EP1309405A1 - Verfahren zur durchführung einer chemischen reaktion - Google Patents
Verfahren zur durchführung einer chemischen reaktionInfo
- Publication number
- EP1309405A1 EP1309405A1 EP01960017A EP01960017A EP1309405A1 EP 1309405 A1 EP1309405 A1 EP 1309405A1 EP 01960017 A EP01960017 A EP 01960017A EP 01960017 A EP01960017 A EP 01960017A EP 1309405 A1 EP1309405 A1 EP 1309405A1
- Authority
- EP
- European Patent Office
- Prior art keywords
- container
- substance
- containers
- set according
- substances
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
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- OMOVVBIIQSXZSZ-UHFFFAOYSA-N [6-(4-acetyloxy-5,9a-dimethyl-2,7-dioxo-4,5a,6,9-tetrahydro-3h-pyrano[3,4-b]oxepin-5-yl)-5-formyloxy-3-(furan-3-yl)-3a-methyl-7-methylidene-1a,2,3,4,5,6-hexahydroindeno[1,7a-b]oxiren-4-yl] 2-hydroxy-3-methylpentanoate Chemical compound CC12C(OC(=O)C(O)C(C)CC)C(OC=O)C(C3(C)C(CC(=O)OC4(C)COC(=O)CC43)OC(C)=O)C(=C)C32OC3CC1C=1C=COC=1 OMOVVBIIQSXZSZ-UHFFFAOYSA-N 0.000 description 4
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Classifications
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- B01L3/00—Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
- B01L3/56—Labware specially adapted for transferring fluids
- B01L3/569—Glassware
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- B01L9/00—Supporting devices; Holding devices
Definitions
- the present invention relates to a method for carrying out a chemical reaction between at least a first substance and a second substance, in which a pre-metered amount of the first substance and a pre-metered amount of the second substance that is molar or graded in terms of molar equivalents Substance are used, on a set of containers containing substances and on an airtight container that contains a pre-metered amount of a substance.
- reaction conditions The conditions under which the substances are brought together until the desired product is formed are called reaction conditions.
- the relationship of the substances to each other with regard to the smallest chemical unit (atom, molecule, complex, etc.) of the substances is called molecular. Ratio or, if the macroscopic expression is used, referred to as the molar ratio of the substances. In most chemical reactions, this ratio is more or less critical, or it is at least important for the experimenter to know this ratio more or less exactly. In research and development, the ratio of the substances to each other is usually more important than the absolute amounts, at least in a certain range, such as a factor of 2.
- the ratios of the substances are mostly determined by their weight or volume with the aid of the atomic or molecular weight.
- the experimenter who can be both an individual and a robot or an automatic or semi-automatic system, first determines the desired ratios of the starting materials before each experiment. Then he decides in which absolute size he will carry out the corresponding experiment, although in most cases this is not absolutely decisive in a certain area.
- he uses the atomic or molecular weight (in the case of mixtures, the mean, etc.) to calculate the macroscopic size to be measured, ie the weight or, via the density, the volume.
- he weighs in the starting materials or separates the determined volume, for example from a storage vessel, and brings the starting materials together under the reaction conditions determined by him.
- the invention is based on the following object.
- a method and a set of containers containing substances are to be created which enable an economical and / or ecological and / or with regard to safety risks to carry out chemical reactions or to prepare them more efficiently.
- Reactions that include ordering, warehousing, weighing or dosing, etc. of the substances required for the corresponding chemical reaction can be improved so that they can be processed more quickly and with less risk.
- the method and the set should preferably be usable in the broadest possible spectrum.
- Claim 116 relates to a use of a set of containers containing substances
- claim 117 relates to a single air-tight closed container and ver ⁇ claim 118 to a use of such containers.
- Preferred design variants result from the dependent patent claims.
- the essence of the invention with regard to the method is that in a method for carrying out a chemical reaction between at least a first substance and a second substance, in which a predosed amount of the first substance and a graded or predefined amount of the first substance are molar equivalents or graded in terms of molar equivalents predosed amount of the second substance are used, at least one of the substances is present in at least one airtightly sealed container which contains a predosed amount of the substance, is essentially completely released therefrom and is used essentially completely in the reaction.
- the at least one substance which as a rule, but not necessarily, has already been packaged airtight in the container by the manufacturer, is generally released shortly before being added to the reaction space or only in the reaction space itself and in the Reaction essentially used completely.
- the vessels each include a premetered amount of a substance which is substantially fully set Free and subsequently reacted
- the vessel is not as in the classical process in which in 'usually a certain amount is removed from a larger vessel, opened, and closed again, but each container is filled, sealed airtight and no longer opened until the substance is converted. This ensures to a far greater extent that exactly the substance that is planned to be implemented is implemented.
- the often dangerous, cost-intensive warehousing which, due to the fact that containers are often no longer completely airtight by the user, odors spreading is considerably reduced.
- the mostly smaller amounts of substance in the pre-dosed containers reduce the potential danger during transport and storage.
- the costs are usually lower for the user, since he can order exactly the amount of substance that he also wants to release and implement in a planned chemical reaction, especially if, as is often the case, only a fraction who plans to use minimum order quantities of conventional containers.
- the substances used have a wide variety of macroscopic manifestations, e.g. Have aggregate states, grain sizes, densities and viscosities and there are also chemicals that e.g. have aggregate states that are difficult to handle under room conditions, e.g. Waxes, substances with a melting point between 10 ° C and 30 ° C, gases and semi-crystalline substances.
- the pre-dosed containers allow these differences to be neutralized, i.e. for the user (researcher, robot, automat, etc.) to make the handling as insignificant as possible.
- the method according to the invention enables the fine chemical supplier to bring the value chain closer to the application without having to violate the user's know-how-critical taboos, in order to be able to offer the user a sustainable and valuable service.
- any space not filled with substance in the container is essentially completely filled with a gas, a mixture of gases or a liquid which is less than 5%, preferably less than 1%, preferably less than 0.1% , 0 contains 2 .
- a gas, a mixture of gases or a liquid which is less than 5%, preferably less than 1%, preferably less than 0.1% , 0 contains 2 .
- the space not filled with substance is essentially completely filled with an inert gas, preferably N 2 , SF 6, a chlorofluorocarbon or a noble gas, in particular Ar, Ne, Xe or He.
- an inert gas preferably N 2 , SF 6, a chlorofluorocarbon or a noble gas, in particular Ar, Ne, Xe or He.
- the container is not intentionally filled with an inert gas during manufacture, the space mentioned is generally filled with air and contains air in relevant quantities 0 2 , the advantages mentioned above apply.
- the inert gas atmosphere is the ideal case, which does not significantly influence the substance or the reaction mixture.
- the substantially completely released substance which is essentially completely used in the reaction, is advantageously at least partially reacted with the at least one further substance.
- ⁇ punch Subminiature which are partially reacted reactive Sub are ⁇ punching and accordingly, for example, oxidation or to hydrolysis sensitive and are accordingly preferably already pre-dosed and packed in the container as described (airtight and under inert gas), so that the user has to take as few actions as possible, such as weighing.
- the substance is a catalyst, inhibitor, starter or an accelerator.
- the substances mentioned in particular are used in chemical reactions in relatively small to very small amounts. Accordingly, the advantages mentioned above apply even more with certain such substances.
- the method according to the invention is characterized in that the container is sealed against organic solvents, preferably generally against organic compounds.
- the container is advantageously impervious to inorganic solvents, preferably generally to inorganic compounds.
- "tight" is to be understood in such a way that the organic compound cannot penetrate the container wall to a significant extent (scale is glass with a container wall thickness of 0.005 mm) without destroying it.
- This has the advantage that if the container comes into contact with organic or inorganic compounds (before or after the container is added to the reaction space, ie also during storage, for example), the substance in it cannot be dissolved or react , This ensures both the quality of the substance and the safety until the container is used, i.e. until the container is opened.
- At least one, preferably at least two, of the substances is advantageously a pure chemical compound.
- the substances are enclosed in an airtight manner in the containers and are only released before the reaction with other substances, the use of such containers for pure chemical compounds makes sense in order to guarantee the purity to a high degree.
- At least one of the substances is advantageously a pure chemical compound in solution or suspension.
- Substances that are offered by the fine chemical suppliers for chemical research and development in solutions or suspensions are often offered in such because they are very sensitive to contact with the environment, e.g. against hydrolysis, oxidation, etc.
- the airtightly sealed containers offer ideal conditions for such substances in particular, since the substance is only released shortly before implementation or even only during minimal handling.
- the chemical reaction is carried out in a, preferably organic, solvent or solvent mixture.
- the substances are released from the container shortly before they are added to a solvent or even in the solvent itself. In the solvent, they are in turn protected from, for example, oxidation with atmospheric oxygen or hydrolysis by atmospheric moisture.
- the use of containers according to the invention therefore makes sense, particularly in solvent chemistry, especially since very sensitive chemical reactions are often carried out in solvents.
- another substance is involved in the method according to the invention which has no stoichiometric influence on the product resulting from the chemical reaction, preferably a catalyst, solvent, activator or inhibitor. In the case of reactions in which catalysts, activators, inhibitors, etc. are involved, it is often necessary to use highly pure chemical compounds in order not to disrupt the process, such as not to "poison" the catalyst, inhibitor or activator. ,
- the implementation is an organic chemical reaction. Most of the reactions carried out in chemical research and development are organic chemical reactions, which means that there is a great need for rationalization in this area. This is also shown by the parallel synthetic processes most frequently used in this field.
- the method is preferably characterized in that at least one of the substances is an organometallic compound.
- organometallic compounds in particular are usually very sensitive to oxidation (e.g. due to atmospheric oxygen) and hydrolysis, it makes particular sense to use this class of compounds in a pre-dosed and airtight manner in containers so that handling outside the reaction space can be reduced to an absolute minimum and thus the quality or the content of the pure organometallic compound is not impaired.
- the chemical reaction preferably takes place in a reaction vessel, preferably the reaction conditions under which the substances react with one another. are brought, differ from the conditions outside the reaction vessel. Especially when the reaction is carried out in a reaction vessel, very special and controlled conditions are often sought. At the same time, efforts should also be made to ensure that the substance is not exposed to the conditions outside the reaction vessel, if at all, or at least only slightly. This can be achieved with relatively little effort by using a pre-dosed substance in an airtight container which is opened shortly before being added to the reaction vessel or only in the reaction vessel itself.
- At least two, preferably a large number of reactions are carried out in parallel, in each of which at least one hermetically sealed container, each containing a pre-metered amount of a substance which is released therefrom, is used.
- the aim is that a user can carry out more reactions per unit of time.
- the use of pre-dosed containers means that time-consuming dosing by the user can be dispensed with, often under conditions that are difficult to control and high concentrations.
- the user adds e.g. simply add a substance pre-dosed in a container to the reaction vessel.
- the reactions advantageously differ at least in one point, either in the reaction conditions or in one of the substances used, in particular the amount thereof. If, for example, the substances used or their amounts vary in reactions carried out in parallel, the user will find a high concentration and a extremely time-consuming calculation, time-consuming weighing or dosing, often under special conditions, is required, which is largely eliminated by adding a substance pre-dosed in a container.
- At least two of the substances are each present in at least one airtight container, each containing a pre-metered amount of a substance, and are essentially completely released therefrom and used in the reaction.
- Most of the advantages mentioned above weigh twice when two substances pre-dosed in containers are used.
- the time-consuming calculation of the molar equivalents is eliminated or is at least greatly simplified.
- the substances in the container or containers advantageously have a molecular weight of less than 10,000, preferably less than 5,000, more preferably less than 10,000. Most opposite. Atmospheric oxygen or water vapor sensitive substances have relatively small molecular weights. For this reason, it is particularly advantageous to add these to the reaction in containers which only release the substances shortly before the reaction or only in the reaction mixture.
- At least one of the substances is released by at least partially, preferably irreversibly, lifting the airtight seal of the container in a reaction vessel.
- the release in the reaction vessel has the advantage that the substance is not contaminated when it is supplied. The irreversible removal of the container from being airtight prevents the container from being closed again.
- At least one of the substances is released by at least partially, preferably irreversibly, lifting the airtight seal of the container directly where the reaction takes place. Because the substance is only released where the reaction takes place, there is a risk of a change in the substance, e.g. with respect to oxidation by atmospheric oxygen, hydrolysis by water vapor, etc., before it starts the reaction, greatly reduced.
- At least one of the substances is at least partially, preferably irreversibly, removed from the airtight seal. released the container and then added to the at least one other substance.
- the at least partial removal of the airtight sealing of the container is preferably carried out by the non-targeted application of a chemical, physical or mechanical action.
- the containers are suitably designed, e.g. a container is fed to a reaction mixture and possibly only later, i.e. during the reaction, or individual containers at certain times during the reaction, for example by exposure to a rotating magnetic stirrer, ultrasound, a solvent, an explosive device of any kind, etc. e.g. irreversibly destroyed and subsequently release the substance.
- This can also be controlled in a targeted manner. This is a sensible external control, especially for reactions, which do not allow or only difficult to add after the start of the reaction, e.g. if the reaction takes place in an airtight container, if necessary under pressure, when carrying out many reactions in parallel, in which it is no longer possible to meter in parallel and simultaneously, etc.
- the at least partial removal of the airtight sealing of the container takes place by opening the container at a container location provided for this purpose, in particular by separating at a predetermined separation location.
- a nominal separation point is available, the advantages described above can be used in a more targeted manner.
- a higher reliability of opening the container is usually achieved.
- the target separation point especially with regard to material, be of a different nature, and at most a compromise can be made with regard to material properties for the relatively small amount of another material, which is used at most for the predetermined breaking point, in such a way that an optimal, more precisely controllable release of the substance is achieved and at most with regard to non-interference the chemical reaction (eg through inert material) can be compromised.
- the container is opened by means of a tool, with which the substance present in the container is then preferably added to the at least one further substance.
- the predosing of the substance in the container can thus be combined with the classic method in which the substance is fed to the reaction mixture without a container, e.g. a tool opens the container and the substance e.g. emits, lets out, blows out, etc. This is also advantageous if a certain substance is to be slowly added. If the tool opens the container shortly before adding it to the reaction vessel, many of the advantages mentioned above are retained. If the tool opens the container in the reaction vessel or even only in the reaction mixture itself and the container releases the substance there, the advantages mentioned above are practically all retained.
- the opening of the container is advantageously carried out by piercing the container, preferably by a two-stage piercing, in which a container wall part is pierced in a first stage and an opposite container wall part is pierced in a second stage, preferably after the first stage the interior of the container solvent agent is supplied.
- a substance can even be metered in as a solution in a solvent while obtaining most of the advantages mentioned above, for example by a robotic needle which is connected to a solvent reservoir, such as in a Gilson ASPEC 233, piercing a part of the container wall which the appropriate amount of solvent is metered in, if necessary repeatedly sucked up for thorough mixing and the solution is again drained into the container and possibly sucked up again and then pierces the opposite part of the container wall and the solution thus prepared is metered directly into, for example, a reaction vessel. With a corresponding device (manual or automated tool), this process can even be carried out directly in the reaction vessel.
- the at least partial removal of the airtight sealing of the container takes place by dissolving the container or a part of the container or by detaching a part of the container.
- a targeted opening of the container can be achieved by e.g. a solvent can be reached outside or inside the reaction vessel.
- the at least partial removal of the airtight sealing of the container takes place by destroying, preferably breaking, the container.
- the opening was described above by a non-targeted physical force.
- the same advantages apply to the destruction of the container. It can, for example, the timing of dosing can be accurately determined, even though the container may be ⁇ already overall at an earlier stage in the reaction vessel have been brought.
- the user can also break a suitable container by hand using gloves directly over the reaction vessel and empty the substance into the reaction vessel. This last variant is simple and opens up the possibility of adding the substance to the reaction mixture without a container while maintaining many of the advantages described above.
- the at least one container is advantageously made of a material that does not influence the reaction, preferably is chemically inert in the reaction, preferably at least partially of an inorganic material.
- the container should not be chemically attacked by the substance (contamination of the substance, danger to the environment, etc.).
- the inside and outside of the container material is inert in a very wide chemical spectrum, so that the same container material can be used for as many substances as possible and therefore less weighing and testing, both by the manufacturer and by the user himself, has to be carried out.
- the container material is inert to most of the substances and reaction mixtures used in chemical synthesis, or at least does not significantly influence most of the reactions.
- the at least one container is preferably at least partially, preferably essentially entirely, made of glass, preferably silicate glass, or a glass-like material.
- Most of the reaction vessels used in organic chemistry today are made of glass. Glass is considered to be very inert and does not affect the reactions in a wide range. Most users know the opportunities and risks of glass.
- glass In addition to HF, there are only a few substances and reaction mixtures used regularly in chemical research and development, to which glass is not resistant or at least not influencing. Glass also does not dissolve in organic and the vast majority of inorganic solvents, which means that if the container is completely added to the reaction mixture, for example, and the substance is thus released directly in the reaction mixture, it easily, eg by filtering it off Reaction solution, can be separated. Furthermore, glass is relatively easy to break, but under certain conditions it is quite suitable as a reasonably stable container. The container wall thickness can be selected, for example, such that the container can be transported relatively easily with good additional packaging, but can be broken up by a magnetic stirrer in a reaction vessel.
- min ⁇ consists least one container at least partially made of polymers.
- polymers especially polyethylene, polypropylene, and for specific hurry applications
- Polytetrafluoroethylene are the most suitable as container materials because they have the chemical stability necessary for such and similar compounds.
- the at least one container is advantageously at least partially made of metal and in particular contains a gaseous substance.
- gaseous substances can be placed in a reaction chamber as a whole, even under pressure, and can be sealed airtight.
- the container can be such that the gas is released into the reaction vessel under certain conditions, e.g. by loosening a glued seam, loosening a second material filled in pores, etc.
- the containers according to the invention can be similar to commercially available disposable laboratory containers, e.g. Test tubes, pipettes, ampoules, syringes, tubes with or without screw caps, etc., which are modified in such a way that irreversible removal of the airtight seal is possible.
- the predosed amount is 1 nmol to 100,000 ol, preferably 1 nmol to 10 r ⁇ ol, more preferably 1 nmol to 1 mol, more preferably 1 nmol to 100 mmol, more preferably 1 nmol to 10 mmol.
- the advantages mentioned above are particularly effective, since the smaller the batch, the more difficult it is to handle the relative accuracy of the metering.
- the vast majority of chemical reactions in chemical research and development are on a scale of less than 10000 mol, most on a scale of less than 10 mol, and especially in chemical engineering. Schung carried out in one of less than 1 mol.
- the containers are particularly efficient in the areas mentioned and in the case of smaller batches, in particular also because the smaller batches in particular are carried out much more frequently and today often in parallel.
- the predosed amount is preferably 1, 2, 5, 10, 20, 50, 100, 200, 500, 10,000, 2,000, 5,000, 10,000, 20,000, 50,000, 10,000, 200 * 000, 500O00, 1 * 000 * 000, 2 * 000 * 000, 5'OOOOOO, 10 * 000 * 000, 20'OOOOOO, 50 * 000 * 000 or 1 * 000 * 000 * 000 nmol, preferably 1, 2 , 5, 10, 20, 50, 100, 200, 500, l'OOO, 2'000, 5 * 000, lO'OOO, 20O00, 50 * 000, 100 * 000, 200 * 000, 500 * 000, 1 * 000 * 000, 2 * 000 * 000, 5 * 000 * 000 or IO'000'OOO nmol.
- the gradations, as usual in money systems, have proven themselves in terms of simplicity of use and are therefore familiar to every user. They are easy to calculate with regard to the overview and calculation of the molar equivalents.
- the pre-metered amount is 1, 10, 100, 100, 100, 100, 100, 1000 or 1,000 nmol, preferably 1, 10, 100, 100, 10 * 000, 100 * 000 or 10 * 000 * 000 nmol.
- a decimal system of graded containers is particularly easy to use with regard to the overview.
- the simplicity and clarity is often gladly taken due into account that compared to the system described above more but not too many Be, ⁇ must be used containers to the appropriate loading the desired accuracy rich to achieve.
- At least a first container with a first pre-metered amount of the first substance at least a second container with a second pre-metered amount of the first substance graded in terms of molar equivalents and at least a third container with a pre-metered amount of the second substance that is molar equivalent to the first pre-metered amount or graded in terms of molar equivalents.
- At least one first container with a first pre-metered amount of the first substance and at least one second container with a second pre-metered amount of the first substance that is graded in molar equivalents with respect to the first pre-metered amount is advantageous to use.
- the user can use container sizes in such a way that he can achieve practically any accuracy, especially if there is a sensible gradation (for example, as described above in a tens system) and not one container for each substance for every mole number in a certain range must have available, which would not only complicate logistics and production, but would also mean a loss of clarity.
- the essence of the invention with regard to the set of containers containing substances is that it contains at least one first container with a first predosed amount of a first substance, at least one second container with a second predosed amount of molar equivalents graded from the first first substance and at least one third container with a pre-metered amount to the first or an integer ⁇ multiple thereof pre-metered amount of a second substance.
- Substances are normally released essentially completely, can be added very conveniently to the reaction space, possibly together with other substances which are added to the reaction space in a conventional manner. Thanks to the pre-metered amounts of the substances, the user can do without the time-consuming weighing or measuring of the substance.
- the substance itself is minimal handling by the user outside the reaction space, i.e. of the space in which the substance is reacted, so that contact with the surroundings of the reaction space, which usually contains atmospheric oxygen and water vapor, is kept to a minimum, which in turn increases the oxidation and / or The risk of hydrolysis is reduced to a minimum, which means that the user is more likely than the classic metering to implement exactly the substance in the purity that he planned to implement.
- the set also has the advantage that not only a sub in a container is present substance pre-dosed, but just punch a set of pre-dosed arranged in containers Sub ⁇ .
- a set of different Reaktio ⁇ can be performed NEN, for example, using at least one first and at least a third container which contain two different substances, possibly additionally with classically added substances.
- Using one or more of the second containers, in which a second quantity of the first substance graded in molar equivalents with respect to the first predosed quantity in the first container is predosed not only can batch sizes be realized which correspond to the first predosed quantity in the first container or a multiple thereof , but also intermediate sizes.
- two reactions can also be implemented in which a first substance is released from a first container in a first reaction and reacted with another substance and a second substance is released from a third container in a second reaction and with another substance is implemented in such a way that the two reactions are molar-equivalent, which can be achieved in that the second predosed substance released from a third container is molar-equivalent to the first predosed amount of the first substance in the first container, or at most using a corresponding number of containers.
- the amount of the predosed second substance in a third container corresponds to an integer multiple (factor z) of the amount of the first substance in a first container
- to carry out a reaction such that x / z equivalents of the first predosed Substance can be reacted with an equivalent of the second substance, where x is the number of first containers used. Since a second pre-metered quantity of the first substance is in turn present in a second container and this is graded to the first pre-metered quantity of the first substance in the first container, further gradations with regard to molar equivalents can be achieved.
- the set of containers containing substances is advantageously composed in such a way that the predosed amount of the second substance in the third container is equivalent to the first predosed amount of the first substance in the first container.
- This ensures that the user carries out a chemical reaction between an amount of the first substance and an amount of the second substance which is mol equivalent to the amount of the first substance or a multiple thereof, at a desired molar ratio of the first substance to the second substance of 1: 1, a ⁇ fold can use a first container with the first substance and one or more third containers with the second substance.
- the Be ⁇ biberiere must be adjusted accordingly.
- the pre-metered amounts of further substances in further containers are molar-equivalent amounts or integral multiples thereof to the pre-metered amount of the first substance in the first container. This enables the user to perform a variety of reactions using the convenient set.
- At least one of the substances is a pure chemical compound, preferably both substances are pure chemical compounds.
- chemical reactions are carried out with pure compounds as starting substances (so-called educts). If the chemical compound is as pure as possible, the user knows exactly what he is using and can then carry out the reaction relatively independently of the supplier of the corresponding fine chemicals.
- pure chemical compounds are offered in purities between 90 and 99,999%. Different degrees of purity, such as 98% and 99% offered. In practice, both are considered pure chemical compounds.
- one advantage of being pre-dosed in a closed container is that the manufacturer of such containers can precisely define their contents and check them for quality, and the containers preferably only release the substance in the reaction vessel. This ensures that the purity, which the manufacturer of the substance specifies, cannot be handled, e.g. Weigh out, the substance outside the reaction vessel suffers. This increases the reproducibility of the reaction.
- the set of substances contained ⁇ Tenden containers comprising a plurality of containers with different substances in various quantitative predosed gene, the amounts being graded in terms of molar equivalents.
- the set of substances becomes more and more advantageous for the user, the more compounds it contains, which the user uses repeatedly. It is expedient in particular to have the most frequently used and the most delicate and most difficult to handle basic chemicals pre-dosed in containers.
- An example of this is sodium hydride (NaH), which is usually offered in suspension in an oil today, which means that it often has to be freed of it by washing with hexane before the reaction. Since NaH is also very sensitive to air, this is a complex, unsafe and labor-intensive work.
- the suspension in oil is primarily offered so that the NaH remains reasonably stable at least during handling and does not react with the air humidity to form NaOH. Due to similar handling difficulties, pre-metering in a closed container is particularly advantageous, for example, for K 2 CO 3 , LiAlH 4 , Na and CH 3 CH 2 COO (COOCH 2 CH 3 ).
- the set of containers containing substances is preferably composed such that the at least one first container has x nmol of the first substance and the at least one second container has y * x / 1,000 nmol of the first substance, where x and y are integers and y is preferably a number from 1 * 001 to 1 * 000 '000, more preferably from 1 * 010 to 100 * 000, even more preferably from 1 * 100 to 10 * 000.
- x and y are integers and y is preferably a number from 1 * 001 to 1 * 000 '000, more preferably from 1 * 010 to 100 * 000, even more preferably from 1 * 100 to 10 * 000.
- the vast majority of substances used in chemical research and development have a purity of less than 99.99% by weight. It therefore makes sense that a gradation is selected for the amounts of substance in the containers, which for most substances is significantly above this value.
- the gradation should not include steps that are too large and the smallest predosed amount of substance should be sufficiently small that, for a desired amount of substance, preferably less than 1,000, more preferably less than 100, more preferably less than 10, containers have to be used and sufficient accuracy is achieved.
- the choice of gradation is a matter of optimization, comparable to the choice of a monetary system, but this adds a third dimension, namely that different substances exist.
- y is 2,000, 3,000, 4,000, 5,000, 6,000, 7,000, 8,000, 9,000 or 10,000, preferably 2,000, 5,000 or 10 * 000, more preferably 5 * 000 or 10 * 000.
- the y between the first and second and that between the second and third containers are not the same size so that intermediate sizes can be introduced and fewer containers have to be used with the same metering accuracy. This, in turn, can significantly increase user friendliness.
- the gradation of a substance of x nmol, 2x nmol, 5x nmol and lOx nmol is particularly advantageous and is also used for example a money system in the tens system that is common today.
- the gradation of a substance of x nmol, 5x nmol and lOx nmol again has the advantage that the user has to handle fewer different container sizes and yet not too many containers in the range mentioned.
- a y of 100,000 the user can still dose exactly to the amount of x nmol and must use a maximum of 10 containers in each case in the range from x nmol to 2y / l'000 nmol, although he may need to add a total of slightly more containers has to handle even fewer different container sizes.
- x is a number from 1 to 1,000,000,000,000, preferably 1 to 10,000,000,000, more preferably 1 to 10,000,000 * 000, even more preferably 1 to 10,000,000. OOO, more preferably 1 to 10,000,000.
- These numbers result from the fact that the set of containers containing substances according to the invention is used in particular in chemical research and development and in this area of application usually in a range from 1 nmol to 100000000000000 nmol, preferably 1 to 10 '000' 000 '000 nmol, more preferably 1 to 1' 000 '000' 000 nmol, more preferably 1 to 100 '000' 000 nmol, more preferably 1 to 10 '000' 000 nmol.
- the advantage of smaller containers is that they are easier to handle and the release of the substance is usually quicker, which prevents concentration effects and other problems.
- the metering in of a substance can be graded in time, which is often necessary in particular in chemical synthesis.
- catalysts are used in relatively small amounts, for example 0.001 to 10% of the amount of stoichiometrically put substances, used. Since in chemical research and in the first phase of chemical development, work is predominantly carried out in a range from 1,000,000 to approx. 1,000,000,000 nmol, a catalyst in this lowest range can still be added by adding a container with a content of 1 nmol to 0.1%.
- x is 1, 2, 5, 10, 20, 50, 100, 200, 500, 1 * 000, 2 * 000, 5 * 000, 10 * 000, 20 * 000, 50O00, 100 * 000, - 200OOO, 5OOOO0, 1 * 000 * 000,
- the set according to the invention advantageously has at least three, preferably at least 5, more preferably at least 10, more preferably at least 100, more preferably at least 1,000 containers with different substances.
- the set of containers with different substances preferably has at least one, preferably at least three, more preferably at least five, further containers with the same substance in the first one
- Amount of the respective substance based on molar equivalents graded amounts ensures that the user has two or more doses of the substances available in containers. This is advantageous because in many reactions the substances are not used in an equimolar amount and other amounts can be achieved by combining containers with different fillings.
- the containers of the different substances are preferably equally graduated in terms of molar equivalents. So that the user only has to think effectively in containers or equivalents and when If the number of containers is as direct as possible to maintain the ratio of the equivalents of the substances to one another and therefore only has to determine the absolute batch size for one substance, it makes sense that not only many substances are available in containers with some gradations, but that Gradations are the same. If this is the case, the user gains an overview and time. Most optimally, the user has all substances in containers in his area of application in such a way that all gradations with regard to container contents in moles are the same and he has no restrictions with regard to the selection of the substance and the selection of accuracy, and yet only with containers whose contents are complete used in the reaction can work.
- Fig. 1 - a longitudinal section of an embodiment of an airtight container according to the invention, which contains a pre-metered amount of a substance;
- FIG. 2 shows a longitudinal section of the container from FIG. 1 before it has been filled with the substance and sealed airtight;
- Figure 3 is a longitudinal section of the container of Figure 2 after the substance has been filled in;
- FIG. 4 - is a sectional view of an apparatus on Implementation of a chemical reaction by means of inventions dung according containers that are destroyed by an Dre ⁇ Henden magnetic stirrer;
- Figure 5 is a perspective view of the apparatus of Figure 4;
- FIG. 6 shows a sectional view of an alternative apparatus for carrying out a chemical reaction with the aid of containers according to the invention which are destroyed by a rotating magnetic stirrer;
- FIG. 7 - a sectional view of a further alternative
- FIG. 8 shows a longitudinal section of an embodiment variant of a container according to the invention, of which a part of the container wall has been pierced with a needle which is just supplying a solvent;
- FIG. 9 shows a longitudinal section of the container and the needle from FIG. 8, the needle having absorbed the solvent with the substance dissolved therein;
- FIG. 10 shows a longitudinal section of the container and the needle from FIG. 8, the needle having pierced the part of the container opposite the puncture site and releasing the solution with the substance;
- FIG. 11 shows a longitudinal section of the container and the needle from FIG. 8, the needle being pulled out of the container again as an alternative to the variant shown in FIG. 10 and releasing the solution with the substance next to it;
- Fig. 12 - a longitudinal section of the container and the needle of Fig. 8, being an alternative to that in the
- 9-11 show variants of the needle without the solvent having previously been sucked up, with the substance dissolved therein, according to the puncture site. pierced the opposite part of the container wall;
- Fig. 13 is a longitudinal section of the container and needle of Fig. 12 after the needle has been withdrawn from the container;
- FIG. 14 shows a longitudinal section of an alternative embodiment variant of an airtightly sealed container according to the invention, which contains a predosed amount of a substance
- 16 is a perspective view of part of an apparatus which is guided by hand or by a robot and with which containers filled with a predosed quantity of a substance are melted off in an airtight manner;
- FIG. 17 shows a perspective view of a part of an alternative apparatus which is guided by hand or by a robot and with which containers filled with a pre-metered amount of a substance under an inert atmosphere . be sealed airtight;
- FIG. 18 shows a perspective view of an exemplary embodiment of a set according to the invention of containers containing 8 substances, which are held in a frame;
- 19 shows a perspective view of an alternative exemplary embodiment of a set of 96 containers containing substances, which are held in a frame;
- FIG. 20 shows a perspective view of an alternative embodiment variant of an airtight container in the form of a cuboid
- FIG. 21 shows a sectional view of an alternative embodiment variant of an airtightly closed container according to the invention in the form of a ball
- FIG. 22 shows a longitudinal section of an alternative embodiment variant of an airtightly closed container according to the invention in the form of a cylinder which has a predetermined breaking point in the middle;
- FIG. 23 shows a longitudinal section of an alternative embodiment variant of an airtight container according to the invention in the form of a cylinder which is provided with a bar code on the outside;
- FIG. 24 shows a longitudinal section of an alternative embodiment variant of an airtightly closed container according to the invention in the form of a cylinder which is provided on the outside with a chemical formula
- FIG. 25 - is a longitudinal section of an alternative embodiment according to the invention a hermetically sealed container in the shape of a ⁇ Zylin idem, which is glued together in the middle;
- 26 shows a longitudinal section of an alternative embodiment variant of an airtight device according to the invention sealed container which has two predetermined breaking points;
- FIG. 27 is a perspective view of 96 container blanks, which are held in a rack and each filled with a predosed amount of a substance and covered with a thin glass plate;
- FIG. 28 the welding of the thin glass plate to the 96 container blanks according to FIG. 27 with the aid of a fire-resistant plate;
- Fig. 28.1 is an enlarged section of Fig. 28 showing an annular hole in the fire resistant plate
- Fig. 29 is a perspective view of the set or kit of containers containing 96 substances obtained in accordance with Figs. 27, 28 and 28.1;
- FIG. 30 shows a perspective view of an alternative exemplary embodiment of a set or kit according to the invention of containers containing 96 substances with an upper and a lower thin glass plate;
- FIG. 31 shows a perspective view of an alternative exemplary embodiment of a container according to the invention, which is to be closed by welding on a thin lid;
- FIG. 32 shows a longitudinal section of the container from FIG. 31 in the closed state
- Fig. 33 is a longitudinal section of the closed container of Fig. 32 which has been pierced with a needle which adds solvent to dissolve the substance; 34 shows a perspective view of an apparatus according to FIG. 4, a container which has not yet been destroyed and which contains a predosed amount of a substance being seen in the reaction solution.
- 35 is a schematic perspective view of an apparatus of parallel reactors to which a set of containers with predosed substances is added in parallel;
- Fig. 36 - a hollow glass rod used to make a blank
- Fig. 38 - a hollow glass rod, which is extended to a very thin glass rod at one point over a length of about 15 cm;
- Fig. 39 the hollow glass rod of Fig. 38, in which the part is cut out which has a thin wall and a desired outer diameter;
- FIG. 40 shows a longitudinal section of an alternative embodiment variant of an airtightly closed container according to the invention in the form of a syringe which is closed on the needle side with a glass film;
- FIG. 41 shows a longitudinal section of an alternative embodiment variant of an airtightly closed container according to the invention in the form of a syringe which is closed on the needle side by a glass wall.
- Figure 1
- the illustrated airtight container 1 contains a pre-metered amount of a substance 2. It comprises a cylindrical hollow body 3 which is sealed airtight at the bottom by a spherical bottom 4 and at the top by a partially spherical cover 5 provided with a melting tip.
- the cylindrical hollow body 3 has the same diameter everywhere with the exception of the base and cover area.
- the wall thickness bi of the cylindrical hollow body 3 is particularly small, for example 0.03 mm, relative to the outside diameter di, which is, for example, 4 mm. On the one hand, this can ensure that the internal volume is as large as possible for given external dimensions, and on the other hand, if glass is used as the exclusive container material, the container 1 is broken under the action of relatively small external forces and the predosed substance 4 is released. Nevertheless, the container is still transportable.
- the cavity 6 is generally filled with air under normal pressure, with sensitive substances 2 or generally advantageously with nitrogen, even more advantageously with argon.
- a small outside diameter di is desirable so that the container 1 can be introduced into a reaction vessel through which the addition point is as small as possible and in which very special conditions must often prevail. So that enough substance can be filled into the container 1, it is tubular, for example with a length of 50 mm.
- the container which has not yet been filled with a pre-metered amount of a substance 2 and is not yet hermetically sealed is also referred to as a blank 1 '. It consists of a cylindrical hollow body 3 ', which is sealed airtight at the lower end by the bottom part 4.
- the entire test tube-shaped blank 1 ' is made from a single material.
- the material used is, for example, metal,
- TM in particular stainless steel, Hastelloy or a titanium alloy, plastic, in particular PTFE, another polyfluorinated plastic, polypropylene, polyethylene, natural stone, in particular granite or gneiss, ceramics, in particular
- TM the other 2 0 3 or MACOR, or a glass, in particular borosilicate glass 3.3.
- Glass is particularly advantageous because it is chemically inert to a large number of chemicals and reaction mixtures used in chemical research and development, and after the pre-dosed ones have been filled in
- the substance 2 can be filled into the blank 1 ', for example, using a commercially available automatic metering device.
- Figure 3
- a precisely (in mmol) pre-metered amount of a substance is filled in and on the other hand the blanks 1 'For a wide range of different substances 2 on the one hand and different amounts on the other hand, a cavity 6 "is normally created, since substance 2 does not conform to eg Volume, but is predosed according to the number of mmol. Since many substances are sensitive to air, i.e. sensitive to oxygen and / or water, it is often necessary to fill the cavity 6 "with a chemically as inert gas as possible before melting.
- a classic apparatus 11 for carrying out chemical reactions comprises an attached reflux condenser 12 with a reflux cooler cooling liquid chamber 26 and a reflux cooler interior 27, an oil bath 13 with oil bath containers 14, a magnetic stirrer motor 15 which is only shown schematically, a magnetic stirrer (often also called magnetic stirrer fish by chemists) 16 (here a two-stage cylinder with a magnetic core which is coated with a layer of PTFE is covered).
- a container 1 is located shortly before the addition to the apparatus for carrying out a chemical reaction. The fragments 18 of an already introduced and broken container are shown.
- the container 1 is added via a reaction vessel opening 19, which is open at the moment, but can be closed with a NS 14.5 cut, for example, by a stopper (not shown).
- the container 1 is added through the opening of the two-necked flask not occupied by the reflux condenser 12.
- the reflux condenser is also connected to the reaction vessel 21 via an NS 14.5 standard ground joint.
- NS 14.5 22 can be seen, which leads to an olive 23, which is provided with a hose 24. It is therefore advantageous to have a slight excess pressure of argon, since it is then ensured that even when the reaction vessel 21 is opened briefly, inert conditions are present at the reaction vessel opening 19 by removing a stopper (not shown).
- the long shape relative to the outer diameter di of the cylindrical container 1 in this exemplary embodiment makes it possible to achieve a relatively large inner volume 10 without losing the advantage that the airtightly sealed container 1 containing a predosed amount of a substance 2 after the airtight sealing can be fed to the reaction vessel 21 through a relatively small opening 19.
- the interior 25 of the reaction apparatus 11, which contains gases or gas mixtures is often filled, for example, with a chemically inert gas such as N 2 or argon. This means that the larger the opening 19 of the reaction vessel 21, the greater the risk that, by opening the reaction vessel 21 necessary for supplying the container 1, the atmosphere in the reaction vessel 21 will be affected by the atmosphere in the vicinity of the reaction vessel 21 is adversely affected.
- WO 98/57738 describes reaction apparatuses which allow the containers 1 to be e.g. can be added fully automatically under very exact conditions through relatively small openings.
- a container 1 which has not yet been destroyed and which is still hermetically sealed and which contains a predosed quantity of a substance 2 can be seen.
- The- This container can now be destroyed relatively relatively at a desired time by switching on the schematically illustrated magnetic stirrer 15 at a certain frequency.
- the exact nature of the container 1, ie for example its thickness, its material or its construction, plays a decisive role in addition to the frequency.
- the container 1 can be designed such that it is destroyed or opened during the smallest movement or only after a large force is applied.
- the rest of the apparatus 11 is the same as in FIG. 4, except that the coolant connection hoses 24 (see FIG. 4) and the argon connection (see 23 and 24 in FIG. 4) are not shown for the sake of clarity.
- the illustrated alternative apparatus 111 comprises a reflux condenser 112 placed on a reaction vessel 21 with a reflux condenser cooling liquid chamber 126 and a reflux condenser interior 127, an oil bath 13 with an oil bath container 14, a shaking device 28, only shown schematically, one shortly before the addition into the reaction vessel 21 located hermetically sealed container 101 with a pre-metered substance 102 for carrying out a chemical reaction, a reaction suspension 117 and remains 118 (indicated by several splinters) of a broken container 101.
- a reaction vessel opening 19 is currently open, but can be closed with a standard ground joint NS 14.5 by means of a plug (not shown)
- the reflux condenser 112 is connected to the reaction vessel 21 via a NS 14.5 standard ground joint 120.
- the container 101 is thrown into the open reaction vessel 21 without excess argon pressure.
- a container 101 has already been added to the reaction vessel 21, which has already been destroyed by shaking with the shaking device 28, depending on the stability of the container, and has already substantially completely released the substance 102.
- Another container 101 is added under a counter-argon flow.
- the container 101 is destroyed in such a way that it moves in the reaction solution mostly in an uncontrolled manner, touching the vessel wall 29 of the reaction vessel 21 once or more and being broken in the process. Since the container 101 is made of relatively thin glass in this exemplary embodiment, this is done relatively easily and, depending on the shaking frequency, with very high reliability. The broken glass is simply left in the reaction solution, which in this case influences the reaction in most other cases at most insignificantly. Furthermore, the broken glass is removed at the desired time.
- a container 101 which is generally filled under normal pressure, for example approximately under normal pressure, as described above, can also be introduced into the reaction vessel 21 of the apparatus 111. If there is then an overpressure on the reaction vessel 21 is applied, the container bursts automatically at a certain overpressure.
- the apparatus 111 largely corresponds to the apparatus 111 described in FIG. 6, with the exception that the reflux cooler connecting hoses 24 are not shown for the sake of clarity.
- a container 201 which is being pierced by a needle 30 controlled manually or by a robot, the substance 302 has not yet been released, but the airtightness of the container 201 has just been lifted.
- the container 201 has the shape of a relatively flat cuboid which is slightly rounded at the edges and ends for production reasons. This shape is preferred for the variant shown in this figure for releasing the substance 302 from the container 201, since the needle 30 can thus hit the container 201 better.
- various further variants of containers are conceivable, in particular when using special needles which have a larger outside diameter c and instead of a needle tip 32 a flat lower end.
- the container 301 according to the invention shown comprises a cylindrical container wall 203 with a wall thickness b 2 , for example 0.03 mm, a spherical base part 204 and a spherical cover part 205.
- a predosed amount of a substance 402 is arranged in the container 301, above which a cavity 206 is located.
- By piercing one by hand or by a sampler or robot passed needle 130 through a container wall part 34, which in this case is part of the cover part 205, into the container 301, it has just been opened irreversibly.
- the needle 130 is feeding a solvent 35 in which the substance 402 is dissolved.
- FIGS. 8, 9 and 11 represent a sequence of work processes
- FIGS. 8, 12 and 13 or 8, 9 and 10 each represent an alternative work process with which a substance takes place in dissolved form as in the previous figures in pure form, for example, can be metered into a reaction vessel.
- the holder 301 is preferably integrated in a rack for holding the container at the bottom of the robot, and that for the outlet 8, 9 and 10 is preferred directly integrated in the gripper (in the chamber in which the container is received).
- a holder it is also conceivable for a holder to be placed directly above an opening or a potential opening of the reaction vessel or in the reaction apparatus itself, in particular if absolutely reliable conditions are required during the addition of the dissolved substance.
- the gripper (not shown) or the needle 130 with the container 301 can carry out the entire sequence within the apparatus, again in particular when absolutely controllable conditions are required.
- the different sequence variants are described, starting from the situation according to FIG. 8 in connection with FIGS. 9-13, the sequences themselves being no longer completely described.
- solution in the present context also includes suspensions, emulsions, a mixture of a liquid and solid particles, which e.g. be kept in suspension by prior shaking, that is to say an imbalance state, etc.
- solution 33 or a part thereof can be drained off and sucked up again, possibly even several times.
- the needle 130 has pierced the bottom part 204 opposite the puncture hole 38 and now releases the absorbed solution 33 again, for example into a reaction apparatus, a reaction vessel or an intermediate container.
- the needle 130 with the absorbed solution 33 has been pulled out of the container 301 here and now releases the solution 33 at another location essentially completely or aliquoted at several other locations.
- the container can, for example, be held in a robot arm and then ejected or simply held in a rack. The essentially completely empty container is then generally thrown away.
- Figure 12
- the needle 130 guided by a robot pierced the bottom part 204 opposite the puncture site by a simple downward movement.
- the needle 130 is pulled out of the container 301 by hand or controlled by a robot. This leaves not only a puncture hole 37 in the bottom part 204 but also a puncture hole 38 in the lid part 204, which automatically ensures pressure equalization in the container when the solution 33 runs out.
- the airtightly closed container 401 contains a pre-metered amount of a substance 302. It comprises a cylindrical hollow body 303 which has a partially spherical bottom with a melting tip and top with a partially spherical bottom 304 Cover 305 is sealed airtight.
- the cylindrical hollow body 303 has the same diameter everywhere except for the base and cover area. 3, the wall thickness b of the cylindrical hollow body 303 is in particular ⁇ sondere relative to the external diameter, for example, is 4 mm, small, for example 0.04mm.
- the cavity 306 is generally filled with air under normal pressure, for sensitive substances 302 or generally advantageously with nitrogen, even more advantageously with argon. For the rest, what has been said in connection with FIG. 1 essentially applies.
- FIGS. 15.1 to 15.4 show the production of container blanks for containers according to FIG. 14 in various process steps.
- a relatively thin-walled glass cylinder 40 with wall thickness b 4 for example 0.05 mm, which is open at the top and bottom is assumed.
- the glass cylinder 40 is melted off at a certain point with a strongly bundled, fine-beam flame 44, which is emitted by a flame generator 45 and is guided and controlled by hand or by a robot (not shown).
- the flame 44 is generated by burning off a conventional gas, which is supplied via lines 47, 48. 15.3, and on the other hand a hollow glass cylinder 40 ', which is closed at the bottom and is approximately shorter by the length of the blank 301'.
- a lower part 42 which has approximately twice the container length, is separated from the glass cylinder 40 'with a flame 44', which is emitted by a flame generator 45 '.
- the flame generator 45 ' can be the same as the flame generator 45.
- Further lower parts 42 can be separated from the remaining glass cylinder part.
- the blanks 1 ', i “, 1" ", etc. are held in holes 63 of a frame 61 in the illustrated embodiment.
- a precisely pre-metered amount of a substance 402', 402 ", etc. is filled in.
- the filled blanks 1 ', 1", 1' '', etc. are filled by hand or by a robot 62, which is shown schematically by the spatial axes, melted apparatus 60 each melted into an airtight container 1 according to FIG. 1.
- the blanks 1 ', 1 ", 1" ", etc. are held in holes 67 of a frame 65 in this alternative embodiment.
- a precisely pre-metered amount of a substance 502 ', 502", etc. is filled in.
- the filled blanks 1', 1 ", 1" ", etc. are then filled in by hand or by a robot 66 1, which is shown schematically by the spatial axes, melted out the melting apparatus 64 to form an airtight container 1 filled with substance 502 according to FIG. 1.
- the container blanks are closed here under a transparent cube 68, for example made of plexiglass or polycarbonate.
- the free space in the cube 68 is completely filled with a chemically relatively inert gas, for example nitrogen, more advantageously a noble gas, for example argon, which means that the space in the air not occupied by the predosed substance 502 tightly sealed container 1 is finally also filled with this chemically relatively inert gas.
- a chemically relatively inert gas for example nitrogen
- a noble gas for example argon
- argon which is heavier than air and consequently accumulates on the substance, e.g. are blown into the blanks 1 ', 1 ", 1"', etc., via a needle attached to the melting apparatus 60 or 64 and attached to a gas line.
- the variant shown in FIG. 17 with a chemically relatively inert gas under a cube 68 has the disadvantage that more gas is generally required, but the often decisive advantage that e.g. with air or the oxygen contained therein, auto-ignitable substances 502 ', 502 ", etc. or hydrolysis-sensitive substances 502', 502", etc. can be filled safely and while maintaining the quality of the substances.
- Containers 1 containing eight substances 602, 702, etc. are held here in holes 71 in a frame 70.
- the same substance is advantageously, but not necessarily, advantageously always per frame or group of frames, but advantageously not necessarily always filled in the same pre-metered amount, since this greatly simplifies and speeds up the filling procedure, especially when it is fully automated, and these racks are then stored and, if necessary, differentiated from a commercially available storage robot to a set 69 of containers 1 - - Assorted substances 602, 702, etc.
- racks of the same substances but not necessarily in the same pre-metered amount. In this case, only different racks form a set of containers with different substances.
- the alternative set 72 shown here comprises 96 containers 802 containing substances 802, 802 ', etc., which are held in holes 74 in a frame 73. Furthermore, what has been said about FIG. 18 applies.
- An alternative embodiment variant of an airtightly sealed container 501 according to the invention which contains a predosed amount of a substance 902, has the shape of a cuboid 403 with a relatively thin wall thickness b 5 , for example 0.02 mm, an inner volume 406 which does not differ from the substance 402 in Claimed is a cover part 405 and a bottom part 404.
- the airtight container 601 which contains a pre-metered amount of a substance 1002, has the shape of a sphere 503 with a relatively small wall thickness b 6 , for example 0.03 mm.
- This example of use is also comparable in terms of convenience in use to the container 1 described in FIG. 1, albeit the volume in comparison to the smallest.
- Cross section is significantly smaller than in the cylindrical container 1 of FIG. 1 and thus the maximum amount of substance 1002 that can be predosed is smaller.
- this container 601 has decisive advantages.
- it can also be metered “pseudo-flowing", for example through lines with a line diameter that corresponds, for example, to four times the ball diameter, directly into a reaction vessel, in particular if a large number of identical containers 601 are used per reaction and the total amount of substance is measured "quasi-volumetric".
- the accuracy suffers, but this does not necessarily have to be relevant for a large number of balls, but the speed is increased considerably.
- the accuracy can be brought to a high level again by means of market-available optical detection or counting systems.
- the airtight container 701 which contains a pre-metered amount of a substance 1102, comprises a cylindrical hollow body 603 with a wall thickness b 7 , for example 0.5 mm, which has a spherical bottom 504 at the bottom and a partially spherical bottom , with a melting tip provided cover 505 airtight.
- the cavity above substance 1102 is labeled 506.
- the cylindrical hollow body 603 has a constriction 76 and a slightly smaller container wall thickness and thus a predetermined breaking point 75.
- the airtight container 801 which contains a pre-metered amount of a substance 1202, comprises a cylindrical hollow body 703 with a small wall thickness b 8 , for example 0.04 mm, which is sealed airtight at the bottom by a spherical base 604 and at the top by a partially spherical cover 605 provided with a melting tip.
- the cavity above substance 1202 is labeled 606.
- the cylindrical hollow body 703 is provided on the outside with a bar code 77 for identifying the substance 1202 in the container, its quantity, its quality, etc.
- the bar code 77 is scratched into the glass container wall, which has the advantage that no additional material has to be used which, depending on the application, would also have to be chemically inert again.
- the airtightly sealed container 901 which contains a pre-metered amount of a substance 1302, comprises a cylindrical hollow body 803 with a small wall thickness b 9 , for example 0.02 mm, which has a spherical base 704 at the bottom and a part at the top spherical cover, provided with a melting tip, is sealed airtight.
- the cylindrical hollow body 803 is provided on the outside with a chemical formula 78 for identifying the substance 1302 located in the container.
- Chemical formula 78 is carved into the glass container wall, which has the advantage that no additional material has to be used, which, depending on the application, would also have to be chemically inert again.
- the airtight container 1001 contains a pre-metered amount of a substance 1302 and a cavity 806 above it. It comprises a cylindrical hollow body 903 with a wall thickness h ⁇ 0 , for example 0.5 mm, which is underneath by a partially spherical, with a Bottom 804 provided with a melting tip and is sealed airtight at the top by a partially spherical cover 805 provided with a melting tip.
- the latter has an adhesive point 79 between two container parts, which can be dissolved, for example, by a solvent or a reaction mixture, so that the container is opened.
- the airtight container 1101 contains a pre-metered amount of a substance 1402 and a cavity 906 above it. It comprises a cylindrical hollow body 1003 with a diameter du, e.g. 4 mm, and a wall thickness bn, e.g. 0.5 mm, which is sealed airtight at the bottom by a partially spherical bottom 904 provided with a melting tip and at the top by a partially spherical lid 905 provided with a melting tip. In the vicinity of the lid 905 and the bottom 904, the cylindrical hollow body 1003 each has a constriction 82 and a slightly smaller container wall thickness and thus a predetermined breaking point 275.
- a diameter du e.g. 4 mm
- a wall thickness bn e.g. 0.5 mm
- This embodiment has the advantage over that shown in FIG. 22 that the sub- punch 1402 can be released faster from the container.
- problems can occur in the container 701 of FIG. 22 in that capillary effects can occur, in particular in the case of small internal cylinder diameters, and a local vacuum delays or even prevents further leakage of liquid or dissolved substances.
- This disadvantage is greatly reduced with the container 1101, since it is opened at two predetermined breaking points 275.
- Containers with even more predetermined breaking points were also produced.
- the easiest way to make it is to scratch the desired spot (over a certain angle or all around) with a diamond cutter.
- 27, 28 and 28.1 show the production of a set 95 according to the invention or a kit of containers 1501 containing 96 substances according to FIG. 29.
- 96 blanks 1 'with a cylindrical hollow body 3 are first arranged in holes 86 of a rack 83 via springs 1500 and filled with a predosed amount of a substance 1502. Then a relatively thin glass plate 87 covering all the blanks 1 'is placed on the open side of the blanks 1' according to arrow 84.
- the annular holes 89 have the same outside diameter ei and the same inside diameter e 2 as the blanks 1 'of the container 1501.
- the heat insulating and fire resistant cores in the holes 89 are held by wire-like connections 90. Heat is then generated with an apparatus 2000 generating 96 flames 2001 and fed through the annular holes 89 to the glass plate 87, as a result of which the blanks 1 ′ of the containers 1501 are melted with their upper edge onto the glass plate 87.
- the procedure described gives the set according to the invention of 96 pre-dosed containers 1501 shown in FIG. 29 or a corresponding kit with 96 containers containing the same substances, which together with at least one further container with another substance forms a set of substances according to the invention Containing containers forms.
- Individual containers 1501 can easily be broken off from this set 95.
- the cover 1005 formed in this way of an individual container 1501 forms a predetermined breaking point or zone, in particular if the wall thickness g of the cylindrical part 3 of the container 1501 is significantly larger.
- an inventive set 195 and a kit comprising the 96 airtight containers 1601 each have a Vordo ⁇ catalyzed amount of a substance 1602 a hollow cylindrical body 1603 a lid 1605 and a bottom 1604.
- the Cavity above substance 1602 is designated 1606.
- the lids 1605 and the bottoms 1604 are formed by melting or gluing a thin glass plate 287 on the bottom and top of the container blanks.
- the airtight containers 1601, each with a pre-dosed substance 1602 are held together by the two plates 287 and can be easily broken out.
- the lid 1605 and the bottom 1604 of an individual container 1601 form a predetermined breaking point or zone.
- An alternative embodiment of a container 1201 according to the invention comprises a cylindrical hollow body 1203 with a wall thickness b 12 , for example 0.7 mm, a spherical bottom 1204 and a threaded part 1207 adjoining the latter above the hollow body 1203.
- the container 1201 contains a pre-metered amount of a substance 1202 and above it a cavity 1206. It can be closed by welding or gluing a relatively thin cover 1205, preferably made of the same material. If desired, the threaded part 1207 allows a removable safety cap to be screwed on. This can be provided with a septum and screwed on before the first piercing.
- the lid of the container can also be attached to the container itself via a precisely defined negative pressure.
- the containers 1201 are manufactured from a metal, for example stainless steel, and are closed in a pressure-tight manner in the opening area with a commercially available rupture disk. The rupture disc can be screwed onto the container 1201 using a cap, which is also made of stainless steel, for example.
- the container 1201 according to FIG. 32 has been pierced with a needle 798 in the area of the lid 1205, which forms a predetermined breaking zone.
- the needle 798 now adds solvent 1208 to dissolve the predosed substance 1202.
- the continuation options result accordingly from FIGS. 9 to 13.
- the apparatus 11 shown corresponds to that according to FIG. 5, but a container 1301 containing a predosed amount of a substance 1302 has been introduced into the reaction vessel and corresponds to the container 1201 according to FIG. 32.
- the container 1301 in the area of the cover designed as a predetermined breaking zone 1305 has been opened irreversibly by the magnetic stirrer rod 16, specifically at a desired point in time.
- the exact nature of the container 1301 or the predetermined breaking zone 1305, ie the thickness and the material or the construction of the predetermined breaking zone 1305, plays a decisive role in addition to the frequency with which the magnetic stirring bar 16 rotates.
- containers 1301 or predetermined breaking zones 1305 can be designed such that they are opened during the smallest movement or only after a relatively large force has been applied. Depending on the construction, there is also a continuous one or even opening in chambers. In addition, the bottom can also be designed as a predetermined breaking zone.
- reaction vessels 121 are held in a frame 140 here.
- Sixteen hermetically sealed containers 297 with pre-metered amounts of substances which are inserted into a plate 290 or into a plate with through holes, which e.g. with a foil, in particular aluminum foil, and possibly also coated, can be pressed simultaneously into the reaction vessels 121 by means of a plate -211 (manually or with a robot). It is also possible to use containers (not shown) (which are necessary in the case of a plate which has been covered and covered with a film) which can be attached to a plate or can be controlled individually, jointly or in groups by hand or by a robot. to be pressed individually, together or in groups into the reaction vessels 121.
- the containers 297 can be opened at the same time.
- 36 to 39 show the production of a very thin glass rod 2004, which can then be used, for example as described in connection with FIGS. 15.1 to 15.4, for the production of blanks for containers according to the invention with a very small wall thickness.
- the thin glass rod 2004 is then cut out according to FIG. 39.
- the airtight container 1701 which contains a pre-metered amount of a substance 1702, is designed in the form of a syringe and comprises an essentially cylindrical hollow body 1703 with a rounded bottom 1704.
- the bottom 1704 has a continuous opening 1705 into which a hollow needle 1706 is welded.
- the opening of the hollow needle 1706 is sealed airtight by a glued or welded thin glass film 1707.
- the cylindrical hollow body 1703 is sealed airtightly over the substance 1702 by a glued or welded thin glass foil 1708.
- the z 'ylindharizzle hollow body 1703 and the base 1704 are preferably made of glass, while the hollow needle 1706 is preferably made of metal.
- a thin glass wall can be provided as part of the container wall, in which case the container 1701 is filled either through the through opening 1705 or before its walls are completed.
- the container 1801 which is sealed in an airtight manner and contains a predosed amount of a substance 1802, is in turn in the form of a syringe and comprises a substantially cylindrical hollow body 1803 with a rounded bottom 1804 and a flange 1807 at its upper end.
- the bottom 1804 has a blind hole 1805, into which a hollow needle 1806 is welded.
- the cylindrical hollow body 1803 is sealed airtight against the hollow needle 1806 on the one hand by the thin remainder of the bottom wall 1804 and on the other hand above the substance 1802 by a thin glass foil 1808 glued or welded to the flange 1807.
- the cylindrical hollow body 1803 and the bottom 1804 are preferably made of glass, while the hollow needle 1806 is preferably made of metal.
- a thin glass wall can be provided as part of the container wall, in which case the container 1801 is filled before its walls are completed.
- Table 1 below lists a set of 50 substances which have been packed in 7 different mmol amounts in glass containers according to FIG. 1 in an airtight manner.
- the percentages in column 2 are purity data.
- the mmol amounts have been adjusted for purity.
- At least 96 containers of each substance have been produced in every quantity.
- Various other exemplary embodiments of containers with substances in different amounts have also been realized in accordance with the patent claims.
- the system is, for example, 2 x 10 ⁇ x , 3 x 10 ⁇ x , 3.01 x 10 ⁇ x or, as described in Table 4, 1.1 x 10 "x etc. mmol or, for example, a composition of containers with 1 x 10 "x , 2 x 10 ""x and 5 x 10 -x etc. or as described in the table above, builds on 1 x 10 ⁇ x and 5 x 10 ⁇ x . In the examples listed here, x is sensibly an even number.
- Example 1 Alkylation of an alcoholate with an alkyl halide (Williamson see ether synthesis)
- the chemist has planned the following reaction, which experts call Williamson's ether synthesis.
- the regulation written below corresponds to the classic implementation of the reaction, that is, the implementation of the reaction. tion without using containers according to the invention and without using the method according to the invention:
- the solvent (dimethylformamide) was introduced into the inertized reaction vessel using a commercially available disposable syringe.
- the alcohol 1 (0.1002 g, 0.106 ml, 1.0 mmol), filled in a 1.0 mmol container, was then thrown into the reaction vessel by hand (briefly manual Open the reaction vessel during the addition).
- the moving magnetic stirrer automatically destroyed the container in this exemplary embodiment.
- the alcohol was subsequently released and dissolved in the dimethylformamide.
- the experimenter then gave a 1.0 mmol container of sodium hydride (0.024 g, 1.0 mmol, 1.0 eq.
- Example 2 Synthesis of a substituted aminocyclohexane library by double reductive mining in the key step
- 2nd stage Y mg or ⁇ l (0.100 mmol, 1.0 eq) of the second aldehyde 4 and 30.2 mg of sodium triacetoxyborohydride 3 (0.15 mmol, 1.5 eq) were added and the reaction mixture was stirred for 10 hours under inert gas at room temperature.
- 1st stage 1.5 ml of dry THF were placed in each reactor.
- a 0.100 mmol container (9.91 mg, 1.00 eq) of aminocyclohexane 1 was added with vigorous stirring. In all cases of intensive container agitation, the reagent is released from the container, in this case irreversible destruction of the glass container.
- a 0.100 mmol and a 0.010 mmol container (total X mg, 1.1 eq) of the first aldehyde 2 (3- or 4-benzyloxybenzaldehyde) were added to the reactor with stirring. After 10 min.
- Example 3 Representation of ⁇ , ⁇ -unsaturated enones by Horner-Emmons reaction
- Table 4 lists a set of 10 substances which have been packaged airtight in 3 different mmol amounts in glass containers according to FIG. 1.
- This system of containers has practically the same ease of use advantage as that described in Table 1.
- a reaction with one equivalent of a first substance (e.g. 1 container from the third column) and 1.1 equivalents of a second substance (1 container from each of the second and third columns).
- the containers are made of an optimally inert plastic (which is usually less widely used than glass).
- other materials can be advantageous since the glass residues (container residues) can damage the cells.
- the results are comparable.
- the containers are not broken (as described in the case of glass containers) (completely or via a predetermined breaking point). After filling the substance under inert conditions, a lid is attached with an adhesive (as small a quantity as possible), which is released by the action of a solvent or physical forces (e.g. strong stirring or ultrasound) and the corresponding substance is thus released.
- the glass residues can be added shortly before or during the addition, for example through a filter (for liquids) or but only be removed during or after the reaction in any way (e.g. filtration, removal of magnetized container residues with a magnetic field, etc.). Since, for example, glass is inert to most substances or physical conditions used in chemical or biochemical research, in most cases it leaves all the options described open and it is up to the user to decide when and if at all, he the container remnants removed. In many cases, especially in the area of chemical development or process development, it can even be advantageous (in terms of effort, etc.) that the container remains, especially in the case of glass, are not removed at all.
- a filter for liquids
- any way e.g. filtration, removal of magnetized container residues with a magnetic field, etc.
- these can be removed, for example, only after the reaction, for example during the workup of the reaction mixture, after the workup of the reaction mixture, etc.
- This not only saves the disposal of the possibly contaminated container remains (potential health hazard, potential environmental hazard, etc.), but also saves the experimenter the time-consuming removal, the use of an expensive tool, etc.
- the container remains are not removed, for example, if the experimenter is only interested in the process data and not in the product.
- the remains of the container can then be disposed of either together with the reaction medium (in this case the product) or with the reprocessing residue. This also has the advantage that the experimenter does not have to dispose of dangerous contaminated container residues in various respects at most, but only a uniform mixture (product mixture or work-up mixture with container residues).
- all containers are in the widest possible millimole range, each filled with the ones usually used in chemical or biochemical research Substances of the same size or of the same size in at least two dimensions.
- This has the advantage that all containers of substances with the most varied fill quantities with regard to mmol can be stored identically and, in particular, can be handled identically by, for example, a robot for storage or synthesis itself and, for example, the reaction vessel openings and others for storage and / or synthesis necessary installations can be easily dimensioned accordingly.
- the substances are mostly used in a certain ratio with regard to the number of atoms or molecules.
- the system according to the invention thus corresponds to a "millimolization" of chemistry.
- the units used are usually mol or milimol and no longer kilograms or liters, as is customary today in the application area described. This is crucial in order to make the entire system compatible and efficient.
- the other substances used in the same or different chemical reactions are advantageously present in the same number of moles in at least one similar container.
- the similar containers Before a number of moles or at least one factor-based number of moles is necessary for a well-functioning system, the similar containers not only make manual work easier, but also make automation or semi-automation easier to implement.
- the experimenter can carry out a chemical reaction in which, for example, he has to combine 10 ⁇ 3 mol of substance A with 1.1 equivalents of substance B by filling 10 containers each filled with 10 ⁇ 4 mol of substance A and 11 containers each filled with 10 ⁇ 4 mol of substance B brings together and the substances are released as described above either shortly before the addition of the container, during the addition of the container or in the reaction vessel itself in the manner described above.
- a gradation should follow in such a way that the experimenter can switch to a next higher container unit if the quantity in the container is large relative to the substance quantity.
- the number of containers per reaction can thus be reduced to a minimum.
- the example described above looks like that it contains 1 container filled with 10 ⁇ 3 mol of substance A with a container filled with 10 ⁇ 3 mol of substance B and a container filled with 10 ⁇ 4 mol of substance B in the manner described matches and carries out the reaction.
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Description
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PCT/CH2001/000485 WO2002013969A1 (de) | 2000-08-14 | 2001-08-09 | Verfahren zur durchführung einer chemischen reaktion |
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DE10059633A1 (de) * | 2000-12-01 | 2002-06-20 | Hte Ag | Verfahren und Vorrichtung zur Überführung von luftempfindlichen Substanzen |
CH704060A1 (de) * | 2010-11-08 | 2012-05-15 | Chemspeed Technologies Ag | Substanzbehältnis für eine chemische Reaktion. |
US10569191B2 (en) * | 2019-07-01 | 2020-02-25 | Elliot Kremerman | Short distillation head comprising a vertical tube filled with a key |
WO2024134396A1 (en) | 2022-12-22 | 2024-06-27 | Ecole Polytechnique Federale De Lausanne (Epfl) | Substance preparation method of capsules and system |
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DE1773584A1 (de) * | 1967-06-13 | 1973-01-04 | Xerox Corp | Reaktionsbehaelter |
US3713985A (en) * | 1970-10-19 | 1973-01-30 | Kantor F | Device and method for testing potency of biological control reagents |
SE380100B (de) * | 1974-02-07 | 1975-10-27 | Monega Anstalt | |
US4153512A (en) * | 1976-04-07 | 1979-05-08 | Fisher Scientific Company | Storage stable antibiotic susceptibility test kit and method of testing |
DE4118538C2 (de) | 1991-06-06 | 1994-04-28 | Maurer Friedrich Soehne | Zweistoffdüse |
DE4419759A1 (de) * | 1994-06-06 | 1995-12-07 | Birsner & Grob Biotech Gmbh | Kompartimentiertes Reaktionsgefäß |
WO1996028248A1 (en) | 1995-03-15 | 1996-09-19 | City Of Hope | Disposable reagent storage and delivery cartridge |
KR970050608U (ko) * | 1996-02-23 | 1997-09-08 | 이근지 | 다중발광 캐미라이트 |
EP0925113B1 (de) * | 1996-09-16 | 2002-07-24 | Alphahelix AB | Patrone und system zum speichern und verteilen von reagenzien |
US5804141A (en) * | 1996-10-15 | 1998-09-08 | Chianese; David | Reagent strip slide treating apparatus |
WO1998057738A1 (de) | 1997-06-16 | 1998-12-23 | Chemspeed Ltd. | Vorrichtung zur parallelen durchführung einer vielzahl von chemischen, biochemischen oder physikalischen verfahren |
-
2001
- 2001-08-09 DE DE50111741T patent/DE50111741D1/de not_active Expired - Lifetime
- 2001-08-09 EP EP01960017A patent/EP1309405B1/de not_active Expired - Lifetime
- 2001-08-09 WO PCT/CH2001/000485 patent/WO2002013969A1/de active IP Right Grant
- 2001-08-09 US US10/344,839 patent/US8709361B2/en active Active
- 2001-08-09 AT AT01960017T patent/ATE349275T1/de active
- 2001-08-09 CA CA002420100A patent/CA2420100C/en not_active Expired - Lifetime
- 2001-08-09 AU AU2001281631A patent/AU2001281631A1/en not_active Abandoned
Non-Patent Citations (1)
Title |
---|
See references of WO0213969A1 * |
Also Published As
Publication number | Publication date |
---|---|
WO2002013969A1 (de) | 2002-02-21 |
EP1309405B1 (de) | 2006-12-27 |
US20040235046A1 (en) | 2004-11-25 |
DE50111741D1 (de) | 2007-02-08 |
US8709361B2 (en) | 2014-04-29 |
CA2420100A1 (en) | 2003-01-31 |
CA2420100C (en) | 2009-07-14 |
AU2001281631A1 (en) | 2002-02-25 |
ATE349275T1 (de) | 2007-01-15 |
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