New 2-(2,4-Dihydroxyphenyl)benzimidazolines
Round 1
Reviewer 1 Report
This paper reports the synthesis and characterization of a couple new 2-(2,4-dihydroxyphenyl)benzimidazoline compounds. Benzimidazole-based compounds are of interest in the field of medicinal/biological chemistry and the two molecules symnthesized bu y the authors represent an potentially interesting contribution to this field. Both compounds are fully and conveniently characterized. I suggest publication of this paper, subjected to a couple of revision.
1) Scheme 1 is not clear and poorly readable and should be adequately corrected by the authors (an error in its insertion in the paper or in the generation of the pdf file has probably occurred).
2) ESI mass spectra of the relevant compound 5a and 5b, cited in the paper main text, should be added within the supporting information.
Author Response
Response to Reviewer’s comments
Dear Reviewer, thank you for your timely review and decision on our manuscript. We are grateful for your correct opinion and encouraging scientific conclusion.
1) Scheme 1 is not clear and poorly readable and should be adequately corrected by the authors (an error in its insertion in the paper or in the generation of the pdf file has probably occurred).
Response: The Scheme 1 is modified in the main text of the manuscript. The pdf. conversion is already done correctly in the revised version of the manuscript.
2) ESI mass spectra of the relevant compound 5a and 5b, cited in the paper main text, should be added within the supporting information.
Response: ESI mass spectra of compounds 5a and 5b do not give information about their structural fragmentation but only on the base mass peak of the products. In this regard, we did not consider it is necessary to introduce them within the supporting information. The mass peaks completely correspond to those for the expected structures and are described in Materials and Methods section:
(5a) HRMS m/z (ESI): calcd for C19H19N2O6- [M-H]- 371.1249, found 371.1250;
(5b) HRMS m/z (ESI): calcd for C21H23N2O6- [M-H]- 399.1562, found 399.1564;
Author Response File: 
Author Response.docx
Reviewer 2 Report
The authors described the synthesis and fully characterization of two 2-(2,4-dihydroxyphenyl)benzimidazolines. I consider that the manuscript meets all requirements to be published in “Molbank” after minor revision. Additional suggestions and comments are included: (1) See lines 12 and 76. 1D and 2D NMR instead of 1D, 2D 1H, 13C-NMR. (2) See introduction. The authors mention that “In this context we recently reported one-pot synthesis of various 2-hydroxyphenylbenzothiazolines as potential antimicrobials [30], as well as the synthesis of new quercetin hybrids with radical scavenging profile [31]”. The most relevant values might be included to complement the paragraph. (3) See Scheme 1. It is overlapped (see PDF version). In addition, the yield, reaction time, and solvent of each step might be included. (4) See Table 1. The solvent might be included. (5) See line 64. two equivalents instead of two excess. (6) See lines 74-75. The authors mention that “Analytically pure samples of monosubstituted benzimidazolines were isolated by column chromatography on silica gel”. The sentence “analytically pure samples” should be carefully revised because you can speak about purity with a chromatogram obtained by HPLC. (7) See lines 76-88. The NMR analysis looks a little confusing and general. It should be improved. It is very important to explain the proton and carbon signals of both aromatic rings. (8) See lines 76-88. The IR analysis might be included. (9) See lines 76-88. The UV-Vis analysis might be included. (10) See lines 118 and 136. The letters “d” and “H” should be in italics. (11) See 3. Materials and Methods. The compounds 5a and 5b are new. Thus, UV-Vis data might be included. (12) HMRS spectra of compounds 5a and 5b might be included in the Supplementary Material (13) UV-Vis spectra of compounds 5a and 5b might be included in the Supplementary MaterialAuthor Response
Response to Reviewer’s comments
Dear Reviewer, thank you for your timely review and decision on our manuscript. We are grateful for your positive opinion and encouraging recommendations. Most of them have been taken into account in the manuscript revision.
(1) See lines 12 and 76. 1D and 2D NMR instead of 1D, 2D 1H, 13C-NMR.
Response: It is modified in the main text of the manuscript.
(2) See introduction. The authors mention that “In this context we recently reported one-pot synthesis of various 2-hydroxyphenylbenzothiazolines as potential antimicrobials [30], as well as the synthesis of new quercetin hybrids with radical scavenging profile [31]”. The most relevant values might be included to complement the paragraph.
Response: The most relevant values in the cited studies are included to the manuscript paragraph.
(3) See Scheme 1. It is overlapped (see PDF version). In addition, the yield, reaction time, and solvent of each step might be included.
(4) See Table 1. The solvent might be included.
Response: The Scheme 1 and Table 1 description are correctly revised in the main manuscript version.
(5) See line 64. two equivalents instead of two excess.
Response: It is corrected in the revised manuscript.
(6) See lines 74-75. The authors mention that “Analytically pure samples of monosubstituted benzimidazolines were isolated by column chromatography on silica gel”. The sentence “analytically pure samples” should be carefully revised because you can speak about purity with a chromatogram obtained by HPLC.
Response: The sentence “analytically pure samples” is correctly revised to “Relatively pure samples (TLC)” in the main manuscript version.
(7) See lines 76-88. The NMR analysis looks a little confusing and general. It should be improved. It is very important to explain the proton and carbon signals of both aromatic rings.
Response: The number of proton and carbon signals of both aromatic rings are considerably explained according to 1H-, 13C-HSQC measurements. See lines 128-136 for compound (5a) and 146-154 for compound (5b) in Materials and Methods section.
(8) See lines 76-88. The IR analysis might be included.
Response: The IR analysis also gives us enough evidence for proving the structure of the analyzed molecules. The IR bands correctly correspond to the expected structural fragments for 5a and 5b. The additional text in Results and Discussion section is added.
(9) See lines 76-88. The UV-Vis analysis might be included.
(11) See 3. Materials and Methods. The compounds 5a and 5b are new. Thus, UV-Vis data might be included.
(13) UV-Vis spectra of compounds 5a and 5b might be included in the Supplementary Material.
Response: The structure of the newly obtained compounds is fully characterized by the primarily used spectral data analysis including 1D, HSQC NMR, IR and MS. Therefore, we believe that additional techniques would not lead to new essential information on the available structural fragments. We consider that the used spectral data adds fair bit of knowledge to the exact structure of the new compounds, including the future perspectives of structure discovering of various N-acylbenzimidazolines.
(10) See lines 118 and 136. The letters “d” and “H” should be in italics.
Response: It is fixed in the revised manuscript version.
(12) HMRS spectra of compounds 5a and 5b might be included in the Supplementary Material
Response: ESI mass spectra of compounds 5a and 5b do not give information about their structural fragmentation but only on the base mass peak of the products. In this regard, we did not consider it is necessary to include them within the Supplementary Materials section. Thus the MS spectra are announced in Materials and Methods section in the main manuscript text.
Author Response File: Author Response.docx
Reviewer 3 Report
Stremski and al describe the synthesis of diethyl 2-(2,4-dihydroxyphenyl)-1H-benzo[d]imidazole-1,3(2H)-dicarboxylates from benzimidazoles, ethyl chloroformate and resorcinol in dichloromethane. The final derivatives were full characterized.
Some improvements are required before publication.
The English language must be checked.
Some inconsistencies:
Line 104: 10 mL/mmol of what?
Lines 59 and 111: the description of table 1 is not clear at all. It refers to the last step and not to the full reaction sequence.
Check the appearance of scheme 1.
Author Response
Response to Reviewer’s comments
Dear Reviewer, thank you for your effort to provide timely review and decision on our manuscript. The suggestions have been taken into account in the manuscript revision.
Line 104: 10 mL/mmol of what?
Response: It is improved in the main text of the manuscript.
Lines 59 and 111: the description of table 1 is not clear at all. It refers to the last step and not to the full reaction sequence.
Check the appearance of scheme 1.
Response: The scheme 1 and the text of table 1 description are corrected in the main text of the manuscript.
Author Response File: Author Response.docx
