Reformatsky Reaction: Synthesis of $\beta$-Hydroxy Esters
The Reformatsky Reaction involves the condensation of an $\alpha$-halo ester (usually $\alpha$-bromo ester) with a carbonyl compound (aldehyde or ketone) in the presence of Zinc metal. The product obtained after acid hydrolysis is a $\beta$-hydroxy ester.
1. General Reaction
Zinc reacts with the $\alpha$-halo ester to form an organozinc reagent, which then attacks the ketone/aldehyde.
Key Components:
- Carbonyl Source: Aldehyde or Ketone.
- Nucleophile Source: $\alpha$-Halo ester (e.g., Ethyl bromoacetate).
- Metal: Zinc dust ($Zn$).
- Solvent: Inert solvents like Benzene, Ether, or THF.
2. Detailed Mechanism
The mechanism is analogous to the Grignard reaction but uses Zinc instead of Magnesium.
Step 1: Formation of Reformatsky Reagent
Zinc inserts into the Carbon-Bromine bond to form an organozinc bromide (Reformatsky Reagent). This exists as a Zinc Enolate.
(Resonance stabilized Zinc Enolate)
Step 2: Nucleophilic Attack
The organozinc reagent (acting as a nucleophile) attacks the electrophilic carbonyl carbon of the aldehyde/ketone.
Step 3: Acid Hydrolysis
Dilute acid is added to hydrolyze the zinc alkoxide intermediate into the final alcohol.
3. Why Zinc and not Magnesium? (Chemoselectivity)
Crucial Concept
Magnesium (Grignard Reagent) is highly reactive and would react with the ester group of the $\alpha$-halo ester molecule itself (Self-reaction/Polymerization).
Zinc (Reformatsky Reagent) is less electropositive and less reactive. The C-Zn bond is less polar than the C-Mg bond. Therefore, the organozinc reagent is reactive enough to attack aldehydes/ketones but inert towards the ester group.
4. Applications and Variations
Synthesis of $\alpha,\beta$-Unsaturated Esters
The $\beta$-hydroxy ester product can be easily dehydrated using acid and heat to form $\alpha,\beta$-unsaturated esters.
$$ R-CH(OH)-CH_2-COOEt \xrightarrow{H^+, \ \Delta} R-CH=CH-COOEt $$Example: Benzaldehyde + Ethyl Bromoacetate
Forms Ethyl 3-hydroxy-3-phenylpropanoate.
5. Summary vs Grignard
| Feature | Grignard Reaction | Reformatsky Reaction |
|---|---|---|
| Metal | Magnesium ($Mg$) | Zinc ($Zn$) |
| Reactivity | Very High (Reacts with esters) | Moderate (Tolerates esters) |
| Halide Type | Alkyl Halide | $\alpha$-Halo Ester |
Reformatsky Quiz
Test your concepts on Organozinc chemistry. 10 MCQs with explanations.
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