Sustainable chemistry: how to produce better and more from less?
DOI: 10.1039/C7GC02006F, Perspective
This review describes the rapid evolution of chemistry in the context of a sustainable development of our society. Written in collaboration between scientists from different horizons, either from public organizations or chemical companies, we aim here at providing recommendations to accelerate the emergence of eco-designed products on the market.
Sustainable chemistry: how to produce better and more from less?
The International Symposium on Green Chemistry (ISGC) organized in 2013, 2015 and 2017 has gathered many senior and young talented scientists from all around the world (2200 attendees in three editions), either from academia or industry. Through outstanding conferences, communications, debates, and round tables, ISGC has been the witness of the rapid evolution of chemistry in the context of a sustainable development of our societies, not only at the scientific and industrial levels but also on education, networking and societal aspects. This critical review synthesizes the different points of view and the discussions having taken place at ISGC and gives a general picture of chemistry, including few scientific disciplines such as catalysis, processes, resource management, and environmental impact, among others, within the framework of sustainable development. This critical review, co-authored by researchers from public organizations and chemical companies (small, medium and large industrial groups) provides criteria and recommendations which, in our view, should be considered from the outset of research to accelerate the emergence of eco-designed products on the market.
Sustainable chemistry is the only mean to generate performant products and long lasting solutions able to generate business and profit for chemical industry. Performance is the best systemic answer for customer needs and our societies. Defining sustainable chemistry is, however, far to be an easy task because chemistry is a highly dynamic system. The sustainability of a value chain is for instance directly depending on the access to energy (and above all to its origin – coal, gas, biomass…) and on the supply of raw materials. In the current economic context, it could be not so easy to predict what will be the best source of energy or raw materials for a desired product in the future. The development of predictive tools is now essential and will represent probably one of the next scientific challenges in the coming years. During the last 20 years, utilization of renewable feedstocks in chemical processes has become a strategy of growing interest but it definitely does not guarantee the establishment of a sustainable chemistry. Indeed, in some cases, it is more sustainable to produce a chemical from a fossil carbon source using decarbonized energy than the reverse. It is very important to distinguish the carbon found in the final product from the carbon content corresponding to the energy which is required the product production (going from raw materials to manufacturing, end of life, etc.). In this area, the concept of biorefinery can help to secure developments and to minimize investments in production plant by mutualizing facilities and R&D initiatives. Cooperation with local producers can also be a valuable way to implement new bio‐based products while favouring sustainable agricultural practices. Whatever the raw materials (renewable or fossil), a complete and systemic life cycle analysis of the whole chain value (from resources to manufacturing, use and end of life) must be performed because it gives us an accurate picture of the overall economic, environmental and societal performances of a product in an application for a defined market. In general, one should never forget that sustainable chemistry should help the society to produce more and better (products). Emergence of sustainable innovations on the market takes a lot of time because chemists have to reinvent chemistry. To achieve our transition to a sustainable society, we must think differently and bring together the worlds of finance, manufacturers, researchers and public authorities. The current method of funding of research and innovation is not satisfying yet because too often based on short‐term projects and with high Technology Readiness Level. Governments have to realize that this funding method slows down, and sometime also hampers, the emergence of future sustainable innovations. Evolution of regulations with the aim of banning toxic, eco‐toxic or poor biodegradable products is an important driver for sustainable innovation. It is now seen and shared as a positive sign providing opportunities to develop systemically better solutions and allowing chemical companies advocating sustainable development and products as a must to stay in the competition. As examples, ban of CFC, replacement of chlorinated or other toxic solvents, substitution of endocrine disruptors lead to better solutions for the global benefit of our societies. Improving public perception and awareness on sustainable chemistry is on the way but more efforts will be needed in the future to definitely contribute to the emergence of eco‐ designed chemicals on the market.
Veratraldehyde is an important chemical used in perfumery, agrochemical, and pharmaceutical industries. Current processes of manufacture of veratraldehyde use homogeneous catalysts, which make them highly polluting, creating problems of disposal of effluents and product purity. In the current work, veratraldehyde was synthesized from O-alkylation of vanillin with an environmentally benign reagent, dimethyl carbonate. A series of potassium loaded La2O3–MgO were prepared by the incipient wetness impregnation method, and their performance was evaluated vis-à-vis MgO, La2O3, La2O3–MgO, and a series of 1–4 wt % K/La2O3–MgO. All catalysts were characterized by different techniques, such as N2 adsorption/desorption, XRD, TGA-DSC, FT-IR, CO2-TPD, and SEM techniques. The effect of different loadings (1–4 wt %) of potassium on La2O3–MgO was studied, among which 2 wt % K/La2O3–MgO showed the best activity and selectivity due to high dispersion of potassium and high basicity in comparison with the rest. The activity of 2 wt % K/La2O3–MgO in O-methylation of vanillin with dimethyl carbonate (DMC) was closely associated with basicity. Various parameters were studied to achieve the maximum yield of the desired product. The maximum conversion was found with catalyst loading of 0.03 g/cm3 and mole ratio of vanillin and DMC of 1:15 at 160 °C in 2 h. The reaction follows pseudo-first-order kinetics for the O-methylation of vanillin. The energy of activation was found to be 13.5 kcal/mol. Scale-up was done using the kinetic model to observe that the process could be scaled up using the process parameters. The overall process is clean and green.
Green Synthesis of Veratraldehyde Using Potassium Promoted Lanthanum–Magnesium Mixed Oxide Catalyst
Green and sustainable drug manufacturing go hand in hand with forward-looking visions seeking to balance the long-term sustainability of business, society, and the environment. However, a lack of harmonization among available metrics has inhibited opportunities for green chemistry in industry. Moreover, inconsistent starting points for analysis and neglected complexities for diverse manufacturing processes have made developing objective goals a challenge. Herein we put forward a practical strategy to overcome these barriers using data from in-depth analysis of 46 drug manufacturing processes from nine large pharmaceutical firms, and propose the Green Aspiration Level as metric of choice to enable the critically needed consistency in smart green manufacturing goals. In addition, we quantify the importance of green chemistry in the often overlooked, yet enormously impactful, outsourced portion of the supply chain, and introduce the Green Scorecard as a value added sustainability communication tool.
The Green Aspiration Level (GAL) has been constructed on four pillars to ensure consistent application, namely (1) clearly defined synthesis starting points,1 (2) unambiguous complete E factor (cEF)2,3 or Process Mass Intensity (PMI) waste metrics, (3) historical averages of industrial drug manufacturing waste, and (4) complexity of the drug’s ideal manufacturing process (Supplementary Figure 6). cEF or PMI can be used interchangeably in GAL-based analysis enabling organizations using either to calculate their green performance scores. cEF and PMI differ by just one unit (Supplementary Equation 6) and share the same commercial waste goal for an average manufacturing step4 – the transformation-GAL or tGAL – that results in negligible numerical differences from the inclusion of one or the other. The pharmaceutical industry has generally adopted PMI. However, our publication utilizes cEF values due to literature prevalence and potentially broader appeal of E factors.5 It is important to note that all reaction and workup materials are included in the analysis, but excluded are reactor cleaning6 and solvent recycling.7 Standardized process starting points are a critical component of the GAL methodology. A starting material for some may be an intermediate for others. Until recently, the scientific community lacked an unambiguous definition of process starting points in the assessment of process greenness. This has been a bothersome source of inconsistency. Failure to define an appropriate starting material can lead to exclusion of significant amounts of intrinsic raw material waste created during earlier stages of manufacture. We therefore utilize these updated definitions of process analysis starting points to ensuring higher quality of data:8
1) The material is commercially available from a major reputable chemical laboratory catalog company, and its price is listed in the (online) catalog. Materials requiring bulk or custom quotes do not qualify as process starting material. AND 2) The laboratory catalog cost of the material at its largest offered quantity does not exceed US $100/mol. Therefore, published literature must be researched if the material does not qualify as process starting material in order to determine its correct intrinsic cEF. However, we realized that determination of literature cEF values is tedious and involves making assumptions since literature procedures are often incomplete compared to internal or external manufacturing batch records. Thus, standardizing Literature cEF quickly became a desirable goal. In order to facilitate literature analysis we introduced Supplementary Equation 7 that just requires determination of literature step count from ≤$100/mol starting materials without having to retrieve literature waste information.9 The literature step multiplier of 37 kg/kg represents the average literature step cEF across the analyzed projects (Supplementary Table 1), so it equals their average literature cEF (76 kg/kg) divided by average literature step count (2.1). The process cEF and Relative Process Greenness (RPG) derived from the simplified calculated cEF literature values are shown next to their progenitors in Supplementary Table 3. We observe that average calculated and manually determined cEF and RPG values are comparable and within 10% of their means across the three development phases. Thus, we consider the simplified method sound and an importtant element to achieving consistency in green process analysis.
A deeper shade of green: inspiring sustainable drug manufacturing
Frank Roschangar, PhD MBA
Pharmaceutical process research director, passionate about accelerating drug development and driving green chemistry.
Feb 2002–Sep 2015DirectorBoehringer IngelheimGermany · Nieder-Ingelheim
Aug 1996–Feb 1998
PostdocThe Scripps Research Institute · Skaggs Institute for Chemical Biology · Prof. K.C. NicolaouUnited States · La Jolla
Aug 1992–Aug 1996
PhD CandidateRice University · Department of ChemistryUnited States · Houston
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Scheme 1. Pfizer’s Commercial Synthesis of sildenafil citrate (Viagra™)
“Green chemistry” refers to the promotion of safe, sustainable, and waste-minimizing chemical processes. The proliferation of green chemistry metrics without any clear consensus on industry standards is a significant barrier to the adoption of green chemistry within the pharmaceutical industry. We propose the Green Aspiration Level™ (GAL) concept as a novel process performance metric that quantifies the environmental impact of producing a specific pharmaceutical agent while taking into account the complexity of the ideal synthetic process for producing the target molecule. Application of the GAL metric will make possible for the first time an assessment of relative greenness of a process, in terms of waste, versus industry standards for the production process of any pharmaceutical. Our recommendations also include a simple methodology for defining process starting points, which is an important aspect of standardizing measurement to ensure that Relative Process Greenness (RPG) comparisons are meaningful. We demonstrate our methodology using Pfizer’s Viagra™ process as an example, and outline aspiration level opportunities for industry and government to dismantle green chemistry barriers.
Overcoming barriers to green chemistry in the pharmaceutical industry – the Green Aspiration Level™ concept
DOI: 10.1039/C4GC01563K, http://pubs.rsc.org/en/content/articlelanding/2015/gc/c4gc01563k#!divAbstract
“ALL FOR DRUGS” CATERS TO EDUCATION GLOBALLY, No commercial exploits are done or advertisements added by me. This article is a compilation for educational purposes only.
P.S. : The views expressed are my personal and in no-way suggest the views of the professional body or the company that I represent
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Convenor of Industrial Green Chemistry World and Founder – Director of Newreka Green Synth Technologies Pvt Ltd
Identifying “green chemistry” industrialisation barriers through case-studies
– Mr. Nitesh Mehta, Founder Director, Newreka Green Synth Technologies Pvt. Ltd., India
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University of Toronto researchers have developed safer, cheaper and more environmentally-friendly techniques to produce compounds commonly used in drugs and perfumes.
Researchers used the new techniques to create active, iron-based catalysts. These catalysts are needed to produce certain compounds used in the drug and perfume industries. read all here