Microwave ovens in the chemistry lab are nothing new. In the 1960s, physical chemists used modified domestic microwave ovens to give their systems a temperature kick while polymer chemists were using them to string out their molecules as long ago as 1967. By the early 1980s, organic chemists began to bring their domestic ovens into the lab and found that what was good enough for cooking the goose was good enough for chemistry too. Various pioneering chemists around the world began to discover that microwave energy could accelerate reactions, boost yields and kick start otherwise impossible reactions.
The problem was that some of those early microwave reactions gave spurious results. Domestic microwave ovens were not up to the job of
making fine chemicals. They produce interference between microwaves so some parts of the reaction mixture get heated a lot more than others, which meant uneven reactions. There was also the risk of explosion.To provide a more consistent menu, companies like Milestone, Personal Chemistry, and CEM Corporation have since developed microwave reactors specifically designed for the chemical laboratory. These machines can precisely control time, temperature, pressure, microwave power, and stirring rate using a personal computer. They also allow chemists to monitor progress accurately using various computer-linked sensors. Built-in robotic systems also make adding and mixing reagents an automatic process. As such the number of chemists carrying out a la carte chemical reactions has increased dramatically.
As with domestic microwave technology that have automatic settings for baked potatoes, defrosting pizza, or making scrambled eggs, the lab machines have automated settings for several heat-driven organic reactions, such as allylation, benzylation, ester hydrolysis, Heck coupling, Mitsunobo, nitro reduction, Suzuki and silylation reactions, which can be strung together.
Among those discovering the benefits of microwaves in the lab are Christopher Strauss and his colleagues at the CSIRO Division of Chemicals and Polymers in Clayton, Victoria, Australia. Strauss' team has found that they can carry out reactions of a compound known as allyl phenyl ether at 200 Celsius in water simply by applying a little pressure to keep the water under control. This has allowed them to generate
several interesting products. Moreover, they have been able to demonstrate that it is possible to use microwave heating to convert alcohol molecules into alkenes and vice versa. Additionally, their approach avoids the need to use a toxic volatile organic solvent or an acid catalyst. This, they say, is making the microwave reaction the obvious choice for the green chemist.Controlling the path chosen by a reaction can be very important. Sometimes there are two possible outcomes, a left-handed product and a right-handed product say. Making pharmaceuticals in just one form can be critical to how well they work as medicines and how safe they are. For example, the painkiller ibuprofen is three times stronger in one form, or enantiomer, than the other. Now, Nikolai Kuhnert and Timothy Danks of Surrey University in England have demonstrated, for the first time, that stereoselective synthesis is possible in the microwave for the synthesis of important building blocks for several pharmaceuticals, the 1,3-oxazolidines.
They have found that a type of reaction known as a condensation in which pure amino alcohols of just one enantiomeric form, such as the natural compounds ephedrine and pseudoephedrine, "condense" with aldehydes releasing a water molecule and resulting in a product can be made to take place with high yields in the microwave. The reaction makes just one enantiomeric form of the product so that any pharmaceuticals made from this enantiomer would be of only one form. The researchers point out that there is no need for any additional purification or separation steps - no so-called "work up", in other words. The reaction's equilibrium is shifted to the more stable enantiomer, which is the compound needed.
Meanwhile, Ajay Bose and his colleagues at the Stevens Institute of Technology, in New Jersey, USA, have found that microwaves allow them to carry out another important class of industrial reactions, the catalytic transfer hydrogenation. They can carry out the reaction in an open reaction vessel with a high-boiling solvent such as ethylene glycol without having to use special pressurised containers, which can be hazardous. The whole reaction takes just a few minutes and the team has synthesised several starting materials for the beta-lactam antibiotics by reducing the chemical groups containing alkene and alkylidene attached to carbon ring molecules. Using open vessels means that the reactions can be scaled up for industry without having to worry about the problems of high pressures.Qian Cheng of the Laboratory of Applied Bioorganic Chemistry at Tohoku University, Japan and colleagues have also found that microwaves help them speed up their reactions. They have worked on an intramolecular cycloadditions. In this reaction a linear molecule is made to react so that it closes up to form a ring. They have used N-substituted oximes, nitrones, and azomethine ylides that have carbon-carbon double bonds to do this reaction. By attaching the starting materials to the surface of a silica gel they can control the pathway taken by the starting material even more effectively.
Their microwave reaction can be used to make a range of compounds known as tricyclic isoxazolidines which are fused together with a pyrrolidine or piperidine ring. Isoxazolidine are another group of chemicals used as the building blocks for many different pharmaceuticals and other fine chemicals.
Fifty years ago, an overheated clamp-stand might have told you your reaction was finished, these days it is more likely to be a 'ping' from a machine.