Interesting new article (Beilstein JOC 2014) on a microwave optimized approach to 2-(4-((1-phenyl-1H-1,2,3-triazol-4-yl)methoxy)phenyl)-1H-benzo[d]imidazoles via a 3-component reaction combination, The group decided that 3 possible combinations were feasible to provide the final compounds depending on how the starting materials were reacted together, Path A — 2 step with the triazole ring formed first then cyclocondensation with the diamine….Path C forms the benzimidazole first followed by   the cycloaddition of the azide to the acetylene susbstrate……and Path B were each of the reactions are taking place under the same set of conditions in one-pot.

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Interestingly —  most people would likely use the same thought process and see if the conditions for forming the benzimidazole or the triazole would work best and what order the strategy should provide the best pathway. In  the process, they reasoned that the conditions would be suitable by simply having all 3 components together in a one-pot reaction…..good for them. If you take a look at the conditions for the imidazole formation, the solvent choice was toluene but in the Cu-mediated triazole formation THF,H2O was used…….and therefore the group next moved to a solvent screen to optimize conditions

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A total of 11 reactions were performed to conclude that some H2O was needed for the reaction to proceed well….solubility likely from the CuSO4. There were some differences in reaction time and temp so it took some time to conclude (see my thoughts on SRC screening and this would have taken 30 minutes tops running all of the reactions at 110C for 20 min).  Once the solvent combination was chosen a series of compounds with changes on both ring systems were made — although there was a little discussion on group substitutions and reaction yields, all products were formed in good to excellent yield — providing an accelerated approach using microwave technology to speed up the reactions, but also to introduce strategic thinking into how the technology could be applied creatively.

Dig into the article a bit — they formed some mechanistic reasoning to the possible pathways for the reactions……which is always fun, and for me, where I take the info and see how it can be applied to other reactions of interest. THERE SHOULD BE A BOOK OF REACTION CONDITIONS, TRANSFORMATIONS…PERFORMED IN MICROWAVE REACTORS…..make it searchable and chemists will devour the chemistry in a number of creative ways.

Enjoy the read.

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