WO1999043684A1

WO1999043684A1 - Synthesis agents containing benzyl magnesium halogenides or allyl magnesium halogenides and method for producing same

Info

Publication number: WO1999043684A1
Application number: PCT/EP1999/000264
Authority: WO
Inventors: Peter Rittmeyer; Uwe Lischka; Dieter Hauk
Original assignee: Chemetall Gmbh
Priority date: 1998-02-28
Filing date: 1999-01-18
Publication date: 1999-09-02
Also published as: DE19808570C1; EP1056750A1

Abstract

The invention relates to synthesis agents containing benzyl magnesium halogenides and allyl magnesium halogenides (Grignard reagents) with 2-methyl-tetrahydrofuran as solvent, and to a method for producing same.

Description

Synthesis agents containing benzyl magnesium halides or allyl magnesium halides and process for their preparation

description

The invention relates to benzylmagnesium halides and allylmagnesium halides containing synthetic agents and a process for their preparation.

Benzyl magnesium halides

MgX

LJ or allyl magnesium halides

^ ^ MgX

(X = Cl, Br, I) are well-known synthesis aids of preparative organic chemistry under the term Gngnard reagents. So far, the benzylmagnesium halides or allylmagnesiumhalogenide have been produced using ethical solvents, such as diethyl ether or tetrahydrofuran (THF). Due to its slight volatility and its low flash point, diethyl ether is reluctant to use for technical purposes; the production of the benzyl magnesium halides m THF is accompanied by an undesirable dimerization of the benzyl radical. The formation of the diaryl compound increases the consumption of magnesium and worsens the yield.

Document EP 0 415 247 A2 discloses a process for the preparation of arylmethyl magnesium halides with tert-butyl ethers, preferably at least 2.5 moles of magnesium per mole of arylmethyl halide. It is also known from document WO 93/12121

Arylmethyl magnesium halide in methyl tert. -Butyl ether (MTBE) at reaction temperatures above 45 ° C, the molar ratio of magnesium to aryl methyl halide is 1: 1 to 2: 1. The manufactured in the MTBE

Arylmethyl magnesium halides have the disadvantage that the organomagnesium compounds formed are only poorly soluble and therefore form suspensions. DE 44 39 003 Cl and WO 93/02086 describe a process for the preparation of benzyl magnesium halide in a solvent of the general formula III

R ¹ \ OR ³

V in

R ^{2 / x} OR ⁴ or in a solvent mixture containing a corresponding solvent, where R ¹ and R ^{2 are} independently a hydrogen, methyl or ethyl radical and R ³ and R ^{4 are} a methyl and / or ethyl radical. Diethoxymethane in particular is listed as an advantageous example of III because this solvent is only slightly water-miscible, which is relevant in the aqueous work-up of a reaction mixture occurring in a Grignard reaction. A disadvantage of the synthetic agent containing benzyl magnesium halide thus produced is the poor stability of the solvent diethoxymethane against strong mineral acids, which are often used in the work-up of the reaction mixtures resulting from Grignard syntheses.

The invention is therefore based on the object of creating a benzylmagnesium halide or allylmagnesium halide-containing synthetic agent which eliminates the disadvantages of the prior art, the solvent of which is, in particular, only slightly water-miscible and, at the same time, stable to mineral acids and which advantageously is only a trace of the by-product as a clear solution contains formed diaryl compound or diallyl compound.

The object on which the invention is based is achieved by a synthesis agent containing benzyl magnesium halide or allyl magnesium halide, which is characterized in that the solvent is 2-methyl-THF or a solvent containing 2-methyl-THF.

It is advantageous to use 2-methyl-THF as a solvent since, in contrast to THF, 2-methyl-THF is not water-miscible and has good solubility for many organic substances. Loss of solvent or product is reduced when using the synthetic agent according to the invention and the recovery of the solvent is simplified. Costs for the solvent can also be reduced by the fact that the inventive Synthesizing agent contains a solvent mixture of 2-methyl-THF and an aromatic solvent. Also, when using 2-methyl-THF it is not necessary to work with magnesium powder (magnesium chips are sufficient) and not at low temperatures to achieve good yields (the reaction temperatures are from -10 ° C. to 100 ° C.).

In particular, the solvent 2-methyl-THF used according to the invention is stable to strong mineral acids when working up a reaction mixture obtained in a Grignard reaction carried out with the synthetic agent according to the invention, which greatly simplifies the working up of such a reaction mixture.

It is also advantageous that the synthetic agents according to the invention allow a higher concentration of active C-Mg bond than with the solvent THF and prove to be more crystallization stable than benzyl magnesium halides or allyl magnesium halides produced in THF solutions. If X = Cl, the synthesis agent according to the invention is obtained after the insoluble magnesium chloride (MgCl ₂ ) formed in the reaction has been separated off as a clear solution which contains only traces of the diaryl compound or diallyl compound formed as a by-product.

The benzylmagnesium halide-containing or allyl magnesium halide-containing synthesis agents according to the invention can carry one or more of the following substituents in the phenyl or allyl group:

- fluorine, chlorine, bromine,

- C _λ to C ₈ alkyl groups

C _x to Cg haloalkyl groups with fluorine and / or chlorine as the halogen atom,

C _x to C ₆ alkoxy groups,

C _x to C ₆ haloalkoxy groups with fluorine and / or chlorine as halogen atom, - C - to C ₆ -alkenyl groups,

C ₃ to C ₆ cycloalkyl groups,

- The trimethylsilyl group and

- The phenyl group or the phenoxy group, which in turn can carry the aforementioned substituents.

Examples of corresponding starting compounds which are of particular importance with regard to their use for organic syntheses in the fields of crop protection agents, pharmaceuticals and dyes are benzyl chloride, benzyl bromide, 2-chlorobenzyl chloride, 2-methoxybenzyl chloride, 4-fluorobenzyl chloride, 4-methylbenzyl chloride, 2.5-

Dimethylbenzyl chloride, 2-chloromethylnaphthalene and 2-chloromethyl-5,6,7, 8-tetrahydronaphthalene.

The synthesis agent according to the invention is further characterized in that it contains benzyl or allyl magnesium halide and dibenzyl or diallyl magnesium in a molar ratio of 1: 0 to 0: 1. The stoichiometry typical of Grignard compounds according to the formula R-Mg-X is not present in the synthetic agent according to the invention. The synthetic agent is to be understood as a mixture of benzyl or allyl magnesium halide and dibenzyl or diallyl magnesium, the molar ratio of the aforementioned compounds depending on the respective substituent, the desired concentration of the solution and the type of halogen. The chloride content of the solutions can be reduced as a result. This leads to lower waste quantities for the user after using the synthetic agent according to the invention.

The synthetic agent according to the invention is produced in such a way that

a) Magnesium in 2-methyltetrahydrofuran or in one

Dispersed solvent mixture which contains 2-methyltetrahydrofuran and metered in a benzyl or allyl halide, b) the reaction temperature is kept in the range from -10 to + 100 ° C, preferably 0 to + 40 ° C, and c) the magnesium halide formed and precipitated during the reaction is separated off.

The subject matter of the invention is explained in more detail in the following 3 exemplary embodiments and in the 2 tables.

example 1

360 g of 2-methyl-THF and 14.7 g (605 mol = 21% excess) of magnesium shavings are placed under a protective gas in a double jacket reactor. 63.2 g (500 mmol) of benzyl chloride are metered in with stirring over the course of 60 minutes. The reaction temperature of the exothermic reaction is limited to 25 to 30 ° C. by cooling. To complete the reaction, the mixture is stirred at 20 ° C. for a further 30 minutes. The precipitated solid and excess magnesium are separated off by filtration. Analysis after hydrolysis of the filtrate:

OH ^" 1.48 mmol / g

Cl ^" 0.5 mmol / g Mg ²⁺ 1.22 mmol / g dibenzyl <0.1%

The analysis shows that the Schlenk equilibrium has shifted and the diorganomagnesium compound has partially formed. The residue is washed two more times with 2-methyl-THF. The total yield (calculated over total base) is 99%. The frit residue consists of MgCl ₂ . Example 2

This example is carried out in accordance with Example 1, but with benzyl bromide as the benzyl halide. Due to the better solubility of MgBr ₂ relative to MgCl ₂ in 2-methyl-THF, no precipitation occurs, a clear solution results. Analysis after hydrolysis of the filtrate:

OH ^" 1.22 mmol / g

Br ^" 1.21 mmol / g Mg ^{2 *} 1.22 mmol / g

The overall yield is 97.8%.

Example 3

13.3 g (547 mmol = 20% excess) of magnesium shavings in 260 g of 2-methyl-THF are placed in a double jacket reactor. 35 g (457 mmol) allyl chloride are added within 100 minutes. The reaction temperature is limited to 30 ° C. by cooling. A white precipitate precipitates out during the addition. The post-reaction time is 60 minutes at 25 ° C. After filtration, a solution is obtained with the following analysis:

OH ^" 1.53 mmol

Cl ^" 0.97 mmol Mg ^2t 1.24 mmol

The residue, consisting of MgCl ₂ , is washed with 2-methyl-THF. The yield is 89%. Table 1

Starting compound solvent mol Mg / yield% mol halide

Ph-CH ₂ CI THF 2.00 80-90

Ph-CH ₂ CI 2-methyl-THF 1, 20 99

Ph-CH ₂ CI 2-methyl-THF 1, 05 98

2-CH ₃ -Ph-CH ₂ CI THF 2.00 78

2-CH ₃ -Ph-CH ₂ CI 2-ethyl-THF 1, 40 97

2-CI-Ph-CH ₂ CI THF 2.00 20

2-CI-Ph-CH ₂ CI 2-methyl-THF 1, 20 86

Ph-CH ₂ Br THF 1, 50 73

Ph-CH ₂ Br THF 2.00 83

Ph-CH ₂ Br 2-methyl-THF 1, 20 98

Allyl-Cl THF 1, 20 73

Allyl-Cl 2-methyl-THF 1, 20 89

Reactions of benzyl chloride (Ph-CH ₂ CI), 2-methyl-benzyl chloride (2-CH ₃ -Ph-CH ₂ CI), 2-chloro-benzyichloride (2-CI-Ph-CH ₂ CI), benzyl bromide (Ph- CH ₂ Br) and allyl chloride with Mg chips.

Reactions with THF are not according to the invention and are used for comparison purposes. Reactions with 2-methyl THF are according to the invention

Table 2

Grignard compound concentration / molar ratio mmol / g R-MgX: R ₂ Mg

Ph-CH ₂ -MgCI 1, 48 1: 0.28

2-CH ₃ -PhCH ₂ -MgCI 1.53 1: 0.36

2-CI-PhCH ₂ -MgCI 1, 29 1: 0.67

Ph-CH ₂ -MgBr 1, 22 1: 0

Allyl-MgCl 1.53 1: 0.29

R-MgX: R ₂ Mg molar ratio in the benzyl- and allylmagnesium halide-containing synthesis agents

Claims

claims

1. Benzylmagnesiumhalogenide or Allylmagnesiumhalogenide containing synthetic agents, characterized in that the Benzylmagnesiumhalogenide or Allylmagnesiumhalogenide are present in 2-methyltetrahydrofuran or in a solvent mixture containing 2-methyltetrahydrofuran.

2. Synthesis agent according to claim 1, characterized in that the benzylmagnesium halides or allylmagnesium halides are present in a mixture of 2-methyltetrahydrofuran and an aromatic solvent.

3. Synthesis agent according to one or more of claims 1 to

2, characterized in that the phenyl group of the benzyl magnesium compound or the allyl magnesium compound carries one or more of the following substituents:

- fluorine, chlorine,

- C _{j ^} to C ₈ alkyl groups,

C to C ₈ haloalkyl groups with fluorine and / or chlorine as the halogen atom,

C _x to C ₃ alkoxy groups,

C _x to C ₃ haloalkoxy groups with fluorine and / or chlorine as the halogen atom,

C ₂ to C ₆ alkenyl groups, C ₃ to C ₆ cycloalkyl groups,

- The trimethylsilyl group and

4. Synthesis agent according to one or more of claims 1 to

3, characterized in that in the synthesis agent a benzyl magnesium halide and 10

Dibenzylmagnesiumverbindung in a molar ratio of 1: 0 to 0: 1 are included.

5. A method for producing a synthetic agent according to one or more of claims 1 to 4, characterized in that

a) dispersing magnesium in 2-methyltetrahydrofuran or in a solvent mixture which contains 2-methyltetrahydrofuran and metering in a benzylmagnesium halide or an allylmagnesium halide,

b) the reaction temperature is kept in the range from -10 to + 100 ° C, preferably 0 to + 40 ° C and

c) the magnesium halide formed and precipitated during the reaction is separated off.