(E)-3-(2,5-Dimethoxyphenyl)-1-{[4-(2,5-dimethoxy-phenyl)-6-((E)-2,5-dimethoxystyryl)-2-thioxo-1,2,3,4-tetrahydropyrimidin-5-yl]}prop-2-en-1-one and (E)-3-(2,5-Dimethoxyphenyl)-1-{[4-(2,5-dimethoxyphenyl)-6-methyl-2-thioxo-1,2,3,4-tetrahydropyrimidin-5-yl]}prop-2-en-1-one
Round 1
Reviewer 1 Report
The authors have resubmitted their paper describing the preparation of two new pyrimidine thiones based compounds. The characterisation is somewhat improved from their prior submission however there are some failures to resolve the full characterisation.
While the compds have now been recrystallised, and mp ranges are provided, there is still no description of the crystal forms. This is rather odd, as well crystallised materials should have distinct forms that can be described. This is compacted by the lack of proof for bulk purity, as the HRMS does not provide proof of bulk purity the authors must provide elemental analysis (preferred) or HPLC data to confirm the compds are pure. I should not that insoluble impurities will of course not show up in NMR or on HPLC as such elemental analysis is needed. Organic compds are rarely 'white' and the authors should refer them as 'colorless'.
Related to the failure to secure elemental analysis is the quality of the NMR data which still show several peaks (low and high field) that appear to be impurities. The authors have invested considerable effort to record and analyse 2D NMFR studies which is good, but would have been better had the compds genuinely been more clean.
There is no UV-vis data despite the fact that these compds are π-conjugated and visible under UV illumination during TLC analysis.
The authors list 13C peaks to 1 dp which is correct, but they should list to 2 dp where 13C peaks need to be clearly differentiated (e.g., 56.4, 56.4 and 112.9, 112.9 and 112.3, 112.3, 112.3 and 55.9, 55.9 and 55.3, 55.3, 55.3).
The authors fail to correctly use the bracketing hierarchy ({[()]}) during their compd nomenclature.
The authors fail to correctly use Sentence case throughout their compd nomenclature (e.g, Title: (E)-3-(2,5-dimethoxyphenyl)-1-[4-(2,5-dimethoxy- ..…. should be (E)-3-(2,5-Dimethoxyphenyl)-1-[4-(2,5-dimethoxy-
The authors do not use a consistent reference style: Journal titles should be abbreviated according to CASSI format: http://cassi.cas.org/search.jsp
If compd 5 is the intermediate to compd 6 then the authors should show this in two ways: 1) they should let compd 5 be fully consumed to enable a higher yield of 6 to form, and 2) they should convert a fully purified sample of 5 into 6 by reintroducing it to the rxn conditions. There assumption that the evidence supports that it is an intermediate is weak.
"The synthesis of compound 4 was performed following the previous article [7] with slight
modification." The authors should clarify what this "slight modification" was and why it was needed.
The authors use the abbreviation DHPM in the abstract and this should be avoided. Please make the abstract more clear and fully comprehendable without requiring the reader to refer to the full text for clarification. Include yields of both products.
The authors have an incorrect title in the SI
orto should be ortho
analog should be analogue
m/z should be in italics
δ should be in italics
Author Response
Dear Reviewer,
herewith I send you the revised manuscript following your suggestions. However we can not fulfill your suggestions to perform separation with HPLC and doing elemental analysis because those instruments are not available in our department.
Best regards,
Hery suwito
Author Response File: 
Author Response.docx
Reviewer 2 Report
in my opinion the manuscript is improved according to my comments and therefore now suitable for publication in Molbank journal.
Author Response
Dear Reviewer,
herewith I send you the revised manuscript following the suggestions of the reviewers.
Best regards,
Hery suwito
Author Response File: Author Response.docx
Reviewer 3 Report
This manuscript reports the synthesis of the compound (E)-3-(2,5-dimethoxyphenyl)-1-(4-(2,5-dimethoxyphenyl)-6-((E)-2,5-dimethoxystyryl)-2-thioxo-1,2,3,4-tetrahydropyrimidin-5-yl)prop-2-en-1-one by an aldol condensation reaction together with a by-side compound which is assumed to be an intermediate molecule. In spite of the authors have improved the reaction yields in comparison to the ones shown on the first manuscript submitted, the reaction yields are poor, 15% and 8%, respectively.
The manuscript could be accepted after minor revisions as followings:
1) On Page 3, line 77, in compound 4, the found mass data 329.0952 is close but not coincident with the calculated one 329.0993. There is a high mass error, this values should be checked.
2) On Page 3, line 80, ‘(d, J = 3.0 Hz, 1H)’ instead of ‘(d, J = 3.0 Hz), 1H)’.
3) On Page 6, line 133, ‘compounds’ should be in plural then, ‘of compounds 5 and 6’.
4) On Page 6, line 149, ‘Supplementary’ instead of ‘Supplelemntary’
5) On Page 7, line 173, ‘condenser’ instead of ‘condensor’
6) On Page 7, lines 180 and 182, ‘compound’ instead of ‘comp.’
7) On Pages 7 and 8, the references format should be checked (abbreviations, semicolons, numbers in bold,…). For example, in references 1, 4, and 6, the journal names should be abbreviated. Then, Organic and Biomolecular Chemistry should be written as Org. Biomol. Chem., and Bioorganic and Medicinal Chemistry Letters should be written as Bioorg. Med. Chem. Lett.
Author Response
Dear reviewer,
Herewith I send you the revised manuscript following your suggestions.
Best regards,
Hery suwito
Author Response File: Author Response.docx
Round 2
Reviewer 1 Report
The authors have improved their manuscript but have not addressed all the points requested by this reviewer. I understand that they are unable to deliver either elemental analysis or HPLC trace to support the bulk purity but they do have NMR data which is reasonable. There are some typographical and grammatical changes that need to be made and I have indicated these in the manuscript appended to this response. In yellow highlight are some issues the authors should double check:
1) include the recryst solvents next to each mp
2) 6.94 (m, 3H), this should be a range not a single value
3) 112.18, 112.18 where 2 dp do not differentiate then add another dp, go to 3 dp here
4) 6.92–0.96 (m, 3H) this is most certainly incorrect
Fix the above and this can be published.
Comments for author File: Comments.docx
Author Response
Dear Reviewer,
herewith I send you the revised manuscript following your corrections (placement of recryst solvent next to mp; the chemical shifts of H-NMR according to signal multiplicity; and correction of the same value of chemical shifts).
Thank you for the corrections and we learn a lot from your corrections.
Best regards,
Hery Suwito
Author Response File: Author Response.docx
This manuscript is a resubmission of an earlier submission. The following is a list of the peer review reports and author responses from that submission.
Round 1
Reviewer 1 Report
The authors report data on two new compounds (3 and 4), which are formed in very low yield (<10%). Both compounds do not appear on a Reaxys database search. As such, the compounds do fit the scope of the journal.
Nevertheless, the characterisation is incomplete. Neither compound has been recrystallised despite sufficient quantities in hand (16-40 mg). Purification is determined by TLC? This is not good enough to support bulk purity. Both compounds must be recrystallised and recharacterized which should include a correct elemental analysis. The authors should describe the crystal form of the recrystallised material and provide good quality copies of both the 1H and 13C NMR spectra that cover the high field range up to 0 ppm. Currently, their spectra appear to have been chopped short, possibly hiding residual solvent peaks. Recrystallisation will give much cleaner material that will lead to superior spectroscopic data. It's a core skill that should not be bypassed.
Since two new compds are being presented, the title should be adjusted to make it clear to the reader that more than one new structure is present.
Furthermore, compound 1, which the authors refer to, is a known compound and they have failed to cite the original paper which describes its high yielding synthesis Synlett, 2009, 1737-1740. I note that in the presented manuscript the authors use TsOH in MeCN while in the Synlett they run a neat rxn. Why the change? The Synlett reports a 92% yield for 1. As such, the comment: 'The synthesis and strucure characterization of compound 1 are not discussed in this paper.' seems to me to be somewhat odd. Please do discuss why you have moved away from the literature protocol.
The authors write: 'The reaction progress of the title compound 3 was monitored with TLC and the reaction was stopped if one of the reactant was not observed again. At the end of the reaction, two spots were observed.' Are the authors sure that this is the end of the rxn? Which reactant disappears (by TLC)? This information would be useful to know.
Schemes should show more details. Over the arrow: rxn conditions, time, temp. Below the arrow: yields.
The details of the rxn and product yields should also be clearly stated in the Abstract.
The IR analysis looks wrong, stretches at 1624 and 1645 cm-1 have been listed as conjugated C=O and C=C, respectively. This simply doesn't make sense. The authors should revisit their assignments.
There are many typographical and grammatical errors. Too many for me to work through. The authors should have the manuscript revised by a professional language editor to fix this.
Some examples:
Title should be in Sentence case, i.e. (E)-3-(2,5-Dimethoxyphenyl)…. not (E)-3-(2,5-dimethoxyphenyl)….
'The synthesis of the title compound are performed' should be 'The synthesis of the title compound was performed'
'2,5-dimethoxy benzaldehyde' should be '2,5-dimethoxybenzaldehyde'
'thio-urea' should be 'thiourea'
'structure' NOT 'strucure'
'references' NOT 'refferences'
'supported' not 'proven'
'm/z' should be in italics
don't use a back slash: '(0.306 g/1 mmol)' use a comma, '(0.306 g, 1 mmol)'
locate the solvent volume after the solvent name i.e. 'and ethanol (7 mL) were placed' NOT 'and 7 mL ethanol were placed' also 'and ethanol (8 mL) were poured' NOT 'and 8 mL ethanol were poured' etc
'Rf' NOT 'Rf'
Bracketing hierarchy ({[()]}) incorrectly used in Conclusions
Author Response
Dear reviewer,
herewith I send you the revised manuscript following your suggestions, including determination of
2D NMR experiment of two new reported compounds.
Author Response File: Author Response.docx
Reviewer 2 Report
The Short Note entitled “(E)-3-(2,5-dimethoxyphenyl)-1-{4-(2,5-dimethoxyphenyl)-6-[(E)-2,5-dimethoxystyryl]-2-thioxo-1,2,3,4-tetrahydropyrimidin-5-yl}prop-2-en-1-one“ submitted by Hery Suwito is suitable for publication in Molbank. Nevertheless, I do not recommend to publish this manuscript for the following reasons.
1. The whole paper has to be carefully corrected (see stated below).
2. There are no melting points for compounts 3 and 4, melting points must be added.
3. Their yields are too low.
4. The authors are requested to submit a novel sound manuscript
I found the following corrections.
Page 1, line 16: synthesis of wide, line 20: Clasien-Schmidt → Claisen-Schmidt, line 28: products, lines 31 and 32: synthons for the synthesis of diverse, line 36: by the Biginelli, line 38: preparation → to be prepared;
Page 2, line 43: derivatives → derivative, line 44: 2,5-dimethoxybenzaldehyde, line 51: was the intermediate, line 64: refferences → references, line 72: The same;
Page 3, line 84: monitoring the reaction, line 88: method). → method. Line 92: 7 mL of ethanol, line 94: 5 mL of ethanol) and 8 mL of ethanol were poured into, line 95: under reflux at, line 96: 5 mL of water, line 99: successfully, line 133: tetrahydropyrimidin;
Page 4, line 123: 6-((E)-2,5-, line 124: successfully, line 129: prepared, line 130: I.I → II, line 142: Quina, F.H.
Author Response
Dear reviewer,
herewith I send you the revised manuscript following your suggestions including the report of
2D NMR experiment of the two compounds.
Thank you for your advice.
Author Response File: Author Response.docx
Reviewer 3 Report
This manuscript reports the synthesis of the compound (E)-3-(2,5-dimethoxyphenyl)-1-(4-(2,5-dimethoxyphenyl)-6-((E)-2,5-dimethoxystyryl)-2-thioxo-1,2,3,4-tetrahydropyrimidin-5-yl)prop-2-en-1-one in poor yield (6.8% yield) by an aldol condensation reaction together with a by-side compound which is an intermediate molecule.
The English language in the manuscript is recommended to be checked by an English native speaker. The manuscript could be accepted after minor revisions as followings.
On page 1, Line 20: “Claisen-Schmidt” instead of “Clasien-Schmidt”
On page 1, Line 22: “vinylogous” instead of “vinylogoues”
On page 1, Line 30: “Besides of” instead of “Beside of”
On page 1, Line 31: “are also potential versatile synthons” instead of “are also potential versatile synthon”
On page 1, Line 34: “styryl” instead of “stryryl”
On page 2, Line 46: “structure characterization” instead of “strucure characterization”
On page 2, Line 53: “by spectroscopic analysis” instead of “by spectroscopy analysis”.
On page 2, Line 64: “references” instead of “refferences”
On page 3, line 92: the number 2 of “compound 2” should be written in bold.
On page 3, line 10: the APT information for the carbon at 129.1 ppm is lost.
On page 3, line 95: “under reflux” instead of “under refluxed”
On page 4, Line 42: “Freitag, R.A.” instead of “Freitag, A.” and “Romano, R.L.” instead of “Romano, L.”
Author Response
Dear reviewer,
Herewith I send you the revised manuscripts following your suggestions including recording new NMR spectra and the discussion of 2D NMR experiment
Thank you for your positive suggestions.
Best regards,
Hery suwito
Author Response File: Author Response.docx
