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.

     

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.     

Zur Chemie der 4-Amino-thiazolin-2-thione, 2. Mitt.

Summary 6-Amino-thiazolo[4,5-c]isothiazole derivatives4 are obtained by addition of hydrogen sulfide to the 4-Amino-thiazoline-5-carbonitrile2 followed by cyclooxidation of the intermediate thioamides3. In the presence of sodium sulfite the hydrolysis of the4-amino-2-methylthio-thiazolium salts5 derived from the title compounds1 yields the4-amino-thiazolin-2-ones6. By their further hydrolysis the 2,4-dioxo-thiazolidin-5-carboxamides8 are formed. The 2-oxo-and 2-thioxo-thiazolo [4,5-d]pyrimidin-7-ones and -thiones available from1 undergo ring opening by hydrolysis to give the substituted 4-amino-6-oxo- and 4-amino-6-thioxo-pyrimidine-5-thiols15a–h and13i–e. They have been isolated as their disulfides14 or 5-alkyl derivativesi.e. the substituted 4-amino-5-alkylthiopyrimidin-6-ones and -thiones16. In analogy, the intermediate 6-amino-7-oxo-thiazolo[4,5-d] pyrimidin-2-thione18 and the 7-amino-thiazolo[4,5-d]-pyrimidin-2-thione24 derived from1 react by ring cleveage to yield the 1,4-and 4,6-diamino-pyrimidin-5-thiole derivatives22 and27, respectively, isolated as their disulfides or alkylthio-derivatives. From the pyrimidine16b the pyrimido[5,4-b]1,4-thiazine derivative18 can be obtained.

     

Syntheses with pyridinium and sulfonium salts of acylated β-enaminonitriles

Summary Pyridinium and sulfonium salts2a–e which can be prepared from 3-amino-2-(-haloacetyl)-crotonitriles and 3-amino-2-(-halo-acetyl)-3-phenyl-acrylonitriles react with malononitrile in the presence of a base to 3-amino-2-pyridinio-phenolates3a,b and 3-amino-2-sulfonio-phenolates3c–e. In an analogous way, 3-amino-2-(diethyloxyphosphoryl)-phenol5a and 3-amino-2-(p-tolyl-sulfonyl)-phenol5b have been prepared. 2,3-Diamino-phenoles6a,b are formed from the pyridinium salts3a,b. The behaviour of the pyridinium salts2a,b towards heterocumulenes has been investigated. Cyanamide leads to the (2-amino-4-hydroxy-pyrid-3-yl)-pyridinium salt8c. Phenylisothiocyanate gives the 3-pyridinio-2-thioxo-pyridin-4-olates9a,b. Carbon disulfide gives rise to 3-pyridinio-2-thioxo-pyridin-4-olate10 or 3-pyridinio-2-thioxo-thiopyran-4-olate11, depending on the substituent at the 6-position. Phenylisocyanate reacts to the pyrimidin-2,4-dione12 with loss of N-methyl-pyridinium chloride. S-methylation of9a and cleavage of the pyridine moiety yields the 3-amino-2-methylthio-pyrid-4-one14. The structures were investigated by¹H and¹³C NMR spectroscopy.

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Synthesen mit Pyridinium- und Sulfoniumsalzen von acetylierten -Enaminonitrilen

Zusammenfassung Pyridinium- und Sulfoniumsalze2a–e, die aus 3-Amino-2-(-halo-acetyl)-crotonsäurenitril und 3-Amino-2-(-halo-acetyl)-zimtsäurenitril hergestellt werden können, reagieren mit Malonsäuredinitril in Gegenwart einer Base zu 3-Amino-2-pyridinio-phenolaten3a,b und 3-Amino-2-sulfonio-phenolaten3c–e. In Analogie wurden 3-Amino-2-(diethyloxyphosphoryl)-phenol5a und 3-Amino-2-(p-tolyl-sulfonyl)-phenol5b erhalten. 2,3-Diamino-phenole6a,b werden aus den Pyridiniumsalzen3a,b gebildet. Das Verhalten der Pyridiniumsalze2a,b gegenüber Heterokumulenen ist untersucht worden. Cyanamid führt zum (2-Amino-4-hydroxy-pyrid-3-yl)-pyridiniumsalz8c. Phenylisothiocyanat liefert die 3-Pyridinio-2-thioxo-pyridin-4-olate9a,b. In Abhängigkeit vom Substituenten in der Position 6 entsteht bei der Reaktion mit Schwefelkohlenstoff ein 3-Pyridinio-2-thioxo-pyridin-4-olat10 oder ein 3-Pyridinio-2-thioxo-thiopyran-4-olat11. Phenylisocyanat reagiert zum Pyrimidin-2,4-dion12 unter Verlust von N-Methyl-pyridiniumchlorid. S-Methylierung von9a und Spaltung des Pyridiniumringes ergibt das 3-Amino-2-methylthio-pyrid-4-on14. Die Verbindungen wurden¹H- und¹³C-NMR-spektroskopisch untersucht.

     

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.     

Base induced cyclization of some quinolines. Formation of fused nitrogen heterocyclic ring system

Condensation of 3,5-dinitro-4-chloro-6-methoxy-2-methylquinoline (1) with benzylamine, ethanolamine and/or thioglycolic acid afforded the quinoline derivatives4 a-c. Cyclization of4 a and4 b with alkali and condensation of1 with glycine in sodium carbonate solution furnish 2H-imidazo[4,5-c]quinoline derivatives5 a-c, respectively. Treatment of5 b with benzaldehyde in presence of zinc chloride gave the styryl derivative6. 1 reacted with sodium azide to give the azido derivative4 d, which upon treatment with phenylhydrazine or sodium borohydride yielded the 4-amino derivative4 3. Moreover,1 was treated with phenylhydrazine to give4 f, which cyclized in 10% sodium hydroxide solution to the corresponding v-triazolo[4,5-c]quinoline 3-oxide derivative7. When however4 f was treated with dilute hydrochloric acid, the corresponding phenylpyrazolo[3,4,5-de]quinoline derivative8 was obtained.

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Baseninduzierte Cyclisierung einiger Chinoline. Darstellung höherer Stickstoff-Heterocyclen

Zusammenfassung Kondensation von 3,5-Dinitro-4-chlor-6-methoxy-2-methylchinolin (1) mit Benzylamin, Ethanolamin und/oder Thioglycolsäure ergab die Chinolinderivate4 a-c. Cyclisierung von4 a und4 b mit Alkali und Kondensation von1 mit Glycin in Natriumcarbonatlösung lieferte 2H-imidazo[4,5-c]chinolin-Derivate5 a-c. Behandlung von5 b mit Benzaldehyd in Gegenwart von Zinkchlorid ergab das Styrylderivat6. 1 wurde mit Natriumazid zum Azidoderivat4 d umgesetzt, das mit Phenylhydrazin oder Natriumborhydrid zum 4-Aminoderivat4 e weiterreagierte.1 ergab mit Phenylhydrazin4 f, das in 10% NaOH-Lösung zum entsprechenden Triazolo[4,5-c]chinolin-Derivat7 cyclisierte. Aus4 f wurde mit verdünnter Salzsäure das Phenylpyrazolo[3,4,5-de]chinolin8 erhalten.

     

Ein Beitrag zur Chemie des 2,3-Dihydro-3-oxo-benzo[b]thiophen-1,1-dioxids Synthesen mit Nitrilen, 86. Mitt.

Summary 2,3-Dihydro-3-oxo-benzo[b]thiophen-1,1-dioxide (1) reacts as CH-acidic component with amidines of orthoesters and anilines resp. to give the anilinomethylene derivates3, 4, and5. With triethyl orthoformiate the hydroxymethylene-compound7 is obtained. Anilino- and phenylhydrazino derivates8 and9 prove the carbonyl activity of1, azo-coupling leads to10, whereas treatment of1 with sulfur and malononitrile yields the benzo[b]thieno[2,3-d]thiophenes11. Introduction of substituents with active NH-functions in position 2 of the dicyanomethylene-product2, such as azocoupling, reaction with phenyl isocyanate and formation of enamines, leads to ring closure reactions between a nitrile and the NH-group. Thereby the phenyl-benzo[4,5]thieno[2,3-c]pyridazines12, the phenyl-1H-benzo[4,5]thieno[2,3-c]pyridines13 and the phenylamino-benzo[4,5]thieno[2,3-c]pyridines14 are obtained.¹³C and¹⁵N-NMR spectroscopy was used as proof of the ring closure reactions.

     

Substituierte 2-Alkoxy-5-amino- und-2,5-diamino-imidazole aus Oxazol-2-yliden-cyanamiden

Summary N-Cyano-S-methyl-isothio-ureases (1) react with -halogen ketones (2) by ring closure yielding the (3H-oxazol-2-yliden)-cyanamides3. by ring transformation, 2-Alkoxy-5-amino-1-phenyl-3H-imidazol-4-yl)-ketones (4) are formed. Primary and secondary amines react with3 to give 2-N-alkylated (2,5-Diamino-1-phenyl-3H-imidazol-4-yl)-ketones.

     

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.     

Synthesis of partially saturated N-substituted 4H-3,1-benzothiazine-2(1H)-thiones

Summary Acid-catalyzed reaction of 2-arylidenecyclohexanones1 with N-substituted dithiocarbamic acids2 gave open-chain addition products3 and4. Dehydration of3 and4 afforded only one of the three possible isomeric N-substituted 4H-3,1-benzothiazine-2(1H)-thiones5 and6.

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Synthese von partiell gesättigten N-substituierten 4H-3,1-Benzothiazin-2-(1H)-thionen

Zusammenfassung Die säurekatalysierte Reaktion von 2-Arylidencyclohexanonen1 mit N-substituierten Dithiocarbaminsäure2 ergab die offenkettigen Additionsprodukte3 und4. Die Dehydratation von3 und4 führte ausschließlich zu einem der drei möglichen N-substituierten 4H-3,1-Benzothiazin-2(1H)-thion-Isomeren5 und6.

     

Die Reaktion von 7,14-Cyclo-7,8-dihydrocodeinon mit Diazomethan

Reaction of 7,14-cyclo-7,8-dihydrocodeinone (1) with diazomethane gives a mixture, from which nine compounds were isolated; the structures of seven (4a–c, 5, 6, 7a and8) could be determined. Insertion of a methylene group between carbon atoms 5 and6 of1 leads with opening of the ether bridge to7a as the major product.

Herrn Univ.-Prof. Dr.G. Zigeuner mit den besten Wünschen zum 60. Geburtstag gewidmet.     

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.

     

Oxadiazole condensed ring systems,II: Synthesis of new 2-aryl-1,3,4-oxadiazolo[3,2-a]-s-triazine-5,7(6H)-diones

Summary The syntheses of 1,3,4-oxadiazolo[3,2-a]-s-triazine-5,7(6H)-diones4 through the condensation of 2-amino-5-aryl-1,3,4-oxadiazoles1 with ethoxycarbonyl isocyanate2 is described. Methylation of4b with trimethyl phosphate yielded the N-methyl derivative5.

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Kondensierte Ringsysteme des Oxadiazols, 2. Mitt. [1]: Synthese von neuen 2-Aryl-1,3,4-oxadiazolo[3,2-a]-s-triazin-5,7(6H)-dionen

Zusammenfassung Die Synthese von 1,3,4-Oxadiazolo[3,2-a]-s-triazin-5,7(6H)-dionen4 durch Kondensation von 2-Amino-5-aryl-1,3,4-oxadiazolen1 mit Ethoxycarbonylisocyanat2 wird beschrieben. Die Methylierung von4b mit Trimethylphosphat gibt das N-Methyl-Derivat5.

     

Synthese von 3,3a-Dihydro-2H,5H-azeto[2,1-b]benzo[d]-1,3-oxazin-2,5-dionen,I

The thioformimidates4, which may be obtained by S-alkylation of the thioformamides3, react with chloroacetylchloride/triethylamine to yield the (3R, 4S/3S, 4R)-3-chloro-4-methylthio-2-azetidinones5. Dehalogenation of5 leads to6, which undergoes ring closure by the action of mercuric oxide. Treatment of8, which may be synthesized by chlorolysis of7, with triethylamine gives also the title compounds9.

     

Synthese von 1,1′-Biphenyl-3-carbonsäure-und 3,5-dicarbonsäurederivaten unter Verwendung von Ethoxymethylenmalononitril

Reaction of ethoxymethylenemalononitrile with ethyl 4-phenylacetoacetate leads to ethyl 1,1-biphenyl-6-amino-5-cyano-2-hydroxy-3-carboxylate (3). Acid or basic hydrolysis of the ester and cyano group of3 affords the new derivatives4,5 and6.7 a, b are obtained bySandmeyer-reaction of3. Basic hydrolysis of7 a gives the 3,5-dicarboxylic acid derivative8.

     

Zur Reaktivität des neuen Codimeren aus Malonitril und Cyanessigester bzw. dimeren Cyanessigester gegenüber Benzilen

Condensation of benzils with 3-amino-2,4-dicyano-crotonic-ester (2a, b) and dimer cyanoacetate (2c, d) resp. leads to 4,5-diaryl-3-pyrroline-2-ylidenecyanoacetates3a-m. It can be shown by¹³C-spectroscopy that in the monosubstituted benzil1c the carbonyl function adjacent to the unsubstituted phenyl reacts with the methylene group of2a orb. With aqueous alkaline the pyrrolines3 rearrange to pyrrolidinones4a-i.¹H-NMR-CIDNP experiments support the assumption of a partial radical character of this rearrangement.

     

3-Alkyl- bzw. 3-Aryl-3,4-dihydro-6-methyl-2(1H)-pyrimidinthione durchDimrothumlagerung von 2-Amino-4H-1,3-thiazinen

The 3,4-dihydro-3,4,4,6-tetramethyl- and 4,4,6-trimethyl-3-phenyl-2(1H)-pyrimidinethione (1 c, d), resp. as well as the corresponding trimethyl compound1 e are formed byDimroth rearrangement of 2-methylamino- and 2-amino-4,6,6-trimethyl-6H-1,3-thiazine (2 a, b) and of 3,6-dihydro-4,6,6-trimethyl-2-phenylimino-2H-1,3-thiazine (3 b), resp. The rearrangement takes place under thermal heterolysis of the 1–6 bond of2 a, b and3 b. The reactive behaviour1 c, d is almost equal to1 e, but the pyrimidine ring of1 d is more labile than those of1 c, e.     

Pyridazines with hetero-atom substituents in position 3 and 5, part VII. Halogenation of 2-aryl-5-hydroxy-pyridazin-3(2H)-ones in position 4

Summary The reaction of 2-ary-5-hydroxy-3(2H)-pyridazinones (1a, b) with bromine yields the 4-bromo derivatives2a, b and with sulfuryl chloride the chloro compounds3a, b are obtained. However, with an excess of chlorine or sulfuryl chloride the 4,4-dichloro-pyridazine-dione4 is produced. Hydrolysis of4 leads to5, and in a similar manner the open chain hydrazone8 is obtained from the carboxylic acid6.

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Pyridazine mit Heteroatom-Substituenten in Stellung 3 und 5, 7. Mitt. Halogenierung von 2-Aryl-5-hydroxy-pyridazin-3(2H)-onen in 4-Stellung

Zusammenfassung Die Reaktion von 2-Aryl-5-hydroxy-pyridazin-3(2H)-onen (1a, b) mit Brom liefert die 4-Bromderivate2a, b, während mit Sulfurylchlorid3a, b erhalten werden. Ein Überschuß von Sulfurychlorid oder Chlorgas gibt jedoch das 4,4-Dichlor-pyridazin-dion4. Die Hydrolyse von4 führt unter Ringöffnung und Decarboxylierung zu5. In analoger Weise gibt die freie Carbonsäure6 das Hydrazon8.

     

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).

     

Pyrimido[4,5-e](1,2,4)-triazolo[3,4-b](1,3,4)-thiadiazine-7,9(6H8H)-diones

Some 5H-pyrimido[4,5-e](1,2,4)-triazolo[3,4-b](1,3,4)-thiadiazine-7,9-(6H,8H)-diones (4 a–d) have been synthesised by the condensation of 3-alkyl-4-amino-5-mercapto-(1,2,4)-triazoles (1 a–d) with 5-bromobarbituric acid (2a). Similarly some 9a-nitro-5H-pyrimido[4,5-e](1,2,4)-triazolo[3,4-b](1,3,4)-thiadiazine-7,9(8H,9aH)-diones (5 a–d) have been obtained by the condensation of1 a–d with 5-bromo-5-nitrobarbituric acid (2b) and final cyclisation withPPA. The structures have been confirmed by PMR spectra and analytical results.

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Pyrimido[4,5-e](1,2,4)-triazolo[3,4-b](1,3,4)-thiadiazin-7,9(6H,8H)-dione

Zusammenfassung Es wurden einige 5H-pyrimido[4,5-e](1,2,4)-triazolo[3,4-b](1,3,4)-thiadiazin-7,9(6H,8H)-dione (4 a–d) mittels Kondensation von 3-Alkyl-4-amino-5-mercapto-(1,2,4)-triazolen (1 a–d) mit 5-Brombarbitursäure (2 a) dargestellt. Des weiteren wurden einige 9a-Nitro-5H-pyrimido[4,5-e](1,2,4)-triazolo[3,4-b](1,3,4)-thiadiazin-7,9(8H,9aH)-dione (5 a–d) über die Kondensation von1 a–d mit 5-Brom-5-nitrobarbitursäure (2 b) und anschließender Cyclisierung mitPPA synthetisiert. Die angeführten Strukturen wurden mittels PMR-Spektren und analytischen Daten abgesichert.