engleski

(E)(Z) Configurational Assignment of 4, 7-Dihydro-4-hydroxyimino-6-Nitro-1, 3-Dioxpins. NMR Problem Solving

NMR spectroscopy provides a set of experiments that allows the complete structure of organic molecules to be inferred in strightforward manner. The procedure of NMR structure elucidation problem solving is shown on the example of 4, 7-Dihydro-4-hydroxyimino-6-nitro-1, 3-dioxepins (1a. R = H, 1b. = 4, 7-dihydro-1, 3-dioxepinyl). In the course of synthesis and/or application of substituted 4, 7-Dihydro-5-nitro-1, 3-dioxepins to the chemistry of pyridoxine (B6 vitamin) the oximes 1 were obtained as byproduct in the Diels-Alder reaction (the step of B6 intermediates synthesis). The 1 was also obtained by direct nitrosation of nitrodioxepins with ethylnitrite. Irrespective of the route of their formation oxymes 1a and 1b have shown similar spectroscopic features, indicating the existence of only one configurational isom in both cases. The investigation was aimed at the chemical and spectroscopic determination of their structures and configurations. Figure. The oxymes were undervent to Beckmann rearrangement, since it is well known standard procedure for elucidation of oxyme stereochemistry. When oxymes are treated with PCl5 or with other reagents, they rearrange to substituted amides. The group that migrates is generally anti(E) to the hydroxyl group. Although thi is not unequivocal, this chemical rearrangement is often used as a method of determining the configuration of the oxyme. Through elucidation of structure of obtained amide one can asume the stereochemistry of rearranged oxyme. Using various mild reagents (methane-, p-toluene- or p-acetyaminobenzensulfochlorides), in the case of Beckmann rearrangement, only O-sulfonate (2) were obtained, while under more drastic conditions using either PCl5 or P2O5 in chloroform, bith oxymes and their sulfonic estersw furnished none of two possible dioxaazocines. In all studied cases, the only isolated product was 4-nitro-5H-furan-2-on (3), resulting fromhydrolysis . Since the Beckman rearrangement did not give any answer on the configuration of oxyme group n 1, these compounds were investigated by various one- and two-dimensional homo- and heteronuclear 1H and 13C NMR correlation spectra (COSY, NOESY, HETCOR and HMBC). Asignment of 1H and 13C spectra were performed using chemical shifts and substituent shifts, H-H and C-H coupling constants and selected irradiation as well as connectivities in two-dimensional homo- and hetero-nuclear correlation spectra. The configuration of oximes 1 Could be assumed 13C gated decoupled spectra as well. It is generally known that the Z-orientation of the lone electron pair to C-H bond gives raise to an increase in magnitude of the corresponding one-bond C-H coupling (cca. 10-15 Hz), as compared to the E-orientation. Ij these reaction conditions, only one isomer was isolated. However, the question was in which for, E or Z, , the isolated oxymes 1a and 1b. The magnitude od 1JC-5H-5 in 1a (163.7 Hz) and 1b (164.0 Hz) might correspond to E –arrangement of the lone electron pair to C5-H bond in parallelism with similar systems (e.g. in acetaldoxyme, 1JC-H is 163.0 Hz for E isomer, while it is even 177.0 Hz for Z- isomer). This finding was supported with differential NOE measurement that showed spatial interaction between N-OH and H-5 and unambigously proved that both oxymes 1a and 1b have E-configuration. The NOE interaction between N-OH and H-5 was also in agreement with ab inition calculated distance between these protons, ammounting to 3.20 A. In conclusion, one can say that the analysis of 1H and 13C chemical shifts, magnitude and patterns of couplings, substituent effect, as well as differential NOE and connectivities in COSY, NOESY, HETCOR and HMBC spectra enabled determination of the structure and configuration of these compounds and are certainly useful in the configurational determination of symilar systems. M. Jadrijević-Mladar Takač, I. Butula, D. Vikić-Topić, M. Dumić ; Chemistry of 1, 3-Dioxepins. XIII. (E)/(Z) Configurational Assignment of 4, 7-Dihydro-4-hydroxyimino-6-nitro-1, 3-dioxepins, Croat. Chem. Acta 71 (1998) 557- 571.

1; 3-Dioxepins; 4; 7-Dihydro-4-hydroxyimino-6-nitro-1; 3-dioxepins; (E)/(Z) Configurational assignment; 1D and 2D NMR spectra; 1H and 13C NMR correlated spectra; Differential NOE

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