Question

What are Grignard reactions?

Answer 1

Grignard reactions are the premier means for `C-C` bond formation.

Explanation:

The Grignard reaction starts with a hydrocarbyl halide, `R-X`. The only restriction on the `R` group, the hydrocarbyl group, is that it DOES NOT contain a electrophilic functional groups such as an alcohol or a carbonyl.

The hydrocarbyl halide may be metallated directly by magnesium flakes. The reaction is usually performed in dry diethyl ether:

`R-X + Mg rarr R-MgX`

The so-called Grignard reagent is solvated by several solvent molecules. It is generally not isolated, but used directly. It reacts as a carbanion, i.e. `R^(delta-)""^(delta+)MgX`, or even as `R^(-)""^(+)MgX`; it has strong carbanionic character.

Addition of a carbonyl reagent results in the following reaction:

`R^(-)""^(+)MgX + H(O=)CR'rarrRC(-O)^(-)""^+(MgX)R'`

In the reaction above you have performed a `C-C` coupling to give a secondary alkoxide; i.e. a direct bond is formed between the Grignard residue, and the ipso carbon of the aldehyde. In terms of organic chemistry, this is a very big deal in that the number of `C-C` bond forming reactions is very small, and the Grignard reaction is undoubtedly the best and most effective of such reactions.

One of the best ways to make a carboxylic acid is to pour your Grignard reagent onto dry ice (and stand back!):

`R^(-)""^(+)MgX + CO_2rarrRC(=O)(-O)^(-)""^+(MgX)`

When the carboxylate salt is treated with `H_3O^+`, the acid results:

`RC(=O)(-O)^(-)""^+(MgX) + H^+"/"H_2O rarr RC(=O)OH + MgXOH`

Note that the product acid is 1 carbon longer than the original Grignard residue.

The Grignard reagent will react with aldehydes to give secondary alcohols after workup, and with ketones to give tertiary alcohols after workup. The Grignard reagent will also react with ethylene oxide to give a primary alcohol that is 2 carbons longer than the original chain. Grignards generally do not react in such a way with alkyl halides unless there are special conditions.

Grignard reactions demand (reasonably) dry solvents and reagents, and care when the reaction is performed (i.e. exclusion of moisture, fast working, being on the ball).

Anyway, you will find all of this in your organic chemistry text. But when you do this in a lab remember to be slick, and work fast.