The continuous microwave reactorHe was the principal inventor of the continuous microwave reactor (CMR)which operates by pumping organic solvents and reactants through amicrowave-transparent vessel held in amicrowave zone.1 The monitoring andcontrolling operations are performed outside the microwave zone and alloworganic reactions to be performed rapidlyand continuously at elevated pressuresand temperatures. With this unit, severaldifficult reactions, including preparationsof highly reactive monomers and the iron-chelating drug deferiprone, havebeen carried out cleanly and easily in hislaboratory.

Chris was instrumental in the technology transfer and CSIRO’s commercial partner, Milestone MLS(Germany and Italy), is now

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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-of-the-art equipment consisted of rudimentary domestic microwave ovensand relatively primitive reaction vesselssusceptible to explosions. There was little fundamental knowledge about theeffects of microwave energy on organicmolecules and it was difficult to obtain auniform energy distribution and to controland measure temperature. In short, thetechnique had shown promise, but was dangerous.

Chris thought that if equipment could be developed to allow the organicchemist to carry out reactions safely andcontrollably, microwave technology could become a valuable tool for cleaner chemical processing.

manufacturing and distributing units globally under licence.

Microwave batch reactor for chemical synthesisChris was also the principal inventor of the microwave batch reactor (MBR), a system that can be operated at pressuresup to 100 atmospheres and temperaturesup to 265 °C under rigorously controlledand monitored conditions in the laboratory.2 The vessels are fabricatedfrom inert materials. Reactions are monitored from within the microwavezone and the computer-driven system has the capability for stirring, samplewithdrawal and reagent introduction, as well as for rapid post-reaction cooling.Microwave power input can be carefullycontrolled and is continuously variable.This reactor is expected to become important for organic synthesis, particularly through the application ofnew techniques such as differential heating and concurrent heating and cooling.

Summary of Chris Strauss’ role in microwave chemistryChris Strauss’ work has helped transformmicrowave chemistry from a laboratorycuriosity into an important field, forwhich dedicated international conferencesare now held regularly. His group is theonly one to have designed, built anddemonstrated microwave reactors for liquid phase organic synthesis at elevatedtemperature and pressure. Until theseinnovations, the equipment for carryingout preparative organic reactions hadchanged little over decades.

Through the MBR and CMR, Chris has anticipated emerging requirements ofindustrial chemical reactors. His systemscan 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-in-time processing and the materials of construction promote short turnaroundtimes. The systems provide for remote,programmable operation and have thepotential for tandem procedures includingdistillative reactions and coupling withcatalytic membranes.

The number of published refereedpapers on microwave-assisted organicsynthesis now exceeds 500. Chris isregarded not only as a pioneer inmicrowave-assisted organic chemistry,but as an authority in the field. By invitation, he has reviewed his work3

Award formicrowave chemistrySusan 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

CG

Chris Strauss of CSIRO with his continuous microwave reactor.

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and presented plenary lectures at international microwave conferences in USA (1995), Canada (1997) and the Czech Republic (1998).

Water as solventChris Strauss was first to recognise thathigh temperature water has properties thatcan be exploited for organic synthesis andproduct isolation. In a broad investigationfacilitated by his microwave equipment,relatively modest differences in tempera-ture afforded substantial variations inproduct distributions.4,5 High-temperatureaqueous conditions had advantages overestablished synthetic procedures and werean attractive alternative to acidic or basiccatalysts 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 oftenwere selective. In some cases, the require-ment was orders of magnitude lower.

Significantly, inorganic salts account for the bulk of industrial chemical wastes.They contaminate soil and ground waterand can lower the pH of atmosphericmoisture and contribute to acid dew oracid rain. For cleaner production theirminimisation is essential. Chris’s workrepresents a major advance in this context.

The preparation of the important synthetic building block, 3-methyl-cyclopent-2-enone, is a good example.6

Earlier workers had used strong base inhigh concentration for the moderatelyyielding preparation and generated sub-stantial amounts of salt in their work-up.His method employed up to 400 timesmore dilute base. Competing reactionswere suppressed, salt formation was lowered and the product was obtained in the highest yield so far reported. Theindustrial viability of the process was

established using a heat-jacketed autoclave and a continuous microwave reactor.

Resin-based isolation methodsChris was also first to develop resinadsorption and ion-exchange techniquesfor isolation and purification of productssynthesised under aqueous conditions.6

Advantages of such non-extractiveprocesses for clean processing includeease of use, high throughput and lowwaste. The resin can be readily recycled,as can the solvent used for desorption.

The preparation of 3-methyl-cyclopent-2-enone exemplified his strate-gy for cleaner production.6 Microwave technology, high-temperature aqueousmedia and resin-based isolation procedures were combined to overcomedifficulties with established methods andto obtain products in high yield.

Catalytic membranesChris has also recognised that catalyticmethods can avoid the use of stoichiomet-ric inorganic reagents. He has developedmethods for retaining catalytic metals onporous glass tubing and investigated thesenovel materials as catalysts for Heck-typecouplings.7

Advantages of palladium on porous glass included resistance to aerial oxidation, ease of manufacture, mechanical strength and thermal stability,recyclability, negligible loss of palladiuminto the reaction mixture and obviation ofair- and temperature-sensitive ligands. Hehas used palladium on porous glass inconjunction with microwave heating tocatalyse reactions. High turnover numberswere obtained in some cases and he alsodiscovered a new tandem coupling–oxidation process.

New and improved reactionsUncatalysed hydrogen transfer Chris also discovered that aldehydes andketones can be reduced to the correspond-ing alcohols by transfer hydrogenation athigh temperature with ethanol, n-propanolor isopropanol as hydrogen donors in the absence of catalysts and base.8 Thepotential environmental benefits includeinexpensive, renewable reagents, minimalwaste and that no inorganic salts are intro-duced or formed.

Catalytic etherificationMost methods for etherification use eitherstrongly acidic or basic conditions and

CG

Pump controllerH.P. pump

Reactants�for processing

Reaction�product

Cryostat

Back pressurecontrol valve�

Reaction column

Safety shield

Microwave cavity

Heat exchanger

Figure 2. Flow diagram of the operationof the continuous microwave reactor.

RACI—and its GreenChemistry Awards

The Royal Australian ChemicalInstitute, founded in 1917, is both the qualifying body in Australia forprofessional chemists and a learnedsociety promoting the science andpractice of chemistry. The Institutehas 9000 members and was granted a Royal Charter in 1932. It is concerned with the teaching andpractice of chemistry and with theapplication of chemistry in industry,academia and government authori-ties. Thus, it represents and caters for the professional needs of allchemists, providing various activitiesand services that encompass the profession of chemistry in Australia.For example, it holds an annualNational Chemistry Week, a NationalConvention every 5 years, and publishes a monthly magazine,Chemistry in Australia.

In 2001 RACI will host the WorldChemistry Congress (incorporatingthe 39th IUPAC Congress, 9th AsianChemical Congress and the AIMECSmeeting) at which Green Chemistryis one of the 5 major themes.

This year RACI has inauguratedGreen Chemistry Challenge Awards to recognise and promote fundamental and innovative chemical methods in Australia that accomplish pollution prevention through sourcereduction and that have broadapplicability in industry, and torecognise contributions to educationin Green Chemistry. The GreenChemistry Challenge Awards areopen to all individuals, groups andorganisations, both nonprofit and for profit, including academia, government, and industry.

The nominated green chemistrytechnology must have reached a significant milestone within the past 5 years in Australia (e.g.beenresearched, demonstrated, imple-mented, applied, patented, etc.) andshould be an example of one or moreof the following 3 focus areas:• the use of alternative synthetic pathways

• the use of alternative reaction conditions

• the design of alternative chemicals

For more information about RACIsee http://www.raci.org.au

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G96 Green Chemistry August 1999

have well documented disadvantages. Thenearly 150 year old Williamson synthesisis still the most common procedure. Itinvolves 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 eliminationof HX from RX can compete. A stoichio-metric amount of waste salt (KX or NaX)is also produced.

Chris has invented a catalytic etherification that produces little organicwaste and that can be carried out withoutthe addition of acid or base.

9

For a symmetrical ether, an excess of alcohol (ROH) and a catalytic amountof RX are heated (see Scheme 1). Asolvolytic displacement reaction betweenRX and ROH affords R2O along with HXor its elements (hereafter referred to asHX; equation 1). The liberated HX reactswith another molecule of ROH to formwater and to regenerate RX (equation 2).If the rates of these forward reactions arecomparable, the concentration of HX willbe low throughout and that of RX willremain relatively constant. Although HXand RX are stoichiometric reactants orproducts in equations 1 and 2, they do notappear in the sum, equation 3. The nettprocess involves condensation of twomolecules of ROH to give R2O plus water.It requires participation by the counterionX- and utilises ostensibly neutral condi-tions. For efficient operation,

CSIRO—where ChrisStrauss works

CSIRO (Commonwealth Scientific and Industrial Research Organisa-tion) is the largest R&D organisationin Australia, employing over 7000staff in areas such as agriculture,minerals and energy, manufacturing,communications, construction, healthand the environment. Chris Straussworks within the Molecular ScienceDivision of CSIRO that employs over300 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 manage-ment sectors of the Australian economy. For further information on CSIRO in general seehttp://www.csiro.au and on theMolecular Science Division in particular seehttp://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 competingelimination reactions. Bromide andiodide possess these properties. It appearsthat a critical participatory role for thecounterion of the acid has not previouslybeen 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 exploitationof the reaction is currently under consideration.

New tandem arylamidationChris has also developed a single-pot synthesis for N-aryl amides which can be conducted as a domino reaction or atandem sequence.10 Before this reaction,there were few, if any, useful literaturemethods for obtaining, in a single step, N-aryl amides from aromatic compoundswhich do not possess an amino function.The new method greatly simplifies theHoechst–Celanese process for the manu-facture of paracetamol. The opportunitiesfor clean processing include atom economy, obviation of isolation andpurification of intermediates, savings in time, raw materials and solvent consumption and avoidance of multiplework-up and cleaning operations.

Avoidance of heat transfer oilsA key step in the preparation of quinolone antibacterial agents involvesthe formation of an amino ketone ringsystem by intramolecular cyclisation of a diethyl N-(aryl)aminomethylene malonate derivative at temperatures near 250 °C. To obviate intermolecularreactions, the condensations are usuallycarried out in high dilution using heattransfer oils consisting of diphenyl etheror a eutectic mixture of diphenyl etherand diphenyl. However, such oils areunacceptable for clean chemical processing.

Chris developed a thermal method for carrying out such Jacobs–Gould reactions in high conversion, rapidly, predictably and controllably, without adiluting heat transfer oil.11 He establisheda continuous process and demonstrated iton a laboratory scale. This was the first

example of a Jacobs–Gould reaction having been performed in such a manner.The procedure accommodates highthroughput, is energy efficient, is low polluting and offers easy work-up.

Indole transformationsDirect, preparative methods utilisinghigh-temperature aqueous media, were developed for indole and indole-2-carboxylic acid from ethylindole-2-carboxylate.12 Yields wereexcellent for these reactions, which werecarried out in 1 hour or less, at tempera-tures up to 270 °C, in the microwavebatch reactor. Avoidance of undesirablecopper salts, high boiling organic basesand 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 Patent5387397, 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.

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