Synthesis and Characterization of 3-Methyl-1-(4-(trifluoromethyl)phenyl)indeno [1,2-c]pyrazol-4(1H)-one

Round 1

Reviewer 1 Report

According to Scifinder-n and Reaxys the title compound is a new one, thus, the paper suits to Molbank.

In Supplimentary to this paper, 1H NMR needs to be integrated and labeled. It also should be presented in the ppm range from -1 to 9 ppm.

In Supplimentary to this paper, 13C NMR needs to be labeled.

Author Response

1. Reviewer 1 comments:

(1)  According to Scifinder-n and Reaxys the title compound is a new one, thus, the paper suits to Molbank.

(2)  In Supplementary to this paper, 1H NMR needs to be integrated and labeled. It also should be presented in the ppm range from -1 to 9 ppm.

(3)  In Supplementary to this paper, 13C NMR needs to be labeled.

1. Authors’ response: The spectra provided for compound 1a were obtained more than 3 years ago from an external institution and were not labeled. Unfortunately, we no longer have access to the high resolution NMR instrument that was used to obtain the original spectra nor the NMR point of contact at that institution. Therefore, I am unable to provide integrated and labeled spectra as requested.

Reviewer 2 Report

The Authors extended their previous observations and studied the reaction of 2-acetyl-1,3-indanedi-one with 4-trifluoromethylphenylhydrazine. The reaction gave a mixture of two pyrazole isomeric products. The major one has already been reported, whereas the minor is a new compound. The reported 19F, 1H, and 13C NMR assignments are in full agreement with the structure of the new product.

The paper reports new and interesting results and is well written. It certainly deserves publication; however, before, it should be carefully checked for misprints, e.g., lines 58, 59, and 240.

Author Response

(1)  The Authors extended their previous observations and studied the reaction of 2-acetyl-1,3-indanedi-one with 4-trifluoromethylphenylhydrazine. The reaction gave a mixture of two pyrazole isomeric products. The major one has already been reported, whereas the minor is a new compound. The reported 19F, 1H, and 13C NMR assignments are in full agreement with the structure of the new product.

(2)  The paper reports new and interesting results and is well written. It certainly deserves publication; however, before, it should be carefully checked for misprints, e.g., lines 58, 59, and 240.

 

240. Authors’ response: We have conducted a thorough editorial check of the manuscript to correct misprints. Included in the corrections were misprints noted in lines 58, 59 and 240. In addition, we have made minor editorial and substantive corrections to the experimental section to include verb tense changes from present to past for consistency as well as added more detailed explanations of the separations used to isolate the pyrazoles obtained in run 1. Finally, we have provided fraction masses following chromatographic separations for runs 2 and 3 for context on the extent of the reaction methods.

Reviewer 3 Report

Although the authors compose the introduction well to justify their research in using 2-acetyl-1,3-indanedione to compare with the unique reactivity of 2-trifluoroacetyl-1,3-indanedione, their characterizations for the two products, 1a and 1b, are not convincing. In this report, they only report the minor product 1a and give a citation for the major product 1b. The citation for 1b, ref. 16,  is informal (a chapter in a book) and difficult to access. The authors did not provide their rationals for their assignments on the regio-isomers of 1a or 1b. If the authors give the reasons for the assignment, it is publishable in molbank.

Minor: The reaction temperature for the conventional heating is not reported.

 

Author Response

(1)  Although the authors compose the introduction well to justify their research in using 2-acetyl-1,3-indanedione to compare with the unique reactivity of 2-trifluoroacetyl-1,3-indanedione, their characterizations for the two products, 1a and 1b, are not convincing. In this report, they only report the minor product 1a and give a citation for the major product 1b. The citation for 1b, ref. 16,  is informal (a chapter in a book) and difficult to access. The authors did not provide their rationale for their assignments on the regio-isomers of 1a or 1b. If the authors give the reasons for the assignment, it is publishable in molbank.

(2)  Minor: The reaction temperature for the conventional heating is not reported.

 

1. Authors’ response: We have redrafted Figure 3 (now Figure 4) to address Reviewer 3’s concern regarding the regioisomeric assignments and the enhanced the discussion of spectral assignments following Figure 4 in order to better support our assignments. In response to item e.(2), we have included the reaction temperature for the conventional synthesis method in the experimental section.

Reviewer 4 Report

This communication is an interesting example of the study of the formation of mixtures of isomeric pyrazoles in the course of various methods for carrying out the condensation reaction and can be published after the authors make minimal edits.

 

The title of a communication:  It would be preferable to use correct IUPAC name for key compound 1a -  3-methyl-1-(4-(trifluoromethyl)phenyl)indeno[1,2-c]pyrazol-4(1H)-one.

Lines 53, 54: In order to avoid inaccurate names for structures 1a and 1b and differentiate these two isomers, I could recommend to use acronyms such as annelated 1H-pyrazole 1a and 2H-pyrazole 1b.

Scheme 1: A reagent(F₃C-C₆H₄-NHNH₂) is missing, which should be drawn either above or in front of the arrow.

Lines 58, 59, 141, 148, 166, 169, 183, 186, 190-192: It is advisable to use the correct names for the compounds, 3-methyl-1-(4-(trifluoromethyl)phenyl)indeno[1,2-c]pyrazol-4(1H)-one (1a) and 3-methyl-2-(4-(trifluoromethyl)phenyl)indeno[1,2-c]pyrazol-4(2H)-one (1b).

Lines 70, 71: It would be desirable if the authors indicated the total overall yield of the mixture of regioisomers 1a and 1b, which they reached in the reaction (conventional method), immediately before chromatography and crystallization. It is also necessary to indicate the ratio of these isomers, which can be easily determined by recording the 1H NMR of the mixture (according to the spectroscopy data, the proton signals of the methyl groups of both isomers vary greatly (2.29 and 2.48 ppm) and can be quantified). Without this information, it is impossible to understand the advantages of the microwave-sonication method proposed by the authors.

Lines 139, 140:  The authors mention in the text of the article about the recrystallization of the obtained isomers, but nowhere is the solvent used for this process given. Not bad if the authors indicate the value of R_f for each of the isomers.

Line 240: “ynthesis should changed to Synthesis

Author Response

(1)  The title of a communication:  It would be preferable to use correct IUPAC name for key compound 1a -3-methyl-1-(4-(trifluoromethyl)phenyl)indeno[1,2-c]pyrazol-4(1H)-one.

(2)  Lines 53, 54: In order to avoid inaccurate names for structures 1a and 1b and differentiate these two isomers, I could recommend to use acronyms such as annelated 1H-pyrazole 1a and 2H-pyrazole 1b.

(3)  Lines 58, 59, 141, 148, 166, 169, 183, 186, 190-192: It is advisable to use the correct names for the compounds, 3-methyl-1-(4-(trifluoromethyl)phenyl)indeno[1,2-c]pyrazol-4(1H)-one (1a) and 3-methyl-2-(4-(trifluoromethyl)phenyl)indeno[1,2-c]pyrazol-4(2H)-one (1b).

(4)  Scheme 1: A reagent (F₃C-C₆H₄-NHNH₂) is missing, which should be drawn either above or in front of the arrow.

(5)  Lines 70, 71: It would be desirable if the authors indicated the total overall yield of the mixture of regioisomers 1a and 1b, which they reached in the reaction (conventional method), immediately before chromatography and crystallization. It is also necessary to indicate the ratio of these isomers, which can be easily determined by recording the 1H NMR of the mixture (according to the spectroscopy data, the proton signals of the methyl groups of both isomers vary greatly (2.29 and 2.48 ppm) and can be quantified). Without this information, it is impossible to understand the advantages of the microwave-sonication method proposed by the authors.

(6)  Lines 139, 140:  The authors mention in the text of the article about the recrystallization of the obtained isomers, but nowhere is the solvent used for this process given. Not bad if the authors indicate the value of R_f for each of the isomers.

(7)  Line 240: “ynthesis should changed to Synthesis.

 

Authors’ response: We have corrected the product nomenclature of the title compound 1a and compound 1b to address Reviewer 4’s concerns in g.(1)-(3) above regarding the IUPAC nomenclature issue. Scheme 1 was corrected in accord with Reviewer 4’s recommendation in item (4). With respect to items (5) and (6), we have added additional discussion regarding TLC analysis with R_f values (new Table 1.) that was done in conjunction with the conventional synthesis method. Unfortunately, during the time when this synthesis was carried out, our NMR was not operational; hence we were unable to acquire proton NMR spectra of the crude reaction mixture to determine relative ratios of 1a/1b prior to separation and immediately after separation was complete. We do, however, have a GC trace obtained following the first column chromatographic elution where the pyrazole isomers co-eluted and have provided a discussion to give context in para. 3.1 and introduce the GC trace in a new figure, Figure 3.