0.5 Grignard reaction  (Page 31/5)

Lab 3: grignard reaction

Objective

The purpose of this laboratory exercise is to perform a classic method for the synthesis of secondary alcohols: the addition of a Grignard reagent to an aldehyde (other than formaldehyde).

Background information

After the most remarkable discovery by Victor Grignard in 1900, organometallic (An organic compound containing a metal atom directly attached to a carbon) compounds are very useful in organic synthesis. This discovery changed the course of organic chemistry and earned him the Nobel Prize in 1912. We now refer to such compounds as Grignard Reagents.

The Grignard reaction is one of the characteristic reactions of carbonyl compounds. It is especially useful as a means of forming new carbon-carbon bonds, something that we haven't seen much of until now. In this type of reaction a C-M bond is present (C=carbon and M=metal) which is covalent in nature. The metal is usually magnesium but lithiummore reactive and is also used. The more polar the C-M bond is, the more will be its reactivity. The reactivity order is known from electrochemical series:

M= Li>K>Ca>Na>Mg>Al>Zn>Fe>Sn etc

Traditionally alkyl magnesium halides are known as Grignard reagent (R-Mg-X).

All kinds of alkyl halides react (Iodides are more reactive than bromides which in turn are more reactive than chlorides) and amazingly, even bromobenzene and other aryl bromides and iodides react easily with magnesium. This is particularly surprising since the aromatic halogen is so unreactive. For example, it is inert to refluxing with aqueous sodium hydroxide at temperatures in excess of 200˚C. The unshared pair of electrons on ether oxygen complexing with the Mg is believed to contribute to the stability of the reagent. Note: Aryl halides (ArX) and vinyl halides that are inert to nucleophilic substitution are reactive with this Grignard reaction.

Preparation and mechanism of grignard reagent:

The mechanism of Grignard reagent (GR) is not clear till today, but it is believed that the reaction is taking place on the metal surface. Since GR does not react with aprotic solvents (e.g. ether, THF etc), these solvents are widely used. The mechanism of formation of GR as follows: it goes via one electron transfer, followed by rapid combination of organic group with the metal center. From the mechanistic point of view, carbon-bromine bond should be broken prior to the reaction with magnesium.

Solutions of some Grignard reagents such as methylmagnesium bromide, ethylmagnesium bromide, and phenylmagnesiumbromides are commercially available. Here is an example of Grignard reaction which explains the effect of solvent.

The Grignard reagent is made from the direct reaction of magnesium with an alkyl halide.

The key to the function of the Grignard reagent is the reversal of the normal polarity of bonds to carbon (This type of reversal of polarity in carbon center is known as Umpolung). Because magnesium is more electropositive than carbon the carbon acquires a $\delta -$ charge whereas carbon, when it has a charge at all, usually has $\delta +$ charge from bonding to halogens, oxygen, and nitrogen.