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Updated: Nov 15, 2025
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Continuous Flow Chemistry: Reaction of Diphenyldiazomethane with p-Nitrobenzoic Acid
Published on: November 15, 2017
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Continuous flow as an enabling technology: a fast and versatile entry to functionalized glyoxal derivatives
Fabio Lima1, Mark Meisenbach, Berthold Schenkel
1Global Discovery Chemistry, Novartis Institutes for Biomedical Research, Novartis Pharma AG, Basel, Switzerland. fabio.lima@novartis.com.
Organic & Biomolecular Chemistry
|March 1, 2021
Summary
This study introduces two organolithium chemistry methods using micro-mixers for efficient glyoxal derivative synthesis. These techniques provide rapid access to valuable building blocks for heterocyclic chemistry.
Area of Science:
- Organic Chemistry
- Synthetic Chemistry
- Flow Chemistry
Background:
- Organolithium chemistry is crucial for synthesizing complex organic molecules.
- Accessing glyoxal derivatives and masked 1,2-dicarbonyl compounds remains a synthetic challenge.
- Unstable intermediates often limit the efficiency and scope of traditional synthetic methods.
Purpose of the Study:
- To develop novel, efficient strategies for synthesizing glyoxal derivatives.
- To utilize micro-mixer technology for handling unstable organometallic intermediates.
- To produce valuable building blocks for heterocyclic chemistry.
Main Methods:
- Employing two complementary organolithium chemistry strategies.
- Utilizing micro-mixer technology for in-line quenching of intermediates with esters.
- Investigating selective mono-addition reactions.
Main Results:
- Successful generation and quenching of unstable organometallic intermediates.
- Observation of selective mono-addition via stabilized tetrahedral intermediates.
- Efficient production of masked 1,2-dicarbonyl compounds with minimized by-products.
Conclusions:
- Flow chemistry, specifically micro-mixer technology, offers advantages for synthesizing glyoxal derivatives.
- These methods provide direct and efficient access to advanced synthetic building blocks.
- The developed approaches enable gram-per-minute production of valuable compounds for heterocyclic synthesis.
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