Quercetin Hybrids—Synthesis, Spectral Characterization and Radical Scavenging Potential

Round 1

Reviewer 1 Report

Dear Authors,

I really enjoyed the work that you have done. I think that is really interesting and I couldn't find any similar research recently. So, this is wonderful for chemistry science. I have read some papers about C-8 substitutions, but never read about benzazoles derivatives.
Your approach is really easy but also really smart, so this will made a widely-read article. However, I think that you need to h improve the result discussion. I will write some commentaries that I think that could help with your work:
- According to the introduction part, I think that the structure is correct and the number and topicality references are good. Be careful with Figure 1 footnote, where Quercetin is written in capitals.

- Results and discussion are also really good although a little bit short. I would like to ask if you have tried more conditions of the reactions. According to your sentece: "The reaction conditions were optimized by varying ratio of the reagents, temperature and time (Table 1)." it seems that you have done but I haven't read it in the main text. If you have done that, please put some commentaries about that. For example, yield modification in production of product 6a when you change temperature or time. There is no problem if you didn't tried, it is just a suggestion about how parameters can affect the synthesis.

- Have you tried a different solvent? Acetonitrile is a good polar aprotic solvent, but maybe you can enhance the yield testing with DMF.

- There are no comments about NMR results. This is really important to understand the link between the benzazoles and quercetin. It can be found just one 2D experiment in the Supplementary Information. For example, COSY trace between H-6 and H-8 must be vanished, or H-8 signal in 1H-NMR must be disappeared. According to your 1H experiments, it seems that all compounds are correct because 6.40 ppm signal is missing... although I expected a higher deshield. Signal at 93.9 ppm in quercetin 13C experiments is also vanished so this support your theory. Please, just discuss it in the main text.

- It is really a pitty that radical scavenging activity show the same results that natural compound. It is clear that keeping the double bond on benzazole structures is the key. Have you tried to prepare a brominated C-2 benzazole and to apply Heck reaction with quercetin? This way will help you to generate the hybrid with the double bond and enhancing the radical scavenging activity. Maybe this could be useful for your future experiments.

- Why do you apply 80ºC in NMR experiments? This high temperature is uncommon to work with natural compounds and derivatives.

- Elucidation of 6b: Why is CH3 underlined? There are no other protons that could be assigned.

Really good work. Waiting for your future research papers.

Author Response

Dear Reviewer, thank you for your effort to provide timely review and decision on our manuscript. "Please see the attachment" file .docx

Author Response File: Author Response.pdf

Reviewer 2 Report

The manuscript by Stremski and coworkers shows the preparation of Quercetin compounds and their role as potential radical scavenger. The authors have a strong experience and know how in the transformation of benzothiazole and benzimidazole derivatives. Quercetin products were prepared in a fashionable multi-component synthetic approach and they were tested as radical scavenger showing interesting activities. The products were fully characterized and the experimental sections is absolutely well described.

Few typos can be corrected, but the manuscript is surely acceptable in Molbank and I suggest the publication.

Author Response

Dear Reviewer, thank you for your timely review and positive decision on our manuscript. 

Author Response File: Author Response.pdf

Round 2

Reviewer 1 Report

Thank you very much for your answers. The manuscript have been improved after your modifications, and thank you for take into account all my comments. It has been nice to discuss the experiments and results with you.