Synthesis and Structural Analysis of Chiral Bis-dihydro[1,3]-naphthoxazines and Imidazolidine Derivatives Prepared by Three-Component Mannich-Type Condensation
, Krasimira Dikova 1, Maya K. Marinova 1, Mariana Kamenova-Nacheva 1, Rusi Rusew 2, Hristina Sbirkova-Dimitrova 2, Boris Shivachev 2,*, Kalina Kostova 1 and Vladimir Dimitrov 1,*Round 1
Reviewer 1 Report
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Author Response
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Reviewer 2 Report
In the paper by Dimitrov, Shivachev and co‑workers, the access to two novel chiral bis‑dihydro[1.3]naphthoxazines and a novel chiral imidazolidine derivative and the punctual spectroscopic, thermogravimetric and diffractive (XRD) characterization thereof. The usefulness of such chiral scaffolds as ligands in affording enantioenriched products of addition of diethylzinc to aldehydes is also shortly discussed. Moreover, the synthesis of a second imidazolidine derivative (already present in the literature) is showed, albeit the authors justify the impossibility of isolating it in pure form, and thus integrate the literature data with a full NMR characterization. The opinion of this reviewer is that the paper is suitable for publication in Crystals, once the following issues will have been fixed:
1) Page 2, line 65: JASCO P2000 polarimeter
2) Page 2, line 72: QSTAR pulsar I instrument/mass spectrometer
3) Page 3, line 133: Analitically calculated molecular weight for C29H30N2O2 is 438.57 Da
4) Page 5, line 207: Please avoid mention Mannich condensation and rather just talk about condensation. Indeed, products 3, 5, 8 and 9 result from a first Mannich condensation between naphthols with formaldehyde and the corresponding amine and a subsequent condensation of the amino and phenolic hydroxyl group of the resulting Mannich adduct with formaldehyde, to afford the 6‑membered cyclic mixed acetal/aminal
5) Page 6, lines 235‑236: Please correct in “the results introduced in entry 5 need” or in “the result introduced in entry 5 needs”
6) Page 7, Table 2: This reviewer does not agree with the way the authors decided to indicate molar ratios: it makes no sense to use molar ratios if they then use decimal numbers. Indeed, in this case it would be correct to employ entire numbers: then, a molar ratio of 1:0.4 becomes 5:2; 1:0.5 becomes 2:1; 1:0.95 becomes 20:19; and so on. Moreover, it is not clear if the yield of 9 indicated at entries 6, 10 and 11 (footnote 5) is an isolated yield or not. In this framework, the authors should clearly state wheter they are talking about an isolated yield or an NMR yield at the beginning of the footnote
7) Page 14, line 391: Please avoid Mannich condensation or at least correct in Mannich type (like in the title, that is fine), for the same reason indicated for what concerns page 5, line 207
8) References, pages 16‑17: Please correct the journal name for all the references: always use abbreviated form!
9) SI, page 1 and onwards: Please specify DEPT 135
10) SI, page 2: The singlet at 1.62 ppm in the 1H NMR spectrum shall not be picked nor integrated! Apart from the fact that it is not possible to ascribe this signal to any proton belonging to compound 3, from the integration of the authors, 31 protons result out of 30! Moreover, in the 13C NMR spectrum, the authors need to better check the picking, because they missed a peak (only 12 out of 13 are picked)
11) SI, page 6: The singlet at 1.61 ppm in the 1H NMR spectrum shall not be picked. Moreover, in the 13C NMR spectrum, the authors need to better check the picking, as they picked 17 out of 13 are peaks.
12) SI, page 13: In the 13C NMR spectrum, the authors need to better check the picking, as they missed a peak (14 out of 15 are picked)
Author Response
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Reviewer 3 Report
The work describes the synthesis of several chiral organic compounds prepared by Mannich-type condensation. The results show the obtaining of the compounds with a great variety of analytical and spectroscopic assays.
In the experimental part, the description of compounds 3 and 5 contain a high degree of spectroscopic characterization, as can be seen in the supplementary material. The same is true for the enathiomers ((S,S)-9) and ((R,R)-9). However, the ((R,R)-9) does not contain its corresponding elemental analysis, which is very characteristic when describing an organic compound.
In the Results and Discussion, no mention is made of the reaction time, whose minimum is 1 day and maximum is almost one week of reaction. Hasn't an attempt been made to reduce the reaction time? Perhaps these are not the optimal conditions. Have you tried to make the reaction targets, using the ligand without the zinc precursor or only using the zinc precursor without the ligand?
The descriptive part of the compounds is well described and complete, while the enantioselective aldehyde reduction reaction needs further development.
Author Response
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Round 2
Reviewer 3 Report
The paper has been revised and much more information from the structure solving part has been included.
With respect to the first question, high resolution does not show the purity of a compound, it only indicates that the desired compound is in the analyzed product. There may be impurities other than the compound, so elemental analysis is a study that does describe the purity of the species. Therefore, I believe that a new organic or organometallic compound should contain elemental analysis.
The rest of the detailed information on the proposed questions are included.
