The facts about simultaneous cooling

It sounds almost paradoxical. Why would anyone try to cool something at the same time they were trying to heat it? In the case of microwave-accelerated synthesis, the answer is enhanced yields. PowerMAX, a new technology that allows simultaneous cooling of a reaction with compressed gas while heating it with a substantial amount of microwave energy (enhanced microwave synthesis), enables more energy to be introduced into the reaction, resulting in significantly higher yields and cleaner chemistries in many reactions.

Though it sounds simple, enhanced microwave synthesis (EMS) has generated a great deal of debate among organic chemists. Much of the debate has been the normal scrutiny any new technology must inevitably face; however, some discussion has centred on the temperature of the reaction.

Some have said that the temperature is actually much higher than the IR sensor is measuring and that the resultant increase in yields is due to the higher temperatures. Much of the work performed on PowerMAX, thus far, has utilised this method of temperature measurement, as most of the instruments currently on the market have IR temperature sensors. CEM recognised that more research using a direct method of temperature measurement was necessary to accurately illustrate the benefits of enhanced microwave synthesis. With that in mind, CEM's scientists began working with the optional fibre optic temperature accessory for CEM's line of microwave synthesis instrumentation, which uses a sensor probe inserted into the vessel to directly measure the temperature of the reactants.

What was found confirmed CEM's theories about PowerMAX. It is already an established fact that the ability of microwave energy to superheat reactants quickly increases yields and decreases side reactions. CEM postulated that since microwave energy is transferred kinetically to the reactants, even greater yields might be achievable, with still fewer side reactions, if the amount of energy introduced to the reactants was increased. Of course, when the power is increased, users run the risk of overheating temperature sensitive reactants and causing degradation of the product. This problem was solved by cooling the reaction with compressed gas on the outside of the reaction vessel, while simultaneously irradiating the sample with up to 300 W of microwave energy. As a result, a significant increase in the yields of many reactions, with no increase in unwanted side reactions, was observed.

The following examples demonstrate findings for two reactions that benefit from the use of PowerMAX, as well as one that PowerMAX did not seem to affect.

The temperatures of the Heck reactions were measured with a fibre optic probe. In addition, the reaction was performed in an open vessel where the temperature of the reaction was limited by the boiling point of the solvent (DMF~153°C). As the temperature of the reactants cannot exceed the boiling point of the solvent, this reaction and the Diels-Alder that follows illustrate that the temperature obviously cannot be the sole reason for the increase in yields. Power also plays a significant role.

The temperature of the PowerMAX reaction closely mirrors the reaction performed using conventional microwave synthesis (CMS); however, the power input is significantly higher than the CMS reaction.

From the GC/MS chromatogram, it can be seen that the PowerMAX reaction converted 45% to the trans-4-aminostilbene product compared to the CMS reaction, which converted only 26% to product. In addition, the CMS reaction also had three unwanted side reactions compared to one using PowerMAX.

In the Diels-Alder reaction, PowerMAX enabled a 27% conversion rate compared to only 1% using CMS. Again, the reactions were performed at atmospheric conditions (open vessel) and the temperatures of the reactions were within a few degrees of each other. The CMS reaction was conducted using 150 W, while the PowerMAX reaction utilised 300 W.

PowerMAX can make a significant difference in product yields for many reactions; however, there are some, such as the following Buchwald reaction, that show little or no increase in product yields. Research on these reactions is ongoing and it would be premature to speculate at this time why the simultaneous cooling method does not appear to provide any significant enhancement for this particular chemistry. This is a clear indication that not all reactions benefit from this process and demonstrates why CEM's instrumentation allows the user to select whether to run a reaction with PowerMAX or under CMS conditions.

The temperature of the PowerMAX reaction follows the CMS reaction until the microwaves are turned off after 20 minutes of energy input. The temperature of the PowerMAX reaction then drops faster than the CMS reaction, due to the cavity temperature. The power input for the CMS reaction is irregular, as the instrument controls the reaction based on its temperature. The PowerMAX energy input remains constant; yet in the final analysis, there is not a significant increase in product yield.

As CEM continues to research the effects of PowerMAX on various types of reactions, they will no doubt continue to find that the technology displays varying degrees of success, depending on the components of the reactions themselves. This is to be expected as different chemistries have their own unique properties. Nevertheless, the PowerMAX technology developed for microwave-accelerated synthesis enhances the benefits of the methodology and offers organic chemists an effective tool for maximising productivity and creating cleaner chemistries.

These examples plus similar input from users confirm the following facts:

• Power input is important - significant increases in yields occur even when the bulk temperature remains low;
• With PowerMAX, the input power can be controlled independently of the bulk temperature;
• PowerMAX allows users to expand the range of chemistries they can perform effectively and optimise those chemistries.

Where do we go from here?

PowerMAX has led CEM's research team to examine the benefits of power spiking reactions, that is the process of rapidly turning the microwave field on and off at its maximum level, to enhance further the kinetic energy transfer effects seen with microwave synthesis. This methodology appears positioned to offer benefits to microwave-accelerated chemistry.