Research and Development Process

1. Organic Chemistry - A Pivotal Science Organic Chemistry plays a pivotal role in R&D in chemical Industry - whether it is pharma R&D , specialty chemical R&D or crop protection R&D. Starting with research and innovation of new drugs or crop protection active ingredients to process research and process development, sophistication and complexity of chemistry has increased. Let us take a look at Crop Protection R&D. Crop protection is crucial to defend the yield of agricultural output. Crops are protected by several technologies. The overwhelmingly widely used method is application of crop protection chemicals to the seed or crop to combat disease, pests and weeds. New molecules are always needed to overcome resistance and environmental challenges. This demand has spurred organic chemists involved in crop protection research to design and synthesize more and more complex molecules. Even for generic agrochemical companies, this means that they require a strong R&D staffed by highly skilled organic chemists and chemical engineers. Take for example insecticides. Starting from simple molecules, the field has seen successive domination by organochlorines, organophosphates, heterocyclic compounds and natural products and their derivatives. Initially the molecules had simpler structural attributes. That is no longer the case. In their search for safer and more effective molecules, reesearchers have made molecules with increasing complexity of structure. Apart from complex functional groups, today’s insecticides may have stereochemical features. These require the R&D chemists to use modern synthetic chemical reactions and approaches to synthesize them. The challenge to chemical engineers comes when the process is transferred from the lab to pilot plant and finally to the plant. The examples of insecticides below illustrate the points raised in this blog. Chemical Structure / Generic Name Inventor Company Inventor Company Trade Name Year of Synthesis /Registration / Current Status Number of steps and key reactions to Synthesize Dupont Maralate 1948 1 Step from Chloral and Anisole Banned since 2002 Methoxychlor Syngenta Curacron 1982 (In USA but not in EU) 4 Steps involving bromination, phosphorylation and S-Alkylation Profenofos Rothamstead Research Station ICI Z-Cypermethrin - Mustang (FMC) 1974 / 1984 >10 ; Also involves chiral synthesis

2. Chemical Structure / Generic Name Inventor Company Inventor Company Trade Name Year of Synthesis /Registration / Current Status Number of steps and key reactions to Synthesize Sumitomo Pesguard 1978 9 + Chiral synthesis or Resolution Esfenvelerate Admire 1986 / 1992 5 steps involving use of NaH . Nihon Tokushu Noyaku Seizo and Later Bayer Cropscience Imidacloprid DuPont Rynoxapyr Coragen 2006 6(Intermediate 1) +4 (Intermediate 2) + 1(Final Step) Chlorantraniliprole Nihon Nohayaku / Bayer Cropscience Belt / Fame (in India) 2005 7 Steps including final coupling with hepta fluoro o- toluidine which requires several steps and a highly fluorinated starting material Flubendiamide

3. Chemical Structure / Generic Name Inventor Company Inventor Company Trade Name Year of Synthesis /Registration / Current Status Number of steps and key reactions to Synthesize Mitsui / BASF Vedira Discovered in 2005, registered in 2020 > 6 steps with intermediates which contain several fluorine atoms Brofanilide In the foreseeable future, the stringent demands from regulators for environmentally safe molecules on one hand and the need for molecules with lower resistance and new modes of action on the other will drive the discovery research in crop protection. In order to find such molecules which can also provide intellectual property protection, research chemists will apply modern and often challenging chemistry to synthesize new compounds. Any organization aspiring to enter either discovery research new molecules or process research for generics would need high ccaliber chemists in it’s R&D. However, it is impossible to have all the knowledge in-house and an organization which can leverage external resources would have a better chance of success. It is in this context that we at InnovaSMART are uniquely positioned to support your organization’s in-house R&D in it’s efforts - be it discovery chemistry in search of new active molecules or process R&D for new generic molecules - because the central strength of InnovaSMART is organic chemistry as applied across domains and a cumulative experience of over 100 years.