From Chapter 12 of Migrdichian's Organic Synthesis
Preparation of Organomagnesium Compounds
The general procedure followed in preparing an organomagnesium halide is as follows:
The required quantity of magnesium; in the form of turnings, 3 mm long and 0.6 mm thick, is placed in a dry flask provided with a sealed stirrer and a
reflux condenser; the air is displaced with a current of dry nitrogen, a little ether and a crystal of iodine are added, then a small amount of the
halide is introduced to initiate the reaction. If reaction fails to proceed spontaneously, the mixture is heated to 45°, although more frequently it
is necessary to apply external cooling in order to moderate the reaction. After the initial vigorous reaction has subsided to some extent, the halide,
mixed with 1 to 3 volumes of ether, is added slowly and at a constant rate, while the liquid in the flask is stirred. After the addition of all the
halide mixture, the flask is heated until the reaction is complete.
It is important that both the reflux condenser and the dropping funnel used for the introduction of the halide-ether mixture, be protected from
atmospheric moisture by means of calcium chloride tubes. The magnesium turnings must be clean and, in particular, free from any oily matter.
Commercial magnesium in the form of turnings or of coarse powder may be used. The quality of magnesium employed may greatly affect the yields
obtained_ The magnesium should be stored dry and, if desirable, it may be washed with pure, dry ether by decantation. The impurities present in the
metal remain as a dark powder alter the completion of the reaction. The metal is used in an amount corresponding to the halide or in slight excess.
The ether must be anhydrous and free from alcohol. Commercial alcohol-free ether distilled over phosphorus pentoxide is satisfactory. The ether may
also be dried by storing it over sodium wire. The halide must be in a very pure form and free from acids, water or alcohol.
It is important that the halide be added slowly in order to avoid the presence of any large excess of unreacted halide and thus to prevent the
reaction
RMgX + XR -. R.R + MgX2
which proceeds quite readily when iodides are employed. This reaction is favored if an excessive amount of iodine is used for initiation of the
reaction.
and
Procedure in Carrying out Grignard Reaction
The Grignard reaction is carried out in the following manner:
The compound dissolved in ether is added to the solution of the organomagnesium halide at such a rate that the solution boils continuously. If the
compound is insoluble in ether, it may be dissolved in benzene, petroleum ether, etc. Solid compounds may be added to an ethereal solution of the
organomagnesium halide in the form of a powder. If there is a possibility of reduction, any temporary excess of the organomagnesium halide is avoided,
by gradually adding the solution of the Grignard reagent to the solution of the compound. The reaction generally proceeds quite rapidly in most cases
The magnesium complex resulting from the reaction is then decomposed, carrying out the operation with great care in order to assure the success of the
preparation and to avoid danger. Rapid dilution and cooling by the addition of water and ice generally accomplishes the desired result.
Decomposition with water results in the formation of magnesium hydroxide. The formation of this compound may be avoided by adding dilute
hydrochloric or sulfuric acid to the diluted, cooled reaction mixture. It is preferable to pour the reaction mixture on ice, and then to add the acid.
If the reaction product is sensitive to acids and likely to polymerize when decomposition is carried out with an acid, ammonium chloride may be used
in place of the acid.
The success of the Grignard reaction often depends upon the rapidity with which the operation is carried out.
The ether, as well as other reagents must be quite dry. The ether is best kept dry by storing it over metallic sodium. The reaction often proceeds
only when ether dried over phosphorus pentoxide is employed, though it has been carried out successfully in some cases with moist ether, using an
excess of the reagent.
If it becomes necessary to employ a high-boiling solvent as the reaction medium, the ether used in the preparation of the organomagnesium halide is
removed as much as possible by distillation under vacuum at 100-105°, and the desired solvent is added. Benzene and ethers of higher alcohols are
suitable solvents. Among the latter, methyl benzyl, methyl cyclohexyl, amyl and butyl ethers are often employed. The use of rubber stoppers should be
strictly avoided, since rubber inhibits the reaction. Glass, or new, paraffin coated cork stoppers are satisfactory.
The rate of reaction is proportional to the concentration of the organomagnesium halide in the solution. The optimum concentration of the reagent
appears to be 30-40%, although occasionally concentrations as high as 70% are employed.
High molecular products may be formed and may separate out in the course of the reaction; if they are liquids, sufficient benzene is added to bring
them into solution. Solids, if they appear, are not readily brought into solution and may cause considerable difficulty.
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