SNAr Reactions on 2-Amino-4,6-dichloropyrimidine-5-carbaldehyde
Round 1
Reviewer 1 Report
The Communication presented can be considered a continuation of the article published by the authors in Tetrahedron Lett. [ref. 19]. The novelty seems to consists in the fact that the change of the alkalinity of the reaction medium led to a different result as compared to the previous work.
Both materials deal with SNAr reaction in which the chlorine atoms of 2-amino-4,6-dichloropyrimidine-carbaldehyde are involved. The presence in the medium of a weak alkaline (TEA) leads to the substitution of one chlorine atom with an amine [ref. 19]. When NaOH is added along with the above-mentioned substitution, a second chlorine substitution occurs as a result of solvolysis. The authors suggest that this succession is due to the increased alkalinity of the reaction medium and to the influence of the first substituted group on the nucleophilicity of the intermediate formed system. But, in the previous article [ref.19] it is shown that the substitution of the second chlorine atom succeeds if the double equivalent of both TEA and amine is used. So the chlorine in the second position is SNAr substituted even in the absence of a strong alkaline environment which seems to contradict the explanation contained in the present Communication.
The use of generally known pyrimidine ring substitution processes, namely SNAr and solvolysis, led to 3 new compounds. Then the sequence SNAr - solvolysis - condensation Claisen-Schmidt present in Scheme 2 generates another 3 compounds. All compounds obtained were correctly characterized. But is it not clear why in the synthesis described in Scheme 2 the first phase of the reaction sequence is present?
In the experimental part the final processing of the reaction mixtures is not specified and the specification that a NaOH pellet has been added for the reaction is completely unusual. It would also have been interesting to expand the range of synthesized compounds to more than 3 +3 products.
The introduction proposed by the authors is very long and contains a series of information not directly related to the communication that loads the proposed material. The English language used is cumbersome so a revision should be made in this regard: for example one sentence extends from line 62 to 68.
However, given the nature of the material as Communication, it could be published but only after clarifying the ambiguities noted above.
Author Response
In the attached file you will find a response to each of the comments and/or suggestions.
Author Response File: 
Author Response.pdf
Reviewer 2 Report
Pyrimidine derivatives are one of the most important units for natural products and biomolecules, therefore their syntheses are also much more attractive to other chemists. The paper by J. Trilleras and co-authors has described the SNAr reactions of 2-amino-4,6-dichloropyrimidine-5-carbaldehyde with amines and/or the solvent of alcohols to give some pyrimidine derivatives. However, the paper is too fragmentary and complicated the text which is difficult to understand.
First of all, this paper by J.Trilleras et al. was used a lot of punctuation marks such as commas, which makes me difficult to understand.
In addition, the authors did not discuss why the expected products (V-X) did not obtain in the reaction conditions, why the yields of compounds III and IV become low compared with I and II, and why other side-products have not been identified in this reaction to give III or IV.
Although it is interesting and evaluate the synthesis of pyrimidine derivatives, the above reasons have ruined their values.
In my opinion, I think they should rewrite the text after checking by native English speakers, and focus on the synthesis of pyrimidine products I and II.
For these reasons, unfortunately, I think the manuscript is not suitable for publication on Molbank. In addition, I strongly recommend the manuscript should be checked by native speakers of English.
Author Response
In the attached file you will find a response to each of the comments and/or suggestions.
Author Response File: Author Response.pdf
Round 2
Reviewer 2 Report
Pyrimidine derivatives are one of the most important units for natural products and biomolecules, therefore their syntheses are also much more attractive to other chemists. The paper by J. Trilleras and co-authors has described the SNAr reactions of 2-amino-4,6-dichloropyrimidine-5-carbaldehyde with amines and/or the solvent of alcohols to give some pyrimidine derivatives. In particular, it is interesting that different compounds can be produced depending on the reaction conditions.
The revised manuscript is much easier to understand than the previous version, although the English still needs to be improved, such as the use of many punctuation marks such as commas. On the other hand, considering their comment on the cover letter, I think this paper would be acceptable for Molbank.
