WO2013157651A1 - Process for producing alpha-hydroxyketone compound - Google Patents
Process for producing alpha-hydroxyketone compound Download PDFInfo
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- WO2013157651A1 WO2013157651A1 PCT/JP2013/061698 JP2013061698W WO2013157651A1 WO 2013157651 A1 WO2013157651 A1 WO 2013157651A1 JP 2013061698 W JP2013061698 W JP 2013061698W WO 2013157651 A1 WO2013157651 A1 WO 2013157651A1
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- 0 Cc1c(*)[n]c*1* Chemical compound Cc1c(*)[n]c*1* 0.000 description 1
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C45/00—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds
- C07C45/61—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
- C07C45/67—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 isomerisation; by change of size of the carbon skeleton
- C07C45/68—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 isomerisation; by change of size of the carbon skeleton by increase in the number of carbon atoms
- C07C45/72—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 isomerisation; by change of size of the carbon skeleton by increase in the number of carbon atoms by reaction of compounds containing >C = O groups with the same or other compounds containing >C = O groups
- C07C45/75—Reactions with formaldehyde
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C319/00—Preparation of thiols, sulfides, hydropolysulfides or polysulfides
- C07C319/14—Preparation of thiols, sulfides, hydropolysulfides or polysulfides of sulfides
- C07C319/20—Preparation of thiols, sulfides, hydropolysulfides or polysulfides of sulfides by reactions not involving the formation of sulfide groups
Definitions
- J. of Organic Chemistry, 50, 603-606 (1985) discloses a method using a. catalyst prepared from 3- methylthiazolium salt and a basic compound
- Chem. Commun. , 47, 573-575 (2011) discloses a method using a catalyst prepared from 3- ( 2 , 4 , 6-trimethylphenyl ) -5 , 6, 7 , 8-tetrahydro- 4H-cycloheptathiazolium salt and a basic compound
- WO 2008/104875 Al discloses a method using a catalyst prepared from N-ethylbenzothiazolium salt and a basic compound.
- the present invention provides the . followings .
- At least one hydrophobic solvent selected from the group consisting of an aromatic hydrocarbon solvent, an aliphatic hydrocarbon solvent, a halo-hydrocarbon solvent and an ether solvent incompatible with water,
- R 1 and R 2 are each independently a hydrogen atom, an optionally substituted alkyl group, an optionally substituted alkoxycarbonyl group, an optionally substituted alkylcarbonyl group, or an optionally substituted aryl group, or R 1 and R 2 are bonded to each other to form a cycloalkene ring with the carbon atoms bonded thereto;
- R 3 is an optionally substituted alkyl group or an aryl group;
- X ⁇ is an anion, a basic compound
- organic bases selected from the group consisting of organic bases, alkali metal salts, and alkaline earth metal salts.
- R 4 is an optionally substituted alkyl group with 1 to 10 carbon atoms, an optionally substituted aryl group with 6 to 20 carbon atoms, or an optionally substituted heteroaryl group with 4 to 10 carbon atoms.
- invention refers to a residue formed by the removal of one hydrogen atom from a linear, branched or cyclic hydrocarbon.
- alkyl group defined by R 1 and R 2 examples include linear, branched or cyclic alkyl groups with 1 to 10 carbon atoms, such as a methyl group, an ethyl group, a propyl group, an isopropyl group, a butyl group, an
- ethoxymethyl group a methoxyethyl group, a benzyl group, a 4 -fluorobenzyl group, a 4-methylbenzyl group, a
- phenoxymethyl group a 2-oxopropyl group, a 2-oxobutyl group, a phenacyl group, and a 2-carboxyethyl group.
- Examples of a substituent which the alkoxycarbonyl group defined by R 1 and R 2 may have include aryl groups with 6 to 10 carbon atoms optionally having an alkoxy group with 1 to 10 carbon atoms, such as a phenyl group, a naphthyl group, a 4-methylphenyl group, and a 4- methoxyphenyl group; alkoxy groups with 1 to 10 carbon atoms optionally having a fluorine atom, such as a methoxy group, an ethoxy group, a propoxy group, an isopropoxy group, a butoxy group, an isobutoxy group,, a sec-butoxy group, a tert-butoxy group, and a trifluoromethoxy group; aralkyloxy groups with 7 to 20 carbon atoms optionally having an alkoxy group with 1 to 10 carbon atoms, such as a benzyloxy group, a 4-methylbenzyloxy group, and a 4- methoxybenzyloxy group
- an aryloxy group with 6 to 10 carbon atoms such as a 3-phenoxybenzyloxy group
- aryloxy groups with 6 to 10 carbon atoms optionally having an alkoxy group with 1 to 10 carbon atoms, such as a phenoxy group, a 2- methylphenoxy group, a 4-methylphenoxy group, and a 4- methoxyphenoxy group
- R 1 and R 2 substituent defined by R 1 and R 2 include a
- fluoromethoxycarbonyl group a trifluoromethoxycarbonyl group, a methoxymethoxycarbonyl group, an
- alkyl group defined by R 3 examples include linear, branched, or cyclic alkyl groups with 1 to 10 carbon atoms, such as a methyl group, an ethyl group, a propyl group, an isopropyl group, a butyl group, an
- R 3 may have include aryl groups with 6 to 10 carbon atoms optionally having an alkoxy group with 1 to 10 carbon atoms, such as a phenyl group, a naphthyl group, a 4-methylphenyl group, and a 4-methoxyphenyl group; alkoxy groups with 1 to 10 carbon atoms optionally having a fluorine atom, such as a methoxy group, an ethoxy group, a propoxy group, an isopropoxy group, a butoxy group, an isobutoxy group, a sec-butoxy group, a tert-butoxy group, and a trifluoromethoxy group; aralkyloxy groups with 7 to 20 carbon atoms optionally having an alkoxy group with 1 to 10 carbon atoms, such as a benzyloxy group, a 4- methylbenzyloxy group, and a 4-methoxybenzyloxy group;
- acyl groups with 2 to. 10 carbon atoms optionally having an alkoxy group with 1 to 10 carbon atoms, such as an acetyl group, a propionyl group, a benzylcarbonyl group, a 4-methylbenzylcarbonyl
- alkyl group having a substituent defined by R 3 examples include a fluoromethyl group, a
- phenoxymethyl group a 2-oxopropyl group, a 2-oxobutyl group, a phenacyl group, and a 2-carboxyethyl group.
- aryl group defined by R 3 examples include aryl groups with 6 to 10 carbon atoms, such as a phenyl group, a 2-methylphenyl group, a 4-methylphenyl group, a naphthyl group, a 2 , 6-diisopropylphenyl group, and a 2,4,6- trimethylphenyl group.
- R 3 in the formula (1) is preferably an aryl group.
- trifluoromethanesulfonate acetate ion optionally having a halogen atom, such as trifluoroacetate and trichloroacetate ion; nitrate ion; perchlorate ion; tetrahaloborate ion such as tetrafluoroborate and tetrachloroborate;
- hexahaloantimonate ion such as hexafluoroantimonate and hexachloroantimonate
- pentahalostannate ion such as
- examples of the compound (1) also include those in which the "chloride” in these compounds (1) is substituted with “iodide”, “bromide”, “methanesulfonate”, “trifluoromethanesulfonate”, “nitrate”, “perchlorate” ,
- an organic base consisting of an organic base, an alkali metal salt such as alkali metal carbonate, and an alkaline earth metal salt such as alkaline earth metal carbonate.
- organic base examples include tertiary amines such as triethylamine, trioctylamine , diisopropylethylamine , and 4-dimethylaminopyridine; nitrogen-containing cyclic compounds such as 1 , 8-diazabicyclo ' [ 5 , 4 , 0 ] -7-undecene and 1, 5, 7-triazabicyclo [4, 4, 0] -5-decene; nitrogen-containing aromatic compounds such as pyridine and imidazole; alkali metal alkoxides such as sodium methoxide and sodium
- alkali metal carbonate examples include sodium carbonate, sodium hydrogen carbonate, potassium carbonate, potassium hydrogen carbonate, lithium carbonate, and lithium hydrogen carbonate.
- alkaline earth metal carbonate examples include magnesium carbonate and calcium carbonate.
- formaldehyde polymer obtained by polymerizing a part of the formaldehyde in formalin.
- the content of formaldehyde in formalin is preferably 10 wt% to 60 wt%.
- the aldehyde compound with 2 to 30 carbon atoms may be an aldehyde compound represented by formula (2)
- alkoxy group with 1 to 10 carbon atoms such as a phenyl group, a naphthyl group, a 4-methylphenyl group, and a 4-methoxyphenyl group
- alkoxy groups with 1 to 6 carbon atoms optionally having a fluorine atom, such as a methoxy group, an ethoxy group, a propoxy group, an
- aryloxy groups with 6 to 10 carbon atoms optionally having an alkoxy group with 1 to 10 carbon atoms, such as a phenoxy group, a 2-methylphenoxy group, a 4-methylphenoxy group, and a 4-methoxyphenoxy group;
- aldehyde compound (2) examples include
- aliphatic aldehydes such as acetaldehyde, propionaldehyde, n-butyraldehyde, n-octylaldehyde , cyclopentanecarbaldehyde, cyclohexanecarbaldehyde, 2-methylpropanal , .
- the aldehyde compound (2) is 3- methylthiopropanal and the obtained a-hydroxyketone
- the aldehyde compound (2) is an aromatic aldehyde and the ⁇ -hydroxyketone compound is 2-hydroxy-l- (substituted or unsubstituted aryl ) ethanone .
- aldehyde compound (2) is 3- arylpropylaldehyde and the ⁇ -hydroxyketone compound is 4- (substituted or unsubstituted aryl ) -2-oxo—1-butanol .
- aldehyde compound (2) commercially available products may be used and also those which are produced by a known method may be used.
- aromatic hydrocarbon solvent examples include toluene, xylene, and chlorobenzene .
- halo-hydrocarbon solvent examples include dichloromethane, dichloroethane, and chloroform.
- the hydrophobic solvent is preferably used in an amount such that a mixture obtained by mixing the compound ( . 1) the basic compound,, formalin, the aldehyde compound (2) and the hydrophobic solvent comprises a water layer and an organic layer separated from each other.
- hydrophobic solvent is preferably used in an amount of 0.1 parts by weight or more and 100 parts by weight or less, based on 1 part by weight in total of formaldehyde in formalin and the aldehyde compound (2) .
- Carbon dioxide may be in either form of gaseous carbon dioxide or dry ice or supercritical carbon dioxide.
- Gaseous carbon dioxide may be diluted with an- inert gas. such as nitrogen.
- the mixing may be carried out under normal pressure or increased pressure.
- formaldehyde which formalin contains and the aldehyde compound (2) can be confirmed by analysis means such as gas chromatography, high performance liquid chromatography, thin layer chromatography, N R, and IR.
- the obtained reaction mixture may be subjected to liquid separation treatment and the mixture containing an organic layer is concentrated to bring out an a- hydroxyketone compound.
- the obtained cc-hydroxyketone compound may be further purified by a purification means such as distillation, and column chromatography.
- the production amount of an ⁇ -hydroxyketone compound per the catalyst amount is calculated according to the following expression.
- the obtained mixture was stirred at 40°C for 6 hours.
- the obtained reaction mixture was cooled to room temperature to obtain a reaction mixture containing 2-hydroxy-l-phenyl- ethanone.
- the yield of 2- hydroxy-l-phenylethanone was 70%.
- Benzaldehyde a raw material, was recovered in an amount of 18%.
- a 200 mL four-neck flask equipped with a semi-lunar stirring blade made of Teflon® was charged with 12.2 g of 3-methylthiopropanal, 15.7 g of 37 wt% formalin, 210 mg of 3- (2, 6-diisopropyl ) phenyl-4, 5-dimethylthiazolium chloride, and 25 g of cyclopentyl methyl ether.
- the obtained mixture was heated to 70°C under nitrogen atmosphere. While the mixture being stirred, 1.2 g of 11% toluene solution of potassium hexamethyldisilazane was added thereto. When the stirring was stopped, the mixture divided into 2 layers: an organic layer and a water layer.
- the obtained mixture was stirred at 70°C for 8 hours.
- the obtained reaction mixture was cooled to room temperature to obtain a reaction mixture containing 4- (methylthio) -2-oxo-l-butanol .
- the yield of 4- (methylthio) -2-oxo-l- butanol which is a cross-coupling isomer was 19%.
- 3- methylthiopropanal a raw material, was recovered in an amount of 37%..
- the production amount of 4- (methylthio) -2- oxo-l-butanol per catalyst amount was 37.6.
- the compound can be produced by a new method. According to the invention, the production amount of an a-hydroxyketone compound per catalyst amount unit can be improved. In the present invention, more economical formalin as a formaldehyde source can be used.
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Abstract
An object of the present invention is to provide a new process for producing an α-hydroxyketone compound. The present invention relates to a process for producing an α-hydroxyketone compound comprising mixing at least hydrophobic solvent selected from the group consisting of an aromatic hydrocarbon solvent, an aliphatic hydrocarbon solvent, a halo-hydrocarbon solvent, and an ether solvent incompatible with water, a compound defined by the formula (1) wherein, R1 and R2 are each independently a hydrogen atom, an optionally substituted alkyl group; R3 is an optionally substituted alkyl group or an aryl group; and X- is an anion, a basic compound, formalin, and an aldehyde compound with 2 to 30 carbon atoms.
Description
DESCRIPTION
PROCESS FOR PRODUCING ALPHA-HYDROXYKETONE COMPOUND TECHNICAL FIELD
[0001]
The present invention relates to a process for
producing an a-hydroxyketone compound..
BACKGROUND ART
[0002]
As a process for producing an α-hydroxyketone compound by cross-coupling reaction of formaldehyde and an aldehyde compound, J. of Organic Chemistry, 50, 603-606 (1985) discloses a method using a. catalyst prepared from 3- methylthiazolium salt and a basic compound; Chem. Commun. , 47, 573-575 (2011) discloses a method using a catalyst prepared from 3- ( 2 , 4 , 6-trimethylphenyl ) -5 , 6, 7 , 8-tetrahydro- 4H-cycloheptathiazolium salt and a basic compound; and WO 2008/104875 Al discloses a method using a catalyst prepared from N-ethylbenzothiazolium salt and a basic compound.
None of these methods teach that water is used as a solvent.
DISCLOSURE OF INVENTION PROBLEM TO BE SOLVED BY THE INVENTION
[0003]
There has been a demand for a new process for
producing an a-hydroxyketone compound. MEANS FOR SOLVING. THE PROBLEM
[0004]
The present invention provides the . followings .
[1] A process for producing an α-hydroxyketone compound comprising mixing
at least one hydrophobic solvent selected from the group consisting of an aromatic hydrocarbon solvent, an aliphatic hydrocarbon solvent, a halo-hydrocarbon solvent and an ether solvent incompatible with water,
a compound represented by the formula (1)
wherein, R1 and R2 are each independently a hydrogen atom, an optionally substituted alkyl group, an optionally substituted alkoxycarbonyl group, an optionally substituted alkylcarbonyl group, or an optionally substituted aryl group, or R1 and R2 are bonded to each other to form a cycloalkene ring with the carbon atoms bonded thereto; R3 is an optionally substituted alkyl group or an aryl group; and X~ is an anion,
a basic compound,
formalin, and
an . aldehyde compound with 2 to 30 carbon atoms.
[2] The process according to the above item [1], wherein a mixture obtained by the mixing comprising a water layer and an organic layer separated from each other.
[3] The process according to the above item [1] or [2], wherein the basic compound is at least one compound
selected from the group consisting of organic bases, alkali metal salts, and alkaline earth metal salts.
[4] The process according to any one of the above items
[1] to [3], wherein R3 is an aryl group..
[5] The process according to any one of the above items [1] to [4], wherein the mixing is carried out in the presence of carbon dioxide.
[6] The process according/to any one of the above items [1] to [5], wherein the aldehyde compound with 2 to 30 carbon atoms is an aldehyde compound represented by the formula (2)
wherein R4 is an optionally substituted alkyl group with 1 to 10 carbon atoms, an optionally substituted aryl group with 6 to 20 carbon atoms, or an optionally substituted heteroaryl group with 4 to 10 carbon atoms.
[7] The process according to any one of the above items
[1] to [6], wherein the aldehyde compound is 3- methylthiopropanal and the α-hydroxyketone compound is 4- methylthio-2-oxo-l-butanol .
[8] The process according to any one of the above items
[1] to [6], wherein, the aldehyde compound is an aromatic aldehyde and the α-hydroxyketone compound is 2-hydroxy-l-
(substituted or unsubstituted aryl ) ethanone .
[9] The process according to one of the above items [1] to [6], wherein the aldehyde compound is 3- ( substituted or unsubstituted aryl ) propionaldehyde and the a-hydroxyketone compound is 4- ( substituted or unsubstituted aryl ) -2-oxo-l- butanol . Effect of the Invention
[0005]
According to the invention, an a-hydroxyketone
compound can be produced by a new method. Mode for Carrying Out the Invention
[0006]
The term "alkyl group" as used in the present
invention refers to a residue formed by the removal of one hydrogen atom from a linear, branched or cyclic hydrocarbon.
The term "aryl group" as used in the present invention
refers to a residue formed by the removal of one hydrogen atom from a benzene ring of an aromatic hydrocarbon.
The term "heteroaryl group" as used in the present invention refers to a. residue formed by the removal of one hydrogen atom from an aromatic hydrocarbon compound which has an aromatic ring containing at least one of hetero atoms such as a nitrogen atom, an oxygen atom, and a sulfur atom.
The term "alkoxycarbonyl group" as used in the present invention refers to a linear, branched or cyclic esterified carboxyl group.
[0007]
Examples of the alkyl group defined by R1 and R2 include linear, branched or cyclic alkyl groups with 1 to 10 carbon atoms, such as a methyl group, an ethyl group, a propyl group, an isopropyl group, a butyl group, an
isobutyl group, a sec-butyl group, a tert-butyl group, a pentyl group, a decyl group, a cyclopropyl group, a 2,2- dimethylcyclopropyl group, a cyclopentyl group, a
cyclohexyl group, and a menthyl group.
[0008]
Examples of a substituent which the alkyl group defined by R1 and R2 may have include aryl groups with 6 to 10 carbon atoms optionally having an alkoxy group with 1 to 10 carbon atoms, such as a phenyl group., a naphthyl group.,
a 4-methylphenyl group, and a 4-methoxyphenyl group; alkoxy groups with 1 to 10 carbon atoms optionally having a
fluorine atom, such as a methoxy group, an ethoxy group, a propoxy grO.up, an isopropoxy group, a butoxy group, an isobutoxy group, a sec-butoxy group, a tert-butoxy group, and a trifluoromethoxy group; aralkyloxy groups with 7 to 20 carbon atoms optionally having an alkoxy group with 1 to 10 carbon atoms, such as a benzyloxy group, a 4- methylbenzyloxy group, and a 4-methoxybenzyloxy group; - aralkyloxy groups with 7 to 20 carbon atoms optionally having an aryloxy group with 6 to 10 carbon atoms, such as a 3-phenoxybenzyloxy group; aryloxy groups with 6 to 10 carbon atoms optionally having an alkoxy group with 1 to 10 carbon atoms, such as a phenoxy group, a 2-methylphenoxy group, a 4-methylphenoxy group, and a 4-methoxyphenoxy group; aryloxy groups with 6 to 10 carbon atoms having an aryloxy group with 6 to 10 carbon atoms, such as a 3- phenoxyphenoxy group; acyl groups with 2 to 10 carbon atoms optionally having an alkoxy group with 1 to 10 carbon atoms, such as an acetyl group, a propionyl group, a
benzylcarbonyl group, a 4-methylbenzylcarbonyl group, a 4- methoxybenzylcarbonyl group, a benzoyl group, a 2- methylbenzoyl group, a 4-methylbenzoyl group, and a 4- methoxybenzoyl group; a carboxyl group; and a fluorine atom.
[0009]
Examples of the alkyl group having a substituent defined by R1 and R2 include a fluoromethyl group, a
trifluoromethyl group, a methoxymethyl group, an
ethoxymethyl group, a methoxyethyl group, a benzyl group, a 4 -fluorobenzyl group, a 4-methylbenzyl group, a
phenoxymethyl group, a 2-oxopropyl group, a 2-oxobutyl group, a phenacyl group, and a 2-carboxyethyl group.
[0010]
Examples of the aryl group defined by R1 and R2
include aryl groups with 6 to 10 carbon atoms, such as a phenyl group, a 2-methylphenyl group, a 4-methylphenyl group, a naphthyl group.
Examples of a substituent which the aryl group may have include alkyl groups with 1 to 10 carbon atoms having a fluorine atom, such as a fluoromethyl group and a
trifluoromethyl group; alkyl groups with 1 to 10 carbon atoms having alkoxy group with 1 to 10 carbon atoms, such as a methoxymethyl group, an. ethoxymethyl group, and a methoxyethyl group; alkoxy groups with 1 to 10 carbon atoms optionally having an alkoxy group with 1 to 10 carbon atoms, such as a methoxy group, an ethoxy group, a propoxy group, an isopropoxy group, a butoxy group, an isobutyloxy group, a sec-butyloxy group, a tert-butyloxy. group, a pentyloxy group, a cyclopentyloxy group, a methoxymethoxy group, an ethoxymethoxy group, and a methoxyethoxy group; alkoxy
groups with 1 to. 10 carbon atoms optionally having, a fluorine atom, such as a fluoromethoxy group and a
trifluoromethoxy group; and a halogen atom such as a fluorine atom and a chlorine atom.
Examples of the aryl group having a substituent include a 4-chlorophenyl group and a 4-methoxyphenyl group.
[0011]
' Examples of the alkoxycarbonyl group defined by R1 and R2 include linear, branched or cyclic alkoxycarbonyl groups with 2 to 11 carbon atoms, such as a methoxycarbonyl group, an ethoxycarbonyl group, a n-propoxycarbonyl group, a n- butoxycarbonyl group, a sec-butoxycarbonyl group, a tert- butoxycarbonyl group, a pentyloxycarbonyl group, a
decyloxycarbonyl group, a cyclopropoxycarbonyl group, and a cyclohexyloxycarbonyl group.
[0012]
Examples of a substituent which the alkoxycarbonyl group defined by R1 and R2 may have include aryl groups with 6 to 10 carbon atoms optionally having an alkoxy group with 1 to 10 carbon atoms, such as a phenyl group, a naphthyl group, a 4-methylphenyl group, and a 4- methoxyphenyl group; alkoxy groups with 1 to 10 carbon atoms optionally having a fluorine atom, such as a methoxy group, an ethoxy group, a propoxy group, an isopropoxy group, a butoxy group, an isobutoxy group,, a sec-butoxy
group, a tert-butoxy group, and a trifluoromethoxy group; aralkyloxy groups with 7 to 20 carbon atoms optionally having an alkoxy group with 1 to 10 carbon atoms, such as a benzyloxy group, a 4-methylbenzyloxy group, and a 4- methoxybenzyloxy group; aralkyloxy groups with 7 to 20 carbon atoms, having. an aryloxy group with 6 to 10 carbon atoms, such as a 3-phenoxybenzyloxy group; aryloxy groups with 6 to 10 carbon atoms optionally having an alkoxy group with 1 to 10 carbon atoms, such as a phenoxy group, a 2- methylphenoxy group, a 4-methylphenoxy group, and a 4- methoxyphenoxy group; aryloxy groups with 6 to 10 carbon atoms having an aryloxy group with 6 to 10 carbon atoms, such as a 3-phenoxyphenoxy group; acyl groups with 2 to 10 carbon atoms optionally having an alkoxy group with 1 to 10 carbon atoms, such as an acetyl group, a propionyl group, a benzylcarbonyl group, a 4-methylbenzylcarbonyl group, a 4- methoxybenzylcarbonyl group, a benzoyl group, a 2- methylbenzoyl group, a 4-methylbenzoyl group, and a 4- methoxybenzoyl group; and a fluorine atom.
[0013]
Examples of the alkoxycarbonyl group having a
substituent defined by R1 and R2 include a
fluoromethoxycarbonyl group, a trifluoromethoxycarbonyl group, a methoxymethoxycarbonyl group, an
ethoxymethoxycarbonyl group, a benzyloxycarbonyl group, a
4-fluorobenzyloxycarbonyl group, a 4- methylbenzyloxycarbonyl group, a phenoxymethoxycarbonyl group, a 2-oxopropoxycarbonyl group, and a 2- oxobutoxycarbonyl group.
[0014]
Examples of the alkylcarbonyl group defined by R1 and R2 include linear, branched, or cyclic alkylcarbonyl groups with 2 to 11 carbon atoms, such as an acetyl group, an ethylcarbonyl group, a propylcarbonyl group, a
butylcarbonyl group, a sec-butylcarbonyl group, a tert- butylcarbonyl group, a pentylcarbonyl group, a
decylcarbonyl group, a cyclopropylcarbonyl group, and a cyclohexylcarbonyl group.
[0015]
Examples of a substituent which the alkylcarbonyl group defined by R1 and R2 may have include aryl groups with 6 to 10 carbon atoms optionally having an alkoxy group with 1 to 10 carbon atoms, such as a . phenyl group, a naphthyl group, a 4-methylphenyl group, and a 4- methoxyphenyl group; alkoxy groups with 1 to 10 carbon atoms optionally having a fluorine atom, such as a methoxy group, an ethoxy group, a propoxy group, an isopropoxy group, a butoxy group, an isobutoxy group, a sec-butoxy group, a tert-butoxy group, a. trifluoromethoxy group, a sec-butyloxy group, a tert-butyloxy group, and a
trifluoromethyloxy group; aralkyloxy groups with 7 to 20 carbon atoms optionally having an alkoxy group with 1 to 10 carbon atoms, such as a benzyloxy group, a 4- methylbenzyloxy group, and a 4-methoxybenzyloxy group;
aralkyloxy groups with 7 to 20 carbon atoms having an aryloxy group with 6 to 10 carbon atoms, such as a 3- phenoxybenzyloxy group; aryloxy groups with 6 to 10 carbon atoms optionally having an alkoxy group with 1 to 10 carbon atoms, such as a phenoxy group, a 2-methylphenoxy group, a 4-methylphenoxy group, and a 4-methoxyphenoxy group;
aryloxy groups with 6 to 10 carbon atoms, having an aryloxy group with 6 to 10 carbon atoms, such as a 3-phenoxyphenoxy group; acyl groups with 2 to 10 carbon atoms optionally having an alkoxy group with 1 to 10 carbon atoms, such as an acetyl group, a propionyl group, a benzylcarbonyl group, a 4-methylbenzylcarbonyl group, a 4 -methoxybenzylcarbonyl group, a benzoyl group, a 2-methylbenzoyl group, a 4- methylbenzoyl group, and a -methoxybenzoyl group; and a fluorine atom.
[0016] .
Examples of the alkylcarbonyl group having a
substituent defined by R1 and R2 include a
fluoromethylcarbonyl group, a trifluoromethylcarbonyl group, a methoxymethylcarbonyl group, an ethoxymethylcarbonyl group, a benzylcarbonyl group, a 4-fluorobenzylcarbonyl
group, a 4-methylbenzylcarbonyl group, a
phenoxymethylcarbonyl group, a 2-oxopropylcarbonyl group, and a 2-oxobutylcarbonyl group.
[0017]
Examples of the cycloalkene ring optionally formed by bonding R1 and R2 to each other through the carbon atoms bonded thereto include cyclopentene ring, cyclohexene ring, and cycloheptene ring.:
[0018]
Examples of the alkyl group defined by R3 include linear, branched, or cyclic alkyl groups with 1 to 10 carbon atoms, such as a methyl group, an ethyl group, a propyl group, an isopropyl group, a butyl group, an
isobutyl group, a sec-butyl group, a tert-butyl group, a pentyl group, a decyl group, a cyclopropyl group, a 2,2- dimethylcyclopropyl group, a cyclopentyl group, a
cyclohexyl group, and. a menthyl group.
[0019]
Examples of a substituent which the alkyl group:
defined by R3 may have include aryl groups with 6 to 10 carbon atoms optionally having an alkoxy group with 1 to 10 carbon atoms, such as a phenyl group, a naphthyl group, a 4-methylphenyl group, and a 4-methoxyphenyl group; alkoxy groups with 1 to 10 carbon atoms optionally having a fluorine atom, such as a methoxy group, an ethoxy group, a
propoxy group, an isopropoxy group, a butoxy group, an isobutoxy group, a sec-butoxy group, a tert-butoxy group, and a trifluoromethoxy group; aralkyloxy groups with 7 to 20 carbon atoms optionally having an alkoxy group with 1 to 10 carbon atoms, such as a benzyloxy group, a 4- methylbenzyloxy group, and a 4-methoxybenzyloxy group;
aralkyloxy groups with 7 to 20 carbon atoms having an aryloxy group with 6 to 10 carbon atoms, such as a 3- phenoxybenzyloxy group; aryloxy groups with 6 to 10 carbon atoms optionally having an alkoxy group with 1 to 10 carbon atoms, such as a phenoxy group, a 2-methylphenoxy group, a 4-methylphenoxy group, and a 4-methoxyphenoxy group;
aryloxy groups with 6 to 10 carbon atoms having an aryloxy group with 6 to 10 carbon atoms, such as a 3-phenoxyphenoxy group; acyl groups with 2 to. 10 carbon atoms optionally having an alkoxy group with 1 to 10 carbon atoms, such as an acetyl group, a propionyl group, a benzylcarbonyl group, a 4-methylbenzylcarbonyl group, a -methoxybenzylcarbonyl group, a benzoyl group, a 2-methylbenzoyl group, a 4- methylbenzoyl group, and a 4-methoxybenzoyl group; a carboxyl group; and a fluorine atom.
[00201
Examples of the alkyl group having a substituent defined by R3 include a fluoromethyl group, a
trifluoromethyl group, a methoxymethyl group, an
ethoxymethyl group, a methoxyethyl group, a benzyl group, a 4-fluorobenzyl group, a 4-methylbenzyl group, a
phenoxymethyl group, a 2-oxopropyl group, a 2-oxobutyl group, a phenacyl group, and a 2-carboxyethyl group.
[0021]
Examples of the aryl group defined by R3 include aryl groups with 6 to 10 carbon atoms, such as a phenyl group, a 2-methylphenyl group, a 4-methylphenyl group, a naphthyl group, a 2 , 6-diisopropylphenyl group, and a 2,4,6- trimethylphenyl group.
[0022]
R3 in the formula (1) is preferably an aryl group.
[0023.]
In the formula (1),. examples of the anion defined by X~ include halide ion such as chloride ion, bromide ion, and iodide ion; alkanesulfonate ion optionally having a fluorine atom, such as methanesulfonate and
trifluoromethanesulfonate ; acetate ion optionally having a halogen atom, such as trifluoroacetate and trichloroacetate ion; nitrate ion; perchlorate ion; tetrahaloborate ion such as tetrafluoroborate and tetrachloroborate;
hexahalophosphate ion such as hexafluorophosphate;
hexahaloantimonate ion such as hexafluoroantimonate and hexachloroantimonate; pentahalostannate ion such as
pentafluorostannate and pentachlorostannate; and optionally
substituted tetraarylborate such as tetraphenylborate, tetrakis (pentafluorophenyl ) borate, and tetrakis [ 3 , 5- bis (trifluoromethyl) phenyl] borate .
[0024]
Examples of the compound represented by formula (1) (hereinafter, sometimes referred to as compound (1))
include 3-ethylbenzothiazolium bromide, 3- butylbenzothiazolium chloride, 3- ( 2 , 6-diisopropyl ) phenyl- 4 , 5-dimethylthiazolium chloride, 3-phenyl-4 ,.5- dimethylthiazolium chloride, 3-benzylthiazolium chloride, 3-benzyl-4-methylthiazolium chloride,. 3-n-butyl-4- methylthiazolium chloride, 3-n-hexyl-4-methylthiazolium chloride, 3-cyclohexyl-4-methylthiazolium chloride, 3-n- octyl-4-methylthiazolium chloride, 3- (2,4,6- trimethyl) phenyl-4 , 5-dimethylthiazolium chloride, 3- [2,4, 6- trimethylphenyl ] -4,5,6, 7-tetrahydrobenzothiazolium chloride, 3- [2, 6-diisopropylphenyl] -4, 5, 6, 7-tetrahydrobenzOthiazolium chloride, and. 5 , 6 , 7 , 8-tetrahydro-3- [2 , 4 , 6-trimethylphenyl ] - 4H-cycloheptathiazolium chloride.
[0025]
In addition, examples of the compound (1) also include those in which the "chloride" in these compounds (1) is substituted with "iodide", "bromide", "methanesulfonate", "trifluoromethanesulfonate", "nitrate", "perchlorate" ,
"tetrafluoroborate" , "tetracr.lcro crate" ,
"hexafluorophosphate", "hexafluoroantimonate",
"hexachloroantimonate", "pentafluorostannate" ,
"pentachlorostannate", "tetraphenylborate" ,
"tetrakis (pentafluorophenyl ) borate", or "tetrakis [ 3 , 5- 'bis ( trifluoromethyl ) phenyl] borate" .
[0026]
Commercially available products may be used for the compound (1) and those which are produced according to the method described in Eur.. J. Org. Chem. , 2025(2004) may also be used.
The compound (1) is preferably used in an amount of 0.001 to 0.5 mol and more preferably 0.005 to 0.3 mol, based on 1 mol of the aldehyde compound with 2 to 30 carbon atoms.
[0027],
A basic compound to be used in the present invention may be at least one compound selected from the group
consisting of an organic base, an alkali metal salt such as alkali metal carbonate, and an alkaline earth metal salt such as alkaline earth metal carbonate.
Examples of the organic base include tertiary amines such as triethylamine, trioctylamine , diisopropylethylamine , and 4-dimethylaminopyridine; nitrogen-containing cyclic compounds such as 1 , 8-diazabicyclo' [ 5 , 4 , 0 ] -7-undecene and 1, 5, 7-triazabicyclo [4, 4, 0] -5-decene; nitrogen-containing
aromatic compounds such as pyridine and imidazole; alkali metal alkoxides such as sodium methoxide and sodium
ethoxide; and alkali metal silylamides such as potassium hexamethyldisilazane .
Examples of the alkali metal carbonate include sodium carbonate, sodium hydrogen carbonate, potassium carbonate, potassium hydrogen carbonate, lithium carbonate, and lithium hydrogen carbonate.
Examples of the alkaline earth metal carbonate include magnesium carbonate and calcium carbonate.
The basic compound is preferably an organic base.
[0028]
The basic compound is preferably used in an amount of 0.1 mol to 2 mol and more preferably 0.5 mol to 1.5 mol, based on 1 mol of the compound (1) .
[0029]
Formalin may contain an alcohol such as methanol as a polymerization inhibitor and may also contain a
formaldehyde polymer obtained by polymerizing a part of the formaldehyde in formalin. The content of formaldehyde in formalin is preferably 10 wt% to 60 wt%. Usually,
commercialized one may be used for formalin.
[0030]
r
The aldehyde compound with 2 to 30 carbon atoms used in the present invention may be a compound having at least
one formyl group in the molecule. The aldehyde compound with 2 to 30 carbon atoms does not include a polymer of formaldehyde.
[0031]
The aldehyde compound with 2 to 30 carbon atoms may be an aldehyde compound represented by formula (2)
wherein R4 is an optionally substituted alkyl group with 1 to 10 carbon atoms, an optionally substituted aryl group with 6 to 20 carbon atoms, or an optionally substituted heteroaryl group with 4 to 10 carbon atoms. Hereinafter, the aldehyde compound represented by formula (2) is
sometimes referred to as aldehyde compound (2) .
[0032]
An a-hydroxyketone compound represented by formula (3)
wherein R4 denotes the same as described above,
is produced by cross-coupling reaction of formaldehyde which formalin contains and the aldehyde compound (2) .
[0033],
Examples of the alkyl group defined by R4 include linear, branched, or cyclic alkyl groups with 1 to 10
carbon atoms, such as a methyl group, an ethyl group, a propyl group, an isopropyl group, a butyl group, an
isobutyl group, a sec-butyl group, a tert-butyl group, a ■pentyl group, a decyl group, a cyclopropyl group, a 2,2- dimethylcyclopropyl group, a cyclopentyl group, a
cyclohexyl group, and a menthyl group.
Examples of a substituent which the alkyl group may have include aryl groups with 6 to 10 carbon atoms
optionally having an alkoxy group with 1 to 10 carbon atoms such as a phenyl group, a naphthyl group, a 4-methylphenyl group, and a 4-methoxyphenyl group; alkoxy groups with 1 to 6 carbon atoms optionally having a fluorine atom, such as a methoxy group, an ethoxy group, a propoxy group, an
isopropoxy group, a butoxy group, an isobutoxy group, a sec-butoxy group, a tert-butoxy group, and a
trifluoromethoxy group; aralkyloxy groups with 6 to 10 carbon atoms optionally having an alkoxy group with 1 to 10 carbon atoms, such as a benzyloxy group, a 4- methylbenzyloxy group, and a 4-methoxybenzyloxy group;
aralkyloxy groups with 6 to 10 carbon atoms having an aryloxy group with 6 to 10 carbon atoms, such as a 3- phenoxybenzyloxy group; aryloxy groups with 6 to 10 carbon atoms optionally having an alkoxy group with 1 to 10 carbon atoms, such as a phenoxy group, a 2-methylphenoxy group, a 4-methylphenoxy group, and a 4-methoxyphenoxy group;
aryloxy groups with 6 to 10 carbon atoms having an aryloxy group with 6 to 10 carbon atoms, such as a 3-phenoxyphenoxy group; acyl groups with 2 to 10 carbon atoms optionally having an alkoxy group with 1 to 10 carbon atoms, such as an acetyl group, a propionyl group, a benzylcarbonyl group, a 4-methylbenzylcarbonyl group, a 4-methoxybenzylcarbonyl group, a benzoyl group, a 2-methylbenzoyl group, a 4- methylbenzoyl group, and a 4-methoxybenzoyl group;
alkylthio groups with 1 to 10 carbon atoms, such as a methylthio group, an ethylthio group, and an isopropylthio group; alkoxycarbonyl groups with 2. to 10 carbon atoms, such as a methoxycarbonyl group and an ethoxycarbonyl group; and a halogen atom such as a fluorine atom, a chlorine atom and bromine atom.
Examples of the alkyl group having a substituent include a chloromethyl group, a fluoromethyl group, a trifluoromethyl group, a methoxymethyl group, an
ethoxymethyl group, a 2-methoxyethyl . group, a
methoxycarbonylmethyl group," a l-ethoxycarbonyl-2 , 2- dimethyl-3-cyclopropyl group, a 3-phenylpropyl group, and a 2-methylthioethyl group.
[0034]
Examples of the aryl group defined by R4 include aryl groups with 6 to 20. carbon atoms, such as a phenyl group, a 2-methylphenyl group, a 4-methylphenyl group, and a
naphthyl group.
Examples of a substituent which the aryl group may have include alkyl- groups with 1 to 10 carbon atoms having a fluorine atom, such as a fluoromethyl group and a
trifluoromethyl group; alkyl groups with 1 to 10 carbon atoms having an alkoxy group with 1 to 10 carbon atoms, such as a methoxymethyl group, an ethoxymethyl group, and a 2-methoxyethyl group; alkoxy groups with 1 to 10 carbon ■ atoms optionally having an alkoxy group with 1 to 10 carbon atoms, such as a methoxy group, an ethoxy group, a propoxy group, an isopropoxy group, a butoxy group, an isobutoxy group, a sec-butoxy group, a tert-butoxy group, a pentyloxy group, a cyclopentyloxy group, a methoxymethoxy group, an ethoxymethoxy group, and a 2-methoxyethoxy group; alkoxy groups with 1 to 10 carbon atoms optionally having a fluorine atom, such as a fluoromethoxy group and a
trifluoromethoxy group; aryloxy groups with 6 to 10 carbon atoms optionally having an alkoxy group with 1 to 10 carbon atoms, such as a phenoxy group, a 2-methylphenoxy group, a 4-methylphenoxy group, and a 4-methoxyphenoxy group;
aryloxy groups with 6 to 10 carbon atoms having an aryloxy group with 6 to 10 carbon atoms, such as a 3-phenoxyphenoxy group; acyl groups with 2 to 10 carbon atoms optionally having an alkoxy group with 1 to 10 carbon atoms, such as an acetyl group, a propionyl group, a benzylcarbonyl group,
a 4-methylbenzylcarbonyl group, and a 4- methoxybenzylcarbonyl group; a nitro group; ,a halogen atom such as a fluorine atom and a chlorine atom; and
alkylenedioxy groups with 1 to 6 carbon atoms, such as a methylenedioxy group.
Examples, of the aryl group having a substituent include a 4-chlorophenyl group, a 4-methoxyphenyl group, and a 3-phenoxyphenyl group.
[0035]
Examples of the heteroaryl group defined by R4 include heteroaryl groups with 4 to 10 carbon atoms which have at least one hetero-atom such as a nitrogen atom, an oxygen atom, and a sulfur atom, such as a pyridyl group, a furyl group, and a 5-methylfuryl group.
Examples of a substituent which the heteroaryl group may have include alkyl groups with 1 to 10 carbon atoms ' having a fluorine atom, such as a fluoromethyl group and a trifluoromethyl group; alkyl groups with 1 to 10 carbon atoms having an alkoxy group with 1 to 10 carbon atoms, such as a methoxymethyl group, an ethoxymethyl group, and a 2-methoxyethyl group; alkoxy groups with 1 to 10 carbon atoms having an alkoxy group with 1 to 10 carbon atoms, such as a methoxy group, an ethoxy group, a propoxy group, an isopropoxy group, a butoxy group, an isobutoxy group, a sec-butoxy group, a tert-butoxy group, a pentyloxy group, a
cyclopentyloxy group, a methoxymethoxy group, an ethoxymethoxy group, and a 2-methoxyethoxy group; alkoxy groups with 1 to 10 carbon atoms, optionally having a
fluorine atom, such as a fluoromethoxy group and a
trifluoromethoxy group; aryloxy groups with 6 to 10 carbon atoms optionally having an alkoxy group with 1 to 10 carbon atoms, such as a phenoxy group, a 2-methylphenoxy group, a 4-methylphenoxy group, and a 4-methoxyphenoxy group;
aryloxy groups with 6 to 10 carbon atoms having an aryloxy group with 6 to 10 carbon atoms, such as a 3-phenoxyphenoxy group; acyl groups with 2 to 10 carbon atoms optionally having an alkoxy group with 1 to 10 carbon atoms, such as an acetyl group, a propionyl group, a benzylcarbonyl group, a..4-methylbenzylcarbonyl group, and a.4- methoxybenzylcarbonyl group; a nitro group; a halogen atom such as a fluorine atom and a chlorine atom.
Examples of the heteroaryl group having a 'substituent include a 2-chloropyridyl group.
[0036]
Examples of the aldehyde compound (2) include
aliphatic aldehydes such as acetaldehyde, propionaldehyde, n-butyraldehyde, n-octylaldehyde , cyclopentanecarbaldehyde, cyclohexanecarbaldehyde, 2-methylpropanal , . 2,2- dimethylpropanal, 3-methylthiopropanal, 2, 2-dimethylbutanal, 1-methylcyclohexanecarbaldehyde, 2 , 2-dimethylnonanal,
methyl 2 , 2-dimethyl-3-oxopropanate , 3-phenylpropionaldehyde , 3- (4-pyridyl) propionaldehyde, 3- (3, 4- dimethoxy) propionaldehyde , 3- (4- carbomethoxy) propionaldehyde, 3-phenylbutylaldehyde, and 2- (2 , , 6-trichlorophertyl ) acetaldehyde; aromatic aldehydes such as benzaldehyde , 4-fluorobenzaldehyde, 4- chlorobenzaldehyde, 4-nitrobenzaldehyde, 3- bromobenzaldehyde , 2-chlorobenzaldehyde , 4- methylbenzaldehyde, 3-methoxybenzaldehyde , 3,4,5- trimethoxybenzaldehyde, 3 , 4-methylenedioxybenzaldehyde, and 1-naphthaldehyde; and heteroaromatic aldehyde such as picolinaldehyde , and nicotinaldehyde .
[0037]
It is . preferable that the aldehyde compound (2) is 3- methylthiopropanal and the obtained a-hydroxyketone
compound is 4-methylthio-2-oxo-l-butanol . It is also preferable that the aldehyde compound (2) is an aromatic aldehyde and the α-hydroxyketone compound is 2-hydroxy-l- (substituted or unsubstituted aryl ) ethanone .
It is also preferable that the aldehyde compound (2) is 3- arylpropylaldehyde and the α-hydroxyketone compound is 4- (substituted or unsubstituted aryl ) -2-oxo—1-butanol .
[0038]
In the present invention, as the aldehyde compound (2), commercially available products may be used and also those
which are produced by a known method may be used.
[0039]
The hydrophobic solvent used in the present invention is selected from the group consisting of an aromatic hydrocarbon solvent, an aliphatic hydrocarbon solvent, a halo^hydrocarbon solvent, and an ether solvent incompatible with water .
Examples of the ether solvent incompatible with water include diethyl ether, methyl tert-butyl ether, and
cyclopentyl methyl ether.
Examples of the aromatic hydrocarbon solvent include toluene, xylene, and chlorobenzene .
Examples of the aliphatic hydrocarbon solvent include pentane, hexane, and heptane.
Examples of the halo-hydrocarbon solvent include dichloromethane, dichloroethane, and chloroform.
The hydrophobic solvent is preferably an aromatic hydrocarbon solvent, an aliphatic hydrocarbon solvent, or an ether solvent incompatible with water, more preferably an aromatic hydrocarbon solvent, and even more preferably toluene.
The hydrophobic solvent is preferably used in an amount such that a mixture obtained by mixing the compound (.1) the basic compound,, formalin, the aldehyde compound (2) and the hydrophobic solvent comprises a water layer and
an organic layer separated from each other. The
hydrophobic solvent is preferably used in an amount of 0.1 parts by weight or more and 100 parts by weight or less, based on 1 part by weight in total of formaldehyde in formalin and the aldehyde compound (2) .
[0040]
Mixing may be carried out in the presence of carbon dioxide. Carbon dioxide may be in either form of gaseous carbon dioxide or dry ice or supercritical carbon dioxide. Gaseous carbon dioxide may be diluted with an- inert gas. such as nitrogen.
The carbon dioxide is preferably used in an amount of 1 mol ' or more based on 1 mol of the basic compound. The upper limit is not limited, but it is 1000 mol or less from the viewpoint of productivity.
[0041]
The mixing order of the aldehyde compound (2) ,
formalin, the compound (1), the basic compound, and the hydrophobic solvent is not limited. A preferable method is a method comprising previously mixing the aldehyde compound (2), formalin, and compound (1), and the hydrophobic- solvent and thereafter mixing the basic compound with them, more preferably a method comprising mixing the basic compound after dissolving the basic compound in a solvent. Mixing may be carried out in carbon dioxide atmosphere.
The mixture obtained by mixing the compound (1), the basic compound, formalin, the aldehyde compound (2), and the hydrophobic solvent comprises a water layer and an organic layer separated from each other.
[0042]
The mixing temperature is preferably in a range of -20°C to 200°C.
[0043]
The mixing may be carried out under normal pressure or increased pressure.
[0044]
Proceeding o"f the cross-coupling reaction of
formaldehyde which formalin contains and the aldehyde compound (2) can be confirmed by analysis means such as gas chromatography, high performance liquid chromatography, thin layer chromatography, N R, and IR.
[0045]
After completion of the cross-coupling reaction-, if necessary, the obtained reaction mixture may be subjected to liquid separation treatment and the mixture containing an organic layer is concentrated to bring out an a- hydroxyketone compound. The obtained cc-hydroxyketone compound may be further purified by a purification means such as distillation, and column chromatography.
[0046]
Examples of the α-hydroxyketone compound include 2- hydroxyacetaldehyde , l-hydroxy-2-nonanone , 2-hydroxy-l- phenylethanone, 2-hydroxy-l- (4-chlorophenyl) ethanone, 2- hydroxy-1- ( 2-fluorophenyl ) ethanone, 4- (methylthio) -2-oxo-l butanol, l-hydroxy-2-propanone , l-hydroxy-2-butanone, 1- hydroxy-2-pentanone, as well as 2-hydroxy-l-cyclohexanone, 4-phenyl-2-oxo-l-butanol, 4- (4-pyridyl) -2-oxo-l-butanol, 4 (3, 4-dimethoxy) -2-oxo-l-butanol, 4- ( 4-carbomethoxy) -2-oxo- l-butanol, 4-phenyl-2-oxo-l-pentanol , and 3- (2,4,6- triehlorophenyl ) -2-oxo-l-propanol .
EXAMPLES
[0047]
Hereinafter, the present invention will be described in more detail by way of Examples.
The production amount of an α-hydroxyketone compound per the catalyst amount is calculated according to the following expression.
(Production amount of α-hydroxyketone compound per the catalyst amount)
= (molar amount of produced a-hydroxyketone
compound) / (molar amount of used compound (1))
[0048]
(Example ' 1 )
After a 50 mL Schlenk flask purged with nitrogen was
charged with 205 mg of benzaldehyde, 460 mg of 38 wt% formalin, 34 mg of 3- ( 2 , 6-diisopropyl ) phenyl-4 , 5- dimethylthiazolium chloride, 2 g of toluene, and 500 mg of dry ice, generated gaseous carbon dioxide was discharged. The obtained mixture was heated to 40°C. After the foaming of carbon dioxide gas subsided, while the mixture being stirred, a solution obtained by dissolving 30 mg of 1,8- diazabicyclo [5, 4, 0] -7-undecene in 100 mg of toluene was added thereto. When the stirring was stopped, the mixture divided into 2 layers: an organic layer and a water layer.
The obtained mixture was stirred at 40°C for 6 hours. The obtained reaction mixture was cooled to room temperature to obtain a reaction mixture containing 2-hydroxy-l-phenyl- ethanone. According to the result of analysis by gas chromatography internal standard method, the yield of 2- hydroxy-l-phenylethanone was 70%. Benzaldehyde, a raw material, was recovered in an amount of 18%. The
production amount of 2-hydroxy-l-phenyl-ethanone per catalyst amount was 14.0.
[0049]
(Example 2)
After a 50 mL Schlenk flask purged with nitrogen was charged with 171 mg of benzaldehyde, 382. mg of 38 wt% formalin, 30 mg of 5, 6, 7, 8-tetrahydro-3- [2, 4, 6- trimethylphenyl ] -4H-cycloheptathiazolium chloride, 2 g of
toluene, and 500 mg of dry ice, generated gaseous carbon dioxide was discharged. The obtained mixture was heated to
40°C. After the foaming of carbon dioxide gas subsided, while the mixture being stirred, a solution obtained. by dissolving 25 mg of 1 , 8-diazabicyclo [ 5 , 4 ,0 ] -7-undecene in 100 mg of toluene was added thereto. When the mixing was stopped, the mixture divided into 2 layers : an organic layer. and a water layer. The obtained mixture was stirred at 40°C for 6 hours. The obtained reaction mixture was cooled to room temperature to obtain a reaction mixture containing 2-hydroxy-l-phenyl-ethanone. According to the result of analysis by gas chromatography internal standard method, the yield of .2-hydroxy-l-phenylethanone was 78%. Benzaldehyde, a raw material, was recovered in an amount of 9%. The production amount of 2-hydroxy-l-phenyl-ethanone per catalyst amount was 16.6.
[0050]
(Example 3)
After a 50 mL Schlenk flask. purged with nitrogen was charged with 240 mg of 4-chlorobenzaldehyde, 410 mg of 38 wt% formalin, 30 mg of 3- ( 2 , 6-diisopropyl ) henyl-4 , 5- dimethylthiazolium chloride, 2 g of toluene, and 500 mg of dry ice, generated gaseous carbon dioxide was discharged. The obtained mixture was heated to 40°C. After the foaming of carbon dioxide gas subsided, while the mixture being
stirred, a solution obtained by dissolving 9 mg of
triethylamine in 100 mg of toluene was added thereto. When the stirring was stopped, the mixture divided into 2 layers: an organic layer and a water layer. The obtained mixture was stirred at 40°C for 6 hours. The obtained reaction mixture was cooled to room temperature to obtain a reaction mixture containing 2-hydroxy-l- ( 4- chlorophenyl ) ethanone . According to the result of analysis by gas chromatography internal standard method, the yield of 2-hydroxy-l- ( 4-chlorophenyl) ethanone was 55%. 4- chlorobenzaldehyde, a raw material, was recovered in an amount of 42%. The production amount of 2-hydroxy-l- (4- chlorophenyl ) ethanone per catalyst amount was 20.2.
[0051]'
(Example 4)
After a 50 mL Schlenk flask purged with nitrogen was charged with 840 mg of 3-methylthiopropanal , 956 mg of 38 wt% formalin, 30 mg of 5 , 6, 7 , 8-tetrahydro-3- ( 2 , 4 , 6- trimethylphenyl ) -4H-cycloheptathiazolium chloride, 2 g of toluene, and 500 mg of dry ice, generated gaseous carbon^ dioxide was discharged. The obtained mixture was heated to 50°C. After the foaming of carbon dioxide gas subsided, while the mixture being stirred, a solution obtained by dissolving 13 mg of 1 , 8-diazabicyclo [ 5 , 4 , 0 ] -7-undecene in 300 mg of toluene was added thereto. When the stirring was
stopped, the mixture divided into 2 layers: an organic layer and a water layer. The obtained mixture was stirred at 50°C for 8 hours. The obtained reaction mixture was cooled to room temperature to obtain a reaction mixture containing 4- (methylthio) -2-oxo-l-butanol . According to the result of analysis by gas chromatography internal standard method, the yield of 4- (methylthio ) -2-oxo-l- butanol was 36%. 3-methylthiopropanal, a raw material, was recovered in an amount of 22%. The production amount of 4-
(methylthio) -2-oxo-l-butanol per catalyst amount was 2.9.8.
[0052]
(Example 5)
After a 50 mL Schlenk flask purged with nitrogen was charged with 1030 mg of 3-methylthiopropanal, 1200 mg of 38 wt% formalin, 35 mg of 3- ( 2 , 6-diisopropyl ) phenyl-4 , 5- dimethylthiazolium chloride, 5 g of toluene, and 500 mg of dry ice, generated gaseous carbon dioxide was discharged. The obtained mixture was heated to 50°C. After the foaming of carbon dioxide gas subsided, while the mixture being stirred, a solution obtained by dissolving 15 mg of 1,8- diazabicyclo [ 5 , 4 , 0 ] -7-undecene in 300 mg of toluene was added thereto. When the stirring was stopped, the mixture divided into 2 layers: an organic layer and a water layer. The obtained mixture was stirred at 50°C for 8 hours. The obtained reaction mixture was cooled to room temperature to
obtain a reaction mixture containing 4- (methylthio) -2-oxo- l-butanol. According to the result of analysis by gas chromatography internal standard method, the yield of 4-
(methylthio) -2-oxo-l-butanol was 23%. 3-methylthiopropanal , a raw material, was recovered in an amount of 27%. The production amount of 4- (methylthio) -2-oxo-l-butanol per catalyst amount was 23.1
[0053]
(Example 6)
A 200 mL four-neck flask equipped with a semi-lunar stirring blade made of Teflon® was charged with 12.2 g of 3-methylthiopropanal, 15.7 g of 37 wt% formalin, 210 mg of 3- (2, 6-diisopropyl ) phenyl-4, 5-dimethylthiazolium chloride, and 25 g of cyclopentyl methyl ether. The obtained mixture was heated to 70°C under nitrogen atmosphere. While the mixture being stirred, 1.2 g of 11% toluene solution of potassium hexamethyldisilazane was added thereto. When the stirring was stopped, the mixture divided into 2 layers: an organic layer and a water layer. The obtained mixture was stirred at 70°C for 8 hours. The obtained reaction mixture was cooled to room temperature to obtain a reaction mixture containing 4- (methylthio) -2-oxo-l-butanol . According to the result of analysis by gas chromatography internal standard method, the yield of 4- (methylthio) -2-oxo-l- butanol which is a cross-coupling isomer, was 19%. 3-
methylthiopropanal , a raw material, was recovered in an amount of 37%.. The production amount of 4- (methylthio) -2- oxo-l-butanol per catalyst amount was 37.6.
[0054]
(Example 7)
After a 50 mL Schlenk. flask purged with nitrogen was charged . with 1.21 g of .3-methylthiopropanal, 1.38 g of 38 wt% formalin, 30 mg of 3-benzylthiazolium bromide, 2.5 g of toluene, and 500 mg of dry ice, generated gaseous carbon dioxide was discharged. The obtained mixture was heated to 50°C. After the foaming of carbon dioxide gas subsided, while the mixture being stirred, a solution obtained by dissolving 18 mg of 1 , 8-diazabicyclo [ 5 , , 0 ] -7-undecene in 300 mg of toluene was added thereto. When the stirring was stopped, the mixture divided into 2 layers: an organic layer and a water layer. The obtained mixture was stirred at 50°C for 6■ hours . The obtained reaction■ mixture was . cooled to room temperature to obtain a reaction mixture containing 4- (methylthio) -2-oxo-l-butanol . According to the result of analysis by gas chromatography internal standard method, the yield of 4- (methylthio) -2-oxo-l- butanol was 9%. 3-methylthiopropanal, a raw material, was recovered in an amount of 80%. The production amount of 4- (methylthio) -2-oxo-l-butanol per catalyst amount was 8.9.
[0055]
(Example 8)
After a 50 mL Schlenk flask purged with nitrogen was charged with 1.34 g of 3-phenylpropionaldehyde, 1.21 g of 37 wt% formalin, 35 mg of 3- ( 2 , 6-diisopropyl) phenyl-4 , 5- dimethylthiazolium chloride, and 3 g of toluene. The obtained mixture was heated to 70°C and a solution obtained by dissolving 14 mg of 1 , 8-diazabicyclo [ 5 , 4 , 0 ] -7-undecene in 300 mg of toluene was added thereto. When the stirring was stopped, the mixture divided into 2 layers: an organic layer and a water layer. The obtained mixture was stirred at 70°C for 4 hours. The obtained reaction mixture' was cooled to' room temperature to obtain a reaction mixture containing 4-phenyl-2-oxo-l-butanol . According to the result of analysis by gas chromatography internal standard method, the yield of 4-phenyl-2-oxo-l-butanol was 53%. 3- phenylpropionaldehyde, a raw material, was recovered in an amount of 33%. The production amount of 4-phenyl-2-oxo-l- butanol per catalyst amount was 53.7. INDUSTRIAL APPLICABILITY
[0056]
According to the invention, an cc-hydroxyketone
compound can be produced by a new method. According to the invention, the production amount of an a-hydroxyketone compound per catalyst amount unit can be improved. In the
present invention, more economical formalin as a formaldehyde source can be used.
Claims
1. A process for producing an. a-hydroxyketone compound, comprising mixing
at least one hydrophobic solvent selected from the group consisting of aromatic hydrocarbon solvents,
aliphatic hydrocarbon solvents, halo-hydrocarbon solvents, and ether solvents incompatible with water,
a compound represented by formula (1) :
wherein, R1 and R2 are each independently a hydrogen atom, an optionally substituted alkyl group, an optionally substituted alkoxycarbonyl group, an optionally substituted alkylcarbonyl group, or an optionally substituted aryl group, or R1 and R2 are bonded to each other to form a cycloalkene ring with the carbon atoms bonded thereto; R3 is an optionally substituted alkyl group or an aryl group; and X~ is an anion,
a basic . compound,
formalin, and
an aldehyde compound with 2 to 30 carbon atoms.
2. The process according to claim 1, wherein a mixture obtained by the mixing comprising a water layer and an organic layer separated from each other.
3. The process according to claim 1 or 2, wherein the basic compound is at least one compound selected from the group consisting of an organic base, an alkali metal salts, and an alkaline earth metal salt.
4. The process according to any one of claims 1 to 3, wherein R3 is an aryl group.
5. The process according to any one of claims 1 to 4, wherein the mixing is carried out in the presence of carbon dioxide.
6. The process according to any one of claims 1 to 5, wherein the aldehyde compound with 2 to 30 carbon atoms is an aldehyde compound represented by formula (2): 
wherein R4 is an optionally substituted alkyl group with to 10 carbon atoms, an optionally substituted aryl group with 6 to 20 carbon atoms, or an optionally substituted heteroaryl group with 4 to 10 carbon atoms.
7. The process according to any one of claims 1 to 6, wherein the aldehyde compound is 3-methylthiopropanal and the a-hydroxyketone compound is 4-methylthio-2-oxo-l- butanol .
8. The process according to any one of claims 1 to 6, wherein the aldehyde compound is an aromatic aldehyde and the a-hydroxyketone compound is 2-hydroxy-l- ( substituted o unsubstituted aryl ) ethanone .
9. The process according to any one of claims 1 to 6, wherein the aldehyde compound is 3- ( substituted or
unsubstituted aryl ) propionaldehyde and the a-hydroxyketone compound is 4- ( substituted or unsubstituted aryl ) -2-oxo-l- butanol .
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| JP2012093655A JP2015071541A (en) | 2012-04-17 | 2012-04-17 | METHOD FOR MANUFACTURING α-HYDROXY KETONE COMPOUND |
| JP2012-093655 | 2012-04-17 |
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| WO2013157651A1 true WO2013157651A1 (en) | 2013-10-24 |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| WO2015112096A1 (en) * | 2014-01-23 | 2015-07-30 | Agency For Science, Technology And Research | Condensation of aldehyde |
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| US5410089A (en) * | 1992-05-04 | 1995-04-25 | Basf Aktiengesellschaft | Preparation of dihydroxyacetone |
| WO2008010609A1 (en) * | 2006-07-21 | 2008-01-24 | Sumitomo Chemical Company, Limited | Process for producing 2-hydroxy-4-(methylthio)butyrate compounds and intermediates thereof |
| WO2008104875A1 (en) | 2007-03-01 | 2008-09-04 | Pfizer Products Inc. | Oxazolidinones as cholesterol absorption inhibitors |
| WO2013035650A1 (en) * | 2011-09-06 | 2013-03-14 | Sumitomo Chemical Company, Limited | Method for producing alpha - hydroxy ketone compound |
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- 2012-04-17 JP JP2012093655A patent/JP2015071541A/en active Pending
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- 2013-04-16 WO PCT/JP2013/061698 patent/WO2013157651A1/en active Application Filing
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| US5410089A (en) * | 1992-05-04 | 1995-04-25 | Basf Aktiengesellschaft | Preparation of dihydroxyacetone |
| WO2008010609A1 (en) * | 2006-07-21 | 2008-01-24 | Sumitomo Chemical Company, Limited | Process for producing 2-hydroxy-4-(methylthio)butyrate compounds and intermediates thereof |
| WO2008104875A1 (en) | 2007-03-01 | 2008-09-04 | Pfizer Products Inc. | Oxazolidinones as cholesterol absorption inhibitors |
| WO2013035650A1 (en) * | 2011-09-06 | 2013-03-14 | Sumitomo Chemical Company, Limited | Method for producing alpha - hydroxy ketone compound |
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2015112096A1 (en) * | 2014-01-23 | 2015-07-30 | Agency For Science, Technology And Research | Condensation of aldehyde |
Also Published As
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| JP2015071541A (en) | 2015-04-16 |
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