Zur Synthese vonendo-konfigurierten Isocamphanderivaten

The syntheses of 46endo-configurated isocamphane derivatives starting from camphenilanic acid (1) are described. Theendo-configuration of the new compounds at position 2 of the bicyclus was retained throughout as has been established by¹H-NMR spectroscopy.

     

Synthesis in the isocamphane series,XVI. The regioselectivity of some lewis acids in the catalyzed Diels-Alder-reaction of cyclopentadiene and mesityloxide

Zusammenfassung The regioselectivity of 9Lewis acids in the catalyzedDiels-Alder-reaction of cyclopentadiene and mesityloxide is described and theendo: exo-ratio of1 a and1 b determined by quantitative HPLC- and¹H-NMR-measurements. The reaction mixture of1 a+1 b normally contains more of theendo epimer1 a, e.g. 31 for1 a1 b, and is therefore in agreement with theendo rule, only TiCl₄ favors theexo epimer1 b.

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Synthesis in the isocamphane series, XVI. The regioselectivity of some lewis acids in the catalyzed Diels-Alder-reaction of cyclopentadiene and mesityloxideShort communication

Teil der Diplomarbeit vonHuber, U., Universität Wien, 1980.     

Isocamphananaloge mandelsäure

The synthesis of some new potentially, nitrogenefree spasmolytics is described. Formally the benzene nucleus in some mandelic acid esters, known by their mild spasmolytic activity, is substituted for the isocamphane bicyclus by a) SeO₂ oxidation of 1-(3,3-Dimethyl-2-exo-norbornyl)-ethanone (5) to the corresponding ketoaldehyde6, b) oxidation of6 to the isocamphane analogous mandelic acid4 and c) esterification of derivatives of4 with isoamylalcohol and benzylalcohol. Attemps to dehydrate the methylester7 to camphenylideneacetic acid methylester (12) by various methods failed, probably because of the ring strain.

Teil der Diplomarbeit vonB. Blach, Universität Wien 1981.     

Über eine neue Synthese von Camphenilansäure und Isocamphenilanaldehyd Synthesen in der isocamphanreihe, 5. Mitt.

Improved procedures for the preparation of the title compounds are described. The new synthesis of camphenilanic acid (6) opens a new way for the preparation ofendo-configurated derivatives of6.

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Herrn Univ.-Prof. Mr. pharm. Dr.K. Jentzsch mit besten Wünschen zum 65. Geburtstag gewidmet.     

Pheromone, 1. Mitt.: (+)-cis-Disparlure: Synthese und Feldtests

Summary A synthesis of (+)-cis-disparlure is described starting from racemic 2-hydroxy-dodecannitrile (2), which is transformed into the O-protected enantiomerically pure cyanohydrine4. Grignardreaction followed by reduction with BH₃ · (CH₃)₂S yields the correspondingthreo-configurated secondary alcohol10. After tosylation and cleavage of theMBE-protective-group (+)-cis-disparlure (14) is obtained by treatment with KOH. Mating disruption field tests exhibited a significantly increased effectiveness of (+)-cis-disparlure as compared to the racemic product.

Unserem verehrten Lehrer Professor Dr. O. Hromatka zum 85. Geburtstag gewidmet     

1,3-Dipolare Cycloadditionen von 3,4-Dihydro-6,7-dimethoxyisochinolinium-N-methoxycarbonylmethylid mit N-substituierten Maleinimiden

Summary 1,3-Dipolar cycloadditions of 3,4-dihydro-6,7-dimethoxyisoquinolinium-N-methoxycarbonylmethylide2 with N-phenyl- and N-methylmaleimide (3 and4) have been investigated. Cycloadducts of theendo- andexo-type were formed, the structure elucidation and conformational analysis of which has been performed by NMR methods.

     

Synthesen in der Isocamphanreihe, 38. Mitt.: Ozonolyse von 2-Acetyl-3,3-dimethylnorborn-5-en und Synthese eines neuen,tricyclischen Ketals mit patchouliartigem Geruch

Summary The ozonolysis ofendo-2-acetyl-3,3-dimethylbicyclo[2.2.1]hept-5-ene (endo-1) and itsexo-epimer (exo-1) is described. The reaction products, after reductive work up as well as after oxidative work up, are characterized. The first procedure furnished the corresponding cyclopentane derivatives in good yield, namely 1,1-dimethyl-2-(1-hydroxyethyl)-3,5-bis-hydroxymethyl cyclopentane (2) as a cristalline compound fromendo-1, the epimeric10 as an oil fromexo-1. The oxidative work up furnished in both cases via keto-enol-tautomerism the same acid, 4-acetyl-5,5-dimethyl-1,3-cyclopentane dicarboxylic acid, characterized as its methyl ester. Selective oxidation of the secondary hydroxyl group in2 lead to the novel, tricyclic, even acid stable ketal17, with very interesting olfactory properties.

Herrn Prof. Dr. Ulrich Schmidt mit den besten Wünschen zum 70. Geburtstag gewidmet     

Der Einfluß von Stickstoffsubstituenten bei der Synthese von 3-Methyl-1,4-Benzoxazinen

Starting from1 the azomethine2 is obtained. The intermediates4 a and4 b of this reaction sequence cause the high yields. Cyclization of theN-alkylderivatives4 d and8 b leads also to an azomethine, which is obtained as its salt11. Cyclization of theN-acetylderivative13 yields however the anamine14. The structures of the new products are established by chemical and spectroscopic methods.

Teile aus der DissertationW. Kropp, Universität Wien, 1977.     

Syntheses and absolute stereochemistry of chiral 9,10-dihydro-9,10-ethanoanthracenes and their tricarbonylchromium complexes

Summary Several chiral mono- and disubstituted 9,10-dihydro-9,10-ethanoanthracenes have been prepared from the corresponding anthracenes. Most of them were separated into enantiomers by chromatography on cellulose triacetate (CTA) and their absolute chiralities established by chiroptical comparison (via their CD spectra) with key compounds of known configuration. From the laevorotatory 1,5-dibromo derivative16 the dextrorotatory dideuterio hydrocarbon (+)(9S, 10S)-20 was obtained.Complexation of 2,6-dimethyl 9,10-dihydro-9,10-ethanoanthracene (+)-25, obtained by enantio-selective chromatography onCTA [with its chirality (9R, 10R) deduced from optical comparison with the 2-monomethyl derivative of known configuration], with Cr(CO)₆ afforded two mono tricarbonyl-chromium complexes [endo(+)-26 andexo(+)-27] as well as the bis-exo,endo-complex (+)-28. Configurational assignments (exo, endo) are based on the absorption patterns of the bridge protons in the¹H-NMR spectra.On leave from Research Institute of Chemical Processing and Utilization of Forest Products, Nanking, P.R. China. mit Cr(CO)₆ lieferte zwei Mono-tricarbonylchrom-Komplexe [endo(+)-26 undexo(+)-27] neben dem Bis-exo,endo-Komplex (+)-28. Die konfigurative Zuordnung (exo,endo) war aufgrund der Absorptionen der Brücken-H-Atome in den¹H-NMR-Spektren möglich.     

δ-Santalolanaloga I Synthesen in der Isocamphanreihe, 27. Mitt.

The synthesis of 4-(3,3-dimethyl-2-exo-norbornyl)-2-methyl-2-buten-1-ol (5), an analogue of -santalol (1) has been described. One route to5 starts with isocamphenilanyl propionic acid (8) which can be prepared in 4 steps from isocamphenilanic acid (9). Also 4 steps lead from8 to the target molecule5 with an overall yield of 24%. By a second and more convergent route, starting from the very easily obtainable bicyclic ketone19, the allylic alcohol5 could be obtained again in 4 steps, but this time with an overall yield of 1.3%. A new and easy synthesis of isocamphenilanyl acetic acid (15), a potential starting material to5, has been described, also the preparation of some new isocamphane derivatives.

26. Mitt:Buchbauer G,Pernold W,Ittner M,Ahmadi MF,Dobner R,Reidinger R (1985) Monatsh Chem 116: 1209     

Preparation and stereoselectivity of 1,3-dipolar cycloaddition of C-glycosyl nitrones to N-arylmaleimides

Summary The cycloaddition of 3-hydroxyglycosyl-N-methylnitrone (1) to N-arylmaleimides gave thesyn isoxazolidines6, whereas 3-acetoxyglycosyl-N-methylnitrone (2) afforded theanti isoxazolidines8 and10. The formation of6 was rationalized by anexo attack, stereoelectronically preferred through the hydrogen bond between the pentose hydroxyl group and one of the carbonyl groups of N-arylmaleimide. The sterically preferredendo attack avoiding the repulsions between N-arylmaleimide and sugar moiety was proposed for addition of2. The structure and steric configuration of the products have been assigned on the basis of¹H- and¹³C-NMR spectroscopy, mainly by nuclear Overhauser effect difference spectroscopy. AM1 calculations of the nitrones and MM2 calculations of the adducts were performed.

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Darstellung und Stereoselektivität der 1,3-dipolaren Cycloaddition von C-Glycosyl-Nitronen an N-Arylmaleimiden

Zusammenfassung Die Cycloaddition von 3-Hydroxyglycosyl-N-methylnitron (1) an N-Arylmaleimide gab diesyn-Isoxazolidine6, mit 3-Acetoxyglycosyl-N-methylnitron (2) wurden hingegen dieanti-Isoxazolidine8 und10 erhalten. Die Bildung von6 wurde mit einemexo-Angriff erklärt, der stereoelektronisch wegen einer Wasserstoffbrückenbindung zwischen der Hydroxylgruppe der Pentose und einer Carbonylgruppe des N-Arylmaleimides bevorzugt wird. Für die Addition von2 wurde ein sterisch bevorzugterendo-Angriff vorgeschlagen, da dabei ungünstige Wechselwirkungen zwischen der N-Arylmaleimid- und der Zuckereinheit vermieden werden. Die Struktur und Stereochemie der Produkte wurde mittels¹H- und¹³C-NMR unter Verwendung von NOE-Differenzmessungen ermittelt. Es wurden auch AM1-Rechnungen für die Nitrone und MM2-Rechnungen für die Addukte durchgeführt.

     

NMR-spektroskopische Untersuchungen zurE/Z-Isomerie von substituierten Dithiocarbazinsäurederivaten

Summary NMR-spectroscopic investigations of substituted dithiocarbacinic acid derivatives show the existence of configurational isomers relative to the C=N double bond, but no tautomerism. We applied chemical shift differences in the¹H-,¹³C- and¹⁵N-NMR-spectra, N - H and C - H coupling constants and NOE difference measurements in the solvents CDCl₃,DMSO-d ₆ and partly CD₃OD in order to discriminate between the isomers and to determine the configurational composition. Compounds4 and5 exist asE-isomers in all solvents, compounds1, 2 and3 as a mixture ofE/Z-isomers. InDMSO-d ₆ theE-form is the preferred isomer.

     

Untersuchungen zur Hydrolyse von 3,5,10,12-Tetramethoxy-3,5,10,12-tetrahydro-[2.2](2,5)furanophan

Hydrolysis of2 in 0.005M-H₂SO₄ yields3, which forms two stereomeric bicyclic compounds4 and5 by ketol addition. In 0,5M-H₂SO₄ 2 yields the furanophane12, which in turn yields the diasteromeric tetracycles9 and10, which on hydrolysis yield theas-indacene11. The structures and configurations of the new compounds were proved by chemical and spectroscopic methods.

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Teilweise aus der Dissertation vonE. Zeisl, Univ. Wien, 1976.     

Derivate der 5,6-Dihydro-2H-pyran-3-carbonsäure

Summary Some derivatives of 5,6-dihydro-2H-pyran-3-carboxaldehyde (7) and of its oxidation product 5,6-dihydro-2H-pyran-3-carboxylic acid (8) have been prepared. The aldehyde derivatives as well as the amides and esters of8 have been tested in an insecticidal/fungicidal/acaricidal screening programme. The methylester35 shows a distinct knock down effect against the fruit flyDrosophila melanogaster.

     

Zur Stereochemie der Vitamin D3-Epoxide Röntgenstrukturanalyse einer 5,6-7,8-Diepoxidverbindung

Epoxidation of vitamin D₃ with benzonitrile ¦H₂O₂¦ KHCO₃ (Payne's reagent) yields exclusively the 5,6-mono-oxirane2. Further epoxidation with the same reagent gives the 5,6-7,8-bisepoxide3 a. Its stereochemistry and therefore the stereochemistry of2 was established by single crystal X-ray analysis of thep-Brbenzoate3b. Thereby for the first time a directive effect of a homoallylic hydroxyl group during thePayne-epoxidation was established.

Herrn Prof.Mihailovic (Universität Belgrad) mit den besten Wünschen zum 60. Geburtstag gewidmet.     

A simple synthesis of 2,4-diaryl-1,3,5-triazines

Summary Arylamidines2 react with 5-methoxymethylen-2,2-dimethyl-1,3-dioxan-4,6-dione5 to give 2,4-diaryl-1,3,5-triazines in moderate to good yields.5 can be comprehended as a formic acid derivative which transfers a C₁-building block. Other formic acid derivatives give only poor to moderate yields of triazines by treatment with amidines. The synthetic method is applicable to aromatic amidines.

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Eine einfache Synthese von 2,4-Diaryl-1,3,5-triazinen

Zusammenfassung Die Arylamidine2 reagieren mit 5-Methoxymethylen-2,2-dimethyl-1,3-dioxan-4,6-dion5 in guten Ausbeuten zu 2,4-Diaryl-1,3,5-triazinen. Verbindung5 kann als Derivat der Ameisensäure aufgefaßt werden, welches einen C₁-Baustein überträgt. Andere Derivate der Ameisensäure ergeben bei Umsetzung mit Amidinen nur schlechte Ausbeuten an Triazinen. Die beschriebene Methode ist auf aromatische Amidine anwendbar.

     

Untersuchungen zur Synthese des Nodusmicin,I: Darstellung von (±)-(1R*,5R*,6R*,7S*8R*,9R*,10R*)-5-Acetyl-7,9-dibenzyloxy-10-hydroxy-8-methylbicyclo[4.4.0]decan-3-on

Summary Our first target on the way towards the synthesis of nodusmicin is the preparation of the title compound. Meso diol1 is partially etherified, then oxidized to the enone. The sterically compressed structure of this compound is the rationale of the highly stereoselective introduction of the substituents. (CH₃)₂CuLi introduces the methyl group and the enolate is captured as silylenol ether, which in turn is transformed to the -hydroxyketone by OsO₄. Reduction leads to the vicinaltrans diol. Protection of theexo-hydroxy group is followed by treatment with sodium in ethanol. Via intramolecular nucleophilic addition, substitution and dechlorination the tetracyclic diketal8 is formed. After exchange of the protective groups and partial hydrolysis of the ketals the tertiary alkohol is obtained with methyl Grignard reagent. Acidic fragmentation yields the desired title compound.

     

Reaktionen mit Dimethylformamid, 1. Mitt.: Synthese von Carbonsäuredimethylamiden

Zusammenfassung Carbonsäure-N,N-dimethylamide können unter Umgehung der Säurechlorid-oder-anhydridstufe direkt aus der Carbonsäure und Dimethylformamid (DMF) in Gegenwart von P₂O₅ dargestellt werden. Diese Methode eignet sich besonders für Säuren, deren Chloride oder Anhydride nicht oder nicht leicht zugänglich sind. Die Darstellung von 10 neuen Carbonsäuredimethylamiden nach diesem Verfahren wird beschrieben. Die Ausbeuten bewegen sich zwischen 40 und 95%. Über die Acetyl-, Benzoyl- und Phenylurethanderivate der Hydroxyphenylcarbonsäuredimethylamide wird berichtet.

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Carboxylic acid N,N-dimethylamides may be obtained directly from the corresponding carboxylic acids and dimethylformamide in the presence of P₂O₅, thus avoiding the preparation of the acid chloride or acid anhydride. The method therefore is particularly useful for reactive or unstable acid derivatives. The preparation of 10 N,N-dimethylamides with 40 to 95% yield, and of the acetyl, benzoyl and phenylurethane derivatives of the N,N-dimethylhydroxyphenylcarboxamides is reported.

     

Reaction of mercury salts with dimethyl tricyclo [4.2.2.02,5]deca-3,7-diene-cis-endo-9,10-dicarboxylate in acetic acid

The reaction of dimethyl tricyclo[4.2.2.0^2,5]deca-3,7-diene-cis-endo-9,10-dicarboxylate with mercury salts Hg(OCOR)₂ (R=CCl₃, CF₃, CH₂Cl) in acetic acid yields a mixture of solvoadducts and products of addition of the anionic moiety of the reagent having thetrans-configuration. In the case of Hg(OCOCCl₃)₂,cis-solvoadduct was detected along with thetrans-isomer. The amount of the addition products is determined by the nature of the mercury salt and increases in the order Hg(OCOCH₂Cl)₂<Hg(OCOCCl₃)₂=Hg(OCOCF₃)₂. The reaction is assumed to involve contact and solvent-separated ion pairs. Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 11, pp. 2173–2176, November, 1999.     

Preparation and steric structure of 3(2H)-pyridazinones and 1,2-oxazin-6-ones fused with three- to six-membered saturated carbocycles or norbornane skeleton

Summary Reactions ofcis-2-(4-methylbenzoyl)-cyclopropane- (1) and-cyclobutanecarboxylic acids (2), the stereoisomeric cyclohexyl homologues (3 and4), and di-endo-3-(4-methylbenzoyl)-bi-cyclo-[2.2.1]heptane-2-carboxylic acid (5) with hydrazines yield the cycloalkane-condensed (3(2H)-pyridazinones6–9 and the norbornane di-endo-fused derivatives10. With hydroxylamine, compounds1 and3–5 were transformed to the cycloalkane- and norbornane-condensed 1,2-oxazin-6-ones11–14. Transformation of3–5 led to thetrans-hexahydroanthrone17a and its methylene-bridged analogue24. From the stereoisomeric hexahydro-1(3H)-isobenzofuranones20 and21, the partly saturated anthrones were also prepared; the products (16b and17b) contain the methyl substituent in position 6. On reduction,16b yield the 2-methyloctahydroanthracene22. The structures of the compounds were proved by¹H and¹³C NMR spectroscopy, making use of NOE, DEPT, and CH-COSY techniques.

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Synthese und räumliche Struktur von mit drei- bis sechsgliedrigen gesättigten Homocyclen oder Norbornan kondensierten 3(2H)-Pyridazinonen und 1,2-Oxazin-6-onen

Zusammenfassung Die Reaktion voncis-2-(4-methylbenzoyl)-cyclopropan-(1) und-cyclobutancarbonsäuren (2), der stereoisomeren cyclohexyl-Homologen (3 und4) und von di-endo-3-(4-methylbenzoyl)-bicyclo[2.2.1]heptan-2-carbonsäure (5) mit Hydrazinen ergibt die cycloalkankondensierten 3(2H)-Pyridazinone6–9 und das methylenüberbrückte di-endo-Derivat10. Die Verbindungen1 und3–5 wurden mit Hydroxylamin zu den cycloalkan- und norbornankondensierten 1,2-Oxazin-6-onen11–14 umgesetzt.3–6 reagierten zumtrans-Hexahydroanthron17a und seinem methylenüberbrückten Analogen24. Die teilweise gesättigten Anthrone wurden auch aus den stereoisomeren Hexahydro-1(3H)-isobenzofuranonen20 und21 hergestellt (16b und17b), wobei der Methylsubstituent jedoch in Position 6 lokalisiert ist. Reduktion von16b ergab das 2-Methyloctahydroanthracen22. Die Strukturen der Verbindungen wurden durch NMR-Spektroskopie abgesichert (¹H,¹³C, DEPT, CH-COSY, NOE).