A HCl-Mediated, Metal- and Oxidant-Free Photocatalytic Strategy for C3 Arylation of Quinoxalin(on)es with Arylhydrazine
Round 1
Reviewer 1 Report
In this manuscript, the authors report a HCl-mediated, metal- and oxidant-free photocatalytic protocol for C3 arylation of quinoxalin(on)es with arylhydrazine. The reaction was performed with broad substate scope. While first part of the manuscript is well presented, but the mechanistic part makes me questions. In my opinion the current manuscript deserves to be published after addressing the next comments:
- The word “quinoxalin(on)es” should not be capitalized everywhere.
- There is no reference on Scheme 1 in the Introduction Part.
- It is interesting why in case of K2CO3 the reaction does work? In this case seems the reaction proceeds not through radical process?
- I’m curious, does the reaction will work with the hydrochloride salt of phenylhydrazine without addition of HCl? Such reaction should be performed.
- Line 70, the meaning of word “N-substrates” not scientific (should be more clarified).
- Line 72, it is better to indicate in which position are alkyl and ester groups.
- Line 73, Bn group is also alkyl actually.
- Line 74, instead of “products” should be “product”; and there is from 53% yield comes? For which product?
- Line 75, instead of “on” should be “at”.
- Line 76, instead of “to” better suited “and”.
- Line 78, instead of “yields” should be “yield”; same in line 93.
- Line 96, instead of “condition” should be “conditions”.
- Did the authors detect the formation of hydrogen gas? In Scheme 3, it is difficult to believe that from HCl the hydrogen gas a formed, what is reductant for such process? So, the authors have to proof the formation of H2, otherwise, have to delete H2 from sentence “with N2 and H2 as mainly byproduct” in the abstract. Same in Line 112.
- There is no title of the paper in ref. 4b.
Author Response
In this manuscript, the authors report a HCl-mediated, metal- and arylhydrazine. The reaction was performed with broad substate scope. While first part of the manuscript is well presented, but the mechanistic part makes me questions. In my opinion the current manuscript deserves to be published after addressing the next comments:
Response: Thanks for your constructive suggestions and we have revised our manuscript according to your suggestions.
- The word “quinoxalin(on)es” should not be capitalized everywhere.
Response: We have corrected this incorrect expression in our manuscript.
2.There is no reference on Scheme 1 in the Introduction Part.
Response: We have added the description to the third paragraph of the manuscript with highlight and corrected the corresponding reference number.
3.It is interesting why in case of K2CO3 the reaction does work? In this case seems the reaction proceeds not through radical process?
Response: According to the previous reports (Green Chem., 2017, 19, 2941-2944; Org. Lett. 2018, 20, 7740-7743; RSC Adv., 2018, 8, 33828-33844; Green Chem., 2019, 21, 2905-2910, etc.), including DABCO and K2CO3 could also excite phenylhydrazine into a phenyl radical, so we think present mechanism is reliable for this transformation.
4.I’m curious, does the reaction will work with the hydrochloride salt of phenylhydrazine without addition of HCl? Such reaction should be performed.
Response: As your suggestion, we then used 4.0 equivalents of phenylhydrazine hydrochloride to instead of phenylhydrazine with the absence of HCl, and no desired product could be obtained. The result had been added to the control experiments section of the manuscript with highlight.
5.Line 70, the meaning of word “N-substrates” not scientific (should be more clarified); Line 72, it is better to indicate in which position are alkyl and ester groups; Line 73, Bn group is also alkyl actually.
Response: We have modified the description to ‘Substrates containing alkyl, aryl, benzyl and ethyl acetate at N1 position proceeded smoothly and provide the corresponding products (3a-3l) from 45 to 82% yield, furthermore, substrates bearing alkyl and ester groups (3a-3f) gave better (71 to 88%) yield than the aryl ones (3g, 3h, 63 and 66%)’ in our manuscript.
6.Line 74, instead of “products” should be “product”; and there is from 53% yield comes? For which product?
Response: We corrected the erroneous statements and deleted the excess description in the manuscript.
7.Line 75, instead of “on” should be “at”.
Response: We corrected the erroneous statements in the manuscript.
8.Line 76, instead of “to” better suited “and”.
Response: We corrected the erroneous statements in the manuscript.
9.Line 78, instead of “yields” should be “yield”; same in line 93.
Response: We corrected the erroneous statements in the manuscript.
10.Line 96, instead of “condition” should be “conditions”.
Response: We corrected the erroneous statements in the manuscript.
11.Did the authors detect the formation of hydrogen gas? In Scheme 3, it is difficult to believe that from HCl the hydrogen gas a formed, what is reductant for such process? So, the authors have to proof the formation of H2, otherwise, have to delete H2 from sentence “with N2 and H2 as mainly byproduct” in the abstract. Same in Line 112.
Response: Based on your suggestion, several experiments were then conducted and no H2 was detected, so we deleted the relevant expression in the manuscript.
12.There is no title of the paper in ref. 4b.
Response: We had added the title of the reference and adjusted its number to 10.
Author Response File: 
Author Response.pdf
Reviewer 2 Report
The authors report on an arylation of two classes of heterocycles using arylhydrazine aided by HCl and blue-light irradiation. This is an interesting transformation which is useful for those in the field. There are 4 journal articles and one patent describing similar chemistry, although the use of HCl seems to be new. However, it could be that several of the other studies also has HCl in the reaction as arylhydrazines also can be purchased as their HCl salts.
I am not convinced that the paper should be accepted as a communication. The rapid publication of the work is not of high importance as several other strategies could be used. Instead, I suggest that the authors provide more experimental and spectroscopic details in a full paper, which will be useful for organic chemists.
Otherwise, the language of the manuscript needs to be improved a bit. A pdf with some suggestions is included.
Comments for author File: Comments.pdf
Author Response
Referee 2: The authors report on an arylation of two classes of heterocycles using arylhydrazine aided by HCl and blue-light irradiation. This is an interesting transformation which is useful for those in the field. There are 4 journal articles and one patent describing similar chemistry, although the use of HCl seems to be new. However, it could be that several of the other studies also has HCl in the reaction as arylhydrazines also can be purchased as their HCl salts.
Response: Thank you for your constructive suggestion. In order to prove the necessity of HCl, we used 4.0 equivalents of phenylhydrazine hydrochloride to instead of phenylhydrazine with the absence of HCl, and there was no desired product could be obtained, indicating that HCl plays an irreplaceable role in the reaction. The result had been added to the control experiments section of the manuscript with highlight.
- I am not convinced that the paper should be accepted as a communication. The rapid publication of the work is not of high importance as several other strategies could be used. Instead, I suggest that the authors provide more experimental and spectroscopic details in a full paper, which will be useful for organic chemists.
Response: As your suggestion, we had changed the manuscript into full paper.
- Otherwise, the language of the manuscript needs to be improved a bit. A pdf with some suggestions is included.
Response: Thank you for your kindly suggestion. We have revised the manuscript according to your advices.
Author Response File: Author Response.pdf
Reviewer 3 Report
This communication describe an efficient photocatalytic C-H arylation of quinoxalinones compounds at room temperature. The reviewer recommend publication of this manuscript with the following comments:
1. Are the reactions conducted under aerobic conditions? If so, the authors need to include "in air" in the general reaction scheme (Scheme 1).
2. The authors proposed a critical role of the Cl radical in the reaction mechanism. Yet, without HCl (with K2CO3), the reaction does proceed with 45% yield. The authors might consider performing a controlled experiment with a different acid to verify the role of Cl in the reaction mechanism.
3. The authors need to specify the HCl solution used. Was concentrated HCl being used? If not, what is the concentration of the HCl? How does water in these reaction might impact the reaction outcome?
Author Response
Reviewer 3: This communication describe an efficient photocatalytic C-H arylation of quinoxalinones compounds at room temperature. The reviewer recommend publication of this manuscript with the following comments:
- Are the reactions conducted under aerobic conditions? If so, the authors need to include "in air" in the general reaction scheme (Scheme 1).
Response: The reaction was carried out in the air and we had changed it in the manuscript with highlight.
- The authors proposed a critical role of the Cl radical in the reaction mechanism. Yet, without HCl (with K2CO3), the reaction does proceed with 45% yield. The authors might consider performing a controlled experiment with a different acid to verify the role of Cl in the reaction mechanism.
|
Entry |
Variation from given conditions |
Yields (%) |
|
1 |
6.0 mol/L HCl was used |
42 |
|
2 |
9.0 mol/L HCl was used |
55 |
|
3 |
HBr instead of HCl |
78 |
|
4 |
H2SO4 instead of HCl |
0 |
|
5 |
HNO3 instead of HCl |
0 |
|
6 |
MeCN/ H2O (v/v=1:1) instead of MeCN |
47 |
|
7 |
H2O instead of MeCN |
trace |
Reaction conditions: 1 (0.2 mmol), 2 (1.5 eq.), HCl (4.0 eq.), MeCN (2.0 mL), blue LED (25 W), r.t., in air, 10 h. b Isolated yields.
Response: As your suggestion, more control experiments were carried out as shown in the table above. It can be concluded that HBr also showed high catalytic activity, while H2SO4 and HNO3 could not take place transformation, indicating that Cl and Br were key factors to activating benzene radicals.
- The authors need to specify the HCl solution used. Was concentrated HCl being used? If not, what is the concentration of the HCl? How does water in these reaction might impact the reaction outcome?
Response: Thanks for your constructive suggestions and the HCl we used in this transformation was concentrated. At the same time, as shown in the table above, changing the concentration of HCl or increasing the amount of H2O in the solvent, the yield will be reduced to varying degrees or even cannot take place, which indicating that H2O had a Inhibitory effect in this transformation.
Author Response File: Author Response.pdf
Round 2
Reviewer 1 Report
The authors have revised the manuscript taking into consideration the comments of the reviewers and answered on my questions. The article can be published in present form.
Author Response
The authors have revised the manuscript taking into consideration the comments of the reviewers and answered on my questions. The article can be published in present form.
Response: Thank you very much for your previous constructive comments on our article and your affirmation of our modified article and wish you a happy day.
Author Response File: Author Response.pdf
Reviewer 2 Report
1Some minor writing issues:
Find enclosed a pdf for inspection.
Line 12: has instead of had
Line 28-31: improve this sentence
Line 47: describe instead of developed
Line 59 : gave lower instead of performed weaker
Line 71-74, splitt into two sentences.
Line 89: were also tested instead of also been researched
Line 95: correct sentence; remove application value.
Experimental:
The experimental section is divided in two parts-correct
Capital first letter for compound name (line 158 and all other)
13C NMR: mark all those carbon signals originating from more than one carbon: example 130. 5 (2C)
Comments for author File: Comments.pdf
Author Response
Referee 2:.Some minor writing issues:
Find enclosed a pdf for inspection.
Response: Thanks for your constructive suggestions and we have revised our manuscript according to your suggestions.
- Line 12: has instead of had.
Response: We have corrected this incorrect expression in our manuscript.
- Line 28-31: improve this sentence.
Response: We have modified the description to ‘Over the past few decades, C-H functionalization has become an important tool in organic synthesis, and a series of researches via the efficient strategy have been carried out on the preparation of functional quinoxalin(on)es, including C-N bond formation, [21-25] C-C formation, [26-28] C-S(O) bond formation. [29-34]’ in our manuscript with highlight.
- Line 47: describe instead of developed.
Response: We have corrected this incorrect expression in our manuscript.
- Line 59 : gave lower instead of performed weaker.
Response: We have corrected this incorrect expression in our manuscript.
- Line 71-74, splitt into two sentences.
Response: As your suggestion, we have modified the description to ‘Substrates containing alkyl, aryl, benzyl and ester groups at N1 position proceeded smoothly and provide the corresponding products (3a–3l) from 45 to 82% yield. Furthermore, substrates bearing alkyl and ester groups (3a–3f) gave better (71 to 88%) yield than the aryl ones (3g, 3h, 63 and 66%).’ in our manuscript with highlight.
- Line 89: were also tested instead of also been researched.
Response: We have changed this statement in our manuscript.
- Line 95: correct sentence; remove application value.
Response: We have removed this superfluous description in our manuscript.
Experimental:
- The experimental section is divided in two parts-correct.
Response: We have combined the two parts in the experimental section.
9.Capital first letter for compound name (line 158 and all other)
Response: We have capitalized the first letter of all the compounds.
10.13C NMR: mark all those carbon signals originating from more than one carbon: example 130. 5 (2C)
Response: We have marked all carbon signals originating from more than one carbon.
