Na₂SO₃-Promoted Heck Coupling and Homo-Coupling of Arylhydrazines at Room Temperature

Round 1

Reviewer 1 Report

Comments and Suggestions for Authors

The authors here represent an important study done for C-C Coupling utilizing arylhydrazines as starting material, the work was represented in a good manner but some issues need to be clarified before publication in catalysts such

1. in the introduction part the author should cite the following reference 

https://doi.org/10.1016/j.poly.2020.114924

2. the authors utilize sodium sulfite as a promotor for the reaction, the proposed mechanism is not proven in which the formation of sulfur is not resealable, authors should find a way to  prove it 

3. Authors should try sodium thiosulfate also.

4. The aryl hydrazine used is aryl hydrazine hydrochloride, are authors trying free aryl hydrazine? or is an acidic medium required?  

Author Response

As for the comments from Reviewer 1,   

The authors here represent an important study done for C-C Coupling utilizing arylhydrazines as starting material, the work was represented in a good manner but some issues need to be clarified before publication in catalysts such

1. in the introduction part the author should cite the following reference 

https://doi.org/10.1016/j.poly.2020.114924

√ Thank you for the professional suggestions. We have added this reference as Reference 7.

2. the authors utilize sodium sulfite as a promotor for the reaction, the proposed mechanism is not proven in which the formation of sulfur is not reasonable, authors should find a way to prove it.

√ Following your constructive advice, we attempted to use more precise mass spectrometry to monitor for the potential formation of elemental sulfur. However, regrettably, we were unable to detect any elemental sulfur. We also reviewed a vast array of literature and found no reports of sodium sulfite oxidizing phenylhydrazine. Consequently, we revised the proposed mechanism. Based on previous research, we suggest that sodium sulfite likely plays a dual role in the reaction process: it serves to stabilize the intermediate diazonium salt and is also capable of coordinating with palladium (II). We have thoroughly revised the mechanism accordingly. We are grateful for your suggestions.

3. Authors should try sodium thiosulfate also.

√ Yes, we have tried sodium thiosulfate as an additive, but the reaction did not yield the expected product. The specific results can be found in Table 1, entry 17.

4. The aryl hydrazine used is aryl hydrazine hydrochloride, are authors trying free aryl hydrazine? or is an acidic medium required?  

√ Yes, we have indeed attempted to involve arylhydrazine directly in the reaction, and it has yielded comparable results. However, due to the difficulty in preserving arylhydrazine as it is prone to deterioration, and the materials available on the market are all the corresponding arylhydrazine hydrochloride salts, in order to facilitate the operation of the reaction, we have used arylhydrazine hydrochloride salts as the raw materials for the reaction.

Reviewer 2 Report

Comments and Suggestions for Authors

The manuscript by Du, Liu and Luo describes Pd-catalyzed mild Heck reaction and homo-coupling of arylhydrazines promoted by Na₂SO₃. This represents a very useful method as it works with broad range of alkenes and arylhydrazines.

 

In the interest of synthetic chemists, the authors should include the results of Heck reaction with unactivated alkenes.

 

Moreover, I would suggest the authors to test few highly electron-rich arylhydrazine for their developed transformations. Since the corresponding highly electron-rich diazonium salts would be explosive in nature and it would justify the importance of the developed method.

 

Finally, the reference for Teck-Peng’s work is missing (Page 1, line 36) and reference 14 should be translated to English.

 

I would recommend accepting this manuscript upon above revisions to meet the high standard of the Catalysts.

 

 

 

Author Response

As for the comments from Reviewer 2,   

The manuscript by Du, Liu and Luo describes Pd-catalyzed mild Heck reaction and homo-coupling of arylhydrazines promoted by Na2SO3. This represents a very useful method as it works with broad range of alkenes and arylhydrazines.

In the interest of synthetic chemists, the authors should include the results of Heck reaction with unactivated alkenes.

√ Thank you for the professional suggestions. We have indeed tried using p-methylstyrene and p-methoxystyrene, two unactivated alkenes, as substrates, but the yields from the reactions were low, only in the twenties, as shown in Scheme 1 (3k and 3l).

 Moreover, I would suggest the authors to test few highly electron-rich arylhydrazine for their developed transformations. Since the corresponding highly electron-rich diazonium salts would be explosive in nature and it would justify the importance of the developed method.

√ We attempted to use p-methoxyphenylhydrazine hydrochloride as a substrate, but the reaction results were quite complex and difficult to separate and purify. It is possible that the highly electron-rich arylhydrazine is too reactive, which is not conducive to participating in the palladium-catalyzed process. We have also added the relevant results to the manuscript (Page 3, line 99).

Finally, the reference for Teck-Peng’s work is missing (Page 1, line 36) and reference 14 should be translated to English.

√ We have added Teck-Peng’s work as reference 16, and in addition, the Chinese reference have been translated into English.

 I would recommend accepting this manuscript upon above revisions to meet the high standard of the Catalysts.

Round 2

Reviewer 2 Report

Comments and Suggestions for Authors

Liu, Luo and co-authors have revised the latest manuscript according to the provided suggestions. Therefore, I would recommend for the publication in Catalysts.