Review History
Unveiling the synthesis and spectral characterizations of novel (E)-furan-2-yl acrylohydrazides: an exploration in molecular design

Reviewer 1 · Jun 25, 2024

Additional comments

On lines 71-72 of the introduction, it is stated “our objective is to delve into the optoelectronic properties of (E)-3-(furan-2-yl) acrylohydrazides.” The objectives of the study have yet to be met.

The analysis and discussion by UV-vis absorbance spectroscopy and cyclic voltammetry remain below an acceptable standard. And without studying the fluorescence properties, the study remains incomplete with respect to the objective of delving into the optoelectronic properties of (E)-3-(furan-2-yl) acrylohydrazides. Both Reviewer 1 and Reviewer 3 acknowledged that the study deserves to be completed by photoluminescence measurements if the focus of the study is on the optoelectronic properties of the molecules.

Without further experimental details the quality of the cyclic voltammograms remain questionable. What is the counter electrode material? What is the diameter of the platinum working electrode? During the cyclic voltammogram experiments was there compensation for the solution internal resistance? Were efforts made to dry the DMSO prior to the CV experiments, and if so, how was the DMSO purified? Was the solvent purged with an inert gas to remove oxygen? Was an attempt made to perform scans at a higher rate, of say 1 V/s, to observe if the peak-to-peak separation changes? In Table 7 the authors should report the standard potential, the average of the Epa and Epc values, which is the thermodynamic value. Lines 551-552 state that “Since we applied sufficiently negative potential, the reduction potentials obtained in Table 7 encompass the reduction of both groups [carbonyl and azomethine]”. This is not necessarily true.

N-acylhydrazones should absorb across the UV-vs region between 200-700 nm rather than merely in the spectral range of 475 to 800 nm (line 501) or 500 to 750 nm (line 635) or 340-800 nm as shown in Figure 6. Those peaks at 500 to 860 nm are not necessarily attributed to intramolecular charge transfers (line 506). The low value of the molar extinction coefficients in Figure 6 suggests n to pi* transitions associated perhaps with the conjugated carbonyl. The quality of the UV spectra can be improved. In Figure 6 there are two discontinuities in the spectra at 480 nm and 700 nm. These could be due to the changing of the lamps (or a software processing deviation). One remedy is reducing the deviation is to measure the spectra at a high concentration so the absorbance will be higher. Another suggestion is for the UV-vis spectra to be measured from 200-700 nm with a different solvent. Rather than using DMSO with a solvent cut-off about 270 nm, the authors should perform measurements in acetonitrile, which has a solvent cut off of 190 nm. More spectral information will be obtained.

In summary, the strength of the manuscript is the synthesis of a series of eight (E)-3-(furan-2-yl) acrylohydrazides, the full standard characterisation of the series of molecules and the conformational equilibrium analysis using various NMR techniques. This content of the manuscript meets the threshold for recommendation for publication in Peer J provided a revised manuscript with the UV, cyclic voltammetry and the optoelectronic objective are removed.

On the other hand, if the current manuscript remains with a focus on the optoelectronic applications of (E)-3-(furan-2-yl) acrylohydrazides then the study still remains too preliminary for publication requiring more clarification, discussion and experiments.

Reviewer 3 · Jun 12, 2024

Additional comments

Report on the revised manuscript (#95383)
Dear Editor, Although the authors have responded to some comments, in my opinion there is still a need for improvement to make this manuscript acceptable; below you will find my comments; some are minor, others are essential points from my point of view.
- Line 30, in the abstract: Since the authors accept my remark concerning the absence of the Z configuration of the C=N double bond, they must remove from the abstract the clause "or syn-periplanar Z (sp Z) and anti-periplanar Z (ap Z)”.
- In the Materials section, specify the device and conditions used to record the IR spectra.
- Line 119: replace the term “purity” by “yield”.
- In the Methods section, ensure that the acronyms of the analysis methods (NMR, UV, IR, etc.) are always in bold. Use the acronym HR-MS instead of HMRS (Lines: 200, 271, 298 and 326)
- Line 154: Schlenk tube (with capitalized S), not schlenk.
Section results and discussion:
- Line 346: 2-carbaldehyde, not 2-caboxaldehyde.
Scheme 1 & Table 1: In the structure of final products 4, the C=N double bond configuration must be of E configuration, as agreed.
Spectral analysis:
- General remark to consider all over the document; the stereochemical descriptors (E, Z, syn, anti…) must be in italic.
- Lines 374 to 379: the content of this paragraph is obvious and therefore useless, the authors should focus more on the NMR data of the final compounds.
- Line 390: Currently, the 13C-NMR data are summarized in Table 4, not in Table 3; by the way, both tables deserve some modifications:
- Current Table 3 is useless, it is just converting percentages that are given in Table 2, into simple fractions.
- In the first line of current Table 4 (that should become 3), I suggest using this order:
N=C(CH3) or N=CH (bold characters of the concerned C), instead of the current one N=CH or N=C(CH3).
Lines 399-401: There is no possible intramolecular hydrogen bonding in compounds 4; the observed solvent effect might be attributed to the possible formation of hydrogen bonding involving the DMSO and the amide NH group, thus increasing its nitrogen atom’s lone pair resonance with the carbonyl and therefore the double bond character of the amide C-N bond, leading to higher rotation barrier, while no such effect is expected in CDCl3.
Line 405: “exhibit lower intensity” this assertion has no meaning in this context; Since no further analyses were performed in MeOH-d4, one can’t say if the observed small signals are due to impurities, or there is duplication with less gap in chemical shift and larger difference of intensity (> 80:20).
Line 407: This last sentence is obvious and its deletion will have no effect on the manuscript’s content.
L422-424: this last sentence is meaningless; my suggestion as follows:
“The duplication of signals belonging to nuclei (1H and 13C) found near the N-acyl group clearly indicates that each compound 4 appears, in DMSO as a mixture of two conformers in variable ratios; in Table 2 and Table 3 (previous Table 4) are summarized the chemical shifts of characteristic duplicated signals for each conformer, with the estimated ration, as deduced from the relative intensity of duplicated protons’ integral”.
- From Line 425 to 447: At this stage, I still have serious reservations about assigning the syn- and anti-conformation, based on the only shown NOESY data. A rigorous assignment would require much more NMR experiments (COSY, HSQC, HMBC) including in various solvents, in order to ascertain the signals assignment. For example, in the NOESY spectrum of compound 4c, the NH signals of both conformers are correlating with N=CH signals of both conformers; the same in the case of 4e!
I am not questioning the existence of the two conformers in each case, I am just not convinced by their attribution. Therefore, I suggest that the authors just point out that the observed duplications reveal the presence of two conformers for each final compound with ratios as deduced from integrals, and by using major and minor instead of syn or anti, in table 2. Consequently, the current Table 5 becomes misleading.
Remark : One possible compromise could be adding a note, where the authors may explain that they suggested tentative assignments of conformers, but one (or more!) reviewer(s) judged that the presented NMR data are not sufficient for stating the proposed assignments.
Scheme 2: The geometry of the C=C double bond of the acryloyl fragment must be corrected in the first and third isomers (from left). Also, for clarity, no need to include the lone pairs’ orbitals in this scheme 2.
Line 507: 4a-h, in bold.
Spectra of current Figure 5 are illegible, it would be more useful to keep and discuss just one (or two) NOESY spectrum, and send the remaining spectra to the SI part, using one page for each spectrum.
Line 508: I am still not sure that the term vibration is appropriate in this context; UV-vis is dealing with electron transitions.
Table 6 (future Table 5): Add a column dedicated to the extinction coefficient, epsilon at lambda max, for each compound.
Regarding the UV-vis data, the authors should determine the optical gap energies using the empirical equation:
Egopt = h/onset = 1242/onset (eV). (see https://doi.org/10.5802/crchim.29), this article may help in restructuring your manuscript. It’s not mine.
These calculated values will be compared with the electrochemical gap energies deduced from CV data.
Discussion of the CV data:
Images of voltammograms in Figure 7 are illegible! I suggest the following:
Keep the collective image to which a half page may be dedicated. Keep one representative individual voltammogram that will be commented in details, while the remaining voltammograms will be added to the SI part, two or four/page. Pay attention to the captions, where should be mentioned the CV conditions and the identity of the analyzed compound 4.
From line 526 to 536: This paragraph which, in its right version could be appropriate in textbooks, should be delated; beside being inappropriate, it contains some misleading assertions (acidic amine nitrogen, nucleophilic attack at the nitrogen of amine…; electrophilic attack at the oxygen…).
The same from line 544 to 546. In electron transfer reactions (chemical, photo- or electrochemical), electrons are abstracted first, from the HOMO molecular orbital, or injected in the LUMO molecular orbital; in the case of conjugated pi-systems, the LUMO orbital is delocalized on the whole conjugated system, therefore we can’t think in term of localized reactive site. For oxidation, the electron may be abstracted from bonding pi-type orbital, or from the non-bonding lone pair, which could be the case with the C=N: nitrogen’s lone pair for compounds 4, but we can’t say of which type will be the HOMO without further investigation (DFT).
Line 548- …: giving the structure of compounds 4, I would not be so sure about the electrons involved during the anodic scan, nor about the precise reduction site. Pi system of these compounds are much more extended than those studied in reference 17. Moreover, except in the case of 4e, which shows two oxidation peaks during the anodic scan, all other compound show only one Ox peak!! To have more insight about the reversibility of electron transfer, CV should have been run at various scan rate, mainly at higher rates.
Line 559: Reference 18 is inappropriate, I can’t see how these results are in line with the studies conducted by Golub et al; in this reference, the authors studied the (preparative) electrochemical oxidative cleavage of particular amides, and have mainly considered the anodic scanning, at various rates.
Line 567: On the basis of which data the authors state “the quasi-reversibility oxidation of the azomethine fragment”?
Line 598-573: Use “the amide nitrogen” instead of “the amine nitrogen” since you are studding N-acyl derivatives, the comparison with ref19 is no more appropriate (E°(amines) << E°(amides)); radical cations of amides are very reactive species, even in neutral or acidic media. The comment suggesting the pH variation depending on the structure of studied compound 4 is out of context; how one can imagine proton transfer between these hydrazides and acetonitrile (pKa of these hydrazide as acids should be around 14-18, or around 8 as bases) while for CH3CN pKa are; about 30 as acid, or < 0 as base).
To make this part more concise with no “hazardous” statements, the authors may consider the following suggestions/modifications:
- Stop the comment at the end of the sentence finishing in the current line 571.
- The authors seem considering the first reduction peak is corresponding to the reverse electron transfer of the Red peak, the scan rate used would not allow observing the reverse ET if there was one; if it was so, we could not determine the frontiers MO energies. This is not the case, in my humble opinion; there are too much differences of potential between the two peaks in each case. The first Ox peak corresponds probably to a one electron oxidation at the azomethine nitrogen (sp2 lone pair), while the only Red peak corresponds to a one electron injection in the delocalized LUMO of the extended pi-system.
From Line 571: Since you the optical gap energies will have calculated, using UV-vis data, you may now calculate the frontiers MO energies using the empirical Bredas et al equation :
E(LUMO) = -(Eonset Red – Eref + 4.4) ev ; and E(HOMO) = -(Eonset Ox – Eref + 4.4) ev ;
Next calculate the electrochemical Egelec = [E(LUMO) – E(HOMO)] ev, and then compare it with the optical one (Egopt), and comment on differences if any (see examples in https://doi.org/10.5802/crchim.29).

Reviewer 1 · Feb 2, 2024

Reviewer 2 · Feb 14, 2024

Additional comments

In this paper, professor the authors designed and synthesized a series of novel (E)-furan-2-yl acrylohydrazides derivatives, and the structures of compound were confirmed by NMR and HRMS. The NMR results indicated the compound with different substitutive group will exhibited different conformation. UV visible results demonstrated the compounds' absorption in the visible range. Cyclical voltammetry results indicated the reversible reduction of our acrylohydrazides on a platinum electrode. Although the performance of compounds 4f and 4h is impressive, I believe that the number of title compounds is low and the substituent type is relatively single. Therefore, I suggest that the authors should synthesize more compounds with different substitutive group to make the rule more obvious. But in general, this works provide a certain contribution to the development of multifunctional materials. As a result, this paper deserve publication in the journal Peer J Organic Chemistry.

Reviewer 3 · Feb 16, 2024