Organocatalysts for the Synthesis of Cyclic Carbonates under the Conditions of Ambient Temperature and Atmospheric CO₂ Pressure

Round 1

Reviewer 1 Report

Comments and Suggestions for Authors

CO2 Utilization is of continuous interest to both environmental and synthetic chemists. Kim et.al. report an interesting article concerning the synthesis of cyclic carbonates from epoxides with CO2 via the hydrogen–bond donor organocatalyst. The reaction conditions are mild, and the scope is quite general. Importantly, a CO2 activation mode is demonstrated by the authors.  Therefore, I support publication in catalysts pending minor revisions.

1. The binding pattern of CAT–1 and epoxides should be considered carefully. The authors state that the 1H NMR spectrum shifted downfield. According to reference 25, the shifting should be obvious. However, for the case the authors report here, it seems that all the 1H NMR spectra only shift a little (0.2 ppm) downfield. The author should check the original data and ensure that all signals are already calibrated to the tetramethylsilane signal (0 ppm) or the residual solvent.

2. Cat-6 should be drawn in the same chemdraw style as the others in the manuscript.

3. The author should double-check the NMR spectra carefully. For example:
   a) In Figure S4, CAT–1 should have 8 peaks, while the author labeled 13 peaks.
   b) For the 2D spectra, there is always a shift between the correlation spots and the 1H NMR signal on the X-axis.
   c) In Figure S8, there is no corresponding 1H NMR signal on the X-axis.

Comments on the Quality of English Language

Minor editing of English language required

Author Response

1. The binding pattern of CAT–1and epoxides should be considered carefully. The authors state that the 1H NMR spectrum shifted downfield. According to reference 25, the shifting should be obvious. However, for the case the authors report here, it seems that all the 1H NMR spectra only shift a little (0.2 ppm) downfield. The author should check the original data and ensure that all signals are already calibrated to the tetramethylsilane signal (0 ppm) or the residual solvent.

 In some cases, the peak shift is large, as in reference 25, but in other cases, as in reference 12 and in our study, the peak shift is less than 0.2 ppm. As pointed out by reviewer 1, NMR experiments were performed with careful calibration to residual solvent. Although the NMR peak shift is small, the downfield shift of the 1H NMR peaks indicated that the adduct between CAT-1 and epoxides exists through weak hydrogen bond.

2. Cat-6 should be drawn in the same chemdraw style as the others in the manuscript.

 As reviewer 1 requested, Figure 3 in the line 85 was revised.

3. The author should double-check the NMR spectra carefully. For example:
   a) In Figure S4, CAT–1should have 8 peaks, while the author labeled 13 peaks.

As reviewer 1 requested, Figure S4 in Supplementary Information was revised.

        b) For the 2D spectra, there is always a shift between the correlation spots and the 1H NMR signal on the X-axis.

 As reviewer 1 requested, Figures S6-S8 in Supplementary Information were revised.

        c) In Figure S8, there is no corresponding 1H NMR signal on the X-axis.

 As reviewer 1 requested, Figure S8 in Supplementary Information was revised.

Reviewer 2 Report

Comments and Suggestions for Authors

In this manuscript, the authors detail the catalytic synthesis of cyclic carbonates from epoxides using a novel organocatalyst comprising of a phenol-triazole linkage containing both H-bond donor for binding substrate and a Lewis basic site for complexing CO2. With this catalyst, they show that carbonate synthesis from epoxides is achieved at room temperature within 12 hours, demonstrating activities that are difficult to achieve with non-metal catalysts. Vicinal disubstituted epoxides have also been shown to transform to carbonates, interestingly with retention of stereochemistry revealing a mechanisms likely involving double inversion. The method should have broad applicability in the synthesis of cyclic carbonates from epoxides.

The manuscript is well written and I have have no major revisions to suggest. However, I do have some questions on the proposed mechanism. The authors propose that after epoxide opening by iodide, with CO2 complexation, that the H-bound alkoxide displaces the CO2 from the triazole. The mechanism would be counterintuitive in that complexation of CO2 should deactivate it towards nucleophilic attack from the alkoxide, indicating an enthalpy raising effect from the triazole that would likely exceed or nearly offset the entropy reduction effect. The presence of a Lewis basic nitrogen was shown to be critical in the catalyst screening assay, so it must contribute to lowering the activation energy. Rather an alternative mechanism that involves displacement of the iodide in intermediate II by the carboxylate, followed by alkoxide attack of the carbamate carbon with concomitant triazole departure, I think would perhaps be a more plausible mechanism. This would give a more convincing enthalpy lowering effect of the trazole. Alternatively, both mechanistic scenarios could be proposed where computation would be needed to differentiate them in a separate study.

-2d in figure 4 has the lowest yield. Do thing that the phenyl is causing iodide attack at the benzylic site leading to some material loss? Would this be worth commenting on? There is some mention of an electronic effect with some groups, but the nature of this effect is not clearly delineated. 

 

Author Response

The manuscript is well written and I have have no major revisions to suggest. However, I do have some questions on the proposed mechanism. The authors propose that after epoxide opening by iodide, with CO2 complexation, that the H-bound alkoxide displaces the CO2 from the triazole. The mechanism would be counterintuitive in that complexation of CO2 should deactivate it towards nucleophilic attack from the alkoxide, indicating an enthalpy raising effect from the triazole that would likely exceed or nearly offset the entropy reduction effect. The presence of a Lewis basic nitrogen was shown to be critical in the catalyst screening assay, so it must contribute to lowering the activation energy. Rather an alternative mechanism that involves displacement of the iodide in intermediate II by the carboxylate, followed by alkoxide attack of the carbamate carbon with concomitant triazole departure, I think would perhaps be a more plausible mechanism. This would give a more convincing enthalpy lowering effect of the trazole. Alternatively, both mechanistic scenarios could be proposed where computation would be needed to differentiate them in a separate study.

We agree with Reviewer 2 about the mechanism. Figure 6 was modified and the phrase ‘Displacement of the iodide in intermediate II by the carboxylate anion generates intermediate III, followed by alkoxide attack of the carbamate carbon with concomitant triazole departure.’ was inserted into line 196.

-2d in figure 4 has the lowest yield. Do thing that the phenyl is causing iodide attack at the benzylic site leading to some material loss? Would this be worth commenting on? There is some mention of an electronic effect with some groups, but the nature of this effect is not clearly delineated. 

2h in Figure 4 gave the lowest yield. As suggested by Reviewer 2, the phrase ‘2h gave the lowest yield because the phenyl in 1h may cause iodide attack at benzylic site, resulting in some yield loss.’ was inserted into line 166.

Reviewer 3 Report

Comments and Suggestions for Authors

This is an interesting and well-written description of the work the authors have completed on the use of coupled phenol/triazole organic catalysts for the synthesis of cyclic carbonates from substituted epoxides under mild conditions.  The experimental work appears to be carefully carried out and the results will be of interest to the greater chemistry community.  The NMR work described is convincing.  The low catalyst load and use of low pressure CO2, coupled with good reaction yields (especially with mono-substituted epoxides) render this a highly useful method for the synthesis of cyclic carbonates.  I have just a few suggestions for improvement:

1.  Line 52:  I don't like using the term "tertiary" to describe the C=N nitrogen atoms in the ring.  I'm not sure it is being used correctly.  I believe the term is typically applied to saturated nitrogen atoms rather than unsaturated.  Perhaps describing them as "pyridine-like" nitrogen atoms instead?

2.  Figure 3:  Please include the structure of CAT-6 in the same way as the other structures for easier comparison.  A separate figure could be provided for the x-ray structure, or simply referring the reader to the SI will suffice.

3.  From what I can gather, no solvent is used in these reactions.  This should be explicitly written in the paper.

4.  Table 2.  PPNCl should be defined.  I had to look this up to know what it was.  The others are common enough to be understood.

With attention to the above, I support publication.  Nice work!

Author Response

1. Line 52:  I don't like using the term "tertiary" to describe the C=N nitrogen atoms in the ring.  I'm not sure it is being used correctly.  I believe the term is typically applied to saturated nitrogen atoms rather than unsaturated.  Perhaps describing them as "pyridine-like" nitrogen atoms instead?

As suggested by Reviewer 3, the word ‘tertiary’ has been replaced with ‘pyridine-’ in lines 47 and 52.

2. Figure 3:  Please include the structure of CAT-6 in the same way as the other structures for easier comparison.  A separate figure could be provided for the x-ray structure, or simply referring the reader to the SI will suffice.

As suggested by Reviewer 3, CAT-6 in Figure 3 was revised.

3. From what I can gather, no solvent is used in these reactions.  This should be explicitly written in the paper.

 As suggested by Reviewer 3, the phrase ‘no solvent used’ was added to the footnotes in Tables 1 and 2.

4. Table 2.  PPNCl should be defined.  I had to look this up to know what it was.  The others are common enough to be understood.

As suggested by Reviewer 3, the full name of PPNCl was added at line 140.

Reviewer 4 Report

Comments and Suggestions for Authors

Kim, Kim, and coworkers reported on the preparation of cyclic carbonates under organocatalytic conditions. Conceptually, the protocol could be seen as a merge of Hirose and D’Elia’s works regarding the H-bonding effects and the formation of transient carbamates to promote the transformation. The reaction conditions are also similar, but I personally appreciated the NMR considerations in the main text, which overall results clear and linear. However, I have to raise some concerns regarding the supporting informations, which are not properly written and often lacks organization as well as some important data (give below), because the risk is to lose the scientific soundness an article in this field should have. I therefore suggest this work for publication but under major revision.

 

Supplementary informations: 

-       The file is still in revision mode and it is slightly confusing: no titles are given to the sections and thereby everything looks mixed and the studies are thrown as a list. I strongly suggest to add titles, sections and comments on the observations. 

-       For each substrate, including the catalyst, must be indicated the procedures, specifying the quantity of materials engaged and obtained. 

-       For the substrate scope, an adapted description of the procedure for each substrate is required. Additionally, explanations should be furnished concerning the purification protocols. Some substrates are already described, so please also add a reference literature where the obtained substrates are compared to for structural confirmation. 

-       Figure S12 does not bring any information to the structure (potato-shaped peaks). I would suggest to remove it. 

-       Figure S13: the proton shifts are not that marked. Please add a comment on this study, stating the reason why the authors made this analysis and to verify what.

-       Figure S25 and S26. I would suggest to provide a proton-by-proton attribution since the peaks are well shaped

Comments on the Quality of English Language

Language is fine, minor editing required

Author Response

-       The file is still in revision mode and it is slightly confusing: no titles are given to the sections and thereby everything looks mixed and the studies are thrown as a list. I strongly suggest to add titles, sections and comments on the observations. 

As suggested by Reviewer 4, Table of Contents and Titles was added in Supplementary Information file.

-       For each substrate, including the catalyst, must be indicated the procedures, specifying the quantity of materials engaged and obtained. 

 I respectfully disagree with Reviewer 4’s comments about the procedure description for all substrates. All known compounds including catalysts were synthesized by the procedure reported in the literature. The purity of the synthesized compounds is considered sufficient by NMR spectra. Additionally, the literatures on cyclic carbonates are provided in Table S1.

-       For the substrate scope, an adapted description of the procedure for each substrate is required. Additionally, explanations should be furnished concerning the purification protocols. Some substrates are already described, so please also add a reference literature where the obtained substrates are compared to for structural confirmation. 

I respectfully disagree with Reviewer 4’s comments about the procedure description for all substrates. All known compounds including catalysts were synthesized by the procedure reported in the literature. The purity of the synthesized compounds is considered sufficient by NMR spectra. Additionally, the literatures on the reported catalysts and cyclic carbonates are provided in Table S1.

-       Figure S12 does not bring any information to the structure (potato-shaped peaks). I would suggest to remove it. 

 I respectfully disagree with Reviewer 4’s comments about the removal of Figure S12. As mentioned in lines 72-77 of the manuscript, we explained why we performed this NMR experiment and what we sought to test. For this purpose, the full-scale NMR spectrum is provided in Figure S11 and specific parts are enlarged in Figures S12 and S13 to demonstrate the difference in chemical shift. In addition, broad peaks in Figure S12 are a natural result due to hydrogen bonding.

-       Figure S13: the proton shifts are not that marked. Please add a comment on this study, stating the reason why the authors made this analysis and to verify what.

We have already mentioned why we did this analysis and what we were trying to verify in lines 72-77 of the manuscript. NMR data to prove this is required in the Supplementary Information. The display of the proton shift in Figure S13 does not seem necessary to clearly show the differences in proton chemical shift.

-       Figure S25 and S26. I would suggest to provide a proton-by-proton attribution since the peaks are well shaped.

As shown in Figures S 25 and S26, a proton-by-proton attribution was provided. All peaks are known in the literature and no further detailed description is necessary. These spectra are ONLY used for the conversion calculation. 

Round 2

Reviewer 4 Report

Comments and Suggestions for Authors

Dear authors, 

 

many thanks for the revision. 

 

However, since 5 out of the 6 points were not completely exhausted and/or answered with quick and imprecise asserts, I therefore do not recommend this article for a publication since the new version, albeit more complete of certain details, still lack some fundamental data impacting on the reproducibility of the protocol.

Author Response

No comment