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Derek Lowe The 2002 Model

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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: Twitter: Dereklowe

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November 1, 2012

Hype, Malpractice, and Scientific Misconduct in Organic Synthesis

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Posted by Derek

That's the word-for-word title of a provocative article by Rolf Carlson and Tomas Hudlicky in Helvetica Chimica Acta. That journal's usually not quite this exciting, but it is proud of its reputation for compound characterization and experimental accuracy. That probably helped this manuscript find a home there, where it's part of a Festschrift issue in honor of Dieter Seebach's 75th birthday.

The authors don't hold back much (and Hudlicky has not been shyabout these issues, either, as some readers will know). So, for the three categories of malfeasance described in the title, the first (hype) includes the overblown titling of many papers:

As long as the foolish use of various metrics continues there is little hope of return to integrity. Young scientists entering academia and competing for resources and recognition are easily infected with the mantra of importance of
publishing in 'high-impact journals' and, therefore, strive to make their work as noticeable as possible by employing excess hype.

It is the reader, not the author, of papers describing synthetic method who should evaluate its merits. Therefore, self-promoting words like 'novel', 'new', 'efficient', 'simple', 'high-yielding', 'versatile', 'optimum' should not be used in the title of the paper if such qualities are not covered by the actual content of the paper.

It also includes the inflation of reaction yields (see that link in the second paragraph above for more on that topic). This is another one that's going to be hard to fix:

Unfortunately, the community has chosen and continues to choose the yield values in submitted manuscripts as a measure of overall quality and/or utility of the report. This, of course, encourages the 􏰛'adjustment' in the values in order to avoid critique. An additional problem in the reported values is the fact that synthesis is performed on small scales, thanks to advances in NMR and other techniques available for structure determination. On milligram scales it is extremely difficult to accurately determine weight and content of a sample, given the equipment available in typical academic laboratory.

The second category, malpractice, is sloppy work, but not outright fraud:

Malpractice, as explained above, is usually not deliberate and derives primarily from ignorance or professional incompetence. The most frequent cases involve improper experimental protocols, improper methods used in characterization of compounds, and the lack of correct citations to previous work.

For example, the authors point out that very, very rarely are any new synthetic methods given a proper optimization. One-variable one-at-a-time changes are worthwhile, but they're not sufficient to explore a reaction manifold, not when these changes can interact with each other. As process chemists in industry know, the only way to explore such landscapes is with techniques such as Design of Experiments (DoE), which try to find out what factors in a multivariate system produce the greatest change in results. Here's an example; the process chemistry literature furnishes many more.

And finally, you have outright scientific misconduct - fraud, poaching of ideas from grant applications and the like, plagiarism in publications, etc. It's hard to get a handle on these - they seem to be increasing, but the techniques to find and expose them are also getting better. Over time, thought, these techniques might just have the effect of making fraud more sophisticated; that would be in line with human behavior as I understand it, and with selection pressure as well. The motives for such acts are with us still, and do not seem to be abating much, so I tend to think that determined miscreants will find ways to do what they want to do.

Thoughts? Some of this paper's points could be put in the "grumblings about the good old days" category, but I think that a lot of it is accurate. I'm not sure how good the old days were, myself, since they were also filled with human beings, but the pressures found today do seem to be bringing on a lot of behaviors we could do without.

Comments (71) + TrackBacks (0) | Category: Chemical News | The Dark Side | The Scientific Literature


1. RB Woodweird on November 1, 2012 8:35 AM writes...

"A Novel and Efficient Synthesis" of just about anything is rarely novel and never efficient.

My own crusade used to involve taking a pen or marker or whatever defacing tool was to hand and crossing out the word "elegant" whenever I saw it in the chemical literature. The curve of Marilyn Monroe's butt was elegant. Chemical transformations may be interesting or unusual or surprising. They are not elegant.

So if you pick up a copy of some journal sometime and see a hand-redacted adjective, it might have me.

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2. Anonymous on November 1, 2012 8:41 AM writes...

This is a can of worms, but what are the votes for the worst in each category? My votes:

Hype: Baran
Misconduct: Corey
Fraud: Tie between JJ LaClair, Bengu Sezen and Dalibor Sames

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3. grouchie on November 1, 2012 8:48 AM writes...

I'll go with the following:

hype: macmillan
misconduct: stork (never wrote a full paper)
fraud: agree with above

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4. Mark on November 1, 2012 9:02 AM writes...

Hype: Baran/Macmillan tie
Misconduct: Nicolaou (his yields are always ridiculous)
Fraud: LaClair

Brutally Honest: Danishefsky and Trost (although I don't think Danishefskys work is the most efficient, I at least trust his work/yields which are sometimes good and sometimes crap.)

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5. Curious Wavefunction on November 1, 2012 9:09 AM writes...

I think most good statisticians would be appalled if they were to encounter standard practices in synthetic organic chemistry.

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6. luysii on November 1, 2012 10:00 AM writes...

The medical literature was full of hype in the 36+ years I had to read it professionally. Here's one example --

My nephew is just starting out in psychology as an undergraduate. He had the following to say after I sent him the above.

"As I've been learning about research methods and reading scientific articles on psychology, I have become more skeptical of "findings" in the field. In addition to the issues surrounding data interpretation, there are also problems with its validity and reliability.

These issues seem to be even more common in psychological research, which is akin to trying to measure the weight of smoke. Not only are there problems with the results, but the operationalization of the concepts being measured can be extremely tricky. Even if one does get significant results, it may not even mean anything for the conceptual variable of interest.

Pondering these issues has actually led me to become extremely interested in statistical analysis. The fact that mathematical concepts can help to address some of these questions is SO cool. I really enjoy using SPSS (a statistical analysis program) to sort through data and examine relationships. I had a meeting with a psychologist who just got her PhD, and it lasted over two hours as she showed me the ins and outs of SPSS. It was fascinating. I'm going to be working on a paper or two, and will hopefully have a published article in a journal by early next year."

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7. anon the II on November 1, 2012 10:05 AM writes...

Much ado about nothing. The problem here is that a lot of people think that organic synthesis is some kind of scientific endeavor. It's really not. It's mostly a mixture of art and engineering. And selling it is how you get famous and make money.

You can use organic synthesis to do science, but that's not what our heros mostly do. They make pretty statues to put in their personal galleries while training others to paint signs in the process.

And one day we'll learn to appreciate LaClair the same way I appreciate Jackson Pollack.

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8. Aspirin on November 1, 2012 10:05 AM writes...

Hype: MacMillan, definitely. On his way to becoming the next KCN (the fact that he is a tyrant in lab helps). I would say that most of Baran's accolades are well-deserved, although he is no RBW.
Misconduct: Corey and H C Brown.
Fraud: LaClair, Sezen, Sames.

I fail to see how not writing a full paper constitutes "misconduct" (Stork). From all accounts that I have read Stork is a great chemist.

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9. anonagain on November 1, 2012 10:27 AM writes...

it'd be ok to do all that stuff if organic chemists (that's unfair, i mean total synthesis people really) were actually doing something valuable.

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10. Justice on November 1, 2012 10:32 AM writes...

^ Yeah, because nucleophilic addn to nitroalkanes and ring opening epoxides with fluoride are oh so valuable, lol. Most of us, across all sub fields, are doing research that matters only to a handful of people.

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11. Richard Apodaca on November 1, 2012 10:54 AM writes...

Am I the only one who finds it ironic in the worst way that the authors of this paper chose to publish it in a journal I can't access?

Hype, malpractice, and misconduct thrive in an environment of limited access.

Contrary to popular belief, there are quite a few open venues in which this paper could have been published. Yet the authors chose not to - why not, I wonder? Could it be that the "foolish use of various metrics" (a journal's 'prestige') affects both practitioners and critics alike?

Shame on Carlson and Hudlicky - they should know better.

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12. SDChemist on November 1, 2012 11:23 AM writes...

At the other end of the spectrum, I repeated several procedures reported by Seebach's group and my yields were always within 3% (plus or minus) of the report. Is this the experience of others?

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13. Tomas Hudlicky on November 1, 2012 11:31 AM writes...

To: Richard Apodaca

From your comment I gather that you are confused...

1. This was an invited paper for a special issue honoring Dieter Seebach-hence Helvetica
2. The above named chemist has been one of the first to criticize the state of affairs in organic chemistry-hence the essay
3. I do not publish in "open" journals because no one reads them
4. If you want a PDF of the article let me know and I will
send you one.
5. Elaborate as to what we should "know better". I am curious...

Hope my explanation helps

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14. Student on November 1, 2012 12:12 PM writes...

Dear Prof. Hudlicky,

You have to realize that many organic chemists agree with you, but are put off by your combative tone. Especially students - nobody likes acknowledging that their exciting results mean less, and we'll do the experiments necessary to prove that our methods are worthwhile.

Take your Synlett for example - it COULD have been an excellent tutorial to those of us who are unenlightened. You COULD have been the one championing a reform of contemporary organic synthesis. But by your tone, you'd rather accuse us of misconduct rather than guide us on the path to more reliable and applicable chemistry. I'm a religious guy so you can guilt me into all sorts of behavioral changes, but I don't think that works on most scientists. They need to be CONVINCED, not SHAMED.

This is what would convince me to follow your lead and start performing critical analyses on the efficiency of my methods: a clear, non-accusatory tutorial on critical analysis. You're right - I didn't get the kind of training in analytical chemistry that's required. I was a bio major before moving into synthesis. It would be nice if someone spelled it out for me, in a high profile journal. Collaborate with industry - I'm sure many process chemists feel strongly about it, and if they could be part of the change that makes academia useful to them, they'll be glad to help.

Maybe this is already published. Then publicize it! Make it visible, and make it attractive! Play the game a little. Get inside our heads and convince us. A lot of us WANT to be convinced. Show us examples where industry has adopted a method BECAUSE of the analysis you're supporting. I'm sure there are plenty. Give a summary of examples. Give quotes, like you normally do, but with a different tone - quotes along the lines of "this looked like a promising method, but fell short of the reported yield, and so we tried something older" that are specific.

I just hate the idea that you're getting a bad rep even though you're trying to make a positive change. I think you make excellent points, and I've met you and I can tell you're passionate about it, but I feel strongly that you're going about it the wrong way.

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15. tomas Hudlicky on November 1, 2012 12:19 PM writes...

To: Student

Thanks for your advice. Sorry, I am not the touchy-feely type-that is too much like tehe 21st century.
The Synlett article spells out what is needed quite clearly.
Be well,

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16. David on November 1, 2012 12:44 PM writes...

Re # 10: At the time of discovery most reactions may not appear to be of value...but that does not necessarily mean they won't at some point. Look at several cross coupling methodologies for example - sure in the final scaled up process there may be a different way of doing things but for quickly synthesizing a range of compounds to generate SAR it represents an easy way. Maybe a bad example but my point is that often things may seem pointless at the time yet find innovative uses which allow Med Chem to synthesise their molecules which have a use. (Unless your comment was sarcastic?)
I also dont agree with the comment that organic synthesis isn't real science - without its developments there would be no Med Chem, ie a 'proper' use of chemsitry.

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17. Felix on November 1, 2012 1:48 PM writes...

The murky numbers synthetic organic chemists put out has been criticized since I was an undergrad. Many reactions are conducted on a small scale and in my experience, their isolated yields are very noisy. However, after reading Hudlicky's paper on the limits of calculating isolated yields and his finding that NMR tended to be fairly accurate, at least compared to other methods of quantitation, I have started to utilize more NMR to screen reactions using internal standards. In my experience, it tends to provide a lot of information in a very reproducible manner. I have tended to favor it over GC/MS now.

Student - Hudlicky also criticizes himself to some extent in the synlett paper: "An astute student of the organic literature may discover that this very author has been guilty of reporting yields in this range from time to time!"

I don't think it's that chemists are actively trying to commit fraud, it is that reactions are noisy and chemists do not want to undersell their research. I have often found that a crude NMR with internal standard often allows me to account for almost all the mass in a reaction, giving me a more solid point of comparison of two reactions. However, it really matters what type of standard is used! I've seen some use DMF, which is probably a poor idea in my experience.

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18. bbooooooya on November 1, 2012 2:35 PM writes...

Organic synthesis as a field needs more Tomas Hudlicky's!

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19. milkshake on November 1, 2012 2:37 PM writes...

Hudlicky has guts the say publicly what many grumble about in private: the rigor of old solid German, US and UK synthetic chemistry got lost because of the grantsmanship and tenure pressure. The chemistry used to be much harder to do in terms of purification and characterization of compounds so people had to be more cautious; naturally there was less tolerance for hype and sloppiness

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20. gippgig on November 1, 2012 2:43 PM writes...

A couple articles in Science News are worth reading:
Odds Are, It's Wrong Science fails to face the shortcomings of statistics; March 27, 2010 p. 26,
Making Data Work Researchers pursue analogy between statistical evidence and thermodynamics, Sept. 8, 2012 p. 26
For an example of the practical application of organic synthesis techniques see Amphotericin primarily kills yeast by simply binding ergosterol, PNAS vol. 109 p. 2234,

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21. Anonymous chemist on November 1, 2012 4:02 PM writes...

Hallelujah! Finally someone has the guts to call a cat a cat! As a postdoc I felt terribly traumatized when my boss forced me to doctor some spectra... Was physically sick afterwards but I was on a J1 visa and my career depended on his recommendation. I learned afterwards that my boss was a "mild" one. My colleague who lied the most on yields works now for a proeminent law firm in Boston...

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22. Eka-silicon on November 1, 2012 6:48 PM writes...

The experiment I would love to see? Send a range of academic labs a vial, and ask: please flash this, isolate the major product, and let us know the yield, with a clean spectra. The dispersion would be staggering.

Keep of rocking T-Hud- the field desperately needs someone to call out the insanity of 90% yield on 1.2 mgs....

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23. Mat Todd on November 1, 2012 7:15 PM writes...

Sounding like a broken record, but the open lab notebooks we use are intended to get around some of these issues by

a) placing things like yields for individual reactions in a context of repeats and/or failures - a 90% yield is perhaps more believable if you see that 5 previous attempts with slightly different conditions gave 50-70% yields, and
b) including raw spectroscopic data, so purity can always be checked - a 90% yield is not 20% ethyl acetate.

Incidentally it's often struck me as odd that results in tables in chemistry papers are usually results from single experiments. Biologists are usually more careful to include sample size and error bars. I think we as a community accept that a table of reaction results with small changes in S/M or catalyst structures (for example) count as a collection of experiments revealing a trend, but the individual points are usually single runs.

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24. Martyn on November 1, 2012 7:45 PM writes...

Prof. Hudlicky,

Can you point to a (recent?) paper that, in your opinion, gets all this stuff right? I'd like to see an example of how it should be done.

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25. Tomas Hudlicky on November 1, 2012 8:32 PM writes...

Well, I was not going to make any more responses but....I HAVE to do it. Here are a few...I am afraid this is a long one...::

To: Eka-silicon:

What a fantastic idea! I was going to say "novel" but caught myself just in time. Yes, indeed, you would get quite a spread. The highest yields would come from Harvard and MIT, of course, the rest of us do not have the star students who are free to violate the laws of Nature. I imagine some folks would actually isolate 1.4 mG out of 1.2 mG, not noticing the cat hairs in the sample...
But there already is a medium for this: Org. Syn. Have you ever seen 98% yields there? No.

To: Mat Todd:

Right. Results of single (i.e., the highest yielding) experiments. No one reports a RANGE anymore.
It's OK. Yet another addiction to quantification and large numbers (invented, no doubt, in the US). Europeans deal with low scores in soccer. Canadians (and Europeans) deal with low scores in hockey. Not Americans. We have to have high football scores and, yes, even higher basketball numbers! We can make six inches sound great if the inch is defined as very small! Funny world we live in....

To: Martyn:

I will have to dig. Send me an email and remind me to send you examples. There are still a few out there that have not been eaten up with self deception....Out of my head, I was impressed with the fact that Barran in his recent paper on germacrane terpenes (ACIE) reported 39%, 45% , etc., yields. There are still people who actually publish what they get-of course, most of the time they get crap from referees because the 70% yields are-oh, so low....Anyway, look up Clayton Heathcock's lycopodine synthesis (Full paper in JACS, 1980s-1982?) I know, that is not recent, but a good example of excellent chemistry and honest reporting. Who gives a F*&^ about yields anyway? If our stuff is at all useful, the process guys will make it >90% in no time. By correctly performed optimization. And from that source, I will believe it!
Optimization is not (and should not) be the province of academics. We should not even use that word because most of us do not know what it means anyway! We should spend our time teaching students how to crystallize solids to CONSTANT melting points!! (What's that?)
Anyway, I had to go on another rant here...

To:The student:
Have you recovered yet? Nothing good ever came from positive reinforcement except a sense of entitlement, which we all have to suffer now, from the young generation. My favorite saying in group meetings (which are still "the old days"): Suck it up and get to work!"

Well, this will do for a while. Thanks for (most of) y'all's comments.

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26. Free Radical on November 1, 2012 8:47 PM writes...

One of the lesser forms of larceny is using separate experimental results for characterization and for yield reporting. We were taught that, if you're reporting a representative result, the % yield and the characterization should be taken from the same result. Or, if reporting a range of yields, that the yield for the material used to characterize should be in the representative range.

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27. Nick K on November 1, 2012 10:28 PM writes...

I'm so glad this issue is out in the open. Frankly, why do people like KC even bother reporting yields? No one has ever believed them, apart from inexperienced grad students, of course...

I've repeated quite a lot of Seebach's work, and have always had excellent results, with yields (real, isolated, pure, solvent-free) within 10% of those he reported. Why can't ALL synthesis papers be like this?

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28. American on November 2, 2012 12:14 AM writes...

"Not Americans. We have to have high football scores and, yes, even higher basketball numbers! We can make six inches sound great if the inch is defined as very small! Funny world we live in...."


Considering the drop in Americans in graduate science programs over the time that yields have been increasing, I'd say this may not be an American problem...funny world we live in.

"Between 1980 and 2000, the percentage of Ph.D. scientists and engineers employed in the United States who were born abroad has increased from 24% to 37%"

And the numbers only get bigger in the foreign area.

At one point in my career, I had a professor tell me that he wished Americans were more like the foreigners, because they always gave him what he wanted...


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29. Kumada on November 2, 2012 2:07 AM writes...

@12 and 27
one reason for the high reproducibility of these recipes is that Prof. Seebach accepted our new products only with a matching ELEMENTAL ANALYSIS, be it salts, resins, or oils. The correct HANDLING of chemicals and equipment, purification techniques like distillation and proper crystallization - the old-fashioned craft - was always at part of the discussions.

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30. Ricardo Ros on November 2, 2012 2:21 AM writes...

Thanks for the article, and nice debate.

As a former analytical chemists, who has done quite a lot of synthesis, I did never understand why some of my peers where reporting false yields. There were very simple tricks to detect this, from the ones who always had x5's on their yields, to the ones who only had odd or even numbers ... there are more sophisticated analyses which are employed by tax agencies which can could be used, easily.

Some one has mentioned it, but one of the issues here is the total neglect of proper analytical chemistry being taught on most universities in the planet. I had to sit in front of experienced chemists in industry, listening, and then convincing them, that NMR is a quantitative technique (we would be talking here PhDs).

With the current hardware and software, it is possible that every single peak on every single NMR can be fully quantified, in an automatic manner. I am still confused as to why much of the population of chemists have decided to behave like cowboy scientists and relax the rigour with which they should be characterising their work.

The reference that this comes from the US is not a valid one, a scientist should be taught over their first few years in academia the tools to correctly conduct themselves in a scientific manner and as a chemists, and it is the neglect on many areas of chemistry which is the root of this problem.

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31. Boekelheide on November 2, 2012 2:24 AM writes...

Whenever I give a talk in front of process chemists, I am citing the Synlett paper, and the audience is nodding - these points are not new to them, they reflect the indispensable and most fundamental requirements when you have to put multi kg's of a compound on a (potato) balance, and someone should repeat it later on. Thanks to your paper, Prof. Hudlicky, there is a higher chance to reach undergraduates with these arguments.

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32. Anonymous on November 2, 2012 3:47 AM writes...

My faith in Orgsyn was depressingly reduced recently..
[Org. Synth. 2013, 90, 41-51: This material is purified by silica gel column chromatography (snip) to furnish 7.62 g (27.3 mmol, 92%) of (E)-N,N-diethyl-2-styrylbenzamide as a light
yellow viscous oil (Note 17). The crude material was dissolved in toluene (10 mL) and then
charged onto a column (diameter = 10 cm, height = 11 cm) of 425 g (1000 mL) of silica gel. The column was eluted with n-hexane/EtOAc = 8:1 (7.0 L) to 2:1 (3.6 L) and 100-mL fractions were collected. Fractions 73-108 were combined.]

Yep, nearly 11 litres of solvent to produce 8g material. 92% yield. Why column it then?

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33. Eka-silicon on November 2, 2012 4:56 AM writes...

If anyone has excess undergrad labour available, I'd love love love to see Benford's law applied to a) certain labs and b) JACS or JOC by decade from say 1950 to now....

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34. Anonymous on November 2, 2012 5:50 AM writes...

I don't think Benford's Law is considered applicable in small numbers of limited range with no powers assocociated with their generation.

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35. Eka-silicon on November 2, 2012 7:02 AM writes...

Anon, see

Diekmann, A. "Not the First Digit! Using Benford's Law to Detect Fraudulent Scientific Data" Journal of Applied Statistics; 34(3), 2007; 321-329.

If it works for regression coefficients, it should work for the first, or better yet, *last* digit of yields. Easy enough to test!

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36. Anonymous on November 2, 2012 7:23 AM writes...

If it applies, the last digit is definitely the one to go for. I would LOVE to see this done.
A while back I went through a complete custom synthesis lab book of mine.
Average yield = 62% IIRC. I guess I'm not KCN material.

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37. Anonymous on November 2, 2012 7:37 AM writes...

When I read posts like this/comments, it makes me sad as all I can think of is Lance Armstrong (i.e. NOWHERE near as bad as that but still finding out that heroes are not all they seem)

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38. Derek Lowe on November 2, 2012 7:58 AM writes...

As much as I'd like to see Benford's law used on reported yield data, I think it would be tricky. You really want underlying data that cover several orders of magnitude - the whole underlying mechanism is the mantissas of the logarithms of the raw numbers. Benford's is also inappropriate for normally distributed data, so a careless application would confuse real randomness with fraud.

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39. tt on November 2, 2012 9:08 AM writes...

While Prof. Hudlicky may be a rather brash and rude messenger (as most tenured professors tend to be), he raises some very valid points. As a rather experienced process chemist, I tend to view most academic reported yields as a suggestion (i.e.-we got some product, but we can't really say how much and what else is in there). I then assume that we can optimize it through DoE and reagent screening, unless there's some impurity that can't be minimized or rejected due to some fundamental mechanistic limitation. I do think "real" yield reporting would be nice, but an average yield of >10 runs isn't really needed. The most helpful thing from my perspective would be some identification of purity, mass balance, and structure of major impurities. I'm continually shocked when speaking with top academics in organic methodology that they have next to zero knowledge of DoE and multivariate analysis. They seem surprised when I explain how one-factor at a time optimization misses interaction effects. I would love to see graduate programs in organic chemistry require some courses in this area. A side effect of some DoE training might be the appreciation of real yields, as inflated ones would throw off the subsequent analysis and stick out.

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40. Tomas Hudlicky on November 2, 2012 9:10 AM writes...

To: #33, Eka-silicon:

Regarding "yields by decade"...I did not apply Benford's law to this issue but I did perform what I called "a poor man's statistical treatment" on two items:

1. The yields by decade, 1950 on for JOC and Org. Syn. only: Open a random issue, write down the first yield number from an experimental, do so ~50 times/decade for JOC, somewhat less for OS, average the numbers.
I do not remember the exact numbers except for the fact that in the 1950s/19690s the average was in low 60%. By 1990s it was mid 80%. Given the fact that the skill level of students is likely LESS today than 50 years ago, it is an amazing trend.
The problem, as I see it, is that today's students (=apprentices) are not taught by professors (=masters), to use Pollanyi's descriptors. (This and other points is discussed in the Outlook chapter in The Way of Synthesis, 2007). They are taught by other students or postdocs while the prof chases money or argues with editors to get his/her paper into JACS. The result is lesser skill level, increased sense of entitlement, and increased sensitivity to be "offended", as demonstrated here by the comment #14...
In Org. Syn. the average really did not change, it was around 65 or 70% for all decades. I made a comment about this in the Chem. Rev. chapter (reference 11, Chem. Rev, 1996, 96, 3-30). I was still nice back then....!

2. The second "stats by sesqui-decade" involved the use of hype in titles. This table is published in our book, The Way of Synthesis, Wiley, 2007, page 198. The numbers were obtained by SciFinder's search, may not be internally accurate but the trends are clear (whatever error there may be it would be of the same magnitude for all decades searched).
A smal sample, the frequency of "novel":

1945-1958 = 836
1960-1974 = 7716
1975-1989 = 44911
1990-2004 = 318963

The other searches were done for:

"new procedure"
"new protocol"
"new AND novel"!!!!---it is sad that someone would actually use this!

The last one is particularly funny, as it means "accomplished with little effort", implying that "anyone can do it". Not sure why people use it.
I can only hope that in my younger years I have not committed this kind of affrontery to print (although I probably may have)...!!!

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41. anon among us on November 2, 2012 10:01 AM writes...

Anyone else find the juxtaposition of this discussion of 'hype' to the discussion of Bradner somewhat poetic?

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42. bad wolf on November 2, 2012 10:05 AM writes...

Thanks for the many comments, Dr. Hudlicky. I have a new hero. Perhaps some of these articles could be combined and expanded into a full book?

Looking back at Derek's previous post i see many people extolling the virtues of DoE, in the midst of several other comments expressing interest and requesting citations or texts they can use to learn the techniques. These requests were never answered.

So, if someone has a way to learn DoE that they can share, please do so. If they just want to brag that they've been doing it all along, please refrain.

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43. Chemjobber on November 2, 2012 11:08 AM writes...

bw: Search in OPRD for a series of lecture transcripts (lectures -> papers) where they go into the details of DoE. Circa 1997-2000 where they go into it pretty closely.

Excellent question, btw.

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44. stop on November 2, 2012 11:20 AM writes...


Get "Way of Synthesis" its a great read.

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45. Chemjobber on November 2, 2012 11:32 AM writes...

bw: Wrong decade. Click on my handle to see one of the ones I was thinking of.

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46. fng on November 2, 2012 12:11 PM writes...

bad wolf,

a good start are the following:
Statistics for Experimenters, Design, Innovation, and Discovery - Hunter

Design and Optimization in Organic Synthesis - Carlson

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47. S. on November 2, 2012 12:48 PM writes...

Especially for total synthesis, I think that you are all just missing the point. It's like asking a chef, "oh you used 2 gr of salt and 400 gr of meat, how many gr is your amazing dinner you cooked?". For me it's all about the new discoveries, the new disconnections, the new reactivities and the novel structures that every group is building... It's all about the endeavors that all synthesis people know to love and hate and survived to say their story, but I guess not everybody can appreciate that so keep on hating on us for a yield or a melting point, you are all better scientists than us after all...

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48. paperclip on November 2, 2012 1:16 PM writes...

I just Googled "new and novel." 4.49 million results! Of course, they're not all about chemistry, but still, yikes!

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49. Joe Q. on November 2, 2012 1:31 PM writes...

@47. S.

Does the romance of total synthesis justify "selective" or outright fraudulent reporting of yields, purity, etc.? This is what people like Hudlicky (and many commenters here) are concerned about, and I don't think they are "missing the point".

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50. MadForit on November 2, 2012 2:34 PM writes...

Very intelligent post, really.
I'm shocked about how hard is nowadays publish something good that doesn't contain in the title the words: nano whatever, self assembly, bioorthogonal, hairpin, DNA strand displacement and so on.
Is not only about the lack of content in the papers (but catchy title as said) , but how sad it is that science became fashion. and fashion is following a trend, science should be progress, not self gratification during conferences.

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51. bad wolf on November 2, 2012 3:39 PM writes...

Thanks chemjobber, stop and fng! Something i can sink my teeth into.

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52. oopalfrootz on November 2, 2012 3:51 PM writes...

I'm very interested to hear about this time when chemistry did not have trends. Exactly how old are you' MadForIt, as fashions in science have been reported for hundreds of years...

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53. oopalfrootz on November 2, 2012 3:51 PM writes...

I'm very interested to hear about this time when chemistry did not have trends. Exactly how old are you' MadForIt, as fashions in science have been reported for hundreds of years...

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54. Canageek on November 2, 2012 3:55 PM writes...

MadForit: You missed 'green'

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55. newnickname on November 2, 2012 4:19 PM writes...

@50 and others: A while back, Derek posted a link to a very funny template document for an Abstract Submission for some Conference (that I don't recall). The authors were "A. B. Black, C. D. Schwartz, D. E. Nero, E. F. Fekete and G. H. Cerny" from the University of Utopia, Nanotown, Utopia.

The subject matter was a "grantproposalo-selective approach" to a library of [almost every buzz-word under the sun].

I wonder if they got funded?

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56. RLR on November 2, 2012 7:05 PM writes...

Way back in the late 70's, I had Danishefsky for the second semester of undergraduate org. chem. (It was so quaint then, that full professors had to teach UNDERGRADUATES!!!). On a regular basis he would refer to a synthesis as 'elegant'. I got the idea that the epitome of organic chemistry was to be considered elegant, like a fashion model or dancer.

Does he still do this? He would also regularly refer to 'garden variety aldehydes and ketones'.

As for current chemical buzzword nirvana - attend the ACS Green Chemistry Conference, held every June. Several years ago, I attended a talk about the facile reduction of xylene using gold nanoparticles coating with an ionic liquid nano-layer, carried out in another ionic liquid. The person was honest and showed the yield of cyclohexane to only be about 50% or so. Otherwise, the talk was a mishmash of every current greenish-nanoish chemical trend.

And don't forget click chemistry!

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58. Anonymous on November 3, 2012 5:06 AM writes...

Not objecting to the point being made but ignoring the fact that flash chromatography became routine in the decade analysis seems a bit retarded. And making any analysis while ignoring that is even more retarded. And purifying 500 g and 0.5 g are really different as well. A process group will happily throw away 20% yield rather than result to chromatography. So a paper directed at making 50 mgs and 50 kilos are going to have different yields and different goals. And sometimes the 50 mg reaction gave a better yield than the 50 kilos because one of them put it through a column and one of them filtered it on a lap filter. Duh.

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59. madForit on November 3, 2012 5:11 AM writes...

@53: you're right, i'm quite young. I assume that fashion have always been part of science, but is not becoming a bit too much?

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60. GladToMoveToProcess on November 3, 2012 8:49 AM writes...

@58: Flash chromatography certainly changed how small scale synthesis is done. Maybe we could come up with a new yield measure, something like "grams of product divided by grams of silica" or "...divided by liters of ethyl acetate."

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61. yolo_chemist on November 3, 2012 10:24 AM writes...

Good read!

As a young chemist I have used a few of these "bad words" before in papers (although i'm not really an organic chemist), but not to a horrible extent.

This article is good for conciseness raising about using these types of words and practices, and I will make sure to be extra careful in the future!

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62. bad wolf on November 3, 2012 6:16 PM writes...

Okay, i found my nomination for ODing on the key words. This is the title and abstract from a recent JACS paper:
"De Novo Asymmetric Synthesis of ... Using Atom-less Protecting Groups" ... highly efficient de novo route ... overall efficiency ... judicious use of asymmetric catalysis and synthetic design... green principles ... bidirectional use of highly stereoselective catalysis ... chemoselective ... atom-less protecting groups ... anomeric directing group ... atom-economical ... divergent set ...only 12 steps...35 stereocenters ...

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63. eugene on November 3, 2012 7:21 PM writes...

So, interesting for me since this post shows up in time for the latest Buchwald 'correction'.

Yields inflated since a column was probably done after the reaction to get those 'clean' NMR spectra. But maybe the crude yield was used, at best. Oh well, the first author is now a professor so it worked out.

Especially relevant to the previous discussion on Pd couplings. Those things like to give you product distributions and different ligands giving such dramatic selectivities in so many different substrates was truly a great achievement. Oh well, I guess it was wrong. Would the paper have still been published with correct yields and selectivities?

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64. eugene on November 3, 2012 7:33 PM writes...

Of course, I shouldn't really talk too much. I've been guilty of some things... even though I report 'accurate' yields. I've used single runs for 'official' yields after making the stuff a few times and being too lazy to record the yields the first few times since I wanted to use it for the next reactions right away and I didn't know if the material would turn out useful and publishable or not. Then I would just do one reaction and if it looks by eye to be about the same ballpark, record the yield for it and report it. Hey, at least it's not inflated. Also the ever popular, make a compound at the end of a project after just for the Elemental (that wasn't used for NMR spectra or yield stuff).

Damn, I'm still too close to my youth to forget my transgressions... But this Buchwald correction seems, way too excessive for me. I was pretty much always of the thinking of "tt" #39. Who really cares what the yield is at the academic paper point as long as it's in the general ballpark and the compound is more or less pure? If industry needs it, they'll optimize it much, much better. It's a waste of time for researchers who are being hounded by bosses to do more and more research to be repeating reactions so many times to get a good 'statistical spread'.

And I've always liked to use NMR for yield determinations with internal standard since I'm lazy and I hate isolating stuff. This idea never seemed to fly by the bosses though, except for one paper where it was impossible to measure yield otherwise.

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65. eugene on November 4, 2012 4:26 AM writes...

Also on combustion analysis, I don't think it's such an excellent idea as the article claims. A good number of my compounds are air sensitive so unless I send to a company that measures it out in the glove box and puts it into the instrument without it having contact air, it's useless. And by the time I do send it out for combustion analysis and it costs a lot of money, I better make sure that my compound is really pure and it is what I think it is by other methods. Each sample costs a lot of money and takes a long time to ship and for them to actually measure it. Then, because the guys don't want to lose our business, I don't put it past them to fudge the findings. That's why sometimes we used to send a sample and put a different expected composition. Just to test the company. One of them failed the test actually.

And then, JACS and co. require

Combustion analysis is useless if it's a technique that we use right at the very end because a journal requires it and if it requires ridiculous values that are within instrumental error. I don't think enough professors appreciate this. Especially not some editors of ACS journals. If it was something we used during research to determine the nature or purity of a compound, then I could see how it would be useful. As it is, I take an NMR (or EPR), and try to recrystallize the stuff or get its mass spec/IR, and while I do this I put a small sample aside for EA at the end of a project (if it will be necessary).

Combustion analysis would actually make more sense in Organometallics (which are my compounds that are air sensitive) as it's often hard to separate the compound from various salts that do not show up in the NMR and you can't even be 100% sure it's pure when you have a crystal. With organics, which are extracted in non-polar solvents, and then an NMR is taken, I don't see how it is useful at all, but is instead an expensive waste of time for all involved.

Melting points I haven't had to bother about that much, but I remember there was one reviewer who insisted I get melting points for all my complexes that are not air-sensitive. So, after discarding about 60% of them, proceeded to watch the rest turning into black powder inside a melting point tube. Genius. Although one of them did melt and re-solidify amazingly. I'm not sure it's a really useful data point though.

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66. Cecil on November 4, 2012 9:38 AM writes...

@56. I had Sam for graduate level synthesis about 6 years ago. He quite often referred to a synthesis as elegant, with the warning that "beauty is in the eye of the reader". But my take is that for a few rare breeds (Sam, EJ, KC) synthesis is art in a rbf. So while the word, and many others are overused, I think for those guys, they really mean it. They see beauty in the formation of a bond. Most others, are just trying to sell their work.

But to get to your question. He has dropped the fruity language...for military references. "Field-tested reactions", "propelling behind enemy lines", and other ridiculous statements.

Pretty much, the guy is extraordinarily esoteric, I always viewed it as a necessary quirk in a field that takes itself to serious.

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67. simon on November 4, 2012 3:43 PM writes...

some of the hype is so imbedded it almost goes unnoticed. Why for instance is carrying out the same reaction as published previously but using a new reagent publishable, whereas reacting two new partners together using the reagent which has already been published considered trivial? The consequence is that we have for instance >18 reagents published to catalyze the Michael addition of morpholine to acrylonitrile (even though it goes spontaneously if you have few minutes). Meanwhile medicinal chemists search in vain for some conditions which react a very wide range of partners without to much fuss (say in >30 yield)

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68. Ed on November 5, 2012 3:59 AM writes...

Even simple the simple job of calculating a yield is frequently botched. Over a fairly extended career, I've found that roughly 5-10% of yields are miscalculated.

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69. Hap on November 5, 2012 8:48 AM writes...

When I was in grad school, we tried not to order large amounts of reagents that we didn't need very much of not because of the expense of the reagents but because of the cost of disposing of what we didn't use. Particularly in a total synthesis which requires large amounts of material out the outset to get even a measureable amount of final product, and where multiple routes will likely be necessary to get there (where the presence of good data on the purity and identity of a compound would be most useful), it seems like it would be a hard sell to advisors (and to funding agencies) to make the kinds of quantities of intermediates and products in a total synthesis necessary to have full chemical workups.

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70. HOMO-LUMO on November 6, 2012 9:27 AM writes...

As people have pointed out with his contribution Prof. Hudlicky (whom I saw in Prague this June but is a shame didnt spoke about this) have provided a significant contribution to make people more aware and conscious about good scientific practices in synthesis however this is just a definition of the symptoms of the disease rather than the causes.

To address the causes is simple:

1) Double-blinded refereeing (refereed and referees don't know their respective identities)

2) Professionalisation of the referees. In a publication some of the key experiments should be checked in the lab of the referee.

3) Change in the national and supranational funding bodies agencies policies to fund science.

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71. Anonymous on November 6, 2012 12:46 PM writes...

Double blinded refereeing (above) is a superb idea! Especially given the likes of Buchwald retractions as shown above, it'd be interesting to see what happened. It would be amazing if it could be implemented though I'd assume people would have issues with it for some reason or other.

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