Efficient and Eco-Friendly Perspectives for C-H Arylation of Benzothiazole Utilizing Pd Nanoparticle-Decorated Chitosan

Round 1

Reviewer 1 Report

In this contribution, Mokhtar and Narasimharao et al. performed an interesting work of  C-H arylation of benzothiazole using Pd@Chitosan catalyst under ultrasonic irradiation. The work has been performed well with a proper design and certainly deserves to be published. Herein, I recommend acceptance of this manuscript. However, I have a minor comment: The introduction is relatively short, which I feel that can be elaborated from the perspective of catalysts via discussing analogous biomass-derived catalyst materials. I believe that this style of discussion will be attractive to the readers. 

Author Response

We appreciate the reviewer's comments and we would like to thank him for his kind recommendation for acceptance.

Reviewer 2 Report

In this manuscript entitled “An efficient and eco-friendly perspectives for C-H arylation of benzothiazole utilizing chitosan decorated Pd nanoparticles”, Mohamed Mokhtar, Katabathini Narasimharao and co-workers described the preparation of Palladium nanoparticles supported on chitosan (named below Pd@Chitosan) as eco-friendly and recoverable catalyst in the ultrasound-assisted direct C-H bond arylation of benzothiazole with aryl iodides and bromides for the synthesis of 2-aryl substituted benzothiazoles. In general, the present work is nice and interesting, and in my opinion it has the potential to be published. However, I think there are various aspects that need to be very carefully addressed before considering its possible acceptance on MDPI Catalysts.

1. First of all, I think that in the introduction the authors should better emphasize the recent interest of synthetic organic chemists in the direct C-H bond arylation reactions under green conditions. In this context, I strongly suggest to add in the bibliography the reference to some very recent reviews on the sustainable protocols for direct C-H bond arylation of (hetero)arenes. Moreover, I think that a broader discussion should be made on the use of non-conventional energy source in direct C-H bond arylation reactions: not only ultrasound-assisted protocols, but also mechanical milling-assisted (DOI: 10.1021/acs.joc.9b01280), IR irradiation-assisted (DOI: 10.1002/cssc.202101070) and of course microwave irradiation-assisted (DOI: 10.1002/chem.201201868) direct arylation reactions. I believe that this point should be well specified in the introduction, even with the support of the above mentioned literature.

2. I think the "Results and Discussion" section needs to be revised. First of all, a first paragraph where authors discuss on the preparation of the catalyst is missing. I know well that the preparation of the catalyst is described in the experimental part on paragraph 3.2, but it is a simple "recipe": in my opinion, a paragraph discussing the preparation method is mandatory. For example, why didn't the authors use the Metal Vapour Synthesis (MVS) method, for the preparation of Palladium nanoparticles? After this first paragraph, the second paragraph should be that one related on Pd@Chitosan characterization. Only after this, the authors should introduce the paragraph "C-H arylation of Benzothiazole", related to the catalytic performance of Pd@Chitosan in the direct C-H bond arylation of benzothiazole.

3. A very important point that, in my opinion, is missing and that it should be introduced in the paper is the palladium loading of Pd@Chitosan catalyst: in other words, the amount of palladium for a given amount of Pd@Chitosan catalyst. This value in my opinion is fundamental, in order to understand the amount of palladium used in the catalytic tests of direct C-H bond arylation: writing that 0.05 g of Pd@Chitosan was used for 2 mmol of benzothiazole (1a) and 2 mmol of 4-iodoacetophenone doesn't mean anything, since the reader does not understand the amount of palladium used in the reaction with respect to the reagents (2 mol%? 5 mol%? or higher?). Therefore, the metal loading of Pd@Chitosan catalyst and the Pd loading in the catalytic tests should be added.

4. Some improvements of Table 1: a) in addition to adding the above mentioned Pd loading for each catalytic test (as I have already written in the point 3 of my report), the authors should add the experimental conditions (mmol of 1, mmol of 2a, temperature, time, etc.) of both US irradiation-assisted and silent reactions, as notes [a] and [b] below the table; b) furthermore, the authors should specify how the yields were determined (pure products after column chromatography or recrystallization purification; determined by 1H-NMR; determined by GC analysis; or other); c) if all the experimental tests (both the US-assisted and the silent ones) were carried out at 80 °C, I believe that the temperature column could be removed, although in that case the temperature must be specified in the experimental conditions of notes [a] and [b] below the table.

5. I noticed some inconsistencies between "Results and discussion" and "Experimental part". In the Results and discussion, authors wrote that equimolar amounts of Benzothiazole (1a) and 4-iodoacetophenone (2a) (2mmol) were used; on the contrary, in the experimental part, a mixture of benzothiazole (1) (0.5 mmol) and aryl halides (0.7 mmol) was used. What is the used amount of the reagents? Furthermore, in the supplementary information, the authors reported only the spectroscopic constants of the products: the weight of each pure product, the yield, as well as the purification conditions are missing.

6. I believe that Scheme 2 and Figure 1 can be condensed into a single Scheme. However, I need some clarification: in the abstract the authors wrote that both iodides and aryl bromides are successfully used in the reaction with benzothiazole. In the optimization of the reaction conditions, the aryl iodide 2a, that is, 4-iodoacetophenone was chosen. In the Scheme 2, the aryl halides were indicated as Ar-X 2a-e, but it is not clear when an aryl iodide and when an aryl bromide was used. This point must be indicated in the new combined Scheme, and also specified in the Supporting Information, related to the preparation of each 2-arylbenzothiazole product 3a-e.

7. One of the weakest points of this work is definitely that concerning the recyclability of the Pd@Chitosan catalyst. It seems a bit curious that the catalyst can be recycled only for one time, providing for the 2nd cycle a yield of the 3a equal to the 1st run, and then no product in the 3rd cycle. First of all, I suggest to extend this part of the work, explaining which model reaction was used for the recycling tests and under which experimental conditions. Furthermore, I believe that other tests need to be carried out (or example hot filtration tests, metal leaching, and so on), in order to understand if metal leaching occurs already during the 1st catalytic cycle, or if a palladium deactivation is observed (for example, due to the coordination of the sulphur atoms of the benzothiadiazole ring).

8. Other minor issues: a) in some points, benzothiazole is indicated as compound 1a, instead of compound 1; b) in some point, benzothiazole was written with the capital letter ("Benzothiazole", instead of "benzothiazole") even if it was not at the beginning of the sentence; c) on lines 237-238, please correct "then A mixture of benzthiazole" with "then a mixture of benzothiazole"; d) in the Supporting Information, the images of 1H-NMR and 13C-NMR of products 3d and 3e are missing.

Author Response

Dear Prof. Dr. Bernadette Chen

We greatly appreciate your kindness that you gave us chance to revise the manuscript ID: catalysts-1876579.

Title: An efficient and eco-friendly perspectives for C-H arylation of benzothiazole utilizing chitosan decorated Pd nanoparticles.

 We keenly revised the reviewed form and modified it according to the reviewer’s comments point by point and we clarify our response at the end of this letter.

We appreciate the reviewer's comments and you could find attached the point by point response to the reviewer's comments.

Kind regards, 

Prof. Dr. Mohamed Mokhtar

Author Response File: Author Response.pdf

Round 2

Reviewer 2 Report

In the revised version of the manuscript “An efficient and eco-friendly perspectives for C-H arylation of benzothiazole utilizing chitosan decorated Pd nanoparticles”, Mohamed Mokhtar, Katabathini Narasimharao and co-workers addressed all the issues listed in my previous report, thus allowing to improve the quality and clarity of the work. I have read this new version very carefully, and I am convinced that the manuscript now meets the standards for publication in MDPI Catalysts, suggesting its acceptance in the present form.