A student reacts methylmagnesium bromide (CH₃MgBr) with acetaldehyde (CH₃CHO), then works up with dilute aqueous acid. What is the organic product?
AAcetone — the Grignard adds a methyl group to give a ketone product
B2-Propanol — the Grignard's nucleophilic carbon adds to the aldehyde carbonyl, giving a secondary alcohol after workup
C1-Propanol — the reaction proceeds through a formaldehyde intermediate to give a primary alcohol
DPropanal — the Grignard reduces the aldehyde while extending the chain by one carbon
RMgX + aldehyde → secondary alcohol. CH₃MgBr adds to CH₃CHO: the nucleophilic carbanion-like carbon attacks the electrophilic carbonyl carbon, forming a magnesium alkoxide with the C skeleton (CH₃)(CH₃)CHOMgBr. Acidic aqueous workup protonates the alkoxide to give 2-propanol (isopropanol), a secondary alcohol. Option A confuses nucleophilic addition with some kind of oxidation; the Grignard does not convert aldehydes to ketones — it adds to them.
Question 2 Multiple Choice
A student wants to synthesize a product using a Grignard reagent, but the substrate molecule also contains a hydroxyl group on the carbon chain. What must the student do before forming the Grignard?
AProceed normally — the hydroxyl group will coordinate to magnesium and improve the reaction's selectivity
BProtect the hydroxyl group, because the -OH proton will instantly destroy the C-Mg bond by protonolysis before any productive reaction can occur
CUse a milder aryl Grignard instead of an alkyl Grignard, since aryl Grignards are less sensitive to protic groups
DCool the reaction to −78°C to slow the protonolysis so the Grignard reaction can compete kinetically
The C-Mg bond is one of the strongest nucleophiles in organic chemistry precisely because it behaves as a carbanion — and carbanions are instantly protonated by any source of acidic hydrogen. A hydroxyl group (pKa ~16) is far more acidic than what the Grignard requires; protonolysis is essentially instantaneous and irreversible. Cooling cannot slow this down. The only solution is to protect the OH group (e.g., as a THP ether or silyl ether) before introducing magnesium, then deprotect at the end. The same applies to NH and COOH groups.
Question 3 True / False
When a Grignard reagent reacts with an ester, two equivalents of RMgX add to give a tertiary alcohol — the reaction does not stop at the ketone intermediate.
TTrue
FFalse
Answer: True
The first addition of RMgX to an ester gives a tetrahedral intermediate that collapses by expelling the alkoxide leaving group, generating a ketone in situ. This ketone is actually more electrophilic and more reactive toward Grignard addition than the original ester. The still-present Grignard immediately adds again, and after acidic workup the product is a tertiary alcohol bearing two identical R groups from the two equivalents of RMgX. Attempts to stop at the ketone stage by using limiting Grignard typically fail — if a ketone product is desired, other organometallic reagents or lower-reactivity acyl equivalents must be used.
Question 4 True / False
Diethyl ether is used as the solvent for Grignard reactions because it is chemically inert and does not interact with the reagent.
TTrue
FFalse
Answer: False
Ether is far from inert in Grignard chemistry — it actively stabilizes the reagent through Lewis acid-base coordination. Magnesium is a Lewis acid; the ether oxygen lone pairs act as Lewis bases, coordinating to Mg and solvating the C-Mg bond. This solvation is essential for the reagent to form and remain stable. Without an ethereal solvent, Grignard reagents often cannot be prepared at all. 'Anhydrous and coordinative' is the accurate description. The critical requirement is that ether be rigorously dry (anhydrous), not that it be inert.
Question 5 Short Answer
Describe the retrosynthetic logic for designing a Grignard synthesis. Given a target alcohol, how do you identify the required Grignard reagent and carbonyl compound?
Think about your answer, then reveal below.
Model answer: In retrosynthesis, disconnect the C-C bond that was formed adjacent to the -OH group. The carbon bearing -OH was originally the electrophilic carbonyl carbon; the carbon on the other side of the disconnect came from the Grignard's R group (the carbanion equivalent). The alcohol class tells you which carbonyl substrate was used: a primary alcohol (RCH₂OH, excluding methanol) implies the Grignard added to formaldehyde; a secondary alcohol (RR'CHOH) implies addition to an aldehyde (R'CHO); a tertiary alcohol (RR'R''COH) implies addition to a ketone. Each target can often be disconnected in multiple ways, giving different valid synthetic routes. For example, 2-pentanol (a secondary alcohol) could be made from ethylmagnesium bromide + propanal, or from propylmagnesium bromide + acetaldehyde — either disconnection is valid.