CA2295048A1

CA2295048A1 - Apparatus for heating/cooling gases,liquids and/or solids in a reaction vessel

Info

Publication number: CA2295048A1
Application number: CA002295048A
Authority: CA
Inventors: Walter Spreiter; Rolf Guller; Seraphin Munch; Hansjorg Tschirky; Thomas Gees
Original assignee: Individual
Current assignee: Chemspeed Ltd
Priority date: 1997-06-16
Filing date: 1998-06-11
Publication date: 1998-12-23
Also published as: JP2002504019A; AU7518798A; WO1998057740A1; DE59800276D1; EP0973607A1; EP0973607B1

Abstract

The invention relates to a device (1) for tempering gases, liquids and/or solids, comprising a hollow body (10) and a tempering tube (13) situated partially inside the hollow body (10) and through which a tempering medium flows. The hollow body (10) is open at the top and bottom. The tempering tube (13) is so arranged that it does not fill the cross section of the opening of the hollow body (10) completely at any point. As a result, gases, liquids or solids can be fed to or removed from the reaction vessel through this device (1).

Description

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Apparatus for Heati.ng/Cooling Gases, Liquids and/or Solids in a Reaction Vessel The present invention relates to an apparatus for heating/cooling gases, liquids and/or solids in a reaction vessel, as defined in the preamble of the independent claim 1.
In the chemical research of the pharmaceutical industry and the universities, it is becoming increasingly important to find as quickly as possible a large number oi_ potential active compounds and then to test these. Sc>me of the chemical research therefore currently re7_at:es to combinatorial chemistry, parallel synthesis and high-speed chemistry. Of central importance in this case is the possibility of being able to use known or novel chemical reaction types as broadly as possible with as little adaptation as possible. A wide temperature range is frequently necessary to carry out corresponding reactions, which in turn require=s the use of an efficient condensation system above the reaction vessels.
The mo=.t varied types of apparatuses have been provided to carry out in parallel a multiplicity of chemical, biological, biochemical or physical processes, in which no efficient cooling of any gases formed is present, addition of solids is not possible, or is possible only with great restriction, due to the structure chosen, which apparatuses, in addition, are either suitable only for specific applications, are constructed in too complicated a manner, are too large or too difficult to operate and/or using which the individual process steps cannot be adequately automated.
An apparatus of this type for carrying out in parallel a rru~ltiplicity of chemical, biochemical, biological or physical processes is distributed under t:he name RAM Synthesizer BHD 1529 by Bohdan Europe, France. It comprises a block to which a multiplicity of reaction vessels a.re detachably attached. If an elevated temperature is required, the lower part of the reaction vessels is heated. The vapours which possibly form can be condensed by a cooling system which cools only the outer surfaces of the corresponding reaction vessels (zone cooling), individual cooling of single reaction vesse:Ls note being possible. A septum plate serves to seal the reaction vessels from the exterior.
The Alclrich company, Switzerland markets 'under the name Cold-Finger Condenser an apparatus for heating/cooling gases, liquids and/or solids in a reaction vessel, which apparatus comprises a hollow body and a hea.ting/cooling tube which leads from the top into the hollow body and partly runs within the hollow body, through which heating/cooling tube, heat.ing/cooling medium is to flow. The hollow body is sea~_ed except for the passages f_or the heating/cooling tube. By means of this heating/cooling apparatus, heating/cooling of gases, liquids and/or solids can be performed within the reaction vessel, even below the connection area of heating/cooling apparatus and reaction vessel.
However, this apparatus has the disadvantage that no access by hollow needle, scoop or spoon is possible through the apparatus into the reaction vessel. Neither gas, liquid nor solids can be fed to the reaction vessel, nor taken out of it, through the apparatus. In addition, series connection of a plurality of such .apparatuses is relatively highly space-consuming,, because of the disposition of the heating/cooling tubes.
In view of the disadvantages of the previously known abovedescribed apparatuses, the object. below underlies the invention. An apparatus of the type mentioned at the outset i.s to be provided for heating/cooling gases, liquids and/or solids in a reaction vessel, in which the addition or removal of gases, liquids or solids into or out of the reaction vessel through the apparatus is possible.
This object is achieved by the apparatus according to the invention, as defined in the independent claim 1. A heating/cooling system according to the invention having a multiplicity of heating/cooling apparatuses and a use according to the invention of a heating/cooling apparatus are defined in the independent claims 8 and 9. Preferred variants are given by the dependent claims.
The essence of the invention is that, in an apparatus for heating/cooling gases, liquids and/or solids in a reaction vessel which comprises a hollow body and a heating/cooling tube which partly runs within the hollow body and through which heating/cooling medium is to flow, the hollow body is open at the top and bottom and the heating/cooling tube is disposed in such a manner that it at no point completely fills the orifice cross-section of the hollow body.
In the apparatus according to the invention, the addition or removal of gases, liquids or solids into or out of the reaction vessel is possible through the apparatus. That is to say that during the addition or removal of gases;, liquids or solids, cooling or heating can be carried out at the same time, which is advantageous for certain applications. In particular, by means of the apparatus according to the invention, a liquid can be f=ed to the reaction vessel, a protective gas, gaseous re~actani~, gaseous catalyst or a solid can be added and/or a pressure equalization can be achieved, for example by means of a feed tool and/or a gas channel, simultaneously with reflex cooling. All of these interventions into the reaction vessel are performed through the same orifice.
The apparatus according to the invention for heating/cooling gases, liquids and/or solids in a reaction vesseJ_ and a heating/cooling system according to the invention having a plurality of such heating/cooling apparatuses and a use according to the invention of such a heating/cooling apparatus are described in more detail below with reference to the accompanying drawings based on illustrative examples.
In the drawings:
Fig, 1 show, a side view of an illustrative example of an apparatus according to the invention;
Fig. 2 shows a top view of the apparatus of Fig. l;
Fig. 3 shows an apparatus according to the invention which is fixed to a flexible coupling and is on two reaction vessf~ls connected by a tube, one of the reaction vessels having a frit;
Fig. 4 shows a simple block having a septum plate attached to the upper side and two illustrative examples of flexible couplings;
Fig. 5 shows a perspective view from above and to one side of an illustrative example of an apparatus for carrying out in parallel a multiplicity of chemical, biochemical, biological or physical processes;
Fig. E> shows a side view of a flexible coupling;
Fig. 7 shows a view through the coupling of Fig. 5 along the line A-A;
Fig. 8 shows a diagrammatic view from the front of a laboratory system having a single block, flexible couplings, heating/cooling apparatuses according to the invention, reaction vessels and a shaking, apparatus;
Fig. 9 shows a space-saving disposition of apparatuses according to the invention connected to one another in series;
Fig. 10 shows a reaction vessel having an integrated heating/cooling chamber;
Fig. l:L shows a partial view of the reaction vessel of Fig. 10 and Figs. 7_2-19 show sections through the reaction vessel of Fig. 11 along the lines B-B, C-C and D-D.
Figures 1 and 2 The depicted apparatus 1 according to the invention for heati.ng/cooling gases, liquids and/or solids in a reaction vessel comprises a hollow body 10 and a heating/cooling tube 13 which partly runs within the hollow bofay 10 and through which heating/cooling medium is to flow.
The hollow body 10 is designed in the form of a tube and is open at the top and bottom. In its upper area, on the inside, it has a standard ground joint surface 1?_ for the detachable attachment of the apparatus 1 to the standard ground joint of a laboratory system or a coupling for a laboratory system and, in its 7_ower area, on the outside, it has a standard ground joint surface 11 for the detachable connection of the apparatus 1 to a reaction vessel.
Instead of standard ground joint connections, threaded connections or other types of attachment are also conceivable.
The heating/cooling tube 13 extends from outside the hollow body 10 laterally into it, out of the bottom of :it, up again into it and again laterally out of it. Due to this disposition, i.n a mounted reaction vesse.l_, cooling can be carried out below the area of connection of reaction vessel and heating/cooling apparatus 1. This can achieve, for example, a gas phase condensing relatively far low down in the reaction vessel, the condensate being collected upstream of the standard ground glass joint and thus remaining in the reaction vessel.
The heating/cooling tube 13 is asymmetrically disposed in the orifice cross-section of the hollow body 10, i.e. is laterally displaced from the centre towards the outside, in order to make space for introducing a :Feed and/or removal tool, e.g. a hollow needle, a scoop or a spoon, and/or the direct addition of, for example, a protective gas, gaseous reactants, gaseous cataly~;t or a solid into the mounted reaction vessel.
The heating~'cooling medium, e.g. water, is advantageously supplied and removed by means of flexible feed and removal lines which are connectable to connectors 1.31, 132 on the heating/cooling tube 13.
The connectors 131, 132 are disposed in such a manner that a disposition as space-saving as possible of a plurality of apparatuses 1 according to the invention is possible. In the present case, the connector 132 is disposed higher than the connector 131. The feed and removal lines c;an serve to connect the heating/cooling tube 13 to a heating/cooling unit, e.g. a cryostat, which provides the heating/cooling medium. When a plurality of apparatuses 1 according to the invention is used, there is the possibility of connecting these in series in a space-saving manner and connecting them to a shared heating/c:ooling unit or to achieve for each individually, with a separate heating/cooling unit, an individually adjustable temperature.
Figure 3 The apparatus 1 according to the invention can in principle be used with many different types of reaction vessels. Advantageously, these should be provided with a connection means, in the present illustrative example a standard ground joint,. for attaching the reacl=ion vessel to the apparatus 1 according to the invention. The shape and capacities of the reaction vessels can be varied in a broad range as a function of the space available and the desired number of reaction vessels used adjacently. Thus, for example, cylindrical reaction vessels having a round or flat bottom, round-bottom flasks, pointed flasks etc.
in particular having capacities of 0.3 ml - 200 ml, are suitable.
The figure shows here two reaction vessels 2', 2" connected by a flexible or rigid tube 21 and a brace 22, which reaction vessels can be used for the filtration. The one end of a filtration tube 23 projects into i~he upper region of the reaction vessel 2", while the other end is fused to a frit 29, e.g. a glass frit, in the bottom region of_ the reaction vessel 2'. By pressure gene ration in the reaction vessel 2' and/or vacuum generation in the reaction vessel 2", filtration can be performed through the frit 24, more precisely in such a manner that not only the filter cake remaining upstream of the frit 24 but also the filtrate is accessible to the intervention of a feed and/or removal apparatus for further processing. The filtration can be performed with simultaneous and/or prior shaking.
The reaction vessel 2' is connected via a standard ground joint. to a heating/cooling apparatus 1 _ 8 _ according to the invention, which itself is attached via a further standard ground joint 2 to a flexible coupling 3.
Figure 4 Heating/cooling apparatuses according to the invention can be det=achably attached, for example, to flexible couplings 3, 3' which are mounted on a rigid block 4 of a 7_aboratory system. Flexible couplings of this type are described in more detail below in connection with Figs. 6 and 7.
The rigid block 4 shown has a multiplicity of through-holes 41, which are sealed on one side by a septum plate 4:2 which is fixed to the topside of the block 9. If required, a septum plate 42 is also dispensed with. To each through-hole 41 can be assigned one respective reaction vessel or one shared reaction vessel can be assigned to a plurality of through-holes 41.
Figure 5 Heating/cooling apparatuses according to the invention can also be used on switching blocks 82 in an apparatus 8 for carrying out in parallel a multiplicity of chemical, biochemical, biological or physical processes. The apparatus 8 shown here comprises a support frame 81 ini=o which are placed two switching blocks 82, in addition to which there is still space for three further switching blocks. The switching blocks 8 are fixed by means of screws, for which the support frame 81 has screw holes 811. In addition, on the support frame 8:l is disposed a starting material vessel frame 83 which serves for storing starting material vials 831. This is designed in such a manner that the starting material vials 831 can be disposed on two levels. 'this serves for better utilisation of the available space and thus to increase the number of starting material vials 831 which can be accommodated.
To hold additional starting material vials or sample removal vials, a holding block or a collecting plate 84 is provided. Solvent dispensing points 85 enable removal of solvents from solvent tanks.
An arm 6 of a sampler serves to carry a hollow needle 61 for handling starting materials or products.
The corner points of the access surface of the hollow needles 61 are marked by needles 61.
There are likewise associated with the apparatus 8, but not: shown here, a shaking system, a vacuum pump, a plurality of gas feed devices, valves 7.5 for the gas feed devices and the vacuum pump, heating/cooling unit:>, a plurality of control units, a diluter and a multiplicity of reaction vessels.
Figures 6 and 7 The flexible coupling 3 shown comprises a block-side part 31 and a reaction-vessel-side part 32, between which is disposed a bellows 33 the function of which is to make the reaction-vessel-side part 32 movable with respect to the block-side part 31, more precisely not only laterally but also in the x, y and z direction. The x, y and z coordinate system shown serves to illustrate the possible directions of motion.
The block-side part 31 is provided with a thread 311, so that the coupling 3 can be screwed into a threaded hole of a rigid block 4 or switching block 82. The reaction-vessel--side part 32 comprises a fixing zone 321 for mounting fastening clamps and a standard ground joint 322 for detac:hably attaching, for example, a heating/cooling apparatus 1 according to the invention, a reaction vessel or another part. The flexible - lU -coupling 3 in addition has a central orifice 34.
The coupling can consist, for example, of plastic or a metal, in particular of teflon, polypropylene, polyethylene or steel sheet.
As an alternative to the bellows 33, a flexible tube, for example, c:an be used, see flexible coupling 3' in Fig. 4. However, a ball-and-socket joint or a biaxial or multiaxial_ socket is also conceivable.
Figure 8 Via flexib7_e couplings 3, here, three heating/cooling apparatuses 1 according to the invention are mounted on a rigid block 4, on which heating/cooling apparatuses are fixed in turn three reaction vesse_Ls 2. The reaction vessels 2 are each firmly sealed on the block with a septum 43 which is in each case fixed by a plastic screw cap 44.
The flexible couplings 3 permit the reaction vessels 2 to f>e shaken with high frequency. For this purpose, the reaction vessels 2 are conducted by a carrier 51 of a shaking unit 5, the shaking motion being performed in the direction of the arrow. In this case, the reaction vessels 2 are shaken together with the heating/cooling apparatuses 1 without the shaking motion being transmitted to the rigid block 4. Owing to the additional. axial flexibility of the flexible couplings 3, even two reaction vessels which are rigidly connected to one another can be shaken.
Furt..hermore, the entire weight of the reaction vessels 2 including their contents does not lie on the shaking unit 5,, so i~hat relatively weak shaking units 5, which produce relatively few vibrations, suffice, which is only what makes it possible to use vibration sensitive peripheral units, such as samplers, robot systems or other automated devices for feeding and/or removing gases and/o.r liquids and/or solids.
An es;~entia:L and critical advantage of the heating/coolinc~ apparatus 1 according to the invention is that, even during the shaking, a liquid, a gas or a solid can be added t:o and/or removed from a reaction vessel 2 without problems through the rigid block 9, ttie flexible coupling 3 and the heating/cooling apparatus l, using a feed and/or removal tool, such as hollow needles 61, scoops or spoons, which is not the case, or is the case only with great limitation, in the case of previously known apparatuses. This is made possible by the heating/cooling tube 13 being displaced in the hollow :body 1.0 laterally offset from the centre towards the oui=side and thus a relatively large amount of space being available for the feed and/or removal of a liquid, a gas. or a solid.
Figure 9 A plurality of heating/cooling apparatuses 1 according to the invention are here connected in series in a particul,srly space-saving arrangement, in each case the inlet of a heating/cooling apparatus 1 being connected to the outlet of an opposite or diagonally adjacent heating/cc>oling apparatus 1 or to a heating/cooling unit which is not shown. The individual heating/cooling apparatuses 1 or their heating/cooling tubes 13 are connected together or to the heating/cooling unit by flexible feed or removal lines 7 which are connected to the connectors 131, 132. The connector 132 is in each case disposed to be higher than the connf~ctor 131, so that in each case two crossing feed or removal lines 7 run at different heights, which perm~_ts a space-saving arrangement of the heating/cooling apparatuses 1. The loop-like mode of connection makes it possible to use a single shared heating/coolinc~ unit for a plurality of heating/cooling apparatuses 1.
Figures 10 to 7.4 Heating/cooling apparatuses 1 according to the invention can also be used together with reaction vessels 2" ', in which a heating/cooling chamber 25 is already integrated,. In the present case, the heating/cooling chamber 25 is fused to the reaction vessel body 26 at the bottom. The heating/cooling chamber 25 has connections 27 and 28 f_or the feed or removal lines and can be used as a cooling chamber or heating chamber. A plurality of heating/cooling chambers 25 can be connected together in a space-saving manner in a similar manner to the heating/cooling apparatuses 1 in Fig. 9.
The reaction vessels 2', 2" which are described in connection with I~ig. 3 can also be furnished with additional heai~ing/cooling chambers 25. In principle, the most varie<~ combinations of the elements described above with all possible types of reaction vessels are conceivable.

Claims

1. Apparatus (1) for heating/cooling gases, liquids and/or solids in a reaction vessel (2; 2'; 2'';
2'''), having a hollow body (10) and a heating/cooling tube (13) which partly runs within the hollow body (10) and through which heating/cooling medium is to flow, characterized in that the hollow body (10) is open at the top and bottom and the heating/cooling tube (13) is disposed in such a manner that it at no point completely fills the orifice cross-section of the hollow body (10).

2. Apparatus (1) according to Claim 1, characterized in that the hollow body (10) is designed in the form of a tube and the heating/cooling tube (13) is disposed in such a manner that, in addition to the heating/cooling tube (13), a hollow needle (61) can be passed through the hollow body (10).

3. Apparatus (1) according to Claim 2, characterized in that the heating/cooling tube (13) is laterally displaced within the tube-like hollow body (10), in particular is disposed only in one hollow body longitudinal half.

4. Apparatus (1) according to one of Claims 1 to 3, characterized in that the hollow body (10) has means for detachably connecting the apparatus (1) to a reaction vessel (2; 2'; 2''; 2'''), in particular a standard ground joint surface (11).

5. Apparatus (1) according to one of Claims 1 to 4, characterized in that the hollow body (10) has means for detachably attaching the apparatus (1) to a laboratory system, e.g. an apparatus for carrying out in parallel a multiplicity of chemical, biochemical, biological or physical processes, or a coupling (3; 3') for a laboratory system, in particular a standard ground joint surface (12).

6. Apparatus (1) according to one of Claims 1 to 5, characterized in that the heating/cooling tube (13) extends from outside the hollow body (10) laterally into the hollow body (10), out of the bottom of the hollow body (10) , up again into the hollow body (10) and again laterally out of the hollow body (10).

7. Apparatus (1) according to Claim 6, characterized in that the lateral entry and the lateral exit of the heating/cooling tube (13) into and out of the hollow body (10), respectively, are offset in height.

8. Heating/cooling system having a multiplicity of heating/cooling apparatuses (1) according to one of Claims 1 to 7, the heating/cooling apparatuses (1) being connected together in series by lines (7) and being supplied with heating/cooling medium from a shared heating/cooling unit.

9. Use of a heating/cooling apparatus (1) according to one of Claims 1 to 7 for heating/cooling gases, liquids and/or solids in a reaction vessel (2;
2'; 2"; 2''') on a laboratory system, for example an apparatus for carrying out in parallel a multiplicity of chemical, biochemical, biological or physical processes.

10. Use according to Claim 9, characterized in that the heating/cooling apparatus (1) is fastened to the laboratory system by a flexible coupling (3; 3').