Questions: Grignard Reagents and Carbon-Carbon Bond Formation

Question 1

A Grignard reagent RMgX is added to excess ethyl acetate (CH₃COOEt), then quenched with aqueous acid. What is the major product?

• A. A secondary alcohol — the Grignard adds once to the ester carbonyl
• B. A tertiary alcohol with two R groups flanking the central carbon
• C. A carboxylic acid — esters hydrolyze under Grignard conditions
• D. An aldehyde — the ester is partially reduced by the Grignard

Answer: (B)

Esters undergo double addition. The first equivalent of Grignard adds to give a tetrahedral intermediate, which collapses by expelling ethoxide to give a ketone intermediate. That ketone is more reactive than the original ester, so a second Grignard equivalent attacks immediately, yielding a tertiary alcohol in which two R groups (from the Grignard) and one methyl group (from the ester carbonyl carbon) surround the central carbon. You cannot stop the reaction at the ketone stage — option A (single addition) would only apply to aldehydes or ketones, not esters.

Question 2

A chemist wants to prepare 2-phenyl-2-propanol via a Grignard reaction. Which combination of starting materials is correct?

• A. PhMgBr + acetone (propan-2-one)
• B. PhMgBr + acetaldehyde (ethanal)
• C. CH₃MgBr + benzaldehyde (PhCHO)
• D. PhMgBr + formaldehyde (methanal)

Answer: (A)

2-Phenyl-2-propanol is Ph–C(CH₃)₂–OH, a tertiary alcohol. Retrosynthetic disconnection of the C–C bond to the carbinol carbon gives PhMgBr + acetone (CH₃COCH₃): phenyl adds to the ketone carbon, which already bears two methyl groups, giving the correct tertiary alcohol. Option B gives Ph–CH(OH)–CH₃ (a secondary alcohol), option C gives the same secondary alcohol from the other direction, and option D gives Ph–CH₂OH (a primary alcohol).

Question 3

A Grignard reagent can be prepared from an alkyl halide that also contains a ketone group elsewhere in the molecule.

• T. True
• F. False

Answer: False

False. The Grignard carbon is an extremely powerful nucleophile and base that immediately reacts with any electrophilic functional group — including ketones, aldehydes, and esters — in the same molecule. An intramolecular reaction would occur before the reagent could be isolated and used synthetically. This functional group incompatibility is one of the central strategic constraints in Grignard chemistry: the starting halide must contain no carbonyl groups, acidic protons (OH, NH, COOH), or other electrophilic sites.

Question 4

Treating a Grignard reagent with CO₂ followed by aqueous acid workup produces a carboxylic acid with one more carbon than the original alkyl halide.

• T. True
• F. False

Answer: True

True. CO₂ acts as a one-carbon electrophile. The Grignard carbanion (R–MgX) attacks the electrophilic carbon of CO₂ to form a magnesium carboxylate (R–CO₂MgX). Aqueous acid workup protonates this to give R–COOH — a carboxylic acid containing exactly one more carbon than the R group derived from the original halide R–X. This reaction is a reliable route to carboxylic acids in synthesis.

Question 5

Why does a Grignard reagent attacking an ester yield a tertiary alcohol rather than the secondary alcohol one might expect by analogy with aldehyde additions?

Model answer: Esters have a leaving group (the alkoxide) attached to the carbonyl carbon; aldehydes do not. The first Grignard addition to an ester generates a tetrahedral intermediate that collapses by expelling the alkoxide, regenerating a carbonyl in the form of a ketone. Because this ketone is more electrophilic than the original ester, a second equivalent of Grignard attacks immediately. The result is a tertiary alcohol with two R groups from the Grignard — not the secondary alcohol that would form if the reaction stopped after one addition.

The mechanistic key is leaving group elimination: esters can unmask a ketone after the first addition, whereas aldehydes and ketones have no leaving group and simply give alkoxides that are protonated on workup. This 'double addition' is unavoidable under normal conditions, which is why esters are specifically chosen (or avoided) in retrosynthetic planning depending on whether a tertiary alcohol is desired.