Environmentally Friendly Nafion-Catalyzed Synthesis of Substituted 2-Ethyl-3-Methylquinolines from Aniline and Propionaldehyde under Microwave Irradiation

Round 1

Reviewer 1 Report

The work is very interesting and fits perfectly into the concept of green chemistry. The manuscript was carefully written and the experiment was well planned and executed. The results are described in detail. The extensive literature (83 items) draws attention. However, the low yield for products 3a, for example 17%, is worrying (Table 1). Such a synthesis is unprofitable. What is the remaining 83%? How the authors explain it. Moreover, schemas should be excluded from the tables (Table 1-4).

Author Response

July 14, 2021

Ms. Ella Cai

Assistant Editor

Catalysts

Email: [email protected]

 

Article title: Environmentally Friendly Nafion-catalyzed Synthesis of Substituted 2-Ethyl-3-Methylquinolines from Aniline and Propionaldehyde Under Microwave Irradiation

Article ID: catalyst-1300309

Article authors: Chieh-Kai Chan *, Chien-Yu Lai and Cheng-Chung Wang *

 

Dear Ms. Ella Cai,

We appreciate that the Editor provides us the chance to revise the manuscript, and the detailed correction by three positive reviewers. We have revised the manuscript in accordance with the suggestions of the reviewers. The suggested changes have been included in the revised manuscript. The manuscript had been rechecked by native English language service, including inappropriate English descriptions.

 

 

First, we have clarified our statement as follows according to the opinion from the Reviewer 1.

Q1 : However, the low yield for products 3a, for example 17%, is worrying (Table 1). Such a synthesis is unprofitable. What is the remaining 83%? How the authors explain it.

A1-1: We can only identified the 45% yield of remaining 83% unknown by-products is N-propylamine. It is reasonably the simple coupling of amine and aldehyde. The intermediate has been drawn in the mechanism study part.

A1-2: In Page 3, Line 92: The sentence “^cMajor unknown products that were obtained.” in the original manuscript has been changed to “^c45% of N-propylamine were obtained.” in the revised manuscript.

Q2 : Moreover, schemas should be excluded from the tables (Table 1-4).

A2-1: To clearly present the corresponding compound structures and related reaction yields of every Scheme in the manuscript, we think that the chemical equation should be included in the above of structures. According to other reviewer’s opinions, all title have been renumbered as follow.

A2-2: In Page 3, Line 89: The title “Table 1” and the chemical equation were retained to clearly present the optimization results.

A2-3:In Page 3, Line 95: The word “Table 2” in the original manuscript has been changed to “Scheme 3” in the revised manuscript.

A2-4: In Page 4, Line 104: The title “Table 2” in the original manuscript has been changed to “Scheme 3” in the revised manuscript.

A2-5: In Page 4, Line 112: The word “Table 3” in the original manuscript has been changed to “Scheme 4” in the revised manuscript.

A2-6:In Page 4, Line 124: The title “Table 3” in the original manuscript has been changed to “Scheme 4” in the revised manuscript.

A2-7: In Page 5, Line 132: The word “Table 4” in the original manuscript has been changed to “Scheme 5” in the revised manuscript.

A2-8:In Page 5, Line 142: The title “Table 4” in the original manuscript has been changed to “Scheme 5” in the revised manuscript.

 

 

We hope that we have clarified our statement such that the Editor can understand our opinions. According to the Reviewer 1’s comments, we return the revised manuscript. We hope that the revised version is acceptable.

 

Sincerely,

 

 

 

 

Dr. Cheng-Chung Wang

Associate Research Fellow

Institute of Chemistry, Academia Sinica

No.128 Academia Road Section 2, Nan-Kang

Taipei, 11529, Taiwan

Tel: 886-2-5572-8618

Fax: 886-2-2783-1237

E-mail: [email protected]

 

Author Response File: Author Response.pdf

Reviewer 2 Report

The paper reports on the synthesis of a series of quinolone by a nafion catalyzed microwave synthesis. The compounds are characterized by NMR. For 4 compounds also the single crystal structure was reported. About this point, why the crystal structure study was carried out on compounds 3p, 5a, 5b, 5d? Please give explanation/motivation of this choice. Moreover, a comment on the solved crystal structures and comparison with literature one would enrich the manuscript. The abstract is too short and more information about the main results (yields, crystal structures…) would be useful. The main criticism is related to the novelty of the reported compounds: are all the compounds already reported in the literature? Which are new if any? If not the corresponding reference should be given and improvements highlighted (larger yields? More green/facile synthesis?).

Then, are the single crystal structure all new? Please add this information in the abstract and introduction or conclusion section. The checkcif test is not mentioned and not available as ESI file. The author must perform checkcif and summarize the main results in the exp. Section where crystal structures are mentioned.

Another doubt: line 71 and many other point within the manuscript: what do authors mean with “entry 15”? Do the mean “batch”? How can author be sure that optimization of reaction condition on compound 3a is representative of all studied samples?

After that the novelty of the work is clearly stated within the manuscript, it can be considered for publication.

 

Minor notes

• Figure 1 should be renamed scheme 1. Scheme 1 becomes thus scheme 2 and scheme 2 and 3 renumbered according to this note and to note n. 2
• Tables 2-4 should become schemes in the opinion of the reviewer
• Line 116: “We next further explored the substrate scope and generality of this transformation”: please rewrite
• Line 152: “Although the physical states were varied”: it is not clear, please explain
• Line 302: why was 5b named “CYL-086” only in this paragraph? Is it a problem calling CYL-086 as 5b also here?
• Line 280: since 2p is monoclinic, beta angle must be reported
• Line 292: since 5a is triclinic, alfa beta gamma angles must be reported
• Line 303: since 5b is triclinic, alfa beta gamma angles must be reported
• Line 323: since 5d is monoclinic, beta angle must be reported
• Line 519-520. The statement “Data is contained within the article, respectively, within the Supporting Information file.” Is not clear. Please rewrite

Author Response

July 14, 2021

Ms. Ella Cai

Assistant Editor

Catalysts

Email: [email protected]

 

Article title: Environmentally Friendly Nafion-catalyzed Synthesis of Substituted 2-Ethyl-3-Methylquinolines from Aniline and Propionaldehyde Under Microwave Irradiation

Article ID: catalyst-1300309

Article authors: Chieh-Kai Chan *, Chien-Yu Lai and Cheng-Chung Wang *

 

Dear Ms. Ella Cai,

We appreciate that the Editor provides us the chance to revise the manuscript, and the detailed correction by three positive reviewers. We have revised the manuscript in accordance with the suggestions of the reviewers. The suggested changes have been included in the revised manuscript. The manuscript had been rechecked by native English language service, including inappropriate English descriptions.

 

 

First, we have clarified our statement as follows according to the opinion from the Reviewer 2.

Q1 : For 4 compounds also the single crystal structure was reported. About this point, why the crystal structure study was carried out on compounds 3p, 5a, 5b, 5d? Please give explanation/motivation of this choice.

A1: These four compounds (3p, 5a, 5b and 5d) were crystalized naturally, we don’t deliberately carry out on them to obtain the crystal data. It means that the crystallization of these four compounds are easier than others. Moreover, based on the reported literatures, no X-ray single crystal analysis for these 4 compounds was reported. We hope Reviewer 2 could understand our explanation/motivation of this choice.

Q2 : Moreover, a comment on the solved crystal structures and comparison with literature one would enrich the manuscript.

A2-1: In Page 7, Lines 172~174: The description of solved crystal structure has been included in the revised manuscript.

A2-2: In Page 7, Table 2: The checkcif test images and crystal data of solved crystal structures have been included in the revised manuscript.

Q3 : The abstract is too short and more information about the main results (yields, crystal structures...) would be useful.

A3-1: In Page 1, Abstract part, Line 11: The sentence “various anilines and propionaldehyde derivatives” has been included in the revised manuscript.

A3-2: In Page 1, Abstract part, Line 12: The word “new chemical” has been included in the revised manuscript.

A3-3: In Page 1, Abstract part, Line 13: The sentence “and the related data was provided” has been included in the revised manuscript.

Q4 : The main criticism is related to the novelty of the reported compounds: are all the compounds already reported in the literature? Which are new if any? If not the corresponding reference should be given and improvements highlighted (larger yields? More green/facile synthesis?).

A4-1: In a comparison of reported literatures, the preparation of 2-ethyl-3-methylquinoline skeleton by using recyclable Nafion particle has not been reported. Moreover, the reaction was conducted in an environmentally friendly system (EtOH as solvent, and Microwave Irradiation as heating source). We think that the novelty still attract some organic chemists in this field.

A4-2: In the 4. Data part, the reported references for the known compounds 3a-3d, 3f, 3i-3k, 3m, 3o and 6a-6c have been included in the revised manuscript.

Q5 : Then, are the single crystal structure all new? Please add this information in the abstract and introduction or conclusion section.

A5-1: After a comparison of reported literatures, these four single crystal structures are all new.

A5-2: In Page 1, Abstract part, Line 12: The word “new chemical” has been included in the revised manuscript.

A5-3: In Page 2, Introduction part, Lines 57~58: The sentence “Four chemical structures are confirmed by X-ray single-crystal diffraction analysis.” has been included in the revised manuscript.

A5-4: In Page 15, Conclusion part, Lines 545~546: The sentence “Four structures were confirmed by single-crystal X-ray crystallography and the analysis was newly reported.” has been included in the revised manuscript.

Q6 : The checkcif test is not mentioned and not available as ESI file. The author must perform checkcif and summarize the main results in the exp. Section where crystal structures are mentioned.

A6-1: In Page 7, Lines 172~174: The description of solved crystal structures has been included in the revised manuscript.

A6-2: In Page 7, Table 2: The checkcif test images and crystal data of solved crystal structures have been included in the revised manuscript.

A6-3: In Supporting Information file, Page S-5~S-7: The checkcif test data for compound 3p has been included in the revised Supporting Information file.

A6-4: In Supporting Information file, Page S-9~S-11: The checkcif test data for compound 5a has been included in the revised Supporting Information file.

A6-5: In Supporting Information file, Page S-13~S-15: The checkcif test data for compound 5b has been included in the revised Supporting Information file.

A6-6: In Supporting Information file, Page S-17~S-19: The checkcif test data for compound 5d has been included in the revised Supporting Information file.

Q7 : Another doubt: line 71 and many other point within the manuscript: what do authors mean with “entry 15”? Do the mean “batch”? How can author be sure that optimization of reaction condition on compound 3a is representative of all studied samples?

A7-1: Each entry means every experiment conducted with slightly adjusted reaction conditions. The results of every entry are shown in Table 1 in the revised manuscript.

A7-2: In organic methodology, organic chemists often applied relatively simple and non-substituted compound to optimize the reaction conditions. It means that we can exclude the electron effect (electron-donating group or electron-withdrawing) for the influence in the reaction.

A7-3: We are not sure that the optimization of reaction condition on compound 3a can completely represent all studied samples. But, in the results for the preparation of compounds 3b-3p, 5a-5s and 6a-h, the products are obtained in 83-93% yields. We think that the results showed the optimal reaction condition is suitable to present all studied compounds.

Q8 : Figure 1 should be renamed scheme 1. Scheme 1 becomes thus scheme 2 and scheme 2 and 3 renumbered according to this note and to note n. 2.

A8-1: In Page 1, Line 28: The word “Figure 1” in the original manuscript has been changed to “Scheme 1” in the revised manuscript.

A8-2: In Page 1, Line 35: The title “Figure 1” in the original manuscript has been changed to “Scheme 1” in the revised manuscript.

A8-3: In Page 2, Line 47: The word “(eq. 1, Scheme 1)” in the original manuscript has been changed to “(eq. 1, Scheme 2)” in the revised manuscript.

A8-4: In Page 2, Line 57: The word “(eq. 2, Scheme 1)” in the original manuscript has been changed to “(eq. 2, Scheme 2)” in the revised manuscript.

A8-5: In Page 2, Line 60: The title “Scheme 1” in the original manuscript has been changed to “Scheme 2” in the revised manuscript.

A8-6: In Page 3, Line 95: The word “Table 2” in the original manuscript has been changed to “Scheme 3” in the revised manuscript.

A8-7: In Page 4, Line 104: The title “Table 2” in the original manuscript has been changed to “Scheme 3” in the revised manuscript.

A8-8: In Page 4, Line 112: The word “Table 3” in the original manuscript has been changed to “Scheme 4” in the revised manuscript.

A8-9: In Page 4, Line 124: The title “Table 3” in the original manuscript has been changed to “Scheme 4” in the revised manuscript.

A8-10: In Page 5, Line 132: The word “Table 4” in the original manuscript has been changed to “Scheme 5” in the revised manuscript.

A8-11: In Page 5, Line 138: The word “Scheme 2” in the original manuscript has been changed to “Scheme 6” in the revised manuscript.

A8-12: In Page 5, Line 142: The title “Table 4” in the original manuscript has been changed to “Scheme 5” in the revised manuscript.

A8-13: In Page 6, Line 148: The title “Scheme 2” in the original manuscript has been changed to “Scheme 6” in the revised manuscript.

A8-14: In Page 6, Line 152: The word “Scheme 3” in the original manuscript has been changed to “Scheme 7” in the revised manuscript.

A8-15: In Page 6, Line 160: The title “Scheme 3” in the original manuscript has been changed to “Scheme 7” in the revised manuscript.

Q9 : Tables 2-4 should become schemes in the opinion of the reviewer.

A9-1: In Page 3, Line 95: The word “Table 2” in the original manuscript has been changed to “Scheme 3” in the revised manuscript.

A9-2: In Page 4, Line 104: The title “Table 2” in the original manuscript has been changed to “Scheme 3” in the revised manuscript.

A9-3: In Page 4, Line 112: The word “Table 3” in the original manuscript has been changed to “Scheme 4” in the revised manuscript.

A9-4: In Page 4, Line 124: The title “Table 3” in the original manuscript has been changed to “Scheme 4” in the revised manuscript.

A9-5: In Page 5, Line 132: The word “Table 4” in the original manuscript has been changed to “Scheme 5” in the revised manuscript.

A9-6: In Page 5, Line 142: The title “Table 4” in the original manuscript has been changed to “Scheme 5” in the revised manuscript.

Q10 : Line 116: “We next further explored the substrate scope and generality of this transformation”: please rewrite.

A10: In Page 5, Lines 128~129: The sentence “We next further explored the substrate scope and generality of this transformation” has been changed to “Next, the substrate scope of propionaldehyde derivatives were investigated in this transformation” in the revised manuscript.

Q11 : Line 152: “Although the physical states were varied”: it is not clear, please explain.

A11-1: In Page 6, Line 167: The sentence “Although the physical states were varied” in the original manuscript has been changed to “Although the shapes of particles became different” in the revised manuscript. A11-2: In Page S-3: The related photo has been shown in the Supporting Information file.

Q12 : Line 302: why was 5b named “CYL-086” only in this paragraph? Is it a problem calling CYL-086 as 5b also here?

A12-1: The name “CYL-086” is the reaction code for the synthesis of compound 5b. We are sorry for that we forgot to change the compound number.

A12-2: In Page 11, Line 335, Compound 5b: The word “CYL-086” has been changed to “5b” in the revised manuscript.

A12-3: In Page 11, Line 335, Compound 5b: The word “CYL-086” has been changed to “5b” in the revised manuscript.

Q13 : Line 280: since 2p is monoclinic, beta angle must be reported.

A13-1: In Page 7, Table 2: The beta angle of 3p is 128.6800(10)^o, and has been included in the revised manuscript.

A13-2: In Page 10, Compound 3p, Line 313: The word “β = 128.6800(10)^o” has been included in the revised manuscript.

Q14 : Line 292: since 5a is triclinic, alfa beta gamma angles must be reported.

A14-1: In Page 7, Table 2: The “alfa, beta and gamma angles” of 5a is “α = 103.454(2)°, β = 97.603(2)° and γ = 111.8150(10)°” , and have been included in the revised manuscript.

A14-2: In Page XX, Compound 5a, Lines 325~326: The “alfa, beta and gamma angles” of 5a is “α = 103.454(2)°, β = 97.603(2)° and γ = 111.8150(10)°” , and have been included in the revised manuscript.

Q15 : Line 303: since 5b is triclinic, alfa beta gamma angles must be reported.

A15-1: In Page 7, Table 2: The “alfa, beta and gamma angles” of 5b is “α = 103.4120(10)°, β = 100.533(2)° and γ = 90.7170(10)°” , and have been included in the revised manuscript.

A15-2: In Page 11, Compound 5b, Lines 337~338: The “alfa, beta and gamma angles” of 5b is “α = 103.4120(10)°, β = 100.533(2)° and γ = 90.7170(10)°” , and have been included in the revised manuscript.

Q16 : Line 323: since 5d is monoclinic, beta angle must be reported.

A16-1: In Page 7, Table 2: The beta angle of 5d is 108.5200(10)°, and has been included in the revised manuscript.

A16-2: In Page 11, Compound 5d, Line 356: The word “β = 108.5200(10)°“ has been included in the revised manuscript.

Q17 : Line 519-520. The statement “Data is contained within the article, respectively, within the Supporting Information file.” Is not clear. Please rewrite.

A17: In Page 15, Line 557: The sentence “Data is contained within the article, respectively, within the Supporting Information file.” has been changed to “All required data is presented in this file.” in the revised manuscript.

 

 

We hope that we have clarified our statement such that the Editor can understand our opinions. According to the Reviewer 2’s comments, we return the revised manuscript. We hope that the revised version is acceptable.

 

Sincerely,

 

 

 

 

Dr. Cheng-Chung Wang

Associate Research Fellow

Institute of Chemistry, Academia Sinica

No.128 Academia Road Section 2, Nan-Kang

Taipei, 11529, Taiwan

Tel: 886-2-5572-8618

Fax: 886-2-2783-1237

E-mail: [email protected]

Author Response File: Author Response.pdf

Reviewer 3 Report

The authors presented an interesting research reach of catalytic runs. However, the results should be more deeply rationalized and the following points should be discussed:

• The authors should explain the mechanism of the Friedlander reaction.
• The authors should describe the properties of Nafion NR50 in terms of chemical structure, acidity, etc.

• The authors should explain the reason why they employed MW irradiation as heating system mentioning its advantages respect to a traditional heating system. For this purpose the authors should cite at least these references:
  - C. Antonetti, S. Fulignati, D. Licursi, A.M. Raspolli Galletti “Turning point toward the sustainable production of 5-hydroxymethyl-2-furaldehyde in water: metal salts for its synthesis from fructose and inulin”, ACS Sustainable Chem. Eng. 2019, 7, 6830-6838.
  - L. Biancalana, S. Fulignati, C. Antonetti, S. Zacchini, G. Provinciali, G. Pampaloni, A.M. Raspolli Galletti, F. Marchetti “Ruthenium p-cymene complexes with α-diimine ligands as catalytic precursors for the transfer hydrogenation of ethyl levulinate to γ-valerolactone”, New J. Chem. 2018, 42, 17574-17586.
• Why metal triflates gave worse performances than the sulfonic acids? The yield was lower because the conversion was lower or the selectivity? If the selectivity was lower, which were the major by-products?
• Which are the differences between the Nafion NR50 and Nafion NR117? Why the latter gave worse performences though it is a liquid catalyst?
• How the solvent can influence the yield?
• Which is the influence of the heating system?
• The authors should specify if the yields are expressed as mol% or wt%. Moreover, the yield is not the only important parameter but also the selectivity should be reported.
• Table 1, entry 18: The authors should identify the unknown by-products in order to hypothesize the mechanism that takes place in toluene.
• Why the authors employed a longer reaction time for the synthesis of quinolinyl ketones?
• The authors attribute to MW a specific role in the mechanism hypothesizing that they do not only speed up the reaction, as generally is reported. This is possible? The authors should support their thesis with some references.
• In the recycle runs the catalyst was only separated or before the subsequent run it was previously washed?

Author Response

July 14, 2021

Ms. Ella Cai

Assistant Editor

Catalysts

Email: [email protected]

 

Article title: Environmentally Friendly Nafion-catalyzed Synthesis of Substituted 2-Ethyl-3-Methylquinolines from Aniline and Propionaldehyde Under Microwave Irradiation

Article ID: catalyst-1300309

Article authors: Chieh-Kai Chan *, Chien-Yu Lai and Cheng-Chung Wang *

 

Dear Ms. Ella Cai,

We appreciate that the Editor provides us the chance to revise the manuscript, and the detailed correction by three positive reviewers. We have revised the manuscript in accordance with the suggestions of the reviewers. The suggested changes have been included in the revised manuscript. The manuscript had been rechecked by native English language service, including inappropriate English descriptions.

 

 

First, we have clarified our statement as follows according to the opinion from the Reviewer 3.

Q1 : The authors should explain the mechanism of the Friedlander reaction.

A1-1: In 2020, we have reported a Nafion^® NR50-catalyzed Friedländer quinoline synthesis work, and has been cited in the reference 69. The related description was also included in the revised manuscript, we think that it is enough to provide the explanation of Friedländer reaction mechanism.

A1-2: In Page 5, Lines 138~141: The sentence “Friedländer quinoline synthesis is the reaction of 2-aminobenzaldehyde with acetylaldehyde to generate quinoline skeleton. In 2020, we have already developed a Nafion^® NR50-catalyzed Friedländer quinoline synthesis, the related mechanism was also reported. [69]” has been included in the revised manuscript.

Q2 : The authors should describe the properties of Nafion NR50 in terms of chemical structure, acidity, etc.

A2-1: In Page 2, Lines 47~51: The sentence “Nafion® is a commercially available synthetic polymer particle which possess ionic properties. [72] Its unique ionic properties result from the copolymerization of incorporating perfluorovinyl ether groups terminated with sulfonate groups onto a tetrafluoro-ethylene (PTFE) skeleton. [73] The chemical structure of Nafion^® NR50 was shown in Scheme 2.” has been included in the revised manuscript.

A2-2: In Page 18, Line 708, reference 72: The sentence “Church, S. (January 6, 2006). "Del. firm installs fuel cell". The News Journal. p. B7.” has been included in the revised manuscript.

A2-3: In Page 18, Line 709, reference 73: The sentence “Mauritz, K. A. and Moore, R. B. State of Understanding of Nafion. Chem. Rev. 2004, 104, 4535-4585.” has been included in the revised manuscript.

Q3 : The authors should explain the reason why they employed MW irradiation as heating system mentioning its advantages respect to a traditional heating system.

A3-1 : Considering the efficiency of microwave irradiation and the boiling point of propionaldehyde, we think that the MW is a better heating source than traditional heating system.

A3-2: In Page 2, Lines 52~53: The sentence “efficiency of microwave irradiation” has been included in the revised manuscript.

A3-3: In Pages 2~3, Lines 79~80: The sentence “It is possible that the boiling point of propionaldehyde is lower than the reaction temperature, and the reaction was conducted in the open system (entry 21).” has been included in the revised manuscript.

A3-4: In Page 3, Lines 83~84: The sentence “Microwave irradiation have attracted considerable attention in the past decade for accelerating the reaction efficiency. [74-75]” has been included in the revised manuscript.

Q4 : For this purpose the authors should cite at least these references: - C. Antonetti, S. Fulignati, D. Licursi, A.M. Raspolli Galletti “Turning point toward the sustainable production of 5- hydroxymethyl-2-furaldehyde in water: metal salts for its synthesis from fructose and inulin”, ACS Sustainable Chem. Eng. 2019, 7, 6830-6838. - L. Biancalana, S. Fulignati, C. Antonetti, S. Zacchini, G. Provinciali, G. Pampaloni, A.M. Raspolli Galletti, F. Marchetti “Ruthenium p-cymene complexes with α-diimine ligands as catalytic precursors for the transfer hydrogenation of ethyl levulinate to γ-valerolactone”, New J. Chem. 2018, 42, 17574-17586.

A4-1: In Page 18, Lines 710~711, reference 74: The sentence “Antonetti, C.; Fulignati, S.; Licursi, D.; Galletti, A. M. R. Turning Point toward the Sustainable Production of 5‐Hydroxymethyl-2-furaldehyde in Water: Metal Salts for Its Synthesis from Fructose and Inulin. ACS Sustainable Chem. Eng. 2019, 7, 6830-6838.” has been included in the revised manuscript.

A4-2: In Page 18, Lines 712~713, reference 75: The sentence “Biancalana, L.; Fulignati, S.; Antonetti, C.; Zacchini, S.; Provinciali, G.; Pampaloni, G.; Galletti, A. M. R.; Marchetti, F. New J. Chem., 2018, 42, 17574-17586.” has been included in the revised manuscript.

Q5 : Why metal triflates gave worse performances than the sulfonic acids? The yield was lower because the conversion was lower or the selectivity? If the selectivity was lower, which were the major by-products?

A5-1: We think that metal triflates gave worse performances than the sulfonic acids is owing to the conversion was lower. In our optimization, AgOTf could promote the reaction to obtain 45% yield of compound 3a. It means that we couldn’t summarize the conversion of all metal triflates is lower than sulfonic acids but most metal triflates. Considering the green chemistry issue and reaction efficiency, the results showed that the performance of Nafion^® NR50 is a better acidic catalyst than other choices.

A5-2: In this synthetic protocol, we think that the selectivity is exclusive to form the 2-ethyl-3-methylquinolines scaffold. No selectivity problem appeared except the formation of compound 7 by controlling equivalent of aldehyde 2e, if we don’t misunderstand Reviewer 3’s comments.

Q6 : Which are the differences between the Nafion NR50 and Nafion NR117? Why the latter gave worse performences though it is a liquid catalyst?

A6-1: Nafion^® NR50 is a solid particle, and Nafion^® NR117 is a solution type contains 10%~15% of water.

A6-2: We guessed that Nafion^® NR117 gave worse performance is owing to its liquid type offering lower efficiency.

Q7 : How the solvent can influence the yield?

A7: We think that the solubility of solvent is a factor but not a big issue in this protocol, though toluene gave lower yield of compound 3a and higher N-propylamine. Ethanol is a cheap reaction solvent and meet green issue, we don’t further explore more chemical solvents.

Q8 : Which is the influence of the heating system?

A8: Owing to the boiling point of propionaldehyde is lower than ethanol, the cyclization reaction should be conducted under reflux condition. Therefore, we think that the closed microwave irradiation system is a better heating source than traditional hot-plate.

Q9 : The authors should specify if the yields are expressed as mol% or wt%. Moreover, the yield is not the only important parameter but also the selectivity should be reported.

A9-1: To clearly express the form of yields, we have specified the all the compound yields are shown in mol%. In this article, we think that the selectivity is exclusive to form the 2-ethyl-3-methylquinolines. No selectivity problem appeared except the formation of compound 7 by controlling equivalent of aldehyde 2e.

A9-2: In Page 8, 3.1 General Information, Lines 193~194: The sentence “The yields are provided in mol% and the corresponding product weight are also shown.” has been included in the revised manuscript.

Q10 : Table 1, entry 18: The authors should identify the unknown by-products in order to hypothesize the mechanism that takes place in toluene.

A10-1: We can only identified the 45% yield of remaining 83% unknown by-products is N-propylamine. It is reasonably the simple coupling of amine and aldehyde. The intermediate has been drawn in the mechanism study part.

A10-2: In Page 3, Line 92: The sentence “^cMajor unknown products that were obtained.” in the original manuscript has been changed to “^c45% of N-propylamine were obtained.” in the revised manuscript.

Q11 : Why the authors employed a longer reaction time for the synthesis of quinolinyl ketones?

A11-1: We want to explore the reaction scope and examine the reaction generalities.

A11-2: In our previous work (Synthesis 2020, 52, 1779-1794.), we found that the quinolinyl chalcones contains some interesting activities. Based on the structure-activity-relationship (SAR), the preparation of diversified quinolinyl chalcones could enrich the data base.

Q12 : The authors attribute to MW a specific role in the mechanism hypothesizing that they do not only speed up the reaction, as generally is reported. This is possible? The authors should support their thesis with some references.

A12 : Owing to the boiling point of propionaldehyde is lower than ethanol, the cyclization reaction should be conducted under reflux condition. Therefore, we think that the closed microwave irradiation system is a better heating source than traditional hot-plate not only speed up the reaction but also the closed system for low boiling point reagents.

Q13 : In the recycle runs the catalyst was only separated or before the subsequent run it was previously washed?

A13 : For the recycle experiments, we only separated the particles by filter paper and washing by ethanol to prevent the residue on the surface. Then, we conducted the subsequent experiment without any process.

 

 

We hope that we have clarified our statement such that the Editor can understand our opinions. According to the Reviewer 3’s comments, we return the revised manuscript. We hope that the revised version is acceptable.

 

Sincerely,

 

 

 

 

Dr. Cheng-Chung Wang

Associate Research Fellow

Institute of Chemistry, Academia Sinica

No.128 Academia Road Section 2, Nan-Kang

Taipei, 11529, Taiwan

Tel: 886-2-5572-8618

Fax: 886-2-2783-1237

E-mail: [email protected]

 

Author Response File: Author Response.pdf

Round 2

Reviewer 2 Report

The issues were solved and the manuscript can be accepted for publication after some minor changes:

Line 84: the efficiency can be increased but not "accelerated": Please correct

Line 128: the meaning of this added sentence is not clear. "substrate scope" in particular should be corrected/explained

line 172-173: the English of the sentence is not correct, please rewrite

line 174: alert in checkcif data are still not mentioned. A sentence like "No alert A and B are present in the checkcif output, as reported in the supplementary information file"

line 543 "the generality of this synthetic protocol is broad" please rewrite

line 545: if "its" is referred to "Nafion NR 50 particles" must be changed in "their" and "exhibits" in "exhibit"

Line 546 : remove "and the analysis was newly reported"

 

Author Response

July 19, 2021

Ms. Snowy Bian

Assistant Editor

Catalysts

Email: [email protected]

 

Article title: Environmentally Friendly Nafion-catalyzed Synthesis of Substituted 2-Ethyl-3-Methylquinolines from Aniline and Propionaldehyde Under Microwave Irradiation

Article ID: catalyst-1300309

Article authors: Chieh-Kai Chan *, Chien-Yu Lai and Cheng-Chung Wang *

 

Dear Ms. Snowy Bian,

We appreciate that the Editor provides us the chance to revise the manuscript, and the detailed correction by three positive reviewers. We have revised the manuscript in accordance with the suggestions of the reviewers. The suggested changes have been included in the revised manuscript. The manuscript had been rechecked by native English language service, including inappropriate English descriptions.

 

 

First, we have clarified our statement as follows according to the opinion from the Reviewer 2.

Q1 : Line 84: the efficiency can be increased but not "accelerated": Please correct.

A1: Line 84: The word “accelerated” has been changed to “increasing” in the revised manuscript.

Q2 : Line 128: the meaning of this added sentence is not clear. "substrate scope" in particular should be corrected/explained.

A2: Line 128: The sentence “Next, the substrate scope of propionaldehyde derivatives were investigated in this transformation” in the original manuscript has been corrected to “We next investigated the scope of substituents on the terminal of propionaldehyde” in the revised manuscript.

Q3 : line 172-173: the English of the sentence is not correct, please rewrite.

A3: Lines 172~173: The sentence “In a comparison of reported literatures, there are four compounds are confirmed by single-crystal X-ray crystallography” in the original manuscript has been changed to “On the basis of the abovementioned results, four new chemical structure are confirmed by single-crystal X-ray crystallography.” in the revised manuscript.

Q4 : line 174: alert in checkcif data are still not mentioned. A sentence like "No alert A and B are present in the checkcif output, as reported in the supplementary information file".

A4: Lines 173~175: The sentence “the corresponding crystal structures and related analysis data are described in Table 2.” in the original manuscript has been changed to “The corresponding crystal structures of 3p, 5a, 5b and 5d, and related data are described in Table 2. Furthermore, no alert A and B are presented in the checkcif output, as reported in the Supplementary Information file.” in the revised manuscript.

Q5 : line 543 "the generality of this synthetic protocol is broad" please rewrite.

A5: Lines 543~544: The sentence “the generality of this synthetic protocol is broad” in the original manuscript has been changed to “this reaction features good functional group tolerance” in the revised manuscript.

Q6 : line 545: if "its" is referred to "Nafion NR 50 particles" must be changed in "their" and "exhibits" in "exhibit".

A6-1: Line 544: The word “exhibits” has been changed to “exhibit” in the revised manuscript.

A6-2: Line 545: The word “its” has been changed to “their” in the revised manuscript.

Q7 : Line 546 : remove "and the analysis was newly reported".

A7: Line 547: The sentence “and the analysis was newly reported” has been removed in the revised manuscript.

 

 

We hope that we have clarified our statement such that the Editor can understand our opinions. According to the Reviewer 2’s comments, we return the revised manuscript. We hope that the revised version is acceptable.

 

Sincerely,

 

 

 

 

Dr. Cheng-Chung Wang

Associate Research Fellow

Institute of Chemistry, Academia Sinica

No.128 Academia Road Section 2, Nan-Kang

Taipei, 11529, Taiwan

Tel: 886-2-5572-8618

Fax: 886-2-2783-1237

E-mail: [email protected]

Author Response File: Author Response.pdf

Reviewer 3 Report

The authors have improved the manuscript according to the comments of the reviewer, thus the article can be now accepted.

Author Response

We thank for Reviewer 3's comments and acceptance.