Some of the advancements in microwave synthesis hasn’t taken place in the cavity, but in the way different instrumentation companies have implemented vessel modifications, temperature sensors and agitation — and as we know these should show the ability to be integrated into the software for easy operation. I am going to speak to a few of these.

Pressure: For a number of years (in both synthesis and microwave digestion) we performed our chemistry without the relief of pressure — and for all practical purposes we were heating bombs in a microwave. Burst discs offered an advancement in thought so that we had a way to get rid of excess vapor pressure if things got out of control for a vessel — better idea, but of course these acted like aerosol cans and sprayed some of the chemistry inside the cavity — lots of cleaning. The next generation of improvement was a VENT-AND-RESEAL (Milestone) mechanism where a spring device would hold a specific amount of pressure generated during the method — so for example if a vessel was to hold 100 bar of pressure then the spring would compress at 100 bar, relieve the vapor pressure, then close again. A version of this can be seen with self-regulating vessels which essentially have a wedge placed down into the vessel and burps on pressure relief then closes again (unfortunately this doesn’t always close perfectly so can cause issues depending on the method). Newer concepts are now seen with SMART VENT (Anton Paar) and ActiVent (CEM). Without exact details each of these modifications, it enables the measurement of excess pressure generated in a reaction or digestion — either by measuring the displacement of a seal or pressure buildup against a cap. The good thing is that the excess gas is removed through the exhaust and away from the reaction vessels. Unfortunately this has its own set of issues — reactions with low boiling amines or digestions that are only partially done will remove important components before they reach their endpoints (i.e. loss of reagent or desired element before completion). Lastly, is a concept to work to raise the boiling points of the contents of a reaction or digestion — in this case the chemistries are pre-pressurized prior to microwave power being delivered. I have talked about this before (SRC technology), and it provides a way to allow reactions to build up pressure but not lose any volatile starting material or element of interest.

A recent article on the ActiVent technology illustrates a Woff-Kishner reduction of a ketone through the hydrazone with the release of N2 during the course of the reaction. While it is a good example of the technique and hardware, I still wonder about the breadth of reactions and the temperatures that can be used for driving difficult reactions or reactions with low-boiling starting materials (laundry list of small m.w. amines in the med chem arsenal). Will be interesting to see and hear people’s thoughts and expanded utility of the reactions performed.

The take home message is that if you need to get to a specific temperature and a specific solvent, make sure your pressure mechanism is appropriately designed for the chemistry. Some added bits: a) if you are going to need high temperature reaction conditions it is best to find a system that accommodates the design of experiment for 270C and pressure capability in the 100 bar or higher range. b) agitation is a must — verify that there is appropriate stirring — cant go from small to large scale without and idea of how the mixing is going c) look for the ability to add gases — this has been an expanded area of research that needs full attention in the microwave community and d) microwave chemistry is highly energetic but easy to use when you have thought out the chemistry.

Happy research!

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