A continuous process for the preparation of Grignard adducts and device for its implementation

The invention relates to a continuous process for the preparation of Grignard adducts, in which the magnesium turnings are mechanically activated in-situ. Furthermore, the invention relates to a device for performing the method according to the invention.

Under the Grignard adduct is to be understood according to the invention a compound of general formula RMgX, wherein R is an alkyl or aryl group and X is a halide.

The Grignard reaction is a popular and frequently used method to make carbon-carbon bonds. Implementation and response technique of Grignard reaction are not changed in the last 100 years mainly.

Usually, the reaction is therefore carried out a batch or fed-batch culture in a batch process. However, a major disadvantage is the long induction period, which is required to activate magnesium. The alkyl or aryl halides can react with the Grignard compound until after the induction phase with the activated magnesium. Were to

Activation of the magnesium already added large amounts of alkyl or aryl halides also to be expected with a strongly exothermic and difficult to be controlled during the Grignard adduct formation. This represents a significant threat to the process reliability. In addition, occur in the set procedure often undesirable side reactions and it must be stirred after complete addition of Haloge-nids still at elevated temperature even in order to achieve complete conversion.

In both the batch method and in the known continuous processes, the Grignard reaction is initiated with special measures.

A chemical activation of magnesium is known for example from US 2,464,685. Here, the magnesium chips are activated by the addition of auxiliary reagent or already produced Grignard reagent. In DE 103 04 006 B3, the formation of the Grignard reagent is also carried out only with the addition of a solution of the halide to be reacted, or an iodine solution. Non-chemical measures to activate magnesium are described in GB 669 756 and DE 195 24 712th GB 669

756 relates to a continuous Grignard reagent synthesis is divided in magnesium by a permanently installed in the reactor cutter into smaller pieces, said fresh, reactive metal surface is produced. In DE 195 24 712, ultrasound is used as an activator in reactions between FLÜS sigen or gaseous and solid reactants.

Chemical activation is disadvantageous from a procedural point of view, as this requires the use of additional materials. however, the activation measures latter expensive equipment and are suitable for this reason, not for large-scale industrial application.

It is an object of the present invention to provide a process for the preparation of Grignard adducts which can be carried out continuously and in which the rule for activation of the magnesium does not have the known from the prior art drawbacks. The activation is effected mechanically in the process and do not require the use of ancillary reagents.

Furthermore, it was an object of the present invention to provide an apparatus for carrying out this method, which is simple apparatus and which is suitable for various production standards.

This object is achieved by the method having the features of claim 1. As regards the apparatus the object is achieved by claim 10 degrees. All other claims define advantageous variants of the invention.

In the continuous process for the preparation of Grignard adducts the reactor a stream consisting fed from an alkyl or aryl halide and an anhydrous solvent, and a further stream consisting of magnesium turnings. The magnesium turnings are thereby mechanically activated in the reactor by friction.

By this procedure, the Grignard active compound can be prepared without the addition of further chemicals in-situ and reacted without intermediate storage or time delay. This saves one process step (one unit operation). In addition, no other auxiliary chemicals such as in the case of chemical activation of magnesium must be stored, thereby reducing the number of the storage container is reduced.

Moreover, the inventive method allows a truly continuous process. While it is necessary in many processes of the prior art to interrupt the process to replenish fresh magnesium shavings magnesium chips in this process are continuously tracked.

The magnesium turnings advantageously have an average size of 0.5 to 3.0 mm.

The mechanical activation of the magnesium turnings is achieved in a process variant by friction of the magnesium chips to each other, preferably by friction caused by vibration, grinding movements, particularly preferably by friction caused by vibrations at a frequency of 20 to 200 Hz.

By friction of the magnesium chips to each other is the passivation layer which is located on the surface of the chips removed. It needed no further measures to activate the magnesium. In particular, to dispense with the addition of auxiliary chemicals. Contamination of the Grignard reagent or the Grignard adduct can be so excluded. Purity and quality of the product are improved accordingly.

The anhydrous solvent is preferably an ether, particularly preferably in diethyl ether, 2-methyl-tetrahydrofuran, tetrahydrofuran, mixtures thereof or mixtures thereof with other organic solvents, especially toluene.

The reactor is heated in one embodiment of the invention to a temperature of 10 to 60 ° C, preferably from 25 to 50 ° C, particularly preferably from 30 to 40 ° C.

Due to the low to moderate reaction temperatures, the reaction may be carried out controlled. The risk that there will be an energy input, which significantly increases the reaction rate undesirable, is low.

In addition, the alkyl or aryl halide to the reactor preferably in a concentration of 0.5 mol / l to 5.0 mol / l, particularly preferably fed in a concentration of 1.0 to 3.0 mol / l.

The high concentrations contribute to that cost savings

can be. It is less solvent than necessary in comparable methods from the prior art.

The mean residence time of the reagents in the reactor should preferably in the range from 1.0 to 20.0 minutes, more preferably from 3.0 to 15.0 minutes, very particularly preferably from 5.0 to 10.0 minutes, lie.

The short residence times will also be ensured without the use of a stirrer, the reaction mixture is well mixed. Each volume element is changed regularly and there are no dead zones.

The magnesium turnings advantageously so fed that is present in the reactor, a molar excess of magnesium turnings in relation to the alkyl or aryl halide, preferably an at least 5-fold molar excess, more preferably an at least 15-fold molar excess, in particular at least 25 -fold molar excess.

The method is preferably characterized in that the alkyl or aryl halide at the output of the reactor used preferably at least 90%, at least 95%, more preferably at least 99%, to the

Grignard adduct or with the reactor additionally supplied fed electrophilic reactant selected from the group consisting of aldehydes, ketones, Carbonsäureestern, thioesters, Boronsäureestern, nitriles, imines, epoxides, disulfides, carbon dioxide, other alkyl or aryl halides or other compounds containing active hydrogen contain polar or double bonds, and mixtures thereof is reacted.

By using the large magnesium excess in connection with the in-situ activation of the magnesium also comparatively slow reaction-aryl and alkyl chlorides may be used to represent the Grignard compound. This means considerable savings potential as aryl and alkyl chlorides in most cases in the acquisition are cheaper than comparable aryl and alkyl bromides.

Moreover, unwanted side reactions can be suppressed by the large excess of magnesium. Coupling of the starting material and product domestic product is effectively reduced.

The device for the preparation of Grignard adducts comprises a reactor with at least one tempering device, at least two inlets and an outlet, a device for mechanical activation and a

A device for continuous conveyance of the magnesium chips, at least one magnesium reservoir and at least one pump for delivering the alkyl or aryl halide.

The device for mechanical activation of the magnesium turnings is advantageously in a vibrator, a vibration and / or a grinding machine and is mounted on or in the reactor or is operatively connected with it for insertion of the shaking or vibratory motion.

The reactor has in one embodiment of the invention, connections and / or windows for analytical instruments and / or sensors, in particular for in-line temperature sensors, pressure sensors and / or optical analysis and display devices on.

Thus, the purity of the compounds can be monitored spectroscopically and it can take place online quality control. In addition, the actual values ​​for pressure, temperature can be detected and fed as actual value in the corresponding control circuits for controlling the process.

The reactor is also preferably a cylindrical inner reaction space, particularly preferably an inner reaction space with a geometric ratio of height: diameter of 3: 1 to 8: 1, particularly preferably an inner reaction space with a geometric ratio of height: diameter of 4: 1 to 6: 1 , to have.

As to the material, it is preferred that the reactor consists of metal, more preferably consists of stainless steel.

Thus it has a high resistance to corrosive substances. This can either be included in the reactants or products or act as intermediates in the Grignard reaction.

The inventive method is intended to e by the following example and the accompanying figures will be explained in greater detail without intending to limit this to the off guide die resulting therefrom.

Exemplary experimental procedure:

In a 3D sintered reactor 15 g filled fresh, untreated Magnesi-umspäne. Subsequently, the feed lines and a thermostat are connected to the reactor. In addition, a vibration motor is attached to the reactor. By switching on the vibration motor, the magnesium chips are first compressed in the interior of the reactor. The reactor is also heated before-by the thermostat to a temperature of 55 ° C to allow a fast initiation of the Grignard adduct. Then, an anhydrous solution of phenyl bromide in tetrahydrofuran is introduced at a concentration of 1 mol / L in the reactor. In order to promote the solution, a syringe pump is used and the flow rate is set at 2 ml / min.

Every few minutes inline-infrared spectra are taken to observe the course of the reaction. Even the first spectrum shows a peak which goes back to the Grignard reagent. The reaction is therefore immediately started. Complete conversion is reached after 15 min run time.

During the start-up phase, an increase is typically observed in temperature. The position of the temperature maximum is dependent on the level with magnesium turnings. As the temperature increases in the start-up phase in the reactor via the thermostat temperature addition, gentle boiling of the solvent THF is observed. The thermostat is then made according to a lower temperature.

Figure 1 shows the reaction equation and three IR spectra recorded at the beginning of the experiment, after the start and after reaching complete conversion.

By varying the flow rate and the temperature of the process can be optimized. In Figure 2 it can be seen that, for a doubling of the flow rate and a lowering of the temperature to 35 ° C incomplete conversion is observed.

Figure 3 shows a flow chart for the inventive method and shows the measuring instruments, analysis or display devices can be used for implementing the method, and the positions at which these are attached. In addition, it is shown that the starting materials are preferably introduced from below into the reactor. 4 The alkyl or Arylhalogenidlösung is conveyed by a pump through the feed line. 1 In addition, an electrophilic compound may optionally be carried out via the supply line 2 into the reactor. 4 The magnesium turnings are held in a storage tank 5 above the reactor. 4 To the reservoir 5 to a device for continuous conveyance of the magnesium chips M2 is mounted, while attached to the reactor 4 to a device for mechanical activation of the magnesium turnings Ml. The Grignard adduct or reaction product is removed from the upper part of the reactor 4 on the line. 3 The apparatus is characterized in that the magnesium turnings and sink in the reactor space opposite to the flow direction of the solution down there to form a layer, in which the chips bear against one another and is produced by a vibrating movement of friction between the chips.

claims

A continuous process for the preparation of Grignard adducts, be the one reactor a stream consisting of an alkyl or aryl halide and an anhydrous solvent, and a further stream comprising fed from magnesium turnings, characterized in that the magnesium turnings are mechanically activated in the reactor by friction ,

A method according to claim 1, characterized in that the magnesium turnings have an average size of 0.5 to 3.0 mm.

A method according to any one of claims 1 or 2, characterized in that the mechanical activation by friction of the magnesium chips to each other, preferably caused by vibration or grinding movements, particularly preferably triggered by vibrations having a frequency of 20 to 200 Hz occurs.

Method according to one of the preceding claims, characterized in that the solvent is an ether, preferably in diethyl ether, 2-methyl-tetrahydrofuran, tetrahydrofuran, mixtures thereof or mixtures thereof with other organic solvents, especially toluene, is.

Method according to one of the preceding claims, characterized in that the reactor is heated to a temperature of 10 to 60 ° C, preferably from 25 to 50 ° C, particularly preferably from 30 to 40 ° C.

Method according to one of the preceding claims, characterized in that the alkyl or aryl halide in a concentration of 0.5 mol / l to 5.0 mol / l, preferably in a concentration of 1.0 to 3.0 mol / l, is supplied.

Method according to one of the preceding claims, characterized in that the mean residence time of the reagents in the reactor is in the range from 1.0 to 20.0 minutes, preferably from 3.0 to 15.0 minutes, more preferably from 5.0 to 10, located 0 minutes.

Method according to one of the preceding claims, characterized in that the magnesium turnings are fed so that is present in the reactor, a molar excess of magnesium turnings in relation to the used alkyl or aryl halide, preferably an at least 5-fold molar excess, more preferably at least 15 -fold molar excess, in particular an at least 25-fold molar excess.

Method according to one of the preceding claims, characterized in that the alkyl or aryl halide at the exit of the reactor used, preferably at least 95%, more preferably at least 99% to the Grignard adduct or with a reactor fed fed in addition to at least 90% electrophilic reactant selected from the group consisting of aldehydes, ketones, Carbonsäureestern, thioesters, Boronsäureestern, nitriles, imines, epoxides, disulfides, carbon dioxide, other alkyl or

Aryl halides or other compounds containing active hydrogen or polar double bonds, and mixtures thereof is reacted.

A device for the preparation of Grignard adducts comprising a reactor with at least one tempering device, at least two inlets and an outlet, means for continuously conveying the magnesium turnings and a device for mechanical activation of the magnesium chips, at least one magnesium reservoir and at least one pump for delivering the alkyl or aryl halide.

Device according to claim 11, characterized in that the device for mechanical activation of the magnesium turnings in a vibrator, a vibration and / or a grinding material and is mounted on or in the reactor or is operatively connected with it for insertion of the shaking or vibratory motion.

12. The apparatus of claim 11 or 12, characterized in that the reactor connections and / or windows for analytical instruments and / or sensors comprising, in particular in-line temperature sensors, pressure sensors and / or optical analysis or display devices.

13. Device according to one of claims 11 to 13, characterized in that the reactor has a cylindrical inner reaction space, preferably an inner reaction space with a geometric ratio of height: diameter of 3: 1 to 8: 1, particularly preferably an inner reaction space with a geometric ratio of height: diameter of 4: 1 to 6: 1.

14. Device according to one of claims 11 to 14, characterized in that the reactor consists of metal, preferably made of stainless steel.