Umwandlung von Cardenoliden durch Mikroorganismen VI. 7β, 11α-Dihydroxydigitoxigenin und Abbau von 7β-Hydroxy-digitoxigenin zum 3β, 7β-Diacetoxy-14-hydroxy-5β, 14β, 17αH-ätiansäure-methylester. Mitteilung über Reaktionen mit Mikroorganismen [1]

Digitoxigenin ( 3 ) was transformed by a Fusarium spec. to 7β-hydroxydigitoxigenin ( 1 ) 1β, 7β-dihydroxydigitoxigenin ( 4 ) and to the hitherto unknown 7β, 11α-dihydroxydigitoxigenin ( 9 ). 7β-acetoxy-digitoxigenin ( 2 ) was degraded to methyl 3β, 7β-diacetoxy-14-hydroxy-5β, 14β, 17αH-etianate ( 11 ).     

Die Aminoalkylierung von Chinoxalinen und Chinoxalonen 6. Mitteilung über grignard-reaktionen mit halogenalkylaminen [1]

Quinoxaline and 2(1H)-quinoxalones react with organomagnesium salts differently from the corresponding phthalazines and quinazolines. 3-Dimethylaminopropyl-magnesiumchloride alkylates quinoxaline easily by addition to the 2 and 3 position forming a tetrahydroquinoxaline 2 , which can be dehydrogenated to the corresponding dialkylated quinoxaline 3 . The monosubstituted dihydroquinoxaline 5 is obtained only with difficulty. It can equally be dehydrogenated, yielding 6 . Quinoxalones react with CH₃MgI, C₆H₅MgBr, (CH₃)₂N? (CH₂)₃? MgCl by addition to the 3,4-C?N bond (not at the CO-group), yielding 11–13 . These dihydroquinoxalones are dehydrogenated to the 3-substituted 2(1H)-quinoxalones 14–16 . Only 3-phenyl-quinoxalone adds a Grignard reagent at the CO group, forming a 2-substituted 3-phenylquinoxaline ( 26 ). 3-Methyl-quinoxalone exhibits an abnormal behaviour: It is deprotonated by the mentioned reagents at the CH3 group, and the 3-methylenequinoxalone-anion so formed attacks another molecule of methylquinoxalone, finally yielding 32 and 33 .     

Chemie von α-Aminonitrilen. 12. Mitteilung. Sondierungen über thermische Umwandlungen von α-Aminonitrilen

Chemistry of α-Amino Nitriles

1 11. Mitteilung: [1].

. Exploratory Experiments on Thermal Reactions of α-Amino Nitriles The paper extends a previously published report [4] on chemical properties of α-amino nitriles and of members of the C₃H₄N₂ ensemble (Scheme 1) as observed in experiments carried out under non-aqueous conditions. The reactions investigated and the observations made are summarized in some detail in the English footnotes (*) referring to Schemes 1–17 and Fig. 1.     

Neue β-Lactam-Antibiotika. Über die Darstellung und Decarbonylierung von 3-Formylcephem-Verbindungen. Modifikationen von Antibiotica, 12. Mitteilung [1]

Benzhydrylic esters of 3-unsubstituted cephem-4-carboxylic acids of types 9 and 10 (Scheme 2) are prepared by decarbonylation of esters of 3-formylcephem compounds of type 2 with tris-triphenylphosphine-rhodium chloride. The preparation of the starting materials 2 and 5 , as well as of the nucleus 13 is described.     

Photoinduzierte Reaktionen von 3-Phenyl-2H-azirinen mit Carbonsäureestern 40. Mitteilung über Photoreaktionen

Irradiation (280–350 nm light) of a benzene solution of 3-phenyl-2H-azirines 1a – e in the presence of carboxylate esters, whose carbonyl groups are activated by electron withdrawing groups situated in the acyl or alkyl moiety, produces 5-alkoxy-3-oxazolines (Tab. 1 and 4, Scheme 2) isolated in 18–82% yield. These heterocycles undoubtedly originate by regiospecific addition of the ester carbonyl group to the azirine-derived benzonitrile-methylide ‘dipole’ (Scheme 1). The 5-(2,′ 2′, 2′-trifluoroethoxy)-3-oxazolines, derived from 2′, 2′, 2′-trifluoroethyl carboxylic esters, on treatment with methanolic hydrogen chloride at low concentration, are smoothly transformed into the corresponding 5-methoxy-3-oxazolines (e.g. 16 → 17 , Tab. 5). Utilizing this process, various hitherto relatively unknown 9. 5-alkoxy-3-oxazolines become accessible. The constitution of the adducts is based essentially on spectral data. The structure of trans-5-methoxy-2,4-diphenyl-5-trifluoromethyl-3-oxazoline (trans- 14 ), the addition product of methyl trifluoroacetate and the benzonitrile-benzylide from 2,3-diphenyl-2H-azirine ( 1d ), was determined by X-ray crystallography (Section 5). Benzonitrile-isopropylide ( 22 ), resulting from the photochemical transformation of 2,2-dimethyl-3-phenyl-2H-azirine ( 1a ), also reacts with S-methyl thiobenzoate to give 2,2-dimethyl-5-methylthio-4,5-diphenyl-3-oxazoline ( 26 ). Ethyl cyanoacetate protonates predominantly the dipolar species derived from 1a at the nitrile C-atom and yields after work-up ethyl α-cyano-cinnamate ( 29 ) and ethyl isopropylidene-cyanoacetate ( 30 ) (Scheme 4). The relative rate of addition (k_rel) of benzonitrile-isopropylide ( 22 ) to methyl α-haloacetates and dimethyl oxalate was determined by competition experiments (Section 6). Log k_rel correlated satisfactorily (r = 0.97) with the pK_a of the acide derived from the ester reactant: log k_rel = ? 1.72 pK_a + 2.58 or with Taft's substituent constants σ*: log k_rel = 2.06 σ* ? 4.11 [k_rel(methyl dichloroacetate) = 1; Section 7.1]. On the basis of the results obtained, the mode of reaction of the so-called benzonitrile-methylide ‘dipole’ is discussed and a model for the transition state of addition of ester-carbonyl groups is proposed that accounts for the observed regiospecifity and steroselectivity.     

Über die 1,2-Verschiebung von Carbonestergruppen bei der Benzilsäureumlagerung von α,β-Dioxobuttersäure-estern. 25. Mitteilung über Reduktone und Tricarbonylverbindungen [1]

In the benzilic acid type rearrangement of t-butyl α,β-dioxobutyrate (VII) the intact t-butoxycarbonyl group is shifted to the β-carbonyl carbon atom.     

Synthesen von Mannich-Basen von Hydroxy-indolen. 3. Mitteilung über synthetische Indol-Verbindungen [1]

The reactivity of hydroxy-indoles under the conditions of the Mannich-reaction has been studied. The electrophilic side-chain enters in each case in a position ortho to the phenolic group. 4-Hydroxy-indole is substituted in the 5-, 5-hydroxy-indole in the 4-, 6-hydroxy-indole in the 7-, and 7-hydroxy-indole probably in the 6-position. The structures of the Mannich bases from 4-, 5- and 6-hydroxy-indole have been confirmed by comparison of the hydroxy-methyl-indoles obtained by reductive desamination with hydroxy-methyl-indoles prepared by unambiguous total synthesis.     

Die Aminoalkylierung von Chinazolinen und Chinazolonen mit Hilfe der GRIGNARD-Reaktion. 5. Mitteilung über GRIGNARD-Reaktionen mit Halogenalkyliminen [2]

Quinazoline is aminoalkylated at C(4) by 3-dimethylaminopropyl-magnesium-chloride in preparative yield to give 3 , and by oxidation 5 , just as aryl and alkyl-magnesiumbromide give 15 , 19 , and 22 . These 4-substituted quinazolines yield by further treatment with the same GRIGNARD compound by 3, 4 or 1, 2-addition 3, 4-di-hydro-quinazolines ( 12 , 16 ) and 1, 2-dihydro-quinazolines ( 13 , 17 , 20 , 23 ), the latter being formed exclusively when the 4-position in the quinazoline is occupied by bulky residues; only the later can be oxidised to give 2,4-disubstituted aromates (cf 14 , 18 , 21 , 24 ). The spectroscopic and physicochemical behaviour of the dihydro compounds and the aromatic and the aromatic compounds are discussed.     

Die Aminoalkylierung von Phtalazinen und Phtalazonen mit Hilfe der GRIGNARD-Reaktion. 4. Mitteilung über GRIGNARD-Reaktionen mit Halogenalkylaminen [1]

Phtalazines and 4(3H)-phthalazones are aminoalkylated in high yield by 3-dimethylaminopropyl-magnesiumchloride. Phthalazines add only one molecule of the GRIGNARD reagent at the C?N-double bond, giving mono-aminoalkylated 1,2-dihydrophthalazines which undergo no further reaction without previous oxydation. Phthalazones react with the carbonyl and the C?N-group yielding in one step di-aminoalkylated dihydrophthalazines. The dihydrophthalazines are easily oxydized with K₃Fe(CN)₆ to the corresponding phthalazines.     

Photochemische Reaktionen. 85. Mitteilung [1]. Zur Photochemie von α, β-Epoxy-eucarvon

Photochemistry of α,β-epoxy-eucarvone . On π,π^*-excitation (λ = 254 nm) 4 isomerizes to the bicyclic ketoaldehyde 5 ; on n,π^*-excitation (λ ? 280 nm) 4 gives 5 , the β,γ-unsaturated ketone 6 , the enone 7 and the cyclobutanone 8 . Scission of the (C—C)-bond of the oxirane 4 would give the dihydrofurane e , which could isomerize to the ketoaldehyde 5 . On the other hand, 4 is assumed to isomerize to the β,γ-unsaturated aldehyde c , which could yield 6 and 7 by photodecarbonylation. The cyclo-butanone 8 is shown to be a photoisomer of the ketone 6 . Furthermore, eucarvol ( 18 ) rearranges by a thermal [1,5]-H-shift to dihydro-eucarvone ( 20 ); on UV.-irradiation 18 gives the bicyclic isomers 27 and 28 .     

Produktion von β-Lactamantibiotika durch Mikroorganismen

β-lactam antibiotics are commercially and clinically important compounds that are produced by bacteria as well as by filamentous fungi. There is a great interest not only to increase the yield of microbial antibiotic production but also to generate new and highly effective antibiotics. It may be foreseen that this aim is reached by the use of in vitro recombinant technology. The biochemical as well as the physiological data which seem to be important for the understanding of β-lactam biosynthesis is filamentous fungi are summarised. In addition, recent technical advances are mentioned which become available through molecular biology. Examples are given to demonstrate the feasability of DNA recombinant technology for biotcchnical applications by introducing novel biosynthetic pathways into fungal β-lactam producers.     

Eine neue Amidinsynthese mit Hilfe der Grignard-Reaktion. 7. Mitteilung über Grignard-Reaktionen [1]

In an unusual manner benzonitrile 5 and the substituted benzonitriles 1 , 14 reacted with benzylmagnesiumhalides to yield, besides dibenzyl, the amidines 7 , 13 , 15 , substituted on the imide nitrogen by a 1,2-diphenyl-vinyl group. The proposed structures are based on NMR. and mass spectra.     

Über die Umsetzung von 1-Phenylpyrazol mit Äthylmagnesiumbromid. 8. Mitteilung über Grignard-Reaktionen [1]

In contrast to butyllithium, ethylmagnesium-bromide reacts with 1-phenyl-pyrazole exclusively by deprotonation, at the ortho position of the phenyl-ring. With nitriles the intermediate 2-(1-pyrazolyl)-phenylmagnesiumbromide gave good to excellent yields of 1-(2-aroyl or 2-hetaroyl-phenyl)-pyrazoles (Table 1, compounds 5a – 5i ); with ketones the corresponding methanol derivatives (Table 2, compounds 6a – 6c ) were found, whilst CO₂ yielded the corresponding 1-(2-carboxyphenyl)-pyrazole ( 3 ). Surprisingly enough, 1-(o-bromo-phenyl)-pyrazole and magnesium did not yield a single product, but a mixture of 3 compounds, which on reaction with 4-benzoylpyridine gave the three alcohols 19 , 20 and 21 .     

Reaktionen von Bleitetraacetat mit alicyclischen Alkoholen,III. Cyclopropyl- und Cyclobutylcarbinole. 18. Mitteilung über Reaktionen mit Bleitetraacetat

When treated with lead tetraacetate, cyclopropylcarbinol and cyclopropylmethylcarbinol do not give β-fragmentation products resulting from the intermediate formation of cyclopropyl radicals; however, cyclopropylmethylcarbinol affords a small amount of a fragmentation product which arises from C_α? C_β bond cleavage involving removal of a methyl radical. In contrast, cyclobutylcarbinol undergoes β-fragmentation in 18% yield with formation of both the unrearranged cyclobutyl acetate and the rearranged cyclopropylmethyl acetate. These results suggest the following order of increasing radical stability: cyclopropyl < methyl < cyclobutyl, whereas the isolation of the isomeric fragmentation acetates in the lead tetraacetate reaction of cyclobutylcarbinol represents further evidence that in the β-fragmentation process the initially produced carbon radical fragment is in major part oxidized to the corresponding carbonium ion before final product formation.     

Reaktionen von Steroiden mit Dialkylaminoschwefeltrifluoriden. I. 11β-Hydroxysteroide. Über STeroide, 233. Mitteilung

Reactions of Steroids with Dialkylaminosulfur Trifluorides. I. 11β-Hydroxysteroids. Reactions of three types of 11β-hydroxy steroids with dialkylaminosulfur trifluorides (DAST) have been studied. 9Δ-unsubstituted 11-alcohols are dehydrated with DAST to Δ⁹⁽¹¹⁾-unsaturated compounds under very mild conditions. 9α-Chloro-11β-hydroxy steroids are quantitatively fluorinated in position 11 yielding the known 9α-chloro-11β-fluoro derivatives. Finally, 9α, 11Δ-fluorohydrins at 0–25° are selectively transformed with DAST into Δ¹¹-9α-fluorides. When the latter reaction is run at lower temperature, the corresponding 11-piperidinesulfinates, products of partial hydrolysis of the alkoxy-dialkylaminosulfur difluoride intermediates postulated by Middleton, can be isolated in high yields. A rational explanation of the results is presented.     

Umlagerung und Spaltung von α, β-Dioxopropionsäureestern in alkalischem Milieu. 28. Mitt. über Reduktone und Tricarbonylverbindungen [1]

The behaviour of α,β-dioxopropionic acid derivatives of the type R? CO? CO? COX (R = phenyl, p-substituted phenyls, CF₃, mesityl; X = OC₂H₅, NH₂) was investigated under benzilic acid rearrangement conditions. Nearly all compounds were cleaved by alkali to give the corresponding acids R? COOH and glyoxylic acid. Only the sterically hindered ethyl β-mesityl-α,β-dioxopropionate underwent rearrangement (after hydrolysis of the ester group); it was shown by ¹⁴C-labelling that the carboxylate group migrates to the β-carbonyl group.     

Die Synthese von Acetylen-carbonyl-Verbindungen durch Fragmentierung von α, β-Epoxy-ketonen mit p-Toluolsulfonylhydrazin. Vorläufige Mitteilung

More than twenty examples illustrate the recently developed oxidoketone-alkynone-fragmentation, whereby α,β-epoxy-ketones are cleaved under mild conditions with p-toluenesulfonyl-hydrazine to give acetylenic ketones or aldehydes.