Etherspaltung an Pyridinen mit ungewöhnlichem Halogenierungsverlauf zu isomeren Diamino-pyridon-carbonitrilen und ihre Verwendung als Kupplungskomponenten

Ether cleavage of the two isomeric diamino-methoxy-pyridine-carbonitriles1 and2 leads to the isomeric 4,6-diamino-2(1H)-pyridone-3-carbonitrile (3 a) and 2,4-diamino-6(1H)-pyridone-3-carbonitrile (4 a), resp. Dependent on the reaction conditions in glacial acetic acid containing hydrogen bromide or potassium iodide the halogenated pyridones (3 b, 4 b–c) can be obtained.pK _s -values and UV-spectra of the pyridones are discussed.3 a and4 a can be used as azo-coupling components, yielding the azo-dyes5 and6. Similarly 4-amino-6-hydroxy-2(1H)-pyridones (7 a–b) are coupled with several aryl- and heteroaryl-diazoniumsalts to form the azo-dyes8 a–g.

Herrn emer. o. Univ.-Prof. Dr.Otto Hromatka zum 80. Geburtstag gewidemet.     

Synthese und Reaktivität von 2- und 3-hydroxylierten Dihydro-1,4-Benzoxazinen

2 can be pyrrolized to yield3 a, which in turn may be hydrolyzed with HCl to3 b. Acetylation of3 a followed by a reaction with trifluoroacetic acid (TFA) gives3 e. Elimination of ethanol from3 a or of water from3 e is not possible. Treatment of1 a with pyridine/acetic anhydride andTFA or with acetic acid/acetic anhydride affords4 a and4 b, resp. Reaction of4 b in benzene/p-toluenesulfonic acid for 2 hours yields both ethers5I and5II, whereas after 6 hours 4-acetyl-4H-1,4-benzoxazine (6) is obtained. The structures of all products are established by chemical and spectroscopic methods.

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

Synthese von 1-Ary1-4-methylthio-2-azetidinonen

TheN-arylthioformimidates4 a-e, which may be obtained byS-alkylation of the thioformanilides3 a-e, react with chloroacetylchloride/triethylamine to yield the (3R,4S/3S,4R)-1-aryl-3-chloro-4-methylthio-2-azetidinones5 a-e and the formanilides6 a-e. Dehalogenation of5 b-e with tri-n-butyltinhydride yield the title compounds7 b-e. Hydrogenolysis of7 b and7 c yields7 f and7 g.

     

DMF acetals as alkylating and cyclizing agents: A facile route to substituted pyrazolo[3,4-d]pyrimidine-4,6(5H,7H)-diones

Summary Several 7-methyl-5-alkyl-2-vinylpyrazolo[3,4-d]pyrimidine-4,6(5H,7H)-diones were prepared. The successful cyclization and alkylation of 6-(-methylbenzylidenehydrazino)-1-methyluracils2a–d using dimethylformamide acetals at high temperature provided6a–d,7a–d, and8a–d. Treatment of6a–d and7a–d with acid afforded 7-methyl-5-alkylpyrazolo[3,4-d]pyrimidine-4,6(5H,7H)-diones9a,b; under the same conditions,3a–d reacted to 7-methylpyrazolo[3,4-d]-pyrimidine-4,6(5H)-dione (4) in good yield.

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DMF-Acetale als Alkylierungs- und Ringschlußreagentien: ein einfacher Weg zu substituierten Pyrazolo[3,4-d]pyrimidin-4,6(5H,7H)-dionen

Zusammenfassung Es wurden verschiedene 7-Methyl-5-alkyl-2-vinylpyrazolo[3,4-d]pyrimidin-4,6(5H,7H)-dione hergestellt. Cyclisierung und Alkylierung der 6-(-Methylbenzylidenhydrazino)-1-methyl-uracile2a–d mit Hilfe von Dimethylformamidacetalen bei hohen Temperaturen ergab6a–d,7a–d und8a–d. Behandlung von6a–d und7a–d mit Säure lieferte die 7-Methyl-5-alkylpyrazolo[3,4-d]pyrimidin-4,6(5H,7H)-dione9a,b; unter den gleichen Bedingungen reagierten3a–d in guter Ausbeute zu 7-Methylpyrazolo[3,4-d]pyrimidin-4,6(5H)-dion (4).

     

Über Darstellung und Reaktivität von 2,4-Diazabicyclo[3.3.1]nonan-3-onen

The 2-cyclohexenones1 a andd resp. react with urea in HCl/EtOH to give 1-hydroxy-4-methyl-7-phenyl- and 1-hydroxy-2,4-diazabicyclo[3.3.1]nonane-3-ones3a and3d resp., whereas the 2-cyclohexenones1b andc resp. transformed by urea to 1,7-dimethyl- and 1-methyl-4-ureido-2,4-diazabicyclo[3.3.1]nonan-3-ones9b andc resp. In the condensation of isophorone1e with urea a product C₁₃H₂₈N₈O₄ of indisdinct structure was formed, whereas the bicyclus3e could not be isolated.Reaction ofAcOAc with3a yielded the 5-methyl-3-oxo-7-phenyl-2,4-diazabicyclo[3.3.1]non-1-ylacetate (15); on heating of3a with acids decomposition to1a and urea took place. NoWagner-Meerwein-rearrangement was observed. The MS-spectra of3a andd are discussed; NMR- and IR-data are reported.No significant herbicidal, fungicidal or insecticidal activity was found in screening-tests on3a.

     

Synthese und Konfigurationszuordnung von potentiell antimikrobiellen 5,6-Dihydroxyisobenzofuranonen

Summary Oxidation of isobenzofuranone1 yielded in a diastereoselective reaction epoxide2. Acidolysis of2 resulted in a mixture oftrans-glycols6 a (88%) and7 a (4%), which were separated by crystallization. The relative configuration of6 a and7 a at the chiral centers 3 a, 5, 6, and 7 a was determined by¹H-NMR-spectroscopy and X-ray analysis of O-acetylated and 7 a-methylated derivatives.

     

Synthese von Benzofuranen durch Cyclodehydrierung von Phenylmalonylheterocyclen

Phenylmalonyl heterocyclic compounds such as the quinolones1a–c or3, benzoquinolizinones6a, b and the phenalenones8a, b can be converted to benzofuranes (2a–c, 7a, b and9a, b) by cyclodehydrogenation with Pd/C in boiling diphenyl ether. 2-Phenylchinchonic acid (10) reacts under the same conditions to the dimeric benzofuroquinoline12: the decarboxylated quinoline11 however gives the monomer13.

Herrn Prof. Dr.G. Zigeuner zur Vollendung seines 60. Lebensjahres gewidmet.     

Vergleichende Reaktivitätsuntersuchungen am neuen Codimeren aus Malonitril und Cyanessigester an Carbonylverbindungen

The reactivity of 3-amino-2,4-dicyano-methyl-(1d) and-ethyl-crotonate (1e), resp., a new type of codimer from malononitrile and cyanoacetate, was investigated. Condensation reactions with aromatic aldehydes (2a-g), with heterocyclic aldehydes (2j-l), nitrosobenzenes (3a-c) ando-hydroxybenz-and-naphtaldehydes (4a-f), resp., are described, the differences in reactivity, compared with dimer malononitrile and dimeric forms of cyanoacetate (1a-c) are negligible. Condensation compounds of1a with cycloalkanones (5a-c) are able to cyclise with sulfur to cycloalkanonothieno-pyridines (6a-b), while the cycloalkano-derivatives of1d gave no ring closure.

Herrn Prof. Dr.O. E. Polansky zum 60. Geburtstag in Erinnerung an gemeinsame Tätigkeiten auf dem Gebiet der Nitrilchemie gewidmet.     

Über die Darstellung der 7R-Oxirane von 5Z- und 5E-10-Oxo-19-norcholecalciferol

Summary The two title compounds12b and13b have been prepared by direct oxidation of the corresponding 10-oxo-19-norcolcalciferol derivatives3c and4c withMCPBA. The generation of12b and13b by treatment of the ⁷ epoxidized ethylisoxazolin adducts of 5Z- and 5E-cholecalciferol8a,8b and9a,9b with Mo(CO)₆ failed, since besides the retroaldol cleavage of the heterocycle a deoxygenation of the oxirane with retention of configuration to the ⁷ double bond occurs.

     

[a]-Anellated carbazoles with antitumor activity: Synthesis and cytotoxicity

Summary The cycloadducts3,5, and7, readily available from methoxy-substituted 3-vinylindoles1 and2, were dehydrogenated withDDQ to the coplanar [a]-anellated carbazoles4,6, and8. Compound4a, also characterized by X-ray structural analysis, shows significant cytotoxicity against K562 und RXF393 human tumor cell lines.

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[a]-Anellierte Carbazole mit Antitumoraktivität: Synthese und Cytotoxizität

Zusammenfassung Die aus den methoxysubstituierten 3-Vinylindolen1 und2 zugänglichen Cycloaddukte3,5 und7 lassen sich mitDDQ zu den coplanar-anellierten Carbazolen4,6 und8 dehydrieren. Verbindung4a, die auch durch eine Röntenstrukturanalyse charakterisiert wurde, zeigt signifikante Cytotoxizität gegen Humantumor-Zellinien (K562 und RXF93).

     

Synthesis and stereochemistry of 8-methyl-5-nitro-1-octalones

Summary Base catalyzedMichael addition of 5-nitropentan-2-one ethylene ketal (1) and cyclohex-2-enone (2), subsequent deprotection, and intramolecular aldol condensation yields the 8-methyl-5-nitro-1-octalone isomers (5a,b). The structure, relative configuration, and conformation of5a and5b were elucidated utilizing the results of¹H and¹³C NMR investigations

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Synthese und Stereochemie von 8-Methyl-5-nitro-octalonen

Zusammenfassung BasenkatalysierteMichael-Addition von 5-Nitropentan-2-on-ethylenketal (1) und Cyclohex-2-enon (2), anschließende Entfernung der Schutzgruppe und darauffolgende Aldolkondensation liefert isomer 8-Methyl-5-nitro-1-octalone (5a,b). Struktur, relative Konfiguration und Konformation von5a und5b wurden mittels¹H- und¹³C-NMR-Spektroskopie aufgeklärt.

     

Über die Reaktionen von 2-Cyclohexenonen mit Guanidin

3-Methyl-5-phenyl-2-cyclohexenone (6 a), 3,5-dimethylcyclohexenone6 b, 3-methylcyclohexenone6 c and 2-cyclohexenone (6 d) resp. react with guanidine in toluene and methanol resp. to give the substituted 2,4-diazabicyclo[3.3.1]nonane-3-imines7 a-d. The condensation of isophorone6 e with guanidine (to form7 e) could not be accomplished. The structures of the compounds7 a-d are deduced from their IR- and NMR-spectra; the mechanism and the steric course of the reaction are discussed. Salts of7 a-d were also prepared.7 a andb showed no significant herbicidal and only small fungicidal and insecticidal activities in screening tests.

Vergleiche auch die 58. und 59. Mitt., Mh. Chem., im Druck.     

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).

     

Über Reaktionen mit Betain, 13. Mitt.: Darstellung von trihalogenacetyl-methyliden und ihrer Salze aus Betainen

Reaction of the betaine1 and pyridinebetaine8 with trifluoroacetic anhydride yields the salts4a or9a and the yellow ylide5, respectively. In an analogous manner8 reacts with trichloroacetic anhydride to give11a. In a competitive reaction the trifluoroacetates6 and10 are also formed. Pyridinebetaine hydrochloride reacts similarily with trichloroacetic anhydride.

12. Mitt.:Wittmann H., Sobhi D., Petio F. A., Z. Naturf.31 b, 850 (1976).     

NMR studies of 4(3H)-quinazolinones and 4(3H)-quinazolinethiones

Summary Unambiguous¹H and¹³C NMR assignments for 4(3H)-quinazolinones1–6 and their corresponding 4-thiones7–12 have been made. This resulted in the revision of the previous assignments for the two benzenoid carbons (C-5 and C-8) of quinazolinones1,2,4, and5. Thionation of the nucleophilic amides1–6 has been found to cause a distinct change in the¹³C chemical shift of particularly C-4, but also of those of C-4a, C-5, and C-8a. One-bond and several long range heteronuclear coupling constants for the compounds have also been measured.

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Kernresonanzspektroskopie von 4(3H)-Chinazolinonen und 4(3H)-Chinazolinthionen

Zusammenfassung Die¹H- und¹³C-NMR-Spektren der 4(3H)-Chinazolinone1–6 und ihrer entsprechenden 4-Thione7–12 wurden zugeordnet. Dabei zeigte sich, daß eine frühere Zuordnung der beiden benzoiden Kohlenstoffe (C-5 und C-8) der Chinazolinone1,2,4 und5 falsch war. Ersatz des Sauerstoffs durch Schwefel in den nukleophilen Amiden1–6 führt insbesondere für C-4, aber auch für C-4a, C-5 und C-8a zu einer deutlichen Änderung der chemischen Verschiebung. Heteronukleare Kopplungskonstanten über eine und über mehrere Bindungen wurden bestimmt.

     

Prins-Reaktionen mit Arylaldehyden, 5. Mitt.: Zur Umsetzung mit 2-Buten und mit Cyclohexen

By reaction of 2-[(1RS, 2RS)-2-hydroxy-1-methyl-propyl]-2-phenyl-1,3-dithiane (1 a) withcis-2-butene oxide, subsequent reduction and acetalizationc-4,t-5-dimethyl-r-2,c-6-diphenyl-1,3-dioxane (3 a) andt-4,c-5-dimethyl-r-2,c-6-diphenyl-1,3-dioxane (3 b) were synthesized as model compounds. For the same purpose by aldol reaction of cyclohexanone and reduction (1RS, 2SR)-2[(RS)-hydroxy-(4-methoxyphenyl)methyl]cyclohexanol (7 a), (1RS, 2RS)-2[(SR)-hydroxy-(4-methoxyphenyl)methyl]cyclohexanol (8 a), and (1RS, 2RS)-2[(RS)-hydroxy-(4-nitrophenyl)methyl]cyclohexanol (8 b) and by acetalization (2 , 4 , 4 a, 8 a)-2,4-bis(4-methoxyphenyl)hexahydro-4H-1,3-benzodioxin (9 a) and (2 , 4 , 4 a, 8 a)-2,4-bis(4-nitrophenyl)hexahydro-4H-1,3-benzodioxin (10 b) were obtained. FromPrins reactions, starting with 2-butene3 a,c-4,c-5-dimethyl-r-2,c-6-diphenyl-1,3-dioxane (3 c),r-4,t-5-dimethyl-c-6-phenyl-1,3,2-dioxathiane-2,2-dioxide (4), and (2Z, 4E)-1,5-diphenyl-4-methyl-2,4-pentadien-1-on (5), and starting with cyclohexene (E)-3-(4-methoxybenzylidene)cyclohexenyl-4-methoxyphenyl ketone (11) have been isolated in low yields.

4. Mitt.:Griengl, H., Nowak, P., Mh. Chem.109, 11 (1978).     

synthesis of sempervirine,a pentacyclic anhydronium indole alkaloid

Summary Sempervirine (2,3,4,13-tetrahydro-1H-benz[g]indolo[2,3-a]quinolizin-6-ium,1) the pentacyclic anhydronium indole alkaloid ofGelsemium sempervirens Ait. f. (Loganiaceae), has been synthesized in three steps from hexahydroisochroman-3-one (6) and N-2-(3-indolyl)-ethylamine (tryptamine,7). The condensation product, N-2-(3-indolyl)-ethyl-2-(hydroxymethyl)-trans-hexahydrophenylacetamide (8) arising from6 and7 on double cyclization with phosphoryl chloride yielded the 3,4-dehydroyohimbane derivative9. Aromatization of rings C and D of compound9 with 2,3-dichloro-5,6-dicyanobenzoquinone (DDQ) in glacial acetic acid, followed by basification, generated sempervirine (1).

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Synthese von Sempervirin, einem pentacyclischen Anhydronium-Indolalkaloid

Zusammenfassung Sempervirin (2,3,4,13-Tetrahydro-1H-benz[g]indolo[2,3-a]chinolizin-6-ium,1), das pentacyclische Anhydronium-Indolalkaloid vonGelsemium sempervirens Ait f. (Loganiceae) wurde ausgehend von Hexahydroisochroman-3-on (6) und N-2-(3-Indolyl)-ethylamin (Tryptamin,7) in 3 Stufen synthetisiert. Das durch doppelte Cyclisierung von6 und7 mit Phosphorylchlorid entstehende Kondensationsprodukt N-2-(3-Indolyl)-ethyl-2-(hydroxymethyl)-trans-hexahydrophenylacetamid (8) ergab das 3,4-Dehydroyohimbanderivat9. Aromatisierung der Ringe C und D von9 mit 2,3-Dichlor-5,6-dicyanobenzochinon (DDQ) in Eisessig und anschließende Einstellung eines basischenpH-Werts lieferte Sempervirin (1).

     

Zur Darstellung von 6-Oxo-2H-pyrano[2,3—c]pyrazolen

By the reaction of 4-dimethylaminomethylene-3-methyl-1-phenylpyrazol-5-one (3) with methylene compounds like malonodinitrile, cyanoacetamide and alkyl cyanoacetate a number of different substituted title compounds may be prepared. The mechanism of this reaction is illucidated by isolation of the intermediate ethenyl compounds7, 8, 11, 14 and16. The reaction therefore is best described as a sequence of addition, elimination and cyclisation with partial hydrolysis.

6. Mitt.:H.-H. Otto undO. Rinus, Arch Pharm. (Weinheim)312, 548 (1979).     

Synthese und Reaktionsverhalten von 3-(Bis(alkylthio)methylen)-3H-isobenzofuran-1-on-und 2-(Bis(alkylthio)methylen)-3(2H)-benzofuranon-Derivaten

Summary 3(Bis(alkylthio)methylene)-3H-isobenzofuran-1-ones2a–e and 2-(bis(alkylthio)methylene)-3(2H)-benzofuranone derivatives4a–c are obtained by reaction of phthalides1a–d or 3(2H)-benzofuranone (coumaranone3), respectively, with carbon disulfide under basic conditions followed by alkylation. The reaction behaviour of the new compounds2 and4 is investigated. 2-((2-Dimethylthio-1-oxo)ethyl)benzoic acid N,N-dimethylamide (7a) and 2-((2-dimethylthio-1-oxo)ethyl)-benzoic acid 2-methylpiperidide (7b) are surprisingly formed instead of the methylthio substitution products by treatment of2a with the corresponding amine in the presence of aluminum chloride.

Herrn Professor Dr. Dr. h. c.Waldemar Adam zum 60. Geburtstag gewidmet     

Über die Umsetzung von Dibenzylidensulfamiden mit Aminen

Addition of amines to dibenzylidene sulfamide1 a yields the correspondingSchiff bases3 a, b and monobenzylidene sulfamide2. Reaction of several dibenzylidene sulfamides1 with various lithium-amides gives N¹-substituted N²-benzylsulfamoyl-benzamidines7 a-k via an intramolecular hydride transfer reaction, whereas by treatment of1 a with sodium amide 2-benzyl-3,5-diphenyl-3,4-dihydro-2H-1,2,4,6-thiatriazine-1,1-dioxide8 is obtained, which on hydrolysis yields9 and11. Alkylation products are described, the isomeric products12a/13a and12b/13b are isolated, their structures are confirmed by synthesis, IR and NMR-spectra.