Synthesis of new triazoloquinoxalines,pyrroloquinoxalines, and pyrimidopyrroloquinoxalines

Summary When 2-hydroxyquinoxaline-3-carboxamide (1) was reacted with POCl₃ inDMF, 2-chloro-3-dimethylaminomethylenecarboxamide (2) was obtained. The chloro compound2 was reacted with thiourea and hydrazine hydrate to give the corresponding mercapto and hydrazino derivatives3 and8, respectively. On the other hand, 2-chloroquinoxaline-3-carbonitrile (13) reacted with ethyl glycinate to the glycinate derivative14 which was cyclized to pyrroloquinoxaline15 by heating with sodium ethoxide. Pyrimidopyrroloquinoxaline derivatives16 and17 were obtainedvia the reaction of15 with formamide and phenyl isothiocyanate, respectively.

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Synthese neuer Triazolochinoxaline, Pyrrolochinoxaline und Pyrimidopyrrolochinoxaline

Zusammenfassung Wenn man 2-Hydroxychinoxalin-3-carboxamid (1) mit POCl₃ inDMF reagieren läßt, erhält man 2-Chlor-3-dimethylaminomethylencarboxamid (2). Die Chlorverbindung2 wurde mit Thioharnstoff und Hydrazinhydrat zu den entsprechenden Mercapto- und Hydrazinderivaten3 und8 umgesetzt. Aus 2-Chlorchinoxalin-3-carbonsäurenitril (13) und Ethylglycinat erhält man14, das durch Erhitzen mit Natriumethylat zum Pyrrolochinoxalin15 cyclisiert wurde. Die Pyrimidopyrrolochinoxalinderivate16 und17 wurden durch Reaktion von15 mit Formamid bzw. Phenylisothiocyanat erhalten.

     

über die Darstellung von kondensierten Azolo-[1,2,4]-triazinen aus heterocyclischen Diazoverbindungen

Diazotized 3-amino-1,2,4-triazole reacted with 1,3-cyclohexanedione or its 5,5-dimethyl derivative to give the tricyclic 1,2,4-triazine derivatives1 a and1 b. With 1,3-indanedione the tetracyclic compound8 was obtained. Compound1 a or the diacetyl derivative4 a are transformed in an acid catalyzed reaction into the fully aromatic system6 a with simultaneous rearrangement. Chemical reductions of systems1, 10 and12 have been investigated and the compounds9, 11 and13 were isolated and identified. Diazotized 2-aminothiazole readily formed the coupling products with reactive methylene compounds, but only14 could be prepared pure by cyclodehydration.     

Reactions of cyclic oxalyl compounds,part 29: A simple synthesis of functionalized 1H-pyrimidines

Summary 4-Benzoyl-5-phenylfuran-2,3-dione (1) and the semicarbazones2, ureas and thioureas6, respectively, combine with loss of water and carbondioxide yielding the 1H-pyrimidine derivatives3 and7, respectively, in moderate yields (30–75%). Hydrolysis of3 b leads to the 1-amino-pyrimidine-2-one4.Cordially dedicated to o. Univ.-Prof. Dr. Hans Junek on the occasion of his 60th birthday     

Studies on 5-aminopyrazole derivatives synthesis of some new fused pyrazole derivatives

5-Amino-4-cyano-3-phenylpyrazole (1) reacts with acrylonitrile or ethyl acrylate to yield 4-cyano-3-phenyl-4,5,6,7-tetrahydro-5-oxopyrazolo-[1,5-a]-pyrimidine (2). With urea, thiourea and ethyl acetoacetate1 gives the pyrazolopyrimidine derivatives6a,6b, and7 respectively. On the other hand, compound1 reacted with benzoylisothiocyanate to give the corresponding thiourea derivative4. Diazotized1 was coupled with malononitrile and ethyl cyanoacetate to yield the pyrazolopyrimidine derivatives10 and11, respectively, whereas on coupling with -chloro acetoacetic ester and with acetylacetone the hydrazones12 and13 were obtained.

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Untersuchungen an 5-Aminopyrazolderivaten. Synthese von verschiedenen neuen kondensierten Pyrazolderivaten

Zusammenfassung Die Reaktion von 5-Amino-4-cyano-3-phenylpyrazol (1) mit Acrylnitril oder Ethylacrylate ergibt 4-Cyano-3-phenyl-4,5,6,7-tetrahydro-5-oxopyrazolo-[1,5-a]-pyrimidin (2). Die Reaktion von1 mit Harnstoff, Thioharnstoff und7. Ethyl acetoacetat ergibt die Pyrazolopyrimidinderivate6a,6b und7. Andererseits entsteht das Thioharnstoffderivat4 durch die Reaktion von1 mit Benzoylisothiocyanat. Diazotiertes1 koppelt mit Malononitril und Ethylcyanoacetat zu den Pyrazolopyrimidinen10 und11, die Kopplung mit -chloroacetoacetic ester und Acetylaceton ergibt jedoch die Hydrazone12 und13.

     

Über die Darstellung von kondensierten Azolo-[1,2,4]-triazinen aus heterocyclischen Diazoverbindungen

Diazotized 3-amino-1,2,4-triazole reacted with 1,3-cyclohexanedione or its 5,5-dimethyl derivative to give the tricyclic 1,2,4-triazine derivatives1 a and1 b. With 1,3-indanedione the tetracyclic compound8 was obtained. Compound1 a or the diacetyl derivative4 a are transformed in an acid catalyzed reaction into the fully aromatic system6 a with simultaneous rearrangement. Chemical reductions of systems1, 10 and12 have been investigated and the compounds9, 11 and13 were isolated and identified. Diazotized 2-aminothiazole readily formed the coupling products with reactive methylene compounds, but only14 could be prepared pure by cyclodehydration.     

微波促进的5-氯-3-甲基-1-苯基-4-吡唑甲醛与氯化N-苯乙酮基吡啶及芳酰肼的缩合反应

5-氯-3-甲基-1-苯基-4-吡唑甲醛(1)在微波辐射下, 与氯化N-苯乙酮基吡啶(2)和取代苯乙酮3在醋酸铵/醋酸体系中一锅煮反应, 高产率地生成了吡唑基取代的吡啶衍生物4a～4e. 1与芳酰肼在微波辐射下反应, 则形成了酰腙类化合物6a～6g. 1与羟胺在微波辐射下缩合可生成肟7a和腈7b的混合物.     

Silylenolether-Funktionalisierung, 3. Mitt. Regioselektive Acylierung von Trimethylsilylenolethern mit 2-Alkoxy-1,3-dioxolanen — Synthese von α- und γ-geschützten Dicarbonylverbindungen

Acylation of silylenol ethers1 and9 yield with 2-alkoxy-2-alkyl(or aryl)-1,3-dioxolanes5 in a simple way by zinc dichloride-diethyl ether-catalysis regioselectively the - and -protected dicarbonyl derivatives6,7, and10. The enhanced reactivity of the cyclic orthoesters5 in this reaction is discussed in comparison with acyclic reagents. The yield is influenced by steric effects at the reaction center.

     

Reactivity of 4-bromomethylquinoline derivatives towards glycine and thioglycolic acid. A new ring system

Condensation of 4-bromomethylquinoline derivatives1 a-1 c with glycine and thioglycolic acid gave the corresponding quinolylmethylglycine and quinolylmethylthioacetic acid derivatives2 a-2 c and2 d-2 f, respectively. Cyclization of2 a-2 f was affected either by polyphosphoric acid or concentrated sulphuric acid to give3 a-3 f. Chlorination of2 a-2 f and3 a-3 f were also accomplished.

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Die Reaktivität von 4-Brommethylchinolin-Derivaten gegenüber Glycin und Thioglycolsäure. Ein neues Ringsystem

Zusammenfassung Die Reaktion von 4-Brommethylchinolin-Derivaten1 a-c mit Glycin und Thioglycolsäure gab die entsprechenden Kondensationsprodukte2 a-c und2d-f.2 a-f konnten mit Polyphosphorsäure bzw. mit konzentrierter Schwefelsäure zu Benzo[c]-2,6-naphthyridinen3 a-f zyklisiert werden.2 a-f und3 a-f waren einer Chlorierung (POCl₃) zugängig.

     

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.

     

Zur Synthese und Struktur derp-Indazolchinone und ihrer Methylierungsprodukte Untersuchungen über Chinone, 8. Mitt.

Summary Thep-benzoquinones5e-j react with diazomethane (after dehydrogenation) to 6-anilino-2e, dimethylamino-2h, phenylthio-2i, and methylthioindazolquinone2j. Methylation with dimethylsulfate of these as well as of the already known indazolquinones 6-toluidino-2f, 6-methylanilino-2g, 5-tert.butyl-2m, 5,6-methyl- (isomer mixture)2l,n, and benz-indazolquinone2o yield the 1-and 2-N-methyl derivatives3 and4. The structure of the 2-methyl derivatives is established by reaction of the corresponding benzoquinones with 3-methylsydnon in the case of4e,4g. UV/VIS-, IR- and¹H-NMR-spectroscopy (in CDCl₃ andDMSO) were used for structure determination. Comparison of the UV/VIS-spectra of2–4 shows that the indazolquinones are existing as 2 H-4,7-diones. For the structure elucidation of the 1- rs. 2-methylderivatives (whichh can be attributed to the methylation products) NMR-spectroscopy is well suited even without knowing the second isomer (solvent-effect). The course of the reaction of quinones with diazomethane and of the methylation reactions of the indazolquinones is discussed.

Herrn Univ.-Prof. Dr. G. Zigeuner zum 70. Geburtstag gewidmet     

Die spontane Etherbrückenöffnung an 7-Oxo-Morphinderivaten

The morphine derivatives1, 4, 7 and10 are potential precursors of 7-oxo-morphine derivatives. Attempts are described to obtain the unknown compounds5, 8, 11 leading to the salutaridine derivatives6, 9 and12. Mechanism and principles are discussed and a new empiric rule is formulated.

     

Syntheses with nitriles,XCV: Deamination of cytosine derivatives

Summary Treatment of 2-formyl-3-dimethylamino-propenenitrile (1a) and 2-ethoxycarbonyl-3-dimethylamino-propenenitrile (1b), resp., with substituted ureas led to the 2-cyano-3-ureidoacrylates2, which can be cyclized under alkaline conditions to give 5-formyl-5-cyano-, and 5-alkoxycarbonyl-2-oxopyrimidine derivatives3,6, and7. Reaction of3 with isopentylnitrite gave a mixture of the deaminated and oxidized product4 and the oxo derivative5, which was acetalized during the separation step. Similar reaction with the alkoxycarbonyl derivatives7 led to the formation of 1-alkyl-5-alkoxycarbonyl-pyrimidine-2,6-diones8a–d.

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Synthesen mit Nitrilen, 95. Mitt.: Deaminierung von Cytosinderivaten

Zusammenfassung Die Reaktion von 2-Formyl-3-dimethylamino-propennitril (1a) und 2-Ethoxycarbonyl-3-dimethylamino-propennitril (1b) mit substituierten Harnstoffen führte zur Bildung der 2-Cyan-3-ureidoacrlate2, welche unter alkalischen Bedingungen zu den 5-Formyl-, 5-Cyan- oder 5-Alkoxycarbonyl-2-oxopyrimidinen3,6 bzw.7 cyclisiert werden konnten. Reaktion von3 mit Isopentylnitrit ergab eine Mischung aus deaminiertem und zugleich oxidiertem Produkt4 sowie dem Oxoderivat5, welches während der Säulentrennung auf Kieselgel zusätzlich acetalisiert worden war. Die ähnliche Reaktion mit den Alkoxycarbonyl-Derivativen7 führte zur Bildung der 1-Alkyl-5-alkoxycarbonyl-pyrimidin-2,6-dione8a–d.

     

Gould-Jacobs reaction of 6-amino-2,3-diphenylquinoxaline

Summary Catalytic hydrogenation of 2,3-diphenyl-6-nitroquinoxaline led to the corresponding amine1 which in turn afforded products3a-i on reaction with alkoxymethylene derivatives2a-i. Thermal cyclization of3b and3f yielded substituted pyrazinoquinolones5b and5f, respectively. Optimal conditions for the successful hydrolysis of ester5b were found. The structures of all products were deduced from their IR, UV,¹H, and¹³C NMR spectroscopic data.Dedicated to Prof.F. Sauter on the occasion of his 65th birthday     

Aromatische Spirane, 21. Mitt: Darstellung von Methylphthalaldehydsäuren und ihren Ethylund Methylestern als Synthone für Synthesen von methylierten 2,2′-Spirobiindandionen

Summary The isomeric methyl phthalaldehydic acids11 were obtained from phthalides4 by bromation (NBS) to the 3-bromo derivatives7 and subsequent hydrolysis with water.4 in turn were accessible from dimethyl methyl benzoates1 by dibromination withNBS and subsequent thermical cyclization to the bromo derivatives3 which, on catalytic dehalogenation, afforded the phthalides4. Reaction of11 with methanol or ethanol gave the pseudo-esters13 and14, resp. Short treatment of11 with diazomethane on the other hand yielded the methyl formyl benzoates15b to15e. Prolonged reaction (several hours) gave the oxiranyl compounds17; in addition, the acetonyl derivatives18 were also found, obviously formed by a double methylene insertion into15. All reactions proceeded with good to excellent yields.

     

Pyridazines with heteroatom substituents in position 3 and 5, part 1: 5-Hydroxy-3(2H)-pyridazinone and its derivatives

Summary The synthesis of the title compound7 was achieved starting with mucochloric acidvia the pyridazinones1,2 and6. The electrolytic ionisation constants for7 were found to be 4.81 (±0.03) and –0.3 (±0.3). Crystal structure analyses were performed for7 and its fixed derivatives6 and9.Dedicated to Prof. Dr. Hans Junek on the occasion of his 60th birthday     

Synthesis and Reactions of Some New Heterocyclic Compounds Related to Pyrrolylthieno[2,3-d]pyrimidines and Thieno[2,3-d][4,5-d]dipyrimidines

Abstract

Condensation of ethyl-5-amino-2,4-diphenylthieno[2,3-d]pyrimidine-6-carboxylate (3a) with 2,5-dimethoxy tetrahydrofurane in acetic acid gives the corresponding 5-pyrrolyl derivative4, which in turn could be easily reacted with hydrazine hydrate in ethanol yielding the carbohydrazide derivative5. Reaction of5 with aromatic aldehydes, acetylacetone, carbon disulfide or phenylisothiocyanate gave pyrrolyl derivatives6,7,8,9 respectively. On the other hand, condensation of 5-(1-pyrrolyl)-6-acetyl-2,4-diphenylthieno[2,3-d]pyrimidine11 with benzaldehyde afforded the corresponding chalcone12, which on treatment with hydrazine hydrate, phenyl hydrazine, or thiourea gave the pyrazolinyl derivatives13,14 and pyrimidinyl derivative15, respectively. Furthermore some new pyrimidothienopyrimidne16,17a–d,19,20a–c were obtained using 5-amino-carboxamide3c as starting material.     

Synthesis of terminally substituted 9-alkylidene-10-methyl acridans

Summary -Substituted undecanals1 and2 reacted with acridine derivatives3 and5 to give the terminally substituted 9-alkylidene-10-methylacridans6. The compounds prepared were highly fluorescent and exhibited chemiluminescent activity.

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Synthese von terminal substituierten 9-Alkyliden-10-methylacridanen

Zusammenfassung Die -substituierten Undecanale1 und2 reagierten mit Acridinderivaten3 und5 zu den terminal substituierten 9-Alkyliden-10-methylacridanen6. Die untersuchten Verbindungen zeigten eine starke Fluoreszenz und waren auch chemilumineszent.

     

Synthese neuer 4-Hydroxybenzonitrilderivate und deren herbizide Eigenschaften

The synthesis of several new derivatives of 2-amino-4-hydroxybenzonitrile2 and their herbicidal screening data are described. Thus, halogenation and furtherSandmeyer-Reaction of2 leads to the 2,3,5-trihalogenated derivatives5 a–e. Reaction of ethyl chloroformate with the amino group of2 gives6 a, acylation7 a, b and8. The 3,5-dihalogenated compounds10 a–e are obtained from6 a and7 a, b by bromination or iodation. The hydroxyl group of6 a, 7 a, b and10 a, c, e reacts with N,N-disubstituted carbamyl chlorides to give6 c, d, 9 a, b, 11, 12 and13 a, b.

     

Phenyl isothiocyanate in heterocyclic synthesis: Novel synthesis of thiazoles,thieno[2,3-b]pyridine,thiophene and thieno[3,2-c]pyridazine derivatives

Summary The enamino nitriles1 and2 react with phenyl isothiocyanate followed by cyclization with -haloketones3 and10 to afford in each case the thiazole5, thiophene11 and the thieno[2,3-b]pyridine derivatives19 and21. Chemical and spectroscopic evidences for the structures of the new compounds are described.

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Phenylisothiocyanate in der Heterocyclensynthese: Neue Synthesen für Thiazol-, Thieno [2,3-b]pyridin-, Thiophen- und Thieno[3,2-c]pyridazin-Derivate

Zusammenfassung Die Enamin-nitrile1 und2 ergaben nach Reaktion mit Phenylisothiocyanaten und nachfolgender Cyclisierung mit -Halogenketonen3 und10 die entsprechenden Thiazole5, die Thiophene11 und die Thieno[2,3-b]pyridine19 und21. Chemische und spektroskopische Untersuchungen wurden als Strukturbeweise für die neuen Verbindungen herangezogen.

     

Zur Chemie der vicinalen Triketone,XII Versuche zur Darstellung vonSchiffschen Basen aus cyclischen,vicinalen Triketonen

The quinolinetrionesTMCH, PCH, MCH and phenalene trione (PT) do not react with aryl isocyanates toSchiff bases^5a, but react by ring contraction to yield the spiro-imidazolidines2 a-d,3 a-e,4 a-b and5 a-cbd. However, reaction of ninhydrine with aryl isocyanates gives the 1:2 adductes1 a-e. Benzal aniline reacts withTMCH, PCH. andPT to yield known phenoxazine derivatives^2c,11. In contrast,PCH orMCH react with benzylidene benzalaniline to yield theSchiff bases7 a-b. which can be transformed into the bisamine8. comparable to the ninhydrine reaction.

Herrn emer. o. Univ. Prof. Dr.Erich Ziegler, Graz, mit besten Wünschen zur Vollendung des 70. Lebensjahres gewidmet.