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Copper(II) complexes formed with sulfonated salan ligands (HSS) have been synthesized, and their coordination chemistry has been characterized using pH-potentiometry and spectroscopic methods [UV-vis, electron paramagnetic resonance (EPR), and electron-electron double resonance (ELDOR)-detected NMR (EDNMR)] in aqueous solution. Several bridging moieties between the two salicylamine functions were introduced, e.g., ethyl (HSS), propyl (PrHSS), butyl (BuHSS), cyclohexyl (cis-CyHSS, trans-CyHSS), and diphenyl (dPhHSS). All of the investigated ligands feature excellent copper(II) binding ability via the formation of a (O-,N,N,O-) chelate system. The results indicated that the cyclohexyl moiety significantly enhances the stability of the copper(II) complexes. EPR studies revealed that the arrangement of the coordinated donor atoms is more symmetrical around the copper(II) center and similar for HSS, BuHSS, CyHSS, and dPhHSS, respectively, and a higher rhombicity of the g tensor was detected for PrHSS. The copper(II) complexes of the sulfosalan ligands were isolated in solid form also and showed moderate catalytic activity in the Henry (nitroaldol) reaction of aldehydes and nitromethane. The best yield for nitroaldol production was obtained for copper(II) complexes of PrHSS and BuHSS, although their metal binding ability is moderate compared to that of the cyclohexyl counterparts. However, these complexes possess larger spin density on the nitrogen nuclei than that for the other cases, which alters their catalytic activity.

The adduct of acetylenedicarboxylic acid and the water-soluble 1,3,5-triaza-7-phosphaadamantane (PTA, 1) in 1:2 molar ratio, was synthesized both in aqueous solution and under anhydrous conditions in a planetary ball mill (pbm). The resulting double phosphabetaine (2) was characterized by 1H-, 13C-, and 31P-NMR spectroscopy, ESI-mass spectroscopy, and elemental analysis, furthermore, its solid-state structure was determined by single crystal X-ray diffraction. SXRD also revealed that in aqueous solution 2 reacted with AgSO3CF3 to yield a 2 D polymer.

We have described earlier that in aqueous solutions, the reaction of 1,3,5-triaza-7-phosphaadamantane (PTA) with maleic acid yielded a phosphonium-alkanoate zwitterion. The same reaction with 2-methylmaleic acid (citraconic acid) proceeded much slower. It is reported here, that in the case of glutaconic and itaconic acids (constitutional isomers of citraconic acid), formation of the corresponding phosphabetaines requires significantly shorter reaction times. The new phosphabetaines were isolated and characterized by elemental analysis, multinuclear NMR spectroscopy and ESI-MS spectrometry. Furthermore, their molecular structures in the solid state were determined by single crystal X-ray diffraction (SC-XRD). Synthesis of the phosphabetaines from PTA and unsaturated dicarboxylic acids was also carried out mechanochemically with the use of a planetary ball mill, and the characteristics of the syntheses in solvent and under solvent-free conditions were compared. In aqueous solutions, the reaction of the new phosphabetaines with Ag(CF3SO3) yielded Ag(I)-based coordination polymers. According to the SC-XRD results, in these polymers the Ag(I)-ion coordinates to the N and O donor atoms of the ligands, however, Ag(I)-Ag(I) interactions were also identified. The Ag(I)-based coordination polymer (CP1.2) formed with the glutaconyl derivative of PTA (1) showed considerable antimicrobial activity against both Gram-negative and Gram-positive bacteria and yeast strains

Water-soluble salan ligands were synthesized by hydrogenation and subsequent sulfonation of salens (N,N&rsquo, bis(slicylidene)ethylenediamine and analogues) with various bridging units (linkers) connecting the nitrogen atoms. Pd (II) complexes were obtained in reactions of sulfosalans and [PdCl4]2&minus, Characterization of the ligands and complexes included extensive X-ray diffraction studies, too. The Pd (II) complexes proved highly active catalysts of the Suzuki&ndash, Miyaura reaction of aryl halides and arylboronic acid derivatives at 80 &deg, C in water and air. A comparative study of the Pd (II)&ndash, sulfosalan catalysts showed that the catalytic activity largely increased with increasing linker length and with increasing steric congestion around the N donor atoms of the ligands, the highest specific activity was 40,000 (mol substrate) (mol catalyst &times, h)&minus, 1. The substrate scope was explored with the use of the two most active catalysts, containing 1,4-butylene and 1,2-diphenylethylene linkers, respectively.

Five new complexes of the type [RuCl2(NHC)(η6-arene)] (4, 5, and 6) and [RuCl(NHC)(η6-arene)(PR3)]Cl (7 and 8) (NHC N-heterocyclic carbene = bmim, emim; arene = benzene, p-cymene; PR3 = PPh3 or pta = 1,3,5-triaza-7-phosphaadamantane) were synthetized and applied as catalysts (together with the known [RuCl2(bmim)(η6-p-cymene)] (3) with and without added PPh3) in racemization of optically active secondary alcohols in toluene. The highest catalytic activity, TOF = 9.3 h−1 (ee as low as 1.3% in 4 h at 95 °C) was observed in racemization of (S)-1-phenylethanol with a catalyst (4 mol%) prepared in situ from 3 and 1 equivalent of PPh3. It is of practical significance that formation of acetophenone byproduct was suppressed to 3.5% by 17% v/v isopropanol in toluene. DFT calculations revealed that the rate determining step in the suggested reaction mechanism was the agostic coordination of hydrogen on the chiral carbon atom of the alcohol substrate.

The newly synthesized mer-trans-[RuCl2(OH2)(PTA)3] (1) is the first compound isolated in solid state containing the Ru(PTA)3-fragment (PTA = 1,3,5-triaza-7-phosphatricyclo[3.3.1.13,7]decane). Dissolution of 1 in aqueous HCl leads to mer-[RuCl3(HPTA)3]Cl2 (2) which is stable in the dark but is transformed into fac-[RuCl3(HPTA)3]Cl2 (3) under visible light. Irradiation with visible light of an aqueous solution of 1 at room temperature or refluxing of the same solution in the dark leads to the formation of [{Ru(PTA)3}2(μ-Cl)3]Cl (4). The dinuclear complex 4 was also formed upon irradiation of solutions of PTA and various Ru(II)-complexes ([RuCl2(DMSO)4], [{RuCl2(η6-p-cymene)}2]) or cis-cis-trans-[RuCl2(DMSO)2(PTA)2]). All complexes were characterized by elemental analysis and NMR spectroscopy, furthermore solid state structures of 2·1.25H2O, 3·HCl·2H2O and 4·9H2O were also determined by single crystal X-ray diffraction. We have investigated the influence of the above photochemical processes on reduction of benzaldehyde and cinnamaldehyde with trans-[RuCl2(PTA)4] and cis-cis-trans-[RuCl2(DMSO)2L2] (L = PTA, (PTA-Me)CF3SO3, (PTA-Bn)Cl; Me = methyl, Bn = benzyl) complexes as catalysts. The effect of visible light on benzonitrile hydration with various Ru(II)-PTA catalysts is also reported.

In this work we have found, that the water-soluble cis,mer-[IrH2Cl(mtppms)3] (mtppms = monosulfonated triphenylphosphine Na-salt) was an excellent catalyst for reduction of terminal alkynes by hydrogen transfer from aqueous HCOOH/HCOONa mixtures. The conversions strongly depended on the pH of the reaction mixtures, and the highest rate of phenylacetylene transfer hydrogenation was observed at pH 3. The same dihydrido-Ir(III) complex actively catalyzed also the hydrogenation of terminal alkynes under mild conditions (T = 50 °C; P(H2) = 2–10 bar). Importantly, both the hydrogenation and hydrogen transfer reductions afforded exclusively the corresponding alkenes as products. Phenylacetylene and its substituted derivatives reacted smoothly, while benzylic and aliphatic alkynes were less reactive or did not react at all. It was also found, that an excess of the mtppms ligand inhibited the reaction. This was rationalized by formation of cisz-[IrH2(mtppms)4]+ which was also confirmed with multinuclear NMR spectroscopy. On the basis of the experimental results, a joint mechanism was suggested for both the hydrogenation and transfer hydrogenation pathways. The mechanism of hydrogenation and transfer hydrogenation of phenylacetylene was also studied by DFT calculations, which revealed several possibilities for protonation of a vinyl intermediate as the crucial step in formation of the styrene product.

1,3,5-Triaza-7-phosphaadamantane (pta, phosphaurotropine) played a special role in the development of aqueous organometallic chemistry and catalysis. The main reason is in its easy synthesis, oxidation stability, versatile possibilities of functionalization, and high solubility not only in water but also in several common organic solvents. Such favourable solubility behaviour allowed straightforward synthesis of pta-containing transition metal complexes from simple, inexpensive, often commercial starting materials. A further advantage of pta and its complexes is in their pronounced tendency to crystallize which allowed determination of solid-state structures of a great number of such compounds. This review covers synthetic procedures of ruthenium(II)-complexes with pta, and N-alkyl-pta derivatives as ligands, as well as their most important reactions in aqueous systems. Ru(II)-pta complexes were employed as catalysts in several important aqueous-phase processes such as selective hydrogenation and transfer hydrogenation of aldehydes, hydration of nitriles, and redox isomerization of allylic alcohols. Hydrogenation of carbon dioxide/bicarbonate and dehydrogenation of formic acid/aqueous formate were also studied with various Ru(II)-complexes of phosphaurotropines. Altogether the results described in this review made a significant positive impact on the development of green chemical processes.

A new, solvent-free method has been developed for the synthesis of 7-(2-carboxy-ethyl)-1,3,5-triaza-7-(phosphoniatricyclo)[3.3.1.13,7]decane (L). It is disclosed here that 1,3,5-triaza-7-phosphaadamantane (PTA) reacted cleanly with acrylic acid in a planetary ball mill resulting in 88% yield of the corresponding P-carboxy-ethyl derivative, in striking contrast to the complete failure of the synthesis of the same product from the same reactants in solution. The resulting phosphabetaine, L gave crystalline 1D coordination polymers with Ag+-salts bearing PF 6 - , p-toluenesulfonate (tos) and trifluoromethanesulfonate (OTf) anions. According to single-crystal X-ray diffraction studies, the solid state structures of these coordination polymers were decisively influenced by the anion of the Ag+-salt used for synthesis. In addition to single-crystal X-ray diffraction, the new Ag-based coordination polymers, namely [Ag(μ3-L-κ3N:O:O’)]n(PF6)n, (1), [Ag(tos)(μ3-L-κ3N:N:O)]n·nH2O, (2), and [Ag(OTf)(μ3-L-κ3N:O:O’)]n, (3) were characterized also by elemental analysis, 1H-, 13C-, and 31P NMR, as well as IR spectroscopies and with ESI mass spectrometry. Determination of the hydrodynamic diameter of the phosphabetaine ligand and its Ag+-complexes by diffusion NMR measurements revealed, that upon dissolution in water these compounds did not retain their polymeric nature.

The water-soluble [RuCl2(pta)(η6-p-cymene)] (pta = 1,3,5-triaza-7-phosphaadamantane) was applied as catalyst in the transposition of allylic alcohols, such as oct-1-en-3-ol in aqueous media. The isomerisation of oct-1-en-3-ol to octan-3-one took place only at pH > 10 buffer solutions or in the presence of alkali metal carbonates. The aqueous solution of “in situ” catalyst ([RuCl2(pta)(η6-p-cymene)] + 2 eq Na2CO3) could be reused in the biphasic isomerization of oct-1-en-3-ol for at least five times without a significant loss of the catalytic activity. It was demonstrated that carbonate is not only a base in this reaction but leads to formation of a highly active catalyst, [Ru(η2-O2CO)(pta)(η6-p-cymene)]. This compound was isolated as crystalline solid and characterized in detail (including X-ray diffraction).

An environment-friendly, convenient, fast and solvent-free mechanochemical approach have been accomplished for the synthesis of several diimidazolium salts and the bridging dinuclear rhodium(I)–N-heterocyclic carbene complexes of the type [{RhCl(cod)}2(μ-di-NHC)] derived from them. The compounds were synthesized also by the classical solvent method and the results of the two approaches were compared. A systematic study of both the mechanochemical and the solvent syntheses has also been carried out to determine the effects of various factors influencing the reactions. This is the first report on the mechanochemical synthesis of poly-NHC metal complexes as well as NHC–Rh complexes in ball mill.

With use of a Pd(II)-sulfosalan complex as a water-soluble catalyst, we have developed an efficient synthesis of biaryls via Suzuki–Miyaura cross-coupling in water under aerobic conditions. The water-insoluble target molecules were isolated by simple filtration in analytical purity after washing with 0.01 M aqueous HCl (20 examples). In most cases, palladium contamination was below 5 ppm considered acceptable for active pharmaceutical ingredients. The established method is scalable, reproducible, and provides biaryl products in isolated yields up to 91%.

1,3,5-triaza-7-phosphaadamantane was alkylated under solvent-free conditions with CH3I, CH3-(CH2)3-Br, Br-(CH2)4-Br, OH-CH2-CH2Br, and CH3CH2OOCCH2Br in a planetary ball mill with yields over 90%. Due to spontaneous resolution, both 1-(2-ethoxy-2-oxoethyl)-3,5-diaza-1-azonia-3,5-diaza-7-phosphaadamantane bromide (4) and (4-bromobutyl)-1-azonia-3,5-diaza-7-phosphaadamantane bromide (5) were obtained in the solid state as conglomerates of enantiomorphic crystals.

With the aim of identifying new types of water-soluble catalyst precursors for modification of biological membranes by homogeneous hydrogenation in aqueous solution and under mild conditions, we have performed detailed equilibrium and spectroscopic characterization of complex formation between nickel(II) or palladium(II) and salan-type ligands sulfonated in their aromatic rings (N,N′-bis(2-hydroxy-5-sulfonatobenzyl)-1,4-diaminoethane (HSS), N,N′-bis(2-hydroxy-5-sulfonatobenzyl)-1,4-diaminopropane (PrHSS) and N,N′-bis(2-hydroxy-5-sulfonatobenzyl)-1,4-diaminobutane (BuHSS)) in the slightly acidic–alkaline pH range. The stability constants of the metal complexes were determined using pH-potentiometry. The catalytic activities of the [Ni(HSS)] and [Pd(HSS)] complexes in hydrogenation and redox isomerization of oct-1-en-3-ol were also studied. The results indicate, that all of the investigated ligands exhibit excellent nickel(II) and palladium(II) binding ability via the formation of (O−,N,N,O−) linked chelate system. Both [Ni(HSS)] and [Pd(HSS)] catalyze the hydrogenation and redox isomerization of oct-1-en-3-ol. [Pd(HSS)] shows excellent activity and the reaction was highly selective to the formation of octan-3-ol. [Ni(HSS)] is also an active and selective catalyst for this hydrogenation reaction and to the best of our knowledge, [Ni(HSS)] is the first nickel(II)-based, hydrolytically stable, water-soluble catalyst bearing sulfonated salan moiety.

Seven new [Ir(NHC)(η4-cod)(L)] complexes (4–9, 11) with NHC = bmim, emim, L = Cl–, H2O, or the water-soluble phosphines mtppms-Na, mtppts-Na3, and pta were synthesized and characterized. Na2[Ir(bmi...

Tubulin is a major molecular target for anticancer drugs. The dynamic process of microtubule assembly and disassembly can be blocked by various agents that bind to distinct sites on tubulin, usually its β-subunit. Among the antimitotic agents that perturb microtubule dynamics, noscapinoids represent an emerging class of agents. In particular, 9'-bromonoscapine (EM011) has been identified as a potent noscapine analog. Here we present high yielding, efficient synthetic methods based on Suzuki coupling of 9'-alkyl and 9'-arylnoscapines and an evaluation of their antiproliferative properties. Our results showed that 9'-alkyl and 9'-aryl derivatives inhibit proliferation of human cancer cells. The most active compounds were the 9'-methyl and the 9'-phenyl derivatives, which showed similar cytotoxic potency in comparison to the 9'-brominated derivative. Interestingly these newly synthesized derivatives did not induce cell death in normal human lymphocytes, suggesting that the compounds may be selective against cancer cells. All of these derivatives, except 9'-(2-methoxyphenyl)-noscapine, efficiently induced a cell cycle arrest in the G2/M phase of the cell cycle in HeLa and Jurkat cells. Furthermore, we showed that the most active compounds in HeLa cells induced apoptosis following the mitochondrial pathway with the activation of both caspase-9 and caspase-3. In addition, these compounds significantly reduced the expression of the anti-apoptotic proteins Mcl-1 and Bcl-2.

New sulfonated tetrahydrosalen-type ligands and their water-soluble palladium(II) complexes have been synthesized. The palladium(II) complexes catalyze the Sonogashira coupling (23 examples) of various aryl halides (including chloroarenes) with terminal alkynes, with good to excellent conversions under mild conditions (80°C, air, no Cu(I) cocatalyst) in aqueous-organic mixtures and turnover frequencies of up to 2790 h(-1) . Under optimized reaction conditions to minimize environmental contamination, diphenylacetylenes can be isolated in 76-98% yield. The aqueous catalyst solution can be recycled four times with decreasing activity; however, yields between 93 and 98% can still be achieved with extended reaction times. Several water-insoluble products can be isolated in excellent yield by simple filtration and purification by washing with water; this method is used, for the first time, for this type of C-C coupling procedure.

The discovery and development of N-heterocyclic carbenes is no doubt one of the biggest success stories in the era of modern chemistry. In the last three decades, poly-N-heterocyclic carbenes have received increasing attention and a large number of reports have been published on the use of poly-NHC complexes in water. This paper is aimed to provide an overall review on poly-N-heterocyclic carbene complexes that are either water-soluble or have applications in aqueous media or both. The first two sections of the review are related to the types and general structural properties of poly-NHCs. The next part deals with the general advantages of using water and the last two sections are about poly-NHC complexes in aqueous media and their applications in various fields including catalysis, photophysics and medicine.

Here we report the transformation of tetracyclic morphinan salutaridine (1) into 2,3,10,11-tetrasubstituted (R)-aporphines. This method serves as another chemical proof of the previously verified biosynthetic connection with pentacyclic morphinan-6,8-diene-type thebaine. In the presence of nucleophiles, this procedure could lead to pharmacologically interesting new tetrasubstituted aporphinoids. The enantioselective synthesis of 7S-salutaridinol (2) has been also achieved in order to investigate the acid-catalyzed reactions of this natural morphinan.

The synthesis of 3-deoxyoripavine (7) was realized as a novel and promising intermediate towards the synthesis of the important class of dopaminergic and/or serotonergic 10-deoxyaporphines and the special pharmacological tool µ opioid antagonist cyprodime. Generally, the preparation of these valuable biologically active compounds was achieved in remarkable yields.

For applications in aqueous media, sulfonated tetrahydrosalen (sulfosalan, HSS) was synthesized by sulfonation of tetrahydrosalen in fuming sulfuric acid. The Pd(II) complex of this ligand, [Pd(HSS)], showed outstanding activity in hydrogenation and redox isomerization of allylic alcohols in homogeneous aqueous solutions or in aqueous–organic biphasic systems (for oct-1-en-3-ol TOF(hydrogenation) = 1580 h–1, TOF(redox isomerization) = 400 h–1). DFT calculations revealed that H2 is activated heterolytically, resulting in a Pd(II)–hydride complex, [Pd(H)(HSS-Hphen)], in which one of the phenolate oxygens is protonated. Both hydrogenation and redox isomerization take place via concerted transfer of a proton and a hydride from the hydrogenated catalyst to the allylic alcohol.

New air-stable, water-soluble Ru(II)–phosphane complexes were synthesized in high purity by the reaction of cis-[RuCl2(dmso)4] with 2 equivalents of 1,3,5-triaza-7-phosphaadamantane (pta) and its N-methyl and N-benzyl derivatives (pta-Me and pta-Bn, respectively). All new complexes were characterized by elementary analysis and spectroscopic methods (NMR, ESI-MS) and the molecular structures of cis-cis-trans-[RuCl2(dmso)2(pta)2], cis-cis-trans-[RuCl2(dmso)2(pta-H)2]Cl2 (obtained in acidic solutions) and that of cis-cis-trans-[RuCl2(dmso)2(pta-Me)2](CF3SO3)2 were determined by single crystal X-ray diffraction. Under mild conditions, cis-[RuCl2(dmso)4] actively catalyzed the transformation of allylic alcohols into the corresponding ketones with 100% selectivity while in the same reaction the new Ru(II)–pta complexes showed moderate activity and selectivity.

The autooxidation phenomenon of apomorphine and the products of this procedure were analytically and pharmacologically studied, however we found that there have been some unclarified details of this filed. Therefore the synthesis and structure of the autooxidation products of three clinically and pharmacologically relevant aporphinoids (apomoprine, N -propyl-norapomorphine and 2-hydroxy- N -propyl-norapomorphine) were thoroughly investigated. The autooxidation of apomorphine achieved at physiological pH resulted two products; one of them is the known tetracyclic, tertiary amino ortho quinone and the hitherto unknown, fluorescent, derivatized phenanthrene-3,4-quinone. Under the same conditions N -propyl congeners resulted only the expected 1,2-dione products. The analytical structure elucidation involved the full 1 H and 13 C NMR assignment, UV and IR characterizations of the four isolated ortho quinone-type products exploiting the possibilities of DFT calculations for geometry optimization, NMR and IR simulations. The phenanthrene-3,4-quinone compound can be relevant in further pharmacological studies of aporphine-related oxidation products due to its potential toxicity and investigated fluorescent character.

A simple and efficient synthesis of amides by selective hydration of aromatic and aliphatic nitriles is described. The catalysts are prepared in situ from easily available Ru-precursors and ligands using water as the solvent. The most active catalyst, is obtained from [RuCl 2 (dmso) 4 ] and benzylated 1,3,5-triaza-7-phosphaadamantane. Of the 16 substrates examined, 92–99% conversions of 14 nitriles were achieved in one hour at reflux temperature.

Hydrogenation of sorbic acid in ethyl acetate with [RhCl(PPh3)3] was studied and compared to the hydrogenation of its K-salt in water catalyzed by [RhCl(mtppms)3]. Aqueous biphasic hydrogenation of sorbic acid with [RhCl(mtppms)3] as catalyst proceeded faster and more selectively than that in homogeneous solutions and afforded trans-hex-2-enoic acid with 80% selectivity.

The reaction is performed with equimolar amounts of aryl iodide and terminal alkyne leading to full conversion upon sufficiently long reaction times and without a copper catalyst.

1,3,5-triaza-7-phosphaadamantane (PTA) was shown to form phosphonium alkanoate zwitterions with unsaturated dicarboxylic acids in water in the absence of strong acids. Solid-state structures of the phosphonium salt (1) derived from maleic or fumaric acids and that of the zwitterionic product (2) of the reaction of PTA with citraconic and mesaconic acids were determined by single-crystal X-ray diffraction. DFT calculations gave insight into the mechanism of the reaction, including the relative reactivity of the four dicarboxylic acids, and revealed the reasons for the lack of phosphonium salt formation by PTA in strongly acidic aqueous solutions.

A simple and efficient synthesis of amides by selective hydration of aromatic and aliphatic nitriles is described. The catalysts are prepared in situ from easily available Ru-precursors and ligands using water as the solvent. The most active catalyst, is obtained from [RuCl 2 (dmso) 4 ] and benzylated 1,3,5-triaza-7-phosphaadamantane. Of the 16 substrates examined, 92–99% conversions of 14 nitriles were achieved in one hour at reflux temperature.

Ion pairs consisting of N-substituted derivatives of 1,3,5-triaza-7-phosphaadamantane (pta-R; R = benzyl, butyl, hexyl) as cations and monosulfonated triphenylphosphine (mtppms) as anion were synthesized and characterized (including X-ray diffraction, too). These ion pairs act as bidentate phosphorus ligands in reactions with [(η6-C10H14)RuCl2]2, yielding mononuclear or dinuclear half sandwich Ru(II) complexes. Bisphosphine 3 of good water-solubility was synthesized in reaction of pta with 1,4-bis(chloromethyl)benzene and used for the synthesis of the water-soluble dinuclear complex [{(η6-C10H14)RuCl2}2(μ-3)]Cl2.

Novel 6-ketolevorphanol analogs with diverse substitution patterns at ring C were synthesized and their binding affinities at the μ,δ and κ opioid receptors were investigated. The in vitro activity of the new analogs was then evaluated in the functional assay based on the electrically-stimulated contractions of the mouse ileum. It was shown that analogs with Δ7,8 bond had no significant potency at any of the opioid receptor types. In contrast, analogs with the saturated ring C were either potent κ agonist or antagonist depending on the absence or presence of the hydroxyl group in position 14.

The one-pot N-demethylation and acid-catalyzed rearrangement of morphinan-N-oxides offers a new, shorter and more efficient route to neuropharmacologically important N-substituted aporphines. An improved procedure is described for the preparation of the starting alkaloid N-oxides using Na2WO4 as catalyst. The transetherification during the rearrangement of codeinone into 2-O-alkyl-norapocodeines is documented.