CS252167B1 - Device for automatic separation of liquid and solid phase - Google Patents

Abstract

The device for automatic separation of liquid and solid phases, especially in chemical reactions, consists of a reaction vessel for activation, into which the reaction solution is dosed from the storage vessel via a valve. The activation vessel is equipped with a frit at the bottom, to which a tube for suction of suspended solid waste into the waste vessel adjoins. Before the reaction, the reaction mixture can be mixed with a stream of inert gas. After the reaction is completed, the liquid phase is discharged via a valve into the reaction vessel for synthesis for further processing and the solid phase is suctioned off via a tube. The entire reaction procedure can be automatically repeated many times. The device has been successfully tested in the synthesis of peptides on an insoluble carrier for the preparation of individual activated components.

Description

(54) Equipment for automatic separation of liquid and solid phase

The apparatus for automatically separating the liquid and solid phases, especially in chemical reactions, is formed by a reaction vessel for activation into which a reaction solution is metered from a storage vessel via a valve. The activation vessel is provided at the bottom with a frit, to which is attached a tube for suction of suspended solid waste into the waste vessel. Before the reaction, the reaction mixture may be stirred with a stream of inert gas. After completion of the reaction, the liquid phase is vented through the valve into the reaction vessel for further processing and the solid phase is aspirated through a tube. The entire reaction procedure can be repeated automatically many times. The device has been successfully verified in the synthesis of peptides on an insoluble carrier for the preparation of individual activated components.

2521B7

The invention relates to an apparatus for the automatic separation of liquid and solid phases, in particular in chemical reactions.

At present there is a general effort to automate some production processes. This automation is also introduced into various branches of the chemical industry, depending on the possibilities and nature of production. Chemical reactions almost always produce waste products, whether gaseous, liquid or solid, in addition to the desired product, which must be separated from the product. They are often toxic, carcinogenic or radioactive substances and their handling brings many difficulties. It is therefore not only the economic aspect of the matter, but also the safety of workers.

When synthesizing peptides on an insoluble carrier, activated amino acid derivatives must be prepared in advance for condensation reactions. Even when using an automatic peptide synthesizer, these components are prepared manually. This is time consuming, it is necessary to work with hazardous substances (N, N‘-dicyclohexylcarbodiimide) and there is an unnecessary overuse of reaction vessels and raw materials.

These drawbacks are overcome by a device consisting of reaction, storage, waste, valve and piping systems according to the invention, characterized in that the activation vessel is connected via the valve to the storage vessel and via the valve is connected to the synthesis vessel, the bottom of the activation vessel being formed by a porous interface to which a tubing is connected through the activation vessel through the valve to the waste vessel, the activation vessel being connected to the inert gas reservoir via valves positioned above and below the activation vessel, another valve above the vessel to activate the orifice into the atmosphere.

The device according to the invention contributes to the improvement of the working environment wherever hazardous substances are handled, since it enables continuous removal of the undesired solid phase and automatic treatment of the liquid fraction.

The device according to the invention is shown schematically in the attached drawing, in longitudinal section.

The drawing shows a simple embodiment of the device according to the invention. The device according to the invention consists of a cylindrical activation vessel 1, provided at its lower end with a porous interface 2, for example a frit. The activation vessel 1 is provided with a tempering jacket 3 as required and is closed at the top and bottom by valves 5 and 6. An activation tube 4 of inert material extends up to the frit 2 and its outer end is inserted into the activation vessel 1. The tubing 4 is provided with a valve 7 in front of the waste container 11. Valves 8 and 9 serve for the inlet and outlet of inert gas which can fully replace the mixing of the reaction mixture without the use of a mechanical stirrer. The reaction components 13 can be continuously fed from the storage vessel 13, which, after reacting in the activation vessel 1, are used for the next reaction in the synthesis vessel 12 and the solid waste is sucked off into the waste vessel 11.

The device according to the invention has this function. A reaction solution with reaction components is metered into the pre-tempered activation vessel 1 via valve 6. The reaction mixture is briefly mixed with a stream of inert gas from the reservoir 14 by opening the valve 9 and closing the valve 10 and allowing it to react further. The valve 5 is then opened and the activated liquid component prepared is added via a frit to the synthesis vessel 12 in which the desired synthesis takes place. The insoluble waste phase precipitated during the reaction in the activation vessel 1 is removed by the tubing 4 by opening the valve 7 and the inert gas stream through the valve 9 expelling the solid phase suspension (in the pre-added solvent with the tubing 4 into the waste vessel 11). After rinsing the activation vessel 1 with a suitable solvent and sucking it through the tubing 4 into the waste vessel 11, the activation vessel 1 is ready for immediate further use.

The device according to the invention has been successfully tested in the automatic preparation of activated components for peptide synthesis on an insoluble carrier. It goes without saying that the device according to the invention can be used wherever there is a need to continuously remove the undesired solid phase and automatically process the liquid fraction.

The following exemplary embodiment of the device according to the invention illustrates, but does not limit in any way.

Example

Via the valve 6, a solution of the desired protected amino acid and a solution of N, Nb-dicyclohexylcarbodiimide is added from the storage vessel 13 to the pre-tempered vessel 1 for activation. The reaction mixture is briefly purged with nitrogen through valve 9 and allowed to react for 10 to 30 min. The valve 3 is then opened and by the flow of nitrogen through the valve 8 the activated component is added to the synthesis vessel 1,2 in which the peptide synthesis takes place. The insoluble N, N'-dicyclohexylurea excreted during the reaction is removed through the tubing 4 (preferably from Teflon or polyethylene) by opening the valve 7 and expelling the nitrogen stream through the valve 9 with a suspension of N, N'-dicyclohexylurea in pre-added methylene chloride. This reaction procedure is repeated until the N, N'-dicyclohexylurea is completely removed. After washing with a suitable solvent, the activation vessel 1 is ready to prepare another activated component.

Claims (4)

SUBJECT An apparatus for automatically separating a liquid and a solid phase, comprising reaction, storage, waste, valve and piping vessels, characterized in that the activation vessel (11) is connected via a valve (6) to the storage vessel (13) and it is connected via a valve (5) to a synthesis vessel (12), the bottom of the activation vessel (1) being formed by a porous interface (2) to which a tubing (4) is connected through the valve (7) with a waste container (11), wherein the activation vessel (1) is connected to the inert gas reservoir (14) via valves (8) and (9) located above and below the activation vessel (1), 10) above the vessel (11) for actuating into the atmosphere. Device according to claim 1, characterized in that the activation vessel (11) is provided with a tempering jacket (3). Device according to claim 1, characterized in that the porous interface (2) is formed by a frit. Device according to claim 1, characterized in that the tube (4) is made of an inert material.