Synthesis and Crystallographic Characterization of X-Substituted 2,4-Dinitrophenyl-4′-phenylbenzenesulfonates†
Round 1
Reviewer 1 Report
Comments to manuscript id chemistry-814313:
This work reports an improved protocol toward 2,4-dinitrophenol esters of a range of substituted benzenesulfonic acids. The new procedure is straightforward in practical terms and eliminates the use of chlorinated solvent and organic amines or pyridine as base. The work is recommended for publication in chemistry but minor corrections are required.
1) Scheme 2: i) Since “Sec” stands for selenium containing amino acid, the reaction lacks the phenol in the list of starting materials; ii) correct O-hNRsel in scheme to read O-hNRSel as used in text.
2) Page 2, first paragraph: “2,4-dinitrophenylpyridinium p-toluenesulfonate” is not a correct name for compound 3, which may be described as the pyridine adduct of 2,4-dinitrophenyl p-toluenesulfonate
3) Relates to 2): Do isolated product 4 and pyridine react to form 3?
4) Scheme 3:
i) minus in circle refers to formal charges; real charges are represented by n+ or n-.
ii) proton loss in third reaction step occurs in the forward not the back direction as indicated; authors may simple formulate the loss of HCl on the forward reaction arrow
iii) 4th step lacks loss of pyridine
5) Table 1: Include product identification number in table to prevent confusion with table entry numbers
6) Page 5, paragraph below Table 1: authors discuss “electronic factors, steric factors or a combination of both” to explain lower reaction yields but report highest yield for sterically most encumbered mesitylenesulfonic acid
7) Conclusions: please clarify what “less environmental impact” means; the procedure still uses high-energy sulfonyl chlorides as starting materials, it is rather the elimination of chlorinated solvent and of organic base
8) Experimental procedures:
i) Authors should provide elemental analysis for all new compounds!
ii) Authors may consider adding 13C NMR and IR spectral data
iii) NMR data for product 4: reference to resonance at 7.49 ppm as a doublet is not correct because an AB type splitting is to be expected (part of spin system that includes multiplet at 7.78-7.71 ppm)
iv) please remove duplicates of 1H NMR data for 2,4-dinitrophenyl 4-methylbenzenesulfonate
v) why does the melting point reported for product 4 in first procedure (125-127°C) differ from those in the other two procedures (200°C)?
vi) please recommend one of the 3 purification procedures reported for product 4
vii) procedure toward pyridine adduct 3: “triethylamine” should read “pyridine”; “p-toluenesulfonate” may read “4-methylbenzenesulfonate” as in other procedures
Author Response
Response to Reviewer # 1:
This work reports an improved protocol toward 2,4-dinitrophenol esters of a range of substituted benzenesulfonic acids. The new procedure is straightforward in practical terms and eliminates the use of chlorinated solvent and organic amines or pyridine as base. The work is recommended for publication in chemistry but minor corrections are required.
- Scheme 2: i) Since “Sec” stands for selenium containing amino acid, the reaction lacks the phenol in the list of starting materials; ii) correct O-hNRsel in scheme to read O-hNRSel as used in text.
Correction made
2) Page 2, first paragraph: “2,4-dinitrophenylpyridinium p-toluenesulfonate” is not a correct name for compound 3, which may be described as the pyridine adduct of 2,4-dinitrophenyl p-toluenesulfonate
Correction made
3) Relates to 2): Do isolated product 4 and pyridine react to form 3?
We did not investigate the reaction of isolated product 4 and pyridine. We will be investigating this reaction later when we can get back to the lab. My inclination is that some product (3) will be formed from isolated product 4 and pyridine. However, the extent of product formation is still to be determined.
4) Scheme 3:
i) minus in circle refers to formal charges; real charges are represented by n+ or n-.
ii) proton loss in third reaction step occurs in the forward not the back direction as indicated; authors may simple formulate the loss of HCl on the forward reaction arrow
iii) 4th step lacks loss of pyridine
All suggested changes based on (i), (ii) and (iii) have been made.
5) Table 1: Include product identification number in table to prevent confusion with table entry numbers
Given that the Table represents optimization and the details are explained in the footnote, confusion with Table entry should be a concern.
6) Page 5, paragraph below Table 1: authors discuss “electronic factors, steric factors or a combination of both” to explain lower reaction yields but report highest yield for sterically most encumbered mesitylenesulfonic acid
The explanation refers to products 1b, 2b and 3b
7) Conclusions: please clarify what “less environmental impact” means; the procedure still uses high-energy sulfonyl chlorides as starting materials, it is rather the elimination of chlorinated solvent and of organic base
Correction made
8) Experimental procedures:
i) Authors should provide elemental analysis for all new compounds!
The HRMS of each new compound has been provided except for compound 3, where data could not be obtained before the COVID-19 shutdown.
ii) Authors may consider adding 13C NMR and IR spectral data
13C NMR data could not be obtained because of lab shutdown due to COVID-19. However, all 1HNMR data are provided in the supplemental information and the spectra are clean.
iii) NMR data for product 4: reference to resonance at 7.49 ppm as a doublet is not correct because an AB type splitting is to be expected (part of spin system that includes multiplet at 7.78-7.71 ppm)
Correction has been made
iv) please remove duplicates of 1H NMR data for 2,4-dinitrophenyl 4-methylbenzenesulfonate
Duplicates have been removed
v) why does the melting point reported for product 4 in first procedure (125-127°C) differ from those in the other two procedures (200°C)?
Correction has been made. It was an error.
vi) please recommend one of the 3 purification procedures reported for product 4
Different workups were used for different reaction conditions. One procedure could not be applied to all reaction conditions.
vii) procedure toward pyridine adduct 3: “triethylamine” should read “pyridine”; “p-toluenesulfonate” may read “4-methylbenzenesulfonate” as in other procedures
Correction made
Author Response File: 
Author Response.pdf
Reviewer 2 Report
The authors developed a facile method to prepare a range of arylsulfonates with easily accessible reagents. The formation of these sulfonates is well characterized with NMR spectroscopy and crystal structures. Overall, the manuscript is well written and ready to be published.
Author Response
The authors developed a facile method to prepare a range of arylsulfonates with easily accessible reagents. The formation of these sulfonates is well characterized with NMR spectroscopy and crystal structures. Overall, the manuscript is well written and ready to be published.
Thanks for your review.
Reviewer 3 Report
The authors developed a new procedure for the synthesis of x-substituted 2,4-dinitrophenyl-4’-phenylbenzenesulfonate, starting from the relative aryl sulfonyl chloride. They mainly states that the use of base as pyridine (required as a acidity scavenger) in DCM yield to pyridine salts, while their alternative using water miscible solvents as THF and acqueous bases determined the formation of the target compounds in nice yields. In addition the hydrolysis of the aryl sulfonyl chloride seemed to be rather less important as expected even in presence of substantial amounts of water. The investigation on biphenyl sulfonyl chloride derivatives and the dependence of the yield on the substitution in para position of the second phenyl ring (H, methyl or fluorine) is rather inconclusive: while it is an interesting insight, if the authors desire to go deeper in an electronic/steric analysis of these series of compounds, they should broad the range of compounds, not only with para substituents (where the steric effects is limited).
The crystallographic analysis is really well done, even if is not really of main importance in a study like these, it is interesting to have. They should focus on how much the two phenyl rings of the biphenyl unit are more or less coplanar to give an answer on the conjugation extension of system, maybe in relation of the yield obtained.
The experimental part is well written and detailed. The NMR spectra in the supporting information show very clean compound.
Missing the 13C-NMR spectra of each compound which I think they should provide (HPLC purities will be also really appreciated).
Table1: in the scheme above the table they should report on the arrow the general condition, like “base” and “solvent” (I know that I am picky) which are the variable of the different entries.
“Entries are presented in order of increasing yield” this is not true, they are from entries 1 to 8 reported in decreasing yields.
Author Response
The authors developed a new procedure for the synthesis of x-substituted 2,4-dinitrophenyl-4’-phenylbenzenesulfonate, starting from the relative aryl sulfonyl chloride. They mainly states that the use of base as pyridine (required as a acidity scavenger) in DCM yield to pyridine salts, while their alternative using water miscible solvents as THF and acqueous bases determined the formation of the target compounds in nice yields. In addition the hydrolysis of the aryl sulfonyl chloride seemed to be rather less important as expected even in presence of substantial amounts of water. The investigation on biphenyl sulfonyl chloride derivatives and the dependence of the yield on the substitution in para position of the second phenyl ring (H, methyl or fluorine) is rather inconclusive: while it is an interesting insight, if the authors desire to go deeper in an electronic/steric analysis of these series of compounds, they should broad the range of compounds, not only with para substituents (where the steric effects is limited).
Thanks for your review and the suggestion for future work. Our plan is to continue to test the versatility of our current method by using other substituted benzene derivatives.
The crystallographic analysis is really well done, even if is not really of main importance in a study like these, it is interesting to have. They should focus on how much the two phenyl rings of the biphenyl unit are more or less coplanar to give an answer on the conjugation extension of system, maybe in relation of the yield obtained.
Thanks for your review and for the suggestion for future work. We will be investigating this and other structural features of these compounds.
The experimental part is well written and detailed. The NMR spectra in the supporting information show very clean compound.
Thanks for your review.
Missing the 13C-NMR spectra of each compound which I think they should provide (HPLC purities will be also really appreciated).
We have all compounds and were planning to obtain the 13CNMR when our labs were forced to shut down due to the COVID-19 pandemic. However, we are confident that our compounds are pure based on information from 1HNMR and other analysis.
Table1: in the scheme above the table they should report on the arrow the general condition, like “base” and “solvent” (I know that I am picky) which are the variable of the different entries.
We have added base and solvent
“Entries are presented in order of increasing yield” this is not true, they are from entries 1 to 8 reported in decreasing yields.
Correction made
Author Response File: Author Response.pdf
