Title of Invention	"METHOD FOR PODUCING TERTIARY AMINE"
Abstract	A process for producing a tertiary amine of the formula (3) which comprises adding a compound of the formula (2) to a mixture of a compound of the formula (1) or a polymerized product thereof and formic acid wherein R3 is hydrogen atom or alkyl having 1 to 3 carbon atoms, wherein R1 and R2 are respectively alkyl having 1 to 3 carbon atoms, and R1 and R2 may form a ring together with a nitrogen atom, wherein R1 to R3 are as defined above.

Title of Invention

"METHOD FOR PODUCING TERTIARY AMINE"

Abstract

A process for producing a tertiary amine of the formula (3) which comprises adding a compound of the formula (2) to a mixture of a compound of the formula (1) or a polymerized product thereof and formic acid wherein R3 is hydrogen atom or alkyl having 1 to 3 carbon atoms, wherein R1 and R2 are respectively alkyl having 1 to 3 carbon atoms, and R1 and R2 may form a ring together with a nitrogen atom, wherein R1 to R3 are as defined above.

Full Text	SPECIFICATION METHOD FOR PRODUCING TERTIARY AMINE TECHNICAL FIELD The present invention relates to a process for producing a tertiary amine. BACKGROUND ART As a method of producing a tertiary amine, it is known dehydration of an alcohol or cyclic ether, as a starting material, together with a primary or secondary amine in the presence of a catalyst under high temperature and high pressure, namely so-called a gas phase reaction (for example, patent literature 1). Also proposed is a method of producing a tertiary amine by a catalytic hydrogenation of an amide compound under high temperature and high pressure (for example, patent literature 2). [patent literature 1] JP1992-342578A [patent literature 2] JP2553049B These methods described in patent literatures 1 and 2 cannot be carried out under mild conditions, since special reaction vessel which is sustainable for a high temperature reaction and a high pressure reaction is required. As for a reaction under mild conditions, there is a method of reacting a secondary amine with an alkyl halide. Although it is actually a reaction under normal pressure, it is necessary to neutralize a hydrogen halide that is inevitably generated after the reaction. The alkyl halide reacts with an alkali used for neutralization, causing decrease of the yield. Moreover, a reactivity of tertiary amine to alkyl halide is generally higher than that of secondary amine, so the reaction proceeds to a quaternary salt, and therefore, secondary amine, tertiary amine and quaternary amine are intermingled in a reaction system. It is not preferable to select this process, because it is not only low in reaction yield but also poor in recovery yield. Moreover, although the separation of secondary amine and tertiary amine is usually performed by a distillation, there are many cases where the difference of the boiling points between tertiary amine and secondary amine as a starting material is very little, especially in methylation reaction, and therefore it results in low yield at the recovery and in increase at the operation steps. An object of the invention is to provide a method for producing a tertiary amine that accomplishes a reaction quantitatively without leaving starting materials unreacted under a mild condition by use of a conventional reaction equipment. DISCLOSURE OF THE INVENTION The present invention provides the following. 1. A process for producing a tertiary amine of the formula (3) which is characterized in that a compound of the formula (2) is added to a mixture of a compound of the formula (1) or a polymerized product thereof and formic acid (Formula Removed) wherein R3 is hydrogen atom or alkyl having 1 to 3 carbon atoms, (Formula Removed) wherein R1 and R2 are respectively alkyl having 1 to 3 carbon atoms, and R1 and R2 may form a ring together with a nitrogen atom, (Formula Removed) wherein R1 to R3 are as defined above. 2. A process according to claim 1 wherein the compound of the formula (2) is a compound having a pyrrolidine ring. 3. A process according to claim 1 wherein the tertiary amine is N-methylpyrrolidine. The present invention provides a process for producing a tertiary amine of the formula (3) which is characterized in that a compound of the formula (2) is added to a mixture of a compound of the formula (1) or a polymerized product thereof and formic acid. Examples of group represented by R3 are a hydrogen atom, ethyl, ethyl, n-propyl, isopropyl and cyclopropyl. Preferable are a hydrogen atom and methyl. Examples of groups represented by R1 and R2 are as follows. Examples of C1-C3 alkyl groups are straight-chain, branched chain or cyclic alkyl groups having 1 to 3 carbon atoms, such as methyl, ethyl, n-propyl, isopropyl and cyclopropyl. Preferable alkyl groups are straight-chain alkyl groups having 1 to 3 carbon atoms. A ring having 5 to 7 atoms may be formed by R1, R2 and nitrogen atom. Examples of rings are pyrrolidine, homopiperidine, piperidine, piperadine and morpholine. Specific examples of compound of the formula (1) are formaldehyde, acetaldehyde, propionaldehyde, butylaldehyde, isobutylaldehyde, paraformaldehyde and para-acetaldehyde. Furthermore, examples of polymers thereof are paraformaldehyde and para-acetaldehyde. Specific examples of compound of the formula (2) are dimethylamine, diethylamine, dipropylamine, di-isopropylamine, methylethylamine, methylpropylamine, ethylpropylamine, methyl-isopropylamine, ethyl-isopropylamine, pyrrolidine, homopiperidine, piperidine, piperazine and morpholine. Examples of tertiary amine of the formula (3) are trimethylamine, triethylamine, diethylmethylamine, methyldipropylamine, methyldi-isopropylamine, ethyldimethylamine, dimethylpropylamine, ethylmethylpropylamine, ethylmethyl-isopropylamine, methylpyrrolidine, ethylpyrrolidine, propylpyrrolidine, isopropylpyrrolidine, butylpyrrolidine, tert- butylpyrrolidine, methylhomopiperidine, ethylhomopiperidine, methylpiperidine, ethylpiperidine, dimethylpiperazine, diethylpiperazine, methylethylpiperazine, methylmorpholine and ethylmorpholine. A detailed description will be given below of the present process. Compound of the formula (1) and formic acid are admixed in a reaction vessel equipped with a reflux condenser. Compound of the formula (1) and formic acid may be used as an aqueous solution. Especially, when formaldehyde or acetaldehyde of low boiling point is used, it is preferable to use them in a form of an aqueous solution or a polymer product. The concentration of formaldehyde in aqueous solution is 20 to 50 %, preferably 30 to 40 %. The concentration of acetaldehyde in aqueous solution is 50 to 95 %, preferably 70 to 90 %. The concentration of formic acid in aqueous solution is 60 to 100 %, preferably 80 % or more. The admixing ratio of compound of the formula (1) and formic acid is 1.0 to 5.0 moles, and preferably 2.0 to 4.0 moles of formic acid to one mole of the compound of the formula (1). In the case of less than 1.0 mole, there is a possibility that the compound of the formula (2) of starting material may remain unreacted, and a by-product, which is formed by connecting the compound of the formula (2) with alkylmethylene, may be generated in a large amount. For example, when the compound of the formula (2) is pyrrolidine, dipyrrolidinomethane is generated as a by-product, and when it is dimethylamine, a large amount of tetramethyldiamino-methane is generated. When more than 5.0 moles is used, a large quantity of alkali is required to recover the product, and there is a possibility to decrease a recovery rate of the desired product because of an increased amount of aqueous layer, as well as it is uneconomical. The molar ratio of the compound of the formula (2) and the compound of the formula (1) is 1.0 to 3.0 moles, and preferably 1.0 to 2.5 moles of the compound of the formula (1) to one mole of the compound of the formula (2). In case of less than 1.0 mole, there is a possibility that the compound of the formula (2) of the starting material may remain unreacted. In case of more than 3.0 moles, a large amount of unreacted compound of the formula (1) remains and it may become difficult to purify at the recovery of the product. Next, the mixture mentioned above is heated. The heating temperature is suitably adjustable depending on the kinds of a compound of the formula (1), usually at the range of 40 to 120 °C, and it is preferable to heat up to the reflux temperature. Although it depends on the boiling point of a starting material to be used, it is desirable to carry it out under high temperature as much as possible so that added amine may react in an instant. In the reaction manner in which 3 components are admixed at a low temperature and followed by raising the reaction temperature, the reaction proceeds so rapidly and there is a possibility that a bumping may happen depending on the balance of the heat of reaction and elimination of C02, which is very dangerous. After that, the compound of the formula (2) is added to the mixture solution mentioned above under reflux. The secondary amines to be added, especially those having a low boiling point, may be preferably used in a form of aqueous solution. The concentration is 30 to 90 %, preferably 40 to 80 %. The reaction is an exothermic reaction, and a dripping method, a brook addition method and the like are therefore exemplified as the addition method in order to prevent a rapid reaction. The addition period may be suitably adjustable according to the amount of a mixture solution, and is usually 5 to 50 %/h, preferably 10 to 30 %/h to the total amount of secondary amine (100 %) to be added. When an addition rate exceeds 50 %/hour, there is a possibility that a bumping may happen depending on the balance of the heat of reaction and elimination of C02, which is very dangerous. The reaction is allowed to continue heating under reflux after the addition to complete the reaction. The reaction temperature is suitably adjustable according to the kinds of a reaction mixture, and usually a range of 40 to 120 °C is preferable, and the reflux temperature is especially preferable. The reaction time is suitably adjustable according to the amount of a reaction mixture, and is usually 1 to 24 hours, preferably 1 to 12 hours, and more preferably 2 to 8 hours. After the completion of the reaction, the reaction mixture is cooled to 10 to 50 °C . Cooling by water is good enough as a cooling method. After cooling, alkali is added, and then organic layer is separated from aqueous layer. Examples of alkali agent to be added are sodium hydroxide, potassium hydroxide, sodium carbonate, potassium carbonate, lithium hydroxide, lithium carbonate and an aqueous solution thereof. Sodium hydroxide, potassium hydroxide or an aqueous solution thereof are preferable. As for the amount of alkali, a solid alkali concentration to the total amount is preferably 10 to 50 %. A preferable temperature for the addition is room temperature to 60 °C . A tertiary amine is separated into an organic layer. When the addition is short in quantity, separation to two layers is not sufficient. Furthermore, it is not preferable, for the distribution rate of a desired amine to organic layer is decreased even if it is separated to two layers. It may be extracted by an organic solvent if necessary. Various organic solvents may be used. Examples are hydrocarbons, halogen solvents and ethers. The desired product is obtained by distillation after extraction. A solvent having a large difference at boiling point compared with that of the amine to be extracted at distillation should be chosen so that the purification process becomes easy. A hydrocarbon of high boiling point is suitably used to extract• an amine of low boiling point. Moreover, ethers or halogen solvents of low boiling point are preferably chosen to extract amines of high boiling point. BEST MODE OF CARRYING OUT THE INVENTION The present invention will be described in detail with reference to the following examples, but is not limited to these examples. Moreover, in the examples and comparative examples, physical properties were measured by the following methods. Identification of tertiary amines Tertiary amines were identified by the measurement results of """H-NMR. The remaining amount of the starting material and the yield of tertiary amine were determined by gas chromatography (GC). ^-NMR: BRUKER 3 0 0MHz GC: SHIMADZU GC14B Column used: Amipack 141 (GL Sciences Inc.) Example 1 Preparation of N-methylpyrrolidine To a four necked flask equipped with a reflux condenser were added 339.65 g (2.95 moles) of 37% aqueous formaldehyde solution (Wako Pure Chemical Industries, Ltd.) and 377.65 g (7.38 moles) of 90% aqueous formic acid solution. Then the mixture was raised to reflux temperature (85 °C) . To the mixture was added dropwise 175.00 g (2.46 moles) of pyrrolidine (Py) through a dropping funnel over a period of about 5 hours. The dropping was always carried out under reflux. After the completion of the dropping, the reaction was continued under reflux (104 XZ) for 6 hours (reaction yield 99%, remaining rate of pyrrolidine 0.3%). After cooling the reaction mixture to room temperature, 625 g of 48% aqueous NaOH solution was added under cooling, with keeping the internal temperature under 5 5 °C . The organic layer (upper layer) of the two separated layers was extracted. The upper layer [214.46 g, recovery rate 98%, constitution of the organic layer: N-methylpyrrolidine 94.7%, Py 0.3%, MeOH (stabilizer for formaldehyde) 0.6%, H20 4.4%] was distilled to obtain 201.23 g (96%) of N-methylpyrrolidine containing less than 50 ppm of methanol, less than 50 ppm of pyrrolidine and less than 50 ppm of H20. The desired product was confirmed by ^-H-NMR. 1H-NMR(D20) 5 1.61(m 4H), 2.14(s 3H), 2.34(m 4H) Examples 2 to 12 Pyrroridine (Py), formaldehyde (HCHO) and formic acid (HCOOH) were reacted under reflux, according to the proportion of amount, dropping period and reaction time described in Table 1, to obtain the desired N-methylpyrrolidine (NMP). The respective yields after distillation are shown in Table 1. Besides, the remaining amount of Py of the starting material was less than 50 ppm in any of the examples. Moreover, paraformaldehyde (Wako Pure Chemical Industries, ltd.) was used in Example 2 and Py was added slowly in Example 3. (Table Removed) Examp1e 13 In the same manner as in Example 1 except for replacing formaldehyde (2.95 moles) with acetaldehyde (Wako Pure Chemical Industries, Ltd., 90% purity) (2.95 moles), N-ethylpyrrolidine was obtained (yield after distillation 95%, less than 50 ppm of pyrrolidine). Comparative Example 1 N-methylpyrrolidine was prepared in the same manner as in Example 1 except for adding formic acid to a mixture solution of pyrrolidine and formaldehyde. Reaction yield was 56% and recovery rate was 20%. (The separation from pyrrolidine was bad, recovery rate greatly decreased and further, the generation of dipyrrolidinomethane of the amount exceeded 20% as the by-product was observed.) Comparative Example 2 N-methylpyrrolidine was prepared in the same manner as in Example 1 except for adding formaldehyde to a mixture solution of pyrrolidine and formic acid. Reaction yield was 75% and recovery rate was 55% (The separation from pyrrolidine was bad and recovery rate greatly decreased. ) Comparative Example 3 To a four necked flask equipped with a reflux condenser were added 100.00 g (1.41 moles) of pyrrolidine, 97.17 g (0.70 mole) of potassium carbonate and 100 ml of methanol, and then was cooled to 0 °C . Gradually was added dropwise 209.56 g (1.48 moles) of methyl iodide with keeping the reaction temperature not to exceed 5 °C. After the completion of the addition, the temperature was raised gradually, and was reacted at 2 5 °C for 10 hours and then for 10 hours under reflux (reaction yield 40%, remaining rate of pyrrolidine 27%) . Purification by distillation was carried out, but it was difficult to separate from the starting material completely. INDUSTRIAL APPLICABILITY Tertiary amines can be produced under mild conditions quantitatively by the present invention. Moreover, the remaining amount of the compound of the formula (2), as the starting material, contained in the desired tertiary amine can be reduced to a trace amount, for example less than 100 ppm, preferably less than 50 ppm. CLAIMS 1. A process for producing a tertiary amine of the formula (3) which comprises adding a compound of the formula (2) to a mixture of a compound of the formula (1) or a polymerized product thereof and formic acid (Formula Removed) wherein R3 is hydrogen atom or alkyl having 1 to 3 carbon atoms, (Formula Removed) wherein R1 and R2 are respectively alkyl having 1 to 3 carbon atoms, and R1 and R2 may form a ring together with a nitrogen atom, (Formula Removed) wherein R1 to R3 are as defined above. 2. A process according to claim 1 wherein the compound of the formula (2) is a compound having a pyrrolidine ring. 3. A process according to claim 1 wherein the tertiary amine is N-methylpyrrolidine. 4. A process according to any one of claims 1 to 3,wherein the remaining amount of a starting material of the compound of the formula (2) contained in the desired tertiary amine is less than 100 ppm. 5. A process according to any one of claims 1 to 3, wherein the remaining amount of a starting material of the compound of the formula (2) contained in the desired tertiary amine is less than 5 0 ppm.

Full Text

SPECIFICATION
METHOD FOR PRODUCING TERTIARY AMINE
TECHNICAL FIELD
The present invention relates to a process for producing a tertiary amine.
BACKGROUND ART
As a method of producing a tertiary amine, it is known dehydration of an alcohol or cyclic ether, as a starting material, together with a primary or secondary amine in the presence of a catalyst under high temperature and high pressure, namely so-called a gas phase reaction (for example, patent literature 1). Also proposed is a method of producing a tertiary amine by a catalytic hydrogenation of an amide compound under high temperature and high pressure (for example, patent literature 2).
[patent literature 1] JP1992-342578A
[patent literature 2] JP2553049B
These methods described in patent literatures 1 and 2 cannot be carried out under mild conditions, since special reaction vessel which is sustainable for a high temperature reaction and a high pressure reaction is required.
As for a reaction under mild conditions, there is a method of reacting a secondary amine with an alkyl halide. Although it is actually a reaction under normal pressure, it is necessary to neutralize a hydrogen halide that is

inevitably generated after the reaction.
The alkyl halide reacts with an alkali used for neutralization, causing decrease of the yield.
Moreover, a reactivity of tertiary amine to alkyl halide is generally higher than that of secondary amine, so the reaction proceeds to a quaternary salt, and therefore, secondary amine, tertiary amine and quaternary amine are intermingled in a reaction system.
It is not preferable to select this process, because it is not only low in reaction yield but also poor in recovery yield. Moreover, although the separation of secondary amine and tertiary amine is usually performed by a distillation, there are many cases where the difference of the boiling points between tertiary amine and secondary amine as a starting material is very little, especially in methylation reaction, and therefore it results in low yield at the recovery and in increase at the operation steps.
An object of the invention is to provide a method for producing a tertiary amine that accomplishes a reaction quantitatively without leaving starting materials unreacted under a mild condition by use of a conventional reaction equipment.
DISCLOSURE OF THE INVENTION
The present invention provides the following.
1. A process for producing a tertiary amine of the formula (3) which is characterized in that a compound of the formula (2) is added to a mixture of a compound of the

formula (1) or a polymerized product thereof and formic acid
(Formula Removed)
wherein R3 is hydrogen atom or alkyl having 1 to 3 carbon atoms,
(Formula Removed)
wherein R1 and R2 are respectively alkyl having 1 to 3 carbon atoms, and R1 and R2 may form a ring together with a nitrogen atom,
(Formula Removed)
wherein R1 to R3 are as defined above.
2. A process according to claim 1 wherein the compound of the formula (2) is a compound having a pyrrolidine ring.
3. A process according to claim 1 wherein the tertiary amine is N-methylpyrrolidine.
The present invention provides a process for producing a tertiary amine of the formula (3) which is characterized in that a compound of the formula (2) is added to a mixture of a compound of the formula (1) or a polymerized product thereof and formic acid.
Examples of group represented by R3 are a hydrogen atom,

ethyl, ethyl, n-propyl, isopropyl and cyclopropyl. Preferable are a hydrogen atom and methyl.
Examples of groups represented by R1 and R2 are as follows.
Examples of C1-C3 alkyl groups are straight-chain, branched chain or cyclic alkyl groups having 1 to 3 carbon atoms, such as methyl, ethyl, n-propyl, isopropyl and cyclopropyl. Preferable alkyl groups are straight-chain alkyl groups having 1 to 3 carbon atoms. A ring having 5 to 7 atoms may be formed by R1, R2 and nitrogen atom. Examples of rings are pyrrolidine, homopiperidine, piperidine, piperadine and morpholine.
Specific examples of compound of the formula (1) are formaldehyde, acetaldehyde, propionaldehyde, butylaldehyde, isobutylaldehyde, paraformaldehyde and para-acetaldehyde. Furthermore, examples of polymers thereof are paraformaldehyde and para-acetaldehyde.
Specific examples of compound of the formula (2) are dimethylamine, diethylamine, dipropylamine, di-isopropylamine, methylethylamine, methylpropylamine, ethylpropylamine, methyl-isopropylamine, ethyl-isopropylamine, pyrrolidine, homopiperidine, piperidine, piperazine and morpholine.
Examples of tertiary amine of the formula (3) are trimethylamine, triethylamine, diethylmethylamine, methyldipropylamine, methyldi-isopropylamine, ethyldimethylamine, dimethylpropylamine, ethylmethylpropylamine, ethylmethyl-isopropylamine,

methylpyrrolidine, ethylpyrrolidine, propylpyrrolidine, isopropylpyrrolidine, butylpyrrolidine, tert-
butylpyrrolidine, methylhomopiperidine, ethylhomopiperidine, methylpiperidine, ethylpiperidine, dimethylpiperazine, diethylpiperazine, methylethylpiperazine, methylmorpholine and ethylmorpholine.
A detailed description will be given below of the present process.
Compound of the formula (1) and formic acid are admixed in a reaction vessel equipped with a reflux condenser. Compound of the formula (1) and formic acid may be used as an aqueous solution. Especially, when formaldehyde or acetaldehyde of low boiling point is used, it is preferable to use them in a form of an aqueous solution or a polymer product. The concentration of formaldehyde in aqueous solution is 20 to 50 %, preferably 30 to 40 %. The concentration of acetaldehyde in aqueous solution is 50 to 95 %, preferably 70 to 90 %. The concentration of formic acid in aqueous solution is 60 to 100 %, preferably 80 % or more.
The admixing ratio of compound of the formula (1) and formic acid is 1.0 to 5.0 moles, and preferably 2.0 to 4.0 moles of formic acid to one mole of the compound of the formula (1). In the case of less than 1.0 mole, there is a possibility that the compound of the formula (2) of starting material may remain unreacted, and a by-product, which is formed by connecting the compound of the formula (2) with alkylmethylene, may be generated in a large amount. For example, when the compound of the formula (2) is pyrrolidine,

dipyrrolidinomethane is generated as a by-product, and when it is dimethylamine, a large amount of tetramethyldiamino-methane is generated. When more than 5.0 moles is used, a large quantity of alkali is required to recover the product, and there is a possibility to decrease a recovery rate of the desired product because of an increased amount of aqueous layer, as well as it is uneconomical.
The molar ratio of the compound of the formula (2) and the compound of the formula (1) is 1.0 to 3.0 moles, and preferably 1.0 to 2.5 moles of the compound of the formula (1) to one mole of the compound of the formula (2). In case of less than 1.0 mole, there is a possibility that the compound of the formula (2) of the starting material may remain unreacted. In case of more than 3.0 moles, a large amount of unreacted compound of the formula (1) remains and it may become difficult to purify at the recovery of the product.
Next, the mixture mentioned above is heated. The heating temperature is suitably adjustable depending on the kinds of a compound of the formula (1), usually at the range of 40 to 120 °C, and it is preferable to heat up to the reflux temperature. Although it depends on the boiling point of a starting material to be used, it is desirable to carry it out under high temperature as much as possible so that added amine may react in an instant. In the reaction manner in which 3 components are admixed at a low temperature and followed by raising the reaction temperature, the reaction proceeds so rapidly and there is a possibility that a bumping

may happen depending on the balance of the heat of reaction and elimination of C02, which is very dangerous.
After that, the compound of the formula (2) is added to the mixture solution mentioned above under reflux. The secondary amines to be added, especially those having a low boiling point, may be preferably used in a form of aqueous solution. The concentration is 30 to 90 %, preferably 40 to 80 %. The reaction is an exothermic reaction, and a dripping method, a brook addition method and the like are therefore exemplified as the addition method in order to prevent a rapid reaction. The addition period may be suitably adjustable according to the amount of a mixture solution, and is usually 5 to 50 %/h, preferably 10 to 30 %/h to the total amount of secondary amine (100 %) to be added. When an addition rate exceeds 50 %/hour, there is a possibility that a bumping may happen depending on the balance of the heat of reaction and elimination of C02, which is very dangerous.
The reaction is allowed to continue heating under reflux after the addition to complete the reaction. The reaction temperature is suitably adjustable according to the kinds of a reaction mixture, and usually a range of 40 to 120 °C is preferable, and the reflux temperature is especially preferable. The reaction time is suitably adjustable according to the amount of a reaction mixture, and is usually
1 to 24 hours, preferably 1 to 12 hours, and more preferably
2 to 8 hours.
After the completion of the reaction, the reaction mixture is cooled to 10 to 50 °C . Cooling by water is good

enough as a cooling method.
After cooling, alkali is added, and then organic layer is separated from aqueous layer. Examples of alkali agent to be added are sodium hydroxide, potassium hydroxide, sodium carbonate, potassium carbonate, lithium hydroxide, lithium carbonate and an aqueous solution thereof. Sodium hydroxide, potassium hydroxide or an aqueous solution thereof are preferable. As for the amount of alkali, a solid alkali concentration to the total amount is preferably 10 to 50 %. A preferable temperature for the addition is room temperature to 60 °C . A tertiary amine is separated into an organic layer. When the addition is short in quantity, separation to two layers is not sufficient. Furthermore, it is not preferable, for the distribution rate of a desired amine to organic layer is decreased even if it is separated to two layers. It may be extracted by an organic solvent if necessary. Various organic solvents may be used. Examples are hydrocarbons, halogen solvents and ethers. The desired product is obtained by distillation after extraction. A solvent having a large difference at boiling point compared with that of the amine to be extracted at distillation should be chosen so that the purification process becomes easy. A hydrocarbon of high boiling point is suitably used to extract• an amine of low boiling point. Moreover, ethers or halogen solvents of low boiling point are preferably chosen to extract amines of high boiling point.
BEST MODE OF CARRYING OUT THE INVENTION

The present invention will be described in detail with reference to the following examples, but is not limited to these examples. Moreover, in the examples and comparative examples, physical properties were measured by the following methods. Identification of tertiary amines
Tertiary amines were identified by the measurement results of """H-NMR. The remaining amount of the starting material and the yield of tertiary amine were determined by gas chromatography (GC). ^-NMR: BRUKER 3 0 0MHz GC: SHIMADZU GC14B
Column used: Amipack 141 (GL Sciences Inc.) Example 1 Preparation of N-methylpyrrolidine
To a four necked flask equipped with a reflux condenser were added 339.65 g (2.95 moles) of 37% aqueous formaldehyde solution (Wako Pure Chemical Industries, Ltd.) and 377.65 g (7.38 moles) of 90% aqueous formic acid solution. Then the mixture was raised to reflux temperature (85 °C) . To the mixture was added dropwise 175.00 g (2.46 moles) of pyrrolidine (Py) through a dropping funnel over a period of about 5 hours. The dropping was always carried out under reflux. After the completion of the dropping, the reaction was continued under reflux (104 XZ) for 6 hours (reaction yield 99%, remaining rate of pyrrolidine 0.3%). After cooling the reaction mixture to room temperature, 625 g of 48% aqueous NaOH solution was added under cooling, with keeping the internal temperature under 5 5 °C . The organic layer

(upper layer) of the two separated layers was extracted. The upper layer [214.46 g, recovery rate 98%, constitution of the organic layer: N-methylpyrrolidine 94.7%, Py 0.3%, MeOH
(stabilizer for formaldehyde) 0.6%, H20 4.4%] was distilled to obtain 201.23 g (96%) of N-methylpyrrolidine containing less than 50 ppm of methanol, less than 50 ppm of pyrrolidine and less than 50 ppm of H20. The desired product was confirmed by ^-H-NMR. 1H-NMR(D20) 5 1.61(m 4H), 2.14(s 3H), 2.34(m 4H)
Examples 2 to 12
Pyrroridine (Py), formaldehyde (HCHO) and formic acid (HCOOH) were reacted under reflux, according to the proportion of amount, dropping period and reaction time described in Table 1, to obtain the desired N-methylpyrrolidine (NMP). The respective yields after distillation are shown in Table 1. Besides, the remaining amount of Py of the starting material was less than 50 ppm in any of the examples. Moreover, paraformaldehyde (Wako Pure Chemical Industries, ltd.) was used in Example 2 and Py was added slowly in Example 3.

(Table Removed)
Examp1e 13
In the same manner as in Example 1 except for replacing formaldehyde (2.95 moles) with acetaldehyde (Wako Pure Chemical Industries, Ltd., 90% purity) (2.95 moles), N-ethylpyrrolidine was obtained (yield after distillation 95%, less than 50 ppm of pyrrolidine). Comparative Example 1
N-methylpyrrolidine was prepared in the same manner as in Example 1 except for adding formic acid to a mixture solution of pyrrolidine and formaldehyde. Reaction yield was 56% and recovery rate was 20%. (The separation from pyrrolidine was bad, recovery rate greatly decreased and further, the generation of dipyrrolidinomethane of the amount exceeded 20% as the by-product was observed.) Comparative Example 2

N-methylpyrrolidine was prepared in the same manner as in Example 1 except for adding formaldehyde to a mixture solution of pyrrolidine and formic acid. Reaction yield was 75% and recovery rate was 55% (The separation from pyrrolidine was bad and recovery rate greatly decreased. ) Comparative Example 3
To a four necked flask equipped with a reflux condenser were added 100.00 g (1.41 moles) of pyrrolidine, 97.17 g (0.70 mole) of potassium carbonate and 100 ml of methanol,
and then was cooled to 0 °C . Gradually was added dropwise 209.56 g (1.48 moles) of methyl iodide with keeping the
reaction temperature not to exceed 5 °C. After the completion of the addition, the temperature was raised gradually, and was reacted at 2 5 °C for 10 hours and then for 10 hours under reflux (reaction yield 40%, remaining rate of pyrrolidine 27%) . Purification by distillation was carried out, but it was difficult to separate from the starting material completely. INDUSTRIAL APPLICABILITY
Tertiary amines can be produced under mild conditions quantitatively by the present invention.
Moreover, the remaining amount of the compound of the formula (2), as the starting material, contained in the desired tertiary amine can be reduced to a trace amount, for example less than 100 ppm, preferably less than 50 ppm.

CLAIMS
1. A process for producing a tertiary amine of the formula (3) which comprises adding a compound of the formula (2) to a mixture of a compound of the formula (1) or a polymerized product thereof and formic acid
(Formula Removed)
wherein R3 is hydrogen atom or alkyl having 1 to 3 carbon atoms,
(Formula Removed)
wherein R1 and R2 are respectively alkyl having 1 to 3 carbon atoms, and R1 and R2 may form a ring together with a nitrogen atom,
(Formula Removed)
wherein R1 to R3 are as defined above.
2. A process according to claim 1 wherein the compound of the formula (2) is a compound having a pyrrolidine ring.
3. A process according to claim 1 wherein the tertiary amine is N-methylpyrrolidine.
4. A process according to any one of claims 1 to 3,wherein the remaining amount of a starting material of the compound of the formula (2) contained in the desired tertiary amine is less than 100 ppm.
5. A process according to any one of claims 1 to 3, wherein the remaining amount of a starting material of the compound of the formula (2) contained in the desired tertiary amine is less than 5 0 ppm.

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Patent Number

279700

Indian Patent Application Number

6286/DELNP/2008

PG Journal Number

05/2017

Publication Date

03-Feb-2017

Grant Date

30-Jan-2017

Date of Filing

18-Jul-2008

Name of Patentee

OTSUKA CHEMICAL CO., LTD

Applicant Address

2-27, OTEDORI 3-CHOME, CHUO-KU, OSAKA-SHI, OSAKA 540-0021, JAPAN.

Inventors:

#	Inventor's Name	Inventor's Address
1	AKINORI OKA,	C/O OTSUKA CHEMICAL CO. LTD., OF 463, KAGASUNO, KAWAUCHI-CHO, TOKUSHIMA-SHI, TOKUSHIMA.771-0193, JAPAN.
2	AKIHIRO NABESHIMA	C/O OTSUKA CHEMICAL CO. LTD., OF 463, KAGASUNO, KAWAUCHI-CHO, TOKUSHIMA-SHI, TOKUSHIMA.771-0193, JAPAN.
3	YOSHINOBU ABE,	C/O OTSUKA CHEMICAL CO. LTD., OF 463, KAGASUNO, KAWAUCHI-CHO, TOKUSHIMA-SHI, TOKUSHIMA.771-0193, JAPAN.
4	HIROAKI TOKUDA	C/O OTSUKA CHEMICAL CO. LTD., OF 463, KAGASUNO, KAWAUCHI-CHO, TOKUSHIMA-SHI, TOKUSHIMA.771-0193, JAPAN.

PCT International Classification Number

C07D 295/02

PCT International Application Number

PCT/JP2007/051124

PCT International Filing date

2007-01-18

PCT Conventions:

#	PCT Application Number	Date of Convention	Priority Country
1	2006-010366	2006-01-18	Japan