Synthesis and Crystal Structures of Halogen-Substituted 2-Aryl-N-phenylbenzimidazoles

Round 1

Reviewer 1 Report

This manuscript ID: molbank-1974915, describes the synthesis of four halogen-substituted 2-aryl-2 N-phenylbenzimidazoles.

The four compounds, bearing bromo- or iodo-substituents in para/meta positions of the phenyl ring, have been characterized by ¹H, ¹³C NMR, UV-vis spectroscopy, and single-crystal X-ray diffraction.

In my opinion, the manuscript is in line with the journal aims. The analyses appear to be clearly described, and communicate the work of the authors.

I recommend publication on Molbank, after the authors address the following comments and minor points. This, in my opinion, can improve the quality of the current version.

-  As reported by the authors the ¹H NMR spectra of the four synthesized compounds show severe overlapping. As reported in figure S1, S3, S5 and S7, all protons show broad, not well resolved signals.

Please explain and provide a specification for this phenomenon.

-  The 1D spectra are of low quality and it is not possible to assign the proton signals based only on these spectra. In my opinion, the only integral values and the number of signals observed in the ¹³C spectra are not sufficient data for this characterization.

I suggest to acquire 2D homonuclear and heteronuclear NMR experiments to perform a reliable analysis that will allow signal assignments.

-   Furthermore, I agree with the authors that the NMR spectra of compounds 1-4 are very similar, but I think that the proton chemical shifts of the para-substituted phenyl (compounds 1 and 3) are different from those of  the meta-substituted phenyl (compounds 2 and 4) and to highlight this a complete proton assignment is necessary.

 

-   Please add the experimental conditions used for NMR spectra acquisition and for UV-vis measurements in the Material and Methods session.

Author Response

Dear colleague,

Thank you very much for careful reading of the manuscript and for your comments. Our responses are presented below:

1. Comment: - As reported by the authors the 1H NMR spectra of the four synthesized compounds show severe overlapping. As reported in figure S1, S3, S5 and S7, all protons show broad, not well resolved signals.

Please explain and provide a specification for this phenomenon.

-  The 1D spectra are of low quality and it is not possible to assign the proton signals based only on these spectra. In my opinion, the only integral values and the number of signals observed in the 13C spectra are not sufficient data for this characterization.

I suggest to acquire 2D homonuclear and heteronuclear NMR experiments to perform a reliable analysis that will allow signal assignments.

-   Furthermore, I agree with the authors that the NMR spectra of compounds 1-4 are very similar, but I think that the proton chemical shifts of the para-substituted phenyl (compounds 1 and 3) are different from those of  the meta-substituted phenyl (compounds 2 and 4) and to highlight this a complete proton assignment is necessary.

 

Reply: We agree with this comment. We measured additional 2D spectra and made the assignment.

 

2. Comment: - Please add the experimental conditions used for NMR spectra acquisition and for UV-vis measurements in the Material and Methods session

Reply: The conditions were added.

Reviewer 2 Report

Review on molbank-1974915 (only crystallographic sections)

 

Refinement procedures and results are sound.

Some minor remarks that should be addressed:

Min/max ΔF values should be included in text para 3.3 on page 5, so looking for supplementary table S1 is not necessary.

Table S2 states the 4 unit cell parameters all measured at equal T = 150 K. Why have the 4 data sets not been collected at equal (low) temperatures? Explain and/or eventually skip table S2.

Atom labelling for compounds 1 and 2 from figure 2 and cif files are not consistent. Those from figure 2 are fine whereas cif labels seem to stem from SHELX-T and should be renamed (then re-deposit).

Author Response

Dear colleague,

Thank you very much for careful reading of the manuscript and for your comments. Our responses are presented below:

1. Comment: Min/max ΔF values should be included in text para 3.3 on page 5, so looking for supplementary table S1 is not necessary.

Reply: The data were added.

2. Comment: Table S2 states the 4 unit cell parameters all measured at equal T = 150 K. Why have the 4 data sets not been collected at equal (low) temperatures? Explain and/or eventually skip table S2.

 

Reply: The table was deleted. Crystal 4 was remeasured at 150 K.

 

3. Comment: Atom labelling for compounds 1 and 2 from figure 2 and cif files are not consistent. Those from figure 2 are fine whereas cif labels seem to stem from SHELX-T and should be renamed (then re-deposit).

 

Reply: Atoms were renamed and the cifs were redeposited.

 

 

Sincerely yours,

Authors

Round 2

Reviewer 1 Report

I appreciate the great efforts that the authors have made in response to my questions and concerns. This revision clarifies almost all the points I raised,  but, in my opinion, there are still issues that could be improved. In particular, for the NMR characterization, again the information is not full.

 In particular, one more  comment I have is that the NMR assignment is still not very well reported, and some experimental details used for the NMR spectra acquisition are not indicated. In the following please find some points I think the authors may still take into account. 

1. Page 2 line 50 The authors say: ‘by using 2D correlation NMR spectroscopy (Figures S7-S9 and S12-S14)’ . Is this referred only to Compound 3 and 4 characterization?  Please clarify.  

2.  Page 4 lines 119-150 Based on the 2D experiments, the chemical shifts should be reported for each proton.

Furthermore, the NMR spectra of all compounds are characterized by peaks with large linewidth, on the contrary the 1D trace along the F2 dimension in 2D spectra seems to have higher resolution. I think that this needs an explanation. Could be this due to technical problems like bad shimming? 

I believe that the spectral characteristics of the complexes are presented correctly, but the data interpretation, especially the NMR characterization, needs further rethinking. While the structure of single crystals is undisputed, usually the structure in solution is also affected by experimental condition, nature of the solvent, conformational equilibrium, etc, that it might make hard the data analysis. And this is the reason why the interpretation of the spectral features needs a deeper analysis to prove the structure in the solid state and in solution in an undoubted way.

Molbank is a communication journal of synthetic chemistry and natural product chemistry and a scope of this journal is the structural elucidation by X-ray crystallography, NMR, etc. of organic, organometallic  compounds and this is the reason for which I encourage the authors to present more NMR details.

Author Response

Dear colleagues,

 

Thank you very much for careful reading of the manuscript and for your comments. Our responses are presented below:

 

Reviewer 1

 

1. Comment: - Page 2 line 50 The authors say: ‘by using 2D correlation NMR spectroscopy (Figures S7-S9 and S12-S14)’ . Is this referred only to Compound 3 and 4 characterization?  Please clarify. 

 

Reply: 2D NMR spectra were recorded for 3 and 4. For 1 and 2, ¹H and ¹³C spectra were assigned similarly. For technical reason, 2D spectra for 1 and 2 were not measured.

 

2. Comment: - Page 4 lines 119-150 Based on the 2D experiments, the chemical shifts should be reported for each proton.

 

Reply: Chemical shifts were reported for each proton, where it was possible and reasonable. For the N-Ph ring, it is difficult to assign signals explicitly to each proton, and, in our opinion, this does not add essential information to elucidate the structures of the compounds.

 

High resolution spectra for 3 and 4 were added. Shimming was fine, but we did not replace the old spectra during the first revision by mistake.

 

Each of the reported compounds 1 – 4 contains three spin systems (halogen-substituted aryl, benzimidazole and N-Phenyl ring). The two former systems were fully assigned based on the obtained NMR data. For the third system, please, see our reply to the comment 2.

For these compounds, it is unlikely to expect conformational equilibrium and/or solvent effect (CDCl₃ was used in all the experiments), so we believe that the set of techniques used in the work undoubtedly confirm their compositions and structures both in solution and in the solid state.

 

Sincerely yours,

Authors