Copper-on-Magnetically Activated Carbon-Catalyzed Azide-Alkyne Click Cycloaddition in Water
, El Mountassir El Mouchtari 1, Hicham Ben El Ayouchia 1,*, Hafid Anane 1, Salah Rafqah 1, Miguel Julve 2 and Salah-Eddine Stiriba 2,*
Tomáš Tobrman
Round 1
Reviewer 1 Report
The manuscript by Aflak et al. describes the preparation and characterization of a copper catalyst on a carbon-iron oxide composite support (Cu-Fe3O4-PAC) and its use in copper-catalyzed azide-alkyne cycloaddition reactions (CuAAC).
Overall, I do not feel that that the results disclosed in the manuscript represent a substantial improvement over the state of the art in the field, neither for what it concerns the catalytic activity of the new system (the optimized CuAAC runs require 18-23 h at r.t. to complete), nor for its recycling. Concerning this latter aspect, it must be pointed out that - contrarily to the claim, in the abstract, that the material is “recyclable up to five runs without any significant loss of its catalytic activity and selectivity”- the data presented in Fig. 9 show some clear drop in the product yield after the first reaction cycle.
Moreover, in my opinion the work suffers from several flaws that make it ill-suited, at least in the present state, for publication in a catalysis journal. The most critical one is the apparent neglect to determine (and, in any case, to report) the actual copper loading in the composite material. Inter alia, this prevents any meaningful comparison with similar catalytic systems from the literature, as demonstrated by Table 3 where the run with the material disclosed in the manuscript is the only one for which the Cu mol% loading cannot be listed. Therefore, a reliable determination of the metal content in the supported system (e.g., by mineralization followed by ICP-AES) is mandatorily required; after that, the mol% of Cu (or, equivalently, the substrate to copper ratio) used in each catalysis run of Table 2 and Scheme 2 should be calculated and properly reported.
Another point of concern is the ‘hot filtration’ control test (page 9): given that all the other CuAAC runs were apparently carried out at r.t., I can hardly understand the reason for performing the test at 50 °C. In fact, lacking any detail on how the experiment was carried out (under air or in a protected atmosphere?), it could well be that the prompt oxidation of Cu(I) in solution masks to a large extent the occurrence of soluble and catalytically active metal species in the regular (r.t.) runs.
The statement (page 7) that: “All the synthesized triazole derivatives were obtained in high purity without further purification (see Supplementary Material)” needs proper analytical evidence, beyond the recording of the NMR spectra provided in the annex. In detail, aside evaluating the content of organic byproducts by, e.g., chromatographic techniques, it would be highly desirable the quantitation of copper and iron in some of the crudes. Besides, this latter task would address one of the motivations behind the proposed approach, thus the expectation that heterogeneous catalytic systems may simplify the removal of copper from the triazole products and provide systems better suited for industrial applications (see page 2).
Lacking any experimental evidence about the structure at the molecular level of the supported catalyst, as well as any kinetic data, a final major questionable aspect in the manuscript is its computational section (pages 10-12). Under these circumstances, it is less than obvious to me why the dinuclear complexes identified by the calculations, and depicted in the cycle in Scheme 3, should bear any relationship to the species involved in the reaction pathway with the (supposedly heterogeneous) system under exam.
Concerning the referencing of previous studies, I think that in some cases the Authors indulge in citing their own work somewhat beyond what is needed by the topic under discussion (refs. 10 and 11 can be an example). At the same time, the logic behind the selection of the examples in Table 3 looks somewhat arbitrary, with many other relevant instances from the literature that are not included in the comparison. In this regard, it does not help the fact that the only review paper on the topic of supported catalysts for CuAAC, published by the same Authors early this year (ref. 17), covers the advances in the field in last five years only.
Author Response
“point-by-point” responses to the reviewers:
Reviewer 1:
The manuscript by Aflak et al. describes the preparation and characterization of a copper catalyst on a carbon-iron oxide composite support (Cu-Fe3O4-PAC) and its use in copper-catalyzed azide-alkyne cycloaddition reactions (CuAAC).
Overall, I do not feel that that the results disclosed in the manuscript represent a substantial improvement over the state of the art in the field, neither for what it concerns the catalytic activity of the new system (the optimized CuAAC runs require 18-23 h at r.t. to complete), nor for its recycling. Concerning this latter aspect, it must be pointed out that - contrarily to the claim, in the abstract, that the material is “recyclable up to five runs without any significant loss of its catalytic activity and selectivity”- the data presented in Fig. 9 show some clear drop in the product yield after the first reaction cycle.
Authors: We unfortunately disagree with the Reviewer because the results described in this contribution represent a substantial improvement of the chemistry of CuAAC, in particular from the heterogeneous catalysis and sustainable chemistry points of view. In fact, the catalytic material is easily separated from the reaction medium by very simple magnetic field application taking advantage of the presence of a magnetic support such as Fe3O4. Yet, the reaction is performed only in water and the yield of the catalytic reaction using recoverable “precatalyst” does only decrease to 92% at the fifth cycle. The catalytic system described herein was prepared from a raw biomass material. All these features make this work a sustainable contribution to the design of heterogeneous catalysts with a sustainable vision; a topic which is still less studied.
The sentence “recyclable up to five runs without any significant loss of its catalytic activity and selectivity” in the abstract was replaced by “recyclable up to five runs with only 8% decline of its activity after the 5th catalytic test.”.
Moreover, in my opinion the work suffers from several flaws that make it ill-suited, at least in the present state, for publication in a catalysis journal. The most critical one is the apparent neglect to determine (and, in any case, to report) the actual copper loading in the composite material. Inter alia, this prevents any meaningful comparison with similar catalytic systems from the literature, as demonstrated by Table 3 where the run with the material disclosed in the manuscript is the only one for which the Cu mol% loading cannot be listed. Therefore, a reliable determination of the metal content in the supported system (e.g., by mineralization followed by ICP-AES) is mandatorily required; after that, the mol% of Cu (or, equivalently, the substrate to copper ratio) used in each catalysis run of Table 2 and Scheme 2 should be calculated and properly reported.
Authors: The copper content in the synthesized catalytic material was determined by Atomic Absorption Spectroscopy (AAS) and the copper mol% loadings are now listed in Table 2.
Another point of concern is the ‘hot filtration’ control test (page 9): given that all the other CuAAC runs were apparently carried out at r.t., I can hardly understand the reason for performing the test at 50 °C. In fact, lacking any detail on how the experiment was carried out (under air or in a protected atmosphere?), it could well be that the prompt oxidation of Cu(I) in solution masks to a large extent the occurrence of soluble and catalytically active metal species in the regular (r.t.) runs.
Authors: ‘hot filtration’ is a typical test which proves that a heterogeneous catalyst truly behaves via heterogeneous fashion. The performance of the hot filtration at high temperature (at 50 °C in the present case), although the catalytic study was done at room temperature, is the best way to prove that the catalytic species is still supported to the employed catalytic support and that no leaching even at somehow harsh conditions does take place.
According to the Reviewer’s opinion, the experiment section of the ‘hot filtration’ test was revised as follows: “The reaction of benzyl azide (1a) and phenylacetylene (2a) was initiated at 50 °C in water under air atmosphere. After 2 hours, the catalyst was recovered by means of an external magnet at the reaction temperature and the filtrate was allowed to react under the same catalytic reaction conditions” (see p 9, lines: 219-221).
The statement (page 7) that: “All the synthesized triazole derivatives were obtained in high purity without further purification (see Supplementary Material)” needs proper analytical evidence, beyond the recording of the NMR spectra provided in the annex. In detail, aside evaluating the content of organic byproducts by, e.g., chromatographic techniques, it would be highly desirable the quantitation of copper and iron in some of the crudes. Besides, this latter task would address one of the motivations behind the proposed approach, thus the expectation that heterogeneous catalytic systems may simplify the removal of copper from the triazole products and provide systems better suited for industrial applications (see page 2).
Authors: We have used the AAS to determine the amount of copper traces in 1,2,3-triazole products and we have found a very low concentration of copper. The results of this analysis were included in the results and discussion section “Furthermore, the percentage of copper particles in the final click product was determined by AAS analysis and it was found to be present in very low concentration (less than 0.3 ppm)” (see p 9, lines: 211-213).
Lacking any experimental evidence about the structure at the molecular level of the supported catalyst, as well as any kinetic data, a final major questionable aspect in the manuscript is its computational section (pages 10-12). Under these circumstances, it is less than obvious to me why the dinuclear complexes identified by the calculations, and depicted in the cycle in Scheme 3, should bear any relationship to the species involved in the reaction pathway with the (supposedly heterogeneous) system under exam.
Authors: In the present work, CuAAC appears to occur on the surface of the heterogeneous catalytic system Cu-Fe3O4-PAC containing catalytically active particle species. The action of these particles in CuAAC should occur at the molecular level. The copper traces found in the triazole product are a proof of that. At such level, the dinuclear copper-acetylide motif is the most stable intermediate being formed during the ligation of organic azide and terminal alkyne, either working under homo- or heterogeneous catalytic conditions.
Concerning the referencing of previous studies, I think that in some cases the Authors indulge in citing their own work somewhat beyond what is needed by the topic under discussion (refs. 10 and 11 can be an example).
Authors: The references 10 and 11 were initially included to show the versatility and function of the 1,2,3-triazole moiety in applied chemical technology.
At the same time, the logic behind the selection of the examples in Table 3 looks somewhat arbitrary, with many other relevant instances from the literature that are not included in the comparison.
Authors: The examples given in Table 3 were nicely selected based on the similarity of the nature of both the catalytic raw material support and the magnetic support. Indeed, there are more examples that this contribution could not cover.
In this regard, it does not help the fact that the only review paper on the topic of supported catalysts for CuAAC, published by the same Authors early this year (ref. 17), covers the advances in the field in last five years only.
Authors: We have added another reference of a review article that covers the performance of CuAAC under heterogeneous conditions (see ref. 20).
[20] Chassaing, S.; Benneteau, V.; Pale, P. When CuAAC 'Click Chemistry' goes heterogeneous. Catal. Sci. Technol. 2015, 6, 923-957.
Reviewer 2 Report
The preparation of an apparently new catalyst for the CuAAC reaction is described in this manuscript. The preparation is and characterization of the catalyst is logical and conforms to standards. The optimization experiments are also adequately performed. The only problem I have is with the ESI:
The compound listed as 3h in the manuscript is not listed in the ESI because the NMR spectra for compound 3h (page S32-S34) do not match the proposed structure.
Some NMR spectra, for example compound 3b, 3c, 3d, 3e, 3g, 3i have spectra listed with the date 2014-2018. Does this mean that the whole work was done for about 8 years? I don't believe that. Or are old spectra used in the work? If so, the purity of the prepared substances cannot be trusted because the spectra do not correspond to reality.
Author Response
“point-by-point” responses to the reviewers:
Reviewer 2:
The preparation of an apparently new catalyst for the CuAAC reaction is described in this manuscript. The preparation is and characterization of the catalyst is logical and conforms to standards. The optimization experiments are also adequately performed. The only problem I have is with the ESI. The compound listed as 3h in the manuscript is not listed in the ESI because the NMR spectra for compound 3h (page S32-S34) do not match the proposed structure.
Authors: We apologize for this mistake. The compound 3h is now listed in the ESI material, including its spectroscopic data and respective NMR and HMRS spectra (see pp S34-S37).
Some NMR spectra, for example compound 3b, 3c, 3d, 3e, 3g, 3i have spectra listed with the date 2014-2018. Does this mean that the whole work was done for about 8 years? I don't believe that. Or are old spectra used in the work? If so, the purity of the prepared substances cannot be trusted because the spectra do not correspond to reality.
Authors: The chemistry described in this manuscript corresponds to the PhD thesis work of first author Dr. N. Aflak, carried out during the last three years. The 1,2,3-triazole products described in this work are not new; they were prepared by us and published elsewhere. Once prepared by us using the present heterogeneous catalytic system, they were analyzed and characterized by TLC, melting point and just 1H NMR to confirm their purity. These data found in this work fit well with those described by us and also by others. Additional old spectra such as 13C NMR, Dept-135 and HRMS were given to provide the reader with a complete set of data.
Reviewer 3 Report
The authors report the cycloaddition reaction of alkynes and azides (CuAAC) catalyzed by a heterogeneous nanocatalyst Cu-Fe3O4-PAC. The obtained catalyst was fully characterized by various methods. This is a well-written and executed study worthy of publication. I have a few suggestions/corrections for the authors to address:
1) Does PAC contain any basic sites? Because the basic conditions are very often required for the formation of acetylide. Or basicity comes from the remaining NaOH?
2) Figure 10. How about to check leaching after 2 hours? Most probably at 80% conversion there some inhibition process of the catalysis by the product is happening and not so big difference in the rates was observed.
3) Table 3. I recommend to provide TON and TOF values to compare the results with literature data? Moreover, the authors could provide the catalyst loading amount in mol% in the manuscript (and not by weight).
4) There is any reason why no reaction in DCM (Table 2, Entry 12)?
5) Did the authors try to reduce the water volume in the reaction (to increase the concentration of reagents), because the reaction proceeds on water and not in water. Furthermore, I’m sure that azide, alkyne and triazole are not soluble in water. So, most probably the catalysis is proceeding on catalyst surface, and not in water.
6) There is problem with integrals in NMR spectra: for compound 3а – at 1.72 ppm the integration of the proton should be deleted; compound 3с – the integrations are incorrect and at 2.17 ppm most probably the signal of acetone and not of the product; compound 3е – at 2.09 ppm the signal is not for the product; etc. The authors have to check carefully the reported data.
7) The recent papers on CuAAC reaction can be cited as well:
Molecules 2022, 27, 16
Applied Organometallic Chemistry 2022, 36, e684
Organometallics 2022, 41, 2154-2169
Nanomaterials 2022, 12, 1070
ACS Appl. Mater. Interfaces 2021, 13, 33091–33101
Journal of Catalysis 2020, 390, 37-45
Author Response
“point-by-point” responses to the reviewers:
Reviewer 3:
The authors report the cycloaddition reaction of alkynes and azides (CuAAC) catalyzed by a heterogeneous nanocatalyst Cu-Fe3O4-PAC. The obtained catalyst was fully characterized by various methods. This is a well-written and executed study worthy of publication. I have a few suggestions/corrections for the authors to address:
1) Does PAC contain any basic sites? Because the basic conditions are very often required for the formation of acetylide. Or basicity comes from the remaining NaOH?
Authors: The PAC raw material may have acidic and basic sites, depending on the pH value of the medium. In our case, many hydroxyl groups are available all throughout the activated carbon resulting from PAC preparation and from the oxidation of Fe ions into Fe3O4. The presence of hydroxyl groups most probably results in the formation of the acetylide.
2) Figure 10. How about to check leaching after 2 hours? Most probably at 80% conversion there some inhibition process of the catalysis by the product is happening and not so big difference in the rates was observed.
Authors: We are very grateful for this suggestion. According to the Reviewer’s suggestion, the leaching was checked after 2 hours (see Figure 10).
3) Table 3. I recommend to provide TON and TOF values to compare the results with literature data? Moreover, the authors could provide the catalyst loading amount in mol% in the manuscript (and not by weight).
Authors: The TON and TOF values as well as the catalyst loading amount (mol%) were added in Tables 2 and 3 as well as in Scheme 2.
4) There is any reason why no reaction in DCM (Table 2, Entry 12)?
Authors: This result may be due to a possible “negative” effect of DCM on the active surface of Cu-Fe3O4-PAC that contains the catalytically active copper species, a fact that needs further investigation in another context.
5) Did the authors try to reduce the water volume in the reaction (to increase the concentration of reagents), because the reaction proceeds on water and not in water. Furthermore, I’m sure that azide, alkyne and triazole are not soluble in water. So, most probably the catalysis is proceeding on catalyst surface, and not in water.
Authors: We fully agree with the Reviewer’s comment that the azide, alkyne and triazole are not soluble in water and the reaction carried out on water. However, the mechanical agitation of reaction mixture using less than 5 mL decreases the surface contact between the reagents and catalyst.
6) There is problem with integrals in NMR spectra: for compound 3а – at 1.72 ppm the integration of the proton should be deleted; compound 3с – the integrations are incorrect and at 2.17 ppm most probably the signal of acetone and not of the product; compound 3е – at 2.09 ppm the signal is not for the product; etc. The authors have to check carefully the reported data.
Authors: All the reported data were checked carefully as shown in the new ESI revised version.
7) The recent papers on CuAAC reaction can be cited as well:
Molecules 2022, 27, 16
Applied Organometallic Chemistry 2022, 36, e684
Organometallics 2022, 41, 2154-2169
Nanomaterials 2022, 12, 1070
ACS Appl. Mater. Interfaces 2021, 13, 33091–33101
Journal of Catalysis 2020, 390, 37-45
Authors: We appreciate the valuable suggestion of these interesting references. The following reference ACS Appl. Mater. Interfaces 2021, 13, 33091–33101 that reports a work, on heterogeneous CuAAC, related to the described in the manuscript was cited in the introduction section.
[22] Vafaeezadeh, M.; Schaumlöffel, J.; Lösch, A.; De Cuyper, A.; Thiel, W. R. Dinuclear Copper Complex Immobilized on a Janus-Type Material as an Interfacial Heterogeneous Catalyst for Green Synthesis. ACS Appl. Mater. Interfaces 2021, 13, 33091-33101
Reviewer 4 Report
I have read carefully the submitted manuscript entitled “Copper-on-magnetically activated carbon-catalyzed azide-alkyne click cycloaddition in water” for publication in Catalyst. The manuscript is clearly written and deals with the still topical issue of the widely used regioselective click reaction. The authors prepared and characterized a new catalyst. Although the authors state that the catalyst is fully characterized, I do not share this view. Some revisions will be necessary before the submitted manuscript can be accepted for publication, a list of which is given below. The list below is by no means all that can be improved, but it represents the minimum necessary.
Expression in molar percent of catalytic species in the reaction is usually used, as the authors report in comparison with similar published catalysts. The fact that the authors report the mass evokes the unknown copper content of the catalyst. Expression in molar percent of catalytic species in the reaction is usually used, as the authors report in comparison with similar published catalysts. The fact that the authors report the mass evokes the unknown copper content of the catalyst. The copper content must be characterized, and the manuscript text edited accordingly.
Figure 7. shows the EDX spectrum of the prepared catalyst. The observed composition is not commented in the text. The phosphorus content is not commented upon, and the presence of cuprous chloride is inferred from the XRD spectrum (Figure 2). In my opinion, not much can be inferred from the above powder diffractogram. Perhaps only the predominance of the amorphous matrix. The cuprous chloride is inferred from the published position of the diffraction line, which is certainly not visible in the diffractogram and must have been deduced subjectively. In the infrared spectrum, Cu-O bonding is discussed, thus how copper is bound? In publications, EDX mapping of the composition is often reported to verify homogeneity of the sample. It might be worthwhile to add. Please add a quantitative description of the composition from EDX in relation to the predicted catalyst composition and complete the manuscript accordingly.
A food for thought for me is the treatment of the mixture after the reaction. Given the fact that the reaction is carried out in water, why is dichloromethane added at the end of the reaction. Instead, I would magnetically separate the catalyst, wash it thoroughly with water, and process up the mixture without the catalyst. Perhaps its activity in subsequent recycling cycles would be higher.
Why is the equimolar ratio of reactants not used in the reaction? If this is really important, point it out in the text.
How was the graph constructed (Figure 10)? It seems to me that not enough points are used. In the case of catalyst separation, the reaction must stop immediately. This is not apparent from the interleaving shown and the point at which catalyst removal occurred is not shown. For the intended purpose it would be better to separate the catalyst at the lower conversion and the specific point in the graph should be indicated. It is also not appropriate to mathematically smooth the curve and, if so, to use the appropriate kinetic equation.
Please complete the procedure for determining the reaction kinetics on the basis of which the reaction time was designed. Or the determination of conversion over time at least for a model example. Simple monitoring of the reaction by thin-layer chromatography is of limited use only for the case where quantitative conversion occurs. The data do not show if the conversion is quantitative and the yield is determined by purification, or if the reaction is terminated at a lower degree of conversion.
Finally, I appreciate the characterization of the compounds prepared by the catalytic reaction in the supplement. However, there is no literature citation with which, in the case of known compounds, spectra and melting points can be compared. There are some discrepancies in some spectra indicating insufficient purity of the prepared substances. Misinterpretation of some spectra is shown. In 13C NMR there is no need to speculate about the assignment of signals to individual carbons. For unknown substances yet, this needs to be indicated on the basis of multidimensional spectra. Only relevant signals should be integrated for this publication. As an example of wrong interpretation is compound 3c. Some signals are from impurities. Therefore, the integration do not correspond with the identified compound, which is of course present in mixture.
In my opinion, for this article it is sufficient to describe how the conversion was determined. From the point of view of a catalytic study, it is not necessary to purify and identify all the prepared substances if they have already been described.
In view of the above, I recommend that the article be re-reviewed after a major revision.
Author Response
“point-by-point” responses to the reviewers:
Reviewer 4:
I have read carefully the submitted manuscript entitled “Copper-on-magnetically activated carbon-catalyzed azide-alkyne click cycloaddition in water” for publication in Catalyst. The manuscript is clearly written and deals with the still topical issue of the widely used regioselective click reaction. The authors prepared and characterized a new catalyst. Although the authors state that the catalyst is fully characterized, I do not share this view. Some revisions will be necessary before the submitted manuscript can be accepted for publication, a list of which is given below. The list below is by no means all that can be improved, but it represents the minimum necessary.
Expression in molar percent of catalytic species in the reaction is usually used, as the authors report in comparison with similar published catalysts. The fact that the authors report the mass evokes the unknown copper content of the catalyst. Expression in molar percent of catalytic species in the reaction is usually used, as the authors report in comparison with similar published catalysts. The fact that the authors report the mass evokes the unknown copper content of the catalyst. The copper content must be characterized, and the manuscript text edited accordingly.
Authors: We thank the Reviewer for this valuable suggestion. The copper content in molar percent found in the heterogeneous catalytic system under study has been included in the revised version.
Figure 7. shows the EDX spectrum of the prepared catalyst. The observed composition is not commented in the text. The phosphorus content is not commented upon, and the presence of cuprous chloride is inferred from the XRD spectrum (Figure 2). In my opinion, not much can be inferred from the above powder diffractogram. Perhaps only the predominance of the amorphous matrix. The cuprous chloride is inferred from the published position of the diffraction line, which is certainly not visible in the diffractogram and must have been deduced subjectively. In the infrared spectrum, Cu-O bonding is discussed, thus how copper is bound? In publications, EDX mapping of the composition is often reported to verify homogeneity of the sample. It might be worthwhile to add. Please add a quantitative description of the composition from EDX in relation to the predicted catalyst composition and complete the manuscript accordingly.
Authors: We agree with reviewer that EDX mapping is an excellent method for the analysis of the chemical composition. Unfortunately, we do not have access to such a facility.
A food for thought for me is the treatment of the mixture after the reaction. Given the fact that the reaction is carried out in water, why is dichloromethane added at the end of the reaction. Instead, I would magnetically separate the catalyst, wash it thoroughly with water, and process up the mixture without the catalyst. Perhaps its activity in subsequent recycling cycles would be higher.
Authors: The clickable 1,2,3-triazole products obtained in this study are water-insoluble solids that precipitate during the catalytic reaction. The final picture is a mixture of the solid catalyst and the solid 1,2,3-triazole. Dichloromethane or ethyl acetate are necessary to dissolve the 1,2,3-triazole derivatives, followed by their separation from the magnetized heterogeneous catalyst by an external magnetic field.
Why is the equimolar ratio of reactants not used in the reaction? If this is really important, point it out in the text.
Authors: No difference was found by using the equimolar ratio of both reactants or a lower excess of organic azide.
How was the graph constructed (Figure 10)? It seems to me that not enough points are used. In the case of catalyst separation, the reaction must stop immediately. This is not apparent from the interleaving shown and the point at which catalyst removal occurred is not shown. For the intended purpose it would be better to separate the catalyst at the lower conversion and the specific point in the graph should be indicated. It is also not appropriate to mathematically smooth the curve and, if so, to use the appropriate kinetic equation.
Authors: In the hot filtration test carried out to prove that the present CuAAC reaction would proceed in a heterogeneous manner, the separation of the catalyst at the lower conversion was done after 2 hours as shown in the graph of Figure 10 in the revised version. No further points were shown in the graph because no conversion of the reactants was detected with the filtrate separated after 2 hours.
Please complete the procedure for determining the reaction kinetics on the basis of which the reaction time was designed. Or the determination of conversion over time at least for a model example. Simple monitoring of the reaction by thin-layer chromatography is of limited use only for the case where quantitative conversion occurs. The data do not show if the conversion is quantitative and the yield is determined by purification, or if the reaction is terminated at a lower degree of conversion.
Authors: The clickable 1,2,3-triazole products were obtained after complete conversion of the reactants as shown by TLC method and their corresponding yields were determined on isolated pure products as confirmed by 1H NMR and melting points. Some of the products were recrystallized when necessary and their yields calculated then.
Finally, I appreciate the characterization of the compounds prepared by the catalytic reaction in the supplement. However, there is no literature citation with which, in the case of known compounds, spectra and melting points can be compared.
Authors: The literature that report melting points of known 1,2,3-triazole products was added in the revised in ESI material for comparison purposes.
There are some discrepancies in some spectra indicating insufficient purity of the prepared substances. Misinterpretation of some spectra is shown. In 13C NMR there is no need to speculate about the assignment of signals to individual carbons. For unknown substances yet, this needs to be indicated on the basis of multidimensional spectra. Only relevant signals should be integrated for this publication. As an example of wrong interpretation is compound 3c. Some signals are from impurities. Therefore, the integration do not correspond with the identified compound, which is of course present in mixture.
Authors: Taking into account the valuable Reviewer’s suggestion, the assignment of signals to each carbon was removed. The ESI material was carefully checked and the data reported therein for compound 3c were reviewed and corrected.
In my opinion, for this article it is sufficient to describe how the conversion was determined. From the point of view of a catalytic study, it is not necessary to purify and identify all the prepared substances if they have already been described.
Authors: The conversion was determined by the calculation of the yield for each product.
In view of the above, I recommend that the article be re-reviewed after a major revision.
Round 2
Reviewer 2 Report
Thank you for your reply regarding old 13C NMR spectra. I thought that was the case. However, I would like to note that publishing of old 13C NMR spectra for new substances is misleading. One of the reasons to publish 13C NMR spectra is to verify the purity and structure of the prepared compounds. Therefore, it is better not to publish 13C NMR for known substances than to publish old spectra.
Author Response
“point-by-point” responses to the reviewers:
Reviewer 2:
Thank you for your reply regarding old 13C NMR spectra. I thought that was the case. However, I would like to note that publishing of old 13C NMR spectra for new substances is misleading. One of the reasons to publish 13C NMR spectra is to verify the purity and structure of the prepared compounds. Therefore, it is better not to publish 13C NMR for known substances than to publish old spectra.
Authors: We thank the reviewer for his/her point of view on the 13C NMR spectra. We included old 13C NMR spectra in the supplementary information in order to provide the readers with a complete accessible set of data of the studied 1,2,3-triazole derivatives, just in case they would like to reproduce the synthesis of a given compound described in this article.
Reviewer 3 Report
Although the authors have carefully revised the manuscript taking into consideration the comments of the reviewers, still I'm not satisfied by answer on my comments No. 3 (no changes made in Table 3 about TOF and TON values) and No. 7 (about citations).
Author Response
“point-by-point” responses to the reviewers:
Reviewer 3:
Although the authors have carefully revised the manuscript taking into consideration the comments of the reviewers, still I'm not satisfied by answer on my comments No. 3 (no changes made in Table 3 about TOF and TON values) and No. 7 (about citations).
Authors: TON and TOF values were added in Table 3 that shows the comparative study of our heterogeneous catalytic system with somehow identical ones, including a comment on such values.
With respect to the references suggested by the reviewer, we did include the following references as: ref. [22]: "ACS Appl. Mater. Interfaces 2021, 13, 33091–33101" and ref. [12]: “Nanomaterials 2022, 12, 1070”. These references are, by the way, the most related to the chemistry of heterogeneous CuAAC reported in our article.
Reviewer 4 Report
The authors have improved the manuscript in accordance with the recommendation. The experiments performed now correspond better to the stated interpretation.
I can still not identify the mentioned (111) crystalline plane of CuCl in Figure 2c.
Please replace 2.2mg with 2.2 mol% in Table 3 Entry 1.
Please for EDX line 149 phosphate replace with phosphorus and chloride with chlorine.
I don't understand why the authors removed the dates for the spectra in the supplementary. The fact that the experiments were done long ago and only now have been compiled into publication form has no bearing on their quality. Moreover, the prepared products are in all cases known from the literature.
The spectra given in the supplement should be reintegrated into a more understandable form. This was not done even in the case of spectrum 3c, where they added acetone with an asterisk, which I have only as the most obvious example of incorrect integration.
If the authors have the printed spectra only and not the original data, then it may be difficult to correct and should be discussed with the editor.
The manuscript in its present form could be in an area of interest for Catalysts readers and can be accepted for publication.
Author Response
“point-by-point” responses to the reviewers:
Reviewer 4:
The authors have improved the manuscript in accordance with the recommendation. The experiments performed now correspond better to the stated interpretation.
I can still not identify the mentioned (111) crystalline plane of CuCl in Figure 2c.
Authors: The new modified Figure 2c shows now clearly the position of crystalline plane of CuCl.
Please replace 2.2mg with 2.2 mol% in Table 3 Entry 1.
Authors: This has been done.
Please for EDX line 149 phosphate replace with phosphorus and chloride with chlorine.
Authors: This has been done.
I don't understand why the authors removed the dates for the spectra in the supplementary. The fact that the experiments were done long ago and only now have been compiled into publication form has no bearing on their quality. Moreover, the prepared products are in all cases known from the literature.
Authors: We think the reviewer for his/her point of view on the 13C NMR spectra. 13C NMR spectra provided in the supplementary information are given to provide the readers with accessible supporting complete set of data of the prepared 1,2,3-triazole products in case the readers would like to reproduce a given compound which is described in this article.
The spectra given in the supplement should be reintegrated into a more understandable form. This was not done even in the case of spectrum 3c, where they added acetone with an asterisk, which I have only as the most obvious example of incorrect integration.
If the authors have the printed spectra only and not the original data, then it may be difficult to correct and should be discussed with the editor.
Authors: We have the electronic version of some spectra. For others, we still have only the printed version.
The manuscript in its present form could be in an area of interest for Catalysts readers and can be accepted for publication.
