Question

Suggest starting materials for the preparation of the following alcohols using a Grignard reagent as one precursor. In each case, state how you might make the Grignard reagent: (a) 2 -methylpropan- 2 \(\mathrm{ol}\) (b) heptan-I-ol; (c) pentan-2-ol.

Short answer

(a) 2-methylpropan-2-ol: CH3MgBr + acetone; (b) heptan-1-ol: C6H13MgBr + formaldehyde; (c) pentan-2-ol: CH3MgBr + butyraldehyde.

Step-by-step solution

Understand the Grignard Reaction

A Grignard reagent (RMgX) can react with a carbonyl compound, such as an aldehyde or ketone, to form alcohols. The R group (alkyl or aryl) in the Grignard reagent attacks the carbonyl carbon, followed by protonation to give the alcohol.

Analyze the Target Alcohol - 2-methylpropan-2-ol

2-methylpropan-2-ol is a tertiary alcohol. Tertiary alcohols can be formed by the reaction of a Grignard reagent with a ketone. For 2-methylpropan-2-ol, the ketone could be acetone (propanone), with the Grignard reagent being methylmagnesium bromide (CH3MgBr).

Synthesize 2-methylpropan-2-ol

React methylmagnesium bromide (CH3MgBr) with acetone (propanone). The methyl group in CH3MgBr attacks the carbonyl carbon of acetone, followed by hydrolysis to give 2-methylpropan-2-ol.

Analyze the Target Alcohol - Heptan-1-ol

Heptan-1-ol is a primary alcohol. Primary alcohols can be synthesized by the reaction of a Grignard reagent with formaldehyde. For heptan-1-ol, the necessary Grignard reagent could be hexylmagnesium bromide (C6H13MgBr).

Synthesize Heptan-1-ol

React hexylmagnesium bromide (C6H13MgBr) with formaldehyde. The hexyl group in the Grignard reagent attacks the carbonyl carbon in formaldehyde, and after hydrolysis, this produces heptan-1-ol.

Analyze the Target Alcohol - Pentan-2-ol

Pentan-2-ol is a secondary alcohol. Secondary alcohols can be produced by reacting a Grignard reagent with an aldehyde. For pentan-2-ol, the suitable aldehyde could be butyraldehyde, and the corresponding Grignard reagent could be methylmagnesium bromide (CH3MgBr).

Synthesize Pentan-2-ol

React methylmagnesium bromide (CH3MgBr) with butyraldehyde. The methyl group in the Grignard reagent adds to the carbonyl carbon of butyraldehyde, and after hydrolysis, pentan-2-ol is formed.

Key concepts

Grignard Reagents

Grignard reagents, named after French chemist Victor Grignard, are organometallic compounds characterized by a metal-carbon bond. These compounds have the general formula RMgX, where R is an organic group (alkyl or aryl), and X is a halogen (chlorine, bromine, or iodine). They are invaluable tools in organic synthesis because they allow the formation of carbon-carbon bonds, which is a crucial step in building complex molecules.
Grignard reagents are typically prepared by adding magnesium metal to an organic halide in an ether solvent like diethyl ether or tetrahydrofuran (THF). These reagents are highly reactive and must be prepared under anhydrous conditions as they can decompose in the presence of water. The organic group, R, in the reagent acts as a nucleophile, meaning it can attack electrophilic centers (such as carbonyl carbons) in other chemical species, leading to the formation of new bonds.

Alcohol Synthesis

The Grignard reaction is a cornerstone in the synthesis of alcohols. By using Grignard reagents, chemists can synthesize primary, secondary, and tertiary alcohols depending on the nature of the carbonyl compound they react with.
Primary alcohols are prepared by reacting Grignard reagents with formaldehyde. This reaction ensures that only one additional carbon atom is added to the alkyl chain. When Grignard reagents react with aldehydes other than formaldehyde, secondary alcohols are formed. Tertiary alcohols result from the reaction between Grignard reagents and ketones, as seen with acetone or other ketones.
The mechanism follows three primary steps: nucleophilic attack by the Grignard reagent on the electrophilic carbonyl carbon, formation of an alkoxide intermediate, and finally hydrolysis to produce the alcohol with the desired structure. Hydrolysis involves adding water or dilute acid, which protonates the alkoxide, converting it to the alcohol.

Organic Chemistry Laboratory Techniques

Working with Grignard reactions requires precision and attention to detail, given the sensitivity of Grignard reagents to moisture. Here are essential techniques to ensure successful experiments:

• Always use dry glassware. Thoroughly drying glassware ensures no water is present, which would destructively hydrolyze the Grignard reagent.
• Use an inert atmosphere, like nitrogen or argon, to prevent the reagent from reacting with moisture in the air. Special equipment, like glove boxes or Schlenk lines, can help maintain the needed anhydrous conditions.
• Avoid overheating. Gentle reflux under controlled conditions ensures the magnesium will react efficiently with the organic halide without degrading sensitive components.

Careful monitoring of reaction parameters and conditions will result in the successful synthesis of the desired alcohols. Stay vigilant, stay dry, and ensure all reagents and solvents are anhydrous before proceeding.