Iodine-Mediated One-Pot Synthesis of Imidazo[1,5-a]Pyridines

Round 1

Reviewer 1 Report

Comments and Suggestions for Authors

In this paper, the authors describe the efficient one-pot synthesis of 3-phenyl-1-(phenylthio)imidazo[1,5-a]pyridine analogues using 2-aminomethylpyridines, benzaldehydes and sodium benzenesulfinates as starting materials. The obtained compounds were fully characterized. The mechanism of the reaction was also proposed based on experimental data. The manuscript is well-written and can be published in this journal after suggestions/corrections addressed:

1) No ¹⁹F spectra are presented for the compounds 4k, 4q, 4s, 4u.

2) No constant couplings are provided in the ¹³C spectra for aromatic carbons in the compounds 4k, 4q, 4s, 4u (should be doublets).

3) The yield for the product 4t is different in Table 2 and in the experimental part (81% vs 78%), what is correct?

Comments on the Quality of English Language

Moderate editing of English language required.

Author Response

Reviewer: 1

In this paper, the authors describe the efficient one-pot synthesis of 3-phenyl-1-(phenylthio)imidazo[1,5-a]pyridine analogues using 2-aminomethylpyridines, benzaldehydes and sodium benzenesulfinates as starting materials. The obtained compounds were fully characterized. The mechanism of the reaction was also proposed based on experimental data. The manuscript is well-written and can be published in this journal after suggestions/corrections addressed:

1) No 19F spectra are presented for the compounds 4k, 4q, 4s, 4u.

2) No constant couplings are provided in the 13C spectra for aromatic carbons in the compounds 4k, 4q, 4s, 4u (should be doublets).

3) The yield for the product 4t is different in Table 2 and in the experimental part (81% vs 78%), what is correct?

Answer:

1: Thank you for your suggestions. We supplemented the 19F NMR spectra of 4k, 4q, 4s, 4u in the revised SI file.

2: Thank you for your suggestion. We have re-supplied the constant coupling in the 13C spectra of aromatic carbons for compounds 4k,4q,4s,4u in the revised SI document.

3: Thank you for your suggestion. I am sorry for my carelessness, the yield of 4t in table 2 should be 81%, I have revised this.

Author Response File: Author Response.pdf

Reviewer 2 Report

Comments and Suggestions for Authors

In this report, Zhi-Bing Dong and colleagues developed an efficient one-pot method for synthesizing 3-phenyl-1-(phenylthio)imidazo[1,5-a]pyridine analogues. Starting with 2-aminomethylpyridines, benzaldehydes, and sodium benzenesulfinates, the method simultaneously forms C-N and C-S bonds under mild conditions. It features a wide range of substrates, high atom utilization, and accessible starting materials. This approach offers short reaction times, moderate to good yields, and holds promise for creating various biologically or pharmaceutically active compounds. This manuscript is suitable for submission after minor revisions.

 

Comments:

1.      Rewrite all the references provided in the manuscript in the Catalysts journal format for clarity and consistency.

2.      Did you attempt to use different solvents like DMSO, CH₃CN, THF, etc., under the optimized standard conditions from entry no. 16 in optimization table 1 to improve the reaction yield?

3.      Did you explore any synthetic utility for this reaction, and have you also tried scaling it up to the gram scale?

4.      In Supporting Information could you purified compound NMRs 4a, 4d, 4e, 4f, 4i, 4l, 4o, 4p, 4q, 4za. Also make compound name correction in Supporting Information 4aa to 4za accordingly.

Author Response

Reviewer: 2

In this report, Zhi-Bing Dong and colleagues developed an efficient one-pot method for synthesizing 3-phenyl-1-(phenylthio)imidazo[1,5-a]pyridine analogues. Starting with 2-aminomethylpyridines, benzaldehydes, and sodium benzenesulfinates, the method simultaneously forms C-N and C-S bonds under mild conditions. It features a wide range of substrates, high atom utilization, and accessible starting materials. This approach offers short reaction times, moderate to good yields, and holds promise for creating various biologically or pharmaceutically active compounds. This manuscript is suitable for submission after minor revisions.

Comments:

1.Rewrite all the references provided in the manuscript in the Catalysts journal format for clarity and consistency.

2.Did you attempt to use different solvents like DMSO, CH₃CN, THF, etc., under the optimized standard conditions from entry no. 16 in optimization table 1 to improve the reaction yield?

3. Did you explore any synthetic utility for this reaction, and have you also tried scaling it up to the gram scale?
4. In Supporting Information could you purified compound NMRs 4a, 4d, 4e, 4f, 4i, 4l, 4o, 4p, 4q, 4za. Also make compound name correction in Supporting Information 4aa to 4za accordingly.

Answer:

1: Thank you for your suggestion. We have referred to Catalysts journal format to rewrite all the references provided in the manuscript.

2: Thank you for your suggestion. We have tried using different solvents like DMSO, CH₃CN, THF, but the yield was not increased. I would not put this information in the manuscript since the results were not satisfactory.

3: Thanks for your suggestions. We performed the gram scale synthesis of product 4a, and the isolated yield in both weight and percentage were marked with yellow background in the revised manuscript.

4: Thanks for your advice, I have repurified compounds 4a,4d,4e,4f,4i,4l,4o,4p,4q,4za and provided new NMR spectra in the SI file. Corrections have also been made to the corresponding compound names in the supporting information.

 

Author Response File: Author Response.pdf

Round 2

Reviewer 1 Report

Comments and Suggestions for Authors

The authors have revised the manuscript in response to my comments, and I believe that the article is now ready for publication.

Comments on the Quality of English Language

Minor editing of English language required.