Propyl Gallate

Round 1

Reviewer 1 Report

This manuscript reports a new methodology for synthesizing propyl gallate. The method let to produce this compound in a green and economic way, and a high reaction yield is obtained by using a heterogeneous acidic catalyst (KHSO₄). Authors have supplied full data characterization.

The manuscript could be accepted after minor revisions as followings.

• On page 3, in the Table 1 it is written ‘Temp’ to indicate ‘temperature’. ‘Temp’ should be replaced by ‘T’.
• On page 4, line 97, ‘column chromatography’ instead of ‘column chromarography’.
• On page 4, line 108, a blank space is lost between ‘in’ and ‘various’.
• On page 4, line 115, ‘Tables 2-6’ instead of ‘Table 2-6’.
• In the footnotes of Tables 2-5 is written that purity was confirmed by TLC (and by melting point as well). However, TLC seems not to be a good technique to determine the compound purity. Could authors explain in detail how they determine these values by TLC?
• On page 6, line 168, it should be written ‘overlapped’ instead of “overlaped”.

Author Response

Please see the attachment.

Author Response File: Author Response.pdf

Reviewer 2 Report

The manuscript entitled “Propyl Gallate” describes a new and useful process for the conversion of gallic acid into propyl gallate (PG) using safe and easy to handle potassium hydrogen sulfate KHSO4 as catalyst. The yield is good (80.2%) and the reaction should be complementary of already reported esterification processes. The work appeared to be carried out with care and various reaction conditions were screened. In addition, new NMR data are provided included unreported 2D NMR spectra. The manuscript is well bibliography provided but few references are missing.

For all these reasons, I believe that this manuscript is worth publishing in Molbank.

In addition, the manuscript should be published after minor revisions noted:

This recent review is missing and must be cited :

Enzymatic synthesis of bioactive compounds with high potential for cosmeceutical application. Appl Microbiol Biotechnol (2016) 100:6519–6543. DOI 10.1007/s00253-016-7647-9

In the abstract, line 19: Please, correct “economic method”  -> “economical method”

In the introduction part:

Line 30, please delete this sentence “all of which readily undergo oxidation”

Line 36, could the authors explain this sentence? : “Natural occurrence of PG has not been reported in the literature”. I don’t really understand what it means

Line 37 Only references 2 and 7 were mentioned, please add all these missing references focused on the synthesis of PG:

• ENHANCEMENT OF PROPYL GALLATE YIELD IN NONAQUEOUS MEDIUM USING NOVEL CELL-ASSOCIATED TANNASE OF Bacillus massiliensis. Preparative Biochemistry & Biotechnology Volume 43, 2013 - Issue 5, 445-455 https://doi.org/10.1080/10826068.2012.745873
• Beena, P.S., Basheer, S.M., Bhat, S.G. et al. Propyl Gallate Synthesis Using Acidophilic Tannase and Simultaneous Production of Tannase and Gallic Acid by Marine Aspergillus awamori Appl Biochem Biotechnol 164, 612–628 (2011). https://doi.org/10.1007/s12010-011-9162-x
• Synthesis of propyl gallate by transesterification of tannic acid in aqueous media catalysed by immobilised derivatives of tannase from Lactobacillus plantarum. Food Chemistry, Vol 128, 2011, Pages 214-217. https://doi.org/10.1016/j.foodchem.2011.02.057
• Synthesis of propyl gallate from tannic acid catalyzed by tannase from Aspergillus oryzae: Process optimization of transesterification in anhydrous media. Journal of Molecular Catalysis B: Enzymatic, Vol 82, 2012, Pages 102-108. https://doi.org/10.1016/j.molcatb.2012.06.003
• One-pot bio-synthesis of propyl gallate by a novel whole-cell biocatalyst. Process Biochemistry, Vol 49, 2014, Pages 277-282. https://doi.org/10.1016/j.procbio.2013.11.009

Please correct the scheme 1. The third reported routes for the synthesis of PG should not be mentioned as i. ii. and iii.  to avoid confusion with the steps involved in a synthesis. In addition, the acid I and propanol II have not to be written twice (right of the scheme).

Line 44: “iso” must be displayed in italics in “N,N’-diisopropylcarbodiimide”

Line 55: replace “N-methyl pyrrolidonium hydrosulfate” by “N-methyl-2-pyrrolidonium hydrogensulfate” (see also line 98)

Lines 65-66:  replace “The use of KHSO4 as a catalyst for the synthesis of PG, however, has not been reported.” By “However, the synthesis of PG using KHSO4 as a catalyst has not been yet reported.”

Line 70: Please, replace “economic” by “economical”

In the part: 2. Results and Discussion

Line 82, replace “grouped” by “classified”

Scheme 2: Reagents and conditions, please replace (1:12.0:0.4) by (1.0:12:0.40)

Line 96, replace: “at large scale” by “on a large scale”

Line 100: The authors wrote: “the preparation of this ionic liquid is quite complicated, and its regeneration requires high energy to evaporate water from the filtrate.” What about freeze-drying to regenerate [Hnmp]HSO4?

Line 108:  Add a space between “in” and “various”

Line 111: Delete “of” between “92.9%” and “yield”

Line 115: Please correct “Tables” 2-6

Table 2: Correct “Effect of the reaction temperature” Table 3: Correct “Effect of the reaction time”

Line 139: replace “time would not boost the yield up” by “time do not improve the yield”. Replace “negligible” by “slight”

Please reformulate this sentence: “Considering the negligible change in product yield between 12 and 13 h reacting time (67.9% vs 68.1%, entries 3 and 4, Table 3), and the fact that no starting material was detected by TLC after 12 h, we used this reaction time of 12 h as the standard for our protocol.”

In the part: 3. Materials and Methods

Concerning the synthetic procedure:

• Because one of the reaction products is water and oxygen is compatible with the esterification, why the reaction is carried out under nitrogen?
• Why the reaction is not conducted in a Dean Stark?
• Has the reaction product dried at 60°C for 3h under vacuum?

In the reference part:

Ref 2: Correct the tittle of the publication “Preparation of Propyl Gallate”

Ref 7:  Please, use the abbreviation of the journal name: J. Mol. Catal. B Enzym.

Ref 12: This reference seems to be off topic

Ref 22: Please, use the abbreviation of the journal name: J. Catal.

Ref 30: The range of pages is missing.

Author Response

Please see the attachment.

Author Response File: Author Response.pdf