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Mother’slittle helperAn Indian company is pioneeringsome key green chemistry concepts.We caught up with Newreka GreenSynth at Chemspec India 2008

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Green chemistry

Reprinted from Speciality Chemicals Magazine June 2008

Mother’s little helperAn Indian company is pioneering some key green chemistry concepts. We caught up with NewrekaGreen Synth at Chemspec India 2008

Although the company stand was locatedright at the back of the hall at ChemspecIndia 2008, it was swarming throughout.

Founder director Nitesh Mehta said: “It has been soamazing. There has been no beating about thebush, it is all real business.” Clearly Newreka GreenSynth Technologies had identified something thatthe Indian chemicals industry wanted.

Although the firm has been active for six years,2008 may prove to be its breakthrough year. InJanuary, alongside SMS Pharmaceuticals, Newrekawon the Indo-US Green Chemistry Network Centre(GCNC) Award for the successful commercialisationof green chemistry-based technologies at the Indo-US Science & Technology Forum Workshop onGreen Chemistry.

The GCNC itself is an umbrella organisation thatgrew out of the India Green Chemistry Chapter ofthe American Chemistry Society Green ChemistryInstitute (ACS GCI) and now encompasses severalcentres, institutions and industries. It organises vari-ous symposia, workshops and training courses tofurther the concept of green chemistry.

The event in Delhi last January, the third in theseries, attracted some 200 delegates from industryand academe. It was addressed by Professor JohnWarner of the Warner Babcock Institute for GreenChemistry, who is widely regarded as one of thefathers of green chemistry.

The ideas behind Newreka actually go back toconversation in a hostel room at IIT Bombay, whereMehta was studying under Bhadresh K. Padia, in1998. The basic idea, Padia says, was that the chem-icals industry sees pollution as something that needsto be controlled when it should rather look at theissue in terms of ‘prevention by recycle at source’.

“The industry always sees effluents and their endof the pipe treatment as a cost centre, when it is pos-sible to transform it into a profit centre through the‘prevention by recycle at source’ approach. Forexample, when you lose selectivity, you lose materi-als in side reactions and it ends up as an effluent,leaving no chance of recycling the mother liquor”says Padia.

“Even if in the laboratory you get 100% selectivity,it is important to ensure proper scale-up throughappropriate mixing, reactor design and engineeringto have uniformity over large-volume operation. Thisis where green engineering plays a critical role in ‘pre-vention by recycle at source’ at industrial scale.”

The key, he adds is ‘prevention, not control’. If theindustry avoids the need for purification steps anddoes not produce effluent because it achieves acomplete recycle at the end of the process, this isnot only ‘green’ but economically sound and com-petitive. Padia and Mehta believe that most chemi-cal processes can actually be reviewed and rein-vented in an entirely green way.

Padia himself is an expert in iron oxide catalysis,process intensification, scale-up, unit processes likereduction, nitration and diazotization-hydrolysis, andunit operations like crystallisation, extraction, filtra-tion and isolation. He founded Newreka along withMehta, the public face of the company, whose inter-ests are in similar areas, and Vineet Shroff, whosemain areas of competence are engineering andindustrial mixing. The company name is a combina-tion Nature’s Enthusiastic World and ‘Eureka’,Archimedes’ joyous cry of scientific discovery.

Over the past ten years, Newreka has grown toabout 100 chemists and engineers, who have car-ried out some 20,000 experiments in unit process-es, with a focus on recyle. Growth was an uphillchallenge, however, because it is very difficult forknowledge-based start-ups, unlike software start-ups, to generate seed capital.

“Knowledge doesn’t show up on a balance sheetand venture capitalists and banks are not interested inthings with a six-to-seven-year turnaround period.Government bodies have their limitations, due to theirbureaucratic set-up and their limited ability to deal withhigh risk-oriented knowledge platforms. and hencethey have shown limited interest,” Mehta admits.

Normally, the investment needed to create newknowledge far exceeds the business returns in theinitial stages creating financial challenges to sustain-ing such knowledge platforms. In the future, Mehtabelieves, there is a need for finances customised toknowledge-based start-ups in the fields of environ-ment and energy.

Originally, Newreka acted as a consultancy butthis did not work. Between 2002 and 2005, it visit-ed every Chemspec, Informex and CPhI showacross the world and found that potential customerswanted more product-based services. Now it has itsown facility in Dombivli in the suburbs of Mumbai.

For the first couple of years, a focus on unitprocess of reduction was the company’s key mar-keting strategy. This was based on the NewrekaReduction Technology (NRT), in which proprietarycatalytic formulations are used in reduction. Morerecently it has expanded to offer systems for otherreactions, including nitration, diazotisation-hydroly-sis, isolation, oxidation, sulphonation, acetylation andFriedel-Crafts.

Thus, Newreka has slowly achieved recognition,culminating in the award at the GCNC symposium.This was based on case studies of its work in twospecific areas - the recycle of mother liquor fromchemical process streams and the use of its propri-etary catalysts to replace harsh with mild conditions- plus its concept of the ‘enviropreneur’.

Mother liquor typically contains raw materials, fin-ished product and both organic and inorganic impu-rities. Depending on the reaction medium, it can beacidic (when sulphuric acid is used in nitration, dia-zotisation, methylation, precipitation, etc.), neutral(when water is used in reduction) or alkaline (whensodium hydroxide is used in fusion, hydrolysis, crys-tallisation, etc.).

The company claims that its Newreka RecycleSolution (NRS), which covers all of these areas, hasseveral important advantages in addition to thegreen chemistry principles it is based on, notably:high selectivity leading to high quality, no need forpurification, the ability to customise catalyst formula-tion, close to theoretical yield and recovery, low cap-ital investments, savings on cost and legislative com-pliance, thus freeing up room for expansion, andbetter access to markets in the developed world.

The first case study of the implementation of theNRS showcased at the GCNC symposium concernedthe intermediate for an anti-AIDS drug made byMatrix Laboratories in India. Conventionally, this is

Enviropreneurs

Individual& society

Government bodies& financial institutions

Universities Selling ideas& scale-up

Sustainablesolutions

GoodROI

Employment &healthy living

Investment on R&D& value for solutions

Empowerment& support

IP &knowledge

Investments &incentives

Industries

Figure 1 - Green partnerships based on enviropreneurs

Green chemistry

Reprinted from Speciality Chemicals Magazine June 2008

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produced by reduction using catalytic hydrogenationwith a pyrophoric Raney Nickel catalyst.

The reaction is carried out to convert R-NO2 to R-NH2 in a high pressure autoclave is hydrogen gas athigh pressure, Raney Nickel and methanol as sol-ven. The spent nickel is filtered and the filtrateundergoes two stages of distillation, isolation and fil-tration, the second of which need another solvent.The end result is two lots of light and dark brownamine and some spent solvent effluent, as well as apoor yield.

Using the NRS, the reaction is carried out to con-vert R-NO2 to R-NH2 in a simple vessel at atmos-pheric conditions, using water as a solvent and pro-prietary catalytic formulations like the NewrekaReduction Catalyst (NRC) and the Newreka GreenCatalyst (NGC). After the reaction, the spent NRC isfiltered out. After crystallisation and centrifuging, off-white amine is produced, along with mother liquorthat can be stored and recycled back into theprocess 25 times.

The main advantages of this are that water can beused as the reaction medium instead of solvent, nohazardous materials are used, the reaction takesplace at atmospheric pressure, neutral pH andbelow 100˚C and that the mother liquor can berecycled 25 times at plant scales and 50 times inlaboratory trials, rather than being treated at the endof the pipe.

The yield is up from 85% to 95% of theoreticaland the whole process is much less energy-inten-sive, leading to substantial savings - thus establish-ing, in Mehta’s view, that ‘prevention by recycle atsource’ is a huge profit centre.

Another factor is the soaring costs of nickel andother noble metals in India, like everywhere else inthe world; prices have increased four- to five-fold inthe past five years. In addition, Indian pharmaceuti-cals companies face much the same pressures astheir Western counterparts to reduce both costs andpollution.

Mehta believes that there is huge potential foriron-based catalysts to replace not just nickel butplatinum and other platinum group metals in catal-ysis. Iron, he observes, is not just cheaper and lesshazardous than these metals, but has proved itssafety to living creatures by the way it is widely usedin natural chemistry, where nickel and other noblemetals are not.

Since it is also ubiquitous and well-nigh inex-haustible, the price of iron remains stable by compar-ison with noble metals. Newreka is now workingintensively on developing new formulations based onnano-iron catalysts using green chemistry principles.

The second case study concerned 3-hydroxyacetophenone, the intermediate for the deconges-tant phenylephrine hydrocholoride. This drug isincreasingly replacing pseudo-ephedrine in the USmarket and its production is growing very fast, butthe conventional process for its manufacture ishighly polluting.

In the conventional process, 3-amino acetophe-none is diazotised with NaNO2 using sulphuric acidas the reaction medium. After the diazotisation-hydrolysis reaction is complete, ethyl acetate is usedas a solvent to extract the product, an aqueous layer

containing sulphuric acid is separated and the ethylacetate layer is taken for distillation to recover theproduct, 3-hydroxy acetophenone.

The process needs additional raw materials likeCuSO4 and acetic acid, which never take part in thereaction. It generates brown-coloured product andhuge quantities of sulphuric acid effluent, achieving65-70% of theoretical yield.

Using the NRS in a patent-pending process, 3-amino acetophenone is diazotised with NaNO2

using sulphuric acid mother liquor as the reactionand extraction medium. Ethyl acetate solvent is notrequired.

After the diazotization-hydrolysis reaction is com-plete, the product is extracted using acidic motherliquor. Following the recovery of product, the entireacidic mother liquor is recycled back in the processafter reacting it with RCat, Newreka’s proprietaryrecycle formulation.

This process, the company claims, led to a 75-times recycle of the reaction medium instead of pro-ducing a highly acidic effluent. Because of theimproved chemoselectivity and the elimination ofside-reactions, sulphuric acid was recycled up to 50times at plant scale and there was no need to useCuSO4 or acetic acid. Yield rose from 75% to 90%of theoretical. As with the neutral mother liquor,water can replace solvent as the extraction mediumand the process is more energy-efficient.

Padia notes that no modification was needed tothe plant in either of these cases and that this appliesto most of Newreka’s work. Only the mixing sys-tems in the reactors were modified to ensure uni-form mixing in every corner of the reactor, thusleading to high chemoselectivity.

Crucial to the success of all this is that Newrekachemists and chemical engineers are required towork together in harmony. “They should be likehusband and wife,” Padia says.

(Some cynical Westerners might say that chemistsand chemical engineers in most firms are very muchlike husband and wife already. They have totally dif-ferent points of view on every subject, they never lis-ten to each other and they invariably blame eachother for anything that goes wrong. But that’s anoth-er story...)

The term ‘enviropreneur’, which Newreka alsoshowcased in Delhi, is a fusion of ‘environment’ and‘entrepreneur’. The idea is to combine the passion of

an environmentalist with the spirit of adventure of anentrepreneur to create wealth from waste and producebenefits for the environment. The word refers to thefirm’s individual workers, who are reqiured to do morethan slot into the role of chemist or chemical engineer,and to the company itself.

Universities, industry, government bodies andNGOs, individuals and society as a whole are alldivided from each other, Mehta says. The former,for instance, are a source of new ideas but lack theability to scale them up or commercialise them;industry has the resources but is impelled by therush to market to stick to existing processes. The‘enviropreneur’ can be a bridge between them,forming mutually beneficial, green partnerships withall of them (Figure 1).

Implementing Newreka technology at a cus-tomer’s site is of necessity a slow process, involvingR&D and plant operatives and others, as well as sen-ior management. “The challenge we face is to showthem that green chemistry is actually a profit centrerather than a cost centre,” Mehta says. “In our expe-rience, green chemistry is always cheaper.”

The process begins with a confidentiality agree-ment, finding out what the customer’s expectationsare, then submitting a detailed proposal and signinga commercial agreement. The R&D process thenbegins, followed by a demonstration of the NRS bya lab demo team, then at plant scale by a separateteam. RCat formulations are then put into action,supported by ongoing optimisation, process intensi-fication and troubleshooting services.

Much, of course, can go wrong at any stage in acountry notoriously reluctant to pay for knowledge.Newreka and its customers work on a 50-50 risk basis.Customers give an initial commitment amount toNewreka to start the work on all aspects of convertingthe conventional process(es) to its technologies.

Typically, a project takes from six to 12 months toimplement and six to nine to break even. If the proj-ect is unsuccessful, customers are offered a choice ofa 50% refund of their initial commitment amount orthe chance to replace the old project with a newone.

To date, Newreka has not done much businessoutside India, though it has fielded many enquiriesfrom the Paracetamol industries in Iran, Bangladesh,Turkey, Pakistan, Egypt and South Africa. Mehta andhis technology implementation team recently spent

Professor John Warner spoke at the workshop in Delhi

Green chemistry

a month in Iran demonstrating how NRS could beused to convert para-nitro phenol to para-aminophenol, a key intermediate in Paracetamol, using awater-based process with more than 100 recycles ofmother liquor and producing off-white and stablepara-amino phenol.

This, Padia adds, could ultimately lead to “a com-plete green solution for Paracetamol”. It also servesas an example of where, according to Mehta, thewell-known 80/20 rule also applies.

“In all industries, 20% of the products create 80%of the pollution,” he says. Converting this 20% togreen chemistry will be more profitable, advancethe technology and will go furthest to reducing pol-lution, significantly impacting the environmentspecifically water bodies.

For this reason, Newreka is not running small-scale projects but is prioritising the 20 products inevery market by bulk. It has, in many cases, workedon them already, generally to develop a green routefor every step of a four- to ten-step synthesis.

Examples in pharmaceuticals other than thosecited already include caffeine, citalopram, triclosan,and, perhaps most interestingly of all, sildenafil cit-rate, the API in Viagra. Rakshit Drugs, India’slargest producer of sildenafil citrate, has imple-mented the NRT in one of the steps in place of cat-alytic hydrogenation by hydrogen gas and RaneyNickel, achieving among other things a 30%reduction in batch time and improved intermedi-ate quality.

In agrochemicals, dicholoro and tricholoro anilinehave been the subjects of projects. Newreka hasalso been working with Shree Hari ChemicalExports on H-acid, a very large volume intermediatefor brown and black dyes. In pigments, it has beenworking with Pidilite Industries, the main producerof Pigment Violet 23

The unit processes of H-acid, Violet 23 andParacetamol, plus DASDA, Phenylephrine andPigment CPC, all consume sulphuric acid. It is usedin vast quantities in both the general chemicalsindustry of Gujarat and Mahrashtra and in thepharemceuticals industry around Hyderabad andBangalore. Therefore, sulphuric acid is a big targetof investment for Newreka.

In addition, Newreka is working on next genera-tion nanocatalysts. Nano-iron compounds and bio-mimicry has huge potential according to Padia. Theformer are very common in nature right from amoe-ba to whales; they are, for example, the naturalmagnets behind homing pigeons, Padia observes.Biomimicry - observing Nature’s own innovation todevelop products and processes - he sees as essen-tial to achieving a sustainable environmental foot-print for the future need of mankind.

“We are always looking at gaps from the eco-nomic and the environmental point of view. Theonly issue, as Professor Warner said in Delhi, is thatthe toolbox is not yet full. We have not yet, forexample, worked on chlorination or brominationbut we will do so and we think that in ten years’ time

there will be a green chemistry solution for everyproblem,” says Mehta.

Newreka sees itself as a global company in thelong term and the Western world is obviously thenext target. Mehta notes that, where India is morefocused on intermediates, the European and USmarkets are more focused on custom synthesis andmanufacturing and there are close relationshipsbetween them and Big Pharma companies.

“The pharmaceuticals industry, creates hugeamounts of waste, around 50-100 kg per kg ofproduct. It is normally difficult to get involved in thisarea once DMFs have been filed and the process ishard to change. However, when patents haveexpired or are about to, there could be more inter-est in our technology,” he concludes. “I have notcome across anyone else doing what we do, so Ibelieve that our business model is unique.”

For further information, please contact:Nitesh H. MehtaFounder DirectorNewreka Green Synth-Technologies Pvt. Ltd.405, MasterMind IVRoyal PalmsAarey ColonyGoregaon (East)Mumbai - 400 065IndiaTel: +91 22 2879 1835E-mail: nitesh.mehta@newreka.co.inWebsite: www.newreka.co.in

Reprinted from Speciality Chemicals Magazine June 2008

www.specchemonline.com