A Convenient Synthesis towards 2-Bromo-2-(methoxy(phenyl)methyl)malononitrile and 2-Iodo-2-(methoxy(phenyl)methyl)malononitrile
Round 1
Reviewer 1 Report
The authors of the paper presented a method for obtaining two novel haloether compounds. These results are new and of practical significance. Unfortunately, the authors have chosen the publication format "short note", which does not allow getting a complete picture of the reaction discussed, but the full version of the paper was announced. This is probably caused by the desire to get some priority and further research will still be continued. There is very little information, which raises a lot of questions. If the scope of this publication does not allow including answers to the questions presented below, then I can recommend that the authors include the information in a future paper. Questions:
1. What caused the need to replace acetonitrile with methanol?
2. What role does methanol play in the reaction mechanism?
3. What is the kinetics of the reaction?
4. Chemical reaction parameters and their dependence on temperature / pressure.
5. Is it possible to replace methanol with other lower alcohols? There are quite a lot of examples in the literature when homologous alcohols (isomers) are used for the synthesis of the same compound.
6. The authors should describe in more detail the properties of the chemicals used, the methodology of the experiment.
Author Response
Dear reviewer：
Thank you for your letter and for the reviewer’s comment concerning our manuscript entitled “A convenient synthesis towards 2-bromo-2-(methoxy(phenyl)methyl)malononitrile and 2-iodo-2-(methoxy(phenyl)methyl)malononitrile” (molbank-1729373 ). Those comments are all valuable and very helpful for revising and improving our paper, as well as the important guiding significance for our researches. We have studied comments carefully and have made correction which we hope meet with approval. Revised portions are marked in red in paper. The main corrections in the paper and the responds to the reviewer’s comments are as flowing:
Point 1: What caused the need to replace acetonitrile with methanol?
Response 1: It was an accident discovery that we originally wanted to synthesis N-[2-Bromo-2,2-dicyano-1-phenylethyl]pyrrolidine-2,5-dione as a raw material, but misused methanol as the solvent. It was found that 2-Bromo-2 -(Methoxy (phenyl)methyl)malononitrile was formed instead of the expected product.
Point 2: What role does methanol play in the reaction mechanism?
Response 2: Chen’s group[Chin. J. Chem. 2012, 30, 830—836] have reported that β, β-dicyanostyrene reacted with NBS catalyzed by NaOAc to give an bromonium ion intermediate A, The second step is an SN2 process in which the three-membered ring (the bromonium ion) was opened by the negative succinimide B to generate product C(as shown in the following figure). We suspected that methanol may not only acts as a solvent in our reaction, but also acts as a nucleophile to attack the onium intermediate to form methoxyl substitution products.
Point 3: What is the kinetics of the reaction?
Response 3：We tested the effect of reactant concentration and temperature on the reaction result. As shown in table S1, higher or lower concentration of reactants has no obvious effect on the reaction rate, while increasing the temperature will significantly accelerating the reaction.
Point 4: Chemical reaction parameters and their dependence on temperature / pressure.
Response 4：The reaction was performed at rt for 24 h, and the condition optimization experiment exhibited that the reaction rate was dependent on reaction temperature.
Point 5: Is it possible to replace methanol with other lower alcohols? There are quite a lot of examples in the literature when homologous alcohols (isomers) are used for the synthesis of the same compound.
Response 5：It is really true as reviewer suggested that more types of alcohols should be tested. We have explored different types of alcohols such as ethanol, isopropanol and tertiary butanol as the reaction solvent. Regrettably, most of the starting material β,β-dicyanostyrene was recovered and a few was converted to benzaldehyde, and the expected product was not observed in those reactions. The relative mechanism is still under further study.
Point 6: The authors should describe in more detail the properties of the chemicals used, the methodology of the experiment
Response 6：We have added more details of the materials and methods in the ESI file according to the review’s comment.
Reviewer 2 Report
The paper reported the double addition of nucleophiles to beta,beta-dicyano styrene obtaining vicinal haloethers. The products are new but the applicability is very limited and no attempt for example to use different alcohols than methanol is present. I suggest to extend the scope of the reaction. Moreover, the text mentions optimization of the experimental conditions (Pag. 2) but no data are reported. Some typying mistakes are present in the text and also the english needs for a revision.
Author Response
Dear reviewer：
Thank you for your letter and for the reviewer’s comment concerning our manuscript entitled “A convenient synthesis towards 2-bromo-2-(methoxy(phenyl)methyl)malononitrile and 2-iodo-2-(methoxy(phenyl)methyl)malononitrile” (molbank-1729373 ). Those comments are all valuable and very helpful for revising and improving our paper, as well as the important guiding significance for our researches. We have studied comments carefully and have made correction which we hope meet with approval. Revised portions are marked in red in paper. The main corrections in the paper and the responds to the reviewer’s comments are as flowing:
Point 1: The paper reported the double addition of nucleophiles to beta,beta-dicyano styrene obtaining vicinal haloethers. The products are new but the applicability is very limited and no attempt for example to use different alcohols than methanol is present. I suggest to extend the scope of the reaction. Moreover, the text mentions optimization of the experimental conditions (Pag. 2) but no data are reported. Some typying mistakes are present in the text and also the english needs for a revision.
Response 1: It is really true as reviewer suggested that more types of alcohols should be tested and more experiment details should be illustrated. We have explored different types of alcohols such as ethanol, isopropanol and tertiary butanol as the reaction solvent. It is disappointing that most of the starting material β,β-dicyanostyrene was recovered and a few was converted to benzaldehyde, and the expected product was not observed in those reactions. The relative mechanism is still under further study. Moreover, The details of the condition optimization was show in table S1.
Round 2
Reviewer 2 Report
Check the english spelling
