Crystal Structure and Computational Study on Methyl-3-Aminothiophene-2-Carboxylate

Yaping Tao,Ligang Han,Zhaojun Liu,Kexi Sun,Wanqiang Liu,Andong Sun,Jianbin Du,Qian Zhang

doi:10.3390/cryst10010019

Abstract

Methyl-3-aminothiophene-2-carboxylate (matc) is a key intermediate in organic synthesis, medicine, dyes, and pesticides. Single crystal X-ray diffraction analysis reveals that matc crystallizes in the monoclinic crystal system P21/c space group. Three matc molecules in the symmetric unit are crystallographically different and further linked through the N–H⋯O and N–H⋯N hydrogen bond interactions along with weak C–H⋯S and C–H⋯Cg interactions, which is verified by the three-dimensional Hirshfeld surface, two-dimensional fingerprint plot, and reduced density gradient (RDG) analysis. The interaction energies within crystal packing are visualized through dispersion, electrostatic, and total energies using three-dimensional energy-framework analyses. The dispersion energy dominates in crystal packing. To better understand the properties of matc, electrostatic potential (ESP) and frontier molecular orbitals (FMO) were also calculated and discussed. Experimental and calculation results suggested that amino and carboxyl groups can participate in various inter- and intra-interactions.

Highlights

Methyl-3-aminothiophene-2-carboxylate is a significantly important intermediate in pharmaceutical products such as anti-hypertensives [1,2], antitumors [3], anti-HIV-1 integrase [4], human cytomegalovirus inhibitors [5], hepatitis C virus inhibitors [6], Xa factor inhibitors [7], antineoplastic PAK4 activase inhibitors [8], phosphatidylinositol 3-kinase PI3K inhibitors [9], and antithrombotic activity drugs [10]
The melting point of matc is about 63–64 ◦ C [14]. It is in the solid state at room temperature, which favors the determination of the crystal structure
Crystal structures were solved by direct methods and refined by the full-matrix least-squares method on F2 using SHELXL-2016 (University of Göttingen, Version 2016, Germany) [16] algorithms in Olex2 (Durham University, 2009, UK) [17]

Summary

Introduction

Methyl-3-aminothiophene-2-carboxylate (matc) is a significantly important intermediate in pharmaceutical products such as anti-hypertensives [1,2], antitumors [3], anti-HIV-1 integrase [4], human cytomegalovirus inhibitors [5], hepatitis C virus inhibitors [6], Xa factor inhibitors [7], antineoplastic PAK4 activase inhibitors [8], phosphatidylinositol 3-kinase PI3K inhibitors [9], and antithrombotic activity drugs [10] It is a key starting material in agrochemical products, providing herbicidal protection through thiafulone or the sulfonylurea herbicide [11].

Methods

Results

Conclusion