Stay Calm with Domino

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

Media Contact

Yoann Coquerel Wiley-VCH

More Information:

http://www.wiley-vch.de

All latest news from the category: Life Sciences and Chemistry

Articles and reports from the Life Sciences and chemistry area deal with applied and basic research into modern biology, chemistry and human medicine.

Valuable information can be found on a range of life sciences fields including bacteriology, biochemistry, bionics, bioinformatics, biophysics, biotechnology, genetics, geobotany, human biology, marine biology, microbiology, molecular biology, cellular biology, zoology, bioinorganic chemistry, microchemistry and environmental chemistry.

Back to home

Comments (0)

Write a comment

Newest articles

Acetylation: a Time-Keeper of glucocorticoid Sensitivity

Understanding the regulatory mechanism paves the way to enhance the effectiveness of anti-inflammatory therapies and to develop strategies to counteract the negative effects of stress- and age-related cortisol excess. The…

Mini satellite wants to take quantum communication to space

Researchers from Jena, Würzburg and Potsdam have successfully developed a design for the smallest system of its kind so far to take highly secure quantum communication to space: Led by…

Results for control of pollutants in water

Brazilian scientists tested a simple and sustainable method for monitoring and degrading a mixture of polycyclic aromatic hydrocarbons, compounds present in fossil fuels and industrial waste. An article published in the journal Catalysis…

Partners & Sponsors