Conformational Analysis of Methoxy- and Methylthio-Substituted Thiophenes by Broadband Rotational Spectroscopy and Computational Chemistry

Abstract Functionalized aromatic heterocycles exhibit strong conformational preferences dependent on the identity of the heteroatom, substituent functional group, and substitution position. In this study, we investigated the conformational landscapes of 2- and 3-substituted methoxy- and methylthio- thiophenes by chirped-pulse Fourier transform microwave spectroscopy. One lowest energy conformation for each molecule was identified due to efficient conformational cooling in the pulsed jet. For three of the four species, the conformational preference orients the substituent group syn to a double bond with all heavy atoms in the plane, while 2-(methylthio)thiophene uniquely adopts a skew conformation in which the barrier to methyl internal rotation is substantially reduced. Quantum chemical calculations, including natural bond orbital analysis, reveal that a balance of steric and stereoelectronic effects determines the lowest energy conformations of these species.