Structural studies by ¹H and ¹³C dynamic n.m.r.: Part III alternative protonation sites in carbonyl conjugated enamines of the type R₁C(O)CHCHNR₂R₃

Abstract

C magnetic resonance spectra of several enamino ketones with secondary and tertiary amino groups were obtained for trifluoroacetic acid solutions. In both series 0-protonation is predominant and the chemical shifts are related to the electron density changes with respect to the parent base. The spectra of the tertiary compounds are interpreted in terms of slow rotation aroand the C-1-C-2 and C-3-N bonds discernible at room temperature. 0-protonated forms of the secondary enamino ketones andergo further reaction on C-2 yielding pyridinium salts. "he mechanism of formation of the quaternary salts is interpreted and the additivity parameters of the 13C n.m.r. chemical shifts in the pyridinium ions is briefly discussed. 13The controversial problem of alternative reaction sites in organic molecules has attracted a great deal of attention. In the case of amides a lengthy controvers has arisen over the predominant site of 0 vs N protonation, the mechanism determining the exchange of the N-H proton and the isomerization around the C-N bond.', 4-7 An entire review has been published recently' concerning the protonation of various systems with a special focus on amides. Few data exist, however, regardin the protonation of carbonyl conjugated enamine~.8-"*'~ There are three nucleophilic centres, namely the 0-, N-and C-2-atoms, in the enamino ketone moiety which can be protonated viz Scheme 1. For this reason we recently investigated the dynamic behaviour" of secondary enamino ketones and studied their nucleophilic properties in acetylation reactions.'2 Following an earlier study,I3 we have currently carried out systematic protonation studies on tertiary and secondary enamino ketones using the 'H and 13C n.m.r. techniques. It was anticipated that the C chemical shifts of the olefinic carbons incorporated 1-7 13between the components of the amide function might act as a probe for testing the changes in the electronic redistribution brought about by 0-, N-or C-2-protonation. To the extent that the changes in 13C shieldings follow the changes in the electronic density in a parallel fashion, during this study we sought a rationale for our findings14 that the secondary enamino ketones I in strong acid media yield pyridinium salts of type V quantitatively;Accordingly, we examined and interpreted the spectra of several tertiary and secondary enamino ketones I and appropriate model compounds dissolved in trifluoracetic acid (TFA) (Tables 1, 2 and 3) in an attempt to establish the protonqtion sites and characterize their 13C chemical shifts.

Silica gel and microwave-promoted synthesis of dihydropyrrolizines and tetrahydroindolizines from enaminones

“…Dissolution in neat protic or Lewis acids (e.g., hydrochloric acid, trifluoroacetic acid, methanesulfonic acid, boron trifluoride etherate) resulted in decomposition if the reactions were left at room temperature overnight, or within ten minutes if the temperature was raised, even to 50 °C ( Table 1 , entries 6–13). The enaminone appeared to be protonated at room temperature, presumably on the oxygen site in accordance with well-established precedents [ 38 – 39 ]; and after ten minutes it could be recovered after neutralization with aqueous sodium hydrogen carbonate ( Table 1 , entries 6, 10). No apparent reaction occurred with dilute hydrochloric acid in ethanol ( Table 1 , entry 14) unless the solution was heated, in which case decomposition took place ( Table 1 , entry 15).…”

Solvent‐Induced Deuterium Isotope Effects in 13C‐ and 15N‐NMR. Spectra of Enaminones

“…In the case of the enaminones 4, 5 and 6 protonation4) occurs on the 0-atom as established earlier [32]. Simultaneously, slow exchange of the H-atom on C(2) is observed as shown for compound 4 in the Figure. The bottom trace represents the spectrum taken immediately after dissolving of the base.…”

“…In the case of compound 7 (type D and E) (Tables I and 2) two different cations are present in solution, corresponding to protonation either on the 0-or on the C(2)atom (the latter process was not discussed previously [32]). The assignment of the…”

Nuclear magnetic resonance investigations of iminium ion intermediates. Part 9. Multinuclear study of the reaction between Lewis acids and vinylogous amides

“…n Owing to coupling through the nitrogen atom thesignals of H(3) are usually broadened in the salts. However the couplings are resolved for compounds(15) and (16); c As these products are obtained as mixtures with compounds (14) or (15),(16) the 'T spectra are not easily assigned.e The 'H spectra show the presence of two compounds (25) and (26.) but ' J1.5…”