C G Green Chemistry August 1999 G97 F OC U S O N . . . ony Barrett is Glaxo Professor of Chemistry and Director of the Wolfson Centre for Organic Chemistry in Medical Science at Imperial. Following his Ph.D. at Imperial under the tutorship of Professor Sir Derek Barton, Professor Barrett was immediately appointed to a lectureship at the College. In 1983 he moved to the USA for 10 years taking in Professorships at Northwestern University and Colorado State before returning to Imperial as Head of Organic Chemistry.Barrett’s research interests cover a wide range of organic chemistry ranging from identification of effective fungicidal agents to olefin metathesis, and optical and imaging materials. This article will focus on Barrett’s work with lanthanide triflates as clean catalysts of potential use to the fine chemicals industry.Tony Barrett’s interest in clean technology started following Kobayashi’s work in the early nineties describing lanthanide triflates as water tolerant Lewis acids. Barrett is also a keen advocate of Trost’s atom economy concepts and much of his work on clean technology has combined these two areas. Nitration One of Professor Barrett’s leading co-workers is Dr Chris Braddock who worked in the group as postdoctoral fellow until his recent appointment to a Lectureship at Imperial in October 1998.On arriving in the group in January 1996 he was challenged to nitrate toluene without using more than one mole equivalent of nitric acid, and without the use of sulfuric acid. Nitroaromatics are key chemical feedstocks for dyes, pharmaceuticals and plastics, but, their synthesis historically uses mixtures of fuming nitric acid and sulfuric acid leading to significant amounts of waste.More recently nitration has been carried out with nitric acid in the presence of Lewis acids such as BF3 but this approach is equally ‘unclean’ since stoichiometric amounts of ‘catalyst’ are required resulting in copious quantities of acidic waste.Rising to this challenge, Braddock’s application of lanthanide triflates to the nitration of toluene was highly successful, with greater than 95% conversion achieved using a single equivalent of nitric acid and a catalytic quantity (10 mol%) of ytterbium triflate. The real benefit of this work was that the only side-product was water, and that the catalyst could be recovered and reused—most unusual for a Lewis acid.EPSRC and Air Products sponsored further work in the area aimed at scoping the reaction and studying the mechanism. On screening the entire series of lanthanide( III) triflates for catalytic activity (for nitration) it became evident that there was a clear relationship between the extent of nitration and the ionic radius of the lanthanide ion with activity increasing as the radius decreased.This led Barrett and Braddock to postulate that the everincreasing electrostatic interaction between the lanthanide ion, and nitric acid was responsible for the increase in activity. Further mechanistic study led to the belief that nitric acid was displacing water in the inner co-ordination sphere of the lanthanide ion, this resulted in the reversible elimination of a proton, as shown.It is this proton that leads to the accentuation of the Brønsted acidity of the nitric acid through formation of a nitronium ion. [Ln(OH2)9]3+ï[Ln(OH2)y(HNO3)]3+ [Ln(OH2)y(HNO3)]3+ï[Ln(OH2)y(NO3)]2+ + H+ H+ + HNO3ï NO2 + + H2O Although this work has not yet been commercialised, Professor Barrett is currently patenting extensions to this technology for which he sees many commercial applications.The rare earth metals are not actually that rare and neither availability nor cost would preclude their use as commercial catalysts. With the current system the recycling technology is different to that available on most industrial plants, Barrett believes however that new plants, designed to use lanthanide catalysts, would be cost effective.A significant advantage for industry would be heterogeneous versions of the catalyst which may be just around the corner. Professor Anthony Barrett In the first of a new series of reports looking at some of the leading workers in the field of green chemistry and clean technology, Mike Lancaster describes some of the work of Tony Barrett’s group at Imperial College of Science, Technology and Medicine, London.‘Barrett believes that new plants, designed to use lanthanide catalysts, would be cost effective’ Tony Barrett’s group at Imperial College of Science, Technology and Medicine TG98 Green Chemistry August 1999 C G F OC U S O N. . . Barrett is a keen supporter of the atom economy concept but at the end of the day chemical instinct is usually a good measure.In terms of chemistry education Tony Barrett is a traditionalist, he firmly believes in teaching fundamental core chemistry and that undergraduate courses should not be modified too much to include latest green chemistry methodology. If he could revolutionise one area of chemistry with clean technology Barrett would choose aromatic transformations —which are at the centre of the fine and speciality chemicals industry.Meanwhile as Chris Braddock starts on an independent career in the area of clean technology he is looking to use metal free asymmetric catalysts (MFAC) such as recyclable carbocations to overcome the problematic issue of toxic metal residues in pharmaceutical products. I’m sure we will be hearing much more about MFAC in the coming few years. Further Reading A.G. M Barrett and D. C. Braddock, Chem. Commun, 1997, 351. S. Kobayashi and I Hachiya, J. Org. Chem., 1994, 59, 3590. B. M. Trost, Angew. Chem., Int. Ed. Engl., 1995, 34, 259. F. J. Walker, A. G. M. Barrett, D. C. Braddock and D. Ramprasad, Chem. Commun., 1997, 613. F. J.Walker, A. G. M. Barrett, D. C. Braddock, R. M. McKinnell and D. Ramprasad, J. Chem. Soc., Perkin Trans. 1, 1999, 867. Esterification with lanthanide(III) triflates Esterification is another reaction that finds widespread use in the chemical industry. At first sight this is green chemistry at its best, the only by-product being water, for example: ROH + AcOH ® ROAc + H2O Chemistry is rarely that simple however; the reaction is reversible and typically a significant excess of either acid or alcohol as well as a strong mineral acid are required to drive the reaction forward.Azeotropic removal of water also drives the reaction but this sometimes requires complex and expensive distillation towers and produces significant amounts of acid waste. Although Lewis acids do catalyse the reaction they offer no benefit in terms of clean technology.Since the lanthanide triflates are stable in water they seemed an obvious choice to Barrett and Braddock. They found that both scandium (III) and lanthanide(III) triflates catalysed the acylation of a range of primary, secondary and tertiary alcohols with acetic acid. Quantitative yields were obtained with primary alcohols such as phenethyl alcohol at room temperature using just 5 mol% Sc(OTf)3, and even the extremely bulky tertiary alcohol 1-adamantanol could be acetylated to 80% conversion within minutes at reflux.The Green Chemistry Movement Within the UK Tony Barrett believes that one of the most important factors in pushing forward clean technology was the establishing of the Institute of Applied Catalysis (iAc) which came out of the Government’s Foresight panel of which he was a member. iAc has been responsible for encouraging and supporting catalyst research in the UK that is at the heart of much clean technology.Indeed Barrett believes more money should be put into the iAc programmes to underpin clean technology themes. One weakness of the current funding programme in the UK is that it is not always related to the needs of society, programmes often being funded for political rather than social need.Two of the most important aspects, in Barrett’s view, to drive new clean technology into industry are the forging of close links between academia and industry at an early stage and the establishment of close working relationships between chemists and chemical engineers so that the process is developed alongside the chemistry.To this end Barrett and Braddock are currently working on establishing a MSci course in ‘Chemistry with Fine Chemicals Processing’ in conjunction with the Department of Chemical Engineering at Imperial. Professor Barrett also attributes much of the success of his long collaboration with Air Products to the significant involvement of engineers. Imperial saw the need to involve industry at an early stage in academic research several years ago.A full-time post, the Director of Strategic Alliances, was created to enable the research work to be marketed and to identify potential industrial partners. This has been of invaluable help to the work of the Barrett group.At the end of the day the key drivers which Barrett thinks will force industry to become more green are financial and legislative. He is starting to see both of these come together in the pharmaceutical industry. There is now much more competition in this area forcing prices down and as the cost of waste rises so new technology is needed. As outsourcing becomes widespread so does the opportunity for new, competitive clean technology. Barrett is however scathing of people and technology jumping on the green bandwagon. As an example he cites biotransformations, generally perceived as being green, but many examples suffer from extremely low turnovers producing huge volumes of waste. One problem we have is defining what ‘green’ is, especially when comparing processes. Professor ‘the key drivers which Barrett thinks will force industry to become more green are financial and legislative’ ‘Barrett believes that clean technology in the UK was pushed forward by the establishing of the Institute of Applied Catalysis’ ‘Barrett would like to see aromatic transformations revolutionised with clean technology’ Visit the Green Chemistry homepage FREE electronic access to full contents of Issue 1 http://www.rsc.org/greenchem