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Z and E rotamers of N ‐formyl‐1‐bromo‐4‐hydroxy‐3‐methoxymorphinan‐6‐one and their interconversion as studied by 1 H/ 13 C NMR spectroscopy and quantum chemical calculations
Author(s) -
Sulima Agnieszka,
Cheng Kejun,
Jacobson Arthur E.,
Rice Kenner C.,
Gawrisch Klaus,
Lee YongSok
Publication year - 2013
Publication title -
magnetic resonance in chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.483
H-Index - 72
eISSN - 1097-458X
pISSN - 0749-1581
DOI - 10.1002/mrc.3909
Subject(s) - conformational isomerism , chemistry , moiety , amide , chemical shift , crystallography , stereochemistry , ab initio , computational chemistry , molecule , organic chemistry
N ‐Formyl‐1‐bromo‐4‐hydroxy‐3‐methoxymorphinan‐6‐one (compound 2 ), an important intermediate in the NIH Opiate Total Synthesis, presumably exists as a mixture of two rotamers ( Z and E ) in both CHCl 3 and DMSO at room temperature due to the hindered rotation of its N‐C18 bond in the amide moiety. By comparing the experimental 1 H and 13 C chemical shifts of a single rotamer and the mixture of compound 2 in CDCl 3 with the calculated chemical shifts of the geometry optimized Z and E rotamers utilizing density functional theory, the crystalline rotamer of compound 2 was characterized as having the E configuration. The energy barrier between the two rotamers was also determined with the temperature dependence of 1 H and 13 C NMR coalescence experiments, and then compared with that from the reaction path for the interconversion of the two rotamers calculated at the level of B3LYP/6‐31G*. Detailed geometry of the ground state and the transition states of both rotamers are given and discussed. Copyright © 2012 This article is a US Government work and is in the public domain in the USA.