Formation of Grignard reagents

Strictly speaking the alkyl halides are esters of the halogen acids, but since they enter into many reactions (t.g., formation of Grignard reagents, reaction with potassium cyanide to yield nitriles, etc.) which cannot be brought about by the other eaters, the alkyl halides are usually distinguished from the esters of the other inorganic acids. The preparation of a number of these is described below. 

The usefulness of the Grignard reagent of 3-bromothiophene is somewhat limited as it can only be prepared by the entrainment method. The simultaneous formation of Grignard reagents from 3-bromothiophene and a fivefold molar excess of ethyl bromide gave, however, a 55% yield of 3-thiophenecarboxylic acid upon carbona-tion. With acetaldehyde, a 55% yield of methyl 3-thienyl carbinol... 

Next to the formation of Grignard reagents, the most important application of this reaction is the conversion of alkyl and aryl halides to organolithium compounds, but it has also been carried out with many other metals, (e.g., Na, Be, Zn, Hg, As, Sb, and Sn). With sodium, the Wurtz reaction (10-93) is an important side reaction. In some cases, where the reaction between a halide and a metal is too slow, an alloy of the metal with potassium or sodium can be used instead. The most important example is the preparation of tetraethyl lead from ethyl bromide and a Pb—Na alloy. 

Formation of Grignard reagent formation of Ciba-Geigy Brogli etal. (1981)... 

The formation of Grignard reagents takes place at the metal surface. Reaction commences with an electron transfer to the halide and decomposition of the radical ion, followed by rapid combination of the organic group with a magnesium ion.1 It... 

We have attempted the low temperature formation of Grignard reagents containing nitrile, ketone and ester functional groups. These reactions were largely unsuccessful, except in the case of 8-bromooctanenitrile. 

The mechanism for the formation of Grignard reagents might involve radicals ... 

SCHEME 2. The initial step in the formation of Grignard reagents... 

A peroxide-free grade o anhydrous tetrahydrofuran (stabilized by 0.025% of 2,6-di- -butyl-4-methyl phenol) is available currently (1966) from Fisher Scientific Co. in 1-lb. bottles. This product as obtained from freshly opened bottles has been found to be suitable for reactions such as the formation of Grignard reagents in which purity of solvent is critical (du Pont Co., unpublished observations). It is standard practice in at least one laboratory to use only tetrahydrofuran (Fisher) from freshly opened bottles and to discard whatever material is not used within 2-3 days. 

Tilstam, U. and Weinmann, H. (2002) Activation of Mg metal for safe formation of Grignard reagents at plant scale. Organic Process Research sj Development, 6, 906-10. 

This process is similar to the formation of Grignard reagents 4 from alkyl halides and Mg(0). In the preparation of Grignard reagents, Mg(0) is oxidized to Mg(II) by the oxidative addition of alkyl halides to form two covalent bonds. 

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