Methyl 6,7-Difluoro-2-[(4-fluorobenzyl)sulfanyl]-4-hydroxyquinoline-3-carboxylate
, Irina A. Novokshonova 1, Maxim V. Musalov 1, Svetlana V. Amosova 1 and Oleg A. Rakitin 2,*Round 1
Reviewer 1 Report
Comments and Suggestions for AuthorsIn this manuscript, Rakitin and co-workers describe the synthesis of 6,7-difluoro-2-[(4-fluorobenzyl)sulfanyl]-4-hydroxyquinoline-3-carboxylate. The synthetic method is simple and practical, and the desired product is obtained in a high yield. The experimental section and spectroscopic analysis are solid. Therefore, this work would be suitable for molbank.
Author Response
The authors are grateful to the reviewer for a kind and highly professional review. There is nothing in the review that the authors should respond to.
Reviewer 2 Report
Comments and Suggestions for AuthorsPlease, cf the attached file
Comments for author File: 
Comments.pdf
I have detected only few errors cf scheme titles
Author Response
The authors are grateful to the reviewer for a kind and highly professional review.
Point 1.
The structure of this paper is a little distabilizing since (i) the § concerning the synthesis and the mecanism of the formation of compound 2 is mentionned before the preparation of compound 1, the starting material; (ii) before the § dealing with the formation of compound 1, some perspectives on the possible transformation of precursor 2, based on literature references, are given. In my opinion, the whole paper should be restructured to make it easier to read. Schemes 1, 2 and 3 : « the » is not necessary, it must be removed.
Response from authors.
The paper is restructured according to your remarks. The first paragraph is replaced from the beginning to the end of the "Results and Discussion" section. The paragraph on the preparation of compound 1 is replaced from the end of the "Results and Discussion" section to the beginning. The discussion of the mechanism of the formation of compound 2 is after the data on the synthesis of compound 2. Then comes a paragraph on perspectives of the possible transformation of compound 2 for the preparation of new fluoroquinolone derivatives.
"The" is removed for Schemes 1, 2 and 3:
Point 2.
Line 135 Scheme 3 not 2.
Response from authors.
We are sorry for this misprint. "Scheme 2" was corrected to "Scheme 3".
Point 3.
References. General remark. Homogeneity of doi must be given and according to molbank notes to authors, they have to be cited as: https://doi.org/then the number not doi alone. Ref 1 to 9, 14 and 17 to 20 doi are missing.
Line 208 a space is missing between M. and quinolones.
Response from authors.
The doi data are changed to the https://doi.org/ form. There are no doi data for patent references, all other references contain the https://doi.org/ form. A space between M. and quinolones was made in Line 208.
Point 4.
Experimental section
Assignments of carbons and protons have been made, so, 2D NMR (e.g. COSY, HSQC…) should be added in order to illustrate these assignments.
Concerning Fluorine Assignments, I agree with the fact that the 3 signals corresponds to the 3 F. But how were these assignments made? In fluorine chemistry, only JHF and JFF can be observed. For C15F only JHF ortho and meta exist, as JHF are smaller than JFF, we can consider that the largest signals can be attributed to C6F and C7F, but C6F and C7F present two ortho coupling constants: JFF and JHF and a meta JHF. These two signals could be similar in width. In conclusion, at -115 ppm the signal is probably that of C15F, but for the signals at -126 and -137 ppm, who is who?
Response from authors.
We agree with your consideration of 19F NMR data. Several C-F spin-spin coupling constants (1JC-F, 2JC-F, 3JC-F, 4JC-F, and 5JC-F) are observed in the 13C NMR spectrum of compound 2 and 3JH-F and 4JH-F spin-spin coupling constants are observed in the 1H NMR spectrum of compound 2. The assignment for C6F and C7F was made based on analysis of the JH-F spin-spin coupling constants in the 1H and 19F NMR spectra. The complete assignment of 1H and 13C NMR chemical shifts of compound 2 was carried out by the analysis of values of spin-spin coupling constants (including 1JC-F, 2JC-F, 3JC-F, 4JC-F, and 5JC-F) and a combination of 1D (1H and 13C NMR) and 2D (1H-1H COSY and 1H-13C HMBC) NMR experiments. 1H-1H COSY and 1H-13C HMBC NMR spectra copies are added to the Supplementary Material.
Round 2
Reviewer 2 Report
Comments and Suggestions for Authorsno more comments and suggestions. The paper is accepted for publication
