Automated thin-film chemical reactor

Abstract

The invention relates to a thin-film chemical reactor capable of operating in a confined environment, the reactor comprising (i) a reaction vessel with a vertical axis; (ii) a feed tube; (iii) an upper portion comprising two openings, one of which receives the tube; (iv) a connection means linking the upper portion and the vessel and comprising a stationary part and a moving part; (v) a drive means for rotating the vessel; (vi) means for sealing the openings; wherein the tube is parallel to or aligned with the vertical axis and extends through the connection means into the vessel.

Description

[0001] AUTOMATED THIN FILM CHEMICAL REACTOR

[0002] Technical field

[0003] The present invention relates to a reactor using the thin film principle for the synthesis of chemical compounds, in particular organic compounds. In particular, the reactor of the invention has the advantages of thin film reactors, is suitable for use in "confined" mode and allows easy automation.

[0004] The present invention further relates to the use of a reactor according to the invention for synthesizing a chemical compound.

[0005] Prior art

[0006] Thin film reactors were developed as part of process intensification (PI) widely used in the food and chemical industries.

[0007] In a "thin film" type reactor in operation, the liquid / fluid reactive medium, containing the reactant(s) and often a solvent or mixture of solvents, is advantageously present in the form of a thin layer or film continuously distributed over a surface of a rotating body, said surface being a "rotation surface" facing towards and coaxial with the axis of rotation of the body. The forces generated by the high-speed rotation of the body act on the liquid reactive medium and cause the formation of a thin and continuous film on the rotation surface. The rotating body may be, for example, a disc or a hollow body such as a conical container or a tube of circular cross-section, their rotation surfaces in all cases having a central axis (and corresponding to an internal surface in the case of a hollow body).

[0008] The low thickness of the film and its spread over the surface generate a very high surface / volume ratio for the film, which advantageously allows for greater and more influential interactions between the film and its environment. This type of reactor thus makes it possible to improve mass and heat transfers within the film and to increase energy distribution, in comparison with a conventional reactor (tank or fixed bed). It also makes it possible to quickly and homogeneously modulate the temperature of the medium, to reduce the overall volumes of the reaction medium (reduced solvent consumption), to improve reaction performance and, above all, to reduce energy consumption with, consequently, a reduction in production costs.

[0009] Various specific configurations of thin film reactors are known in the prior art. These are most commonly referred to as spinning disk reactors (SDR), rotating tube reactors (RTR) and vortex fluidic device (VFD). Each has its own advantages and disadvantages.

[0010] A rotating disk reactor (SDR) consists of a disk arranged substantially horizontally in a collection tank. The disk has a diameter ranging from about 60 mm to about 500 mm and typically rotates on a vertical axis of rotation at a very high speed, up to several thousand revolutions per minute (rpm). In this reactor, the liquid reaction medium is continuously fed to the center of the rotating disk on its upper surface from where it flows radially outward due to the rotation of the disk. The thin film, formed under high acceleration fields, is characterized by high shear rates, intense surface undulations and a very short residence time ( <l min).Consequently, this type of reactor is of particular interest for operating very rapid and / or highly exothermic reactions that require large heat dissipation (such as nitrations, sulfonations, Darzens processes, crystallizations and exothermic condensations). Known SDR type reactors operate only in "continuous flow" mode (as opposed to "batch" or "confined" mode). The typical flow rate is 5 ml / second for a 100 mm diameter disc.

[0011] A rotating tube reactor (RTR), on the other hand, consists of a hollow cylinder rotating around its longitudinal axis, which is usually mounted horizontally. The liquid reaction medium is introduced at one end of the rotating cylinder (feed zone) and centrifugal forces form a continuous film on the inner surface of the cylinder creating an annular flow. The reaction products are collected at the opposite end of the cylinder (discharge zone). Rotating tube reactors therefore also operate only in "continuous flow" mode and are also applicable to reactions with a very short residence time. They are mainly used for the continuous preparation and separation of chemicals as well as for distillation, liquid-liquid extraction and the preparation of nanoparticles. Two categories can be distinguished depending on the rotational speed of the cylinder and the reactor design.This is referred to as low shear or high shear RTR. For example, in a low shear RTR, the rotating hollow cylinder has a rotational speed that is generally less than 1000 rpm and the thin film formed on the inner surface of the cylinder has a thickness between 0.7 and 1.4 mm. This technology has, for example, been applied to the transesterification of canola oil into biodiesel using a basic catalyst. Using methanol and sodium hydroxide as catalysts, a conversion of 98% was achieved with residence times of 40 seconds. The high shear rotary reactor, on the other hand, uses rotational speeds of up to 15000 rpm (revolutions per minute). However, the industrial feasibility of rotating tube reactors has not yet been demonstrated and scaling up this type of device is very complicated.

[0012] Finally, a vortex fluidic device (VFD) type reactor, such as that described in international application WO2012034164A2, comprises a hemispherical tube, made of borosilicate glass or quartz (OD5-10 mm), having a longitudinal axis, an internal surface, a closed end and an open end (accommodating fluid supply means). In this device, the tube rotates around the longitudinal axis and the angle of the longitudinal axis relative to the horizontal is variable, from greater than 0 degrees to less than 90 degrees. The rotation speed can range from 1 to 10,000 rpm, so that a thin film (<200 m) of liquid forms along the wall of the tube, based on a laminar flow or a turbulent flow, depending in particular on the speed and the angle of inclination and the continuous flow rate.According to application WO2012034164A2, the inclination of the tube would increase the shear force and therefore improve mixing, and also facilitate the exit of fluids from the tube under continuous flow conditions (which has the disadvantage of requiring large volumes of liquid). Finally, in this device, an extraction means is also positioned substantially next to the open end of the tube (upper part of the reactor) and allows the reaction products to be extracted from the tube (in continuous flow mode). A VFD type reactor can also operate in confined mode by carrying out the reaction in a sealed tube. In this configuration, the reactor only allows the use of a relatively small reaction volume (of the order of 1 mL). In addition, the liquid / vapor equilibrium point inside the sealed tube is reached quickly and the pressure increases very quickly in the tube, especially if the reaction requires heating.Therefore, in addition to the low accessible volume, the tolerance of borosilicate glass or quartz tubes to positive pressure also severely limits the range of reactions possible with this VFD reactor in confined mode. Finally, the addition of reagents into the tube and its sealing are done manually.

[0013] There are also other rotating devices described in the literature that allow use in confined mode and provide access to automation of the addition of reagents / solvents or the removal of products. However, these devices are very complex. For example, in document US5156809, a robotic arm is provided that retracts from the rotating reactor once the addition of reagents has been carried out, in order to allow the closure / sealing of the reactor.

[0014] Thus, in view of the known devices described above, there is indeed an interest in having a thin film reactor, providing the known and aforementioned advantages of such a reactor, usable in confined mode (therefore suitable for relatively long reaction times), with a wide range of possible reactions and parameters (nature of the reactants, pressure, temperature, time and reaction volume), and allowing simple automation of the process of adding reactants and removing products (thus avoiding manual operations as much as possible and allowing the addition of reactants during rotation).

[0015] Objectives of the invention

[0016] An objective of the present invention is to overcome the drawbacks of the state of the art, in particular those described above.

[0017] In particular, an objective of the invention is to provide a thin film reactor allowing use in confined mode.

[0018] Another objective of the invention is to provide a thin film reactor allowing reactions to be carried out with relatively long residence times, in particular in comparison with a reactor operating in continuous mode. Another objective of the invention is to provide a thin film reactor allowing automation, in particular automation of the supply of reactants / solvents, the extraction of reaction products and rinsing.

[0019] Another objective of the invention, in at least one of its embodiments, is to provide a thin film reactor allowing a wide range of reactions to be carried out (compatible with a wide range of reagents and solvents) and a wide range of reaction parameters / operating conditions.

[0020] Another objective of the invention, in at least one of its embodiments, is to provide a thin film reactor making it possible to carry out the chemical synthesis of radioactive compounds, in particular sensitive to the effects of radiolysis.

[0021] Another objective of the invention, in at least one of its embodiments, is to provide a thin film reactor allowing the use of relatively large reaction volumes (up to 100 ml for example).

[0022] Another objective of the invention, in at least one of its embodiments, is to provide a thin film reactor allowing reactions to be carried out under pressure.

[0023] Yet another objective of the invention, in at least one of its embodiments, is to provide a thin film reactor allowing the automatic control and adjustment of reaction parameters (pressure, temperature, rotation speed, etc.).

[0024] Description of the invention

[0025] To avoid the drawbacks of prior art reactors and in order to achieve the aforementioned objectives, the present invention provides a thin film chemical reactor, suitable for use in confined mode, comprising:

[0026] 1) a reaction vessel comprising a vertical axis and walls defining an interior volume;

[0027] 2) a tube for the introduction of at least one reagent and for the extraction of at least one reaction product,

[0028] 3) an upper part comprising: o a first opening receiving the tube; o a second opening; 4) a connecting means providing a sealed fluid connection between the upper part and the reaction vessel and comprising: o a static part connected in a sealed manner to the upper part; o a mobile part connected in a sealed manner to the reaction vessel

[0029] /

[0030] 5) a drive means allowing rotation (i) of the reaction tank around said vertical axis and (ii) of the movable part of the connecting means;

[0031] 6) means for confining the tube and the second opening; said tube being integral with the upper part, parallel to or on the vertical axis of the tank and extending through the connecting means to the interior volume of the tank.

[0032] The invention is thus based on a new and inventive approach. Indeed, the inventors have found, surprisingly, that the specific configuration of the reactor provided according to the invention makes it possible to achieve all of the objectives.

[0033] Thus, in particular, the reactor of the invention makes it possible to carry out thin film reactions, thanks to the rotation of the reaction vessel by the drive means, and allows closure / sealing of the reactor thanks to the confinement means and therefore use in confined (or “batch”) mode.

[0034] It also provides access to a wide range of chemical reactions and operating conditions. In particular, it makes it possible to carry out, efficiently using the thin film technique: reactions with relatively long residence times (in comparison with the time accessible via a continuous mode reactor which is generally of the order of a minute or less); reactions involving isotopes sensitive to radiolysis: radiolysis can in fact be limited by increasing the surface / reaction volume ratio in the reactor of the invention; and

[0035] It also allows the performance of reactions with relatively large volumes (up to 100 ml for example) and reactions under pressure (up to 10 bar or even beyond). Finally, it allows simple and rapid automation of the supply of reagents / solvents, the extraction of reaction products and the rinsing / emptying of the tank. This makes it possible in particular to quickly and easily carry out several chemical reactions one after the other without the intervention of an operator in "semi-continuous" mode (for example, in order to identify optimal conditions for the same reaction or to synthesize in several successive batches a product of interest in large quantities) or to carry out a "multi-step" reaction (with 2 or 3 successive chemical reactions). This automation (avoiding manual handling) is also very advantageous when reactions involving radioactive isotopes are envisaged.

[0036] The invention also relates to the use of the innovative reactor for synthesizing a chemical compound.

[0037] In a preferred embodiment according to the present invention, the reaction vessel, the tube, the upper part, the connecting means and the containment means are capable of withstanding a pressure between 0.01 and 10 bar.

[0038] In a preferred embodiment according to the present invention, the reaction vessel and the connecting means are capable of withstanding a temperature of up to 120°C.

[0039] In a preferred embodiment according to the present invention, the reactor comprises a heating means, preferably radiative or hot air, of the reaction vessel.

[0040] In a preferred embodiment according to the present invention, the reactor comprises means for irradiating the reaction vessel with one or more wavelengths adapted to cause a targeted photochemical reaction.

[0041] In a preferred embodiment according to the present invention, the connecting means further comprises a rotation shaft in fluid connection with the movable part and with the reaction vessel. According to this embodiment, preferably, the rotation shaft comprises a thread. Also preferably, the reactor comprises a connection means between the rotation shaft and the reaction vessel. Also preferably, the chemical reactor comprises a bearing, preferably a ball bearing, between the fixed upper part and the rotation shaft. In a preferred embodiment according to the present invention, the reactor further comprises a temperature sensor of the reaction vessel, preferably an infrared type sensor.

[0042] In a preferred embodiment according to the present invention, the reactor further comprises a control unit configured to automatically and / or remotely control said reactor.

[0043] The invention also relates to the use of the innovative reactor for synthesizing a chemical compound and, advantageously, for synthesizing a chemical compound involving radioactive isotopes.

[0044] Other characteristics, details and advantages of the invention will emerge from the description and figures given below, without limitation. In particular:

[0045] Figure 1 shows a simplified diagram of an embodiment of the reactor according to the invention (cross section).

[0046] Figure 2 shows examples of shapes of the reaction vessel according to the invention (cross section).

[0047] Figure 3 shows a diagram of a part of the reactor according to the invention (cross section).

[0048] Figures 4 and 5 show a diagram of another embodiment of the reactor according to the invention, from two different viewing angles (in cross section).

[0049] In the figures, identical or similar elements bear the same references.

[0050] In this description and the claims, it is clearly understood that the terms "a", "an" or "the" mean "at least one" and are not to be limited to "a single one", unless explicitly stated otherwise. Furthermore, when a range of values ​​is stated, the ends are included. Finally, all integral and sub-range values ​​within a numerical range / range are expressly included as if explicitly written.

[0051] In the present description and claims, the expression "thin film" relates to the related field, in particular the field of rotating chemical reactors, and is well understood by the person skilled in the art. In the present description and claims, the expression "confined mode", as opposed to "continuous mode", relates to the related field, in particular the field of rotating chemical reactors, and is well understood by the person skilled in the art. It is also sometimes called "batch mode" and implies a reactor hermetically sealed / isolated from the external environment.

[0052] The reactor according to the invention provides access, depending on the rotation speed when the reactor is in operation and the reaction volume, to film thicknesses of a few millimeters, in particular < 2 mm.

[0053] An embodiment of the reactor according to the invention is illustrated schematically in Figure 1. In this embodiment, the tube (4) is on the vertical axis (3).

[0054] According to the invention, the thin film chemical reactor (1) according to the present invention comprises: a reaction vessel (2) comprising a vertical axis (3) and walls defining an interior volume; a tube (4) for the introduction of at least one reactant and for the extraction of at least one reaction product, an upper part (5) comprising a first opening (6) receiving the tube (4) and a second opening (7); a connecting means (8) providing a sealed fluid connection between the upper part (5) and the reaction vessel (2) and comprising a static part (9) connected in a sealed manner to the upper part (5) and a movable part (10) connected in a sealed manner to the reaction vessel (2); a drive means (11) allowing the rotation (i) of the reaction vessel (2) around said vertical axis (3) and (ii) of the movable part (10) of the connecting means (8); means (12, 12') for confining the tube (4) and the second opening (7);said tube (4) being integral with the upper part (5), parallel to or on the vertical axis (3) of the tank (2) and extending through the connecting means (8) to the interior volume of the tank (2). According to the invention, the reaction tank (2) comprises walls (for example, side walls and a bottom) which form an interior volume, which makes it possible to accommodate the reaction medium, comprising said at least one reagent, in particular liquid or gaseous and optionally a solvent. The walls isolate the interior volume from the external environment, thus creating the conditions for controlling the chemical reaction.;

[0055] According to the invention, the reaction tank (2) comprises a vertical axis (3) around which said tank (2) is capable of rotating, thanks to the drive means (11), in order to render the reaction medium in the form of a thin film.

[0056] According to the configuration of the reactor (1) according to the invention, the reaction vessel (2) has an opening, in particular wide and / or flared, at its upper end, allowing fluid connection with the connecting means (8) and allowing the tube (4) to immerse in the interior volume of the vessel (2).

[0057] In a preferred embodiment according to the present invention, the reaction vessel (2) has a shape defined by a side surface and a bottom, and such that, in a cross-section, the side surface is substantially straight and forms an angle with respect to the vertical axis (3) of less than 10°, preferably less than 5°. The side surface may be composed of several substantially straight segments, each of the segments forming an angle with respect to the vertical axis (3) of less than 10°, preferably less than 5°. This is particularly advantageous for forming a thin film, of low and homogeneous thickness and with a high exchange surface (or a large reaction surface / reaction volume ratio).In particular, this allows, for reaction volumes of the order of 1 to 100 ml, that the entire lateral surface of the tank can receive a film that is homogeneous in height and whose thickness is less than 10 mm, preferably less than 5 mm or better less than 2 mm. In addition, this allows homogeneous heating of the film (due to the fairly constant average heating-film distance). Comparatively, other shapes are less suitable. For example, a spherical tank (balloon type) will show, for the same internal volume, the same reaction volume and the same rotation speed, a lower surface ratio and less homogeneous heating.

[0058] Preferably, according to this latter embodiment, the tank (2) has a flat, hemispherical, conical or truncated conical bottom. This is of interest in order to extract the reaction products from the tank, via the tube (4), in particular in the case where the end of the tube (4) in the interior volume of the tank is flush with said bottom but without coming into contact with it.

[0059] Most preferably, according to this latter embodiment, the tank (2) has a cylindrical shape with a flat, hemispherical, conical or truncated conical bottom. This makes it possible to further optimize the formation of the film and its surface / volume ratio. Figure 2 shows, by way of example, two possible and advantageous configurations in the reactor of the invention (the dimensions are given in millimeters in the figure). Figure 2 (a) illustrates a cylindrical-shaped tank, the main walls of which are slightly inclined (the angle is of the order of 3°) relative to the vertical axis (3) and a conical bottom. This tank shape is also that shown in Figure 1. Figure 2 (b) illustrates a tank (2) of cylindrical shape with a hemispherical bottom. This latter design is particularly suitable for certain materials, such as quartz, which have specific physical constraints.The reaction tank (2) may advantageously comprise a flare on its upper part (opposite the bottom), as shown in Figures 2 (a) and 2 (b), which in particular facilitates the connection with the connecting means (8).

[0060] The reaction vessel (2) can advantageously be made of plastic (e.g. PEEK or Teflon), stainless steel, ceramic (silicon carbide), glass or quartz. The material can be chosen in particular according to the chemical reaction to be carried out in the reactor, for example, according to the presence of corrosive components, according to the temperature, pressure, etc.

[0061] The reaction vessel (2) accommodates the tube (4), which allows the easy introduction or removal of components (reagents, solvents, by-products or reaction products) from / into the vessel (2), even during reaction / rotation. Preferably, the tube (4) is arranged on the vertical axis (3) or parallel to it. Most preferably, the tube (6) is arranged on the vertical axis (3). Also most preferably, the tube (4), extending to the interior volume of the vessel (2) such that its end is close to the wall of the vessel (or the bottom of the vessel) or even flush with said wall but without coming into contact with it. This is advantageous in order to more easily extract reaction products using the tube (4), which then plunges into the reaction medium / volume.The configuration, combining a reaction vessel (2) with a vertical rotation axis (3) and a tube (4) on or parallel to this axis (3), allows the use of a straight ("non-bent") tube (4) which, moreover, does not have to be retracted / removed entirely from the device during rotation. This allows easy automation, with a simple device compared to the state of the art, for the addition / removal of compounds from the reaction vessel (2) during reaction / rotation.

[0062] The reaction vessel (2) is further fluidically connected to the upper part (5), by means of and through the connecting means (8), in a sealed manner. This configuration allows the interior volume of the vessel (2) to be fluidically connected to the external environment via the upper part (5), in particular by means of the first opening (6) and the second opening (7).

[0063] The first opening (6) accommodates the tube (4), the latter being integral with the upper part (5). The first opening (6) is thus mainly used to feed and empty the reaction vessel (2). According to the invention, a tube (4) is inserted into this first opening (6) to reach the interior volume of the vessel (2) through the connecting means (8). The tube (4) therefore successively passes through the upper part (5) and the connecting means (8). It extends at one of its ends outside the reactor (1) and at the other end into the interior volume of the reaction vessel (2).

[0064] The second opening (7) allows, depending on requirements, for example a pump, a vent, an inert gas or reactive gas supply and / or a pressure sensor to be connected. The second opening (7) can be arranged parallel or perpendicular (laterally on the upper part (5)) to the vertical axis (3), depending on requirements and the space available around the reactor. The presence of a vent is advantageous in that it allows, in a confined mode, to discharge a gaseous reaction by-product during the reaction, thereby shifting the reaction equilibrium and / or to balance the pressure in the reactor. This is also not possible in the confined mode reactor of the state of the art (VFD type), which is sealed in such a mode

[0065] It is understood that the upper part (5) according to the invention may comprise one or more other openings, beyond the first (6) and the second opening (7) according to the invention, depending on the needs. The reactor according to the invention may comprise a pressure sensor connected to the second opening (7) but this sensor may also be positioned elsewhere on the reactor.

[0066] The reaction vessel (2) is fluidically and tightly connected to the upper part (5) by a connecting means (8), this connecting means (8) further comprising a static part (9) and a movable part (10). This configuration allows the reaction vessel (2) to be able to rotate, in particular around the movable part (10), and this independently of the upper part (5). This advantageously makes it possible to obtain a configuration compatible with the automation of the reactor (1).

[0067] Preferably, the connecting means (8) comprises silicon carbide and / or graphite. This composition gives the connecting means (8) resistance to a wide range of pressure, for example from 0.01 bar to 10 bar, as well as to high temperatures (at least up to 120°C). These materials are furthermore compatible with a very wide variety of chemical reactions, potentially involving corrosive components. Preferably, if the static part (9) of the connecting means (8) comprises silicon carbide, the moving part (10) comprises graphite, and vice versa. This combination of different materials increases the durability of the connecting means (8) and prevents wear effects.

[0068] Alternatively, the connecting means (8) may comprise ferromagnetic materials, which can withstand up to a temperature of about 80°C.

[0069] According to one embodiment, the connecting means (8) further comprises a rotation shaft (13) in fluid connection with the movable part (10) on the one hand and the reaction tank (2) on the other hand. The shaft (13) is preferably hollow in order to ensure the aforementioned fluid connection, and preferably of cylindrical shape.

[0070] The rotation shaft (13) preferably has a thread allowing it to be screwed onto the tank (2) in a watertight manner.

[0071] Preferably, the connection between the reaction vessel (2) and the movable part (10) is ensured in a sealed manner by a connection means (14). The latter may preferably include a central hole, preferably threaded to fit a rotation shaft (13). Preferably, the central hole of the connection means allows the fluidic connection between the interior volume of the vessel (2) and the movable part (10) of the connecting means (8), and finally with the upper part (5). Preferably, this connection means is fixed in a sealed manner to the reaction vessel (2) using a clamping ring.

[0072] According to one embodiment, the chemical reactor comprises a bearing (15), preferably a ball bearing, between the upper part (5) and the rotation shaft (13).

[0073] Figure 3 illustrates a configuration, according to an embodiment of the invention, of the upper part (5)-connecting means (8)-rotation shaft (13) assembly. According to this configuration, for example and advantageously, the rotation shaft is inserted into the ball bearings and the upper part (5) covers the ball bearings which makes it possible to keep "compressed", for example by means of a "circlip", the bearing / shaft / moving part of the connecting means assembly with the fixed part of the connecting means.

[0074] Figures 4 and 5 show schematically an embodiment of the reactor according to the invention, from two different viewing angles.

[0075] According to the invention, the reaction tank (2) is connected to a drive means (11) which allows rotation (i) of the reaction tank (2) around said vertical axis (3) and (ii) of the movable part (10) of the connecting means (8). Preferably, the reaction tank (2) comprises a means for receiving the drive means such as for example a thread, a groove, a pulley.

[0076] According to one embodiment, the drive means (11) comprises a motor. It may also comprise a motor-transmission couple, the transmission, for example a belt, being capable of driving the connection means. The connection means may then advantageously comprise a means for receiving said transmission, such as a pulley, a thread or a groove. An example of a drive means and its arrangement is illustrated in Figure 5, comprising a motor (11'), a transmission belt (11") and a receiving means (11'") in the form of a pulley).

[0077] Preferably, the drive means (11) also comprises a speed sensor. The interior volume of the reaction vessel (2) can be isolated, for example under pressure, by closing the openings (6, 7) using the confinement means (12, 12'), thus putting the reactor in "confined mode". In other words, the confinement means (12, 12') make it possible to isolate said interior volume from said reaction vessel (2). For example, the confinement means (12, 12') can be solenoid valves, for example, one for each opening (6, 7) or in other words, one for the tube (4) and one for the second opening (7).

[0078] In a preferred embodiment, the chemical reactor (1) comprises a heating means (16). The heating means (16) is preferably positioned outside the reaction vessel (2), close to it. In particular, it is a means for heating the walls of the reaction vessel (2). An example arrangement of the heating means according to the invention is illustrated in Figure 5.

[0079] This heating means (16) may be hot air or radiative. More preferably, this heating means is radiative. For example, an infrared lamp (halogen, ceramic or quartz for example) is particularly suitable. This allows targeted and localized heating, therefore energy efficient, of the reaction vessel (2). In addition, this radiative heating method minimizes or even eliminates the inertia often present in conductive or convective type heating means.

[0080] In a preferred embodiment, the chemical reactor (1) comprises a means for irradiating the reaction vessel (2) with one or more wavelengths suitable for causing a targeted photochemical reaction. This irradiation means may be in addition to the heating means. It is particularly advantageous for carrying out photochemical reactions, in combination with the thin film technique which allows very good penetration of light into the reaction medium.

[0081] In a preferred embodiment, the chemical reactor comprises a temperature sensor (17) of the reaction vessel (2), preferably an infrared type sensor. This sensor makes it possible to monitor in real time the temperature of the reaction vessel (2) (and therefore of the reaction medium) with an almost instantaneous response and thus a fine and rapid regulation, if necessary. This type of sensor makes it possible to measure the temperature remotely, without direct contact with the reaction vessel (2), which is advantageous when the latter is rotating. An example of arrangement of the temperature sensor (17) according to the invention is illustrated in Figures 4 and 5.

[0082] In addition, the reactor advantageously comprises a reagent / product distribution and sampling system (18) fluidly connected to the first opening (6) via the tube (4). This reagent / product distribution and sampling system (18) advantageously comprises in particular one or more reagent and / or solvent reservoir(s), one or more product collection bottle(s), valves, one or more syringe pumps and / or one or more pump(s).

[0083] Furthermore, the chemical reactor (1) may comprise a control unit which makes it possible to control the reactor in an automated and / or remote manner, in particular allowing the monitoring and automatic adjustment of reaction parameters (pressure, temperature, rotation speed, reaction equilibrium, etc.).

[0084] Preferably, the control unit according to the invention is connected to one or more of these means: the confinement means, the drive means, a heating means, an irradiation means, a rotation sensor, a speed sensor, a pressure sensor, a temperature sensor, a reaction monitoring means (for example, a spectroscopic sensor of the Raman, UV and / or IR type), a system for introducing reagent(s) and / or solvent, a product extraction system, and / or a draining and / or cleaning system.

[0085] Furthermore, the chemical reactor (1) may comprise an enclosure (19), intended to provide a structure for holding certain elements of the reactor (1). It is for example made of steel or aluminum walls. An example of such an enclosure (1) according to the invention is illustrated in Figures 4 and 5. Furthermore, the chemical reactor (1) may comprise one or more cooling means (20), intended to reduce the temperature in the area where it is positioned, in particular to allow its control upwards or downwards in the reaction vessel in combination with the heating means (16). A cooling means is thus advantageous when it is positioned close to the reaction vessel. A cooling means may be, in addition or alternatively, provided close to the upper part (5), so as to control heating which may occur due to rotation.A cooling means may be, in addition or alternatively, in the enclosure and near the heating means, so as to control heating in the enclosure and at the heating means.

[0086] An example of a cooling means suitable according to the invention consists of a ventilation system or fan, as illustrated in Figures 4 and 5, near the tank (20), near the upper part (20') and in the enclosure and near the heating means (20").

[0087] The reactor (1) of the invention may also comprise, as illustrated in Figures 4 and 5, a pump (21), for example a membrane pump, in fluid connection to the confinement means (12') of the second opening (7), in particular via a valve.

[0088] The reactor (1) of the invention may also comprise, as illustrated in Figures 4 and 5, a vent (22) in fluid connection with the confinement means (12') of the second opening (7), in particular in the form of a valve.

[0089] The reactor (1) of the invention may also comprise, as illustrated in Figures 4 and 5, an inert gas inlet valve (23) in fluid connection with the confinement means (12') of the second opening (7), for example a nitrogen or argon inlet valve. This makes it possible to purge the reaction medium from the tank (2) via the tube (4) under positive pressure of said inert gas, in particular in the case where the end of the tube (4) in the interior volume of the tank (2) is flush with the bottom but without coming into contact with it (the tube is then "immersed" in the reaction medium).

[0090] Examples

[0091] Two types of reaction (Examples 1 and 2) were carried out in a reactor such as that illustrated in Figures 4 and 5. Example 1

[0092] The following procedure was implemented to achieve the synthesis of the compound phenylimidazo[l,2-a]pyridine.

[0093] The tank used was of shape and dimensions according to Figure 2(a) and was made of 316L stainless steel. The tube (4) was made of PEEK (1.6 mm external diameter; 1 mm internal diameter) and extended into the interior volume of the tank (2) by skimming the bottom of the tank without coming into contact with it.

[0094] First, the tank (2) was rotated using a motor assembly (1 1 '), belt (1 1 ") and receiving means (1 1 '") (remote motor) at a speed of 910 rpm.

[0095] Then, an ON / OFF valve (12), in fluid connection with the tube (4) on the one hand and a reagent / product distribution and sampling system (18) on the other hand, was activated (ON) in order to introduce into the rotating tank (2) via the tube (4), in the order:

[0096] 3 ml of a 0.293 mg / ml solution of 2-bromoacetophenone in DMF;

[0097] 3 ml of a 0.140 mg / ml solution of 2-aminopyridine in DMF; and 0.5 ml of pure DMF.

[0098] A homogeneous thin film of 2 mm thickness was formed on the side walls of the tank (2) due to rotation.

[0099] Valve (12) is then closed (OFF) in order to isolate the tank (2) (the other valves of the reactor were also closed).

[0100] The tank (2) was then heated to a set point of 90°C using a 300W halogen lamp (16) controlled by an electronic dimmer. Temperature regulation was carried out using an IR temperature sensor (17).

[0101] An ON / OFF valve (12') in fluid connection with the second lateral opening on the one hand and a diaphragm valve-pump pair (21) on the other hand was then activated (ON). A vacuum of 250 kPa was applied in the tank (2) by means of the pump (21), in order to promote the extraction of the volatile by-products of the reaction (HBr, H2O). The valve directly connected to the pump was also opened. After 10 min of maintaining the set temperature, the vacuum applied and the rotation at 910 rpm, the medium was cooled to 40°C using a fan (20) and then atmospheric pressure was restored inside the tank by means of a vent valve (22) in fluid connection with the second lateral opening, in parallel with the pump (21).

[0102] The rotation of the tank (2) was then stopped and the liquid reaction medium was thus lodged in the bottom of the tank.

[0103] The tank (2) was then put under positive pressure (+0.7 bar) thanks to a nitrogen inlet in the form of a valve (23), connected for example to a nitrogen cylinder (not shown), which was activated (ON). In this way, the reaction medium was evacuated from the tank (2) to the system (18), in particular to a collection bottle, via the tube (4) which was immersed.

[0104] Example 2

[0105] The following procedure was implemented to perform the radiosynthesis of a Ga-68 labeled PSMA tracer.

[0106] The tank used was of the shape and dimensions shown in Figure 2(a) and was made of silicon carbide. The tube (4) was made of PEEK (1.6 mm external diameter; 1 mm internal diameter) and extended into the interior volume of the tank (2) by skimming the bottom of the tank without coming into contact with it.

[0107] Gallium-68 was obtained from a Galliapharm® generator from Eckert & Ziegler (not shown in Figures 4 and 5) fluidly connected to the reagent / product distribution and sampling system (18). Gallium-68 was eluted from the generator by an ultrapure 0.1 M HCl solution. The first fraction (1.5 ml) was sent to a waste bottle and the second fraction (3.5 ml) was directed to a vented plastic bottle placed in an activimeter. A measurement of the radioactivity (185-370 MBq) of the obtained gallium-68 acid solution was carried out. This was then sent by a reagent / product distribution and sampling system (18) into the tank (2) via the tube (4), the valve (12) in fluidic connection with the tube (4) on the one hand and the system (18) on the other hand being activated (ON).

[0108] An aqueous solution (HPLC grade) of the precursor (50 μl, 1 g / l) is previously diluted with an aqueous solution (HPLC grade) of NaOAc (purity >99%) 0.4 M; 1.2 ml. This basic solution was introduced into the tank (2) via the tube (4), using the system (18), the valve (12) being activated (ON).

[0109] Once the addition of the reagents is complete, the valve (12) is closed (OFF) as well as the valve (12') in fluid connection with the second opening (7), in order to isolate the tank (2).

[0110] The tank (2) was rotated using a motor assembly (1 1 '), belt (1 1 ") and receiving means (1 1 '") at a speed of 710 rpm.

[0111] The tank (2) was then heated to a set point of 95°C using a 300 W halogen lamp (16) controlled by an electronic dimmer. Temperature regulation was carried out using an IR temperature sensor.

[0112] (17) . The temperature rise took about 2 minutes and then the reactor was left rotating at 710 rpm and 95°C for 15 minutes. Then, heating and rotation were stopped.

[0113] Valves (12) and (12') were then activated (ON). In addition, a nitrogen supply in the form of a valve (23), connected for example to a nitrogen cylinder (not shown), was opened in order to facilitate the transfer of the reaction medium to the system

[0114] (18), in particular towards a collection bottle.

[0115] Then, the tank (2), rotated at 710 rpm, was rinsed with 2 x 5 ml of water injected via the tube (4). The rinsing waters were transferred to the same collection bottle. The total collected volume (crude reaction + washing waters) was then manually pre-purified on a Wafers tO8 short plus cartridge. The cartridge was rinsed with 5 ml of water (aqueous purification phase) then manually eluted with 1.5 mL of 96% ethanol (ethanol phase). The ethanol phase, the aqueous phase and the cartridge were measured for their radioactivity. The ethanol phase was analyzed by HPLC.

[0116] The ethanol phase contains 91% of the starting activity, the tC18 cartridge 4% and the aqueous purification phase 4% as well. The activity percentages are given with the decay correction. These data indicate that the residual activity contained in tank (2) is not significant.

[0117] The radiochemical purity obtained by HPLC is > 90%. Thus, the reactor according to the invention makes it possible to carry out thin film reactions, providing the known advantages of this principle, to be used in confined mode and allowing easy automation, in particular of the supply of reagents / solvents, the extraction of reaction products and the rinsing of the tank. It also makes it possible to carry out a wide range of reactions (compatible with a wide range of reagents and solvents) and a wide range of reaction parameters / operating conditions (for example, under pressure), to carry out the chemical synthesis of radioactive compounds, and to access relatively long reaction / residence times (10 and 15 minutes in the examples provided) and relatively high volumes (>6 ml in example 1).

[0118] It is understood that the present invention is in no way limited to the embodiments described above and that many modifications may be made thereto without departing from the scope of the appended claims.

Claims

CLAIMS 1. Thin film chemical reactor (1), suitable for use in confined mode, comprising: a reaction vessel (2) comprising a vertical axis (3) and walls defining an interior volume; a tube (4) for the introduction of at least one reactant and for the extraction of at least one reaction product, an upper part (5) comprising: o a first opening (6) receiving the tube (4); o a second opening (7); a connecting means (8) providing a fluidic and sealed connection between the upper part (5) and the reaction vessel (2) and comprising: o a static part (9) connected in a sealed manner to the upper part (5); o a movable part (10) connected in a sealed manner to the reaction vessel (2); a drive means (11) allowing rotation (i) of the reaction vessel (2) around said vertical axis (3) and (ii) of the movable part (10) of the connecting means (8); means (12, 12') for confining the tube (4), and the second opening (7);said tube (4) being integral with the upper part (5), parallel to or on the vertical axis (3) of the tank (2) and extending through the connecting means (8) to the interior volume of the tank (2).; 2. Chemical reactor according to the preceding claim, characterized in that the reaction vessel has a shape defined by a lateral surface and a bottom, and such that, on a cross-section, said lateral surface is substantially straight and forms an angle with respect to the vertical axis (3) of less than 10°.

3. Chemical reactor according to one of the preceding claims, characterized in that the reaction vessel (2), the tube (4), the upper part (5), the connecting means (8) and the containment means (12, 12') are capable of withstanding a pressure between 0.01 and 10 bar.

4. Chemical reactor according to one of the preceding claims, characterized in that the reaction vessel (2) and the connecting means are capable of withstanding a temperature of up to 120°C.

5. Chemical reactor according to one of the preceding claims, characterized in that it comprises a heating means (16), preferably radiative or hot air, of the reaction tank (2).

6. Chemical reactor according to one of the preceding claims, characterized in that it comprises a means of irradiating the reaction tank (2) with one or more wavelength(s) adapted to cause a targeted photochemical reaction.

7. Chemical reactor according to the preceding claim, characterized in that said connecting means (8) further comprises a rotation shaft (13) in fluid connection with the movable part (10) and with the reaction tank (2).

8. Chemical reactor according to the preceding claim, characterized in that said rotation shaft (13) comprises a thread.

9. Chemical reactor according to one of claims 7 and 8, characterized in that it comprises a connection means (14) between said rotation shaft (13) and the reaction tank (2).

10. Chemical reactor according to one of claims 7 to 9, characterized in that it comprises a bearing (15), preferably a ball bearing, between said upper part (5) and the rotation shaft (13). 1 1. Chemical reactor according to one of the preceding claims, characterized in that it comprises a temperature sensor (17) of the reaction tank, preferably an infrared type sensor.

12. Chemical reactor according to one of the preceding claims, characterized in that it comprises a control unit configured to control said reactor automatically and / or remotely.

13. Use of a reactor according to one of claims 1 to 12, for synthesizing a chemical compound.

14. Use according to the preceding claim, involving radioactive isotopes.

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