JP2001048849A - Production of aminoalcohol - Google Patents

Abstract

PROBLEM TO BE SOLVED: To obtain the subject aminoalcohol in high yield with industrial advantage by allowing a specific cyclic hamiacetal to react with a specific amine and hydrogen in the presence of a hydrogenation catalyst. SOLUTION: A cyclic hemiacetal of formula I [(n) is 0 or 1; R1 and R2 are each H, a (substituted) monovalent saturated hydrocarbon or the like; and R3-R5 are each H or a (substituted) monovalent aromatic hydrocarbon], for example, 2-hydroxytetrahydropyran or the like, a primary amine of formula: R6-NH2 [R6 is a (substituted) monovalent saturated hydrocarbon or the like], e.g. dimethylamine or the like and hydrogen are allowed react with each other in the presence of a hydrogenation catalyst to prepare a compound of the formula. In a preferred embodiment, the amount of the compound of formula I is 2.0-4.0 moles per mole of the primary amine. The amount of the hydrogenation catalyst is preferably 0.005-0.1 pt.wt. per 1 pt.wt. of the compound of formula I. The partial pressure of the hydrogen in the reaction system is 0.5-100 atm, the reaction temperature is preferably 40-140 deg.C and the reaction time is 0.5-20 hours.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

[0001] The present invention relates to a method for producing an amino alcohol. More specifically, the present invention provides a carbon skeleton in which at least two of the three organic groups, which are classified as tertiary amines and are bonded to a nitrogen atom, have a hydroxyl group consisting of four or five carbon atoms. To an amino alcohol having a chemical structure bonded to the nitrogen atom through

[0002]

2. Description of the Related Art For two or more of three organic groups, which are classified as tertiary amines and are bonded to a nitrogen atom, a chemical structure in which a hydroxyl group is bonded to the nitrogen atom via a carbon skeleton. N-alkyldiethanolamine, triethanolamine, and the like are currently industrially available as amino alcohols. These amino alcohols are synthesized by reacting an alkylamine or ammonia with ethylene oxide.

[0003]

In the above-mentioned known synthesis method, the number of carbon atoms in the ring of the starting ethylene oxide is 2 or less.
Therefore, the number of carbon atoms in the carbon skeleton between the hydroxyl group and the tertiary nitrogen atom in the obtained amino alcohol is necessarily limited to two. Thus, the present invention relates to a tertiary amine, wherein at least two of the three organic groups bonded to the nitrogen atom have a carbon skeleton of 3 between the hydroxyl group and the nitrogen atom. As described above, it is an object of the present invention to provide a method capable of industrially advantageously producing an amino alcohol having 4 or 5 in particular.

[0004]

According to the present invention, the above objects are attained by providing the following production method (A) or (B).

[Manufacturing method (A)] Formula (1)

[0006]

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(Wherein, n represents 0 or 1; R ¹ and R ² each independently represent a hydrogen atom, a monovalent saturated hydrocarbon group which may have a substituent or a substituent. Represents a good monovalent aromatic group or a divalent saturated hydrocarbon group in which R ¹ and R ² may be bonded to each other to have a substituent;
R ³ , R ⁴ and R ⁵ each represent a hydrogen atom, a monovalent saturated hydrocarbon group which may have a substituent or a monovalent aromatic group which may have a substituent. )

A cyclic hemiacetal represented by the formula (2):

[0009]

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(Wherein, R ⁶ represents an optionally substituted 1
Represents a monovalent saturated hydrocarbon group or a monovalent aromatic group which may have a substituent. )

Wherein a primary amine and hydrogen represented by the formula (1) are reacted in the presence of a hydrogenation catalyst.

[0012]

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(Wherein, n, R ¹ , R ² , R ³ , R ⁴ , R
⁵ and R ⁶ are as defined above. )

A method for producing an amino alcohol represented by the formula:

[Production method (B)] The cyclic hemiacetal represented by the above formula (1) is reacted with a primary amine represented by the above formula (2), and the resulting reaction mixture is subjected to a hydrogenation reaction. A method for producing an amino alcohol represented by the above formula (3).

[0016]

BEST MODE FOR CARRYING OUT THE INVENTION Hereinafter, the present invention will be described in detail.

The production methods (A) and (B) according to the present invention use the cyclic hemiacetal represented by the above formula (1) and the primary amine represented by the above formula (2) as main raw materials. They are common in that the target substance is an amino alcohol represented by the formula (3).

In the above formula (1) representing a cyclic hemiacetal which is one of the raw materials, R ¹ and R ² are each a hydrogen atom, a monovalent saturated hydrocarbon group which may have a substituent or or represents an aromatic group or a monovalent to have a substituent, or R ¹ and R ² represents a bond and 2 may have a substituent and divalent saturated hydrocarbon group to each other; R ^3, R ⁴ and R ⁵ each represent a hydrogen atom, a monovalent saturated hydrocarbon group which may have a substituent, or a monovalent aromatic group which may have a substituent.

Here, R ¹ , R ² , R ³ , R ⁴ and R
Examples of the monovalent saturated hydrocarbon group which may have a substituent which may be each represented by ⁵ include a substituent such as a methyl group, an ethyl group, a propyl group, an isopropyl group, a butyl group and an isobutyl group. An alkyl group having no substituent; a cycloalkyl group having no substituent such as a cyclopentyl group, a cyclohexyl group, a 2-methylcyclohexyl group, a cyclooctyl group; and at least a part of hydrogen atoms of the alkyl group or the cycloalkyl group exemplified above is an alkoxy group. Group, a formyl group protected in an acetal type, an alkyl group having a substituent, a cycloalkyl group having a substituent, and the like having a chemical structure substituted with a hydroxyl group. Examples of the monovalent aromatic group which may have a substituent represented by R ¹ , R ² , R ³ , R ⁴ and R ⁵ include, for example, a phenyl group, a tolyl group, and a naphthyl An aryl group having no substituent such as a group; an aromatic heterocyclic group having no substituent such as a pyridyl group; an aralkyl group having no substituent such as a benzyl group; Aryl group having a substituent, aryl group having a substituent, aromatic hetero ring having a substituent having a chemical structure in which at least a part of hydrogen atoms of an aralkyl group is substituted with an alkoxy group, a formyl group protected in an acetal form, a hydroxyl group, or the like. And an aralkyl group having a group or a substituent.

In the above formula (1), examples of the divalent saturated hydrocarbon group which may have a substituent which may be represented by R ¹ and R ² bonded to each other include, for example, ethylene group , Tetramethylene group, pentamethylene group or other unsubstituted alkylene group; a chemistry in which at least a part of the hydrogen atoms of the alkylene group are substituted with an alkoxy group, an acetal-protected formyl group, a hydroxyl group, or the like. Examples include a substituted alkylene group having a structure. In the divalent saturated hydrocarbon group which may have a substituent, the number of carbon atoms in the main chain (excluding carbon atoms in side chains) between two bonds is in the range of 2 to 11. It is preferred that

In the above formula (1) representing a cyclic hemiacetal, n represents 0 or 1. When n represents 0, the cyclic hemiacetal represented by the formula (1) has a 5-membered ring (that is, tetrahydrofuran ring) structure, and n is 1
In the formula, the cyclic hemiacetal has a structure of a 6-membered ring (that is, a tetrahydropyran ring). Specific examples of the cyclic hemiacetal represented by the above formula (1) include 2-hydroxytetrahydropyran, 2-hydroxy-3-methyltetrahydropyran, and 2-hydroxy-
4-methyltetrahydropyran, 2-hydroxy-5
Methyltetrahydropyran, 2-hydroxy-6-methyltetrahydropyran, 2-hydroxy-6-isobutyl-4-methyltetrahydropyran, 2-hydroxy-
Pyran compounds such as 1-oxaspiro [5.5] undecane; and 2-hydroxytetrahydrofuran;
-Hydroxy-3-methyltetrahydrofuran, 2-hydroxy-4-methyltetrahydrofuran, 2-hydroxy-5-methyltetrahydrofuran, 3-ethyl-2
-Hydroxytetrahydrofuran, 5,5-dimethyl-
2-hydroxytetrahydrofuran, 3,4-dimethyl-2-hydroxytetrahydrofuran, 3,5-dimethyl-2-hydroxytetrahydrofuran, 2-hydroxy-5-methyl-5- (4-methylpentyl) tetrahydrofuran, 2-hydroxy-3 Furan-based compounds such as-(hydroxymethyl) tetrahydrofuran, 5-cyclohexyl-2-hydroxytetrahydrofuran, 1-oxa-2-hydroxyspiro [4.5] decane and the like can be mentioned.

The above-mentioned cyclic hemiacetal can be synthesized by a known method. Among them, equation (4)

[0023]

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(Wherein, n, R ¹ , R ² , R ³ , R ⁴ and R ⁵ are as defined above, and the configuration relating to the carbon-carbon double bond is E configuration or Z configuration.)

The method for synthesizing a cyclic hemiacetal, which comprises subjecting an alkenol compound to a hydroformylation reaction, is preferable because it can be produced at low cost on an industrial scale. Specific examples of the alkenol-based compound corresponding to the case where n is 1 in the formula (4) are as follows: 1-butene-4
-Ol, 3-penten-1-ol, 2-methyl-1
-Buten-4-ol, 3-methyl-1-butene-4-
All, 1-penten-4-ol, 4-methyl-1-
Penten-4-ol, 2,6-dimethyl-1-hepten-4-ol, 4-cyclohexyl-1-butene-4
1-buten-4-ol-based compounds such as -ol and 1- (2-propenyl) -1-cyclohexanol. Specific examples of the alkenol-based compound corresponding to the case where n is 0 in the formula (4) include 1-propen-3-ol, 2-methyl-1-propen-3-ol, and 1-butene-3. -Ol, 3-methyl-1-buten-3-ol, 2-buten-1-ol, 2-butene-
1,4-diol, 2-methyl-2-buten-1-ol, 3,7-dimethyl-1-octen-3-ol,
-1-propen-3 such as cyclohexyl-1-propen-3-ol, 1-vinyl-1-cyclohexanol
-All-based compounds.

In the hydroformylation reaction of the alkenol compound represented by the above formula (4), various reaction methods according to known methods can be used.
A method comprising reacting the alkenol compound with carbon monoxide and hydrogen in the presence of a rhodium compound and a tertiary organic phosphorus compound can be employed. As a known reaction method, for example, JP-A-60-204779, JP-A-62-201881 and the like describe a method for hydroformylation of 2-methyl-1-buten-4-ol, JP-A-51-29412, JP-A-3-261775, JP-A-6-87782, JP-A-6-166553 and the like describe a method for hydroformylation of allyl alcohol. In addition,
When the cyclic hemiacetal obtained by the hydroformylation reaction of the alkenol compound is used as a raw material in the present invention, the cyclic hemiacetal includes:
Distillation of the reaction mixture obtained by the hydroformylation reaction, purification of cyclic hemiacetal obtained by subjecting to separation and purification operations such as recrystallization can be used, but cyclic hemiacetal, rhodium compound, A hydroformylation reaction mixture containing a tertiary organophosphorus compound, a reaction by-product and the like may be used as it is, or a crude cyclic mixture obtained by subjecting the reaction mixture to a simple separation operation. Hemiacetal may be used.

In the above formula (2), which represents a primary amine which is one of the raw materials, R ⁶ is an optionally substituted substituent.
Represents a monovalent saturated hydrocarbon group or a monovalent aromatic group which may have a substituent.

Here, the monovalent saturated hydrocarbon group which may have a substituent which may be represented by R ⁶ includes, for example, methyl group, ethyl group, propyl group, butyl group, isobutyl group, Unsubstituted alkyl groups such as t-butyl group, octyl group and 2-ethylhexyl group; unsubstituted cycloalkyl groups such as cyclohexyl group, 2-methylcyclohexyl group and cyclooctyl group; alkyl groups exemplified above Alternatively, at least a part of the hydrogen atoms of the cycloalkyl group is an alkoxy group (eg, methoxy group, ethoxy group, etc.), a formyl group protected with an acetal type, a hydroxyl group, a disubstituted amino group (eg, dimethylamino group, diethylamino group, An alkyl group having a substituent having a chemical structure in a form substituted with a morpholino group or the like (eg, a 2-hydroxyethyl group, 2-hydroxypropyl group) or a cycloalkyl group having a substituent. Examples of the optionally substituted monovalent aromatic group represented by R ⁶ include an unsubstituted aryl group such as a phenyl group, a tolyl group, a mesityl group, and a naphthyl group. An aromatic heterocyclic group such as an unsubstituted aralkyl group or a pyridyl group such as a benzyl group or a phenethyl group; and at least a part of the hydrogen atoms of the above-mentioned aryl group, aralkyl group or aromatic heterocyclic group is an alkoxy group. , An aryl group having a substituent, an aralkyl group having a substituent or an aromatic heterocycle having a substituent having a chemical structure of a formyl group, a hydroxyl group, a disubstituted amino group or the like protected in an acetal type And the like. The aromatic group has 6 to 14 carbon atoms.
Is preferably within the range.

Specific examples of the primary amine represented by the above formula (2) include methylamine, ethylamine, isopropylamine, propylamine, isobutylamine, butylamine, t-butylamine, octylamine, (2-ethylhexyl) amine, Cyclohexylamine, N-
(3-aminopropyl) morpholine, aniline, o-toluidine, m-toluidine, p-toluidine, p-phenetidine, mesitidine, 4-amino-3-methyl-N,
N, -diethylaniline, 2-aminopyridine, 3-aminopyridine, 4-aminopyridine, α-naphthylamine, benzylamine, phenethylamine, ethanolamine, N, N-dimethylethylenediamine, 3- (dimethylamino) propylamine, 3 -Methoxypropylamine and the like.

The primary amine used in the reaction according to the production methods (A) and (B) may be in the form of a salt. Examples of usable salts include salts formed from primary amines and protic acids such as hydrochloric acid, sulfuric acid, nitric acid, acetic acid, and propionic acid. Representative examples of the salt include methylammonium chloride, di (methylammonium sulfate), nitric acid (methylammonium), methylammonium acetate, methylammonium propionate, and the like.

Next, the above-mentioned production method (A) of the production method of the present invention will be described.

In the production method (A), the use ratio of the cyclic hemiacetal represented by the formula (1) and the primary amine represented by the formula (2) (or a salt thereof) is not necessarily limited, but the stoichiometry Typically, 2 moles per mole of primary amine
Since moles of the cyclic hemiacetal are reacted, it is preferable to use the cyclic hemiacetal in a range of 1.8 to 10 moles per mole of the primary amine, and 2.0 to 4.0 moles.
More preferably, it is used in a molar range.

When a primary amine (or a salt thereof) is charged into the reaction system in the reaction according to the production method (A), the form of the primary amine is not necessarily limited, and the primary amine may be charged as it is. Alternatively, the mixture may be diluted with a solvent and charged. Specific examples of the solvent for primary amine dilution include water, methanol, ethanol, propanol, diethyl ether, tetrahydrofuran, dioxane, pentane, hexane, cyclohexane, benzene, toluene, xylene, and the like. Alternatively, two or more kinds can be used in combination. In addition, 1
When a salt of a primary amine and a protonic acid is used as the primary amine, good results may be obtained when a basic compound is present in the reaction system. Specific examples of the basic compound include lithium hydroxide, sodium hydroxide, potassium hydroxide, lithium acetate, sodium acetate, potassium acetate,
Examples include triethylamine, tributylamine, trioctylamine, pyridine and the like. When the basic compound is used, the amount of the basic compound is usually 10 mol or less, preferably 2 mol or less, per 1 mol of the salt of the primary amine.

In the reaction according to the production method (A), the above-mentioned cyclic hemiacetal, the above-mentioned primary amine and hydrogen are reacted in the presence of a hydrogenation catalyst. As the hydrogenation catalyst, a catalyst generally used in a catalytic hydrogenation reaction can be used, and examples thereof include a catalyst containing a metal such as palladium, rhodium, nickel, and platinum as an active component. These hydrogenation catalysts may be in the form of a metal itself as an active component; a metal oxide thereof; an alloy of the metal and another metal; a metal (an oxide or an alloy) as an active component may be activated carbon, alumina, silica gel,
Any of a catalyst with a carrier supported on a carrier such as diatomaceous earth may be used. The amount of hydrogenation catalyst used is
Although not necessarily limited, it is usually 0.000 to 1 part by weight of the cyclic hemiacetal represented by the formula (1).
Within the range of 1 to 0.2 part by weight, from the viewpoint of the reaction rate and the production cost of the target amino alcohol, 0.005 to 0 part by weight per part by weight of the cyclic hemiacetal represented by the formula (1). It is preferably in the range of 1 part by weight.

In the reaction according to the production method (A), the use of a solvent is not always necessary, but a solvent may be used as long as the reaction is not adversely affected. Examples of usable solvents include water; alcohol solvents such as methanol, ethanol and propanol; ether solvents such as diethyl ether, tetrahydrofuran and dioxane; hydrocarbon solvents such as pentane, hexane, cyclohexane, benzene, toluene and xylene. Solvents and the like can be mentioned, and one kind can be used alone or two or more kinds can be used in combination. When a solvent is used, the amount used is usually in the range of 0.1 to 10 parts by weight based on 1 part by weight of the cyclic hemiacetal represented by the formula (1).

In the reaction according to the production method (A), hydrogen is brought into contact with a mixture containing the cyclic hemiacetal, the primary amine and a hydrogenation catalyst. As a form of the contact, for example, a form comprising the presence of hydrogen gas in the atmosphere of the reaction system in which the mixture was present,
Examples include a mode in which hydrogen gas is introduced (bubbled) into the mixture. Although the partial pressure of hydrogen in the reaction system is not necessarily limited, it is usually 0.1.
It is in the range of 5 to 100 atmospheres (absolute pressure). In addition, a gas (for example, nitrogen, argon, etc.) other than hydrogen may be contained in the gas phase part of the reaction system as long as it does not adversely affect the predetermined reaction.

In the reaction according to the production method (A), the reaction temperature is not necessarily limited, but is usually 20 to
A temperature in the range of 180 ° C is employed, and from the viewpoint of high reaction rate and high selectivity to the target amino alcohol, it is preferable to employ a temperature in the range of 40 to 140 ° C. The time required for the reaction according to the production method (A) is not necessarily limited. For example, the conversion of the primary amine determined by a quantitative analysis means such as gas chromatography and / or the amino represented by the formula (3) The reaction time (residence time in the case of the continuous reaction operation) can be appropriately set based on the selectivity to alcohol. However, it is usually in the range of 0.5 to 20 hours.

As the operation of the reaction according to the production method (A), various methods can be adopted as desired.
The reaction can be performed without using a special apparatus (for example, a high-temperature and high-pressure oven). For example, using a general-purpose apparatus, cyclic hemiacetal, primary amine (may be a salt thereof) and hydrogenation The reaction can be carried out batchwise, semi-batchwise or continuously by mixing the catalyst by means such as stirring under a hydrogen gas atmosphere under a predetermined temperature and a predetermined hydrogen pressure. During the reaction, there is no particular restriction on the mixing order and mixing speed of each component,
All of the liquid or solid components (ie, the cyclic hemiacetal, the primary amine and the hydrogenation catalyst) to be subjected to the reaction may be mixed at once and the reaction may be started, or the cyclic hemiacetal and the primary amine may be mixed. One component and a hydrogenation catalyst may be charged into a reactor, and the remaining components may be reacted while being added into the reactor. In the latter case, various forms such as continuous addition and intermittent addition in a plurality of times can be adopted as a form in which some components are added during the reaction.

For a sufficient time until the middle of the reaction,
In the case of employing such a condition that the added amount of the cyclic hemiacetal is less than 2 mols per 1 mol of the primary amine, side reactions such as condensation between the cyclic hemiacetals can be suppressed, and The yield and selectivity of the amino alcohol represented by the formula (3) can be increased. In that respect, a semi-batch reaction operation consisting of performing a reaction while adding a cyclic hemiacetal to a mixture of a primary amine and a hydrogenation catalyst, a cyclic hemiacetal,
It is preferable to continuously supply the primary amine and the hydrogenation catalyst to the reaction system, and to conduct the reaction while continuously extracting a part of the reaction mixture from the reaction system.

After completion of the reaction according to the production method (A), the objective amino alcohol represented by the above formula (3) is
For example, high purity can be obtained by removing the hydrogenation catalyst from the obtained reaction mixture by filtration or centrifugation, and then subjecting the obtained mixture to separation / purification operations such as distillation, crystallization, and column chromatography. be able to.

Next, the manufacturing method (B) of the manufacturing method of the present invention will be described.

The production method (B) includes a step of reacting a cyclic hemiacetal represented by the above formula (1) with a primary amine represented by the above formula (2), and a reaction mixture obtained in the reaction step is hydrogenated. And a step of producing an amino alcohol represented by the above formula (3) by subjecting it to an addition reaction operation.

In the reaction between the cyclic hemiacetal and the primary amine according to the production method (B), the cyclic hemiacetal and the primary amine according to the production method (A) are excluded except that hydrogen and a hydrogenation catalyst are unnecessary. And the reaction in the presence of a hydrogenation catalyst for hydrogen. That is, both reactions involve cyclic hemiacetal and 1
Ratio of use with primary amine (or its salt), use form of primary amine (or its salt) (whether as it is or in solution form), optional when primary amine to be used is a salt Type and amount of basic compound that can be used for the reaction, type and amount of solvent that can be used arbitrarily (however, it is preferable not to use water), reaction temperature, reaction time (however, criteria for setting the reaction time) Is the conversion of the primary amine), the reaction equipment, the order of addition of the cyclic hemiacetal and the primary amine (which may be a salt thereof) (whether batch addition, continuous or intermittent addition), reaction mode ( Conditions such as batch type, semi-batch type or continuous type) overlap.

However, it is sometimes preferable that the reaction between the cyclic hemiacetal and the primary amine is carried out while removing generated water out of the reaction system, since the reaction is accelerated. As a method for removing generated water during the reaction, a method of distilling water out of the system, a method of physically or chemically absorbing water into a drying agent, and the like can be employed. When a method of distilling water out of the system is adopted, an organic solvent capable of forming an azeotropic mixture with water, such as benzene, toluene, pentane, cyclohexane, and petroleum ether, is allowed to exist in the reaction system, and the organic solvent and the organic solvent It is preferred to distill water in the form of a boiling mixture. When a method of absorbing water into a desiccant is employed, the desiccant may be a physical desiccant such as molecular sieves, calcium chloride, magnesium sulfate, or sodium sulfate; or a chemical desiccant such as calcium hydride or lithium aluminum hydride. A desiccant or the like can be used. When water is removed from the reaction system in the form of an azeotrope with an organic solvent, the obtained azeotrope is subjected to a process such as phase separation and contact with a drying agent, and then the collected organic solvent is removed. It can be supplied to the reaction system and reused.

The reaction mixture obtained by the reaction between the cyclic hemiacetal and the primary amine according to the production method (B) is a condensation reaction product of two molecules of the cyclic hemiacetal and one molecule of the primary amine. Equation (5)

[0046]

Embedded image

(Wherein, n, R ¹ , R ² , R ³ , R ⁴ , R
⁵ and R ⁶ are as defined above. )

It is presumed that the compound represented by the formula (1) exists. However, since the condensation reaction product has low stability, in the production method (B), the above-mentioned reaction mixture is directly used without isolating the condensation reaction product, or a concentration operation by evaporating and removing low-boiling substances. After performing simple processing operations such as the above, it is subjected to the next hydrogenation operation.

In the hydrogenation reaction operation for the reaction mixture obtained by the reaction between the cyclic hemiacetal and the primary amine, a hydrogenation reaction method which can be used in ordinary hydrogenation of enamine can be employed. A process which comprises contacting the mixture with hydrogen in the presence of a hydrogenation catalyst is industrially advantageous. Examples of usable hydrogenation catalysts include, for example, catalysts containing a metal such as palladium, rhodium, nickel, and platinum as an active component. These hydrogenation catalysts may be in the form of a metal itself as an active component; a metal oxide thereof; an alloy of the metal and another metal; a metal (an oxide or an alloy) as an active component may be activated carbon, alumina, Any of a catalyst with a carrier, which is supported on a carrier such as silica gel or diatomaceous earth, may be used. The amount of the hydrogenation catalyst to be used is not necessarily limited, but usually, the reaction mixture obtained by the reaction of the cyclic hemiacetal and the primary amine (even the mixture obtained by performing a simple post-treatment after the reaction) Good) in the range of 0.01 to 20% based on the weight of the material subjected to the hydrogenation reaction operation, and from the viewpoint of the reaction rate and the production cost of the target amino alcohol, 0.5 to 0.5%. Preferably, the weight is in the range of 10%.

In the hydrogenation reaction according to the production method (B), the use of a solvent is not always necessary, but a solvent may be used as long as it does not adversely affect the predetermined reaction. Examples of usable solvents include water; alcohol solvents such as methanol, ethanol, and propanol;
Ether solvents such as diethyl ether, tetrahydrofuran and dioxane; hydrocarbon solvents such as pentane, hexane, cyclohexane, benzene, toluene and xylene; and the like. One kind may be used alone, or two or more kinds may be used in combination. Can be. When a solvent is used, the amount used is usually the amount of hydrogenation in the reaction mixture obtained by the reaction between the cyclic hemiacetal and the primary amine (or a mixture obtained by performing a simple post-treatment after the reaction). It is not more than 10 times the weight of the material subjected to the reaction operation.

In the hydrogenation reaction according to the production method (B), a reaction mixture obtained by a reaction between a cyclic hemiacetal and a primary amine (may be a mixture obtained by performing a simple treatment after the reaction) and hydrogenation A mixture containing a catalyst (hereinafter, this mixture is referred to as a “hydrogenation mixture”) is brought into contact with hydrogen. As a form of the contact, for example, a form comprising the presence of hydrogen gas in the atmosphere of the reaction system in which the mixture for hydrogenation was present,
Hydrogen gas is introduced into the hydrogenation mixture (bubbling)
And the like. Although the partial pressure of hydrogen in the reaction system is not necessarily limited,
Usually, it is in the range of 0.5 to 100 atm (absolute pressure).
As long as the reaction is not adversely affected,
A gas other than hydrogen (eg, nitrogen, argon, etc.) may be contained in the gas phase of the reaction system.

In the hydrogenation reaction according to the production method (B), the reaction temperature is not necessarily limited, but usually a temperature in the range of 20 to 180 ° C. is employed, so that the reaction rate is high and the above-mentioned target is used. From the viewpoint of high selectivity to the amino alcohol represented by the formula (3), 40 to 14
It is preferred to employ a temperature in the range of 0 ° C.

The time required for the hydrogenation reaction according to the production method (B) is not necessarily limited. For example, the time required for the amino alcohol represented by the above formula (3) determined by quantitative analysis means such as gas chromatography can be used. The reaction time (residence time in the case of a continuous reaction operation) can be appropriately set based on the selectivity. However, usually, 0.5 to
Within 20 hours.

As the operation of the hydrogenation reaction according to the production method (B), various methods can be adopted as desired. The reaction can be carried out without using a special apparatus (for example, a high-temperature and high-pressure oven). For example, a reaction mixture obtained by reacting a cyclic hemiacetal with a primary amine using a general-purpose apparatus is used. And the hydrogenation catalyst are mixed under a hydrogen gas atmosphere under a predetermined temperature and a predetermined hydrogen pressure by means such as stirring, so that the reaction can be carried out batchwise, semi-batchwise or continuously. it can.

In the production method (B), after completion of the hydrogenation reaction, for example, the hydrogenation catalyst is removed from the obtained reaction mixture by filtration or centrifugation, and then the obtained mixture is subjected to distillation, crystallization, By subjecting to a separation / purification operation such as column chromatography, the objective amino alcohol represented by the above formula (3) can be obtained with high purity.

The amino alcohol represented by the above formula (3) obtained by the production method (production method (A) and production method (B)) of the present invention is classified as a tertiary amine, and is bonded to a nitrogen atom. An amino alcohol having a chemical structure in which two or more of the three organic groups have a hydroxyl group bonded to the nitrogen atom via a carbon skeleton composed of four or five carbon atoms. Due to its chemical structure, the amino alcohol is derived from a fiber auxiliary, an emulsifier, a plasticizer, a gas absorbent, a rust inhibitor, a cosmetic raw material, a synthetic detergent, shoe polish, a polish, a wax, a surfactant, and a cutting oil. , Lubricating oil additives, insect repellent additives, organic solvents, pH regulators, neutralizers, urethanization catalysts and the like. In addition, by acrylate or methacrylate of hydroxyl group, acrylic resin, thermoplastic elastomer, resin modifier, adhesive, ion exchange resin, fiber treatment agent, ultraviolet curing ink, paint, adhesive, electron beam It is useful as a raw material for curable inks, paints and adhesives, and radiation-curable inks, paints and adhesives.

[0057]

The present invention will be described below in more detail with reference to examples, but the present invention is not limited by these examples.

Example 1 [Reaction of 2-hydroxy-4-methyltetrahydropyran, methylamine and hydrogen] In a 300 ml-volume electromagnetically stirred autoclave equipped with a gas inlet and a sampling port, 40% by weight was used.
41 grams of methylamine aqueous solution (methylamine content:
530 mmol) and 1.80 g of 5% palladium carbon (hydrogenation catalyst), and the inside atmosphere was replaced with hydrogen gas. When the temperature reached 80 ° C., the pressure became about 3.8 atm (gauge pressure). The pressure in the autoclave was adjusted to 5 atm (gauge pressure) by introducing hydrogen gas. 2 in the autoclave
139 grams (1160 mmol) of -hydroxy-4-methyltetrahydropyran were fed over 4 hours. After the end of the supply of 2-hydroxy-4-methyltetrahydropyran,
The reaction was pursued by continuing the reaction for an additional 6 hours. During these reaction periods, hydrogen gas was constantly supplied so that the pressure in the autoclave was maintained at 5 atm (gauge pressure), thereby replenishing the hydrogen consumed during the reaction. During these periods, the reaction temperature was maintained at 80 ° C. After completion of the reaction, the autoclave was cooled, the internal liquid was drawn out, and palladium carbon was removed by filtration to obtain a filtrate. When this filtrate was analyzed by gas chromatography, the peak of methylamine as a raw material was not confirmed, and N, N-bis (5-hydroxy-3
106.0 grams (493 mmol) of methylamine (methylpentyl) (conversion based on methylamine used: 100)
%; Selectivity: 93%; yield: 93%). In addition, the analysis conditions in gas chromatography are as follows.

Column: G-100 (trade name: manufactured by The Chemicals Inspection Association) Column temperature: After maintaining at 100 ° C. for 4 minutes, the temperature was raised to 280 ° C. at a rate of 16 ° C./min. Detector: FID

The filtrate obtained above was purified by distillation to obtain 92.0 g of N, N-bis (5-hydroxy-3-methylpentyl) methylamine (boiling point: 165 ° C.).
(4.5 mmHg)). In addition, the obtained N, N-bis (5
The ¹ H-NMR (60 MHz) data of (-hydroxy-3-methylpentyl) methylamine is as follows.

Δ (ppm): 0.92 (d; 6H, J = 6 Hz), 0.73
-2.04 (m; 10H), 2.16 (s; 3H), 2.35 (t; 4H, J = 7H
z), 3.63 (t; 4H, J = 6Hz), 3.98 (s; 2H)

Example 2: [Reaction of 2-hydroxy-4-methyltetrahydropyran, butylamine and hydrogen] In a 300 ml-volume electromagnetically stirred autoclave equipped with a gas inlet and a sampling port, 40 g of butylamine (548 g) was added. Mmol) and 1.80 g of 5% palladium carbon (hydrogenation catalyst), and the inside atmosphere was replaced with hydrogen gas. When the temperature reached 80 ° C., the pressure inside the autoclave was adjusted to 5 atm (gauge pressure) by introducing hydrogen gas. 140 grams (1170 mmol) of 2-hydroxy-4-methyltetrahydropyran were fed into the autoclave over 4 hours. After the end of the 2-hydroxy-4-methyltetrahydropyran feed, a further 2 hours at 80 ° C. and then 100
The reaction was pursued by continuing the reaction at <RTIgt; During these reaction periods, hydrogen gas was constantly supplied so that the pressure in the autoclave was maintained at 5 atm (gauge pressure), thereby replenishing the hydrogen consumed during the reaction. After the reaction, cool the autoclave,
The filtrate was obtained by extracting the internal solution and removing the palladium carbon by filtration. When the filtrate was analyzed by gas chromatography, the peak of butylamine as a raw material was not confirmed, and 139 g of N, N-bis (5-hydroxy-3-methylpentyl) butylamine was detected (5%).
(09 mmol) (conversion based on butylamine used):
100%; selectivity: 93%; yield: 93%). When the obtained filtrate was purified by distillation, N,
130 g of N-bis (5-hydroxy-3-methylpentyl) butylamine were obtained (boiling point: 175 ° C. (1.0 mm
Hg)). Further, ¹ the resulting N, N-bis (5-hydroxy-3-methylpentyl) butylamine H-
NMR (60 MHz) data is as follows.

Δ (ppm): 0.67-2.72 (m; 23H), 2.0
7-2.74 (m; 6H), 3.37-3.90 (m; 4H), 4.14 (s; 2H)

Example 3 [Reaction of 2-hydroxy-4-methyltetrahydrofuran, methylamine and hydrogen] In a 300 ml electromagnetic stirring type autoclave equipped with a gas inlet and a sampling port, 40% by weight was prepared.
41 grams of methylamine aqueous solution (methylamine content:
530 mmol) and 1.60 g of 5% palladium carbon (hydrogenation catalyst) were added, the inside atmosphere was replaced with hydrogen gas, and the temperature was raised to 80 ° C. When the temperature reached 80 ° C., the pressure inside the autoclave was adjusted to 5 atm (gauge pressure) by introducing hydrogen gas. In the autoclave,
119 grams (1160 mmol) of 2-hydroxy-4-methyltetrahydrofuran were fed over 4 hours. After the completion of the supply of 2-hydroxy-4-methyltetrahydrofuran, the reaction was continued by further continuing the reaction for 2 hours. During these reaction periods, hydrogen gas was constantly supplied so that the pressure in the autoclave was maintained at 5 atm (gauge pressure), thereby replenishing the hydrogen consumed during the reaction. During these periods, the reaction temperature was raised to 80 ° C.
Maintained. After completion of the reaction, the autoclave was cooled, the internal liquid was drawn out, and palladium carbon was removed by filtration to obtain a filtrate. When this filtrate was analyzed by gas chromatography, no peak of methylamine as a raw material was confirmed, and 104 g (514 mmol) of N, N-bis (4-hydroxy-3-methylbutyl) methylamine was used (the used methyl). Conversion based on amine: 100
%; Selectivity: 97%; yield: 97%). When the obtained filtrate was purified by distillation, N, N-
99.4 g of bis (4-hydroxy-3-methylbutyl) methylamine was obtained (boiling point: 137 ° C. (3.0 mmH
g)). ¹ H-NM in the obtained N, N-bis (4-hydroxy-3-methylbutyl) methylamine
The data of R (60 MHz) is as follows.

Δ (ppm): 0.91 (d; 6H, J = 6 Hz), 0.65
−2.02 (m; 6H), 2.23 (s; 3H), 2.42 (t; 4H, J = 6 Hz),
3.37 (d; 4H, J = 5Hz), 5.61 (s; 2H)

Example 4 (1) [Reaction of 2-hydroxy-4-methyltetrahydropyran with butylamine] A glass 3 having an internal volume of 300 ml and equipped with a stirrer.
After replacing the atmosphere inside the flask with nitrogen gas,
52.9 grams (440 mmol) of hydroxy-4-methyltetrahydropyran and molecular sieves 3
0 g was added and the temperature of the internal liquid was brought to 2 ° C. by cooling in an ice-water bath. 14.6 g (200 mmol) of butylamine was dropped into the internal liquid under stirring to supply the internal liquid over 5 minutes while maintaining the temperature of the internal liquid at 10 ° C. or lower. After completion of the dropwise addition, stirring was continued at 10 ° C. for another 30 minutes. After the stirring, the solution portion of the obtained reaction mixture was analyzed by gas chromatography, and no peak of butylamine as a raw material was confirmed (conversion: 100%). The reaction mixture was filtered to remove the molecular sieves, and the filtrate was filtered.
4.1 grams were obtained.

(2) [Hydrogenation reaction operation on the obtained reaction mixture] 20 g of the obtained filtrate was introduced with 80 ml of isopropyl alcohol and 2.0 g of 5% palladium carbon (hydrogenation catalyst) by gas introduction. The sample was placed in a 300 ml electromagnetic stirring type autoclave equipped with a mouth and a sampling port. After replacing the internal atmosphere with hydrogen gas, the temperature was raised to 80 ° C. while the pressure was maintained at about 8.0 atm (gauge pressure) by supplying hydrogen gas. The reaction was carried out for 2 hours while maintaining the temperature at 80 ° C. Further, the temperature was raised to 100 ° C. and the reaction was continued for 4 hours to drive the reaction. In addition,
During these reaction periods, the pressure in the autoclave was maintained at 8.0 atm (gauge pressure) by constantly supplying hydrogen gas. After completion of the reaction, the autoclave was cooled, the internal liquid was drawn out, and palladium carbon was removed by filtration to obtain a filtrate. The filtrate was analyzed by gas chromatography to find that 17.6 g (64 mmol) of N, N-bis (5-hydroxy-3-methylpentyl) butylamine was produced (based on the butylamine used). Yield: 87%).

[0068]

According to the production method of the present invention, two or more of the three organic groups, which are classified as tertiary amines and are bonded to a nitrogen atom, have four or five hydroxyl groups. An amino alcohol having a chemical structure bonded to the nitrogen atom via a carbon skeleton consisting of atoms can be produced in a high yield from a raw material that is easily available and handled. Reaction conditions and complicated post-treatment operations are unnecessary. Thus, according to the present invention,
There is provided a method by which the above-mentioned amino alcohol can be industrially advantageously produced.

Continued on front page F-term (reference) 4H006 AA01 AA02 AC52 BA21 BA24 BA25 BA26 BA30 BA55 BE20 BN10 BU32 4H039 CA71 CH10

Claims (3)

[Claims] (1) Formula (1) (Wherein n represents 0 or 1; R ¹ and R ² are each a hydrogen atom, a monovalent saturated hydrocarbon group which may have a substituent or a monovalent group which may have a substituent. R ¹ and R ² represent a divalent saturated hydrocarbon group which may have a substituent by bonding to each other; R ³ , R ⁴ and R ⁵ each represent hydrogen Atom, monovalent saturated hydrocarbon group which may have a substituent or 1 which may have a substituent
Represents a valent aromatic group. A) a cyclic hemiacetal represented by the formula (2): (Wherein, R ⁶ represents a monovalent saturated hydrocarbon group which may have a substituent or a monovalent aromatic group which may have a substituent.) Is reacted in the presence of a hydrogenation catalyst, characterized by the following formula (3): (Wherein, n, R ¹ , R ² , R ³ , R ⁴ , R ⁵ and R ⁶
Is as defined above. )). 2. Formula (1) (Wherein n represents 0 or 1; R ¹ and R ² are each a hydrogen atom, a monovalent saturated hydrocarbon group which may have a substituent or a monovalent group which may have a substituent. R ¹ and R ² represent a divalent saturated hydrocarbon group which may have a substituent by bonding to each other; R ³ , R ⁴ and R ⁵ each represent hydrogen Atom, monovalent saturated hydrocarbon group which may have a substituent or 1 which may have a substituent
Represents a valent aromatic group. ) Is converted to a cyclic hemiacetal of formula (2) (Wherein R ⁶ represents a monovalent saturated hydrocarbon group which may have a substituent or a monovalent aromatic group which may have a substituent). And subjecting the resulting reaction mixture to a hydrogenation reaction, characterized by the formula (3): (Wherein, n, R ¹ , R ² , R ³ , R ⁴ , R ⁵ and R ⁶
Is as defined above. )). (3) Formula (3) (Wherein n represents 0 or 1; R ¹ and R ² are each a hydrogen atom, a monovalent saturated hydrocarbon group which may have a substituent or a monovalent group which may have a substituent. R ¹ and R ² represent a divalent saturated hydrocarbon group which may have a substituent by bonding to each other; R ³ , R ⁴ and R ⁵ each represent hydrogen Atom, monovalent saturated hydrocarbon group which may have a substituent or 1 which may have a substituent
R ⁶ represents a monovalent aromatic group;
Represents a monovalent saturated hydrocarbon group or a monovalent aromatic group which may have a substituent. ).