1-(Dicyanomethylene)-3-hydroxy-1H-indene-2-carboxylic Acid

Round 1

Reviewer 1 Report

Comments and Suggestions for Authors

The article by O. A. Rakitin et al. describes the synthesis and structure characterization of 1-(dicyanomethylene)-3-hydroxy-1H-indene-2-carboxylic acid, an intermediate for the synthesis of 3-methylene-2,3-dihydro-1H-inden-1-ones, a promising class of non-fullerene acceptors for organic solar cells. The target compound was obtained via a Perkin-type transformation of 2-(3-oxoisobenzofuran-1(3H)-ylidene)malononitrile with tert-butyl acetoacetate in the presence of acetic anhydride and triethylamine, and its structure was established by means of elemental analysis, high-resolution mass spectrometry, ¹H NMR, ¹³C NMR, IR spectroscopy and mass-spectrometry.

The synthetic method here proposed is simple, rapid, and satisfactorily efficient.

Several issues, though, must be addressed, before acceptance for publication:

1. The mechanism of the Perkin-type transformation should be described with a proper representation.
2. The assignment of ¹H and ¹³C NMR ( at least the most diagnostic) signals should be provided. I suggest putting the data in a proper Table. Also, diagnostic IR signals and MS fragments should be assigned.
3. The definition of the enol moiety is probably the most delicate issue. The authors stated that: “…the signal of the hydroxyl group obviously coincides with the signal of water in DMSO-d6, which is confirmed by an increase in the integral of water at δ = 3.36 ppm when compound 5 is dissolved in DMSO-d6 by approximately three protons.” Why so obvious? No integration of the water signal was provided in the submitted spectra. I’m not confident with this demonstration: could you provide more convincing evidence? If not, the x-ray analysis of a crystal would define it more precisely.
4. Melting Point < 300 °C? What does this mean? Decomposition? Please provide a stricter range value….

 

This reviewer sustains that the work will merit publication in molbank after all point will be acknowledged.

Author Response

Reviewer 1 The authors are grateful to the reviewer for a kind and highly professional review.

Point 1. The mechanism of the Perkin-type transformation should be described with a proper representation.

Response from authors. The article has been updated to include a discussion of the mechanism of formation of compound 5 in the light of the Perkin reaction.

Point 2. The assignment of 1H and 13C NMR (at least the most diagnostic) signals should be provided. I suggest putting the data in a proper Table. Also, diagnostic IR signals and MS fragments should be assigned.

Response from authors. The article added assignment of 1H and 13C NMR signals, IR signals and MS peaks for the most reliable signals.

Point 3. The definition of the enol moiety is probably the most delicate issue. The authors stated that: “…the signal of the hydroxyl group obviously coincides with the signal of water in DMSO-d6, which is confirmed by an increase in the integral of water at δ = 3.36 ppm when compound 5 is dissolved in DMSO-d6 by approximately three protons.” Why so obvious? No integration of the water signal was provided in the submitted spectra. I’m not confident with this demonstration: could you provide more convincing evidence? If not, the x-ray analysis of a crystal would define it more precisely.

Response from authors. 1-(Dicyanomethylene)-3-hydroxy-1H-indene-2-carboxylic acid 5 does not form single crystals and we were unable to perform X-ray analysis. Unfortunately, we were unable to find a signal from one of the OH groups in the 1H NMR spectrum of compound 5 in various deuterated solvents. We hypothesized that OH signal was contained in the water signal in DMSO-d6 together with the water signal in the hydrate of compound 5. When compound 5 was added to DMSO-d6, there was a significant increase in the water signal relative to the signal in dimethyl sulfoxide. Based on this fact, we think that one of the signals of the hydroxy group coincides with the signal of water in the solvent. To confirm our assumption, we attach the 1H NMR spectrum of pure DMSO-d6, as well as the 1H NMR spectrum after dissolving a sample of the compound 5 in the same DMSO-d6. Figure 1. 1H NMR spectrum of DMSO-d6 Figure 2. 1H NMR spectrum of the compound 5 in the same DMSO-d6

Point 4. Melting Point < 300 °C? What does this mean? Decomposition? Please provide a stricter range value…

Response from authors. The melting point of compound 5 is more than 300 °C, corrected in the text of the article.

Author Response File: Author Response.pdf

Round 2

Reviewer 1 Report

Comments and Suggestions for Authors

I've read with interest the revised version of the work. Regrettably I think that the final structure hasn't been certified correctly yet. 

Without an X-ray analysis, provide a 1H NMR with a wider windows. Are you sure that the signal at 10 ppm corresponds to the carboxylic acid, instead of the enol OH? have you tried to record wider at 13-14 ppm to look for the CO2H?

I'm sorry, but also the mechanism is still unclear to me: can you provide a detailed mechanism proposal with curved arrows? How does the acetyl group got lost in HCl?

 

Author Response

Reviewer 1

The authors are grateful to the reviewer for a kind and highly professional review.

Point 1.

Without an X-ray analysis, provide a 1H NMR with a wider windows. Are you sure that the signal at 10 ppm corresponds to the carboxylic acid, instead of the enol OH? have you tried to record wider at 13-14 ppm to look for the CO2H?

Response from authors2.

We have included ¹H NMR spectrum with a wider window up to 14 ppm to the Supplementary Materials. Unfortunately, we did not find any new signal in the weak area of the spectrum. The appearance of an additional signal of the hydroxyl group was confirmed by an increase in the water integral at δ = 3.36 ppm when dissolving compound 5 in DMSO-d₆ by approximately three protons.

Point 2.

I'm sorry, but also the mechanism is still unclear to me: can you provide a detailed mechanism proposal with curved arrows? How does the acetyl group got lost in HCl?

Response from authors.

The mechanism of Perkin reaction is unclear in the literature. It is assumed [ref. 21] that the elimination of the acetyl group is the first step of this reaction. Indeed, as the respected reviewer suggests, this step and the rearrangement of the addition product occur under basic conditions [refs. 19-22]. The corresponding changes have been made to Scheme 4.