GB2538040A

GB2538040A - Flow reactor and method of conducting flow reactions

Info

Publication number: GB2538040A
Application number: GB1502679.2A
Authority: GB
Inventors: Richard Guthrie Duncan; David Whyatt Adam
Original assignee: Vapourtec Ltd
Current assignee: Vapourtec Ltd
Priority date: 2015-02-18
Filing date: 2015-02-18
Publication date: 2016-11-09
Anticipated expiration: 2035-02-18
Also published as: GB201502679D0; GB2538040B

Abstract

A continuous flow reactor for the reaction of one liquid reagent with another liquid reagent. The reactor has an inner tube, the inner tube defining a first flow path 130 along at least part of the length of the inner tube 102; an outer tube 104, the outer tube enclosing at least a section of the inner tube along its length, so that a second flow path 132 is defined by the space between the outer tube and the inner tube along the length of the tubes; and the inner tube having a plurality of holes (142, fig 6c) through the thickness of the inner tube, the holes being spaced longitudinally along the section of the inner tube enclosed by the outer tube. Flow reactors according to the invention are particularly suited for liquid-liquid reactions and may involve at least one highly reactive reagent. A method of performing flow reactions is also provided.

Description

FLOW REACTOR AND METHOD OF CONDUCTING FLOW REACTIONS

Field of the Invention

The present invention relates to flow reactors and methods of conducting flow reactions It is particularly, but not exclusively, concerned with flow reactors which enable liquid-liquid reactions involving at least one highly reactive reagent.

Background of the Invention

Over the last 150 years various methods have been developed for safely and reliably undertaking the synthesis of new compounds utilising highly reactive reagents in batch reactors. Reactions that fall under this description are nitrations and reactions using organo-metallic reagents amongst many others. As batch reactions the methods broadly required the reactive reagent (nitric acid or Butyl lithium for example) to be slowly added into a dilute solution of the starting material maintained at a low temperature (sometimes as low as -70 degrees C). Vigorous agitation as the reagent is added is required to ensure thorough mixing. Once the addition is complete the mixed solution is allowed to warm to room temperature while vigorous stirring is maintained. Particularly for larger reactors, the surface area to volume ratio of batch reactors is low and therefore the ability of a larger batch reactor to remove heat from the reactants is limited. Extreme care must therefore be exercised to maintain the reactor at a low temperature and prevent overheating. Overheating in some cases can result in a runaway reaction, which is clearly undesirable.

Today, continuous flow reactors are increasingly being used to undertake many fast and potentially hazardous reactions that use highly reactive reagents. For hazardous reactions continuous flow reactors offer a significantly safer alternative to batch reactors for a number of reasons. In particular, the inventory of hazardous material in the reactor at any time is lower. The surface area to volume ratio of these flow reactors can also be between 10 and 1000 times greater than in typical batch reactors which provides for good heat transfer both for dissipation of exothermic reaction heat and for active cooling. The mixing within these reactors is both predictable and rapid which results in good mass transfer.

However, when processing highly reactive reagents, existing continuous flow reactors can have limitations, particularly at larger scale (lower surface area to volume ratio) and/or when the reactants being processed are highly concentrated (or even neat). The main limitation is caused by rapid heating immediately after the mixing point. If the reactants are both concentrated and highly reactive then the temperature rise immediately following the mixing point can approach adiabatic temperature rises as shown in Figure 1 which plots the reactor temperature for a simple tubular reactor measured at the reactor wall against distance from a 1-mixer used for neat nitration of acetophenone (0.5 ml/min) with neat fuming nitric acid (1.0 ml/min). Figure 1 shows that there was a temperature increase of 15 degrees C measured within 10 cm of the mixing point. It is interesting to note that the faster the mixing then the closer to adiabatic the temperature rise will be. Although the temperature is quickly brought under control, the resulting hotspot will, at best have a detrimental effect on the selectivity of the reaction and at worst result in over-reaction and the potential for exothermic decomposition of the product.

In continuous flow reactors, one method for preventing over-reaction that has been adopted by process chemists has been the method of partial additions, shown schematically in Figure 2. Here reactants A and B are being reacted in a reactor 10 to produce product E. Whilst reactant A is pumped directly into the reactor 10 by pump 11, reactant B (which is typically the highly reactive reactant) is supplied to the reactor by three separate paths, each separately controlled by pumps 12, 13 and 14. The reactor 10 has three conceptually Cif not physically) distinct stages 15, 16 and 17 so that by the time the reaction mixture reaches the point 18 where the second path of reactant B (pumped by pump 13) is introduced, all of the original amount of reactant B (pumped by pump 12) has been fully reacted (and, ideally, any temperature increase has dissipated). However this process is cumbersome as it requires either multiple pumps or complex flow splitting therefore limiting the number of possible mixing points.

For gas-liquid reactions, in 2012 Cambridge University, UK published a tube in tube reactor (Koos et al. "Teflon AF-2400 mediated gas-liquid contact in continuous flow methoxycarbonylations and in-line FTIR measurement of CO Concentration"; Org. Biomol.

Chem. 2011, 9, 6903-6908). A similar reactor is discussed in Yang et al., "Mass Transport and Reactions in the Tube-in-Tube Reactor, Org. Process Res. Dev., 2013, 17(6), pp 927933 and is shown schematically in Figures 3a) and 3b. This reactor has a tubular gas permeable membrane 20 inside either a PTFE or stainless steel outer tube 21. The gas is fed into the outer cavity 22 formed between the membrane 20 and the outer tube 21 while the reagents flow through the inner tube formed of the gas permeable material (Teflon AF 2400). In this way the gas can be continually fed into the reaction mixture through the complete length of the reactor. Reactors have been constructed where the flow is in the opposite direction, i.e. gas flowing on the inside of the membrane 20 and permeating to the outer cavity 22 (Figure 3b)).

Summary of the Invention

At their broadest, aspects of the present invention provide for flow reactors and methods for performing flow reactions which use tube-in-tube reactors wherein the inner tube has a plurality of small apertures or holes which permit a liquid reagent in one flow path to mix with another liquid reagent in another flow path.

A first aspect of the present invention provides a continuous flow reactor for the reaction of one liquid reagent with another liquid reagent, the continuous flow reactor comprising: an inner tube, the inner tube defining a first flow path along at least part of the length of the inner tube; an outer tube, the outer tube enclosing at least a section of the inner tube along its length, so that a second flow path is defined by the space between the outer tube and the inner tube along the length of the tubes; and the inner tube having a plurality of holes through the thickness of the inner tube, the holes being spaced longitudinally along the section of the inner tube enclosed by the outer tube.

The holes allow the reagent fed into one of the flow paths to pass through the holes in the inner tube and mix with the reagent fed into the other flow path and thus react with the reagent in that other flow path.

The two liquid reagents can be fed into the separate flow paths and only combine once one of the reagents has passed through one of the holes into the flow path of the other reagent.

By providing a plurality of holes along the inner tube, the position of the reaction between the reagents can be controlled to take place at many different points along the length of the reactor. This can avoid the situation where the reagents are mixed at a single entry point into the reactor, whilst not requiring complex flow splitting arrangements or multiple pumps to feed separate stages of the reactor.

Thus the reactor of this aspect may be particularly suited for carrying out exothermic reactions and in particular highly exothermic reactions and for carrying out reactions involving highly reactive reagents.

By controlling the reaction to take place at a plurality of separate locations spaced along the length of the reaction (which, as with conventional flow reactors, may have a total length of several metres), the temperature rise caused by the reaction has diminished or even totally disappeared by the time that the reagents reach the next hole. Therefore the overall temperature of the reactor and/or reagents can be managed and controlled and the possibility of over-reaction or subsequent decomposition of the reaction product can be reduced or avoided entirely.

The reactor may further include a feeding section which is arranged such that one liquid reagent can be exclusively fed into the first flow path and another liquid reagent can be exclusively fed into the second flow path.

The feeding section is preferably connected to one end of the reactor so that the different reagents can be fed into different flow paths without mixing prior to entering the reactor.

Many different configurations of the feeding section are possible. In one particular embodiment, the feeding section includes a sleeve arranged around the inner tube such that the inner tube passes completely through the feeding section whilst the outer tube terminates in the feeding section. A connector in the sleeve allows a reagent to be fed to the second flow path.

The size and number of holes may be chosen to give a reasonable pressure drop at the designed range of flowrates and taking into account the viscosity of the reagents intended to be used.

The diameters of the holes are preferably between 0.005 and 0.060 mm and more preferably between 0.015 mm and 0.040 mm.

Whilst the holes are spaced longitudinally along the inner tube, there may also be a distribution of the holes in a circumferential direction around the inner tube. This may improve mixing of the reagents. Furthermore, at any point on the inner tube where a hole is present, further holes may also be present which are distributed around the circumference of the inner tube at that point. These additional holes may provide for additional flow of the reagent from one flow path into the other, and may allow the individual holes to be made smaller.

However, as cutting holes in a plurality of different circumferential positions around the tube creates practical difficulties in the manufacture of the inner tube, there are preferably either one or two holes at each longitudinal position on the inner tube, and if there are two holes, these are diametrically opposed. If the holes are cut by laser cutting, then it may be possible to cut diametrically opposed holes at the same time as each other without moving the tube although this can result in its own difficulties and so a single hole at any one longitudinal position is preferred.

The reactor is preferably used and/or configured within an apparatus such that there is a pressure drop across all of the holes in the same direction. This pressure drop can ensure that the reagent in the flow path on the higher pressure side of the holes always flows through the holes, so that there is only ever flow in one direction through the holes.

This arrangement is particularly preferred where one of the reagents is highly reactive.

When conducting a reaction in which a highly reactive reagent is involved, it is preferable that the mixing of the reagents and therefore the reaction takes place in an environment where the reagent(s) which are not highly reactive are in excess and where a small quantity of the highly reactive reagent can be fed into the other reagent(s) at selected points along the reactor. Thus the pressure drop across the holes can ensure that the highly reactive reagent is always the reagent passing through the holes.

Typically the pressure drop across the holes will be chosen to be in the range 0.05 bar to 10 bar. This range of pressure will ensure there is no reversal of the flow direction in any section along the length of the reactor.

One way in which this pressure drop across the holes can be provided is by arranging the reactor such that one end of either the first flow path or the second flow path is closed so that liquid flowing in that flow path can only exit that flow path by passing through the holes into the other flow path.

By closing off one end of one of the flow paths, the reagent which is fed into that flow path is forced to exit the flow path through the holes as there is no other route for it. The pressure of the fluid in the flow path which has a closed off end is generally higher than that in the flow path in which the fluid exits the reactor at the distal end.

In some embodiments, the distal end of the second flow path (i.e. the end of the outer tube) is closed, thereby forcing the reagent fed into the second flow path to pass through the holes into the first flow path. This configuration has the advantage that the first flow path is better suited to mixing of the reagents as it is essentially a tube, compared to the annular shape of the second flow path which may be relatively thin and therefore difficult for the reagents to properly mix around the entirety of the annulus.

In these embodiments, the inner tube may also have a plurality of static mixing elements on its inner surface to aid mixing of the reagents in the first flow path. These static mixing elements may take the form of baffles, vanes or similar.

In other embodiments, the distal end of the first flow path (i.e. the end of the inner tube) is closed, thereby forcing the reagent fed into the first flow path to pass through the holes and into the second flow path. This configuration has the advantage that the second flow path is closer to the outer surface of the reactor and so cooling/heating of the reaction products in the second flow path is easier and/or more effective.

The choice between whether the reaction takes place in the first or second flow paths and the relative advantages of each approach apply equally to other arrangements in which there is a pressure drop across the holes in one direction.

The longitudinal spacing between any two adjacent holes can be chosen so that the excess heat generated from the exothermic reaction between the two reagents at a first of the holes has entirely or substantially dissipated by the time that the mixture of reaction products and additional reagent reaches the subsequent hole along the flow path. The preferred longitudinal spacing in such circumstances will be a balance between the amount of reagent reacting at each point (the diameter of the holes), the desired reaction rate within the reactor (and therefore the overall length of the reactor), the heat generated by the reaction and the active or passive cooling that can be applied to the reactor between the holes.

For most reactions and reactors, the longitudinal spacing between any two adjacent holes is preferably between 5 cm and 50 cm.

In embodiments where neither of the flow paths is closed at the distal end, the reactor may further comprise an extracting section, the extracting section allowing liquid leaving the second flow path to be extracted separately from the liquid leaving the first flow path. The extracting section may be configured in substantially the same manner as the feeding section described above.

The reactor of the present aspect may include any combination of some, all or none of the above described preferred and optional features.

The reactor of the above aspect may operate by carrying out a method according to the third aspect of this invention, described below, but need not do so.

The reactor of the first aspect may be incorporated in an apparatus for continuous flow reactions. That apparatus may include the additional components which are well known in flow chemistry reaction apparatus such as supply units, pumps, temperature control devices, valves and other control devices and/or product collection devices.

A second aspect of the present invention provides an apparatus for continuous flow reactions, the apparatus comprising: a continuous flow reactor according to the above first aspect, including any of the optional or preferred features of that aspect in any combination; a first pump for pumping a liquid reagent into the first flow path; and a second pump for pumping another liquid reagent into the second flow path.

Preferably the reactor and pumps are configured to maintain a first liquid reagent in one of the flow paths at a higher pressure than a second liquid reagent in the other flow path thereby causing a pressure difference across the holes so that the mixing of the reagents occurs in the flow path of the second liquid reagent.

By arranging the reactor and pumps so that there is a pressure difference across the holes it can be ensured that there is only flow in one direction through the holes and so the reaction between the reagents takes place in a particular one of the flow paths.

Preferably in this situation, the first liquid reagent is more reactive than the second liquid reagent. Accordingly, the apparatus is configured so that the reactive reagent always passes through the holes to mix in the flow path of the reactor into which the less reactive reagent is fed. This ensures that the reaction between the reagents only occurs in an environment in which there is an excess of the less reactive reagent, thereby enabling the reaction to be controlled.

The reactor and pumps are preferably configured such that the pressure drop across each hole is in the range 0.05 bar to 10 bar.

The apparatus may further comprise a chiller or a heater for controlling the temperature of the reagents in the reactor. The apparatus of this aspect is highly suited to highly exothermic reactions and so a chiller or a high flow rate fan arrangement to take away heat from the reactor is typically provided.

The apparatus of the present aspect may include any combination of some, all or none of the above described preferred and optional features.

The apparatus of the present aspect may operate by carrying out a method according to the third aspect of this invention, described below, but need not do so.

A third aspect of the present invention provides a method for performing a continuous flow reaction, the method comprising the steps of: feeding a liquid reagent into a first flow path formed by an inner tube; feeding another liquid reagent into a second flow path defined by the space between the inner tube and an outer tube which encloses a section of the inner tube along its length, such that one of the liquid reagents passes through a plurality of holes through the thickness of the inner tube to mix with the other reagent, the holes being spaced longitudinally along the section of the inner tube enclosed by the outer tube.

The holes allow the reagent fed into one of the flow paths to pass through the inner tube and mix with the reagent fed into the other flow path and thus react with the reagent in that other flow path.

Thus the method of this aspect may be particularly suited for carrying out exothermic reactions and in particular highly exothermic reactions and for carrying out reactions involving highly reactive reagents.

By controlling the reaction to take place at a plurality of separate locations spaced along the length of the reactor (which, as with conventional flow reactors, may have a total length of several metres), the temperature rise caused by the reaction has diminished or even totally disappeared by the time that the reagents reach the next hole. Therefore the overall temperature of the reactor and/or reagents can be managed and controlled and the possibility of over-reaction or subsequent decomposition of the reaction product can be reduce or avoided entirely.

However, as cutting holes in a plurality of different circumferential positions around the tube creates practical difficulties in the manufacture of the inner tube, there are preferably either one or two holes at each longitudinal position on the inner tube, and if there are two holes, these are diametrically opposed. If the holes are cut by laser cutting, then diametrically opposed holes can be cut at the same time as each other without moving the tube, although this can result in its own difficulties and so a single hole at any one longitudinal position is preferred.

Preferably a first liquid reagent is fed into one of the flow paths of the continuous flow reactor at a higher pressure than a second liquid reagent is fed into the other flow path so that the mixing of the reagents occurs in the flow path of the second liquid reagent. This can ensure that there is a pressure drop across all of the holes in the same direction. This pressure drop can ensure that the reagent in the flow path on the higher pressure side of the holes always flows through the holes, so that there is only ever flow in one direction through the holes.

This arrangement is particularly preferred where one of the reagents is highly reactive. When conducting a reaction in which a highly reactive reagent is involved, it is preferable that the mixing of the reagents and therefore the reaction takes place in an environment where the reagent(s) which are not highly reactive are in excess and where a small quantity of the highly reactive reagent can be fed into the other reagent(s) at selected points along the reactor. Thus the pressure drop across the holes can ensure that the highly reactive reagent is always the reagent passing through the holes.

The longitudinal spacing between any two adjacent holes can be chosen so that the excess heat generated from the exothermic reaction between the two reagents at a first of the holes has entirely or substantially dissipated by the time that the mixture of reaction products and additional reagent reaches the subsequent hole along the flow path. The preferred longitudinal spacing in such circumstances will be a balance between the amount of reagent reacting at each point (the diameter of the holes), then desired reaction rate within the reactor (and therefore the overall length of the reactor), the heat generated by the reaction and the active or passive cooling that can be applied to the reactor between the holes.

The method of the present aspect may include any combination of some, all or none of the to above described preferred and optional features The method of the present aspect may be carried out using a flow reactor according to the above first aspect or an apparatus according to the above second aspect.

A fourth aspect of the present invention provides a method of manufacturing the continuous flow reactor according to the above first aspect, including any of the optional or preferred features of that aspect in any combination, the method including the steps of: winding the inner tube onto a mandrel; laser cutting holes through the thickness of the inner tube along the length of the inner tube under an inert atmosphere; and enclosing at least a section of the inner tube in the outer tube By winding the inner tube onto a mandrel before laser cutting the holes, the positions at which the holes are cut can be carefully and precisely controlled in the laser cutting process.

Laser cutting the holes is preferred, although other cutting methods can be used to manufacture the reactor of the above first aspect. Laser cutting provides a highly accurate method for cutting holes of the small size desired for the reactors of the first aspect above.

Brief Description of the Drawings

Embodiments of the invention will now be described by way of example with reference to the accompanying drawings in which: Figure 1 is a graph showing the reactor temperature for a highly exothermic reaction conducted in a conventional flow reactor and has already been described; Figure 2 is a schematic illustration of a known flow reactor using the partial additions method and has already been described; Figures 3a and 3b illustrate the operation of a gas-liquid flow reactor and have already been described; Figure 4 shows a reactor according to an embodiment of the present invention; Figure 5 is an exploded view of the reactor of Figure 4; and Figures 6a-6c show, respectively a cut away through the reactor tube of a reactor according to an embodiment of the present invention, a linear cross-section of the reactor and a transverse cross-section of the reactor.

Detailed Description

Figure 4 shows a continuous flow reactor 100 according to an embodiment of the present invention. Figure 5 shows an exploded view of the continuous flow reactor 100.

The continuous flow reactor 100 comprises two tubes and a number of other components. The two tubes are an inner tube 102 and an outer tube 104. Additional components include: a feeding section 106, an extracting section 108, inner tube connector assemblies 112 and 114, outer tube connector assemblies 116, a cylindrical support section 120 and connector valves 122 and 124.

Figures 6a shows a cut-away through the reactor tubes 102, 104 of the reactor shown in Figures 4 and 5. Figure 6b shows a linear cross-section of the reactor tubes 102, 104 and Figure 6c shows a transverse cross-section of the reactor tubes 102, 104.

The inner tube 102 has a number of holes 140, through the thickness of the inner tube 102 as shown in Figures 6b and 6c.The inner tube 102 has an inner tube wall 142, the holes 140 being through the thickness of the inner tube wall 142. The holes 140 are spaced longitudinally along a section of the length of the inner tube 102. The spacing between adjacent holes 140 is indicated by 'Dim A' in Figure 6b. It will be appreciated that the spacing between adjacent holes 140 could be constant or varying along the length of the tube according to the design requirements of the reactor. Typically the spacing between adjacent holes 140 will range between 5 cm and 50 cm.

When assembled (as shown in Figures 4 and 5) the outer tube 104 encloses the section of the length the inner tube 102 with the holes 140 along it. The inner tube 102 defines a first flow path 130 along the length of the inner tube. The space between the inner tube 102 and the outer tube 104 defines a second flow path 132 along the length of the tubes.

Connectors 122, 124 are attached at each end of the outer tube as shown in Figure 5. The connectors 122, 124 attach the inner tube 102 and the outer tube 104 to the feeding section 106 and the extracting section 108. The connector valves 122, 124 form a seal between the outer tube 104 and the feeding section 106 and the extracting section 108 respectively. The connectors 122, 124 prevent any leakage of reagents at the join between the outer tube and the feeding section 106 and extracting section 108 respectively.

The feeding section 106 is configured to allow a first liquid reagent to be fed exclusively into the first flow path 130, whilst also allowing a second liquid reagent to be fed exclusively into the second flow path 132.

In the embodiment of Figure 5 the feeding section 106 is configured to allow inner tube 102 to run through it, and connect directly to a connector assembly 112. The feeding section 106 has a second side opening 107 to allow a connector assembly 116 to be attached to feed a reagent into the second flow path 132. The connector assemblies 112, 116 are suitable for connecting a pumped and potentially pressurised liquid reagent supply to the continuous flow reactor 100.

The extracting section 108 may be similarly configured to allow liquid on the first flow path to be extracted separately from liquid on the second flow path 132. The extracting section 108 has an inner tube connector assembly 114 and may also have an outer tube connector assembly (not shown) for connection of the flow path outputs to further parts of the system.

However, in a preferred embodiment, one of the flow paths is blocked at a point distal from the feeding section 106, thereby forcing all reagent fed into that flow path to pass through the holes 140 into the other flow path and thereby react with the reagent flowing in the other flow path. Therefore the extracting section 108 may only need to be configured to take reacted product from one of the flow paths, for example the first flow path 130 along the interior of the inner tube 102 as shown in Figure 5.

In one embodiment of the invention, a first liquid reagent may be fed into one of the flow paths at a higher pressure than a second liquid reagent is fed into the other flow path 132.

The pressure difference across the holes 140 along the length of the inner tube 102 causes the first liquid reagent to flow through the holes. This ensures that the reaction occurs in the flow path of the second liquid reagent.

This pressure differential is achieved in the preferred embodiment described above by blocking the distal end of one of the flow paths, thereby causing the only available exit for the first reagent to be the holes 140 leading to the other flow path.

It is possible for the first reagent (i.e. the one at higher pressure) to be fed into either flow path. The reasons for choosing to feed the first reagent into one or other of the flow paths are discussed in more detail in relation to the method according to an embodiment of the present invention below.

In addition to the holes 140 being spaced longitudinally along the inner tube 102, the holes 140 may also be distributed around the circumference of the inner tube. Indeed, the holes 140 need not be arranged in any regular pattern either longitudinally or circumferentially at all, although regular repeating patterns will generally ensure more controlled mixing and are much easier to produce.

It will be appreciated that a plurality of holes of small area around the circumference can allow a similar flow rate of reagent flow through them as one larger hole. Where there are a plurality of holes around the circumference of the inner tube 102 at any point, they allow the reagents to mix and react in more than one location around the circumference, thus distributing the reaction over a larger area/volume of the flow path in which the reaction is taking place. However, having only a single hole at any point along the length of the inner tube may allow for more precise control over the flow rate through and/or the pressure drop across the hole.

The diameter of the holes cut in the inner tube 102 will depend on the design of the reactor and can be selected for the particular reaction or reactions which are intended to be carried out in that reactor. Typically the diameters of the holes are between 0.005 and 0.060 mm and preferably between 0.015 mm and 0.040 mm. The diameter of the holes can be chosen so that the pressure drop across the holes when the continuous flow reactor is in normal operation can range from 0.05 bar to 10 bar.

In certain embodiments different sized holes can be used in different locations along the length of the inner tube according to the requirements of the reaction to be performed. For example, the diameter of the holes may increase or decrease along the length of the inner tube away from the feeding section. This allows the rate of flow of the reagent through the holes in the inner tube to be adjusted as the concentration of the reagents varies along the length of the continuous flow reactor 100. Similar effects can be achieved by changing the spacing between equal sized holes 140 along the length of the reactor. Reducing hole size (or increasing spacing) along the length of the inner tube will cause smaller amounts of reagent to flow the holes which may be desirable as the flow path in which the reaction is occurring will be carrying both the product of the reaction and the reagent fed to it and therefore the reagent will be present in a lower concentration further along the reactor. Increasing hole size (or decreasing spacing) may be desirable where it is advantageous to increase the excess of one reagent over the other as the reaction progresses to completion.

Although the holes 140 provided in this embodiment are circular, the skilled person will appreciate that other shapes of hole can be used, for example slits. However, circular holes are generally the easiest to manufacture.

The cylindrical support structure 120 is has two annular plates 126, 128 and a plurality of pillars 129 which connect and separate the plates 126, 128 when the reactor is assembled.

The outer tube is wrapped around the pillars 129 and may be woven between the pillars, or wrapped in multiple layers as is known in the art. This arrangement allows for sufficient air or other heat transfer fluid flow around the outer tube to aid with heat dissipation while also providing a space efficient support structure for the outer tube. The skilled person will appreciate that other support structures and configurations of the outer tube may be used in reactors according to the present invention.

The inner tube 102 and the outer tube 104 may be constructed from a range of different materials. These materials include fluropolymers (such as PFA, PTFE, FEP), polyether ether ketone (PEEK), stainless steel, HasteHoy® or any combination of the above materials. The choice of materials for the tubes will typically be based on the reagents to be reacted, the temperature and pressure requirements as well as weight and cost considerations.

The continuous flow reactor 100 can be used as part of an apparatus for continuous flow reactions. The apparatus may, for example, include a first pump for pumping a first liquid reagent into the first flow path 130, and a second pump for pumping a second liquid reagent into the second flow path 132. The pumps are connected to the continuous flow reactor by respective connector assemblies 112, 116 The pumps are operated so that the reagents are pumped into the reactor 100 in substantially stoichiometric ratio, taking into account the concentrations of the reagents. This ensures that, provided that complete mixing takes place, the product which exits the reactor is completely reacted and that there are only small quantities of unreacted reagent in the product. In many situations, the rate of pumping of one of the reagents is deliberately set to be marginally higher than required for the stoichiometry of the reaction so that the product will only contain residue of one of the reagents. If one of the reagents is highly reactive, then the other reagent can be chosen as the reagent to be in excess.The pumps may be operated so that one pump pumps a first liquid reagent into one of the flow paths at a higher pressure than the other pump pumps a second liquid reagent into the other flow path. The resulting pressure drop across the holes 140 in the inner tube 102 will ensure that the first liquid reagent flows through the holes. Therefore the reaction that occurs between the two reagents will occur in the flow path of the second liquid reagent.

This arrangement is particularly useful and preferred if the first liquid reagent is more reactive than the second liquid reagent, as it allows the rate of mixing of the first liquid reagent into the second liquid reagent, and thus the rate of reaction that occurs, to be controlled. The rate of mixing can be controlled by the difference in pumping pressure between the first reagent and the second reagent. The mixing rate can also be controlled by the design of the holes in the inner tube of the reactor.

The continuous flow reactor 100 may also be used with a chiller and/or a heater. The chiller/heater may be used to maintain or vary the temperature of the reagents as they flow through the reactor. The temperature of the reagents which are pumped into the continuous flow reactor may also be controlled In a method of manufacturing a reactor according to an embodiment of the invention uses a highly accurate cutting technique to cut the holes 140 with a high degree of precision. Preferably, the cutting technique ensures the holes are a consistent diameter all the way through the hole. One suitable method of accurately cutting the holes to size is to use laser cutting under an inert atmosphere. In the method according to this embodiment, the holes are cut by first winding the inner tube 102 onto a mandrel, before putting the mandrel into a laser cutting machine. The mandrel can be moved along its longitudinal axis and rotated as desired to position the inner tube 102 relative to the cutting head of the machine.

In certain configurations, and depending on the desired spacing of holes along the inner tube, the mandrel may be chosen so that no rotation of the mandrel is required in the cutting process as the holes are spaced by the circumferential distance between one winding of the inner tube and the next, and so all of the holes can be cut from the same radial position.

The laser cutting machine may be configured to only cut through one thickness of the inner tube wall 142, thereby arranging one hole at any longitudinal position on the inner tube 102.

Alternatively, the laser cutting machine may be configured to cut through both thicknesses of the inner tube wall 142 so that two diametrically opposed holes are created in the inner tube at the same longitudinal position, but this requires careful control of the focal length of the laser cutting machine.

This method allows an inner tube of over 10 m in length to have holes efficiently and accurately cut into it whilst keeping the tube in a highly compact and controllable arrangement.

A method of carrying out a continuous flow reaction according to an embodiment of the present invention involves feeding two liquid reagents into a continuous flow reactor 100 such as that described in relation to the embodiments above. A liquid reagent is fed into a first flow path 130 formed by the inner tube 102. Another liquid reagent is fed into a second flow path 132 defined by the space between the inner tube 102 and the outer tube 104 which encloses a section of the inner tube 102 along its length. Typically, two pumps are used to feed the liquid reagents into the continuous flow reactor 100, but other feed arrangements can be used. The connector assemblies 112, 116 are used to connect the continuous flow reactor 100 to the pumps.

The two liquid reagents mix through a plurality of holes 140 in the inner tube 102 which allow a reagent in one flow path to pass through and mix with the other reagent in the other flow path. Thus the position of the reaction is controlled by the position of the holes, and the reaction can be spread along a length of the reactor.

A first liquid reagent is fed into one of the flow paths of the continuous flow reactor 100 at a higher pressure than a second liquid reagent is fed into the other flow path, so that a pressure drop is created across all of the holes 140 in the same direction and the mixing of the reagents only occurs in the flow path of the second liquid reagent. This may be achieved by blocking off the distal end of the flow path into which the first liquid reagent is fed, thereby creating an obstruction and forcing the first reagent to pass through the holes and mix with the second reagent. Alternatively, first liquid reagent can be pumped into the continuous flow reactor 100 at a higher pressure than the second liquid reagent.

The feeding of the reagents and configuration of the reactor (including the size of the holes 140) are chosen so that the pressure drop across the holes between the first and second reagents is in the range 0.05 to 10 bar. The diameters of the holes are between 0.005 and 0.060 mm and preferably between 0.015 mm and 0.040 mm In some reactions, one of the reagents will be more reactive than the other reagent. Indeed, the methods of embodiments of the present invention are particularly suited for carrying out flow reactions involving highly reactive reagents such as nitric acid or Butyl lithium (or other organo-metallic reagents) In such reactions, the more reactive reagent is provided at the higher pressure to prevent any reaction from taking place in the flow path that the more reactive reagent is supplied to and ensuring that the reaction always takes place in an environment in which there is an excess of the less reactive reagent(s). The rate of flow of the reactive reagent into the other reagent can be controlled by the difference in pressure between the first reagent and the second reagent. The flow rate can also be controlled by the design of the holes in the inner tube of the reactor.

In one arrangement the more reactive reagent is fed into the second flow path 132, thereby causing the reaction to occur in the first flow path 130. This may be advantageous as the first flow path provides a better space for complete mixing and therefore complete reaction of the reagents as it is a single tubular space inside the inner tube 102, rather than the annular space of the second flow path which is distributed circumferentially around the reactor and may be relatively thin if it is intended to be of similar cross-sectional area to the first flow path 130. The first flow path 130 may also include static mixing elements such as baffles or vanes to improve the mixing of the reagents.

In an alternative arrangement, where the more reactive reagent is fed into the first flow path 130, the exothermic reaction will occur in the second flow path 132. This may be advantageous as the second flow path 132 has a larger surface area to volume ratio than the first flow path 130 and can therefore dissipate any generated heat more efficiently. External temperature control (for example from airflow driven by fans or active chilling (or heating)) can also be more easily and effectively directed at the liquid mixture in the second flow path as the first flow path 130 is insulated from the surrounding environment by the liquid in the second flow path 132 as well as the inner tube 102.

The method of this embodiment is of particular use in carrying out exothermic reactions.

Depending on the reaction to be carried out, the reactor used in the reaction can be selected so that adjacent holes 140 along the inner tube 102 are spaced sufficiently apart that the heat generated by the exothermic reaction occurring at one hole is substantially or completely dissipated before the reagents reach the next hole along the flow path. This prevents a build-up of heat in the reactor 100 and the reagents and so can prevent or control the thermal runaway of the reaction and/or decomposition of the reaction product.

The reaction products and any unreacted reagents are extracted from the reactor and stored.

A further pump may be used, and valves may be provided which direct the flow of the product into a selected receptacle, or to a series of receptacles.

The reagents are preferably fed into the reactor at rates which reflect the stoichiometry of the reaction, so that the amount of unreacted reagents emerging from the reactor can be minimised. Generally the rates are chosen such that there is a deliberate marginal oversupply of one of the reagents, thereby avoiding the possibility of further reaction outside of the reactor due to different reagents being oversupplied at different times (which may arise due to natural variations in the supply if the reagents are supplied in the exact ration required for the reaction).

While the invention has been described in conjunction with the exemplary embodiments described above, many equivalent modifications and variations will be apparent to those skilled in the art when given this disclosure. Accordingly, the exemplary embodiments of the invention set forth above are considered to be illustrative and not limiting. Various changes to the described embodiments may be made without departing from the spirit and scope of the invention.

In particular, although the methods of the above embodiments have been described as being implemented in the reactors and apparatuses of the embodiments described, the methods and apparatuses of the present invention need not be implemented in conjunction with each other, but can be implemented on alternative reactors or apparatuses or using alternative methods respectively.

All references referred to above are hereby incorporated by reference.

Claims

CLAIMS1. A continuous flow reactor for the reaction of one liquid reagent with another liquid reagent, the continuous flow reactor comprising: an inner tube, the inner tube defining a first flow path along at least part of the length of the inner tube; an outer tube, the outer tube enclosing at least a section of the inner tube along its length, so that a second flow path is defined by the space between the outer tube and the inner tube along the length of the tubes; and the inner tube having a plurality of holes through the thickness of the inner tube, the holes being spaced longitudinally along the section of the inner tube enclosed by the outer tube.
2. A continuous flow reactor according to claim 1 further comprising a feeding section which is arranged such that one liquid reagent can be exclusively fed into the first flow path and another liquid reagent can be exclusively fed into the second flow path.
3. A continuous flow reactor according to claim 1 or claim 2 wherein the diameters of the holes are between 0.005 and 0.050 mm.
4. A continuous flow reactor according to any one of claims 1 to 3 wherein one end of either the first flow path or the second flow path is closed so that liquid flowing in that flow path can only exit that flow path by passing through the holes into the other flow path.
5. A continuous flow reactor according to claim 4 wherein the end of the second flow path is closed and wherein the inner tube has a plurality of static mixing elements on its inner surface to aid mixing of the reagents in the first flow path.
6. A continuous flow reactor according to any one of the preceding claims wherein the longitudinal spacing between any two adjacent holes is between 5 cm and 50 cm.
7. A continuous flow reactor according to any one of the preceding claims further comprising an extracting section, the extracting section allowing liquid leaving the second flow path to be extracted separately from the liquid leaving the first flow path.
An apparatus for continuous flow reactions, the apparatus comprising: a continuous flow reactor according to any one of the preceding claims; a first pump for pumping a liquid reagent into the first flow path; and a second pump for pumping another liquid reagent into the second flow path.
9. An apparatus according to claim 8 wherein the reactor and pumps are configured to maintain a first liquid reagent in one of the flow paths at a higher pressure than a second liquid reagent in the other flow path thereby causing a pressure difference across the holes so that the mixing of the reagents occurs in the flow path of the second liquid reagent.
10. An apparatus according to claim 9 wherein the first liquid reagent is more reactive than the second liquid reagent.
11. An apparatus according to claim 9 or claim 10 wherein the reactor and pumps are configured such that the pressure drop across each hole is in the range 0.05 bar to 10 bar.
12. An apparatus according to any one of claims 8 to 11 further comprising a chiller or a heater for controlling the temperature of the reagents in the reactor.
13. A method for performing a continuous flow reaction, the method comprising the steps of: feeding a liquid reagent into a first flow path formed by an inner tube; feeding another liquid reagent into a second flow path defined by the space between the inner tube and an outer tube which encloses a section of the inner tube along its length, such that one of the liquid reagents passes through a plurality of holes through the thickness of the inner tube to mix with the other reagent, the holes being spaced longitudinally along the section of the inner tube enclosed by the outer tube.
14. The method according to claim 13 wherein a first liquid reagent is fed into one of the flow paths of the continuous flow reactor at a higher pressure than a second liquid reagent is fed into the other flow path so that the mixing of the reagents occurs in the flow path of the second liquid reagent.
15. The method according to claim 14 wherein the feeding of the reagents and the holes through the thickness of the inner tube are chosen so that the pressure drop across each hole is in the range 0.05 bar to 10 bar.
16. The method according to claim 14 or claim 15 wherein the first reagent is more reactive than the second reagent.
17. The method according to any one of claims 13 to 16 wherein the reaction between the first and second reagents is exothermic.
18. The method according to claim 17 wherein the holes are spaced apart so that the heat generated by the exothermic reaction occurring at each hole is dissipated between adjacent holes.
19. A method of manufacturing the continuous flow reactor of any one of claims 1 to 7, the method comprising the steps of: winding the inner tube onto a mandrel; laser cutting holes through the thickness of the inner tube along the length of the inner tube under an inert atmosphere; and enclosing at least a section of the inner tube in the outer tube.