A New Series of Tungstophosphoric Acid-Polymeric Matrix Catalysts: Application in the Green Synthesis of 2-Benzazepines and Analogous Rings

Round 1

Reviewer 1 Report

As it is outside my area of expertise, I am unable to review the first part (preparation and characterization of solid catalyst). In the second part, the authors applied their newly synthesized catalyst to the Pictet-Spengler-type cyclization of N-aralkyl sulfonamides in the presence of trioxane to give the corresponding benzo[c]azepines. Control experiments revealed that the acidity of these catalysts is crucial to induce high reactivity. In addition, the inclusion of acidic components (TPA) in the polymeric matrix seemed to be important since low reactivity was observed with the use of bulk TPA. These results highlight the potential of these PMTPA as recyclable acid catalysts. This reviewer recommends the publication of this manuscript after some revisions noted below.

1) If possible, please compare the reactivity as well as chemoselectivity of PMTPA with also conventional acid catalysts (BF3·OEt2, MeAlCl2, etc.).

2) In Table 7, substrates with no substituent on the benzene ring were only examined. I wondered about the regioselectivity during the cyclization process with a meta-substituted substrate.

Author Response

We are grateful to the reviewers for the comments and suggestions they made to improve our manuscript.

• If possible, please compare the reactivity as well as chemoselectivity of PMTPA with also conventional acid catalysts (BF₃OEt₂, MeAlCl₂, etc.).

According with Reviewer #1 a Table with comparative results using different acid catalysts were including:

Table 8 shows comparative results for the N-(3,4-dichlorobenzylsulfonyl)-2,3,4,5-tetrahydro-1H-benzo[c]azepine synthesis using different acid catalysts. Better results are obtained using heterogeneous catalysts based on HPAs (Table 8, entries 3-5), probably due to the milder conditions than the methanesulphonic acid/ trifluoracetic acid and methanesulphonic / acetic anhydride media (Table 8, entries 1 and 2).

Table 8. Use of different catalysts on N-(3,4-dichlorobenzylsulfonyl)-2,3,4,5-tetrahydro-1H-benzo[c]azepine synthesis.

Entry	Catalyst	Yields (%)	Reference
1	Methanesulphonic acid/ trifluoroacetic acid	68	[30]
2	Methanesulphonic acid/ acetic anhydride	70	[30]
3	H6P2W18O62/SiO2	84	[31]
4	H14[NaP5W30O110]/SiO2	81	[32]
5	PLMTPA60/40100	83	This work

 

2) In Table 7, substrates with no substituent on the benzene ring were only examined. I wondered about the regioselectivity during the cyclization process with a meta-substituted substrate.

 For this work, we choose to test the catalytic activity of the new catalysts only with the benzene ring without substituent. According with the proposed mechanism, electro-donating groups as methoxy or methyl, especially in ortho position respect of the cyclisation atom, would favor the benzazepine synthesis.

Author Response File: Author Response.pdf

Reviewer 2 Report

Title: “A new series of tungstophosphoric acid-polymeric matrix catalysts: Application in green synthesis of 2-benzazepines and analogous rings”

In this research article, the authors have synthesized a new series of composite materials based on tungstophosphoric acid (TPA) included in a polymeric matrix of polyacrylamide (PLM), with a TPA:PLM ratio of 20:80, 40:60, and 60:40 and characterized by FT-IR, XRD, ³¹P MAS-NMR, TGA-DSC, and SEM-EDAX. The authors have used these PLMTPA materials as efficient and recyclable noncorrosive catalysts for the synthesis of 2-benzazepines and related compounds. Good yields and high purity were achieved by a Pictet-Spengler variant reaction between N-aralkylsulfonamides and s-trioxane in soft reaction conditions at 70 °C in 3 h. The best catalyst in the optimized reaction conditions, PLMTPA60/40₁₀₀ was reused six times without loss of activity. All the references are in proper format. This research article could be accepted as is in “Catalysts” after addressing the below comments.

1)    Authors should improve the quality of Scheme II (mechanism).

2)    Authors should try this reaction with other substrates to synthesize substituted benzazepines.

3)    Also, the authors should try to improve the English language throughout the manuscript.  

Author Response

We are grateful to the reviewers for the comments and suggestions they made to improve our manuscript .

• Authors should improve the quality of Scheme II (mechanism).

As the Reviewer suggest, the quality of Scheme II was improved (See file)

• Authors should try this reaction with other substrates to synthesize substituted benzazepines.

For this work, we choose to test the catalytic activity of the new catalysts only with the benzene ring without substituent. According with the proposed mechanism, electro-donating groups as methoxy or methyl, especially in ortho position respect of the cyclisation atom, would favor the benzazepine synthesis. Moreover, electro-donating groups in the second ring (Ar₁) activate this ring toward the electrophilic attack, producing huge amount of the subproduct resulting for the cyclisation on this ring, and the consequent decrease in the benzazepine yield. 

• Also, the authors should try to improve the English language throughout the manuscript.  

According to Reviewer #2 suggestion, the English was revised, and some typos were corrected (in green in the manuscript).

Author Response File: Author Response.pdf