In-situ NMR-based methodology for screening and optimisation of heterogenised organocatalytic systems

Lead Research Organisation: University of Manchester
Department Name: Chem Eng and Analytical Science

Abstract

The goal of this proposal is to develop and validate an in-situ Nuclear Magnetic Resonance (NMR)-based screening and optimisation methodology for heterogenised organocatalytic systems, able to monitor and evaluate catalyst activity, transport and surface interactions at a pore-scale level in such functionalised materials. Batch reaction studies combined with in-situ 1H and 13C NMR spectroscopy, diffusion and relaxation techniques will give new and exclusive insights into these systems by providing quantitative data on intra-pore kinetics, diffusion and adsorption, which will be able to direct catalyst formulation and reaction design by evaluating the controlling interactions and mass transport phenomena of the various reactant/solvent/product species within the pores of the heterogenised catalytic system, hence aid selection of optimal reaction parameters such as choice of suitable solvents, solid supports, pore size and type of linker to immobilise the organocatalyst on support. The validation of this methodology in heterogenised organocatalysis will be a significant step forward towards effective screening and development of these materials, which can be expanded to other related technologies using functionalised porous materials.

Planned Impact

The project will benefit stakeholders with impact in the following areas: (i) Industry and commercial sector; (ii) Outreach and engagement of scientific community; (iii) Environmental policy and the wider society; (iv) Training and skill development.

(i) Industry and commercial sector
Heterogenised organocatalysts, if properly implemented on an industrial scale, will contribute to reduce current costs to industry associated with the use of homogeneous catalysts, by reducing material and energy costs associated to expensive separation procedures and catalyst loss/disposal. In addition heterogenised organocatalysts can be used in packed-bed reactors for continuous operation, increasing productivity, allowing easier process control and decreasing maintenance level. The industrial exploitation will be maximised by a close collaboration with Johnson Matthey (JM), a leading catalyst and chemical company, which is fully supporting the proposal and will provide industrially relevant raw materials, technical expertise and guidance for industrial exploitation. Using the strong links of the PI's School with important pharmaceutical companies, such as AstroZeneca, GSK and Pfizer, with a high interest in fine chemicals, it will be possible to involve the wider industrial community.

(ii) Outreach and engagement of scientific community
The project covers various scientific areas, which will benefit several communities from organic to physical chemistry, from catalysis to spectroscopy; hence it represents a great opportunity for cross-disciplinary exchange of knowledge, which will be enabled by attending various UK and international conferences; visits and seminars across the UK and internationally through the network of external collaborator Prof Armando Carlone; organising a dedicated workshop supported by the IChemE Catalysis Special Interest Group (SIG).

(iii) Environmental policy and the wider society
This project will have a positive impact on both environment and the wider society. Developments in the area of heterogenised organocatalysts will be able to address many societal issues related to the chemical industry, such as reduction of waste and energy consumption, efficient use of resources as well as a decrease in the environmental footprint of chemical processes. The strong expertise of the PI's School in sustainability and corporate responsibility will provide an ideal platform for enhancing such impact. The project will reach people beyond those directly involved in it, including undergraduate students, through organisation of satellite research projects on sustainability and life cycle analysis of these processes; the wider public will be reached using the links and social media of the University for public engagement. The IChemE channels will be used to further promote project outcomes.

(iv) Training and skill development
The inter-disciplinary nature of the project will develop highly skilled scientists, who will gain a broad range of skills and knowledge. The people involved on this project will deal with a variety of disciplines, including materials science, catalysis, organic chemistry and spectroscopy, hence will acquire a broad set of skills as well as a multi-perspectives approach to scientific problems. The interaction with leading academics from different areas, most notably catalysis, NMR and organic synthesis, will contribute in developing important interface management and communication skills, which is paramount in the current scientific and technological landscape, whereby projects are often highly multi-disciplinary. The collaboration with JM will also benefit by providing the possibility to interact with the commercial sector, carry out research work in industrial facilities as well as developing important skills required by the industry. Hence, the project will develop highly skilled scientists with a broad range of knowledge, which will benefit the whole UK economy and R&D sector.
 
Description The project aims at developing a new methodology based on Nuclear Magnetic Resonance methods to screen and rationalise the behaviour of organocatalysts immobilised over solid supports, an area that has a strong potential to improve sustainability in the fine chemical industry but has so far remained under-exploited due to the lack of understanding of these systems. In initial work carried out on the project two important discoveries have been made:

- By using NMR relaxation methods for monitoring surface interactions of solvents used in the catalysed oxidation of aldehydes to esters with NHC organocatalyst immobilised over solids we discovered that solvents with a high strength of interaction for the catalyst surface are inhibiting the catalytic activity. This strongly suggests that a way for improving catalytic activity in those processes is by optimising solvent selection. Indeed, we were able to select solvents that give catalytic performances over organocatalysts immobilised over solids similar to those of the same organocatalysts in the homogeneous liquid-phase, which is one of the sought-after goals for these processes.These findings are now subject of a publication currently being finalised.

- We have also discovered that in some reactions using proline-immobilised organocatalysts, the use of green solvents such as water and ethanol, does not lead to any activity when the reaction is carried out in the homogeneous phase but we observe a remarkable activity when the proline is immobilised over a solid support. This finding is of high importance as it suggests that potentially it is possible to use green solvents to carry out such reactions and in conjunction with an heterogeneous catalytic process. Current work is ongoing to further investigate this phenomenon.
Exploitation Route Once further studies will be carried out in the next few months, the aim is to get in touch with pharmaceutical industries interested in flow chemistry in order to discuss potential development of greener organocatalytic processes using organocatalysts immobilised over solids. The project has already created a new academic collaboration with groups working extensively in organic synthesis for pharmaceuticals, in particular the group of Prof. Alessandro Massi from the University of Ferrara, who is currently collaborating on part of the project.
Sectors Chemicals,Healthcare,Manufacturing, including Industrial Biotechology,Pharmaceuticals and Medical Biotechnology

URL https://www.qub.ac.uk/schools/SchoolofChemistryandChemicalEngineering/Events/2020-uk-catalysis-conference/
 
Description The results obtained so far are a subject of a publication being finalised. In addition, we are currently discussing with AstraZeneca about their involvement in a follow-up proposal whereby the exploratory studies of this project will be taken to a further level in order to carry out feasibility studies related to the commercial aspect of this research.
First Year Of Impact 2019
Sector Chemicals,Environment,Pharmaceuticals and Medical Biotechnology
Impact Types Societal,Economic

 
Description Collaboration with Haldor Topsøe 
Organisation Haldor Topsoe A/S
Country Denmark 
Sector Private 
PI Contribution Using the methodological approach currently used on this EPSRC project we have attracted the interest of Haldor Topsøe for understanding transport by diffusion in catalytic materials used by the company.
Collaborator Contribution The partner gave us a series of catalytic materials to study using NMR and provided work on catalyst characterisation and other data that will form part of a joint paper.
Impact - Consultancy work - Research paper in preparation - Invited talks at Haldor Topsøe headquarter in Denmark
Start Year 2019
 
Description Collaboration with Johnson Matthey 
Organisation Johnson Matthey
Department Johnson Matthey Technology Centre
Country United Kingdom 
Sector Private 
PI Contribution We are currently screening solid catalysts for organic synthesis; results will be disclosed to the company in the next few months in order to discuss follow-up work to be doing. In addition, the development of bench-top NMR measurements currently being run in the project is of particular interest for the company for their R&D capabilities in catalyst development.
Collaborator Contribution The partner provided us with access to research facilities for catalyst characterisation.
Impact A first meeting on preliminary initial results has taken place, which will be followed up by an update meeting in the next few months to report updates on the project and discuss further access to research facilities needed.
Start Year 2019
 
Description Collaboration with University of Bologna 
Organisation University of Bologna
Country Italy 
Sector Academic/University 
PI Contribution We are working with Prof. Villiam Bortolotti from the University of Bologna on Fast Field Cycling (FFC) NMR measurements of functionalised porous materials, which are closely related to the type of materials studied in this project. We have synthesized and supplied him with materials for NMR measurements using his specialised equipment.
Collaborator Contribution Prof. Villiam Bortolotti is currently performing FFC NMR measurements and data analysis for our samples.
Impact We are currently finishing measurements and started drafting a research manuscript aiming at a joint publication and further collaboration in the near future.
Start Year 2019
 
Description Collaboration with University of Sheffield 
Organisation University of Sheffield
Country United Kingdom 
Sector Academic/University 
PI Contribution The PI has established a collaboration with Dr Marco Conte on using NMR relaxation techniques to study solvent effects in porous catalysts used for sugar conversion and we are currently performing measurements using similar NMR techniques used in this project.
Collaborator Contribution The University of Sheffield has provided us with materials to investigate and characterise.
Impact A manuscript on the work is currently under preparation.
Start Year 2019
 
Description Collaboration with University of Trieste 
Organisation University of Trieste
Country Italy 
Sector Academic/University 
PI Contribution The group of Prof. Paolo Fornasiero has been interested in the methodologies used in this project for studying surface modifications in photocatalysts for organic synthesis. As such, we are doing several characterisation measurements of photocatalysts supplied by his group and currently writing a joint manuscript.
Collaborator Contribution They have been providing us materials and expertise in synthesis and screening of photocatalysts.
Impact We are currently writing a joint manuscript and starting working on new ideas related to our initial results.
Start Year 2019
 
Description Collaboration with the University of L'Aquila and the University of Ferrara 
Organisation University of Ferrara
Country Italy 
Sector Academic/University 
PI Contribution We are currently working with the University of Ferrara is collaborating on the project by helping doing experimental work on catalyst screening as well as NMR diffusion and relaxation measurements on materials provided by them for carrying out oxidation of aldehydes to esters using NHC catalysts. We have screened several reactions assessing the effect of solvents and we have also done novel characterisation on heterogenized NHC catalysts using pulsed-field Gradient (PFG) NMR diffusion as well as NMR T1 and T2 relaxation. We are currently writing a joint article on the results. We are also working with Dr Armando Carlone on proline-immobilised catalysts and we are doing a whole range of activities, ranging from synthesis of organocatalysts, immobilisation over solid supports, testing and NMR measurements. We are currently screening a whole range of reaction parameters, including type of linkers used for immobilising the organocatalysts, different solvents as well as porous solids with different morphology and textural properties. As an additional side-project, we have also been working on aggregation of peptides in solution for performing organic synthesis.
Collaborator Contribution The group of Prof. Alessandro Massi at the University of Ferrara has put a dedicated PDRA to work on our collaboration by developing catalytic materials and doing futher recation screening and reproducibility tests. The group of Dr Armando Carlone at the University of L'Aquila has send to our lab in Manchester a PhD student who is currently helping us on organic synthesis activitie srelated to the project.
Impact - A poster on NHC catalysts collaboration with the University of Ferrara has been presented at the UK Catalysis Conference 2020. The collaboration involved aspects of NMR spectroscopy, organic chemistry and physical chemistry. - An abstract has been accepted at the International Congress on Catalysis 2020 in San Diego. The collaboration involved aspects of NMR spectroscopy, organic chemistry and physical chemistry.
Start Year 2019
 
Description Collaboration with the University of L'Aquila and the University of Ferrara 
Organisation University of L'Aquila
Country Italy 
Sector Academic/University 
PI Contribution We are currently working with the University of Ferrara is collaborating on the project by helping doing experimental work on catalyst screening as well as NMR diffusion and relaxation measurements on materials provided by them for carrying out oxidation of aldehydes to esters using NHC catalysts. We have screened several reactions assessing the effect of solvents and we have also done novel characterisation on heterogenized NHC catalysts using pulsed-field Gradient (PFG) NMR diffusion as well as NMR T1 and T2 relaxation. We are currently writing a joint article on the results. We are also working with Dr Armando Carlone on proline-immobilised catalysts and we are doing a whole range of activities, ranging from synthesis of organocatalysts, immobilisation over solid supports, testing and NMR measurements. We are currently screening a whole range of reaction parameters, including type of linkers used for immobilising the organocatalysts, different solvents as well as porous solids with different morphology and textural properties. As an additional side-project, we have also been working on aggregation of peptides in solution for performing organic synthesis.
Collaborator Contribution The group of Prof. Alessandro Massi at the University of Ferrara has put a dedicated PDRA to work on our collaboration by developing catalytic materials and doing futher recation screening and reproducibility tests. The group of Dr Armando Carlone at the University of L'Aquila has send to our lab in Manchester a PhD student who is currently helping us on organic synthesis activitie srelated to the project.
Impact - A poster on NHC catalysts collaboration with the University of Ferrara has been presented at the UK Catalysis Conference 2020. The collaboration involved aspects of NMR spectroscopy, organic chemistry and physical chemistry. - An abstract has been accepted at the International Congress on Catalysis 2020 in San Diego. The collaboration involved aspects of NMR spectroscopy, organic chemistry and physical chemistry.
Start Year 2019
 
Description Erasmus+ traineeship with the University of Naples 
Organisation University of Naples
Country Italy 
Sector Academic/University 
PI Contribution Our group will have three Erasmus+ trainees working on their final research projects for 5 months on projects related to this EPSRC award and will help the current PDRA working on the project in carrying out research activities.
Collaborator Contribution The trainees will help the PDRA working on the project to carry out research tasks related to this award.
Impact The trainees have had their contract signed and will start their work in April so outcomes on this are not ready yet.
Start Year 2020
 
Description Junior school visit in China 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Schools
Results and Impact This was a visit to a junior high school in Shenyang, China, whereby approximately 30 pupils (age of 13 year old) attended a research presentation, which included topics treated in this research project (made it suitable for their level of understanding). The presentation resulted in a high interest of the pupils in the UK academic system as well as possibilities for doing a degree in the UK, in particular at the University of Manchester.
Year(s) Of Engagement Activity 2019