John D. Hayler

Key green chemistry research areas—a perspective from pharmaceutical manufacturers

In 2005, the ACS Green Chemistry Institute (GCI) and the global pharmaceutical corporations developed the ACS GCI Pharmaceutical Roundtable to encourage the integration of green chemistry and green engineering into the pharmaceutical industry. The Roundtable has developed a list of key research areas. The purpose of this perspective is to summarise how that list was agreed, provide an assessment of the current state of the art in those areas and to highlight areas for future improvement.

CHEM21 selection guide of classical- and less classical-solvents

A selection guide of common solvents has been elaborated, based on a survey of publically available solvent selection guides. In order to rank less classical solvents, a set of Safety, Health and Environment criteria is proposed, aligned with the Global Harmonized System (GHS) and European regulations. A methodology based on a simple combination of these criteria gives an overall preliminary ranking of any solvent. This enables in particular a simplified greenness evaluation of bio-derived solvents.

A survey of solvent selection guides

Several solvent selection guides have been published, in different formats, reflecting the culture of their institutions. The data given in these guides have been compiled, and where possible combined, in order to allow a ranking comparison. Of the 51 solvents considered, an acceptable alignment of the classifications could be met, permitting a ranking into four categories: recommended, problematic, hazardous and highly hazardous. 17 solvents (33%) could not be unequivocally ranked by this simplified analysis, thus reflecting differences in the weighing of criteria between the institutions.

Updating and further expanding GSK's solvent sustainability guide

GlaxoSmithKline (GSK) has previously reported on the development of a GSK solvent guide, the incorporation of lifecycle impact and the expansion of the guide including a customisable version intended for posting in different business areas. This guide has recently been enhanced by: (1) adding 44 additional solvents, many of which have literature claims to be “green”; (2) adjusting the way in which multiple health, environment, safety, and waste categories are combined to reach a single composite score and colour assignment; (3) updating the data behind all scores, especially toxicology and health hazard assessment, and revising the methodology to reflect current guidelines and data. The full methodology behind this work is hereby shared. The new GSK Solvent Sustainability Guide enables GSK scientists to objectively assess solvents. It facilitates both comparison of individual sustainability criteria, and a composite score and colour for rank ordering, incorporating multiple facets of sustainability.

Green chemistry measures for process research and development

A set of metrics has been developed which enables a simple assessment to be made of batch processes in terms of waste, energy usage, and chemistry efficiency. It is intended to raise awareness of green chemistry by providing a tool to assist chemists in monitoring progress in the reduction of environmental impact as they design new routes and modify processes.

Development of GSK's reagent guides – embedding sustainability into reagent selection

Reagent guides ranking commonly used reagents for 15 transformations have been developed to reduce the environmental impact of drug discovery and development. Reagents have been scored by a combination of health, safety and environmental risk phrases, life cycle analysis (where possible) and an assessment of the chemistry including considerations of atom efficiency, stoichiometry, work-up and other issues. Guides covering alkene reduction, amide formation, C–H bromination, C–H chlorination, deoxychlorination, epoxidation, ester formation, ether formation, fluorination, iodination, ketone reduction, nitro reduction, oxidation of alcohols to aldehydes and ketones, reductive amination and sulfur oxidation are shared, with an explanation of the methodology behind their generation.

A deeper shade of green: inspiring sustainable drug manufacturing

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.

A Direct and High Yielding Route to 2-(5-Tetrazolyl) Substituted Benzopyran-4-ones: Synthesis of Pranlukast

Abstract A direct and high yielding route to 2-(5-tetrazolyl)benzopyran-4-ones 1, including pranlukast 1a is described. This involves the Claisen condensation reaction between the relevant hydroxyacetophenone 2 and the ethyl ester of tetrazole-2-carboxylic acid 5 to give the 1,3-diketone 6, which is then cyclised to give the desired benzopyran-4-ones 1.

Correction: CHEM21 selection guide of classical- and less classical-solvents

Correction for ‘CHEM21 selection guide of classical- and less classical-solvents’ by Denis Prat, et al., Green Chem., 2015, DOI: 10.1039/c5gc01008j.

Inspiring process innovation via an improved green manufacturing metric: iGAL

Following our goal to devise a unified green chemistry metric that inspires innovation in sustainable drug manufacturing across the pharmaceutical industry, we herein disclose joint efforts by IQ, the ACS GCI PR and academia, leading to the significantly improved ‘innovation Green Aspiration Level’ (iGAL) methodology. Backed by the statistical analysis of 64 drug manufacturing processes encompassing 703 steps across 12 companies, we find that iGAL affords an excellent proxy for molecular complexity and presents a valuable molecular weight-based ‘fixed’ goal. iGAL thereby accurately captures the impact of green process inventiveness and improvements, making it a useful innovation-driven green metric. We conclude by introducing the comprehensive, yet easy-to-use and readily adaptable Green Chemistry Innovation Scorecard web calculator, whose graphical output clearly and effectively illustrates the impact of innovation on waste reduction during drug manufacture.