DE2017351B2 - Process and reactor for chemical reactions on insoluble carriers by means of a reaction liquid - Google Patents

Description

The invention relates to a method for carrying out chemical reactions on insoluble ones Carriers by means of a reaction liquid with the carrier arranged in front of a solid-impermeable one and a semi-permeable wall (frit) permeable to liquids through which the Allows reaction liquid to flow, as well as a reactor for carrying out this process, in particular for peptide synthesis with a semipenneable wall (frit) provided in a vessel through which a reaction liquid can obstruct, which, however, holds back the carrier.

Such reactors are available as shaking, stirring, gassing and pulsation devices in operation at various locations. In these reactors, the resin particles which are to be kept in contact with reagent liquids and for this purpose shaken or opened Other ways to move diffusely, but still have a chance of coming into contact with the reagent liquids to withdraw. In addition, the mechanical movement of a resin results in reactors with built-in glass frit according to the shaking, stirring and gassing apparatus mentioned unwanted comminution of the resin particles (risk of clogging), as a frit like a friction and Grinding surface acts. All reactors mentioned have the rest, measured on the area of the reactor only a small, liquid-permeable frit. They also need an external one for emptying Effect like pressure or vacuum. Finally, slow down with the pulsation apparatus mentioned Liquid residues are very difficult to wash out, especially since they only run dry under the force of gravity.

The invention is based on the stated disadvantages of the aforementioned reactors by using a different process and a different reactor.

To solve this, the invention provides for the following process steps to be combined:

a) the semipermeable wall is allowed to rotate and the carrier is attached to it under the centrifugal force the wall on;

b) the reaction liquid is circulated through the support and the semipermeable wall.

A reactor for carrying out this process is according to the invention by the constriction as follows Features marked;

a) A centrifugal drum is arranged in the vessel, the jacket of which is made of semipermeable Material consists and together with the wall of the vessel forms an annular gap that at the top with an outlet for the passing through the jacket of the centrifugal drum Liquid is provided;

b) the outlet is connected to an inlet in the centrifugal drum.

Centrifuges are known per se (»Laborationsteehnik of inorganic chemistries by B. Keil. Berlin, 1961, pp. 201 to 202 and Ullmann's Encyclopedia der technical chemistry, 3rd edition 1951, first volume: Chemical apparatus construction and process engineering, S, 510 to 512 and 517). With the known Solid-liquid sieve centrifuges are not, however, a chemical reaction between Liquid components, but rather a separation a liquid from a solid with which it has previously entered into a mixture. In the invention however, it is a matter of carrying out reactions between two liquids.

In the case of the tleactor according to the invention, that becomes treating resin intensely permeated by liquids without shaking itself or on others Way to have to be moved diffusely. This also allows the porous wall of the centrifugal jacket do not act as a friction or grinding surface on the carrier. No resin particle or other carrier can also avoid contact with reaction liquids in the rotating reactor beaker.

The rotational movement of the reactor beaker lets regulate themselves uniformly and can be reversed without changing the effect. The construction and Drive effort is minimal; in particular, there is also no need for a rotation to an up-and-down movement to be reshaped, as is the case with Schütiel apparatus, and there material stress, Means noise and construction effort. The emptying process is also in the reactor with rotating, porous reaction beaker has been significantly improved by the favorable ratio from liquid-permeable to impermeable surface, resulting in short emptying times and none Clogging leads. When the drain is opened, the porous rotor spins very quickly and completely Solution in or washing media.

The invention is illustrated below with reference to schematic drawings of an exemplary embodiment explained in more detail. It shows

F i g. Figure 1 is a cross section taken through the vertical center line of a reactor according to the invention

F i g. 2 to 5 different phases of the operating reaction vessel of the reactor according to Fig.1.

The in the figures and in particular in F i g. The reactor shown has an underframe 1 as well a reaction vessel 2 attached to this, within which the reaction beaker 3 is rotatably mounted is.

The underframe 1 consists of an annular base plate 10, a likewise annular cover plate 12 and spacer sleeves 14, which by means of stud bolts 16, which reach through the base plate and engage with their ends in Gcwindelöcher 18 of the cover plate, braced to form a rigid frame are. The heads of the stud bolts also serve as feet for setting up the underframe a base 20. If necessary, simple threaded bolts can also be used instead of the stud bolts, which are tightened by means of nuts 22, which are screwed onto the thread 24 of the threaded bolts, to achieve level compensation for the underframe.

An electric motor is mounted on the base plate 10 by means of vibrating metal elements 28; the drive of the electric motor can in a conventional manner, not shown, preferably speed control take place.

An output shaft stub 30 protrudes vertically from the top of the electric motor 26 above, which is provided with a longitudinal keyway 32. On the stub shaft 30 is a post The cup-like sleeve part 34, which is open at the bottom, is pushed on, which has a threaded hole in its sleeve wall 36 38, into which a grub screw 40 is screwed into the keyway 32 on the output shaft stub engages and the sleeve part 34 against Relative rotation with respect to the output shaft stem 30 secures.

An annular permanent pole piece 44 is inserted into an annular step 42 on the upper end face of the sleeve part 34 in such a way that its outer surface is aligned with the remaining outer surface of the sleeve part 34. In the central opening of the annular pole piece ao an expansion screw is screwed into a threaded bore in de ^r upper end face of the sleeve member 34 46, and is connected via a friction lining 48 in non-sliding engagement with the inner surface of the annular pole piece 44. It is understood that the induced by Securing of the sleeve part 34 and pole piece 44 against relative rotation can also be made in other known ways.

The reaction vessel 2 consists of a cover! 50, a bottom 52 and a glass cylinder 54, the with its free ends each engages in a recess 56 or 58 in the cover 50 or base 52 and at its end faces on an O-shaped sealing ring 60 or 62 in the cover 50 or bottom 52 supports. The two ring seals 60 and 62 are in corresponding annular grooves in the cover 50 or bottom 52 inserted. The lid 50, the glass cylinder 54 and the bottom 52 are by means of stud bolts 64 clamped together, initially by spacer sleeves inserted between cover 50 and base 52 grab, are tensioned by nuts 68 against the bottom 52, so that the cover 50, the Glass cylinder 54 and bottom 52 form the inherently rigid reaction vessel, and also free ones End portions 70 have which engage through bores 72 in the cover plate 12 and on the underside thereof are again braced by nuts 74. The reaction vessel 2 is thereby connected to the sub-frame.

It should also be noted that between the bottom of the reaction vessel 2 and the cover plate 12 of the Underframe 1 still has an umbrella ring 76 on the stud bolt 64 using additional clamping nuts 78 is switched on.

The bottom 52 of the reaction vessel 2 has a centrally protruding one which is made in one piece with it and in its jacket area there is a narrowly designed nozzle 80, which on its upper: · end face 82 is formed closed and in the center, center of the upper end face with a bearing seat 60 is provided. Between the jacket of the sleeve part 34 and the pole piece 44 on the one hand and the inner surface of the connecting piece, - 80 on the other hand, a narrow annular gap 86 is formed to allow the rotation of the former When driving the electric motor 65, do not share by touching the inner wall of the connecting piece is hindered. On the end face of the pole piece 44 is also preferably for the same reason a not particularly shown distance opposite

the upper end 82 of the nozzle 80 is provided.

The reaction beaker 3 consists of a base part 90, a jacket 94 made of sintered polytetrafluoroethylene, which is embedded in an annular groove 92 in the base part 90 and which is thickened on both sides at its upper edge, and a diaphragm 98 which protrudes radially inward from this upper edge and which in the middle at 100 protrudes inwardly in a funnel shape.

Apart from the glass cylinder 54 , all of the components contributing to the inner surface of the reaction vessel 2 and to the inner and outer surface of the reaction beaker 3 are made of polytetrafluoroethylene or at least their surface is correspondingly coated to be corrosion-resistant.

The bottom part 90 of the reaction beaker 3 has an upwardly protruding indentation 102 which is provided on its upper end face with a closure 104 , in the center of which a bearing cone 106 is cut out. which together with the bearing tip 84 results in a tip bearing of the reaction beaker 3 on the bottom 52 of the reaction vessel 2. An annular, permanently magnetic counter-pole piece 108 to the pole piece 44 is embedded radially within the indentation 102. This is held by an intermediate sleeve 110 radially on the outside and also from below by its flange 112 protruding radially outwards from below. The intermediate sleeve 110 is rigidly attached to the bottom part 90 of the reaction beaker 3. A corresponding rigid attachment (not shown) is provided between the base part 90 and the attached semi-permeable jacket 94 and between the latter and the panel 98.

The intermediate sleeve 110 serves as a slide bearing on the outer jacket surface of the connecting piece and thus supplements the bearing effect of the pin bearing 84, 106.

Underneath the bottom part 90 of the reaction beaker 3, a wide conical collecting groove 120 serving to draw off reaction liquid is recessed, the bottom of which is connected to a channel 122 leading radially in the bottom 52 of the reaction vessel to the outside, to which a liquid discharge line 124 is connected.

A cover insert 126 is inserted centrally in the cover 50 of the reaction vessel, sealed against the cover 50 by an O-shaped ring seal 128 and fastened by means of screw bolts 130 and retaining nuts 134 embedded in bores 132 of the cover 50.

The cover insert 126 contains various feed lines 140, 142 and 144, for example for reagent solution, washing medium and inert gas; in addition, it can also be provided with a ventilation opening (not shown).

In summary, the structure results, in short, as follows:

The reactor made of polytetrafluoroethylene and glass, which is resistant to almost all chemicals, is perfect Constructed closed and works on the principle of a washing machine. It essentially consists from the reaction vessel 2 and a rotor 3 as a reaction cup inside, the side wall of which is made of porous sintered polytetrafluoroethylene through which liquids pass can, but solids cannot.

The volume of this beaker, which connects the magnetic field coupling 44, 108 to the drive 26 , is only slightly smaller than the total volume of the reactor or reactor vessel 2. The rotor is loaded with solid carrier material through the screw-on cover insert 126 in the housing cover 50. This cover insert also carries polytetrafluoroethylene hose feed-throughs 140, 142 and 146 for reagent solutions, washing media and in-

»O ertgas; a central opening in the lid is used for Bleeding the system.

The bottom 52 of the reaction vessel is designed on the inside as an annular channel 120 and is provided with a drainage opening 122 for liquids.

hen. The functioning of this reactor is as follows:

a) In the reaction beaker, the rotor, there is _ao the carrier material 150, usually a swellable,

but insoluble polystyrene bead polymer see Fig. 2.

b) In order to cause a chemical reaction on this resin, a reagent solution flows when the

_a5 open vent into the reactor. Then all supply and discharge lines are closed by Vent / fe. The reaction beaker now begins to rotate for the liquid to penetrate the resin intensively. This supply

₃ “If a centrifugal force is gradually exerted, it is shown in FIG. 3, where 152 denotes a parabolic mirror of the reaction liquid.

c) The resin adheres to the porous wall 94 of the rotor hurled. The reagent solution enters the

Centrifugal force due to the resin and the wall 94 of the rotating beaker is pushed upward in the narrow space between the rotor jacket 94 and the vessel 54 and passed back into the rotating beaker at the reactor cover 50. This favors the diagonally downwardly directed diaphragm 98, 100 at the upper edge of the reaction beaker, which at the same time prevents resin from escaping from the rotor. A vertical liquid circuit is formed, which leads to an intensive penetration of the carrier resin with reagent solution. This state is shown in FIG. λ illustrates.

d) If the drainage tube 124 at the bottom of the reactor is opened, the reaction vessel is automatically emptied by the centrifugal effect of the rotating rotor. Incoming washing media flush out reagent residues from the resin in the same way (a to d) by repeating the described process of penetrating the carrier with liquid and subsequent emptying by centrifuging several times with pure solvents.

In FIG. 5 it is shown how, in this state, the carrier material adheres to the inner wall of the rotor after it has been converted, while the liquid is drawn off according to the arrow 154 .

1 sheet of drawings

Claims (7)

Claims; 1. Process for carrying out chemical reactions on insoluble carriers by means of a reaction liquid with the carrier arranged in front of a solid-impermeable one and a semi-permeable wall (frit) permeable to liquids through which the reaction liquid is allowed to flow, marked ic by combining the following process steps: a) the semipermeable wall is allowed to rotate and the carrier is placed on the wall under the centrifugal force; ^1S b) the reaction liquid is circulated through the carrier and the semipermeable Wall 2. Reactor for carrying out the method ao according to claim 1, in particular for peptide synthesis with a semipermeable wall (frit) provided in a vessel, through one Reaction liquid can pass through, but which holds back the carrier, marked as by combining the following features: a) in the vessel (2) a centrifugal drum (3) is arranged, the jacket (94) from the semipermeable material is made up and together with the wall (54) of the vessel forms an annular gap, the upper one with an outlet represented for the liquid passing through the jacket of the centrifugal drum is; b) the outlet is connected to an inlet in the centrifugal drum (3). 3. Reactor according to claim 2, characterized in that the reaction vessel (2) is closed is and that the reaction beaker (3) by a bridging the wall of the reaction vessel Magnetic coupling (44,108) can be driven. 4. Reactor according to claim 2 or 3, characterized in that the reaction vessel consists of a cover (50, 126) provided with supply lines and a preferably cylindrical vessel jacket (54) and one with a discharge line (122) for reaction liquid that is led to the side provided bottom (52) and that the cover, jacket and bottom are sealed against each other (60, 62) are releasably clamped together (64). 5. Reactor according to one of claims 2 to 4, characterized in that the jacket (94) of the Reakt ^: onsbechers (3) is cylindrical and that an inwardly protruding diaphragm (98,100) is provided on the upper edge of the reaction beaker. 6. Reactor according to one of claims 2 to 5, characterized in that the vessel jacket (54) consists of glass and all to the inner surface of the reaction vessel (2) as well as to the inner and outer surface of the reaction cup (3) contributing components made of polytetrafluoroethylene manufactured or at least superficially corrosion-resistant in a corresponding manner are coated. 7. Reactor according to one of claims 2 to 6, ^6s characterized in that the bottom (52) of the reaction vessel (2) is formed with a centrally projecting nozzle (80) that the bottom of the reaction beaker (3) a slidingly encompassing the nozzle Has indentation (102) and that on the end face (82) of the connecting piece a bearing pin (84) is formed which engages in a bearing cone (106) on the lower end face (104) of the indentation of the reaction beaker.