Synthesis of 3-Aroyl-4-heteroarylpyrrole Derivatives by the Van Leusen Method

Round 1

Reviewer 1 Report

The article entitled "Synthesis of 3,4-disubstituted pyrrole derivatives by the van Leusen method” focuses on the synthesis of 3 final compounds based on pyrrole and 3 intermediates. This is short communication which is limited to the synthesis of compounds and their structure characterization. This is in line with the scope of the journal Molbank. The manuscript should be improved before publication. The list of issues:

1. NMR, HR-MS and IR spectra of final compounds 8a, 8b and 8c should be provided as SI or link to repository. The Authors write: “Supplementary Materials: The following are available online. Copies of NMR and HR-MS spectra for compound 8a, 8b and 8c.” however I did not find these spectra.
2. Were the compounds 6a-c described during the first time? If yes NMR, HR-MS and IR spectra should be provided.
3. In my opinion title is too general. The Authors should think about it.
4. The quality of texts in Scheme 1 should be improved

Author Response

A general review of the manuscript has been done to improve its wording and clarify some paragraphs. Also, following the suggestions of the referees, we have used the editing services offered at https://www.mdpi.com/authors/english. English Editing ID english-39729.

Comments and Suggestions for reviewer 1						Change made for the authors
	Yes		Can be improved	Must be improved	Not applicable	The information contextualized to the synthesis of these three new compounds is extended. A brief description of classical methodologies and the growing recognition of isocyanide-based substituted pyrrole synthesis is included.
Does the introduction provide sufficient background and include all relevant references?	( )		(x)	( )	( )
Are the methods adequately described?		( )	( )	(x)	( )	Methods are described in detail and cited appropriately.
Are the results clearly presented?		( )	(x)	( )	( )	Chemical detail is included, and the wording is improved. A possible reaction mechanism and discussion is also included.
Are the conclusions supported by the results?		( )	(x)	( )	( )	The wording was improved.
1.       NMR, HR-MS and IR spectra of final compounds 8a, 8b and 8c should be provided as SI or link to repository. The Authors write: “Supplementary Materials: The following are available online. Copies of NMR and HR-MS spectra for compound 8a, 8b and 8c.” however I did not find these spectra.						Supplementary materials file is attached that includes spectral data of compounds 6a-c and spectra of compounds 8a-c.
2.       Were the compounds 6a-c described during the first time? If yes NMR, HR-MS and IR spectra should be provided.						Compounds 6a-c were preliminarily published. Reference is included.
3.       In my opinion title is too general. The Authors should think about it.						To give greater specification, the title is modified a little to “Synthesis of 3-aroyl-4-heteroarylpyrroles derivatives by the van Leusen method”.
4.       The quality of texts in Scheme 1 should be improved.						Done.

Reviewer 2 Report

The paper by Trilleras et al reports the synthesis of 3 new substituted pyrroles using a literature procedure (Hoogenboom, Tet. Lett., 1972). There is nothing particularly novel reported, but the structures are new and hence worth reporting. The chemistry appears to have been carried out competently and the structures confirmed by NMR and high resolution MS. However, no actual spectra were provided to this reviewer for perusal.

 

The main problem is that the English is very poor, making the paper quite difficult to read. The authors need to find an English-speaking chemist who can correct the English. Such services are available on-line. I cannot recommend publication in its present form.

 

One further point, the authors discuss the mechanism of pyrrole ring formation on page 2 (lines 63-67). The paper would be improved if an actual mechanism (with curly arrows) were provided (a picture is worth a thousand words).

Author Response

A general review of the manuscript has been done to improve its wording and clarify some paragraphs. Also, following the suggestions of the referees, we have used the editing services offered at https://www.mdpi.com/authors/english. English Editing ID english-39729.

 

Comments and Suggestions for reviewer 2					Change made for the authors
	Yes	Can be improved	Must be improved	Not applicable
Are the results clearly presented?	( )	( )	(x)	( )	Chemical detail is included, and the wording is improved. A possible reaction mechanism and discussion is also included.
The paper by Trilleras et al reports the synthesis of 3 new substituted pyrroles using a literature procedure (Hoogenboom, Tet. Lett., 1972). There is nothing particularly novel reported, but the structures are new and hence worth reporting. The chemistry appears to have been carried out competently and the structures confirmed by NMR and high-resolution MS. However, no actual spectra were provided to this reviewer for perusal.					Supplementary materials file is attached that includes spectral data of compounds 6a-c and spectra of compounds 8a-c.
The main problem is that the English is very poor, making the paper quite difficult to read. The authors need to find an English-speaking chemist who can correct the English. Such services are available on-line. I cannot recommend publication in its present form.					We have requested editing services listed at https://www.mdpi.com/authors/english
One further point, the authors discuss the mechanism of pyrrole ring formation on page 2 (lines 63-67). The paper would be improved if an actual mechanism (with curly arrows) were provided (a picture is worth a thousand words).					A possible reaction mechanism and discussion is also included.

 

Round 2

Reviewer 1 Report

The manuscript has been improved. However, 1H-NMR spectrum  of 8a (SI materials) reveals peaks 7.85, 7,83, 5.53 (ppm) which indicates insufficient purity of this compound. The origin of these peaks should be explained or compound 8a should be purified.

Author Response

Explanatory note on ¹H-NMR and 2D spectra were included.

The signals at 7.85, 7.83 and 5.53 ppm, correspond to trace impurities in the solvent (DMSO-d₆). The 2D experiments (HSQC and HMBC) do not show correlation between the signals, allowing the correct identification of the chemical compound. The 2D-NMR spectra (HSQC and HMBC), together with the HRMS signal within 0.0009 mass units, are evidence for the composition of the new compound 8a.

Therefore, the analysis was not repeated. To avoid these signals in the spectra of the other compounds (8b and 8c), fresh solvent was used, from a recently opened container.

We use MDPI English editing service (English editing ID: English-39729), and suggested changes have been included.

Author Response File: Author Response.pdf