This is a knowledge base on chemical synthesis using laboratory microwave reactors.

Helpful Hints for Successful Microwave Synthesis

Here are some important facts to consider when you perform microwave synthesis experiments.

Accurate temperature measurement

The key parameter for comparing microwave assisted experiments and transferring optimized methods to other reactors or applying other technologies is the reaction temperature. State-of-the-art microwave reactors are equipped with an IR sensor to monitor the temperature externally, on the corresponding vessel surface. However, IR sensors are not always able to reflect the real internal reaction temperature. Consequently, an internal temperature measurement of a reaction mixture in addition to the IR temperature (Figure 4) should be considered, since there are certain issues which may falsify the IR measurement:
    

  • Exothermic reactions: An externally mounted sensor naturally has a slow response time. Consequently, immediate temperature changes are not detectable with IR sensors.

  • Thick vessel walls: For reaction vessels to withstand high temperatures and pressures, the vessel walls have to be very thick. This thickness will falsify the IR signal, resulting in monitored temperatures which are significantly lower than the actual internal reaction temperature.

  • Weakly microwave-absorbing reaction mixtures: If a reaction mixture does not interact with microwaves at all, the reaction vessel will be heated rather than the vessel content. As a result, the vessel surface will be hotter than its content, resulting in higher monitored IR values that no longer reflect the correct reaction temperature.


For a comprehensive review on the importance of temperature monitoring in microwave chemistry, refer to the highly informative publication “How to measure reaction temperature in microwave-heated transformations ” C. O. Kappe, Chem. Soc. Rev. 2013, 42, 4977-4990.

 

Microwave reaction vessel with IR sensor and internal fiber optic probe for simultaneous temperature measurement.

 Simultaneous IR and internal temperature monitoring provides accurate temperature values as well as valid information about the reaction progress. This approach can be taken for monitoring a reaction process online (e.g. in the synthesis of polymers).
Figure 4: Microwave reaction vessel with IR sensor and internal fiber optic probe for simultaneous temperature measurement.

 
For accurate temperature monitoring, internal fiber optic probes are necessary. Optimal information about the reaction process is provided by simultaneous internal and IR temperature measurement.

 

Heating-while-cooling

Impressive effect of heating-while-cooling on the temperature distribution in the reaction mixture.

Figure 5: Heating profile of a microwave-
assisted experiment. After 100 seconds,
the cooling is activated in addition to
microwave heating. As the diagram shows, the IR and internal temperature results significantly differ under heating-while-cooling conditions. Users who only rely on IR temperature values run the risk of erroneous results.
 

The term heating-while-cooling refers to microwave experiments in which reaction mixtures are heated via microwave irradiation while the reaction vessel is simultaneously cooled with compressed air. Consequently, due to additional cooling, more microwave power is introduced into the reaction mixture in order to maintain the set temperature.

 

Heating-while-cooling is usually employed by chemists who think that introducing more power into a reaction mixture under a constant temperature has a beneficial effect on the reaction outcome. In fact, this has already been proven wrong.[1] The only beneficial effect of simultaneous cooling is the reduction of heat generated by exothermic reactions.

If reactions are performed under heating-while-cooling conditions, the use of an internal temperature sensor is highly recommendable! An IR sensor will not reflect the actual temperature of the reaction mixture, because the sensor only measures the temperature of the reaction vessel, which is cooled by the compressed air stream. Consequently, the IR sensor will always show significantly lower temperatures (Figure 5).


Under heating-while-cooling conditions, the internal temperature can be up to 60 °C higher than the measured IR temperature. An internal temperature sensor is essential for heating-while-cooling!

 

Open vessels?

It is often stated that the use of a microwave reactor for refluxing a reaction mixture (no sealing and pressurizing of the reaction vessel!) can have beneficial effects on a chemical reaction compared to the use of a hotplate as a heat source. However, this is not true, since the reaction temperatures in a microwave-heated reflux experiment and a conventionally heated reflux experiment are similar (i.e. the boiling point of the used solvent). Consequently, the results will also be similar for both heating modes, since the key parameter for the reaction progress is always the reaction temperature.

The significant impact of the reaction temperature is defined in the Arrhenius Equation. It states as a rule of thumb that a temperature increase of 10 °C doubles the reaction rate. Based on this rule, a simple calculation already illustrates the principle (see Table 2).

 

Table 2: Example calculation of reaction times according to Arrhenius' Law

 

The Arrhenius Equation is always valid, independent of the heat source. Therefore, reflux heating at 80 °C under microwave irradiation will give similar results as heating at the same temperature under conventional conditions. If the results were different, this would mean that the microwave power (and not the temperature) had an additional influence on the reaction behavior, which would suggest that non-thermal microwave effects were involved. However, the existence of such non-thermal effects has recently been proven wrong.[2]

 

In fact, the most important advantage of microwave heating in an open-vessel system – the possibility of superheating reaction mixtures far above the boiling point of the used solvent – has been proven to be completely lost, as the following example shows.

 

 

Figure 6: Biginelli Cyclocondensation

The reaction shown in Figure 6 has been performed in three different setups:

  • Oil bath reflux
  • Microwave reflux
  • Microwave sealed vessel

 

 

 

 

Table 3: Experiment conditions and yields for
the Biginelli reaction (Figure 6) with different heating modes.
 

Table 3 contains a summary of the reaction conditions and yields for the above mentioned three different setups. The results (isolated yields) clearly show that the reaction could only be significantly enhanced under sealed vessel conditions and at higher temperatures (entry C).


Under open vessel conditions, the reaction proceeded very much like the conventionally heated experiment - no enhancement at all was observed, although microwave irradiation was used for heating.

 
Open-vessel microwave heating will not result in any rate enhancements compared to conventional heating, since the reaction temperatures are similar in both cases (limited by the boiling point of the used solvent). Only sealed vessels offer the proven advantages of microwave chemistry!

 

Ultimate heating efficiency - Silicon Carbide (SiC) for ultimate heating efficiency

Microwave chemistry generally relies on the ability of a reaction mixture to efficiently absorb microwave energy, taking advantage of the microwave dielectric heating phenomena of dipolar polarization or ionic conduction.  Consequently, the reaction mixture must be microwave absorbing for efficient heating in the microwave field. However, there are some commonly used organic solvents  which cannot be heated with microwave irradiation, since their microwave absorbance  is very poor (e.g. hexane, toluene, dichloromethane, etc.). Such solvents can be heated efficiently using SiC accessories in different shapes for individual use (Figure 7).

 


Figure 7: Different microwave reactor accessories made of silicon carbide: (a) reaction vessel  (next to a standard borosilicate vial), (b) microtiter plates, (c) passive heating elements.

The efficiency of SiC is demonstrated with the heating curve in Figure 8. While heating toluene in a glass vial takes almost 10 minutes, this very weakly absorbing solvent is heated to 250 °C within 1 minute only in a SiC vessel under microwave irradiation.

 

Figure 8: Heating curves of 5 mL toluene in a SiC vessel (red curve) and in a standard borosilicate glass (gray curve). The temperature was controlled with an internal fiber optic probe.
 The efficiency of SiC is demonstrated with the heating curve in Figure 8. While heating toluene in a glass vial takes almost 10 minutes, this very weakly absorbing solvent is heated to 250 °C within 1 minute only in a SiC vessel under microwave irradiation.

 


SiC efficiently heats non-polar reaction mixtures in the microwave field
and provides reliable results due to optimal temperature homogeneity.

 

[1] M. A. Herrero, J. M. Kremsner, C. O. Kappe J. Org. Chem. 2008, 73, 36-47 

[2] C. O. Kappe, B. Pieber, D. Dallinger Angew. Chem. Int. Ed. 2012, 51, 2–9