WO2007083839A1 - Méthode de production d'une amine tertiaire - Google Patents

Méthode de production d'une amine tertiaire Download PDF

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Publication number
WO2007083839A1
WO2007083839A1 PCT/JP2007/051124 JP2007051124W WO2007083839A1 WO 2007083839 A1 WO2007083839 A1 WO 2007083839A1 JP 2007051124 W JP2007051124 W JP 2007051124W WO 2007083839 A1 WO2007083839 A1 WO 2007083839A1
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WO
WIPO (PCT)
Prior art keywords
formula
compound
tertiary amine
reaction
pyrrolidine
Prior art date
Application number
PCT/JP2007/051124
Other languages
English (en)
Japanese (ja)
Inventor
Akinori Oka
Akihiro Nabeshima
Yoshinobu Abe
Hiroaki Tokuda
Original Assignee
Otsuka Chemical Co., Ltd.
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Otsuka Chemical Co., Ltd. filed Critical Otsuka Chemical Co., Ltd.
Priority to CN2007800017566A priority Critical patent/CN101360726B/zh
Priority to JP2007555017A priority patent/JP4994246B2/ja
Publication of WO2007083839A1 publication Critical patent/WO2007083839A1/fr

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Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D295/00—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms
    • C07D295/02—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms containing only hydrogen and carbon atoms in addition to the ring hetero elements

Definitions

  • the present invention relates to a method for producing a tertiary amine.
  • Patent Document 1 Japanese Patent Laid-Open No. 04-3-4 2 5 7
  • Patent Document 2 Patent No. 2 5 5 3 0 4 9
  • Patent Documents 1 and 2 require special reaction vessels such as a high-temperature reaction and a high-pressure reaction and cannot be performed under mild conditions.
  • An object of the present invention is to provide a method for producing a tertiary amine which can be quantitatively terminated without leaving raw materials under a mild condition in a general reaction apparatus. Disclosure of the invention
  • the present invention relates to the following inventions.
  • a method for producing a tertiary amine of formula (3) comprising adding a compound of formula (2) to a mixture of a compound of formula (1) or a polymer thereof and formic acid.
  • R 3 represents a hydrogen atom or a C 1 -C 3 alkyl group.
  • R 1 and R 2 represent an alkyl group of Ci Cg. These I 1 , R 2 and a nitrogen atom may form a ring.
  • the present invention is a process for producing a tertiary amine of formula (3), wherein a compound of formula (2) is added to a mixture of a compound of formula (1) or a polymer thereof and formic acid.
  • R 3 Specific examples of the group represented by R 3 are as follows. Examples thereof include a hydrogen atom, a methyl group, an ethyl group, an n-propyl group, an isopropyl group, and a cyclopropyl group, and a hydrogen atom and a methyl group are preferable.
  • the groups represented by ⁇ 1 to! ⁇ 2 are specifically as follows.
  • Examples of the aralkylyl group of CC shu to CC 33 include methethylyl group, ethityryl group, nn--propylopyryl group, isopsopropypropyl group, cycloplopropyl group.
  • Listed here are straight-chain, branched-chain, or cyclic aralkyloxy groups having 11 to 33 carbon atoms such as groups. Totoga can be completed.
  • As a preferable aralkylalkyl group a straight-chain aralkylalkyl group having a carbon number of 11 to 33 is preferable. .
  • 55 to 77 ring rings may be formed to form 55.
  • ring rings such as pipyrrololyridin, hohomomopipiperiperidin, pipepiperiglidin, pipepipera radidin, momorol hololin, etc. Togaga can be completed. .
  • Johorrum Muir Ardede Hyde As a compound of the formula ((11)), specifically, it is as follows. . Johorrum Muir Ardede Hyde, Acetet Ar Ardede Hyde, Pupropylopionon Ardede Hyde, Puptyl Luar Ardede Hyde, Yisosobutytil Ardede Hyde, Papa Examples include Larajoholm Mua Arrude Dehydro, Papara La Seteto Arle Dede Hyde, and the like. . In addition, examples of 1100 and its superpolymerized compounds include Papara La Hojo Mum Ar Ardede Hyde, Papara La Alcede Ar Ardede Hyde, etc. You can be .
  • class 33 class of the formula ((33)) for example, Totririmichichiruruminmin, Totoririechi // Lereaamiminin, Dijechitylrumethichirurua Mimmin, Metetylrudipipilopyramilamine, Methicino Resoropyopopiropirupirminmin, Vetitylrudimethipylpyramiminmin, Djimemetichi Lupropropylamine ,, methicylrupropylamine, 2200 Memethitinorerepipyrrololyridinine, etheticinorepipyrrololyridinin, puprolonorepyrrolidine, isopropinorepyrrolidine, butinorepyrrolidine, tert-butylpyrrolidine, methylhomopiperidine, ethylhomopiperidine , Methylbiberidine, eth ⁇ piperidine, dimethylinopiperazine, cetino
  • the production method of the present invention is specifically as follows.
  • the compound of formula (1) opiformic acid is mixed.
  • the compound of formula (1) and formic acid can also be used in an aqueous solution. Especially low boiling When using formaldehyde or acetonitrile, it is preferable to use it in an aqueous solution or a polymer.
  • the concentration of the aqueous formaldehyde solution is 20 to 50%, preferably 30 to 40%.
  • the concentration of the aqueous solution of cetaldehyde is 50 to 95%, preferably 70 to 90%.
  • the concentration of the formic acid aqueous solution is 60 to 100%, preferably 80% or more.
  • the mixing ratio of the compound of formula (1) and formic acid is 1.0 to 5.0 mol, preferably 2.0 to 4.0 mol of formic acid with respect to 1 mol of the compound of formula (1). If the amount is less than 1.0 mol, the compound of the formula (2) of the raw material may remain, and a large amount of by-products formed by linking the compound of the formula (2) with alkylmethylene is formed. End up. For example, when the compound of the formula (2) is pyrrolidine, dipyrrolidinomethane is produced as a by-product, and when dimethylamine is used, a large amount of tetramethyldiaminomethane is produced. If the amount exceeds 5.0 mol, a large amount of alkali is required for removal, which is uneconomical and may increase the amount of water layer and reduce the recovery rate of the target product.
  • the molar ratio of the compound of the formula (2) and the compound of the formula (1) is 1.0 to 3.0 mol, preferably 1.0, of the compound of the formula (1) to 1 mol of the compound of the formula (2). 0 to 2.5 moles is good.
  • the amount is less than 1.0 mol, the raw material compound of the formula (2) may remain.
  • the amount exceeds 3.0 mol, a large amount of the unreacted compound of the formula (1) remains, and purification may be difficult at the time of removal.
  • the heating temperature may be appropriately adjusted depending on the type of the compound of the formula (1), but is usually preferably in the range of 40 to 120 ° C., and particularly preferably heated to the reflux temperature. Although it depends on the boiling point of the raw material used, it is desirable to carry out the process at as high a temperature as possible so that the added amine reacts instantaneously.
  • the reaction mode in which the temperature is increased by mixing the three components at a low temperature causes the reaction to proceed abruptly, and depending on the heat of reaction and the de-CO 2 balance, bumping may occur, which is extremely dangerous.
  • the secondary amine to be added is preferably used in an aqueous solution, especially if it has a low boiling point.
  • the concentration is 30 to 90%, preferably 40 to 80%.
  • Examples of the addition method include a dropping method and a trickle addition method so that the reaction is exothermic and does not occur rapidly.
  • the addition time may be appropriately adjusted depending on the amount of the mixed solution, but it is usually 5 to 50% / h, preferably 100%, based on the total amount of secondary amine to be added (10.0%). % Z h is good.
  • the addition rate is 50 ° /. If the value exceeds h, there is a possibility of sudden boiling depending on the balance between the heat of reaction and de-co 2 and it is very dangerous.
  • the reaction temperature may be appropriately adjusted depending on the kind of the reaction mixture, but usually it is preferably in the range of 40 to 120 ° C, particularly the reflux temperature.
  • the reaction time may be appropriately adjusted depending on the amount of the mixture, but is usually 1 to 24 hours, preferably 1 to 12 hours, and more preferably 2 to 8 hours.
  • reaction solution After completion of the reaction, the reaction solution is cooled to 10 to 50 ° C.
  • the cooling method may be water cooling.
  • Al force After cooling, add Al force and separate the organic and aqueous layers.
  • an alkaline agent to be added sodium hydroxide, hydroxy hydroxide, sodium carbonate, carbonated lithium, lithium hydroxide, lithium carbonate or an aqueous solution thereof can be used.
  • sodium hydroxide, potassium hydroxide, or an aqueous solution thereof is preferable.
  • the amount of alkali to be added the total amount of solid aluminum is preferably 20 to 50%.
  • the addition temperature should be between room temperature and 60 ° C. Tertiary amines are separated into organic layers. If the addition amount is small, two-layer separation is not sufficient, and even if two layers are separated, the distribution ratio of the target amine to the organic layer is not preferable.
  • an organic solvent can be used.
  • organic solvents can be used.
  • hydrocarbons, halogenated solvents and ethers can be mentioned.
  • the desired product is obtained by distillation. When distilling, select one that has a large difference between the boiling point of the extracted amine and the boiling point of the extraction solvent to facilitate purification.
  • low boiling point amines high boiling point hydrocarbon solvents, etc. 6 2007/051124 is suitable.
  • the tertiary amine was — identified from NMR measurements. The residual amount of raw materials and the yield of tertiary amine were determined by gas chromatography (GC).
  • N-ethyl Pyrrolidine yield after distillation: 95%, pyrrolidine less than 50 ppm
  • Comparative Example 1 N-methylpyrrolidine was produced in the same manner as in Example 1 except that formic acid was added to a mixed solution of pyrrolidine and formaldehyde. Reaction yield 56%, take-off yield 20% (Separation from pyrrolidine was poor, take-out yield was greatly reduced, and formation of by-product dipyrrolidinomethane was confirmed in an amount exceeding 20%.
  • N-methylpyrrolidine was produced in the same manner as in Example 1 except that formaldehyde was added to a mixed solution of pyrrolidine opalic acid. Reaction yield 75%, removal yield 55% (The separation from pyrrolidine was poor and the removal yield was greatly reduced.) Comparative Example 3
  • tertiary amine can be produced almost quantitatively under mild conditions.
  • the residual amount of the compound of the formula (2) contained in the target tertiary amine can be made very small, for example, 100 ppm or less, preferably 5 O ppm or less. Can do.

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)

Abstract

La présente invention concerne une méthode de production d'une amine tertiaire de formule (3) ci-dessous, caractérisée en ce qu'un composé de formule (2) ci-dessous est ajouté au mélange d'un composé de formule (1) ou d'un produit polymérisé dudit composé avec l'acide formique. (1) (Dans la formule, R3 représente un atome d'hydrogène ou un groupement alkyle en C1-C3.) (2) (Dans la formule, R1 et R2 représentent chacun un groupement alkyle en C1-C3, et R1 et R2 peuvent former un cycle avec un atome d'azote.) (3) (Dans la formule, R1-R3 sont tels que définis ci-dessus.)
PCT/JP2007/051124 2006-01-18 2007-01-18 Méthode de production d'une amine tertiaire WO2007083839A1 (fr)

Priority Applications (2)

Application Number Priority Date Filing Date Title
CN2007800017566A CN101360726B (zh) 2006-01-18 2007-01-18 叔胺的制备方法
JP2007555017A JP4994246B2 (ja) 2006-01-18 2007-01-18 第３級アミンの製造方法

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
JP2006010366 2006-01-18
JP2006-010366 2006-01-18

Publications (1)

Publication Number Publication Date
WO2007083839A1 true WO2007083839A1 (fr) 2007-07-26

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PCT/JP2007/051124 WO2007083839A1 (fr) 2006-01-18 2007-01-18 Méthode de production d'une amine tertiaire

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JP (1) JP4994246B2 (fr)
CN (1) CN101360726B (fr)
TW (1) TW200736218A (fr)
WO (1) WO2007083839A1 (fr)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2012518013A (ja) * 2009-02-17 2012-08-09 マリンクロッド インコーポレイテッド ノルモルフィナンの還元的アルキル化のためのプロセス

Families Citing this family (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
KR102073445B1 (ko) * 2012-07-31 2020-02-04 다우 글로벌 테크놀로지스 엘엘씨 올레핀 중합 촉매 활성화제의 제조 방법
CN116478046A (zh) 2022-01-13 2023-07-25 浙江新化化工股份有限公司 一种以仲胺为原料制备叔胺的方法

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
CHELUCCI G. ET AL.: "Synthesis of 1-substituted 2-[(2S)-2-pyrrolidinyl]pyridine from L-proline", SYNTHESIS, no. 12, 1990, pages 1121 - 1122, XP003016001 *
LIU T.-J. ET AL.: "Synthesis of N-methyl pyrrolidine", JINGXIYU ZHUANYONG HUAXUEPIN, vol. 12, no. 10, 2004, pages 24 - 25, XP003016002 *

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2012518013A (ja) * 2009-02-17 2012-08-09 マリンクロッド インコーポレイテッド ノルモルフィナンの還元的アルキル化のためのプロセス
US8431701B2 (en) 2009-02-17 2013-04-30 Mallinckrodt Llc Process for the reductive alkylation of normorphinans

Also Published As

Publication number Publication date
JPWO2007083839A1 (ja) 2009-06-18
CN101360726A (zh) 2009-02-04
CN101360726B (zh) 2011-10-12
TWI337603B (fr) 2011-02-21
TW200736218A (en) 2007-10-01
JP4994246B2 (ja) 2012-08-08

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