CHEM 231 Lab

Technique Primer

Microwave-assisted Synthesis
Domestic microwave ovens have been in use for over forty years, and their advantages of speed and convenience are well known. The advent of microwave heating in the laboratory is a relatively recent development, but they have quickly become an indispensible tool for the synthetic chemist. In a dedicated microwave reactor (Figure 1), reactions can be run in sealed vials under carefully controlled conditions at temperatures up to 200C and pressures up to 20 bar. This provides the means to heat reactions much higher than conventional open-vessel conditions, in which the maximum temperature is limited to the boiling point of the solvent. heating. As it turns out, the electromagnetic field couples more strongly to polar solvents, so they heat up more quickly. The so-called loss tangent (tan ) is the best measure of how well a substance couples to microwave energy (Table 1)the higher the loss tangent, the stronger the absorption. The microwave reactor has a setting (absorption level) to correct for this variability.
Solvent Ethylene glycol Ethanol Dimethylsulfoxide 2-Propanol Formic acid Methanol Nitrobenzene 1-Butanol 2-Butanol 1,2-Dichlorobenzene 1-Methyl-2-pyrrolidone Acetic acid tan 1.350 0.941 0.825 0.799 0.722 0.659 0.589 0.571 0.447 0.280 0.275 0.174 Solvent N,N -Dimethlformamide 1,2-Dichloroethane Water Chlorobenzene Chloroform Acetonitrile Ethyl acetate Acetone Tetrahydrofuran Dichloromethane Toluene Hexane tan 0.161 0.127 0.123 0.101 0.091 0.062 0.059 0.054 0.047 0.042 0.040 0.020

Table 1. Loss tangents (tan ) of selected solvents. Another solvent parameter to consider is its vapor pressure. While a sample can be heated above its boiling point (up to 250C), the maximum pressure is still 20 bar. Temperature-pressure curves for a few common solvents are presented in Figure 2 as a rough guide.
CH2Cl2 EtOH MeOH
acetone
200

Figure 1. The Biotage Initiator microwave reactor (left) and a 2-5 mL reaction vial (right). The ability to achieve higher temperatures is the biggest advantage of microwave reactors. As the Arrhenius equation demonstrates, higher reaction temperature results in a larger rate constant and consequently faster reactions (and lower reaction times). This rate acceleration can be estimated using the Arrhenius equation. For example, if we assume a typical activation energy (Ea) of 14 kcal/mol and consider changing the temperature from 300K to 310K, then the rate acceleration would be:
k 2 Ae e e 0.76 2.1 k1 Ae Ea / RT 1 e 14,000 /(1.986)( 300)
Ea / RT 2 14, 000 /(1.986)( 310)

25

20

pressure (atm)

15

10

0 40 60 80 100 120 140 TC 160 180 220

In other words, raising the temperature of the reaction roughly doubles the reaction rate. This is a very useful (albeit approximate) rule of thumb. Thus, a reaction that takes 8 hours at 40C would be expected to take only 30 minutes at 80C. Not only is the maximum attainable temperature higher, but the rate of heating is also much more rapid. Instead of relying on conduction, samples are heated by the coupling of microwave radiation with the solvent, a phenomenon known as dielectric

Figure 2. Pressure-temperature curves for selected solvents (approximate). When preparing a sample for a microwave reactor, the following guidelines should be observed: the total volume (VT) must be between 2-5 mL temperature cannot exceed 250C maximum pressure is 20 bar no solid material should be on the vial walls a stir bar must always be used vials should be opened and worked up in a hood

Rule of Thumb: for every 10C increase, the reaction rate doubles

H2O