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Post by Jean-Marie Bassett - Moderator on Dec 15, 2015 16:27:16 GMT
One of the features of continuous flow chemistry is that one can choose the flow rate. Can we use this to our advantage to increase the production rate?
At the same time we need to ensure high yield. Is it therefore feasible to work at high temperatures and pressures to achieve this?
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Post by Johannes Schakel on Dec 24, 2015 9:27:13 GMT
Jean-Marie,
Higer temperatures and pressures are of course relative concepts.
The higher the requirements the more difficult it becomes.
Not only should the reactors be able to control these high temperatures and pressures, also the auxilary equipement (HTM, pumps, measurementsystems etc.) face higher demands.
This requires good cooperation between client, systems supplier and suppliers of auxilary equipment.
Never the less, boundries are being pushed and flowsystems with temperatures of upto 300°C and PN100 are currently in use.
To investigate if higher temperatures and pressures are an advantage a versitile lab system are key.
What impact does higer temperature/pressure have on your reaction and can we define the benefits of higher temperature and pressures.
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Post by Jean-Marie Bassett - Moderator on Jan 4, 2016 15:46:17 GMT
I am sure others would like to comment. Can we consider the scenario that involves very short residence times, hence allowing high temperatures to cause a very fast reaction? how many people have tried this?
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Post by patrickkaiser on Jan 8, 2016 7:47:58 GMT
Hi all,
I agree with Johannes comment, the application of increased pressure and temperature leads to increased equipment requirements. It is the question if additional investment in such equipment may be compensated by increased productivity and reduced production cost. As Johannes has stated, this question has to be addressed early in process development. From my own experience, turn key systems for lab scale are not available for all requirements, so we did some stuff in-house to run e.g. high temperature flow reactions (300°C).
Another point is the stability of the process, you have to know the temperature limit, which your reaction can handle without changing the reaction profile in an undesired way. We had good experience with DSC or ARC measurements.
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Post by David Gunn on Jan 11, 2016 10:39:12 GMT
Interesting topic and one that has been used quite a bit in 2015 -- temperatures and pressures have been commercialized and are being used for several things: new chemical entities in medicinal chemistry, route scouting around poor reaction, solubility and inadequate choice of solvents, and the movement away from added reagents often used to help push reactions along -- all this done with the right choice of solvent, temperature and pressure. ThalesNano Phoenix allows reaction optimization by modification of temperature, pressure and flow rate on the fly. 2 zone PID control coupled with a back pressure regulator and micro HPLC pump (hahaha well there does need to be an oven and coil or cartridge) allows for making difficult reactions faster, cleaner and safer.....and yes, much higher production rates as shown in the literature.
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Post by Alain Merschaert on Jan 12, 2016 7:54:47 GMT
Hello, we have been looking to high temperature reactions (in our case up to about 200°C) with some success. An important aspect is the right choice of solvent to minimize pressure generation. Dipolar aprotic solvent (NMP, sulfolane) have high thermal stability (no issue up to 200°C in our applications) and can be removed from the product by extractive aqueous work-up (although sometimes with multiple washes). In many cases other high boiling solvents can be used but then, if not soluble in water, need an efficient technology for separation from the product, hence development of membrane technology (eg for nanofiltration) might be of high interest.
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Post by tonywarr on Jan 12, 2016 11:58:19 GMT
High temperatures and pressure can and have been used to accelerate reactions and therefore achieve increased throughputs from relatively small pieces of equipment.
It is worth bearing in mind that high temperature is relative. If everyone does a class of reactions (say organo-lithium) at -70C then 0C is high temperature. If the best solvent carries out a reaction at 20C, then applying pressure and carrying it out at 120C might (and has) give high throughput whilst controlling yield and quality. Both these two examples have been done at just over 100 tonnes/year for a block buster pharmaceutical KSM in very small modular kit. Further, high pressure can accelerate in some cases reactions like hydrogenations such as ones we have done at 100bar. The catch is that chemistry doesn't always like you for pushing the boundaries. There are rules of thumb that can be used, but unless the core reaction and side-reactions are characterised care should be taken before assuming. Does equipment get more complicated - sometimes. Sometimes it gets simpler because the physical size comes down and the equipment manufacture (and trials) can be simplified. Accelerating reactions needs care with residence time selection to achieve optimum output. As you accelerate reactions, they can and do get to a point where the mixing is critical. We have had to take great care with mixing with reactions of less than 1s... Understand your chemistry and then you push it as hard as possible in the best direction.
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Post by anilkumar on Jan 13, 2016 2:52:18 GMT
We have developed a reactor (Hastelloy Tube) capable of carrying our reactions using 500 C and 350 Bar. Our experience has been very good to carry out reactions at high temperature. What i feel is that both the main reaction as well as the side reactions have a rate and generally the rate of main reaction is always faster than the side reaction (this is why it is called main reaction). By increasing the temperature, we could increase both the rates, however the rate of main reaction increases much faster leading to situations wherein no side reaction was observed when residents times were very short (in order of few seconds). In fact some of the product which were thermally unstable also could be obtained pure at high temperature as rate of degradation was bypassed using very small resident time at high temperature. So there are lot of benefits in doing reactions at high temperature. Also one can get surprise results wherein different (interesting) results obtained under these conditions which are difficult to rationalize apriori.
Therefore, one has to try with their reaction as i feel one gets more benefit by increasing the rate of reaction. If the benefits outweigh the cost, just go ahead.
Also why not try increasing the rate of reaction using shear-force via FUMI (Forced Uniform Molecular Interdiffusion) reactors (Spinning Disk). In this situation, one can increase the rate of the reaction without increasing the temperature. So if the reactions are temperature sensitive, use this method.
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Post by tonywarr on Jan 13, 2016 9:38:05 GMT
Don't get me wrong, high temperatures and pressures can and do accelerate reactions, but around some temperatures new reactions start. That is the activation energy aspect of the kinetics. As you increase temperature reactions will accelerate and also new reactions will potentially kick off. The rule of thumb is 'doubling' for every 10C, but the reason that this is only a rule of thumb is that they differ and are not all the same. Sometimes you are lucky and sometimes not, sometimes the desired reaction accelerates faster than the side reactions, sometimes not. The more functionality you have (or complexity) you have in a molecule the more issues can arise. The great thing is that with the right equipment, as has been said, this can be tested and the right course taken. If the reaction is mixing limited then equipment like spinning disk (or other) can be employed.
First understand the chemistry and the kinetics, then the mixing limitations... Incidentally I'm an engineer, not a chemist saying this! However the combined efforts of chemistry, engineering and the right equipment can get to the heart of the problem relatively quickly.
I have a reaction now that we tried to accelerate and we can, but at -40C a new impurity starts to form. Flow can operate close to -40C for various reasons whereas the batch alternative need to keep well clear -70C or below. (I know this isn't high temperature, the point is the activation energy issue!)
The other aspect, is that I'm in pharmaceuticals where we are very sensitive to impurities.
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Post by Jon on Jan 15, 2016 19:59:31 GMT
One of the advantages of flow is that you can tune the system to avoid extreme conditions present in batch reactors. We see this a lot in cryogenic batch reactions that run with similar or better efficiency/ selectivity.
So while you can import extreme conditions to flow, a primary driver of migrating to flow is avoiding these sorts of environments
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Post by Jon on Jan 15, 2016 20:00:11 GMT
One of the advantages of flow is that you can tune the system to avoid extreme conditions present in batch reactors. We see this a lot in cryogenic batch reactions that run with similar or better efficiency/ selectivity.
So while you can import extreme conditions to flow, a primary driver of migrating to flow is avoiding these sorts of environments
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Post by Klemens Obermaier on Feb 8, 2016 16:00:21 GMT
Hello to everybody in this thread,
There are two issues mixed up!
Extreme conditions can be,
1) if you drive your reactor to the limits (300°C, 100bar, solvent-free) --> matter of equipment
2) if you drive your reaction to the limits (10°C below degradation/decomposition temperature) --> matter of engineering
Our experience is that most of the people working in flow use 2) to accelerate their reaction. In this case the so called "extreme conditions" are usually far below 300°C/100bar. 1) is pretty cool for unusual chemistry such as supercritical processes.
To gain this conditions is pretty easy if you can work in steel or Hastelloy. Has anybody experience with high pressure/temperature using other materials?
Best regards
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