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Short Note
Peer-Review Record

(±)-2-{[4-(4-Bromophenyl)-5-phenyl-4H-1,2,4-triazol-3-yl]sulfanyl}-1-phenyl-1-ethanol

Molbank 2021, 2021(3), M1268; https://doi.org/10.3390/M1268
Reviewer 1: Anonymous
Molbank 2021, 2021(3), M1268; https://doi.org/10.3390/M1268
Received: 28 May 2021 / Revised: 12 July 2021 / Accepted: 2 August 2021 / Published: 6 August 2021
(This article belongs to the Section Organic Synthesis)

Round 1

Reviewer 1 Report

I consider that the manuscript meets all requirements to be published in “Molbank” after major revision. I consider that a better explanation towards preference of major tautomer in solution (NMR) versus solid state (IR) might be improved and clarified for readers because authors have all evidences to support it; however, the explanations are very general. The following comments and suggestions are included:  

(1) See title. (±) instead of (R,S). It might be modified in all manuscript.

(2) See line 13. elemental analysis instead of by elemental analysis.

(3) See introduction. (a) Relevant biological activities related to 4,5-disubstituted-4H-1,2,4-triazole-3-thiol moiety might be included, and (b) relevant synthetic procedures for the synthesis of 4,5-disubstituted-4H-1,2,4-triazole-3-thiol might be explained.    

(4) See introduction. The paragraph corresponding to lines 25-29 as well as scheme 1 should be shifted to results and discussion instead of introduction.  

(5) See lines 41-44. Some relevant references might be included to support it.

(6) See lines 48-51. It is important to include relevant information related to IR spectroscopy, including the frequency of both NH and C=S stretching vibrations.

(7) See scheme 3. The dissolvent might be specified on the arrow.

(8) See line 66. Scheme 4 instead of Schme 4.

(9) See scheme 4. ¿Why did you use ethanol as solvent? ¿which was the yield using methanol as a solvent? It could be included the reason to choose ethanol instead of methanol (¿reactivity versus green solvent?)

(10) The IR, 1D and 2D NMR analysis for explaining the formation of the alcohol 6 from ketone 5 is very general. The structural analysis might be improved.  

(11) The IR, 1D and 2D NMR analysis for explaining the formation of the ketone 5 from thiol 5 is very general. The structural analysis might be improved.  

(12) A short conclusions might be included.  

(13) According to the guideline of “Molbank”, the MS spectrum of compounds 4, 5, and 6 could be included in the Supplementary Material.

(14) See lines 89-96. (a) IR vibration modes might be included, (b) color, melting point, and Rf value including its corresponding eluent might be included, (c) MS data could be included, and (d) I did not find the 2-NH signal in the 15N NMR reporting data ¿why? The 15N NMR analysis might be included in the manuscript to support the preference towards the tautomeric form (4b) (see affirmations into lines 48-51); however, ¿why did you use the name of the thiol tautomer (see line 89)?     

(15) See Materials and Methods. Information about each equipment might be included. See the guideline of “Molbank” or any paper recently published in Molbank.  

(16) See Materials and Methods. I really did not understand the 15N NMR reporting data. For instance: the compound 4 [275.6 (1-N)], compound 5 [175.1 (1-N)], and compound 6 [175.1 (3-N)] ¿Each molecule has three different 15N signals? ¿why do you report only one 15N signal? Although the chemical shifts for compounds 5 and 6 are the same, the assignation is very different. It might be carefully revised to support the major tautomer in solution (NMR) versus solid state (IR and/or NMR).     

Author Response

(1) See title. (±) instead of (R,S). It might be modified in all manuscript.

It has been modified.

(2) See line 13. elemental analysis instead of by elemental analysis.

It has been modified.

(3) See introduction. (a) Relevant biological activities related to 4,5-disubstituted-4H-1,2,4-triazole-3-thiol moiety might be included, and (b) relevant synthetic procedures for the synthesis of 4,5-disubstituted-4H-1,2,4-triazole-3-thiol might be explained.

Relevant biological activities were included.

General relevant synthetic route was included

   (4) See introduction. The paragraph corresponding to lines 25-29 as well as scheme 1 should be shifted to results and discussion instead of introduction.  

The paragraph and scheme 2 (former 1) have been moved to results and discussion.

(5) See lines 41-44. Some relevant references might be included to support it.

In the literature known to us we have not found any reference related to such tautomeric equilibrium to be demonstrated by NMR.

(6) See lines 48-51. It is important to include relevant information related to IR spectroscopy, including the frequency of both NH and C=S stretching vibrations.

The thione-thiol tautomeric equilibrium is shifted in solvent (DMSO-d6) and the IR spectrum is performed in solid pellet. In the solid phase the equilibrium is different and cannot be demonstrated by IR spectra alone.

(7) See scheme 3. The dissolvent might be specified on the arrow.

The solvent has been specified on the arrow

(8) See line 66. Scheme 4 instead of Schme 4.

It has been modified.

(9) See scheme 4. ¿Why did you use ethanol as solvent? ¿which was the yield using methanol as a solvent? It could be included the reason to choose ethanol instead of methanol (¿reactivity versus green solvent?)

EtOH 96% was used according to the literature recipe. A study on NaBH4 reduction using other alcohols was not done in this article.

(10) The IR, 1D and 2D NMR analysis for explaining the formation of the alcohol 6 from ketone 5 is very general. The structural analysis might be improved.  

The explanation of formation of alcohol by reduction of ketone group has been introduced.

 

(11) The IR, 1D and 2D NMR analysis for explaining the formation of the ketone 5 from thiol 5 is very general. The structural analysis might be improved.  

The explanation of ketone formation by S-alkylation of 4-(4-bromophenyl)-5-phenyl-4H-1,2,4-triazole-3-thiol has been introduced.

(12) A short conclusions might be included.  

A short conclusions have been included.

(13) According to the guideline of “Molbank”, the MS spectrum of compounds 4, 5, and 6 could be included in the Supplementary Material.

The HRMS spectra of novel compounds (Ketone and alcohol) have been included in supplementary materials.

(14) See lines 89-96. (a) IR vibration modes might be included, (b) color, melting point, and Rf value including its corresponding eluent might be included, (c) MS data could be included, and (d) I did not find the 2-NH signal in the 15N NMR reporting data ¿why? The 15N NMR analysis might be included in the manuscript to support the preference towards the tautomeric form (4b) (see affirmations into lines 48-51); however, ¿why did you use the name of the thiol tautomer (see line 89)?     

For the compound 4-(4-bromophenyl)-5-phenyl-4H-1,2,4-triazole-3-thiol we consider that it is not relevant to introduce IR data, color aspect, melting point, TLC and HRMS spectra because it is only raw material and not a new compound. Only 1H, 13C and 1H-15N HMBC NMR spectra have been introduced from which this tautomeric equilibrium can be demonstrated.

(15) See Materials and Methods. Information about each equipment might be included. See the guideline of “Molbank” or any paper recently published in Molbank.  

Information about each equipment have been included.

(16) See Materials and Methods. I really did not understand the 15N NMR reporting data. For instance: the compound 4 [275.6 (1-N)], compound 5 [175.1 (1-N)], and compound 6 [175.1 (3-N)] ¿Each molecule has three different 15N signals? ¿why do you report only one 15N signal? Although the chemical shifts for compounds 5 and 6 are the same, the assignation is very different. It might be carefully revised to support the major tautomer in solution (NMR) versus solid state (IR and/or NMR).  

For the compound 4-(4-bromophenyl)-5-phenyl-4H-1,2,4-triazole-3-thiol we have two cross-peak: one at 183.1 ppm corresponding to long range coupling between 4-N and aromatic protons from ortho positions and another at 275.6 ppm corresponding to long range coupling between 1-N and 2-N-H protons which prove the shift of tautomeric equilibrium to the thione form in DMSO-d6.

In the ketone (compound 11, after renumbering) and alcohol (compound 12, after renumbering) we have in 1H-15N HMBC only the cross-peak between 4-N (at 175.1 ppm) and aromatic protons from ortho positions. It was a drafting error with 3-N.

Round 2

Reviewer 1 Report

I consider that the manuscript meets all requirements to be published in “Molbank” after minor revision. Authors performed all modification suggested by reviewers in the manuscript and supplementary material. Only three aspects to have present:  

(1) See lines 22-23, name/lastname of authors and title of the manuscript should be included.

(2) See references, the DOI of each article should be included. Moreover, some references are not unified (see the guideline of “Molbank” or any paper recently published here).

(3) See lines 200-221. The following information should be included in the manuscript according to the guideline of “Molbank” (see any paper recently published here): 

Supplementary Materials: it is ok 

Author Contributions: Investigation, data curation, writing—original draft preparation, X.X.; conceptualization, resources, writing—review and editing, X.X. All authors have read and agreed to the published version of the manuscript. 

Funding: it is ok 

Institutional Review Board Statement: Not applicable. 

Informed Consent Statement: Not applicable. 

Data Availability Statement: The data presented in this study are available in this article. 

Acknowledgments: ?????? (it is optional) 

Conflicts of Interest: The authors declare not conflicts of interest. 

Sample Availability: Not available.

Author Response

(1) See lines 22-23, name/lastname of authors and title of the manuscript should be included.

It's all corrected.

(2) See references, the DOI of each article should be included. Moreover, some references are not unified (see the guideline of “Molbank” or any paper recently published here).

The DOI for each article provided with DOI, has been included to references.

(3) See lines 200-221. The following information should be included in the manuscript according to the guideline of “Molbank” (see any paper recently published here): 

Supplementary Materials: it is ok 

Author Contributions: Investigation, data curation, writing—original draft preparation, X.X.; conceptualization, resources, writing—review and editing, X.X. All authors have read and agreed to the published version of the manuscript. 

Funding: it is ok 

Institutional Review Board Statement: Not applicable. 

Informed Consent Statement: Not applicable. 

Data Availability Statement: The data presented in this study are available in this article. 

Acknowledgments: ?????? (it is optional) 

Conflicts of Interest: The authors declare not conflicts of interest. 

Sample Availability: Not available.

It's all corrected.

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