Engineering Synthetic Reactions in CO2 and Water

Lead Research Organisation: University of Birmingham
Department Name: Chemical Engineering

Abstract

The chemical industry uses large volumes of organic solvents in the synthesis of compounds. This work breaks completely new ground in demonstrating that water and carbon dioxide can be used as environmentally benign solvents in the manufacture of organic compounds for the pharmaceutical and fine chemical industries. A novel high pressure flow reactor will be built that will allow engineers and scientists to take advantage of the complementary solvent powers of carbon dioxide and water. Carbon dioxide and water will be intimately contacted through an emulsion generated by an ultrasonic device. This will enable compounds of differing polarities to be soluble in either solvent and so reactions can occur at the solvent interface. The reactor therefore has the potential to be used for the manufacture of a wide range of organic chemicals for industry. It is clear that the high value added chemical industry sector will need to move to the continuous flow mode in order to improve efficiency and economy of scale as well as to contain the issues of waste disposal. The reactor will address this requirement and will also remove the stumbling block associated with high pressure (supercritical) carbon dioxide reactions by side stepping the problems associated with the solubility of polar compounds in non-polar carbon dioxide.
 
Description This one year research project has demonstrated using water and CO2 alone as solvents to make useful chemicals. This has clear benefits to health and the environment, but also has benefits from a process point of view. In some reactions it was possible to separate the product from the reaction mixture by depressurising the CO2 or decanting the product from the top of the water phase and therefore alleviated the need for organic solvents in the separation step.



The research has side-stepped the problems associated with the solubility of polar compounds in pressurised CO2 through the development of a novel high pressure system that has enabled compounds of differing polarities to be intimately contacted through a water-CO2 emulsion generated by an ultrasonic source. A high pressure ultrasonic system was designed and constructed to enable the formation of these emulsions at elevated conditions. The power density, emulsion size, volume fraction and stability were characterised using a high pressure view flow cell constructed in-house. Over the conditions studied the emulsions were found to be CO2 in water emulsions with average sizes of 0.5 microns at a power density of 0.4 W/cm3 at 20 kHz.



The system was validated by studying a number of industrially important reactions, such as the Suzuki-Miyaura (SM) reaction, reductive aminations and propargylamine synthesis. The SM reaction proceeds in an alkali environment, however the pH of the water-CO2 emulsions was too low for the reaction to give high yield. Even with high mole equivalents of sodium hydroxide base, and using iodobenzene as the aryl halide the reaction only gave a 41% yield at 80 oC, 160 bar. Lower temperature and weaker bases (sodium- and potassium carbonate) gave poorer yields. Pressure was found to have a positive effect on yield.



The research progressed to a reaction that proceeded favourably under acidic conditions. Reductive aminations were conducted using simple carbonyl compounds and primary amines with chemical reducing agents in a one-pot process at room temperature and 80 bar for one hour. The results showed mixed success with aniline yielding higher product (76 to 89%) due to its lower pKa value. 4-methoxybenzylamine with a higher pka gave lower yield and was observed by high pressure IR spectroscopy to sequester the CO2 more strongly hindering its participation in the reaction. In order to understand the effect of process conditions and to reduce chemical costs the formation of the imine, an intermediate in the reductive amination, was studied. The formation of CO2-water emulsions was found to enhance imine yield, compared to systems containing water alone. In systems where CO2 was present but no emulsions were formed the yield was less than that of water alone. Low pressure (40 bar) resulted in imine yields between 58 to 70%, whereas higher pressure (105 and 140 bar) gave lower yields over the entire temperature range. Higher temperature led to an increased kinetics and imine yield, however above 85 oC the yield became independent of temperature at higher pressure (140 bar) due to lack of emulsion formation.

Where reactant concentration resulted in the formation of an excess phase high imine yields were obtained, which were attributed to reactant availability at the emulsion interphase as a result of enhanced mass transfer from sonication.



Preliminary studies into propargylamine synthesis showed favourable results. The reaction of piperidine, benzaldehyde and phenylacetylene using a copper iodide catalyst gave the oxazolidine product in 80% (unoptimised). This exceeds literature values for the same reaction conducted in supercritical CO2. Importantly, the product fixes CO2 into its structure which is beneficial from an environmental perspective, but in addition sub-stoichiometric amounts of catalyst were used which has favourable industrial implications. This research has broken new ground in creating a new environmentally benign synthesis process.
Exploitation Route The technology is currently being explored to process food products and waste. As well as the above, the results showed that elevated pressure sonication could also be used to cause cell death. We have since applied this technology to process dairy products and have shown that an equivalent pasteurisation can be undertaken at less than 20-fold the energy requirement used in normal pasteurisation. We have filed a patent in this area and have been working with a major multi-national dairy through Innovate UK to further develop this technology.
Sectors Agriculture

Food and Drink

Chemicals

Energy
 
Description Findings have been used by other workers in the field and industry. The project led to two follow-on TSB funded projects which have yielded a patent. The findings are currently being used in the diary industry to stabilise a waste product into a valuable source of protein that can be used as animal feed. We are also undertaking preliminary work to extend the technology into powder formulations.
First Year Of Impact 2014
Sector Agriculture, Food and Drink,Chemicals,Environment,Manufacturing, including Industrial Biotechology
Impact Types Economic
 
Description Science without Borders
Amount £87,000 (GBP)
Organisation Government of Brazil 
Sector Public
Country Brazil
Start 08/2013 
End 09/2016
 
Description Technology Strategy Board
Amount £33,140 (GBP)
Funding ID 12686-84175 (TS/J002690/1) 
Organisation Innovate UK 
Sector Public
Country United Kingdom
Start 11/2010 
End 01/2012
 
Description Technology Strategy Board
Amount £256,000 (GBP)
Funding ID TS/K004018/1 
Organisation Innovate UK 
Sector Public
Country United Kingdom
Start 01/2013 
End 04/2015
 
Title INHIBITION OF MICROBIAL AND CELLULAR GROWTH IN SUBSTANCES 
Description The invention provides a method of treating a food, beverage or cosmetic to inhibit microbial or cellular growth, comprising subjecting the substance to low frequency ultrasound under elevated gas pressure at between 10 and 100 bar, more typically 20 and 500 bar. Also provided is an apparatus for treating a substance which is a food, beverage or cosmetic to inhibit microbial or cellular growth in the food, beverage or cosmetic comprising : (i) a substance inlet (ii) a pressurisation zone, the pressurisation zone comprising a pressurising gas inlet and low frequency ultrasonic generator; and (iii) a depressurisation zone. 
IP Reference WO2015052506 
Protection Patent application published
Year Protection Granted 2015
Licensed No
Impact None as yet. The technology in the patent is being demonstrated at pilot scale with a multi-national dairy
 
Description Article in the Institute of Mining Magazine 
Form Of Engagement Activity A magazine, newsletter or online publication
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Industry/Business
Results and Impact Media Coverage with specialist press. Article in Institute of Mining Magazine about manufacturing a kayak from aerospace composite waste. There was increased interest in my research and led to an uptake of the research by other media channels.
Year(s) Of Engagement Activity 2016
URL http://www.iom3.org/news/2016/mar/16/exhume-team-creating-kayak-recycled-carbon-fibre-international-...
 
Description Presentation at CSIRO Victoria, Australia 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Participants in your research and patient groups
Results and Impact Talk sparked questions and discussion afterwards

Led to collaborative research with CSIRO
Year(s) Of Engagement Activity 2010