Condensed phase conformational isomerization of 5-[3-(1,3-dioxo-1,3-dihydro-isoindol-2-yl)-propoxy]-3-methyl-1H-pyrazole-4-carboxylic acid methyl ester

Abstract

Presence of ester group adjacent to methyl group in a pyrazole ring system results in a flexible hydrogen bond. This bond can be freely rotate to generate the conformational isomers. Conformational isomers can be separated if the barrier to rotation or the energy difference between the two configurations is large. In the present study, in solution state, this spinning is so fast that it was difficult to predict the conformational change whereas the condensation of molecules in solid state, existence of two conformations have been predicted.

Aryl Naphthoates: A Conformational Analysis Supported by Single-Crystal X-Ray Diffraction

“…The conformation of the ester group, linking the two aromatic systems, is anti-periplanar with torsion angles c(C2 0 -O2-C3-C1 0 ) between 1718 and 1768. These results are in agreement with the preferred Z conformation found in the ester group O3C3O2C2 0 [2][3][4][5][6] and also predicted by theoretical calculations (see above). However, there is a strong twist in the ester part with respect to the C-O single bond (Fig.…”

“…Torsion C angle refers to the preferred conformation around the C(O)-O-R ester function. As described above, the Z conformation of esters is expected to be more stable than the E conformation [2][3][4] (Chart 1). In a previous work, phenyl esters of cinnamic acid showed that the Z conformation was 4.91 kcal mol À1 more stable than its E counterpart.…”

“…Looking at the whole molecule, the mobility on four chemical bonds is important to consider: (1) the aforementioned bond connecting the methyl carbonyl group with the phenyl ring; (2) the bond between the phenyl and the oxygen bridge C(sp 2 )-O(sp 3 ); (3) the ester linkage C(O)-O, and (4) the bond between the carbonyl group and the naphthyl moiety (1-C10H7 or 2-C10H7). The conformation of esters of the type ÀC(O)-O-R (case 3) has been the subject of essential investigation since a very long time, revealing that the Z conformation is favoured over the E counterpart [2][3][4][5][6] (Chart 1). One of the reasons is the steric repulsion between the R groups in the E conformation.…”