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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

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July 9, 2013

A Microwave Argument

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Posted by Derek

Since I was talking about microwave heating of reactions here the other week, I wanted to mention this correspondence in Angewandte Chemie. Oliver Kappe is the recognized expert on microwave heating in chemistry, and recently published an overview of the topic. One of the examples he cited was a report of some Friedel-Crafts reactions that were accelerated by microwave heating. The authors did not take this very well, and fired back with a correspondence in Ang. Chem., clearly feeling that their work had been mistreated in Kappe's article. They never claimed to be seeing some sort of nonthermal microwave effect, they say, and resent the implication that they were.

Kappe himself has replied now, and seems to feel that Dudley et al. are trying to have things both ways:

In their Correspondence, Dudley and co-workers have suggested that we attempt to impugn their credibility by associating their rationalization for the observed effect with the concept of nonthermal microwave effects. This is clearly not the case. On the contrary, we specifically state in the Essay that “The proposed effect perhaps can best be classified as a specific microwave effect involving selective heating of a strongly microwave-absorbing species in a homogeneous reaction mixture (”molecular radiators).“ As we have already pointed out, our Essay was mainly intended to provide an overview on the current state-of-affairs regarding microwave chemistry and microwave effects research. Not surprisingly, therefore, out of the incriminated 22 uses of the word ”nonthermal“ in our Essay, this word was used only twice in reference to the Dudley chemistry, and in both of these instances in conjunction with the term ”specific microwave effect“.

The confusion perhaps arises since in the original publication by Dudley, the authors provide no clear-cut classification (thermal, specific, nonthermal) of the microwave effect that they have observed. In fact, they do not unequivocally state that they believe the effect is connected to a purely thermal phenomenon, but rather invoke arguments about molecular collisions and the pre-exponential factor A in the Arrhenius equation (for example: “Chemical reactions arise from specific molecular collisions, which typically increase as a function of temperature but also result from incident microwave irradiation”). Statements like this that appear to separate a thermal phenomenon from a microwave irradiation event clearly invite speculation by non-experts about the involvement of microwave effects that are not purely thermal in nature. This is very apparent by the news feature in Chemistry World following the publication of the Dudley article entitled: “Magical microwave effects revived. Microwaves can accelerate reactions without heating”

Based on his own group's study of the reaction, Kappe believes that what's going on is local superheating of the solvent, not something more involved and/or mysterious. His reply is a lengthy, detailed schooling in microwave techniques - why the stated power output of a microwave reactor is largely meaningless, the importance (and difficulty) of accurate temperature measurements, and the number of variables that can influence solvent superheating. The dispute here seems to be largely a result of the original paper trying to sound coy about microwave effects - if they'd played things down a bit, I don't think this whole affair would have blown up.

But outside of this work, on the general topic of nonthermal microwave reaction effects, I side with Kappe (and, apparently, so do Dudley and co-authors). I haven't seen any convincing evidence for microwave enhancement of reactions that doesn't come down to heating (steep gradient, localized superheating, etc.)

Comments (13) + TrackBacks (0) | Category: Chemical News


COMMENTS

1. Dave on July 9, 2013 10:24 AM writes...

Couldn't this be viewed as a version of photochemistry, only in the (very) far infrared region of the spectrum? Of course, there aren't many chemical bonds which would respond (absorb energy) at microwave frequencies. And, to get the maximal benefit, one would need to tune the microwave frequency to the energy of the particular bond needing to be altered (and, it's not easy to tune the frequency of the magnetron used in virtually all microwave ovens, although it might be possible to build a similar system using a klystron, or some other microwave producing device).

Dave

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2. Anonymous on July 9, 2013 10:28 AM writes...

I have found that a Diels-Alder reaction goes faster when the lab radio is on. Has anyone else experienced this?

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3. anon the ii on July 9, 2013 11:02 AM writes...

It occurred to me about 13 years ago, while a CEM technical guy was demonstrating their heating while cooling microwave device, that if it was possible to selectively dump microwaves into a bond and do chemistry, some physics dude would have figured it out a long time before. Something so fundamental would not have been discovered by a bunch of organic chemists tossing a bunch of stuff in a flasks and bombarding it with microwaves. Besides, from all that p-chem stuff that we had to take as undergrads, the energetics didn't seem right. What happened to quantum mechanics? So I told the dude that his device was bulls.... and walked away. I understood the advantages heating stuff really hot in a sealed vial in a metal box as opposed to a vat of hot oil, but this heating while cooling was stupid. I later found out that I narrowly missed being punched out by the dude for calling him a liar. Good thing I walked away.

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4. a. nonymaus on July 9, 2013 11:39 AM writes...

If there was anything to non-thermal microwave reactions, it would only be seen in the gas phase at low pressure. It is simply impossible to selectively excite a rotational mode of a solute in a liquid bath, since the relaxation time is shorter than the rotational period. Of course, there are people who go and do very high excitation number rotational spectroscopy in UHV conditions but I don't know if they see any unusual effects in terms of mode-selected rearrangements of rotationally hot molecules.

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5. sciencemonkey on July 9, 2013 11:48 AM writes...

@3 anon, I don't have experience with this field, but maybe heating + cooling is still useful in the context of local solvent superheating to form the product, but keeping the overall solution cool to avoid product degradation.

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6. Cytirps on July 9, 2013 1:52 PM writes...

I have seen only 1 microwave example which cannot be reproduced in an oil bath. Whenever I ran a microwave reaction with nitrogen rich compounds in DMSO, it ended up in an explosion. When I repeated it in a CEM reactor with a RB flask, I could see gas bubbles (SO2?) erupted from the RB flask at temperature (~120 deg.C) way below the bp of DMSO. The same reaction went peaceful by heating it in an oil bath.

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7. BG on July 9, 2013 4:25 PM writes...

DMSO starts to appreciably disproportionate at 90 deg. C into dimethyl sulfide, and it can explode if you heat it too high. Superheating may have been decomposing it, which was probably why it exploded.

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8. Han on July 9, 2013 5:41 PM writes...

I've seen a lot of strange stuff, but I've never seen anything to make me believe there's one all-powerful nonthermal microwave effect.

There's no mystical energy field that controls my destiny.

It's all a lot of simple tricks and nonsense.

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9. Orion on July 9, 2013 9:37 PM writes...

I had a double decarboxylation (sealed flask!!!) that really only worked in a microwave and just gave decomp in an oil bath. Pretty decent scale for microwave too (>50g; it was a serious piece of equipment). Worked perfectly every time, so never put much effort into optimizing conventional conditions to match, and the intermediate never made it to the process guys.

Not to take any sides, but is the inter-system crossing really so fast that this can't be investigated spectroscopically. I think it would be quite a trick to make a MW-NMR instrument (hell, maybe with the same transmitter since it's the same chunk of spectrum!) if you can prevent frying the receiver circuitry. Heat-pulse-listen; heat-pulse-listen...

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10. anon on July 10, 2013 2:02 PM writes...

#3, selectively exciting certain bonds was what my dad did his PhD on, several decades ago. he was indeed a physical chemist (actually he told me that since it was a fad at the time for organiker to refer to themselves as physical-organic chemists, the pchem guys took to calling themselves chemical physicists).

they used an IR laser in their studies, not a microwave oven. nondestructive, isomer-selective laser chemistry was demonstrated to a certain extent, but the scope was very limited (small, simple molecules, in the gas phase, low pressure). it's not difficult to imagine some of the limitations that prevented laser chemistry from going mainstream, though it might quite hard to delineate all of them. still, as i understand it coherent control is still an active area of study (and a good way to get into Science, apparently).

a microwave oven is a slightly different animal, but some of the same principles and limitations apply

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11. vasili on July 11, 2013 5:22 AM writes...

9.Orion, have you tried that decarboxylation in flow.
The fact that it didn't work with an oil bath is maybe due to the time needed to reach that high T, which is instantaneous with MW and so it is using flow chemistry. At 0.1 g it can worl with an oil bath by try to reach 180 degrees with 20 mL reaction solution, it takes some time to reach that and enough to decompose the material.

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12. Orion on July 11, 2013 9:28 AM writes...

@11

We didn't have a flow apparatus at the time, but would certainly have wanted to try it if we did (this was >8 years ago at a now inactive facility). The reaction was run in water, with no other reagents. The temperature was well over 100C (don't remember exactly) and run in a pressure flask. Despite targeting the same temperature in MW as in an oil bath, the reaction consistently went to completion by MW in minutes, while took all day in the oil bath.

How well does flow equipment handle super-heating solvents? I'm sure it could be made to work, but also suspect a week of conventional optimizations would get there too.

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13. Anonymous on July 11, 2013 9:54 AM writes...

@2: I tried making a thiadiazole from an oxalimidate which was very messy and gave extremely low yields under conventional conditions. After turning to the microwave, the simultaneous heating/cooling effect gave no edge over the bad yields previous. Finally I decided to blast the reaction contents with Michael Jackson's "Billie Jean". Result: 2% improvement in yield! I was chuffed :-)

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