Microwave-assisted Synthesis
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 200°C 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
tan
Solvent
tan
Ethylene glycol Ethanol Dimethylsulfoxide 2-Propanol Formic acid Methanol Nitrobenzene 1-Butanol 2-Butanol 1,2-Dichlorobenzene 1-Methyl-2-pyrrolidone Acetic acid
1.350 0.941 0.825 0.799 0.722 0.659 0.589 0.571 0.447 0.280 0.275 0.174
N,N -Dimethlformamide 1,2-Dichloroethane Water Chlorobenzene Chloroform Acetonitrile Ethyl acetate Acetone Tetrahydrofuran Dichloromethane Toluene Hexane
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.
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 40°C would be expected to take only 30 minutes at 80°C. 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
H2O
200
220
25
20
15
10
5
0 40
14, 000 /(1.986)( 310)
k 2 Ae e e 0.76 2.1 k1 Ae Ea / RT 1 e 14,000 /(1.986)( 300)
acetone
Ea / RT 2
CH2Cl2 EtOH MeOH
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 300°K to 310°K, then the rate acceleration would be:
pressure (atm)
Figure 1. The Biotage Initiator microwave reactor (left) and a 2-5 mL reaction vial (right).
Another solvent parameter to consider is its vapor pressure. While a sample can be heated above its boiling point (up to 250°C), the maximum pressure is still 20 bar. Temperature-pressure curves for a few common solvents are presented in Figure 2 as a rough guide.
60
80
100
120
140
160
180
T°C
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 250°C 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 10°C increase, the reaction rate doubles
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 200°C 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
tan
Solvent
tan
Ethylene glycol Ethanol Dimethylsulfoxide 2-Propanol Formic acid Methanol Nitrobenzene 1-Butanol 2-Butanol 1,2-Dichlorobenzene 1-Methyl-2-pyrrolidone Acetic acid
1.350 0.941 0.825 0.799 0.722 0.659 0.589 0.571 0.447 0.280 0.275 0.174
N,N -Dimethlformamide 1,2-Dichloroethane Water Chlorobenzene Chloroform Acetonitrile Ethyl acetate Acetone Tetrahydrofuran Dichloromethane Toluene Hexane
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.
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 40°C would be expected to take only 30 minutes at 80°C. 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
H2O
200
220
25
20
15
10
5
0 40
14, 000 /(1.986)( 310)
k 2 Ae e e 0.76 2.1 k1 Ae Ea / RT 1 e 14,000 /(1.986)( 300)
acetone
Ea / RT 2
CH2Cl2 EtOH MeOH
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 300°K to 310°K, then the rate acceleration would be:
pressure (atm)
Figure 1. The Biotage Initiator microwave reactor (left) and a 2-5 mL reaction vial (right).
Another solvent parameter to consider is its vapor pressure. While a sample can be heated above its boiling point (up to 250°C), the maximum pressure is still 20 bar. Temperature-pressure curves for a few common solvents are presented in Figure 2 as a rough guide.
60
80
100
120
140
160
180
T°C
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 250°C 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 10°C increase, the reaction rate doubles
