What solvents are appropriate to use?
To absorb microwave energy, either the solvent has to be polar, or the reaction mixture must contain ions. Good solvents are polar solvents like methanol, ethanol, NMP (N-Methylpyrrolidinone) or DMF (N, N-Dimethylformamide).

Can non-polar or ‘microwave transparent’ solvents be used?
Although non-polar solvents are microwave transparent, the reagents are often good absorbers capable of generating sufficient heat. Hence it is advisable to run these reactions as concentrated as possible.

Alternatively a small amount of a strong absorber, such as NMP, DMF, or a salt, may be added. When adding these, it is very important that they form a homogenous solution with the solvent.

What are the recommended volumes for the vials?
The recommended volumes are:

· 0.2 – 0.5 mL for the extra small vial
· 0.5 – 2 mL for the small (conical) vial
· 2 – 5 mL for the medium (round bottom) vial
· 8 – 20 mL for the large vial.

What type of reactions can be run using Microwaves?
Almost all types of reactions that are room temperature and higher, can be performed by microwave heating. Even reactions that are traditionally carried out below 0ºC can sometimes be accelerated by microwave ‘flash’ heating. The only exceptions are reactions that are explosive or those that are extremely exothermic.

Is there any chemistry that is not suitable for the instrument?
All general rules of precaution when organic synthesis is performed also apply to microwave assisted synthesis. Thus, reactions with risks of explosions or those that are extremely exothermic should not be performed in the instrument. For example Hydrogen peroxide should not be heated to high temperatures, regardless of the technique, because it is explosive.
When working with reaction mixtures that contain large amounts of ions or those that release gases, e.g. conc. hydrochloric acid or de-carboxylations, extra precaution is advisable. For gaseous reactions the rapid heating rate can generate high pressures very quickly within a closed vessel system. Such reactions can often be performed at low concentrations while providing a larger ‘head-space’ volume.

High absorbing chemicals, example metals, could damage the reaction vessels if they are not properly mixed into the reaction. A small amount sticking to the glass wall of the vial can create a local hot spot that can melt the glass. For example, a grain of palladium can create a local flashover with temperatures up to 800ºC. This might occur early in the process so the temperature recorded by the IR-sensor may only be 40-60ºC. A solution to this problem is to add the palladium (and other solids) to the vial first followed by solvent, to wash it down the sides. In general, keep metals and solids below the solvent surface.

Can I use solid phase reagents?
Yes. Many commonly used resins have been found to be stable at high temperatures for short time periods. Various polystyrene resins have been heated up to 250 °C.

Can metals be used?
Yes. Metals can be used in powder or granulated form; however, care must be taken to keep the metals contained within a solvent. Metals should never be heated in a microwave system without solvent.

Can heterogeneous reactions be heated using microwaves?
Yes. If the heterogeneous reaction contains metals or a high absorbing solid (base), make sure that these are not sticking to the vial walls.

Can I perform neat reactions using microwaves?
Yes. However, neat reactions are not recommended if the mixture consists of high microwave absorbers e.g. metals, strong acids, bases or charged molecules.

Can reductions be done using microwave irradiation?
Yes. This is usually performed using transfer hydrogenation.

Start with a low concentration (<0.2 mmol) and a low temperature (between 100-140ºC) for about 3 mins. If after cooling there is residual pressure in the process vial, insert a needle through the vent-port in the lid to release the pressure prior to lid opening.

Is there a good source for generating CO in a reaction mixture while using microwave irradiation?
Yes. Mo(CO)6 liberates CO at 150ºC (1). DMF will decompose in the presence of KOtBu to liberate CO and HN(CH3)2 at 180ºC or higher (2).

1) Kaiser, N-F. K.; Hallberg, A.; Larhed, M., J. Combi. Chem., 2002, 4 (2), 109-111

2) Wan, Y.; Alterman, M.; Larhed, M.; Hallberg, A., J. Org. Chem., 2002, 67, 6232-6235

Can reactions be performed under an inert atmosphere?
It is easy to flush the process vial with an inert gas, if needed. But for a large number of reactions the use of inert atmosphere is not necessary because of the short reaction times, the high reaction rates, and the sealed process vials.

How much material do you usually put in a vial? (maximum amount?)
This depends on the chemistry. A general guideline can be 0.5 mmol in 2.5 ml (0.2 M).

Can I use cooling-while-heating?
Yes. Please note that when cooling is applied during a reaction, the temperature inside the vial will be higher than the recorded value. That is, the true temperature will be higher than the reaction temperature shown in the software. The magnitude of this difference depends on the type of reaction and the solvent, but is likely to be significantly higher.

Click here to read more about "Cooling-while-heating"