Monday, July 7, 2014

Do industrial chemical reactions languish in obscurity?

With reference to the mention of my original work on proline catalysis in the ACS national award vignette for Benjamin List, it is stated that “the reactions’ mechanics were ill defined, and they therefore had been widely viewed as exotic exceptions to the prevailing dogma that only enzymes and metal complexes can act as highly enantioselective, synthetically useful catalysts” (C&EN, March 17, page 49). 
In other words, it seems the Hajos discovery slowed scientific progress. The fact is that despite early patent filing, it took five years before our paper was published in a prominent ACS journal in 1974. Eleven years later, Claude Agami and associates in Paris were the first to name this proline-catalyzed Robinson annulation the Hajos-Parrish reaction (Chem. Commun. 1985, DOI: 10.1039/c39850000441). 
It is possible that a great number of researchers originally overlooked our discovery. This is most likely not because of ill-defined mechanisms but because it resulted from industrial rather than academic research. However, the real giants of synthetic organic chemistry did recognize its value and used it. One outstanding example is the posthumous paper of Robert Burns Woodward in the total synthesis of erythromycin (J. Am. Chem. Soc. 1981, DOI: 10.1021/ja00401a049). 
I wish to emphasize that at age 88 I am not seeking recognition, just unbiased reporting. 
Zoltan G. Hajos
Monroe Township, N.J.
Upon pondering this letter some (and reading the List summary by J.F. Tremblay that Dr. Hajos was responding to), I might suggest another reason that the Hajos paper didn't get enough attention. It seems to me that academic publishing of a new reaction discovery follows a pattern where there are multiple small publications (Org. Letts, what have you) and then a big JACS communication ultimately followed by traveling seminars and review papers and the like. It seems to me that's not the path that successful industrial reactions (and their discoverers) take, where patenting and commercialization are the end-goals.

There's probably a lot of backstory that I'm not understanding here.

UPDATE: What I am saying, I suppose, is this: A modern academic chemistry discovery comes with a human PR machine (the PI) who is incentivized by tenure, grant proposals, etc. to make a lot of noise about their discovery. Seems to me that's less the case for industrialists. Would be interesting to know if professors back in the day were as determined to get the world to know about their work as PIs seem to be today. (Not that it is a bad thing!) 


  1. Anyone else like the throwaway allusion to "the real giants of synthetic organic chemistry?"

    1. Yes, the "real giants of chemistry" publish papers two years after their death. With 48 co-authors. The corresponding author seems to have come to a sad end himself not long afterwards.

      By the way, the writer for the List story doesn't seem to have much of a STEM background himself, so perhaps this slight was more unintentional than "biased".

    2. Honestly, I didn't know about Professor Sakan's fate. I knew about the ill fate of Wallace Hume Carothers (April 27, 1896 – April 29, 1937) the leader of organic chemistry at DuPont, credited with the invention of nylon.
      I agree with bad wolf concerning the "innocence" of the writer; the material furnished to him had to be most likely "biased".

  2. The axiom "Publish or Perish" has been around a long time as gauge for academic success, particularly pre-tenure professorships, therefore not sure that aspect for PI desire to seek attention has drastically changed since "back in the day" (when ever that was).

    I am not clear on why he jumps to interpretation the "discovery slowed scientific progress" related to statements on "ill-defined" mechanisms since even most academic publications typically only offer speculation in the beginning unless happen upon details that can inform how reactions works. As far as Hajos' complaint regarding prejudiced view of industrial verses academic research there probably was (and still is) some truth to that being a factor where often publications out of industrial labs, with a few exceptions, are considered less significant relative to a Big Name/Uni source. That general perspective is not entirely unanticipated as CJ points out the paths of publications are quite different where Patents focus more often on establishing IP territory and not as well as truly educating others (forget supposed criteria for enabling those skilled in the arts). Because they have freedom to do so and funding system promotes this strategy academics frequently do perform multiple follow-up and expansions to demo chemistry (or define mechanisms) they discover, which again generate more publications, that facilities application and awareness. Alternatively it is fairly uncommon for industry to have as much elaborations since will have moved on to address new issues of urgency and lack of abundance in citaion would argue that its always harder for recognition to flow the industrial lab way. It was always understood going into industry would likely be more financially rewarding with few citations verses academics would have more papers and possible recognition ( and a few select profs could also garner nice compensation supplemented by consulting to industry).

  3. CJ: I agree in total with Dr. Hajos about his explanation. Another reason was perhaps the inability (or innocence!) of synthetic organic chemists to agree then that an asymmetric center could be efficiently created in a practical way using a chiral catalyst (enzyme like)! It had to wait until early eighties when the plethora of investigators from the likes of Sharpless, Evans etc. to realize that it was a possibility. But, I would rate Dr. Hajos elegant discovery as being seminal that allowed others create chiral catalysts that is continuing even to this day.

  4. I also agree, industrial research has often been less referenced, less read also, especially in the days of printed material. There is also, I believe, the fact that since the "rediscovery" of organocatalysis in the early 2000s, there has been a turf war on who did what first and who deserves the medals. Many, if not most of the editorials, opinion articles and similar shorts are thus biaised by slight twists and bends to favor one's own position. Yes the 'modern' crowd studied mechanisms and details in more depth, but the original papers by Hajos and peers, as well as the then ongoing debates on mechanisms about these reactions, did not overlook questioning how the reaction worked.
    But because a key point in a mechanism, structure, or chain of events leading to a new subfield of our science is often the difference between acknowledgment in paper introductions or by the Nobel committee, these small alterations and subtle influences on how the general chemistry community interprets the timeline of discoveries do matter.