A Simple and Effective Protocol for the Pechmann Reaction to Obtain 4-Methylcoumarin Derivatives Using a High-Speed Mixer Ball Mill Process

Round 1

Reviewer 1 Report

Manuscript entitled ''  A simple and effective protocol for the von Pechmann reaction 2 to obtain 4-methyl-coumarin derivatives using a high-speed 3 mixer ball mill process '' by

 Kouznetsov  et al. deals with the development of mechanochemical method for synthesis of coumarin derivatives by the employment of von Pechmann reaction . 

The article is well-written and easy to follow. The reference section gives a good literature overview and it is appropriate. There is high quality in this paper and it is of general interest to readers of Chemistry, particularly the ones dealing with organic synthesis, heterocyclic chemistry, and green chemistry. Hence, I would suggest that the manuscript should be accepted for publication in Chemistry with minor changes.

Points to address:

-The authors should in the introductory section better delineate the current protocol from mechanochemical Pechmann reaction published in Green Chem. 2022, 24(6), 2429–2437. This could be given in the visual form in Figure.

- Mass spectral data and elemental analysis data should be added to the Electronic Supplementary Information (ESI).

Tables 2 and 3 state that the identity of the products 3a-g was confirmed by their IR, 1H NMR, 13C NMR, mass spectral data and elemental analyses. However, mass spectral data are missing from ESI, as well as the description of the MS instrumentation. In addition, elemental analysis data are not given in SI.

- Supplementary Information (ESI): 1H NMR spectrum of (3b) is merged together with 13C NMR spectrum - these spectra should be given separately and with better resolution

- For all products, 1H and 13 C NMR spectra (pictures) should be given in ESI

Minor editing required

Author Response

Please see the attached file.

Author Response File: Author Response.pdf

Reviewer 2 Report

This manuscript describes the use of mechanical ball-milling to prepare coumarin derivatives in the presence of InCl₃ with the Pechmann condensation reaction. As the authors note, mechanochemical methods have already been used to avoid the energy-intensive, solution-based routes traditionally used to synthesize coumarins. The chief interest here is in preparing 4-methyl derivatives, and in particular, 7-amino-4-methyl-coumarin, a fluorescent probe. The principal value in the manuscript is in the optimization studies undertaken that minimize catalyst use while maintaining yield. In general, the paper is suitable for publication in Chemistry, and will be read with interest by the synthetic organic community. There are a few items that the authors should attend to first, however:

1)    The equipment used is termed a “mixer mill” (e.g., line 105), but this term often refers to equipment that can deliver higher energy and especially, has higher capacity than the dental amalgamator described in the manuscript (the largest jar has 2 mL capacity). None of the coumarins were prepared in greater than 0.5 g yields, so it is unclear whether the optimized conditions will still be appropriate at a larger scale. The readers should at least be notified that the catalyst/ball size/time conditions are designed for small-scale reactions and may not be applicable if scaled up.

2)    The finding that a larger ball size leads to higher yields (page 5, lines 184–190) is not particularly surprising. It has been known for some time that larger balls lead to increased energy input per collision (Emmerling, F., et al. Org. Process Res. Dev. 2017, 21, 655); the Emmerling paper could be referenced.

3)    The weight of the stainless-steel balls used in grinding should be specified (not all 304 steel is the same).

Typos/usage:

The English needs to be addressed throughout the manuscript, with too many instances to list separately.

One item that is reflected in the title of the paper itself, however, is the inconsistent use of the term “(von)Pechmann reaction”. Although “von Pechmann” is given in the title, it repeatedly alternates with “Pechmann”. For example, on the first two pages, it is “von Pechmann” on lines 29 and 59, but “Pechmann” on lines 33, 47, and 72. (Note that the Keywords list contains “Pechmann reaction”.) Usually, the type of reaction being discussed in the manuscript is referred to as a “Pechmann condensation” (as on lines 153 and 168); I am not familiar with the use of the term “von Pechmann reaction”, even though I realize that it is named after Hans von Pechmann. In any case, the authors should use consistent terminology throughout the paper.

See above.

Author Response

Please see the attached file.

Author Response File: Author Response.pdf