Synthesis and Spectroscopic Characterization of Furan-2-Carbaldehyde-d
Round 1
Reviewer 1 Report
The manuscript is compliant with the journal's content. The presentation of the results is clear, concise and sufficiently backed up by the experimental results.
Comment regarding the content:
line 38: for the poor yields argument, adding the respective yields on the scheme would be illustrative
There are some typos/language mistakes that would need correction:
line 27: route
line 30: known literature methods
line 31: from
line 32: Starting
line 35: formylation
line 37: instead of deuterated water, D2O could be used as previously
line 44: straightforward
line 35 vs line 46: different spellings used for Vilsmeyer
line 47: presented
line 80: MHz
line 84: determined, residual
line 85: expected
line 89: recorded
line 111: Figure 4
line 132: Figure 6, characteristic
line 148: instead received obtained
Author Response
Dear reviewer,
thank you for your welcome support improvement our manuscript.
We revised all your suggestions accordingly.
Reviewer 2 Report
Authors have described an interesting protocol for synthesising furan-2-carbaldehyde-d using adapted Vielsmeier condition (DMF-d7 and (COCl)2). The product was obtained in quantitative yield (99%). The structure of the product was confirmed by spectra analyses and discussed. I suggest publishing the article after a minor revision. In the text, the authors present quantitative yield, but in Scheme 1 the presented yield is 93% (yield after distillation). It should be changed to 99%. They also described that all described methods suffer from demanding multiple steps, expensive starting materials and/or poor yield in relation to the expensive materials. In my opinion, yields for all methods at Scheme 1 should be added.
Author Response
Dear reviewer,
thank you for your welcome support improving our manuscript.
We revised all your suggestions accordingly.
The yields for the literature known methods were supplemented in Figure 1.
The description of the yield clarified. Distillation with the appropriate procedural material loss is an option and not necessary because the purity of the “raw” product is 97%.
Reviewer 3 Report
Reviewer comments: Furan-2-Carbaldehyde-d synthesis article.
The timeliness of the article might be justified with an additional sentence or two giving reference to those who have used the deuterated carbaldehyde. There are a half dozen references in SciFinder, one of which is listed as Niu et al [17]. Two involved reaction of the deuterated carbaldehyde with Grignard reagents. Are there additional reasons for wanting or needing the deuterated carbaldehyde? The paper should have some discussion in the “Results and Discussion” section. For example, the authors should explain how and why the presented procedure is superior to the method reported by Chadwick et al [reference 13], in 1973. List the reasons that the presented procedure is superior to the DMF/POCl3 method. The Chadwick procedure needs less time (4 h stirring at room temperature). Both methods list purification by distillation. Oxalyl chloride and POCl3 are inexpensive, with POCl3 being the less expensive. Both methods use DMF-d7. From the viewpoints of time and expense, it would appear that the POCl3 method would have the edge.
Another opportunity for discussion is the m/z peak seen in both mass spectra at m/z 95 to form an acylium ion. Furan loses 1 from 96 (an H) and the deuterated furan loses 2. These facts further substantiate the presence of the D on the carbonyl group.
Another possible discussion point could be for the distillation. Does distillation of the product at
atmospheric pressure lead to decomposition?
The presentation of spectra is excellent. Comments are also excellent.
There are some grammatical and usage issues: Line 16: Change received to obtained. Line 31: Change form to from. Line35: Change to: Vilsmeier reduction of 3 using DMF/POCl313; Line 47: presented. Line 51: Change choose to chose. Line 58: dichloromethane (DCM, 20 mL) was added and other places in procedure where DCM was used. Line 69: pressure to give 2.7g ….. delete “was received”. Line 73: Delete “We recommend to store” ..Add The product was stored under inert gas…… Line 75: Change discoloration to decomposition. Line 80: Since “data” is the plural form of datum, change was to were. Line 93: Change received to distilled. Line 102: Change mole to molecular ion. Line 104: Add the peak at 95 to the list. It represents a major fragment.
As for the procedure, it gives extensive detail, particularly when compared with the lack of detail found in reference 13, for the procedure using POCl3
There were some changes suggested.
Author Response
Dear reviewer,
thank you for your welcome support improving our manuscript.
We revised all your suggestions accordingly.
The yields for the literature known methods were supplemented in Figure 1.
The description of the yield was clarified. Distillation with the appropriate procedural material loss is an option, but not necessary because the purity of the “raw” product was 97%.
Regarding your suggestion we supplement the manuscript as follow:
“However, some reactions using furfural-d (1) for the synthesis of deuterated compounds were described before[17, 21, 22, 23].”
Regarding your suggestion we supplement the manuscript as follow:
“Compared to the earlier described Vilsmeier protocol[13] the atom economy of the used DMF-d7 was maximized because of the quantitative yield (99%). The applied extraction / evaporation workup yield a product purity of about 97% (1H-NMR) and allow the direct use of the material for subsequent reactions without distillation.”
Regarding your suggestion we adjust figure 3 and supplement the manuscript as follow:
“The fragmentation loss of the aldehyde H- or D-atom form a furanyl-acylium ion fragment with m/z = 95 in both cases. The mass differences of 2 Dalton between the mole peaks (97 m/z) and the furanyl-acylium fragment (95 m/z) substantiate the location of the D on the carbonyl group of 1. Comparison of other fragments (int. > 20%) shows nearly identical patterns (m/z = 67, 51, 39, 30) for both molecules. Only the intensities of m/z = 39 / 40 differ and may be assigned to different H/D fragments.”
Thank you for your support
