Grignard reagents hazard

Fire Hazards. The hazards associated with the manufacture, transport and use of Grignard reagents are related to the flammability of the solvents employed and the exothermic reactions involved in their preparation and use. 

Grignard reagent sparingly soluble benzene (HAZARD) added to dissolve it... 

Reactions of organomagnesium compounds with dialkyl sulfates or alkyl sulfonates often give satisfactory yields of the products of displacement of sulfate or sulfonate. Side-reactions have been observed, but they can often be avoided for example, an excess of the sulfate or sulfonate should be used with Grignard reagents, as some is consumed by nucleophilic attack by halide ion [A]. The dialkyl sulfates are reactive, but hazardous. Toluenesulfonates (tosylates) are less reactive, but their reactions are catalysed by copper complexes the reactions of trifluoromethanesulfonates (triflates) are catalysed by nickel complexes. Reactions of Grignard reagents with secondary tosylates appear to follow an Sn2 mechanism, with inversion of configuration [43],... 

Addition of N-(benzyloxycarbonyl)-(S)-proline methyl ester to phenylmagnesium chloride to give (S)-a,a-diphenyl-2-pyrrolidinemethanol (3 steps, 5 isolations, 0-50% yield from (S)-proline) ref. 5e and 5g. It should be noted that 6-10 equiv of the Grignard reagent are required to drive this reaction to completion. Quenching the excess phenylmagnesium bromide affords benzene-an environmental and health hazard. 

By-products of the decomposition of Grignard reagents are an additional concern. As with flammable organic halides, there is a potential for the release of hazardous hydrogen halide vapors (HCl, HBr). If the fire involves certain Grignard reagents (notable phenylmagnesium halide), the hazardous hydrocarbon, benzene, may be released. 

Grignard reagents can be prepared readily in a hydrocarbon medium (toluene, xylene) if 1 mole of THF is present per mole of halide. The process is economical, and there is no fire hazard since the THF is bound to the Grignard reagent. 

In the synthesis of (S -2-acetyltetrahydrofuran, the Grignard reagent MeMgCl is very reactive and not easy to handle on a large scale. This results in safety and hazard issues at an industrial scale. In addition, selectivity issues result from over-alkylation to the tertiary alcohol, an undesired consecutive reaction. This impurity level must be kept <0.2% (Scheme 3.3). 

Hydrazines may also be obtained via amidocuprates (Eq. 47)54 but the yields are low. Addition of Grignard reagents to diazonium salts provides azo compounds, which may be reduced to hydrazines. Yields in the former reaction are often low and the requirement to use dry diazonium salts adds a potential hazard. The best yields are obtained with o-benzenedisulfonimide salts (Eq. 48).191... 

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