Improved Process for the Continuous Acylation of 1,3-Benzodioxole

Round 1

Reviewer 1 Report

The manuscript of Oreste Piccolo et al reports on the use of a heterogeneous Brønsted acidic catalyst for the acylation of 1,3-benzodioxole in a continuous flow reactor.

A similar process has been reported recently under batch conditions by other authors (ref 13) and there is one example for a continuous flow experiment in a patent submitted by the latter group.

The authors of the present report found the elevated temperature used in the patent unsuitable for continuous flow experiments, but this can be caused by several factors. At the same time, I feel that a detailed report on continuous flow experiments could be published.

At the same time, the manuscript discloses very few data. No exact data are given for batch experiments (e.g. Table 1). The analytical method for the determination of the concentration of starting material and product is described very carefully, so relevant data could have been added. No exact data can be found for the experiments with either other metal-salt catalyst or SiliaBond Propylsulfonic Acid that are said to have been tested under batch conditions.

Beside good conversion and selectivity, the lifetime of the catalyst is also an important issue in a continuous reaction, so the activity at least for a couple of hours on stream should be tested.

As a summary the present paper can be published only after major revision.

Some other remarks and typos:

page 1 line 15: substoichiometric

page 1 line 39: could be recycled twice instead of worked for three times

(to be precise: in the original publication it was recycled four times, with only a little loss of activity in the last two cycles)

page 1, line 41: submitted a patent application independently of us

page 1 line 42: induced us instead of pulsed us

page 2 line 45: were not reproducible instead of were not possible to duplicate

page 4 lines 130,131: the mass spectra of the byproducts are not given correctly (m/z/rel. intensity)

page 5 line 187 propionyl chloride

page 6 line 238 Aquivion

Some minor typos should be corrected and some of the wording might be changed

Author Response

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Author Response File: Author Response.pdf

Reviewer 2 Report

In this manuscript, Piccolo and colleagues present their findings on the continuous acylation of 1,3-benzodioxole, employing a recyclable heterogeneous substechiometric catalyst. Several aspects of the text pose challenges for both readers and myself in comprehension. Therefore, I recommend a significant revision before considering the acceptance of this manuscript in Molecules.

Please find detailed comments below:

1. The reference [2] is unclear and difficult to comprehend. Further clarification or revision is necessary.

2. In the abstract, the statement "In a short time (30 min), the conversion was about 73% with a selectivity of about 60% of the acylated product" should be revised to include exact data rather than approximate values for clarity.

3. In the sentence, "The main impurity was 1,3-benzodioxole that can be separated by distillation and recycled in the present industrial process," consider using "The unconverted starting material" instead of "The main impurity" for improved clarity.

4. It is advisable to include a scheme in the background section to illustrate the drawbacks of previous methods and highlight the advantages of the current work.

5. The term "selectivity" requires clarification in this manuscript. It is suggested that the authors explicitly define it, possibly as the ratio between yield and conversion, supported by real and exact data and a clear description.

6. Regarding Table 3, it is unclear whether the yields provided are GC yields or isolated yields. If the data represents GC yields, please include the isolated yields for some optimal conditions to enhance the comprehensibility of the results.

please see the Comments and Suggestions for Authors

Author Response

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Author Response File: Author Response.pdf

Reviewer 3 Report

According to the abstract, the catalyst maintained its reactivity and selectivity for at least 5 cycles, but I didn't see the reusability and recycling potential of the catalyst graphically.

In the several times, it has been written "100°C, 20°C, 250°C, …" that it should be "100 °C"

The names of all compounds must be carefully and must be in italics, [d] should be [d] "1-(benzo[d][1,3]dioxol-5-yl)propan-1-one (in the several times).

The format of references is not the same.

It is ok.

Author Response

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Author Response File: Author Response.pdf

Round 2

Reviewer 1 Report

The introduction has been rewritten and now describes well the backgorund. Some data are disclosed on the preliminary experiments obtained with Zn- Aquivion (although exact data on other metal containig catalysts and SilicaBond Sulfonic Acid are still missing and they are only evaluated as less effective (tor the former) and a promising alternative (for the latter)).

The catalyst si shown to have good activity even after 6 hours on stream.

some minor points have also been corrected.

Reviewer 2 Report

Accept in present form