Über die Synthese von 4,9-Dihydro-9-(2-dimethylaminoäthyl)-4-methyl-thieno[3,4-b][1,5]benzodiazepin-10-on

The synthesis of the title compound6 c, starting with the condensation of o-phenylenediamine and methyl 4-oxotetrahydrothiophene-3-carboxylate (1) to 1.3.4.9-tetrahydrothieno[3.4-b] [1.5]benzodiazepin-10-one (2), is described. The structures of other products of this condensation, 1.3-dihydro-1-[3-(2.5-dihydrothienyl)]-benzimidazol-2-one (3) and 1.3-dihydro-1-[3-(2.3-dihydrothienyl)]-benzimidazol-2-one (4), are confirmed by their¹H-NMR-spectra and by the¹H-NMR-spectra of their desulfurization products.     

Nitrenes-XV: 1-Hydroxymethyl-4,5-dimethoxy-7H-azirino[1,2-a]-indole-7a-carboxylic acid γ-lactone,a nitrene addition compound

Triethyl phosphite deoxygenation of α-(6-nitroveratrylidene)-γ-butyrolactone 1 under moderate conditions affords a mixture of 3-(6-nitroveratryl)-2(5H)-furanone 5, α-(6-ethylaminoveratrylidene)-γ-butyrolactone 6 and 1-hydroxymethyl-4,5-dimethoxy-7H-azirino[1,2-a]indole-7a-carboxylic acid γ-lactone 7, in addition to 3,4-dihydro-7,8-dimethoxy[1,3-a]oxazino[3,4-a]indol-1-one 2, ethyl 5,6-dimethoxyindole-2-carboxylate 3, and 2,3-dihydro-6,7-dimethoxyfuro[2,3-b]quinoline 4, obtained under more drastic reaction conditions.The isolation of lactones 5 and 7 provides strong evidence for the intermediacy of nitrenes in this reaction which appears to provide the first example of intramolecular aziridine formation from a nitro-aromatic compound and triethyl phosphite.     

Enantioselective cathodic reduction of some prochiral ketones in the presence of (−)-N,N′-dimethylquininium tetrafluoroborate at mercury cathode

This work describes preparative scale enantioselective cathodic reduction of some prochiral ketones, viz. 3,4-dihydro-1(2H)-naphthaleneone, 2-octanone, 1-phenyl-2-propanone, E-3-octen-2-one, 1-octyn-3-one, 1-undecyn-3-one, 1-tetradecyn-3-one at mercury pool in N,N-dimethyl formamide (DMF)–2-propanol (9.5:0.5), using tetrabutylammonium tetrafluoroborate (TBA·BF₄), as supporting electrolyte and (−)-N,N′-dimethylquininium tetrafluoroborate (DMQ·2BF₄), as a enantioselective inductor. The products obtained were corresponding (S)-alcohols in 24–70% ee.     

Tubakialactones A–E,new polyketides from the endophytic fungus Tubakia sp. ECN-111

Three new isocoumarins and two new phthalides, tubakialactones A–E (1–5), together with three known polyketides including (R)-3,4-dihydro-4-hydroxyl-6,8-dimethoxy-4-methyl-3-methylene-1H-2-benzopyran-1-one (6), (?)-5,7-dimethoxy-3-methyl-1(3H)-isobenzofuranone (7), and isosclerone (8) were found in the endophytic fungus Tubakia sp. ECN-111 isolated from the leaves of Houttuynia cordata. The chemical structures of the new compounds were determined by spectroscopic analyses, including extensive 2D-NMR experiments. The absolute configuration of 3 and 7 was determined by optical rotation and circular dichroism.     

Oxidation of lignin model compounds in water with dioxygen and hydrogen peroxide catalysed by metallophthalocyanines

Water-soluble metallophthalocyanines and metalloporphyrins were tested as catalysts for the aqueous oxidations of 3,4-dimethoxybenzyl alcohol (1), 4-hydroxy-3-methoxytoluene (3) and 3,4-dimethoxytoluene (8) with dioxygen and with hydrogen peroxide. Cobalt phthalocyaninetetra(sodium sulfonate) (CoPcTS) catalysed the reactions of dioxygen with 1 to form only 3,4-dimethoxybenzaldehyde (2) and with 3 to form 2,2′-dihydroxy-3,3′-dimethoxy-5,5′-dimethylbiphenyl (4) and other, unidentified products at 70–85 °C and pH ⩾ 8, while the other catalysts were inactive. The most active catalyst for the oxidations of 1, 3 and 8 with hydrogen peroxide was FePcTS in acidic solution: alcohol 1 produced aldehyde 2 and 2-hydroxymethyl-5-methoxy-1,4-benzoquinone; phenol 3 produced dimer 4, 3-methoxy-4-hydroxybenzyl alcohol and a dimer with one hydroxymethyl group; 3,4-dimethoxytoluene (8) produced 2-methyl-5-methoxy-1,4-benzoquinone. Cationic latex particles had little effect on the oxidations.     

Cyclization reactions of 1,3-dibromopropan-2-ol, 2,3-dibromopropan-1-ol and 1-bromomethyloxirane with 6-amino-2,3-dihydro-2-thioxo-4(1H)-pyrimidinone

The cyclization reactions, carried out in strongly- or weakly-basic media, are described. Sometimes, 7-amino-2,3-dihydro-3-hydroxymethyl-5H-thiazolo[3,2-a]pyrimidin-5-one is separated out, together with 8-amino-3,4-dihydro-3-hydroxy-2H,6H-pyrimido[2,1-b][1,3]thiazin-6-one, as the principal product. A mechanism of reaction, during which the cyclizating agents are changed into oxirane derivatives, is proposed. The results of single-crystal X-ray investigations on 8-amino-3,4-dihydro-3-hydroxy-7-nitroso-2H,6H-pyrimido[2,1-b][1,3]thiazin-6-one (R = 0.035 for 1013 reflections), and on 7-hydroxymethyl-6,7-dihydrothiazolo[3,2-a][1,2,3]triazolo[4,5-d]pyrimidin-9(1H)-one (R = 0.027 for 1607 reflections) are reported.     

Synthesis of certain substituted pyrimidines as potential schistosomicidal agents

A convenient route is reported for the synthesis of seven new pyrimidine derivatives namely: 2-bromometh-yl-4,6-dimethoxypyrimidine ( 3 ), 2-dibromomethyl-4,6-dimethoxypyrimidine ( 4 ), 2-acetoxymethyl-4,6-dimeth-oxypyrimidine ( 5 ), 2-hydroxymethyl-4,6-dimethoxypyrimidine ( 6 ), 4,6-dimethoxypyrimidine-2-carboxaldehyde ( 7 ), 2-acetoxymethyl-6-methoxy-3,4-dihydropyrimidin-4-one ( 8 ) and 2-hydroxymethyl-3,4-dihydro-6-methoxy-pyrimidin-4-one ( 9 ).     

Quinazolines and 1,4-benzodiazepines. XLVI. Photochemistry of nitrones and oxaziridines

The cyclic nitrones 7-chloro-1,3-dihydro-5-phenyl-2H-1,4-benzodiazepin-2-one 4-oxide ( 5a ) and 1,3-dihydro-7-methylthio-5-phenyl-2H-1,4-benzodiazepin-2-one 4-oxide ( 5b ) are photoisomerized to readily isolable oxaziridines, 7-chloro-4,5-epoxy-5-phenyl-1,3,4–5-tetrahydro-2H-1,4-benzodiazepin-2-one ( 6a ) and 4,5-epoxy-5-phenyl-1,3,4,5-tetrahydro-7-methylthio-2H-1,4-benzo-diazepin-2-one ( 6b ). Oxaziridine 6b upon further irradiation gave ring expansion and ring contraction products, 4,6-dihydro-2-phenyl-9-methylthio-5H-1,3,6-benzoxadiazocin-5-one ( 7b ) and 4-benzoyl-3,4-dihydro-6-methylthioquinoxalin-2(1H)-one ( 8b ) respectively. The ring contraction product, 4-benzoyl-6-chloro-3,4-dihydroquinoxalin-2(1H)-one ( 8a ), was obtained from irradiation of oxaziridine 6a .     

Synthesis of alkylphenanthrenes from naphthylalkylidenemalonodinitriles. A route to 1-methyl-, 2-methyl-, and 1,2-dimethylphenanthrene

The study has been carried out to evaluate the feasibility of synthesis of 1-methyl-, 2-methyl-, 1,2-dimethyl-, and 1-ethyl-2-methylphenanthrene through the annulation of the naphthalene system with the exploitation of the dicyanovinyl moiety of 2-naphthylalkylidenemalonodinitriles as an active electrophile in cold solutions of concentrated sulfuric acid. 2-(2-Naphthyl)propanal (3), 1-(2-naphthyl)propan-2-one (9), 3-(2-naphthyl)butan-2-one (14), and 3-(2-naphthyl)pentan-2-one (19) had been condensed with malonodinitrile to afford 2-naphthylalkylidenemalonodinitriles which were then cyclised to give 4-amino-1-methylphenanthrene-3-carbonitrile (5), 4-amino-2-methylphenanthrene-3-carbonitrile (11), 4-amino-1,2-dimethylphenanthrene-3-carbonitrile (16), and 4-amino-1-ethyl-2-metylphenanthrene-3-carbonitrile (21). The nitrile function has been removed from the aminonitriles, with the exception of 21, through hydrolysis and decarboxylation in alkaline ethanolic solutions under elevated pressure (∼3 MPa) and temperature 220-230°C to give the respective 4-amino-methylphenanthrenes. Diazotisation of the phenanthreneamines and the reaction with hypophosphorus acid has lead to the methylphenanthrenes in moderate yields (50-52%).     

First straightforward synthesis of 1-hydroxy-3,4-dihydro-1H-benz[g]isochromene-5,10-dione and structure revision of a bioactive benz[g]isochromene-5,10-dione from Psychotria camponutans

For the first time, a synthesis of 1-hydroxy-3,4-dihydro-1H-benz[g]isochromene-5,10-dione (3), which is claimed to be a bioactive compound isolated from Psychotria camponutans, was achieved with a phthalide annulation reaction using 3-cyano-1(3H)-isobenzofuranone (5) and 5,6-dihydropyran-2-one (6) and subsequent reduction of the lactone moiety in the key steps. However, full spectral characterization of the synthesized target compound revealed that the isolated compound is not 1-hydroxy-3,4-dihydro-1H-benz[g]isochromene-5,10-dione (3). Structure revision shows the previously isolated compound to be the known psychorubrin (2).     

Oxygen replacement by fluorine in carbonyl derivatives of perfluoroaromatic compounds and isomerization of perfluoroindan-1,3-dione to perfluoro-3-methylenephthalide under the action of HF/SbF5

When acted upon by HF/SbF₅ at 95 °C, carbonyl groups of perfluorinated acetophenone (10), 3,4-dihydronaphthalen-1(2H)-one (8), 2,3-dihydronaphthalene-1,4-dione (9), benzocyclobutenone (6), benzocyclobutenedione (7) and indan-1-one (1) are converted into difluoromethylene groups to give the corresponding perfluoroaromatic products. Perfluoroindan-2-one (5), under the same conditions, is transformed to bis(perfluoroindan-2-yl) ether (21). On heating with HF/SbF₅, perfluoroindan-1,3-dione (2) isomerizes into perfluoro-3-methylenephthalide (4) at 95 °C, and gives 4,5,6,7-tetrafluoro-3-trifluoromethyl-phthalide (14) at 130 °C. Compound 4 in the absence of a solvent dimerizes giving perfluorodispiro[phthalide-3,1′-cyclobutane-2′,3″-phthalide] (18), and when heated with SbF₅ at 130 °C, it is converted into perfluoro-3-methylphthalide (3). When acted upon by HF/SbF₅ at 95 °C, perfluorinated benzoic acid (12) and phthalic anhydride (13) give the corresponding products with trifluoromethyl groups.     

Pseudoazulene. reaktionen von fulvenen mit 3,6-dicarbomethoxy-1,2,4,5-tetrazin

Fulvenes (1) react with 3,6-dicarbomethoxy-1,2,4,5-tetrazine (2) to give 4a,5-dihydro-2H-cyclopenta[d]pyridazines (3), which can be transformed with mangandioxide to the dehydrocompounds 4. Through 1,6-addition of hydrogen pseudoazaazulenes of the 2H-cyclopenta[d]pyridazin type (6) are obtained. Oxidative C-C-connection of these compounds yields dehydrodimers (10), which on hydrogenation give bis-pseudoazaazulenes (11).     

Polynucleotide analogues. VI. Synthesis and characterization of alternating copolymers of maleic anhydride and dihydropyran containing guanine derivatives

2-Amino-6-chloropurine was reacted with 2-(tosyloxymethyl)-2,3-dihydro-2H-pyran to give 2-(2-amino-6-chloropurin-9-ylmethyl)-2,3-dihydro-2H-pyran ( 3 ) and its N⁷-isomer ( 4 ), which were treated with 5% aqueous trimethylamine to result in 2-(guanin-9-ylmethyl)-2,3-dihydro-2H-pyran ( 5 ) and its N⁷-isomer ( 6 ), respectively. 2-(N²-Acetylguanin-9-yl-methyl)-3,4-dihydro-2H-pyran ( 7 ) and 2-(N²-acetylguanin-7-ylmethyl)-3,4-dihydro-2H-pyran ( 8 ), obtained by acetylation of compounds 5 and 6 , were copolymerized with maleic anhydride to give the alternating copolymers 9 and 10 , and they were hydrolyzed to result in poly[ {2-(guanin-9-ylmethyl)tetrahydropyran-5,6-diyl} {1,2-dicarboxyethylene}] ( 11 ) and poly[ {2-(guanin-7-ylmethyl)tetrahydropyran-5,6-diyl} {1,2-dicarboxyethylene}] ( 12 ), re-spectively. Polymer 11 showed hypochromicity whereas 12 exhibited hyperchromicity in aqueous solutions. Polymers 11 and 12 in aqueous solutions showed very strong excimer fluorescence with the maximum intensities at 432 and 446 nm, respectively, at room tem-perature. The two polymers showed polyelectrolyte effects, e.g., very high GPC molecular weights as well as reduced viscosities at low concentrations in water. Normal behavior was retained by addition of inorganic salts. Sodium salts of polymers 11 and 12 migrated to the anode by electrophoresis and both showed two bands. © 1995 John Wiley & Sons, Inc.     

Unambiguously confirmed structure of 2-phenacylidene-1,2-dihydro-4H-pyrido[2,3-b]pyrazin-3-one and 3-phenacylidene-3,4-dihydro-1H-pyrido[2,3-b]pyrazin-2-one

To determine the structures of two isomeric products, 2-phenacylidene-1,2-dihydro-4H-pyrido[2,3-b]pyrazin-3-one (2) and 3-phenacylidene-3,4-dihydro-1H-pyrido[2,3-b]pyrazin-2-one (3) obtained by condensation of 2,3-diaminopyridine (1) with ethyl benzoylpyruvate [1–3], these compounds were hydrolyzed to give 2-methyl-4H-pyrido[2,3-b]pyrazin-3-one (4) and 3-methyl-1H-pyrido[2,3-b]pyrazin-2-one (5) , respectively [4,5]. Both hydrolysates 4 and 5 were hydrogenated to afford 2-methyl-1,2-dihydro-4H-pyrido[2,3-b]pyrazin-3-one (6) and 3-methyl-3,4-dihydro-1H-pyrido[2,3-b]pyrazin-2-one (7) . The latter compound was identical with an unequivocally synthesized compound providing proof for the structures of all these compounds.     

A convenient synthesis of (z)-3-(α-alkoxycarbonyl-α-cyanomethylene)-2-oxo-1,2,3,4-tetrahydroquinoxalines and related compounds

(Z)-3-(α-Alkoxycarbonyl-α-cyanomethylene)-2-oxo-1,2,3,4-tetrahydroquinoxalines 3 and (Z)-3-(α-alkoxycarbonyl-α-cyanomethylene)-3,4-dihydrobenzo[g]quinoxalin-2(1H)-ones 5 possessing various alkoxycarbonyl groups were prepared in good yields directly from the reaction of dialkyl (E)-2,3-dicyanobutendioates 1 with o-phenylenediamine ( 2 ) or with 2,3-diaminonaphthalene ( 4 ), respectively. Furthermore, 2,3-diaminopyridine ( 6 ) and 3,4-diaminopyridine ( 7 ) were reacted with the diethyl ester 1b to give (Z)-2-(α-cyano-α-ethoxycarbonylmethylene)-1,2-dihydro-4H-pyrido[2,3-b]pyrazin-3-one ( 8 ) and (Z)-3-(α-cyano-α-ethoxycarbonylmethylene)-3,4-dihydro-1H-pyrido[3,4-b]pyrazin-2-one ( 9 ), respectively. The structural studies of 3, 5, 8 , and 9 were carried out by nmr experiments in some details.     

Synthesis of 12-acetoxy-1, 3-dodecadiene,an insect sex pheromone of the red bollworm moth,from a butadiene telomer

8-Phenoxy-1, 6-octadiene (1) formed by the Pd-catalyzed telomerization of butadiene with phonol was converted to 8-phenoxy-6-octen-1-ol (3). The alcohol 3 was converted to 8-iodo-1-phenoxy-2-octene (5). The Grignard reagent 7 prepared from 4-chloro 1-butyl tetrahydropranyl ether was coupled with the iodide 5 by the catalysis of CuI and bipyridyl to give 12-phenoxy-10-dodecen-1-ol (9), which was converted to 12-acetoxy-1-phenoxy-2-dodecene (10). Finally, 12-acetoxy-1, 3-dodecadiene (11) was obtained by the palladium catalyzed elimination of phenol from phenoxyacetoxy-dodecene (10).     

Synthese von imidazo[1,5-a]- und pyrazino[1,2-a]benzimidazolen

1,2-Dihydro-3H-imidazo[1,5-a]benzimidazoles (6), 1-oxo-1,2-dihydro-3H-imidazo[ 1,5-a] benzimidazoles (8), 3H-imidazo[1,5-a]benzimidazoles (7), 3-oxo-1,2,3,4-tetrahydro-pyrazino[1,2-a] benzimidazoles (12), and 3,4-dioxo-1,2,3,4-tetrahydro-pyrazino[1,2-a]benzinudazoles (13) were synthesized from 2-α-aminobenzyl (benzhydryl)-benzimidazoles (2).     

Poronitins A and B, 4-pyrone and 4-pyridone derivatives from the elephant dung fungus Poronia gigantea

New 4-pyrone and 4-pyridone derivatives, poronitins A (1) and B (2), and a new isocoumarin, 3,4-dihydro-6,8-dimethoxy-4-hydroxy-4-methyl-3-methyleneisochromen-1-one (3), were isolated from cultures of the elephant dung fungus, Poronia gigantea. The structures were elucidated on the basis of the NMR and MS data. Poronitin A (1) and known (R)-5-methylmellein were detected in all cultures (4 strains) of P. gigantea, which suggested that these metabolites maybe useful as chemotaxonomic markers.     

Preparation of novel heterocyclic systems from isatoic anhydrides

Isatoic anhydride ( 1a ) and 5-chloroisatoic anhydride ( 1b ) were treated with 2-(1-methylhydrazino)ethanol ( 2 ) to produce 2-aminobenzoic acid 2-(2-hydroxyethyl)-2-methylhydrazide ( 3a ) and its 5-chloro analog 3b , respectively. Treatment of 3a and 3b with carbon disulfide gave, respectively, 2,3-dihydro-3-[(2-hydroxyethyl)methylamino]-2-thioxo-4-(1H)quinazolinone ( 4a ) and its 6-chloro analog 4b . Compounds 4a and 4b afforded 5,6-dihydro-5-methyl-2-thioxo-4H,8H-[1,3,5,6]oxathiadiazocino[4,5-b]quinazolin-8-one ( 5a ) and its 10-chloro analog 5b , respectively, upon treatment with thiophosgene. Compound 5a could be produced directly from 3a and thiophosgene. Treatment of 4a and 4b with trifluoroacetic anhydride followed by potassium carbonate gave 3,4-dihydro-4-methyl-2H,6H-[1,3,4]thiadiazino[2,3-b]quinazolin-6-one ( 7a ) and its 8-chloro analog 7b , respectively. Treatment of 4a with thionyl chloride also gave 7a , but 4b and thionyl chloride afforded a mixture of 7b and 8-chloro-3,4-dihydro-4-methyl-2H,6H-[1,3,4]oxadiazino[2,3-b]quinazolin-6-one ( 10 ). The dimethyl analogs of 4a and 4b ( 13a and 13b ) upon treatment with thiophosgene afforded 3,4-dihydro-2,2,4-trimethyl-2H,6H-[1,3,4]oxadiazino[2,3-b]quinazolin-6-one ( 14a ) and its 8-chloro analog 14b , respectively.