Related Experiment Video
Updated: Jun 19, 2025
06:52
Synthesis of Esters Via a Greener Steglich Esterification in Acetonitrile
Published on: October 30, 2018
35.6K
A green Heck reaction protocol towards trisubstituted alkenes, versatile pharmaceutical intermediates
Giacomo Rossino1, Giorgio Marrubini1, Margherita Brindisi2
1Department of Drug Sciences, University of Pavia, Pavia, Italy.
Frontiers in Chemistry
|July 25, 2024
Summary
This study presents a green Heck reaction protocol for synthesizing trisubstituted alkenes, crucial for pharmaceuticals. The optimized method uses microwave irradiation and a reusable catalyst, offering an efficient and eco-friendly approach.
Area of Science:
- Organic Chemistry
- Green Chemistry
- Medicinal Chemistry
Background:
- The Heck reaction is vital for synthesizing biologically relevant scaffolds and active pharmaceutical ingredients (APIs).
- Existing green Heck reaction protocols are highly efficient for terminal alkenes but less so for internal olefins, which yield challenging trisubstituted alkenes.
- Developing efficient and sustainable methods for trisubstituted alkene synthesis is crucial for pharmaceutical development.
Purpose of the Study:
- To implement a green Heck reaction protocol for the efficient synthesis of trisubstituted alkenes.
- To optimize reaction conditions using design of experiments (DoE) for a sustainable and scalable process.
- To develop a method for converting isomeric byproducts into desired conjugated E-alkenes, minimizing waste.
Main Methods:
- A design of experiments (DoE) study was conducted to identify optimal reaction parameters including catalyst, solvent, base, and temperature.
- Microwave (mw) irradiation was employed to accelerate reaction times.
- A supported palladium catalyst (Pd EnCat®40) was used for easy recovery and reuse.
- A subsequent isomerization procedure was developed to convert byproducts into the desired E-alkene.
Main Results:
- An optimized green Heck reaction protocol was established using EtOH as the solvent, microwave irradiation, and Pd EnCat®40 catalyst.
- The protocol demonstrated broad substrate scope for various aryl bromides and internal olefins.
- An efficient isomerization method was developed to convert isomeric byproducts into the thermodynamically favored E-alkene, enhancing overall yield and reducing waste.
Conclusions:
- The developed Heck reaction protocol provides a green, efficient, and user-friendly method for synthesizing diverse trisubstituted alkenes.
- This approach is valuable for producing key pharmaceutical intermediates and final products.
- The integration of microwave irradiation, supported catalysts, and waste-reduction strategies highlights a significant advancement in sustainable organic synthesis.
Keywords:
DOEHeck reactioncatalysisdesign of experimentsgreen solventsmicrowavestrisubstituted alkenesMore Related Videos
![Mizoroki-Heck Cross-coupling Reactions Catalyzed by Dichloro{bis[1,1',1''-phosphinetriyltripiperidine]}palladium Under Mild Reaction Conditions](/_next/image?url=https%3A%2F%2Fcloudfront.jove.com%2FCDNSource%2Fteasers%2F51444.jpg&w=3840&q=50)
11:44Mizoroki-Heck Cross-coupling Reactions Catalyzed by Dichloro{bis[1,1',1''-phosphinetriyltripiperidine]}palladium Under Mild Reaction Conditions
Published on: March 20, 2014
25.4K
09:54Chemoselective Preparation of 1-Iodoalkynes, 1,2-Diiodoalkenes, and 1,1,2-Triiodoalkenes Based on the Oxidative Iodination of Terminal Alkynes
Published on: September 12, 2018
7.7K
Related Concept Videos
01:27Radical Substitution: Allylic Bromination
5.0K
In organic synthesis, the formation of products can be altered by changing the reaction conditions. For example, a dibromo addition product is formed when propene is treated with bromine at room temperature. In contrast, propene undergoes allylic substitution in non-polar solvents at high temperatures to give 3-bromopropene. In order to avoid the addition reaction, the bromine concentration must be kept as low as possible throughout the reaction. This can be achieved using N-bromosuccinimide...
5.0K
02:27Preparation of Alkynes: Alkylation Reaction
10.0K
Introduction
Alkylation of terminal alkynes with primary alkyl halides in the presence of a strong base like sodium amide is one of the common methods for the synthesis of longer carbon-chain alkynes. For example, treatment of 1-propyne with sodium amide followed by reaction with ethyl bromide yields 2-pentyne.
Alkylation of terminal alkynes with primary alkyl halides in the presence of a strong base like sodium amide is one of the common methods for the synthesis of longer carbon-chain alkynes. For example, treatment of 1-propyne with sodium amide followed by reaction with ethyl bromide yields 2-pentyne.
10.0K
00:51Base-Promoted α-Halogenation of Aldehydes and Ketones
3.4K
α-Halogenation of aldehydes and ketones is a reaction involving the substitution of α hydrogens with halogens in the presence of a base. The reaction begins with the abstraction of α hydrogen by the base to produce a nucleophilic enolate ion. This intermediate undergoes a subsequent nucleophilic substitution with the halogen to produce a monohalogenated carbonyl compound. If the starting substrate has more than one α hydrogen, it is difficult to stop the reaction...
3.4K
01:38Preparation of Alcohols via Substitution Reactions
5.8K
Overview
Alcohols can be synthesized from alkyl halides via nucleophilic substitution reactions. The highly polar carbon-halogen bond in the substrate makes halide a good leaving group. The hydroxide ion or water can act as a nucleophile to take the place of halide and form an alcohol. The substitution reactions occur via two different reaction pathways, SN1 or SN2, depending on the nature of carbon attached to the halide.
Primary alcohols are synthesized from primary alkyl halides, and the...
Alcohols can be synthesized from alkyl halides via nucleophilic substitution reactions. The highly polar carbon-halogen bond in the substrate makes halide a good leaving group. The hydroxide ion or water can act as a nucleophile to take the place of halide and form an alcohol. The substitution reactions occur via two different reaction pathways, SN1 or SN2, depending on the nature of carbon attached to the halide.
Primary alcohols are synthesized from primary alkyl halides, and the...
5.8K
01:26Synthesis of α-Substituted Carbonyl Compounds: The Stork Enamine Reaction
3.3K
α-Substituted ketones or aldehydes can be synthesized from enamines by the Stork enamine reaction, named after its pioneer Gilbert Stork. Enamines are useful synthetic intermediates where the lone pair on nitrogen is in conjugation with the C=C bond. They resemble enolate ions, as the resonance forms of both species have a nucleophilic α carbon.
3.3K
01:11Nucleophilic Aromatic Substitution: Elimination–Addition
4.0K
Simple aryl halides do not react with nucleophiles. However, nucleophilic aromatic substitutions can be forced under certain conditions, such as high temperatures or strong bases. The mechanism of substitution under such conditions involves the highly unstable and reactive benzyne intermediate. Benzyne contains equivalent carbon centers at both ends of the triple bond, each of which is equally susceptible to nucleophilic attack. This 50–50 distribution of products is...
4.0K