New routes to the activation of organic molecules

Lead Research Organisation: University of Nottingham
Department Name: Sch of Chemistry


Phosphorus compounds are widely used in Chemistry. They are often used in agriculture, materials, medicines and for the activation of organic molecules (such as carboxylic acids). Often the synthesis of these useful compounds uses, toxic, hazardous and/or energy intensive processes and reagents, examples include: PCl5, PCl3, POCl3, phosgene, Cl2 etc. In order to move to a more sustainable future, chemists must develop alternative reagents and methods that are, safer, more stable and therefore easier to use.

The most common transformation used by the pharmaceutical industry is amide bond synthesis, representing 1 in 7 reactions performed. As a result, a wide range of coupling (activating) reagents have been developed to couple carboxylic acids with amine nucleophiles. Phosphorus (V) activating reagents are popular (e.g. T3P, DPPA, BOP etc.) as these reagents produce water soluble by-products that can easily be removed by aqueous washing. However, the synthesis of these compounds requires the use of PCl5. Other issues are also presented with the use of phosphorous activating reagents, such as toxicity, water sensitivity and the production of high molecular weight by-products (this applies to BOP), which leads to poor atom economy.

This project aims to address these problems by using other non-toxic, low molecular weight phosphorus reagents as coupling partners, which can be sourced without the need to use chlorine gas and/or other toxic and moisture sensitive reagents.

Proposed solution and methodology

Withheld due to confidentiality reasons.

Planned Impact

This CDT will have a positive impact in the following areas:

PEOPLE. The primary focus is people and training. Industry needs new approaches to reach their sustainability targets and this is driving an increasing demand for highly qualified PhD graduates to lead innovation and manage change in the area of chemicals production. CDT based cohort training will provide industry ready scientists with the required technical competencies and drive to ensure that the sector retains its lead position in both innovation and productivity. In partnership with leading chemical producers and users, we will provide world class training to satisfy the changing needs of tomorrow's chemistry-using sector. Through integrated links to our Business School we will maximise impact by delivering dynamic PhD graduates who are business aware.

ECONOMY. Sustainability is the major issue facing the global chemical industry. Not only is there concern for our environment, there is also is a strong economic driver. Shareholders place emphasis on the Dow Jones Sustainability Index that tracks the performances of the sector and engenders competition. As a result, major companies have set ambitious targets to lower their carbon footprints, or even become carbon neutral. GSK CEO Sir Andrew Witty states that "we have a goal to reduce our emissions and energy use by 45% compared with 2006 levels on a per unit sales basis... " Our CDT will help companies meet these challenges by producing the new chemistries, processes and people that are the key to making the step changes needed.

SOCIETY. The diverse range of products manufactured by the chemical-using industries is vital to maintain a high quality of life in the UK. Our CDT will have a direct impact by ensuring a supply of people and new knowledge to secure sustainability for the benefit of all. The role of chemistry is often hidden from the public view and our CDT will provide a platform to show chemical sciences in a positive light, and to demonstrate the importance of engineering and applications across biosciences and food science.
The "green and sustainable" agenda is now firmly fixed in the public consciousness, our CDT will be an exemplar of how scientists and engineers are providing solutions to very challenging scientific and technical problems, in an environmentally benign manner, for the benefit of society. We will seek sustainable solutions to a wide range of problems, whilst working in sustainable and energy efficient facilities. This environment will engender a sustainability ethos unique to the UK. The CNL will not only serve as a base for the CDT but also as a hub for science communication.
Public engagement is a crucial component of CDT activities; we will invite input and discussion from the public via lectures, showcases and exhibition days. The CNL will form a hub for University open days and will serve as a soft interface to give school children and young adults the opportunity to view science from the inside. Through Dr Sam Tang, public awareness scientist, we have significant expertise in delivering outreach across the social spectrum, and she will lead our activities and ensure that the CDT cohorts engage to realise the impact of science on society. Martyn Poliakoff, in his role as Royal Society Foreign Secretary, will ensure that our CDT dovetails with UK science policy.

KNOWLEDGE. In addition to increasing the supply of highly trained people, the results of the PhD research performed in our CDT will have a major impact on knowledge. Our student cohorts will tackle "the big problems" in sustainable chemistry, and via our industrial partners we will ensure this knowledge is applied in industry, and publicised through high level academic outputs. Our knowledge-based activities will drive innovation and economic activity, realising impact through creation of new jobs and securing the future.


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Description So far, a new method for synthesising important chemical bonds has been developed. The focus of this work negates the need to use toxic chlorine containing molecules and relies on the removal hydrogen atoms from non-toxic, stable molecules. The synthesis uses starting materials that are abundant in the earths crust (copper and phosphorus) and atmosphere (oxygen).
Exploitation Route If a pharmaceutical company/or chemicals manufacturer wants to use; cheap and safe materials which have few environmental concerns, the developed route would be an ideal platform for meeting the given criteria.
Sectors Chemicals,Pharmaceuticals and Medical Biotechnology

Description GlaxoSmithKline 
Organisation GlaxoSmithKline (GSK)
Department Research and Development GSK
Country United Kingdom 
Sector Private 
PI Contribution Developed new methods/in the process of developing new methods for synthesising important chemical bonds within the pharmaceutical industry and related.
Collaborator Contribution Suggestions on improvements and key areas to investigate have been made. The opportunity to do a placement (commencing Summer 2020), which I can use their resources/equipment to carry out research.
Impact TBC.
Start Year 2018
Description Cheltenham Science Festival 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Public/other audiences
Results and Impact We developed a stand to make the public aware of the type of research we do at the University. The stand was title Atoms, Energy, Impact and it was broken down into three parts. The Atoms area consisted of a process chemistry board game, making the public aware of the goals of a process chemist/scientist and the influencing factors for decision making. The Energy area used a bike to power a miniature city (model of Nottingham) to display the effect of energy/grid scale storage and clean methods of generating electricity.
The impact area was made up of a life cycle assessment to teach the public about sustainability and promoting awareness of influencing factors.
Year(s) Of Engagement Activity 2019
Description Chemistry of Beer 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Public/other audiences
Results and Impact We hosted an event at the pub, with various different activities and experiments relating to the science of beer. We also invited specialist researchers from brewing science and related to talk about there research to the general public.
Year(s) Of Engagement Activity 2019
Description Science festival 
Form Of Engagement Activity Participation in an open day or visit at my research institution
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Undergraduate students
Results and Impact Set up outreach stand and taught general public and potential future students the kind of research that is undertaken withing the chemistry department and doctoral training centre.
Year(s) Of Engagement Activity 2019
Description What's in your waste? 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Public/other audiences
Results and Impact Invited the general public to the University to make aware/discuss aspects of sustainability and methods that improve sustainability at home. The event was accompanied by professional speakers and engagement activities.
Year(s) Of Engagement Activity 2019