Our flow reactor range has already been established in the top 4 Agrochemical companies globally at being able to improve a number of previously restricted chemistries such as hydrogenation, oxidation, or ozonolysis. However, the search for new heterocycles to discover new pesticides or herbicides is of the utmost importance. Below you can find some examples of how our flow reactor range can help you in making novel molecules or improving synthesis routes.
Hydrogenation of heterocycles to produce novel compounds
It has already been well established that the H-Cube Series make significant advances for hydrogenation in terms safety, speed, and capabilities, but how can they generate new molecules. One method is to utilize their high pressure capability (100 bar, 1450 psi) coupled with short residence times in order to selectively reduce a heterocycle in a potential molecule in order to dramatically alter its properties. A simple illustrative example is given below. Standard batch equipment do not typically have the reaction parameter capabilities or the ability to react selectively, so this is really only specific to the H-Cube®.
The main advantage of this method is that you can use chemical material that is currently available to you from your stock. This means compounds could be tested quickly and cheaply.
Generation of novel heterocycles using high temperature flash synthesis
Heterocyclic carbonyl compounds e.g. quinolones, pyridopyrimidinones, naphthyridinones are important structural motifs in various biological active compounds (e.g. norfloxacin, nalidixic acid). One of the most practical approaches for their synthesis is the thermal cyclisation of the appropriate open chain intermediates containing suitably substituted 3 carbon extension on the nitrogen. Such intermediates can be derived either from a condensation product of formaldehyde acetal and a CH-acidic methylene containing precursor (e.g. malonic ester, Meldrum’s acid), or cyano-acetic acid ester by Gould-Jacobs type of reaction.
Using this method in combination with the Phoenix Flow Reactor™ at temperatures in excess of 300°C and high pressure, to utilize low boiling point solvents at these high temperatures, we were able to generate a series of bicyclic compounds.
If you utilize 5 or 6 member S, O, or N type heterocyclic anilines, then novel heterocyclic scaffolds can be made in this manner very effectively and very quickly.
Please also see our appolcation note here.