Regio- and stereoselective 1,3-dipolar cycloaddition of arylnitrile oxides to 5-acetoxy-2(5H)-furanone

Summary Arylnitrile oxides undergo regio- and stereo-specific 1,3-dipolar cycloaddition reactions with 5-acetoxy-2(5H)-furanone. In each case a single product3a–3g results from ananti approach to the 5-acetoxy substituent, the oxygen of the 1,3-dipole being attached to C-4 of furan. Under similar conditions 5-benzoyloxy-2(5H)-furanone yields3h–3i. The structures of the adducts were determined by¹H- and¹³C-NMR spectroscopy.

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Regio- und stereoselektive 1,3-dipolare Cycloaddition von Arylnitriloxiden mit 5-Acetoxy-2(5H)-furanon

Zusammenfassung Arylnitriloxide reagieren mit 5-Acetoxy-2(5H)-furanon in einer regio- und stereoselektiven 1,3-dipolaren Cycloaddition. In jedem der untersuchten Fälle ergaben sich die einheitlichen Produkte3a–3g als Folge eineranti-Annäherung an den 5-Acetoxysubstituenten, wobei der Sauerstoff des 1,3-Dipols an das C-4 des Furans addiert. Unter ähnlichen Bedingungen ergab 5-Benzoyloxy-2(5H)-furanon die Produkte3h–3i. Die Strukturen der Addukte wurden mittels¹H-und¹³C-NMR bestimmt.

     

Natural product chemistry,part 137: Oxidation of acridone alkaloids: Synthesis of 5-methoxyacronycine

Summary Epoxidation of the acridone alkaloid acronycine (1) resulted in hydroxylation at the aromatic ring giving 5-hydroxyacronycine (3). The same reaction on 1,3-dimethoxy-10-methyl-9(10H)-acridinone (5) gave 1,3-dimethoxy-2-hydroxy-10-methyl-9(10H)-acridinone (6), 1,3-dimethoxy-2-hydroxy-4-peroxy-10-methyl-9(10H)-acridinone (8), and 1,3-dimethoxy-2,4-diperoxy-10-methyl-9(10H)-acridinone (9).

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Naturstoffchemie, 137. Mitt.: Oxidierung von Acridonalkaloiden: Synthese des 5-Methoxyacronycins (Kurze Mitt.)

Zusammenfassung Die Epoxidierung des Acridonalkaloids Acronycin führte zu einer Hydroxylierung des aromatischen Rings, wobei 5-Hydroxyacronycin (3) entstand. Die gleiche Reaktion mit 1,3-Dimethoxy-10-methyl-9(10H)acridinon (5) ergab 1,3-Dimethoxy-2-hydroxy-10-methyl-9(10H)acridinon (6), 1,3-Dimethoxy-2-hydroxy-4-peroxy-10-methyl-9(10H)acridinon (8) und 1,3-Dimethoxy-2,4-diperoxy-10-methyl-9(10H)acridinon (9).

     

4-Phosphoranylidene-5(4H)-oxazolones II. Reactions with alkylating agents

Summary When treated with alkyl halides at 20–90°C without solvent or in acetonitrile, 4-phosphoranylidene-5(4H)-oxazolones (1) give 4-C-alkylation products4 in good yields. Alkylation of1 with alkyl triflates in CH₂Cl₂ at room temperature results in O-alkylation products5. No O-to 4-C-alkylation rearrangement can be observed. The spectroscopic properties of the alkylation products are reported and discussed.

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4-Phosphoranyliden-5(4H)-oxazolone, 2. Mitt. Reaktionen mit Alkylierungsreagentien

Zusammenfassung Behandlung von 4-Phosphoranyliden-5(4H)-oxazolonen (1) mit Alkylhalogeniden bei 20–90°C ohne Lösungsmittel oder in Acetonitril liefert in guten Ausbeuten die 4-C-alkylierten Produkte4. Alkylierung von1 mit Alkyltriflaten in CH₂Cl₂ bei Raumtemperatur ergibt O-alkylierte Produkte (5). E6 wurde keine Umlagerung von O-alkylierten zu C-alkylierten Verbindungen beobachtet. Die spektroskopischen Eigenschaften der Alkylierungsprodukte werden berichtet und diskutiert.

     

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.

     

Über Dihydro-3-thioxo-3H-1,2-dithiolo[4,3-d]pyrimidin-5(4H)-one und Dihydro-3H-1,2-dithiolo[4,3-d]pyrimidin-3,5(4H)-dithione Über Heterocyclen, 34. Mitt.

Zusammenfassung Dihydro-3-thioxo-3H-1,2-dithiolo[4,3-d]pyrimidin-5(4H)-one (2) geben bei Methylierung 4-Methylderivate (2) bzw. Tetrahydro-3-methylthio-5-oxodithiolopyrimidiniumsalze (6); aus den Dithionen (3) entstehen 5-Methylthio-bzw.5-Methylthio-4-methylderivate (4) bzw. Tetrahydro-3-methylthio-5-thioxodithiolopyrimidiniumsalze (6). Peressigsäure führt2 in das Tetrahydrodithiolopyrimidiniumhydrogensulfat (10) über.2 bzw.3 geben mit Phenylhydrazin 3-Phenylhydrazone; Tetrahydro-3-methylthiodithiolopyrimidiniumjodide (6) reagieren mit Aminen bei Anwesenheit vonHMPT zu den 3-Iminoverbindungen.10 gibt mit Methylketonen und Wasserstoffakzeptoren 3-Acylmethylendihydrodithiolopyrimidin-5(4H)-one.

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Dihydro-3-thioxo-3H-1.2-dithiolo[4.3-d]pyrimidin-5(4H)-ones and dihydro-3H-1.2-dithiolo[4.3-d]pyrimidin-3,5(4H)-dithiones

Dihydro-3-thioxo-3H-1.2-dithiolo[4.3-d]pyrimidine-5(4H)-ones (2) give on methylation 4-methylderivatives (2) and tetrahydro-3-methylthio-5-oxodithiolopyrimidinium salts (6) resp.; from dithiones (3) arise 5-methylthio-resp. 5-methylthio-4-methylderivatives (4) resp. tetrahydro-3-methylthio-5-thioxo-dithiolopyrimidinium salts (6). Peracetic acid converts2 to tetrahydrodithiolopyrimidinium hydrogensulphate10. 2 and3, resp. give with phenylhydrazine 3-phenylhydrazones. Tetrahydro-3-methylthiodithiolopyrimidiniumiodides (6) react with amines in presence ofHMPT to 3-iminocompounds.10 gives with methyl ketones and hydrogen acceptors 3-acylmethylendihydro-dithiolopyrimidine-5(4H)-ones.

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Herrn Prof. Dr.E. Ziegler zum 60. Geburtstag gewidment.     

Über Heterocyclen, 22. Mitt.: 3,4,6,7-Tetrahydro-5H-pyrrolo[3,4-d]pyrimidin-2(1H), 5-dione

Zusammenfassung Tetrahydro-6-brommethyl-2-oxopyrimidin-5-carbonsäureester reagieren mit Ammoniak bzw. Benzylamin zu Tetrahydro-5H-pyrrolo[3,4-d]pyrimidin-2(1H), 5-dionen. Mit 2-Aminopyridin (A) bilden sich Tetrahydro-6-(2-pyridylaminomethyl)-2-oxopyrimidin-5-carbonsäureester, Tetrahydro-5H-pyrrolo[3,4-d]pyrimidin-2(1H), 5-dione sowie 5-Äthoxycarbony]-2,3,5,6-tetrahydro-2-oxospiro(pyrimidin-4(1H), 2(3H)-1H-imidazo[1,2-a]pyridinium)bromide.

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Heterocycles XXII: 3.4.6.7-Tetrahydro-5H-pyrrolo [3.4-d]-pyrimidine-2(1H)-5-diones

Tetrahydro-6-bromomethyl-2-oxopyrimidine-5-carboxylates react with ammonia and benzylamine, resp., to give tetrahydro-5H-pyrrolo[3.4-d]pyrimidin-2(1H), 5-diones. With 2-aminopyridine (A) tetrahydro-6-(2-pyridylaminomethyl)-2-oxopyrimidine-5-carboxylates, tetrahydro-5H-pyrrolo[3.4-d]pyrimidine-2(1H). 5-diones as well as 5-ethoxycarbonyl-2.3.5.6-tetrahydro-2-oxospiro(pyrimidin-4(1H)-2(3H)-1H-imidazo[1.2-a]-pyridinium) bromides are formed.

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Herrn Prof. Dr.O. Hromatka zum 65. Geburtstag gewidmet.     

Transformation of 5-Oxo Substituted Fused Pyran-2-ones. Lactam Versus Hydrazone Formation

6, 7-Dihydrocyclopenta[b]pyran-2, 5-dione 1 was converted with hydrazines to fused pyridine-2(1H)-ones of type a. In contrast, 2H-1-benzopyran-2, 5-diones 2–4 gave under the same reaction conditions 5-hydrazonobenzopyrans of type b. Calculated heats of formation matched experimental findings.     

Preparation of 5-Cyano-4,6-dimethyl-2H-pyran-2-one and 3-Cyano-5-methoxy-4-methyl-5H-furan-2-one via a One-Pot,Domino-Knoevenagel Process

5-Cyano-4,6-dimethyl-2H-pyran-2-one (1) has been prepared via a simple one-pot domino-Knoevenagel reaction starting from ethyl acetoacetate (2) and cyanoacetone (3). Similarly, a new racemic 3-cyano-5-methoxy-4-methyl-5H-furan-2-one (7) has been prepared from 1,1-dimethoxyacetone (6) and cyanoacetic acid (4). The new alkylidene derivatives (Z/E)-ethyl-4-cyano-3-methylbut-3-enoate (5), (Z/E)-ethyl 5-amino-4-cyano-3-methyl-5-oxopent-3-enoate (9), and (2,2-dimethoxy-1-methylethylidene)malononitrile (11) have been prepared via the Knoevenagel reactions. The easy access to these new compounds in good yields shows that ammonium acetate/acetic acid–catalyzed Knoevenagel reactions and domino-Knoevenagel reactions have a broad scope of application.     

The Improved Preparation of 7,8-Dihydro-Quinoline-5(6H)-One and 6,7-Dihydro-5H-1-Pyrindin-5-one

Compounds 7,8-dihydroquinoline-5(6H)-one (3) and 6,7-dihydro-5H-1-pyrindin-5-one (5) are formed by new methods from 1,3-diketone compound, ammonium acetate and 1,1,3,3-tetraethoxylpropane.

     

Synthesis and selected transformations of 1-(5-methyl-1-aryl-1H-1,2,3-triazol-4-yl)ethanones and 1-[4-(4-R-5-methyl-1H-1,2,3-triazol-1-yl)phenyl]ethanones

By cycloaddition of arylazides to acetylacetone are obtained derivatives of 1,2,3-triazole. In the reaction of 1-[5-methyl-1-(R-phenyl)-1H-1,2,3-triazol-4-yl] ethanones (IIa–IIe) and 1-[4-(4-R-5-methyl-1H-1,2,3-triazol-1-yl)phenyl] ethanones (VIIa-VIIe) with isatin are obtained 2-[1-(R-phenyl)-5-methyl-1H-1,2,3-triazol-4-yl]-4-quinolinecarboxylic acids (IIIa–IIIe) and 2-[4-(4-R-5-methyl-1H-1,2,3-triazol-1-yl)phenyl] -4-quinolinecarboxylic acids (IXa, IXb), respectively. We found that 1-[5-methyl-1-(R-phenyl)-1H-1,2,3-triazol-4-yl] ethanones (IIa–IIe) readily transform into [5-methyl-1-(R-phenyl)-1H-1,2,3-triazol-4-yl] acetic acids (IVa–IVc) by the method of Wilgerodt-Kindler. The (5-methyl-1-phenyl-1H-1,2,3-triazol-4-yl)acetic acid reacts with 5-phenyl-4-amino-4H-1,2,4-triazol-3-thiol affording 6-[(5-methyl-1-phenyl-1H-1,2,3-triazol-4-yl) methyl]-3-phenyl[1,2,4] triazolo[3,4-b] [1,3,4] thiadiazole (VI). Original Russian Text ? N.T. Pokhodylo, R.D. Savka, V.S. Matiichuk, N.D. Obushak, 2009, published in Zhurnal Obshchei Khimii, 2009, vol. 79, no. 2, pp. 320–325.     

Experimental and computational investigations on the high binding-selectivity of pyrimidine derivatives by a pillar[5]arene

The binding selectivity of an adenine-monofunctionalized pillar[5]arene (H) with a series of pyrimidine derivatives were investigated through ¹H NMR experiments and density functional theory (DFT) study. High binding-selectivity was demonstrated. Typically, H displayed very strong binding strength with 6-(2,4-dioxo-3, 4-dihydropyrimidin-1 (2H)-yl)hexanenitrile (G1) [K_a >10⁵ M^?1], up to about 3000-fold as compared with 1-hexylpyrimidine-2,4(1H, 3H)-dione (G5) [K_a = 31 M^?1]. The strong binding ability of H with G1 was due to the cooperative multiple hydrogen bond, dipole-dipole, C-H···π and π···π interactions. The high binding-selectivity was also verified by calculation results. The calculated interaction energy (ΔE_i) of G1?H was ?12.92 Kcal·mol^?1 while that of G5?H was ?2.85 Kcal·mol^?1.     

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).

     

Prins-Reaktionen mit Arylaldehyden, 3. Mitt.

By reaction of excess benzaldehyde with cyclohexene in presence of sulfuric acid besider-2,c-4-diphenyl-(t-4aH,c-8aH)-hexahydro-4H-1,3-benzodioxin (2) andr-4-phenyl-(t-4aH,c-8aH)-hexahydro-4H-1,3,2-benzodioxathiin-2,2-dioxide (3),trans-2-benzyloxycyclohexyl phenyl ketone (5) and (E)-3-benzylidene-1-cyclohexenyl phenyl ketone (6) are obtained. The formation of5 and6 is shown to proceed via an acid catalyzedCannizzaro reaction of benzaldehyde.

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2. Mitt.:H. Griengl undK. P. Geppert, Mh. Chem.107, 675 (1976).     

取代吡唑-5-酰基杂环衍生物的合成、结构与生物活性

为了寻求新的含吡唑双杂环先导化合物. 用4-取代-1-甲基-3-乙基-5-吡唑甲酰氯与2-噻唑烷酮、2-噻唑硫酮、2-噁唑烷酮等含氮杂环反应得到了12个含吡唑环的双杂环化合物. 化合物结构用IR, ¹H NMR, MS和元素分析进行了表征. 并用X射线单晶衍射法测定了化合物3-(1-甲基-3-乙基-4-硝基-5-吡唑甲酰基)-噁唑烷-2-酮(3k)的晶体结构. 晶体为单斜晶系, P2₁/n (#14)空间群, a＝1.52175(3) nm, b＝0.52970(1) nm, c＝1.58185(3) nm, β＝104.893(4), V＝1.2323(4) nm³, Z＝4, D_c＝1.45 g/cm³, F(000)＝560.00, R₁＝0.064, wR₂＝0.193. 初步生物活性实验结果表明, 在25 mg/L浓度下, 3-(1-甲基-3-乙基-4-硝基-5-吡唑甲酰基)-噻唑烷-2-酮(3c), 3-(1-甲基-3-乙基-4-硝基-5-吡唑甲酰基)-噻唑烷-2-硫酮(3g)对水稻稻瘟病菌(Pyricularia oryzae)的抑制活性达到40%. 在500 mg/L浓度下, 3-(1-甲基-3-乙基-4-溴-5-吡唑甲酰基)-噻唑烷-2-酮(3d), 3-(1-甲基-3-乙基-4-溴-5-吡唑甲酰基)-噁唑烷-2-酮(3l)对稻黑尾叶蝉(Nephotettix cinc-ticeps)的抑制活性达到53.37%.     

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.

     

Über Tetrahydro-6-methyl- bzw. 6-phenyl-2-oxopyrimidin-5-carbonsäuren und ihre Derivate Über Heterocyclen, 48 Mitt

Tetrahydro-6-methyl- and-6-phenyl-2-oxopyrimidine-5-carboxylic acids5, 8 resp are obtained on hydrogenolysis of the corresponding benzyl esters4, 7; 1-methyl compounds (5, 8) are also formed by hydrolysis of the ethyl and benzyl esters (3, 4, 6, 7) in alcoholic KOH. Benzyl esters4 which are unsubstituted at position1 are converted by alcoholic KOH into ethyl esters3. Phenols convert3, 4, 5, depending on the substituent in position 1, into 6-hydroxyphenyltetrahydro-2(1H)-pyrimidinones (10) or di(tri)phenylalkanes11, 12. Bromination of the pyrimidine-carboxylic acids5 or of the tert butyl esters18 leads to the 6-bromomethyl- and dibromomethyl derivatives15, 16, which are easily transformed into furo-[3,4-d]pyrimidines17. Thermal decarboxylation of carboxylic acids5 c, f, g lead to dihydro-2(1H)-pyrimidinones13 a, c, d.     

Über die Synthese von 5-Phenyl-1H-thieno[3,4—e]1,4-diazepin-2(3H)-on

The synthesis of 5-phenyl-1H-thieno[3.4—e]1.4-diazepin-2(3H)-one (16), its alkylation in position 1 and the preparation of the intermediate 3-(4-aminothienyl)-phenylketone (8) are described. In addition thieno[3.4—b]pyridin-2(1H)-one (7) is described.     

Oxazepines and thiazepines,XXIV synthesis of optically active 2,3-dihydro-2-methyl-1,5-benzoxazepin-4(5H)-ones

Summary 2,3-Dihydro-2(R)-methyl-1,5-benzoxazepin-4(5H)-one [(R)-3] and its enantiomer (S)-3 have been synthesized via the optical resolution and subsequent chemical transformations of (±)-3-(2-nitrophenoxy)butyric acid (1). Compounds (R)-3 and (S)-3 were converted into optically active 1,5-benzoxazepines (R)-7–(R)-14 and (S)-15–(S)-32.

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Oxazepine und Thiazepine, XXIV: Darstellung optisch aktiver 2,3-Dihydro-2-methyl-1,5-benzoxazepin-4(5H)-one

Zusammenfassung 2,3-Dihydro-2(R)-methyl-1,5-benzoxazepin-4(5H)-on [(R)-3] und sein Enantiomeres (S)-3 wurden durch Racemattrennung und weitere chemische Umsetzungen von (±)-3-(2-Nitrophenoxy)buttersäure (1) dargestellt. Die Verbindungen (R)-3 und (S)-3 wurden in die optisch aktiven 1,5-Benzoxazepine (R-7 bis (R)-14 und (S)-15 bis (S)-32 übergeführt.

     

Ni-Catalyzed desilylative annulation of benzamides and acrylamides with alkynylsilanes: Access to 3-Methyleneisoindolin-1-one and 5-Methylene-1H-pyrrol-2(5H)-one derivatives

Abstract

The nickel-catalyzed desilylative annulation of C(sp²)–H bonds of benzamides and acrylamides with alkynylsilanes assisted by 8-aminoquinolyl directing group has been reported. A variety of benzamides and acrylamides were compatible in this protocol to construct various 3-methyleneisoindolin-1-one and 5-methylene-1H-pyrrol-2(5H)-one derivatives with Z-configuration selectivity in moderate to high yields.     

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.