TW201138950A

TW201138950A - Method of manufacturing a reactor and set of reactors

Info

Publication number: TW201138950A
Application number: TW099133351A
Authority: TW
Inventors: Dominique Roberge; Norbert Kockmann; Michael Gottsponer; Markus Eyholzer
Original assignee: Lonza Ag
Priority date: 2010-05-12
Filing date: 2010-09-30
Publication date: 2011-11-16

Abstract

A method of manufacturing a target reactor having a flow-channel system in which a plurality of reactants continuously flowing into said target reactor are mixed and interconvert to form a target volumetric flow-rate (f2) of a product continuously flowing out of said target reactor, wherein the smallest hydraulic diameter (dh2) of said target reactor is calculated based on the relationship dh2=dh1(f2/f1)3-n/7-n in a turbulent or transitional turbulent flow, wherein n is a non-integer number with 1 > n ≥ 0, between the corresponding smallest hydraulic diameter (dh1) of a standard reactor having the same fluidic type of flow-channel system, f1 is a standard volumetric flow-rate of said standard reactor carrying out the same interconversion, and f2 is said target volumetric flow-rate.

Description

201138950 六、發明說明：【發明所屬之技術領域】本發明係關於一種反應器（特別是歐洲專利EP 1 839 739 A1中揭露的微反應器'）以及反應器組之製造方法。【先前技術】作為反應器的範例，如揭露於歐洲專利EP 1 839 739 A1的一種微反應器。反應器是為一種或多種反應劑或離析物的反應 (通常包括兩種或多種反應劑的混合）提供的反應裝置，在一定程度上在混合過程中和/或混合後通過加熱或冷卻或熱緩衝所述反應劑進而控制所述反應劑的反應。由例如 EP-A-0688242 、 EP-A-1031375 、 WO-A2004/045761 和 US-A-2004/0109798可知其他於小區域内實施化學反應的其他微反應器。在反應器中實施的化學反應可分為各種反應類型。根據本發明的方法所製造的反應器優選設計實施所謂B型反應。B型反應，例如Wittig反應或芳香胺通過雙烯酮的乙醯醯化，是快速和溫度敏感型的反應，典型反應時間範圍為丨秒至1〇分鐘。反應溫度或溫度狀況對B型反應至為重要。因此混合和滯留區的體積必須適合流速’從而使工藝反應劑在微反應器内於明確條件下（即溫度狀況）保留明夸時間。在合適反應器如微反應器的開發中，首先需確定其中所發生的化學反應’所需的體積流速.，即其輸出（每單元時間）以及-可能為這些因素的後果_反應器的確切類型及原理設計等。在沒有反應器滿足所有條件的情況下，可（應當）對宜進行定制。在除所需目標體積流速外所有要求已由—種反應器滿足 4 201138950 時，至少有三種選擇可實現所需的目標體積流速（應指出，不損失一般性，適當時，此處通過目標反應器方式提高體積流速也稱為“放大”，儘管本發明的方法理所應當適用於減少該體積流速，稱為“縮減，，）。 (1)可擴大反應劑的混合《然而，該步驟不利於，例如，混口效果、生熱、’/儿降現象、乳化等。（2)可增加反應器的數量，即所謂數增放大或平行化。然而，由於所有偶聯反應器中的化學計量學始終無法完全相等，不利地需要強化控制單獨微反應器中每一個的反應參數形成物理分離的“反應通道,，。此外，清潔工作更為大規模，且隨著包括的反應器越多，清潔單獨反應器中每一個的時間安排越為複雜。（3)所用的反應器可被尺寸放大。然而，這無法通過僅通過“延伸，，該反應器（即，其流體通道系統）實;見，因為由於混洗條件，特別在所謂的混合區中，這將導致流體動力學的變化，進而改變反應條件。以增加反應器可月匕的體積流速進而提高其£產能力（工程解決方案而非調節化學及物理反應參數）為目的所用的術語“尺寸放大”，優選在此使用上述術語“放大”。【發明内容】、本發明之一目的在於提供一種反應器與反應器組之製造 T法，其由設計生產相同產物但體積流速不同於目標反應器的 ^準反應器起始’製造目標反應器（特別是微反應器^通過流入該目標反應器的多種反應劑或離析物於該目標反應器中的化學反應得到所需產物的目標體積流速的方法。以上目的可通過根據申請專利範圍丨特徵的方法解決。在從屬申請專利範圍中定義其有利的更改。申請專利範圍5涉及 201138950 一組標準反應器和目標反應器，該目標反應器可根據申請專利範圍1的方法製造。根據本發明（申請專利範圍1 )，在製造目標反應器的方法中，該目標反應器具有流動通道系統’，其中連續流入所述目標反應器的多種反應劑被混合並轉化形成連續流出所述目標反應器的產物的目標體積流速/2，其中所述目標反應器的最小液力直徑（U基於湍流或過渡湍流中與具有相同流體類型的流動通道糸統的標準反應器的相應最小液力直徑（dhi)乏間的如下關係計算 dh2 =^hy γ ( 1) 其中《為非整數數值且1>於0，A為實施相同轉化的標準反應器的標準體積流速，A為該目標體積流速。所述最小液力直把位於多種反應劑混合的區域（下文稱為“混合區，，）。在包括多個串聯連接工藝板的模組反應器中，該“流動通道系統”理所當然為按下文所述以合適接頭互聯的每一個單獨工藝板的“子流動通道系統”總和，且這些子流動通道系統中第一和最後一個分別經合適接頭連接至一個或多個泵及接受容器。因此上文所述“流體類型，，可由如下特徵表徵或可結合如下特徵：（1)該流動通道系統主要在二維空間中延伸；（2)該流動通道系統包括：（a)梃應通道，多種反應劑中每一種至少一個，其合併進行反應的多種反應劑，（b)迂回流動通道，（c)至少一個排出通道，用以排出待生產的產物，以及（d)接頭（埠），用於内#和外部連接，即，介於泵和微反應器多個供應通道之間的入口端’具有-個以上工藝板時介於多個工藝板中一對工藝 201138950 板之間的連接端，以及介於該微反應器至少— 夕個排出通道與產物收集裝置（諸如，容器或反應後滯留容稽1 只J之間的出口端；以及（3)該it回結才籌的形狀及財使得該适回流動通道包括至少兩個區類型，至少一個湍流流動混合區，装、、、〒主要以瑞流方式發生化學反應以及多種反應劑的渦旋（此處雷諾數範圍為 200-2_)，且其中最小液力直徑確定（這進而可視為混合區的特徵），以及至少一個基本層流滯留區，其特徵在於寬度、高度及長度，其主要任務並非混合（壓降），而是以層流方式熱交換。作為旁注，應認識到混合還發生於滯留區，儘管比例很小。在滯留區中觀察的混合作用也稱為第二混合。最後，混合由彎曲或邊緣處生成的渦流所引導，其將隨通道行進。應當明碑指出’考慮到湍流混合區和層流滞留區各自的作用，其放大標準彼此不g。因此，在湍流條件下，“混合的放大標準，，為每單位體積的能ϊ輸入。在更高流速下，針對該能量輸入所計算的液力直徑可由等式（1)表示。由更高的壓降可得更大的能量消耗。壓降的主要因素由混合區引起，且混合區為高流速下運作微反應器時必須關/主的主要區域。例如’流速由1〇〇 mL/min上升至200 mL/min，該混合區液力直徑增加的因數約為134。該情況在滯留區中有所不同。此處，有可能維持該板的相同幾何形狀（寬 X咼），而增加其長度，如技術人員所顯而易見。如上所述，滞留區的主要任務在於熱交換而非混合。因此，滯留區的放大標準並非液力直彳里’而是保持通道幾何形狀恒定（盡可能長）。然而’在一些高體積流速的情況下，可能值得提高通道高度但保持相同通道寬度，例如由〇 5 X 5 mm2至0.5 X 8 mm2或0.5 X 10 mm2。由於熱交換非常關鍵，通道寬度為該區的關鍵放大因數， 201138950 並在由小板變為大板時保持恒定。因此，本發明的理念為，基於上述標準反應器的物理數值 ^及該目標反應器所需具有的目標體積流速製造目標反應器。如上文所述，它（不損失一般性）在此指如下情況：適當時由標準反應器的放大所得的目標反應器，即，當力>力時，本發明的原理理所當然地同等適用於/1>/2的（縮減）情泥。替代性表不，本發明的理念在於，在體積流速由已有或已知反應器的/l提尚至目標反應器的時，避免多個反應器的平行化❶如上文曰示在匕們之間破定混合效力的決定性的物理數值在於混合區入口與出口間的壓降（由混合區流速及幾何形狀得到），而非入口壓的絕對值（由促進反應劑流動的泵裝置提供）。事實上，與電學中電阻的電壓降相當（物理上及術語學上）的壓降才疋傳遞至系統的能量、此處該反應劑流體以及混合效力的 $度。具體而言，轉移至根據本發明的反應劑混合物的能量約為70%，而滯留區相應值約為25%或更少。該能量的剩餘部分被傳遞至接頭（配件）❶有利地，該壓降可在沿該流動的主要區域（即，混合區）容易地測得。此外，除上述流體通道系統外，根據本發明，該標準反應器未受限制；它可以為模組或非模組型反應器。對於模組反應器’所述流動通道系統可由EP 1 839 739 A1所揭露的微反應器中的板狀工藝模組形成。下文給出等式（1)的短推導。在其中流動幾乎為完全層流的長直通道區中（即，滯留區）’以及其中流動接近完全湍流的短通道區中（即，混合區），流動系統的壓損由包括動能並忽視勢能的Bernoum等式表示。針對術語學’應指出此處的通道被分為混合區與層流區，其間 201138950 歇排列並具有單獨長度L，其中每一個混合區為如同珍珠串的 /扣&元件（屬流位置）的串聯。重要的有效液力直徑&位於該此合疋件内的通道部分，下文縮寫為“混合元件内的通道，，。由於液力直控dh，i負責混合和渦流以及與之相關的能量損失，層流 &被忽略以得到近似值。具有單獨長度1^和單獨液力直徑屯，;時，N個混合元件的總壓力損失可由如下等式得到其中％為第i個混合元件内的特徵流體速度，^為摩擦係數’而Re為指數為《的雷諸數。母個混合元件可由其特徵液力直徑&及其長度£表徵。我們發現在放大或縮減過程中兩種長度尺度的比率應保持恒定，以實現進入流動系統的類似流動條件以及類似能量輸入，其導致類似混合時間中的類似混合效率。對於混合區内的通道，該壓損可表達為如下等式： (3) 分母中雷諾數Re的指數„取決於混合區中通道中的流動方式。對於全屬流或全滿流，„分別為制。在複雜思合元件中，主要為介於直層流和全湍流之間的過渡流，導致”為非整數數值，其值介於_。特別在接近〇的區域（主要為瑞流或幾乎全端流），對偏差的容限高於接近丨的區域（主要為層流^對於T形混合區中Re介於議和1GGG的流動方式我們發現指數約為 1/3。 201138950 結合等式2和3，並採用液力直徑Μ x平均流體速度[m，])的近似及採用等式3的推理如dh=(/7w)1/2以及Re = dhw/v=/7vdh ’該液力直徑屯為：樂〆广f ⑷ 其中V表示動力學速度[mY3]，，表示體積流速[ιηγι]，p表示密度[kgm-3]。本發明的發明人發現’混合效率強烈依賴於局部能量消耗速率，即，在至少兩種流動混合過程中轉化的壓能損失，以及該通道的幾何形狀。該通道引導該流動並引起流動偏轉。除剪切力外，新流動垂直力作用於該流體之上並生成次級流動結構、渦流以及再迴圈區。為避免疑慮，初級流動結構為微通道中由反應器材料形成的硬編碼流動結構。通過替代性混合元件或重複偏差流動快速改變該類次級流動渦流導致有效流動混合。為生成這些次級流動結構及渦流，該流體需要由流體壓力所消耗的機械能。因此’我們使用每單位體積的壓降作為混合的量度，以能量消耗速率ε表示：201138950 VI. Description of the Invention: [Technical Field] The present invention relates to a reactor (particularly the microreactor disclosed in European Patent No. EP 1 839 739 A1) and a method of manufacturing the reactor group. [Prior Art] As an example of a reactor, a microreactor is disclosed in the European patent EP 1 839 739 A1. A reactor is a reaction unit provided for the reaction of one or more reactants or educts (generally comprising a mixture of two or more reactants), to some extent by heating or cooling or heat during and/or after mixing. The reactants are buffered to control the reaction of the reactants. Other microreactors that perform chemical reactions in small areas are known from, for example, EP-A-0688242, EP-A-1031375, WO-A 2004/045761, and US-A-2004/0109798. The chemical reactions carried out in the reactor can be divided into various reaction types. The reactor produced according to the process of the invention is preferably designed to carry out a so-called B-type reaction. Type B reactions, such as the Wittig reaction or the acetylation of aromatic amines by diketene, are rapid and temperature sensitive reactions with typical reaction times ranging from leap seconds to 1 minute. The reaction temperature or temperature condition is critical to the Type B reaction. Therefore, the volume of the mixing and retention zone must be adapted to the flow rate' so that the process reactant remains in the microreactor under definite conditions (i.e., temperature conditions) for a significant time. In the development of a suitable reactor such as a microreactor, it is first necessary to determine the volumetric flow rate required for the chemical reaction taking place, ie its output (per unit time) and - possibly the consequences of these factors - the exact reactor Type and principle design. In the absence of a reactor that satisfies all of the conditions, it may be (should) be tailored. At least 3 options are available to achieve the desired target volumetric flow rate, except for the required target volumetric flow rate, which meets the requirements of 4 201138950 (it should be noted that without loss of generality, where appropriate, where Increasing the volumetric flow rate is also referred to as "amplification", although the method of the present invention should be adapted to reduce the volumetric flow rate, referred to as "reduction,". (1) The mixing of the reactants can be expanded. "However, this step is disadvantageous. For example, mixing effect, heat generation, '/child drop phenomenon, emulsification, etc. (2) can increase the number of reactors, so-called number amplification or parallelization. However, due to the chemistry in all coupling reactors Metrology is never completely equal, and it is disadvantageously necessary to strengthen the control of each of the individual microreactors to form a "reaction channel" for physical separation. In addition, the cleaning work is much larger, and as more reactors are included, the timing of cleaning each of the individual reactors becomes more complicated. (3) The reactor used can be enlarged in size. However, this cannot be achieved by simply "extending, the reactor (ie its fluid channel system); see, because due to the mixing conditions, especially in the so-called mixing zone, this will result in a change in fluid dynamics, and thus Changing the reaction conditions. The term "size enlargement" is used for the purpose of increasing the volume flow rate of the reactor at a monthly rate and thereby increasing its productivity (engineering solution rather than adjusting chemical and physical reaction parameters), preferably using the above term " SUMMARY OF THE INVENTION [0009] It is an object of the present invention to provide a T-process for the manufacture of a reactor and a reactor set which is manufactured by the manufacture of the same product but with a different volumetric flow rate than the target reactor. A target reactor (particularly a microreactor) a method of obtaining a desired volume flow rate of a desired product by a chemical reaction of a plurality of reactants or educts flowing into the target reactor into the target reactor. The scope of the method is solved by the method. The advantageous changes are defined in the scope of the subordinate patent application. 5 relates to a group of standard reactors and target reactors of 201138950, which can be manufactured according to the method of claim 1. According to the invention (patent scope 1), in the method of manufacturing a target reactor, the target reactor Having a flow channel system 'where a plurality of reactants continuously flowing into the target reactor are mixed and converted to a target volume flow rate of 2 for continuous product exiting the target reactor, wherein the minimum hydrodynamic diameter of the target reactor (U is calculated based on the following relationship between the corresponding minimum hydraulic diameter (dhi) of a standard reactor in a turbulent or transitional turbulent flow channel with the same fluid type as dh2 =^hy γ ( 1) where "is a non-integer Values and 1> at 0, A is the standard volumetric flow rate of a standard reactor performing the same conversion, and A is the target volumetric flow rate. The minimum hydraulic force is located in a region where a plurality of reactants are mixed (hereinafter referred to as "mixing zone, , in a modular reactor comprising a plurality of series connected process plates, the "flow channel system" is of course suitable as described below The sum of the "sub-flow channel systems" of each individual process board interconnected, and the first and last of these sub-flow channel systems are respectively connected to one or more pumps and receiving vessels via suitable joints. The fluid type may be characterized by or may be combined with the following features: (1) the flow channel system extends primarily in a two-dimensional space; (2) the flow channel system comprises: (a) a accommodating channel, each of a plurality of reactants At least one of a plurality of reactants combined to carry out the reaction, (b) a bypass flow passage, (c) at least one discharge passage for discharging the product to be produced, and (d) a joint (埠) for internal # and An external connection, that is, an inlet end between the pump and the microreactor multiple supply channels' having more than one process plate, a connection between a pair of process boards 201138950 plates among a plurality of process plates, and At least the outlet of the microreactor and the product collection device (such as the outlet end between the container or the post-reaction retention capacity J; and (3) the shape of the it-return and The suitable flow channel comprises at least two zone types, at least one turbulent flow mixing zone, and the chemical reaction of the charge, the main charge, and the vortex of the plurality of reactants (wherein the Reynolds number ranges from 200 to 2) And wherein the minimum hydraulic diameter is determined (which in turn can be regarded as a feature of the mixing zone), and at least one basic laminar flow retention zone characterized by width, height and length, the main task of which is not mixing (pressure drop), but Heat exchange in laminar flow. As a side note, it should be recognized that mixing also occurs in the detention zone, albeit at a very small scale. The mixing effect observed in the retention zone is also referred to as the second mixing. Finally, the mixing is guided by the eddy currents generated at the bend or edge, which will travel with the channel. It should be clearly stated that 'the amplification criteria are not related to each other considering the respective roles of the turbulent mixing zone and the laminar retention zone. Therefore, under turbulent conditions, the "mixed amplification standard is the energy input per unit volume. At higher flow rates, the calculated hydraulic diameter for this energy input can be represented by equation (1). The pressure drop allows for greater energy consumption. The main factor of the pressure drop is caused by the mixing zone, and the mixing zone is the main zone that must be closed/main when operating the microreactor at high flow rates. For example, the flow rate is 1 〇〇 mL / Min rises to 200 mL/min, and the factor of increase in the hydraulic diameter of the mixing zone is about 134. This situation is different in the retention zone. Here, it is possible to maintain the same geometry (width X咼) of the plate, and Increasing its length, as will be apparent to the skilled person, as mentioned above, the main task of the detention zone is heat exchange rather than mixing. Therefore, the amplification criteria of the retention zone is not in the hydraulic straightness, but rather the channel geometry is kept constant (as far as possible Long). However, in some high volume flow rates, it may be worthwhile to increase the channel height but maintain the same channel width, for example from 〇5 X 5 mm2 to 0.5 X 8 mm2 or 0.5 X 10 mm2. The key, the channel width is the key magnification factor for this zone, 201138950 and remains constant as it changes from a small plate to a large plate. Therefore, the concept of the invention is based on the physical values of the above standard reactors and the required reactor Having a target volumetric flow rate to produce a target reactor. As described above, it (without loss of generality) herein refers to the case where the target reactor is obtained by amplification of a standard reactor as appropriate, that is, when force > force The principle of the present invention is of course equally applicable to the (reduced) situation of /1>/2. The alternative is that the concept of the present invention is that the volumetric flow rate is increased from the existing or known reactors. Avoiding the parallelization of multiple reactors when aiming at the reactor, as shown above, the decisive physical value for determining the mixing efficiency between the two is the pressure drop between the inlet and outlet of the mixing zone (by the mixing zone flow rate and geometry) The shape is obtained, not the absolute value of the inlet pressure (provided by the pump device that promotes the flow of the reactants). In fact, the voltage drop (physical and terminological) is equivalent to the voltage drop in the electrical resistance. The energy delivered to the system, here the reactant fluid, and the effectiveness of the mixing is $. Specifically, the energy transferred to the reactant mixture according to the present invention is about 70%, and the corresponding value of the retention zone is about 25%. Or less. The remainder of the energy is transferred to the joint (accessory). Advantageously, the pressure drop can be readily measured along the main area of the flow (i.e., the mixing zone). In addition, in addition to the fluid passage system described above According to the invention, the standard reactor is not limited; it can be a modular or non-modular type reactor. For the module reactor, the flow channel system can be used in the microreactor disclosed in EP 1 839 739 A1. The formation of a plate-like process module. The short derivation of equation (1) is given below. In the long straight channel region where flow is almost completely laminar (ie, the retention zone)' and the short channel in which the flow approaches near full turbulence In the zone (ie, the mixing zone), the pressure loss of the flow system is represented by the Bernoum equation including kinetic energy and ignoring potential energy. For the terminology' it should be pointed out that the channels here are divided into a mixed zone and a laminar zone, with 201138950 resting and having a separate length L, each of which is like a pearl string/ample & component (genus flow position) The tandem. Important effective hydraulic diameter & the portion of the passage located in the fitting, hereinafter abbreviated as "the passage in the mixing element," due to direct hydraulic control dh, i is responsible for mixing and eddy currents and associated energy losses , laminar flow & is ignored to obtain an approximation. With a separate length 1 ^ and a separate hydraulic diameter 屯, the total pressure loss of the N mixing elements can be obtained by the following equation where % is the characteristic of the ith hybrid element The fluid velocity, ^ is the coefficient of friction 'and Re is the number of the index. The parent mixing element can be characterized by its characteristic hydraulic diameter & and its length. We found two length scales during the enlargement or reduction process. The ratio should be kept constant to achieve similar flow conditions into the flow system and similar energy input, which results in similar mixing efficiencies in similar mixing times. For channels in the mixing zone, the pressure loss can be expressed as the following equation: (3) The index of the Reynolds number Re in the denominator „ depends on the flow pattern in the channel in the mixing zone. For a full or full flow, „is a system. In a complex thinking element, mainly a transition flow between a straight stream and a full turbulence, resulting in a non-integer value with a value between _. Especially in the area close to the sputum (mainly turbulent or almost full-end flow), the tolerance to the deviation is higher than the area close to 丨 (mainly laminar flow ^ for the flow pattern of Re and the 1GGG in the T-shaped mixed zone) We find that the index is about 1/3. 201138950 Combine equations 2 and 3, and use the approximation of the hydraulic diameter Μ x average fluid velocity [m,]) and the reasoning using equation 3 such as dh=(/7w)1/ 2 and Re = dhw/v=/7vdh 'The hydraulic diameter 屯 is: 乐〆广f (4) where V represents the kinetic velocity [mY3], which represents the volumetric flow rate [ιηγι], and p represents the density [kgm-3]. The inventors of the present invention have found that the mixing efficiency is strongly dependent on the local rate of energy consumption, i.e., the loss of pressure energy converted during at least two flow mixing processes, as well as the geometry of the channel. This channel directs the flow and causes flow deflection. In addition to the shear force, a new flow vertical force acts on the fluid and creates a secondary flow structure, vortex, and recirculation zone. For the avoidance of doubt, the primary flow structure is a hard-coded flow structure formed by the reactor material in the microchannel. Rapid changes in this type of secondary flow vortex by alternative mixing elements or repeated deviation flows result in efficient flow mixing. To create these secondary flow structures and eddies, the fluid requires mechanical energy consumed by fluid pressure. Therefore, we use the pressure drop per unit volume as a measure of mixing, expressed as the energy consumption rate ε:

Apf Apw £ =;卞 (5) ' ' ... · · ... 通過將發生壓力損失的有效通道長度AL近似為所有混合元件的總長，我們將AL定義為。·在混合通道中消耗的能量越多’由於更小的次級流體結構（即，渦流和再迴圈區）而導致的混合時間越短，並在混合的最後測量中發生種類擴散。該種類擴散，即，該混合時間tm [s]可通過Schmidt數Sc、動力學速度v[m2s·3]與主要種類的擴散的比例表示： (6) 201138950Apf Apw £ =;卞(5) ' ' ... · · ... By defining the effective channel length AL for pressure loss to the total length of all mixing elements, we define AL as . • The more energy is dissipated in the mixing channel The shorter the mixing time due to the smaller secondary fluid structure (i.e., the eddy current and the recirculation zone), and the type of diffusion occurs in the final measurement of the mixing. The species is diffused, that is, the mixing time tm [s] can be expressed by the ratio of the Schmidt number Sc, the dynamic velocity v[m2s·3] and the diffusion of the main species: (6) 201138950

屍合係數 Cm 由 Bourne[J,R. Bourne，Org.Process Res. Dev. 7’ 2003, 471-508]提供，其卷吸比例為17.3。現在該液力直徑可與該體積流速和該典型混合時間關聯： dhThe cadaver coefficient Cm is provided by Bourne [J, R. Bourne, Org. Process Res. Dev. 7' 2003, 471-508], and has a entrainment ratio of 17.3. The hydraulic diameter can now be associated with the volumetric flow rate and the typical mixing time: dh

Cm Sc (cf \ ) l24 7 J ⑺ 對於多數微反應器的.工業應用，典型壓力損失的適當範圍為1.0、5.0和20bar’混合時間的適當範圍為〇·卜0.01和〇 001 秒。用於工業應用的微反應器中指數„的合適值範圍從〇 (全湍流）至約1/4 (過渡和低湍流）至約1/3 (層狀渦流）。由於低混合效率’此處不考慮指數”為1的完全層流。採用如下液力直徑和壓降的關係：Cm Sc (cf \ ) l24 7 J (7) For industrial applications in most microreactors, the typical range of typical pressure loss is 1.0, 5.0 and 20 bar'. The appropriate range for mixing time is 0.01·b 0.01 and 001 001 sec. Suitable values for the index „ in microreactors for industrial applications range from 〇 (full turbulence) to about 1/4 (transition and low turbulence) to about 1/3 (layered eddy current). Due to low mixing efficiency 'here A full laminar flow with an index of 1 is not considered. The following relationship between hydraulic diameter and pressure drop is used:

Ap = iLtCf pv d\- (10) 補償壓降所需的泵功率可表達為： (11) 〔手〆库㈣料類似的混合時間，直徑與體積流速的比« 遵#上文的等式1。 ⑴ dh'2=dh\t 與在合適流動方式（㈣㈣)和過«流為n=_ 1/3))中y指數的範例為3/7 = 0·4286 (最佳），以及分別為和2/5—-G.4(兩者均得到可接受的物理參數） 201138950 之相比’全層流方式（n=1，即，在微反應器中低效混合）的指數為2/6 == 0.3333。因此，為實現可接受和相當的以可接受的壓降（吒’需要泵功率）和能量消耗（即，輸入流動的能量）表示的混合時間和效率’該指數應當在〇 4286和〇4的較窄範圍内。在合適湍流/過渡流動比例例如1/4和1/3與非適合比例1相比於10倍流動增加下的最佳所需液力直徑證明瞭離開優選”範圍時的巨大變化。根據等式i，在湍流至過渡流動方式1/4 (75%) 和1/3 (約66%)的1〇倍流動增加分別導致了小5 〇%和6 8%的最佳液力直徑。這種偏差可被忽略。相反地，在5〇%湍流至過渡流動比例下的10倍流動增加導致了小24 5%的最佳液力直徑。在離開優選η範圍時所需泵功率的變化也报大。對於1〇倍流速增加’小約7%的液力直徑需要接近雙倍的泵功率以在瑞流方式下實現類似的混合時間。小33%的液力直徑需要接近職的系功率。在相tbm的值大讓的餘下流速增加聰對應了長2倍的混合時間。因此，過小的直徑需要過大的泵功率，而過大的直捏導致過慢的混合。通道幾何形狀，流財式（由#諾數值確定，該值為（流速X液力直徑）和動力學逮度之間的比例，其應當大於⑽， =於3〇〇)以及祕。流動通道的液力或當量球徑dh通常 :的::二：，其中A為橫截面積’ U為該流動通道橫截面=·、潤周長。與上述雷諾數值&的_可通過其定義建立， r ΡΜ/μ，dh為所述液力錢。其絲量錢 …以及動力學速度μ。應當指出，等式⑴僅對滿流有效， 12 201138950 這是由EP 1 839 739階露的與c由职路的微反應器明顯混合區的放大及其修改所得的限制。 ’ 儘管在標準反應器和目標反應器之間的基本設計保持不變❻技術人員可知可適當採用多種物理變數來將標準反應器的體積流速改變為目標反應器的體積流速。最優選地可根據本發明將給定尺寸放大為下—個更大的尺寸，即，例如，由聽Μ 面積§量工藝板至DIN Α4面積當量工藝板，在混合區具有1/3 至1/7範圍内的因數的壓降變化，而該混合區的寬度和高度每二提同的因數為1.3至1.4。—般而言，在放大過程中不應削減最】冰留時間。其他變數為迂回結構的“纏繞，，數量，纏繞的“變中田及其寬度和高度，滯留區的體積，其例如可作為增加體積流迷的後果而被擴大。對於滯留區的變化，應指出壓降的減少並非印留區擴大的線性函數，因為入口端也對壓降產生作用。根據本發明的優選方面，該目標反應器為微反應器。應指出’如上所述’此處的微反應器包括至少一個具有多個混合元件的混合區，其中反應劑混合物在每個混合元件内通過時損失相同的能量。根據本發明的第二方面定義了一個標準反應器和目標反應器的組’.其可在該標準反應器基礎上製造，且上述方法保持了標準反應器的化學反應性能。應指出’該方法和根據本發明製造的該反應器優選地但不限於在藥物開發的臨床Ι-ΠΙ期中使用，其中，從I期至III期’測試中需要的人員數以及待測試醫學物質的數量上升。【實施方式】. 13 201138950 以下將參照附圖就本發明的具體實施例進行詳細說明。在下文中，根據本發明的方法將參考相同申請人的Ερ ι 839 739 A1中揭露的微反應器（作為標準反應器的範例）進行描述。當然’根據本發明的方法可應用至任意其他具有可通過上述引用的微反應器的相同參數確定流體動力學的反應器。總體而言’該標準反應器可以是生成所需產物的任意現有反應器，所述反應器包括至少一種湍流方式和至少一種層流方式，但具有不同的（即更大或更小的）所需產物的禮積流替代性地，該標準反應器可以是生成所需產物的目標導向開發過程、的結果，該開發過程可構成根據本發明的方法的初始步驟。這種目標導向的開發過程可起始于生成所需產物的最初目標，因此，可包括通過由初始反應器原型至能夠生成具有所需品質和化學鑒定特徵的產物的最終反應器原型的各個階段設計和構造合適的（標準）反應器的典型工程過程。換言之，該目‘導向過程的主要方面是得到反應器原型，其能夠生成所需化學產物，而非形成該產物的特定目標體積流速，且它可被用作標準反應器。士根據本發明，可採用包括至少一種湍流方式和至少一種層 :方式的例如能夠生成任意量的所需產物的標準反應器來製化此實現所需產物的所需目標體積流速的目標反應器。換言 =’根據本發明的方法起始于能夠生成具有才目同品質和相同化于鑒定特徵的所需產物，但體積流速不符合所需目標體積流速的合適標準反應器。卜本發明的申請人開發的用於B型化學反應的標準反應器的 ^例為彼露於EP 1 839 739 A1的微反應器。第1-3圖對應於 9 73 9八1的第ι、2以及17圖，顯示了該種已知微反應 201138950 圖對應於EP 1 839 739 A1的第3-6 1和混合模組2，作為該已知微反應器的總體模組構造。第4. 圖’顯示了溫度調節模組器的各種工藝模組的範例。如第1、2以及3圖所示的微反應器包括了第一框架裝置 1〇，第一熱交換模組7, 熱交換模組8，作為另一交換模組7，作為另一工作為工藝模組的熱調節模組1，第二Ap = iLtCf pv d\- (10) The pump power required to compensate for the pressure drop can be expressed as: (11) [handle bank (four) material similar mixing time, ratio of diameter to volume flow rate « 遵# above equation 1. (1) dh'2=dh\t and the example of the y-index in the appropriate flow pattern ((iv)(iv)) and over-_flow is n=_ 1/3) is 3/7 = 0·4286 (best), and Compared with 2/5--G.4 (both get acceptable physical parameters), the full-laminar flow mode (n=1, ie, inefficient mixing in the microreactor) has an index of 2/1 compared to 201138950. 6 == 0.3333. Therefore, in order to achieve acceptable and comparable mixing time and efficiency expressed in terms of acceptable pressure drop (吒 'requires pump power) and energy consumption (ie, input flow energy)' the index should be at 〇4286 and 〇4 In a narrower range. The optimum required hydraulic diameter at a suitable turbulence/transition flow ratio such as 1/4 and 1/3 compared to the unsuitable ratio 1 over a 10 fold flow increase demonstrates a large change from the preferred "range". i, 1 ( (75%) and 1/3 (about 66%) of the turbulent to transitional flow increases by 1 〇, resulting in an optimum hydraulic diameter of 5 〇 % and 6 8%, respectively. The deviation can be ignored. Conversely, a 10x flow increase at 5〇% turbulence to the transition flow ratio results in a 245% optimal hydraulic diameter. The change in pump power required when leaving the preferred η range is also reported. Large. For a 1 〇 flow rate increase, a hydraulic diameter of about 7% requires nearly double the pump power to achieve a similar mixing time in the reefer mode. A small 33% hydraulic diameter requires close to the system power. The increase in the value of the phase tbm allows the remaining flow rate to increase by 2 times the mixing time. Therefore, too small a diameter requires excessive pump power, while excessive straight pinching results in too slow mixing. Channel geometry, flow type (determined by #诺值, this value is (flow rate X hydraulic diameter) and dynamics catch The ratio between the two should be greater than (10), = at 3 〇〇) and secret. The hydraulic or equivalent spherical diameter dh of the flow channel is usually: : 2: where A is the cross-sectional area ' U is the cross section of the flow channel =·, Run perimeter. With the above Reynolds value & _ can be established by its definition, r ΡΜ / μ, dh for the hydraulic money. Its silk volume ... and the dynamic velocity μ. It should be noted that the equation (1) Valid only for full flow, 12 201138950 This is a limitation of the amplification of the apparent mixing zone of the microreactor with the c-road by EP 1 839 739 and its modifications. 'Although in standard reactors and target reactors The basic design between the two remains unchanged. The skilled person will appreciate that a variety of physical variables can be suitably employed to vary the volumetric flow rate of the standard reactor to the volumetric flow rate of the target reactor. Most preferably, the given size can be scaled down to the next according to the present invention - a larger size, that is, for example, a pressure drop from a hearing plate area to a DIN Α 4 area equivalent process plate, with a factor of 1/3 to 1/7 in the mixing zone, and the mixing zone The width and height of each two are the same as 1 .3 to 1.4.—In general, the maximum ice retention time should not be reduced during the amplification process. Other variables are the “winding, number, winding” of the twisted structure, the width of the field and its width and height, and the volume of the detention zone. For example, it can be expanded as a consequence of increasing the volume flow. For changes in the retention zone, it should be noted that the reduction in pressure drop is not a linear function of the expansion of the footprint, since the inlet end also acts on the pressure drop. In a preferred aspect, the target reactor is a microreactor. It should be noted that 'as described above' the microreactor comprises at least one mixing zone having a plurality of mixing elements, wherein the reactant mixture is lost as it passes through each mixing element The same energy. According to a second aspect of the invention, a standard reactor and a group of target reactors are defined. It can be manufactured on the basis of the standard reactor, and the above method maintains the chemical reaction performance of the standard reactor. It should be noted that the method and the reactor made in accordance with the present invention are preferably, but not limited to, used in the clinical practice of drug development, wherein the number of personnel required from the Phase I to Phase III test and the medical substance to be tested The number has risen. [Embodiment] 13 201138950 A specific embodiment of the present invention will be described in detail below with reference to the accompanying drawings. In the following, the method according to the invention will be described with reference to a microreactor (as an example of a standard reactor) disclosed in the same applicant's Ερ ι 839 739 A1. Of course, the process according to the invention can be applied to any other reactor having fluid dynamics that can be determined by the same parameters of the microreactor cited above. In general, the standard reactor can be any existing reactor that produces the desired product, the reactor comprising at least one turbulent flow mode and at least one laminar flow mode, but having different (ie larger or smaller) Alternatively, the standard reactor may be the result of a target-oriented development process that produces the desired product, which may constitute the initial steps of the method according to the invention. This goal-oriented development process can begin with the initial goal of producing the desired product, and thus can include various stages of the final reactor prototype from the initial reactor prototype to the ability to produce products of the desired quality and chemically characterized characteristics. A typical engineering process for designing and constructing a suitable (standard) reactor. In other words, the main aspect of the 'guided process' is to obtain a prototype of the reactor that is capable of producing the desired chemical product rather than the specific target volumetric flow rate at which the product is formed, and which can be used as a standard reactor. According to the present invention, a standard reactor comprising at least one turbulent flow mode and at least one layer: for example capable of producing any amount of desired product can be used to produce the desired target volumetric flow rate for achieving the desired target volume of the desired product. . In other words = the method according to the invention starts with a suitable standard reactor capable of producing a desired product having the same quality and identity as the identified feature, but at a volumetric flow rate that does not meet the desired target volumetric flow rate. An example of a standard reactor developed by the applicant of the present invention for a type B chemical reaction is the microreactor of EP 1 839 739 A1. Figures 1-3 correspond to Figures 1, 2, and 17 of 9 73 9 8.1, showing that the known micro-reaction 201138950 corresponds to the third to sixth embodiment of EP 1 839 739 A1 and the hybrid module 2, As the overall modular construction of the known microreactor. Figure 4. shows an example of the various process modules of the temperature regulation module. The microreactors as shown in Figures 1, 2 and 3 comprise a first frame device 1 , a first heat exchange module 7 , a heat exchange module 8 , as another exchange module 7 , as another work Process module thermal regulation module 1, second

和第二框架裝置1〇、9 吳組4、5和6 (以該順序分別夾在兩個熱 -框架裝置9之間）。因此，在所述第一 9之間可交替提供第一或第二熱交換模組 7、8和工藝模組1-6。如圖1、2所示，兩個拉杆13將第一和第一框架裝置10、9彼此推近，從而將堆疊的熱交換模組7、8 和工藝模組1-6彼此壓緊。在微反應器系統元件周圍設置拉杆 13並在接觸該熱交換模組的7、8的框架裝置1〇、9的表面中央提供空腔（見第3圖），可在該微反應器系統元件的周圍獲得高壓力。又在第5和ό圖中顯示的溫度調節模組1作為第一工藝模組提供。所述溫度調節模組1包括第一反應性流體通路1Α，其溝通第一反應性流體入口端1 c和第一反應性流體出口端1F，還包括第一反應性流體通道1B ’其溝通第二反應性流體入口端 1D和第二反應性流體出口端1E。第一反應性流體通過該第一反應性流體入口端1C提供至該第一反應性流體通路ία。第二反應性流體通過該第二反應性流體入口端1D提供至該第-反應性流體通路1B。此外，所述溫度調節模組1包括第一和第二板1M、1N (第6圖）’其通過焊接等方式彼此連接。在接觸該第一和/或第二板1M、1N的表面時該正弦式反應流體通路 λ 15 201138950 ΙΑ、1B通過蝕刻、研磨等方式切割。在通過所述第一反應流體通路1A流向所述第一反應流體出口端1F時，所述第一反應流體的溫度通過夾入了所述溫度調節模組1的兩個熱交換模組 7、8調節。流經所述熱交換模組7、8的熱交換流體通過經接觸所述溫度調節模組的板1M、1N的該熱交換模組的板7N、8M 的熱傳導向所述第一反應流體提供或去除熱量。在第6和7圖中顯示的混合模組2作為第二工藝模組提供。儘管未具體顯示，所述混奋模組2包括了與上述溫度調節模組1類似的第一和第二板。在所述混合模組中提供了包括混合段2G和第一滯留段21的反應流體通路2A。與所述反應流體通路2A連通的第一反應流體入口端2C通過外部連接（未圖示）與該溫度調節模組1的該第一反應流體出口端1F連接。同樣與該反應流體通路2 A連通的第二反應流體入口端2 D類似地與該溫度調節模組1的第二反應流體出口端1E連接。因此，在通過所述溫度調節模組1後，該第一和第二反應流體分別流入混合模組2内的通路2A的混合段2G，其中所述兩種反應流體彼此混合。如第7圖中放大顯示的混合段2G的幾何形狀可通過適當選擇以最佳方式混合該反應流體。混合後，所得的工藝流體流入反應流體通路2A的該第一滯留段21，其基本上形成為平坦的通道，從而提供該工藝流體的基本層流。在該混合段 2G和該第一滯留段21内的混合和滯留過程中，該化學反應可通過夾入所述混合模組2的兩個熱交換模組8、7進行溫度控制。通過反應流體出口端2E離開反應流體通路2A的工藝流體進入各滯留模組3-6，其中該工藝流體受到鄰近每一個滯留模組的兩個熱交換模組7、8的溫度控制，如前文所述的溫度調 16 201138950 節模組1和混合模組2。通過此方式，該溫度流體可在經最後的工☆模組出口端6D離開該微反應器系統元件之前流經所有後續的滯留模組4-6。在每一個滯留模組3_6中的滞留時間可通過滞留體積定義，即’容納該工藝流體的通路3Α·6Α的分段（1 χ高）X 長度，除以流速。因此，通過提供單個通路的不同寬度、長度和/或高度，可獲得不同的滯留時間。通過將不同的滯留模組與不同的通路4何形狀結合’可以幾乎任意選擇滯留時間。 Θ模、.且1 -6中的反應流體通路可通過钱刻、研磨等方式微結構化。由於該熱交換模組7、8為單獨製造，它們製造為非微結構化形式，從而降低成本。此外，由於所述熱交換模組 7、8不與反應劑接觸，它們無需耐受腐姓或高工藝壓力，從而允許使用優化熱傳遞的材料。上述微反應器由於其模組結構提供了高靈活性，並允許將不同的混合通道幾何形狀與不同的滞留模組組合，從而提供任意選擇的滯留時間，特別是對於Β型反應。所述工藝模組W 的每一個受到兩個相鄰熱交換模組7、8的溫度控制。由於轨傳遞僅通過熱交換模組7、8和工藝模組W的板ιμ_8μ、刚Ν 的熱傳導實現，無需進行密封。此外，有利m藝㈣Μ 可針對其中容納的反應劑進行優化，例如耐腐韻和/或麗力，同時該熱交換模組7、8不盥該及庙鈿拉艇 ^ „ 密封特徵進行優化、劑接觸，可針對熱傳遞和/或對於DIN Α5尺寸微反應H，即板的表面積與聰α5相近 =微反應器，假定流速為例如⑽mI/min，工藝模組的通路長 ^為刪·，通路高度約$ 1〇麵，通路寬度㈣ .麵，可在樣本測試中實現每個模組的滯留時間為6-22And the second frame means 1 〇, 9 武 groups 4, 5 and 6 (between the two heat-frame devices 9 respectively in this order). Therefore, the first or second heat exchange modules 7, 8 and the process modules 1-6 are alternately provided between the first 9. As shown in Figures 1 and 2, the two tie rods 13 push the first and first frame members 10, 9 closer together, thereby pressing the stacked heat exchange modules 7, 8 and the process modules 1-6 against each other. A tie rod 13 is disposed around the microreactor system component and a cavity is provided in the center of the surface of the frame means 1 , 9 contacting the heat exchange modules 7, 8 (see Fig. 3), in which the microreactor system components are Get high pressure around. The temperature adjustment module 1 shown in the fifth and fourth figures is provided as the first process module. The temperature adjustment module 1 includes a first reactive fluid passage 1Α that communicates a first reactive fluid inlet end 1 c and a first reactive fluid outlet end 1F, and further includes a first reactive fluid passage 1B' A second reactive fluid inlet end 1D and a second reactive fluid outlet end 1E. A first reactive fluid is supplied to the first reactive fluid passage ία through the first reactive fluid inlet end 1C. A second reactive fluid is supplied to the first-reactive fluid passage 1B through the second reactive fluid inlet end 1D. Further, the temperature adjustment module 1 includes first and second plates 1M, 1N (Fig. 6) which are connected to each other by welding or the like. The sinusoidal reactive fluid passage λ 15 201138950 ΙΑ, 1B is cut by etching, grinding, or the like upon contact with the surface of the first and/or second plates 1M, 1N. When flowing through the first reaction fluid passage 1A to the first reaction fluid outlet end 1F, the temperature of the first reaction fluid passes through the two heat exchange modules 7 of the temperature adjustment module 1 8 adjustment. The heat exchange fluid flowing through the heat exchange modules 7, 8 is supplied to the first reaction fluid through heat conduction through the plates 7N, 8M of the heat exchange module contacting the plates 1M, 1N of the temperature regulation module Or remove heat. The hybrid module 2 shown in Figures 6 and 7 is provided as a second process module. Although not specifically shown, the hybrid module 2 includes first and second plates similar to the temperature adjustment module 1 described above. A reaction fluid passage 2A including the mixing section 2G and the first retention section 21 is provided in the mixing module. The first reaction fluid inlet end 2C communicating with the reaction fluid passage 2A is connected to the first reaction fluid outlet end 1F of the temperature adjustment module 1 by an external connection (not shown). The second reaction fluid inlet end 2D, which is also in communication with the reaction fluid passage 2A, is similarly coupled to the second reaction fluid outlet end 1E of the temperature regulating module 1. Therefore, after passing through the temperature adjustment module 1, the first and second reaction fluids respectively flow into the mixing section 2G of the passage 2A in the mixing module 2, wherein the two reaction fluids are mixed with each other. The geometry of the mixing section 2G as shown enlarged in Figure 7 can be optimally mixed by appropriate selection. After mixing, the resulting process fluid flows into the first retentate section 21 of the reaction fluid passage 2A which is formed substantially as a flat passage to provide a basic laminar flow of the process fluid. During the mixing and retention of the mixing section 2G and the first retention section 21, the chemical reaction can be temperature controlled by the two heat exchange modules 8, 7 sandwiched by the mixing module 2. The process fluid exiting the reaction fluid passage 2A through the reaction fluid outlet end 2E enters each of the retention modules 3-6, wherein the process fluid is controlled by the temperature of the two heat exchange modules 7, 8 adjacent to each of the retention modules, as previously described The temperature is adjusted to 16 201138950 module 1 and hybrid module 2. In this manner, the temperature fluid can flow through all of the subsequent retention modules 4-6 before exiting the microreactor system components via the final IE module exit end 6D. The residence time in each of the retention modules 3_6 can be defined by the retention volume, i.e., the segmentation (1 χ height) X length of the passage 3 Α·6 容纳 accommodating the process fluid, divided by the flow rate. Thus, different residence times can be obtained by providing different widths, lengths, and/or heights of individual passages. By combining different retention modules with different paths 4 and shape, the residence time can be chosen almost arbitrarily. The reaction fluid path in the mold, and in 1 to 6 can be microstructured by means of engraving, grinding, or the like. Since the heat exchange modules 7, 8 are manufactured separately, they are manufactured in a non-microstructured form, thereby reducing costs. Moreover, since the heat exchange modules 7, 8 are not in contact with the reactants, they do not need to withstand corrosion or high process pressure, thereby allowing the use of materials that optimize heat transfer. The microreactor described above provides high flexibility due to its modular construction and allows for the combination of different mixing channel geometries with different retention modules to provide an arbitrarily selected residence time, particularly for Β-type reactions. Each of the process modules W is temperature controlled by two adjacent heat exchange modules 7, 8. Since the rail transfer is realized only by the heat transfer modules 7, 8 and the plate ιμ_8μ of the process module W, and the heat conduction of the crucible, no sealing is required. In addition, it is advantageous to optimize the reactants contained therein, such as corrosion resistance and/or Lili, while the heat exchange modules 7, 8 are not optimized for the sealing characteristics of the temple and the boat. Agent contact, for heat transfer and / or for the DIN Α 5 size micro-reaction H, that is, the surface area of the plate is close to the C5 α = microreactor, assuming a flow rate of, for example, (10) mI / min, the length of the process module is deleted, The height of the path is about $1〇, the width of the path (four). The surface can be used to achieve a retention time of 6-22 per module in the sample test.

S 17 201138950 秒《因此可實現總體滯留時間最大為30分鐘。順帶地，通過對現有流動通道系統的磨銑和改變混合區的尺寸，DIN Α4尺寸微反應器可模擬原始的DIN A5尺寸微反應器，即，邊緣長度不變。 - 對於上述微反應器的構造和操作方式的其他技術細節可參考 EP 1 839 739 A1。一般而言：’如上所述，作為製造實現所需產物目標體積流速的目標反應器的起始點#標準反應器具肴此種流動通道.系.. 統’其中連續流入該標準反應器的多種反應劑被混合並轉化形成連續流出該標準反應器的所需產物的體積流速^。該（最大）體積流速/!取決於流動通道系統（最小液力直徑，流動通道系統長度，壓力，溫度狀況）和反應劑（粘度，反應性）兩者的多種流動湘關鑒定特徵。參考EP i 839 739 A1中披露的微反應器，該種流動通道系統包括，例如，第4和5圖中所示的溫度調節模組1的流體通路1A和1B，以及第6和7圖中所示的混合模組2的流體通路2G、2A和21。由能夠生成具有所需品質和所需鑒定特徵的產物但具有不同於目標體積流速h的體積流速Λ的標準反應器開始，可製造能夠生成相同產物的目標體積流速力的目標反應器。標準反應器的體積流速/,可通過’例如測量或計算方式確定。當該標準反應器為例如EP 1 839 739 A1所披露的由各自包含子流 1道系統的多個藝模組的組合形成的模組反應器時，作為 ,流動通道系統總和的完全流動通道系統應當遵循根據本發明的方法，其巾在該完全流動通道系統巾僅有—個最小液力直徑。， 18 201138950 根據本發明的方法，標準反應器流動通道系統的最小液力直徑dh“最小標準液力直徑）可通過例如測量或計算的方式確定，且目標反應器的相應最小液力直徑^匕（最小目標液力直徑）可基於標準反應器的最小液力直徑dhi、標準反應器的標準體積流速/丨以及目標反應器的目標體積錢/2之間明確的關係計算得到。如上所述，根據本發明，優選地適用如下等式： /- \3/7 dh2=dhl ήτ (1) 计算dh2後，目標反應器的流動通道系統的剩餘設計參數，例如長度、形狀等’可由本領域技術人員根據相應的需求容易地確定和調整。確定和調整該流動通道剩餘的設計參數後，该目標反應器的外部尺寸可相對標準反應器進行變化。· 第8A和8B圖反應了根據本發明的方法的理念。具體而言’第8A和8B目顯示了作為標準反應器和目標反應器的板狀工藝模組的範例的兩個混合模組，其具有不同尺寸（外部尺寸），並基本上具有彼此不同的形狀，例如相應流體通道系統的路線和長度，以及它們各自的放大和縮減。第8A圖中所示的混合模組可被視為代表了標準反應器，第8B圖中的混合模組可被視為代表了目標反應器。儘管相應流動通道系統的形狀以及该板狀工藝模組的外部尺寸具有差異，這些工藝模組的總體構造原理是相同的。如上文對第4_6圖的描述，第8八和圖所示的每一個模組由兩個具有流動通道系統的板構件形成，或者採用上述術語：其中結合了 “子流動通道系統，，。第8A 和8B圖揭示了所示的珲回結構在突出部平面内延伸，該突出部平面（例如，對於模組反應器）可以是相應模組延伸的平面。 19 201138950 第8A和8B圖所示的混合模組可被結合進入EP 1 839 739 Al 中彼露的結構的微反應器以代替上述混合模組1。第8A和8B圖分別顯示了 2號尺寸和3號尺寸的微反應器’其處於正確空間關係（然而，並非約DIN 6 : DIN 5當量面積的比例）。在每種情況下清楚顯示了湍流混合區丨〇和層流滯留區20。可以看到’包括湍流混合區1〇和層流滯留區2〇的流動通道系統的基本設計是相同的，儘管纏繞30的數量和迂回結構的變幅40彼此不同。其結構細節可參見ep 1 839 739 A1。第9圖顯示了不同子流動通道系統的混合區部分，其中每種情況的圓圈為渴輪混合單元的截面。第一列的範例僅包括渦輪混合元件，第二列為渦輪和SL_混合元件的混合物，最後一列為渦輪和sz-混合元件的混合物。術語“SL”和“sz，，為唯象性質，它們各自的結構類似於相應大寫字母的組合。這些以及其他混合器形式顯示於第10圖。其中圖幻至f)分別被稱為τ接觸器、Y-接觸器、正切混合器、彎管、32：混合器和Lz混合器c 具體而言，第9圖中從第一到第四排分別顯示了 i號尺寸、: 號尺寸、3號尺寸和4號尺寸的各種微反應器的工藝模組的流動通道部分的示範性結構，其參數“混合寬度，，、‘‘混合高度，,、“滞 =高度”和“滯㈣度”根據下文表i，其中3號尺寸可被視為我標準反應H ’ 1號和2號尺寸可被視為代表縮減目， 4號尺寸可被視為代表放大目標反應器。相應地，當^尺寸 =為代域準反應m號尺切被視為絲_目標及 :’而3戒和4號尺寸可被視為代表放大目標反應器以此類推。 20 201138950 表流速反應器混合混合滞留滯留 [ml/min] 尺寸寬度南度寬度南度 1-10 1 0.2 0.5 5 0.3/0.5/1.5 50-150 2 0.5 1.2 5 0.5/1.0/2.0 100-300 3 0.7 1.75 10 0.5/1.0/2.0 200-1000 4 1.0 2.2 10/20 0.5/1.072.0 如上所述’一旦a十鼻得到表徵目標反應器流動通道系統的最小液力直徑dh ’可採用標準反應器作為有關構造總體原理的範例製造目標反應器。基於特定最小液力直徑，該目標反應器與標準反應器的區別主要僅在於混合區的幾何形狀；滯留I 的幾何形狀可被採用。如第8A和8B或第9圖所示，在從標準反應器製造目標反應器時，儘管構造的基本原理保持相同，不僅液力直徑將變化’流動通道系統的長度也會變化。考慮如下事實，目標反應器的目標體積流速與標準反應器的標準體積流. 速相比更大或更小，目標反應器流動通道系統的其他結構= 數’例如長度、纏繞數、除最小液力直徑外的所有其他直徑等，可被定義並調整以綠立該目標反應器的合適流動特性。最終的外部尺寸，即，該目標反應器的尺寸是該目標反應器的流動通道系統的所有設計特徵的定義和調整的結果。綜上所述，雖然本發明已用較佳實施例揭露如上，非用以限定本發明’本發明所屬技術領域中具有通常知識者， =不脫離本發明之精神和範#可作各種之更輕 ^此本發明之保護範圍當視後附之中請專利範圍所界S 17 201138950 sec "Therefore, the overall residence time can be up to 30 minutes. Incidentally, by milling the existing flow channel system and changing the size of the mixing zone, the DIN Α4 size microreactor can simulate the original DIN A5 size microreactor, ie the edge length is constant. - For further technical details on the construction and operation of the above microreactors, reference is made to EP 1 839 739 A1. In general: 'As mentioned above, as the starting point of the target reactor for the production of the desired target volumetric flow rate of the desired product #标准反应装置(s) This type of flow channel is a system that continuously flows into the standard reactor. The reactants are mixed and converted to form a volumetric flow rate ^ of the desired product continuously flowing out of the standard reactor. This (maximum) volumetric flow rate /! depends on a variety of flow identification characteristics of the flow channel system (minimum hydraulic diameter, flow channel system length, pressure, temperature conditions) and reactant (viscosity, reactivity). Reference is made to the microreactor disclosed in EP i 839 739 A1, which comprises, for example, fluid passages 1A and 1B of the temperature regulating module 1 shown in Figures 4 and 5, and in Figures 6 and 7 The fluid passages 2G, 2A and 21 of the hybrid module 2 are shown. Starting from a standard reactor capable of producing a product having the desired quality and desired identification characteristics but having a volumetric flow rate 不同于 different from the target volume flow rate h, a target reactor capable of producing a target volumetric flow rate force of the same product can be produced. The volumetric flow rate / of the standard reactor can be determined by, for example, measurement or calculation. When the standard reactor is a modular reactor formed by a combination of a plurality of art modules each comprising a substream system, as disclosed in EP 1 839 739 A1, as a complete flow channel system for the sum of the flow channel systems The method according to the invention should be followed in that the towel has only a minimum hydraulic diameter in the full flow channel system. 18 201138950 According to the method of the invention, the minimum hydraulic diameter dh "minimum standard hydraulic diameter" of a standard reactor flow channel system can be determined, for example, by measurement or calculation, and the corresponding minimum hydraulic diameter of the target reactor (Minimum target hydraulic diameter) can be calculated based on a clear relationship between the minimum hydrodynamic diameter dhi of the standard reactor, the standard volumetric flow rate / 丨 of the standard reactor, and the target volume of the target reactor. According to the invention, the following equation is preferably applied: /-\3/7 dh2=dhl ήτ (1) After calculating dh2, the remaining design parameters of the flow channel system of the target reactor, such as length, shape, etc., can be The personnel can easily determine and adjust according to the corresponding requirements. After determining and adjusting the remaining design parameters of the flow channel, the external size of the target reactor can be changed with respect to the standard reactor. · Figures 8A and 8B reflect the invention according to the present invention. The concept of the method. Specifically, '8A and 8B show examples of slab process modules as standard reactors and target reactors. Two hybrid modules having different sizes (outer dimensions) and having substantially different shapes from each other, such as the route and length of the respective fluid channel system, and their respective enlargement and reduction. The mixing shown in Figure 8A The module can be considered to represent a standard reactor, and the hybrid module in Figure 8B can be considered to represent the target reactor. Although the shape of the corresponding flow channel system and the external dimensions of the plate-like process module are different, The overall construction principle of these process modules is the same. As described above with respect to Figure 4-6, each of the modules shown in Figures 8 and is formed by two plate members having a flow channel system, or by the above terms: Which combines the "sub-flow channel system,". Figures 8A and 8B illustrate the illustrated meandering structure extending in the plane of the projection, which projection plane (e.g., for a modular reactor) may be a plane in which the respective modules extend. 19 201138950 The hybrid module shown in Figures 8A and 8B can be incorporated into the microreactor of the structure disclosed in EP 1 839 739 Al in place of the hybrid module 1 described above. Figures 8A and 8B show the size 2 and size 3 microreactors, respectively, in the correct spatial relationship (however, not in the ratio of DIN 6: DIN 5 equivalent area). The turbulent mixing zone 层 and the laminar stagnation zone 20 are clearly shown in each case. It can be seen that the basic design of the flow channel system including the turbulent mixing zone 1〇 and the laminar flow retention zone 2〇 is the same, although the number of windings 30 and the variable width 40 of the bypass structure are different from each other. The structural details can be found in ep 1 839 739 A1. Figure 9 shows the mixing zone portion of the different sub-flow channel systems, where the circle for each case is the cross section of the thirsty wheel mixing unit. The first column example includes only the turbine mixing elements, the second column is a mixture of turbine and SL_mixing elements, and the last column is a mixture of turbine and sz-mixing elements. The terms "SL" and "sz," are phenomenological properties, and their respective structures are similar to the combination of corresponding uppercase letters. These and other mixer forms are shown in Figure 10. Where phantom to f) are referred to as τ contacts, respectively. , Y-contactor, tangential mixer, elbow, 32: mixer and Lz mixer c Specifically, the first to the fourth row in Figure 9 shows the size of i, the size of the number, and 3 An exemplary structure of the flow channel portion of the process module of various microreactors of size and size 4, with parameters "mixing width,", "mixing height", "hysteresis = height" and "lag (four) degrees" According to Table i below, where size 3 can be considered as my standard reaction H'1 and size 2 can be considered to represent the reduced size, size 4 can be considered to represent the amplification target reactor. Accordingly, when ^ size = for the domain quasi-reaction m-cut is considered as the wire_target and :' and the 3 and 4 sizes can be considered to represent the amplification target reactor and so on. 20 201138950 Table Flow Rate Reactor Mixing Retention Retention [ml/min] Size Width South Width South 1-10 1 0.2 0.5 5 0.3/0.5/1.5 50-150 2 0.5 1.2 5 0.5/1.0/2.0 100-300 3 0.7 1.75 10 0.5/1.0/2.0 200-1000 4 1.0 2.2 10/20 0.5/1.072.0 As mentioned above 'once a ten nose is characterized by the minimum hydrodynamic diameter dh ' of the target reactor flow channel system can be used standard reactor The target reactor is fabricated as an example of the overall principle of construction. Based on a particular minimum hydraulic diameter, the target reactor differs from the standard reactor primarily only in the geometry of the mixing zone; the geometry of the retention I can be employed. As shown in Figures 8A and 8B or Figure 9, when the target reactor is fabricated from a standard reactor, although the basic principles of construction remain the same, not only will the hydraulic diameter vary - the length of the flow channel system will vary. Consider the fact that the target volumetric flow rate of the target reactor is larger or smaller than the standard volumetric flow rate of the standard reactor, and other structures of the target reactor flow channel system = number 'eg length, number of windings, minimum liquid All other diameters, etc. outside the force diameter, can be defined and adjusted to green the appropriate flow characteristics of the target reactor. The final external dimension, i.e., the size of the target reactor, is the result of the definition and adjustment of all design features of the flow channel system of the target reactor. In the above, although the present invention has been disclosed in the above preferred embodiments, it is not intended to limit the invention to the ordinary skill in the art to which the invention pertains, and may be made lighter without departing from the spirit and scope of the invention. ^The scope of protection of the present invention is regarded as the scope of the patent

S 21 201138950 【圖式簡單說明】第1圖顯示一種已知微反應器系統元件的立體視圖；第2圖顯示第i圖所示的微反應器系統元件旋轉鮮的立體視圖；第3圖顯示第i圖所示的微反應器系統的縱向切面；第4圖顯示第丨圖所示的微反應器系統元件的熱調節模組的正面剖視圖；第5圖顯示第4圖的熱調節模組的左視圖；第6圖顯示第1圖所示的微反應器系統元件的混合模組的正面剖視圖；第7圖顯示第6圖中以“χ”指出的左上角的放大視圖；第8八和8Β圖分別顯示2號尺寸的標準反應器的工藝/混合模組以及3號尺寸的放大目標反應㈣工藝/混合模組；。第9圖顯示標準反應器、縮減目標反應器和放大目標反應器的工藝模組的三種不同形狀的流動通道部分；以及第10圖概要地顯示本發明所用的不同混合器形式。主要元件符號說明】 1 熱調節模組 1Α 第一反應性流體通路 1Β 第一反應性流體通道 1C 第一反應性流體入口端 1D 第二反應性流體入口端 1Έ 第二反應性流體出口端 1F 第一反應性流體出口端 22 201138950 1M 第一板 IN 第二板 2 混合模組 2A 反應流體通路 2C 第一反應流體入口端 2D 第二反應流體入口端 2E 反應流體出口端 2G 混合段 21 第一滯留段 3、4、5、6 滯留模組 3A-6A 通路 6D 工藝模組出口端 7 第一熱交換模組 8 第二熱交換模組 9 第二框架裝置 10 第一框架裝置 13 拉杆 20 層流滯留區 30 纏繞 40 迂回結構的變幅 23S 21 201138950 [Simplified illustration of the drawings] Fig. 1 shows a perspective view of a known microreactor system component; Fig. 2 shows a perspective view of the microreactor system component shown in Fig. i; The longitudinal section of the microreactor system shown in Figure i; Figure 4 shows a front cross-sectional view of the thermal conditioning module of the microreactor system component shown in Figure ;; Figure 5 shows the thermal conditioning module of Figure 4. Figure 6 shows a front cross-sectional view of the hybrid module of the microreactor system component shown in Figure 1; Figure 7 shows an enlarged view of the upper left corner indicated by "χ" in Figure 6; And the 8Β diagram shows the process/mixing module of the standard reactor of size 2 and the amplification target reaction of the size 3 (4) process/mixing module; Figure 9 shows three differently shaped flow channel portions of a standard reactor, a reduced target reactor, and a process module that amplifies the target reactor; and Figure 10 schematically shows the different mixer forms used in the present invention. Main component symbol description] 1 Thermal regulation module 1Α First reactive fluid path 1Β First reactive fluid channel 1C First reactive fluid inlet end 1D Second reactive fluid inlet end 1Έ Second reactive fluid outlet end 1F A reactive fluid outlet end 22 201138950 1M first plate IN second plate 2 mixing module 2A reaction fluid passage 2C first reaction fluid inlet end 2D second reaction fluid inlet end 2E reaction fluid outlet end 2G mixing section 21 first retention Section 3, 4, 5, 6 Retention Module 3A-6A Path 6D Process Module Outlet 7 First Heat Exchange Module 8 Second Heat Exchange Module 9 Second Frame Device 10 First Frame Device 13 Tie Rod 20 Laminar Flow Retention zone 30 Winding 40 Width of the structure

Claims

201138950 VII. Patent application scope: 1. A method for manufacturing a target reactor, the target reactor having a flow channel system, wherein a plurality of reactants continuously flowing into the target reactor are mixed and converted to form a continuous flow out of the target reactor Target volumetric flow rate (/2) of the product, wherein the minimum hydraulic diameter (dh2) of the target reactor is based on the corresponding minimum hydraulic diameter of a standard reactor in a turbulent or transitional turbulent flow channel system having the same fluid type The following relationship between (dhl) is calculated / X - rf 7 - λ ^ Α 2 = dh \ , J \ ) where "is a non-integer value and 1 > 〇, Α is the standard reactor for carrying out the same transformation The standard volume flow rate 'y*2 is the target volume flow rate. 2. The method of claim 1, wherein i/3 > w 2 〇 is preferably 1/4 of 1/4. 3. The method of claim 1 or 2, wherein dh2 > dhl. 4. The method of any one of claims 1-3, wherein the reactor is a microreactor comprising at least one mixing zone having a plurality of mixing elements. a standard reactor and a target reactor set, the standard reactor comprising a flow channel system, wherein a plurality of reactants continuously flowing into the standard reactor in a turbulent or transitional turbulent flow are mixed and converted to a standard volumetric flow rate (7) And said target reactor comprises a flow channel system of the same fluid type, wherein a plurality of reactants continuously flowing into said target reactor are mixed and converted to a target volumetric flow rate (/2), wherein the minimum hydrodynamic force of the standard reactor The relationship between the diameter (dhi) and the corresponding minimum hydraulic diameter (dh2) of the target reactor is:

24 201138950 where "is a non-integer value and ι > β〇. 6. As in the standard reactor and target reactor group described in claim 5, 1/3 of a?20, preferably 1/4 2 «0. 7. The standard reactor and target reactor group 'where dh2 > dhi as described in claim 5 or 6. S 25