Corante

About this Author
DBL%20Hendrix%20small.png College chemistry, 1983

Derek Lowe The 2002 Model

Dbl%20new%20portrait%20B%26W.png After 10 years of blogging. . .

Derek Lowe, an Arkansan by birth, got his BA from Hendrix College and his PhD in organic chemistry from Duke before spending time in Germany on a Humboldt Fellowship on his post-doc. He's worked for several major pharmaceutical companies since 1989 on drug discovery projects against schizophrenia, Alzheimer's, diabetes, osteoporosis and other diseases. To contact Derek email him directly: derekb.lowe@gmail.com Twitter: Dereklowe

Chemistry and Drug Data: Drugbank
Emolecules
ChemSpider
Chempedia Lab
Synthetic Pages
Organic Chemistry Portal
PubChem
Not Voodoo
DailyMed
Druglib
Clinicaltrials.gov

Chemistry and Pharma Blogs:
Org Prep Daily
The Haystack
Kilomentor
A New Merck, Reviewed
Liberal Arts Chemistry
Electron Pusher
All Things Metathesis
C&E News Blogs
Chemiotics II
Chemical Space
Noel O'Blog
In Vivo Blog
Terra Sigilatta
BBSRC/Douglas Kell
ChemBark
Realizations in Biostatistics
Chemjobber
Pharmalot
ChemSpider Blog
Pharmagossip
Med-Chemist
Organic Chem - Education & Industry
Pharma Strategy Blog
No Name No Slogan
Practical Fragments
SimBioSys
The Curious Wavefunction
Natural Product Man
Fragment Literature
Chemistry World Blog
Synthetic Nature
Chemistry Blog
Synthesizing Ideas
Business|Bytes|Genes|Molecules
Eye on FDA
Chemical Forums
Depth-First
Symyx Blog
Sceptical Chymist
Lamentations on Chemistry
Computational Organic Chemistry
Mining Drugs
Henry Rzepa


Science Blogs and News:
Bad Science
The Loom
Uncertain Principles
Fierce Biotech
Blogs for Industry
Omics! Omics!
Young Female Scientist
Notional Slurry
Nobel Intent
SciTech Daily
Science Blog
FuturePundit
Aetiology
Gene Expression (I)
Gene Expression (II)
Sciencebase
Pharyngula
Adventures in Ethics and Science
Transterrestrial Musings
Slashdot Science
Cosmic Variance
Biology News Net


Medical Blogs
DB's Medical Rants
Science-Based Medicine
GruntDoc
Respectful Insolence
Diabetes Mine


Economics and Business
Marginal Revolution
The Volokh Conspiracy
Knowledge Problem


Politics / Current Events
Virginia Postrel
Instapundit
Belmont Club
Mickey Kaus


Belles Lettres
Uncouth Reflections
Arts and Letters Daily
In the Pipeline: Don't miss Derek Lowe's excellent commentary on drug discovery and the pharma industry in general at In the Pipeline

In the Pipeline

« Dimebon Comes Crashing to Earth | Main | Mental Health Break: The Alkali Metals Show Their Personalities »

March 4, 2010

Flowing, Not So Gently

Email This Entry

Posted by Derek

I've written both here and elsewhere about flow chemistry, the technique where you pump your reactions through a reaction tube of some sort rather than mixing them up in a flask. And I freely admit that I have a fondness for the idea, but it's definitely not the answer to every problem.

For one thing, I tend to like the idea of sending reactants over a bed of catalyst or solid-supported reagent (what I call Type II or Type III flow reactions in that 2008 link above). Type I reactions, in my scheme, are the ones where you just use a plain tube or channel, and all the reactants are present in solution. A big advantage of those, as far as I can tell, is to handle tricky intermediates that you wouldn't want to have large amounts of or to control potential runaway exothermic reactions. There's also the possibility of running the reaction stream through some solid-phase purifications and scavengers, the way Steve Ley and his group like to work, which is convenient since you're already pumping the stuff along anyway.

But the sorts of reactions that you often see in the flow-chemistry equipment brochures. . .well, that's something else again. More than one outfit has earnestly tried to sell me a machine based on how well it did a Fischer esterification. My problem wasn't that the reaction was discovered almost in Neanderthal times - it was that Thag run reaction in round bottom flask, work fine, not need flow reactor. I mean, really, this is a nonexistent problem and needs no solution.

So I read this new paper in Angewandte Chemie with interest. The authors are looking at some standard catalytic organic transformations and comparing them carefully between batch mode and a flow setup. They stipulate at the beginning that flow chemistry has the advantages mentioned above, but they're wondering about what it can do for more ordinary chemistry:

"In addition to these developments, general and rather sweeping claims have been made that microreactor systems accelerate organic reactions and that lower catalyst loadings and higher yields can routinely be achieved in these systems compared to those of reactions carried out in flasks. Despite these potential advantages, examples of successful implementation of microflow reaction technologies in either academic organic synthesis or industrial process research and manufacturing remain more isolated than these reports would suggest. However, the implication is that it is only a matter of time before microflow reactors will dominate laboratory studies aimed at both fundamental research and practical applications of complex organic reactions, with our current mode of operation in reaction flasks ultimately becoming a relic of the past. It seems therefore worthwhile to examine the assumptions behind this viewpoint to provide a critical analysis of “flask versus flow” as a means for effecting reactions."

What they find is that there's very little difference. A catalyzed aldol reaction that was studied under flow conditions by the Seeburger lab is shown to perform identically to a batch reaction, if you make sure to run them at the same temperature and with the same catalyst loading. The paper then looks at asymmetric addition of diethyl zinc to benzaldehyde, a model reaction that I often wish would disappear from human consciousness so it would afflict us no more. But here, too, under more challenging heat-transfer conditions, flow showed no differences from batch. The authors point out that this reaction is, in fact, run under industrial conditions, but not in a flow apparatus. Rather, it's done in batch mode, but though good old slow addition of reagent, which also gives you control over exotherms.

The authors specifically exempt all supported-reagent chemistry from their analysis, so that preserves what I like about flow systems. But for homogeneous reactions, the only time they can see an advantage for the flow reactors is when there's a potential for a dangerous rise in temperature. So now we'll see what some of the more flow-oriented people have to say in reply. . .

Comments (28) + TrackBacks (0) | Category: Chemical News | Life in the Drug Labs


COMMENTS

1. milkshake on March 4, 2010 9:15 AM writes...

I could see an advantage of a flow reactor with a reaction that is both fast and exothermic and prone to over-reaction (=the desired product craps up either because of its thermal instability or a tendency to react further with the used reagent). The problem with such a finnicky reactio is that it can take lot longer to optimize under continuous flow conditions vs batch loading - flow systems simply have more variables. So it makes a perfect sense to consider it in process, but it is not something I would give the first try when attempting to make few grams of intermediate in a medchem lab.

Then there are natural fits like using a flow column with immobilized (expensive) enzyme for things like kinetic resolution of a racemate. Thats something I would actually consider doing in the lab.

Permalink to Comment

2. dearieme on March 4, 2010 9:21 AM writes...

I think you'll find that "flow chemistry" used to be called Chemical Engineering.

Permalink to Comment

3. processchemist on March 4, 2010 9:41 AM writes...

Old story, and my remarks are old too...
1) microreactors have been probably the most hyped technology in process chemistry. If you really need a continuous reactor, you can always use a couple of pumps, a tube or a small flask, and get the same result with less paranoia about clogging.
2) as milshake said, countinous reactors are good for criogenic or highly exothermic reactions when the contact time is a problem (the longer is the feed time, the more byproducts you get). But, who needs asymmetric addicions of lithium alkyls to ketones or imines? (Actually, few months ago crossed my way a wishful scale up projection of an halogen-lithium exchage on a pyridine: REJECTED!)

The last thing are "continuous microwave reactors": a technology far too expensive to run simple suzuki couplings that require some catalist, toluene and potassium carbonate in a simple batch reactor.

Permalink to Comment

4. SPRITY on March 4, 2010 9:48 AM writes...

My favorite flow chemistry is a SNAr reaction with methylamine in methanol at 100 deg.C for 10 min. Please let me know if there is a batch method without using a pressure reactor.

Permalink to Comment

5. CRO Cowboy on March 4, 2010 10:40 AM writes...

There will be plenty of second hand flow reactors and H cubes on the market here in the UK once all the site cloures happen.

Permalink to Comment

6. Lillywhite Chemist on March 4, 2010 11:25 AM writes...

SPRITY - what do you think a microreactor does when you compress your solutions into a capilliary tube and heat them... Get a microwave vial put the reagents in a cap it then heat it how the hell you like, in a microwave (sexy), in a heat-on block (safety), in an oil bath (showing my age there...) or whit a frikin hair dryer for all I care, it's a thermal reaction is all!!!

Permalink to Comment

7. Hap on March 4, 2010 11:26 AM writes...

I thought flow chemistry was supposed to avoid the difficulties with altering conditions upon scale-up, effectively making production chemistry scale-independent (and making it easier to run things continuously and thus on smaller scale, as well). Some of this may just be chemical engineering, but it still seems useful, even if doesn't magically improve yields (like microwave chemistry, with the same problems). It seems like, if you could get the chemistry to work in flow on lab scale, it would remove some of the optimization needs (or if the process people get it to work in flow, they could number up rather than scale up, and not need to reoptimize for large-scale manipulation). Or is this view just more hype?

Permalink to Comment

8. anon the II on March 4, 2010 11:27 AM writes...

What amazes me over and over again is that no matter how much organic chemistry we know, when someone comes along and waves some new technology at us, a significant fraction of us go all stupid. It's happened with photochmemistry, molecular modeling, electrochemistry, combichem, SCFC, microwaves and, more lately, flow chemistry. What flow chemistry is and is not capable of doing should be pretty obvious from first principles and shouldn't even require much research. Maybe it would be useful to know some statistics on precipitation in reactions so we might have an idea, up front, how often we'll lose an afternoon cleaning out an instrument rather than filtering off the solids and getting on with our lives.

Same for microwave reactors. They gave us the ability to heat the crap out of reactions without the worry of permanent disfiguration from an exploding oil bath. Period. Useful instruments but the same organic chemistry.

Permalink to Comment

9. anon the II on March 4, 2010 11:31 AM writes...

Present company excluded, of course.

Permalink to Comment

10. CMCguy on March 4, 2010 11:31 AM writes...

I would turn this around and argue if there is little difference then "why not use flow reactions to run experiemnts?" This can be easier and more convenient once get over learning hurdles to get comfortable with the techniques that are foreign to classically taught skills. As #3 processchemist points out don't necessary need fancy microreactors so can assemble for items around the lab. One can imagine have a set up that can be cleaned-in-place by appropriate solvent cycling so used time after time with disassembly (although having and cleaning RB glassware is not a barrier in industry as was in grad school). The other advantage is that if have to make quantity compound(s) the scale-up considerations are simplified. Yes this is how ChemEs and hopefully process chemists already think however would benefit most research/medchem types to expand their mental boundaries and practical capabilities.

Permalink to Comment

11. processchemist on March 4, 2010 11:52 AM writes...

@Hap

"I thought flow chemistry was supposed to avoid the difficulties with altering conditions upon scale-up, effectively making production chemistry scale-independent"

Sure. But if you have a continuous reactor you must arrange a continuous isolation process (and this can be really tricky), or, solved the reaction problem, you have some classical batch style unit operations to have the isolated/purified product (involving more diluite starting solutions, usually).

Last but not least, you still have a reaction to be optimized (with some kind of unfamiliar parameters for most chemists like contact time, filling time, spatial velocities...). And how many chemists today have a good background about reaction optimization?

Permalink to Comment

12. Old Timer on March 4, 2010 12:07 PM writes...

Are there any good examples of microreactors designed as reaction screening tools? Being able to set up 100 reactions to run through the microreactor with MS analysis instead of 96 well plates (or a cheap student)? References would be appreciated.

Permalink to Comment

13. mad on March 4, 2010 12:12 PM writes...

It comes down to how hard the scale up is vs using the flow chemistry.

Scale up is not trivial in science or bussiness. Most MBAs think its just about using a "giant beaker" and this cause much grief for scientists. Flow chemistry solves a lot of big problems ( ex thermodynamics) Its a good area to put effort. If you have a lab set up for it the bench chmists might suprise the process chemists on how well we can optimize. ;)

Permalink to Comment

14. SPRITY on March 4, 2010 12:14 PM writes...

#6 It is just a simple experiment to try in your lab. Once the methylamine solution is heated, all the methylamine would go into the head space and SNAr would not occur. It does not matter whether it is in a RB flask or microwave crimp vial. Before flow reactor, I had to pressurized the reaction mixture with argon in a steel pressure reactor just to keep the methylamine in solution. The back pressure regulator keep the volatile reagents in solution.

Permalink to Comment

15. Placebo on March 4, 2010 1:36 PM writes...

What about a series of CSTRs (Continuous Stirred Tank Reactors), each one feeding the next? In one limit (one reactor), this becomes a batch process and in the other limit (infinite number), this becomes a "flow system". Any use for such things in the lab?

Like tubular reactors, CSTRs are just classical chemical engineering, nothing new here.

Permalink to Comment

16. Unemployed processchemist on March 4, 2010 2:06 PM writes...

Processchemist @3
I have built several continuous flow systems in the past using pumps and flasks. One was a continuous phosgenator to make Isocyanates. It was fun to see the looks on the Managements faces when we explained that the 250ml of water white liquid in a glass dropping funnel(feeding a reactor at 140ºC) was liquid phosgene. We converted a batch plant to a continuous phosgenation plant based on that work.
Any Development/process chemist can build a flow system with the kit in a basic lab(might have to buy some pumps)

Permalink to Comment

17. Robert Ashe on March 4, 2010 2:18 PM writes...

Used correctly, flow reactors offer significant benefits for both process development and manufacturing:

Process development
A lab experiment run under batch conditions delivers a single sample of product. If performed under flow conditions, a wide range of process variables can be scanned in one experiment. This is particularly useful for process optimisation.

Manufacturing
The pharmaceutical/fine chemical industries are amongst the least efficient of all process industries (see Improving Pharmaceutical Product Development and Manufacturing, Pradeep Suresh & Prabir K. Basu). One of the contributing factors of this is linked to the imitations of large batch equipment. Flow equipment can improve process conditions in the following ways:

Mixing
For some processes, mixing can make the difference between yields of 65% yield and 95%. A large batch reactor delivers less than 5 W/l of mixing energy and suffers from problems of mixing uniformity. A flow reactor can uniformly deliver 1000+ W/l of mixing energy.

Plug flow
Unlike batch reactors, most (but not all) flow reactors deliver plug flow. This improves product/reactant separation and improves reaction time control. These factors can contribute to significant improvements in selectivity and reduce unwanted side reactions. Plug flow increases the average concentration of reactants in the early stages of a reaction. For nth order reactions this can reduce reaction time by an order of magnitude or more.

Heat transfer
A large batch reactor delivers between 10 and 100 W/l of heating/cooling energy. A flow reactor can deliver 100,000 W/l of heating/cooling energy. This permits the use of leaner reaction mixtures and higher reaction temperatures for shorter periods (since the product can be heated and cooled within seconds compared to many minutes or hours in a large batch reactor)

To date, much of the interest in flow chemistry has focussed on research using micro or small tubular reactors. For clean fast reactions these work well and can be scaled out (numbering up) or scaled up. Where there is any tendency to foul or block however, simple tubular reactors or static mixers are generally unsuitable. Immiscible liquids and gas/liquid mixtures can also present problems. For these more difficult process conditions and slower reactions, multistage CSTRs and oscillatory flow reactors offer a better solution.

Permalink to Comment

18. processchemist on March 4, 2010 2:54 PM writes...

@16 unemployed processchemist

My experience with flow reactors dates back to my university days (I did my experimental work in a chemical engeneering department). Early in my career I worked the on development of a continuous enzymatic process, with a downstream continuous liquid/liquid extraction unit and continuous evaporation/crystallization. In the following years, never again.

@17
Mr Ashe, your post sounds a bit like product advocacy (more than a bit, maybe).
With a simple, cheap multiplace small scale apparatus (I won't say the brand names) and a properly setted DOE screening (multivariation of parameters) in a single run and with 2 hours of HPLC time a chemist skilled in the art can dramatically improve reactions and crystallizations.
I say it again, flow chemistry is a great technique, but of limited scope in the pharma field. And for contract manufacturers/custom chemistry firms it's not so sexy to have it in a technology portfolio. Customers are mostly unattracted.
If "The pharmaceutical/fine chemical industries are amongst the least efficient of all process industries" there are solid reasons, and some of them are absolutely good (the complexity of the products), others not (the rush to market , the unwillingness to go back to the regulator for a better manufacturing process etc). To prospect a throughput like the one of the bulk chemical plants with flow chemistry in THIS sector is just pure hype, in my humblest opinion.

Permalink to Comment

19. mikeymedchem on March 4, 2010 3:06 PM writes...

I have to say, that this article reiterates what I've said from the beginning when we started investigating flow chemistry in my lab (and what I say whenever I work on any chemical technology project...including microwaves). Every tool will have its use. The temptation to overgeneralize and hype any given technology beyond where the science has demonstrated only serves to detract from its ultimate impact.

We technophiles need to resist the urge to find a new "hammer", and then use it on everything we see, just because everything suddenly seems to be a "nail".

Permalink to Comment

20. CMCguy on March 4, 2010 4:40 PM writes...

#18 processchemist while I also saw #17 as a sales pitch I think he is correct that pharma is relatively and highly inefficient in the process/manufacturing side, particularly if compare to petro, polymer and other bulk chemicals. Complexity may be a contributor however from the economic/throughput view continuous processes usually are better even if only for portions of the route. IMHO its more systematic, of which you point to a several factors, R&D chemists (medchem and then many process) do not think flow-though options (not trained/no experience) and because of demand/rush in early development build off conventional practice (even if think about it no time to study/demo has happened to me several times). This then creates the Titanic movement that can not turn and because parallels established development and regulatory procedures easier to follow. Face questions that are very different such as definition of a Lot? Controls and Analytical outside the norm too so are more hurdles but can be done.

Cut through the hype and heed #19 mickymedchem as a tool. I know continuous is not 100% applicable or beneficial but to ignore potential is poor approach. In reality most drug production is relatively small size chemistry-wise and because industry has been able to charge many times COGs it has not mattered. Costs and other pressures actually should motivate more efficiency and introduction continuous reactions may be a means to help.

Permalink to Comment

21. StillKicking on March 4, 2010 5:57 PM writes...

I saw Ley give a talk where he imagined a world where you enter your desired product into a computer, it devises a scheme, robots pick the appropriate catalysts/scavengers/ etc. in cartridge format and assemble a multi-step flow system, reagents are pumped in appropriately, and voila, pure product (after multiple steps) pours out of the pipe. I want some of what he's smoking!

Permalink to Comment

22. Anonymous on March 5, 2010 6:52 AM writes...

@CMC

the main problems about poor efficiency, imho, are about the shape of pharma development in the last 10 years (the lowest budget of ever on chemistry).
Efficiency is matter of research and understanding. Research is seen as a pure cost, and we all see the pressure about cutting costs. Every tool has his proper use and his advantages. None of them is the magic wand that will solve the problem. Last thing I need is some manager that thinks that buying some microreactors will be translated in a +10% of incomes.

Permalink to Comment

23. Lillywhite Chemist on March 5, 2010 7:56 AM writes...

SPRITY - Please note I don't have time to optimise your reactions for you but, just plug a search into SciFinder with Ar-X and methylamine and as of this morning the first hit you pull back is a nice J. Med. Chem. ref (ISSN: 0022-2623) where they do an SnAr with ammonia or MeNH2 in DMSO thermally, no flash equipment, no, pressure, no nothing, and get ~80 yield. Nuff said!

Permalink to Comment

24. Sceptic on March 6, 2010 4:31 AM writes...

It seems to me that if Prof Ley told pharma that the way ahead was to throw starting materials at the wall to increase efficiency, then we would go off to find the people in our groups with the best throwing arm.
He does some nice synthesis but it's the same old story - you need the right tool for the job and the knowledge of many tools and techniques. He has also got very rich from pharma funding! Nice work if you can get it.

Permalink to Comment

25. Anonymous on March 6, 2010 5:20 AM writes...

#23 "the first hit you pull back is a nice J. Med. Chem. ref (ISSN: 0022-2623) where they do an SnAr with ammonia or MeNH2 in DMSO thermally, no flash equipment, no, pressure, no nothing, and get ~80 yield. Nuff said!"

Which just about sums up most medicinal chemists' understanding of organic chemistry. I used to spend a large part of my life dealing with the combichem designs of the design visionaries at Big Blue, most of whom would happily mix electron deficient and electron rich Ar-X hets in their designs as if it made no difference to the chemistry.

#14 SPRITY - time to revise your physical chemistry, the methylamine will be in equilibrium between the head space and solution and is typically there in large excess. You can of course perform SNAr chemistry in a sealed tube or microwave vial - the trick is to not blow the cap off. That does limit the temperature that you can run at so there isn't so much of an advantage from the thermal effect - I usually managed about 140 degrees C with methylamine in methanol and it can work quite nicely. The electronics of your Ar-X are way more important than the technique.

Permalink to Comment

26. John Harrold on March 6, 2010 8:42 AM writes...

I now spend most of my time analyzing PKPD data. However, I am the product of a chemically engineering-military industrial complex. So when I read stuff like this, I tend to think of more industrial implications. In fact when I was in grad school, there was a guy in my department (he was a catalysis fellow) who worked in this area of flow based microreactor systems.

So, when considering flask versus flow on the bench scale, it may not matter. But when you start to scale things up to make products both cost effectively and in bulk, continuous processes are generally preferred to batch processes.

Like placebo mentioned above, CSTRs and tubular reactors are pretty normal stuff for chemical engineers. Heck, I'd say these flow systems are very similar to packed bed reactors, and when I read the post above the first thing I thought of was a catalytic converter.

So from an industrial perspective they need to show improvements in some combination of: energy efficiency (minimized heat loss and/or easy recovery), reduced maintenance costs, reductions in capital investments, better control (reductions in deviations from product specifications), and reduced down time.

These are pretty much the factors which determine whether they will be adopted industrially.

Permalink to Comment

27. Medicinal chemist (i.e. oraganic plus lots of other stuff) on March 10, 2010 7:57 AM writes...

#25 Anonymous - "Which just about sums up most medicinal chemists' understanding of organic chemistry."

What a disgusting sweeping generalisation. How do you think all the medchemists are trained? Not by Buchwald that's for sure. Please do share your enlightening background which makes you so much better than the rest of us who have to understand chemistry, biology, physchem, compchem, pharmacology, receptor kinetics, process chem... I hope you get my drift.

Permalink to Comment

28. FLM on March 12, 2010 7:07 AM writes...

Sorry, bit of text got lost in the up loading process
_________________________________________

Hi, From and engineering perspective, there is no difference between a 5 min "all in batch" reaction in the microwave, and a the same reaction, at the same temperature and concentration in a tube reactor with a 5 min residence time.

In both cases the molecules experience a sudden increase in temperature, followed by a sudden drop in temperature 5 min later.

The molecules experience the same conditions, the fact that they move about makes no difference, as they all move about at the same rate. Hence they will react identically.

If you look for benefits, there key benefits in (at least) four important areas:

(1) heat is removed faster, so temperature is better controlled. This allows one to do lab v exothermic reactions with out the risk of a run away reaction.

(2) Mixing of the feed streams is consistent, and with a well desinged mixer element (not a T mixer!!) fast mixing sensitive reactions will produce the desired result consistently:
Reactions are mixing sensitive when charging B to A:

A+B-v fast-> Product, Product + B --fast--> Dimer

or when charging A to B&C:

A+B -- v fast--> product
A+C --fast--> by product).

Results for these reactions in fed batch reactors will vary with scale and equipment as the rate of mixing at the feed point is not consistent.

(iii) The ability to quench
Many reactions result in unstable reaction mixtures. In a continuous reactor these can easily be quenched by either a large drop in temperature, or by mixing with a quench solution.

In batch, reaction mixtures unstable on the time scale of less then 30 min will case scale up problems, as addition times on scale up will invariably increase (less hear removal, limited flowrates). A good example of this is the need for cryogenic reactions: the low temperature slows down the intermediates/products decomposition, done in flow these reactions can often be completed at room temperature if one ensures the highly reactive intermediate is formed in the feed mixing zone, and than within seconds reacts with the substrate/quench.

(iv) slow reactions.
At times reactions take 10s of hours or even days. Flow reactions are easily done under pressure, so superheating of the solvent is not an issue. Assuming the reaction doubles every 10C, a 60C rise in temperature will reduce the reaction time 60 times, So hours become minutes...

I am sure there are other avantages as well (e.g. quick to do FED).

So what about the reactors? micro reactors, mini reactors coils does it realy matter? From the molecules point of view, it does not, it has no idea where it is, and how fast it moves. All it needs is the right temperature, and the right reagents at the right concentrations.

Where micro reactors have made a big impact, is in the SCALE down of flow reactions. For new chemicals, early in development (fine, pharma and agrochemicals) material available is limited. So a run with a 1/4 inch tube reactor will require tens of grams, and liters of solutions. Far to big a scale for most chemists early in the development chain.

Enter micro reactors... suddenly all the benefits of continuous processing became available to synthetic chemists on a 1/1000 to 1/10 gram scale, and for 5 mL coils, a scale up to 1-100 grams is easily achieved.

Over hyped? yes probably, just like microwaves, there no "magical" effect on the chemistry... the molecules still dont know where they are. But it did open up avenues for development of continuous processes to any chemists interested, not just the specialists.

The key challenge for flow chemistry is not the equipment. Engineering firms have generated small, medium and large scale continuous processing plants since the mid 19th century (e.g. the Solvay process!). The key challenge is to enable chemists to develop processes for either batch or continuous equipment what ever is most appropriate. This will widen the range of transformations available to the chemists, and thus allows him a wider choice of routes. And that, in the long term will lead to economic, and ecological benefits to those who embrace it

Permalink to Comment

POST A COMMENT




Remember Me?



EMAIL THIS ENTRY TO A FRIEND

Email this entry to:

Your email address:

Message (optional):




RELATED ENTRIES
How Not to Do It: NMR Magnets
Allergan Escapes Valeant
Vytorin Actually Works
Fatalities at DuPont
The New York TImes on Drug Discovery
How Are Things at Princeton?
Phage-Derived Catalysts
Our Most Snorted-At Papers This Month. . .