(Z)-2′-((Adamantan-1-yl)thio)-1,1′-dimethyl-2′,3′-dihydro-[2,4′-biimidazolylidene]-4,5,5′(1H,1′H,3H)-trione

Round 1

Reviewer 1 Report

The authors present their interesting work on the reaction of 3-methyl-2-thioxoimidazolidin-4-one with 1,3-dehydroadamantane that leads to an unexpected side-product.  The by-product is indeed unexpected and likely warrants publication.  The paper is well written.  However, I'd ask the authors to consider the following:

1.  Line 34: please direct the reader to compound 2 in Scheme 1 so that they can properly visualize this unusual structure.

2.  Line 51:  the authors specify a "small amount", but it would be helpful to estimate the % yield of the side product.

3.  Compound 3 is novel as well.  Is this compound going to be presented elsewhere?  If so, a reference or footnote should be added.

4.  A complete experimental procedure for the synthesis and isolation of compound 5 needs to be included.  The formation of 4 (and 5) suggest there is an excess of 1 present, but I cannot confirm that in the absence of an experimental procedure.  Also, could NMR spectra for this compound be included in supporting information?

5.  Formation of 5 suggests that oxygen must be present.  In the absence of oxygen (i.e., if the reaction is conducted under N2), is this product still observed?

6.  Finally, a plausible mechanism for formation of compounds 4 and 5 should be included as a scheme.  Formation of 4 is relatively straightforward, but formation of 5 is not nearly as obvious.

7.  Finally, the authors state that formation of compounds such as 4 is well known.  Are there examples of oxidation of compounds such as 5 to diones like 5?

I would encourage the authors to incorporate the changes above in a revised version of the paper. 

Author Response

The authors present their interesting work on the reaction of 3-methyl-2-thioxoimidazolidin-4-one with 1,3-dehydroadamantane that leads to an unexpected side-product.  The by-product is indeed unexpected and likely warrants publication.  The paper is well written.  However, I'd ask the authors to consider the following:

1. Line 34: please direct the reader to compound 2 in Scheme 1 so that they can properly visualize this unusual structure.

Direction added.

2. Line 51: the authors specify a "small amount", but it would be helpful to estimate the % yield of the side product.

Estimated yield of the side product added.

3. Compound 3 is novel as well. Is this compound going to be presented elsewhere?  If so, a reference or footnote should be added.

Compound 3 along with some other similar compounds will be presented later in manuscript for IJMS or Molecules.

4. A complete experimental procedure for the synthesis and isolation of compound 5 needs to be included. The formation of 4 (and 5) suggest there is an excess of 1 present, but I cannot confirm that in the absence of an experimental procedure.  Also, could NMR spectra for this compound be included in supporting information?

Experimental procedure added. Excess of 1 was used indeed. Unfortunately we were not able to acquire NMR spectra for compound 5. A sample was lost on its way from XRD to NMR. Prior the submission of this manuscript we contacted the academic editor and SI (Molecules from Side Reactions II) editor and were informed that it could be considered without a full spectroscopic characterization. In this case only XDR data available for compound 5.

5. Formation of 5 suggests that oxygen must be present. In the absence of oxygen (i.e., if the reaction is conducted under N2), is this product still observed?

As soon as it is rather difficult to obtain compound 2 and yield of compound 5 was 3% it is not rational to conduct experiments just to check the influence of conditions on the by-product yield. But suggestion itself is very reasonable. Thank you. We will take it into account and conduct reactions of compound 2 with other 2-thiohydantoins in inert atmosphere and investigate if analogues of compound 5 would be observed. This data will be presented in above mentioned IJMS or Molecules manuscript with the reference on the present paper.

6. Finally, a plausible mechanism for formation of compounds 4 and 5 should be included as a scheme. Formation of 4 is relatively straightforward, but formation of 5 is not nearly as obvious.

Added Scheme 3 with plausible mechanism for formation of compounds 4 and 5.

7. Finally, the authors state that formation of compounds such as 4 is well known. Are there examples of oxidation of compounds such as 5 to diones like 5?

Formation of the diones like 5 as far as we know is not known. Several 2-thiohydantoin reviews do not contain such reactions (10.1080/17415993.2011.643550; 10.32383/appdr/112124). However, a reaction of 2-thiohydantoins with aldehydes at position 4, which is one of the most common reactions for 2-thiohydantoins is very similar. Both reactions accompanied with double bond formation and isolation of water molecule.

I would encourage the authors to incorporate the changes above in a revised version of the paper.

Thank you for the review.

Author Response File: Author Response.pdf

Round 2

Reviewer 1 Report

Thanks to the authors for addressing the suggested changes.  I find their answers satisfactory.  I would only suggest that in Scheme 3 that the first step be attack of a first-formed enol from the carbonyl group onto the C=S bond as that would be more plausible.  With that small change, I support publication.

Author Response

Thanks to the authors for addressing the suggested changes.  I find their answers satisfactory.  I would only suggest that in Scheme 3 that the first step be attack of a first-formed enol from the carbonyl group onto the C=S bond as that would be more plausible.  With that small change, I support publication.

Thank you for the review. We have updated mechanism in Scheme 3.