Montmorillonite K10: An Efficient Organo-Heterogeneous Catalyst for Synthesis of Benzimidazole Derivatives

Round 1

Reviewer 1 Report

The manuscript presents an interesting application of using cheap clay-based catalyst for synthesis of benzimidazole derivatives. The concept of the studies is very interesting, however, in my opinion, crucial modifications for the manuscript should be done before consideration.

• The English language needs crucial modifications; I suggest that the authors get editing help from someone with full professional proficiency in English to revise the entire English writing through the manuscript.
• The structure of the Introduction is somewhat loosely organized and thus leading the logical confusion to the reader, please re-write the introduction. In the introduction the authors mentioned the advantages of using clay-based catalyst in heterogeneous catalysis, however, authors missed to give different example of using waste materials for synthesising Lewis acid based catalyst such as from aluminium foil waste as in 3, 1545-1550.10.1002/slct.201702660. Please elaborate more in that section to improve the introduction section.
• Have the authors compared their results with Fe2O3- MgO-Zeolite or any type of zeolite as the chemical composition of your catalyst is similar to zeolite-type catalysts?
• Most of the references are quite old and needs updating.
• Have you performed any post characterizations for the spent catalyst after reaction?

Author Response

Dear Editor,

Thank you for the patience you have had in waiting for my answer. We submit now the revised version of the paper. We have carefully addressed all of yours and reviewer’s comments.

The changes made in the revised manuscript are clearly highlighted.

We provide a pdf version of the revised manuscript.

Reviewer 1

The manuscript presents an interesting application of using cheap clay-based catalyst for synthesis of benzimidazole derivatives. The concept of the studies is very interesting, however, in my opinion, crucial modifications for the manuscript should be done before consideration.

• The English language needs crucial modifications; I suggest that the authors get editing help from someone with full professional proficiency in English to revise the entire English writing through the manuscript.

Answer:

We revised the manuscript making all the appropriate corrections

• The structure of the Introduction is somewhat loosely organized and thus leading the logical confusion to the reader, please re-write the introduction. In the introduction the authors mentioned the advantages of using clay-based catalyst in heterogeneous catalysis, however, authors missed to give different example of using waste materials for synthesing Lewis acid based catalyst such as from aluminium foil waste as in 3,1545-1550.10.1002/slct.201702660. Please elaborate more in that section to improve the introduction section.

Answer:

We organized the structure of the introduction. In addition, we reported the sentence “The synthesis of Lewis acid heterogeneous catalysts from waste materials has become increasingly popular over the last years [25], as in the case of  sulfonic-acid-functionalized activated carbon prepared from matured tea leaf, tested for synthesis of 2-substituted benzimidazole and benzothiazole [26].

25. Osman, A. I.; Abu-Dahrieh J. K.; McLaren M.; Laffir F.; Rooney D. W. Characterisation of Robust Combustion Catalyst from Aluminium Foil Waste. ChemistrySelect, 2018, 3, 1545-1550.
26. Goswami, M.; Dutta, M.M.; Phukan, P. Sulfonic-acid-functionalized activated carbon made from tea leaves as green catalyst for synthesis of 2-substituted benzimidazole and benzothiazole. Res Chem Intermed, 2018, 44, 1597–1615

• Have the authors compared their results with Fe2O3- MgO-Zeolite or any type of zeolite as the chemical composition of your catalyst is similar to zeolite-type catalysts?

Answer:

We reported the sentence  “Other different zeolites have been tested for the synthesis of benzimidazoles but the experimental procedures do not show selectivity [92-94]“

92. Hegedüs, A.; Hell, Z.;  Zeolite‐Catalyzed Environmentally Friendly Synthesis of Benzimidazole Derivatives Synthetic Communications, 2009, 36(15):3625-3630
93. Khanday, W. A.; Tomar, R. Conversion of zeolite—A in to various ion-exchanged catalytic forms and their catalytic efficiency for the synthesis of benzimidazole Catalysis Communications, 2014, 43, 5, 141-145
94. Saberi A. Efficient synthesis of Benzimidazoles using zeolite, alumina and silica gel under microwave irradiation Iran. J. Sci. Technol., 2015, 39, 7-10.

• Most of the references are quite old and needs updating.

Answer:

We reported the sentence  “Numerous methods are reported for the condensation of substituted o-phenylenediamine with aldehydes catalyzed by metal triflate such as Sc(OTf)₃ or Yb (OTf)₃ [9], TiCl₃OTf [10], different oxidizing agents [11-14] and lanthanides as Lewis-acid catalysts [15,16]” reporting the corresponding references

9. Liyan, F.; Wen, C.; Lulu, K. Highly chemoselective synthesis of benzimidazoles in Sc(OTf)3-catalyzed system. Heterocycles 2015, 91, 2306 - 2314
10. Bahrami, K.; Khodaei, M.M.; Kavianinia, I. H2O2/HCl as a new and efficient system for synthesis of 2-substituted benzimidazoles. Journal of Chemical Research. 2006, 12, 783-784
11. Ma, H.; Han, X.; Wang, Y.; Wang, J. A simple and efficient method for synthesis of benzimidazoles using FeBr3 or Fe(NO3)3·9H2O as catalyst. ChemInform. 2007, 38, 1821– 1825
12. Du, L-H.; Wang, Y-G. A rapid and efficient synthesis of benzimidazoles using hypervalent iodine as oxidant. Synthesis. 2007, 5, 675-678.
13. Sontakke, VA.; Ghosh, S.; Lawande, P.P.; Chopade, B.A.; Shinde, V.S. A simple, efficient synthesis of 2-aryl benzimidazoles using silica supported periodic acid catalyst and evaluation of anticancer activity. ISRN Organic Chemistry. 2013, 1-7.
14. Kumar, K.R.;, Satyanarayana, P.V.V.; Reddy, BS. NaHSO4-SiO2 promoted synthesis of benzimidazole derivatives. Archives of Applied Science Research. 2012, 4, 1517-1521
15. Venkateswarlu, Y.; Kumar, S.R.; Leelavathi, P. Facile and efficient one-pot synthesis of benzimidazoles using lanthanum chloride Organic and Medicinal Chemistry Letters. 2013, 3, 7, 2-8.
16. Martins, G.M.; Puccinelli, T.; Gariani, R.A.; Xavier, F.R.; Silveira, C.C.; Mendes, S.R. Facile and efficient aerobic one-pot synthesis of benzimidazoles using Ce(NO3)3·6H2O as promoter. Tetrahedron Letters, 2017, 58, 1969-1972.

• Have you performed any post characterizations for the spent catalyst after reaction?

Answer:

No characterization was carried out after the recycling process, having found that there is no loss of catalytic activity. To demonstrate the efficiency of the recycled catalyst, we performed a series of reactions without using any solvents and any treatments of the spent catalyst. Finally, we compared the obtained data in this way with those ones observed in our previous experiments (Figure 1). The whole process is therefore considered eco-sustainable and competitive compared to classic synthetic processes

Author Response File: Author Response.docx

Reviewer 2 Report

This would be an acceptable paper if some minor revisions were carried out. 

A major issue to me is the description of the actual reaction conditions.  In some cases, e.g. Table 1, there is no mention of microwave radiation being used.  I presume that the temperature is what is controlled in the microwave reactor – that is not clear in the text but was somewhere in the experimental.  It would be useful as a Table footnote.  In any case, I should not have to assume anything.  In cases where MW radiation is used as in Table 1, this should be explicit in the equation and in the Table footnotes.  In the reactions where products are actually isolated and in the experimental procedure, it should be extremely clear what was actually done – someone trying to repeat this should explicitly know the procedure.  This issue of what was actually done is a problem too in the cases where the product is isolated.  Specifically, it is not at all clear to me how was the excess aldehyde was removed.  That is not described. It may have been removed at reduced pressure but that seems more implausible for something like 4-nitrobenzaldehyde that has a lower vapor pressure.  Even for benzaldehyde, it is normally difficult to remove >95% from an oil by evaporation and I would have expected some small signals for that excess reagent in some of the product spectra.  Last, I am not an expert in terms of knowing physical properties of benzimidazoles.  However, I do know that some of these materials are solids.  That is true for 2-phenylbenzimidazole and likely for many if not most of the other products.  Thus, there should be a m.p. given.  That defines purity and is a trivial amount of experimental work.  Should I presume the authors have ¹H and ¹³C NMR data?  That too should be made clear.  Finally, the term solvent free as used here is a problem for me in that the overall reaction requires ethyl acetate.  I fail to understand how a reaction is solvent free if a solvent has to be used to isolate the product.  Why would anyone care about a reaction if it produced a 50/50 mixture of a benzimidazole derivative and an aldehyde?  Further, if I were concerned about solvent, I would compare this to typical benzimidazole syntheses.  They typically are carried at concentrations of  0.2 – 1.0 M.  In contrast the chemistry here is effectively carried out at <0.1 M since 12 mL of ethyl acetate are required for a 1 mmol synthesis.  In terms of sustainable chemistry, I do not understand the difference between adding the solvent after or during the reaction if solvent has to be added to isolate products or separate products and catalysts.

I’ve some issues with the prose throughout and with some of the data presentation.  The yields are given to a precision that is meaningless.  The authors may have isolated 96.6% of product in one reaction but 96% is more than enough precision.  There are some typos.  Footnote a in Table 2 and 3 discussing discussing the wt% catalyst loading is incoherent.  Examples with prose include line 94 (while I question the theory here it is just speculation but the wording should be ‘it is due’), line 100 ‘a . . . . methods’ mixes singular and plural, line 106 ‘starting vs start material’, line 109, dancing bears perform, reactions do not.  I could continue this for more than 15 lines but this randomly chosen short segment illustrates the prose issues.  I was particularly annoyed with the wrong spelling of phenylenediamine as that is something that is not a language issue but reflects poor proofreading by the authors.

While this work has some issues with prose and the descriptions, while I personally do not know of similar microwave promoted syntheses, I found this work interesting enough for publication.  With the modifications above and better characterization of the products, this work merits publication.

Author Response

Dear Editor,

Thank you for the patience you have had in waiting for my answer. We submit now the revised version of the paper. We have carefully addressed all of yours and reviewer’s comments.

The changes made in the revised manuscript are clearly highlighted.

We provide a pdf version of the revised manuscript.

Reviewer 2

• This would be an acceptable paper if some minor revisions were carried out. 

A major issue to me is the description of the actual reaction conditions.  In some cases, e.g. Table 1, there is no mention of microwave radiation being used.  I presume that the temperature is what is controlled in the microwave reactor – that is not clear in the text but was somewhere in the experimental.  It would be useful as a Table footnote.  In any case, I should not have to assume anything.  In cases where MW radiation is used as in Table 1, this should be explicit in the equation and in the Table footnotes. 

Answer:

In Table 1, footnote c, entries 8 and 9, we reported the times (5 min) and the temperature (60 ° C) and "^cReaction mixture under MW irradiation; the temperature controlled in the microwave reactor.

In Table 2, footnote a, we reported “^a General reaction conditions: 1 mmol of o-PDA and 2 mmol of aldehyde are added to 20% mw to o-amine of MK10. The reaction was conducted in a Synthos 3000 microwave oven (Anton-Paar) at 60°C for 5 min. The reaction mixture was then washed with AcOEt (3 x 3 mL) and filtered to obtain MK10. The combined organic phases were dried over Na₂SO₄, filtered and evaporated under reduced pressure to give the corresponding products 1a-8a”

• In the reactions where products are actually isolated and in the experimental procedure, it should be extremely clear what was actually done – someone trying to repeat this should explicitly know the procedure.  This issue of what was actually done is a problem too in the cases where the product is isolated.  Specifically, it is not at all clear to me how was the excess aldehyde was removed.  That is not described. It may have been removed at reduced pressure but that seems more implausible for something like 4-nitrobenzaldehyde that has a lower vapor pressure.  Even for benzaldehyde, it is normally difficult to remove >95% from an oil by evaporation and I would have expected some small signals for that excess reagent in some of the product spectra. 

Answer:

Excess aldehyde, after the complete conversion of OPD, occurs in the case in which we use aldehydes with electron attracting groups, such as p-chlorine benzaldehyde and p-nitro benzaldehyde. In this case only the monosubstituted product is obtained which can be separated from the excess of benzaldehyde through chromatographic separation.

We reported in Table 2, footnote c, “^c Product a was not detected. Only the corresponding 2-substituted derivative, 4b and 5b (Conversion 98% and 97% respectively of OPD calculated from GC/MS) were detected by GC / MS”.

In addition we reported  “The reactions performed with aldehydes containing electron withdrawing groups such as p-chloro or p-nitro benzaldehyde (entries 4 and 5, Table 2) did not afford the disubstituted derivative but the corresponding 2-monosubstituted benzimidazoles “(4b and 5b) in good yields (detected by GC/MS). In this case the monosubstituted product can be separated from the excess of benzaldehyde through chromatographic separation”.

• Last, I am not an expert in terms of knowing physical properties of benzimidazoles.  However, I do know that some of these materials are solids.  That is true for 2-phenylbenzimidazole and likely for many if not most of the other products.  Thus, there should be a m.p. given.  That defines purity and is a trivial amount of experimental work.  Should I presume the authors have ¹H and ¹³C NMR data?  That too should be made clear. 

Answer:

The obtained compounds were characterized by GC / MS, H-NMR and C-NMR. The data are reported in the S.I. and are comparable with the obtained data for the synthesis of benzimidazoles with Erbium triflate [98] and with Active Deep Eutectic Solvent [50].

• Finally, the term solvent free as used here is a problem for me in that the overall reaction requires ethyl acetate.  I fail to understand how a reaction is solvent free if a solvent has to be used to isolate the product.  Why would anyone care about a reaction if it produced a 50/50 mixture of a benzimidazole derivative and an aldehyde?  Further, if I were concerned about solvent, I would compare this to typical benzimidazole syntheses.  They typically are carried at concentrations of  0.2 – 1.0 M.  In contrast the chemistry here is effectively carried out at <0.1 M since 12 mL of ethyl acetate are required for a 1 mmol synthesis.  In terms of sustainable chemistry, I do not understand the difference between adding the solvent after or during the reaction if solvent has to be added to isolate products or separate products and catalysts.

Answer:

A green solvent as ethyl acetate, (Catherine M. Alder, John D. Hayler, Richard K. Henderson, Anikó M. Redman, Lena Shukla, Leanna E. Shuster, Helen F. Sneddon  Updating and further expanding GSK’s solvent sustainability guide, Green Chem., 2016, 18, 3879–3890) was used during the  workup process (3x 3ml) in order to obtain the isolated product and at the same time to wash the MK10, removing organic residues on catalyst surface. The recovered catalyst was dried in an oven (50° C) to remove traces of solvent. To demonstrate the efficiency of the catalyst recycled, we performed a series of reactions without using any solvent and treatment of the spent catalyst. Finally, we compared the data obtained in this way with those ones observed in our previous experiments (Figure 1). The whole process is therefore considered eco-sustainable and competitive compared to classic synthetic processes

• I’ve some issues with the prose throughout and with some of the data presentation.  The yields are given to a precision that is meaningless.  The authors may have isolated 96.6% of product in one reaction but 96% is more than enough precision.  There are some typos.  Footnote a in Table 2 and 3 discussing discussing the wt% catalyst loading is incoherent.  Examples with prose include line 94 (while I question the theory here it is just speculation but the wording should be ‘it is due’), line 100 ‘a . . . . methods’ mixes singular and plural, line 106 ‘starting vs start material’, line 109, dancing bears perform, reactions do not.  I could continue this for more than 15 lines but this randomly chosen short segment illustrates the prose issues.  I was particularly annoyed with the wrong spelling of phenylenediamine as that is something that is not a language issue but reflects poor proofreading by the authors.

Answer:

We changed: “this due” with “it is due” (line 98); “we present a new and selective synthetic methods” with “we present a new and selective synthetic method” (line 100); “start material” with “starting material’ (line 106); the sentence “The reaction mixture, stirred at room temperature for 2 h, performed using the diamine and benzaldehyde in a 1:1 and 1:2 molar ratio respectively (Table 1, entries 1 and 2). The performance of a reaction monitored by thin layer chromatography (TLC) and gas chromatography/mass spectrometry (GC/MS) analysis.” With “The reaction mixture, stirred at room temperature for 2 h, is executed using the diamine and benzaldehyde in a 1:1 and 1:2 molar ratio respectively (Table 1, entries 1 and 2). The reaction is monitored by thin layer chromatography (TLC) and gas chromatography/mass spectrometry (GC/MS) analysis.” We changed o-phenylenediamine with o-PDA abbreviation

• While this work has some issues with prose and the descriptions, while I personally do not know of similar microwave promoted syntheses, I found this work interesting enough for publication.  With the modifications above and better characterization of the products, this work merits publication.

Answer:

we made all the suggested corrections. We thank for the patience and rigor shown when reading our manuscript

Author Response File: Author Response.docx

Reviewer 3 Report

The authors of this manuscript present a new and selective synthetic methods to obtain benzimidazole derivatives in solvent free condition reaction testing the MK10 as heterogeneous catalyst. 

The described method seems highly efficient and economic and it surely deserves further exploitation. As for the manuscript itself I would like to draw the attention to a few points as follows:

1. The following studies also present the synthesis of benzimidazole using MK10. Please add a short discussion on how your method compares with these reports and include the references.

• Rostamizadeh, S., Amani, A.M., Aryan, R. et al. Very fast and efficient synthesis of some novel substituted 2-arylbenzimidazoles in water using ZrOCl₂·nH₂O on montmorillonite K10 as catalyst. Monatsh Chem 140, 547–552 (2009). https://doi.org/10.1007/s00706-008-0087-1
• Subrat Jyoti Borah and Diganta Kumar Das, Modified Montmorillonite: An Active Heterogeneous Catalyst for the Synthesis of Benzimidazoles, Journal of Chemical and Pharmaceutical Research, 2018, 10(7): 118-123 

2. There quite a few grammar and syntax errors "first methodologies synthetic reported" instead of " the first synthetic methodolody reported herein", "The reaction yields are decidedly high, the work-up procedures of the reaction easy and convenient, an increase in selectivity and the possible recycle of catalyst without waste formation." - there is no verb for the last two sentences... Please, examine the text thoroughly for such errors.

3. Is there or isn't there any Supporting information???? There was NO attached file. Are the NMRs in the suporting information. There is no reference as to what is included in the SI.

4. What scale was this reaction applied for?? can it be used for a large scale synthesis since there is a statement in the end "it has been shown that the reaction process is applicable in the industrial field"

5. Please check footnote a of table 2 and 3. They are almost the same although they refer to the selectivity issue and 1 mmol of aldehyde should be used.

Author Response

Dear Editor,

Thank you for the patience you have had in waiting for my answer. We submit now the revised version of the paper. We have carefully addressed all of yours and reviewer’s comments.

The changes made in the revised manuscript are clearly highlighted.

We provide a pdf version of the revised manuscript.

Reviewer 3

The authors of this manuscript present a new and selective synthetic methods to obtain benzimidazole derivatives in solvent free condition reaction testing the MK10 as heterogeneous catalyst. 

The described method seems highly efficient and economic and it surely deserves further exploitation. As for the manuscript itself I would like to draw the attention to a few points as follows:

• The following studies also present the synthesis of benzimidazole using MK10. Please add a short discussion on how your method compares with these reports and include the references.

1. Rostamizadeh, S., Amani, A.M., Aryan, R. et al.Very fast and efficient synthesis of some novel substituted 2-arylbenzimidazoles in water using ZrOCl₂nH₂O on montmorillonite K10 as catalyst. Monatsh Chem 140, 547–552 (2009). https://doi.org/10.1007/s00706-008-0087-1
2. Subrat Jyoti Borah and Diganta Kumar Das, Modified Montmorillonite: An Active Heterogeneous Catalyst for the Synthesis of Benzimidazoles, Journal of Chemical and Pharmaceutical Research, 2018, 10(7): 118-123 

Answer:

We reported the sentence “Recently, a simple and eco-friendly protocol for the synthesis of some novel substituted 2-arylbenzimidazoles was developed using ZrOCl₂·nH₂O supported on montmorillonite K10 [89]. The synthetic process involves only the formation of the 2-benzimidazole derivative, requires the preparation of catalyst and the use of water as a solvent. Moreover, acid treated modified montmorillonite clay was used as catalyst precursor for the synthesis of benzimidazoles but the pretreatment of the catalyst and the use of toluene as a solvent makes the synthetic process unsustainable [90]”

89. Rostamizadeh, S., Amani, A.M., Aryan, R. et al. Very fast and efficient synthesis of some novel substituted 2-arylbenzimidazoles in water using ZrOCl2·nH2O on montmorillonite K10 as catalyst. Monatsh Chem 140, 547–552 (2009). https://doi.org/10.1007/s00706-008-0087-1
90. Subrat Jyoti Borah and Diganta Kumar Das, Modified Montmorillonite: An Active Heterogeneous Catalyst for the Synthesis of Benzimidazoles, Journal of Chemical and Pharmaceutical Research, 2018, 10(7): 118-123 

• There quite a few grammar and syntax errors "first methodologies synthetic reported" instead of " the first synthetic methodology reported herein", "The reaction yields are decidedly high, the work-up procedures of the reaction easy and convenient, an increase in selectivity and the possible recycle of catalyst without waste formation." - there is no verb for the last two sentences... Please, examine the text thoroughly for such errors.

Answer:

We changed “The first methodologies synthetic reported" with " first synthetic methodology herein reported " and "The reaction yields are decidedly high, the work-up procedures of the reaction easy and convenient, an increase in selectivity and the possible recycle of catalyst without waste formation." With “The reaction yields are decidedly high, the work-up procedures of the reaction are easy and suitable, an increase in selectivity and the possible recycle of catalyst without waste formation are demonstrated.

• Is there or isn't there any Supporting information???? There was NO attached file. Are the NMRs in the suporting information. There is no reference as to what is included in the SI.

Answer:

The compounds obtained were characterized by GC / MS, H-NMR and C-NMR. The data are reported in the S.I. and are comparable with the data obtained for the synthesis of benzimidazoles with Erbium triflate [98] and with Active Deep Eutectic Solvent [50].

• What scale was this reaction applied for?? can it be used for a large scale synthesis since there is a statement in the end "it has been shown that the reaction process is applicable in the industrial field"

Answer:

We changed the sentence reporting “To demonstrate the potential industrial applicability of green procedure, the model reaction was tested for a large scale using 10 mmol of o-phenylendiammine, 20 mmol of benzaldehyde and the respective amount of MK10”

• Please check footnote a of table 2 and 3. They are almost the same although they refer to the selectivity issue and 1 mmol of aldehyde should be used.

Answer:

We changed footnote a of Table 3 reporting the sentence “General reaction conditions: 1 mmol of o-PDA and 1 mmol of aldehyde are added t to 20% mw to amine of MK10. The reaction was conducted in a Synthos 3000 microwave oven (Anton-Paar) at 60°C for 5 min. The corresponding products monosubstituted benzimidazole 1b-8b were isolated as previously described to obtain disubstituted benzimidazoles (footnote a, Table 2)”

Author Response File: Author Response.docx

Round 2

Reviewer 1 Report

The comments have been addressed thus my recommendation is the accept decision 

Reviewer 3 Report

The authors have adequately addressed the suggested corrections