JP2002143670A - Continuous reaction method - Google Patents
Continuous reaction methodInfo
- Publication number
- JP2002143670A JP2002143670A JP2000343300A JP2000343300A JP2002143670A JP 2002143670 A JP2002143670 A JP 2002143670A JP 2000343300 A JP2000343300 A JP 2000343300A JP 2000343300 A JP2000343300 A JP 2000343300A JP 2002143670 A JP2002143670 A JP 2002143670A
- Authority
- JP
- Japan
- Prior art keywords
- raw materials
- reaction
- liquid raw
- tubular reactor
- temperature
- Prior art date
- Legal status (The legal status 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 status listed.)
- Pending
Links
Landscapes
- Physical Or Chemical Processes And Apparatus (AREA)
- Thiazole And Isothizaole Compounds (AREA)
- Accessories For Mixers (AREA)
Abstract
Description
【０００１】[0001]
【発明の属する技術分野】本発明は連続反応方法に関
し、詳しくは、管状反応器で複数の液体原料を連続的に
反応させる方法に関するものである。The present invention relates to a continuous reaction method, and more particularly to a method for continuously reacting a plurality of liquid raw materials in a tubular reactor.
【０００２】[0002]
【従来の技術】管状反応器で複数の液体原料を非攪拌条
件下で連続的に均一反応させる方法は公知である（株式
会社 工業調査会 1960年11月20日発行「化学装置設計
ハンドブック」743−744頁を参照）。2. Description of the Related Art A method for continuously and uniformly reacting a plurality of liquid raw materials in a tubular reactor under non-stirring conditions is known ("Chemical Equipment Design Handbook", published by the Industrial Research Council, November 20, 1960, 743). -See page 744).
【０００３】[0003]
【発明が解決しようとする課題】しかしながら、反応が
短時間で終了し、且つ、所望の反応温度よりも温度が高
い条件では副反応が生じる均一反応系では、管状反応器
の場合、反応温度や滞留時間の制御が難しく、目的とす
る有機化合物の収率や純度が低下するという問題があっ
た。However, in a homogeneous reaction system in which the reaction is completed in a short time and a side reaction occurs at a temperature higher than a desired reaction temperature, in the case of a tubular reactor, the reaction temperature or There was a problem that it was difficult to control the residence time and the yield and purity of the target organic compound were reduced.
【０００４】[0004]
【課題を解決するための手段】本発明者はこの問題点を
解決すべく鋭意検討した結果、複数の原料と生成物が互
いに均一に混合しうる連続的な均一反応系において、反
応熱により上昇した液体の温度の最高値が所望の反応温
度になるように、予め、量的比率と温度とが調節された
複数の液体原料をピストンフロー形式の混合器に別々に
供給し、該混合器で混合された均一な混合液を管状反応
器に導いて連続的に反応させることにより、目的とする
有機化合物が高収率、高純度で得られることを見出し、
本発明を完成した。The present inventors have made intensive studies to solve this problem, and as a result, in a continuous homogeneous reaction system in which a plurality of raw materials and products can be uniformly mixed with each other, the reaction temperature increases due to the heat of reaction. A plurality of liquid raw materials whose quantitative ratio and temperature have been adjusted in advance so that the highest value of the temperature of the liquid obtained becomes the desired reaction temperature are separately supplied to a piston flow type mixer, and the mixture is supplied to the mixer. By guiding the mixed homogeneous mixture to a tubular reactor and continuously reacting, it was found that the intended organic compound was obtained in high yield and high purity,
The present invention has been completed.
【０００５】即ち、本発明は、管状反応器で複数の液体
原料を連続的に反応させて目的とする有機化合物を得る
方法において、反応熱により上昇した液体の温度の最高
値が所望の反応温度になるように、予め、複数の液体原
料の量的比率と各原料の温度を調節し、該量的比率と温
度が調節された複数の液体原料をピストンフロー形式の
混合器により混合し、得られた均一な混合液を管状反応
器で非攪拌条件下で反応させることを特徴とする連続反
応方法を提供するものである。以下、本発明を詳細に説
明する。That is, the present invention relates to a method for obtaining a target organic compound by continuously reacting a plurality of liquid raw materials in a tubular reactor, wherein the maximum value of the temperature of the liquid raised by the heat of reaction is a desired reaction temperature. In advance, the quantitative ratio of the plurality of liquid raw materials and the temperature of each raw material are adjusted, and the plurality of liquid raw materials whose quantitative ratio and temperature are adjusted are mixed by a piston flow type mixer to obtain It is intended to provide a continuous reaction method characterized by reacting the obtained homogeneous mixture in a tubular reactor under non-stirring conditions. Hereinafter, the present invention will be described in detail.
【０００６】[0006]
【発明の実施の形態】本発明は管状反応器で複数の液体
原料を連続的に反応させる方法であり、管状反応器は細
長直管でもコイル状でもよいが、原料及び生成物は反応
器では均一な液相を形成しているものである。又、本発
明の反応方法は管状反応器の一端から、ピストンフロー
形式の混合器により均一に混合された複数の液体原料を
連続的に流入させ、上記反応器の他端から生成物を連続
的に流出させるものである。従って、管状反応器では複
数の原料と生成物の重量の和は一定であり、反応混合物
は反応器内をピストンフローしており、生成物の濃度は
流動方向に高くなる。本発明の方法は、反応器内におけ
る反応混合物の滞留時間と温度を適正な範囲に規制する
必要がある連続反応に好適に用いられる。DESCRIPTION OF THE PREFERRED EMBODIMENTS The present invention is a method for continuously reacting a plurality of liquid raw materials in a tubular reactor. The tubular reactor may be an elongated straight tube or a coil. It forms a uniform liquid phase. Further, in the reaction method of the present invention, a plurality of liquid raw materials uniformly mixed by a piston flow type mixer are continuously flowed from one end of a tubular reactor, and a product is continuously flowed from the other end of the reactor. Is to be spilled to Therefore, in a tubular reactor, the sum of the weights of a plurality of raw materials and products is constant, the reaction mixture is piston-flowed in the reactor, and the concentration of the products increases in the flow direction. The method of the present invention is suitably used for a continuous reaction in which the residence time and temperature of a reaction mixture in a reactor need to be controlled within appropriate ranges.
【０００７】本発明の方法は、ピストンフロー形式の混
合器により均一に混合された複数の液体原料を前記管状
反応器の一端から連続的に流入させるものであるが、複
数の液体原料はその１つ又は２つ以上が溶媒を含む溶液
であってもよい。又、反応器内における反応混合物の滞
留時間を適正な範囲に規制するためには、ピストンフロ
ー形式の混合器の下流側の管状反応器の長さを適宜調整
する方法が好ましい。According to the method of the present invention, a plurality of liquid raw materials uniformly mixed by a piston flow type mixer are continuously introduced from one end of the tubular reactor. One or two or more may be solutions containing a solvent. In order to regulate the residence time of the reaction mixture in the reactor within an appropriate range, it is preferable to appropriately adjust the length of the tubular reactor downstream of the piston flow type mixer.
【０００８】本発明の方法で反応させる一方の液体原料
としては、例えば、２−プロピリデン−４−ブロモアセ
ト酢酸メチル及び、該化合物と反応に不活性な有機溶媒
との溶液等が挙げられる。又、本発明の方法で反応させ
る他方の液体原料としては、例えば、チオ尿素と反応に
不活性な有機溶媒との溶液等が挙げられる。上記の反応
に不活性な有機溶媒としては、例えば、トルエン、キシ
レン等の芳香族炭化水素類、へキサン、へプタン等の脂
肪族炭化水素類、ジクロロメタン、ジクロロエタン、ク
ロロホルム、１−クロロブタン、クロロベンゼン等のハ
ロゲン化炭化水素類、ジエチルエーテル、ｔ−ブチルメ
チルエーテル、テトラヒドロフラン、ジメトキシエタン
等のエーテル類、アセトン、メチルエチルケトン、メチ
ルイソブチルケトン等のケトン類、Ｎ，Ｎ−ジメチルホ
ルムアミド、Ｎ−メチルピロリドン等のアミド類、メタ
ノール、エタノール、１−プロパノール等のアルコール
類や水が挙げられる。２−プロピリデン−４−ブロモア
セト酢酸メチルとチオ尿素との反応におけるモル比は、
好ましくは１：0.9〜１：５、より好ましくは１：１〜
１：1.05の範囲である。又、上記反応における反応温度
は好ましくは０〜３５℃、より好ましくは２３〜２７℃
の範囲であり、反応時間は好ましくは５〜２０分であ
り、特に好ましくは約１０分である。[0008] Examples of one of the liquid raw materials to be reacted by the method of the present invention include methyl 2-propylidene-4-bromoacetoacetate and a solution of the compound and an organic solvent inert to the reaction. Examples of the other liquid raw material to be reacted by the method of the present invention include a solution of thiourea and an organic solvent inert to the reaction. Examples of the organic solvent inert to the above reaction include aromatic hydrocarbons such as toluene and xylene, aliphatic hydrocarbons such as hexane and heptane, dichloromethane, dichloroethane, chloroform, 1-chlorobutane, chlorobenzene and the like. Halogenated hydrocarbons, ethers such as diethyl ether, t-butyl methyl ether, tetrahydrofuran and dimethoxyethane; ketones such as acetone, methyl ethyl ketone and methyl isobutyl ketone; N, N-dimethylformamide, N-methylpyrrolidone and the like Examples include amides, alcohols such as methanol, ethanol, and 1-propanol, and water. The molar ratio in the reaction between methyl 2-propylidene-4-bromoacetoacetate and thiourea is:
Preferably 1: 0.9 to 1: 5, more preferably 1: 1 to 1
1: in the range of 1.05. The reaction temperature in the above reaction is preferably 0 to 35 ° C, more preferably 23 to 27 ° C.
And the reaction time is preferably from 5 to 20 minutes, particularly preferably about 10 minutes.
【０００９】[0009]
【実施例】以下、実施例により本発明を更に詳細に説明
するが、本発明はこれらの例により、何ら限定されるも
のではない。なお、例中の部及び％は、それぞれ、重量
部及び重量％を表す。EXAMPLES The present invention will be described in more detail with reference to the following Examples, which should not be construed as limiting the present invention. In the examples, parts and% indicate parts by weight and% by weight, respectively.
【００１０】参考例１ 酢酸３５６０部を１−クロロブタン３６９００部に溶解
させ、得られた溶液に約−３０℃で４−ブロモアセト酢
酸メチル２５３５０部、ピロピオンアルデヒド１７２２
０部及びピペリジン１２６０部の３成分をそれぞれ独立
に６時間かけて同時に滴下した。同温度で２時間攪拌
し、得られた反応混合物を１．４％塩酸水溶液３７８０
０部中に注ぎ、５℃まで昇温後、分液した。得られた有
機層を約５℃で亜硫酸水素ナトリウム水溶液４２６００
部で洗浄し、油層を水３６３００部で洗浄して、２−プ
ロピリデン−４−ブロモアセト酢酸メチル２６７００部
を含む１−クロロブタン溶液７３２００部を得た。Reference Example 1 3560 parts of acetic acid were dissolved in 36900 parts of 1-chlorobutane, and the resulting solution was added at about -30 ° C with 25350 parts of methyl 4-bromoacetoacetate and 1722 parts of pyropionaldehyde.
0 parts and 1260 parts of piperidine were simultaneously and independently added dropwise over 6 hours. The mixture was stirred at the same temperature for 2 hours, and the obtained reaction mixture was treated with a 1.4% aqueous hydrochloric acid solution (3780).
The mixture was poured into 0 parts, heated to 5 ° C., and separated. The obtained organic layer was treated at about 5 ° C. with an aqueous solution of sodium hydrogen sulfite (42600).
The oil layer was washed with 36300 parts of water to obtain 73200 parts of a 1-chlorobutane solution containing 26700 parts of methyl 2-propylidene-4-bromoacetoacetate.
【００１１】実施例１ チオ尿素を１９．５％含むＮ，Ｎ−ジメチルホルムアミ
ド溶液を図１のタンクＴ1内で調製し、［液体原料１］
とした。別途、参考例１で得た１−クロロブタン溶液の
１８７０部を図１のタンクＴ2に仕込み、１−クロロブ
タン溶液中の２−プロピリデン−４−ブロモアセト酢酸
メチル量に対して、１．４倍重量の１−クロロブタンと
１．４倍重量のアセトンとを加え、約−２０℃に冷却し
て、［液体原料２］を得た。容量１Ｌ、エレメント数18
個のスタティックミキサーＭと、これに連結された直管
状の反応器Ｒ（容量180Ｌ）へ、液体原料１及び液体原
料２を、各々、毎時248ｋｇ及び毎時809ｋｇの速度で、
ポンプＰ1及びポンプＰ2により同時に注入した。断熱系
における反応時の混合物の平均滞留時間は約10分であ
り、温度は25℃に保たれていた。なお、［液体原料２］
はスタティックミキサーＭ内に入る前に予め冷却され
た。反応器Ｒから出た混合物は熱交換器Ｅ2により予め
冷却された後、タンクＳ内で約−２０℃に冷却した１−
クロロブタン中に注入された。１−クロロブタン中に注
入された反応混合物の中の（Ｚ）−２−（２−アミノチ
アゾール−４−イル）−２−ペンテン酸メチルの臭化水
素付加塩の収率は、約６４％であった。又、（Ｅ）−２
−（２−アミノチアゾール−４−イル）−２−ペンテン
酸メチルの臭化水素付加塩の収率は、約２５％であっ
た。［Ｅ／Ｚ＝２８／７２］[0011] N containing 19.5% Example 1 thiourea, to prepare a N- dimethylformamide in the tank T 1 of the FIG. 1, [Liquid material 1]
And Separately, were charged 1870 parts of 1-chlorobutane solution obtained in Reference Example 1 to a tank T 2 of the FIG. 1, based on 2-propylidene-4-Buromoaseto methyl acetate content in 1-chlorobutane solution, 1.4 times by weight Of 1-chlorobutane and 1.4 times the weight of acetone were added, and the mixture was cooled to about −20 ° C. to obtain [Liquid material 2]. 1L capacity, 18 elements
The liquid raw material 1 and the liquid raw material 2 were fed into the static mixer M and the straight tubular reactor R (capacity: 180 L) connected thereto at a speed of 248 kg / h and 809 kg / h, respectively.
It was simultaneously injected by the pump P 1 and the pump P 2. The average residence time of the mixture during the reaction in the adiabatic system was about 10 minutes and the temperature was kept at 25 ° C. [Liquid raw material 2]
Was pre-cooled before entering the static mixer M. After the mixture leaving the reactor R is in advance cooled by the heat exchanger E 2, and cooled to about -20 ° C. in the tank S 1-
Injected into chlorobutane. The yield of the hydrogen bromide addition salt of methyl (Z) -2- (2-aminothiazol-4-yl) -2-pentenoate in the reaction mixture injected into 1-chlorobutane is about 64%. there were. Also, (E) -2
The yield of the hydrogen bromide addition salt of methyl- (2-aminothiazol-4-yl) -2-pentenoate was about 25%. [E / Z = 28/72]
【００１２】[0012]
【発明の効果】本発明によれば、目的とする有機化合物
が高純度、高収率で得られる。According to the present invention, the desired organic compound can be obtained with high purity and high yield.
【図１】実施例１で用いた反応装置。FIG. 1 shows a reaction apparatus used in Example 1.
Ｔ1，Ｔ2，Ｓ・・タンク、Ｍ・・スタティックミキサ
ー、Ｒ・・管状反応器、Ｅ1，Ｅ2・・熱交換器T 1 , T 2 , S tank, M static mixer, R tubular reactor, E 1 , E 2 heat exchanger
───────────────────────────────────────────────────── フロントページの続き (51)Int.Cl.7 識別記号 ＦＩ テーマコート゛(参考） Ｃ０７Ｄ 277/40 Ｃ０７Ｄ 277/40 Ｆターム(参考） 4C033 AD13 AD16 AD18 4G035 AB37 AC01 4G037 BA01 EA01 4G075 AA13 AA62 AA63 BD04 BD15 BD22 CA02 CA80 DA02 DA12 EB21 EC06 EC11 ED20 ──────────────────────────────────────────────────続 き Continued on the front page (51) Int.Cl. 7 Identification symbol FI Theme coat ゛ (Reference) C07D 277/40 C07D 277/40 F-term (Reference) 4C033 AD13 AD16 AD18 4G035 AB37 AC01 4G037 BA01 EA01 4G075 AA13 AA62 AA63 BD04 BD15 BD22 CA02 CA80 DA02 DA12 EB21 EC06 EC11 ED20
Claims (3)
応させて目的とする有機化合物を得る方法において、反
応熱により上昇した液体の温度の最高値が所望の反応温
度になるように、予め、複数の液体原料の量的比率と各
原料の温度を調節し、該量的比率と温度が調節された複
数の液体原料をピストンフロー形式の混合器により混合
し、得られた均一な混合液を管状反応器で非攪拌条件下
で反応させることを特徴とする連続反応方法。1. A method for obtaining a target organic compound by continuously reacting a plurality of liquid raw materials in a tubular reactor so that the maximum value of the temperature of the liquid raised by the heat of reaction becomes a desired reaction temperature. In advance, the quantitative ratio of the plurality of liquid raw materials and the temperature of each raw material are adjusted, and the plurality of liquid raw materials whose quantitative ratio and temperature are adjusted are mixed by a piston flow type mixer, and the obtained uniform A continuous reaction method comprising reacting a mixed solution in a tubular reactor under non-stirring conditions.
ックミキサーである請求項１に記載の方法。2. The method according to claim 1, wherein the mixer of the piston flow type is a static mixer.
に記載の方法。3. The method according to claim 1, wherein the reaction is performed in an adiabatic system.
The method described in.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP2000343300A JP2002143670A (en) | 2000-11-10 | 2000-11-10 | Continuous reaction method |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP2000343300A JP2002143670A (en) | 2000-11-10 | 2000-11-10 | Continuous reaction method |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| JP2002143670A true JP2002143670A (en) | 2002-05-21 |
Family
ID=18817693
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2000343300A Pending JP2002143670A (en) | 2000-11-10 | 2000-11-10 | Continuous reaction method |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JP2002143670A (en) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN110252236A (en) * | 2019-07-08 | 2019-09-20 | 湖北仙粼化工有限公司 | A kind of diethanol monoisopropanolamine production multiple spot mixing reactor |
| WO2019187497A1 (en) * | 2018-03-27 | 2019-10-03 | 株式会社カネカ | Flow type reactor and manufacturing facility including same |
-
2000
- 2000-11-10 JP JP2000343300A patent/JP2002143670A/en active Pending
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2019187497A1 (en) * | 2018-03-27 | 2019-10-03 | 株式会社カネカ | Flow type reactor and manufacturing facility including same |
| JPWO2019187497A1 (en) * | 2018-03-27 | 2021-03-18 | 株式会社カネカ | Flow reactor and manufacturing equipment with it |
| US11235304B2 (en) | 2018-03-27 | 2022-02-01 | Kaneka Corporation | Flow reactor and manufacturing facility comprising the flow reactor |
| JP7239559B2 (en) | 2018-03-27 | 2023-03-14 | 株式会社カネカ | Flow type reactor and manufacturing equipment having the same |
| CN110252236A (en) * | 2019-07-08 | 2019-09-20 | 湖北仙粼化工有限公司 | A kind of diethanol monoisopropanolamine production multiple spot mixing reactor |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| JP3560652B2 (en) | Mixing method | |
| Sprecher et al. | Acyl azide synthesis and curtius rearrangements in microstructured flow chemistry systems | |
| CN106714801A (en) | Continuous flow carboxylation reaction | |
| CN112321496B (en) | Method for synthesizing 2-amino-3-chloro-5-trifluoromethylpyridine | |
| CN109232363B (en) | Synthetic method of 3-selenocyanoindole compound | |
| CN102617385A (en) | Methylene method for producing acetochlor | |
| JP2002143670A (en) | Continuous reaction method | |
| CN110283082A (en) | A kind of preparation method of 3- phenylpropylamine | |
| CN108358806B (en) | Continuous synthesis method of m-acetamidophenol | |
| CN112979579B (en) | Low-temperature diazonium salt continuous preparation method of halogenated thiazole compound | |
| CN107353211A (en) | The synthetic method of enamine compound and the synthetic method of aromatic aldehyde compound | |
| CN112876416B (en) | Diaryl formyl substituted pyrazole compound and preparation method thereof | |
| CN112574070B (en) | Synthesis method of substituted urea compound | |
| CN112358404A (en) | Preparation method of 2-chloro-6-methylaniline | |
| JPH06122667A (en) | Continuous preparation of 3-cyano-3,5,5-trimethylcyclo- hexanone | |
| JP2002519409A (en) | Method for producing 2-nitro-5- (phenylthio) -aniline | |
| CN102341361A (en) | Chemical process for the production of haloalkenone ethers | |
| WO2007090464A1 (en) | Process for preparing letrozole | |
| US4328369A (en) | Process for the production of 2,6-dinitro-N-alkyl-anilines | |
| EP0169375A2 (en) | Process for producing 2-tert.-butyl-4,5-dichloro-3(2H)-pyridazinone | |
| RU2819796C2 (en) | Method of obtaining plant growth regulator | |
| CN113620837B (en) | Preparation method of anastrozole intermediate 3, 5-di (2-cyano-propyl-2-yl) bromotoluene | |
| CN113831295B (en) | Method for synthesizing rosuvastatin ester by using continuous flow tubular reactor | |
| TW201835036A (en) | Method for preparation of 1-methyl-3-(trifluoromethyl)-1H-pyrazol-5-ol | |
| CN108822060B (en) | 3-aryl substituted oxetane and preparation method thereof |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20040915 |
|
| A977 | Report on retrieval |
Free format text: JAPANESE INTERMEDIATE CODE: A971007 Effective date: 20070711 |
|
| A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20070717 |
|
| A02 | Decision of refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A02 Effective date: 20071204 |