The continuous microwave reactor He was the principal inventor of the continuous microwave reactor (CMR) which operates by pumping organic solvents and reactants through a microwave-transparent vessel held in a microwave zone.1 The monitoring and controlling operations are performed outside the microwave zone and allow organic reactions to be performed rapidly and continuously at elevated pressures and temperatures.With this unit, several difficult reactions, including preparations of highly reactive monomers and the iron-chelating drug deferiprone, have been carried out cleanly and easily in his laboratory. Chris was instrumental in the technology transfer and CSIRO’s commercial partner, Milestone MLS (Germany and Italy), is now F EAT U R E G94 Green Chemistry August 1999 here were fewer than five papers on microwave-assisted organic synthesis when Dr Chris Strauss entered the field in 1988.The state-ofthe- art equipment consisted of rudimentary domestic microwave ovens and relatively primitive reaction vessels susceptible to explosions. There was little fundamental knowledge about the effects of microwave energy on organic molecules and it was difficult to obtain a uniform energy distribution and to control and measure temperature. In short, the technique had shown promise, but was dangerous.Chris thought that if equipment could be developed to allow the organic chemist to carry out reactions safely and controllably, microwave technology could become a valuable tool for cleaner chemical processing. manufacturing and distributing units globally under licence.Microwave batch reactor for chemical synthesis Chris was also the principal inventor of the microwave batch reactor (MBR), a system that can be operated at pressures up to 100 atmospheres and temperatures up to 265 °C under rigorously controlled and monitored conditions in the laboratory.2 The vessels are fabricated from inert materials.Reactions are monitored from within the microwave zone and the computer-driven system has the capability for stirring, sample withdrawal and reagent introduction, as well as for rapid post-reaction cooling. Microwave power input can be carefully controlled and is continuously variable. This reactor is expected to become important for organic synthesis, particularly through the application of new techniques such as differential heating and concurrent heating and cooling.Summary of Chris Strauss’ role in microwave chemistry Chris Strauss’ work has helped transform microwave chemistry from a laboratory curiosity into an important field, for which dedicated international conferences are now held regularly. His group is the only one to have designed, built and demonstrated microwave reactors for liquid phase organic synthesis at elevated temperature and pressure.Until these innovations, the equipment for carrying out preparative organic reactions had changed little over decades. Through the MBR and CMR, Chris has anticipated emerging requirements of industrial chemical reactors. His systems can be easily cleaned, an important consideration in lowering waste output.They also are portable, multi-purpose, self-contained and do not require an external boiler. Capabilities for just-intime processing and the materials of construction promote short turnaround times. The systems provide for remote, programmable operation and have the potential for tandem procedures including distillative reactions and coupling with catalytic membranes.The number of published refereed papers on microwave-assisted organic synthesis now exceeds 500. Chris is regarded not only as a pioneer in microwave-assisted organic chemistry, but as an authority in the field. By invitation, he has reviewed his work3 Award for microwave chemistry Susan Cumming from Howard Florey Institute describes the achievements of Chris Strauss from the CSIRO who has received the Royal Australian Chemical Institute (RACI) Inaugural Green Chemistry Challenge Award T C G Chris Strauss of CSIRO with his continuous microwave reactor.Green Chemistry August 1999 G95 F E AT U R E and presented plenary lectures at international microwave conferences in USA (1995), Canada (1997) and the Czech Republic (1998).Water as solvent Chris Strauss was first to recognise that high temperature water has properties that can be exploited for organic synthesis and product isolation.In a broad investigation facilitated by his microwave equipment, relatively modest differences in temperature afforded substantial variations in product distributions.4,5 High-temperature aqueous conditions had advantages over established synthetic procedures and were an attractive alternative to acidic or basic catalysts in organic solvents at lower temperatures.When addition of acid or base was necessary, less agent was usually required than for processes at and below 100 °C and the reactions often were selective. In some cases, the requirement was orders of magnitude lower. Significantly, inorganic salts account for the bulk of industrial chemical wastes.They contaminate soil and ground water and can lower the pH of atmospheric moisture and contribute to acid dew or acid rain. For cleaner production their minimisation is essential. Chris’s work represents a major advance in this context. The preparation of the important synthetic building block, 3-methylcyclopent- 2-enone, is a good example.6 Earlier workers had used strong base in high concentration for the moderately yielding preparation and generated substantial amounts of salt in their work-up.His method employed up to 400 times more dilute base. Competing reactions were suppressed, salt formation was lowered and the product was obtained in the highest yield so far reported. The industrial viability of the process was established using a heat-jacketed autoclave and a continuous microwave reactor.Resin-based isolation methods Chris was also first to develop resin adsorption and ion-exchange techniques for isolation and purification of products synthesised under aqueous conditions.6 Advantages of such non-extractive processes for clean processing include ease of use, high throughput and low waste.The resin can be readily recycled, as can the solvent used for desorption. The preparation of 3-methylcyclopent- 2-enone exemplified his strategy for cleaner production.6 Microwave technology, high-temperature aqueous media and resin-based isolation procedures were combined to overcome difficulties with established methods and to obtain products in high yield.Catalytic membranes Chris has also recognised that catalytic methods can avoid the use of stoichiometric inorganic reagents. He has developed methods for retaining catalytic metals on porous glass tubing and investigated these novel materials as catalysts for Heck-type couplings.7 Advantages of palladium on porous glass included resistance to aerial oxidation, ease of manufacture, mechanical strength and thermal stability, recyclability, negligible loss of palladium into the reaction mixture and obviation of air- and temperature-sensitive ligands.He has used palladium on porous glass in conjunction with microwave heating to catalyse reactions. High turnover numbers were obtained in some cases and he also discovered a new tandem coupling– oxidation process.New and improved reactions Uncatalysed hydrogen transfer Chris also discovered that aldehydes and ketones can be reduced to the corresponding alcohols by transfer hydrogenation at high temperature with ethanol, n-propanol or isopropanol as hydrogen donors in the absence of catalysts and base.8 The potential environmental benefits include inexpensive, renewable reagents, minimal waste and that no inorganic salts are introduced or formed.Catalytic etherification Most methods for etherification use either strongly acidic or basic conditions and C G Pump controller H.P. pump ReactantsF E AT U R E C G G96 Green Chemistry August 1999 have well documented disadvantages. The nearly 150 year old Williamson synthesis is still the most common procedure.It involves substitution of an alkyl halide (RX) by a strongly basic alkoxide or phenoxide (e.g. KOR or NaOR) and so is unsuitable if base catalysed elimination of HX from RX can compete. A stoichiometric amount of waste salt (KX or NaX) is also produced. Chris has invented a catalytic etherification that produces little organic waste and that can be carried out without the addition of acid or base.9 For a symmetrical ether, an excess of alcohol (ROH) and a catalytic amount of RX are heated (see Scheme 1).A solvolytic displacement reaction between RX and ROH affords R2O along with HX or its elements (hereafter referred to as HX; equation 1). The liberated HX reacts with another molecule of ROH to form water and to regenerate RX (equation 2). If the rates of these forward reactions are comparable, the concentration of HX will be low throughout and that of RX will remain relatively constant.Although HX and RX are stoichiometric reactants or products in equations 1 and 2, they do not appear in the sum, equation 3. The nett process involves condensation of two molecules of ROH to give R2O plus water. It requires participation by the counterion X- and utilises ostensibly neutral conditions.For efficient operation, CSIRO—where Chris Strauss works CSIRO (Commonwealth Scientific and Industrial Research Organisation) is the largest R&D organisation in Australia, employing over 7000 staff in areas such as agriculture, minerals and energy, manufacturing, communications, construction, health and the environment. Chris Strauss works within the Molecular Science Division of CSIRO that employs over 300 staff in Melbourne and Sydney.Its research programs are designed to assist the development of industries related to the medical, pharmaceutical, chemicals, polymers, water treatment and waste management sectors of the Australian economy. For further information on CSIRO in general see http://www.csiro.au and on the Molecular Science Division in particular see http://www.molsci.csiro.au X- should be a good leaving group (to satisfy equation 1), an effective nucleophile (to accommodate equation 2) and a weak base to minimise competing elimination reactions.Bromide and iodide possess these properties. It appears that a critical participatory role for the counterion of the acid has not previously been envisaged or recognised.RX + ROH " R2O + HX (1) HX + ROH " RX + H2O (2) 2 ROH " R2O + H2O (3) Scheme 1. Pathway for catalytic ether synthesis The potential for commercial exploitation of the reaction is currently under consideration. New tandem arylamidation Chris has also developed a single-pot synthesis for N-aryl amides which can be conducted as a domino reaction or a tandem sequence.10 Before this reaction, there were few, if any, useful literature methods for obtaining, in a single step, N-aryl amides from aromatic compounds which do not possess an amino function.The new method greatly simplifies the Hoechst–Celanese process for the manufacture of paracetamol. The opportunities for clean processing include atom economy, obviation of isolation and purification of intermediates, savings in time, raw materials and solvent consumption and avoidance of multiple work-up and cleaning operations.Avoidance of heat transfer oils A key step in the preparation of quinolone antibacterial agents involves the formation of an amino ketone ring system by intramolecular cyclisation of a diethyl N-(aryl)aminomethylene malonate derivative at temperatures near 250 °C.To obviate intermolecular reactions, the condensations are usually carried out in high dilution using heat transfer oils consisting of diphenyl ether or a eutectic mixture of diphenyl ether and diphenyl. However, such oils are unacceptable for clean chemical processing. Chris developed a thermal method for carrying out such Jacobs–Gould reactions in high conversion, rapidly, predictably and controllably, without a diluting heat transfer oil.11 He established a continuous process and demonstrated it on a laboratory scale. This was the first example of a Jacobs–Gould reaction having been performed in such a manner.The procedure accommodates high throughput, is energy efficient, is low polluting and offers easy work-up.Indole transformations Direct, preparative methods utilising high-temperature aqueous media, were developed for indole and indole-2-carboxylic acid from ethyl indole-2-carboxylate.12 Yields were excellent for these reactions, which were carried out in 1 hour or less, at temperatures up to 270 °C, in the microwave batch reactor. Avoidance of undesirable copper salts, high boiling organic bases and heat transfer oils made the methods environmentally benign.References 1 T. Cablewski, A. F. Faux and C. R. Strauss, J. Org. Chem., 1994, 59, 3408; C. R. Strauss and A. F. Faux, US Patent 5 387 397, 1995; C. R. Strauss and A. F. Faux, Eur.Patent, 0437480, (1994). 2 K. D. Raner, C. R. Strauss, R. W. Trainor and J. S. Thorn, J. Org. Chem., 1995, 60, 2456; C. R. Strauss, K. D. Raner, R. W. Trainor and J. S. Thorn, Aust. Patent, 677876, 1997 and other applications pending. 3. C. R. Strauss and R. W. Trainor, Aust. J. Chem., 1995, 48, 1665. 4 L. Bagnell, T. Cablewski, C. R. Strauss and R. W. Trainor, J. Org. Chem., 1996, 61, 7355. 5 J. An, L. Bagnell, T. Cablewski, C. R. Strauss, and R. W. Trainor, J. Org. Chem., 1997, 62, 2505. 6 L. Bagnell, M. Bliese, T. Cablewski, C. R. Strauss, and J. Tsanaktsidis, Aust. J. Chem., 1997, 50, 921. 7 J. Li, A. W.-H. Mau and C. R. Strauss, Chem. Commun., 1997, 1275. 8. L. Bagnell and C. R. Strauss, Chem. Commun., 1999, 287. 9. L. Bagnell, T. Cablewski and C. R. Strauss, Chem. Commun., 1999, 283. 10 T. Cablewski, P. A. Gurr, K. D. Raner and C. R. Strauss, J. Org. Chem., 1994, 59, 5814. 11. C. R. Strauss, Aust. J. Chem., 1999, 52, 83. 12. C. R. Strauss and R. W. Trainor, Aust. J. Chem., 1998, 51, 703.