[curiouscat]

I found this paper's abstract intriguing, almost ridiculous but was wondering what others think:

"Phthalaldehyde and 1,4-cyclohexanedione react in the 2:1 molar ratio via a crossed aldol condensation in sub- and supercritical water to produce 6,13-pentacenequinone. The reaction conditions were optimized at 77% yield at 250 °C for 60 min with the starting molar ratio of 2:1:800 for phthalaldehyde, 1,4-cyclohexanedione and water, respectively."

Why would anyone try a reaction in a 800x solvent excess. Does this make sense, as a chemist? As an engineer I find it hard to believe this can ever be workable commercially, just due to the large excess of water.

Looking that the authors published in the journal "Green Chemistry" I'd assume they imply some utility to this scheme, not merely the science of it?

http://pubs.rsc.org/en/Content/ArticleLanding/2009/GC/b914784p

Have others have had a chance to carry out a reaction with a 800x excess of solvent ever? (Even adjusting for the molar -> mass fractions that's still like working at 0.5% concentrations)

[discodermolide]

Well I can't read the paper but 800 X excess of solvent seems to be somewhat excessive.
Perhaps they are trying to be greener than green?

[curiouscat]

Well I can't read the paper but 800 X excess of solvent seems to be somewhat excessive.
Perhaps they are trying to be greener than green?

Thanks!

What motivated me to post was I keep coming up with papers that report great yields (which excites the engineer in me as a competitive pathway) and then when you go deeper , you find that they work with ridiculously large excesses of solvents or amazingly low concentrations.

Now I could understand this in some circumstances e.g. (1) Making an amazingly expensive product (2) Elucidating mechanisms or kinetics (3) Making a novel molecule.

But for ordinary molecules these reaction conditions seem bizarre, especially when introductions sell the new route as cheap, green, safe etc. Why do editors turn a blind eye?

Maybe I'm ranting (apologies!), but I'd really love to hear more Chemist perspectives on what counts as a reasonable reaction condition.

[discodermolide]

I suppose reasonable reaction conditions are those that deliver the desired product in the required quality and yield.
The optimisation never stops, there is always something you can tweak.

[Corribus]

Could be solubility related in this instance.

[DrCMS]

This I'm afraid is chemists taking rubbish.  I've previously criticised Chemical Engineers for not knowing enough chemistry but this is the exact opposite; chemists who have not thought through the chemical engineering problems of their "brilliant" invention.  The cost in energy and equipment utilisation to use ~1200 moles (adjusting for yield) of water @250°C  to make 1 mole of product is ridiculous and in no way at all "green".  They should be ashamed to publish such useless information and the journal should be ashamed to have published it.

[curiouscat]

This I'm afraid is chemists taking rubbish.  I've previously criticised Chemical Engineers for not knowing enough chemistry but this is the exact opposite; chemists who have not thought through the chemical engineering problems of their "brilliant" invention.  The cost in energy and equipment utilisation to use ~1200 moles (adjusting for yield) of water @250°C  to make 1 mole of product is ridiculous and in no way at all "green".  They should be ashamed to publish such useless information and the journal should be ashamed to have published it.

Thank you DrCMS. Glad you guys agree.

[curiouscat]

Could be solubility related in this instance.

What did you mean? Because the feeds are insoluble in H2O the use a large excess of it?

[Corribus]

I didn't read the article - just ruminating.  If the reactants are poorly soluble in the reaction solvent, stands to reason one might need a lot of solvent to bring them into solution.  Not saying it's an efficient way to do things.  That was just the first thought that hit me. Admittedly, reading the paper would help, because it's hard for me to tell just from the abstract what the details of the reaction are.

By the way, the reaction product seems to be a direct precursor to pentacene, a high value molecule because of its relevance to organic optical materials. It's not a particularly easy molecule to make in high yield. If the authors here are able to produce this precursor in 77% yield using a one pot synthesis, the energy cost issues mentioned by DrCMS may be slightly overstated - at least compared to other existing synthetic methods. I point out also that the workup and purification here seems to be pretty simple (filtration only, if the abstract is any guide) compared to expensive and time consuming chromatography that often is required for other synthetic routes.

All things need to be put into perspective, in other words, and I'd be hesitant to impugn the authors for publishing this article without first analyzing what the relative energy costs are for synthesizing (and purifying) an equivalent mass of pentacene (or this precursor) via another route. As I say, I didn't read the article, but considering all the truly fraudulent science that's out there, this one seems to be fairly innocuous. You know, pick your battles and all that.

My two cents.

[curiouscat]

By the way, the reaction product seems to be a direct precursor to pentacene, a high value molecule because of its relevance to organic optical materials. It's not a particularly easy molecule to make in high yield. If the authors here are able to produce this precursor in 77% yield using a one pot synthesis, the energy cost issues mentioned by DrCMS may be slightly overstated - at least compared to other existing synthetic methods. I point out also that the workup and purification here seems to be pretty simple (filtration only, if the abstract is any guide) compared to expensive and time consuming chromatography that often is required for other synthetic routes.

Interesting perspective. Thanks. I'm trying to get the paper. If I do, I'll post a deeper summary.

[DrCMS]

@Corribus the following synthesis was taken from "An Improved Synthesis of Pentacene:
Rapid Access to a Benchmark Organic Semiconductor" Chandrani Pramanik and Glen P. Miller in Molecules 2012, 17, 4625-4633.

"Pentacene-6,13-dione. Aqueous NaOH (10%, 5.96 g, 149 mmol) was slowly added to a solution of
o-phthalaldehyde (10 g, 74.6 mmol) and 1,4-cyclohexanedione (4.18 g, 37.3 mmol) in ethanol
(460 mL) under a N2 atmosphere. The solution turned from yellow to golden brown to dark brown
before a yellow solid corresponding to pentacene-6,13-dione precipitated. After stirring the reaction
mixture for four hours, the crude reaction mixture was filtered and washed with ethanol, water, and
methanol until the washings were colorless. The solid residue was dried under vacuum to obtain 11.02 g
(96% yield) of bright yellow pentacene-6,13-dione."

In other words this is a quicker, lower temperature, higher yielding, higher utilisation synthesis from the same starting materials in a relatively "green" solvent.  Now tell me the high temp water synthesis is needed.

[Corribus]

@DrCMS

Your citation was published 3 years after the one curiouscat mentions in the opening post. I don't think you can use this as supporting evidence that the former publication was "unneeded".

Even if the one you mention had been published first, though, I'm not sure this really means anything. Alternative synthetic procedures, many of them less efficient than ones already known, get published all the time. You think there is no value in this?  We should keep a list of such fools and ban them from the scientific community? Don't you think your condemnation is a pinch strong, here? Your gripe seems to be that some chemists failed to take into account chemical engineering principles that would presumably be important for scale up to an industrial application. Well take a look at the chemical literature in general: this is hardly a unique thing, is it? And besides, I'd argue it's kind of beside the point of what most academic chemists are really trying to accomplish. I think we can still learn about chemistry from explorations of all experimental means of achieving a desired end, even if they ultimately turn out to be inferior to means that are already available. 99.999% of what is published in the chemical literature probably ultimately turns out to be useless, irrelevant, cost-inefficient, energy-inefficient, or superseded by something allegedly better in a week's time anyway... so we can be really cynical and conclude we shouldn't be doing any of it, or agree that this is just the nature of the process. You never know ahead of time what's going to be useful and what isn't, do you?  Yeah, maybe the water route here isn't energy efficient in the long run (although, it's a much more complicated question than a simple comparison between two procedures) and maybe there are better ways to get to pentacene. But who's to say someone else won't take this water-based synthetic route and adapt it for use toward the synthesis of something else that can't presently be made another way?

*shrug*

If the science is sound and approach is new, my philosophy is that it merits being part of the scientific literature. And certainly nobody should be ashamed about something like that. I guess in the end I take your point about chemical engineering and the green aspect (although what does "green" even mean anyway?), but, respectfully, I think the calls for shame on the part of the authors and the journal are a little overboard.

[orgopete]

If the science is sound and approach is new, my philosophy is that it merits being part of the scientific literature. And certainly nobody should be ashamed about something like that. I guess in the end I take your point about chemical engineering and the green aspect (although what does "green" even mean anyway?), but, respectfully, I think the calls for shame on the part of the authors and the journal are a little overboard.

I too am a bit more sanguine about this. Now that DrCMS has provided another prep, let's compare. I only looked at phthaldehyde. The molar ratio of phthaldehyde to water in DrCMS's route is 1:342 and the green ratio is 1:400. I have no comment on green, but...

[curiouscat]

I too am a bit more sanguine about this. Now that DrCMS has provided another prep, let's compare. I only looked at phthaldehyde. The molar ratio of phthaldehyde to water in DrCMS's route is 1:342 and the green ratio is 1:400. I have no comment on green, but...

Nice!

[DrCMS]

@ orgopete  do you maths again the original water prep is 2:1:800 moles the one I quoted was 2:1:210 moles.
One works at room temp to give a very high yield while the other needs 4 time more solvent, high temperature and pressure and only gives an OK yield.

@ Corribus the prep I quoted from the 2012 paper was not new work they just used that prep to get the starting material for the novel bit they were writing about.  The prep was based on earlier work reported in the literature but I can not get to them from my home PC.

@both of you if you really think academic chemists should re-invent the wheel over and over and over quoting lower and lower yield from increasingly complicated method to "push" forward our understanding fair enough but I think that is pissing in the wind and a waste of funding. 

The fact that lots of other chemistry papers show very little thought or understanding of cost and scale up does not excuse it in this case.  It means they ALL need to try harder.

I am sick of academics getting funding for blue skies research that is just a huge waste of effort.  As it's now my money as a tax payer they are wasting I've had enough of it.  Academics seem to think research with a real world goal is below them. 

I still think this is poor work reported just to get a publication.  Journals should reject more work that is not an improvement on previous work.