JP2014196264A - Production method of n-acylamino acid - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a method for producing N-acylamino acid at good yield under mild reaction conditions without going through a complicated step.SOLUTION: In a solvent, in the presence of at least one catalyst selected from the group consisting of the following catalysts (A) and (B): (A) a catalyst carrying at least one selected from the group consisting of noble metals and noble metal oxides on a cobalt oxide; and (B) a catalyst carrying a cobalt oxide and at least one selected from the group consisting of noble metals and noble metal oxides on a carrier, and in the presence of hydrogen, reaction of 3-(methylthio)propionaldehyde, an amide compound represented by the formula (1) (where Rand Reach independently represent a hydrogen atom, a hydrocarbon group which may be substituted, or a heterocyclic group which may be substituted) and a carbon monoxide gives N-acylamino acid.

Description

  The present invention is useful as a raw material for animal feed additives such as methionine, a raw material for producing pharmaceuticals and agricultural chemicals, and is described as an N-acylamino acid represented by formula (2) (hereinafter referred to as N-acylamino acid (2)). Relates to a method of manufacturing).

  The N-acylamino acid (2) is useful as a raw material for animal feed additives (for example, methionine), a raw material for producing medical pesticides, and the like.

For example, in Patent Documents 1 and 2, an aldehyde and an amide are reacted under pressure of a synthesis gas (a mixed gas of carbon monoxide and hydrogen) in the presence of a cobalt carbonyl complex catalyst (such as Co ₂ (CO) ₈ ). A method for synthesizing N-acylamino acids (amide carbonylation reaction) is described. This cobalt carbonyl complex catalyst is a zero-valent cobalt complex, which reacts under high pressure conditions of carbon monoxide in order to stabilize the cobalt complex and prevent the formation of insoluble high-order carbonyl clusters and cobalt precipitates. Need to do. Therefore, it is difficult to scale up, and even if a relatively inexpensive cobalt catalyst is used, there are problems in that it is disadvantageous in terms of production cost under such severe reaction conditions, and the environmental load is also increased. If the cobalt carbonyl complex catalyst is not purified by sublimation or the like immediately before use, it is difficult to express the desired catalytic activity. Furthermore, this catalyst is highly toxic because of the coordination of carbon monoxide (carbonyl group), and careful handling is required for handling such as transportation and storage.
Patent Document 3 discloses that by reacting 3- (methylthio) propionaldehyde with acetamide in a solvent in the presence of palladium bromide, triphenylphosphine, lithium bromide and sulfuric acid under pressure of carbon monoxide. A method for obtaining N-acetylmethionine has been described. However, in this method, it is necessary to add triphenylphosphine, lithium bromide and sulfuric acid in addition to palladium bromide which is a catalyst. Since these are dissolved in the reaction solution, complicated isolation and purification operations are required to isolate the target N-acetylmethionine after completion of the reaction.

Special table 2008-501737 gazette Special table 2008-501738 gazette Special table 2001-505871 gazette

Any of the above-mentioned methods has problems such as a complicated reaction system, a need to carry out the reaction under high pressure conditions, and complicated handling of the catalyst.
An object of the present invention is to provide a method for producing an N-acylamino acid (2) in a good yield under mild reaction conditions without using complicated cobalt carbonyl complex catalysts and without complicated steps. Is to provide.

（式中、Ｒ¹およびＲ²は、それぞれ独立して、水素原子、置換されていてもよい炭化水素基または置換されていてもよい複素環基を表す）で示されるアミド化合物と、一酸化炭素とを反応させることを特徴とする、式（２）：

（式中、Ｒ¹およびＲ²は、それぞれ前記と同じである）で示されるＮ−アシルアミノ酸の製造方法。
（２）前記コバルト酸化物がＣｏ₃Ｏ₄である、（１）に記載の製造方法。
（３）前記貴金属および貴金属酸化物からなる群より選ばれる少なくとも１種が、金、パラジウムおよびパラジウム酸化物からなる群より選ばれる少なくとも１種である、（１）または（２）に記載の製造方法。
（４）上記（１）〜（３）のいずれかに記載の製造方法によって製造された式（２）で示されるＮ−アシルアミノ酸と、アンモニアおよび水からなる群より選ばれる少なくとも１種とを接触させることを特徴とする、式（３）：

（式中、Ｒ²は前記と同じである）で示されるアミノ酸の製造方法。 As a result of intensive studies to solve the above problems, the present inventor has found a solution means having the following configuration, and has completed the present invention.
(1) At least one catalyst selected from the group consisting of the following catalysts (A) and (B) in a solvent:
(A) A catalyst in which at least one selected from the group consisting of noble metals and noble metal oxides is supported on cobalt oxide (B) At least selected from the group consisting of cobalt oxides, noble metals and noble metal oxides on a carrier 3- (methylthio) propionaldehyde in the presence of one supported catalyst and hydrogen, and formula (1):

(Wherein R ¹ and R ² each independently represents a hydrogen atom, an optionally substituted hydrocarbon group or an optionally substituted heterocyclic group), and monoxide Formula (2), characterized by reacting with carbon:

(Wherein R ¹ and R ² are the same as defined above, respectively).
(2) The manufacturing method according to (1), wherein the cobalt oxide is Co ₃ O ₄ .
(3) The production according to (1) or (2), wherein at least one selected from the group consisting of the noble metal and the noble metal oxide is at least one selected from the group consisting of gold, palladium and palladium oxide. Method.
(4) N-acylamino acid represented by formula (2) produced by the production method according to any one of (1) to (3) above and at least one selected from the group consisting of ammonia and water Formula (3), characterized in that it is contacted:

(Wherein R ² is the same as defined above).

  According to the production method of the present invention, the desired N-acylamino acid (2) can be obtained in good yield under mild reaction conditions without going through complicated steps.

<Method for producing N-acylamino acid represented by formula (2)>
The method for producing N-acylamino acid (2) according to the present invention comprises at least one catalyst selected from the group consisting of the following catalysts (A) and (B) in a solvent:
(A) A catalyst in which at least one selected from the group consisting of noble metals and noble metal oxides is supported on cobalt oxide (B) At least selected from the group consisting of cobalt oxides, noble metals and noble metal oxides on a carrier In the presence of a catalyst on which one species is supported and hydrogen, 3- (methylthio) propionaldehyde, a specific amide compound, and carbon monoxide are reacted.

  The specific amide compound used in the present invention is represented by the following formula (1).

In the formula (1), R ¹ and R ² each independently represent a hydrogen atom, an optionally substituted hydrocarbon group or an optionally substituted heterocyclic group.
It does not specifically limit as a hydrocarbon group, For example, an alkyl group, an alkenyl group, an alkynyl group, a cycloalkyl group, a cycloalkenyl group, an aryl group etc. are mentioned, A C1-C24 hydrocarbon group is preferable.

  As an alkyl group, a C1-C24 alkyl group is preferable, for example, methyl group, ethyl group, n-propyl group, isopropyl group, n-butyl group, isobutyl group, sec-butyl group, tert-butyl group Pentyl group, hexyl group, heptyl group, octyl group, nonyl group, decyl group, undecyl group, dodecyl group, tridecyl group, tetradecyl group, pentadecyl group, hexadecyl group, heptadecyl group, octadecyl group, nonadecyl group, icosyl group, eicosyl Group, henicosyl group, heneicosyl group, docosyl group, tricosyl group, tetracosyl group and the like.

  The alkenyl group is preferably an alkenyl group having 2 to 24 carbon atoms, for example, vinyl group, allyl group, 2-methylallyl group, isopropenyl group, 1-propenyl group, 1-butenyl group, 2-butenyl group, 3 -Butenyl group, 1-methyl-1-propenyl group, 1-methyl-2-propenyl group, 2-methyl-1-propenyl group, 2-methyl-2-propenyl group, 1-pentenyl group, 2-pentenyl group, 3-pentenyl group, 4-pentenyl group, 1-methyl-1-butenyl group, 2-methyl-1-butenyl group, 3-methyl-1-butenyl group, 1-methyl-2-butenyl group, 2-methyl- 2-butenyl group, 3-methyl-2-butenyl group, 1-hexenyl group, 2-hexenyl group, 3-hexenyl group, 4-hexenyl group, 5-hexenyl group, 1-methyl-1-pen Nyl group, 2-methyl-1-pentenyl group, 4-methyl-3-pentenyl group, 2-ethyl-1-butenyl group, 2-heptenyl group, 2-octenyl group, 2-nonenyl group, 2-decenyl group, 2-undecenyl group, 2-dodecenyl group, 2-tridecenyl group, 2-tetradecenyl group, 2-pentadecenyl group, 2-hexadecenyl group, 2-heptadecenyl group, 2-octadecenyl group, 2-nonadecenyl group, 2-icosenyl group, Examples include 2-eicosenyl group, 2-henicosenyl group, 2-heneicosenyl group, 2-docosenyl group, 2-tricosenyl group, 2-tetracocenyl group and the like.

  The alkynyl group is preferably an alkynyl group having 2 to 24 carbon atoms. For example, ethynyl group, 1-propynyl group, 2-propynyl group, 1-butynyl group, 2-butynyl group, 3-butynyl group, 1-methyl 2-propynyl group, 1-pentynyl group, 2-pentynyl group, 3-pentynyl group, 4-pentynyl group, 1-methyl-3-butynyl group, 2-methyl-3-butynyl group, 1-hexynyl group, 2 -Hexynyl group, 3-hexynyl group, 4-hexynyl group, 5-hexynyl group, 2-heptynyl group, 2-octynyl group, 2-noninyl group, 2-decynyl group, 2-undecynyl group, 2-dodecynyl group, 2 -Tridecynyl group, 2-tetradecynyl group, 2-pentadecynyl group, 2-hexadecynyl group, 2-heptadecynyl group, 2-octadecynyl group, 2-nonadecini Group, 2-Ikoshiniru group, 2-Eikoshiniru group, 2-Hen'ikoshiniru group, 2-Hen'eikoshiniru group, 2-Dokoshiniru group, 2-Torikoshiniru group, such as 2-Tetorakoshiniru group.

  The cycloalkyl group is preferably a cycloalkyl group having 3 to 8 carbon atoms, and examples thereof include a cyclopropyl group, a cyclobutyl group, a cyclopentyl group, a cyclohexyl group, a cycloheptyl group, and a cyclooctyl group.

  The cycloalkenyl group is preferably a cycloalkenyl group having 3 to 8 carbon atoms, and examples thereof include a cyclopropenyl group, a cyclobutenyl group, a cyclopentenyl group, a cyclohexenyl group, a cycloheptenyl group, and a cyclooctenyl group.

  As the aryl group, an aryl group having 6 to 18 carbon atoms is preferable, and examples thereof include a phenyl group, a naphthyl group, an anthracenyl group, a phenanthryl group, a tolyl group, and a xylyl group.

Moreover, it does not specifically limit as a heterocyclic group, For example, a heteroaryl group, a heteroaralkyl group, etc. are mentioned, A C3-C10 heterocyclic group is preferable.
The heteroaryl group is preferably a heteroaryl group having 3 to 9 carbon atoms, and examples thereof include a pyridyl group, a quinonyl group, a pyrrolyl group, an imidazolyl group, a furyl group, an indolyl group, a thienyl group, and an oxazolyl group.
The heteroaralkyl group is preferably a heteroaralkyl group having 5 to 10 carbon atoms, and examples thereof include a pyridylmethyl group, a quinolylmethyl group, an indolylmethyl group, a furylmethyl group, and a pyrrolylmethyl group.

The hydrocarbon group and the heterocyclic group may be unsubstituted or may have a substituent.
When the hydrocarbon group is an alkyl group, an alkenyl group, or an alkynyl group, examples of the substituent include a halogen atom (for example, fluorine, chlorine, bromine, etc.) and a cycloalkyl group having 3 to 6 carbon atoms (for example, a cyclopropyl group). 1-methylcyclopropyl group, cyclobutyl group, cyclopentyl group, 1-methylcyclopentyl group, cyclohexyl group and the like, and alkoxy groups having 1 to 4 carbon atoms (for example, methoxy group, ethoxy group, n-propoxy group, isopropoxy group) Group, n-butoxy group, sec-butoxy group, isobutoxy group, tert-butoxy group, etc.), thioalkoxy groups having 1 to 4 carbon atoms (for example, thiomethoxy group, thioethoxy group, thiopropoxy group, thiobutoxy group, etc.), C 3 and C 4 alkenyloxy groups (eg, allyloxy groups, 2-pro Nyloxy group, 2-butenyloxy group, 2-methyl-3-propenyloxy group, etc.), aralkyloxy group having 7 to 20 carbon atoms, aryl group having 6 to 18 carbon atoms (for example, phenyl group, naphthyl group, anthracenyl group) Group, phenanthryl group, etc.), aryloxy group (eg, phenyloxy group, naphthyloxy group, etc.), alkanoyl group having 2 to 7 carbon atoms, allyloyl group having 7 to 19 carbon atoms, 2 to 7 carbon atoms Alkanoylamino group, alkylsulfonylamino group having 1 to 6 carbon atoms, alkoxycarbonylamino group having 2 to 6 carbon atoms, benzylcarbonylamino group, arylsulfonylamino group having 6 to 18 carbon atoms, aminocarbonyl group, carbon Examples thereof include alkoxycarbonyl groups having 1 to 6 numbers.
In particular, when the hydrocarbon group is an alkyl group, examples of the alkyl group substituted with an aryl group having 6 to 18 carbon atoms include benzyl group, phenethyl group, 3-phenylpropyl group, benzhydryl group, trityl group, trityl group, and the like. Examples include aralkyl groups such as phenylethyl group, (1-naphthyl) methyl group, and (2-naphthyl) methyl group.

  When the hydrocarbon group is a cycloalkyl group, a cycloalkenyl group or an aryl group, examples of the substituent include a halogen atom, a cycloalkyl group having 3 to 6 carbon atoms, an alkoxy group having 1 to 4 carbon atoms, and a carbon number Is a thioalkoxy group having 1 to 4 carbon atoms, an alkenyloxy group having 3 and 4 carbon atoms, an aralkyloxy group having 7 to 20 carbon atoms, an aryl group having 6 to 18 carbon atoms, an aryloxy group, and 2 to 2 carbon atoms. An alkanoyl group having 7 carbon atoms, an aryloyl group having 7 to 19 carbon atoms, an alkanoylamino group having 2 to 7 carbon atoms, an alkylsulfonylamino group having 1 to 6 carbon atoms, an alkoxycarbonylamino group having 2 to 6 carbon atoms, Benzylcarbonylamino group, arylsulfonylamino group having 6 to 18 carbon atoms, aminocarbonyl group, alkoxycarbonyl group having 1 to 6 carbon atoms, etc. Substituents and alkyl groups having 1 to 6 carbon atoms (for example, methyl group, ethyl group, n-propyl group, isopropyl group, n-butyl group, isobutyl group, sec-butyl group, tert-butyl group, pentyl group) Hexyl group, etc.), alkenyl groups having 2 to 6 carbon atoms (for example, vinyl group, 1-propenyl group, 2-propenyl group, 1-butenyl group, 2-butenyl group, 3-butenyl group, 1-methyl- 2-propenyl group, 2-methyl-2-propenyl group, 1-pentenyl group, 2-pentenyl group, 3-pentenyl group, 4-pentenyl group, 1-methyl-2-butenyl group, 2-methyl-2-butenyl group Group, 1-hexenyl group, 2-hexenyl group, 3-hexenyl group, 4-hexenyl group, 5-hexenyl group and the like, and an aralkyl group having 7 to 20 carbon atoms (for example, benzyl group, phenyl group, Nechiru group, naphthylmethyl group).

  Examples of the substituent in the heterocyclic group include a halogen atom, a cycloalkyl group having 3 to 6 carbon atoms, an alkoxy group having 1 to 4 carbon atoms, a thioalkoxy group having 1 to 4 carbon atoms, and 3 carbon atoms. And alkenyloxy group having 4 to 7 carbon atoms, aralkyloxy group having 7 to 20 carbon atoms, aryl group having 6 to 18 carbon atoms, aryloxy group, alkanoyl group having 2 to 7 carbon atoms, and aryloyl having 7 to 19 carbon atoms Group, alkanoylamino group having 2 to 7 carbon atoms, alkylsulfonylamino group having 1 to 6 carbon atoms, alkoxycarbonylamino group having 2 to 6 carbon atoms, benzylcarbonylamino group, aryl having 6 to 18 carbon atoms Sulfonylamino group, aminocarbonyl group, alkoxycarbonyl group having 1 to 6 carbon atoms, alkyl group having 1 to 6 carbon atoms, alkenyl group having 2 to 6 carbon atoms, carbon There are exemplified above substituents, such as an aralkyl group having 7 to 20.

Specific examples of the amide compound represented by the formula (1) include acetamide, benzamide, propionamide, N-methylacetamide, fatty acid amide, acrylamide, cinnamic acid amide, phenylacetic acid amide, acetanilide and the like.
Among these, compounds in which R ² is a hydrogen atom are preferably used, and acetamide is particularly preferable and is advantageously employed in the present invention.

  The amide compound represented by the formula (1) is preferably used in a proportion of 1 mol, more preferably 1.05 to 2 mol, per 1 mol of 3- (methylthio) propionaldehyde.

Examples of the solvent used in the present invention include organic solvents and ionic liquids.
Examples of the organic solvent include alcohols (eg, methanol, ethanol, isopropyl alcohol), ethers (eg, 1,4-dioxane, tetrahydrofuran, ethylene glycol dimethyl ether, tert-butyl methyl ether, dibutyl ether, cyclopentyl methyl ether). Etc.), esters (eg, ethyl acetate, butyl acetate, etc.), N-methylpyrrolidinone, N-ethylpyrrolidinone, 1,3-dimethyl-2-imidazolidinone, dimethyl sulfoxide, acetone, acetonitrile, benzonitrile, sulfolane, N, N-dimethylformamide, N, N-dimethylacetamide, toluene, acetic acid and the like can be mentioned. Among these, esters are preferable, and ethyl acetate is particularly preferable. Only 1 type may be used for a solvent and it may use 2 or more types together.

The ionic liquid is a salt that is liquid at a relatively low temperature, preferably a salt having a melting point of less than 100 ° C., and more preferably a salt that is liquid under atmospheric conditions (20 ° C., 0.1 MPa). The ionic liquid is composed of a cation and an anion, and examples of the cation include substituents such as imidazolium cation, pyridinium cation, pyrrolidinium cation, phosphonium cation, ammonium cation, guanidinium cation, and isouronium cation. The cation which may have is mentioned. Examples of the anion include halogen ion, sulfate ion, sulfonate ion, imide, borate ion, phosphate ion, antimonate ion, tetracarbonylcobaltate ion, trifluoroacetate ion, decanoate ion, and the like.
Specific examples of ionic liquids include 1-ethyl-3-methylimidazolium hexafluorophosphate, 1-ethyl-3-methylimidazolium tetrafluoroborate, 1-butylpyridinium bromide, 1-butyl-3-methylimidazolium. Hexafluorophosphate, 1-butyl-3-methylimidazolium tetrafluoroborate, 1-hexyl-3-methylimidazolium hexafluorophosphate, 3-methyl-1-octadecylimidazolium hexafluorophosphate, 3-methyl-1- Examples include tetradecylimidazolium tetrafluoroborate, 1-butyl-2,3-dimethylimidazolium hexafluorophosphate, and the like.

  The solvent is preferably used in a proportion of 0.5 to 100 times by mass, more preferably 30 to 70 times by mass with respect to 3- (methylthio) propionaldehyde. When two or more solvents are used in combination, the total amount is preferably within this range.

The catalyst used in the present invention is at least one catalyst selected from the group consisting of the following catalysts (A) and (B).
(A) A catalyst in which at least one selected from the group consisting of noble metals and noble metal oxides is supported on cobalt oxide.
(B) A catalyst in which a cobalt oxide and at least one selected from the group consisting of noble metals and noble metal oxides are supported on a carrier.

  If the above reaction (amide carbonylation reaction of 3- (methylthio) propionaldehyde) is performed with a cobalt oxide alone or with a catalyst in which only a cobalt oxide is supported on a carrier, the catalytic activity is insufficient. Therefore, the catalyst must be activated by reduction treatment at a high temperature (for example, 300 ° C. or higher) in advance, or the reaction must be performed in the presence of high-pressure synthesis gas. However, as in the production method of the present invention, by using at least one selected from the group consisting of noble metals and noble metal oxides together with cobalt oxide, the desired N-acylamino acid (with good yield under mild conditions) 2) is obtained.

Examples of the cobalt oxide include Co ₃ O ₄ , CoO, and Co ₂ O _3. Among these, Co ₃ O ₄ is preferable. Only one type of cobalt oxide may be used, or two or more types of cobalt oxides having different compositions and physical properties (shape, particle size, etc.) may be used in combination. The average particle diameter of the cobalt oxide is preferably 500 nm or less, more preferably 100 nm or less, and still more preferably 20 nm or less. If the average particle diameter of the cobalt oxide is within such a range, the number of rotations of the catalyst per unit time can be increased. The average particle diameter of the cobalt oxide is determined by, for example, observation with a transmission electron microscope (TEM). Specifically, the average particle size is determined by observing the catalyst with a TEM to create a cobalt oxide particle size distribution and calculating the average particle size. As a cobalt oxide, a commercial item may be used, for example, what was prepared by methods, such as baking a cobalt compound in the atmosphere of oxidizing gas, may be used.
Examples of cobalt compounds include cobalt halides, inorganic salts (for example, sulfates, nitrates, etc.), acetates, acetylacetonate compounds, alkene coordination compounds, amine coordination compounds, pyridine coordination compounds, carbon monoxide. Examples include a coordination compound, a phosphine coordination compound, and a phosphite coordination compound.

  The cobalt oxide is preferably 0.00010 to 0.80 mol, more preferably 0.010 to 0.20 mol, still more preferably 0.020 to 1 mol per mol of 3- (methylthio) propionaldehyde. It is used at a ratio of 0.10 mol.

Examples of the noble metal include gold, palladium, platinum, ruthenium, rhodium, iridium, osmium and silver. Examples of the noble metal oxide include oxides such as gold, palladium, platinum, ruthenium, rhodium, iridium, osmium and silver. Among these, at least one selected from the group consisting of gold, palladium, and palladium oxide is preferable.
Moreover, in preparation of catalyst (A) and (B), it is not necessary to use at least 1 sort (s) chosen from the group which consists of a noble metal and a noble metal oxide as a raw material. At least one precursor compound selected from the group consisting of noble metals and noble metal oxides (hereinafter sometimes referred to as “noble metal compounds”) is used as a raw material, and finally selected from the group consisting of noble metals and noble metal oxides. At least one kind may be supported. Such noble metal compounds are not particularly limited as long as they are compounds containing these noble metals. For example, halides, inorganic salts (for example, sulfates, nitrates, etc.), acetates, acetylacetonate compounds of these noble metals. Alkene coordination compounds, phosphine coordination compounds, phosphite coordination compounds, and the like. Among these, gold, palladium, a gold compound, or a palladium compound is preferable. Such noble metal compounds may be used alone or in combination of two or more.

Examples of the gold compound include Au (CO) Cl, AuClP (C ₂ H ₅ ) ₃ , AuClP (CH ₃ ) ₃ , AuCl (PPh ₃ ) ₃ , (CH ₃ ) ₂ (C ₅ H ₇ O ₂ ) Au , (CH ₃ ) ₂ Au (CF ₃ COCHCH ₃ ), AuBr ₃ , AuCl, AuCl ₃ , AuCN, AuI, Au ₂ O ₃ , HAuBr ₄ .4H ₂ O, HAuCl ₄ .4H ₂ O, and the like.
Examples of the palladium compound include PdCl ₂ , PdI ₂ , PdO, Pd (CH ₃ COO) ₂ , PdSO ₄ , Pd (NO ₃ ) ₂ , [Pd (NH ₃ ) ₄ ] Cl ₂ .H ₂ O, Na _2. PdCl ₄ , Pd (PPh ₃ ) ₄ , [PdCl ₂ (C ₈ H ₁₂ )] and the like can be mentioned.

In the catalyst (B), the carrier is not particularly limited as long as it is generally used as a carrier for a solid catalyst, and any of inorganic compounds and organic compounds can be employed. Examples of the support include inorganic oxides such as silica (SiO ₂ ), aluminum oxide (alumina), titanium oxide, cerium oxide, zirconium oxide, magnesium oxide, tungsten oxide, and iron oxide, or a combination of these inorganic oxides. Examples thereof include oxide, activated carbon, carbon black, organic polymer, zeolite, clay, and diatomaceous earth. Among these, inorganic oxides are preferable, and silica or alumina is more preferable.
Only 1 type may be used for a support | carrier and it may use 2 or more types together. Moreover, the shape of a support | carrier is not specifically limited, It is arbitrary shapes, such as a dense body and a porous body.

  In the catalyst (A), the amount of at least one selected from the group consisting of a noble metal supported on a cobalt oxide and a noble metal oxide is not particularly limited, and is usually 0.5 atomic% or more based on the whole catalyst. , Preferably 1 atom% or more, more preferably 2 atom% or more, and usually 50 atom% or less, preferably 30 atom% or less, more preferably 20 atom% or less. In the present invention, “1 atom%” means the mole% of noble metal atoms relative to the total number of moles of cobalt atoms and moles of noble metal atoms contained in the catalyst. Cobalt oxidation used as a raw material for catalyst preparation The number of moles of cobalt atoms contained in the product (or a cobalt compound as a raw material for the cobalt oxide) and the number of noble metal atoms contained in at least one selected from the group consisting of noble metals and noble metal oxides (or noble metal compounds). It can be obtained by calculating the mol% of the noble metal atom in the total with the number of moles. For example, when a catalyst is prepared using 1 mol of a gold compound converted to a gold atom and 9 mol of a cobalt compound converted to a cobalt atom, the gold atom is present at 10 atom% in the catalyst. .

By setting the amount of at least one selected from the group consisting of a noble metal and a noble metal oxide to the above ratio, a higher catalytic activity is exhibited and the reaction efficiency per catalyst is further increased.
The content of at least one selected from the group consisting of noble metals and noble metal oxides contained in the catalyst (B) is not particularly limited, and is preferably 0.1 to 10% by mass. The content of the cobalt oxide is not particularly limited, and is preferably 1 to 30% by mass.

The loading method in the catalysts (A) and (B) is not particularly limited, and examples thereof include an impregnation method, a coprecipitation method, a precipitation precipitation method, and an ion exchange method. Specifically, in the case of the catalyst (A), for example, the following method (i) or (ii) may be mentioned.
(I) A method in which a precipitate obtained by a coprecipitation method from a solution containing a cobalt compound and a noble metal compound is baked in an oxidizing gas atmosphere.
(Ii) A method in which a cobalt oxide is contact-treated with a solution containing a noble metal compound and then baked in an oxidizing gas atmosphere or an inert gas atmosphere. Note that the contact treatment refers to impregnating cobalt oxide with a solution or immersing cobalt oxide in the solution.

In the case of the catalyst (B), for example, the following method (iii) can be mentioned.
(Iii) A method in which a support is contact-treated with a solution containing a cobalt compound and a noble metal compound, and then fired in an atmosphere of an oxidizing gas. The contact treatment refers to impregnating the carrier with the solution or immersing the carrier in the solution.

The oxidizing gas used in the firing is a gas containing an oxidizing substance, and examples thereof include an oxygen-containing gas. The oxygen concentration is usually about 1 to 30% by volume. As the oxygen source, air, pure oxygen, or the like is preferably used, and diluted with an inert gas as necessary. As the oxidizing gas, air is preferable.
Examples of the inert gas include nitrogen, carbon dioxide, helium, argon, and the like, and diluted with water vapor as necessary.
The firing temperature is preferably 50 to 450 ° C, more preferably 200 to 400 ° C. Note that baking may be performed in a reducing gas atmosphere as long as the cobalt oxide can maintain an oxide state. The reducing gas is a gas containing a reducing substance, and examples thereof include a hydrogen-containing gas, a carbon monoxide-containing gas, and a hydrocarbon-containing gas.

  After the precipitate in the method (i), the contact treatment in the method (ii), or after the contact treatment in the method (iii), drying may be performed before firing. As a drying method, a conventionally known method can be employed, the drying temperature is usually from room temperature to about 120 ° C., and the pressure is usually from 0.001 to 1 MPa, preferably atmospheric pressure. Drying may be performed in an air atmosphere or an inert gas atmosphere (for example, nitrogen, helium, argon, oxygen dioxide, or the like).

  The average particle diameter of the supported noble metal or noble metal oxide is preferably 0.2 nm or more, more preferably 0.5 nm or more, preferably 50 nm or less, more preferably 20 nm or less, and further preferably 10 nm or less. The average particle diameter of the noble metal or noble metal oxide is determined by observation with a transmission electron microscope (TEM) as described above.

In the present invention, the amide carbonylation reaction is performed in the presence of hydrogen and carbon monoxide. The molar ratio of carbon monoxide to hydrogen (carbon monoxide / hydrogen) is preferably 1/1 to 9/1, more preferably 1/1 to 5/1, and further preferably 2/1 to 4/1. .
The reaction temperature is preferably 60 to 140 ° C, more preferably 80 to 120 ° C. Although the pressure in the reaction system may be normal pressure, the reaction is preferably carried out under a pressure of 0.1 to 25 MPa, more preferably 1 to 18 MPa in absolute pressure. When the reaction is performed under pressure, the reaction may be performed using a mixed gas of hydrogen and carbon monoxide, and an inert gas (such as nitrogen or helium) may be used to adjust the pressure. The reaction may be carried out in any of continuous, semi-continuous and batch systems.
Prior to the amide carbonylation reaction, hydrogen pretreatment of the catalyst may be performed for the purpose of enhancing the catalytic activity of the heterogeneous catalyst. The hydrogen pretreatment may be performed under conditions of 0.1 MPa or more and 70 to 200 ° C., for example, by introducing hydrogen gas. The hydrogen pretreatment time is usually 5 to 400 minutes, preferably 30 to 240 minutes.

  According to the production method of the present invention, the N-acylamino acid (2) can be produced in good yield. The reaction mixture containing the N-acylamino acid (2) may be further subjected to a post-treatment step. A post-processing process is not specifically limited, It can select suitably. If necessary, purification treatment such as filtration, washing, distillation, and crystallization is performed, and the obtained N-acylamino acid (2) is used in various applications.

<Method for producing amino acid represented by formula (3)>
N-acylamino acid (2) is used, for example, for the production of an amino acid represented by the following formula (3) (hereinafter referred to as “amino acid (3)”).

（式中、Ｒ²は前記と同じである）。

(Wherein R ² is as defined above).

This amino acid (3) can be obtained by ammolysis (ammonolysis) or hydrolysis of the N-acylamino acid (2). That is, in the method for producing amino acid (3) according to the present invention, N-acylamino acid (2) obtained by the above production method is brought into contact with at least one kind of ammonia and water.
The contact temperature between the N-acylamino acid (2) and at least one selected from the group consisting of ammonia and water is not particularly limited, and is preferably contacted at, for example, about 110 to 180 ° C. The contact time is not particularly limited, and for example, it is preferable to contact for about 0.5 to 24 hours. Moreover, you may use an organic solvent when making it contact.

  When N-acylamino acid (2) is contacted with ammonia (in the case of ammonolysis), an amide compound represented by the following formula (4) is obtained as a by-product in addition to amino acid (3).

（式中、Ｒ¹は前記と同じである）。

(Wherein R ¹ is as defined above).

This amide compound represented by the formula (4) can be reused as a raw material of the amide compound represented by the above formula (1) or as an amide compound represented by the above formula (1) (R ² is a hydrogen atom). .

  On the other hand, when the N-acylamino acid (2) is contacted with water (in the case of hydrolysis), in addition to the amino acid (3), a carboxylic acid represented by the following formula (5) is obtained as a by-product.

（式中、Ｒ¹は前記と同じである）。

(Wherein R ¹ is as defined above).

  The carboxylic acid represented by the formula (5) can be reused as an amide compound represented by the above formula (1) by amidation. Hydrolysis may be performed in the presence of a base or acid other than ammonia.

For example, when N-acylamino acid (2) in which R ² is a hydrogen atom is used, methionine is obtained as amino acid (3).

  The mixture after the contact treatment may be further subjected to a post-treatment step. A post-processing process is not specifically limited, It can select suitably. Purification processing such as filtration, washing, distillation, and crystallization is performed as necessary, and the obtained amino acid (3) is used for various applications.

  EXAMPLES Hereinafter, although an Example and a comparative example are given and this invention is demonstrated concretely, this invention is not limited to these Examples.

(Preparation Example 1: Preparation of 5.0 atomic% Au / Co ₃ O ₄ )
HAuCl ₄ .4H ₂ O (0.412 g, 1.00 mmol) and Co (NO ₃ ) ₂ .6H ₂ O (5.50 g, 18.9 mmol) were dissolved in 200 mL of distilled water. Then, the obtained solution was added at once to a solution of Na ₂ CO ₃ (2.6 g, 24.5 mmol) dissolved in 200 mL of distilled water and stirred for 3 hours.
When the stirring was stopped, a solid was precipitated, so the supernatant of the solution was discarded. After adding 100 mL of distilled water to the precipitate and stirring for 5 minutes, the solid was separated from the supernatant using a centrifuge and the supernatant was discarded. This operation was repeated 4 times, dried at 100 ° C. for 12 hours and then calcined in air at 400 ° C. for 3 hours to obtain 5.0 atomic% Au / Co ₃ O ₄ (1.480 g). The obtained 5.0 atomic% Au / Co ₃ O ₄ was observed with a TEM, and a particle size distribution was created to obtain an average particle size. Au was 2.5 nm and Co ₃ O ₄ was 15 nm.

(Preparation Example 2: Preparation of 3.5 atomic% PdO / Co ₃ O ₄ )
Co (NO ₃ ) ₂ .6H ₂ O (5.50 g, 18.9 mmol) was dissolved in 200 mL of distilled water. The resulting solution was then added to a solution of Na ₂ CO ₃ (2.43 g, 22.9 mmol) dissolved in 200 mL of distilled water. The resulting precipitate was filtered and washed with 100 mL of distilled water three times. The obtained solid was dried at 100 ° C. for 12 hours and then calcined in air at 400 ° C. for 4 hours to obtain Co ₃ O ₄ (1.28 g).
Next, 1.0007 g of the obtained Co ₃ O ₄ was added to a solution of Pd (NO ₃ ) ₂ (104.3 mg, 0.452 mmol) dissolved in 1.1 mL of distilled water at room temperature and stirred for 10 minutes. Thereafter, the obtained solution was freeze-dried to remove water, and the obtained solid was calcined in air at 400 ° C. for 3 hours to give 3.5 atomic% PdO / Co ₃ O ₄ (1.0286 g). Obtained. The obtained 3.5 atomic% PdO / Co ₃ O ₄ was observed with a TEM, and a particle size distribution was created to obtain an average particle size. Pd was 2 nm and Co ₃ O ₄ was 15 nm.

(Preparation Example 3: Preparation of 1% by mass PdO / 20% by mass Co ₃ O ₄ / SiO ₂ )
Co (NO ₃ ) ₂ .6H ₂ O (461.1 mg, 1.58 mmol) and Pd (NO ₃ ) ₂ (12.7 mg, 0.055 mmol) were dissolved in 1.0 mL of distilled water. To this solution, 500 mg of silica gel (Q-10, particle size 75 to 150 μm: manufactured by Fuji Silysia Chemical Ltd.) was added and suspended. Thereafter, the obtained suspension was subjected to freeze-drying to remove water, and the obtained solid was calcined in air at 400 ° C. for 4 hours to give 1% by mass PdO / 20% by mass Co ₃ O ₄ / SiO _2. (628 mg) was obtained.

(Preparation Example 4: Preparation of 1% by mass PdO / 20% by mass Co ₃ O ₄ / Al ₂ O ₃ )
Co (NO ₃ ) ₂ .6H ₂ O (460.5 mg, 1.58 mmol) and Pd (NO ₃ ) ₂ (12.8 mg, 0.055 mmol) were dissolved in 1.0 mL of distilled water. To this solution, 500 mg of alumina (γ-Al ₂ O ₃ , AKP-G015: manufactured by Sumitomo Chemical Co., Ltd.) was added and suspended. Thereafter, the obtained suspension was freeze-dried to remove water, and the obtained solid was calcined in air at 400 ° C. for 4 hours to give 1% by mass PdO / 20% by mass Co ₃ O ₄ / Al _2. O ₃ (547 mg) was obtained.

Example 1
A stainless steel reactor equipped with a thermocouple, stirrer, gas supply line and liquid supply line is charged with 5.0 atomic% Au / Co ₃ O ₄ (10 mg) obtained in Preparation Example 1 and 10 mL of ethyl acetate. And stirred. While stirring, the temperature in the reactor was raised to 98 to 102 ° C. Note that hydrogen was introduced into the gas phase in the reactor, and the pressure in the reactor was set to 2 MPa (gauge pressure).
Next, the mixture was kept at 98 to 102 ° C. for 3 hours with stirring, and then cooled to about 5 to 35 ° C. After cooling, 200 mg (2 mmol) of 3- (methylthio) -propionaldehyde and 177 mg (3 mmol) of acetamide were placed in the reactor and stirred. A gas mixture of carbon monoxide and hydrogen (carbon monoxide / hydrogen = 3/1 (molar ratio)) was introduced into the gas phase portion in the reactor so that the pressure in the reactor was 4 MPa (gauge pressure). .
Furthermore, stirring was performed, and the temperature in the reactor was raised to 78 to 82 ° C., kept at this temperature for 20 hours, and then cooled to 5 to 35 ° C. After cooling, the reaction mixture was analyzed by capillary electrophoresis. As a result, the conversion of 3- (methylthio) -propionaldehyde was 89%, and N-acetylmethionine relative to the theoretical yield based on 3- (methylthio) -propionaldehyde. The yield of was 68%.

(Example 2)
Instead of 5.0 atomic% Au / Co ₃ O ₄ (10 mg), 1 mass% PdO / 20 mass% Co ₃ O ₄ / SiO ₂ (32.5 mg) obtained in Preparation Example 3 was used. The reaction was carried out in the same procedure as in Example 1. When the reaction solution was analyzed by capillary electrophoresis, the conversion of 3- (methylthio) -propionaldehyde was 81%, and the yield of N-acetylmethionine relative to the theoretical yield based on 3- (methylthio) -propionaldehyde. Was 71%.

(Example 3)
The same as Example 1 except that 3.5 atomic% PdO / Co ₃ O ₄ (10 mg) obtained in Preparation Example 2 was used instead of 5.0 atomic% Au / Co ₃ O ₄ (10 mg). The reaction was performed according to the procedure. When the reaction solution was analyzed by capillary electrophoresis, the conversion of 3- (methylthio) -propionaldehyde was 89%, and N-acetylmethionine was 60% of the theoretical yield based on 3- (methylthio) -propionaldehyde. The yield was obtained.

Example 4
In a stainless steel reactor equipped with a thermocouple, stirrer, gas supply line and liquid supply line, 3.5 atomic% PdO / Co ₃ O ₄ (0.050 g) obtained in Preparation Example 2 and 50 mL of ethyl acetate were added. And stirred. While stirring, the temperature in the reactor was raised to 98 to 102 ° C. Note that hydrogen was introduced into the gas phase in the reactor, and the pressure in the reactor was set to 2 MPa (gauge pressure).
Next, the mixture was kept at 98 to 102 ° C. for 3 hours with stirring, and then cooled to about 5 to 35 ° C. After cooling, 1.05 g (10.0 mmol) of 3- (methylthio) -propionaldehyde and 0.90 g (15.0 mmol) of acetamide were placed in the reactor and stirred. A gas mixture of carbon monoxide and hydrogen (carbon monoxide / hydrogen = 3/1 (molar ratio)) was introduced into the gas phase portion in the reactor so that the pressure in the reactor was 13 MPa (gauge pressure). .
Furthermore, stirring was performed, and the temperature in the reactor was raised to 78 to 82 ° C., held at this temperature for 6 hours, and then cooled to 5 to 35 ° C. After cooling, the reaction solution was analyzed by liquid chromatography. The conversion of 3- (methylthio) -propionaldehyde was 93%, and N-acetylmethionine relative to the theoretical yield based on 3- (methylthio) -propionaldehyde. The yield of was 62%.

(Example 5)
Instead of 3.5 atomic% PdO / Co ₃ O ₄ (0.050 g), 1 mass% PdO / 20 mass% Co ₃ O ₄ / SiO ₂ (0.0325 g) obtained in Preparation Example 3 was used. The reaction was performed in the same procedure as in Example 4 except for the above. When the reaction solution was analyzed by liquid chromatography, the conversion of 3- (methylthio) -propionaldehyde was 81%, and the yield of N-acetylmethionine relative to the theoretical yield based on 3- (methylthio) -propionaldehyde. Was 41%.

(Example 6)
Instead of 3.5 atomic% PdO / Co ₃ O ₄ (0.050 g), 1% by mass PdO / 20% by mass Co ₃ O ₄ / Al ₂ O ₃ (0.0325 g) obtained in Preparation Example 4 was used. The reaction was performed in the same procedure as in Example 1 except that it was used. When the reaction solution was analyzed by liquid chromatography, the conversion of 3- (methylthio) -propionaldehyde was 86%, and the yield of N-acetylmethionine relative to the theoretical yield based on 3- (methylthio) -propionaldehyde. Was 66%.

(Comparative Example 1)
A stainless steel reactor equipped with a thermocouple, stirrer, gas supply line and liquid supply line was charged with 5.26 g (0.050 mol) 3- (methylthio) propionaldehyde and 3.01 g (0.050 mol) acetamide. , Palladium (II) bromide and triphenylphosphine complex 0.10 g (0.0001 mol), lithium bromide 1.54 g (0.0175 mol), sulfuric acid 0.05 g (0.00051 mol), and N -51.50 g of methylpyrrolidinone was added and stirred. While stirring, the temperature in the reactor was raised to 118 to 122 ° C. Carbon monoxide was introduced into the gas phase portion in the reactor, and the pressure in the reactor was 6 MPa (gauge pressure).
Next, the mixture was held at 118 to 122 ° C. for 12 hours with stirring, and then cooled to about 5 to 35 ° C. to obtain 59.70 g of an N-methylpyrrolidinone solution of acetylmethionine. When this solution was analyzed by liquid chromatography, the yield of N-acetylmethionine relative to the theoretical yield based on 3- (methylthio) -propionaldehyde was 9%.

  Thus, according to the method of the present invention, it is possible to obtain N-acylamino acid (2) useful as a raw material for animal feed additives, a raw material for producing medical pesticides, etc. in a higher yield than the conventional production method. it can.

Claims (4)

In a solvent, at least one catalyst selected from the group consisting of the following catalysts (A) and (B):
(A) A catalyst in which at least one selected from the group consisting of noble metals and noble metal oxides is supported on cobalt oxide (B) At least selected from the group consisting of cobalt oxides, noble metals and noble metal oxides on a carrier In the presence of one supported catalyst and hydrogen,
3- (methylthio) propionaldehyde and
Formula (1):

(Wherein R ¹ and R ² each independently represents a hydrogen atom, an optionally substituted hydrocarbon group or an optionally substituted heterocyclic group);
Carbon monoxide,
(2), characterized by reacting

(Wherein R ¹ and R ² are the same as defined above, respectively). The manufacturing method according to claim 1, wherein the cobalt oxide is Co ₃ O ₄ .   The production method according to claim 1 or 2, wherein at least one selected from the group consisting of the noble metal and the noble metal oxide is at least one selected from the group consisting of gold, palladium and palladium oxide. An N-acylamino acid represented by the formula (2) produced by the production method according to claim 1 and at least one selected from the group consisting of ammonia and water are brought into contact with each other. Formula (3):

(Wherein R ² is the same as defined above).