Written by Albert T. Sneden, VCU Department of Chemistry with revisions by L.M. Moses
The carbonyl group, as well as other electrophilic functional groups, undergoes facile reactions with nucleophilic reagents. Among the most useful nucleophilic reagents are those classified as organometallic reagents since the by-product of the reaction is usually an insoluble metallic salt.
One of the most common organometallic reagents is a Grignard reagent which, when allowed to react with an electrophilic organic functional group, results in the formation of a new carboncarbon bond leading to a new, more complex organic product.
The Grignard reagent, named after the French chemist Victor Grignard who developed the reagent as a useful organic intermediate, is a organomagnesium halide derived from the reaction of an organohalide with magnesium metal in an anhydrous aprotic solvent, usually diethyl ether
(Eq. 1). Theoretically, most organohalides will form Grignard reagents, but organobromides or organoiodides are usually chosen because they are more reactive than organochlorides.
Organofluorides are usually too unreactive to form Grignard reagents. With simple organohalides, those without steric hindrance around the reactive site, the yield of the Grignard reagent will normally be 80-90%.
It is necessary to form the Grignard reagent under strictly anhydrous conditions since the reagent is very reactive, acting as a carbanion (base), and will react with any water present, even atmospheric moisture, resulting in the destruction of the Grignard reagent by conversion of the alkyl or aryl group back to the parent hydrocarbon (Eq. 2).
The organic portion of the organohalide (R) may be any alkyl or aryl group, as long as it does not contain another reactive functional group elsewhere in the molecule. The other reactant should also contain only one reactive functional group. In simple cases, the only functional group which will not react with a Grignard reagent is an ether (R-O-R) group. If either the alkyl halide or the substrate with which the Grignard reagent will react contains a functional group with an acidic hydrogen such as a hydroxyl (-OH), an amine (-NH2 or -NHR), a sulfhydryl (SH), or a carboxylic acid (-CO2H), the Grignard reagent will react with the acidic hydrogen in a manner similar to the reaction with water. This is essentially an acid-base reaction in which the basic Grignard reagent is neutralized by the acidic proton, and will occur in preference to reaction at the electrophilic site. This type of reaction again results in the destruction of the
Grignard reagent by conversion of the alkyl or aryl group back to the parent hydrocarbon (Eq. 3).
The organohalide from which the Grignard reagent is prepared also cannot contain any electrophilic functional group. Groups such as aldehydes (-CHO), ketones (RCOR), esters (COOR), epoxides, and even alkyl halides will react with Grignard reagents. Generally, the substrate with which the Grignard reagent is allowed to react will contain one of these functional groups. The Grignard reagent is rarely isolated because it is so reactive, particularly with water in the atmosphere. Instead, the Grignard reagent is allowed to react immediately upon formation with an electrophilic substrate. As noted above, the electrophilic site will usually be a carbonyl or epoxide carbon, although an alkyl halide can also be used to form a larger alkane. Carbon dioxide can also be used to give a carboxylic acid as a product. The typical products for a variety of electrophilic substrates are listed in Table 1. Note that ketones and esters both give tertiary alcohols as products, but the products may be different. A ketone will add one equivalent of the
Grignard reagent, whereas the ester