Stobbe Condensation: Definition, Examples, Reagents and Mechanism

stobbe condensation definition:

Stobbe condensation is a formation of alkylidene succinic acids or their monoesters by the base-mediated condensation of ketones and aldehydes with dialkyl succinates. reagents and mechanism we will discuses in this regard accordingly.

General reagents and condition of the Stobbe Condensation:

1. In Stobbe Condensation there is no restriction on the carbonyl component it may have hydrogens at its α-position. aromatic-, α,β-unsaturated aldehydes and ketones as well as aliphatic ones are commonly used;
2. the diesters are mainly limited to succinic esters and their substituted derivatives, but certain α,ω-diesters that do not undergo competitive Dieckmann condensation will afford Stobbe products;
3. upon mild acidic work-up the primary product is an alkylidene succinic acid monoester;
4. when symmetrical ketones are condensed, only one alkene stereoisomer is produced, although unsymmetrical ketones provide a mixture of alkene stereoisomers.
5. A variety of products may be formed in Stobbe Condensation, when the carbonyl component has α-protons because of double bond migration under the reaction conditions.

Drawbacks of the Stobbe condensation:

1. The aldehyde or ketone substrate will undergoes self-condensation
2. Cannizzaro reaction can take place with of aromatic aldehydes
3. Highly enolizable ketones give  low yields.
4. In Stobbe condensation too reactive ketones may undergo acylation (Claisen reaction) at their α-position by the dialkyl succinate.

Mechanism of Stobbe Condensation:

The first step of the Stobbe condensation is; the base will deprotonate the succinate at the α-carbon to offer an ester enolate that, in situ, go through an aldol reaction with the carbonyl compound to form a β-alkoxy ester intermediate.

The following intramolecular acyl substitution gives rise to a γ-lactone intermediate which undergoes ring-opening and concomitant double bond development upon deprotonation by the alkoxide ion. Under certain conditions, the lactone intermediate can be separated.

Applications of Stobbe Condensation:

Stobbe Condensation is used to substitute a propionic acid residual for the carbonyl group in aromatic ketones.

When combined with the Friedel-Crafts reaction, this condensation can yield naphthols, indones, and tetralones.

synthesis of γ-keto acids, irreversible ring-opening reactions. synthesis of tree carbon chain

Related Reaction :

• aldol condensation
• benzoin condensation
• Acyloin Condensation
• Claisen Condensation/Claisen Reaction
• Darzens Glycidic Ester Condensation
• Knoevenagel Condensation

References :

1. sciencedirect
2. https://chemistry-europe.onlinelibrary.wiley.com/doi/10.1002/cber.188101402192
3. https://chemistry-europe.onlinelibrary.wiley.com/doi/10.1002/cber.188702001150
4. https://pubs.acs.org/doi/abs/10.1021/jo00897a008
5. The Mechanism of the Stobbe Condensation