Axially Dissymmetric Diphosphines in the Biphenyl Series: Synthesis of (6,6′-Dimethoxybiphenyl-2,2′-diyl)bis(diphenylphosphine)(‘MeO-BIPHEP’) and Analogues via an ortho-Lithiation/Iodination Ullmann-Reaction Approach

The new axially dissymmetric diphosphines (R)- and (S)-(6,6′-dimethoxybiphenyl-2,2′-diyl)bis(diphenyl phosphine) ((R)- and (S)- 5a ; ‘MeO-BIPHEP’) and the analogues (R)- and (S)- 5b and 5c have been synthesized in enantiomerically pure form. These ligands have become readily available by a synthetic scheme which employs, as key steps, an ortho-lithiation/iodination reaction of the (m-methoxyphenyl)diprienylphosphine oxides 8 and a subsequent Ullmann reaction of the resulting iodides 9 to provide the racemic bis(phosphine oxides) 10 . The bis(phosphine oxides) 10 subsequently are resolved with (?)-(2R,3R)- and (+)-(2S,3S)-O-2,3-dibenzoyltartaric acid and reduced to diphosphines 5 . The Ullmann reaction constitutes a new and efficient route to 2,2′-bis(phosphinoyl)-substituted biphenyl systems. Absolute configurations were established for (R)- 5a by X-ray analysis of the derived Pd complex (R,R)- 17a , and for 5b and 5c by means of ¹H-NMR comparisons of the derived Pd complexes 16 or 17 , respectively, and by means of CD comparisons. The MeO-BIPHEP diphosphine 5a proved to be as efficient as the previously described BIPHEMP diphosphine ((6,6′-dimethylbiphenyl-2,2′-diyl)bis(diphenylphosphine)) in enantioselective isomerizations and hydrogenations.     

Zur Photochemie von 1, 2-Benzisoxazolen in stark saurer Lösung

On the Photochemistry of 1, 2-Benzisoxazoles in Strongly Acidic Solution The 1, 2-benzisoxazoles 1a, 1b and 1d when dissolved in 96% sulfuric acid and irradiated through a quartz filter with a mercury high-presure lamp yield, after work-up, mixtures of 2, 5- and 2, 3-dihydroxy-acylbenzenes ( 2 and 3 , respectively; cf. Schemes 1 and 3 and Table 1). Irradiation of 3, 5-dimethyl-1, 2-benzisoxazole ( 1c ) in 96% sulfuric acid leads to the formation of 2, 3-dihydroxy-5-methyl-acetophenone ( 3c ) in only 6% yield (cf. Table 1). It is assumed that the 1, 2-benzisoxazolium ions react in the excited singlet state by heterolytic cleavage of the N, O-bond to yield the corresponding aryl oxenium ions 7 in the singlet ground state (see Scheme 5). Reaction of 7 with HSO ₄ ? ions, present in 96% sulfuric acid, yields, after hydrolysis, the dihydroxy compounds 2 and 3 . Photolysis of 3-methyl-1, 2-benzisoxazole ( 1b ) in diluted sulfuric acid (0,5 to 9 M ) in methanol or water leads only to the formation of 2-amino-phenol ( 6 ; see Scheme 3), presumable via photo-isomerization of 1b to 2-methylbenzoxazole ( 5b ) which then is hydrolyzed to give 6 .     

Photochemische Cycloadditionen von 3-Phenyl-2H-azirinen mit Benzoyl-, Äthoxycarbonyl- und Vinylphosphonaten 34. Mitteilung über Photoreaktionen

The irradiation of the 3-phenyl-2H-azirines 1a–c in the presence of diethyl benzoylphosphonate ( 8 ) in cyclonexane solution, using a mercury high pressure lamp (pyrex filter), yields the diethyl (4, 5-diphenyl-3-oxazolin-5-yl)-phosphonates 9a–c (Scheme 3). In the case of 1b a mixture of two diastereomeric 3-oxazolines, resulting from a regiospecific but non-stereospecific cycloaddition of the benzonitrile-benzylide dipole 2b to the carbonyl group of the phosphonate 8 , was isolated. Benzonitrile-isopropylide ( 2a ), generated from 2,2-dimethyl-3-phenyl-2H-azirine ( 1a ), undergoes a cycloaddition reaction to the ester-carbonyl group of diethyl ethoxycarbonylphosphonate ( 15 ) with the same regiospecificity to give the 3-oxazoline derivative 16 (Scheme 5). The azirines 1a–c , on irradiation in benzene in the presence of diethyl vinylphosphonate ( 17 ) give non-regiospecifically the Δ¹-pyrrolines 13a–c and 14a–c (Scheme 6).     

Zur Biosynthese des Strychnins. 135. Mitteilung über Alkaloide

From the feeding of young plants of Strychnos nux-vomica with [¹⁴C]-1-and [¹⁴C]-2-acetate it could be deduced that the C-atoms 22 and 23 were derived from acetate. [¹⁴C]-2-mevalonate, [¹⁴C]-2-geraniol and [¹⁴C]-2-geranyl pyrophosphate were also incorporated into strychnine. The distribution of radioactivity in the «mevalonate-strychnine» was in agreement with the monoterpenoid hypothesis. Feeding experiments especially with [¹⁴C]-tryptophane showed that the main production centre of the alkaloid lay in the roots and that only a small part of it was carried to the leaves. Tritium labelled WIELAND GUMLICH aldehyde as well as N_(a)-[¹⁴C]-1-acetyl WIELAND GUMLICH aldehyde were not converted into strychnine by S. nux-vomica.     

Darstellung,Kristall- und Molekülstruktur von Triphenylphosphinoxidhydrochlorid (C6H5)3PO · HCl

On Phosphazo Compounds from Nitriles. IV. The Reaction of Tri, Di, and Monochloroacetonitrile with [Cl₃P?N? PCl₃]Cl. Improved Preparation of [Cl₃P?N? PCl₃]Cl Trichloroacetonitrile reacts with P₂NCl₇ to give Cl₃C? CCl₂? N?PCl₂? N?PCl₃ I , dichloroacetonitrile to give Cl₂C?CCl? N?PCl₂? N?PCl₃ II , and chloroacetonitrile to give the ring compound III . Preparation, n.m.r. and mass spectra of the new compounds are described. The mechanism of formation is discussed. An improved procedure for the preparation of P₂NCl₇ is given.     

Strukturuntersuchungen an Siliziden

Zusammenfassung Die Struktur der isotypen Phasen V₃Si₂, Nb₃Si₂, Ta₃Si₂ und Cr₃Si₂ wurden nach dem Vorschlag vonAronsson (RaumgruppeD _2d ¹¹) gerechnet. Die röntgenographische Analyse dieser Phasen spricht mehr für eine Zusammensetzung von M₅Si₃.Im System Nb–Si und Ta–Si wurde eine isotype Phase gefunden, die als Hoch- bzw. Tieftemperaturmodifikation der M₃Si₂-Phasen angesprochen werden kann. Sie läßt sich tetragonal indizieren.Die durch Kohlenstoff stabilisierten M₅Si₃-Phasen mitD 8₈-Typ bilden bei V₅Si₃–Nb₅Si₃ eine lückenlose Mischreihe, während bei dem Paar V₅Si₃–Zr₅Si₃ möglicherweise eine geringe Mischungslücke besteht.VSi₂ und NbSi₂ sind ebenfalls im festen Zustande lückenlos mischbar; das System VSi₂–MoSi₂ zeigt eine sehr starke Löslichkeit auf der VSi₂-Seite. MoSi₂ nimmt dagegen nur wenig VSi₂ auf.Mit 2 Abbildungen.Herrn Professor Dr.Emil Abel aus Anlaß seines 80. Geburtstages in aufrichtiger Verehrung gewidmet.     

Development of a chemical vapor sensor using piezoelectric quartz crystals with coated unusual lipids

Piezoelectric quartz crystal sensors were developed using lipids with various properties for highly sensitive detection of chemical vapors. Lipids with varying lengths of alkyl chains were coated onto 10 MHz AT-cut quartz crystal resonators and the response of these modified crystals to chemical vapors were measured. It was shown that hydrophilic compounds, such as ethanol and methanol, could be recognized efficiently by lipids having shorter alkyl chains, whereas lipids with longer alkyl chains showed affinity to more hydrophobic vapors, such as toluene, hexane and cyclohexane. Frequency changes caused by adsorption of alcohols could be enhanced when cholesterol was co-immobilized in the lipid layer. To confirm the assumption that the sensor-response might be affected by the properties of lipids derived from acyl chains, we have examined the effects of two types of newly synthesized unusual lipids on sensor response. When lipids having one triple bond each at different positions on their alkyl chains were coated onto quartz crystals separately, lower responses were observed compared to responses obtained for a sensor with immobilized, saturated phosphatidylcholine. Lipids containing -branched acyl chains, however, showed good affinity for organic vapors, and sensor responses improved 4–5-fold. Moreover, these sensors were shown to have sensitivity of the same order as the humans' sense of smell (10⁻⁵–10⁻⁶ w/w in liquid paraffin) when measured using standard odorants (isovaleric acid, skatole, etc.) for an olfactometry established in Japan.     

Photochemie von in 4-Stellung substituierten 5-Methyl-3-phenyl-isoxazolen.44. Mitteilung über Photoreaktionen

Photochemistry of 4-substituted 5-Methyl-3-phenyl-isoxazoles. 4-Trideuterioacetyl-5-methyl-3-phenyl-isoxazole ([CD₃CO]- 27 ), upon irradiation with 254 nm light, was converted into a 1:1 mixture of oxazoles [CD₃CO]- 35 and [CD₃]- 35 (Scheme 13). This isomerization is accompagnied by a slower transformation of ([CD₃CO]- 27 ) into [CD₃]- 27 . Irradiation of the isoxazole derivatives 28, 29, 30 and (E)- 31 yielded only oxazoles 36, 37, 38 and (E), (Z)- 39 ; no 4-acetyl-5-alkoxy-2-phenyl-oxazole, 2-acetyl-3-methyl-5-phenyl-pyrrole or 2-acetyl-4-methoxycarbonyl-3-methyl-5-phenyl-pyrrole, respectively, were formed (Scheme 9 and 10). Similarly (E)- 32 gave a mixture of (E), (Z)- 40 only (Scheme 11). Upon shorter irradiation, the intermediate 2H-azirines (E), (Z)- 41 could be isolated (Scheme 11). Photochemical (E)/(Z)-isomerization of the 2-(trifluoro-ethoxycarbonyl)-1-methyl-vinyl side chain in all the compounds 32, 40 and 41 is fast. At 230° the isoxazoles (E)- and (Z)- 32 are converted into oxazoles (E), (Z)- 40 . The same compounds are also obtained by thermal isomerization of the 2H-azirines (E), (Z)- 41 . The most probable mechanism for the photochemical transformations of the isoxazoles, as exemplified in the case of the isoxazole 27 , is shown in Scheme 13. A benzonitrile-methylide intermediate is postulated for the photochemical conversion of the 2H-azirines into oxazoles. 2H-Azirines are also intermediates in the thermal isoxazole-oxazole rearrangement. It is however not yet clear, if the thermal 2H-azirine-oxazole transformation involves the same transient species as the photochemical reaction. A mechanism for the photochemical isomerization of the 2H-azirine 11 to the oxazole 15 is proposed (Scheme 3).     

Herstellung neuer polycyclischer Verbindungen durch intramolekulare Diels-Alder-Reaktionen von Cyclohexa-2,4-dien-1-on-Abkömmlingen

Synthesis of new polycyclic compounds by means of intramolecular Diels-Alder reactions of cyclohexa-2,4-dien-1-one derivatives Thermal rearrangement of mesityl penta-2,4-dienyl ether ( 1 ), consisting of the isomers E (93%) and Z (7%), furnished, besides mesitol, the two mesityl penta-1,3-dienyl ethers 2 (24%) and 3 (3%), and the two tricyclic ketones 4 (4,5%) and 5 (12,5%) (Scheme 1). A probable mechanism for this formation of 2 involves a [1,5]-hydrogen shift in (Z)- 1 . Isomerisation of (E)- 1 to (Z)- 1 at 145° occurs via reversible sigmatropic [3,3]- and [5,5]-rearrangements of (E)- 1 to the cyclohexadienones 38 and 39 respectively (see Chapter A p. 1710, and Scheme 15). Formation of 3 from either (Z)- 1 or 2 is rationalized by a series of pericyclic reactions as outlined in Chapter A and Scheme 16. The tricyclic ketones 4 and 5 are undoubtedly formed by internal Diels-Alder reactions of the 6-pentadienyl-cyclohexa-2,4-dien-1-one 6 (Scheme 2). In fact, at 80° 6 is converted into 4 (5%) and 5 (35%). At 80° the cyclohexadienone derivative 7 furnished the corresponding tricyclic ketones 8 (15%) and 9 (44%) (Scheme 2). 5 and 9 contain a homotwistane skeleton. 8 and 9 are easily prepared by reaction of sodium 2,6-dimethylphenolate with 3-methyl-penta-2,4-dienyl bromide at ambient temperature, followed by heating, and finally separation by cristallization and chromatography. The cyclohexadienones 6 and 7 have mainly (E)-configuration. Here too (E) → (Z) isomerization is a prerequisite for the internal Diels-Alder reaction, and this partly takes place intramolecularly through reversible Claisen and Cope rearrangements (Scheme 17). On the other hand, experiments in the presence of 3,5-d₂-mesitol have shown (Table 1) that intermolecular reactions, involving radicals and/or ions, are also operating (see Chapter B , p. 1712). Two different modi (I and II) exist for intramolecular Diels-Alder reactions (Scheme 18). Whereas only modus I is observed in the cyclization of 5-alkenyl-cyclohexa-l,3-dienes, in that of (2)-cyclohexadienones 6 and 7 (Scheme 2) both modi are operating. Only in modus 11-type transitions is the butadienyl conjugation of the side chain retained, so that modus 11-type addition is preferred (Chapter C p. 1716). Analogously to the synthesis of the tricyclic ketones 4 , 5 , 8 and 9 , the tricyclic ketone 15 (Scheme 4) and the tetracyclic ketone 11 (Scheme 3) are prepared from mesitol, pentenyl bromide and cycloheptadienyl bromide, respectively. From the polycyclic ketones derivatives such as the alcohols 16 , 17 , 18 , 19 , 23 , 24 and 25 (Schemes 9 and 11), policyclic ethers 20 , 21 , 22 and 26 (Scheme 10), epoxides 30 , 32 (Scheme 13), diketones 31 , 33 (Scheme 13) and ether-alcohols 35 and 36 (Scheme 14) have been prepared. Most of these conversions show high stereoselectivity.     

Designing new metal affinity peptides by random mutagenesis of a natural metal-binding site

The metal-binding site of a Helicobacter pylori ATPase 439 (heli(WT)-tag) was successfully used as a new fusion peptide for immobilized metal ion affinity chromatography (IMAC). It produced higher yields than the frequently used his6-tag. Due to stronger binding of the peptide to metal ions, harsher elution conditions were, however, necessary. This undesired side-effect was overcome by modifying the heli(WT)-tag by polymerase chain reaction-directed mutagenesis. The modified tags were screened by an automated high-throughput IMAC system, leading to a heliM14-tag peptide that could be eluted under conditions similar to those of the his6-tag but at the same time produced 20% higher yields of the desired protein.