4-Methyl-7-((2-((5-methyl-1,3,4-thiadiazol-2-yl)thio)ethyl)thio)-coumarin

Round 1

Reviewer 1 Report

The authors described the synthesis of 4-methyl-7-((2-((5-methyl-1,3,4-thiadiazol-2-yl)thio)ethyl)thio)-2 coumarin. I consider that manuscript meets all requirements to be published after major revision. The NMR reporting data should be carefully revised. I recommend including HRMS and IR data to complement these important results. Additional suggestions and comments are included: (1) See lines 10-12, introduction. The redaction of the first paragraph should be improved. (2) See introduction. I consider that some relevant examples of coumarins and 1,3,4-thiadiazole with important biological activities should be drawn in Figure 1. For instance, ¿are there commercially available drugs containing both heterocycles?   (3) See line 18, introduction. The letter “H” should be in italic. It should be modified in the manuscript. (4) See line 21, introduction. According to coumarins with anticancer activity [19-23], the very recent article published can be included (See https://doi.org/10.1016/j.molstruc.2022.134414).    (5) See lines 47-55. A short analysis of the IR spectrum should be included. (6) See 3.2. Synthesis of 2-((2-chloroethyl)thio)-5-methyl-1,3,4-thiadiazole. (a) Chemical shifts of proton signals should be included with 2 instead 3 decimals after the point (i.e. 2.74 instead of 2.741), (b) J in cursive and the unit Hz should be included (i.e. J = 7.1 Hz instead of J 7.1), (c) ppm is absent, among others mistakes. (7) ¹H NMR (600 MHz, CDCl₃) d 2.74 (s, 3H, CH₃), 3.65 (t, 2H, J = 7.1 Hz, CH₂-S), 3.90 (t, 2H, J = 7.1 Hz, CH₂-Cl) ppm. ¹³C{¹H} NMR (150 MHz, CDCl₃) d 15.68 (CH₃), 35.36 (CH₂-S), 42.33 (CH₂-Cl), 163.88 (Cq-2), 165.48 (Cq-5) ppm. Please, it should be used as a guide for the next molecule. (8) See 3.2. Synthesis of 2-((2-chloroethyl)thio)-5-methyl-1,3,4-thiadiazole. HRMS and IR data should be included in both manuscript and Supplementary Material.   (9) 3.3. Synthesis of 4-methyl-7-((2-((5-methyl-1,3,4-thiadiazol-2-yl)thio)ethyl)thio)-coumarin. Information about the recrystallization process should be included (i.e. ¿solvent? and ¿under normal pressure? ¿at room temperature?) (10) 3.3. Synthesis of 4-methyl-7-((2-((5-methyl-1,3,4-thiadiazol-2-yl)thio)ethyl)thio)-coumarin. HRMS and IR data should be included in both manuscript and Supplementary Material.   (11) 3.3. Synthesis of 4-methyl-7-((2-((5-methyl-1,3,4-thiadiazol-2-yl)thio)ethyl)thio)-coumarin. (a) Chemical shifts of proton signals should be included with 2 instead 3 decimals after the point, (b) J in cursive and the unit Hz should be included (i.e. ⁴J = 1.1 Hz instead of ⁴J 1.1), (c) ppm is absent, (d) Chemical shifts of carbon signals should be included with 2 instead 3 decimals after the point, and (e) type of deuterated solvent and frequency should be included in both ¹H and ¹³C{¹H} NMR. (12) See conclusion, lines 150-153. It could be improved because it looks very similar to the abstract. (13) See references. According to the guideline of Molbank, the DOI of each article should be included.

Comments for author File: Comments.pdf

Author Response

To the Editor of

Molbank

Sofia, November 21, 2022

 

Thank you very much for the time you and the other associate Editors have devoted to handle this submission. We are very grateful to you and Reviewer for the help permitting us to improve significantly the manuscript quality.

All corrections in the manuscript, inserted according to the Reviewer’s recommendations, are inserted as Track Changes.

The answers to the Reviewer’s recommendations are listed bellow:

The authors described the synthesis of 4-methyl-7-((2-((5-methyl-1,3,4-thiadiazol-2-yl)thio)ethyl)thio)-2 coumarin. I consider that manuscript meets all requirements to be published after major revision. The NMR reporting data should be carefully revised. I recommend including HRMS and IR data to complement these important results. Additional suggestions and comments are included:

(1) See lines 10-12, introduction. The redaction of the first paragraph should be improved.

(2) See introduction. I consider that some relevant examples of coumarins and 1,3,4-thiadiazole with important biological activities should be drawn in Figure 1. For instance, ¿are there commercially available drugs containing both heterocycles?

The introduction is supplemented according to the suggestions.

(3) See line 18, introduction. The letter “H” should be in italic. It should be modified in the manuscript.

It is now in Italic.

(4) See line 21, introduction. According to coumarins with anticancer activity [19-23], the very recent article published can be included (See https://doi.org/10.1016/j.molstruc.2022.134414).

This reference is inserted; ref. 24.

(5) See lines 47-55. A short analysis of the IR spectrum should be included.

The IR spectrum is briefly described in the text.

(6) See 3.2. Synthesis of 2-((2-chloroethyl)thio)-5-methyl-1,3,4-thiadiazole. (a) Chemical shifts of proton signals should be included with 2 instead 3 decimals after the point (i.e. 2.74 instead of 2.741), (b) J in cursive and the unit Hz should be included (i.e. J = 7.1 Hz instead of J 7.1), (c) ppm is absent, among others mistakes.

These corrections are inserted.

(7) 1H NMR (600 MHz, CDCl3)  2.74 (s, 3H, CH3), 3.65 (t, 2H, J = 7.1 Hz, CH2-S), 3.90 (t, 2H, J = 7.1 Hz, CH2-Cl) ppm. 13C{1H} NMR (150 MHz, CDCl3)  15.68 (CH3), 35.36 (CH2-S), 42.33 (CH2-Cl), 163.88 (Cq-2), 165.48 (Cq-5) ppm. Please, it should be used as a guide for the next molecule.

These corrections are inserted.

(8) See 3.2. Synthesis of 2-((2-chloroethyl)thio)-5-methyl-1,3,4-thiadiazole. HRMS and IR data should be included in both manuscript and Supplementary Material.

HRMS and IR spectra are inserted in the Experimental part and Supplementary Material.

(9) 3.3. Synthesis of 4-methyl-7-((2-((5-methyl-1,3,4-thiadiazol-2-yl)thio)ethyl)thio)-coumarin. Information about the recrystallization process should be included (i.e. ¿solvent? and ¿under normal pressure? ¿at room temperature?)

This information is given at the beginning of sub-chapter 3.4. Crystallography. The temperature and pressure are additionally inserted.

(10) 3.3. Synthesis of 4-methyl-7-((2-((5-methyl-1,3,4-thiadiazol-2-yl)thio)ethyl)thio)-coumarin. HRMS and IR data should be included in both manuscript and Supplementary Material.

HRMS and IR spectra are inserted in the Experimental part and Supplementary Material.

(11) 3.3. Synthesis of 4-methyl-7-((2-((5-methyl-1,3,4-thiadiazol-2-yl)thio)ethyl)thio)-coumarin. (a) Chemical shifts of proton signals should be included with 2 instead 3 decimals after the point, (b) J in cursive and the unit Hz should be included (i.e. 4J = 1.1 Hz instead of 4J 1.1), (c) ppm is absent, (d) Chemical shifts of carbon signals should be included with 2 instead 3 decimals after the point, and (e) type of deuterated solvent and frequency should be included in both 1H and 13C{1H} NMR.

The most part of these recommendations are taken into account. The proton spectra are given with 3 decimals because that is the accuracy of 600 MHz Bruker apparatus used.

(12) See conclusion, lines 150-153. It could be improved because it looks very similar to the abstract.

The conclusions are improved.

(13) See references. According to the guideline of Molbank, the DOI of each article should be included.

The doi numbers are inserted.

 

Faithfully yours,

Prof. Dr. Vanya Kurteva

Round 2

Reviewer 1 Report

The authors described the synthesis of 4-methyl-7-((2-((5-methyl-1,3,4-thiadiazol-2-yl)thio)ethyl)thio)-2 coumarin. The authors performed most of the modifications suggested by reviewers. I consider that manuscript meets all requirements to be published after minor revision. Some suggestions are included: (1) See 3.2. Synthesis of 2-((2-chloroethyl)thio)-5-methyl-1,3,4-thiadiazole. (a) The unit ppm should be included at the end of both ¹H and ¹³C NMR reporting data, and (b) chemical shifts of proton signals should be included with 2 instead 3 decimals after the point like: ¹H NMR (600 MHz, CDCl₃) δ 2.74 (s, 3H, CH₃), 3.65 (t, 2H, J = 7.1 Hz, CH₂-S), 3.90 (t, 2H, J = 7.1 Hz, CH₂-Cl) ppm. (2) See 3.3. Synthesis of 4-methyl-7-((2-((5-methyl-1,3,4-thiadiazol-2-yl)thio)ethyl)thio)-coumarin. (a) The unit ppm should be included at the end of both ¹H and ¹³C NMR reporting data, and (b) chemical shifts of proton signals should be included with 2 instead 3 decimals after the point. (3) See IR reporting data of both compounds 2 and 3. The most important bands should be specified like 1719 (n C=O), 1600 (n C=C), among others relevant bands.   

Author Response

Thank you very much for the time you and the other associate Editors have devoted to handle this submission. We are very grateful to you and Reviewers for the help permitting us to improve significantly the manuscript quality.

We apologise, we did not see the comments of Reviewer 1. Here are our answers:

The authors described the synthesis of 4-methyl-7-((2-((5-methyl-1,3,4-thiadiazol-2-yl)thio)ethyl)thio)-2 coumarin. The authors performed most of the modifications suggested by reviewers. I consider that manuscript meets all requirements to be published after minor revision. Some suggestions are included:

(1) See 3.2. Synthesis of 2-((2-chloroethyl)thio)-5-methyl-1,3,4-thiadiazole. (a) The unit ppm should be included at the end of both 1H and 13C NMR reporting data, and

The units are inserted.

(b) chemical shifts of proton signals should be included with 2 instead 3 decimals after the point like: 1H NMR (600 MHz, CDCl3) δ 2.74 (s, 3H, CH3), 3.65 (t, 2H, J = 7.1 Hz, CH2-S), 3.90 (t, 2H, J = 7.1 Hz, CH2-Cl) ppm.

As answered to Reviewer 2, the proton spectra are given with 3 decimals because that is the accuracy of 600 MHz Bruker apparatus used.

(2) See 3.3. Synthesis of 4-methyl-7-((2-((5-methyl-1,3,4-thiadiazol-2-yl)thio)ethyl)thio)-coumarin. (a) The unit ppm should be included at the end of both 1H and 13C NMR reporting data, and

The units are inserted.

(b) chemical shifts of proton signals should be included with 2 instead 3 decimals after the point.

As answered to Reviewer 2, the proton spectra are given with 3 decimals because that is the accuracy of 600 MHz Bruker apparatus used.

(3) See IR reporting data of both compounds 2 and 3. The most important bands should be specified like 1719 (n C=O), 1600 (n C=C), among others relevant bands.

These two bands are specified. For the rest, we prefer don’t to speculate.

 

Faithfully yours,

Prof. Dr. Vanya Kurteva