Hi, my name’s Omar Jina, Chief Sales Officer of the AGI UK of companies. AGI UK is the parent of a number of different companies, including Syrris, leaders in batch and flow chemistry, Dolomite, innovators in microfluidic and droplet technology, Glass Solutions, experts in scientific and architectural glassware and also Centeo, who specialise in temperature control modules for biological applications. So I’d like to introduce you today to Max Drobot, Head of Applications for the group and Max is going to teach us a bit about flow chemistry. So, Max –
Thank you, Omar. First, a very quick word about Syrris. Syrris is a company based in England, near Cambridge, which designs, develops and manufactures equipment for R&D chemists, with a strong focus on automation and ease of use. Our products cover batch chemistry and flowchemistry.
So, all of us are familiar with batch chemistry, that’s how we were taught chemistry and that’s how most of us are still doing chemistry. The type of glassware we are using are round bottom flasks such as this one for very small scale, or for larger scale we can go up to a jacketed reactor such as this one. In flow chemistry, we’ve got a different approach to how you would do your reactions and instead of using standard reactors, people are using what’s called a microreactor. These microreactors can be a glass microreactor, such as this one, with etched channels of about 100mm diameter, or you can also use tube reactors, with the length of fluoropolymer of metal tube wrapped around a heat exchanger. Or you can also use glass columns, such as this one, which can be packed with a solid and enables you to handle solids as well as liquids in flow chemistry.
So what’s happening in these reactors? What is flow chemistry? Well, in flow chemistry, the key thing is: everything is continuous. So, reagent starting materials and reactants are continuously pumped into a microreactor, where they are mixed and exposed to reaction parameters, such as temperature. The reaction happens, the product forms and the product leaves as a continuous stream. So compared to batch, which is a traditional way of doing chemistry, where you load everything into a reactor and then start heating and mixing, the product forms and then to recover the product you have to stop everything, do a workup and filter. Whereas in flow, your reagents are continually pumped and the product leaves as a continuous stream. So it’s a continuous process, it’s not a start and stop process like with batch. Reaction parameters for batch are typically temperature, mixing, reaction time and concentration. In flow chemistry, key reaction parameters are very similar, but with a slight difference. So instead of reaction time, people are talking about residence time, instead of concentration, people are more interested with molarity ratios and temperature is still very important. Mixing, as we are going to see with the next few slides, is not as critical and instead, people prefer to focus on pressure.
So, let’s talk about the key reaction parameters in a bit more detail, starting with residence time. What is residence time? Residence time is how long every fraction of the reaction mixture is spent in the microreactor, from the point where it is mixed and exposed to reaction conditions up to the point where it leaves the microreactor. The formula to calculate it is given by volume of the reactor divided by the flow rate. The formula allows us to see that there are two ways of controlling the residence time in a flow chemistry experiment. The first one, the obvious one, is to change the size of your reactor, so you can do a reaction on a small scale like this one and then if you to increase the residence time, you can increase the volume of the reactor and move on to a Tube Reactor, such as this one with a volume 4x 16x bigger and the residence time will increase accordingly. The second way of controlling the residence time is by changing the flow rate. For that, you need a very accurate and smooth pump such as a Syrris Asia Pump. If you increase the flow rate, then your residence time will diminish, if you slow down the flow rate, then the residence time will increase. Also, not only can you play with residence time, you can also play with the ratio between different reagents. So, for example, at the same concentration, if you pump one reagent twice as fast as the other one, then you are introducing twice the amount of material in your microreactor and the ratio will be 2:1 in terms of molarity. Talking about the other key reaction parameters, I mentioned mixing. So mixing is not as essential in flow as it is in batch. The reason for that is because we are in laminar flow conditions, because of the very small channel diameter, flow conditions are laminar, which means that the mixing is diffusion-limited. Because of that, it is highly reproducible and ultra-fast. Another key parameter is temperature. So again, because of the very small volume of the internal solutions, you’ve got a high surface-to-area ratio and the heat can be brought very quickly into your reaction and can be dispensed very quickly as well. So you’ve got a high heat transfer and because of that, temperature control is usually much better than what you would have in Batch. The final one is pressure. I mentioned that people like to pressurize the flow reactors and the first reason why you would want to do that is is very easy to do, the reactor volume is so small that there is no real risk in pressurizing it, compared to Batch. When you pressurize a flow reactor, you can heat your solvent above the standard boiling point, which is called super-heating, and you can also handle gas and liquids together and make sure that the gas diffuses in the liquid first. The standard simple flow chemistry is between two miscible liquids. You can also have heterogeneous flow chemistry using a solid and a liquid, for example by using the column that I showed earlier on, if you pack that with a solid reagent and flow a liquid reagent through that, then you have a heterogeneous experiment. You can also have gas liquid and combine three types, gas liquid and solid. You can also have immiscible fluid like aqueous and organic as well, which will form little reaction slugs and your reaction will happen at the same rate as it would in batch.
So why do people want to do Flow Chemistry? Well, they want to do flow chemistry because of the range of benefits that they can only see in flow. Things like faster reactions, safer reactions, more control overall, so reactions that are cleaner. You can also do very fast reaction optimization. Once one of your experiments has left the microreactor, then it’s obviously solvent, it is clean, and the next experiment can start, so it can scan a wide range of reaction conditions very quickly. And things like integration of analytical devices or workup are very easy to achieve as well. I want to finish with an example of chemistry that has been published by a renowned group, which is Steve Ley’s group from the University of Cambridge, who are worthy experts in flow chemistry. They published a paper that demonstrates the synthesis of pharmaceutical active ingredients, starting from very simple starting materials. The full process is done in seven steps and is all one continuous process, there is no workup in between, no stopping in between. They exploit all the benefits of flow chemistry, super heating to 80°c, using gas liquids and solids. All of these in one continuous process. So, I hope that this short talk convinced you that flow chemistry can be very beneficial for your process and for your science. Syrris is a world leader in flow chemistry with systems like the Syrris Asia flow chemistry system, and if you are interested in finding out more about it, please go to www.syrris.com
Asia Flow Chemistry
A revolutionary range of advanced flow chemistry products from Syrris, Asia has been designed by chemists for chemists to enable the widest variety of chemical reactions and ultimate ease of use.