DE2017351C3 - 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 arrangement of the carrier in front of a for solids un-

* £ permeable and semi-permeable for liquids Wall (frit) through which the reaction liquid is allowed to flow, and a reactor to carry out this method, in particular for peptide synthesis with a pre-

^ao seen semipermeable wall (frit), through which a reaction liquid can pass, but which 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 should be kept in contact with reagent liquids and shaken or opened for this purpose 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;

So a) A centrifugal drum is arranged in the vessel, the jacket of which consists of the semipermeable material and, together with the Wall of the vessel forms an annular gap, the top with an outlet for through the mania tel de »liquid passing through the centrifugal drum is provided;

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

<t

Centrifuges are known per se (»Laboratory drive of the electric motor can not be shown in a

technology of inorganic chemistry «from 8. Wedge, conventional way, preferably speed-controlled

Berlin, 1961, pp. 201 to 202 and Uilmann's Encyclopedia.

pädie der technical chemistry, 3rd edition 1951, central from the top of the electric motor 2β

ster band; Chemical apparatus construction and process 5 a downforce shaft protrudes vertically behind

technik, pp. 510 to 512 and 517). In the known pben, the one with a longitudinal keyway 32

Solid-liquid sieve centrifuges are each provided. On the Wejlensturarael 30 there is an after ■

but not about a chemical reaction between the pot-like HUJs part 34 open at the bottom.

Liquid-resistant areas, but rather a separation that has a threaded hole in its sleeve wall 3d.

tion of a liquid from a solid, with which the formation 38 has, into which a grub screw 4β is inserted

she has entered a mixture beforehand. When the screw is screwed into the keyway 32 on the output shaft

Finding, however, it is about reactions lenstummel engages and the sleeve part 34 against

to perform between two liquids. Relative rotation with respect to the output shaft

In the reactor according to the invention, the mel 30 is secured

treated skin intensively of liquids through 15 In an annular step 42 on the upper face of the

penetrated, without shaking itself or on other sleeve part 34 is an annular Pennanentpol-

Way to have to be moved diffusely. As a result, piece 44 inserted so that its outer surface with

the porous wall of the centrifugal jacket can also be aligned with the remaining jacket surface of the sleeve part 34

not as a friction or grinding surface on the carrier in the central opening of the annular pole piece

works. No resin particle or other carrier can be ao is »an expansion screw 46 in a threaded hole

is also located in the rotating reactor beaker in the upper end face; les sleeve parts 34.

Avoid contact with reaction liquids. unscrews and is via a friction lining 48 in not

The rotational movement of the Rtdktorbechers allows sliding engagement with the inner surface of the ring conveying

regulate itself uniformly and can without changing the pole piece 44. Skh understands that the

of the effect can be reversed. The construction 35 by securing the sleeve part 34 and PoI-

and drive effort is minimal; in particular piece 44 against relative rotation also on others

also does not need to be able to be done in a rotational manner in an up-and-down manner.
Movement to be reshaped, as is the case with shaking The reaction vessel 2 consists of a lid

apparatus is the case and there material loading 50, a floor 52 and a glass cylinder 54, the

stung. Noise and construction effort mean 30 with its free ends each. into a recess

tet. Furthermore, the emptying process in the reactor 56 or 58 engages in the cover 50 or base 52

with a rotating, porous reaction beaker essential and at its end faces an O-shaped one

Lent has been improved by the favorable ratio of sealing ring 60 and 62 in the cover 50 and bottom

from liquid permeable to impermeable 52 is supported. The two ring seals 60 and 62

Surface, resulting in short emptying times and no 35 are in corresponding annular grooves in the lid

Clogging leads. When the drain 50 or floor 52 is opened, inserted. The lid 50, the

the porous rotor flings very quickly and completely - glass cylinder 54 and the bottom 52 are

dig solutions or washing media. bolt 64 clamped together, initially through

The invention will be seen in the following with reference to di-

matic drawings on an exemplary embodiment 40 punch sleeves, by means of nuts 68 against the base

ipiel explained in more detail It shows the 52 are stretched so that the cover 50, the

Fig. 1 shows a through the vertical center line of a glass cylinder 54 and the bottom 52 that is inherently rigid

Reactor according to the invention guided cross-section reaction vessel form, and also still free

and end portions 70, jie through bores 72

F i g. 2 to 5 different phases of the operation 45 grip in the cover plate 12 and on its underside

located reaction vessel of the reactor according to turn by nuts 74 are braced. Through this

F i g. 1. the reaction vessel 2 is connected to the subframe

The in the figures and in particular in F i g. 1 bound.

The reactor shown has an underframe 1 and it should also be noted that between the floor 52 a reaction vessel 2 attached to this, in 50 of the reaction vessel 2 and the cover plate 12 of the Within this the reaction beaker 3 rotatably mounted underframe 1 and an umbrella ring 76 on the standing device is. bolt 64 using additional clamping nut

The underframe 1 consists of an annular tern 78 is turned on.

Bottom plate 10, a likewise ring-shaped top The bottom 52 of the reactor, sgefäßes 2 has a Plate 12 and spacer sleeves 14, which are made in one piece with him by means of stud bolts 55, rake centrally 16, which extend through the base plate and narrow in its jacket area and with their ends in threaded holes 18 of the formed connecting piece 80, which is on its upper front cover plate intervene, ropes 8i are designed to be closed to form a rigid frame and are in the center The heads of the stud bolts also serve to the upper end face with a bearing point 84 is provided early as feet for setting up the underframe on 60. Between the coat of the sleeve part a base 20. Optionally, instead of 34 and pole piece 44, one can on the one hand uno the inner surface the stud bolt use simple threaded bolts, the connecting piece 8 · on the other hand is a narrow ring die by means of nuts 22 which are formed on the thread 24 of the gap 86 to allow the rotation of the first threaded boizea are screwed on, are tensioned, called parts when driving the electric motor 26 in order to ensure that the undercarriage is level, it does not 85 act through contact with the inner wall of the horse, zens is hindered. On the face of the pole piece

An electric motor 26 44 is preferably also on the base plate 10 for the same reason

mounted by Schwingnaetallelemente 28; the distance opposite to you, not particularly shown

the upper end 82 of the nozzle 80 is provided.

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

Except for the glass cylinder 54, all are to the inner surface of the reaction vessel 2 as well as to the inner one and outer surface of the reaction cup 3 contributing components made of polytetrafluoroethylene or at least superficially coated in a corresponding manner to be corrosion-resistant.

The bottom part 90 of the reaction beaker 3 has an upwardly protruding indentation 102 which its upper end face is provided with a closure 104, in the center of which a bearing cone 106 is recessed, which together with the bearing tip 84 is a tip storage of the reaction beaker 3 on the Bottom 52 of the reaction vessel 2 results. An annular permanent is located radially within the indentation 102 Magnetic counter pole piece 108 embedded in the pole piece 44. This is made up of an intermediate sleeve 110 radially outward and from its flange 112 protruding radially outward from below, also from held down. The intermediate sleeve 110 is rigidly attached to the bottom part 90 of the reaction beaker 3. A corresponding rigid attachment, not shown, is between the bottom part 90 and the attached one semi-permeable jacket 94 and between this and the screen 98 is provided.

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

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

Centrally in the lid 50 of the reaction vessel is a lid insert 126 through an O-shaped ring seal 128 sealed against the cover 50 and inserted centrally and by means of screw bolts 130 and in Bores 132 of the cover 50 mounted retaining nuts 134.

The lid insert 126 contains various feed lines 140, 142 and 144, e.g. for reagent solution, Washing medium and inert gas; it can also have a ventilation opening (not shown) to be seen.

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 cup, which the magnetic field coupling 44, 108 connects 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 feedthroughs 140, 142 and 146 for reagent solutions, washing media and inert gas; a central opening in the lid is used for Bleeding the system.

The bottom 52 of the reaction vessel is formed on the inside as an annular channel 120 and with a drain opening 122 for liquids

“5 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

" _S opened vent in the reactor. Then all supply and discharge lines are closed by valves. The reaction beaker now begins to rotate for the liquid to penetrate the resin intensively. This state of a gradually acting centrifugal force is shown in FIG. 3, where 152 denotes a parabolic mirror of the reaction liquid.

c) The resin is thrown against the porous wall 94 of the rotor. The reagent solution enters the

Centrifugal force because of through the resin and the wall 94 of the rotating cup, is pushed upwards in the narrow space between the rotor jacket 94 and the vessel 54 and passed on the reactor lid 50 back into the rotating rotating beaker. This favors the diagonally downward diaphragm 98, 100 at the top of the reaction beaker, which at the same time prevents resin from leaking out of the rotor. A vertical fluid circuit is formed which leads to an intensive penetration of the carrier resin with reagent solution. This state is shown in FIG. 4 illustrates.

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

6o FIG. 5 shows 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.

For this purpose 2 sheets of drawings

43 8

Claims (7)

Patent 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 seraipermeable wall (frit) permeable to liquids through which the reaction liquid is allowed to flow by combining the following process steps: a) the semipermeable wall is allowed to rotate and the carrier is placed under centrifugal force on the wall; b) the reaction liquid is circulated through the carrier and the semipermeable Wan ± 2. Reactor for carrying out the method according to spoke 1, in particular for peptide synthesis with a semipermeable wall (frit) provided in a vessel, through one Reaction liquid can pass through, which, however, holds back the carrier, marked by combining the following features: a) in the vessel (2) a centrifugal drum (3) is arranged, the jacket (94) from the semipermeable material and together with the wall (54) of the vessel one The ring spit forms the top with an outlet for the through the jacket of the centrifugal drum Hindu titrete liquid represented is; b) the outlet is with an inlet in the Centrifugal drum (3) connected. 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, shell 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 Reaction beaker (3) is cylindrical and that at the top of the reaction beaker one inward protruding aperture (98,100) is provided. 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 produced or at least superficially corrosion-resistant in a corresponding manner are coated. 7. Reactor according to one of claims 2 to 6, characterized in that the bottom (52) of the Reaction vessel (2) is designed with a centrally projecting nozzle (80) that the bottom of the reaction beaker (3) has an indentation (102) slidingly encompassing the nozzle and that on the end face (82) of the nozzle a laying tip (84) is formed, which in a Bearing cone (X06) engages on the lower end face (104) of the indentation of the reaction beaker