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

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-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 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 NLO response with the highest β values.

Green synthesis of novel spiropyrazoline-indolinones in neutral deep eutectic solvents and DFT studies

“…The non-bonding effects in the molecules were added using Grimme’s empirical dispersion correction [ [42] , [43] , [44] ] as implemented in Gaussian 09. The said method has been benchmarked earlier by us on a variety of similar studies and others as well and it proved to produce good results [ [45] , [46] , [47] , [48] , [49] , [50] , [51] ]. Solvent effects were added through the Polarizable Continuum Model (PCM) [ [52] , [53] , [54] , [55] , [56] , [57] , [58] ] added through Truhlar’s SMD parameter [ 59 ].…”