Photodimerization of (E)-3-(2,6-Difluorophenyl)-1-(4-methoxyphenyl)prop-2-en-1-one in the Crystalline Solid State
Round 1
Reviewer 1 Report
The authors described a simple synthesis of the title compound 1 and characterized it using 1H and 13C NMR, mass spectrometry and X-ray crystallography. Irradiation of chalcone 1 in the crystalline state produced the syn-head-to-head (β-truxinic) photodimer in result of [2+2] photocycloaddition. It is assumed that the reaction proceeds in a triplet-excited state.
A minor remark.
In the Introduction, the authors wrote: "The photodimerization product formed upon the irradiation of 1 in the crystalline solid state was carefully characterized by 1H and 13C NMR and the crystallographic structures were determined using X-ray crystallography."
From this statement one could assume that photodimerization product was characterized not only by NMR, but also by X-ray crystallography. However, the crystallographic data were reported only for chalcone 1.
Author Response
Referee 1
- A minor remark.
- In the Introduction, the authors wrote: "The photodimerization product formed upon the irradiation of 1 in the crystalline solid state was carefully characterized by 1H and 13C NMR and the crystallographic structures were determined using X-ray crystallography."
- From this statement one could assume that photodimerization product was characterized not only by NMR, but also by X-ray crystallography. However, the crystallographic data were reported only for chalcone 1.
Answer: The statement was corrected in the text (page 2, line 78), which now reads: The photodimerization product formed upon the irradiation of 1 in the crystalline solid state was carefully characterized by 1H and 13C NMR and mass spectrometry.
Reviewer 2 Report
The manuscript was described photodimerization of chalcone derivatives in solid state. In fact, dimerization in solution probably leads to the formation of the four isomers, the ratio of products maybe depends on thermal and/or kinetic stability and other conditions. In solid state, the obtained isomer maybe depends on the orientation of the molecule in crystals. The authors largely succeeded the formation of the only beta-truxinic in this method.
This study was much attractive and should be published in this journal. Before it, I have only one uncertainty, so the authors had better clarify it.
In UV-vis spectral change in photolysis, the time dependent measurement could probably be carried by utilization of each another crystal, not same crystal. Did these crystals have the almost same shape? Reaction rate of photolysis depends on the shape (surface area) of crystals, I think.
In addition, I wonder the photolysis really completed. Because I doubt whether the irradiation light could reach the center of crystal. I also think that only 1H NMR spectrum in Figure 5 does not necessarily the completely consumption of chalcone. First, the authors said Figure S1 is 1H NMR spectrum of chacone(1) in line 89, however, the signal assignment was not consistent with the description in "3. materials and methods". this spectrum in Figure S1 show the one of products after photolysis not chalcone, didn't it? So since I could not compare the spectra, it can seem also that the signals assigned in "3. materials and methods" may remain in Figure 5.
Author Response
Referee 2
- This study was much attractive and should be published in this journal. Before it, I have only one uncertainty, so the authors had better clarify it.
- In UV-vis spectral change in photolysis, the time dependent measurement could probably be carried by utilization of each another crystal, not same crystal. Did these crystals have the almost same shape? Reaction rate of photolysis depends on the shape (surface area) of crystals, I think.
Answer: The UV-visible experiments were carried out in dichloromethane solution, and in the preparation of the analyzed solutions at different irradiation times, the same crystalline material deposited on the walls of a test tube was used, which after different samplings to obtain the X-ray crystallography data were identical in all cases.
- In addition, I wonder the photolysis really completed. Because I doubt whether the irradiation light could reach the center of crystal. I also think that only 1H NMR spectrum in Figure 5 does not necessarily the completely consumption of chalcone. First, the authors said Figure S1 is 1H NMR spectrum of chalcone 1 in line 89, however, the signal assignment was not consistent with the description in "3. materials and methods". this spectrum in Figure S1 show the one of products after photolysis not chalcone, didn't it? So since I could not compare the spectra, it can seem also that the signals assigned in "3. materials and methods" may remain in Figure 5.
Answer: It is important to point out that the 1H NMR spectrum shown in Figure 5 refers to the material obtained after 120 h of irradiation with (E)-3-(2,6-difluorophenyl)-1-(4-methoxyphenyl) prop- 2-in-1-one (1). After this irradiation time, conversion to products of about 60% was obtained. Thus, the observed spectrum is expected to contain contributions from both the starting material and the corresponding photodimer. What is most relevant in this spectrum is the appearance of absorption of cyclobutane protons with the chemical shift at 5.29/5.25 and 4.86/4.82 ppm (J=6.69 Hz).
Reviewer 3 Report
The manuscript by Netto-Ferreira and co-workers presents the synthesis, characterization and photochemistry of a new fluorinated chalcone. The article details possible photoproducts with a presumed particular species (beta-truxinic) formed.
In general, the article is well written and clear. However, I do have several concerns. First and foremost, GCMS was principally used to examine photoproducts. All of the proposed photoproducts would have an identical mass, thus in my mind this is not conclusive. The geometry based on the solid-state structure strongly indicates that the only reasonable photoproduct is beta-truxinic. 2D NMR might also yield more information about that product. However, given statements in the manuscript, there is an even more conclusive method of characterization: X-ray crystallography. The authors perform a solid-state transformation of the parent chalcone, and presumably (from statements on page 9, line 281 “The resulting single crystals were …” this is direct indication that the photodimerization retains a single crystal. Moreover, if it did not, the photoproduct could be crystallized to confirm the structure.
With regards to the crystallography, the authors measured data at room temperature, which is not an issue. However, the data resolution is only to 40 deg in 2-theta (1 angstrom). This is well below the generally accepted minimum publishable resolution of 0.83 A (and higher if possible). There is no indication of why the data were only recorded to 1.0 A. The instrument that was used can certainly measure to 0.8 A. Furthermore, the authors are using a deprecated version of SHELXL. The version that is used does not incorporate modern best practices. Given that the most recent version of Prof. Sheldrick’s refinement programs have been available since 2018, the authors should obtain a copy and refine their structure using more modern software. This will incorporate many data that are missing from the current CIF. CheckCIF on the current CIF shows a significant number of A-Alerts that can, and should be, addressed. Especially because this manuscript is centered around a crystal structure.
The only significant change to the manuscript I would suggest is removing the list of bond distances from the Figure caption for Figure 1. They are not exceptional in any way and do not add new, meaningful information to the manuscript. The torsion angles are acceptable because they highlight features discussed in the body text. The phrase “Selected Angles” in the caption should be changed to “Selected Torsion Angles”.
The article is generally sound, however, the crystallographic study requires some further inspection. I would also suggest that if possible the photoproduct be structurally characterized which would add a significant impact to the statements and claims.
Author Response
Referee 3
- In general, the article is well written and clear. However, I do have several concerns. First and foremost, GCMS was principally used to examine photoproducts. All of the proposed photoproducts would have an identical mass, thus in my mind this is not conclusive.
Answer: The referee is correct in stating that all possible photoproducts of chalcone 1 photodimerization have identical mass and that, in principle, mass spectrometry data would be inconclusive. This concern was even made explicit in the manuscript when we stated (page 7, line 211): "...Despite the difficulty in identifying the resulting photodimers in cycloaddition reactions employing mass spectrometry...”
Because of this difficulty, we decided on an approach in which the focus of the mass spectrometry analysis was investigating of the fragmentation mechanism. Thus, the observed MacLafferty rearrangement was essential for us to conclude the stereospecific formation of the b-truxinic isomer, as explained in the manuscript (page 7, line 212): "...it can be suggested that, specifically for the syn head-to-head photodimer (b-truxinic) formed in the photodimerization reaction of 1, the presence of the extremely important fragment at m/z 275 indicates a fragmentation mode known as MacLafferty rearrangement that can unequivocally confirm the presence of the b-truxinic structure."
- The only significant change to the manuscript I would suggest is removing the list of bond distances from the Figure caption for Figure 1.
Answer: The referee's suggestion to remove the list of bond distances from the caption in Figure 1 was accepted. Also, the term Selected Angles contained in the same caption was changed to Selected Torsion Angles.
- The article is generally sound; however, the crystallographic study requires some further inspection. I would also suggest that if possible, the photoproduct be structurally characterized which would add a significant impact to the statements and claims.
Answer: The authors are in full agreement with the referee's opinion on the X-ray crystallographic data. We would be very interested in accepting your extremely relevant suggestions. Unfortunately, as indicated in the Acknowledgment of this manuscript, shortly after carrying out the crystallography experiments, the researcher in charge of the laboratory, Professor Jairo Bordinhão, passed away. Consequently, the laboratory had to shut down its activities and, therefore, it will not be possible to meet the referee's request since there is no other instrument available and neither the most recent version of Prof. Sheldrick's refinement programs.
Round 2
Reviewer 3 Report
pg 3 line 117-119 - rephrase "Crystallographic structure for 1 is shown in Figure 1 and contain atomic coordinates expressed in angstroms (A) and selected bond lengths."
Suggest: "The crystallographic structure for 1 is shown in Figure 1, with selected intramolecular interactions shown in Figure 1b.
Atomic coordinates are not expressed in Angstrom units. Moreover they are not shown in tFigure 1. They are in supplementary data. The caption for Fig. 1 has been revised and bond distances have been removed. There is no need to state this in the body text.
pg 3 line 122 -- change the Angstrom symbol to a degree symbol.
Author Response
Referee 3, round 2
Comment: pg 3 line 117-119 - rephrase "Crystallographic structure for 1 is shown in Figure 1 and contain atomic coordinates expressed in angstroms (A) and selected bond lengths."
Suggestion: "The crystallographic structure for 1 is shown in Figure 1, with selected intramolecular interactions shown in Figure 1b.
Answer: the text was changed following the referee's suggestion, and now it reads: “The crystallographic structure for 1 is shown in Figure 1, with selected intramolecular interactions shown in Figure 1b.”
Comment: Atomic coordinates are not expressed in Angstrom units.
Suggestion: pg 3 line 122 -- change the Angstrom symbol to a degree symbol.
Answer: atomic coordinates were changed to a degree symbol.
Author Response File: 
Author Response.pdf
