Editorial Reproducibility of Synthetic Results - American Chemical

Nov 21, 2014 - Development are reproducible, since most have been carried out many times by different experimenters in the process of scale up. But I ...
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Editorial Reproducibility of Synthetic Results

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carry out this rewritten procedure in the laboratory. One purpose of the patent system is to provide enough detail for the person of ordinary skill in the art to be able to reproduce the experiment, but that is not as easy as it sounds if the procedure given lacks sufficient detail. OPRD’s current position (and I hope the new editor agrees with this) is that experimental procedures are essential to the main part of the manuscript and should not be relegated to Supporting Information. However, because of limitations of space, the author may not be able to provide all the information (s)he wishes but could provide additional details of the procedure as part of the Supporting Information if he/she so desires. Whilst it is a bit early for New Year’s resolutions, perhaps in 2015 we can all resolve to make sure that experimental write ups are always in sufficient detail to allow easy reproducibility by a skilled worker.

recently came across a letter to the editor of C&E News [Vol. 91(21), p 4], which I had filed in my folder of “ideas for future editorials”. This was a 2013 letter from Rick Danheiser, the editor of Organic Syntheses, in which he pointed out that in the period 1982−1995 about 12% of the recipes submitted to that excellent series for checking had to be rejected because the results could not be reproduced. This was surprising in view of the additional information required by Organic Syntheses and the detailed procedures required to try to ensure reproducibility. We must assume that the authors themselves had reproduced the results at some time in their laboratories (presumably before submission), so the failures were even more surprising. In 2005−7 revised instructions were issued to guide authors in preparing even more detailed experimental procedures than had been required before so that, now, more than 95% of submissions to Organic Syntheses have been checked with satisfactory reproducibility. But why not 100%? Clearly the reactions work in the laboratory of the submitting author using the quality of the reagents in that laboratory and therefore should work in any laboratory if the procedures are written up correctly Hopefully 100% of procedures from Organic Process Research & Development are reproducible, since most have been carried out many times by different experimenters in the process of scale up. But I know, from personal experience, that when procedures are transferred from one laboratory to another, such as during outsourcing, reproducibility can sometimes be an issue. So I would like to hear from any reader who has had difficulty with an OPRD experimental, so that we can alert others and publish a correction to the offending procedure. My first guess is that failure to specify the quality and source of reagents and/or solvents (especially water content) can lead to trace impurities inhibiting or promoting the reaction and hence varying results. Second, rates of addition of reagents and the exact temperature profile during the addition can lead to significant variations. Even if the reaction works according to the prior methodology, the workup procedure may not be described in enough detail (How many times have you read in the literature that the reaction was worked up in the usual way!), particularly when quenches (possibly exothermic?) are taking place and hydrolysis can be an issue. These are all areas where a significant change can have occurred. Even in manufacture, with a validated process and with change control procedures in action we know that batch-to-batch variation can still occur and batch failures occasionally happen, so reproducibility is never 100% (much to the plant manager’s chagrin!). The patent literature also comes in for a lot of criticism, some of it justified, and there have been many court cases where the reproducibility of results has come into question. We (at Scientific Update LLP) are often engaged by lawyers to look at the issue of reproducibility of patented procedures, so one of the first things we are asked to do is to write out in detail what we think the procedure means and only then get someone to © 2014 American Chemical Society



Trevor Laird, Editor-in-Chief AUTHOR INFORMATION

Notes

Views expressed in this editorial are those of the author and not necessarily the views of the ACS.

Published: November 21, 2014 1259

dx.doi.org/10.1021/op500341h | Org. Process Res. Dev. 2014, 18, 1259−1259