(7E)-3-(4-Methoxyphenyl)-7-[(4-methoxyphenyl)methylidene]-4,5,6,7-tetrahydro-3aH-indazole
Round 1
Reviewer 1 Report
This paper presents a molecular structure of the titled indazole derivative. A database search to confirm the originality of the structure indicates no record found in previous publications. The results presented in this paper may be approved for publication, but this manuscript should be revised before acceptance, because the main text contains grammatical errors and unclear descriptions to be improved. For the revision of this paper, the authors should refer to the following problems.
- Page #1, Line #24-26: “The indazole ring importance ... led to many chemists...”. This sentence should be revised to make this explanation clearer.
- Page #1, Line #28: The word “synthetic” of “The general synthetic for the last-mentioned” is grammatically incorrect.
- Page #1, Line #30: “were also showed” should be “also showed”.
- Page #2, Line #55: “was occurred” should be “occurred”.
- Page #2, Line #57-60: “The used of ... , there was only followed by ...”. This sentence is not understandable, which should be revised appropriately.
- Page #2, Line #77: The product yield lacks weight unit.
- Page #2, Line #80: The multiplet resonances for 1H NMR lack ppm ranges.
Author Response
Thank you for your comments and suggestions. The manuscript has been revised according to your
Suggestions. I hope the revised manuscript fulfills your expectations.
The following is the response to reviewers' comments:
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No |
Reviewer comments |
Answer |
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1 |
Page #1, Line #24-26: “The indazole ring importance ... led to many chemists...”. This sentence should be revised to make this explanation clearer. |
It has been revised to be: Due to the importance of the indazole ring in drug development, many chemists were motivated. They took the initiative to develop different methods for this heterocycle synthesis. |
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2 |
Page #1, Line #28: The word “synthetic” of “The general synthetic for the last- mentioned” is grammatically incorrect. |
It has been revised to be: The general synthesis method for the compounds was by condensation of α,β-unsaturated carbonyl with hydrazine in ethanol as solvent. |
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3 |
Page #1, Line #30: “were also showed” should be “also showed”. |
It has been revised |
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4 |
Page #2, Line #55: “was occurred” should be “occurred”. |
It has been revised |
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5 |
Page #2, Line #57-60: “The used of ... , there was only followed by ...”. This sentence is not understandable, which should be revised appropriately. |
It has been revised to be: Reaction condition with glacial acetic acid as a solvent and reflux temperature caused dehydration to obtain α, β-unsaturated imine moiety and accompanied by dehydrogenation of heterocycle: 3,3a,4,5,6,7‐hexahydro‐2H‐indazole to be 4,5,6,7‐tetrahydro‐3aH‐indazole. |
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6 |
Page #2, Line #77: The product yield lacks weight unit. |
The weight unit has been added: Recrystallization from ethyl acetate afforded the pure compound (3) as a pale yellow powder in 61% yield (106 mg) and......... |
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7 |
Page #2, Line #80: The multiplet resonances for 1H NMR lack ppm ranges. |
The H-NMR data has been revised to be: 1H-NMR (500 MHz, CDCl3) δ, ppm: 7.53 (d, J = 8 Hz, 2H, H-Ar), 7.32 (d, J = 8 Hz, 2H, H-Ar), 7.10 (s, 1H, CH=), 6.89 (dd, J = 8 Hz, 4H, H-Ar), 3.84-3.85 (t, J = 2-4 Hz, 1H, 3a-H, little overlap with protons of OCH3), 3.84 (s, 3H, OCH3), 3.82 (s, 3H, OCH3), 2.77 - 2.79 (m, 4H, 4-H and 6-H), 1.86 - 1.88 (m, 2H, 5-H). |
Author Response File: 
Author Response.pdf
Reviewer 2 Report
n the paper by Hariyanti et al. the synthesis of a substituted indazole derivative is reported by condensation of hexahydro-2H-indazole 1 with 4-methoxybenzaldehyde in the presence of AcOH.
The methodology is well-established and thus the synthetic approach is not very original. Despite that, one puzzling observation concerns the fact that in going from substrate 1 to product 3 the condensation reaction is accompanied by the formal loss of a hydrogen molecule along the CH-NH bond of the starting material, giving rise to a compound with one extra C=N double bond.
By checking the literature, it can be found that the same product (albeit in its tautomeric enamine form) has already been prepared by means of a different procedure, see V. N. Nuriev et al., Russ. J. Org. Chem. 2016, 52, 389. In that case, the desired structure was indeed obtained by final oxidation with a Fe(III)-based reagent.
In view of the above, I think that the present contribution can be published on Molbank, but to do that the authors should check which was the actual product formed (hydrogenated / enamine / imine), and provide a rationale for the apparent oxidation following condensation. In addition, they should reference the above-mantioned paper, and check the differences between the 1H-NMR spectrum reported there and that of their manuscript; in particular, in the present work the triplet identified at 3.85 ppm is not clear and a coupling constant should be provided to show that it is compatible with the proposed structure. Furthermore, in the 13C-NMR spectrum only five aliphatic signals are visible while the structure proposed by the authors features six aliphatic carbons.
Finally, I found some flaws in the use of english language throughout the paper and therefore recommend an extensive editing of that aspect before publication.
Author Response
REPLY TO REVIEWER 2
Thank you for your comments and suggestions. The manuscript has been revised according to your
Suggestions. I hope the revised manuscript fulfills your expectations.
The following is the response to reviewers' comments:
|
No |
Reviewer comments |
Answer |
|
1 |
the same product (albeit in its tautomeric enamine form) has already been prepared by means of a different procedure, see V. N. Nuriev et al., Russ. J. Org. Chem. 2016, 52, 389. The authors should check which was the actual product formed (hydrogenated / enamine / imine), and provide a rationale for the apparent oxidation following condensation. In addition, they should reference the above-mantioned paper,
|
The product formed was dehydrogenation product of heterocycle: 3,3a,4,5,6,7‐hexahydro‐2H‐indazole (in its pyrazoline ring).
Probable dehydrogenation of the pyrazoline ring following condensation due to aerobic aromatization. The released H2O was then dehydrated by glacial acetic acid.
The reference paper has been added: [11] Nuriev, V.N, Vatsadze, I.A., Sviridenkova, N.V., Vatsadze, S.Z. Synthesis of 3,7-Disubstituted Hexahydro and Tetrahydro-2H-indazoles from Cross-Conjugated Dienones. Russ J Orang Chem, 2016, 52 (3), 389–396. |
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2 |
Check the differences between the 1H-NMR spectrum reported there and that of their manuscript; in particular, |
In the H-NMR spectrum, the main difference structure of the two compounds is clearly observed. In compound 3, the proton peak of 3a-H appears at 3.84-3.85 ppm and lacks proton NH at 9.91 ppm, while in the tautomer form, the NH proton appears at 9.91 ppm and lacks the proton peak at 3.85 ppm. |
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3 |
In the present work the triplet identified at 3.85 ppm is not clear and a coupling constant should be provided to show that it is compatible with the proposed structure. |
The triplet identified at 3.84-3.85 (t, J = 2-4 Hz, 1H, 3°-H, little overlap with protons of OCH3, so it is not too clear. The coupling constant has been added. The J = 2-4 Hz is compatible with the proposed structure. |
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4 |
Furthermore, in the 13C-NMR spectrum only five aliphatic signals are visible while the structure proposed by the authors features six aliphatic carbons.
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The aliphatic carbon signal at 55.488 ppm appeared higher than the carbon signal at 55.382 ppm. We calculate that signal at 55.488 ppm is from two carbon atom, while the signal at 55.382 ppm is from one carbon.
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5 |
Finally, I found some flaws in the use of english language throughout the paper and therefore recommend an extensive editing of that aspect before publication. |
The English language has been edited. If it is not enough, it will be edited by MDPI editing services. |
Author Response File: Author Response.pdf
Round 2
Reviewer 2 Report
The authors made a reasonable effort to meet the reviewer's demands, and therefore the manuscript can now be published
