Here is another account of moving from a conventional 2-step process into a tandem microwave promoted reaction. Seems easy enough – just mix all of the reagents together. Well, it never quite works that way…..if I do nothing else on the site but change people’s mindset away from nuking a reaction as a last resort or somehow thinking this is magic and if something doesn’t work conventionally then let’s give the microwave a chance…..that simply doesn’t help and certainly will drive you away from the technology without understanding the limits and scope. Heating a bad reaction higher is just a bad reaction at higher temperature.

A report on the synthesis of 2-hydrazolyl-4-thiazolidinones bears an example of this thought process. 4-Thiazolidinones are recognized as an important class of heterocycles in several areas of pharmaceutical research so the application can be viewed with some value. The better conventional approaches involve a 2-step reaction sequence with an aldehyde and a thiosemicarbizide to give the carbazone, which can then be treated with maleic anhydride (thia-Michael and ring closure) to give the desired heterocycle. This group went stepwise to make sure that each step was efficient and compared the time and yield with conventional steps.

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Conventional 2-step

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Comparison of each step

Lastly, they felt pretty comfortable combining all of the steps and reagents in one microwave method. I always find it interesting when there is some thought going into the process — look through their rationale for the process and mechanism scheme  — I believe these types of processes are underutilized in medicinal chemistry approaches in the industrial setting, but not haven’t heard good reasons why.

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All in one-pot

An resulting compounds made:

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Table of thiazolidinones and yields for the tandem mw reactions