Grignard formation

While attempts were made to prepare the ethoxysilanes via the classic Grignard reaction, only phenyldimethylethyoxysilane was prepared in this manner. The Grignard reaction proved to be unsuitable for the preparation of the four para-substitutcd phenyldimethylethoxysilanes either because of sensitivity to Grignard formation or difficulty in isolating the product from the reaction mixture since the by-product salts were unfilterable. Therefore, all four silanes (p-chlorophenyl, p-methoxyphenyl, p-tolyl and p-trifluoromethylphenyldimethyl-ethoxysilane) were prepared via an organolithium reaction. 

An ice bath was used to control the reaction temperature during Grignard formation. 

Organolithium compounds may be made by a similar oxidative insertion reaction from lithium metal and alkyl halides. Each inserting reaction requires two atoms of lithium and generates one equivalent of lithium halide salt. As with Grignard formation, there is really very little limit on the types of organolithium that can be made this way. 

The submitters initiated Grignard formation by adding a few milliliters of a solution of 142.8 g (1.2 mol) of propargyl bromide in 560 mL of anhydrous ether. If the reaction does not begin, they suggest that the flask be heated with a warm stream of air from a heat gun. ... 

In 1961 it was reported that the reaction of chiral l-bromo-l-methyl-2,2-diphenylcyclopropane (51) with magnesium metal produced a partially optically active Grignard reagent . It was suggested that the racemization observed occurred in the Grignard formation step. In 1964 it was also established that the racemization occurred... 

Further confirmation of the surface nature of Grignard formation is the observation that when THF-ds and diethyl ether-djo were used as solvent only 28% and 6% deuterium, respectively, were found in the hydrocarbon fraction of the reaction . The source of hydrogen atoms is the disproportionation of the surface radicals. Moreover, the yield of hydrocarbons from reaction in THF is only 1.0-1.5 % whereas in diethyl ether the yield is 20%. This is in accord with the greater solvating power of THF which removes the metal organic species from the surface of the magnesium. Recent XPS analysis of the Grignard formation reaction is consistent with the surface nature of the reaction . 

Annino and his coworkers have postulated a mechanism for the reaction at the zinc surface patterned after the one proposed by Walborsky and coworkers for Grignard formation The organozinc intermediate formed is rapidly hydrolyzed by the protonic solvent. Note also that the reaction of zinc, in ethanol-10 % KOH, with chiral l-bromo-l-methyl-2,2-diphenylcyclopropane (51) yielded l-methyl-2,2-diphenylcyclopropane (49) with 21 % retention of configuration a result comparable to the 15% retention that is found in Grignard formation. 

What does not happen is Grignard formation at the aryl chloride - bromides are more reactive than chlorides towards Grignard formation. Furthermore, nucleophilic attack occurs at the carbonyl group and not at the C=N group of the electrophile. This is because C=N is less electrophOic than C=0 (N is less electronegative than O) and also because attack at C=N would destroy the aromaticity of the pyridine ring. 

The formation of vinyl Grignard reagent by direct interaction of optically active (4-methylcyclohexylidene)bromomethane 27 with magnesium metal also occurs with partial racemization. Here, too, the racemization occurred in the Grignard formation step. 

B. Halogen Effect on the Stereochemistry of the Grignard Formation Reaction... 

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