Development of a New Arylamination Reaction Catalyzed by Polymer Bound 1,3-(Bisbenzimidazolyl) Benzene Co(II) Complex and Generation of Bioactive Adamanate Amines

Round 1

Reviewer 1 Report

After the changes made by the authors, I recommned its publication.

Author Response

we corrected the english grammer in the ms

Reviewer 2 Report

The reviewer read the revised manuscript carefully.
However, the reviewer should mention several points which should be revised.
The figure of L4 in Figure 3 is incompletion.
How is the meaning of colored 2a, 4d, and 4e in Table 3? 
The angles of word "Co" in Figure 4 are inadequacy.
In this relation to the Figure 4, the reviewer cannot understand well the word "a concerted mechanism". It seems that the proposed mechanism is a typical.
In the previous reviewing, the reviewer mentioned several points. But, several points were not corresponded.
Although general procedure for catalytic C-N bond formation was shown, a catalyst quantity of this supported catalyst is not
described. How is the incorporation ratio of Co in PS-Co(BBZN)Cl2?
In this relation, the authors should show the used amounts (e.g. g, mg) of
reagents, supported catalyst, an additional ligand, base, and solvent in the representative procedure.
The reviewer thinks "12 mol%" is inadequate to understand this finding.
About 3c and 3e in the experimental section, coupling constants between C and F are not assigned.
This reviewer considers that this manuscript is exactly worthy of publication in Catalysts.
However, above issues are considered and revised before publication.

Additional comments.
The authors show "unbound Co(BBZN)Cl2". Did the author use this complex for the present conditions as a catalyst?
If so, how is the reactivity difference between PS-Co(BBZN)Cl2 and unbound Co(BBZN)Cl2?
Several sentences are reassessed yet. For example, the word "Cs2Co3" in the footnote in Table 1.

Author Response

Reviewer 2.

Please ensure that your revised manuscript follows the journal-specific guidelines listed below:

1. Address: The figure of L4 in Figure 3 is incompletion

Author’s response: Complied. Phosphorous has been included.

2. How is the meaning of colored 2a, 4d, and 4e in Table 3?

Author’s response: Complied. The structures of the compounds are given initially in Table 2 and table 3.

3. The angles of word "Co" in Figure 4 are inadequacy.

Author’s response: Complied. The structure has been redrawn with appropriate bond angles.

4. In this relation to the Figure 4, the reviewer cannot understand well the word "a concerted mechanism". It seems that the proposed mechanism is a typical.

Author’s response: Complied. The word concerted has been removed.

5. In the previous reviewing, the reviewer mentioned several points. But, several points were not corresponded.

Author’s response: Complied.

6. Although general procedure for catalytic C-N bond formation was shown, a catalyst quantity of this supported catalyst is not described. How is the incorporation ratio of Co in PSCo(BBZN)Cl₂?

Author’s response: We thank the reviewer for his valuable comment. We included the data related to metal incorporation in supplementary table 1. Based on % of incorporation of N & Co in the catalyst, which was obtained through elemental and metal ion analysis, the complex formed on the polymer support is about 0.0053 moles/g of the polymer support, which in turn corresponds to 7.16 % of Co that is available in the catalyst.

7. About 3c and 3e in the experimental section, coupling constants between C and F are not assigned.

Author’s response: Complied. The coupling constant between C and F has been calculated and included in experimental procedure.

8. Additional comments: The authors show "unbound Co(BBZN)Cl2". Did the author use this complex for the present conditions as a catalyst? If so, how is the reactivity difference between PS-Co(BBZN)Cl2 and unbound Co(BBZN)Cl2?

Authors response: The reactivity difference PS-Co(BBZN)Cl2 and unbound Co(BBZN)Cl2 has been not compared.

Reviewer 3 Report

for comments, see the docx file

Comments for author File: Comments.pdf

Author Response

Reviewer 3

1. General remark: spaces, subscript and superscript have to be check : not checked (ie line 105 CsCo3 instead of CsCO3 ; line 116 the presence , , line 110 1H and 13C NMR, also in table 4 reaction conditions….there are others to be checked…) mL not ml cf table 4

Author’s response: Complied. All the technical errors suggested by the reviewer have been incorporated in the manuscript.

2. Fig 47 in the mechanism [Co] must be written horizontal not vertical (not changed).

Authors response: Complied. The structure has been redrawn with appropriate bond angles.

3. Table 1 yeild must be changed into yield (%).

Author’s response: Complied.

4. line 105 table 2“ aConditions: admantane-bromo compounds 4-chloro aniline (PS-Co(BBZN)Cl2) (15 mol%)”conditions are not clear note a) Cobalt complex 15 mol% (?) but what are the amount of compound 1, compound 2 and ligands?

Author’s response: Complied. The quantity of compounds and ligands has been mentioned in conditions.

5. Moreover, in order to study the scope and the limitation of this reaction, various haloaromatic compounds with various substituted amines were tested. For all of these reactions an important parameter is missing: the exact reaction time. cf line 114. The following sentence has not been changed: “the majority of reactions were completed within 10h. “. How can results been compared if the reaction time is not the same. However, compared to the first version, I have noticed that some experimental results have been removed.

Authors response: The sentences with respect to time point has been rewritten and corrected.

Round 2

Reviewer 2 Report

The reviewer read the revised manuscript carefully again.
The reviewer points out several points which should be considered.
Why were the word "Co" in Figure 4 tilted to 90 degrees?
The authors answered the question about the incorporation ratio of Co in PSCo(BBZN)Cl2.
Exactly, the authors explain the detail in the author response to report.
However, no explanation of this detailed explanation is in the manuscript or the supplementary information.
About 3e in the experimental section, the coupling constant between C and F is not assigned yet.
The authors should show the all used amounts (e.g. g, mg) including reagents 2, base, and solvent in the representative procedure.
Also, in the optimized conditions, 12 mol% of supported Co complex was used. However, the authors
show the procedure using 15 mol% of the supported Co complex. This is not the representative procedure, the reviewer thinks.
This reviewer considers that this manuscript is exactly worthy of publication in Catalysts.
However, above issues are considered and revised before publication.

Additional comments.
Because the authors show "unbound Co(BBZN)Cl2", the reviewer wonders about the reactivity difference
between Co(BBZN)Cl2 and unbound Co(BBZN)Cl2. It is assumed that the authors have prepared the "unbound Co(BBZN)Cl2".

Author Response

Reviewer 2

1. Why were the word "Co" in Figure 4 tilted to 90 degrees?

Response: The mistake has been rectified in the revised manuscript.

2. 
   The authors answered the question about the incorporation ratio of Co inPSCo(BBZN)Cl₂.
   Exactly, the authors explain the detail in the author response to report.However, no explanation of this detailed explanation is in the manuscript or the supplementary information.

Response: The details have been included in the revised manuscript (Page 2-3, lines 75-78).

3. About 3e in the experimental section, the coupling constant between C and F is not assigned yet.The authors should show the all used amounts (e.g. g, mg) including reagents 2, base, and solvent in the representative procedure.

Response: We added the coupling constant between C and F as JCF = 53.4 Hz. Also, all the chemicals quantity used in the reaction was mentioned in the revised version.

4. Also, in the optimized conditions, 12 mol% of supported Co complex was used. However, the authorsshow the procedure using 15 mol% of the supported Co complex. This is not the representative procedure, the reviewer thinks.

Response: Thank you for your observation. The typo error was corrected.

5. 
   Additional comments.
   Because the authors show "unbound Co(BBZN)Cl₂", the reviewer wonders about the reactivity differencebetween Co(BBZN)Cl₂ and unbound Co(BBZN)Cl₂. It is assumed that the authors have prepared the "unbound Co(BBZN)Cl₂".

Response: Unbound Co(BBZN)Cl₂ was prepared for the comparison of the structure and reactivity of the polymer supported catalyst [PS-Co(BBZN)₂Cl₂. Since the unbound catalyst did not exhibit appreciable reactivity, focus has been given on the polymer supported complex. Moreover, the unbound catalyst could not be recycled. Considering these aspects, only polymer supported complex has been emphasized here.

Reviewer 3 Report

Some comments have still not been taken into account

• line 103 Yield (%) instead of Yeild (%)
• Fig 4 in the mechanism [Co] must be written horizontal not vertical (always not changed)
• lines 129-131 instead of 5a, 5b, 5c , 5e and also for 5d, 5f and 5g give the corresponding entries  ie : .....in good to excellent yields (entries 1, 2, 3 and 5), but .....a loss in yield (entries 4, 6 and 7) with no improvement ....

Table 2 entry 13 (last one): This experiment was added and the number 2q corresponds to o-toluidine. Authors have not changed the number 2q in table 3 entry 2, it is not toluidine!

By making this change, authors should think about changing the numbers of some amines in the table 3 namely those of the entries 2 and 3. Entry 5  table 3, authors could add the structure of the amine 2p as they did for amines of the entries 1, 2 and 3.

line 108 dimesityl instead of dimessityl

lines 120, 121 entries instead of entry

Author Response

Reviewer 3

Comments and Suggestions for Authors

Some comments have still not been taken into account

1. line 103 Yield (%) instead of Yeild (%)

Response:The mistake has been rectified in the revised manuscript.

2. Fig 4 in the mechanism [Co] must be written horizontal not vertical (always not changed)

Response: The mistake has been rectified in the revised manuscript.

3. lines 129-131 instead of 5a, 5b, 5c , 5e and also for 5d, 5f and 5g give the corresponding entries  ie : .....in good to excellent yields (entries 1, 2, 3 and 5), but .....a loss in yield (entries 4, 6 and 7) with no improvement ....

Response: Thank you for the suggestion , we changed  in revised manuscript.

4. Table 2 entry 13 (last one): This experiment was added and the number 2q corresponds to o-toluidine. Authors have not changed the number 2q in table 3 entry 2, it is not toluidine!

Response: Thank you for the valuable findings, we have in cooperated the suggested corrections.

5. By making this change, authors should think about changing the numbers of some amines in the table 3 namely those of the entries 2 and 3. Entry 5  table 3, authors could add the structure of the amine 2p as they did for amines of the entries 1, 2 and 3.

Response: Thank you for your observation, correction has done in revised manuscript.

6. line 108 dimesityl instead of dimessityl

Response: Thank you for your observation, correction has done in revised manuscript.

7. lines 120, 121 entries instead of entry

Response: Thank you for your observation, correction has done in revised manuscript.

This manuscript is a resubmission of an earlier submission. The following is a list of the peer review reports and author responses from that submission.

Round 1

Reviewer 1 Report

The manuscript entitled “Development of new arylamination reactioncatalyzed by polymer bound 1,3-(bisbenzimidazolyl)benzene Co(II) complex and generation of bioactive adamanate amines” submitted by Rangappa, Basappa and coworkers, reports the preparation and characterization of a polymer  supported Co(II) complex [PS-Co(BBZN)Cl2] and its application as a catalyst in arylamination reactions. Although immobilized catalysts are always an interesting  study subject, this manuscript presents an incomplete report that needs further work to be done in order to be acceptable. Some aspects trhat could be addressed are the following:

1)      Only one brominated reagent has been tested. The aplicabilty of this system should be tested with some other brominated substrates.

2)      Although the main advantage of immobilizing catalytic centers on polymeric materials is the recyclability of the catalysts, this aspect has not been studied at all. Furthermore, leaching of catalytically active molecular species into the reaction medium has to be ruled out.

3)      The observed effect of bidentate ligands is not elucidated. Some discussion should be provided.

4)      The mechanistic proposal is only based in previous reports in literature devoted to similar systems. Could theoretical or experimental evidences be explored?  Some aspects of such mechanism remain unclear: a)

a)       While the Synthesized cobalt complex contains a Co(II) center, the oxidative addition should occur from a Co(I) species. Any idea of the initial reductant?

b)      Taking into account the 1,3-(bisbenzimidazolyl)benzene fragment that coordinates de cobakt center and the bidentate additional ligand, only 2 available coordination sites remain available. Hoever, the porposed mechanism requires 3 available coordination sites.

Once some of these aspects are addressed the manuscript could be acceptable.

Reviewer 2 Report

This report shows a new polymer-supported cobalt complex. This is applicable to the C-N bond-forming
reaction of aryl bromides with aniline derivatives. Although this complex seems to be effective for this
reaction to give products, the details of this supported-complex are not unclear.
The preparation method of homogeneous complex, Co(BBZN)Cl2 was described, whereas PS-Co(BBZN)Cl2 is not written.
Although general procedure for catalytic C-N bond formation was shown, a catalyst quantity of this supported catalyst is not
described. How many ratio of cobalt does this supported complex include? How is the incorporation ratio of Co
in the preparation of PS-Co(BBZN)Cl2.
In addition, the authors should show the representative procedure employing the reaction of 1a with 2a with used amounts of
reagents, supported catalyst, an additional ligand, base, and solvent.
What did the authors use as references for BBZN-Co complex toward the C-N formation reaction. If so, the authors should
refer those references. In the present manuscript, these are not clear.
In this relation, I think the refered review report [12] is not suitable, which mainly covers phosphine ligands for the
coupling reactions. Also, the reviewer wonder about the role of additional ligands such as L3, which are critical for this reaction.
How do the authors think of this role, e.g. simple supplemental ligation or ligand exchange to form a L3-ligated Co complex?
In addition, the reviewer suggests that the the whole sentences are reassessed (e.g. Page 3, line 89,
"catalycatl", Table 1, footnote "Cs2Co3", Table 2, footnote "CS2CO3" and so on.)
Where are the compound "2c", "2d", "2e", "2f", and "3" in this manuscript?
The reviewer thinks that the reference [33] is not related to the proposed mechanism, which does not include the present transformation.
Therefore, this reviewer considers that this manuscript is worthy of publication in Catalysts
after above issues are considered and revised before publication.

Additional comments for NMR assignments.
About 4c and 4e, coupling constants between C and F are not assigned.

Reviewer 3 Report

This paper deals with the arylamination reaction using a cobalt polymer supported catalyst issued from [PS-Co(BBZN)Cl₂] . The first part concerns the formation of such cobalt complex and the last one its evaluation in the Buchwald hartwig reaction. For that, authors have selected six bidentate ligands. In order to determine the best conditions of the reaction, they have only study the amount of [PS-Co(BBZN)Cl₂] and the nature of the ligands before studying the arylamination reaction of an adamentyl derivative.

As a model for this reaction, the amination of  the bromoadamentyl derivative 1a with 4-chloroaniline was studied  but why 1,4 dioxane and cesium carbonate has been chosen, respectively as solvent and base and why so high temperature has been used (100 °C)? It is known that the nature of the solvent and the base can have an influence on the reaction and perhaps depending on these two parameters lower temperature and a lower amount of catalyst could be used.

Moreover, in order to study the scope and the limitation of this reaction, various halo aromatic compounds with various substituted amines were tested. For all of these reactions an important parameter is missing: the exact reaction time cf line 114 the majority of reactions were completed within 10h. How can results been compared if the reaction time is not the same (longer time = higher efficiency (yield ) cf table 1 entries 18 and 20 : 86% yield after 10h and 69% after 6h)?

Concerning the ortho substitution (only one substitution) a single example is given: fluoro aniline;  the 62% yield is it due to the reaction time, the electronic effect of the fluorine or the steric hindrance. As the steric hindrance could affect the reaction, it is difficult to compare 2i and 2o and also what about reaction time?

Aniline with other substituents must be tested ie o-toluidine, 2-aminoacetophenone, 2-chloroaniline. It is difficult to compare polysubstituted aniline 2p (Me, Cl and the substituted benzyl group; all of them having different electronic effect; Me is in ortho position but it is not an electron withdrawing group) to aniline 2i and 2o.

Ligne 84 and  table 1 entry  1  control experiments established the importance of the cobalt complex in the presence of the ligand, ie no ligand = no reaction but if we consider entries 2 to 9 in the presence of ligands  there is  no reaction. What could happen if the reaction was performed without ligands but in the presence of 10, 12 or 15 mol% of the cobalt complex?

Lines 25 and  92  robustness,  robust???  Not clear

• line 87 – 92 not clear at all : with ligands L5, L6 product is formed (ie entries 12, 13, 16,17 table 1)
  “Screening of various classes of ligands (Fig. 3) to improve the yield revealed that the use of phosphine based ligand BINAP (L3) or Xphose (L4) gave improved yields at different catalycatl concentrations (table 1, entry 10,11,14,15), whereas the other ligands such as bidentate ligands (L1, L2) and N-heterocyclic carbine ligands (L5, L6) yielded no products indicating the high role of selectivity of ligands in the forward reaction.”

Lines 95-96 : not clear : it is not the same ligand entries 18 and 19 but it is the same loading of the catalyst.  entry 20 is compared to entries 18 and 19 instead of entry 18 only.

“Further investigation revealed that there was no considerable improvement in yield when the catalyst load was increased to 15 mol% (Table 1, entry 18, 19) whereas the yield dropped to 69% when the reaction time was reduced to 6 h with 15 mol% catalyst (Table 1, entry 20).”

Line 100 adamantanewith

Line 102 yeild ? and % missing

line 103 conditions are not clear Cobalt complex 15 mol% but what are the amount of 1, 2 and ligand?

Line 122  % missing

Fig 47 mechanism [Co] horizontal not vertical

general remark: spaces, subscript and superscript have to be check

To conclude, some experiments are missing or have not been performed in the right way to be compared to others.