Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Stay Calm with Domino

26.03.2012
Preparation of Benzodiazepine-Containing Drugs

Drugs such as sedatives, hypnotics, and anticonvulsants often contain a benzodiazepine moiety. They are useful in the treatment of, for example, anxiety, insomnia, agitation, and seizures.

The 1,5-benzodiazepin-2-one skeleton in particular is considered a ¡°privileged¡± scaffold in medicinal chemistry and drug development. The pharmacological importance of benzodiazepine derivatives therefore justifies new efforts for their synthesis. As recently reported in the European Journal of Organic Chemistry, a Columbian/French team led by Yoann Coquerel and Jean Rodriguez have now introduced a general domino sequence to provide new synthetic entry to 1,3-dihydro-2H-1,5-benzodiazepin-2-ones.

An important focus of modern organic synthesis is economy, and many transformations have been developed to allow the creation of molecular complexity and functional diversity in a single chemical operation. These transformations are best performed with polyfunctionalized substrates in which the distinct reactive groups react selectively in a well-defined order to give a single product. ¦Á-Oxo ketenes exhibiting two carbonyl groups and one double bond distributed over three carbon atoms are highly reactive molecules that fall into this class of compounds.

¦Á-Oxo ketenes have already been used to prepare a number of heterocycles, and the scientists have already shown that these compounds can be obtained through the rearrangement of 2-diazo-1,3-dicarbonyl compounds. The team was further interested in the reactions of 2-diazoalkane-1,3-diones with bis(N-nucleophiles) in a domino sequence to prepare the desired benzodiazepine derivatives.

Although synthetic routes to benzodiazepines exist, they are often sensitive to the type of substrate and the reaction conditions; moreover, these methods usually require long reaction times and are often complicated by side reactions. Importantly, using their domino methodology and without any additives, the researchers found that microwave irradiation of a 1:1 mixture of a set of diazo compounds with o-phenylenediamine furnished a series of bi- and tricyclic 1,3-dihydro-2H-1,5-benzodiazepin-2-ones, which are among the most promising compounds containing the benzodiazepine structure. The authors postulate that the reaction follows this sequence: rearrangement, nucleophilic addition, and intramolecular imination. This reaction represents a new and advantageously complementary synthetic approach to a valuable class of drug-like compounds.

Author: Yoann Coquerel, Aix-Marseille Universit¨¦ (France),
http://www.ism2.univ-cezanne.fr/permanents/COQUEREL.php
Title: Microwave-Assisted Domino Benzannulation of ¦Á-Oxo Ketenes: Preparation of 1,3-Dihydro-2H-1,5-benzodiazepin-2-ones

European Journal of Organic Chemistry, Permalink to the article: http://dx.doi.org/10.1002/ejoc.201200093

Yoann Coquerel | Wiley-VCH
Further information:
http://www.wiley-vch.de

More articles from Life Sciences:

nachricht Topologische Quantenchemie
21.07.2017 | Max-Planck-Institut für Chemische Physik fester Stoffe

nachricht Topological Quantum Chemistry
21.07.2017 | Max-Planck-Institut für Chemische Physik fester Stoffe

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Manipulating Electron Spins Without Loss of Information

Physicists have developed a new technique that uses electrical voltages to control the electron spin on a chip. The newly-developed method provides protection from spin decay, meaning that the contained information can be maintained and transmitted over comparatively large distances, as has been demonstrated by a team from the University of Basel’s Department of Physics and the Swiss Nanoscience Institute. The results have been published in Physical Review X.

For several years, researchers have been trying to use the spin of an electron to store and transmit information. The spin of each electron is always coupled...

Im Focus: The proton precisely weighted

What is the mass of a proton? Scientists from Germany and Japan successfully did an important step towards the most exact knowledge of this fundamental constant. By means of precision measurements on a single proton, they could improve the precision by a factor of three and also correct the existing value.

To determine the mass of a single proton still more accurate – a group of physicists led by Klaus Blaum and Sven Sturm of the Max Planck Institute for Nuclear...

Im Focus: On the way to a biological alternative

A bacterial enzyme enables reactions that open up alternatives to key industrial chemical processes

The research team of Prof. Dr. Oliver Einsle at the University of Freiburg's Institute of Biochemistry has long been exploring the functioning of nitrogenase....

Im Focus: The 1 trillion tonne iceberg

Larsen C Ice Shelf rift finally breaks through

A one trillion tonne iceberg - one of the biggest ever recorded -- has calved away from the Larsen C Ice Shelf in Antarctica, after a rift in the ice,...

Im Focus: Laser-cooled ions contribute to better understanding of friction

Physics supports biology: Researchers from PTB have developed a model system to investigate friction phenomena with atomic precision

Friction: what you want from car brakes, otherwise rather a nuisance. In any case, it is useful to know as precisely as possible how friction phenomena arise –...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Closing the Sustainability Circle: Protection of Food with Biobased Materials

21.07.2017 | Event News

»We are bringing Additive Manufacturing to SMEs«

19.07.2017 | Event News

The technology with a feel for feelings

12.07.2017 | Event News

 
Latest News

NASA looks to solar eclipse to help understand Earth's energy system

21.07.2017 | Earth Sciences

Stanford researchers develop a new type of soft, growing robot

21.07.2017 | Power and Electrical Engineering

Vortex photons from electrons in circular motion

21.07.2017 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>