Grignard Synthesis of Triphenylmethanol

Carbon-carbon bonds are the basis of organic chemistry. Attaching carbons and other organic molecules together we can create new molecules and carry out even more reactions to further manipulate our product. In 1912 F. A. Victor Grignard won the Nobel Prize for his discovery of a new reagent, a “rignard Reagent” used in such a reaction, coined “Grignard Reaction”. The Grignard Reagent is made up of organomagnesium, an organometallic molecule, or a molecule with both an organic and metal component. These reagents differ by the character of the carbon-metal bond and can be categorized as ionic, polar covalent, and covalent.

The difference in electronegativity between the metal and carbon atoms makes ionic organometallic reagents highly reactive. These substantial differences in electronegativity induce a separation of charge where the electrons are not evenly distributes over the entire molecule. As a result, these compounds can be difficult to control. Examples include NaCH3 and KCH2CH2CH3. The metals in both of these compounds have an oxidation of +1, which puts leaves a positive charge on the metal and a negative charge on the organic group. This makes the molecule even more unstable because typically these organic groups do not like a negative charge.

Polar covalent organometallic reagents contain a covalent bond between the carbon atom and the metal. These compounds are also highly reactive and, however the differences in electronegativity are not as great as ionic reagents. As a result they are much easier to control. An example of a polar covalent organometallic reagent is n-butyl lithium. This popular reagent has strong bacidity and is nucleophillic. As the name suggests, Covalent organometallic reagents have a completely covalent bond between the carbon atom and the metal.

In this case, there is only a small difference in the respective electronegativities and there is little charge separation. Thus, these compounds are relatively stable and non-reactive, they are rarely used in Griignard reactions. Typical Grignard Reactions use the polar covalent organometallic reagent with a moderate reactivity. They are more easily controllable. To form the Grignard Reagent, one would insert magnesium into a carbon-halogen bond, yielding R-Mg-X. This happens because of the hemolytic cleavage of an R-X bond and the subsequent Mg-X radical attaching on the R group radical.

Several factors affect the formation of the Grignard Reagent. First is the nature of the halogen in the R-X bond. According to period trends, C-X strength decreases as it moves down in a group because the halogen’s orbital size increases while the carbon’s remain constant. The difference in size creates an orbital overlap resulting in an weak bond. Iodine has the weakest bond due to its large orbital followed by bromine and chlorine, with the strongest being fluorine. Flourine is not used in a Grignard Reagent because it is overly reactive and unstable.

Small halides are also not used because they can spread out the negative charge in the molecule and strengthen the C-X bond. A weaker C-X bond is preferred to facilitate the insertion of magnesium. The nature of the R group present is also important. Specifically the bond dissociation energy of a molecule reflects teh stability of the initial and final states. A lower BDE ensures stability and lowers the likelihood of hemolytic cleavage and eventual formation of a Grignard. Benzyllic radical R groups are the most stable due to electron delocalization in their resonance structure.

Allylic radical R groups are also stable as their double bonds allow for similar resonance stabilization. Tertiary, Secondary, and Primary radicals follow in stability. They are followed by methyl radicals and finally phenyl radicals. The solvent used to form the Grignard is important. Ethers are the most common solvent used for Grignard synthesis. Ethers like diethyl ether or THF are good solvents because they are non-reactive and can split the halogen of one molecule and the magnesium of the other. The solvent must also be volatile so that its’ vaporization blocks water vapor from affecting the reaction.

This phenomenon is known as the “blanket effect” and is critically important because water can stop the reaction and/or create unwanted products. The reflux apparatus also helps keep water out of the reaction container while the reagents are being dissolved and heated to increase reactivity. Primary use of a Grignard reagent is as a nucleophile. In this reaction, the negatively charged carbon atom on the Grignard reagent attacks the partially positive charged carbon of the carbony group forming a new C-C bond. The R group thus adds tot he carbonyl carbon and the carbonyl oxygen eventually gets protonated to become an alcohol.

Grignard Reactions can thus create a ketone, a carboxylic acid, tertiary, secondary, or primary alcohol. Finally, after the Grignard reaction has completed, purification and characterization techniques are applied to assure the synthesis was successful. Purification is best done through recrystallization as used in previous experiments and some ways of characterization include measuring a melting range and collecting IR and H-NMR data. In general a more narrow melting range is more desirable as it ensures the sample is pure. A melting range that matches the literature value also ensures the desired molecule has been identified.