A ¹H and ¹³C NMR study of N‐formylmorphinans and their 6,14‐bridged derivatives; Comparison with N‐Me and NH analogues

Abstract

~~ ~The 'H NMR and I3C NMR spectra of N-formylated morphinans were compared with those of the N-methyl and N-demethyl analogues. The magnitude of the changes in chemical shift of C-9, C-16 and C-10 depended crucially on the nature of the substituent at nitrogen. For the 6a,l4aethenoisomorphinans and 6~,14/?-ethenomorphinans, the proton chemical shifts of the 6,14-etheno bridge across ring C are differently affected by the nitrogen atom. In the 6a,14a-ethenoisomorphinans, the vinylic proton shifts are found between 65.3 and 5.9, whereas in the 68,148-ethenomorphinans these proton signals are found downfield from 66.0. A similar, but opposite, anisotropy effect of the nitrogen is observed for the 88-proton. These results are important for the elucidation of the structures of these types of compounds.

Z and E rotamers of N‐formyl‐1‐bromo‐4‐hydroxy‐3‐methoxymorphinan‐6‐one and their interconversion as studied by 1H/13C NMR spectroscopy and quantum chemical calculations

“…The calculations also indicate that the C‐16 syn to oxygen in E (δ 37.59) is better shielded than the C‐16 anti to oxygen in Z (δ 44.31); the respective experimental peaks for the C‐16 of the E and Z are observed at δ 34.34 and 40.53. These syn / anti effects arise from the magnetic anisotropy of the amide group, and are also in agreement with the previous finding that both C‐9 and C‐16 of N ‐formylmorphinans syn to oxygen are better shielded . Whereas the difference between the calculated and the experimental 13 C chemical shifts of compound 2 ranges from 2 to 13 ppm, the calculated value for the C‐1 bonded to bromine is approximately 23 ppm larger than the experimental.…”

10-Substituted 11-Oxygenated (R)-Aporphines: Synthesis, Pharmacology, and Modeling of 5-HT1AReceptor Interactions

“…In contrast, N-demethylation of 16 using 1-chloroethyl chloroformate, as reported by Olofson et al, 12a gives an excellent yield of the corresponding norcodeine derivative under comparably mild conditions and with a simplified workup procedure in comparison to other methods. 16 N-Demethylation 12a of 16 followed by hydrolysis of the resulting acetate gave 17 17 (Scheme 2). Reductive amination of propanal 18 with 17 afforded 18, 19 which was demethylated using a modified version of the protocol reported by Rice 20 to produce 19.…”

Recent Developments in the Chemistry of Thebaine and its Transformation Products as Pharmacological Targets

“…By the application of this procedure Maat and his colleagues obtained the N-formyl nor-derivative of 27 [82] and thoroughly examined the stereochemistry of the cycloaddition on this system [83,84].…”

“…They established two different procedures for the preparation of 5 -hydroxymethylthebaine (83): one of them was performed via the attack of thebaine anion (72) by chloromethanol, the other synthetic route was based on the reduction of 5 -carbethoxythebaine (76) produced previously with Gates' method [113]. The 5 -hydroxymethylthebaine (83) was used for the direct formation of 6,14-ethenomorphinans and reacted with acryloyl chloride to yield thebaine-5 -methyl acrylate (84). This latter product was then subjected to an unusual intramolecular cycloaddition to transform the morphinandiene backbone into a double bridged, highly rigid system (Scheme 31) [113].…”