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Mother’s
little helper
An Indian company is pioneering
some key green chemistry concepts.
We caught up with Newreka Green
Synth at Chemspec India 2008
Green chemistry



Mother’s little helper
An Indian company is pioneering some key green chemistry concepts. We caught up with Newreka
Green Synth at Chemspec India 2008


A
         lthough the company stand was located
         right at the back of the hall at Chemspec
         India 2008, it was swarming throughout.
Founder director Nitesh Mehta said: “It has been so
amazing. There has been no beating about the                                  Universities               Selling ideas   Sustainable               Industries
                                                                                                          & scale-up      solutions
bush, it is all real business.” Clearly Newreka Green
Synth Technologies had identified something that                                      IP &                                                    Investment on R&D
the Indian chemicals industry wanted.                                              knowledge                                                  & value for solutions
   Although the firm has been active for six years,                                                              Enviropreneurs
2008 may prove to be its breakthrough year. In
January, alongside SMS Pharmaceuticals, Newreka                                   Investments &                                                 Empowerment
won the Indo-US Green Chemistry Network Centre                                      incentives                                                    & support
(GCNC) Award for the successful commercialisation
                                                                             Government bodies             Good          Employment &              Individual
of green chemistry-based technologies at the Indo-                          & financial institutions                                               & society
                                                                                                           ROI            healthy living
US Science & Technology Forum Workshop on
Green Chemistry.
   The GCNC itself is an umbrella organisation that
grew out of the India Green Chemistry Chapter of
the American Chemistry Society Green Chemistry              Figure 1 - Green partnerships based on enviropreneurs
Institute (ACS GCI) and now encompasses several
centres, institutions and industries. It organises vari-       Padia himself is an expert in iron oxide catalysis,            For the first couple of years, a focus on unit
ous symposia, workshops and training courses to             process intensification, scale-up, unit processes like        process of reduction was the company’s key mar-
further the concept of green chemistry.                     reduction, nitration and diazotization-hydrolysis, and        keting strategy. This was based on the Newreka
   The event in Delhi last January, the third in the        unit operations like crystallisation, extraction, filtra-     Reduction Technology (NRT), in which proprietary
series, attracted some 200 delegates from industry          tion and isolation. He founded Newreka along with             catalytic formulations are used in reduction. More
and academe. It was addressed by Professor John             Mehta, the public face of the company, whose inter-           recently it has expanded to offer systems for other
Warner of the Warner Babcock Institute for Green            ests are in similar areas, and Vineet Shroff, whose           reactions, including nitration, diazotisation-hydroly-
Chemistry, who is widely regarded as one of the             main areas of competence are engineering and                  sis, isolation, oxidation, sulphonation, acetylation and
fathers of green chemistry.                                 industrial mixing. The company name is a combina-             Friedel-Crafts.
   The ideas behind Newreka actually go back to             tion Nature’s Enthusiastic World and ‘Eureka’,                    Thus, Newreka has slowly achieved recognition,
conversation in a hostel room at IIT Bombay, where          Archimedes’ joyous cry of scientific discovery.               culminating in the award at the GCNC symposium.
Mehta was studying under Bhadresh K. Padia, in                 Over the past ten years, Newreka has grown to              This was based on case studies of its work in two
1998. The basic idea, Padia says, was that the chem-        about 100 chemists and engineers, who have car-               specific areas - the recycle of mother liquor from
icals industry sees pollution as something that needs       ried out some 20,000 experiments in unit process-             chemical process streams and the use of its propri-
to be controlled when it should rather look at the          es, with a focus on recyle. Growth was an uphill              etary catalysts to replace harsh with mild conditions
issue in terms of ‘prevention by recycle at source’.        challenge, however, because it is very difficult for          - plus its concept of the ‘enviropreneur’.
   “The industry always sees effluents and their end        knowledge-based start-ups, unlike software start-                 Mother liquor typically contains raw materials, fin-
of the pipe treatment as a cost centre, when it is pos-     ups, to generate seed capital.                                ished product and both organic and inorganic impu-
sible to transform it into a profit centre through the         “Knowledge doesn’t show up on a balance sheet              rities. Depending on the reaction medium, it can be
‘prevention by recycle at source’ approach. For             and venture capitalists and banks are not interested in       acidic (when sulphuric acid is used in nitration, dia-
example, when you lose selectivity, you lose materi-        things with a six-to-seven-year turnaround period.            zotisation, methylation, precipitation, etc.), neutral
als in side reactions and it ends up as an effluent,        Government bodies have their limitations, due to their        (when water is used in reduction) or alkaline (when
leaving no chance of recycling the mother liquor”           bureaucratic set-up and their limited ability to deal with    sodium hydroxide is used in fusion, hydrolysis, crys-
says Padia.                                                 high risk-oriented knowledge platforms. and hence             tallisation, etc.).
   “Even if in the laboratory you get 100% selectivity,     they have shown limited interest,” Mehta admits.                  The company claims that its Newreka Recycle
it is important to ensure proper scale-up through              Normally, the investment needed to create new              Solution (NRS), which covers all of these areas, has
appropriate mixing, reactor design and engineering          knowledge far exceeds the business returns in the             several important advantages in addition to the
to have uniformity over large-volume operation. This        initial stages creating financial challenges to sustain-      green chemistry principles it is based on, notably:
is where green engineering plays a critical role in ‘pre-   ing such knowledge platforms. In the future, Mehta            high selectivity leading to high quality, no need for
vention by recycle at source’ at industrial scale.”         believes, there is a need for finances customised to          purification, the ability to customise catalyst formula-
   The key, he adds is ‘prevention, not control’. If the    knowledge-based start-ups in the fields of environ-           tion, close to theoretical yield and recovery, low cap-
industry avoids the need for purification steps and         ment and energy.                                              ital investments, savings on cost and legislative com-
does not produce effluent because it achieves a                Originally, Newreka acted as a consultancy but             pliance, thus freeing up room for expansion, and
complete recycle at the end of the process, this is         this did not work. Between 2002 and 2005, it visit-           better access to markets in the developed world.
not only ‘green’ but economically sound and com-            ed every Chemspec, Informex and CPhI show                         The first case study of the implementation of the
petitive. Padia and Mehta believe that most chemi-          across the world and found that potential customers           NRS showcased at the GCNC symposium concerned
cal processes can actually be reviewed and rein-            wanted more product-based services. Now it has its            the intermediate for an anti-AIDS drug made by
vented in an entirely green way.                            own facility in Dombivli in the suburbs of Mumbai.            Matrix Laboratories in India. Conventionally, this is


Reprinted from Speciality Chemicals Magazine June 2008

                                                                         www.specchemonline.com
Green chemistry

produced by reduction using catalytic hydrogenation
with 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 at
high pressure, Raney Nickel and methanol as sol-
ven. The spent nickel is filtered and the filtrate
undergoes 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 brown
amine and some spent solvent effluent, as well as a
poor 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 Newreka
Reduction Catalyst (NRC) and the Newreka Green               Professor John Warner spoke at the workshop in Delhi
Catalyst (NGC). After the reaction, the spent NRC is
filtered out. After crystallisation and centrifuging, off-   containing sulphuric acid is separated and the ethyl       an environmentalist with the spirit of adventure of an
white amine is produced, along with mother liquor            acetate layer is taken for distillation to recover the     entrepreneur to create wealth from waste and produce
that can be stored and recycled back into the                product, 3-hydroxy acetophenone.                           benefits for the environment. The word refers to the
process 25 times.                                               The process needs additional raw materials like         firm’s individual workers, who are reqiured to do more
    The main advantages of this are that water can be        CuSO4 and acetic acid, which never take part in the        than slot into the role of chemist or chemical engineer,
used as the reaction medium instead of solvent, no           reaction. It generates brown-coloured product and          and to the company itself.
hazardous materials are used, the reaction takes             huge quantities of sulphuric acid effluent, achieving          Universities, industry, government bodies and
place at atmospheric pressure, neutral pH and                65-70% of theoretical yield.                               NGOs, individuals and society as a whole are all
below 100˚C and that the mother liquor can be                   Using the NRS in a patent-pending process, 3-           divided from each other, Mehta says. The former,
recycled 25 times at plant scales and 50 times in            amino acetophenone is diazotised with NaNO2                for instance, are a source of new ideas but lack the
laboratory trials, rather than being treated at the end      using sulphuric acid mother liquor as the reaction         ability to scale them up or commercialise them;
of the pipe.                                                 and extraction medium. Ethyl acetate solvent is not        industry has the resources but is impelled by the
    The yield is up from 85% to 95% of theoretical           required.                                                  rush to market to stick to existing processes. The
and the whole process is much less energy-inten-                After the diazotization-hydrolysis reaction is com-     ‘enviropreneur’ can be a bridge between them,
sive, leading to substantial savings - thus establish-       plete, the product is extracted using acidic mother        forming mutually beneficial, green partnerships with
ing, in Mehta’s view, that ‘prevention by recycle at         liquor. Following the recovery of product, the entire      all of them (Figure 1).
source’ is a huge profit centre.                             acidic mother liquor is recycled back in the process           Implementing Newreka technology at a cus-
    Another factor is the soaring costs of nickel and        after reacting it with RCat, Newreka’s proprietary         tomer’s site is of necessity a slow process, involving
other noble metals in India, like everywhere else in         recycle formulation.                                       R&D and plant operatives and others, as well as sen-
the world; prices have increased four- to five-fold in          This process, the company claims, led to a 75-          ior management. “The challenge we face is to show
the past five years. In addition, Indian pharmaceuti-        times recycle of the reaction medium instead of pro-       them that green chemistry is actually a profit centre
cals companies face much the same pressures as               ducing a highly acidic effluent. Because of the            rather than a cost centre,” Mehta says. “In our expe-
their Western counterparts to reduce both costs and          improved chemoselectivity and the elimination of           rience, green chemistry is always cheaper.”
pollution.                                                   side-reactions, sulphuric acid was recycled up to 50           The process begins with a confidentiality agree-
    Mehta believes that there is huge potential for          times at plant scale and there was no need to use          ment, finding out what the customer’s expectations
iron-based catalysts to replace not just nickel but          CuSO4 or acetic acid. Yield rose from 75% to 90%           are, then submitting a detailed proposal and signing
platinum and other platinum group metals in catal-           of theoretical. As with the neutral mother liquor,         a commercial agreement. The R&D process then
ysis. Iron, he observes, is not just cheaper and less        water can replace solvent as the extraction medium         begins, followed by a demonstration of the NRS by
hazardous than these metals, but has proved its              and the process is more energy-efficient.                  a lab demo team, then at plant scale by a separate
safety to living creatures by the way it is widely used         Padia notes that no modification was needed to          team. RCat formulations are then put into action,
in natural chemistry, where nickel and other noble           the plant in either of these cases and that this applies   supported by ongoing optimisation, process intensi-
metals are not.                                              to most of Newreka’s work. Only the mixing sys-            fication and troubleshooting services.
    Since it is also ubiquitous and well-nigh inex-          tems in the reactors were modified to ensure uni-              Much, of course, can go wrong at any stage in a
haustible, the price of iron remains stable by compar-       form mixing in every corner of the reactor, thus           country notoriously reluctant to pay for knowledge.
ison with noble metals. Newreka is now working               leading to high chemoselectivity.                          Newreka and its customers work on a 50-50 risk basis.
intensively on developing new formulations based on             Crucial to the success of all this is that Newreka      Customers give an initial commitment amount to
nano-iron catalysts using green chemistry principles.        chemists and chemical engineers are required to            Newreka to start the work on all aspects of converting
    The second case study concerned 3-hydroxy                work together in harmony. “They should be like             the conventional process(es) to its technologies.
acetophenone, the intermediate for the deconges-             husband and wife,” Padia says.                                 Typically, a project takes from six to 12 months to
tant phenylephrine hydrocholoride. This drug is                 (Some cynical Westerners might say that chemists        implement and six to nine to break even. If the proj-
increasingly replacing pseudo-ephedrine in the US            and chemical engineers in most firms are very much         ect is unsuccessful, customers are offered a choice of
market and its production is growing very fast, but          like husband and wife already. They have totally dif-      a 50% refund of their initial commitment amount or
the conventional process for its manufacture is              ferent points of view on every subject, they never lis-    the chance to replace the old project with a new
highly polluting.                                            ten to each other and they invariably blame each           one.
    In the conventional process, 3-amino acetophe-           other for anything that goes wrong. But that’s anoth-          To date, Newreka has not done much business
none is diazotised with NaNO2 using sulphuric acid           er story...)                                               outside India, though it has fielded many enquiries
as the reaction medium. After the diazotisation-                The term ‘enviropreneur’, which Newreka also            from the Paracetamol industries in Iran, Bangladesh,
hydrolysis reaction is complete, ethyl acetate is used       showcased in Delhi, is a fusion of ‘environment’ and       Turkey, Pakistan, Egypt and South Africa. Mehta and
as a solvent to extract the product, an aqueous layer        ‘entrepreneur’. The idea is to combine the passion of      his technology implementation team recently spent


                                                                                                               Reprinted from Speciality Chemicals Magazine June 2008

                                                                         www.specchemonline.com
Green chemistry

a month in Iran demonstrating how NRS could be                In agrochemicals, dicholoro and tricholoro aniline   there will be a green chemistry solution for every
used to convert para-nitro phenol to para-amino           have been the subjects of projects. Newreka has          problem,” says Mehta.
phenol, a key intermediate in Paracetamol, using a        also been working with Shree Hari Chemical                  Newreka sees itself as a global company in the
water-based process with more than 100 recycles of        Exports on H-acid, a very large volume intermediate      long term and the Western world is obviously the
mother liquor and producing off-white and stable          for brown and black dyes. In pigments, it has been       next target. Mehta notes that, where India is more
para-amino phenol.                                        working with Pidilite Industries, the main producer      focused on intermediates, the European and US
   This, Padia adds, could ultimately lead to “a com-     of Pigment Violet 23                                     markets are more focused on custom synthesis and
plete green solution for Paracetamol”. It also serves         The unit processes of H-acid, Violet 23 and          manufacturing and there are close relationships
as an example of where, according to Mehta, the           Paracetamol, plus DASDA, Phenylephrine and               between them and Big Pharma companies.
well-known 80/20 rule also applies.                       Pigment CPC, all consume sulphuric acid. It is used         “The pharmaceuticals industry, creates huge
   “In all industries, 20% of the products create 80%     in vast quantities in both the general chemicals         amounts of waste, around 50-100 kg per kg of
of the pollution,” he says. Converting this 20% to        industry of Gujarat and Mahrashtra and in the            product. It is normally difficult to get involved in this
green chemistry will be more profitable, advance          pharemceuticals industry around Hyderabad and            area once DMFs have been filed and the process is
the technology and will go furthest to reducing pol-      Bangalore. Therefore, sulphuric acid is a big target     hard to change. However, when patents have
lution, significantly impacting the environment           of investment for Newreka.                               expired or are about to, there could be more inter-
specifically water bodies.                                    In addition, Newreka is working on next genera-      est in our technology,” he concludes. “I have not
   For this reason, Newreka is not running small-         tion nanocatalysts. Nano-iron compounds and bio-         come across anyone else doing what we do, so I
scale projects but is prioritising the 20 products in     mimicry has huge potential according to Padia. The       believe that our business model is unique.”
every market by bulk. It has, in many cases, worked       former are very common in nature right from amoe-
on them already, generally to develop a green route       ba to whales; they are, for example, the natural         For further information, please contact:
                                                                                                                   Nitesh H. Mehta
for every step of a four- to ten-step synthesis.          magnets behind homing pigeons, Padia observes.
                                                                                                                   Founder Director
   Examples in pharmaceuticals other than those           Biomimicry - observing Nature’s own innovation to
                                                                                                                   Newreka Green Synth-Technologies Pvt. Ltd.
cited already include caffeine, citalopram, triclosan,    develop products and processes - he sees as essen-       405, MasterMind IV
and, perhaps most interestingly of all, sildenafil cit-   tial to achieving a sustainable environmental foot-      Royal Palms
rate, the API in Viagra. Rakshit Drugs, India’s           print for the future need of mankind.                    Aarey Colony
largest producer of sildenafil citrate, has imple-            “We are always looking at gaps from the eco-         Goregaon (East)
mented the NRT in one of the steps in place of cat-       nomic and the environmental point of view. The           Mumbai - 400 065
alytic hydrogenation by hydrogen gas and Raney            only issue, as Professor Warner said in Delhi, is that   India
Nickel, achieving among other things a 30%                the toolbox is not yet full. We have not yet, for        Tel: +91 22 2879 1835
reduction in batch time and improved intermedi-           example, worked on chlorination or bromination           E-mail: nitesh.mehta@newreka.co.in
                                                                                                                   Website: www.newreka.co.in
ate quality.                                              but we will do so and we think that in ten years’ time




                                                                                                          Reprinted from Speciality Chemicals Magazine June 2008

                                                                      www.specchemonline.com

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Newreka Green Synth Technologies : Pioneering in the field of Green Chemistry

  • 1. Magazine Mother’s little helper An Indian company is pioneering some key green chemistry concepts. We caught up with Newreka Green Synth at Chemspec India 2008
  • 2. Green chemistry Mother’s little helper An Indian company is pioneering some key green chemistry concepts. We caught up with Newreka Green Synth at Chemspec India 2008 A lthough the company stand was located right at the back of the hall at Chemspec India 2008, it was swarming throughout. Founder director Nitesh Mehta said: “It has been so amazing. There has been no beating about the Universities Selling ideas Sustainable Industries & scale-up solutions bush, it is all real business.” Clearly Newreka Green Synth Technologies had identified something that IP & Investment on R&D the Indian chemicals industry wanted. knowledge & value for solutions Although the firm has been active for six years, Enviropreneurs 2008 may prove to be its breakthrough year. In January, alongside SMS Pharmaceuticals, Newreka Investments & Empowerment won the Indo-US Green Chemistry Network Centre incentives & support (GCNC) Award for the successful commercialisation Government bodies Good Employment & Individual of green chemistry-based technologies at the Indo- & financial institutions & society ROI healthy living US Science & Technology Forum Workshop on Green Chemistry. The GCNC itself is an umbrella organisation that grew out of the India Green Chemistry Chapter of the American Chemistry Society Green Chemistry Figure 1 - Green partnerships based on enviropreneurs Institute (ACS GCI) and now encompasses several centres, institutions and industries. It organises vari- Padia himself is an expert in iron oxide catalysis, For the first couple of years, a focus on unit ous symposia, workshops and training courses to process intensification, scale-up, unit processes like process of reduction was the company’s key mar- further the concept of green chemistry. reduction, nitration and diazotization-hydrolysis, and keting strategy. This was based on the Newreka The event in Delhi last January, the third in the unit operations like crystallisation, extraction, filtra- Reduction Technology (NRT), in which proprietary series, attracted some 200 delegates from industry tion and isolation. He founded Newreka along with catalytic formulations are used in reduction. More and academe. It was addressed by Professor John Mehta, the public face of the company, whose inter- recently it has expanded to offer systems for other Warner of the Warner Babcock Institute for Green ests are in similar areas, and Vineet Shroff, whose reactions, including nitration, diazotisation-hydroly- Chemistry, who is widely regarded as one of the main areas of competence are engineering and sis, isolation, oxidation, sulphonation, acetylation and fathers of green chemistry. industrial mixing. The company name is a combina- Friedel-Crafts. The ideas behind Newreka actually go back to tion Nature’s Enthusiastic World and ‘Eureka’, Thus, Newreka has slowly achieved recognition, conversation in a hostel room at IIT Bombay, where Archimedes’ joyous cry of scientific discovery. culminating in the award at the GCNC symposium. Mehta was studying under Bhadresh K. Padia, in Over the past ten years, Newreka has grown to This was based on case studies of its work in two 1998. The basic idea, Padia says, was that the chem- about 100 chemists and engineers, who have car- specific areas - the recycle of mother liquor from icals industry sees pollution as something that needs ried out some 20,000 experiments in unit process- chemical process streams and the use of its propri- to be controlled when it should rather look at the es, with a focus on recyle. Growth was an uphill etary catalysts to replace harsh with mild conditions issue in terms of ‘prevention by recycle at source’. challenge, however, because it is very difficult for - plus its concept of the ‘enviropreneur’. “The industry always sees effluents and their end knowledge-based start-ups, unlike software start- Mother liquor typically contains raw materials, fin- of the pipe treatment as a cost centre, when it is pos- ups, to generate seed capital. ished product and both organic and inorganic impu- sible to transform it into a profit centre through the “Knowledge doesn’t show up on a balance sheet rities. Depending on the reaction medium, it can be ‘prevention by recycle at source’ approach. For and venture capitalists and banks are not interested in acidic (when sulphuric acid is used in nitration, dia- example, when you lose selectivity, you lose materi- things with a six-to-seven-year turnaround period. zotisation, methylation, precipitation, etc.), neutral als in side reactions and it ends up as an effluent, Government bodies have their limitations, due to their (when water is used in reduction) or alkaline (when leaving no chance of recycling the mother liquor” bureaucratic set-up and their limited ability to deal with sodium hydroxide is used in fusion, hydrolysis, crys- says Padia. high risk-oriented knowledge platforms. and hence tallisation, etc.). “Even if in the laboratory you get 100% selectivity, they have shown limited interest,” Mehta admits. The company claims that its Newreka Recycle it is important to ensure proper scale-up through Normally, the investment needed to create new Solution (NRS), which covers all of these areas, has appropriate mixing, reactor design and engineering knowledge far exceeds the business returns in the several important advantages in addition to the to have uniformity over large-volume operation. This initial stages creating financial challenges to sustain- green chemistry principles it is based on, notably: is where green engineering plays a critical role in ‘pre- ing such knowledge platforms. In the future, Mehta high selectivity leading to high quality, no need for vention by recycle at source’ at industrial scale.” believes, there is a need for finances customised to purification, the ability to customise catalyst formula- The key, he adds is ‘prevention, not control’. If the knowledge-based start-ups in the fields of environ- tion, close to theoretical yield and recovery, low cap- industry avoids the need for purification steps and ment and energy. ital investments, savings on cost and legislative com- does not produce effluent because it achieves a Originally, Newreka acted as a consultancy but pliance, thus freeing up room for expansion, and complete recycle at the end of the process, this is this did not work. Between 2002 and 2005, it visit- better access to markets in the developed world. not only ‘green’ but economically sound and com- ed every Chemspec, Informex and CPhI show The first case study of the implementation of the petitive. Padia and Mehta believe that most chemi- across the world and found that potential customers NRS showcased at the GCNC symposium concerned cal processes can actually be reviewed and rein- wanted more product-based services. Now it has its the intermediate for an anti-AIDS drug made by vented in an entirely green way. own facility in Dombivli in the suburbs of Mumbai. Matrix Laboratories in India. Conventionally, this is Reprinted from Speciality Chemicals Magazine June 2008 www.specchemonline.com
  • 3. Green chemistry produced by reduction using catalytic hydrogenation with 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 at high pressure, Raney Nickel and methanol as sol- ven. The spent nickel is filtered and the filtrate undergoes 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 brown amine and some spent solvent effluent, as well as a poor 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 Newreka Reduction Catalyst (NRC) and the Newreka Green Professor John Warner spoke at the workshop in Delhi Catalyst (NGC). After the reaction, the spent NRC is filtered out. After crystallisation and centrifuging, off- containing sulphuric acid is separated and the ethyl an environmentalist with the spirit of adventure of an white amine is produced, along with mother liquor acetate layer is taken for distillation to recover the entrepreneur to create wealth from waste and produce that can be stored and recycled back into the product, 3-hydroxy acetophenone. benefits for the environment. The word refers to the process 25 times. The process needs additional raw materials like firm’s individual workers, who are reqiured to do more The main advantages of this are that water can be CuSO4 and acetic acid, which never take part in the than slot into the role of chemist or chemical engineer, used as the reaction medium instead of solvent, no reaction. It generates brown-coloured product and and to the company itself. hazardous materials are used, the reaction takes huge quantities of sulphuric acid effluent, achieving Universities, industry, government bodies and place at atmospheric pressure, neutral pH and 65-70% of theoretical yield. NGOs, individuals and society as a whole are all below 100˚C and that the mother liquor can be Using the NRS in a patent-pending process, 3- divided from each other, Mehta says. The former, recycled 25 times at plant scales and 50 times in amino acetophenone is diazotised with NaNO2 for instance, are a source of new ideas but lack the laboratory trials, rather than being treated at the end using sulphuric acid mother liquor as the reaction ability to scale them up or commercialise them; of the pipe. and extraction medium. Ethyl acetate solvent is not industry has the resources but is impelled by the The yield is up from 85% to 95% of theoretical required. rush to market to stick to existing processes. The and the whole process is much less energy-inten- After the diazotization-hydrolysis reaction is com- ‘enviropreneur’ can be a bridge between them, sive, leading to substantial savings - thus establish- plete, the product is extracted using acidic mother forming mutually beneficial, green partnerships with ing, in Mehta’s view, that ‘prevention by recycle at liquor. Following the recovery of product, the entire all of them (Figure 1). source’ is a huge profit centre. acidic mother liquor is recycled back in the process Implementing Newreka technology at a cus- Another factor is the soaring costs of nickel and after reacting it with RCat, Newreka’s proprietary tomer’s site is of necessity a slow process, involving other noble metals in India, like everywhere else in recycle formulation. R&D and plant operatives and others, as well as sen- the world; prices have increased four- to five-fold in This process, the company claims, led to a 75- ior management. “The challenge we face is to show the past five years. In addition, Indian pharmaceuti- times recycle of the reaction medium instead of pro- them that green chemistry is actually a profit centre cals companies face much the same pressures as ducing a highly acidic effluent. Because of the rather than a cost centre,” Mehta says. “In our expe- their Western counterparts to reduce both costs and improved chemoselectivity and the elimination of rience, green chemistry is always cheaper.” pollution. side-reactions, sulphuric acid was recycled up to 50 The process begins with a confidentiality agree- Mehta believes that there is huge potential for times at plant scale and there was no need to use ment, finding out what the customer’s expectations iron-based catalysts to replace not just nickel but CuSO4 or acetic acid. Yield rose from 75% to 90% are, then submitting a detailed proposal and signing platinum and other platinum group metals in catal- of theoretical. As with the neutral mother liquor, a commercial agreement. The R&D process then ysis. Iron, he observes, is not just cheaper and less water can replace solvent as the extraction medium begins, followed by a demonstration of the NRS by hazardous than these metals, but has proved its and the process is more energy-efficient. a lab demo team, then at plant scale by a separate safety to living creatures by the way it is widely used Padia notes that no modification was needed to team. RCat formulations are then put into action, in natural chemistry, where nickel and other noble the plant in either of these cases and that this applies supported by ongoing optimisation, process intensi- metals are not. to most of Newreka’s work. Only the mixing sys- fication and troubleshooting services. Since it is also ubiquitous and well-nigh inex- tems in the reactors were modified to ensure uni- Much, of course, can go wrong at any stage in a haustible, the price of iron remains stable by compar- form mixing in every corner of the reactor, thus country notoriously reluctant to pay for knowledge. ison with noble metals. Newreka is now working leading to high chemoselectivity. Newreka and its customers work on a 50-50 risk basis. intensively on developing new formulations based on Crucial to the success of all this is that Newreka Customers give an initial commitment amount to nano-iron catalysts using green chemistry principles. chemists and chemical engineers are required to Newreka to start the work on all aspects of converting The second case study concerned 3-hydroxy work together in harmony. “They should be like the conventional process(es) to its technologies. acetophenone, the intermediate for the deconges- husband and wife,” Padia says. Typically, a project takes from six to 12 months to tant phenylephrine hydrocholoride. This drug is (Some cynical Westerners might say that chemists implement and six to nine to break even. If the proj- increasingly replacing pseudo-ephedrine in the US and chemical engineers in most firms are very much ect is unsuccessful, customers are offered a choice of market and its production is growing very fast, but like husband and wife already. They have totally dif- a 50% refund of their initial commitment amount or the conventional process for its manufacture is ferent points of view on every subject, they never lis- the chance to replace the old project with a new highly polluting. ten to each other and they invariably blame each one. In the conventional process, 3-amino acetophe- other for anything that goes wrong. But that’s anoth- To date, Newreka has not done much business none is diazotised with NaNO2 using sulphuric acid er story...) outside India, though it has fielded many enquiries as the reaction medium. After the diazotisation- The term ‘enviropreneur’, which Newreka also from the Paracetamol industries in Iran, Bangladesh, hydrolysis reaction is complete, ethyl acetate is used showcased in Delhi, is a fusion of ‘environment’ and Turkey, Pakistan, Egypt and South Africa. Mehta and as a solvent to extract the product, an aqueous layer ‘entrepreneur’. The idea is to combine the passion of his technology implementation team recently spent Reprinted from Speciality Chemicals Magazine June 2008 www.specchemonline.com
  • 4. Green chemistry a month in Iran demonstrating how NRS could be In agrochemicals, dicholoro and tricholoro aniline there will be a green chemistry solution for every used to convert para-nitro phenol to para-amino have been the subjects of projects. Newreka has problem,” says Mehta. phenol, a key intermediate in Paracetamol, using a also been working with Shree Hari Chemical Newreka sees itself as a global company in the water-based process with more than 100 recycles of Exports on H-acid, a very large volume intermediate long term and the Western world is obviously the mother liquor and producing off-white and stable for brown and black dyes. In pigments, it has been next target. Mehta notes that, where India is more para-amino phenol. working with Pidilite Industries, the main producer focused on intermediates, the European and US This, Padia adds, could ultimately lead to “a com- of Pigment Violet 23 markets are more focused on custom synthesis and plete green solution for Paracetamol”. It also serves The unit processes of H-acid, Violet 23 and manufacturing and there are close relationships as an example of where, according to Mehta, the Paracetamol, plus DASDA, Phenylephrine and between them and Big Pharma companies. well-known 80/20 rule also applies. Pigment CPC, all consume sulphuric acid. It is used “The pharmaceuticals industry, creates huge “In all industries, 20% of the products create 80% in vast quantities in both the general chemicals amounts of waste, around 50-100 kg per kg of of the pollution,” he says. Converting this 20% to industry of Gujarat and Mahrashtra and in the product. It is normally difficult to get involved in this green chemistry will be more profitable, advance pharemceuticals industry around Hyderabad and area once DMFs have been filed and the process is the technology and will go furthest to reducing pol- Bangalore. Therefore, sulphuric acid is a big target hard to change. However, when patents have lution, significantly impacting the environment of investment for Newreka. expired or are about to, there could be more inter- specifically water bodies. In addition, Newreka is working on next genera- est in our technology,” he concludes. “I have not For this reason, Newreka is not running small- tion nanocatalysts. Nano-iron compounds and bio- come across anyone else doing what we do, so I scale projects but is prioritising the 20 products in mimicry has huge potential according to Padia. The believe that our business model is unique.” every market by bulk. It has, in many cases, worked former are very common in nature right from amoe- on them already, generally to develop a green route ba to whales; they are, for example, the natural For further information, please contact: Nitesh H. Mehta for every step of a four- to ten-step synthesis. magnets behind homing pigeons, Padia observes. Founder Director Examples in pharmaceuticals other than those Biomimicry - observing Nature’s own innovation to Newreka Green Synth-Technologies Pvt. Ltd. cited already include caffeine, citalopram, triclosan, develop products and processes - he sees as essen- 405, MasterMind IV and, perhaps most interestingly of all, sildenafil cit- tial to achieving a sustainable environmental foot- Royal Palms rate, the API in Viagra. Rakshit Drugs, India’s print for the future need of mankind. Aarey Colony largest producer of sildenafil citrate, has imple- “We are always looking at gaps from the eco- Goregaon (East) mented the NRT in one of the steps in place of cat- nomic and the environmental point of view. The Mumbai - 400 065 alytic hydrogenation by hydrogen gas and Raney only issue, as Professor Warner said in Delhi, is that India Nickel, achieving among other things a 30% the toolbox is not yet full. We have not yet, for Tel: +91 22 2879 1835 reduction in batch time and improved intermedi- example, worked on chlorination or bromination E-mail: nitesh.mehta@newreka.co.in Website: www.newreka.co.in ate quality. but we will do so and we think that in ten years’ time Reprinted from Speciality Chemicals Magazine June 2008 www.specchemonline.com