2-(2-(4-Methoxyphenyl)-4,9-dimethyl-7-oxo-7H-furo[2,3-f]chromen-3-yl)acetic Acid

Round 1

Reviewer 1 Report

The synthesis of two novel 7-oxo-7H-furo [2,3-f] chromen-3-yl) acetic acids is reported by means of a three-component reaction developed in one-pot. The article is suitable for publication in Molbank since it includes:

• the preparation of two novel compounds in good yields (68 and 74%)
• a good background about the importance of this family of compounds, and previous synthetic attempts of similar compounds
• a good characterization of them
• reaction mechanism
• comprehensive experimental part including easy to follow procedures

For manuscript improvement, I just suggest:

1. Improve some English language expressions
   1. Page 1, line 8: “we describe a new approach towards the synthesis…” instead of “we elaborated new approach to the synthesis...”
   2. Page 1, line 36: “In the present communication, we report that…” instead of “In the present communication, we have shown that”
   3. Page 1, line 43: “furocoumarin derivatives 4.” instead of “furocoumarin derivatives 4a and 4b.”
2. Page 2, line 44: Have the authors use different amounts of arylglyoxals? The use of a 6-fold excess does not provide a good E factor. The addition of some information regarding the optimal conditions is welcome.
3. Page 1 (lines 13-14) and page 2 (line 70): The product full characterization by ¹H, ¹³C-NMR spectroscopy and high-resolution mass-spectrometry needs to be improved for publication in Molbank, in fact melting point values are also included (one over 300 ºC, I imagine that it did not help under the equipment temperature range). I would additionally include:
   1. Retention factor in a determined eluent, which it could help in the reaction monitorization
   2. Infrared spectroscopy, which would help to assure the presence of determined functionalities (also include the spectra in the supporting information)
4. Page 3, lines 80 and 82: Add the amount in grams for both 2a and 2b: “arylglyoxal hydrate 2 (6 mmol)”
5. Page 3, lines 80 82: “Et3N (6 mmol, 0.61 g)” trimethylamine is a liquid at room temperature, are you sure that you are measuring mg instead of mL? It sounds weird to add a liquid by weight instead of using a micropipette
6. General: use capital letter for L when refereeing to liters (instead of l)

Author Response

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Author Response File: Author Response.pdf

Reviewer 2 Report

This paper reports extension of previous work from this group to furochromene derivatives, and this by using a similar methodology. Although chemistry is properly designed and performed, this paper describes only two new molecules which is clearly not sufficient for a publication, even as a Communication. Further it has clearly no urgent character. Therefore it is obviously to early at this stage to submit such a paper. The reviewer would suggest to extend this work into one or the other possibilities, as indicated below:

• The first, most obvious, would be to screen the scope and limitations of this methodology by looking at different substituents, both on the hydroxycoumains and on the aryl glyoxals (this group has already used around 10 different substrates like this in previous papers…). By having 10-20 examples would make this method significant.
• The second would be to cooperate with specialists to explore the photophysical properties of these new scaffolds. The authors write: «Generally, products of this type are used as active photosensitizers in PUVA (psoralen and UVA) therapy. Thus, furocoumarins can be employed in treatment of various skin diseases [15–22]». Therefore it would be fruitful to explore the properties of these new molecules in these areas.
• In the same way the authors write: «Numerous representatives of furocoumarins possess significant biological activity [8–14]». Therefore it would be also a good idea to explore the biological properties of these new molecules.
• Of course, these possibilities can be considered in parallel: more molecules screened in several areas would be ideal…..

In conclusion, it is too early to publish this paper: significant extensions and developments have to be initiated before it can become a significant contribution to organic chemistry and related areas.

Author Response

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Author Response File: Author Response.pdf

Reviewer 3 Report

The work presented by Lichitsky et al. describes the synthesis of two new substituted furo[2,3-f]coumarin-based acetic acid derivatives, throughout a one-pot multicomponent strategy recently and successfully applied by the same authors for the obtainment of furan based compounds of great importance in biology and medicinal chemistry. The experimental protocol is solid and the two new compounds are well-characterized. However, the scope appears to be weak and the procedure is not properly explained.

Herein some observations/modifications the authors should address:

- Page 1, Title: the coumarin derivatives actually synthesized are two. It should be clarified from the title, otherwise it would be misleading.

- Following the previous point, if the procedure cannot be applied for the obtainment of other derivatives, it should be discussed within the results. Also, if there are other particular reasons for which the authors are focused on the synthesis of 4a and 4b, they should mention them. On this regard, the new compounds presented should be at least five, in order to corroborate the protocol, since they are not sufficient for a short communication, as the data are presented.

- The authors say that a 6-fold excess of arylglyoxals, Meldrum’s acid and triethyamine is needed for consuming coumarin 1. Moreover, from the procedures the authors presented, it appears that the aforementioned reagents are used in a total 12-fold excess, which seems peculiar for all the reagents. Can they give a reasonable explanation for this evidence?

- The authors call their procedure “telescoped”, although from their previous work and the mechanism they proposed, it appears to be more like a “cascade” process (based on the fact that all the reactants are mixed together and not added sequentially and that the reaction proceeds only from the formation of the previously gained intermediate). Also, do the authors have any (previous) mechanistic evidence? This should be addressed.

In conclusion, I believe that the work submitted by Lichitsky et al. is part of a stimulating topic concerning the application of low-cost synthetic protocols for the obtainment of furan-based fragment of high added-value.

Therefore, I would recommend this work for publication on Molbank, provided the authors will modify the manuscript accordingly.

Kind regards

Author Response

Please see the attachment

Author Response File: Author Response.pdf

Round 2

Reviewer 3 Report

The revised version presented by Lichitsky et al. is well prepared and the answer to the reviewer’s comments are complete and exhaustive.

Therefore, I would recommend the revised version of this work for publication on Molbank.

Kind regards