Open AccessDesign, synthesis, and spasmolytic activity of thiophene-based derivatives via Suzuki cross-coupling reaction of 5-bromothiophene-2-carboxylic acid: their structural and computational studies
Author(s) -
Nasır Rasool,
Hafiz Mansoor Ikram,
Ammara Rashid,
Nazia Afzal,
Muhammad Alı Hashmı,
Muhammad Naeem Khan,
Ayesha Khan,
Imran Imran,
Hafiz Muhammad Abdur Rahman,
Syed Adnan Ali Shah
Publication year - 2020
Publication title -
turkish journal of chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.239
H-Index - 46
eISSN - 1303-6130
pISSN - 1300-0527
DOI - 10.3906/kim-1911-51
Subject(s) - chemistry , thiophene , reactivity (psychology) , density functional theory , carboxylic acid , suzuki reaction , electronic effect , computational chemistry , molecular orbital , carboxylate , combinatorial chemistry , molecule , medicinal chemistry , stereochemistry , organic chemistry , catalysis , palladium , medicine , alternative medicine , pathology
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 - 10f ) were obtained from the coupling reaction of 5-bromothiophene-2-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 EC 50 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 NLO response with the highest β values.