a method of reacting malonic acid diester with chlorite has been reported (see Patent Document 6). Although the method described in Patent Document 6 is superior to the prior art known before Patent Document 6, it has been found that there is room for improvement in implementation on an industrial scale.
  • An object of the present invention is to provide a method for directly oxidizing an active methylene moiety of a dioxopropane compound in one step without previously modifying an active methylene moiety of a dioxopropane compound such as malonic acid diester. Furthermore, an object of the present invention is to provide an industrially preferable method capable of producing an industrially useful trioxopropane compound such as ketomalonic acid diester on an industrial scale and solving the above-mentioned problems. is there.
  • the carboxylic acid compound such as acetic acid described in Patent Document 6 may also serve as a solvent in addition to the role as a reaction catalyst, and a large amount in a scaled-up industrial scale implementation. There is concern about the discharge of acidic waste liquid.
  • Another object of the present invention is to provide a method for producing industrially useful trioxopropane compounds such as ketomalonic acid diesters without discharging a large amount of acidic waste liquid.
  • R 1 and R 2 may be the same or different, and each may be 1 or 2 C 1 -C 6 alkyl groups optionally substituted by the same or different R 3 , 1 or 2 or more identical or different R may C 3 substituted by 3 ⁇ C 6 cycloalkyl group, one or more identical or different R 4 by an optionally substituted aryl group, 1 or 2 or more Heteroaryl group, hydroxyl group, optionally substituted by the same or different R 4 , 1 or 2 or more C 1 -C 6 alkoxy groups optionally substituted by the same or different R 3 , 1 or 2 or more the same or different optionally substituted by R 3 C 3 ⁇ C 6 cycloalkoxy group, one or more identical or different R 4 by an optionally substituted aryloxy group, 1 Represents two or more identical or different optionally substituted by R 4 heteroaryloxy group, Or, R 1 and R 2 together, one or more identical or different R 3 by optionally substituted C 2 even though ⁇ C 5 alkylene
  • R 1 and R 2 may be the same or different and each is a C 1 -C 6 alkyl group optionally substituted by one or two or more of the same or different R 3, or one or more of the same or different C 3 -C 6 cycloalkyl group optionally substituted by different R 3 , one or more aryl groups optionally substituted by the same or different R 4 , one or more same or different R A heteroaryl group optionally substituted by 4 , a hydroxyl group, one or more C 1 -C 6 alkoxy groups optionally substituted by the same or different R 3 , one or more same or different A C 3 -C 6 cycloalkoxy group optionally substituted by R 3 , Or, R 1 and R 2 together, one or more identical or different R 3 by optionally substituted C 2 even though ⁇ C 5 alkylene group, one or more identical or different R 3 -O- may be substituted by (C 1 ⁇ C 4 alkylene)
  • R 1 and R 2 may be the same or different and each represents a hydroxyl group, a C 1 -C 6 alkoxy group optionally substituted by one or more same or different R 3 , or R 1 and R 2 are taken together to form a 6- to -O- (C 1 -C 3 alkylene) -O- group optionally substituted by one or more of the same or different R 3.
  • R 3 represents a C 1 -C 6 alkyl group, a C 3 -C 6 cycloalkyl group, a hydroxyl group, a C 1 -C 6 alkoxy group, or a halogen atom, according to any one of [1] to [5] A process for producing a trioxopropane compound.
  • R 1 and R 2 may be the same or different and each represents a C 1 -C 6 alkyl group, a phenyl group, a hydroxyl group, a C 1 -C 6 alkoxy group, Or, R 1 and R 2 together form a —CH 2 CH 2 CH 2 — group, —O—CH 2 —O— group, or —O—C (CH 3 ) 2 —O— group.
  • the method for producing a trioxopropane compound according to any one of [1] to [7], wherein a 6-membered ring may be formed.
  • R 1 and R 2 may be the same or different and each represents a C 1 -C 6 alkyl group, a phenyl group, a C 1 -C 6 alkoxy group, Alternatively, R 1 and R 2 may be combined to form a —CH 2 CH 2 CH 2 — group to form a 6-membered ring, according to any one of [1] to [8] A method for producing the described trioxopropane compound.
  • R 1 and R 2 may be the same or different and each represents a hydroxyl group, a C 1 -C 6 alkoxy group, Alternatively, R 1 and R 2 may be combined to form a 6-membered ring by forming a —O—CH 2 —O— group or a —O—C (CH 3 ) 2 —O— group.
  • R 1 represents a C 1 -C 6 alkyl group, a phenyl group
  • R 2 represents a C 1 -C 6 alkyl group, a C 1 -C 6 alkoxy group
  • R 1 and R 2 may be combined to form a —CH 2 CH 2 CH 2 — group to form a 6-membered ring, according to any one of [1] to [10] A method for producing the described trioxopropane compound.
  • the Lewis acid catalyst is represented by the following general formula (4): MZ n (4) (Wherein M represents a metal ion, Z represents an anion, and n is an integer of 1 to 4)
  • M represents a metal ion
  • Z represents an anion
  • n is an integer of 1 to 4
  • M consists of aluminum, gallium, thallium, scandium, titanium, vanadium, chromium, manganese, iron, ruthenium, cobalt, rhodium, iridium, nickel, palladium, platinum, copper, silver, gold, zinc, hafnium, cerium and bismuth At least one metal ion selected from the group;
  • Z is a halide ion, oxide ion, acetate ion, sulfate ion, nitrate ion, trifluoromethanesulfonate ion, perfluorooctanesulfonate ion, or acetylacetonate ion, according to [15] or [16]
  • a method for producing a trioxopropane compound is a method for producing a trioxopropane compound.
  • M is an ion of at least one metal selected from the group consisting of scandium, vanadium, iron, cobalt, rhodium and hafnium;
  • the trioxopropane according to any one of [15] to [18], wherein Z is a halide ion, oxide ion, acetate ion, sulfate ion, trifluoromethanesulfonate ion, or perfluorooctanesulfonate ion.
  • M is an ion of at least one metal selected from the group consisting of vanadium, iron, cobalt, rhodium and hafnium;
  • the trioxopropane according to any one of [15] to [19], wherein Z is a halide ion, oxide ion, acetate ion, sulfate ion, trifluoromethanesulfonate ion, or perfluorooctanesulfonate ion.
  • M is an ion of at least one metal selected from the group consisting of scandium and hafnium;
  • Lewis acid catalyst is scandium (III) triflate, vanadium oxide (V), vanadium oxide sulfate (IV), manganese (II) sulfate, iron (II) acetate, cobalt (II) chloride, cobalt sulfate (II) , Cobalt acetate (II), cobalt (II) acetylacetonate, rhodium acetate (II), nickel chloride (II), nickel acetate (II), hafnium (IV) triflate, hafnium (IV) perfluorooctane sulfonate, cerium (IV) The method for producing a trioxopropane compound according to any one of [15] to [22], which is triflate, bismuth (III) triflate, or a mixture thereof.
  • Lewis acid catalyst is scandium (III) triflate, vanadium oxide (V), vanadium oxide sulfate (IV), iron (II) acetate, cobalt (II) chloride, cobalt (II) sulfate, cobalt (II) acetate , Rhodium (II) acetate, hafnium (IV) triflate, hafnium (IV) perfluorooctane sulfonate, or a mixture thereof, The production of the trioxopropane compound according to any one of [15] to [23] Method.
  • Lewis acid catalyst is vanadium oxide (V), vanadium oxide sulfate (IV), iron (II) acetate, cobalt (II) chloride, cobalt (II) sulfate, cobalt (II) acetate, rhodium acetate (II) , A method for producing a trioxopropane compound according to any one of [15] to [24], which is hafnium (IV) triflate, hafnium (IV) perfluorooctane sulfonate, or a mixture thereof.
  • the method of the present invention provides an industrial method for producing trioxopropane compounds such as ketomalonic acid diester.
  • the active methylene moiety of the dioxopropane compound can be directly oxidized in one step without previously modifying the active methylene moiety of the dioxopropane compound such as malonic acid diester.
  • the method of the present invention does not use a carboxylic acid compound such as acetic acid as a reaction catalyst in expectation of an effect as a solvent, a large amount of acidic waste liquid on an industrial scale can be discharged. Can be manufactured without.
  • a carboxylic acid compound such as acetic acid
  • the method of the present invention can select mild reaction conditions, has good operability, and can produce trioxopropane compounds such as ketomalonic acid diesters under simple conditions suitable for industrialization.
  • the notation by an element symbol such as C 1 to C 6 and a subscript number indicates that the number of elements of the group described subsequently is in a range indicated by the subscript number.
  • the carbon number is 1 to 6.
  • the C 3 -C 6 cycloalkyl group refers to a cyclic alkyl group having 3 to 6 carbon atoms.
  • Examples of the C 3 -C 6 cycloalkyl group include, but are not limited to, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, and the like.
  • aryl group examples include phenyl, 1- or 2-naphthyl and the like.
  • the heteroaryl group is a 5- to 10-membered member having a hetero atom selected from one or more (for example, 1 to 4, preferably 1 or 2) nitrogen atom, oxygen atom and sulfur atom in addition to the carbon atom. It represents a ring, preferably a 5- to 7-membered aromatic heterocyclic group.
  • heteroaryl groups include, but are not limited to, furyl, thienyl, pyrazolyl, pyridyl, quinolinyl, and the like.
  • heteroaryl groups include, for example, 2- or 3-furyl, 2- or 3-thienyl, 1-, 3-, 4- or 5-pyrazolyl, 2-, 3- or 4-pyridyl , 2- or 8-quinolyl and the like, but are not limited thereto.
  • C 1 -C 6 alkoxy group means a (C 1 -C 6 alkyl) -O— group (where C 1 -C 6 alkyl has the same meaning as described above).
  • Examples of the C 1 -C 6 alkoxy group include methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, sec-butoxy, isobutoxy, tert-butoxy, n-pentyloxy, isopentyloxy, neopentyloxy, Examples thereof include, but are not limited to, n-hexyloxy, isohexyloxy, 3,3-dimethylbutyloxy and the like.
  • C 3 -C 6 cycloalkoxy group means a (C 3 -C 6 cycloalkyl) -O— group (wherein C 3 -C 6 cycloalkyl has the same meaning as described above).
  • Examples of C 3 -C 6 cycloalkoxy groups include, but are not limited to, cyclopropyloxy, cyclobutyloxy, cyclopentyloxy, cyclohexyloxy, and the like.
  • An aryloxy group means an (aryl) -O- group (wherein aryl has the same meaning as described above).
  • Examples of the aryloxy group include phenoxy, 1- or 2-naphthoxy and the like.
  • the heteroaryloxy group means a (heteroaryl) -O- group (wherein heteroaryl has the same meaning as described above).
  • heteroaryloxy group include, but are not limited to, furyloxy, thienyloxy, pyrazolyloxy, pyridyloxy, quinolinyloxy, and the like. More specific examples of heteroaryl groups include, for example, 2- or 3-furyloxy, 2- or 3-thienyloxy, 3-, 4- or 5-pyrazolyloxy, 2-, 3- or 4-pyridyloxy , 2- or 8-quinolyloxy and the like, but are not limited thereto.
  • the halogen atom is a fluorine atom, a chlorine atom, a bromine atom or an iodine atom.
  • R 1 and R 2 may together form a ring” means that the R 1 group and R 2 group together form a divalent group to form a ring.
  • Examples of the divalent group formed by combining R 1 group and R 2 group include C 2 -C 5 alkylene group, —O— (C 1 -C 4 alkylene) -group, and —O— ( Examples thereof include, but are not limited to, a C 1 -C 3 alkylene) -O— group.
  • the alkylene group means a divalent group obtained by removing two hydrogens from a linear alkane, and examples thereof include a methylene group, an ethylene group, and an n-propylene group.
  • the alkylene group may be substituted with the substituent R 3 as described above.
  • R 1 and R 2 may be the same or different, and each may be 1 or 2 C 1 -C 6 alkyl groups optionally substituted by the same or different R 3 , 1 or 2 or more identical or different R may C 3 substituted by 3 ⁇ C 6 cycloalkyl group, one or more identical or different R 4 by an optionally substituted aryl group, 1 or 2 or more Heteroaryl group, hydroxyl group, optionally substituted by the same or different R 4 , 1 or 2 or more C 1 -C 6 alkoxy groups optionally substituted by the same or different R 3 , 1 or 2 or more the same or different optionally substituted by R 3 C 3 ⁇ C 6 cycloalkoxy group, one or more identical or different R 4 by an optionally substituted aryloxy group, 1 Represents two or more identical or different optionally substituted by R 4 heteroaryloxy group, Or, R 1 and R 2 together, one or more identical or different R 3 by optionally substituted C 2 even though ⁇ C 5 alkylene
  • dioxopropane compound represented by the general formula (2) include malonic acid, dimethyl malonate, diethyl malonate, di-n-propyl malonate, diisopropyl malonate, and di-n-butyl malonate.
  • the dioxopropane compound is preferably dimethyl malonate, diethyl malonate, di-n-propyl malonate, diisopropyl malonate, di-n-butyl malonate, diisobutyl malonate, disec-butyl malonate, di-malonate.
  • the dioxopropane compound (raw material compound) represented by the general formula (2) is a known compound, or a compound that can be produced by, for example, a known method.
  • R 1 and R 2 are as defined in the above general formula (2). It is a trioxopropane compound represented by these.
  • dimethyl ketomalonate diethyl ketomalonate, methyl 2,3-dioxo-3-phenylpropionate, ethyl 2,3-dioxo-3-phenylpropionate, 2,2-dimethyl-1,3-dioxane- 4,5,6-trione, 1,2,3-cyclohexanetrione and the like, more preferably diethyl ketomalonate, ethyl 2,3-dioxo-3-phenylpropionate, 2,2-dimethyl-1, Examples include 3-dioxane-4,5,6-trione, 1,2,3-cyclohexanetrione, and the like.
  • chlorous acid compound Chlorous acid compound
  • chlorous acid compound Chlorous acid compound
  • chlorite compounds selected from chlorous acid or chlorite are used.
  • the chlorite may be a salt formed by chlorite ions and cations, but is not limited thereto.
  • the cation include a metal cation and an onium cation, but are not limited thereto.
  • metal cations include alkali metal ions (for example, lithium ions, sodium ions, potassium ions, or cesium ions); alkaline earth metal ions (for example, magnesium ions, calcium ions, barium ions, etc.); earth metal ions (For example, aluminum ions); zinc group ions (for example, zinc ions); transition metal ions (for example, copper ions, silver ions, nickel ions, manganese ions, iron ions, etc.) It is not limited to these.
  • onium cations include ammonium ions (NH 4 + ); linear or branched C 1 -C 8 alkyl groups or quaternary ammonium ions having a phenyl group (for example, tetramethylammonium ion, tetrabutylammonium ion, tetraoctylammonium ion) , Trimethylbutylammonium ion, trimethyloctylammonium ion, tributylmethylammonium ion, trioctylmethylammonium ion, etc.); a quaternary phosphonium ion having a linear or branched C 1 -C 8 alkyl group or phenyl group (for example, tetramethylphosphonium) Ions, tetrabutylphosphonium ions, tetraphenylphosphonium ions, etc.), but are not limited thereto.
  • ammonium ions NH 4 +
  • the salt (amine salt) of chlorous acid and amines can also be illustrated.
  • amines that form salts include methylamine, dimethylamine, trimethylamine, ethylamine, diethylamine, triethylamine, propylamine, dipropylamine, tripropylamine, butylamine, dibutylamine, tributylamine, diisopropylethylamine, hydrazine, methylhydrazine, Examples include, but are not limited to, pyridine, 2-methylpyridine, 3-methylpyridine, 4-methylpyridine, 2,4-dimethylpyridine, quinoline, aniline, or N, N-diethylaniline. is not.
  • These chlorites may be anhydrous or hydrated. These chlorites may be single salts or double salts.
  • chlorite compound examples include, for example, chlorous acid; alkali metal chlorite including lithium chlorite, sodium chlorite, sodium chlorite trihydrate, potassium chlorite and the like. Salt; Chlorine including magnesium chlorite, magnesium chlorite trihydrate, calcium chlorite, calcium chlorite trihydrate, barium chlorite, or barium chlorite dihydrate Acid alkaline earth metal salts; Earth chlorite metal salts such as aluminum chlorite; Zinc chlorite group salts such as zinc chlorite dihydrate; Copper chlorite (II), Copper chlorite (III), chlorite transition metal salts such as silver chlorite, nickel chlorite dihydrate, or manganese chlorite; ammonium chlorite; chlorite quaternary such as tetramethylammonium chlorite Ammonium salt; chlorous acid ( , 4-dinitrophenyl) quaternary phosphonium salts such as triethylphosphonium; methylamine chlorite, tripropy
  • the chlorite compound is preferably a chlorite, more preferably an alkali metal chlorite or an alkaline earth metal chlorite.
  • Alkali metal chlorates are more preferred, sodium chlorite or potassium chlorite is more preferred, and sodium chlorite is more preferred.
  • These chlorous acid compounds can be used in any form such as a liquid or solid containing only a chlorite compound, or an aqueous solution or a solution of a solvent other than water. Examples of solvents other than water include, but are not limited to, solvents that can be used in the method of the present invention described later.
  • the chlorous acid compound may be supplied as an aqueous solution.
  • concentration of the chlorous acid compound in the case of an aqueous solution is not particularly limited, but 5% by mass to 80% by mass, 5% by mass to 60% by mass, 5% by mass to 50% by mass, 5% by mass to 40% by mass, 5% to 30%, 5% to 25%, preferably 10% to 80%, 10% to 60%, 10% to 50%, 10% to 40% by weight
  • Examples include a range of 10% by mass to 30% by mass, 10% by mass to 25% by mass, and 10% by mass to 20% by mass.
  • the amount of the chlorous acid compound used in the present invention may be any amount as long as the reaction proceeds sufficiently, but from the viewpoint of yield, by-product suppression, economic efficiency, etc., the general formula (2) A range of usually 1.0 to 15.0 mol, preferably 1.5 to 5.0 mol, more preferably 2.0 to 3.5 mol can be exemplified with respect to 1 mol of the dioxopropane compound represented. .
  • Lewis acid (Lewis acid) Subsequently, the Lewis acid used in the method of the present invention will be described. A Lewis acid is used in the method of the present invention.
  • the general formula (4) MZn (4) (Wherein M represents a metal ion, Z represents a counter anion of M, and n is an integer of 1 to 4)
  • M represents a metal ion
  • Z represents a counter anion of M
  • n is an integer of 1 to 4
  • Z in the general formula (4) is a halide ion, oxide ion, acetate ion, sulfate ion, nitrate ion, trifluoromethanesulfonate ion (CF 3 SO 3 ⁇ ), perfluorooctanesulfonate ion (C 8). Examples thereof include, but are not limited to, F 17 SO 3 ⁇ ) and acetylacetonate ion (acac).
  • Z in the general formula (4) is preferably a halide ion, oxide ion, acetate ion, sulfate ion, trifluoromethanesulfonate ion (CF 3 SO 3 ⁇ ), perfluorooctanesulfonate ion (C 8 F 17 SO 3 ⁇ ), acetylacetonate ion (acac) and the like, more preferably halide ion, oxide ion, acetate ion, sulfate ion, trifluoromethanesulfonate ion (CF 3 SO 3 ⁇ ), perfluoro An octanesulfonate ion (C 8 F 17 SO 3 ⁇ ) can be mentioned.
  • Lewis acid used in the present invention include aluminum chloride, scandium (III) trifluoromethanesulfonate, vanadium oxide (V), vanadium oxide sulfate (IV), manganese (II) sulfate, iron acetate (II ), Cobalt (II) chloride, cobalt (II) sulfate, cobalt (II) acetate, cobalt (II) acetylacetonate, rhodium (II) acetate, nickel (II) chloride, nickel (II) acetate, hafnium (IV) Examples thereof include, but are not limited to, trifluoromethane sulfonate, hafnium (IV) perfluorooctane sulfonate, cerium (IV) trifluoromethane sulfonate, and bismuth (III) trifluoromethane sulfonate.
  • examples thereof include sulfonate, cerium (IV) triflate, bismuth (III) triflate, and more preferably scandium (III) triflate, vanadium oxide (V), vanadium oxide sulfate (IV), iron (II) acetate, cobalt chloride.
  • the amount of Lewis acid used in the present invention may be any amount as long as the reaction proceeds sufficiently, but is represented by the general formula (2) from the viewpoints of yield, by-product suppression and economic efficiency.
  • the amount is usually 0.005 to 1.0 mol, preferably a catalytic amount, that is, 0.01 to 0.5 mol, more preferably 0.03 to 0.3 mol, still more preferably, per 1 mol of the dioxopropane compound.
  • solvent The method of the present invention can be carried out without a solvent, but can be carried out in the presence of a solvent.
  • an aqueous solvent can be used as the solvent in the method of the present invention.
  • an aqueous solvent can be used as the solvent in the method of the present invention.
  • the above-mentioned chlorous acid compound is used as an aqueous solution, it can be carried out sufficiently only with an aqueous solvent derived from an aqueous solution of a chlorous acid compound. Furthermore, it can also carry out using solvents other than water.
  • the solvent used in the present invention it is preferable to use a polar solvent from the viewpoint of affinity between the raw material compound and the chlorite compound, reactivity, and the like.
  • the polar solvent used in the present invention is preferably water, carboxylic acid, nitriles, ketones, alcohols, esters, acid anhydrides, amides, sulfoxides, or sulfones, more preferably , Water, nitriles, ketones, alcohols, esters, amides, etc., more preferably water, nitriles, alcohols, etc., more preferably water, nitriles, etc. Especially preferred is water. Water is preferred because it is simple and inexpensive.
  • the polar solvent is a solvent having a relative dielectric constant of 5 or more.
  • the relative permittivity is a value described in the Chemical Society of Japan, “Chemical Handbook” (Basic), Rev. 5, I-770-777, Maruzen, 2004.
  • the solvent used in this reaction is preferably a polar solvent having a relative dielectric constant of 5 or more, more preferably a polar solvent having a relative dielectric constant of 7 or more, more preferably a polar solvent having a relative dielectric constant of 17 or more, and a relative dielectric constant of 20 or more.
  • the polar solvent is particularly preferred.
  • this reaction is an oxidation reaction, for example, when there is a concern about the amount of heat generated by the reaction when it is carried out on a large scale, by appropriately adopting a method such as dividing or dropping raw materials, The exotherm accompanying the reaction may be controlled.
  • Example 1 Method for producing diethyl ketomalonate using cobalt (II) acetate (Example 1-1)
  • Example 2 Method for producing diethyl ketomalonate using cobalt (II) chloride
  • Cobalt (II) was added instead of cobalt (II) acetate, and the equivalent of Lewis acid to diethyl malonate was changed as shown in Table 1 below. Except that, diethyl ketomalonate was obtained in the same manner as in Example 1-1.
  • the yield of the target compound was calculated by an area percentage method by analyzing a part of the reaction mixture by GC. The results are summarized in Table 1.
  • Example 2 The results of Example 2 indicate that cobalt (II) chloride is also useful as a catalyst in the synthesis of a trioxopropane compound, like cobalt (II) acetate. Surprisingly, it has been clarified that increasing the equivalent to the dioxopropane compound causes a decrease in yield.
  • Example 3 From the results of Example 3, it was found that the target product was obtained in a relatively high yield even when the equivalent of Lewis acid to the dioxopropane compound was only 0.01 equivalent.
  • Example 4 Method for producing diethyl ketomalonate using iron (II) acetate
  • Example 1 except that iron (II) acetate was added instead of cobalt (II) acetate and the reaction time was changed as shown in Table 3 below.
  • Table 3 The yield of the target compound was calculated by an area percentage method by analyzing a part of the reaction mixture by GC. The results are summarized in Table 3.
  • Example 6 Method for producing diethyl ketomalonate using hafnium (IV) triflate 34.8 mg (0.045 mmol) of hafnium (IV) triflate and 123.6 mg of sodium chlorite (1.08 mmol in terms of purity) were dissolved in 3 mL of water. Thereafter, 144.2 mg (0.9 mmol) of diethyl malonate was added, and the reaction mixture was stirred at room temperature for 12 hours. The reaction mixture was quenched with saturated aqueous sodium thiosulfate (1 mL) and diluted with water (10 mL). The aqueous layer was extracted with dichloromethane (3 ⁇ 25 mL). The obtained organic layers were combined and dried over anhydrous sodium sulfate.
  • the conversion of the starting compound was determined by 1 H-NMR analysis of the crude product using durene (1,2,4,5-tetramethylbenzene) as an internal standard.
  • the crude product was purified by column chromatography, and the target compound, diethyl ketomalonate, was obtained in 89% yield.
  • Example 7 Production Method of Diethyl Ketomalonate Using Various Lewis Acids Diethyl ketomalonate was obtained in the same manner as in Example 6 except that Lewis acids listed in the following Table 5 were used instead of hafnium (IV) triflate. The yield of the target compound was determined by 1 H-NMR analysis of the crude product using durene (1,2,4,5-tetramethylbenzene) as an internal standard. The results are summarized in Table 5.
  • PTLC thin-layer chromatography
  • Example 10-2 5,5-Dihydroxy-2,2-dimethyl-1,3-dioxane was prepared in the same manner as in Example 10-1, except that hafnium (IV) triflate was added instead of hafnium (IV) perfluorooctane sulfonate. -4,6-dione was obtained.
  • the yield of the target compound was 50% by 1 H-NMR analysis of the crude product using durene (1,2,4,5-tetramethylbenzene) as an internal standard.
  • Example 10 shows that this reaction is applicable not only to malonic acid compounds such as diethyl malonate but also to cyclic 1,3-diketone compounds such as 1,3-cyclohexanedione. .

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
  • Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
  • Heterocyclic Compounds That Contain Two Or More Ring Oxygen Atoms (AREA)

Abstract

L'invention concerne un nouveau procédé de production d'un composé trioxopropane. La présente invention concerne un procédé de production d'un composé de trioxopropane représenté par la formule générale (1), le procédé étant caractérisé par la réaction d'un composé dioxopropane représenté par la formule générale (2) avec un composé d'acide chloreux en présence d'un catalyseur acide de Lewis.
PCT/JP2017/037351 2016-12-05 2017-10-16 Procédé de production d'un composé trioxopropane Ceased WO2018105237A1 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
JP2018554847A JP7030059B2 (ja) 2016-12-05 2017-10-16 トリオキソプロパン化合物の製造法

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
JP2016-236100 2016-12-05
JP2016236100 2016-12-05

Publications (1)

Publication Number Publication Date
WO2018105237A1 true WO2018105237A1 (fr) 2018-06-14

Family

ID=62490902

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/JP2017/037351 Ceased WO2018105237A1 (fr) 2016-12-05 2017-10-16 Procédé de production d'un composé trioxopropane

Country Status (3)

Country Link
JP (1) JP7030059B2 (fr)
TW (1) TW201829363A (fr)
WO (1) WO2018105237A1 (fr)

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN110452119A (zh) * 2019-08-30 2019-11-15 苏州汉德创宏生化科技有限公司 一种酮基丙二酸二乙酯单水合物的合成方法
CN110818541A (zh) * 2019-11-14 2020-02-21 大连理工大学 一种(e)-1-芳基-4,4,4-三氟丁-2-烯-1-酮化合物的制备方法

Families Citing this family (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN115819230A (zh) * 2022-11-17 2023-03-21 苏州汉德创宏生化科技有限公司 一种羰基丙二酸二酯的合成方法

Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPH08151346A (ja) * 1994-11-25 1996-06-11 Kao Corp ケトマロン酸の製造方法
WO2010150548A1 (fr) * 2009-06-26 2010-12-29 イハラケミカル工業株式会社 Procédé de production de composés d'acide cétomalonique ou d'hydrates de ceux-ci
JP2015020975A (ja) * 2013-07-19 2015-02-02 イハラケミカル工業株式会社 ケトマロン酸化合物の製造方法
WO2015122361A1 (fr) * 2014-02-17 2015-08-20 イハラケミカル工業株式会社 Procédé de production en continu d'un composé d'acide cétomalonique utilisant un réacteur continu

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPH08151346A (ja) * 1994-11-25 1996-06-11 Kao Corp ケトマロン酸の製造方法
WO2010150548A1 (fr) * 2009-06-26 2010-12-29 イハラケミカル工業株式会社 Procédé de production de composés d'acide cétomalonique ou d'hydrates de ceux-ci
JP2015020975A (ja) * 2013-07-19 2015-02-02 イハラケミカル工業株式会社 ケトマロン酸化合物の製造方法
WO2015122361A1 (fr) * 2014-02-17 2015-08-20 イハラケミカル工業株式会社 Procédé de production en continu d'un composé d'acide cétomalonique utilisant un réacteur continu

Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN110452119A (zh) * 2019-08-30 2019-11-15 苏州汉德创宏生化科技有限公司 一种酮基丙二酸二乙酯单水合物的合成方法
CN110818541A (zh) * 2019-11-14 2020-02-21 大连理工大学 一种(e)-1-芳基-4,4,4-三氟丁-2-烯-1-酮化合物的制备方法
CN110818541B (zh) * 2019-11-14 2020-09-29 大连理工大学 一种(e)-1-芳基-4,4,4-三氟丁-2-烯-1-酮化合物的制备方法

Also Published As

Publication number Publication date
TW201829363A (zh) 2018-08-16
JP7030059B2 (ja) 2022-03-04
JPWO2018105237A1 (ja) 2019-10-24

Similar Documents

Publication Publication Date Title
JP5548685B2 (ja) ケトマロン酸化合物又はその抱水体の製造法
EP1626045A1 (fr) Methodes de production de 2-chloro-5-fluoropyridine 3-substitue ou de son sel
EP2868647B1 (fr) Procédé de production d'acétate de (E)-2-isopropyl-5-méthyl-2,4-hexadiényl
JP7030059B2 (ja) トリオキソプロパン化合物の製造法
KR20150026729A (ko) 알코올류의 산화 방법
AU2015216279B2 (en) Method for continuously producing ketomalonic acid compound using flow reactor
EP2526081B1 (fr) Procédé de production de dérivés d'acides aryl- et hétéroarylacétique
RU2662441C1 (ru) Способ получения производных 2-(хлорфенокси)-пропионовой кислоты
Siry et al. Oxidative transformations of 6-trifluoromethyl-2H-thiopyran as a route to fluoro-containing thiopyranosides
RU2529029C1 (ru) Способ получения 1-(3-феноксифенил)бутан-1,3-диона
RU2491270C2 (ru) Способ получения 1-гидроксиадамантан-4-она
RU2707190C1 (ru) Способ получения ацетилацетона
CN109081826B (zh) 氧化剂ibx的制备方法
RU2507191C1 (ru) Способ получения 1-гидроксиадамантан-4-она (кемантана)
EP0410758A2 (fr) Procédé pour production de dérivés optiquement actifs d'acide propionique
De Buyck et al. Structure and Reactivity of a Stable Oxirane Derived from 2, 2, 6, 6‐Tetrachloro‐3, 3, 5‐Trimethylcyclohexanone and Methanolic Sodium Methoxide
JPH0475230B2 (fr)
EP0022440A1 (fr) Procédé de préparation de produits d'addition de Michael et leur conversion en ibuprofène, un composé inhibant l'inflammation
CN105523922A (zh) 一种罗氟司特中间体的制备方法
KR20010038273A (ko) α-케토카르복시산 유도체의 제조방법

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: 17878525

Country of ref document: EP

Kind code of ref document: A1

ENP Entry into the national phase

Ref document number: 2018554847

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: 17878525

Country of ref document: EP

Kind code of ref document: A1