Substituent-modulated Conformation and Supramolecular Assembly of Tetronamides

KARAK, M.; ACOSTA, J.A.M.; BARBOSA, L.C.A.*; SAROTTI, A.M.; DA SILVA, C. C.; BOUKOUVALAS, J.; MARTINS, F. T.

CRYSTAL GROWTH & DESIGN

AMER CHEMICAL SOC

Lugar: Washington; Año: 2016 vol. 16 p. 5798 - 5810

1528-7483

The structures of nine compounds (1−9) bearing the 4-aminofuran-2(5H)-one scaffold (commonly known as tetronamide, C4H5NO2) and two decorating Aromatic/hetero- aromatic moieties with two stereocenters have been determined. Tetronamides bearing at the 5-position a phenyl moiety (1 and 2, 3-chloro derivatives with either a 4-p-tolylamino or 4-p-bromophenylamino substituent), an o-bromopyridyl moiety (3, a 3-bromo-4-p-tolylamino derivative), or an o-tolyl moiety (4, a 3-bromo-4-p-tolylamino derivative) adopt a U-shaped conformation. This conformation is stabilized by an intra-molecular contact involving either the phenyl o-CH moiety (1 and 2) or the substituent at the ortho position (3 and 4) and the π system of the N-phenyl ring. The other five tetronamides (5−9) are not present with such an intramolecular contact. In fact, these last five compounds are not U-shaped and feature the presence at the 5-position of a p-biphenyl moiety (5 and 7, 3-bromo-4-p-tolylamino diastereomers differing as 5R and 5S), a p-methoxyphenyl moiety (6, a 3-chloro 4-p-bromophenylamino derivative), or a 5-chlorofuran-2-yl moiety (8 and 9, 3-chloro-4-p-tolylamino diastereomers differing as 5R and 5S). Crystal structures of a 5,5-disubstituted tetronamide bearing m-nitrophenyl moieties (10) and a parent tetronamide without a substituent at the 5-position (11d) reinforce the conformational trend found in 1−9. Furthermore, OH···O centrosymmetric dimers are formed only in the crystal structures of the U-shaped tetronamides. Chain motifs assembledthrough OH···O and NH···O hydrogen bonds are preferred in the line-shaped tetronamides. Furthermore, the conformer energies were calculated in both the gas and solution phases (B3LYP/6-31G*). The lowest-energy conformations feature an intramolecular N−H···O hydrogen bond as in the crystal structure of 7. In the U-shaped tetronamides, the crystal structure conformations are similar to the third or fourth energetically ranked stable calculated conformer. Therefore, it is concluded that the substitution pattern in the U-shaped tetronamides allows for accessible secondary minimum-energy conformations that are easily adopted in the crystal structure as a result of their compatibility with the robust centrosymmetric O−H···O dimer formation.