JP2006124344A - Apparatus and method for continuous synthesis - Google Patents

Apparatus and method for continuous synthesis Download PDF

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JP2006124344A
JP2006124344A JP2004316793A JP2004316793A JP2006124344A JP 2006124344 A JP2006124344 A JP 2006124344A JP 2004316793 A JP2004316793 A JP 2004316793A JP 2004316793 A JP2004316793 A JP 2004316793A JP 2006124344 A JP2006124344 A JP 2006124344A
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solvent
raw material
reaction tube
heavy
light
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Kenichiro Kurono
野 健一郎 黒
Maiko Tomita
田 麻衣子 冨
Toru Miyougadani
徹 茗荷谷
Kazuhiro Chiba
葉 一 裕 千
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Moritex Corp
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Moritex Corp
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Priority to PCT/JP2005/019543 priority patent/WO2006046530A1/en
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    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J19/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
    • B01J19/24—Stationary reactors without moving elements inside
    • B01J19/2415—Tubular reactors
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J19/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
    • B01J19/0006—Controlling or regulating processes
    • B01J19/0013—Controlling the temperature of the process
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
    • B01J2219/00002—Chemical plants
    • B01J2219/00027—Process aspects
    • B01J2219/0004—Processes in series

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Abstract

<P>PROBLEM TO BE SOLVED: To continuously produce the objective synthetic substance simply by continuously flowing solvents containing a raw material dissolved therein. <P>SOLUTION: An apparatus (1) for continuous synthesis is designed to use 2 kinds of solvents having different specific gravities and assuming compatibility/phase separation properties according to the temperature, react a first raw material (X) soluble in the lightweight solvent having a low specific gravity and a second raw material (Y) soluble in the heavy solvent having a large specific gravity in a compatible region and continuously produce the synthetic substance (Z) soluble only in either one of the lightweight solvent and the heavy solvent. The apparatus is equipped with a reaction tube (2) provided with a temperature controller for maintaining the upper stage and the lower stage at a phase separation temperature of each solvent and maintaining the middle stage at the compatible temperature of the solvents, a lightweight solvent feed system (5L) for feeding the first raw material (X) together with the lightweight solvent from the lower end thereof and a heavy solvent feed system (5H) for feeding the second raw material (Y) together with the heavy solvent from the top thereof. Furthermore, a synthetic substance recovering port (12L) for recovering the solvent in which the synthetic substance (Z) is dissolved therein is formed. <P>COPYRIGHT: (C)2006,JPO&NCIPI

Description

本発明は、比重が異なり温度に応じて相溶性／相分離性を呈する二種類の溶媒を用いて、二種類以上の原料反応させて合成物を連続的に生成する連続合成装置及び方法に関し、特に、ペプチド、蛋白質、ＤＮＡ、ＲＮＡ、多糖類などオリゴマー、ポリマー類の合成に適している。   The present invention relates to a continuous synthesis apparatus and method for continuously producing a synthesized product by reacting two or more kinds of raw materials using two kinds of solvents having different specific gravity and exhibiting compatibility / phase separation depending on temperature, In particular, it is suitable for the synthesis of oligomers and polymers such as peptides, proteins, DNA, RNA and polysaccharides.

近年、核酸（ＤＮＡ）、タンパク質に続く第三の鎖状生命分子として、糖鎖分子が注目されている。
糖鎖とは、グルコースやガラクトース等の８種類の単糖がつながったものであり、一般的には、数個〜十数個の単糖がつながった糖鎖をオリゴ糖、それ以上のものが多糖と呼ばれている。 In recent years, sugar chain molecules have attracted attention as a third chain life molecule following nucleic acids (DNA) and proteins.
A sugar chain is a chain of 8 monosaccharides such as glucose and galactose. Generally, a sugar chain of several to a dozen or more monosaccharides is linked to an oligosaccharide and more. It is called a polysaccharide.

この糖鎖分子は、ヒトを構成する約６０兆個の全ての細胞表面を覆い、細胞間の認識や相互作用に関わる働きを有している。
そして、細胞自身に異常を来たすと、細胞表面にある糖鎖も乱れ、癌、慢性疾患、感染症、免疫不全などの異常や、肉体及び神経系、脳機能の老化につながる。
例えば、細胞が癌化すると糖鎖の構造変化が起こり、コレラ菌やインフルエンザウィルスなどは、細胞表面に存する特定の糖鎖を認識し結合することにより細胞内に侵入して感染することが知られている。
したがって、糖鎖の分子認識脳を解明することにより、新しい原理に基づく医薬品や食品を開発することができ、さらには、病気の予防や治療に役立てることができるなど幅広い応用が期待される。 This sugar chain molecule covers the surface of all about 60 trillion cells constituting humans and has a function related to recognition and interaction between cells.
If an abnormality occurs in the cell itself, sugar chains on the cell surface are disturbed, leading to abnormalities such as cancer, chronic diseases, infectious diseases, immunodeficiencies, and aging of the body, nervous system, and brain function.
For example, structural changes in sugar chains occur when cells become cancerous, and Vibrio cholerae and influenza viruses are known to enter and infect cells by recognizing and binding to specific sugar chains on the cell surface. ing.
Therefore, by clarifying the molecular recognition brain of sugar chains, it is possible to develop pharmaceuticals and foods based on a new principle, and further, a wide range of applications such as being useful for disease prevention and treatment are expected.

この基礎研究としてまず糖鎖を人工的に合成するため、温度に応じて相溶性状態と相分離性状態とに可逆的に変化する溶媒システムを用いて糖鎖ペプチドなどを合成する方法が提案されている。
特開２００３−１８３２９８ As basic research, in order to synthesize sugar chains artificially, a method of synthesizing sugar peptides and the like using a solvent system that reversibly changes between a compatible state and a phase-separated state according to temperature was proposed. ing.
JP 2003-183298 A

これは、第一原料及び第二原料を反応させて合成物を生成する際に、比重が異なり、常温で相分離性／５０℃前後で相溶性を呈する二種類の溶媒を用いる。
そして、例えば、比重の軽い軽量溶媒としては第一原料及び合成物を溶かし第二原料を溶かさない液体が選定され、比重の重い重量溶媒としては第一原料及び合成物を溶かさず第二原料を溶かす液体が選定されている。 This uses two kinds of solvents that have different specific gravity when they are reacted with the first raw material and the second raw material and exhibit phase separation at room temperature / compatible at around 50 ° C.
For example, a liquid that dissolves the first raw material and the compound and does not dissolve the second raw material is selected as the light solvent having a low specific gravity, and the second raw material is dissolved in the heavy solvent having a high specific gravity without dissolving the first raw material and the compound. The liquid to be dissolved is selected.

そして、まず、第一原料を溶かした軽量溶媒と、第二原料を溶かした重量溶媒を反応容器に所定量注入すると、常温で溶媒同士が相分離性を呈し、軽量溶媒と重量溶媒が分離される。
次いで、反応容器を５０℃に加熱して攪拌させると、溶媒同士が相溶性を呈して溶け合うので、夫々の溶媒中に溶けていた第一原料及び第二原料が相溶性溶媒中で反応し、合成物が生成される。
最後に、溶媒を常温に戻すと、溶媒同士が相分離性を呈し、軽量溶媒と重量溶媒が分離され、生成された合成物は重量溶媒には溶けないので軽量溶媒中に存在することとなり、この軽量溶媒中から合成物を抽出することにより目的とする合成物が得られる。 First, when a predetermined amount of a light solvent in which the first raw material is dissolved and a heavy solvent in which the second raw material is dissolved is injected into the reaction vessel, the solvents exhibit phase separation at room temperature, and the light solvent and the heavy solvent are separated. The
Next, when the reaction vessel is heated to 50 ° C. and stirred, the solvents are compatible with each other, so that the first raw material and the second raw material dissolved in each solvent react in the compatible solvent, A composite is produced.
Finally, when the solvent is returned to room temperature, the solvents exhibit phase-separation properties, the light solvent and the heavy solvent are separated, and the resulting composition does not dissolve in the heavy solvent, so it will be present in the light solvent, By extracting the synthesized product from this light solvent, the intended synthesized product can be obtained.

しかしながら、このようなバッチ処理は非効率的であり、反応を行なう度に溶媒を入れ替えたり、昇温／降温させて温度コントロールするのも面倒であり、自動化するには困難であった。
特に、目的とする合成物を得るのに反応を何回も繰り返さなければならない場合は、合成物が溶けた軽量溶媒を別の反応容器に移して、次に反応させる第二原料を溶かした重量溶媒を入れ、同様の反応処理を必要な回数だけ繰り返さなければならないという面倒があった。 However, such batch processing is inefficient, and it is troublesome to change the solvent each time the reaction is performed, and to control the temperature by raising / lowering the temperature, which is difficult to automate.
In particular, when the reaction must be repeated many times to obtain the target compound, the weight of the second raw material to be reacted next is transferred to another reaction vessel with the light solvent in which the compound is dissolved. It was troublesome that the same reaction treatment had to be repeated as many times as necessary by adding a solvent.

そこで本発明は、溶媒を移し変えることなく流しつづけるだけで、目的とする合成物を連続的に生成することができるようにすることを技術的課題としている。   Therefore, the present invention has a technical problem to be able to continuously produce a target compound simply by continuing to flow without changing the solvent.

この課題を解決するために、本発明は、比重が異なり温度に応じて相溶性／相分離性を呈する二種類の溶媒を用い、比重の軽い軽量溶媒に溶ける第一原料と、比重の重い重量溶媒に溶ける第二原料を相溶性領域で反応させ、軽量溶媒及び重量溶媒のいずれか一方にのみ溶ける合成物を連続的に生成する連続合成装置であって、上段及び下段が溶媒の相分離温度に維持され、中段が溶媒の相溶温度に維持される温度制御装置を備えた反応管と、その下端から第一原料を軽量溶媒と共に供給する軽量溶媒供給系と、その上端から第二原料を重量溶媒と共に供給する重量溶媒供給系を備えると共に、合成物が溶けた溶媒を回収する合成物回収口が形成されたことを特徴とする。   In order to solve this problem, the present invention uses two kinds of solvents having different specific gravity and exhibiting compatibility / phase separation depending on temperature, a first raw material that is soluble in a light solvent having a low specific gravity, and a weight having a high specific gravity. A continuous synthesizer in which a second raw material that is soluble in a solvent is reacted in a compatible region to continuously produce a compound that is soluble only in either a light solvent or a heavy solvent, the upper and lower stages being the phase separation temperature of the solvent A reaction tube equipped with a temperature control device in which the middle stage is maintained at the solvent compatibility temperature, a lightweight solvent supply system for supplying the first raw material together with a light solvent from the lower end thereof, and a second raw material from the upper end thereof. In addition to the weight solvent supply system that supplies the solvent together with the weight solvent, a composition recovery port for recovering the solvent in which the composition is dissolved is formed.

本発明の連続合成装置によれば、反応管内を上昇する軽量溶媒と、反応管内を流下する重量溶媒が中段に達すると相溶性を呈し、夫々に溶けている第一原料と第二原料が反応し、反応管上段まで上昇した軽量溶媒中には生成された合成物が溶けている。
したがって、第二原料が溶けた重量溶媒を反応管に所要量充填した状態で、第一原料が解けた軽量溶媒を供給しつづければ、合成物が溶けた軽量溶媒が反応管の上端に形成された合成物回収口から流出し、連続的に合成物を生成することができるという効果がある。 According to the continuous synthesizer of the present invention, the lightweight solvent rising in the reaction tube and the heavy solvent flowing down in the reaction tube reach compatibility when they reach the middle stage, and the first raw material and the second raw material, respectively, react with each other. However, the synthesized product is dissolved in the lightweight solvent that has been raised to the upper stage of the reaction tube.
Therefore, if you continue to supply the light solvent that the first raw material has melted while filling the reaction tube with the required amount of the heavy solvent in which the second raw material has dissolved, the light solvent that has dissolved the compound will form at the top of the reaction tube. It is effective that it can flow out from the synthesized product recovery port and continuously produce a synthesized product.

また、反応管を多段に接続して、前段の反応管で生成された合成物を次段の反応管の第一原料として順送りすることにより、夫々の反応管で順次反応を行わせれば、目的とする合成物を得るために何度も反応を繰り返さなければならない場合に溶媒を流すだけで複数種類の反応を順次行わせることができるという効果がある。
さらに、各反応管で同じ反応を繰返し行わせれば、供給した原料を効率良く反応させることができるという効果がある。 In addition, if the reaction tubes are connected in multiple stages and the reaction product is sequentially sent in the respective reaction tubes by sequentially feeding the synthesis product produced in the previous reaction tube as the first raw material of the next reaction tube, When the reaction must be repeated many times in order to obtain the synthesized product, there is an effect that a plurality of types of reactions can be sequentially performed only by flowing a solvent.
Furthermore, if the same reaction is repeatedly performed in each reaction tube, the supplied raw material can be efficiently reacted.

本例では、目的とする合成物を連続的に生成することができるようにするという課題を、合成物を溶かす溶媒を移し変えることなく流しつづけるだけで達成できるようにした。   In this example, it was made possible to achieve the task of continuously producing the target compound simply by flowing it without changing the solvent in which the compound is dissolved.

図１は本発明に係る連続合成装置の説明図、図２はその使用方法を示す説明図、図３は他の実施形態を示す説明図、図４はその使用方法を示す説明図、図５はさらに他の実施形態を示す説明図、図６はその使用方法を示す説明図である。   FIG. 1 is an explanatory diagram of a continuous synthesis apparatus according to the present invention, FIG. 2 is an explanatory diagram showing how to use it, FIG. 3 is an explanatory diagram showing another embodiment, FIG. 4 is an explanatory diagram showing how to use it, FIG. FIG. 6 is an explanatory view showing still another embodiment, and FIG. 6 is an explanatory view showing a method of using the same.

図１に示す連続合成装置１は、比重が異なり温度に応じて相溶性／相分離性を呈する二種類の溶媒を用い、比重の軽い軽量溶媒に溶ける第一原料と、比重の重い重量溶媒に溶ける第二原料を相溶性領域で反応させ、例えば軽量溶媒にのみ溶ける合成物を連続的に生成するものである。   The continuous synthesizer 1 shown in FIG. 1 uses two kinds of solvents having different specific gravity and exhibiting compatibility / phase separation depending on the temperature. The first raw material is soluble in a light solvent having a low specific gravity and the heavy solvent having a high specific gravity. The second raw material that melts is reacted in the compatible region, and for example, a synthetic product that is soluble only in a light solvent is continuously generated.

この連続合成装置１は、軽量溶媒に溶けた第一原料と、重量溶媒に溶けた第二原料を反応させる反応管２と、その反応管２の長手方向に任意の温度分布を形成する温度制御装置３を備えている。   This continuous synthesis apparatus 1 includes a reaction tube 2 for reacting a first raw material dissolved in a light solvent and a second raw material dissolved in a heavy solvent, and temperature control for forming an arbitrary temperature distribution in the longitudinal direction of the reaction tube 2. A device 3 is provided.

温度制御装置３は、反応管２の上段、中段、下段の温度管理を個別に行う冷熱器４Ｕ、４Ｍ、４Ｄを備え、上下両段を各溶媒の相分離温度（例えば室温）に維持すると共に、中段を各溶媒の相溶温度（例えば５０℃）に維持している。
これにより、上段及び下段では軽量溶媒と重量溶媒が溶け合うことなく完全に分離され、中段では軽量溶媒と重量溶媒が完全に溶け合う相溶性を呈する。 The temperature control device 3 includes chillers 4U, 4M, and 4D that individually manage the upper, middle, and lower temperatures of the reaction tube 2, and maintain the upper and lower stages at the phase separation temperature (for example, room temperature) of each solvent. The middle stage is maintained at a compatible temperature (for example, 50 ° C.) of each solvent.
As a result, the light and heavy solvents are completely separated from each other in the upper and lower stages, and the light and heavy solvents are completely dissolved in the middle stage.

また、反応管２には、その下端側から第一原料を軽量溶媒と共に供給する軽量溶媒供給系５Ｌと、その上端側から第二原料を重量溶媒と共に供給する重量溶媒供給系５Ｈが接続されている。
軽量溶媒供給系５Ｌは、軽量溶媒のみを貯留した溶媒タンク６Ｌと、第一原料を溶かした状態で軽量溶媒を貯留した原料タンク７Ｌが、切換バルブ８Ｌを介してポンプ９Ｌに接続され、ポンプ９Ｌの吐出口が軽量溶媒供給管１０Ｌを介して反応管２の下端面から所要長さ上方へ突出された流入口１１Ｌに接続されている。
重量溶媒供給系５Ｈは、重量溶媒のみを貯留した溶媒タンク６Ｈと、第二原料を溶かした状態で重量溶媒を貯留した原料タンク７Ｈが、切換バルブ８Ｈを介してポンプ９Ｈに接続され、ポンプ９Ｈの吐出口が重量溶媒供給管１０Ｈを介して反応管２の上端面から所要長さ下方へ突出された流入口１１Ｈに接続されている。
また、反応管２の上端面には反応管２内を上昇してきた軽量溶媒を流出させる軽量溶媒流出口（合成物回収口）１２Ｌが開口形成されて回収タンク１３に接続され、下端面には、反応管２内を流下してきた重量溶媒を流出させる重量溶媒流出口１２Ｈが開口形成されて廃液タンク１４に接続されている。
そして、各流入口１１Ｌ及び１１ＨにはオンオフバルブＶ１及びＶ３が設けられ、流出口１２Ｌ及び１２Ｈには流量調整弁Ｖ２及びＶ４が設けられている。
なお、図示は省略するが反応管の中段には攪拌器が設けられている。 The reaction tube 2 is connected to a lightweight solvent supply system 5L that supplies the first raw material together with the light solvent from the lower end side thereof, and a heavy solvent supply system 5H that supplies the second raw material together with the heavy solvent from the upper end side thereof. Yes.
In the light solvent supply system 5L, a solvent tank 6L storing only a light solvent and a raw material tank 7L storing a light solvent in a state where the first raw material is dissolved are connected to a pump 9L via a switching valve 8L. Is connected to an inflow port 11L protruding upward from the lower end surface of the reaction tube 2 by a required length via a lightweight solvent supply tube 10L.
In the heavy solvent supply system 5H, a solvent tank 6H that stores only the heavy solvent and a raw material tank 7H that stores the heavy solvent in a state where the second raw material is dissolved are connected to a pump 9H via a switching valve 8H. Is connected to an inflow port 11H protruding downward from the upper end surface of the reaction tube 2 by a required length via a heavy solvent supply tube 10H.
In addition, a light solvent outlet (synthetic product recovery port) 12L through which the light solvent that has risen in the reaction tube 2 flows out is formed at the upper end surface of the reaction tube 2 and connected to the recovery tank 13, and the lower end surface is connected to the lower end surface. A heavy solvent outlet 12H through which the heavy solvent flowing down in the reaction tube 2 flows out is formed to be connected to the waste liquid tank 14.
Then, each inlet 11L and 11H are provided on-off valves V 1 and V 3, the flow control valve V 2 and V 4 are provided on the outlet 12L and 12H.
Although not shown, a stirrer is provided in the middle stage of the reaction tube.

以上が本発明の一構成例であって、次にその作用について説明する。
まず、図２（ａ）に示すように、溶媒タンク６Ｌ及び６Ｈから、軽量溶媒（例えばシクロヘキサン）と重量溶媒（ＤＭＦ／ＤＭＡ溶液）を１：１で反応管２内に貯留すると、これらは室温では相分離性を呈するので、軽量溶媒と重量溶媒が上層及び下層に分離する。
ここで、温度制御装置３により各冷熱器４Ｕ、４Ｍ、４Ｄの温度をコントロールし、反応管２の上段及び下段を相分離温度に維持し、中段を相溶温度に維持すると、図２（ｂ）に示すように、反応管２の中段に軽量溶媒と重量溶媒が溶け合った相溶領域２Ｍが形成され、上段には軽量溶媒領域２Ｕ、下段には重量溶媒領域２Ｄが形成される。 The above is one configuration example of the present invention, and the operation thereof will be described next.
First, as shown in FIG. 2 (a), when a light solvent (for example, cyclohexane) and a heavy solvent (DMF / DMA solution) are stored 1: 1 in the reaction tube 2 from the solvent tanks 6L and 6H, these are room temperature. Then, since the phase separation property is exhibited, the light solvent and the heavy solvent are separated into an upper layer and a lower layer.
Here, when the temperature of each of the coolers 4U, 4M, and 4D is controlled by the temperature control device 3, the upper and lower stages of the reaction tube 2 are maintained at the phase separation temperature, and the middle stage is maintained at the compatible temperature, FIG. ), A compatible region 2M in which a light solvent and a heavy solvent are dissolved is formed in the middle stage of the reaction tube 2, a light solvent area 2U is formed in the upper stage, and a heavy solvent area 2D is formed in the lower stage.

この状態で、図２（ｃ）に示すように、各原料タンク７Ｌ及び７Ｈからポンプ９Ｌ及び９Ｈにより第一原料Ｘ（例えば、シクロヘキサン可溶性担体（（Ｃ１８Ｈ３７Ｏ）３Ｃ６Ｈ２ＣＯＨ））：（３，４，５−トリオクタデシルオキシフェニル）メタン−１−オール）及び第二原料Ｙ（例えば（Ｆｍｏｃ−Ｖａｌ−）２−Ｏ（９−フルオレニルメトキシカルボニル）バリン）を供給し、その供給流量に応じて夫々の流出口１２Ｌ及び１２Ｈの流量制御弁Ｖ２及びＶ４を調節しておく。
これにより、第一原料Ｘを溶かした軽量溶媒は反応管２の下段に沈んだ重量溶媒より比重が軽いので上方に移動し、軽量溶媒流出口１２Ｌから軽量溶媒が回収タンク１３に流出される。
第二原料Ｙを溶かした重量溶媒は反応管２の上段の軽量溶媒より比重が軽いので下方に流下し、重量溶媒流出口１２Ｈから重量溶媒が廃液タンク１４に流出される。
ていく。 In this state, as shown in FIG. 2C, the first raw material X (for example, cyclohexane-soluble carrier ((C 18 H 37 O) 3 C 6 H 2 COH) is supplied from the raw material tanks 7L and 7H by the pumps 9L and 9H. )): (3,4,5-trioctadecyloxyphenyl) methane-1-ol) and second raw material Y (for example, (Fmoc-Val-) 2 -O (9-fluorenylmethoxycarbonyl) valine) is supplied. and, previously to adjust the flow control valve V 2 and V 4 outlets 12L and 12H each in accordance with the supply flow rate.
As a result, the light solvent in which the first raw material X is dissolved has a lower specific gravity than the heavy solvent that sinks in the lower stage of the reaction tube 2 and moves upward, and the light solvent flows out from the light solvent outlet 12L to the recovery tank 13.
The heavy solvent in which the second raw material Y is dissolved has a specific gravity lighter than that of the lighter solvent in the upper stage of the reaction tube 2 and flows down. The heavy solvent flows out from the heavy solvent outlet 12H to the waste liquid tank 14.
To go.

このとき反応管２の下段及び上段は相分離温度に維持されているので、軽量溶媒と重量溶媒が溶け合うことなく中段の相溶領域２Ｍに達し、反応管２内を攪拌すれば、軽量溶媒及び重量溶媒の夫々に溶けている第一原料Ｘと第二原料Ｙが互いに反応して合成物ＸＹが生成される。
合成物ＸＹは軽量溶媒に溶けて重量溶媒には溶けないので、相溶領域に存在する軽量溶媒に溶け込んで軽量溶媒と共に上方に移動する。
したがって、軽量溶媒流出口１２Ｌから回収タンク１３に流出された軽量溶媒には合成物ＸＹが溶け込んでいるので、これを抽出することにより目的とする合成物ＸＹを得ることができる。 At this time, since the lower stage and the upper stage of the reaction tube 2 are maintained at the phase separation temperature, the light solvent and the heavy solvent reach the middle compatible region 2M without being mixed with each other. The first raw material X and the second raw material Y, which are dissolved in each of the heavy solvents, react with each other to produce a composite XY.
Since the composite XY dissolves in the light solvent and does not dissolve in the heavy solvent, it dissolves in the light solvent existing in the compatible region and moves upward together with the light solvent.
Therefore, since the synthesized product XY is dissolved in the lightweight solvent that has flowed out from the lightweight solvent outlet 12L to the recovery tank 13, the target synthesized product XY can be obtained by extracting this.

なお、上述の説明では、合成物が軽量溶媒に溶ける場合について説明したが、重量溶媒に溶ける場合は、重量溶媒流出口１２Ｈを合成物回収口として回収タンク１３を接続し、軽量溶媒流出口１２Ｌに廃液タンク１４を接続すればよい。   In the above description, the case where the compound is dissolved in the light solvent has been described. However, when the compound is dissolved in the heavy solvent, the recovery tank 13 is connected using the heavy solvent outlet 12H as the compound recovery port, and the light solvent outlet 12L. What is necessary is just to connect the waste liquid tank 14 to.

図３は本発明に係る連続合成装置の他の実施形態を示す。図１と共通する部分は同一符号を付して詳細説明を省略する。
本例の連続合成装置２１は、反応管２Ａ〜２Ｃが直列に多段連結されており、第一反応管２Ａで第一原料Ｘと第二原料Ｙ１を反応させて合成物Ｚ１を生成し、この合成物Ｚ１を第二反応管２Ｂの第一原料として他の第二原料Ｙ２と反応させて合成物Ｚ２を生成し、この合成物Ｚ２を第三反応管２Ｃの第一原料としてさらに他の第二原料Ｙ３と反応させて合成物Ｚ３を生成する。 FIG. 3 shows another embodiment of the continuous synthesis apparatus according to the present invention. Portions common to those in FIG. 1 are denoted by the same reference numerals, and detailed description thereof is omitted.
Continuous synthesis apparatus 21 of this embodiment, the reaction tube 2A~2C are multistage connected in series, the first material X and the second material Y 1 are reacted to produce a compound Z 1 in the first reaction tube 2A the composite of Z 1 and as the first raw material is reacted with another second material Y 2 of the second reaction tube 2B generates a composite material Z 2, the composite Z 2 first third reaction tube 2C As a raw material, it is further reacted with another second raw material Y 3 to produce a composite Z 3 .

各反応管２Ａ〜２Ｃには、その下端から第一原料を個別に供給する軽量溶媒供給系２２Ａ〜２２Ｃと、その上端から第二原料Ｙ１〜Ｙ３を個別に供給する重量溶媒供給系２３Ａ〜２３Ｃを備えている。
第一反応管２Ａの軽量溶媒供給系２２Ａは、溶媒タンク６Ｌと原料タンク７Ｌが切換バルブ８Ｌを介してポンプ９Ｌに接続され、その吐出口が重量溶媒供給管１０Ｌを介して重量溶媒流入口１１Ｌに接続されている。
第二及び第三反応管２Ｂ、２Ｃの軽量溶媒供給系２２Ｂ、２２Ｃは、前段の反応管２Ａ、２Ｂで生成された合成物Ｚ１、Ｚ２を流入させることができるように、軽量溶媒流入口１１Ｌをその前段の反応管２Ａ、２Ｂの軽量溶媒流出口１２Ｌに接続する連通管で形成されている。 In each of the reaction tubes 2A to 2C, a lightweight solvent supply system 22A to 22C for supplying the first raw material individually from the lower end thereof, and a heavy solvent supply system 23A for supplying the second raw materials Y 1 to Y 3 individually from the upper end thereof. To 23C.
In the light solvent supply system 22A of the first reaction tube 2A, a solvent tank 6L and a raw material tank 7L are connected to a pump 9L via a switching valve 8L, and a discharge port thereof is connected to a heavy solvent inlet 11L via a heavy solvent supply tube 10L. It is connected to the.
The lightweight solvent supply systems 22B and 22C of the second and third reaction tubes 2B and 2C allow the lightweight solvent flow so that the composites Z 1 and Z 2 produced in the previous reaction tubes 2A and 2B can flow in. It is formed by a communication pipe that connects the inlet 11L to the lightweight solvent outlet 12L of the reaction tubes 2A and 2B at the preceding stage.

また、各重量溶媒供給系２３Ａ〜２３Ｃは、溶媒タンク６Ｈと原料タンク７Ｈが切換バルブ８Ｈを介してポンプ９Ｈに接続され、その吐出口が重量溶媒供給管１０Ｈを介して重量溶媒流入口１１Ｈに接続されている。   In each heavy solvent supply system 23A to 23C, a solvent tank 6H and a raw material tank 7H are connected to a pump 9H via a switching valve 8H, and a discharge port thereof is connected to a heavy solvent inlet 11H via a heavy solvent supply pipe 10H. It is connected.

これによれば、図４で示すように、第一反応管２Ａでは、軽量溶媒供給系２２Ａより軽量溶媒に溶かされて供給される第一原料Ｘ（例えばシクロヘキサン可溶性担体（（Ｃ１８Ｈ３７Ｏ）３Ｃ６Ｈ２ＣＯＨ））：（３，４，５−トリオクタデシルオキシフェニル）メタン−１−オール）と、重量溶媒供給系２３Ａより重量溶媒に溶かされて供給される第二原料Ｙ１（例えば（Ｆｍｏｃ−Ｖａｌ−）２−Ｏ（９−フルオレニルメトキシカルボニル）バリン）が相溶領域２Ｍで反応して合成物Ｚ１（例えば〔ＳＣ〕−Ｖａｌ−Ｆｍｏｃ：可溶性担体結合バリン−Ｆｍｏｃ）が生成される。
次いで、第二反応管２Ｂでは、軽量溶媒供給系２２Ｂを介して第一原料として供給された前記合成物Ｚ１が、重量溶媒供給系２３Ｂより重量溶媒に溶かされて供給される第二原料Ｙ２（例えば１０％Ｅｔ２ＮＨ：ジエチルアミン）が相溶領域２Ｍで反応して合成物Ｚ２（例えば〔ＳＣ〕−Ｖａｌ−ＮＨ：可溶性担体結合バリン−ＮＨ）が生成される。
そして、第三反応管２Ｃでは、軽量溶媒供給系２２Ｃを介して第一原料として供給された前記合成物Ｚ２が、重量溶媒供給系２３Ｃより重量溶媒に溶かされて供給される第二原料Ｙ３（例えばＦｍｏｃ−Ｇｌｙ−ＯＢｔ：Ｆｍｏｃ−グリシン−ｔ−ブトキシカルボニル）が相溶領域２Ｍで反応して合成物Ｚ３（例えば〔ＳＣ〕−Ｖａｌ−Ｆｍｏｃ）：可溶性担体結合バリン−グリシン−Ｆｍｏｃ）が生成される。 According to this, as shown in FIG. 4, in the first reaction tube 2A, the first raw material X (for example, cyclohexane-soluble carrier ((C 18 H 37 O ) 3 C 6 H 2 COH)): (3,4,5-trioctadecyloxyphenyl) methane-1-ol) and the second raw material Y 1 that is supplied after being dissolved in the heavy solvent from the heavy solvent supply system 23A. (e.g. (Fmoc-Val-) 2 -O ( 9- fluorenyl methoxycarbonyl) valine) react with phase溶領range 2M compound Z 1 (e.g. [SC] -Val-Fmoc: soluble carrier bound valine - Fmoc) is generated.
Then, the second reaction tube 2B, the second raw material the compound Z 1 which is supplied as the first raw material via a light solvent feed system 22B is supplied dissolved in the weight solvent than the weight solvent supply system 23B Y 2 (eg, 10% Et 2 NH: diethylamine) reacts in the compatible region 2M to produce a synthetic Z 2 (eg, [SC] -Val-NH: soluble carrier bound valine-NH).
In the third reaction tube 2C, the composite Z 2 supplied as the first raw material via the lightweight solvent supply system 22C is dissolved in the heavy solvent from the heavy solvent supply system 23C and supplied. 3 (eg Fmoc-Gly-OBt: Fmoc-glycine-t-butoxycarbonyl) reacts in the compatible region 2M to produce a synthetic Z 3 (eg [SC] -Val-Fmoc): soluble carrier-bound valine-glycine-Fmoc ) Is generated.

このように本例では、各反応管２Ａ〜２Ｃの夫々に各重量溶媒供給系２３Ａ〜２３Ｂより第二原料Ｙ１、Ｙ２、Ｙ３を供給しながら、反応管２Ａの軽量溶媒供給系２２Ａから第一原料Ｘを供給すると、軽量溶媒に運ばれる第一原料は各反応管２Ａ〜２Ｃに順次供給され、夫々の反応管２Ａ〜２Ｃで合成反応が順次実行され、第三反応管２Ｃで目的とする合成物Ｚ３が生成される。 Thus, in this example, while supplying the second raw materials Y1, Y2, and Y3 from the respective heavy solvent supply systems 23A to 23B to the respective reaction tubes 2A to 2C, the first from the lightweight solvent supply system 22A of the reaction tube 2A. When the raw material X is supplied, the first raw material transported to the light solvent is sequentially supplied to the reaction tubes 2A to 2C, the synthesis reaction is sequentially performed in the respective reaction tubes 2A to 2C, and the target is supplied to the third reaction tube 2C. synthetic product Z 3 is generated.

なお本例では、合成物Ｚ１〜Ｚ３が軽量溶媒に溶ける場合について説明したが、重量溶媒に溶ける場合は、図示は省略するが、各反応管２Ａ〜２Ｃに個別に第一原料を供給する軽量溶媒供給系２２Ａ〜２２Ｃとして、溶媒タンク６Ｌと原料タンク７Ｌが切換バルブ８Ｌを介してポンプ９Ｌに接続され、その吐出口が軽量溶媒供給管１０Ｌを介して軽量溶媒流入口１１Ｌに接続すればよい。
また、各重量溶媒供給系２３Ａ〜２３Ｃは、第三反応管２Ｃの重量溶媒供給系２３Ｃが、溶媒タンク６Ｈと原料タンク７Ｈが切換バルブ８Ｈを介してポンプ９Ｈに接続され、その吐出口が重量溶媒供給管１０Ｈを介して重量溶媒流入口１１Ｈに接続されている。
第二及び第一反応管２Ｂ、２Ａの重量溶媒供給系２３Ｂ、２３Ａは、第三反応管２Ｃ、２Ｂで生成された合成物Ｚ３、Ｚ２を流入させることができるように、重量溶媒流入口１１Ｈを反応管２Ｃ、２Ｂの重量溶媒流出口１２Ｈに接続する連通管で形成すればよい。 In this example, the case where the composites Z 1 to Z 3 are dissolved in the light solvent has been described. However, when the compound Z 1 to Z 3 is dissolved in the heavy solvent, the first raw material is supplied individually to each of the reaction tubes 2A to 2C, although illustration is omitted. As the lightweight solvent supply systems 22A to 22C, the solvent tank 6L and the raw material tank 7L are connected to the pump 9L via the switching valve 8L, and the discharge port is connected to the lightweight solvent inlet 11L via the lightweight solvent supply pipe 10L. That's fine.
In each heavy solvent supply system 23A to 23C, the heavy solvent supply system 23C of the third reaction tube 2C is connected to a pump 9H through a switching valve 8H. The solvent tank 6H and the raw material tank 7H are connected to a pump 9H. The solvent supply pipe 10H is connected to the heavy solvent inlet 11H.
The heavy solvent supply system 23B, 23A of the second and first reaction tubes 2B, 2A allows the flow of the heavy solvent flow so that the composites Z 3 , Z 2 produced in the third reaction tubes 2C, 2B can flow in. What is necessary is just to form the inlet_port | entrance 11H with the communicating pipe | tube connected to the heavy solvent outflow port 12H of reaction tube 2C, 2B.

図５は本発明に係る連続合成装置の他の実施形態を示す。図１及び図３と共通する部分は同一符号を付して詳細説明を省略する。
本例の連続合成装置３１は、反応管２Ａ〜２Ｃが直列に多段連結されており、各反応管２Ａ〜２Ｃで、第一原料Ｘと第二原料Ｙを反応させて合成物Ｚを生成する同じ反応を繰返し行わせえることにより、原料Ｘ、Ｙを無駄無く高効率で反応さるものである。 FIG. 5 shows another embodiment of the continuous synthesis apparatus according to the present invention. Portions common to FIGS. 1 and 3 are denoted by the same reference numerals, and detailed description thereof is omitted.
In the continuous synthesizer 31 of this example, reaction tubes 2A to 2C are connected in multiple stages in series, and the first raw material X and the second raw material Y are reacted in each reaction tube 2A to 2C to generate a composite Z. By allowing the same reaction to be repeated, the raw materials X and Y are reacted with high efficiency without waste.

各反応管２Ａ〜２Ｃには、その下端から第一原料を個別に供給する軽量溶媒供給系２２Ａ〜２２Ｃと、その上端から第二原料を個別に供給する重量溶媒供給系３３Ａ〜３３Ｃを備えている。   Each of the reaction tubes 2A to 2C includes a lightweight solvent supply system 22A to 22C that individually supplies the first raw material from its lower end and a heavy solvent supply system 33A to 33C that individually supplies the second raw material from its upper end. Yes.

第一反応管２Ａの軽量溶媒供給系２２Ａは、溶媒タンク６Ｌと原料タンク７Ｌが切換バルブ８Ｌを介してポンプ９Ｌに接続され、その吐出口が、軽量溶媒供給管１０Ｌを介して軽量溶媒流入口１１Ｌに接続されている。
第二及び第三反応管２Ｂ、２Ｃの軽量溶媒供給系２２Ｂ、２２Ｃは、前段の反応管２Ａ、２Ｂで余った第一原料Ｘを順次前段の反応管２Ｂ、２Ｃに流入させることができるように、軽量溶媒流入口１１Ｌをその前段の反応管２Ａ、２Ｂの軽量溶媒流出口１２Ｌに接続する連通管で形成されている。 In the light solvent supply system 22A of the first reaction tube 2A, a solvent tank 6L and a raw material tank 7L are connected to a pump 9L through a switching valve 8L, and a discharge port thereof is connected to a light solvent inlet through a light solvent supply tube 10L. 11L.
The lightweight solvent supply systems 22B and 22C of the second and third reaction tubes 2B and 2C can sequentially flow the remaining first raw material X in the previous reaction tubes 2A and 2B into the previous reaction tubes 2B and 2C. In addition, the light solvent inlet 11L is formed by a communication pipe that connects the light solvent outlet 12L of the preceding reaction tubes 2A and 2B.

また、第三反応管２Ｃの重量溶媒供給系３３Ｃは、溶媒タンク６Ｈと原料タンク７Ｈが切換バルブ８Ｈを介してポンプ９Ｈに接続され、その吐出口が重量溶媒供給管１０Ｈを介して重量溶媒流入口１１Ｈに接続されている。
第二及び第一反応管２Ｂ、２Ａの重量溶媒供給系３３Ｂ、３３Ａは、第三反応管２Ｃ、２Ｂで余った第二原料Ｙを順次前段の反応管２Ｂ、２Ａに流入させることができるように、重量溶媒流入口１１Ｈを後段の反応管２Ｃ、２Ｂの重量溶媒流出口１２Ｈに接続する連通管で形成されている。 Further, in the heavy solvent supply system 33C of the third reaction tube 2C, a solvent tank 6H and a raw material tank 7H are connected to a pump 9H through a switching valve 8H, and a discharge port of the heavy solvent supply system 33C through a heavy solvent supply tube 10H. It is connected to the inlet 11H.
The heavy solvent supply systems 33B and 33A of the second and first reaction tubes 2B and 2A can sequentially flow the remaining second raw material Y in the third reaction tubes 2C and 2B into the previous reaction tubes 2B and 2A. In addition, the heavy solvent inlet 11H is formed by a communication pipe that connects the heavy solvent outlet 12H of the reaction tubes 2C and 2B in the subsequent stage.

これによれば、図６に示すように、第一原料Ｘが軽量溶媒供給系２２Ａを介して第一反応管２Ａに供給され、第二原料Ｙが重量溶媒供給系３３Ｃを介して第三反応管２Ｃに供給される。
そして、夫々の反応管２Ａ〜２Ｃで反応し切れなかった余剰第一原料Ｘが軽量溶媒供給系２２Ｂ、２２Ｃを介して順次後段の反応管２Ｂ、２Ｃへ、また、余剰第二原料Ｙが重量溶媒供給系３３Ｂ、３３Ａを介して順次前段の反応管２Ｂ、２Ａへ供給される。 According to this, as shown in FIG. 6, the first raw material X is supplied to the first reaction tube 2A via the lightweight solvent supply system 22A, and the second raw material Y is supplied to the third reaction via the heavy solvent supply system 33C. Supplied to the tube 2C.
Then, the surplus first raw material X that has not been reacted in each of the reaction tubes 2A to 2C is sequentially transferred to the subsequent reaction tubes 2B and 2C through the lightweight solvent supply systems 22B and 22C, and the surplus second raw material Y is weighted. Sequentially supplied to the previous reaction tubes 2B and 2A through the solvent supply systems 33B and 33A.

すなわち、第一反応管２Ａでは、軽量溶媒供給系２２Ａを介して供給された第一原料Ｘと、反応管２Ｃ、２Ｂで反応されずに残った僅かな余剰第二原料Ｙが相溶領域２Ｍで合成物Ｚが生成されるので、余剰第二原料Ｙはほとんど全てが反応に供される。
次に、第二反応管２Ｂでは、反応管２Ａで生成された僅かな合成物Ｚと大量の第一原料Ｘが軽量溶媒供給系２２Ｂを介して供給され、その第一原料Ｘが反応管２Ｃで反応されずに残った少なめの余剰第二原料Ｙと相溶領域２Ｍで反応するので、余剰第二原料Ｙはやはりほとんど全てが反応に供される。
そして、第三反応管２Ｃでは、反応され部に残った少量の第一原料Ｘと合成物Ｚが、軽量溶媒供給系２２Ｃを介して供給され、その少量の第一原料Ｘが重量溶媒供給系３３Ｃを介して供給される第二原料Ｙと反応するので、第一原料Ｘはそのほとんど全てが反応に供される。 That is, in the first reaction tube 2A, the first raw material X supplied via the lightweight solvent supply system 22A and the slight surplus second raw material Y left unreacted in the reaction tubes 2C and 2B are in the compatible region 2M. Since the synthesized product Z is generated, almost all of the surplus second raw material Y is subjected to the reaction.
Next, in the second reaction tube 2B, a slight amount of the synthesized product Z produced in the reaction tube 2A and a large amount of the first raw material X are supplied via the lightweight solvent supply system 22B, and the first raw material X is supplied to the reaction tube 2C. The remaining second raw material Y reacts in the compatible region 2M with the remaining second raw material Y remaining unreacted, so that almost all of the surplus second raw material Y is still subjected to the reaction.
In the third reaction tube 2C, a small amount of the first raw material X and the composite Z remaining in the reaction part are supplied via the lightweight solvent supply system 22C, and the small amount of the first raw material X is supplied to the heavy solvent supply system. Since it reacts with the second raw material Y supplied via 33C, almost all of the first raw material X is subjected to the reaction.

このように本例では、三回繰り返して同じ反応を行わせているので、原料を余剰させることなくその全量を反応に供することができ、高効率の反応を行わせることができるという効果がある。   Thus, in this example, since the same reaction is performed three times, the entire amount can be used for the reaction without surplus of raw materials, and there is an effect that a highly efficient reaction can be performed. .

以上述べたように、本発明は、比重が異なり温度に応じて相溶性／相分離性を呈する二種類の溶媒を用いて、原料を供給しながらこれらを反応させて、ペプチド、蛋白質、ＤＮＡ、ＲＮＡ、多糖類などオリゴマー、ポリマー類など目的とする合成物を連続的に生成する用途に適用することができる。   As described above, the present invention uses two types of solvents having different specific gravities and exhibiting compatibility / phase separation depending on temperature, and reacting them while supplying raw materials to produce peptides, proteins, DNA, The present invention can be applied to applications for continuously producing desired synthetic products such as RNA and polysaccharides such as polysaccharides and polymers.

本発明に係る連続合成装置の説明図。Explanatory drawing of the continuous synthesis apparatus which concerns on this invention. その使用方法を示す説明図。Explanatory drawing which shows the usage method. 他の実施形態を示す説明図。Explanatory drawing which shows other embodiment. その使用方法を示す説明図。Explanatory drawing which shows the usage method. さらに他の実施形態を示す説明図。Explanatory drawing which shows other embodiment. その使用方法を示す説明図。Explanatory drawing which shows the usage method.

符号の説明Explanation of symbols

１、２１、３１ 連続合成装置
２、２Ａ〜２Ｃ 反応管
３ 温度制御装置
５Ｌ、２２Ａ〜２２Ｃ 軽量溶媒供給系
５Ｈ、２３Ａ〜２３Ｃ ３３Ａ〜３３Ｃ 重量溶媒供給系


1, 21, 31 Continuous synthesis apparatus 2, 2A to 2C Reaction tube 3 Temperature control apparatus 5L, 22A to 22C Light solvent supply system 5H, 23A to 23C 33A to 33C Heavy solvent supply system


Claims (6)

比重が異なり温度に応じて相溶性／相分離性を呈する二種類の溶媒を用い、比重の軽い軽量溶媒に溶ける第一原料と、比重の重い重量溶媒に溶ける第二原料を相溶性領域で反応させ、軽量溶媒及び重量溶媒のいずれか一方にのみ溶ける合成物を連続的に生成する連続合成装置であって、
上段及び下段が溶媒の相分離温度に維持され、中段が溶媒の相溶温度に維持される温度制御装置を備えた反応管と、その下端から第一原料を軽量溶媒と共に供給する軽量溶媒供給系と、その上端から第二原料を重量溶媒と共に供給する重量溶媒供給系を備えると共に、合成物が溶けた溶媒を回収する合成物回収口が形成されたことを特徴とする連続合成装置。 Using two types of solvents with different specific gravity and exhibiting compatibility / phase separation depending on temperature, the first raw material that dissolves in a light solvent with a low specific gravity and the second raw material that dissolves in a heavy solvent with a high specific gravity are reacted in the compatibility region. A continuous synthesizer that continuously produces a compound that is soluble only in either a light solvent or a heavy solvent,
A light-weight solvent supply system for supplying a first raw material together with a light solvent from a reaction tube having a temperature control device in which the upper and lower stages are maintained at the solvent phase separation temperature and the middle stage is maintained at the solvent compatibility temperature. And a synthetic solvent recovery port for recovering the solvent in which the synthetic product is dissolved, and having a heavy solvent supply system for supplying the second raw material together with the heavy solvent from the upper end thereof. 前記反応管が直列に多段連結され、各反応管には夫々異なる第一原料又は第二原料を供給する溶媒供給系と、前段又は後段の反応管で生成された合成物を次段の反応管の第一原料又は第二原料として供給する溶媒供給系を備えた請求項１記載の連続合成装置。   The reaction tubes are connected in multiple stages in series, and each reaction tube is supplied with a solvent supply system that supplies a different first raw material or second raw material, and a product produced in the preceding or subsequent reaction tube is connected to the subsequent reaction tube. The continuous synthesis apparatus according to claim 1, further comprising a solvent supply system for supplying the first raw material or the second raw material. 前記反応管が直列に多段連結され、最前段の反応管から第一原料を軽量溶媒と共に供給する軽量溶媒供給系と、最後段の反応管から第二原料を重量溶媒と共に供給する重量溶媒供給系を備え、前段の反応管の余剰第一原料が順次後段の反応管の第一原料として供給されると共に、後段の反応管の余剰第二原料が順次前段の反応管の第二原料として供給される請求項１記載の連続合成装置。   The reaction tube is connected in multiple stages in series, and a lightweight solvent supply system that supplies the first raw material together with a light solvent from the frontmost reaction tube, and a heavy solvent supply system that supplies the second raw material together with the heavy solvent from the last reaction tube The surplus first raw material in the preceding reaction tube is sequentially supplied as the first raw material in the subsequent reaction tube, and the surplus second raw material in the subsequent reaction tube is sequentially supplied as the second raw material in the preceding reaction tube. The continuous synthesis apparatus according to claim 1. 比重が異なり温度に応じて相溶性／相分離性を呈する二種類の溶媒を用い、比重の軽い軽量溶媒に溶ける第一原料と、比重の重い重量溶媒に溶ける第二原料を相溶性領域で反応させ、軽量溶媒及び重量溶媒のいずれか一方にのみ溶ける合成物を連続的に生成する連続合成方法であって、
上段及び下段が溶媒の相分離温度に維持され、中段が溶媒の相溶温度に維持される温度制御装置を備えた反応管に、その下端から第一原料を軽量溶媒と共に供給し、その上端から第二原料を重量溶媒と共に供給して、合成物を溶かす軽量溶媒又は重量溶媒を供給しながら前記中段領域で合成物を連続的に生成させ、当該溶媒と共に回収する連続合成方法。 Using two types of solvents with different specific gravity and exhibiting compatibility / phase separation depending on temperature, the first raw material that dissolves in a light solvent with a low specific gravity and the second raw material that dissolves in a heavy solvent with a high specific gravity are reacted in the compatibility region. A continuous synthesis method for continuously producing a compound that is soluble only in either a light solvent or a heavy solvent,
A first raw material is supplied from the lower end to the reaction tube equipped with a temperature control device in which the upper stage and the lower stage are maintained at the phase separation temperature of the solvent, and the middle stage is maintained at the compatibility temperature of the solvent. A continuous synthesis method in which a second raw material is supplied together with a heavy solvent, a light solvent or a heavy solvent that dissolves the compound is supplied, and a synthetic product is continuously generated in the middle stage region and recovered together with the solvent. 直列に多段連結された各反応管に夫々異なる第一原料又は第二原料を供給すると共に、前段又は後段の反応管で生成された合成物を次段の反応管の第一原料又は第二原料として供給し、最終段で生成された合成物を溶媒と共に回収する請求項４記載の連続合成方法。   A different first raw material or second raw material is supplied to each reaction tube connected in multiple stages in series, and the composite produced in the preceding or subsequent reaction tube is used as the first raw material or second raw material in the subsequent reaction tube. The continuous synthesis method according to claim 4, wherein the synthesized product produced in the final stage is recovered together with a solvent. 直列に多段連結された反応管のうち、最前段の反応管から第一原料を軽量溶媒と共に供給し、最後段の反応管から第二原料を重量溶媒と共に供給し、前段の反応管で余った余剰第一原料を順次後段の反応管の第一原料として供給すると共に、後段の反応管で余った余剰第二原料を順次前段の反応管の第二原料として供給する請求項４記載の連続合成方法。
Of the reaction tubes connected in series in multiple stages, the first raw material is supplied together with the light solvent from the first reaction tube, the second raw material is supplied together with the heavy solvent from the last reaction tube, and the surplus is left in the previous reaction tube. The continuous synthesis according to claim 4, wherein the surplus first raw material is sequentially supplied as a first raw material in a subsequent reaction tube, and the surplus second raw material in a subsequent reaction tube is sequentially supplied as a second raw material in a previous reaction tube. Method.
JP2004316793A 2004-10-29 2004-10-29 Apparatus and method for continuous synthesis Pending JP2006124344A (en)

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