10.7:
Alcohols from Carbonyl Compounds: Grignard Reaction
Alcohols are prepared from carbonyl compounds via carbonyl addition reactions using strong bases like Grignard reagents.
Grignard reagents are organomagnesium halides with a characteristic C–Mg covalent bond.
The greater electronegativity of carbon induces an ionic character in the bond, resulting in a partial negative charge on the carbon atom. This makes the Grignard reagent a strong carbon nucleophile.
On the other hand, carbonyl compounds such as aldehydes and ketones function as carbon electrophiles.
In a Grignard reaction, as magnesium coordinates to the carbonyl oxygen, oxygen pulls the electron density from the carbonyl group, making the carbonyl carbon a better electron acceptor and a stronger electrophile.
The carbanionic group of the Grignard reagent adds to the electrophilic carbon, forming a σ bond in the alkoxide ion.
In the subsequent step, the alkoxide is protonated using either dilute acid or water to form the corresponding alcohol.
Different classes of alcohols are formed depending on the carbonyl functional group undergoing the reaction.
Barring formaldehyde, which gives primary alcohols, all other aldehydes give secondary alcohols on reaction with a Grignard reagent.
The addition of a Grignard reagent to a ketone generates a tertiary alcohol.
Interestingly, the Grignard reagent does not add to the carbonyl group of a carboxylic acid. If made to react, the reagent acts as a strong base and abstracts the acidic proton from the –COOH group.
However, carboxylic acid derivatives like esters and acid chlorides react with a Grignard reagent to give a ketone, which subsequently converts into a tertiary alcohol.
10.7:
Alcohols from Carbonyl Compounds: Grignard Reaction
Grignard reagents are one of the most commonly used reagents used to synthesize alcohols from carbonyl compounds. Grignard reagents are organomagnesium halides with a highly polar carbon–magnesium bond. Due to the partial ionic nature of the C–Mg bond, the carbon functions as a strong nucleophile and attacks electrophiles like carbonyl carbon.
Magnesium from the reagent coordinates with carbonyl oxygen, further reducing the carbonyl carbon's electron density. Thus, the carbonyl carbon is a stronger electrophile. The carbanionic group of the reagent then attacks this electrophilic carbon to form an alkoxide ion. In the following step, the alkoxide ion is protonated using dilute acid or water to give alcohol.
Different classes of alcohols are formed depending on the type of carbonyl compounds undergoing the reaction. When reacted with a Grignard reagent, formaldehyde converts to a primary alcohol, while all other aldehydes form secondary alcohols. Ketones, on the other hand, give tertiary alcohols. The carbonyl group in a carboxylic acid does not welcome nucleophilic additions with the Grignard reagent. Instead, the reagent acts as a strong base and abstracts a proton from the acid's –COOH group. The derivatives of carboxylic acid, such as esters and acid chlorides, react with two equivalents of Grignard reagent to form tertiary alcohols with a ketone intermediate.