Method for manufacturing magnesium amides

Abstract

A method for manufacturing amidomagnesium halogenides and admixtures thereof with alkali metal salts in aparotic, organic solvents, compounds obtained according to the method and use thereof in synthesis chemistry, for example for deprotonizing enolizable systems, functionalized aromatics and heteroaromatics.

Claims

1. A process for forming an amidomagnesium halogenide of formula RRNMgX, the process comprising: reacting, in an aprotic organic solvent or solvent mix, magnesium and an organic halide of formula R.sup.1X in the presence of a protic amine of formula RRNH and an alkali metal salt of formula MY to produce a mixture comprising an amidomagnesium halogenide of formula RRNMgX and an alkali metal salt of formula MY; wherein: the organic halide of formula R.sup.1X is selected from the group consisting of methyl chloride, methyl bromide, ethyl chloride, ethyl bromide, n-propyl chloride, iso-propyl chloride, n-propyl bromide, iso-propyl bromide, n-butyl chloride, sec-butyl chloride, tert-butyl chloride, n-butyl bromide, sec-butyl bromide, tert-butyl bromide, n-pentyl chloride, iso-pentyl chloride, sec-pentyl chloride, tert-pentyl chloride, n-pentyl bromide, iso-pentyl bromide, sec-pentyl bromide, tert-pentyl bromide, n-hexyl chloride, n-hexyl bromide, chlorobenzene, bromobenzene, benzyl chloride and benzyl bromide; M is lithium, sodium or potassium, Y is selected from the group consisting of chloride, bromide, iodide and OZ, wherein OZ represents an alcoholate anion and Z is selected from an organic, branched or unbranched, saturated or unsaturated aliphatic or aromatic carbon fragment which is between one and 20 carbon atoms or is selected from R.sup.2R.sup.3R.sup.4Si, wherein R.sup.2, R.sup.3 and R.sup.4 are independently selected from the group consisting of saturated, unsaturated, branched, unbranched, functionalized, unfunctionalized aliphatic, cyclic, heterocyclic or aromatic organic fragments of 1 to 20 carbon atoms; and the protic amine of formula RRNH is selected from the group consisting of dimethylamine, diethylamine, di-n-propylamine, di-iso-propylamine, di-n-butylamine, di-sec-butylamine, di-tert-butylamine, dicyclohexylamine, N-tertbutyl-iso-propylamine, hexamethyldisilazane, piperidine, and 2,2,6,6-tetramethylpiperidine, wherein the molar ratio of RRNH to R1X is between 0.7 to 1.5.

2. The process of claim 1, wherein the magnesium is in the form of chips, shavings, raspings, granules or a powder.

3. A process according to claim 1, wherein the magnesium is activated by addition of iodine, trimethylsilyl chloride, a previously prepared Grignard solution of formula R.sup.1MgX or a previously prepared product RRNMgX or admixtures thereof with an alkali metal salt.

4. A process according to claim 3, wherein the Grignard solution of formula R.sup.1MgX or previously prepared product RRNMgX and or admixtures thereof with an alkali salt is in an amount between 0.01 and 50 mol % relative to the magnesium.

5. A process according to claim 1, wherein the magnesium is in an excess of between 10 and 200% relative to the organic halide of formula R.sup.1X.

6. A process according to claim 1, wherein the aprotic organic solvent is a mixture of ethers and hydrocarbons.

7. A process according to claim 1, wherein the organic halide of formula R.sup.1X forms volatile gases during the process.

8. A process according to claim 1, wherein the wherein R.sup.1, R.sup.2, R.sup.3, R.sup.4, R and R are independently selected from the group consisting of: methyl, n-propyl, iso-propyl, n-butyl, sec-butyl, tert-butyl, pentyl, hexyl, heptyl, octyl, cyclohexyl, phenyl, and benzyl.

9. A process according to claim 1, wherein the product RRNMgX has a concentration between 5 and 80 wt %.

10. A process according to claim 1, wherein M is lithium or potassium.

11. A process according to claim 10, wherein the alkali metal salt is selected from the group consisting of lithium chloride, lithium bromide, lithium methoxide, lithium ethoxide, lithium n-propoxide, lithium-iso-propoxide, lithium tert-butoxide, lithium tert-amoxide, lithium trimethysilyl oxide and lithium tri-tert-butylsilyl oxide.

12. A process according to claim 1, wherein an excess of 0-50% of alkali metal salt, based on the desired molar ratio of MY to RRNMgX, is provided.

13. A process according to claim 7, wherein an excess of 0-50% of alkali metal salt, based on the desired molar ratio of MY to RRNMgX, is provided.

14. A process according to claim 1, wherein: the organic halide is metered into the aprotic organic solvent or solvent mix after the magnesium and the protic amine are placed in the aprotic organic solvent or solvent mix; or the protic amine and the organic halide are metered into the aprotic organic solvent or solvent mix either as a mixture or individually in parallel, after the magnesium is placed in the aprotic organic solvent or solvent mix.

15. A process according to claim 1, wherein the process comprises reacting, in the aprotic organic solvent or solvent mix, ingredients consisting of magnesium, the organic halide, the protic amine, and the alkali metal salt.

Description

EXAMPLES

(1) The invention is explained with the aid of the following examples without being limited to them. Specialists trained in the field of chemistry will recognize that these examples also point to other procedures that are not specified here in order to obtain the amidomagnesium halogenides (RRNMgX) that are produced in accordance with the invention and the admixture thereof with alkali-metal salts (MY). Many variations and modifications are therefore possible that constitute subject matter of the present invention.

(2) All the experiments were carried out in an argon atmosphere with the use of Schlenk techniques. Technical raw materials were employed. As regards magnesium, Mg-raspings were employed, although in accordance with the invention other grades of magnesium that are suitable for Grignard production can also be used.

(3) In order to illustrate the efficiency of the method, the production of TMPMgCl/LiCl in THF and in THF/toluene, of TMPMgCl in THF/toluene and also of DIPAMgCl/LiCl in THF/toluene was chosen. In order to produce TI-IF solutions iso-propyl chloride was used as the organic halogenide (R.sup.1X); in order to produce THF/toluene solutions benzyl chloride was used. It is known that organic bromides (R.sup.1Br) are generally better suited for Grignard production than the corresponding chlorides (R.sup.1Cl). Thus the choice made underlines the generality of the method. LiCl was chosen as the alkali metal salt, although other alkali-metal salts that are soluble in the medium can also be used.

(4) The examples are explained in the following. The precise quantities of the preparation, excesses, reaction and metering times and also reaction and metering temperatures are specified in Tables 1, 3 and 5. The results of analysis and evaluation of the experiments, including the yields, are specified in Tables 2, 4 and 6.

(5) The precise content and the composition of the charges were determined analytically. The content of magnesium was determined complexometrically, the content of lithium by flame-emission spectroscopy, the content of chloride argentometrically, the content of total base acidimetrically and the amine content according to Kjeldahl after hydrolysis. The active base was determined according to Watson-Eastham.

(6) The identity and purity of the isolated products was confirmed by GC/MS investigations after derivatization and .sup.1H- and .sup.13C-NMR measurements.

Example 1: Production of TMPMgCl/LiCl in THF/Toluene from Mg, LiCl, TMPH and Benzyl Chloride with Activation of the Magnesium with TMPMgCl/LiCl in THF/Toluene

(7) Magnesium, THF, lithium chloride, TMPMgCl/LiCl in THF/toluene are suspended in a double-jacket reactor with stirrer, metering station and reflux condenser and stirred for 30 minutes at room temperature. Subsequently, the total quantity of TMPH is added quickly in one portion. Then approximately 5 mol % of the total quantity of benzyl chloride were added quickly. The initiation of the reaction could be established by an immediate noticeable rise in temperature. The residual quantity of benzyl chloride was metered continuously. After a secondary reaction, the solution was filtered. A brownish, clear solution was obtained.

Example 2: Production of TMPMgCl in THF/Toluene from Mg, TMPH and Benzyl Chloride with Activation of the Magnesium with TMPMgCl in THF/Toluene

(8) Magnesium, THF, TMPMgCl in THF/toluene are suspended in a double-jacket reactor with stirrer, metering station and reflux condenser and stirred for 30 minutes at room temperature. Subsequently, the total quantity of TMPH was added quickly in one portion. Then approximately 5 mol % of the total quantity of benzyl chloride were added quickly. The initiation of the reaction could be established by an immediate noticeable rise in temperature. The residual quantity of benzyl chloride was metered continuously. After a secondary reaction, the solution was filtered. A brownish, clear solution was obtained.

Example 3: Production of TMPMgCl/LiCl in THF from Mg, LiCl, TMPH and iso-PrCl with Activation of the Magnesium with Iso-PrMgCl in THF

(9) Magnesium, THF, lithium chloride and iso-PrMgCl in THF are suspended in a double-jacket reactor with stirrer, metering station and reflux condenser and stirred for 30 minutes at room temperature. The total quantity of TMPH was added quickly in one portion. The quantity that is required for the reaction of iso-PrMgCl with TMPH to give the desired product according to Figure 1 is taken into consideration in the total quantity of TMPH. Approximately 5 mol % of the total quantity of iso-PrCl were added quickly. The initiation of the reaction could be established by an immediate noticeable rise in temperature. The residual quantity of iso-PrCl was metered continuously. After a secondary reaction, the solution was filtered. A brownish, clear solution was obtained.

Example 4: Production of DIPAMgCl/LiCl in THF/Toluene from Mg, LiCl, DIPAH and Benzyl Chloride without Activation of the Magnesium

(10) Magnesium, THF, lithium chloride and the total quantity of DIPAH are placed in a double-jacket reactor with stirrer, metering station and reflux condenser. Approximately 5 mol % of the total quantity of benzyl chloride were added quickly. The initiation of the reaction could be established by an immediate noticeable rise in temperature. The residual quantity of benzyl chloride was metered continuously. After a secondary reaction, the solution was filtered. A brownish, clear solution was obtained.

(11) TABLE-US-00001 TABLE 1 Production parameters for TMPMgCl/LiCl in THF/toluene and TMPMgCl in THF/toluene Metering Secondary TMPH BC.sup.1 Mg LiCl Mg-activation Temp. time reaction Example g mmol g mmol g mmol g mmol THF g mmol substance C. min min C. 1 85.91 608.17 67.22 531.01 26.8 1102.4 29.45 694.74 287.8 20.90 TMPMgCl.sup.2 25 240 120 25 2 78.00 552.17 66.95 528.87 24.9 1024.3 515.2 21.50 TMPMgCl.sup.3 25 300 120 25 .sup.1BC = benzyl chloride; .sup.2TMPMgCl/LiCl in THF/toluene: active base AB = 0.96 mmol/g; .sup.3TMPMgCl in THF/toluene: active base AB = 0.66 mmol/g.

(12) TABLE-US-00002 TABLE 2 Results for the Examples from Table 1 OH Mg Cl Li TMPH AB.sup.1 LiCl.sup.2 Ratio Yield.sup.3 Concentration Example mmol/g mmol/g LiCl:AB % AB.sup.4 % LiCl.sup.5 % TMPH.sup.5 Weight % 1 2.30 1.10 2.18 1.03 1.23 1.05 1.03 0.98 91.3 68.5 93.4 21.0 2 1.50 0.75 0.77 0.77 0.71 88.6 92.1 13.8 .sup.1AB = active base; .sup.2over Li; .sup.3isolated yield without wash solutions; .sup.4relative to quantity of benzyl chloride BC; .sup.5relative to quantity used.

(13) TABLE-US-00003 TABLE 3 Production parameters for TMPMgCl/LiCl in THF Metering Secondary TMPH iso-PrCl Mg LiCl Mg-activation time reaction Example g mmol g mmol g mmol g mmol THF g mmol substance Temp. C. min min C. 3 89.30 632.17 44.80 570.41 16.0 659.8 25.34 597.78 340.7 56.80 iso-PrMgCl.sup.1 45 200 90 45 .sup.1iso-PrMgCl in THF: active base AB = 1.33 mmol/g.

(14) TABLE-US-00004 TABLE 4 Results for the Examples from Table 3 OH Mg Cl Li TMPH AB.sup.1 LiCl.sup.2 Ratio Yield.sup.3 Concentration Example mmol/g mmol/g LiCl:AB % AB.sup.4 % LiCl.sup.5 % TMPH.sup.5 Weight % 3 2.33 1.08 2.19 1.11 1.23 1.07 1.11 1.04 92.4 91.4 95.8 21.4 .sup.1AB = active base; .sup.2over Li; .sup.3isolated yield without wash solutions; .sup.4 relative to quantity of iso-PrCl; .sup.5relative to quantity used.

(15) TABLE-US-00005 TABLE 5 Production parameters for DIPAMgCl/LiCl in THF/toluene Metering Secondary DIPAH.sup.1 BC.sup.2 Mg LiCl Mg-activation time reaction Example g mmol g mmol g mmol g mmol THF g mmol substance Temp. C. min min C. 4 69.27 684.55 82.67 653.05 33.5 1375.98 30.10 710.07 772.9 25-35 260 25 100 .sup.1DIPAH = Di-iso-propylamine; .sup.2BC = benzyl chloride.

(16) TABLE-US-00006 TABLE 6 Results for the Examples from Table 5 OH Mg Cl Li DIPAH AB.sup.1 LiCl.sup.2 Ratio Yield.sup.3 Concentration Example mmol/g mmol/g LiCl:AB % AB.sup.4 % LiCl.sup.5 % TMPH.sup.5 Weight % 4 1.36 0.71 1.33 0.60 0.69 0.63 0.60 0.95 89.9% 78.7% 93.9% 10.1 .sup.1AB = active base; .sup.2over Li; .sup.3isolated yield without wash solutions; .sup.4relative to quantity of benzyl chloride BC; .sup.5relative to quantity used.