5-(6-Hydroxy-6-methyl-5-oxoheptan-2-yl)-2-methyl Phenyl Acetate
Round 1
Reviewer 1 Report
The paper entitled "5-(6-Hydroxy-6-methyl-5-oxoheptan-2-yl)-2-methyl phenyl acetate by Maya Damayanti Rahayu, Susi Kusumaningrum, Hayun Hayun presents a convenient access to the title compounds. The observed selectivity is interesting and provided experimental procedure is sufficient to be repeated by others. Concerning the presentation I have several objections:
The overall length should be reduced; the details of NMR interpretation can be skipped. In particular Figure 1&2 should be shifted to the SI file.
Figure 3 with a lot of arrows is confusing and is not much help for the reader. The meaning of colors is not given. (Suggestion: Instead the authors might prepare a larger structure of the target molecule where they insert C-shift values at the atom position and eventually H-shifts. If assignment is not unequivocal interchangeable values can be marked with asterisk.)
The mechanism in Scheme 2 is not informative. Although it is generally accepted that a cyclic permanganate ester is formed as an intermediate this cannot explain why in this case neither diol is formed (neutral-basic conditions) nor cleavage (acidic condition) occurred. So this scheme should be omitted.
Some misprints/inaccurateness in the experimental part should be corrected: decimal comma should be a point (line 105, 111). Doublet in line 109 requires a coupling constant.
The quality of schemes is inconsistent and needs improvement.
The quality of English is low (several incomplete sentences).
Author Response
REPLY TO REVIEWER 1
Thank you for your comments and suggestions. The manuscript has been revised according to your suggestions:
1. The overall length of the manuscript has been reduced: NMR interpretation only shows the structural changes that occur. The figure has been shifted to the SI file, while figure 2 is maintained because reviewer 2 asks to discuss the HMBC spectrum in greater detail.
2. To show a more clear correlation between 1H and 13C, I replace figure 3 with table 1 (HMBC correlation of the title compound)
3. Scheme 2: The proposed reaction mechanism of oxidation..........................has been omitted.
4. Some misprints/inaccurateness in the experimental part has been corrected: decimal comma has been corrected to a point (line 105, 111). Doublet in line 109 also has been added with a coupling constant.
5. The quality of the scheme also has been improved.
6. The quality of English also has been improved.
Regards,
Authors
Reviewer 2 Report
Rahayu et al. report on the oxidative functionalization of acetyl xanthorrizol using KMnO4. They present a detailed account of the reaction, a compelling rationalization for the observed product, and extensive characterization data to prove the identity of the molecule. The oxidation process described regarding this molecule has not been reported in the literature. Publication is recommended. Following are a few suggestions to improve the quality of the manuscript for publication,
a. The yield should be stated in the main text and also in Scheme 1.
b. Relatedly, the outcome of the process can be better understood via identification of any side products. Were any observed by TLC, and what are their structures?
c. Does the overoxidation occur in this case? If yes, were there any such products isolated?
d. Is the treatment with H2O2 necessary? Products is purified by the column chromatography and treatment with H2O2 might affect the yield.
e. Following are the grammatical mistakes / sentence correction
Line 28 – no report the (preposition missing) should be no repot of the
Line 29 – check the following: O-acetyl-xanthorrizol
Line 38 and 39 – reword the sentence; results of the FTIR are not clearly interpreted
Line 98 – keep either the word or chemical formula
Line 104 – It should be 51.9% not 51,9%
f. The 13C chemical shifts in Figure 1. Perhaps limit the picked values to only show chemical shifts to the hundredths position? This is a minor point.
g. Figures 2 and 3 should be discussed in greater detail in the text. The discussion should guide the reader as to what signals are indicative of which correlations. And describe the color-coding,etc.
Author Response
REPLY TO REVIEWER 2
Thank you for your comments and suggestions. The following points of the manuscript have been revised according to your suggestions:
a. The yield has been stated in the main text and also in Scheme 1.
e. We also have made corrections the grammatical mistakes:
Line 28: “However, no report the.....” (preposition missing) has been revised to be “However, there is no report of the ....”
Line 29, 32, and 86: O-acetyl-xanthorrizol has been corrected to be 1-O-acetyl-xanthorrizol (according to the name of the compound used by Aguilar, 2001)
Line 38 and 39: results of the FTIR has been rewritten to be “The FTIR spectrum of the compound 2 exhibited the appearance of hydroxyl, carbonyl ester, and carbonyl ketone bands at 3482, 1762 and 1710 cm-1.”
Line 98: chemical formula has been omitted
Line 104: 51,9% has been corrected to be 51.9%.
f. Figure 1 (DEPT spectrum) is shifted to the SI file.
g. Figure 2 is become to be Figure 1. This figure has been improved by adding the structure of the compound completed with numbering on the carbon atom of the compound and adding the proton number at X-axis and carbon number at Y-axis of the HMBC spectrum to show correlations of proton signals and carbon signals.
Figure 3 is replaced by table 1 (HMBC correlations for the title compound) to make it easier in showing the correlations:
α = H - C correlation due to a two-bond coupling
β = H - C correlation due to a three-bond coupling
γ = H – C correlation due to a four-bond coupling
Regarding side products and some questions.
Q: The outcome of the process can be better understood via identification of any side products. Were any observed by TLC, and what are their structures?
A: Based on the TLC analysis, there is at least one side product. It has a higher polarity than the main product (smaller Rf value). The intensity of the side products spot is weak, so we do not interest to isolate it yet. In this short note manuscript, we pay attention only on the main product of the reaction.
Q: Does the overoxidation occur in this case? If yes, were there any such products isolated?
A. We do not know the overoxidation occur or not.
Q. Is the treatment with H2O2 necessary? Products are purified by the column chromatography and treatment with H2O2 might affect the yield.
A. The addition of H2O2 solution is necessary to decolorize the brown color formed after the reaction. The addition was done after stirring for 1 h, and all the violet color from permanganate ion has disappeared, indicating the oxidation reaction by permanganate ion was finished. So the addition of H2O2 does not reduce the amount of permanganate ion.
H2O2 reacts significantly with dye (Nisar et al., 2011, African J Environment Sci Tech 5(11): 916-923). H2O2 is a lower oxidizing agent than KMnO4, and in this experiment, H2O2 was added 2-3 drops only to decolorize the solution. So I think this treatment may not affect the yield.
Regards,
Authors.
Round 2
Reviewer 1 Report
The text has been significantly improved and essential modifications were done by authors. I recommend publication in the present form.
