Design, synthesis, and spasmolytic activity of thiophene-based derivatives via Suzuki cross-coupling reaction of 5-bromothiophene-2-carboxylic acid: their structural and computational studies

Through detailed insight into frontier molecular orbitals of the compounds and their different reactivity descriptors, it was found that the compounds 10c and 5c are the most reactive, while 10a is the most stable in the series.

📌 3 Key Takeaways

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Objective & Hypothesis:In the current research work, a facile synthesis of a series of novel thiophene-based derivatives of 5-bromothiophene-2-carboxylic acid (1) have been synthesized.

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Key Findings & Data:All analogs (5a-5e, 10a-10t) were obtained from the coupling reaction of 5-bromothiophene2-carboxylic acid (1) and different arylboronic acids with moderate-to-good yields under controlled and optimal conditions.

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Conclusion & Impact:Through detailed insight into frontier molecular orbitals of the compounds and their different reactivity descriptors, it was found that the compounds 10c and 5c are the most reactive, while 10a is the most stable in the series.

🔬Design:Research Article

📍Scope:Comprehensive Sample

⚙️Variables:Suzuki cross-coupling reaction · 5-bromothiophene-2-carboxylic acid · density functional theory

Abstract

In the current research work, a facile synthesis of a series of novel thiophene-based derivatives of 5-bromothiophene-2-carboxylic acid (1) have been synthesized. All analogs (5a-5e, 10a-10t) were obtained from the coupling reaction of 5-bromothiophene2-carboxylic acid (1) and different arylboronic acids with moderate-to-good yields under controlled and optimal conditions. The structures of the newly synthesized compounds were characterized through spectral analysis and their spasmolytic activity, and most of the compounds exhibited potentially good spasmolytic effect. Among the synthesized analogs, compound phenethyl 5-(3,4-dichlorophenyl)thiophene-2-carboxylate (10d) particular showed an excellent spasmolytic effect with an EC50 value of 1.26. All of the compounds were also studied for their structural and electronic properties by density functional theory (DFT) calculations. Through detailed insight into frontier molecular orbitals of the compounds and their different reactivity descriptors, it was found that the compounds 10c and 5c are the most reactive, while 10a is the most stable in the series. Furthermore, compounds 10c and 5c showed a very good NW response with the highest beta values.

Keywords

Suzuki cross-coupling reaction 5-bromothiophene-2-carboxylic acid density functional theory spasmolytic activity

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Cite This Article

RASOOL, N., IKRAM, H. M., RASHİD, A., AFZAL, N., HASHMİ, M. A., KHAN, M. N., KHAN, A., IMRAN, I., RAHMAN, H. M. A., SHAH, S. A. A. (2020). Design, synthesis, and spasmolytic activity of thiophene-based derivatives via Suzuki cross-coupling reaction of 5-bromothiophene-2-carboxylic acid: their structural and computational studies. Turkish Journal of Chemistry, Cilt: 44 - Sayı: 5, 1410–1422. https://ajindex.com/articles/212684

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