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.

     

The preparation of 5-(2-aminophenyl)-1,3,4-oxadiazole-2(3H)-one and its rearrangement to 3-amino-2,4(1H,3H)-quinazolinedione

When anthranilic acid hydrazide is reacted with 1,1-carbonyldiimidazole inTHF 5-(2-aminophenyl)-1,3,4-oxadiazole-2(3H)-one (4) is formed. It can also be prepared from 1-o-aminobenzoyl-4,4-dimethylsemicarbazide which eliminates methylamine when boiled withDMF. On heating the 5-(2-aminophenyl)-1,3,4-oxiadiazole above its melting point it rearranges to 3-amino-2,4(1H,3H)-quinazolinedione (5).

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Die Darstellung von 5-(2-Aminophenyl)-1,3,4-oxadiazol-2(3H)-on und dessen Umlagerung in 3-Amino-2,4(1H,3H)-chinazolindion

Zusammenfassung Bei der Reaktion von Anthranilsäurehydrazid mit 1,1-Carbonyldiimidazol inTHF wird 5-(2-Aminophenyl)-1,3,4-oxadiazol-2(3H)-on (4) gebildet. Dieses kann auch aus 1-o-Aminobenzoyl-4,4-dimethylsemicarbazid dargestellt werden, welches beim Kochen mitDMF Methylamin eliminiert. Beim Erhitzen von 5-(2-Aminophenyl)-1,3,4-oxadiazol über seinen Schmelzpunkt tritt Umlagerung zu 3-Amino-2,4(1H,3H)-chinazolindion (5) ein.

     

2,4-Bis(4-methylpheylthio)-1,3,2λ5,4λ5-dithiadiphosphetan-2,4-dithion: Ein neues Reagens zur Schwefelung von N,N-disubstituierten Amiden

2,4-Bis(4-methylphenylthio)-1,3,2λ⁵,4λ⁵-dithiadiphosphetane-2,4-dithione: A New Reagent for Thiation of N,N-Disubstituted Amides As a new reagent for the thiation of amides, the easily accessible 2,4-bis(4-methylphenylthio)-1,3,2λ⁵,4λ⁵-dithiadiphosphetane-2,4-dithione ( 9 ) shows a remarkable selectivity. This selectivity – the preferred thiation of N,N-disubstituted amides – is complementary to the one of the well known Lawesson reagent. Thiation of diamides of type 2 with 9 leads via cyclization of the corresponding dithiodiamides to 1,3-thiazole-5(4H)-thiones 1 (Scheme 3).     

Synthesen,spektroskopische Eigenschaften von Alkylmercaptoalkylaminomethylensulfonamiden und chemisches Reaktionsverhalten von 1,1-Bis-(dimethylamino)-ethylen

Syntheses of isothioureas3a–3e and 1-aza-butadiene-derivatives4a–4e are described, starting from bis-alkylmercaptomethyleneimides1a-1e and 1,1-bis-(dimethylamino)-ethylene (2). Reactions of isonitriledichlorides5a–5c with alkylmercaptanes and aromatic amines in the presence ofn-Butyl-lithium yield the isothio-ureas6a–6c;7 with2 gives — in the presence of triethylamine—the 1-azabutadienederivative8. The sulfoneamides9a–9e yield with2 the amidines10a–10e.11 resp.13 react with2 to the compounds12 and14 in relatively good yields.

Herrn KollegenHans Musso, Karlsruhe, mit den besten Wünschen zum 60. Geburtstag, in dankbarer Erinnerung an die gemeinsame Karlsruher Zeit, gewidmet.     

Zum Reaktionsverhalten von 2,4-Dioxohexahydro-1,3,5-triazin

Summary 2,4-Dioxohexahydro-1,3,5-triazin (DHT) reacts with formaldehyde and secondary amines (Mannich reaction) to the corresponding 1,3,5- or 1,5-aminomethyl-DHTs (1a–8a or1b–11b).DHT and formaldehyde give the methylol compounds12a,12b, and12c. Alkylation ofDHT with alkyl halides in presence of base and dimethyl-sulfoxide as the solvent affords the tri-N-alkyl derivatives14–22. 1,5-Dimorpholinomethyl-DHT (1b) can be alkylated in position 3 with alkyl halides. The morpholinomethyl groups in positions 1 and 5 behave as protecting groups and are easily removable. Thus, it is possible to introduce different alkyl substituents into the molecule. The reaction of1b with dihaloalkanes results in a coupling of twoDHT moleculesvia the nitrogen in position 3 (compounds26–29).

Herrn Professor Dr. mult.Friedrich Asinger zum 90. Geburtstag gewidmet     

A study of the Claisen rearrangement of 7-(3-phenyl-2-propenyloxy)-3-phenyl-(4H)-1-benzopyran-4-one derivatives

Summary The Claisen rearrangement of 7-(3-phenyl-2-propenyloxy)-3-phenyl-(4H)-1-benzopyran-4-one (2 a) gave 7-hydroxy-8-(1-phenyl-2-propenyl)-3-phenyl-(4H)-1-benzopyran-4-one (3 a) and 2,3-dihydro-2,6-diphenyl-3-methyl-(7H)furo[2,3-h]-1-benzopyran-7-one (7 a). 2-Methyl-7-(3-phenyl-2-propenyloxy)-3-phenyl-(4H)-1-benzopyran-4-one (2 b) afforded4 b and7 b. 8-Methyl-7-(3-phenyl-2-propenyloxy)-3-phenyl-(4H)-1-benzopyran-4-one (12) gave only the alkali soluble product 7-hydroxy-8-methyl-6-(1-phenyl-2-propenyl)-3-phenyl-(4H)-1-benzopyran-4-one (13).3 a,4 b, and13 were further cyclized in acidic medium to9 a,10 b, and14 followed by dehydrogenation.This paper is dedicated to Dr. F. M. Dean, Department of Organic Chemistry, Robert Robinson Laboratories, University of Liverpool, Liverpool, U. K., on his retirement     

Synthesen und Eigenschaften ethinylierter und trimethylsilylethinylierter Molekülsysteme mit 1,6-Methano[10]annulen-Partialstruktur

2-Trimethylsilylethinylated 1,6-methano[10]annulene1 a was obtained by reaction of 2-bromo-1,6-methano[10]annulene with trimethylsilylacetylene in the presence of bis-(triphenylphosphin-)-Pd (II) chloride and Cu(I) and also by reaction of 1,1-diiodo-2-(1,6-methano[10]annulene-2-yl)-ethene (2) withn-buthyl-lithium followed by hydrolysis.1 a reacts with 2N NaOH to 2-ethinyl-1,6-methano[10]annulene (1 b). 2,7- and 2,10-dibromo-1,6-methano[10]annulene can be substituted to give the trimethylsilylethinylated compounds3 a–6 a, which then can be transformed with 2N NaOH into the desilylated products3 b–5 b.

Wolfgang Kraus, Stuttgart-Hohenheim, mit den besten Wünschen in Freundschaft zum 60. Geburtstag gewidmet     

Zur Synthese von (±)-cis-1,2-Epoxy-3-oxo-alkyl-phosphonsäureestern—Phosphonomycinanaloga

Treatment of dialkyl-3-oxo-1-alkenylphosphonates1 with OsO₄-H₂O₂ affords the (±)-threo-glycols2, which were characterised as their corresponding diacetates3. The derivatives2 were transformed into the mono-(tert-butyl-dimethylsilylether)-compounds4 and5. Subsequent treatment withp-toluene-sulfonyl chloride yields6 and7, which can be converted to (±)-cis-1,2-epoxy-3-oxoalkylphosphonates8 with tetrabutylammonium fluoride (TBAF). Sometimes thetrans-derivatives9 can be found just as the tosyloxyphosphonates11 and12 as by-products. In two cases the 1,2-dicarbonyl compounds10 were obtained.

Herrn Kollegen Prof. Dr.E. Ziegler zum 70. Geburtstag gewidmet.     

New method of synthesis of 1,1-bis(trialkylsilyl)- and bis(trialkylgermyl)germacyclopenta-2,4-dienes

The reactions of 1,1-dichloro-2,3,4,5-tetraphenyl-1-germacyclopenta-2,4-diene (1), magnesium, and R₃ECl (E = Si, Ge) under mild conditions (20 °C, THF) gave 1,1-bis(trimethylsilyl)-2,3,4,5-tetraphenyl-1-germacyclopenta-2,-4-diene (2a) and 1,1-bis(triethylgermyl)-2,3,4,5-tetraphenyl-1-germacyclopenta-2,4-diene (2b) respectively. The reaction is versatile and applies to the compounds R₃ECl (E = Si, Ge) that do not react with magnesium.__________Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 10, pp. 2234–2236, October, 2004.     

Studies on sigmatropic rearrangements: Thermal rearrangement of 3-(meta-substituted aryloxymethyl) coumarins

Summary At elevated temperatures, the 3-(meta-substituted aryloxymethyl) coumarins3a–e and3g–k undergo sigmatropic rearrangements to give the hydroxylated 3-benzylcoumarins4a–e and4g–k. Upon methylation and subsequent oxidation with N-bromo succinimide, the 3-(chlorosubstituted benzyl) coumarins4a,4m and4n afford 3-(chlorosubstituted benzoyl) coumarins8a,8m, and8n.

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Untersuchungen von sigmatropen Umlagerungen: Thermische Umlagerung von 3-meta-substituierten Aryloxymethylcumarinen

Zusammenfassung Bei erhöhter Temperatur reagieren die 3-meta-substituierten Aryloxymethylcumarine3a–e und3g–k über eine sigmatrope Umlagerung zu den hydroxylierten 3-Benzylcumarinen4a–e und4g–k. Methylierung der 3-chlorsubstituierten Benzoylcumarine4a,4m und4n, gefolgt von Oxidation mit N-Bromsuccinimid, ergibt die 3-chlorsubstituierten Benzoylcumarine8a,8m und8n.

     

ZurFischer-Indol-Umlagerung sterisch gehinderter Systeme, 6. Mitt.: Reaktionen mit cyclischen Oxalylverbindungen, 22. Mitt.

The N,N-diphenylhydrazones1 and7 combine with oxalyl chloride yielding the corresponding 2,3-dihydropyrrole-2,3-diones (2), the indeno[1,2—b]pyrrol-2,3-dion derivative8 a and the 1-diphenylamino-4,5-tetrahydrobenz[g]indol-2,3-dione (8 b).2 can be rearranged into the pyrrolo[2,3—b]indole systems3 by thermolysis in decaline. Heating of3 a gives ethyl 1,2-diphenyl-indole-3-carboxylate5, while3 b under the same conditions is converted into the (indolyl-)glyoxylic acid derivative4. The diaza-propellanes9 are synthesized by thermolysis of8 in decaline. Oxidative hydrolysis of9 leads to the indole derivatives10, which on the other hand are made byFischer indole synthesis starting with7.     

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.

     

Chinazolincarbonsäuren, 10. Mitt. Synthese von 1-Methyl-2,4-dioxo-chinazolin-3-yl-essigsäure, 2,4-Dioxo-chinazolin-1-yl-essigsäuren, 2,4-Dioxo-1,3-chinazolindiessigsäuren und deren Estern

2,4-Dioxo-quinazolin-1-yl-acetic acid esters (2) were prepared by the reaction of either 3,1-benzoxazine-2,4-diones (1) with urea in the melt or in solution or of the substituted anthranilic acid ester4 with potassium cyanate in acid solution. The anthranilamides5 with trichloromethyl chloroformate (diphosgene) gave also2. Alkaline hydrolysis of2 affords the 2,4-dioxo-quinazolin-1-yl-acetic acids (3), which were independently obtained by the sequence5 6 7. 2,4-Dioxo-1,3-quinazolinediacetic acids (11) were synthesized from1 and glycine ester. Reaction of8 with ethyl chloroformate gave9 and treatment of the latter with KOH furnished the potassium salt10, which was converted to11 by acids.Quinazoline-2,4-dione (12) with ethyl bromoacetate yielded13 and with chloroacetonitrile14. 13 was hydrolyzed to11. 14 could not be converted into11.1-Methyl-3,1-benzoxazine-2,4-dione (15) was transformed under similar conditions into 1-methyl-2,4-dioxo-quinazolin-3-yl-acetic acid (16).

     

Synthesen mit Nitrilen,LXXV Zur Reaktivität der Dimeren von Malononitril und Cyanessigester gegenüber Dimethylformamid-dimethylacetal

Reaction of malononitrile dimer (1) and the codimer from cyanoacetate and malononitrile (2) with dimethylformamide-dimethylacetal (DMFDMA) leads to the monocondensation products5 a, b. The isomeric codimer3, however, gives the amidine6. Ring closure reactions of5 a with ammonia and primary aliphatic and aromatic amines yield 2,4-diamino-3,5-pyridinedicarbonitriles7 a–j, in the case of5 b the 4-amino-1,2-dihydro-2-oxo-3,5-pyridinedicarbonitriles8 b–i. Reactions of1 and2 with an excess ofDMFDMA give the biscondensation products11 a, 11 b.11 b reacts with primary aromatic amines to give the pyridine derivatives13. The structure of13 was confirmed by hydrolytical cleavage to the dicyano-aminopyridone14. Treatment of13 with concentrated hydrochloric acid leads to the pyridopyrimidine derivatives15.

     

Cyclisierung von Oligomeren des Malodinitrils mit Amidinen Synthesen mit Nitrilen, 55. Mitt

Condensation of formamidine-acetate with dimeric malononitrile (1 a) leads to 2,4-diamino-3,5-pyridine-dicarbonitrile (3 a), with acetamidine-HCl the methyl derivative3 b is obtained. Reaction of the codimer of malononitrile and methyl cyanoacetate (1 b) with formamidine yields the aminopyridine3 c, while acetamidine and benzamidine, resp. with1 b react to the 1,4-dihydro-4-pyrimidinylidene-methyl-cyanoacetates4 a-b.

     

Die Reaktion von Naphth[1,2-d]indolen mit Natrium in Äthanol

The reactivity of naphth[1,2-d]indoles1a, 3a and6 towards sodium in ethanol was studied.1a yields2, 3a the nor-product3b and dihydrothebainone-dihydromethine (4). Bt reaction of6, octahydrophenanthrenes7a and7b are obtained, the structures of which were elucidated byHofmann degradation to8a and8b.     

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.

     

New syntheses of 2,4-diaminopyrroles and aminopyrrolinones

Summary Oxazolin-2-ylidene-malononitriles3a–d, obtainable from thioketenaminals and -halogen-ketones, react with primary and secondary amines to afford 2,4-diamino-pyrroles5a–h. Mercaptobenzen as nucleophilic agent gives the 4-amino-2-phenylthio-pyrrole5j. Analogously, cyano-(3,5-diphenyl-3H-oxazol-2-ylidene)-acetic acid methyl esters were prepared as intermediates for the synthesis of 2-amino-4-oxo-pyrrolines10a–d. The isomeric 4-amino-2-oxo-pyrrolines13a–d can be obtained from 4-amino-2-methoxy-pyrroles, which serves as proof for the position of substituents. The structures were investigated by¹H and¹³C NMR spectroscopy.

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Neue Synthesen von 2,4-Diaminopyrrolen und Aminopyrrolinonen

Zusammenfassung Die Oxazolin-2-yliden-malononitrile3a–d. die aus Thioketenaminalen und -Halogenketonen erhalten wurden, reagieren mit primären und sekundären Aminen zu den 2,4-Diaminopyrrolen5a–h. Mercaptobenzol als nukleophiles Reagens liefert 4-Amino-2-phenylthiopyrrol (5j). Analog wurden Cyan-(3,5-diphenyl-3H-oxazol-2-yliden)-essigsäuremethylester als Zwischenprodukte für die Synthese der 2-Amino-4-oxo-pyrroline10a–d hergestellt. Die isomeren 4-Amino-2-oxo-pyrroline13a–d können aus den 4-Amino-2-methoxy-pyrrolen11a,b erhalten werden, was als Nachweis für die Position der Substituenten dient. Die Verbindungen wurden¹H- und¹³C NMR-spektroskopisch untersucht.

     

Stereochemie vonGrignard-Reaktione mit 2-(N-Methylanikino)-cyclopentanonen

TheGrignard reactions of the 2-anilinocyclopentanones (1 a and1 b) with CH₃MgI and C₆H₅CCMgBr, giving the 2-anilinocyclopentanols2 a, 2 b, and2 c, and the synthesis oftrans-1-methyl-2-(4-chloro-N-methylanilino)-cyclopentanol (4), which was used as a reference compound of known stereochemistry, are described. IR spectroscopic investigations of2 a, 2 b, and2 c as compared with4 lead to the conclusion that2 a, 2 b, and2 c have the structures ofcis-2-(N-methylanilino)-cyclopentanols.     

[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).