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).     

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.     

Oxydative Kupplung von Indolinen und 1,2,3,4-Tetrahydrochinolinen mit Kaliumpermanganat. 153. Mitteilung über Alkaloide

It is shown that treatment of indolines like 4a-methyl-1,2,3,4,4a,9a-hexahydrocarbazole ( 1 ) and even indoline-alkaloids like 5 or 6 (cf. scheme 1) with KMnO₄ in boiling acetone solution leads to the indolenines 10, 29 and 33 , respectively, and, in relatively high yields, to N,N′- or C,N-coupling products (cf. schemes 2 and 5). The results of the oxidation of 6- or 8-methoxy-indolines are shown in schemes 3 and 4, respectively. Analogous ‘dimeric’ dehydrogenation products are observed when tetrahydroquinolines ( 8 and 9 , resp.) are treated with KMnO₄ (cf. schemes 7 and 8, resp.). The formation of the bis-compounds is almost certainly due to the coupling of two intermediate indolenyl or tetrahydroquinolyl radicals. The cleavage of the hydrazine derivatives 11 or 17 (scheme 9) also leads to ‘dimeric’ C,N-coupling products. By heating the hydrazine derivative 17 with aqueous HCl, a complete cleavage into indoline 2 and the indolenines 16 and 20 is observed. The reaction is rationalized in scheme 10. So far no naturally occurring alkaloids related to the above mentioned C,N-coupling products have been found.     

Zur Struktur und Reaktivität von stannylierten Propylaminen und -sulfiden. Kristall- und Molekülstruktur von Bis(3-dimethylchlorostannylpropyl)sulfid S(CH2CH2CH2SnMe2Cl)2

Structure and Reactivity of Stannylated Propyl Amines and Propyl Sulfides. Crystal and Molecular Structure of Bis(3-chlorodimethylstannylpropyl)sulfide S(CH₂CH₂CH₂SnMe₂Cl)₂ The synthesis and reactivity of stannylated propyl amines and propyl sulfides, respectively, E(CH₂CH₂CH₂SnMe₃)₂ ( 1 , E ? NMe; 2 E ? S) and N(CH₂CH₂CH₂SnMe₃)₃ 3 are reported. 1 and 3 react with dimethyl dichlorostannane under thermal cyclisation to 1,5-dimethyl-5-chloro-1aza-5-stannabicyclo[3.3.0^1,5]octane Me(Cl)Sn(CH₂CH₂CH₂)₂NMe 4 and 5-chloro-1-aza-5-stannatricyclo[3.3.3.0^1,5]-undecane ClSn(CH₂CH₂CH₂)₃N 5 , respectively. The reaction of 2 with dimethyl dichlorostannane leads to the formation of bis(3-chloro-dimethylstannylpropyl)sulfide S(CH₂CH₂CH₂SnMe₂Cl)₂ 6 , whereas the treatment of 2 with tin tetrachloride yields the bis(3-di-chloro-methylstannylpropyl)sulfide S(CH₂CH₂CH₂SnMeCl₂)₂ 7 . The ¹H, ¹³C, and ¹¹⁹Sn NMR data are discussed. 6 crystallizes in the ortho-rhombic space group Pna2₁ with the unit cell parameters a = 2275.0(1), b = 733.6(2), c = 1062.0(4) pm, V = 1.77273 nm³, Z = 4. The structure was refined to a final R value of 0.041. Both tin atoms adopt distorted trigonal bipyramidal configurations as a result of intramolecular interactions with the bridging sulphur. The sulphur and the chlorine atoms occupy the apical positions. The Sn? S distances amount to 309.7(4) and 311.8(4) pm.     

Photochemie von tricyclischen β, γ-γ′, δ′-ungesättigten Ketonen. 50. Mitteilung über Photoreaktionen

Photochemistry of tricyclic β, γ-γ′, δ′-unsaturated ketones The easily available tricyclic ketone 1 (cf. Scheme 1) with a homotwistane skeleton yielded upon direct irradiation the cyclobutanone derivative 3 by a 1,3-acyl shift. Further irradiation converted 3 into the tricyclic hydrocarbon 4 . However, acetone sensitized irradiation of 1 gave the tetracyclic ketone 5 by an oxa-di-π-methane rearrangement. Again with acetone as a sensitizer the ketone 5 was quantitatively converted to the pentacyclic ketone 6 . The conversion 5 → 6 represents a novel photochemical 1,4-acyl shift. The possible mechanisms are discussed (see Scheme 7). The tricyclic ketone 2 underwent similar types of photoreactions as 1 (Scheme 2). Unlike 5 the tetracyclic ketone 9 did not undergo a photochemical 1,4-acyl shift. The epoxides 10 and 14 derived from the ketones 1 and 2 , respectively, underwent a 1,3-acyl shift upon irradiation followed by decarbonylation, and the oxa-di-π-methane rearrangement (Schemes 3 and 4). The diketone 18 derived from 1 behaved in the same way (Scheme 5). The tetracyclic diketone 21 cyclized very easily to the internal aldol product 22 under the influence of traces of base (Scheme 5). Upon irradiation the γ, δ-unsaturated ketone 24 underwent only the Norrish type I cleavage to yield the aldehyde 25 (Scheme 6).