JP2001097932A - Method for producing aminoalcohol - Google Patents

Abstract

PROBLEM TO BE SOLVED: To produce an aminoalcohol having hydroxy group connected through a main chain containing 4 or 5 carbon atoms to amino group and classified as a primary amine or a secondary amine from a readily available and easily handleable raw material in high yield. SOLUTION: A cyclic hemiacetal represented by formula (1) (n denotes 0 or 1) is reacted with a nitrogen-containing compound represented by formula (4): R-NH2 (R denotes a monovalent saturated hydrocarbon group which may have a substituent group or a monovalent aromatic group which may have a substituent group) and hydrogen in the presence of a hydrogenating catalyst to produce an aminoalcohol represented by formula (2) (n and R are each as defined above).

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

TECHNICAL FIELD The present invention relates to a method for producing an amino alcohol. More specifically, the present invention relates to a method for producing an amino alcohol in which the main chain of the alkylene group between the hydroxyl group and the amino group has 4 or 5 carbon atoms and is classified as a primary or secondary amine.

[0002]

2. Description of the Related Art Currently, among amino alcohols classified as primary amines, industrially produced compounds include 2-aminoethanol and 3-amino-1-propanol. The former 2-aminoethanol is
Manufactured by reacting ethylene oxide with ammonia (JP-A-11-90238), the latter 3-amino-1-propanol is obtained by reducing 3-hydroxypropiononitrile with a Raney nickel catalyst or the like. It is manufactured (Japanese Unexamined Patent Publication No.
No. 9963).

[0003] Among amino alcohols classified as secondary amines, industrially produced compounds include ethanolamines such as 2- (methylamino) ethanol. Such ethanolamines are produced by reacting an alkylamine with ethylene oxide.

[0004]

However, the number of carbon atoms in the main chain of the alkylene group between the hydroxyl group and the amino group of the amino alcohol classified as the above-mentioned primary amine or secondary amine depends on the amount used. The former is necessarily limited to 2 or 3, and the latter is limited to 2, due to restrictions on raw materials and reaction paths. Therefore, there is a problem that an amino alcohol having 4 or more (particularly 4 or 5) carbon atoms between a hydroxyl group and an amino group cannot be industrially produced by the above-mentioned production method.

Incidentally, it is classified as a primary amine or a secondary amine, and the number of carbon atoms in the main chain of the alkylene group between the hydroxyl group and the amino group is 4 or 5, and is synthesized in a laboratory. As an amino alcohol, 4-amino-2-
Methyl-1-butanol or 5- (methylamino) -1
-Pentanol has been reported. Specifically, the former is synthesized in a laboratory by reacting 2-methyl-4-aminobutyric acid with lithium aluminum hydride in tetrahydrofuran solvent for 6 hours under reflux condition (J. Amer. Chem. Soc. , 81,4946
(1959)). In the latter case, after mixing hydrochloric acid and dihydropyran, an aqueous methylamine solution is added to the mixture, and the resulting crude reaction solution is extracted and concentrated, and then reacted with sodium borohydride in an ethanol solvent. (21% isolated yield; dihydropyran-based) (J. Chem. Soc. Perkin Tr).
ans. I 1375 (1989)). Therefore, it is conceivable to apply these laboratory manufacturing techniques to industrial manufacturing.

[0006] However, these laboratory manufacturing techniques are:
Expensive reaction materials such as lithium aluminum hydride, dihydropyran, and sodium borohydride must be used, and the handling of the reaction materials is not easy, post-reaction operations after the reaction are complicated, and new reaction equipment is installed. It is necessary and it is hard to say that this is an industrially advantageous method.

The present invention relates to an industrial process for producing an amino alcohol having 4 or 5 carbon atoms in the main chain of an alkylene group between a hydroxyl group and an amino group and classified as a primary or secondary amine. It is an object of the present invention to provide a method which can be advantageously manufactured.

[0008]

SUMMARY OF THE INVENTION The present inventor has proposed that a specific cyclic hemiacetal is reacted with ammonia or a primary amine and hydrogen at the same time, or that a specific cyclic hemiacetal is reacted with ammonia or a primary amine. It has been found that the above object can be achieved by further reacting hydrogen after the reaction, and the present invention has been completed.

That is, the first aspect of the present invention provides an equation (1)

[0010]

Embedded image

A cyclic hemiacetal represented by the formula: wherein n represents 0 or 1;

[0012]

Embedded image R-NH ₂ (4) (wherein, R represents a hydrogen atom, 1 may have a substituent monovalent saturated hydrocarbon group or an optionally substituted monovalent aromatic group Is reacted in the presence of a hydrogenation catalyst to give a compound of formula (2)

[0013]

Embedded image

Wherein n and R are as defined above, and a process for producing an amino alcohol is provided.

The second aspect of the present invention relates to the following equation (1).

[0016]

Embedded image

A cyclic hemiacetal represented by the formula (4) is represented by the formula (4):

[0018]

Embedded image R-NH ₂ (4) (wherein, R represents a hydrogen atom, 1 may have a substituent monovalent saturated hydrocarbon group or an optionally substituted monovalent aromatic group ), And then reacted with a nitrogen-containing compound represented by
The compound is further reacted with hydrogen in the presence of a hydrogenation catalyst to obtain a compound of formula (2)

[0019]

Embedded image

Wherein n and R are as defined above, and a method for producing an amino alcohol is provided.

[0021]

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

The first aspect of the present invention is to simultaneously react the above-mentioned cyclic hemiacetal of the formula (1), the nitrogen-containing compound of the formula (4) and hydrogen in the presence of a hydrogenation catalyst.
This is a method for producing the amino alcohol of the formula (2) in one reaction step from the cyclic hemiacetal of the formula (1). Further, the second invention provides a method wherein the cyclic hemiacetal of the above formula (1) is first reacted with a nitrogen-containing compound of the formula (4), and then further reacted with hydrogen in the presence of a hydrogenation catalyst. And a method for producing an amino alcohol of the formula (2) in two reaction steps from a cyclic hemiacetal of the formula (1).

First, the raw materials used in the first and second inventions will be described.

The cyclic hemiacetal of the formula (1), which is one of the starting materials, is specifically 2-hydroxy-4-methyltetrahydropyran (when n = 1) or 2-hydroxy-4-methyltetrahydrofuran ( n = 0).

The cyclic hemiacetal used in the present invention is
It can be synthesized by a known method. Among them, equation (3)

[0026]

Embedded image

A method for synthesizing a cyclic hemiacetal by hydroformylation of an alkenol compound represented by the formula (where n represents 0 or 1) is preferable because it can be produced at low cost on an industrial scale. The alkenol-based compound corresponding to the case where n = 1 in the formula (3) is 2
-Methyl-1-buten-4-ol, wherein the alkenol compound corresponding to the case where n = 0 is 2-methyl-
1-propen-3-ol.

In the hydroformylation reaction of the alkenol compound represented by the above formula (3), various reaction methods according to known methods can be used.
A method comprising reacting an alkenol compound of the formula (3) with carbon monoxide and hydrogen in the presence of a rhodium compound and a tertiary organic phosphorus compound can be preferably applied. For example, JP-A-60-19781, JP-A-60-204778, JP-A-60-20777
No. 9, JP-A-62-201881, etc.
A method for hydroformylation of methyl-1-buten-4-ol is described, and JP-A-3-261776,
JP-A-9-52888 describes a method for hydroformylation of 2-methyl-1-propen-3-ol.

When the cyclic hemiacetal obtained by the hydroformylation reaction of the alkenol compound of the formula (3) is used as a raw material in the present invention, the reaction mixture obtained by the hydroformylation reaction is distilled.
A purified product of cyclic hemiacetal obtained by separation and purification operations such as recrystallization can be used, but contains cyclic hemiacetal, rhodium compound, tertiary organic phosphorus compound, reaction by-products, etc. The form of the hydroformylation reaction mixture may be used as it is, or a crude cyclic hemiacetal obtained by subjecting the reaction mixture to a simple separation operation may be used.

The nitrogen-containing compound of the formula (4), which is one of the raw materials, includes ammonia (when R is a hydrogen atom) and a primary amine (where R is a monovalent saturated group which may have a substituent). A hydrocarbon group or a monovalent aromatic group which may have a substituent).

When the nitrogen-containing compound of the formula (4) is ammonia, either liquid ammonia or aqueous ammonia can be used.

When the nitrogen-containing compound of the formula (4) is a primary amine, R in the formula (4) is, as described above,
Represents a monovalent saturated hydrocarbon group which may have a substituent, or a monovalent aromatic group which may have a substituent. Here, as the monovalent saturated hydrocarbon group which may have a substituent of R,
For example, methyl group, ethyl group, propyl group, butyl group,
Unsubstituted alkyl groups such as isobutyl group, t-butyl group, octyl group and 2-ethylhexyl group; cycloalkyl groups having no substituent groups such as cyclohexyl group, 2-methylcyclohexyl group and cyclooctyl group; At least some of the hydrogen atoms of the alkyl or cycloalkyl group are alkoxy groups (eg, methoxy group, ethoxy group, etc.), formyl groups protected with an acetal type, hydroxyl groups, disubstituted amino groups (eg, dimethylamino group, An alkyl group having a substituent having a chemical structure substituted with a diethylamino group, a morpholino group, or the like (eg, 2-
Hydroxyethyl group, 2-hydroxypropyl group, etc.)
Or a cycloalkyl group having a substituent. Examples of the monovalent aromatic group which may have a substituent for R include a phenyl group, a tolyl group, a mesityl group,
An unsubstituted aryl group such as a naphthyl group; an unsubstituted aralkyl group such as a benzyl group or a phenethyl group; an aromatic heterocyclic group such as a pyridyl group; an aryl group, an aralkyl group or an aromatic heterocyclic group exemplified above. Alkoxy group, at least a part of the hydrogen atom, a formyl group protected in acetal form, a hydroxyl group, having a chemical structure of a form substituted by a disubstituted amino group, etc., an aryl group having a substituent,
Examples include an aralkyl group having a substituent or an aromatic heterocyclic group having a substituent. The number of carbon atoms contained in the aromatic group is preferably in the range of 6 to 14.

Specific examples of the primary amine included in the nitrogen-containing compound of the formula (4) 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.

Incidentally, these primary amines may be in the form of a salt. Examples of usable salts include, for example,
And salts formed from a secondary amine and a protic acid 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 first invention will be described.

As described above, the first aspect of the present invention is to provide a cyclic hemiacetal of the formula (1), a nitrogen-containing compound of the formula (4) (ammonia or a primary amine), and hydrogen as a hydrogenation catalyst. By reacting simultaneously in the presence of the compound, the cyclic hemiacetal of the formula (1) can be reacted with the compound of the formula (2)
Is a method for producing an amino alcohol.

In the first invention, the ratio of the nitrogen-containing compound of the formula (4) to the cyclic hemiacetal of the formula (1) is not necessarily limited. However, since the cyclic hemiacetal of the formula (1) is an equivalent of the aldehyde, the cyclic hemiacetal reacts with the nitrogen-containing compound of the formula (4) without reacting with the nitrogen-containing compound of the formula (4). There is a possibility that hydrogen may be added or self-condensation may occur, and there is a concern that the economical efficiency during production may be reduced. Therefore, unintended hydrogenation reaction and self-condensation reaction are suppressed,
In consideration of the volumetric efficiency of the reactor, the amount of the nitrogen-containing compound of the formula (4) is preferably 0.9 to 50 mol, more preferably 1 to 20 mol, per 1 mol of the cyclic hemiacetal used. Range.

When ammonia is charged into the reaction system, the form of the ammonia is not necessarily limited, and the ammonia may be charged as it is, or may be diluted with a solvent and charged. As a specific example of the solvent for ammonia dilution,
Water, methanol, ethanol, propanol, diethyl ether, tetrahydrofuran, dioxane, pentane, hexane, cyclohexane, benzene, toluene,
Xylene and the like. These solvents may be used alone or
More than one kind can be mixed and used.

When a primary amine (or a salt thereof) is charged into the reaction system, the form of the primary amine is not necessarily limited, and the primary amine may be charged as it is, and the primary amine may be diluted with a solvent. You may be charged. Specific examples of the solvent for diluting the primary amine include water, methanol, ethanol, propanol, diethyl ether, tetrahydrofuran, dioxane, pentane, hexane, cyclohexane, benzene, toluene, xylene and the like. Or a mixture of two or more.

When a salt formed from 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 such a basic compound include:
Lithium hydroxide, sodium hydroxide, potassium hydroxide,
Lithium acetate, sodium acetate, potassium acetate, triethylamine, tributylamine, trioctylamine,
Pyridine and the like. When such a basic compound is used, its use amount is usually 10 mol or less, preferably 2 mol or less, per 1 mol of the primary amine salt.

As the hydrogenation catalyst used in the first invention, a catalyst generally used in a catalytic hydrogenation reaction can be used. For example, a metal such as palladium, rhodium, nickel and platinum can be used as an active component. Can be mentioned.

The form of these hydrogenation catalysts includes a metal as an active component itself; a metal oxide thereof; an alloy of the metal and another metal; and a metal (which may be an oxide or an alloy) as an active component. , Alumina, silica gel, diatomaceous earth and the like, and any other supported catalyst. The amount of the hydrogenation catalyst used is not necessarily limited, but is preferably in the range of 0.0001 to 0.2 parts by weight per 1 part by weight of the cyclic hemiacetal of the formula (1). From the viewpoint of the production cost of amino alcohol, the amount is more preferably in the range of 0.005 to 0.1 parts by weight.

The use of a solvent is not always necessary, but a solvent can be used as long as it does not adversely affect a predetermined reaction. Examples of usable solvents include water; alcohol solvents such as methanol, ethanol, propanol, 1-butanol and 1-octanol; ether solvents such as diethyl ether, tetrahydrofuran and dioxane; pentane, hexane, cyclohexane, benzene, Examples thereof include hydrocarbon solvents such as toluene and xylene. One type may be used alone, or two or more types may 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).

Hydrogen is replaced by a cyclic hemiacetal of formula (1)
Examples of the form in which the mixture is brought into contact with the mixture containing the nitrogen-containing compound of the formula (4) and the hydrogenation catalyst include, for example, a form in which hydrogen gas is present in the atmosphere of a reaction system in which the mixture is present; And the like (hydrogen gas is introduced (bubbled)). The partial pressure of hydrogen in the reaction system is not necessarily limited, but is usually in the range of 0.5 to 150 atm (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.

The reaction temperature is not necessarily limited, but a temperature in the range of 20 to 180 ° C. is employed, and from the viewpoint of high reaction rate and high selectivity to the target amino alcohol, the reaction temperature is 40 ° C. It is preferred to employ a temperature in the range of ~ 140 ° C.

The time required for the reaction is not necessarily limited. For example, the conversion of cyclic hemiacetal and / or the conversion determined by quantitative analysis means such as gas chromatography.
Alternatively, the reaction time (residence time in the case of a continuous reaction operation) can be appropriately set based on the selectivity to the formed amino alcohol, but is usually in the range of 0.5 to 20 hours.

For the operation of the reaction, 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 kettle).
Using a general-purpose device, the cyclic hemiacetal of the formula (1), the nitrogen-containing compound of the formula (4) and the hydrogenation catalyst are mixed under a hydrogen gas atmosphere at a predetermined pressure and at a predetermined temperature.
The reaction can be carried out batchwise, semi-batchwise or continuously by mixing by means such as stirring. In the reaction, there is no particular limitation on the mixing order and mixing speed of each component, and all liquid or solid components (ie, cyclic hemiacetal, nitrogen-containing compound and hydrogenation catalyst) to be subjected to the reaction are mixed at once. The reaction may be started,
Alternatively, one of the cyclic hemiacetal and the nitrogen-containing compound 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.

When a means is selected such that the nitrogen-containing compound of the formula (4) is present in the reaction system in such a proportion that the nitrogen-containing compound of the formula (4) is in a large excess with respect to the cyclic hemiacetal of the formula (1) during most of the reaction. In addition, side reactions such as condensation between the cyclic hemiacetals of the formula (1) can be suppressed, and the yield and selectivity of the target amino alcohol can be increased. In that respect, a semi-batch reaction operation comprising adding a cyclic hemiacetal to a mixture of a nitrogen-containing compound of the formula (4) and a hydrogenation catalyst while carrying out the reaction, a cyclic hemi-acetal of the formula (1) A continuous reaction in which the acetal, the nitrogen-containing compound of the formula (4) and the hydrogenation catalyst are continuously supplied to the reaction system, and the reaction is performed while continuously extracting a part of the reaction mixture from the reaction system. Operation is preferred.

After completion of the reaction, the target compound of the above formula (2)
The amino alcohol is, for example, by removing the hydrogenation catalyst from the obtained reaction mixture by filtration or centrifugation, and then subjecting the resulting mixture to a separation / purification operation such as distillation, crystallization, or column chromatography. , Can be obtained with high purity.

Next, a second manufacturing method of the present invention will be described.

As described above, according to the second production method of the present invention, the cyclic hemiacetal of the formula (1) is first reacted with the nitrogen-containing compound of the formula (4), and then reacted in the presence of a hydrogenation catalyst. This is a method of producing an amino alcohol of the formula (2) from the cyclic hemiacetal of the formula (1) in two reaction steps by further reacting with hydrogen. Here, when the cyclic hemiacetal of the formula (1) is reacted with the nitrogen-containing compound of the formula (4), at least the nitrogen-containing compound is a primary amine (R may have a substituent. (In the case of a monovalent saturated hydrocarbon group or a monovalent aromatic group optionally having a substituent))

[0052]

Embedded image

(Where n and R are as described above)
It seems that the amino ether represented by

In the reaction of the cyclic hemiacetal of the formula (1) with the nitrogen-containing compound of the formula (4) according to the second aspect of the present invention, except that hydrogen and a hydrogenation catalyst are not required,
In the presence of a hydrogenation catalyst in the production method of the present invention, in the same manner as in the reaction of the cyclic hemiacetal of the formula (1), the nitrogen-containing compound of the formula (4) and hydrogen. That is, the ratio of the cyclic hemiacetal of the formula (1) to the nitrogen-containing compound of the formula (4) in the second aspect of the present invention, the usage form of the nitrogen-containing compound of the formula (4) (whether as it is or in the form of a salt) In the form of a solution, etc.), the type and amount of a basic compound which can be optionally used when the nitrogen-containing compound of the formula (4) used is in the form of a salt of a primary amine, and which can be optionally used The type and amount of the solvent, the reaction temperature, the reaction time (however, the criteria for setting the reaction time are the conversion of the cyclic hemiacetal of the formula (1)), the reaction equipment, the cyclic hemiacetal and the nitrogen-containing compound. Conditions regarding the order of addition of compounds (point of batch addition, continuous or intermittent addition), reaction mode (point of batch system, semi-batch system or continuous system), etc. are the same as in the first invention. can do.

However, when the cyclic hemiacetal of the formula (1) is reacted with the nitrogen-containing compound of the formula (4), the reaction is carried out while removing generated water outside the reaction system, since the reaction is accelerated. May be preferred. As a method for removing generated water during the reaction, a method of distilling water out of the system,
A method in which water is physically or chemically absorbed by a desiccant 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.

In the second invention, after the reaction between the cyclic hemiacetal of the formula (1) and the nitrogen-containing compound of the formula (4) is completed, the obtained reaction mixture is distilled, crystallized, and subjected to column chromatography. In some cases, the reaction product can be isolated by subjecting it to a separation / purification operation such as the above.However, when the stability is low, the reaction mixture is treated as it is or after a simple treatment such as concentration. It is preferable to provide for the addition reaction.

As the hydrogenation reaction of the above reaction mixture in the second invention, a hydrogenation reaction method which can be used in ordinary hydrogenation of enamine can be employed, but the reaction mixture is reacted 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 starting material of the formula (1)
0.0001 to 1 part by weight of the cyclic hemiacetal
The amount is preferably in the range of 0.2 part by weight, and from the viewpoint of the reaction rate and the production cost of the target amino alcohol, the amount is preferably 0.1 part by weight.
More preferably, the amount is in the range of 005 to 0.1 parts by weight.

In the hydrogenation reaction according to the second aspect of the present invention, 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; methanol, ethanol, propanol, 1-butanol and 1-butanol.
Alcohol solvents such as octanol; ether solvents such as diethyl ether, tetrahydrofuran and dioxane; pentane, hexane, cyclohexane, benzene,
Examples thereof include hydrocarbon solvents such as toluene and xylene. One type may be used alone, or two or more types may be used in combination. When using a solvent, the amount used is usually
It is in the range of 0.1 to 10 parts by weight per 1 part by weight of the cyclic hemiacetal of the formula (1) of the starting material.

In the hydrogenation reaction according to the second aspect of the present invention, hydrogen is brought into contact with a reaction mixture containing a hydrogenation catalyst. The form of the contact may be, for example, in the atmosphere of a reaction system in which the mixture is present. In which hydrogen gas is present, and a mode in which hydrogen gas is introduced (bubbled) into the mixture. The partial pressure of hydrogen in the reaction system is not necessarily limited, but is usually in the range of 0.5 to 100 atm (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 second aspect of the present invention, the reaction temperature in the hydrogenation reaction is not necessarily limited, but usually a temperature in the range of 20 to 180 ° C. is employed, so that the reaction speed is high and the desired amino acid is used. From the viewpoint of high selectivity to alcohol, it is preferable to employ a temperature in the range of 40 to 140 ° C.

The time required for the reaction is not necessarily limited. For example, the reaction time (in the case of a continuous reaction operation) is determined based on the selectivity to the formed amino alcohol determined by quantitative analysis means such as gas chromatography. Can be appropriately set, but usually 0.5 to 2
Within 0 hours.

As the operation of the hydrogenation reaction in the second invention, various methods can be adopted as desired. The reaction can be carried out without using a special device (for example, a high-temperature and high-pressure kettle). For example, using a general-purpose device, the cyclic hemiacetal of the formula (1) and the nitrogen-containing compound of the formula (4) can be used. By mixing the reaction mixture with the compound and the hydrogenation catalyst under a hydrogen gas atmosphere and under the conditions of a predetermined temperature and a predetermined hydrogen pressure by means such as stirring, a batch system, a semi-batch system or a continuous system is used. The reaction can be performed.

For the hydrogenation reaction in the second aspect of the present invention, a reaction mixture of the cyclic hemiacetal of the formula (1) and the nitrogen-containing compound of the formula (4) is used, and When unreacted cyclic hemiacetal and nitrogen-containing compound remain, these unreacted raw materials may be converted to the amino alcohol of the formula (2) in the hydrogenation reaction system. Needless to say, such a case is also included in the present invention.

After the completion of the hydrogenation reaction, the amino alcohol of the formula (2), which is the target substance, is removed from the reaction mixture obtained by, for example, removing the hydrogenation catalyst by filtration or centrifugation, and then separating the resulting mixture. High purity can be obtained by subjecting to separation and purification operations such as distillation, crystallization, and column chromatography.

The amino alcohol of the formula (2) obtained by the first and second production methods of the present invention described above is
Amino alcohols in which the hydroxyl group and the amino group are linked by a main chain containing 4 or 5 carbon atoms, and are classified as primary or secondary amines. This amino alcohol is derived from its chemical structure, and is derived from dye materials, emulsifiers, rust inhibitors, neutralizers, pH regulators, shoe ink materials, synthetic detergents, fiber auxiliaries, organic solvents, cutting oils, wax materials, paints Raw materials, printing ink raw materials, flocculant raw materials, adhesive raw materials, polishing agents, gas purifiers, lubricating oil additives, urethane foaming catalysts, azo dye mild volatiles, anion exchange resin raw materials, fuel oil sludge inhibitors, fuel Oil sludge dispersant, wax emulsifier, fiber treatment raw material, epoxy resin low temperature polymerization accelerator, epoxy resin curing accelerator, water-soluble paint synthetic resin solubilizer, emulsion paint alkali stabilizer, urethane coating catalyst, fiber flexibility Raw materials, rubber stabilizers,
It can be used for a wide range of applications such as rubber strength improvers and paper processing agent raw materials.

Among the amino alcohols of the formula (2) obtained by the first and second production methods of the present invention,
Amino-3-methyl-1-pentanol, 4- (methylamino) -2-methyl-1-butanol and 5- (methylamino) -3-methyl-1-pentanol are novel compounds and have been used in a wide range of fields. The use of can be expected.

[0067]

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, ammonia and hydrogen] In a 300-ml electromagnetic stirring autoclave equipped with a gas inlet and a sampling port, 1.7 g of Raney nickel was placed. 36.0 g of 2-hydroxy-4-methyltetrahydropyran (95% purity, 295 mmol)
l), 100 g of a 25% aqueous ammonia solution (1470 mmol as ammonia, 5 times the molar amount to 2-hydroxy-4-methyltetrahydropyran), and 30 g of 1-octanol were added, and the inside atmosphere was replaced with hydrogen gas. Was set to 2.0 atm (gauge pressure). Next, the temperature of the mixture was raised to 80 ° C. When the temperature reached 80 ° C., the pressure in the autoclave became about 3.0 atm (gauge pressure). Furthermore, the pressure in the autoclave is increased to 5 atm (gauge pressure) by introducing hydrogen gas.
And

By continuing the reaction in this state for 6 hours, the reaction was pursued. 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 the completion of the reaction, the autoclave was cooled, the internal liquid was drawn out, and Raney nickel was removed by filtration to obtain a filtrate. The filtrate was analyzed by gas chromatography to find that the starting material, 2-hydroxy-
No peak of 4-methyltetrahydropyran was confirmed,
5-amino-3-methyl-1-pentanol is 32.1
g (274 mmol) (conversion based on 2-hydroxy-4-methyltetrahydropyran: 100%; selectivity: 93
%; Yield: 93%). In addition, the analysis conditions in gas chromatography are as follows.

Column: G-300 (trade name: manufactured by The Chemical Inspection Association) Column temperature: After holding at 100 ° C. for 4 minutes, the temperature was raised to 220 ° C. at a rate of 12 ° C./min. Detector: FID

The filtrate obtained above was purified by distillation to find that 5-amino-3-methyl-1-pentanol contained 1
8.6 g were obtained (boiling point: 101 ° C. (0.8 mmH
g)). The NMR data of this compound is shown below.

¹ H-NMR: δ (ppm): 0.91
(D; 3H, J = 6 Hz), 1.23-1.79 (m;
5H), 2.18 (s; 3H), 2.64-2.83
(M; 2H), 3.56-3.73 (m; 2H)

Example 2 [Reaction of 2-hydroxy-4-methyltetrahydrofuran, ammonia and hydrogen] Instead of 2-hydroxy-4-methyltetrahydropyran, 2-hydroxy-4-methyltetrahydrofuran was replaced by 3
Example 1 except that 0.1 g (295 mmol) was used.
A reaction operation and a post-treatment operation were carried out according to the procedures described in the above. as a result,
No peak of 2-hydroxy-4-methyltetrahydrofuran, which is a raw material, was confirmed, and 4-amino-2-methyl-
28.0 g (271 mmol) of 1-butanol (2-
(Conversion based on hydroxy-4-methyltetrahydrofuran: 100%; selectivity: 92%; yield: 92%).

Example 3 [Reaction of 2-hydroxy-4-methyltetrahydrofuran, ammonia and hydrogen] In a 300 ml-volume electromagnetically stirred autoclave equipped with a gas inlet and a sampling port, 1.2 g of Raney nickel was added. 62.0 g (608 mmol) of -hydroxy-4-methyltetrahydrofuran, 62.0 g of a 25% aqueous ammonia solution (912 m 2 as ammonia)
mol, 1.5 times the mol of 2-hydroxy-4-methyltetrahydrofuran), and the inside atmosphere was replaced with hydrogen gas.
The temperature was raised to ° C. When the temperature reached 80 ° C., the pressure became about 3.0 atm (gauge pressure). The pressure in the autoclave was adjusted to 5 atm (gauge pressure) by introducing hydrogen gas.

The reaction was continued for 8 hours in this state to pursue the reaction. 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 the completion of the reaction, the autoclave was cooled, the internal liquid was drawn out, and Raney nickel was removed by filtration to obtain a filtrate. The filtrate was analyzed by gas chromatography to find that the starting material, 2-hydroxy-
No peak of 4-methyltetrahydrofuran was confirmed,
55.1 g of 4-amino-2-methyl-1-butanol
(535 mmol) (conversion based on 2-hydroxy-4-methyltetrahydrofuran: 100%; selectivity: 88
%; Yield: 88%).

Example 4: [Reaction of 2-hydroxy-4-methyltetrahydropyran, ammonia and hydrogen] The diatomaceous earth was supported in a 300-ml electromagnetic stirring type autoclave equipped with a gas inlet and a sampling port. Nickel catalyst (nickel content 52%)
4.0 g and 15 ml of 1-butanol were charged, and the inside of the autoclave was replaced with hydrogen at 10 atm (gauge pressure) three times. Next, 64.2 g of ammonia (3.8 m
ol), hydrogen was added at a partial pressure equivalent to 10 atm (gauge pressure), and the autoclave was heated to 140 ° C. At this time, the internal pressure of the autoclave was 125 atm (gauge pressure). By supplying hydrogen here, a total pressure of 140
Atmospheric pressure (gauge pressure) was used. There 2-hydroxy-4-
65.9 g of methyltetrahydropyran (purity 95%, 5
(40 mmol) was fed over 1 hour, followed by 4 hours to drive the reaction. At this time, by continuously supplying hydrogen gas such that the pressure in the autoclave is maintained at 140 atm (gauge pressure) during the reaction period after starting the feeding of 2-hydroxy-4-methyltetrahydropyran, the reaction is continued. Was replenished with the consumed hydrogen.
During these periods, the reaction temperature was maintained at 140 ° C.

After the completion of the reaction, the autoclave was cooled, and after releasing the pressure of ammonia, the internal solution was removed, and the nickel catalyst was removed by filtration to obtain a filtrate. The filtrate was analyzed by gas chromatography to find that the starting material 2
No peak of -hydroxy-4-methyltetrahydropyran was confirmed, and 60.8 g (520 mmol) of 5-amino-3-methyl-1-pentanol (conversion rate based on 2-hydroxy-4-methyltetrahydropyran: 100)
%; Selectivity: 96%; yield: 96%).

Example 5: [Reaction of 2-hydroxy-4-methyltetrahydrofuran, ammonia and hydrogen] 55.1 g (540 mmol) of 2-hydroxy-4-methyltetrahydrofuran instead of 2-hydroxy-4-methyltetrahydropyran Example 4 except used
The reaction was carried out in the same manner as

After completion of the reaction, the reaction filtrate was analyzed by gas chromatography to find that the starting material, 2-hydroxy-
No peak of 4-methyltetrahydrofuran was confirmed,
52.7 g of 4-amino-2-methyl-1-butanol
(512 mmol) (conversion based on 2-hydroxy-4-methyltetrahydrofuran: 100%; selectivity: 95
%; Yield: 95%).

Example 6: [Reaction of 2-hydroxy-4-methyltetrahydrofuran, methylamine and hydrogen] In a 300 ml-volume electromagnetically stirred autoclave equipped with a gas inlet and a sampling port, 1.7 g of Raney nickel was placed. 40.0 g of 2-hydroxy-4-methyltetrahydrofuran (95% purity, 373 mmol)
1) and 43.3 g of a 40% aqueous solution of methylamine (559 mmol as methylamine, 2-hydroxy-4-
(1.5 times the molar amount of methyltetrahydrofuran), and the inside atmosphere was replaced with hydrogen gas.
The pressure was set to 0 atm (gauge pressure), and the temperature was raised to 80 ° C. 80 ℃
At which point the pressure was about 3.0 atmospheres (gauge pressure). The pressure in the autoclave was adjusted to 5 atm (gauge pressure) by introducing hydrogen gas.

The reaction was continued by keeping the reaction for 6 hours in this state. 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 the completion of the reaction, the autoclave was cooled, the internal liquid was taken out, and Raney nickel was removed by filtration to obtain a filtrate. The filtrate was analyzed by gas chromatography to find that the starting material, 2-hydroxy-
No peak of 4-methyltetrahydrofuran was confirmed,
40.1 g (343 mmol) of 4- (methylamino) -2-methyl-1-butanol (2-hydroxy-4-
Conversion based on methyltetrahydrofuran: 100%; selectivity: 92%; yield: 92%). In addition, the analysis conditions in gas chromatography are as follows.

Column: G-300 (trade name: manufactured by The Chemical Inspection Association) Column temperature: After holding at 100 ° C. for 4 minutes, the temperature was raised to 220 ° C. at a rate of 12 ° C./min. Detector: FID

The filtrate obtained above was purified by distillation to obtain 28.3 g of 4- (methylamino) -2-methyl-1-butanol (boiling point: 74 ° C. (2 mmH
g)). The NMR data of this compound is shown below.

¹ H-NMR: δ (ppm): 0.89
(D; 3H, J = 6 Hz), 1.64-2.03 (m;
3H), 2.15-2.98 (m; 2H), 2.40
(S; 3H), 3.77 (s; 2H), 3.09-4.
17 (m; 2H)

Example 7: [Reaction of 2-hydroxy-4-methyltetrahydropyran, methylamine and hydrogen] 2-Hydroxy-4-methyltetrahydropyran was replaced with 4-hydroxy-4-methyltetrahydropyran.
Example 6 except that 7.5 g (373 mmol) was used.
A reaction operation and a post-treatment operation were carried out according to the procedures described in the above. as a result,
No peak of 2-hydroxy-4-methyltetrahydropyran as a raw material was confirmed, and 5- (methylamino) -3 was not observed.
43.4 g (332 mm) of -methyl-1-pentanol
ol) (2-hydroxy-4-methyltetrahydropyran conversion: 100%; selectivity: 89%; yield: 89
%) Was found to be included.

The filtrate obtained above was purified by distillation to obtain 31.0 g of 5- (methylamino) -3-methyl-1-pentanol (boiling point: 81 ° C. (2.0 mm
Hg)). The NMR data of this compound is shown below.

¹ H-NMR: δ (ppm): 0.82
(D; 3H, J = 6 Hz), 1.04-2.00 (m;
5H), 2.15-2.95 (m; 2H), 2.40
(S; 3H), 2.96 (s; 2H), 3.15-3.
77 (m; 2H)

Example 8: (1) [Reaction between 2-hydroxy-4-methyltetrahydropyran and 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,
Hydroxy-4-methyltetrahydropyran 118 g
(975 mmol) and 60 g of molecular sieves, and the temperature of the internal liquid was adjusted to 2 ° C. by cooling in an ice-water bath. 87.8 g of butylamine (1200 mmo
By dropping l) into the internal liquid under stirring, the internal liquid was supplied 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 completion of the stirring, the solution portion of the obtained reaction mixture was analyzed by gas chromatography, and it was found that 3.3 g of the starting material 2-hydroxy-4-methyltetrahydropyran was contained (inversion). Rate: 97
%). The reaction mixture was filtered to remove molecular sieves, and 210 g of a filtrate was obtained.

The filtrate obtained above was purified by distillation to obtain 125 g of a fraction containing 94.6% of 2- (butylamino) -4-methyltetrahydropyran (boiling point:
94-8 ° C (9.0 mmHg)). NMR of this compound
The data is shown below.

¹ H-NMR: δ (ppm): 0.70-
2.10 (m; 15H), 2.35-4.18 (m; 6
H)

(2) [Hydrogenation reaction operation on the obtained reaction mixture] 20.0 g (111 mmol) of the obtained distillate
Together with 80 ml of isopropyl alcohol and 2.0 g of Raney nickel (hydrogenation catalyst) were placed in a 300 ml electromagnetic stirring type autoclave equipped with a gas inlet and a sampling port. After replacing the internal atmosphere with hydrogen gas, while maintaining the pressure at about 8.0 atm (gauge pressure) by supplying hydrogen gas,
The temperature was raised to 80 ° C. The reaction was carried out for 2 hours while keeping 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. During these reaction periods, the pressure inside the autoclave was increased to 8.0 by constantly supplying hydrogen gas.
Atmospheric pressure (gauge pressure) was maintained.

After the completion of the reaction, the autoclave was cooled, the internal liquid was drawn out, and Raney nickel was removed by filtration to obtain a filtrate. The filtrate was analyzed by gas chromatography to find that 5- (butylamino) -3-
14.7 g (85 mmo) of methyl-1-pentanol
l) It was found to be formed (yield based on 2- (butylamino) -4-methyltetrahydropyran: 7)
7%).

Example 9 (1) [Reaction of 2-hydroxy-4-methyltetrahydrofuran, ammonia and hydrogen] 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,
45 g of hydroxy-4-methyltetrahydrofuran (4
41 mmol) and the temperature of the internal liquid was brought to 2 ° C. by cooling in an ice-water bath. 90 g of a 25% aqueous ammonia solution (1324 mmol as ammonia, 3 times the molar amount of 2-hydroxy-4-methyltetrahydrofuran) was dropped into the internal liquid under stirring, thereby maintaining the temperature of the internal liquid at 10 ° C or lower. And fed over 10 minutes. After completion of the dropwise addition, stirring was continued at 10 ° C. for another 30 minutes.

After completion of the stirring, the solution portion of the obtained reaction mixture was analyzed by gas chromatography to find that the starting material 2-hydroxy-4-methyltetrahydrofuran was 1%.
It was found that 1.6 g was contained (conversion rate: 74).
%).

(2) [Hydrogenation reaction operation on the obtained reaction mixture] The obtained mixture (about 135 g) was mixed with 4.1 g of Raney nickel (hydrogenation catalyst) together with a gas inlet and a sampling port. It was placed in a 300 ml electromagnetically stirred autoclave. 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 8 hours while keeping the temperature at 80 ° C. During these reaction periods, the pressure in the autoclave was maintained at 8.0 atm (gauge pressure) by constantly supplying hydrogen gas.

After the completion of the reaction, the autoclave was cooled, the internal liquid was drawn out, and Raney nickel was removed by filtration to obtain a filtrate. The filtrate was analyzed by gas chromatography to find that 4-amino-2-methyl-1
It was found that 36.9 g (358 mmol) of -butanol was produced (yield based on 2-hydroxy-4-methyltetrahydrofuran: 81%).

[0101]

According to the production method of the present invention, a hydroxyl group and an amino group are linked by a main chain containing 4 or 5 carbon atoms, and a primary amine or a secondary amine Can be produced from raw materials that are easy to obtain and handle in high yield, and special reaction equipment, special reaction conditions and complicated post-treatment operations are unnecessary. Therefore, the present invention provides a method capable of industrially producing the above-mentioned amino alcohol advantageously.

 ──────────────────────────────────────────────────続 き Continuing on the front page (72) Katsushi Nagata, Inventor, Katsura, Kamisu-cho, Kashima-gun, Ibaraki Pref. Kuraray Co., Ltd. F-term in company Kuraray (reference) 4H006 AA01 AA02 AB84 AC41 AC52 BA21 BA24 BA25 BA26 BA30 BA55 BB11 BB14 BB15 BB25 BC10 BC19 BC35 BD20 BE20 BN10 BU32 4H039 CA60 CA71 CB30 CD30

Claims (8)

[Claims] (1) Formula (1) (Wherein n represents 0 or 1), a cyclic hemiacetal represented by the formula (4): R-NH ₂ (4) (where R is a hydrogen atom, A monovalent saturated hydrocarbon group or a monovalent aromatic group optionally having substituent (s)) and hydrogen in the presence of a hydrogenation catalyst to give a compound of the formula (2) Embedded image (Wherein, n and R are as defined above), a method for producing an amino alcohol. 2. Formula (1) (Wherein n represents 0 or 1) by converting a cyclic hemiacetal represented by the formula (4) into R-NH ₂ (4) (where R represents a hydrogen atom and Represents a monovalent saturated hydrocarbon group or a monovalent aromatic group which may have a substituent).
The compound is further reacted with hydrogen in the presence of a hydrogenation catalyst to obtain a compound of formula (2) (Wherein, n and R are as defined above), a method for producing an amino alcohol. 3. The method according to claim 1, wherein the nitrogen-containing compound is reacted in an amount of 0.9 to 50 mol per 1 mol of the cyclic hemiacetal.
The manufacturing method as described. 4. The production method according to claim 1, wherein 1 to 20 mol of the nitrogen-containing compound is reacted with 1 mol of the cyclic hemiacetal. 5. The formula (3) Wherein n is as defined above, by reacting the alkenol-based compound with carbon monoxide and hydrogen in the presence of a rhodium compound and a tertiary organic phosphorus compound. The production method according to any one of claims 1 to 4, wherein a cyclic hemiacetal is obtained, and the cyclic hemiacetal is used for a reaction with a nitrogen-containing compound. 6. A 5-amino-3-methyl-1-pentanol. 7. 4- (methylamino) -2-methyl-1
-Butanol. 8. A 5- (methylamino) -3-methyl-1
-Pentanol.