Ethyl 5-Hydroxy-2-methyl-1-(pyridin-2-ylmethyl)benzo[g]indole-3-carboxylate
Round 1
Reviewer 1 Report
Comments and Suggestions for AuthorsThe communication by Carraro et al describes the synthesis and characterization of ethyl 5-hydroxy-2-methyl-1-(pyridine-2-2 ylmethyl)benzo[g]indole-3-carboxylate from easily accessible starting compounds in two steps. The overall yield is quite low, although the synthetic procedure is very simple. For example, the first step (formation of imine/enamine) was reported to give an 85 % isolated yield in acetonitrile with a catalytic amount of iodine (Tetrahedron Letters 2013, 54(23), 2929 – 2933). I’m also pretty sure the yield of the second step could be improved too. I appreciate thorough characterization including HSQC NMR. I only wonder why NMR peaks are not assigned in both spectra.
Minor points: 13C NMR shifts should be rounded to only one decimal place. The 13C-APT experiment would be better to distinguish between carbons carrying odd or even numbers of hydrogens.
Nonetheless, the communication can be published in Molbank after minor revision.
Author Response
Comment 1: [The overall yield is quite low, although the synthetic procedure is very simple. For example, the first step (formation of imine/enamine) was reported to give an 85 % isolated yield in acetonitrile with a catalytic amount of iodine (Tetrahedron Letters 2013, 54(23), 2929 – 2933).]
Response 1: We agree with the principle, anyway we added (page 2 lines 48-50) a brief discussion over iodine catalyzed synthesis of enamine, explaining why iodine is not the best catalyst choice (furthermore isolation procedure from Tetrahedron Letters 2013, 54(23), 2929 was not described, so we preferred not to use it).
Comment 2: [ I’m also pretty sure the yield of the second step could be improved too.]
Response 2: We tried to improve the yield of this kind of synthesis in our previous cited pubblication, but some substrate gives very low yields. The low yield of the second step is not unprecedent in Nenitzescu synthesis, especially if the reaction is not perfectly homogenous, we added as well a possible explanation involving chelation of zinc by enamine (page 2 line 53).
Comment 3: [I only wonder why NMR peaks are not assigned in both spectra.]
Response 3: We thank the reviewer for the suggestion, we added assignements.
Comment 4: [13C NMR shifts should be rounded to only one decimal place.]
Response 4: We rounded the numbers as suggested.
Comment 5: [The 13C-APT experiment would be better to distinguish between carbons carrying odd or even numbers of hydrogens.]
Responde 5: We used the sign of HSQC integrals to asses carbons carrying odd or even numbers of hydrogens.
Reviewer 2 Report
Comments and Suggestions for AuthorsThe manuscript from Satta et. al. describes the synthesis of Ethyl 5-hydroxy-2-methyl-1-(pyridin-2-2 ylmethyl)benzo[g]indole-3-carboxylate over two reaction steps. Although the overall yield is not high, the easiness of the method and the reduced use of hazardous solvents make this approach very interesting, since only green solvents are employed, and no chromatographic steps are required. In addition, the synthesis of this molecule has not been previously described in literature. Therefore, publication is recommended after revision of minor issues.
1) The abbreviation “e.g.” is correctly written throughout the manuscript, except in line 24 where it should be corrected.
2) The first sentence of the results section may result confusing. I would suggest to form shorter sentences on this paragraph to gain clarity.
3) In the description of the spectroscopic data of compounds, the term “CHLOROFORM-d” might be replaced by CDCl3.
4) In the references section, some of the journal names are abbreviated but others are not. References 9, 11, 14, 15 and 17 should be revised.
Publication is recommended after revision of these minor issues.
Author Response
Comment 1: [The abbreviation “e.g.” is correctly written throughout the manuscript, except in line 24 where it should be corrected.]
Response 1: We thank the reviewer, line 24 on page 1 was corrected
Comment 2: [The first sentence of the results section may result confusing. I would suggest to form shorter sentences on this paragraph to gain clarity.]
Response 2: We thank the reviewer for the advice. The first sentence of the results section was reformulated and split in two. (page 2 line 47)
Comment 3: [ In the description of the spectroscopic data of compounds, the term “CHLOROFORM-d” might be replaced by CDCl3.]
Response 3: “CHLOROFORM-d” was replaced by CDCl3, for consistency we changed “DMSO-d6” with (CD3)2SO (page 3 lines 82, 85, 100, 105 ).
Comment 4: [In the references section, some of the journal names are abbreviated but others are not. References 9, 11, 14, 15 and 17 should be revised.]
Response 4: We apologize for the oversight, due to Zotero malfunction. Journal abbreviations were introduced in References section were appliable. (page 5 and 6)
