Aminyloxide (nitroxide)—XXIV: Empirische ermittlung der spindichteverteilung in aminyloxiden

¹⁷O-Labelled aminyloxides 1–8 (dialkyl-, alkylaryl-, diaryl-, acylaminyloxides and amidinyloxides) have been prepared by various methods. The ESR spectra of 1a and 4 have been measured in various solvents, showing a very good correlation between a^N respectively a^O and the E_T-values of solvents. From the solvent-dependence of the coupling constants of 1a Q-values have been evaluated for the simplified equation aⁱ = Q_iiⁱ × pⁱ (Q_NN^N = 33.1 G; Q_oo^o = 35.3 G). These values were used to calculate the spin density ?^N and ?^o of the aminyloxides 1–8. The Q-values are shown to be reasonable by summation of the spin density of all positions for the radicals 4–7. which gives one with only small deviations. In most of these radicals in which the unpaired electron is delocalized into the conjugated π-system ?^N is reduced significantly, as compared to dialkyl-ammyloxides, whereas ?⁰ is only lowered to a small extent.     

Aminyloxide—XVIII : ESR-spektroskopische untersuchung der tautomerie beim “hydrolyseprodukt des porphyrexids”

The hydrolysis of porphyrexine 2a yields 3a not 1a, as was shown by means of the ¹⁵N-labelled compound 2c. Analysis of the ESR spectra of radicals 4 derived from 3 shows that in dimethylsulfoxide these radicals exist in the tautomeric form B whereas in dioxan they exist in form A. The stabilization of form B in dimethylsulfoxide is shown to be due to a specific effect of the solvent.     

Aminyloxide (nitroxide)—XXXI : Untersuchung der spindichteverteilung in verschiedenen aminyloxid-typen mit hilfe O-markierter radikale

¹⁷O-Labelled aminyloxides 4 and 7 have been prepared either by direct reaction of the intermediate aminyl radicals 3 and 6 generated by various methods, with ¹⁷O-enriched oxygen, or by spin trap reactions performed with ¹⁷O-labelled 2-methyl-2-nitrosopropane (8) and 2-methyl-2-nitropropane (13) respectively. Reaction of ¹⁷O-labelled tert-butylhydroxylamine with phosgen yielded 11 which was transformed to the radicals 4d and 4f. Using equations (3) and (4) the spin density ^N_NO and ^O_NO was derived for some dialkylaminyloxides (for instance 4c X=CF₃) and tert-butylaminyloxides with conjugated groups (4 X=CO-R, COCl, COOR, COONR₂, CN). The spin density distribution in these radicals is discussed. An attempt to calculate the spin density in radicals 4 (X=OR, NR₂ and SR) with aid of (3) and (4) yields too large values. For this reason we suggest that the aminyloxide group is non-planar in these radicals.     

Aminyloxide (nitroxide)—XXI : Unterschiedliches verhalten von N-hydroxyisatin und isatinyl-N-oxid bei reaktionen mit N-nucleophilen

Isatinyl-N-oxide (2) reacts with primary aliphatic amines at 2-position yielding radicals 5 whereas the parent compound N-hydroxyisatin is attacked at 3-position by N-nucleophiles. Alternative structures to 5 were excluded by comparison of ESR coupling constants with those of several model compounds.     

Elektrochemische untersuchung von bis(diphenyldithiophosphin) disulfid

The electrochemical behaviour of bis(diphenyldithiophosphine)disulphide (RSSR) and mercuric diphenyldithiophosphinate [(RS)₂Hg] in ethanol-lithium perchlorate and ethanol-sulphuric acid media was studied by the methods of classical polarography, and electrolysis at controlled-potential and at a rotating disc platinum electrode. The data obtained show that RSSR is not reduced directly on the dropping mercury electrode but is adsorbed. It then undergoes a rapid chemical reaction causing the formation of (RS)₂Hg, which is electroactive. The electrolysis at controlled potential proves that (RS)₂Hg undergoes a two-electron reduction, giving diphenyldithiophosphinic acid (RSH) as a main product, whereas the oxidation of RSH leads to the production of (RS)₂Hg. Regardless of the fact that the chemical and adsorption equilibria during reduction of RSSR and (RS)₂Hg are complex, the coulometric generation of RSH is not difficult to achieve, and permits the use of RSSR as a coulometric reagent.     

Kinetische untersuchung der reversiblen dimerisierung von o-phenylendioxidimethylsilan

The reversible dimerisation of o-phenylenedioxydimethylsilane (2,2-dimethyl-1,3,2-benzodioxasilole) has been studied by ¹H NMR spectroscopy. The kinetics of this reaction can be described quantitatively by a bimolecular 10-ring formulation reaction and a monomolecular backreaction. The thermodynamic and kinetic parameters are: ΔH⁰ = ?43 kJ mol^?1; ΔS⁰ = ?112 J mol^?1 K^?1; ΔG⁰₂₉₈ = ?9.6 kJ mol^?1; ΔH³₂₉₈ = 57 kJ mol^?1; ΔS³₂₉₈ = ?129 J mol^?1 K^?1; ΔG³₂₉₈ = 96 kJ mol^?1; E_a = 60 kJ mol^?1; A = 3.17 × 10⁶ l mol^?1 s^?1. Remarkable is the low activation energy of formation of the ten-membered ring, considering that two SiO bonds have to be cleaved during the reaction. Transition states and possible structures of the ten-membered heterocycle are discussed.     

Ermittlung der Solvolysenkonstante von Nitrosylchlorid in Methanol

The equilibrium constantK of the methanolysis of nitrosyl chloride was determined. The activities of HCl and CH₃OH in methanolic solutions of hydrogen chloride have been already published. The equilibrium was established from the right side by adding known amounts of methyl nitrite to methanolic hydrochloric acid (0–18m). The equilibrium concentration of NOCl was measured by means of aPulfrich photometer. For 25°C it was foundK=14.1, for 15°CK=18.9, and for 0.5°CK=30.3. From these results the thermodynamic functions of the methanolysis of nitrosyl chloride ΔG°, ΔH° and ΔS° were calculated.     

Ermittlung der absoluten Konfiguration von Indolinalkaloiden durch Vergleiche der Optischen Rotationsdispersionen ihrer N(a)-Acylderivate

A further application of Optical Rotatory Dispersion (ORD) for indole alkaloids containing an N-acylindoline chromophore has completely substantiated an earlier assignment of the absolute configuration of Aspidosperma alkaloids and has extended the general scope of this method, allowing assignments to the absolute configuration of N(a)-acetyl-aspidospermatidine and limatine.     

Untersuchungen zum elektronischen einfluss von organylliganden: IV. 13C-NMR-spektroskopische untersuchung der gegenseitigen beeinflussung von organylliganden in triethylzinnorganylverbindungen

By means of ¹³C NMR spectroscopy, the coupling constants ¹J(¹¹⁹Sn¹³C_Et) of 18 compounds of the SnEt₃R type (R = organo group) have been measured. These coupling constants have been shown to reflect the change induced by R in the s-content of the tin hybrid orbitals of the SnCEt bonds. The series of the influence of R obtained on the basis of the coupling constant mentioned as a parameter is compared with a trans-influence series of R obtained on organo-mercury compounds. Occurring differences are attributed to different modes of bonding of the group R at the central atom.     

Stereochemie von Metallocenen, 20. Mitt.: Die Ermittlung der optischen Reinheit der Methylferrocen-α-carbonsäure (40. Mitt. über Ferrocenderivate)

Zusammenfassung Die optische Reinheit der Methylferrocen--carbonsäure (1) wurde mit Hilfe zweier Methoden ermittelt. Die Isotopenverdünnung unter Verwendung von (²H₁-Methyl)ferrocen--carbonsäure sowie ein Verfahren, das auf der Auswertung der Intensitätsverhältnisse diastereotoper Protonen in denNMR-Spektren der -Phenäthylamide von1 (verschiedener Drehung) beruht, lieferten übereinstimmende Ergebnisse: [] _d für optisch reines1 beträgt 55,6±1,0° bzw. 54±3°. Der durch Racematspaltung von1 gefundene Wert beträgt 51,5±0,8° (bzw. 53±2°)³. Damit sind die Drehungen aller 90, mit1 bereits früher chemisch korrelierten Ferrocenderivate, wenn überhaupt, nur geringfügig zu korrigieren.

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The optical purity of methylferrocene--carboxylic acid (1) was determined by two methods: isotope dilution, employing (²H₁-methyl)ferrocene--carboxylic acid, and a procedure based on the evaluation of the relative intensities of diastereotopic protons in theNMR-spectra of the -phenethylamides of1 having different rotations. By both methods corresponding results were obtained: optically pure1 has an []d of 55.6±1.0° and 54±3°, resp. The value for1 as found by optical resolution is 51.5±0.8° and 53±2°, resp.³. Hence, the rotations of all 90 ferrocene derivatives previously correlated with1 by unambiguous chemical methods have—if at all—to be corrected only slightly.

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Mit 2 Abbildungen

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19. Mitt.:H. Falk undG. Haller, Mh. Chem.99, 1103 (1968).

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39. Mitt.:K. Schlögl undHeidelore Soukup, Mh. Chem.99, 927 (1968).     

Stereochemie von Metallocenen, 11. Mitt.: Die Temperaturabhängigkeit der optischen Rotationsdispersion von α-disubstituierten Ferrocenderivaten: Ermittlung von Konformationsgleichgewichten

Measurements of the temperature dependence of the molecular amplitudes of the Cottoneffects of optically active, α-substituted methylferrocenes [R=COMe, CH=CH₂, C(Me)=CH₂ and C(Cl)=CH₂] in the region of the ?ferrocene absorption band” (around 440 nm) and comparison with corresponding cyclic derivatives prove the preponderance of energetically preferred conformers; these are present in the equilibrium in amounts of 75–90% (cf. Table 4). Therefore, the optical rotatory power of α-disubstituted ferrocene derivatives seems to be caused primarily by these conformational equilibria: The preferred positions of the groups involved (C=O, C=C) relative to the residue of the molecule perturb the inherently symmetrical ?ferrocene chromophore” (which thereby is placed into a chiral environment) and determine the sign of its Cotton effect.     

Ermittlung der Vergleichbarkeit einer Analysenmethode im Falle der Bestimmung von Medikamenten in Plasma

Zusammenfassung Die Vergleichbarkeit (Reproduzierbarkeit) der Resultate spielt bei der Beurteilung der Qualität einer Analysenmethode eine wichtige Rolle. Ein geeignetes Maß für die Vergleichbarkeit bildet der Variationskoeffizient der Versuchsresultate. Er wird mit Hilfe von unabhängigen Mehrfachbestimmungen an der gleichen Probe berechnet. Dabei ist zu beachten, daß der Variationskoeffizient konzentrationsabhängig sein kann.Bei den Bestimmungen von Medikamenten in Plasma für pharmakokinetische Studien sind die Plasmamengen oft klein, so daß höchstens Doppelbestimmungen durchgeführt werden können. In der vorliegenden Arbeit wird an Beispielen aus der Praxis gezeigt, wie in solchen Fällen mit meist vorhandenen Daten, ohne zusätzlichen experimentellen Aufwand, eine brauchbare Abschätzung des durchschnittlichen Variationskoeffizienten einer Methode erfolgen kann.

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Evaluation of the reproducibility of an assay for the determination of drugs in plasma

Summary The precision (reproducibility) of the results is of great importance for characterizing the quality of an analytical procedure. As a measure of the precision the coefficient of variation of the results can be used. It may be calculated by means of multiple independent determinations on the same sample. It is necessary to examine if the coefficient of variation is concentration-dependent or not.In the determinations of drugs in plasma for pharmacokinetic studies the amounts of plasma are often very small and allow only double determinations. In this paper it will be shown with the aid of practical examples how in these cases the mean coefficient of variation of an assay can be calculated.

     

untersuchung der Molekularassoziation des (p-Chlorbenzolsulfonamido)benzolthiophosphonsäure-O-äthylesters mit Hilfe der IR-Spektroskopie

O-Ethyl (p-chlorobenzenesulfonamido)benzenethiophosphonate (1) is shown to be associated by hydrogen-bonding by means of its i.r. spectrum in CCl₄ solution. Quantitative examination allows to determine the dissociation konstantK, the temperature dependence of which leads to a H-value of 8.3 kcal/mole. From this value it is concluded that the associated molecules are cyclic dimers2. The comparison of the H- and pK-values with the corresponding data of other compounds which form cyclic dimers, shows that the strength of the hydrogen bonding is greater in those compounds which possess smaller pK-values.

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XLIV. Mitt.:L. Almasi, N. Popovici undJ. Zsakó, Chem. Ber.106, 1384 (1973).     

Spektrophotometrische untersuchung der ternaren systeme ruthenium(iii) - zitrat - nitrosonaphthol

Reactions of ruthenium(III) with nitrosonaphthols were studied in weakly acidic media using various spectrophotometric methods. Mixtures of complexes are usually obtained; in citratebuffered medium the complexes I : I and I :3 are formed. Both nitrosonaphthols can be applied for detection of ruthenium(III) in weakly acidic media.     

Polarographische untersuchung der extraktions-gleichgewichte von bleikomplexen ausgewählter zweizähniger liganden

Polarographic studies of the extraction equilibria of lead complexes with bidentate ligandsThe extraction curves of the lead complexes with 19 bidentate ligands have been determined by polarographic measurements of the lead concentration in the aqueous phase. The pH_{$\text{1}\text{2}$} values and the extraction constants are reported; the influence of citrate used as masking agent is considered. Replacement of oxygen by sulfur in a given ligand leads to an increase in the extraction constant. The extraction constants of acylthioacetanilide complexes were found to be smaller than those of the analogous acylthioureas.     

Chemie der pleuromutiline-VI : Vergleichende untersuchung der 13C-NMR spektren des tricyclischen diterpens mutilin und einer reihe von mutilinderivaten

The ¹³C NMR spectra of the diterpenes pleuromutilin,¹ mutilin,¹ and related compounds are discussed in detail. The complete assignment of the signals to the individual C-atoms of the tricyclic system is based on comparisons of spectra as well as increment calculations. The syntheses of the investigated compounds are described, if they were not mentioned in earlier papers.