I recently published a chapter of my PhD thesis as a full paper in RSC Advances. The reviewers' comments are worth sharing. I'd like to thank the editors of RSC advances for their professional handling of the situation. Things could have gone badly for all concerned if not for their careful and thoughtful efforts.
My article is titled "Bromo–nitro substitution on a tertiary alpha carbon—a previously uncharacterized facet of the Kornblum substitution". It is a complex subject and thus became a very long article of 18 pages. It was very polished by the time we submitted it. About one month after submission we received the following response:
| Thank you for your submission to RSC Advances, published by the Royal Society of Chemistry. I sent your manuscript to reviewers and I have now received their reports which are copied below. We sought an additional report on this occasion as we felt that there was insufficient information from the first two reports to make an informed decision. I have carefully evaluated your manuscript and the reviewers’ reports, and the reports indicate that some revisions are necessary. Please submit a revised manuscript which addresses all of the reviewers’ comments. Further peer review of your revised manuscript may be needed. When you submit your revised manuscript please include a point by point response to the reviewers’ comments and highlight the changes you have made. Full details of the files you need to submit are listed at the end of this email. Editor. REVIEWER REPORT(S): Referee: 1 Recommendation: Reject Comments: This manuscript describes a very specialized work and the kinetic study is of moderate importance. The manuscript is too long and presented in an inattractive way. I do not recommend publication. Additional Questions: Does the work significantly advance the understanding or development in this field? : No Are the conclusions of the work convincing and sufficiently supported by experimental evidence?: No Is the experimental section sufficiently detailed to allow others to reproduce the work?: Yes Are the reported claims adequately discussed in the context of the literature?: Yes Are the number of tables and figures in the manuscript appropriate and clear?: No Referee: 2 Recommendation: Major revisions Comments: The authors have reported a Kornblum reaction on a tertiary carbon next to a carbonyl group and have examined the reaction kinetics carefully. In addition they have also proposed several possible mechanisms. The results are interesting and should be published. However, I do think that the manuscript needs a major overhaul in order for it to be accepted by the journal of RSC Advances. One major problem associated with the manuscript is the drawings. Since the authors mentioned that part of it was taken from a Ph. D thesis, it is understandable for the poor quality of drawings. However, for a publication in a privileged journal such as RSC Advances, the authors need to produce better quality figures. Some of the bond angles are just random. Please redraw figures 2,3,13,14,15 and 16. They also need to adjust the size of all drawings to match the font size of the text. In table 1, entries 31 and 33, the two entries “benzyl in place of phenyl” and “butyl in place of phenyl” are not appropriate since they are not R groups. Additionally the language used in this manuscript is too casual to be in a scientific article, please change some of the everyday phrases used here and there. Additional Questions: Does the work significantly advance the understanding or development in this field? : Yes Are the conclusions of the work convincing and sufficiently supported by experimental evidence?: Yes Is the experimental section sufficiently detailed to allow others to reproduce the work?: Yes Are the reported claims adequately discussed in the context of the literature?: Yes Are the number of tables and figures in the manuscript appropriate and clear?: Yes Referee: 3 Recommendation: Accept Comments: The Kornblum substitution represents the replacement of a halogen atom by a nitro group on an organic molecule. Historically, this reaction has been discovered in more than half a century ago, and has been frequently employed to prepare aliphatic nitro compounds. Although using primary and secondary alkyl halides can produce corresponding products in moderate to high yields, related reactions with tertiary halides receive much less success. In this manuscript, authors reported a Kornblum substitution reaction occurring on tertiary alkyl halide sites alpha to an anilide carbonyl, which can afford products in 70-99% yields. Regarding the debate on mechanisms of the Kornblum substitution for tertiary alkyl halides, authors has investigated from the perspective of substitution rates for substrates with different functionalities. They proposed a negatively charged transition state during the process comparing to typical SN1/SN2 mechanisms for Kornblum reactions, as the Hammett plots showed a positive ρ value. Additional Questions: Does the work significantly advance the understanding or development in this field? : Yes Are the conclusions of the work convincing and sufficiently supported by experimental evidence?: Yes Is the experimental section sufficiently detailed to allow others to reproduce the work?: Yes Are the reported claims adequately discussed in the context of the literature?: Yes Are the number of tables and figures in the manuscript appropriate and clear?: Yes |
We took a close look at all of the comments and wrote the following statement to address the comments and describe changes that we made.
| We have read the comments made by the three reviewers and we have done our absolute best to address these. We remain open to our article being published in RSC Advances. While it is our view that referee 1 read our manuscript carelessly and without an open mind, we would be pleased if you would pass on our thanks to referees 2 & 3 for their careful and thoughtful work. We explain below why we disagree with the sentiment of referee 1. We here address the reviewers’ comments and state any changes made. Referee 1: This manuscript describes a very specialized work and the kinetic study is of moderate importance. The manuscript is too long and presented in an inattractive way. I do not recommend publication. · The kinetic study was necessary for the Hammett plots in order for us to infer a negatively charged transition state and show that this reaction goes by way of a different mechanism to standard Kornblum substitutions. It also serves to give chemists who try this reaction in the future an idea of how quickly to expect the reaction to be complete. · We acknowledge that the manuscript is long, but it is our view that, given the complex nature of the subject material, a long article was necessary in order to fully describe and investigate. As the title states, this is a previously uncharacterized facet of a name reaction. This meant that a review into the original works and a great deal of data both had to be included in detail. While we have endeavoured to keep it as pithy as possible, we feel that any further culling of material would diminish the impact of the work. · It disappoints us that Referee 1 found our mode of presentation to be inattractive. But since the referee does not describe in what way they feel the manuscript to be inattractive, it is impossible for us to remedy. Referee 2: The authors have reported a Kornblum reaction on a tertiary carbon next to a carbonyl group and have examined the reaction kinetics carefully. In addition they have also proposed several possible mechanisms. The results are interesting and should be published. However, I do think that the manuscript needs a major overhaul in order for it to be accepted by the journal of RSC Advances. One major problem associated with the manuscript is the drawings. Since the authors mentioned that part of it was taken from a Ph. D thesis, it is understandable for the poor quality of drawings. However, for a publication in a privileged journal such as RSC Advances, the authors need to produce better quality figures. Some of the bond angles are just random. Please redraw figures 2,3,13,14,15 and 16. They also need to adjust the size of all drawings to match the font size of the text. In table 1, entries 31 and 33, the two entries “benzyl in place of phenyl” and “butyl in place of phenyl” are not appropriate since they are not R groups. Additionally the language used in this manuscript is too casual to be in a scientific article, please change some of the everyday phrases used here and there. · We feel that Referee 2’s comment that “Some of the bond angles are just random” is an overstatement. We have had a close look at the bond angles in all of our figures and we can find only one that needs a very minor adjustment—the alkene shown on the bottom right of figure 2. We have updated this figure to give the alkene a bond angle of 120°. The Referee asks for us to re‑draw figures 2, 3, 13, 14, 15 and 16. As mentioned above we have re-drawn figure 2 with a slight correction to the bond angle of the alkene. Figure 3 however has nothing wrong with the bond angles. In fact we have drawn these same two compounds in our 2014 paper that was published in RSC Advances. This paper is reference number 10 in the manuscript. For the full version see: [M. J. Leonard, A. R. Lingham, J. O. Niere, N. R. C. Jackson, P. G. McKay and H. M. Hügel. Alternative synthesis of the anti-baldness compound RU58841. RSC Advances, 2014, 27, 4, p14143–14148.]; you will note that in figure 5 of this paper the bond angles are identical to what is drawn in figure 3 of our current manuscript. Figures 13–16 are our suggested mechanisms. We have drawn here transition state intermediate species that, by necessity, have some non-standard bond angles. These non-standard bond angles have been kept to a minimum. They are not ‘random’ and drawing them any other way would make the depiction of these species ambiguous and unreadable. · We would like to address Referee 2’s comment that “Since the authors mentioned that part of it was taken from a Ph. D thesis, it is understandable for the poor quality of drawings.”. While the content was taken from Matthew’s PhD thesis, all of the figures were re‑drawn for this manuscript. We therefore have changed the preamble near the top of page 1 slightly, so as to add the word ‘content’. So “The following is taken, in part, from the PhD thesis of the primary author, Matthew Leonard.” has been changed to “The following content is taken, in part, from the PhD thesis of the primary author, Matthew Leonard.”. · The Referee states that “They also need to adjust the size of all drawings to match the font size of the text.”. Does Referee 2 mean to ask us to change the atom font size to match that of the text? This would make the atom labels unusually small and very difficult to read. Or does the referee want the images made smaller? We again feel that this would make the images hard to follow in what is a very complex piece of subject matter. Either way we feel that this request is a curly one that is not easily remedied and does not need remedying in the first place. Anyone who has worked for a long time in the field of synthetic organic chemistry would know that atom sizes and their fonts can hardly ever be matched to the font size of the text. The atom and font sizes need to be presented in whatever way is appropriate for the reader to be able to easily comprehend them along with the surrounding text. We feel that we have done this and that Referee 2 is being difficult by making this request. We therefore have left all of the drawings in the figures ‘as is’. · We know that benzyl and n‑butyl are not R groups but we placed them in Table 1 so as to save space, as we were aware that ours was already a very long article. Given Referee 2’s comment, we have given further thought the inclusions of compounds 31–34 in Table 1. We have come to the conclusion that we disagree with Referee 2 on this matter. It is not ambiguous to describe these compounds as “benzyl in place of phenyl” and “n‑butyl in place of phenyl” because the image of the backbone of the compound library moiety is placed right beside these two entries. We also briefly describe the use of these two compounds in the text immediately below. We feel therefore that a chemist who reads this article will find it easy to understand what we mean. It is important that these four compounds be left in Table 1 as this table denotes compound numbers for all of the novel compounds that are characterized at the end of the article. Any alteration to the way these compounds are described in Table 1 would add extra length to the article without conveying any more information to the reader. As we feel that unnecessary inclusions should be avoided, we have left this section ‘as is’. · We have tried to use scientific language as much as possible without losing any of the meanings that we wished to convey. We have combed through the manuscript and found that any of the language that may appear casual at first is in fact necessary in order to convey our meanings to the reader with the greatest possible brevity. Referee 3: The Kornblum substitution represents the replacement of a halogen atom by a nitro group on an organic molecule. Historically, this reaction has been discovered in more than half a century ago, and has been frequently employed to prepare aliphatic nitro compounds. Although using primary and secondary alkyl halides can produce corresponding products in moderate to high yields, related reactions with tertiary halides receive much less success. In this manuscript, authors reported a Kornblum substitution reaction occurring on tertiary alkyl halide sites alpha to an anilide carbonyl, which can afford products in 70-99% yields. Regarding the debate on mechanisms of the Kornblum substitution for tertiary alkyl halides, authors has investigated from the perspective of substitution rates for substrates with different functionalities. They proposed a negatively charged transition state during the process comparing to typical SN1/SN2 mechanisms for Kornblum reactions, as the Hammett plots showed a positive ρ value. · We thank Referee 3 for putting so much thought into our findings. It is an excellent affirmation for us to know that the way in which we presented this complex topic could be readily comprehended. |
One week later we received the following email from RSC Advances:
| Thank you for submitting your revised manuscript to RSC Advances. After considering the changes you have made, I am pleased to accept your manuscript for publication in its current form. I have copied any final comments from the reviewer(s) below, for transparency. You will note that the previous reviewer (2) has recommended major revisions. However, given that their grievances revolve mainly around the overall presentation of the manuscript, as opposed to pertinent issues regarding the discussion or experimental work, it is my opinion that further revision at this stage would be redundant and would only delay publication. Please note that if you have requested Accepted Manuscript publication we will publish your article shortly and send you an email once it is available online. We will also email you information on how to access your RSC Advances article proofs shortly. Editor. REVIEWER REPORT(S): Referee: 2 Recommendation: Major revisions Comments: The author has not addressed all the problems raised before. Instead he has tried to argue his way out. I don’t know whether the author has downloaded the PDF version of his paper or not, the quality of the overall paper is not that great. Clearly the drawings are too big and some of the drawings are ugly. Please just download any JACS paper and see how they present their drawings. As for the two entries in Table 1, it seems that the author does not know the meaning of “precision”. If benzyl or butyl is not a R group, then they should not be in that box. In light of all the above, I can not recommend its acceptation by the journal. Additional Questions: Does the work significantly advance the understanding or development in this field? : Yes Are the conclusions of the work convincing and sufficiently supported by experimental evidence?: Yes Is the experimental section sufficiently detailed to allow others to reproduce the work?: Yes Are the reported claims adequately discussed in the context of the literature?: Yes Are the number of tables and figures in the manuscript appropriate and clear?: No |
I wrote back to RSC Advances:
Dear Editors,
That is great news! We are very pleased to have our paper published in RSC Advances. We can see that the referees comments would have made the matter unclear and we'd like to thank you for taking an interest and looking so closely and so carefully at our paper.
That is great news! We are very pleased to have our paper published in RSC Advances. We can see that the referees comments would have made the matter unclear and we'd like to thank you for taking an interest and looking so closely and so carefully at our paper.
| Bromo–nitro substitution on a tertiary alpha carbon—a previously uncharacterized facet of the Kornblum substitution. Matthew J. Leonard, Peter G. McKay and Anthony R. Lingham. RSC Advances, 2015, 5, page 76401 - 76418. Received 26-Jul-2015, Accepted 03-Sep-2015. DOI: 10.1039/C5RA14798K. | ||
