Solvent-Free, One-Pot, Multicomponent Synthesis of Xanthene Derivatives
Round 1
Reviewer 1 Report
In this paper, Bosica and co-workers describe a simple one-pot multicomponent synthesis of different benzoxanthenones (17 examples), starting from a 1,3-cyclohexanedione derivative (16 examples with dimedone and 1 example with 1,3-cyclohexanedione), an aldehyde (13 aromatic aldehydes, 1 heteroaromatic aldehyde and 3 aliphatic aldehydes), and a naphthol (16 examples with 2-naphthol and 1 example with 1-naphthol). Mechanistically, the three reactants were linked together through two condensations and a conjugate addition. Optimal reaction conditions were found using 24 mol% of 30% w/w DABCO/Amberlyst-15 heterogeneous catalyst at 120 ºC without any solvent. Importantly, the catalyst can be recycled and reused six times without losing significant catalytic activity.
Authors point out that this methodology is environmentally friendly when considering atom economy and E-factor. The manuscript is written correctly, the experimental work is well described, and the products are adequately characterized in the “Materials and Methods”. In addition, copies of IR, 1H NMR and 13C NMR spectra are provided as Supplementary Information.
I found this study of synthetic interest and recommend it for publication in Catalysts.
Minor concerns and corrections.
1. Lines 17-18: “supported heteropoly acid” must be “supported heteropolyacid”
2. Line 33: “agents [7-9].8In recent years…” must be “agents [7-9]. In recent years”
3. Line 41: “model rection” must be “model reaction”
4. Compound numbers in the main text must be in bold, as in Tables and Schemes.
5. A formal aspect, considering parenthesis in, for instance, text lines 145-148: “…carbon of benzaldehyde (2a). The intermediate formed (5) gets protonated by the catalyst, which bears one of the methylene hydrogens from the enolization step, forming intermediate 6. The high reaction temperature employed fa-vours a dehydration step to form the Knoevenagel intermediate (7). The next step is the Michael addition reaction of 2-naphthol (3a) to the Knoevenagel intermediate (7)…” It must be “…carbon of benzaldehyde (2a). The intermediate formed 5 gets protonated by the catalyst, which bears one of the methylene hydrogens from the enolization step, forming intermediate 6. The high reaction temperature employed fa-vours a dehydration step to form the Knoevenagel intermediate 7. The next step is the Michael addition reaction of 2-naphthol (3a) to the Knoevenagel intermediate 7…”
To be consistent, this needs to be corrected throughout the text.
8. A minor discrepancy regarding atom economy and E-factor. Authors apply directly AE = ΣMWProducts /ΣMWReactants ´ 100 (90.77% in the model reaction). However, they do not consider the stoichiometry of the reaction. Ideally, 1:1:1 (aldehyde:diketone:naphthol). Optimal conditions 1.3:1:1. Mass of the reaction product / Mass of the starting materials ´ 100 = 80%.
9. References style.
Author Response
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Author Response File: 
Author Response.pdf
Reviewer 2 Report
The manuscript submitted by Bosica et al. describes an one-pot synthesis of xanthene derivatives catalyzed by an efficient heterogeneous catalyst under green conditions.
The scope of this procedure is broad allowing to synthesize xanthenes bearing electron-donating and electron-withdrawing groups in moderate to high yields. The reactions run under solventless conditions and using an heterogeneous catalyst that can be recovered and reused.
The manuscript is well written, and the discussion are clear and concise. However, there are some mistakes that must be corrected and some changes in the main text must be made. Thus, in Scheme 2, authors should change the numbers of intermediates. I suggest using roman numbers for these ones (consider that these changes must be made in the main text).
In line 171, page 8, authors indicate that the low reactivities of electron-rich and alkyl chain (such as heptanal) aldehydes is due to positive mesomeric effects, but this effect are not present in alkyl chain aldehydes. Please, change this sentence.
Regarding the section 3.5, page 11-14, the are lots mistakes in the 1H NMR spectra because, for almost every compounds, the diastereotopic protons at position 8 are given as “AB quartet” when this signal correspond to a “AB system”. Please, correct it. Moreover, for compound 4c, C-F coupling constants must be indicated. In addition, for compounds 4d and 4g, authors give peaks as doublet or doublet doublet when these coupling are not correct. Please, check it.
The follow mistakes should be corrected:
- Table 3, drawing for compounds 4a, 4b, 4c, 4d, 4e are mixing.
- Table foot 3: two different size letters are used.
Considering on the previous comments, I think that this work could be published in Catalysts after authors make the suggestions and correct the mistakes.
Comments for author File: Comments.pdf
Author Response
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Author Response File: Author Response.pdf
Reviewer 3 Report
The following manuscript, "One-pot Synthesis of Xanthene Derivatives under Green Conditions," utilizes amberlyst-15 (and DABCO) as a catalyst to perform a multicomponent synthesis of diazabicyclo derivatives.
There are minor points that need to be revised by the authors.
1. Author needs to revise the paper's title to "Solvent-free One-Pot Multicomponent Synthesis of Xanthene Derivatives" or another title (depending on the authors), as the current title is a bit confusing. One of the major reasons that the author used various precursors for the synthesis while secondly, the greener conditions only contain solvent-free reactions and not catalyst-free. Authors could use the atom economy of the reaction as one of the highlighting points.
2. Please improve the choice of words and break complex sentences into simpler forms for easy understanding for readers. For example, saying Amberlyst-15 is the novel catalyst is a vague statement, as it is not newer and various forms of Amberlyst-15 are already used in the past.
3. After Table 1, there should be a figure showing all the structures of the compounds, as it would improve the paper's readability.
4. Authors need to verify the synthesis 4q and how the 4q is different than other compounds. Please justify when similar substituent precursors resulted in other regioisomers.
5. Some of the NMR are very well characterized, while others are not characterized; please make them uniform.
Author Response
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Author Response File: Author Response.pdf
