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Field of the invention

The present invention relates to a chamber for a multifunctional chemical reactor comprising a plurality of chambers, connected to each other in series.

Background of the invention

The chemical reactor of the present invention is particularly, albeit not exclusively, usable for the production of active pharmaceutical ingredients.

In this technical field, the reactions that must take place for the production of the active pharmaceutical ingredients and of the intermediate compounds are primarily performed by means of technologies known as "batch" technologies, wherein the reactants are loaded inside the reactor and the reaction products are unloaded from the same reactor after a suitable reaction time, known in the art as batch time, has passed. The type of reactor that is commonly is the so-called "stirred batch reactor", which is provided with a stirrer to place into intimate contact the reactants and with an outer jacket wherein a diathermic fluid circulates that receives the heat produced from the reactant system or provides the heat required by the reactant system.

There are multiple reasons why this technology is primarily adopted. Among these, the main reason is represented in that the stirred batch reactor is particularly suitable for producing different types of reaction, involving different reactants in a liquid, solid or gaseous phase. This reactor can thus be used as multifunctional equipment, sequentially usable to perform processes that are even very different from each other. The fact of being able to dedicate one reactor for the production of various products is advantageously usable in cases wherein the production of substances in batches of reduced amounts and for limited periods is required, as frequently occurs in the sector of production of active pharmaceutical ingredients. On completion of the production of a substance, the same reactor is immediately usable for the production of a different substance, thus allowing a constant use of the reactor.

Again in the field of special polymers, the prevalent reaction technology is batch technology. Special polymers find wide application in glues, paints, wall paintings, sectors in which a multiplicity of formulates optimised to provide specific performance are used. The polymers used differ in chemical composition, being formed by mixtures of monomers belonging to the same family, in average molecular weight, in the distribution of the molecular weights, and in that they are produced in solution or in aqueous emulsion. Polyamides and polyacrylates are examples of polymer classes that offer these diversification characteristics. In this case, batch technologies again offer the possibility to prepare multiple types of polymer with the same reactor, and this explains the preference so far given to the batch technique.

As an alternative to batch reactors, even in the technical field of active pharmaceutical ingredients and fine chemical intermediates, the continuous processes have recently become increasingly established (Chemical Reactions and Processes under Flow Conditions, S. V: Luis and F. Garcia-Verdugo Ed., RCS, Cambridge, 2010). Of the reasons for this trend, the main reasons are the following:

- in continuous processes the working equipment operates in steady state, i.e. under constant temperature, pressure and local composition conditions; consequently, the operating conditions can be precisely controlled with a complete guarantee on the constancy of the quality of the substance produced. This characteristic is of particular importance in the production of active pharmaceutical ingredients;

- the good control of reaction conditions allows reaction times to be reduced, normally obtaining higher productivities with respect to batch processes. This allows the volumes of the equipment to be reduced, with a consequent decrease in investment costs and an increase in the intrinsic safety of process, arising from the reduction of the amount of reactants contained in the system;

- the continuous processes also allow an easy and controlled recycling of the solvents, reducing the use thereof and the waste and thereby determining a reduced environmental load of the processes.

The use of continuous reactors is also preferable in the case of polymerisation reactions, which, due to their exothermicity characteristics and their kinetics, are more difficult to control in other types of reactors. As regards continuous reactions, two basic types of reactor are in use: the continuous stirred tank reactor (also known by the acronym CSTR), and the plug- flow reactor (also known by the acronym PFR). PFR reactors, which, with respect to CSTR reactors, offer more useful performance kinetics, the reactor technology has developed a variety of specific types (Levenspiel, O. Chemical Reaction Engineering, 3rd Edition, New York, JonhWiley, 1999). In the context of continuous reactions there are moreover known tubular, homogeneous phase reactors, gas liquid bubble reactors, solid-liquid fixed bed reactors.

New types of reactors have recently been proposed, for a specific use in the continuous preparation of fine chemical products and of active pharmaceutical ingredients. For example, patent WO 28068019 describes a continuous reactor consisting of a series of cells, wherein the stirring is obtained by shaking. The main drawback determined by the stirring by shaking is that due to this very characteristic, this reactor is ill-suited to a passage of scale from the pilot dimensions to those of industrial production. Patent WO 2006/136850 on the other hand claims a chamber reactor wherein the stirring is obtained by means of a pulsation system, which causes stirring in each chamber. In this case, the main drawback is represented in that, all the chambers being interconnecting to each other,the reactor is characterised by a high degree of back mixing, and in order to obtain satisfactory performance it is therefore necessary to use of cylindrical geometries with a very high length to diameter ratio.

Other continuous reactors are described in DE 2224569, US 4138544 and GB 1078663.

All the above-cited reactors for continuous reactions are generally dedicated to just one type of reaction, for example in a homogeneous, or gas-liquid, or solid- liquid or other type of phase, and are not easily usable as multifunctional equipment. They are moreover characterised by a fixed reaction volume. These reactors thus have the disadvantage of having to be sized on a specific type of reaction, and of not being easily usable in different production. This rigidity of use decreases the industrial interest of continuous processes, in that each process requires a specific dedicated system, with a proliferation of investment costs that cannot be supported by productions of limited amounts of end product. There is thus a need to provide a continuous reactor of the PFR type usable in the industrial field and having the characteristics of multifunctionality, being able to produce different types of reactions, with different residence times and operating conditions, while at the same time ensuring, for each reaction, excellent performance in terms of mixing of the reactants, so as to overcome all the drawbacks cited with reference to the cited prior art.

Summary

In accordance with a first aspect of the invention, the above-mentioned technical problem is resolved by a chamber for a chemical reactor, comprising:

- a lower base provided with a through hole,

- an upper opening axially opposed to the lower base,

- a perimeter wall extending between the lower base and the upper opening,

- an internal volume extending between said lower base, said upper opening and said perimeter wall,

- a hydraulic guard provided with at least one lower end and at least one upper end, respectively closer to and more distant with respect to said lower base, said upper and lower ends respectively communicating with said internal volume and said through hole, so as to form a fluid passageway between said through hole and said lower end through said upper end, said hydraulic guard comprising an inner cylinder, extending between said through hole and said upper end, and an outer cylinder, fitted onto said inner cylinder and extending between said lower end and a closed bottom,

- a rotating shaft connected to said outer cylinder,

- a weir passing through the lower base,

- said chamber being characterised in that said weir is slidingly coupled to a second through hole of said lower base so that a first axial end of said weir is positioned with respect to the lower base at an intermediate height between the respective heights of said lower end and upper end of said hydraulic guard and that

- said outer cylinder is provided with a plurality of blades, adapted to cause a stirring state in a fluid contained in said chamber. In accordance with a second aspect of the invention, the above-mentioned technical problem is also resolved by means of a multifunction chemical reactor comprising a plurality of chambers according to one of the preceding claims, said chambers being stacked together by placing in reciprocal contact said lower base of one of said chambers with said upper opening of another of said chambers, all the rotating shafts of the reactor being connected to each other so that all the outer cylinders of said reactor are simultaneously rotatable.

In particular, it is provided that the lower axial end of the weir of an overlying chamber is plunged into the portion of the underlying chamber occupied by a liquid.

The present invention provides a cascade of continuous reactors stirred in a constructively and operationally simple manner, with the characteristics of being able to manage multiphase reactions in a wide range of conditions in a single compact equipment.

By varying the height of the weirs in each chamber it is also possible to vary the volume of the liquid in each chamber, thus obtaining a wide-spectrum multifunctional reactor, as in the case of the use of batch reactors.

The presence of a blade system provided on the rotating part of the hydraulic guard makes it possible to obtain an effective stirring level within the reactor.

In one embodiment of the invention, a screw feeder that is integral with the rotating shaft is provided for use, within the hydraulic guard. This allows high viscosity systems to be treated, allowing the continuous production of polymers.

Brief description of the drawings

Further characteristics and advantages of the present invention will become clearer from the following detailed description of preferred, but non-exclusive embodiments, illustrated by way of a non-limiting example, with reference to the accompanying drawings, wherein:

figure 1 is a cross-sectional side view of a chamber of a chemical reactor according to the present invention;

- figure 2 is a plan view of the chamber of figure 1 ; figures 3a,b, one two cross-sectional side views of two respective embodiments of a chemical reactor consisting of a plurality of superimposed chambers, identical to those of figure 1 ;

figure 4 is a side view of a detail of the chamber of figure 1 ;

- figure 5 is a cross-sectional side view of an embodiment of a chamber of a chemical reactor according to the present invention.

Detailed description of the invention

With initial reference to figures 1 and 2, a chamber for a multifunctional chemical reactor is globally indicated by 1. The chamber 1 is of a predominantly cylindrical form with central axis of symmetry X and is provided with a lower base 2, an upper opening 8, which is axially opposite the lower base 2 and a cylindrical perimeter wall 5 extending between the lower base 2 and the upper opening 8. The lower base 2 is axially delimited by a first convex, conical surface 2a facing the upper opening 8 and an opposite, flat surface 2b. Between conical surface 2a, the upper opening 8 and the perimeter wall 5 is defined an internal volume V of the chamber 1 , susceptible to accommodating a plurality of reactants and reaction products. In general, in the internal volume V there will normally be present a liquid phase arranged in contact with the lower base 2 and a gas phase overlying the liquid phase and thus closer to the upper opening 8.

The lower base 2 comprises a first through hole 2c which is coaxial with the axis X.

Along the perimeter wall 5 is provided a jacket wherein a diathermic fluid is circulated to adjust the reaction temperature by providing or removing heat as a function of the specific reaction that must take place in the internal volume V.

According to another embodiment of the invention (not represented) the heat exchange between the perimeter wall 5 and the internal volume V is produced by an electric heating device.

In proximity of the upper opening 8, the perimeter wall 5 is provided with an upper conduit 16 for collecting the gaseous phase from the top of the internal volume V of the chamber 1 , when it is not desired for the gaseous phase to be sent to the upper chamber. The chamber 1 comprises a side weir 3, having a tubular form, and arranged so as to be passing through a second through cylindrical through hole 12 obtained in the lower base 2 in parallel to the axis X. The weir 3 is internally hollow and axially extends in a direction parallel to the X-axis between a first axial end 3a inside the internal volume V and a second opposite axial end 3b, protruding from the lower base 2, from the part of flat surface 2b. The weir 3 is coupled to the hole 12 so as to be slidable with respect thereto, so as to adjust the distance between the first axial end 3a and the lower base 2 of the chamber 1.

The chamber 1 further comprises a hydraulic guard 4 placed at the central axis X. The hydraulic guard 4 is formed by two, respectively inner and outer, cylinders 6, 7 that are coaxial to the axis X. The inner cylinder 6 is integral with the lower base 2 and projects with respect thereto towards the internal volume V. The inner cylinder 6 is open at the opposite, respectively upper and lower axial ends 6a,b. The lower axial end 6b is coincident with the through hole 2c of the lower base 2, so that the upper axial end 6a is placed in communication with the through-hole 2c through the inner cylinder 6. The outer cylinder 7 is fitted onto the inner cylinder 6 and comprises two, respectively upper and lower, opposite axial ends 7a, b. The lower end 7b is open, faces the conical surface 2a and communicating with the internal volume V. The opposite upper end 7a consists of a closed base so as to provide a fluid passage P between the through hole 2c and the lower end 7b of the outer cylinder 7, through the upper end 6a of the inner cylinder 6.

The upper end 7a is rigidly constrained to a rotating shaft 9, passing inside of the inner cylinder 6 and coaxial with respect to the axis X. The rotating shaft 9 is rotatable about the axis thereof, which is coincident with the X-axis, for the movement of the outer cylinder 7. The outer cylinder 7 comprises a cylindrical side skirt 7c to which are rigidly constrained a plurality of blades 10 (two blades 10 diametrically opposite with respect to the X-axis in the example of figures 1 and 2), radially extending to the side wall 5 so that when the outer cylinder 7 is placed in rotation about the X-axis by means of the rotating shaft 9, the blades stir the liquid present in the internal volume V of the chamber 1. The stirring obtained by means of the rotation of the outer cylinder 7 also allows the reactions wherein a solid phase to be managed. According to another embodiment of the invention (not represented) the outer cylinder 7 comprises a plurality of blades, radially extending to the X axis to stir the liquid present in the hydraulic guard 4 between the inner and outer cylinders 6, 7. With reference to figure 4, in an embodiment of the present invention particularly usable for liquid-solid fixed-bed reactions, the outer cylinder 7 of the hydraulic guard 4 comprises a basket 17 with mesh walls usable to accommodate a solid reactant, such as a catalyst in tablet form for example. When the outer cylinder 7 is placed in rotation, the basket 17 is crossed by the liquid, thus placing the solid phase in intimate contact with the solid reactant.

The weir 3 is adjustable in height with respect to the lower base 2, so that the first axial end 3a inside the volume V can be positioned at an intermediate height between the lower end 7b of the outer cylinder 7 and the top end 6a of the inner cylinder 6 of the hydraulic guard 4.

In other embodiments of the present invention, in order to facilitate the transit of fluids through the hydraulic guard 4, the use of a screw feeder integral with the rotating shaft 9 is provided.

With reference to figure 5, in an embodiment of the present invention particularly usable for reactants consisting of high viscosity fluids, for example molten polymers, in the chamber 1 a weir 30 that is coaxial to the X axis is provided. The weir 30 is coincident with the inner cylinder 6 of the hydraulic guard 4 of the embodiment of figure 4, the upper end 6a of which is thus coincident, in the embodiment of figure 5, with a free end 30a of the weir 30. Again with reference to the embodiment of figure 5, the chamber 1 also includes a screw feeder 35 internal to the weir 30 and integral with the rotating shaft 9, so as to ensure the transfer of the high viscosity solution from the upper chamber to the underlying chamber, with a maximum flow rate that is a function of the speed of rotation of the shaft 9, and thus of the screw feeder 35, and a minimum flow rate dependant on the flow of the reactant system.

In a further embodiment (not represented), the chamber 1 is provided, in the upper part thereof, with a heat exchanger to condense any vapours developed by the reactants, thus producing a reactor capable of treating reactant systems at boiling. In all the above-described embodiments (figures 1 , 2 and 5), the lower base 2 of the chamber 1 comprises a first lower conduit 13 that connects to each other two holes respectively placed on the conical surface 2a, in proximity of the perimeter wall 5, and on an outer edge of the lower base 2. A second lower conduit 14 for the collection or the delivery of liquid respectively from or to the internal volume V are also integral in supporting the conical surface 2a. The conduits 13 and 14 allow the simultaneous and independent delivery to the chamber of a liquid stream and a gaseous stream, and the conduit 13 in particular is positioned so as to be able to drain the content of the chamber at the end of operation. There is further provided a thermometric sensor 15 for controlling the temperature in the internal volume V. The first lower conduit 13, the second lower conduit 14 and sensor 15 are extended between the internal volume V and the outside of the chamber 1 oriented, in a plan view of the chamber 1 (figure 2), according to respective radially oriented directions with respect to the axis X.

With reference to figures 3a, b, a chemical reactor 100 consists of a plurality of chambers 1 that are stacked together (ten chambers 1 in the example represented in figure 3a, two chambers 1 in the example represented in figure 3b). In the simplest case (figure 3b), the chemical reactor 100 consists of a pair of respectively overlying and underlying chambers, and is obtained by placing in reciprocal contact the flat surface 2b of the lower base 2 of the overlying chamber with the upper opening 8 of the underlying chamber. The chambers 1 are reciprocally arranged so that the weirs 3 of two adjoining chambers do not interfere with each other. In the example of figure 3a,b each chamber 1 is rotated by 180° around the axis X with respect to the underlying chamber, so that the respective weirs 3 of two adjoining chambers are diametrically opposite with respect to the axis X.

The rotating shaft 9 of each chamber 1 is connected to the upper end 7a of the outer cylinder 7 of the underlying chamber, so that all the cylinders 7 are simultaneously rotatable.

The diathermic fluid that circulates in the respective jacket of each perimeter wall 5 of each chamber 1 allows adjustment of the temperature of each chamber 1 independently of the others. Each of the weirs 3 of each chamber 1 is adjusted in height so that the second axial end 3b is plunged into the liquid phase of the underlying chamber 1. The volume of the liquid phase contained in each chamber 1 may vary between a minimum, corresponding to the one in which the free surface of the liquid phase is aligned with the lower end 7b of the outer cylinder 7 and a maximum, corresponding to the one in which the free surface of the liquid phase is aligned with the upper end 6a of the inner cylinder 6 hydraulic guard 4.

The hydraulic guard 4 of each chamber 1 prevents the upper opening 8 of each chamber 1 from being in direct communication with the respective upper opening of 8 of the adjoining chambers, providing a sequence of segregated chambers also as regards the respective gaseous phases. This provision is important in the case of gas-liquid reactions or for reactions that take place once the boiling temperature in a liquid has been reached. The hydraulic guard 4 prevents the passage of the gaseous phase from each chamber 1 to the chamber immediately below. The passage of a gaseous stream through the inner cylinder 6, from each chamber 1 to the chamber immediately above, is on the other hand permitted. The height of each weir 3 can be adjusted to vary the volume of liquid contained in each chamber 1 , according to the method described below.

Initially the height of the weirs 3 is adjusted in each chamber 1 in so as to define the desired sequence of residence times in each chamber of the reactor 100. Usually the liquid reactants are fed into the uppermost chamber of the reactor 100 at a controlled rate and such as to provide the desired residence time. Thereafter, the liquid of one chamber passes through the respective weir 3 in the immediately underlying chamber, and so forth, until it exits from the lower base 2 of the lowermost chamber of the reactor 100. By increasing the height of the weirs 3, the volume of liquid contained in each chamber and in the entire reactor can be increased while maintaining the overall residence time unchanged, i.e. the flow and thus, proportionally, the potential of the entire reactor, can be increased. Thus, the same reactor can therefore produce at different potentials, and follow, for example, the production increases in the development phase of a product.

The diameter of the weirs and selected so as to allow the passage of suspended solids, so that the reactor 100 can also be used for systems containing a suspension, for example of a catalyst in powder form, or for reactions that produce a solid product, the field of use thereof only being limited only by the concentration of the solid and of its fluidity characteristics.

The following examples illustrate the operation of the invention in respective typical cases of chemical reactions.

A first example relates to the use of the reactor 100 for homogeneous liquid phase reactions. For such use, one or more solutions containing the reactants are fed into the upper chamber of the reactor, at a flow rate established so as to achieve the desired residence time, given the volume of liquid contained in the stack of stirred chambers. Each chamber is thermostated at the desired temperature by means of heat exchange on the perimeter wall 5 of each chamber 1. The desired degree of stirring is obtained by adjusting the speed of rotation of the shaft. The liquid passes through the corresponding weir 3 from each chamber to the immediately underlying chamber, until it exits the lower base 2 of the lowermost chamber.

If required, supplementary deliveries can be obtained in the intermediate chambers of the reactor 100, through the respective lower conduits 13 or 14.

A second example relates to the use of the reactor 100 for gas-liquid reactions. In this case, delivery of the liquid is managed as in the previous example. The gaseous stream is on the other hand delivered into the liquid contained in the lower chamber. From there it passes through the hydraulic guard of the chamber immediately above into the liquid contained therein, in which it is dispersed by the effect of the stirring imparted by the blades 10. The gaseous stream that is freed from the liquid passes into the upper chambers with the same mechanism, rising along the reactor 100 until it exits from the upper opening 8 of the uppermost chamber.

A third example relates to the use of the reactor 100 for liquid-solid reactions in suspension. In this case the reactor 100 is managed as in the first example with the difference that a reactant solution consisting of a suspension of a solid, for example, a catalyst, is delivered into the uppermost chamber. A fourth example relates to the use of the reactor 100 for gas-liquid-solid reactions in suspension. The liquid and solid phases are managed as in the previous third example while the gaseous phase is managed as in the second example.

A fifth example relates to the use of the reactor 100 for liquid-solid fixed-bed reactions, wherein the variant of the outer cylinder 7, comprising the basket 17 (figure 4) is used, wherein a catalyst in tablet form is placed. By rotating the outer cylinder 7, the basket 17 is crossed by the liquid phase, placing it in intimate contact with the catalyst. The flow of the liquid phase is managed as in the first example.

A sixth example relates to the use of the reactor 100 for gas-liquid-solid fixed bed reactions. In this case, the structure of the reactor 100 and the management of the liquid stream are the same as described for the fifth example. The management of the gaseous stream takes place as in the second example.

A seventh example relates to the use of the reactor for polymerisation reactions: the mixture of monomers in solution and, separately, a mixture containing the mixture of initiators, are fed into the upper chamber of the reactor 100. The solution exits the upper chamber through the respective weir 30 inside the hydraulic guard (figure 5). The screw feeder 35 forces the reactant liquid to pass from the upper chamber to the chamber immediately below at a rate that depends on the speed of rotation and the pitch of the screw, and is in any case such as to transfer all the solution that is presented at the free end 30a of the weir 30. The volume of solution present in the chamber is thus determined by the height of the free end 30a. The heat can be exchanged on the wall, or if the system is at boiling point, on a heat exchanger housed in the upper part of the chamber.

The invention thus allows the aims defined with reference to the cited prior art to be achieved, thus providing a reaction chamber 1 and a reactor 100 of the multifunctional PFR type usable in the industrial field, which allow reactions of a different type to be produced, with different residence times and operating conditions, and at the same time ensuring excellent performance for each reaction in terms of mixing of the mixing of the solid, liquid and gaseous reactions.