Eco-friendly methoximation of aromatic aldehydes and ketones using MnCl2.4H2O as an easily accessible and efficient catalyst

Methoximes are important as a class of intermediates and products, among fine chemicals and specialties. The development of a new, facile and efficient method for their synthesis is reported. The methoximes were properly accessed from the corresponding aromatic aldehydes and ketones in good to excellent yields, under mild conditions, employing the inexpensive and environmentally friendly MnCl2.4H2O as a catalyst (at low loading and without the addition of ligand), in EtOH at 50°C. The scope of the process was systematically assessed.


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Decision letter (RSOS-201654.R0) The editorial office reopened on 4 January 2021. We are working hard to catch up after the festive break. If you need advice or an extension to a deadline, please do not hesitate to let us know --we will continue to be as flexible as possible to accommodate the changing COVID situation. We wish you a happy New Year, and hope 2021 proves to be a better year for everyone.

Dear Dr Bracca:
Manuscript ID: RSOS-201654 Title: "Eco-friendly methoximation of aromatic aldehydes and ketones using MnCl2.4H2O as an easily accessible and efficient catalyst" Thank you for submitting the above manuscript to Royal Society Open Science. Your paper was sent to reviewers and their comments are included at the bottom of this letter. I apologise that this has taken longer than usual.
In view of the concerns raised by the reviewers, the manuscript has been rejected in its current form. However, a new manuscript may be submitted which takes into consideration these comments.
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Your resubmitted manuscript should be submitted by 13-Jul-2021. If you are unable to submit by this date please contact the Editorial Office.
We look forward to receiving your resubmission. On behalf of the Subject Editor Professor Anthony Stace and the Associate Editor Dr Annette Trunschke ********************************************** REVIEWER(S) REPORTS: Associate Editor Comments to Author (): RSC Associate Editor: Comments to the Author: There are two conflicting expert opinions, Reviewer 1 recommends rejection due to lack of novelty, Reviewer 2 recommends acceptance after minor revisions. But Reviewer 2 also asks for comparison of the available work with the state of the art. This reinforces my decision to recommend rejection of the manuscript. The authors may resubmit. However, they should then provide a powerful justification of what is new about the paper and what new insights it will provide for catalysis research in general.

RSC Subject Editor:
Comments to the Author: (There are no comments.) Reviewers' Comments to Author: Reviewer: 1 Comments to the Author(s) The paper reports an eco-friendly methoximation of aromatic aldehydes and ketones using MnCl2 4H2O as an easily accessible and efficient catalyst. This work collects standard data on the target subjects, but any exciting aspects are not well included. This is just the addition of new one example without conceptual large innovative steps. Most of the presented data are just standard data on what we usually collect in similar research. In addition, it is not very general and deep comparisons. This work may have values as the addition of new data sets for the specialized research community, but do not have large impacts. With these reasons, I do not recommend the publication of this work.
Reviewer: 2 Comments to the Author(s) In this work, a manganese(II)-catalysed methoximation reaction for aromatic aldehydes and ketones based on the easily available MnCl2.4H2O reagent was developed. The transformation, which is of considerable substrate scope, does not require the addition of an external ligand and features a low catalyst loading. I think this is a good work, providing interesting results and advance in this catalysis field. Thus, I recommend it to publish after minor revisions.

Can authors give a comparision with the benckmark catalysts previously reported in literatures ?
Author's Response to Decision Letter for (RSOS-201654.R0) See Appendix A.

RSOS-210142.R0
Review form: Reviewer 1 Is the manuscript scientifically sound in its present form? Yes

Recommendation?
Accept with minor revision (please list in comments)

Comments to the Author(s)
The authors have addressed the novelty of this work compared to previous literature. This work describes the utilization of manganese(II) chloride as a catalyst for methoximation of aromatic aldehydes and ketones. This work can be accepted after the following minor revisions: 1. Why MnCl2.4H2O provides the best catalytic activity for methoximation of ketones compared to other manganese salts? 2. How about the purity of the manganese chloride salt? Does the purity influence the catalytic activity? 3. Comparison with other catalysts reported in the literature for methoximation of aldehydes and ketones should be provided.

Do you have any ethical concerns with this paper? Yes
Have you any concerns about statistical analyses in this paper? Yes 6 Recommendation? Accept as is

Comments to the Author(s)
The revised version seems fine.

Decision letter (RSOS-210142.R0)
We hope you are keeping well at this difficult and unusual time. We continue to value your support of the journal in these challenging circumstances. If Royal Society Open Science can assist you at all, please don't hesitate to let us know at the email address below.
Dear Dr Bracca: Title: Eco-friendly methoximation of aromatic aldehydes and ketones using MnCl2.4H2O as an easily accessible and efficient catalyst Manuscript ID: RSOS-210142 Thank you for submitting the above manuscript to Royal Society Open Science. On behalf of the Editors and the Royal Society of Chemistry, I am pleased to inform you that your manuscript will be accepted for publication in Royal Society Open Science subject to minor revision in accordance with the referee suggestions. Please find the reviewers' comments at the end of this email. I apologise it has taken longer than usual to be able to send you this decision.
The reviewers and handling editors have recommended publication, but also suggest some minor revisions to your manuscript. Therefore, I invite you to respond to the comments and revise your manuscript.
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Supplementary files will be published alongside the paper on the journal website and posted on the online figshare repository (https://figshare.com). The heading and legend provided for each supplementary file during the submission process will be used to create the figshare page, so please ensure these are accurate and informative so that your files can be found in searches. Files on figshare will be made available approximately one week before the accompanying article so that the supplementary material can be attributed a unique DOI. ************************************* RSC Associate Editor Comments to the Author: (There are no comments.) ************************************** Reviewer comments to Author: Reviewer: 1 Comments to the Author(s) The authors have addressed the novelty of this work compared to previous literature. This work describes the utilization of manganese(II) chloride as a catalyst for methoximation of aromatic aldehydes and ketones. This work can be accepted after the following minor revisions:

Decision letter (RSOS-210142.R1)
We hope you are keeping well at this difficult and unusual time. We continue to value your support of the journal in these challenging circumstances. If Royal Society Open Science can assist you at all, please don't hesitate to let us know at the email address below.

Dear Dr Bracca:
Title: Eco-friendly methoximation of aromatic aldehydes and ketones using MnCl2.4H2O as an easily accessible and efficient catalyst Manuscript ID: RSOS-210142.R1 It is a pleasure to accept your manuscript in its current form for publication in Royal Society Open Science. The chemistry content of Royal Society Open Science is published in collaboration with the Royal Society of Chemistry.
The comments of the reviewer(s) who reviewed your manuscript are included at the end of this email.
Please see the Royal Society Publishing guidance on how you may share your accepted author manuscript at https://royalsociety.org/journals/ethics-policies/media-embargo/. After publication, some additional ways to effectively promote your article can also be found here https://royalsociety.org/blog/2020/07/promoting-your-latest-paper-and-tracking-yourresults/.
Thank you for your fine contribution. On behalf of the Editors of Royal Society Open Science and the Royal Society of Chemistry, I look forward to your continued contributions to the Journal. We have received the message containing your decision with regards to our manuscript (RSOS-201654). As you mentioned in the mail, there are two conflicting opinions, but you have indicated that your decision was based on the lack of a performance comparison, asked by both Reviewers and the opinion of Reviewer 1 (lack of novelty), whose exact words were: "any exciting aspects are not well included", "without conceptual large innovative steps" and "it is not very general and deep comparisons […???]").
We also thank your answer to our mails, sent in order to clarify some points before submitting our revision. Through your today's message ("I can confirm that unfortunately there was indeed an administrative error whereby the Supporting Information file was not supplied to the reviewers"), we have confirmed the source of a big part of the reviewers' requests.
Regarding the Supporting Information file, I would like to offer a plausible explanation and my apologies, if needed. The originally submitted manuscript required some language and text polishing to pass the technical check. We conjecture that at the time the polished version was uploaded, the Supporting Information file accompanying the original submission was somehow deleted and not reuploaded, so it was not available for review. Hence the requests made by both reviewers.
In order to provide a proper answer to both reviewers, this revised version is uploaded along with the corresponding Supporting Information file, which includes the couple of detailed Tables (see pages S30-S32) found in its original version. The Tables contain the requested comparison for the same compounds we synthesized, at the state of the art. In one of the Tables a comparison with the general literature is made, whereas in the other, we compared the performance of the Mn(II)-based method with that of our previously published Ce(III)-based approach.
The first Table clearly reflects the importance of our findings and the benefits of our method compared with the general literature (reduced amounts of reagents, lower temperature, less time, better yields, avoidance of objectionable reagents/solvents, etc., and even an easier work-up). Perhaps our method does not get all the records (reduced..., lower..., less…, better…) simultaneously and in all cases, but a quick look at the Table and comparison with the results in the paper (or in the second Table) should clearly inform the reader that our method makes a difference. In addition, drawbacks of existing methods and the need of alternative and improved methodologies are now more clearly and extensively stated in the manuscript.
In addition, in the comparison with the state of the art it should be also taken into account that the method has several positive distinctive features: 1-It is eco-friendly by design, since MnCl2.4H2O and NaOAc are classified as GRAS chemicals [compare for instance with a single titanium based paper, or even with our own Ce(III) method]; 2-It employs the less toxic and inexpensive ethanol as solvent (MeOH and 2-PrOH are more expensive and more toxic); 3-It is comparatively very efficient (in general, better than available alternatives, or a suitable complement for them); 4-It uses an economic and easily accessible catalyst, at a low catalyst load and without the requirement of a special external ligand (these aspects were correctly captured by Reviewer 2), also leaving some room for improvement (out of scope of the current manuscript). Therefore, we understand that these Tables, two key pieces of information, should fully satisfy both reviewers.
Regarding the novelty issue raised by the first reviewer, at least the following aspects mentioned in the manuscript should be taken into account: 1-Some more expensive aniline derivatives have been developed for use in the area of biorthogonal chemistry. However, they have specific features and requirements (compatible with cells life, dilute solutions, useful at essentially neutral pH, etc.). Besides them, there are essentially no studies regarding the catalysis/acceleration of the methoximation reaction, as confirmed by an additional Reaxys search. Our work is novel because it comes to fulfil an important objective need for catalytic methoximation options.