Green Chemistry’s Contribution to the Kamal Qureshi Protocol: Comparing Various Activating Modes, the Use of Bentonitic Clay as the Catalyst, and the Use of a Green Solvent

Round 1

Reviewer 1 Report

Comments and Suggestions for Authors

Abstract

The authors should include at least one numerical data point to support the claim that the proposed method is more efficient or sustainable compared to the other mentioned alternatives.

Introduction

Add a more precise statement regarding the novelty of the work, explicitly comparing it with existing methods in the literature (Lines 80–94).

Reformulate the last paragraph with a clear statement of the research purpose (Lines 106–111), ensuring that the objective is explicitly highlighted and articulated with greater precision.

Table 1: It is recommended to add a column with the average performance of each method if available in the literature. It should be specified whether the conditions are solvent-free or require high temperatures for all processes, at least for the most relevant parameters.

Results and Discussion

In the Section 2.1, 3xplain the rationale for the selected parameters and their effect on reaction efficiency (Lines 125–131). Additionally, information on the standard deviation or the number of repetitions should be included to support the reliability of the data. Also, better explain the difference in efficiency between the indicated devices (Lines 136–140).

In Section 2.2, include an explanation of the physical mechanisms behind each method and their impact on the reaction (e.g., how cavitation in US influences reactivity or how differential energy absorption affects the reaction in NIR and MW) (Lines 143–154).

In the Section 2.4, a comparative table with experimental values versus reported literature values should be included for greater clarity.

In Section 2.5, it is necessary to explain why certain aldehydes resulted in higher yields or faster reactions than others, as shown in Table 4. Additionally, a better justification for the need to use FAB⁺-MS in the mentioned cases is recommended, along with a more detailed explanation of adduct formation.

In this chapter, it is also recommended to provide a detailed analysis of a relevant aspect regarding the advantages and challenges of applying this process in the industry (costs, time, required equipment).

Materials and Methods

Although the provided information allows for an understanding of the experimentation conducted, the structuring should be improved, and certain experimental parameters should be justified more clearly. Some lengthy paragraphs could be divided to enhance readability and comprehension. Additionally, it is recommended to subdivide certain sections with subtitles for better content organization.

Likewise, it is necessary to justify the selection of certain reaction conditions, such as the amount of catalyst (10 mg of TAFF®), reaction times, and stirring speeds in the different devices. It should be clarified whether these parameters are based on previous studies or have a specific starting point.

Laso, some information on the analysis conditions, such as temperature, run times, or solvents used, is missing for the analytical techniques (GC-MS, NMR, FAB⁺-MS).

Conclusions

Between lines 306 and 315, the novelty of the mechanocatalytic method should be highlighted in comparison with conventional techniques.

It is also recommended to include a brief section on potential improvements, large-scale optimization, or applications in other reactions. Additionally, it is important to specify whether more environmentally friendly alternatives exist to replace acetone as a solvent.

 

Author Response

Please see the attachment

Author Response File: Author Response.pdf

Reviewer 2 Report

Comments and Suggestions for Authors

The MS by René Miranda Ruvalcaba et al. describes DIM® and several of its analogs (3,3’-diindolylmethanes) synthesis under the green chemistry protocol. Indol-3-yl carbinol was evaluated using mechanochemistry (as the best mode) in comparison with near-infrared and microwave electromagnetic irradiations and ultrasound). The mechanochemical methodology was extended to produce a set of fifteen DIMs. All synthetic protocols are well-presented, the results are green and compared with the literature. The presented data are in the scope of Catalysts and can be published as is.

Author Response

Please see the attachment

Author Response File: Author Response.pdf

Reviewer 3 Report

Comments and Suggestions for Authors

In this study, the authors presented a green chemistry approach to improving the Kamal-Qureshi protocol for synthesizing diindolylmethanes (DIMs), utilizing mechanochemistry (TCh-HSBM) as an energy-efficient activation method compared to ultrasound (US), near-infrared (NIR), and microwave (MW) irradiation. They highlighted the use of a bentonitic clay (TAFF®) as a green catalyst and acetone as a green solvent, while real-time reaction monitoring via GC-MS supports process efficiency. The study contributes to sustainable chemistry principles by optimizing reaction conditions and validating the reaction mechanism, offering potential scalability for pharmaceutical applications. Thus, I suggested that this paper to be accepted after minor revisions. Followed are detailed comments.

1. While mechanochemistry (TCh-HSBM) is presented as the best activation mode, a more detailed quantitative comparison of reaction yields and efficiency between the different activation methods would strengthen the claim.
2. The paper does not address whether the bentonitic clay catalyst (TAFF®) is reusable or how it degrades over multiple reaction cycles. Investigating its long-term stability and regeneration potential would enhance its practical applicability.
3. Acetone is labeled as a green solvent, but further comparison with other bio-based or low-toxicity solvents could confirm whether it is the best choice in terms of safety and sustainability.
4. The blue symbols of “Al” and “Si” in Figure 1 are unclear, a better interpretation is required.
5. The error bar in Figure 2 is weird, it does not look like actual error bars, which need additional attentions.

Author Response

Please see the attachment

Author Response File: Author Response.pdf