LabTips: Would You Benefit From Microwave-Assisted Organic Synthesis in Your Lab?

 <span>LabTips:</span> Would You Benefit From Microwave-Assisted Organic Synthesis in Your Lab?

Conventional Versus Microwave Heating

Heat has been used to induce chemical synthesis since the Bunsen burner was invented in 1855. Other heating devices, including air and oil baths, hot plates, ovens, rotary evaporators, and heating mantles, have since all but replaced the Bunsen burner. All these devices apply traditional (or conductive) heating, which is the transfer of heat from the device to the reaction vessel to the reaction mixture. From ramping up to temperature, to lack of fine control over the bulk reaction temperature, to cooling the bulk reaction, conductive heating is energy inefficient and slow.

During the development of novel products, the bottleneck of conventional chemical synthesis is optimization of reaction steps, many of which require heating for long periods of time. Although conductive heating eventually gets chemists where they want to go, microwave-assisted heating under controlled conditions is now also used for any application that requires heating of a reaction mixture, since it dramatically reduces reaction times. Microwaves travel through the vessel wall, which is usually almost transparent to microwaves, for direct interaction with components of the reaction mixture. Heating is a result of dielectric heating effects on dipoles and/or ions, with rapid conversion of kinetic energy into heat. Therefore, microwave heating occurs rapidly and remotely, and since microwaves travel at the speed of light, they can be turned off instantly when the reaction mixture reaches the temperature set point. In other words, microwave heating is energy efficient and fast.

Anton Paar Microwave Synthesis Family

Microwaves for the Chemistry Lab—30-year History

Microwave energy was initially used to heat food. In the mid-1980s, kitchen microwaves were first used in the laboratory for chemical syntheses. The first experiments were performed in sealed PTFE (polytetrafluoroethylene) or glass vessels without measuring temperature or pressure. Despite the rapid, uncontrolled heating of organic solvents in sealed vessels and frequent violent explosions, the advantages provided by microwave-accelerated reaction rates led to increasing use of domestic ovens during the first 15 years of microwave-assisted organic synthesis. Over the last 15 years, the collegial relationship between investigators and instrument manufacturers has fostered ongoing development of dedicated, sophisticated instruments. A wide range of dedicated microwave reactors provide safety, controlled conditions, and the ability to accurately monitor and measure reaction parameters. There are now thousands of publications on microwave-assisted organic synthesis, and it is safe to say that it is an established standard method.

Advantages of Microwaves for Organic Synthesis

  • Faster reaction times/rapid optimization: Microwave energy enhances organic reactions by reducing chemical reaction times—in the best cases, hours are reduced to minutes. Or, put another way, the reaction rate of microwave-induced organic reactions is 10- to 1000-fold faster than conventional synthesis.* Microwave technology enables reactions to be optimized in parallel, resulting in markedly reduced development time.
  • Higher product yields: Rapid heating to the target temperature inhibits the formation of byproducts, leading to greater purity and yield increases of 10% to 30%.*
  • Energy-efficient heating.

Advantages of Microwave-Assisted Organic Synthesis in Dedicated Reactors

  • Broad dynamic temperature range/wide range of applications: Microwave technology now allows reactions at temperatures up to 300 °C. This dynamic range enables such processes as ring expansion at the low end of the range, coupling and substitution reactions, and superheating. Dedicated microwave reactors that accommodate sealed reaction vessels throughout the process act as autoclaves, leading to temperatures up to 300 °C and pressures to 80 bar. Solvents heated to far above their boiling point can dramatically reduce reaction times.
  • Safety: Instrument manufacturers consider safety the highest priority and have developed numerous safety features, including explosion-proof reactors, shutdown mechanisms for overheating and overpressurization, and venting mechanisms for sealed-vessel reactions. Dedicated reactors have continuous power output to minimize the risk of thermal runaways and reduce the occurrence of hot spots.
  • Excellent parameter control: Dedicated reactors employ infrared sensors to control reaction temperatures, pressure sensors for monitoring the pressure in sealed vessels, and built-in magnetic stirrers to provide uniform temperature distribution. In addition, immersing fiber-optic temperature probes are available for even more accurate measurement of reaction mixtures.
  • “Green chemistry”: Near-critical water, accessible using the highest-performance microwave vessels, has less polarity and is more effective at dissolving organic substrates. The increased use of water by industry is considered to be more environmentally benign than organic solvents, and such processes enable easy separations of the solvent, organic reactants, and products.
  • Required by most major scientific journals: There are good scientific and practical reasons why dedicated instruments are preferred over household microwaves, such as imprecise measurements, safety problems, and poor reproducibility.

Refined and Dedicated Microwave Instruments and Accessories

Within the last decade, microwave-assisted organic synthesis has come into its own. Instrument manufacturers have designed and continue to design reliable and versatile microwave instrumentation that fulfills the requirements of modern academic and industrial research. Instruments are available that cover the entire range of microwave synthesis applications, from small-scale laboratory research and discovery to kilolab processing, along with accessories that enable flexibility.

Direct scale-up from development to larger quantities is key, requiring accurate internal temperature measurement and the ability to obtain those data. With accurate data, an optimized protocol can be applied to any scale-up without losing efficiency.

Important considerations include:

  • Installed Power: Different manufacturers have differing power maximums on the magnetrons in the microwave. Higher power ratings generally lead to higher microwave field density, which can enable heating of some solvents that don’t interact as well with the microwave field.
  • Consumable Costs: Microwaves have come down significantly in price since they first were introduced, but still are more of an investment than a Bunsen burner. Don’t stop your analysis at the initial price of the microwave; consider the consumables costs to get a picture of the total cost of the microwave system.
  • Cameras: One drawback of microwave systems is that they aren’t transparent—you can’t typically see inside. If your reactions have precipitates or color changes that are important to monitor for reaction progress, an internal camera can help reduce the time for optimization.
  • Scale-Up Options: If you plan on scaling up your research into the kilolab, be sure to ask about options for direct scaleup. Using a system that enables scaleup without reoptimization of the reaction can save months on your research timeline.
  • Silicon Carbide: Regardless of microwave power, some solvents just don’t interact with the microwave field because they lack the dipole moment required. Silicon carbide (SiC) strongly absorbs microwave energy and rapidly transfers thermal energy to microwave-transparent nonpolar reaction mixtures. SiC is also chemically inert, so it can be used to heat these nonpolar solvents. Look for vessels, plates, and inserts that can help if you use such solvents.
  • Internal Temperature Monitoring: All microwave reactors use an infrared temperature sensor to monitor the temperature of the reaction vial. Because of the time required for heat transfer from the reaction to the outer vessel wall, this temperature can vary markedly from the actual temperature of the reaction. If your reactions are very exothermic, you may want to consider internal temperature monitoring for better reaction control and characterization.

*Rajasekhar, K.K.; Ananth, V.S. et al. Comparative study of conventional and microwave induced synthesis of selected heterocyclic molecules. Int. J. ChemTech Res. 2010, 2, 592‒7.

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