EP1723153A1

EP1723153A1 - Method for producing alkyl lithium compounds and aryl lithium compounds by monitoring the reaction by means of ir-spectroscopy

Info

Publication number: EP1723153A1
Application number: EP05733858A
Authority: EP
Inventors: Wilfried Weiss; Dirk Dawidowski; Walter Pleyer; Frank KRÜCKEL
Original assignee: Chemetall GmbH
Current assignee: Chemetall GmbH
Priority date: 2004-02-27
Filing date: 2005-02-24
Publication date: 2006-11-22
Also published as: CN1922192A; WO2005082911A1; DE102004009445A1; US20070152354A1

Abstract

The invention relates to a method for producing alkyl lithium compounds and aryl lithium compounds by reacting lithium metal with alkyl or aryl halogenides in a solvent, the concentration of the alkyl/aryl halogenide and the alkyl/aryl lithium compound being detected according to an in-line measurement in the reactor by means of IR spectroscopy, and an exact recognition of the end point of the dosing of the halogenide constituents being carried out by evaluation of the IR measurement. Said method enables an optimum reactive process and reaction yield. The identification of the respective concentration of the educt and the product is a reliable reactive process. The yield of the reaction is also optimised by determining the end point of the halogenide dosing, as is the purity of the product due to a lower concentration thereof during the reaction.

Description

Process for the preparation of alkyl lithium compounds and aryllithium compounds by reaction monitoring using IR spectroscopy

The invention relates to a method for producing alkyl lithium compounds and aryllithium compounds by reaction monitoring using IR spectroscopy.

Alkyl lithium compounds and aryllithium compounds are produced by the reaction of lithium metal with alkyl halides or aryl halides. The desired organolithium compound and the corresponding lithium halide are formed. A detailed description of this method can be found in WO 95/01982.

The reaction:

2 Li + R-Cl => Li-R + Li-Cl + by-products

is strongly exothermic (dH> -300 kJ / mol) and therefore bears a high risk potential if the reaction is uncertain. Follow-up reactions can also occur, such as the well-known Wurtz reaction:

Li-R + R-Cl => R-R + Li-Cl

or to free-radical or free radical-anionic side reactions, e.g.

Li + R-Cl => LiCI + R ^π => radical reactions of R ^π =>

which lead to reductive dehydrohalogenation or proportioning and thus reduce the purity and yield.

The reaction therefore requires constant control of the reaction. Inhibition of reaction and the formation of by-products and secondary products Avoid yourself only if you know the concentration of the reactants and run the reaction under optimal conditions.

In order to ensure a high reaction yield with regard to the alkyl or aryl halide used, lithium is usually used in excess, which means a loss of added value, since the metal is expensive to obtain by high-temperature electrolysis. It is therefore desirable to reduce the excess as much as possible and to use the starting materials as stoichiometrically as possible. Here, however, there is a risk that the reaction is easily run over and excess alkyl or aryl halide remains in the finished reaction solution and, as a result of the Wurtz reaction that then takes place, soluble or very fine lithium chloride is formed which interferes with the further use of the product.

Due to the heterogeneous reaction process, the following difficulties can arise during synthesis:

The start of the reaction can be delayed: the Li metal surface is often rendered inert and the reaction is inhibited; Accumulated alkyl or aryl halogen compounds can then react spontaneously, and the heat of reaction released suddenly can get out of control. (See WO 96/40692, where these adverse phenomena are described in detail.)

The course of the reaction can be disturbed: the Li halide that forms during the reaction encrusts the Li metal surface required for the reaction; the reaction may stop. By Wurtz-Kuppluπg

R-Li + R-Hal → R-R + Li-Hal

(R = alkyl radical or aryl.est, shark = halide) the yield decreases. This phenomenon occurs increasingly with increasing steric stress in the order n-, s-, t-alkyl halide. The formation of biphenyls is increasingly observed in the aryl halides.

Difficulties in temperature control can lead to high reaction temperatures at which the undesired Wurtz reaction is favored, as well as undesirable decomposition of the alkyl lithium compounds

Li-CH ₂ -CH ₂ -R → Li-H + CH ₂ = CH-R

may occur.

If the dosing of the alkyl or aryl halide is too fast, it accumulates and poses an increasing thermal hazard due to the high heat of reaction. The extent of by-products and secondary products also increases, which means less product yield and undesirably high impurities.

If the dosing of the alkyl or aryl halide is too slow, the reaction falls asleep and comes to a standstill, it has to be restarted with the dangers mentioned above.

Inaccurate detection of the end point of the reaction leads to incorrect dosing of the alkyl or aryl halide and thus to losses in yield and contamination in the product. On the one hand, it is to be avoided that active lithium remains in the reaction space, which leads to an insufficient yield in relation to lithium and to residues of active lithium which have to be decomposed dangerously. On the other hand, an overdose of alkyl or aryl halide leads to its remaining in the filtered reaction solution, which extends the post-reaction time. This in turn leads to subsequent reactions such as the Wurtz reaction, the product yield is reduced and a particularly fine lithium chloride is formed. This can still be used as ionic chloride Detect for a long time in the reaction solution ultimately precipitates in a very fine form and leads to considerable problems in the filtration.

In order to master the difficulties listed, it is desirable to always know the concentration of the alkyl or aryl halide and the concentration of the alkyl or aryllithium compound in the reaction mixture, in order to be able to draw conclusions about the course of the reaction and also from a safety point of view to be able to avoid heat build-up.

DE 10162332 A1 proposes to follow the reaction by measuring the heat. However, this is only a very general method and involves many error variables, such as heat transfer and radiation, pressure and temperature fluctuations, etc. Furthermore, DE 10162332 A1 generally suggests analyzing the alkyl halide content using an IR spectrometer.

Hardwick (Philip Hardwick, "FT-IR Applications in Alkyllithium Manufacturing", Fine, Specialty & Performance Chemicals, June 2002) suggests using Fourier Transform IR spectroscopy in the near-IR range for the dilution of concentrated alkyl lithium solutions. Near-IR (NIR) means the wavelength range from 0.75 to 2.5 μm (Römpp, Chemie-Lexikon). The system described by Hardwick provides for the IR light beam to be guided back and forth to the sample space by means of glass fibers, whereby the measurement can be carried out in transmission or reflection. Sapphire windows are used. The disadvantage of this system is a non-product-specific measurement in the NIR range, i.e. the measurement requires calibration. This system also cannot be used to monitor the reaction of Li metal with alkyl halides, since the Li metal attacks the sapphire windows and it is not possible to distinguish between the harmonics of the starting material and product in this wavelength range.

The object of the invention is therefore to overcome the disadvantages of the prior art and to show a method in which the specific Concentrations of the alkyl halide used and the alkyl lithium compound obtained in the reaction mixture are indicated.

The object is achieved by a process for the preparation of alkyl or aryllithium compounds by reacting lithium metal with alkyl or aryl halides in a solvent, the concentration of the alkyl or aryl halide and of the alkyl or aryllithium compound being measured by in-line measurement in the reactor IR spectroscopy is recorded.

This enables optimal reaction management and reaction yield. This knowledge of the respective concentration of starting material and product ensures reliable reaction management.

FTIR spectroscopy allows the solution concentrations of starting materials, products as well as by-products and by-products to be recorded in short time intervals (e.g. 2 seconds to 2 minutes). With a suitable arrangement, the sensitivity of the detection goes down to the range of 0.01%. This makes IR spectroscopy a suitable means of monitoring the progress of a reaction in solution. The IR absorption is linked to the concentration via the Lambert-Beer law, the intensity of the absorption serves as a measure, its relative course can thus be used as a semi-quantitative criterion for the evaluation without calibration. However, a defined wavelength range can also be calibrated specifically and thus enables an exact quantitative determination of the concentration.

The benefits for the synthesis of lithium organyls in the manner described above can be illustrated as follows:

The solid Li _(s) decreases in the course of the reaction with the alkyl aryl halide (for example R-Cl), insoluble Li halide ( _S ) being formed which grows on the Li surface, covers it and the desired reaction withdraws.

The following generally applies to the reaction rate of the synthesis: RG = - 1 / α * d [R-Cl] / dt = k „[Li-R] ^p [Li-Cl] ^q [by-products] '/ [Li] ^s

In the reaction solution, the concentrations of R-Cl and Li-R and, in certain cases, those of the by-products and secondary products can be determined using IR spectroscopy. The insoluble components Li _(S ) and LiCI _(S) cannot be determined, so that the above equation is simplified and can be evaluated via the concentration curve of R-Cl and R-Li:

RG = - 1 / α * d [R-Cl] / dt = k _m [Li-R] ^p

The course of the concentration profiles of R-Cl and R-Li over time can thus be used as an aid for assessing the course of the reaction. It is now possible to vary the reaction conditions and to assess their influence on the course of the reaction. This makes IR spectroscopy a tool that helps to achieve the optimum yield of Li-R, increase product purity and reduce the formation of by-products and secondary products, so that real process optimization can take place.

To increase the sensitivity of the measurement arrangement of the FTIR device, some optimization measures are recommended:

The light paths must be kept short and losses due to stray light avoided, which is achieved by using focusing mirrors. Recent developments are towards developing suitable fiber optic cables.

A particularly sensitive detector is also necessary, preferably it is cooled with liquid nitrogen (MCT detector). Recent developments aim at the use of Peltier elements. The required detection limit for the alkyl or aryl halide is in the range of 0.1 - 0.01%

It is also preferred to carry out the measurements under a protective gas such as nitrogen or argon. The IR device must be operated under explosion protection, or must e.g. separated by a protective wall in a non-explosion-proof

Stand space isolated. If the optics break, a shut-off valve ensures that the pyrophoric product suspension cannot come into contact with the hot IR source and the electrical components. External influences on the IR source and the laser, such as temperature fluctuations, should be avoided, which is done by a special thermostat.

Likewise, the light beam and the IR source must be protected from moisture and CO ₂ , which is done by flushing with protective gas such as argon or nitrogen.

It is also necessary to use a voltage regulator and damper to ensure stable operation of the device and to protect against failures.

The device can be controlled via a PLC. The device can be controlled using specially written macros and, if necessary, "switched" to another product in which the quantification of the starting material and the product are stored.

A test can be carried out using a macro (comparison of master background with newly recorded background), which indicates whether the system is operating normally.

Via a specially built-in window in the IR device, you can determine from an LED display whether the ball valve has closed due to a liquid intrusion or excessive pressure in the arm.

The sensor (diamond window) is cleaned after each reaction via a dip tube using a spray of the solvent used.

A commercially available device in the IR range of 600 - 4000 cm ^{"1 is} used as the IR device (for example ASI / Mettler-Toledo: ReactIR or MP). The alkyl / aryl halide and the alkyl / aryllithium compound are identified using a substance-specific one or statistically developed method (chemometric, for example with the help of the Mettler / ASI software ConcIRT) and serves as the basis for the quantitative Detection of the concentration of starting material and product, which is determined on a substance-specific basis,

eg band-specific in the fingerprint area: cm ^"1 cm ^{" 1} Me-Li = 957, 1056 Me-Cl = 667

Et-Li = 903, 1077 Et-Cl = 660.973, 1281 n-BuLi = 968, 1376 n-BuCI = 660.729 958.1243 s-Buli = 807.908, s-BuCI = 615.670.845 1057, 1158.1329 i-Buli = 799.938 , i-BuCI = 690.737, 1011.1158.1363 1262 t-Buli = 772.945 t-BuCI = 576.810, 1130 1158.1270 Hex-Li = 872.946 Hexyl-Cl = 652.729, 1042 1463

Ph-Li = 702 Ph-Cl = 683, 702, 737.903, 1023, 1085, 1447

There are several options for assignment and different methods for evaluation and quantification, such as

- Band height, band area - Height or area to zero line - Height or area to baseline - Height or area to a baseline point Height or area to 2 baseline points - or using statistical methods such as P-Matrix or PLS (partial least square). The sensitivity of the detection of a component can be increased if the solvent is subtracted and / or the changes in a spectrum are also subtracted from one another.

The possibility of quantification results from the application of Lambert-Beer law, which describes the relationship between the absorbed light and substance concentration:

Ig l ₀ / l = e * c * d = E

after which the absorption at a certain wavelength is proportional to the concentration c and the irradiated layer thickness d. The size l _0/1 is the intensity ratio before and after the sample run, the Ig is called extinction (absorption) and e the extinction coefficient (M. Hesse, Spectroscopic Methods in Organic Chemistry, Georg Thieme Verlag 1991)

By determining the concentration of starting material and product in the reaction mixture, the reaction can be optimally managed in terms of safety and conversion. This is particularly evident when other methods such as measuring the temperature or heat dissipation are too imprecise or fail completely, e.g. is the case with reactions in a vacuum, where a simultaneous dependence on pressure / temperature and heat transfer is difficult. However, this vacuum mode of operation is preferred if thermal stress and undesired secondary and subsequent reactions (Wurtz reaction, decomposition) are to be avoided.

The subject matter of the invention is illustrated by the following examples. The principle of reaction monitoring by means of IR is first illustrated using the example of the synthesis of t-butyllithium. It is made qualitatively clear here that only a certain amount of t-butyl chloride may be metered in in order to achieve a maximum product yield, in this case not the usual stoichiometry according to: 2 Li + 1 R-Hal => 1 R-Li + 1 LiCI

but according to

3 Li + 1 t-BuCI => 1 t-BuLi + 1 Li / ΪLiCI

It must be observed, since the lithium is coated with LiCI and then a further penetration of the voluminous t-butyl chloride through the LiCI shell is no longer possible for steric reasons.

Example 1: Production of t-butyllithium in pentane at 20 ° C., determination of the optimal stoichiometry,

10.5 g of lithium powder (1518 mmol) in 300 ml of pentane were placed in the reactor at 20 ° C. and activated with 10 ml of prefabricated t-Buli solution. 70.3 g of t-butyl chloride (759 mmol = 100 mol%) were then metered in continuously over 144 minutes.

Figure (1) shows the observed course, with the IR absorption bands for: t-butyl chloride, t-butyllithium and 2-methylpropene as a by-product:

From the course of the reaction it is easy to determine that the maximum t-butyllithium formation is reached at a dosage time of 96 minutes, corresponding to an amount of 66.6 mol% of t-butyl chloride; with further dosing there is a side reaction with the formation of 2-methyl-propene and the breakdown of already formed t-butyllithium by the Wurtz reaction. From a semi-quantitative perspective, the t-butyllithium content drops by 84% from a maximum of = 66% at 108 minutes to 55% at the end of the reaction = 160 minutes (relative).

A product yield of 263 mmol (35% yield) was isolated. In the

Balance sheet means that with an optimal dosage of 66 mol% t

Butyl chloride a yield of 506 mmol t-butyllithium could have been achieved, but this by the further addition of 33 mol% = 253 mmol t- Butyl chloride was reduced again to 505-253 = 251 mmol by side reactions.

The explanation is trivial: the lithium is surrounded by a layer of lithium chloride at a dosage of 66.6 mol%. As a result, the t-butyl chloride diffuses and reacts in proportion to butane and 2-methyl-propene and / or reacts under the Wurtz reaction. The conversion of lithium with t-butyl chloride is therefore most advantageously carried out using a stoichiometry according to:

3 Li + 1 t-BuCI => 1 t-Buli + 1 Li / LiCI

the metering rate of the t-butyl chloride being regulated so that as little as possible accumulates in the reaction solution.

Example 2: Preparation of t-butyllithium in cyclohexane at 40 ° C, stoichiometry: + 83 mol% t-butyl chloride

13.8 g of lithium powder (1984 mmol) in 180 g of cyclohexane were placed in the 500 ml double-jacket reactor, activated with 6 g of prefabricated t-Buli solution and heated to 40.degree. A mixture of t-butyl chloride, which contained 1% MTBE, was metered in.

Figure (2) shows the course of the reaction, autoscaled with the y-axis as the IR absorption band of t-butyl chloride (not quantified, i.e. in analogy to Lambert-Beer law):

To start the reaction, 3 times 1 ml of t-butyl chloride was metered in, the accumulation and the subsequent degradation can be seen to form t-butyllithium.

The t-butyl chloride was added continuously over a period of 1.25 hours to 3.0 hours, and a total of 76.5 g of t-butyl chloride (826 mmol) were metered in. From the course it can easily be seen that the t-butyichloride first accumulates, up to a maximum of 0.0108 absolute at 1.5 hours, and then drops off at 1.7 hours = 0.0046 absolute. Thereafter, the t-butyl chloride rose steadily and more or less uniformly to the end of the dosage at 3 hours to 0.010 absolute, and then decreased again during the after-reaction.

The corresponding curve, Figure (3), with the y-axis as the IR absorption band of t-butyllithium is shown below:

At the beginning of the continuous metering, the IR band height of the t-butyllithium was 1.5 hours = 0.0164 absolute. At the end of the dosing, the band height at 3.0 hours = 0.208 absolute. Then it increased again slightly during the post-reaction, at the end of 4 h it is 0.212 absolute.

The theoretically calculated value for the yield of t-butyllithium is 22.8% (826 mmol), analytically found 12.7% (410 mmol), corresponding to a yield of only 50%. Only 62% of the optimal (66.6 mol% based on Li =) 660 mmol was reached. From the comparatively stable final concentration of t-butyllithium it can only be concluded that under the given reaction conditions (40 ° C in cyclohexane) there is already a considerable side reaction, i.e. the formation of 2-methyl-propene and 2-methylpropane (250 mmol = 30 mol%), and the Wurtz reaction (166 mmol = 20 mol%).

The example shows that in order to increase the yield it is necessary to keep the concentration of t-butyl chloride as low as possible in order to avoid undesired side reactions.

Example 3: Preparation of n-butyllithium, reaction at the boiling point

A dispersion of about 250 kg of lithium powder with a content of 1-3% sodium in 1400 kg of hexane was placed in the reactor. The dosage of the n Butyl chloride was carried out in 3 phases with varying dosing speeds for the start phase, main phase and end phase:

The total time was approx. 280 minutes (4.6 h). The heat of reaction released of approx. 335 kJ / mol of butyl chloride was used in the 1st phase (light-off phase) to heat the reaction mixture from room temperature to the boiling point temperature, during phases 2 and 3 the heat of reaction was then removed via evaporative cooling. With a theoretical amount of 1632 kg of n-butyl chloride, a product solution with a content of 44.2% butyllithium (with 100% conversion) would be obtained.

Figures (4) and (5) show (autoscaled) the course of the reaction with the quantified values for n-butyllithium and n-butyl chloride.

In Figure (4) the y-axis (in% by weight) is assigned to n-butyllithium:

In Figure (5) the abscissa (% by weight) is assigned to n-butyl chloride:

It can be seen that the reaction started almost immediately, but a slight content of n-butyl chloride persisted for up to 30 minutes, which then dropped back to 0 by about 3 hours (with a butyllithium content of about 31%) to increase. The dosing of the n-butyl chloride was stopped at a content of 0.7%. The butyllithium content here was 41.8%.

Up to this point (280 minutes), 1577 kg of n-butyl chloride had been metered in. The resulting theoretical concentration of n-butyllithium is 43.3%, analytically a content of 42.1% was found, corresponding to a yield of 97.1% based on n-butyl chloride.

Example 4: Preparation of n-butyllithium

The reactor was filled with the Li dispersion as described above and reacted with n-butyl chloride in the manner described. Figure (6) shows the autoscaled IR diagram with the content of n-butyl chloride as the y-axis: You can see a slight accumulation of n-butyl chloride in the start-up phase and again an increasing increase after 3 hours of dosing (30.7% n-butyllithium), the dosing was stopped after 4 h 26 minutes, with a n-butyl chloride content of 0 , 92% and a metered amount of 1581 kg.

Figure (7) shows the corresponding autoscaled diagram with the y-axis as the concentration of n-butyllithium.

One sees the continuous increase from n-butyllithium to the end of dosing at 4 hours and 44 minutes to a content of 41.0%, during the post-reaction the butyllithium content rises slightly to 41.1% at 6 hours and 20 minutes.

The calculated concentration in this case amounts to 43.4% n-butyllithium, analytically a content of 41.1% was found, corresponding to a yield of 94.7% based on n-butyl chloride.

Example 5: Production of s-butyllithium in vacuum at 40 ° C and a pressure of 290 mbar

This example demonstrates that a quantification of the IR bands is not absolutely necessary, but - based on the validity of the Lambert-Beer law - also about the band height a tracking and semi-qualitative evaluation of the reaction is possible.

A dispersion of 230 kg of lithium and 4 kg of sodium in 1450 kg of hexane was placed in the reactor at room temperature and the vacuum was set to 290 mbar. The s-butyl chloride was metered in in the manner mentioned above, that the reaction was first started in a start-up phase. After the reaction had started, the reaction mixture warmed to the boiling point (40 ° C./290 mbar) as a result of the heat of reaction liberated and the s-butyl chloride was metered in continuously. The end point of the dosage was experimentally set to a maximum value Band height of the s-butyl chloride with which the highest yield of s-butyllithium was achieved.

Figure (8) shows the IR curve with the IR band height of the s-butyl chloride as the y-axis in an auto-scaled representation

One can clearly see the accumulation of s-butyl chloride during the starting phase, which subsided after 1 hour and 15 minutes and is followed by an only gradually increasing content of s-butyl chloride until the addition at 5 hours and 40 minutes at a band height of 0 , 00154 is stopped.

The illustration clearly shows that at the end of the dose the concentration of s-butyllithium with an IR level of 0.48 is below the maximum concentration at 5 h 52 minutes with an IR level of 0.49, which is explained by a subsequent reaction.

See the corresponding autoscaled representation of the reaction with the y-axis as IR height for s-butyllithium: Figure (9)

A theoretically calculated concentration of 43.8% contrasts with an analytically found concentration of 41.8%, corresponding to a yield of 95.4% based on s-butyl chloride. ,

Example 6: Production of hexyllithium in vacuum at 40 ° C and a pressure of 290 mbar

A dispersion of 180 kg of lithium and 4 kg of sodium in 1050 kg of hexane at RT was placed in the reactor and the vacuum was set to 290 mbar. The n-hexyl chloride was metered in in the manner mentioned above, so that the reaction was first started in a starting phase , After the reaction had started, the reaction mixture warmed up to the boiling point (40 ° C./290 mbar) due to the heat of reaction being released and the n-hexyl chloride was metered in continuously. The end point was fixed to a maximum value of the band height of the n-hexyl chloride, which in this case was 1440 kg, which corresponds to a theoretical final concentration of 51.1%. A concentration of 48.8% was found, corresponding to a yield of 95.5% based on n-hexyl chloride. The corresponding IR diagram (Figure 10) with hexyllithium (relative as ordinate) shows the continuous increase in concentration up to the end of the reaction at 260 minutes (dosing time + after-reaction).

The corresponding IR diagram (Figure 11) with hexyl chloride (relative as ordinate) shows the accumulation in the reaction mixture from 150 minutes to the end of the dosing at 235 minutes (relative IR maximum = 0.00264), then the rapid decrease during the short post-reaction until 260 minutes

Example 7: Preparation of Pheπyllithium in dibutyl ether at 35 ° C.

14.3 g of lithium powder (2065 mmol) were placed together with 0.2 g of lithium hydride in 200 g of dibutyl ether with 0.6 g of biphenyl as catalyst (4 mmol) in a jacketed reactor at T (i) = 35 ° C. The reaction was initiated by adding 2.4 g of chlorobenzene. After the reaction had started successfully, 96.5 g of chlorobenzene (857 mmol) were metered in continuously over the course of 4 hours and the reaction was continued for 2 hours. A sample is taken, it showed a reaction conversion of 98.3% with a content of 3.091 mmol phenyllithium / g. The reaction mixture was cooled to room temperature and stirred overnight. The renewed sampling showed a content of 3.037 mmol phenyllithium / g corresponding to a conversion of 96.6% based on chlorobenzene.

The course of the IR bands for phenyllithium (relative as ordinate) is shown in Figure 12.

You can see the start of the reaction and the slow post-reaction after the end of dosing at 4500 minutes (= maximum chlorobenzene). In comparison, the corresponding IR diagram with chlorobenzene (relative as ordinate) shows the delayed rise at the start of the reaction and clearly the slow decay during the post-reaction (Figure 13).

Claims

claims

1. A process for the preparation of alkyl and aryl lithium compounds by reaction of lithium metal with alkyl or aryl halides in a solvent, characterized in that the concentration of the alkyl / aryl halide and the alkyl / aryl lithium compound by in- Iine measurement in the reactor is recorded by means of IR spectroscopy.

2. The method according to claim 1, characterized in that an IR spectrometer in the wavenumber range 600 to 4000 cm ^"1 is used.

3. The method according to claim 1 or 2, characterized in that an absolute total reflection cell (ATR cell) with a diamond sensor and high sensitivity is used as the IR probe, the ATR cell being immersed directly in the reaction mixture and undergoes a special seal, the measuring arrangement being explosion-protected and being flushed with an inert gas such as argon or nitrogen.

4. The method according to any one of claims 1 to 3, characterized in that the complete measuring arrangement is equipped with a safety valve to prevent the emergence of pyrophoric material in the event of mechanical damage to the sensor.

5. The method according to any one of claims 1 to 4, characterized in that the device is thermostatted and secured against external electrical fluctuations to ensure stable measured value acquisition.

6. The method according to any one of claims 1 to 5, characterized in that aliphatic (such as methyl lithium, ethyl lithium, propyllithium, butyllithium with all isomers, hexyllithium, octyllithium) or aromatic lithium alkyl compounds (such as phenyllithium, tolyllithium, mesityllithium) are obtained.

7. The method according to any one of claims 1 to 6, characterized in that the solvent is aliphatic hydrocarbons (such as pentane, hexane, heptane, octane) and cycloaliphatic hydrocarbons (such as cyclopentane, cyclohexane or methylcyclohexane) or aromatic hydrocarbons (such as toluene, xylene or mesitylene ) or ethers (such as diethyl ether, diisopropyl ether, dibutyl ether, methyl tert-butyl ether, tetrahydrofuran, 2-methyltetrahydrofuran) or mixtures thereof.

8. The method according to any one of claims 1 to 7, characterized in that the method is carried out at normal pressure or in a vacuum or in the overpressure range.

9. The method according to any one of claims 1 to 8, characterized in that the method is carried out at temperatures from - 120 ° C to 100 ° C.